Pituitary Cancer

A Comprehensive Review of Alternative Therapeutic Approaches for Nausea and Vomiting Relief in Pregnancy

Alternative medication is used for treating the common problems associated with pregnancy. 80% of women suffer from morning sickness during pregnancy. Treatment during pregnancy via using non-pharmacological therapy is quite popular all over the world as it is safe and has no negative effects on the fetus. Nausea and vomiting are one of the most prominent problems faced by pregnant women. Acupressure and Aromatherapy have been used by pregnant ladies nowadays for relieving nausea and vomiting symptoms. Conventional therapies also aid in medication of morning sickness in pregnancy duration that covers drugs like Antiemetics, Corticosteroids, Antihistaminic, IV fluids and Vitamin-B6 supplements. Many scientific studies have demonstrated that few drugs that come under conventional treatment cause severe birth defects and stillbirth. This is the leading reason pregnant women prefer to use herbs instead of using conventional medical treatment. The prospective of this review article is to find out the alternative and conventional therapeutic approaches for alleviating the symptoms of morning sickness during pregnancy.

Arsenic Exposure and Amyloid Precursor Protein Processing: A Focus on Alzheimer's Disease

Background: Arsenic is present in above permissible safe limits in groundwater, soil, and food, in various areas of the world. This is increasing exposure to humankind and affecting health in various ways. Alternation in cognition is one among them. Epidemiological research has reflected the impact of arsenic exposure on children in the form of diminished cognition.

Aims: Considering this fact, the present study reviewed the impact of arsenic on amyloid precursor protein, which is known to cause one of the commonest cognitive disorders such as Alzheimer’s disease.

Methods: The present study reviews the arsenic role in the generation of amyloid-beta from its precursor that leads to Alzheimer’s disease through the published article from Pubmed and Scopus.

Description: According to the findings, regular, long-term exposure to arsenic beginning in infancy changes numerous arsenic level-regulating regions in the rat brain, which are related to cognitive impairments. Arsenic also affects the BBB clearance route by increasing RAGE expression. Arsenic triggers the proamyloidogenic pathway by increasing APP expression and subsequently, its processing by β-secretase and presenilin. Arsenic also affects mitochondrial dynamics, DNA repair pathway and epigenetic changes. The mechanism behind all these changes is explained in the present review article.

Conclusion: A raised level of arsenic exposure affects the amyloid precursor protein, a factor for the early precipitation of Alzheimer’s disease.

Artemisinin Attenuates Isoproterenol-induced Cardiac Hypertrophy via the ERK1/2 and p38 MAPK Signaling Pathways

Background: Artemisinin (ART) is mainly derived from Artemisia annua, a traditional Chinese medicinal plant, and has been found to affect cellular biochemical processes, such as proliferation, angiogenesis, and apoptosis, in addition to its antimalarial properties. However, its effect on cardiac hypertrophy and the underlying mechanisms remain unclear.

Objectives: This study aimed to investigate the effect of ART on cardiac hypertrophy and explore its possible mechanisms.

Materials and Methods: A rat model was established by intraperitoneal injection of isoproterenol (ISO) for 3 days, and the degree of myocardial hypertrophy was compared among 5 groups: a control (CON) group, an ISO group, and groups treated with different doses of ART (7 mg/kg/d, 35 mg/kg/d, and 75 mg/kg/d). Echocardiography was used to evaluate cardiac function and structure. The cross-sectional area of cardiomyocytes was measured by hematoxylin and eosin (H&E) staining. The heart weight (HW), body weight (BW), and tail length were measured, and the HW/tail length ratio and the HW/BW ratio were calculated. H9c2 rat cardiomyocytes were cultured, and different amounts of ART were added 2 hours before ISO stimulation. Phalloidin staining was used to evaluate the degree of cell hypertrophy. The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were quantified in rat plasma and cell supernatant using enzyme-linked immunosorbent assay (ELISA), while the expression levels of p- ERK1/2, p-JNK, and p-p38 MAPK were assessed in the myocardium and H9c2 cells via western blot analysis.

Results: Intragastric administration of ART at a dosage of 35 mg/kg/d or over mitigated the early-stage cardiac hypertrophy induced by ISO in rats led to a reduction in left ventricular posterior wall diastolic thickness, interventricular septal thickness at diastole, lowered ANP and BNP levels, as well as a decrease in HW/tail length and HW/BW ratio. In vitro studies demonstrated that ART at a concentration of 100 μM inhibited ISO-mediated hypertrophy of H9c2 cells. The ISO group showed a higher p-ERK/GAPDH ratio and p-p38 MAPK/GAPDH ratio than the control group both in vivo and in vitro. Although the p-JNK/GAPDH ratio was increased in the ISO group, there was no statistical difference. The p-ERK/GAPDH and p-p38/GAPDH ratios were significantly lower in the ART group than in the ISO group.

Conclusion: The mechanism of ART against cardiac hypertrophy was related to inhibition of the ERK1/2 and p38 MAPK signaling pathways.

Peptides for Dual Targeting of ErbB1 and ErbB2: Blocking EGFR Cell Signaling Transduction Pathways for Cancer Chemotherapy

Cancer is one of the most deadly diseases involving dysregulated cell proliferation. Chemotherapeutic drugs have serious drawbacks of nonspecific toxicity and drug resistance. Tyrosine kinases are a significant class of enzymes of protein kinases. The four members of the trans-membrane family of tyrosine kinase receptors known as the human epidermal growth factor receptors (EGFR), ErbB1/HER1, ErbB2/HER2/neu, ErbB3/HER3, and ErbB4/HER4, are overexpressed in many forms of cancer. These receptors are crucial for cell division, invasion, metastasis, angiogenesis, and uncontrolled activation of cancer cells. In this context, an attractive combination of anticancer drug targets is ErbB1 and ErbB2. Numerous cancer types exhibit overexpression of ErbB1 and ErbB2, which is linked to poor prognosis and causes resistance to ErbB1-targeted therapy. Further, it has been reported in recent years that the use of peptides as anticancer agents have the potential to circumvent the drawbacks of the currently used chemotherapeutic drugs. Among them, short peptides have several advantages when compared to small molecules. The present report reviews the importance of tyrosine kinases as targets for cancer, the role of peptides as therapeutic agents, and the investigations that have been carried out by earlier workers for targeting both ErbB1 and ErbB2 using therapeutic peptides.

Deep Learning-based Thigh Muscle Investigation Using MRI For Prosthetic Development for Patients Undergoing Total Knee Replacement (TKR)

Background: A prosthetic device is designed based on the quantitative analysis of muscle MRI which will improve the muscle control achieved with functional electrical stimulation/ guided robotic exoskeletons. Electromyography (EMG) provides muscle functionality information while MRI provides the physiological and functionality of muscles. The sensor feedbacks were used for the bionic prosthesis, but the length of muscle using image processing was not correlated .

Objective: To investigate and perform qualitative and quantitative assessment of thigh muscle using MRI. The objective of the work is to improve the existing VAG signal classification method to diagnose abnormality using MRI for patients undergoing Total knee replacement (TKR).

Methods: A deep learning method for qualitative and quantitative assessment of thigh muscle is done using MRI. In existing prosthetic devices, electrical measurements of a person’s muscles are obtained using surface or implantable electrodes. Several methods were used for the classification and diagnostic processes. The existing methods have drawbacks in feature extraction and require experts to design the system. This work combines medical image processing and orthopaedic prosthetics to develop a therapeutic method.

Results & Discussion: This design provides much more precise control of prosthetic limbs using the image processing technique. The hybrid CNN swarm-based method measures the muscle structure and functions. Along with the sensor readings, these details are combined for prosthetic control. The implementation was carried out in MATLAB, Sketchuppro, and Arduino IDE.

Conclusion: A combined swarm intelligence and deep learning method were proposed for qualitative and quantitative assessment of thigh muscle. The prosthetic device choice was done from the scanned MRI image like Humerus-T prosthetics, segmental prosthesis and arthrodesis prosthesis. The investigation was done for the Total knee replacement (TKR) approach.

Design and Development of Hypertuned Deep learning Frameworks for Detection and Severity Grading of Brain Tumor using Medical Brain MR images

Background: Brain tumor is a grave illness causing worldwide fatalities. The current detection methods for brain tumors are manual, invasive, and rely on histopathological analysis. Determining the type of brain tumor after its detection relies on biopsy measures and involves human subjectivity. The use of automated CAD techniques for brain tumor detection and classification can overcome these drawbacks.

Objective: The paper aims to create two deep learning-based CAD frameworks for automatic detection and severity grading of brain tumors – the first model for brain tumor detection in brain MR images and model 2 for the classification of tumors into three types: Glioma, Meningioma, and Pituitary based on severity grading.

Methods: The novelty of the research work includes the architectural design of deep learning frameworks for detection and classification of brain tumor using brain MR images. The hyperparameter tuning of the proposed models is done to achieve the optimal parameters that result in maximizing the models' performance and minimizing losses.

Results: The proposed CNN models outperform the existing state of the art models in terms of accuracy and complexity of the models. The proposed model developed for detection of brain tumors achieved an accuracy of 98.56% and CNN Model developed for severity grading of brain tumor achieved an accuracy of 92.36% on BraTs dataset.

Conclusion: The proposed models have an edge over the existing CNN models in terms of less complexity of the structure and appreciable accuracy with low training and test errors. The proposed CNN Models can be employed for clinical diagnostic purposes to aid the medical fraternity in validating their initial screening for brain tumor detection and its multi-classification.

Combination of Contrast-enhanced FlAIR and Contrast-enhanced T1WI: A Quick and Efficient Method in Detecting Brain Metastases of Lung Cancers

Background: Some patients with suspected brain metastases (BM) could not tolerate longer scanning examinations according to the standardized MRI protocol.

Objective: The purpose of this study was to evaluate the clinical value of contrast-enhanced fast fluid-attenuated inversion recovery (CE FLAIR) imaging in combination with contrast-enhanced T1 weighted imaging (CE T1WI) in detecting BM of lung cancer and explore a quick and effective MRI protocol.

Material and Methods: In 201 patients with lung cancers and suspected BM, T1WI and FLAIR were performed before and after administration of gadopentetate dimeglumine. Two radiologists reviewed pre- and post-contrast images to determine the presence of abnormal contrast enhancement or signal intensity and decided whether it was metastatic or not on CE T1WI (Group 1) and CE FLAIR (Group 2). The number, locations and features of abnormal findings in two groups were recorded. Receiver Operating Characteristic (ROC) analyses were conducted in three groups: Group 1, 2 and 3(combination of CE FLAIR and CE T1WI).

Results: A total of 714 abnormal findings were revealed, of which 672 were considered as BM and 42 nonmetastatic. Superficial and small metastases(≤10mm) in parenchyma and ependyma, leptomeningeal and non-expansive skull metastases were typically better seen on CE FLAIR. The areas under ROC in the three groups were 0.720,0.887 and 0.973, respectively. Group 3 was significantly better in diagnostic efficiency of BMs than Group 1 (p<0.0001) or Group 2 (p=0.0006).

Conclusion: The combination of CE T1WI and CE FLAIR promotes diagnostic performance and results in better observation and characterization of BM in patients with lung cancers. It provides a quick and efficient way of detecting BM.

Latest Developments in Magnetic Resonance Imaging for Evaluating the Molecular Microenvironment of Gliomas

The 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System has brought a transformative shift in the categorization of adult gliomas. Departing from traditional histological subtypes, the new classification system is guided by molecular genotypes, particularly the Isocitrate Dehydrogenase (IDH) mutation. This alteration reflects a pivotal change in understanding tumor behavior, emphasizing the importance of molecular profiles over morphological characteristics. Gliomas are now categorized into IDH-mutant and IDH wildtype, with significant prognostic implications. For IDH-mutant gliomas, the concurrent presence of Alpha-Thalassemia/mental retardation syndrome X-linked (ATRX) gene expression and co-deletion of 1p19q genes further refine classification. In the absence of 1p19q co-deletion, further categorization depends on the phenotypic expression of CDKN2A/B. Notably, IDH wildtype gliomas exhibit a poorer prognosis, particularly when associated with TERT promoter mutations, EGFR amplification, and +7/-10 co-deletion. Although not part of the new guidelines, the methylation status of the MGMT gene is crucial for guiding alkylating agent treatment. The integration of structural and functional Magnetic Resonance Imaging (MRI) techniques may play a vital role in evaluating these genetic phenotypes, offering insights into tumor microenvironment changes. This multimodal approach may enhance diagnostic precision, aid in treatment planning, and facilitate effective prognosis evaluation of glioma patients.

A Review on Psoriasis Pathophysiology, Clinical Appearance, and Pharmacotherapeutic Interventions

A chronic skin condition called psoriasis can manifest as plaque, flexural, guttate, pustular, and erythrodermic lesions, among other clinical symptoms. Sixty million people are believed to be affected by psoriasis worldwide. In India, the frequency ranges from 0.44 to 2.8%, with males affected two times more frequently than females in their third or fourth decade of life. An immune-mediated inflammation condition with a sizable genetic component is psoriasis. Due to its connection to psoriatic arthritis and the increased prevalence of cardiometabolic, hepatic, and psychiatric problems, a thorough and interdisciplinary strategy for treatment is required. Corticosteroids and analogs of vitamin D are examples of topical treatments for psoriasis. Phototherapy includes NB-UVB, psoralen, and ultraviolet radiation (PUVA). Standard systemic treatments include methotrexate, acitretin, and ciclosporin. This disease is useful for physicians and scientists since it might be used as a model for research into the underlying causes of chronic inflammation. It is also crucial for clinical trial scientists as a first-choice disease indication for preliminary research of new pathogenesis-based treatment approaches. This review covers both the therapeutic choices that have resulted from the analysis of the aggressive psoriatic pathways and the processes involved in the onset and progression of the disease. We start by writing regarding the important cell kinds and inflammatory mechanisms that initiate and maintain psoriatic inflammation. Next, we discuss how skin flora interacts with heredity, related epigenetic processes, and the pathogenesis of psoriasis. Finally, we provide a thorough analysis of recently targeted medications as well as well-known, extensively used treatments.

An MRI-only Three-dimensional Cephalometry Protocol based on the Integrated and Modular Architecture of the Human Head

Background: Currently, three-dimensional cephalometry measurements are mainly based on cone beam computed tomography (CBCT), which has limitations of ionizing radiation, lack of soft tissue information, and lack of standardization of median sagittal plane establishment.

Objectives: This study investigated magnetic resonance imaging (MRI)-only based 3D cephalometry measurement based on the integrated and modular characteristics of the human head.

Methods: Double U-Net CycleGAN was used for CT image synthesis from MRI. This method enabled the synthesis of a CT-like image from MRI and measurements were made using 3D slicer registration and fusion.

Results: A protocol for generating and optimizing MRI-based synthetic CT was described and found to meet the precision requirements of 3D head measurement using MRI midline positioning methods reported in neuroscience to establish the median sagittal plane. An MRI-only reference frame and coordinate system were established enabling an MRI-only cephalometric analysis protocol that combined the dual advantages of soft and hard tissue display. The protocol was devised using data from a single volunteer and validation data from a larger sample remains to be collected.

Conclusion: The reported method provided a new protocol for MRI-only cephalometric analysis of craniofacial growth and development, malformation occurrence, treatment planning, and outcomes.

CAD System Design for Pituitary Tumor Classification based on Transfer Learning Technique

Background: A brain tumor is an asymmetrical expansion by cells inevitably emulating amid them. Image processing is a vibrant research area where the handing out of the image in the medical field is an exceedingly tricky field. In this paper, an expert algorithm is suggested for the detection of pituitary brain tumors from MR images.

Methods: The preprocessing techniques (smoothing, edge detection, filtering) and segmentation techniques (watershed) are applied to the online data set. The transfer learning technique is used as a classifier whose performance is measured in terms of classification accuracy. Resnet 50, Inception V3VGG16, and VGG19 models are used as classification algorithms. The proposed model is validated using different machine learning techniques considering hybrid features.

Results: 96% accuracy was obtained employing the Inception V3 model & 95% accuracy was attained using hybrid GLDS and GLCM features employing Support Vector Machine algorithm while 93% was attained using Probabilistic Neural Network and k Nearest Neighbor techniques.

Conclusion: Computer-aided systems gave much faster and more accurate results than image processing techniques.1.0% accuracy improvement was observed while using Inception V3 over GLDS + GLCM + SVM and 2.1% accuracy improvement using GLDS + GLCM + SVM over GLDS + GLCM + kNN.

Medical Image Processing based on Generative Adversarial Networks: A Systematic Review

Background: Generative adversarial networks (GANs) have demonstrated superior data generation capabilities compared to other methods, making them popular for use in medical image applications. These features have intrigued researchers in the medical imaging field, resulting in a swift implementation of these techniques in various conventional and novel applications such as image reconstruction, segmentation, detection, classification, and cross-modality synthesis. A comprehensive review of recent medical imaging breakthroughs will benefit researchers interested in this field. In this review, we aimed to introduce the origin, principle, and extended forms of GANs and summarize the state-of-the-art progress of GAN-based medical image processing methods.

Methods: We searched the literature for studies on Google Scholar and PubMed using the keywords “Segmentation,” “Classification,” “medical image,” and “generative adversarial network.” Specifically, the initial search revealed 5423 publications after the removal of duplicated and non-accessible fulltext publications. Then, after the title and abstract screening, 680 underwent full-text screening. Finally, 121 studies were included in our final analysis after full-text screening.

Results: The date range of the studies covered in this review is from January 1, 2017, to the present. After a thorough screening and qualification assessment, 121 studies involving GAN-based applications in seven areas of medical images were included in the final methodological review. These areas included synthesis, classification, segmentation, conversion, reconstruction, denoising, and lesion detection. We further classified and summarized these papers into clinical applications, classification methods, and imaging modalities.

Conclusion: We thoroughly examined the latest research progress of GAN-based medical image augmentation. These techniques effectively alleviate the challenge of limited training samples for medical image diagnosis and treatment models. Furthermore, several critical issues associated with GANs, such as pattern collapse, instability, and lack of interpretability, require attention in future research.

Automated Brain Tumour Detection and Classification using Deep Features and Bayesian Optimised Classifiers

Purpose: Brain tumour detection and classification require trained radiologists for efficient diagnosis. The proposed work aims to build a Computer Aided Diagnosis (CAD) tool to automate brain tumour detection using Machine Learning (ML) and Deep Learning (DL) techniques.

Materials and Methods: Magnetic Resonance Image (MRI) collected from the publicly available Kaggle dataset is used for brain tumour detection and classification. Deep features extracted from the global pooling layer of Pretrained Resnet18 network are classified using 3 different ML Classifiers, such as Support vector Machine (SVM), K-Nearest Neighbour (KNN), and Decision Tree (DT). The above classifiers are further hyperparameter optimised using Bayesian Algorithm (BA) to enhance the performance. Fusion of features extracted from shallow and deep layers of the pretrained Resnet18 network followed by BA-optimised ML classifiers is further used to enhance the detection and classification performance. The confusion matrix derived from the classifier model is used to evaluate the system's performance. Evaluation metrics, such as accuracy, sensitivity, specificity, precision, F1 score, Balance Classification Rate (BCR), Mathews Correlation Coefficient (MCC) and Kappa Coefficient (Kp), are calculated.

Results: Maximum accuracy, sensitivity, specificity, precision, F1 score, BCR, MCC, and Kp of 99.11%, 98.99%, 99.22%, 99.09%, 99.09%, 99.10%, 98.21%, 98.21%, respectively, were obtained for detection using fusion of shallow and deep features of Resnet18 pretrained network classified by BA optimized SVM classifier. Feature fusion performs better for classification task with accuracy, sensitivity, specificity, precision, F1 score, BCR, MCC and Kp of 97.31%, 97.30%, 98.65%, 97.37%, 97.34%, 97.97%, 95.99%, 93.95%, respectively.

Conclusion: The proposed brain tumour detection and classification framework using deep feature extraction from Resnet 18 pretrained network in conjunction with feature fusion and optimised ML classifiers can improve the system performance. Henceforth, the proposed work can be used as an assistive tool to aid the radiologist in automated brain tumour analysis and treatment.

Classification of Brain Tumours in MRI Images using a Convolutional Neural Network

Introduction: Recent advances in deep learning have aided the well-being business in Medical Imaging of numerous disorders like brain tumours, a serious malignancy caused by unregulated and aberrant cell portioning. The most frequent and widely used machine learning algorithm for visual learning and image identification is CNN.

Methods: In this article, the convolutional neural network (CNN) technique is used. Augmentation of data and processing of images is used to classify scan imagery of brain MRI as malignant or benign. The performance of the proposed CNN model is compared with pre-trained models: VGG-16, ResNet-50, and Inceptionv3 using the technique which is transfer learning.

Results: Even though the experiment was conducted on a relatively limited dataset, the experimental results reveal that the suggested scratched CNN model accuracy achieved is 94%, VGG-16 was extremely effective and had a very low complexity rate with an accuracy of 90%, whereas ResNet- 50 reached 86% and Inception v3 obtained 64% accuracy.

Conclusion: When compared to previous pre-trained models, the suggested model consumes significantly less processing resources and achieves significantly higher accuracy outcomes and a reduction in losses.

Impact of COVID-19 on Endometriosis Patients: An Integrative Review

Background: During the COVID-19 pandemic, people's lives worldwide have undergone extensive changes. The pandemic has worsened the condition of patients with chronic diseases like women with endometriosis.

Objective: This study aims to summarize available evidence on the impact of the COVID-19 pandemic on physical symptoms, mental health, and medical care of patients with endometriosis.

Methods: In the present integrative review using PRISMA guidelines, related articles published from December 2019 to July 2023 in databases including MEDLINE, Science Direct, Scopus, and Google Scholar in the English language were extracted.

Results: After evaluating the criteria for inclusion and exclusion, a total of 23 articles were chosen and examined. This study represents an open window to investigate the impact of COVID-19 on women with endometriosis. The COVID-19 pandemic has affected the symptoms, mental well-being, and medical care of women with endometriosis.

Conclusions: There is a perceived necessity to provide supportive care for patients during pandemic restrictions. Remote work has had an unanticipated advantage, and it is recommended that women with endometriosis continue to work from home after COVID-19 to maintain their workplace effectiveness.

The Impact of the COVID-19 Pandemic on Women’s Health: A Review

During any crisis, whether it is health, economic, or environmental, people are more likely to experience stress, anxiety, and other psychological issues that jeopardize their general well-being. The Coronavirus, or COVID-19, is considered a global pandemic that affects millions of persons. Many people of different ages have significantly suffered from mental illness as a result of COVID-19, especially women affected vulnerable. As per the report, the death rates of men have doubled in comparison with women; this epidemic shows a bigger influence on the health of women than men. Even quarantine impacts make the females afraid, bewildered, and feel alone, which is terrible for them, as it also disturbs their health, such as pregnancy, sexual life, postpartum depression, etc. This review article reveals the COVID-19 impact on the health of women and finds a way to prevent and manage the health implications in women at various periods throughout their lives.

A Complete Overview of the Polycystic Ovarian Syndrome with Recent Advancement in Clinical Trial

Background: Polycystic ovarian syndrome (PCOS) has emerged as one of the most common endocrine and metabolic disorders seen in women of childbearing age throughout the whole world. The complex pathophysiology, different diagnostic criteria, and various manifestations attached to several environmental factors, including lifestyle influences, have made it one of the most difficult disorders to treat in recent times. In addition, inadequate knowledge among patients and a lack of dedicated approved medications have only enhanced the difficulties in treating such a heterogeneous disorder.

Objective: The main objective of this review-type paper is to provide a detailed overview of PCOS along with the current concept of a clinical stance in this complex multigenic disorder.

Method : The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents, the keywords “PCOS; hirsutism; psychological burden; obesity” and others of a similar nature were utilized.

Conclusion: PCOS is a complicated hormonal, metabolic, and psychological condition with many different clinical manifestations. It is among the most prevalent causes of infertility. Before considering any medication choices, lifestyle modifications should be considered the primary therapeutic prescription for PCOS-related infertility. According to recent studies, PCOS does not affect the risk of ovarian or breast cancer, but it does raise the risk of endometrial cancer in women of all ages. These results suggest that PCOS may increase the risk of gynaecological cancer morbidity. The following stage is ovulation stimulation, which is best accomplished with letrozole and is followed by clomiphene citrate. Women who had not responded to the first-line oral ovulatory medicine were given gonadotropins as a backup. Early detection of girls with a high propensity to develop PCOS will be made possible by a comprehensive knowledge of the condition's etiology. Adolescent PCOS will be better managed overall, related comorbidities will be prevented, and quality of life will increase with customized therapeutic approaches.

Treatment of Menopausal Symptoms with Herbal Medicines: A Review

Background: Menopause refers to the natural process of the “cessation of the menstrual cycle.” This phase predominantly affects aged women and can lead to various symptoms such as hot flashes, insomnia, night sweats, and sexual dysfunction, among others. Unfortunately, many women remain unaware of this condition, and some even choose to overlook the symptoms. However, those who recognize the symptoms consult with a doctor, who may recommend Hormone replacement therapy (HRT). Initially, Hormone replacement therapy (HRT) can be effective, but prolonged use can result in side effects. To mitigate these effects, there is a need to explore and investigate herbal therapies as an alternative treatment for menopausal symptoms.

Objective: The objective of this review is to explore and summarize various herbs used in managing menopausal symptoms as an alternative to hormone replacement therapy. Methods: For this review, we conducted a literature survey spanning from 1998 to 2023. We used keywords such as menopause, endocrinology, hormone replacement therapy, and herbs used for reducing menopausal symptoms to search databases such as Google Scholar, PubMed, and SciDirect. Relevant data were sourced from various journals like Plos One, JAMA, Frontier, Drug in Context, MDPI, Molecules, BMC Women's Health, Research Gate, Heliyon, Elsevier, Taylor & Francis, Nutrients, JMM, Wiley, OXFORD, Hindawi, Clinical Phytoscience, Pharmaceuticals, Phytomedicine, and Menopause: The Journal of The North American Menopause Society.

Results: The literature review encompassed 40 research articles and 200 review articles, including randomized controlled trials. The findings revealed that several herbal plants, including Curcuma longa, Zingiber officinale, Foeniculum vulgare, Trigonella foenum, Actaea racemosa, Glycyrrhiza glabra, Oenothera biennis, Trifolium pratense, Humulus lupulus, Vitex agnus-castus, Valeriana officinalis, Linum usitatissimum, Cannabis sativa, and Asparagus racemosus, have shown efficacy in treating menopausal symptoms.

Conclusion: In conclusion, medicinal plants can play a significant role in managing acute menopausal syndrome. The intent of this review is to highlight the most recent research on estrogenic plants for medicinal purposes and their therapeutic impact on cognitive deficiencies brought on by estrogen shortage during menopause and aging.

The Role of Neuronal Pathways in Gastrointestinal Cancers: Targets for Prevention and Treatment

In recent decades, the mortality and morbidity of Gastrointestinal (GI) cancer have remarkably increased, especially in younger individuals. Recent studies revealed that neuronal connections play an active part in GI tumor initiation and progression. Also, studies showed neurotransmitters and neuropeptides drive the activation of various oncogenic pathways downstream of neural receptors within cancer cells, underscoring the importance of neural signaling pathways in GI tumor malignancy. These studies show that the humoral and nervous pathways can transfer signals of tumors to the brain. But, the exact mechanism of this regulation from the brain to the gut is still unknown. In this review, we summarized the mechanism of the neuronal pathway in the regulation of promotion or suppression of GI cancer and oncogene activation, and we summarize recent findings linking the nervous system to GI tumor progression and highlight the importance of targeting neural mechanisms in GI tumor therapy.

Cancer Stem Cells and Treatment of Cancer: An Update and Future Perspectives

Cancer stem cells (CSCs) play an essential role in tumour progression and metastasis. Stem cell ability of self-renewal enables it to persist over time, thereby contributing to cancer relapse or recurrence and also resistance to current therapies. Therefore, targeting CSCs emerged as a promising strategy of cancer treatment. CSCs exhibit differentiation, self-renewal, and plasticity, they contribute to formation of malignant tumours, also favors, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Coventional cancer treatments predominantly target cancer cells that are not CSCs, CSCs frequently survive, eventually leading to relapse. This article focuses on the development of novel therapeutic strategies that combine conventional treatments and CSC inhibitors to eradicate cancer cells and CSCs, for the better and permanent treatment. However, the diversity of CSCs is a significant obstacle in the development of CSC-targeted therapies, necessitating extensive research for a better understanding and exploration of therapeutic approaches. Future development of CSC-targeted therapies will rely heavily on overcoming this obstacle.

Nutritional and Health Benefits of Cereals and Grains

The consumption of cereals and grains, along with whole grain food, is considered a healthy food that has various health benefits. Minerals, proteins, carbohydrates, and vitamins are present in the diet of many people. Phytochemicals play an essential role in combating oxidative stress and are present in high amounts in grains. These phytochemicals are also known as secondary metabolites that are present in plants. The nutritional components of basil (Ocimum basilicum), chia (Salvia hispanica), flax (Linum usitatissimmum), Proso millet (Panicum miliaceum), and oat (Avena sativa) are analyzed. Seeds are considered a good source of omega-3 and omega-6 fatty acids that have a significant impact on human health. The high amount of tocopherol (vitamin E) is due to the high content of polyunsaturated fatty acids (PUFAs). γ-Tocopherol is an antioxidant nutrient that usually blocks the formation of carcinogenic nitrosamines from nitrites present in food in the stomach. This review provides detailed information on the nutritional and health benefits of these cereals and grains, in which all the major components have been discussed. Conclusively, the potential use of these cereals and grains alone and by mixing them with other food products is also discussed which may enhance the nutritional content of the food product.

Inclusive Exploration of Harmonizing and Alternative Treatments for Hypothyroidism

A clinical syndrome known as hypothyroidism occurs due to a shortage of thyroid hormone as a result of decreased production, abnormal distribution, or no action of thyroid hormones. The most typical clinical symptoms included are dry skin, hair loss, weight gain, painful-prolonged periods, infertility, balance problems, slow speech, bradycardia, hypothermia, fatigue, anxiety & depression, joint pain, and indigestion. Basically, age, gender, the severity of the ailment, and a few other factors affect the various signs and symptoms of hypothyroidism. The limitations of allopathic modalities necessitate the investigation of alternative treatment options. Future healthcare initiatives for the poor world will increasingly depend on CAM approaches to these concerns because lifestyle, diet, obesity, lack of exercise, and stress are significant contributing factors to the development of hypothyroidism. This review's objective is to provide information on herbs as well as complementary and alternative medications which are grouped into five major domains: Biologically Based therapies, Manipulative body-based therapies, Mind body-based therapies, and the whole Medical system. These have traditionally been used to treat thyroid dysfunction. The distribution of diseases in emerging nations is altering as a result of globalization. Hence the existing and potential roles of CAM techniques in the general practice of medicine are illustrated in these approaches. Scientists are being compelled to consider traditional herbal medical treatments and CAM therapy in order to combat adverse medication occurrences, high treatment costs, and compliance problems thus described in this review paper.

Molecular Mechanisms of Polyphenols in Management of Skin Aging

The natural process of skin aging is influenced by a variety of factors, including oxidative stress, inflammation, collagen degradation, and UV radiation exposure. The potential of polyphenols in controlling skin aging has been the subject of much investigation throughout the years. Due to their complex molecular pathways, polyphenols, a broad class of bioactive substances present in large quantities in plants, have emerged as attractive candidates for skin anti-aging therapies. This review aims to provide a comprehensive overview of the molecular mechanisms through which polyphenols exert their anti-aging effects on the skin. Various chemical mechanisms contribute to reducing skin aging signs and maintaining a vibrant appearance. These mechanisms include UV protection, moisturization, hydration, stimulation of collagen synthesis, antioxidant activity, and anti-inflammatory actions. These mechanisms work together to reduce signs of aging and keep the skin looking youthful. Polyphenols, with their antioxidant properties, are particularly noteworthy. They can neutralize free radicals, lessening oxidative stress that might otherwise cause collagen breakdown and DNA damage. The anti-inflammatory effects of polyphenols are explored, focusing on their ability to suppress pro-inflammatory cytokines and enzymes, thereby alleviating inflammation and its detrimental effects on the skin. Understanding these mechanisms can guide future research and development, leading to the development of innovative polyphenol-based strategies for maintaining healthy skin.

A Complex Condition; Polycystic Ovary Syndrome (PCOS): A Review of its Recent Advanced Treatment

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting women worldwide. It refers to a condition that often has ‘poly’ liquid containing sacks around ovaries. It affects reproductive-aged females, giving rise to menstrual and related reproductive issues. PCOS is marked by hormonal imbalance, often resulting in hyperandrogenism. Women with PCOS might experience abnormal insulin activity and complications such as acne, mood swings, hirsutism, obesity, and infertility. The disease is linked with severe clinical ailments such as type 2 diabetes (T2DM), cardiovascular diseases (CVDs), and cancer. A faulty lifestyle, neuroendocrine factors, genetic causes, and androgen exposures often cause PCOS. The approach of society towards physiological problems such as PCOS in women is that it must be under the veil that is the ultimate barrier to the early diagnosis of PCOS. Thus, this review summarizes the causes, symptoms, pathophysiology, diagnosis, and possible treatment (medical, herbal, and lifestyle improvement, acupuncture, and bariatric surgery) related to PCOS.

An Exquisite Analysis on the Significance of Nutrient Supplementation in the Holistic Management of Poly-cystic Ovarian Syndrome

The complex heterogeneous disorder known as polycystic ovarian syndrome (PCOS) includes endocrine, reproductive, metabolic, psychological, and other pathological aspects. Yet, nothing is understood regarding the cause of PCOS. Insulin resistance and hyperandrogenism are major contributors to the pathophysiology of PCOS, according to various studies. Because of this, a lot of PCOS treatment regimens include changing a person's lifestyle through practices, like exercise, nutrition, and vitamin supplementation. Recent studies have indicated a number of nutrients, including vitamins, minerals, and vitamin-like substances, for the therapy of PCOS since they all have at least one functional characteristic in the pathways that are affected by PCOS. As a result, it is claimed that PCOS may be caused by a vitamin or mineral deficiency. It is the goal of this review to conduct a critical literature analysis on nutritional supplementation for the management of PCOS.

Essential Fatty Acids along the Women’s Life Cycle and Promotion of a Well-balanced Metabolism

Linoleic acid (ω-6 LA) and α-linolenic acid (ω-3 ALA) are essential fatty acids (EFA) for human beings. They must be consumed through diet and then extensively metabolized, a process that plays a fundamental role in health and eventually in disease prevention. Given the numerous changes depending on age and sex, EFA metabolic adaptations require further investigations along the women’s life cycle, from onset to decline of the reproductive age. Thus, this review explains women’s life cycle stages and their involvement in diet intake, digestion and absorption, the role of microbiota, metabolism, bioavailability, and EFA fate and major metabolites. This knowledge is crucial to promoting lipid homeostasis according to female physiology through well- directed health strategies. Concerning this, the promotion of breastfeeding, nutrition, and physical activity is cardinal to counteract ALA deficiency, LA/ALA imbalance, and the release of unhealthy derivatives. These perturbations arise after menopause that compromise both lipogenic and lipolytic pathways. The close interplay of diet, age, female organism, and microbiota also plays a central role in regulating lipid metabolism. Consequently, future studies are encouraged to propose efficient interventions for each stage of women's cycle. In this sense, plant-derived foods and products are promising to be included in women’s nutrition to improve EFA metabolism.

Multiomics Analysis of Disulfidptosis Patterns and Integrated Machine Learning to Predict Immunotherapy Response in Lung Adenocarcinoma

Background: Recent studies have unveiled disulfidptosis as a phenomenon intimately associated with cellular damage, heralding new avenues for exploring tumor cell dynamics. We aimed to explore the impact of disulfide cell death on the tumor immune microenvironment and immunotherapy in lung adenocarcinoma (LUAD).

Methods: We initially utilized pan-cancer transcriptomics to explore the expression, prognosis, and mutation status of genes related to disulfidptosis. Using the LUAD multi- -omics cohorts in the TCGA database, we explore the molecular characteristics of subtypes related to disulfidptosis. Employing various machine learning algorithms, we construct a robust prognostic model to predict immune therapy responses and explore the model's impact on the tumor microenvironment through single-cell transcriptome data. Finally, the biological functions of genes related to the prognostic model are verified through laboratory experiments.

Results: Genes related to disulfidptosis exhibit high expression and significant prognostic value in various cancers, including LUAD. Two disulfidptosis subtypes with distinct prognoses and molecular characteristics have been identified, leading to the development of a robust DSRS prognostic model, where a lower risk score correlates with a higher response rate to immunotherapy and a better patient prognosis. NAPSA, a critical gene in the risk model, was found to inhibit the proliferation and migration of LUAD cells.

Conclusion: Our research introduces an innovative prognostic risk model predicated upon disulfidptosis genes for patients afflicted with Lung Adenocarcinoma (LUAD). This model proficiently forecasts the survival rates and therapeutic outcomes for LUAD patients, thereby delineating the high-risk population with distinctive immune cell infiltration and a state of immunosuppression. Furthermore, NAPSA can inhibit the proliferation and invasion capabilities of LUAD cells, thereby identifying new molecules for clinical targeted therapy.

Unveiling the Molecular Mechanism of Diosmetin and its Impact on Multifaceted Cellular Signaling Pathways

Background: Diosmetin is an O-methylated flavone and the aglycone part of the flavonoid glycosides diosmin that occurs naturally in citrus fruits. Pharmacologically, diosmetin is reported to exhibit anticancer, antimicrobial, antioxidant, oestrogenic, and anti-inflammatory activities.

Objective: This comprehensive review was aimed to critically explore diverse pharmacological activities exhibited by diosmetin. Along with that, this review can also identify potential research areas with an elucidation of the multifactorial underlying signaling mechanism of action of diosmetin in different diseases.

Methods: A comprehensive collection of evidence and insights was obtained from scientific journals and books from physical libraries and electronic platforms like Google Scholar and PubMed. The time frame selected was from year 1992 to July 2023.

Results: The review delves into diosmetin's impact on cellular signaling pathways and its potential in various diseases. Due to its ability to modulate signaling pathways and reduce oxidative stress, it can be suggested as a potential versatile therapeutic agent for mitigating oxidative stressassociated pathogenesis.

Conclusion: The amalgamation of the review underscores diosmetin's promising role as a multifaceted therapeutic agent, highlighting its potential for drug development and clinical applications.

Invasive Fungal Infections in the Paediatric Intensive Care Unit: A Hong Kong Study

Introduction: Invasive fungal infections (IFI) cause significant mortality and morbidity in the Paediatric Intensive Care Unit (PICU). Early recognition and prompt treatment of invasive fungal infections are important. This article reviewed the mortality and morbidity of IFIs in the PICU of Hong Kong Children’s Hospital.

Methods: A retrospective review of all PICU admissions from April 2019 to May 2021 was performed. The following data were retrieved: age, gender, diagnosis, comorbidity, clinical manifestation, type of fungus, duration of stay at PICU, absolute neutrophil count, use of immunosuppressive therapy, presence of central venous catheter and use of total parental nutrition. The primary outcomes were the incidence and mortality of IFIs among PICU patients. The secondary outcomes were risk factors for developing IFI in PICU and clinical course of IFIs. Numerical variables were compared between groups by Mann-Whitney U test and categorical variables by Fisher’s exact test.

Results: There were 692 PICU admissions over the study period from April 2019 to May 2021. The crude mortality was 3% (n=24 death cases) in the PICU. Fourteen patients (2%) fulfilling the criteria for IFIs were identified using hospital electronic record system and according to PICU documentation. Eight of these 14 patients (57%) had hematological malignancy, 2 (17%) had solid tumours and 4 had non-oncological conditions. Eight (57%) patients were neutropenic with absolute neutrophil count less than 1x 109 at diagnosis of IFI. Ten (71%) had received immunosuppressive therapy including steroid, cyclosporin A, Mycophenolate mofetil (MMF), Sirolimus or tacrolimus. 12 (86%) had had central venous catheter. Eight (57%) were on parenteral nutrition. IFIs due to Rhizopus or Aspergillus infection (5/14), or in post-haematopoietic stem cell transplant patients (5/14) were associated with non-survival (p = 0.031).

Conclusion: All patients with IFIs managed in the PICU had haemato-oncology diseases or were recipients of stem cell transplantation. IFIs with Rhizopus or Aspergillus as a group were associated with high mortality in the PICU. Awareness of this pathology with prompt diagnosis and treatment may improve the outcome of these infections and reduce the mortality.

Approaches Towards Better Immunosuppressive Agents

Several classes of compounds are applied in clinics due to their immunosuppressive properties in transplantology and the treatment of autoimmune diseases. Derivatives of mycophenolic acid, corticosteroids and chemotherapeutics bearing heterocyclic moieties like methotrexate, azathioprine, mizoribine, and ruxolitinib are active substances with investigated mechanisms of action. However, improved synthetic approaches of known drugs and novel derivatives are still being reported to attempt better accessibility and therapeutic properties. In this review article, we present the synthesis of the designed chemical structures based on recent literature reports concerning novel compounds as promising immunosuppressive drugs. Moreover, some of the discussed derivers revealed also other types of activities with prospective medicinal potential.

Recent Updates on Oncogenic Signaling of Aurora Kinases in Chemosensitive, Chemoresistant Cancers: Novel Medicinal Chemistry Approaches for Targeting Aurora Kinases

The Aurora Kinase family (AKI) is composed of serine-threonine protein kinases involved in the modulation of the cell cycle and mitosis. These kinases are required for regulating the adherence of hereditary-related data. Members of this family can be categorized into aurora kinase A (Ark-A), aurora kinase B (Ark-B), and aurora kinase C (Ark-C), consisting of highly conserved threonine protein kinases. These kinases can modulate cell processes such as spindle assembly, checkpoint pathway, and cytokinesis during cell division. The main aim of this review is to explore recent updates on the oncogenic signaling of aurora kinases in chemosensitive/chemoresistant cancers and to explore the various medicinal chemistry approaches to target these kinases. We searched Pubmed, Scopus, NLM, Pubchem, and Relemed to obtain information pertinent to the updated signaling role of aurora kinases and medicinal chemistry approaches and discussed the recently updated roles of each aurora kinases and their downstream signaling cascades in the progression of several chemosensitive/chemoresistant cancers; subsequently, we discussed the natural products (scoulerine, Corynoline, Hesperidin Jadomycin-B, fisetin), and synthetic, medicinal chemistry molecules as aurora kinase inhibitors (AKIs). Several natural products' efficacy was explained as AKIs in chemosensitization and chemoresistant cancers. For instance, novel triazole molecules have been used against gastric cancer, whereas cyanopyridines are used against colorectal cancer and trifluoroacetate derivatives could be used for esophageal cancer. Furthermore, quinolone hydrazine derivatives can be used to target breast cancer and cervical cancer. In contrast, the indole derivatives can be preferred to target oral cancer whereas thiosemicarbazone-indole could be used against prostate cancer, as reported in an earlier investigation against cancerous cells. Moreover, these chemical derivatives can be examined as AKIs through preclinical studies. In addition, the synthesis of novel AKIs through these medicinal chemistry substrates in the laboratory using in silico and synthetic routes could be beneficial to develop prospective novel AKIs to target chemoresistant cancers. This study is beneficial to oncologists, chemists, and medicinal chemists to explore novel chemical moiety synthesis to target specifically the peptide sequences of aurora kinases in several chemoresistant cancer cell types.

Current Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease

Acetylcholine (ACh) is ubiquitously present in the nervous system and has been involved in the regulation of various brain functions. By modulating synaptic transmission and promoting synaptic plasticity, particularly in the hippocampus and cortex, ACh plays a pivotal role in the regulation of learning and memory. These procognitive actions of ACh are mediated by the neuronal muscarinic and nicotinic cholinergic receptors. The impairment of cholinergic transmission leads to cognitive decline associated with aging and dementia. Therefore, the cholinergic system has been of prime focus when concerned with Alzheimer’s disease (AD), the most common cause of dementia. In AD, the extensive destruction of cholinergic neurons occurs by amyloid-β plaques and tau protein-rich neurofibrillary tangles. Amyloid-β also blocks cholinergic receptors and obstructs neuronal signaling. This makes the central cholinergic system an important target for the development of drugs for AD. In fact, centrally acting cholinesterase inhibitors like donepezil and rivastigmine are approved for the treatment of AD, although the outcome is not satisfactory. Therefore, identification of specific subtypes of cholinergic receptors involved in the pathogenesis of AD is essential to develop future drugs. Also, the identification of endogenous rescue mechanisms to the cholinergic system can pave the way for new drug development. In this article, we discussed the neuroanatomy of the central cholinergic system. Further, various subtypes of muscarinic and nicotinic receptors involved in the cognition and pathophysiology of AD are described in detail. The article also reviewed primary neurotransmitters that regulate cognitive processes by modulating basal forebrain cholinergic projection neurons.

Exposure to Endocrine-disrupting Chemicals and Environmental Toxins Attributing to Polycystic Ovarian Syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by excess androgen and infertility due to anovulatory failure. A significant fraction of the world's population is affected by the infertility condition known as PCOS. Due to the disease's complicated nature and overlapping symptoms, diagnosis of the condition is frequently challenging. Exogenous compounds or combinations known as endocrine-disrupting chemicals (EDCs) can imitate the effects of steroid hormones and obstruct their metabolism. EDCs and this condition have recently been the subject of intensive research to better understand the possible contribution of these substances to the pathophysiology of PCOS. It was shown that EDC exposure can be connected to PCOS in either a direct or indirect way since PCOS is linked to higher levels of oxidative stress and inflammation, which lead to obesity, insulin resistance, and infertility. This review's objective is to investigate how exposure to environmental contaminants affects the etiology of polycystic ovarian syndrome.

Catechin Protects against Lipopolysaccharide-induced Depressive-like Behaviour in Mice by Regulating Neuronal and Inflammatory Genes

Background: Many studies have suggested that tea has antidepressant effects; however, the underlying mechanism is not fully studied. As the main anti-inflammatory polyphenol in tea, catechin may contribute to the protective role of tea against depression.

Objective: The objective of this study is to prove that catechin can protect against lipopolysaccharide (LPS)-induced depressive-like behaviours in mice, and then explore the underlying molecular mechanisms.

Methods: Thirty-one C57BL/6J mice were categorized into the normal saline (NS) group, LPS group, catechin group, and amitriptyline group according to their treatments. Elevated Plus Maze (EPM), Tail Suspension Test (TST), and Open Field Test (OFT) were employed to assess depressive- like behaviours in mice. RNA sequencing (RNA-seq) and subsequent Bioinformatics analyses, such as differential gene analysis and functional enrichment, were performed on the four mouse groups.

Results: In TST, the mice in the LPS group exhibited significantly longer immobility time than those in the other three groups, while the immobility times for the other three groups were not significantly different. Similarly in EPM, LPS-treated mice exhibited a significantly lower percentage in the time/path of entering open arms than the mice in the other three groups, while the percentages of the mice in the other three groups were not significantly different. In OFT, LPS-treated mice exhibited significantly lower percentages in the time/path of entering the centre area than those in the other three groups. The results suggested that the LPS-induced depression models were established successfully and catechin can reverse (LPS)-induced depressive-like behaviours in mice. Finally, RNA-seq analyses revealed 57 differential expressed genes (DEGs) between LPS and NS with 19 up-regulated and 38 down-regulated. Among them, 13 genes were overlapped with the DEGs between LPS and cetechin (in opposite directions), with an overlapping p-value < 0.001. The 13 genes included Rnu7, Lcn2, C4b, Saa3, Pglyrp1, Gpx3, Lyz2, S100a8, S100a9, Tmem254b, Gm14288, Hbb-bt, and Tmem254c, which might play key roles in the protection of catechin against LPS-induced depressive-like behaviours in mice. The 13 genes were significantly enriched in defense response and inflammatory response, indicating that catechin might work through counteracting changes in the immune system induced by LPS.

Conclusion: Catechin can protect mice from LPS-induced depressive-like behaviours through affecting inflammatory pathways and neuron-associated gene ontologies.

The Golden Spice for Life: Turmeric with the Pharmacological Benefits of Curcuminoids Components, Including Curcumin, Bisdemethoxycurcumin, and Demethoxycurcumins

Background: Turmeric (Curcuma longa L.), belonging to the Zingiberaceae family, is a perennial rhizomatous plant of tropical and subtropical regions. The three major chemical components responsible for the biological activities of turmeric are curcumin, demethoxycurcumin, and bisdemethoxycurcumin.

Methods: The literature search included review articles, analytical studies, randomized control experiments, and observations, which have been gathered from various sources, such as Scopus, Google Scholar, PubMed, and ScienceDirect. A review of the literature was carried out using the keywords: turmeric, traditional Chinese medicine, traditional Iranian medicine, traditional Indian medicine, curcumin, curcuminoids, pharmaceutical benefits, turmerone, demethoxycurcumin, and bisdemethoxycurcumin. The main components of the rhizome of the leaf are α-turmerone, β-turmerone, and arturmerone.

Results: The notable health benefits of turmeric are antioxidant activity, gastrointestinal effects, anticancer effects, cardiovascular and antidiabetic effects, antimicrobial activity, photoprotector activity, hepatoprotective and renoprotective effects, and appropriate for the treatment of Alzheimer's disease and inflammatory and edematic disorders.

Discussion: Curcuminoids are phenolic compounds usually used as pigment spices with many health benefits, such as antiviral, antitumour, anti-HIV, anti-inflammatory, antiparasitic, anticancer, and antifungal effects. Curcumin, bisdemethoxycurcumin, and demethoxycurcumin are the major active and stable bioactive constituents of curcuminoids. Curcumin, which is a hydroponic polyphenol, and the main coloring agent in the rhizomes of turmeric, has anti-inflammatory, antioxidant, anti-cancer, and anticarcinogenic activities, as well as beneficial effects for infectious diseases and Alzheimer's disease. Bisdemethoxycurcumin possesses antioxidant, anti-cancer, and anti-metastasis activities. Demethoxycurcumin, which is another major component, has anti-inflammatory, antiproliferative, and anti-cancer activities and is the appropriate candidate for the treatment of Alzheimer's disease.

Conclusion: The goal of this review is to highlight the health benefits of turmeric in both traditional and modern pharmaceutical sciences by considering the important roles of curcuminoids and other major chemical constituents of turmeric.

Current and Emerging Pharmacological Therapies for Cushing's Disease

Cushing’s Disease (CD), hypercortisolism due to pituitary ACTH secreting neuroendocrine neoplasm, is associated with increased morbidity and, if untreated, mortality in about half of the affected individuals. Consequently, the timely initiation of effective treatment is mandatory. Neurosurgery is the first line and the only potentially curative treatment; however, 30% of patients will have persistent disease post-surgery. Furthermore, a small percentage of those initially controlled will develop hypercortisolism during long-term follow- up. Therefore, patients with persistent or recurrent disease, as well as those considered non-eligible for surgery, will need a second-line therapeutic approach, i.e., pharmacotherapy. Radiation therapy is reserved as a third-line therapeutic option due to its slower onset of action and its unfavorable profile regarding complications. During the past few years, the understanding of molecular mechanisms implicated in the physiology of the hypothalamus-pituitary-adrenal axis has evolved, and new therapeutic targets for CD have emerged. In the present review, currently available treatments, compounds currently tested in ongoing clinical trials, and interesting, potentially new targets emerging from unraveling molecular mechanisms involved in the pathophysiology of Cushing’s disease are discussed.

Hypophysitis Induced by Sintilimab in the Treatment of Bladder Cancer: A Case Report

Background: Immune checkpoint inhibitors (ICIs), as novel antitumor drugs, have been widely used in the clinic and have shown good antitumor effects. However, their widespread use has also led to the emergence of various immune-related adverse events (IrAEs). Hypophysitis is a rare but serious IrAE. Due to its complex and changeable clinical manifestations, hypophysitis may be easily overlooked, leading to delayed diagnosis and treatment.

Case Presentation: A 68-year-old male patient was diagnosed with bladder cancer (T2bNXM0) in October 2021. He received two cycles of immunotherapy with sintilimab and chemotherapy with gemcitabine and cisplatin (GC). One month after the second treatment, he gradually developed recurrent fever, anorexia, drowsiness, and delirium. Laboratory examination revealed hyponatremia, decreased adrenocorticotropic hormone, and hypocortisolemia. The pituitary MRI showed no abnormality. The patient was diagnosed with immunotherapy-induced hypophysitis (IH) caused by sintilimab, leading to downstream endocrine disorders. With hormone replacement therapy, he was in a good mood, had a good appetite, and made an overall recovery.

Conclusion: Immunotherapy-induced hypophysitis (IH) can result in a severe adrenal crisis, and prompt recognition and diagnosis are crucial. Clinicians must remain vigilant for the possibility of IH in patients who exhibit recurrent fever, anorexia, cognitive decline, and personality changes following ICI treatment. It is imperative to consider this diagnosis early to initiate appropriate management promptly.

Interplay between LncRNA/miRNA and TGF-β Signaling in the Tumorigenesis of Gynecological Cancer

Gynecologic cancers are among the most common malignancies with aggressive features and poor prognosis. Tumorigenesis in gynecologic cancers is a complicated process that is influenced by multiple factors, including genetic mutations that activate various oncogenic signaling pathways, including the TGF-β pathway. Aberrant activation of TGF-β signaling is correlated with tumor recurrence and metastasis. It has been shown that non-coding RNAs (ncRNAs) have crucial effects on cancer cell proliferation, migration, and metastasis. Upregulation of various ncRNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs), has been reported in several tumors, like cervical, ovarian, and endometrial cancers, but their cellular mechanisms remain to be investigated. Thus, recognizing the role of ncRNAs in regulating the TGF-β pathway may provide novel strategies for better treatment of cancer patients. The present study summarizes recent findings on the role of ncRNAs in regulating the TGF-β signaling involved in tumor progression and metastasis in gynecologic cancers.

Human Data on Pharmacokinetic Interactions of Cannabinoids: A Narrative Review

Concomitant use of cannabinoids with other drugs may result in pharmacokinetic drug-drug interactions, mainly due to the mechanism involving Phase I and Phase II enzymes and/or efflux transporters. Cannabinoids are not only substrates but also inhibitors or inducers of some of these enzymes and/or transporters. This narrative review aims to provide the available information reported in the literature regarding human data on the pharmacokinetic interactions of cannabinoids with other medications. A search on Pubmed/Medline, Google Scholar, and Cochrane Library was performed. Some studies were identified with Google search. Additional articles of interest were obtained through cross-referencing of published literature. All original research papers discussing interactions between cannabinoids, used for medical or recreational/adult-use purposes, and other medications in humans were included. Thirty-two studies with medicinal or recreational/adult-use cannabis were identified (seventeen case reports/series, thirteen clinical trials, and two retrospective analyses). In three of these studies, a bidirectional pharmacokinetic drug-drug interaction was reported. In the rest of the studies, cannabinoids were the perpetrators, as in most of them, concentrations of cannabinoids were not measured. In light of the widespread use of prescribed and non-prescribed cannabinoids with other medications, pharmacokinetic interactions are likely to occur. Physicians should be aware of these potential interactions and closely monitor drug levels and/or responses. The existing literature regarding pharmacokinetic interactions is limited, and for some drugs, studies have relatively small cohorts or are only case reports. Therefore, there is a need for high-quality pharmacological studies on cannabinoid-drug interactions.

Unlocking the Benefits of Fasting: A Review of its Impact on Various Biological Systems and Human Health

Fasting has gained significant attention in recent years for its potential health benefits in various body systems. This review aims to comprehensively examine the effects of fasting on human health, specifically focusing on its impact on different body’s physiological systems. The cardiovascular system plays a vital role in maintaining overall health, and fasting has shown promising effects in improving cardiovascular health markers such as blood pressure, cholesterol levels, and triglyceride levels. Additionally, fasting has been suggested to enhance insulin sensitivity, promote weight loss, and improve metabolic health, thus offering potential benefits to individuals with diabetes and metabolic disorders. Furthermore, fasting can boost immune function, reduce inflammation, enhance autophagy, and support the body's defense against infections, cancer, and autoimmune diseases. Fasting has also demonstrated a positive effect on the brain and nervous system. It has been associated with neuroprotective properties, improving cognitive function, and reducing the risk of neurodegenerative diseases, besides the ability of increasing the lifespan. Hence, understanding the potential advantages of fasting can provide valuable insights for individuals and healthcare professionals alike in promoting health and wellbeing. The data presented here may have significant implications for the development of therapeutic approaches and interventions using fasting as a potential preventive and therapeutic strategy.

Body Fat Distribution Contributes to Defining the Relationship between Insulin Resistance and Obesity in Human Diseases

The risk for metabolic and cardiovascular complications of obesity is defined by body fat distribution rather than global adiposity. Unlike subcutaneous fat, visceral fat (including hepatic steatosis) reflects insulin resistance and predicts type 2 diabetes and cardiovascular disease. In humans, available evidence indicates that the ability to store triglycerides in the subcutaneous adipose tissue reflects enhanced insulin sensitivity. Prospective studies document an association between larger subcutaneous fat mass at baseline and reduced incidence of impaired glucose tolerance. Case-control studies reveal an association between genetic predisposition to insulin resistance and a lower amount of subcutaneous adipose tissue. Human peroxisome proliferator-activated receptorgamma (PPAR-γ) promotes subcutaneous adipocyte differentiation and subcutaneous fat deposition, improving insulin resistance and reducing visceral fat. Thiazolidinediones reproduce the effects of PPAR-γ activation and therefore increase the amount of subcutaneous fat while enhancing insulin sensitivity and reducing visceral fat. Partial or virtually complete lack of adipose tissue (lipodystrophy) is associated with insulin resistance and its clinical manifestations, including essential hypertension, hypertriglyceridemia, reduced HDL-c, type 2 diabetes, cardiovascular disease, and kidney disease. Patients with Prader Willi syndrome manifest severe subcutaneous obesity without insulin resistance. The impaired ability to accumulate fat in the subcutaneous adipose tissue may be due to deficient triglyceride synthesis, inadequate formation of lipid droplets, or defective adipocyte differentiation. Lean and obese humans develop insulin resistance when the capacity to store fat in the subcutaneous adipose tissue is exhausted and deposition of triglycerides is no longer attainable at that location. Existing adipocytes become large and reflect the presence of insulin resistance.

Interplay of G-proteins and Serotonin in the Neuroimmunoinflammatory Model of Chronic Stress and Depression: A Narrative Review

Introduction: This narrative review addresses the clinical challenges in stress-related disorders such as depression, focusing on the interplay between neuron-specific and pro-inflammatory mechanisms at the cellular, cerebral, and systemic levels.

Objective: We aim to elucidate the molecular mechanisms linking chronic psychological stress with low-grade neuroinflammation in key brain regions, particularly focusing on the roles of G proteins and serotonin (5-HT) receptors.

Methods: This comprehensive review of the literature employs systematic, narrative, and scoping review methodologies, combined with systemic approaches to general pathology. It synthesizes current research on shared signaling pathways involved in stress responses and neuroinflammation, including calcium-dependent mechanisms, mitogen-activated protein kinases, and key transcription factors like NF-κB and p53. The review also focuses on the role of G protein-coupled neurotransmitter receptors (GPCRs) in immune and pro-inflammatory responses, with a detailed analysis of how 13 of 14 types of human 5-HT receptors contribute to depression and neuroinflammation.

Results: The review reveals a complex interaction between neurotransmitter signals and immunoinflammatory responses in stress-related pathologies. It highlights the role of GPCRs and canonical inflammatory mediators in influencing both pathological and physiological processes in nervous tissue.

Conclusion: The proposed Neuroimmunoinflammatory Stress Model (NIIS Model) suggests that proinflammatory signaling pathways, mediated by metabotropic and ionotropic neurotransmitter receptors, are crucial for maintaining neuronal homeostasis. Chronic mental stress can disrupt this balance, leading to increased pro-inflammatory states in the brain and contributing to neuropsychiatric and psychosomatic disorders, including depression. This model integrates traditional theories on depression pathogenesis, offering a comprehensive understanding of the multifaceted nature of the condition.

Decoding Artificial Intelligence in Neuroscience: Applications Beyond Diagnosis

Background: Artificial Intelligence has witnessed exponential expansion in health care applications. The article pronounces the dynamic excellence AI is achieving in the healthcare discipline of neuroscience.

Objective: The paper highlights basic concepts of AI and acmes the interdisciplinary collaboration of Computational neuroscience, Cognitive science, and AI. Also, the article draws out important findings related to AI in neuroscience amongst its diverse application in the various disciplines. An ephemeral overview of applications of AI-based constructs in neurological disorders namely Neuroinflammation, Schizophrenia, Parkinson’s disease, Epilepsy, Autism spectrum disorder, Alzheimer’s disease, Brain tumor and Anesthesiology has been demonstrated in the present work.

Methods: The method includes the collection of data from different search engines like google Scholar, PubMed, ScienceDirect, SciFinder, etc. to get coverage of relevant literature for accumulating appropriate information regarding AI, neuroscience, and their linkages.

Results: These considerations are made to expand the existing literature on the progressing role of AI in the management of neurological disorders.

Conclusion: The exponential expansion in the development of AI-based systems might aid in addressing the prevailing limitations in the domain of neurological disorders and neuroscience.

A Comprehensive Review on Targeted Cancer Therapy: New Face of Treatment Approach

Cancer is one of life's most difficult difficulties and a severe health risk everywhere. Except for haematological malignancies, it is characterized by unchecked cell growth and a lack of cell death, which results in an aberrant tissue mass or tumour. Vascularization promotes tumor growth, which eventually aids metastasis and migration to other parts of the body, ultimately resulting in death. The genetic material of the cells is harmed or mutated by environmental or inherited influences, which results in cancer. Presently, anti-neoplastic medications (chemotherapy, hormone, and biological therapies) are the treatment of choice for metastatic cancers, whilst surgery and radiotherapy are the mainstays for local and non-metastatic tumors. Regrettably, chemotherapy disturbs healthy cells with rapid proliferation, such as those in the gastrointestinal tract and hair follicles, leading to the typical side effects of chemotherapy. Finding new, efficient, targeted therapies based on modifications in the molecular biology of tumor cells is essential because current chemotherapeutic medications are harmful and can cause the development of multidrug resistance. These new targeted therapies, which are gaining popularity as demonstrated by the FDA-approved targeted cancer drugs in recent years, enter molecules directly into tumor cells, diminishing the adverse reactions. A form of cancer treatment known as targeted therapy goes after the proteins that regulate how cancer cells proliferate, divide, and disseminate. Most patients with specific cancers, such as chronic myelogenous leukemia (commonly known as CML), will have a target for a particular medicine, allowing them to be treated with that drug. Nonetheless, the tumor must typically be examined to determine whether it includes drug targets.

Inflammation and Mental Health Disorders: Immunomodulation as a Potential Therapy for Psychiatric Conditions

Mood disorders are the leading cause of disability worldwide and their incidence has significantly increased after the COVID-19 pandemic. Despite the continuous surge in the number of people diagnosed with psychiatric disorders, the treatment methods for these conditions remain limited. A significant number of people either do not respond to therapy or discontinue the drugs due to their severe side effects. Therefore, alternative therapeutic interventions are needed. Previous studies have shown a correlation between immunological alterations and the occurrence of mental health disorders, yet immunomodulatory therapies have been barely investigated for combating psychiatric conditions. In this article, we have reviewed the immunological alterations that occur during the onset of mental health disorders, including microglial activation, an increased number of circulating innate immune cells, reduced activity of natural killer cells, altered T cell morphology and functionality, and an increased secretion of pro-inflammatory cytokines. This article also examines key studies that demonstrate the therapeutic efficacy of anti-inflammatory medications in mental health disorders. These studies suggest that immunomodulation can potentially be used as a complementary therapy for controlling psychiatric conditions after careful screening of candidate drugs and consideration of their efficacy and side effects in clinical trials.

Survey on the Techniques for Classification and Identification of Brain Tumour Types from MRI Images Using Deep Learning Algorithms

A tumour is an uncontrolled growth of tissues in any part of the body. Tumours are of different types and characteristics and have different treatments. Detection of a tumour in the earlier stages makes the treatment easier. Scientists and researchers have been working towards developing sophisticated techniques and methods for identifying the form and stage of tumours. This paper provides a systematic literature survey of techniques for brain tumour segmentation and classification of abnormality and normality from MRI images based on different methods including deep learning techniques. This survey covers publicly available datasets, enhancement techniques, segmentation, feature extraction, and the classification of three different types of brain tumours that include gliomas, meningioma, and pituitary and deep learning algorithms implemented for brain tumour analysis. Finally, this survey provides all the important literature on the detection of brain tumours with their developments.

Biological Effects and Mechanisms of Taurine in Various Therapeutics

More than two hundred years ago, taurine was first isolated from materials derived from animals. It is abundantly found in a wide range of mammalian and non-mammalian tissues and diverse environments. Taurine was discovered to be a by-product of the metabolism of sulfur only a little over a century and a half ago. Recently, there has been a renewed academic interest in researching and exploring various uses of the amino acid taurine, and recent research has indicated that it may be useful in the treatment of a variety of disorders, including seizures, high blood pressure, cardiac infarction, neurodegeneration, and diabetes. Taurine is currently authorised for the therapy of congestive heart failure in Japan, and it has shown promising results in the management of several other illnesses as well. Moreover, it was found to be effective in some clinical trials, and hence it was patented for the same. This review compiles the research data that supports the prospective usage of taurine as an antibacterial, antioxidant, anti-inflammatory, diabetic, retinal protective, and membrane stabilizing agent, amongst other applications

Epigenetic Effects of Psychoactive Drugs

Currently, and globally, we are facing the worst epidemic of psychoactive drug abuse resulting in the loss of hundreds of thousands of lives annually. Besides alcohol and opioid use and misuse, there has been an increase in illicit abuse of psychostimulants. Epigenetics is a relatively novel area of research that studies heritable alterations in gene expression. Long-term administration of psychoactive drugs may lead to transcriptional changes in brain regions related to drug-seeking behaviors and rewards that can be passed down transgenerationally. Epigenetic biomarkers such as DNA methylation and histone modifications contribute to disease diagnoses. This review aims to look at the epigenetic modifications brought forth by psychoactive drug abuse.

The Role of Different Medicinal Herbs in Treatment of Polycystic Ovary Syndrome: A Review

Polycystic ovary syndrome (PCOS/PCOD) indicates a common, multifactorial endocrine condition marked by polycystic ovaries, chronic anovulation, and hyperandrogenism, resulting in asymmetric menstrual periods, hirsutism, acne, and infertility. Standard treatment for PCOS is often accompanied by adverse effects, and is ineffective in certain situations, refutation-based medical guidance accented an integrative progress. Furthermore, women suffering from PCOS may benefit from alternative treatments. Herbal treatment includes herbs that have a phytoestrogenic and non-estrogenic nature, including Mentha spicata, Panax ginseng, Glycyrrhiza glabra, Aloe barbadensis, Cinnamomum zeylanicum, Matricaria chamomilla, Trigonella foenum-graecum, Linum usitatissimum, and Zingiber officinale, which are effective and safe. This review focuses on the reproductive endocrine effects of phytomedicine as a choice treatment so as to PCOD and accompanying oligo/amenorrhoea, acne, hirsutism, and infertility.

COVID-19 and Anti-COVID-19 Vaccination: Potential Damages to the Thyroid Gland

Structure of the Blood Brain Barrier and its Role in the Transporters for the Movement of Substrates across the Barriers

For the brain to operate normally and to develop with structural integrity in addition to neuronal function, blood-brain barrier present in brain capillaries serves as a vital barrier mechanism. In addition to the transport barrier created by membranes, transporters, and vesicular processes, the structure and function of the BBB are summarised. The physical barrier is created by endothelial tight junctions. The permeability and transport of molecules between extracellular fluid and plasma are constrained by the presence of tight junctions between neighbouring endothelial cells. Each solute must pass through both membranes in the luminal and abluminal divisions. The functions of the neurovascular unit are described, with special emphasis on the pericytes, microglia, and astrocyte endfeet. The luminal membrane contains five separate facilitative transport mechanisms, each of which is exclusive to a few substrates. Nevertheless, the import of big-branched and aromatic neutral amino acids is facilitated by two key carriers (System L and y+) in the plasma membrane. It is asymmetrically present in both membranes. The sodium pump Na⁺/K⁺-ATPase is highly expressed in the abluminal membrane, where many Na⁺ dependent transport mechanisms move amino acids against its concentration gradient. The trojan horse strategy, which uses molecular tools to bind the medication and its formulations, is also preferred in drug delivery. The BBB's cellular structure, the transport systems unique to each substrate, and the necessity to identify transporters with changes that assist the transfer of various medications have all been changed in the current work. Nevertheless, to rule out the BBB passage for the new class of neuroactive medications, the mixing of traditional pharmacology and nanotechnology needs to be focused on outcomes that show promise.

Vitamin D: Production, Metabolism, and Impact on Human Health

Background and Objective: Vitamins play an important role in maintaining proper health and wellness of the body. The deficiency of any of them may lead to serious health consequences. In the current scenario, deficiency of vitamin D has become a very prevalent and underdiagnosed health issue throughout the world. The purpose of this review is to briefly describe the importance, present market condition, and role of vitamin D supplements in COVID-19 in India, as well as how this has influenced the current situation.

Methods: Literature survey was carried out using various online search engines like Google Scholar, Science Direct, Springer, PubMed, etc. offline libraries were also used for the compilation of the data.

Results: It is evident from the study that the deficiency of vitamin D is associated with a lot of health problems, including cancer, diabetes, bone health deterioration, cardiovascular disorders, etc. This deficiency may occur due to an unhealthy lifestyle, mal-absorption, or decreased synthesis in the body. Vitamin D levels in the body can also be correlated with COVID-19 and the immunity of an individual.

Conclusion: From this study, the importance of vitamin D levels in the human body can easily be understood. Various evidence of its connection with the COVID-19 pandemic is also available, though many studies in the area are still required. Altogether, increasing instances of vitamin D deficiency is a matter of great concern.

Gut Microbiome and Insomnia: A Mini-Review

Background: The gut microbiome (microorganisms present in our gut) has emerged as an important determinative factor in a variety of diseases and health conditions. One new area in which the role of the gut microbiome is of intense interest is its role in various neurological manifestations, including insomnia, the most common sleep disorder. In this mini-review, we aim to highlight the latest research developments concerning the association between the gut microbiome and insomnia and summarize gut-brain interaction for a better understanding of the role of microbiota in insomnia.

Methods: Our search results included publications written in English from the year 2010 up to the year 2022. We used Pubmed, Google Scholar, and ScienceDirect to search for original articles pertaining to the relationship between the gut microbiome and insomnia using the following search terms: “Gut-brain Axis and Insomnia,” “Brain and Gut Microbiome,” ” Gut-brain Homeostasis”, and “Circadian Rhythm and Gut Microbiome”. Relevant articles from the reference list were reviewed in order to collect additional information.

Results: Studies have shown that the microbiome-gut-brain axis is thus associated with the development of insomnia. The gut microbiome can have an important role in the development of insomnia. On the other hand, insomnia can also modulate the gut microbiome. However, scientific work in this field is limited as relevant scientific research is at the initial state.

Conclusion: Bacteria present in the gut send signals to the brain via the vagus nerve by stimulating the afferent neurons of the enteric nervous system and influencing sleep quality and stress reactivity of the hypothalamic-pituitary-adrenal axis. The gut microbiome also communicates with the nervous system via the neuroendocrine pathway through various metabolic products. Insomnia also influences the structure and function of the gut microbiome.

Significance of Beta-Blocker in Patients with Hypertensive Left Ventricular Hypertrophy and Myocardial Ischemia

Background: Arterial Hypertension (HTN) is a key risk factor for left ventricular hypertrophy (LVH) and a cause of ischemic heart disease (IHD). The association between myocardial ischemia and HTN LVH is strong because myocardial ischemia can occur in HTN LVH even in the absence of significant stenoses of epicardial coronary arteries.

Objective: To analyze pathophysiological characteristics/co-morbidities precipitating myocardial ischemia in patients with HTN LVH and provide a rationale for recommending beta-blockers (BBs) to prevent/treat ischemia in LVH.

Methods: We searched PubMed, SCOPUS, PubMed, Elsevier, Springer Verlag, and Google Scholar for review articles and guidelines on hypertension from 01/01/2000 until 01/05/2022. The search was limited to publications written in English.

Results: HTN LVH worsens ischemia in coronary artery disease (CAD) patients. Even without obstructive CAD, several pathophysiological mechanisms in HTN LVH can lead to myocardial ischemia. In the same guidelines that recommend BBs for patients with HTN and CAD, we could not find a single recommendation for BBs in patients with HTN LVH but without proven CAD. There are several reasons for the proposal of using some BBs to control ischemia in patients with HTN and LVH (even in the absence of obstructive CAD).

Conclusion: Some BBs ought to be considered to prevent/treat ischemia in patients with HTN LVH (even in the absence of obstructive CAD). Furthermore, LVH and ischemic events are important causes of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death; these events are another reason for recommending certain BBs for HTN LVH.

The Protective Effects of Silymarin on the Reproductive Toxicity: A Comprehensive Review

The reproductive system is extremely vulnerable to chemotherapy drugs, ionizing radiation, toxic heavy metals, chemicals, and so on. These harmful stimuli are able to induce oxidative damage, apoptosis, inflammation, and other mechanisms in the reproductive organs, leading to different adverse reproductive effects. It was shown that using medicinal plants (medicinal herbs) can be an effective medication for the prevention and treatment of multiple health conditions. Silymarin is a medicinal herb extract, obtained from the seeds of Silybum marianum. This herbal agent is a nontoxic agent even at relatively high physiological dose values, which suggests that it is safe for use in the treatment of different diseases. The hepato-, neuro-, cardio- and nephro-protective effects of silymarin have been assessed previously. The protective activities of silymarin can point to anti-oxidant, anti-apoptotic, anti-inflammatory, anti-fibrotic, immunomodulatory, and membrane-stabilizing properties. In this review, we aim to summarize current studies on the protective potentials of silymarin against reproductive toxicity. The molecular mechanisms of silymarin protection against cellular toxicity are also studied. Moreover, the findings obtained from improved formulations and delivery systems of silymarin have been addressed.

Cancer Detection Based on Medical Image Analysis with the Help of Machine Learning and Deep Learning Techniques: A Systematic Literature Review

Background: Cancer is a deadly disease. It is crucial to diagnose cancer in its early stages. This can be done with medical imaging. Medical imaging helps us scan and view internal organs. The analysis of these images is a very important task in the identification and classification of cancer. Over the past years, the occurrence of cancer has been increasing, so has been the load on the medical fraternity. Fortunately, with the growth of Artificial Intelligence in the past decade, many tools and techniques have emerged which may help doctors in the analysis of medical images.

Methodology: This is a systematic study covering various tools and techniques used for medical image analysis in the field of cancer detection. It focuses on machine learning and deep learning technologies, their performances, and their shortcomings. Also, the various types of imaging techniques and the different datasets used have been discussed extensively. This work also discusses the various preprocessing techniques that have been performed on medical images for better classification.

Results: A total of 270 studies from 5 different publications and 5 different conferences have been included and compared on the above-cited parameters.

Conclusion: Recommendations for future work have been given towards the end.

The Key Roles of Makorin RING Finger Protein 3 (MKRN3) During the Development of Pubertal Initiation and Central Precocious Puberty (CPP)

Puberty is initiated from the continuous and growing pulsatile secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus and then the activation of the hypothalamic-pituitary-gonadal (HPG) axis. Numerous factors involve pubertal initiation, whose abnormality may come from the dysfunction of these regulators. Makorin RING finger protein 3 (MKRN3) inhibits the secretion of GnRH and plays indispensable roles during the development of pubertal onset, and mutations of MKRN3 showed the commonest genetic cause of central precocious puberty (CPP). Recently, growing studies have revealed the functional mechanisms of MKRN3 in the pubertal initiation and the occurrence of CPP. In this review, we mainly summarized the research advances on the roles of MKRN3 in the development of pubertal onset and their underpinning mechanisms, contributing to a better understanding of the precise mechanisms of pubertal initiation and the pathogenesis of CPP.

Cannabinoids Receptors in COVID-19: Perpetrators and Victims

COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral infections, and attenuation of ALI and ARDS. Therefore, the present narrative review aimed to summarize the possible immunological role of CBs in COVID-19. The effects of CBs are controversial, although they have beneficial effects via CB2 receptors and adverse effects via CB1 receptors against ALI, ARDS, and hyperinflammation, which are hallmarks of COVID-19. The present narrative review has shown that CBs effectively manage ALI and ARDS by suppressing pro-inflammatory cytokines, which are common in COVID-19. Therefore, CBs may be used to manage COVID-19 because of their potent anti-inflammatory effects, suppressing pro-inflammatory cytokines and inhibiting inflammatory signaling pathways.

Immunotherapy-Associated Hypophysitis under Anti-PD1: Two Case Reports

Background: Immunotherapy-associated hypophysitis is an uncommon adverse event. However, if not handled properly, it could lead to fatal sequelae.

Case Presentations: Case 1. A 66-year-old man presented to our hospital with hyponatremia. He had low plasma levels of adrenocorticotropin and cortisol. The patient had a history of non-small cell lung cancer and had undergone 16 cycles of immunotherapy with sintilimab, a monoclonal antibody against programmed cell death protein 1 (PD1). He was diagnosed with adrenal insufficiency secondary to immunotherapy-associated hypophysitis and received a physiological dose of glucocorticoids. Upon discharge, he has prescribed a continued course of hormone replacement therapy combined with immunotherapy. Case 2. The second case profiled here involved a 58- year-old patient diagnosed with gastric antrum cancer. After ten months of immunotherapy with carrelizumab, a human high-affinity immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody drug, the patient was referred to the Endocrinology Department at our medical centre for adrenal nodules and intolerance of anorexia. He also suffered from hypophysitis and was prescribed hormone replacement therapy combined with immunotherapy.

Conclusion: This article discusses the clinical characteristics, diagnosis, treatment, and subsequent follow-up for immunotherapy-associated hypophysitis in the context of two case reports. Based on our findings and observations, we conclude that patients with immunotherapy should regularly be referred to endocrine-related follow-up during tumour treatment.

A Revision of Polymeric Nanoparticles as a Strategy to Improve the Biological Activity of Melatonin

Drug delivery systems based on nanotechnology exhibit a number of advantages over traditional pharmacological formulations. Polymeric nanoparticles are commonly used as delivery systems and consist of synthetic or natural polymers that protect drugs from degradation in physiological environments. In this context, indolamine melatonin has been associated with several biological functions, including antioxidant, antitumor, immunoregulatory, neuroprotective, and cardioprotective effects. However, its availability, half-life, and absorption depend upon the route of administration, and this can limit its therapeutic potential. An alternative is the use of polymeric nanoparticle formulations associated with melatonin to increase its bioavailability and therapeutic dose at sites of interest. Thus, the objective of this review is to provide a general and concise approach to the therapeutic association between melatonin and polymeric nanoparticles applied to different biological disorders and to also highlight its advantages and potential applications compared to those of the typical drug formulations that are available.

Melatonin in Reproductive Medicine: A Promising Therapeutic Target?

Melatonin, mainly released from the pineal gland, also produced in the reproductive organs and cells, plays important roles in rhythms of the sleep-wake cycle, retardation of ageing processes, and antioxidant/anti-inflammatory functions. As a key mediator in reproductive systems, melatonin is participated in the reproductive process via regulating gamete and embryo development and influences reproductive diseases and pregnancy outcomes. The underlying mechanisms include epigenetic and other regulations, which are interesting for exploring new targets in the prevention and treatment of reproductive diseases. This review discusses the relationship between melatonin and reproductive functions and dysfunction, as well as potential clinical applications of melatonin in reproductive medicine. Notably, Developmental Origins of Health and Diseases (DOHaD) is closely linked to reproduction, this article is the first to review the new progress in studies on the possible relationship between melatonin and DOHaD.

Growth Hormone Excess: Implications and Management

Acromegaly is described as the oversecretion of growth hormone (GH) and, subsequently, insulin-like growth factor 1 (IGF-1), ascribed in most cases to a pituitary adenoma. This disease presents a progressive disfigurement, along with other systemic manifestations, which altogether diminishes the quality of life in the patients. Prolonged exposure to abnormally high levels of GH and IGF-1 levels results in cardiovascular, cerebrovascular, and pulmonary dysfunction which overall produces a fall in life expectancy. Timely diagnosis and further treatment decreased the mortality rate of the patients and showed an improvement in the quality of life. Surgical procedures, advanced radiation therapy tools, and the availability of pharmacological compounds that act on pituitary growth hormone-producing cells have enabled an improved approach to treating the disease. Pharmacological treatment is currently an important management option, and it may also be the first-line treatment in patients with acromegaly who do not benefit from or are ineligible for first-line surgical procedures. From its inception until 2021, we used a comprehensive search strategy on Medline/PubMed, Scopus, Embase, Web of Science, and the Cochrane Library electronic databases. All human research articles and review articles published in English were considered for the review. In this review, we describe the clinical implications and management of patients with acromegaly, consisting of scientific improvements underlying the developing understanding of pathogenesis and diagnosis, associated comorbidities and mortality rate with the disease, and major improvements in the treatment of the disease, along with novel strategies including quality of life and patient-reported outcomes.

Involvement of Metabolites and Non-coding RNAs in Diseases

Non-coding RNAs have a role in gene regulation and cellular metabolism control. Metabolism produces metabolites which are small molecules formed during the metabolic process. So far, a direct relationship between metabolites and genes is not fully established; however, pseudogenes and their progenitor genes regulate health and disease states. Other non-coding RNAs also contribute to this regulation at different cellular processes. Accumulation and depletion of metabolites accompany the dynamic equilibrium of health and disease state. In this study, metabolites, their roles in the cell, and the link between metabolites and non-coding RNAs are discussed.

Bisphenol A-Induced Endocrine Dysfunction and its Associated Metabolic Disorders

Bisphenol A (BPA) is an endocrine-disrupting chemical widely present in many consumer goods that poses a significant threat to our health upon exposure. Humans are exposed to BPA, which directly or indirectly causes endocrine dysfunctions that lead to metabolic disorders like obesity, fatty liver diseases, insulin resistance, polycystic ovarian syndrome, and other endocrine- related imbalances. The duration, quantity, and period of exposure to BPA, especially during the critical stage of development, determine its impact on reproductive and non-reproductive health. Because of its endocrine-disrupting effects, the European Chemical Agency has added BPA to the candidate list of chemicals of very serious concern. Due to its estrogenic properties and structural similarities with thyroid hormones, BPA disrupts the endocrine system at different levels. It interacts with estrogen receptors at the molecular level and acts as an antagonist or agonist via an estrogen receptor-dependent signaling pathway. In particular, BPA binds to G-protein coupled receptors and estrogen receptors, activating signaling pathways that influence cellular apoptosis, proliferation, differentiation, and inflammation. BPA acts as an obesogen that promotes adipogenesis and correlates with increased lipid accumulation and elevated expression of adipogenic markers. As a metabolic and endocrine disruptor, BPA impairs cellular homeostasis by increasing oxidative mediators and decreasing antioxidant enzymes, resulting in mitochondrial dysfunction. Due to its endocrine-disrupting properties, BPA exposure induces endocrine dysfunctions, causing metabolic syndrome. This review article gives recent development and novel insights into the cellular and molecular mechanisms of BPA-induced endocrine dysfunctions and their associated metabolic disorders.

Marine-derived Natural Products as Anticancer Agents

Cancer is a deadly human disease on the rise due to changes in lifestyle, nutrition, and global warming. Cancer is characterized by uncontrolled, disordered, and undesired cell division. About 60% of cancer medicines approved by the FDA are made from natural ingredients. Intensive efforts over the last decade to better understand the vast chemical diversity provided by marine life have resulted in an intriguing \"marine pipeline\" of potential anticancer clinical and preclinical treatments. The molecular targets of marine products as anticancer drugs, as well as different reported compounds acting on distinct targets, are the topic of this review.

Curcumin Combats against Organophosphate Pesticides Toxicity: A Review of the Current Evidence and Molecular Pathways

Organophosphate compounds are regarded as a class of pesticides that are used in farming. Their extensive use, especially in developing countries, is a serious public health problem. Numerous studies have shown the effects of these toxins on various parts of the human and other vertebrates’ bodies, including the cardiovascular, hepatobiliary, renal, and reproductive systems. Curcumin is a polyphenol compound obtained from the rhizome of the Curcuma longa. Curcumin has been known as a dietary spice, food additive, and traditional medicine since many years ago. In recent decades, the medicinal characteristics, clinical aspects, and biological activity of curcumin have been extensively examined. The most examined positive characteristics of curcumin are its anti- inflammatory and anti-oxidant qualities. This review will deal with the pharmacological properties of curcumin as well as an update of currently available studies in terms of curcumin’s uses and function against organophosphate pesticides-induced toxicity on different human organs.

Melanocortin Receptors: Emerging Targets for the Treatment of Pigmentation, Inflammation, Stress, Weight Disorders and Sexual Dysfunction

Melanocortins are tiny protein molecules formed by the post-translational cleavage of proopiomelanocortin. These are bioactive peptides that are responsible for human and lower animal pigmentation patterns, energy homeostasis, and sexual function modulation. These peptides regulate numerous physiological functions by being generated in the central nervous system and peripheral tissues. Melanocortins elicit their varied biological effects by binding to a separate family of G protein, two primary proteolytic enzymes, proconvertases 1 and 2, according to recent research. These breakthroughs have opened up new avenues for research into the role of melanocortins, antagonists, and receptors in a number of physiological activities.

Leprosy Reactions: Clinical Pharmacologist Perspective with Repurposed Medications

The elimination of leprosy has been possible with the available anti-leprotic drugs. However, the lepra reactions usually occur months or years after multi-drug therapy completion, and continue to be a formidable challenge mainly owing to its role in causing nerve damage and disability. Corticosteroids are commonly used but they lead to systemic complications, and hence require dose reduction and adjunct therapy with a different target. Various drugs with different targets have been identified and are in practice to treat lepra reactions. The newer targets can include genetic and tissue targets in the skin and nerve. Thalidomide treatment reducing pentraxin-3, toll-like receptor antagonists, minocycline, apremilast, immunomodulators, and tenidap can be helpful in lepra reaction. Other modalities to manage lepra reactions include plasma exchange, intravenous immunoglobulins, and immunotherapy. Most of these treatments are based only on the pathological process of the reaction and tend to be incomplete leading to recurrence. Newer multimodal approaches are required based on various biomarkers (genetic, tissue, serological), which can be monitored to prevent the recurrence of reactions. Hence, there is a need for newer targets and drugs to be identified for the management of lepra reactions.

Kinase Inhibitors Involved in the Regulation of Autophagy: Molecular Concepts and Clinical Implications

All cells and intracellular components are remodeled and recycled in order to replace the old and damaged cells. Autophagy is a process by which damaged, and unwanted cells are degraded in the lysosomes. There are three different types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy has an effect on adaptive and innate immunity, suppression of any tumour, and the elimination of various microbial pathogens. The process of autophagy has both positive and negative effects, and this pertains to any specific disease or its stage of progression. Autophagy involves various processes which are controlled by various signaling pathways, such as Jun N-terminal kinase, GSK3, ERK1, Leucine-rich repeat kinase 2, and PTEN-induced putative kinase 1 and parkin RBR E3. Protein kinases are also important for the regulation of autophagy as they regulate the process of autophagy either by activation or inhibition. The present review discusses the kinase catalyzed phosphorylated reactions, the kinase inhibitors, types of protein kinase inhibitors and their binding properties to protein kinase domains, the structures of active and inactive kinases, and the hydrophobic spine structures in active and inactive protein kinase domains. The intervention of autophagy by targeting specific kinases may form the mainstay of treatment of many diseases and lead the road to future drug discovery.

2,5-Diketopiperazines: A Review of Source, Synthesis, Bioactivity, Structure, and MS Fragmentation

Background: 2,5-Diketopiperazines (DKPs), also called cyclic dipeptides, are the simplest peptide derivatives in nature that are formed by the condensation of two amino acids. They are an important category of bioactive substances with various structures.

Objective: This review focuses on the natural sources, synthetic processes, biological properties and MS fragmentation regularity of simple DKPs, in order to provide a reference for exploring future scientific and therapeutic potentials of these compounds.

Methods: Pertinent information was collected and organized from several electronic scientific databases (e.g., Web of Science, China Knowledge Resource Integrated, ScienceDirect, PubMed, Wanfang Data and Google Scholar), PhD and MS dissertations. There are 107 articles published from the early 20th century to 2021 that were reviewed in this work.

Results: DKPs have been obtained from a broad range of natural resources, including fungi, bacteria, plants, and animals, and have been synthesized by chemical and biological methods. DKPs have various pharmacological activities, including anticancer, antibacterial, antithrombotic, neuron protective, analgesic, and other activities. Mass spectrometry is the most common method for the structural analysis of DKPs. DKPs can be quickly screened and identified by MS according to the mass spectrum fragmentation pattern.

Conclusion: As a category of relatively unexplored compounds, DKPs have been demonstrated to have various bioactivities, especially with antitumor and antibacterial activities. However, the existing research on DKPs is still in the early stage, and their application in drug development needs to be further studied.

Targeting the Cancer Stem Cells in Endocrine Cancers with Phytochemicals

Endocrine cancer is an uncontrolled growth of cells in the hormone-producing glands. Endocrine cancers include the adrenal, thyroid, parathyroid, pancreas, pituitary, and ovary malignancy. Recently, there is an increase in the incidence of the most common endocrine cancer types, namely pancreatic and thyroid cancers. Cancer stem cells (CSCs) of endocrine tumors have received more attention due to their role in cancer progression, therapeutic resistance, and cancer relapse. Phytochemicals provide several health benefits and are effective in the treatment of various diseases including cancer. Therefore, finding the natural phytochemicals that target the CSCs will help to improve cancer patients' prognosis and life expectancy. Phytochemicals have been shown to have anticancer properties and are very effective in treating various cancer types. Curcumin is a common polyphenol found in turmeric, which has been shown to promote cellular drug accumulation and increase the effectiveness of chemotherapy. Moreover, various other phytochemicals such as resveratrol, genistein, and apigenin are effective against different endocrine cancers by regulating the CSCs. Thus, phytochemicals have emerged as chemotherapeutics that may have significance in preventing and treating the endocrine cancers.

Ascending Flaccid Paralysis Secondary to Hypokalemia in A Cancer Patient using Abiraterone - A Case Report

Background: Prostate cancer (PC) is the most common type of neoplasm in men and the fourth leading cause of mortality in Brazil. The prostate cancer refractory metastatic castration can be treated with abiraterone acetate (AA).

Case Presentation: Its use has been associated with increased survival. However, there are also side effects associated with the use of this drug, such as severe electrolyte disturbances.

Conclusion: The objective is to report the clinical case of a patient with castration-resistant metastatic prostate cancer who developed ascending flaccid paralysis secondary to severe hypokalemia, probably due to hyperaldosteronism secondary to the use of Abiraterone Acetate, despite the use of Prednisone.

Male Reproductive Dysfunction and Pharmacological Action of Curcumin: A Concise Review

Background: Male reproductive dysfunctions are the results of the malfunctioning of one or more cellular components due to several factors, including exposure to heavy metals, reactive oxygen species, smoking and alcohol, genital infection, lifestyle, hormonal disorders, and unhealthy diet. However, it has been widely reported that curcumin possesses pharmacological potential, which could ameliorate the effects of these factors on male reproductive dysfunctions.

Introduction: This review discusses the pharmacological activities of curcumin, its ameliorating effects on male reproductive dysfunction, especially on sperm disorders, steroidogenic toxicity, immune-regulatory activity, apoptotic toxicity, and oxidative toxicity, along with its possible mechanisms regarding male reproductive dysfunction.

Methods: The terms, such as \"Curcumin\" together with \"testis\", \"sperm\", \"male reproductive function\", and \"testosterone\", were searched on Google Scholar, Pubmed, and Scopus. Relevant literature was also assessed.

Results: Curcumin was found to mitigate the adverse effects on hormone levels, cellular apoptotic activity, oxidative stress, and histopathological damages. It also inhibited the activation of the mitogen-activated protein kinase (MAPK) pathway, increased semen quality, sperm motility, and concentration, and restored the IL-1β, TNF-α, and MCP-1 levels in the reproductive tissues. Furthermore, curcumin has been shown to increase mRNA, cytoplasmic Bcl-2, 3β-HSD, and 17β- HSD and Nrf2 expression, γ-GCS, and GSH-Px levels, the number of TUNEL-positive cells, and to reduce levels of LDH-x, and LDH activities.

Conclusion: Curcumin exerts pharmacological activities, which improve the male reproductive functions, indicating how curcumin affects various testicular processes. This will be imperative as a measure to enhance male fertility.

Gene Therapy for Chronic Traumatic Brain Injury: Challenges in Resolving Long-term Consequences of Brain Damage

The gene therapy is alluring not only for CNS disorders but also for other pathological conditions. Gene therapy employs the insertion of a healthy gene into the identified genome to replace or replenish genes responsible for pathological disorder or damage due to trauma. The last decade has seen a drastic change in the understanding of vital aspects of gene therapy. Despite the complexity of traumatic brain injury (TBI), the advent of gene therapy in various neurodegenerative disorders has reinforced the ongoing efforts of alleviating TBI-related outcomes with gene therapy. The review highlights the genes modulated in response to TBI and evaluates their impact on the severity and duration of the injury. We have reviewed strategies that pinpointed the most relevant gene targets to restrict debilitating events of brain trauma and utilize vector of choice to deliver the gene of interest at the appropriate site. We have made an attempt to summarize the long-term neurobehavioral consequences of TBI due to numerous pathometabolic perturbations associated with a plethora of genes. Herein, we shed light on the basic pathological mechanisms of brain injury, genetic polymorphism in individuals susceptible to severe outcomes, modulation of gene expression due to TBI, and identification of genes for their possible use in gene therapy. The review also provides insights on the use of vectors and challenges in translations of this gene therapy to clinical practices.

Gene Therapy, A Potential Therapeutic Tool for Neurological and Neuropsychiatric Disorders: Applications, Challenges and Future Perspective

Neurological and neuropsychiatric disorders are the main risks for the health care system, exhibiting a huge socioeconomic load. The available range of pharmacotherapeutics mostly provides palliative consequences and fails to treat such conditions. The molecular etiology of various neurological and neuropsychiatric disorders is mostly associated with a change in genetic background, which can be inherited/triggered by other environmental factors. To address such conditions, gene therapy is considered a potential approach claiming a permanent cure of the disease primarily by deletion, silencing, or edition of faulty genes and by insertion of healthier genes. In gene therapy, vectors (viral/nonvial) play an important role in delivering the desired gene to a specific region of the brain. Targeted gene therapy has unraveled opportunities for the treatment of many neurological and neuropsychiatric disorders. For improved gene delivery, the current techniques mainly focus on designing a precise viral vector, plasmid transfection, nanotechnology, microRNA, and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapy. These latest techniques have great benefits in treating predominant neurological and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder, as well as rarer diseases. Nevertheless, all these delivery methods have their limitations, including immunogenic reactions, off-target effects, and a deficiency of effective biomarkers to appreciate the effectiveness of therapy. In this review, we present a summary of the current methods in targeted gene delivery, followed by the limitations and future direction of gene therapy for the cure of neurological and neuropsychiatric disorders.

A Focused Review on Molecular Signalling Mechanisms of Ginsenosides Anti-Lung Cancer and Anti-inflammatory Activities

Background: Ginseng (Panax ginseng Meyer) is a cultivated medicinal herb that has been widely available in the Asian region since the last century. Ginseng root is used worldwide in Oriental medicine. Currently, the global mortality and infection rates for lung cancer and inflammation are significantly increasing. Therefore, various preventative methods related to the activity of ginsenosides have been used for lung cancer as well as inflammation.

Methods: Web-based searches were performed on Web of Science, Springer, PubMed, and Scopus. A cancer statistical analysis was also conducted to show the current ratio of affected cases and death from lung cancer around the world.

Results: Ginsenosides regulate the enzymes that participate in tumor growth and migration, such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), extracellular signalregulated kinases 1/2 (ERK1/2), the gelatinase network metalloproteinase-2 (MMP-2/9) and activator protein 1 (AP-1). In addition, ginsenosides also possess anti-inflammatory effects by inhibiting the formation of proinflammatory cytokines (tumor necrosis factor-α) (TNF-α) and interleukin-1β (IL-1β) and controlling the activities of inflammatory signalling pathways, such as NF-κB, Janus kinase2/signal transducer, and activator of transcription 3 (Jak2/Stat3).

Conclusion: In several in vitro and in vivo models, P. ginseng showed potential beneficial effects in lung cancer and inflammation treatment. In this review, we provide a detailed and up-to-date summary of research evidence for antilung cancer and anti-inflammatory protective effects of ginsenosides and their potential molecular mechanisms.

Indoleamine 2,3-dioxygenase (IDO)-activity in Severe Psychiatric Disorders: A Systemic Review

Background: Indoleamine 2,3-dioxygenase (IDO) activity is induced by cellular immune activation and therefore associated with inflammatory diseases, among others psychiatric disorders. This review aims to elucidate IDO activity reflected by kynurenine (KYN) to tryptophan (TRP) ratio in severe mental disorders.

Methods: A systematic literature search in MEDLINE and EMBASE was conducted targeting clinical trials in English language measuring KYN/TRP in individuals with a diagnosis of depression, bipolar disorder, or schizophrenia.

Results: Five out of 15 studies found higher levels of KYN/TRP in depression compared to a control group while the same amount found no difference. Moreover, three studies showed lower levels. In bipolar disorder, four out of six, and in psychotic disorders, three out of four trials found higher levels in patients compared to controls. There are only two studies comparing KYN/TRP in major depression and bipolar disorder, showing conflicting results. Eight studies focused on associations between KYN/TRP and clinical parameters, whereas two studies found positive correlations between KYN/TRP and severity of depressive symptoms. In contrast, four studies did not show an association. IDO activity during specific psychiatric treatment was analyzed by eight studies.

Conclusion: In summary, this review demonstrates an inconsistency in the findings of studies investigating KYN/TRP in severe mental disorders. Although there are hints that inflammation associated with TRP catabolism towards the KYN pathway via elevated IDO activity seems likely, no conclusive statements can be drawn. Presumably, the consideration of influencing factors such as inflammatory processes, metabolic activities and psychological/neuropsychiatric symptoms are pivotal for a deeper understanding of the underlying mechanisms.

Genistein in the Treatment of Hypertension: A Review

Genistein, a natural compound belonging to the group of isoflavones has a confirmed positive effect in such diseases as hormone-dependent cancers, osteoporosis, and cardiovascular diseases, including arterial and pulmonary hypertension. The multiway hypotensive effect is based on vasodilation with simultaneous inhibition of vasoconstriction and RAA interference. It impacts both vascular smooth muscles and endothelium due to its influence on many molecular pathways and peptides; among them: protection against oxidative stress, RhoA/Rho pathway inhibition, enhancing cAMP activation, modification of cellular calcium influx, and the increase of eNOS concentrations. Despite little research on genistein effect on pulmonary hypertension, it seems that the natural compound reduces harmful hypoxia effects and, consequently, inhibits vessels remodelling. In our review, we present mechanisms of lowering blood pressure and juxtapose in vivo research on both animal and human models. On the basis of our results, it might be deduced that the abovementioned isoflavone seems to be a safe and effective hypotensive drug. Its impact on arterial and pulmonary hypertension should be further estimated, both in monotherapy, and in combination treatment.

Oncostatin M: Risks and Benefits of a Novel Therapeutic Target for Atherosclerosis

Background: Cardiovascular disease (CVD) is a leading cause of death worldwide. It is predicted that approximately 23.6 million people will die from CVDs annually by 2030. Therefore, there is a great need for an effective therapeutic approach to combat this disease. The European Cardiovascular Target Discovery (CarTarDis) consortium identified Oncostatin M (OSM) as a potential therapeutic target for atherosclerosis. The benefits of modulating OSM - an interleukin (IL)-6 family cytokine - have since been studied for multiple indications. However, as decades of high attrition rates have stressed, the success of a drug target is determined by the fine balance between benefits and the risk of adverse events. Safety issues should therefore not be overlooked.

Objective: In this review, a risk/benefit analysis is performed on OSM inhibition in the context of atherosclerosis treatment. First, OSM signaling characteristics and its role in atherosclerosis are described. Next, an overview of in vitro, in vivo, and clinical findings relating to both the benefits and risks of modulating OSM in major organ systems is provided. Based on OSM’s biological function and expression profile as well as drug intervention studies, safety concerns of inhibiting this target have been identified, assessed, and ranked for the target population.

Conclusion: While OSM may be of therapeutic value in atherosclerosis, drug development should also focus on de-risking the herein identified major safety concerns: tissue remodeling, angiogenesis, bleeding, anemia, and NMDA- and glutamate-induced neurotoxicity. Close monitoring and/or exclusion of patients with various comorbidities may be required for optimal therapeutic benefit.

The Role of NF-κB in Myocardial Ischemia/Reperfusion Injury

Acute myocardial infarction (AMI) is a threat to human life and physical health worldwide. Timely reperfusion is very important to limit infarct size and protect ischemic myocardium. Unfortunately, it has also caused severer myocardial damage, which is called “myocardial ischemia/ reperfusion injury (MIRI)”. There is no effective clinical treatment for it. Over the past two decades, biological studies of NF-κB have improved the understanding of MIRI. Nuclear Factor-κB (NF-κB) is a major transcription factor associated with cardiovascular health and disease. It is involved in the release of pro-inflammatory factors and apoptosis of cardiomyocytes. Recent studies have shown that inhibition of NF-κB plays a protective role in acute hypoxia and reperfusion injury. Here we review the molecular regulation of NF-κB in MIRI, better understanding of NF-κB signaling mechanisms related to inflammation and crosstalk with endogenous small molecules. We hope this review will aid in improving therapeutic approaches to clinical diagnosing. This review provides evidence for the role of NF-κB in MIRI and supports its use as a therapeutic target.

Comprehending the Role of Endocrine Disruptors in Inducing Epigenetic Toxicity

Endocrine disruptors are natural or man-made chemicals that interfere with the body’s endocrine system leading to hormone synthesis and production defects. These chemicals are categorized as plasticizers and cosmetic chemicals, heavy metals, phytoestrogens, pesticides, detergents, surfactants, and flame retardants. Some of the most common endocrine disruptors are dioxins, bisphenol A, phthalates, perchlorate, perfluoroalkyl, and poly-fluoroalkyl substances (PFAs), phytoestrogens, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCB), triclosan, atrazine, lead, arsenic, mercury, organophosphate pesticides, and glycol ethers. Epigenetic alterations such as DNA methylation, histone modification, and miRNA regulation have been observed to play a major role in many diseases such as cancer, neurodegenerative diseases, PCOS, cardiovascular diseases, and various other disorders. In recent times, there has been a focus on endocrine-disrupting chemicals in epigenetic alterations. This review concentrates on estrogen and androgen disrupting effects, placental, and fetal effects, thyroid disrupting effects, and transgenerational effects of endocrine disruptors.

BPS and BPF are as Carcinogenic as BPA and are Not Viable Alternatives for its Replacement

Background: Plastic polymers are omnipresent, and life without them is virtually impossible. Despite the advantages provided by the material, conventional plastic also has harmful effects on the environment and human health. Plastics release microplastics and compounds, such as BPA, which is a xenoestrogen and once absorbed by the body, have an affinity for estrogen receptors α and β, acting as an agonist on human cells, being an endocrine disrupter able to cause various diseases and acting as a potential neoplastic inducer. BPS and BPF are BPA’s analogs, a proposed solution to solve its harmful effects. The analogs can be found in daily use products and are used in several industrial applications.

Objectives: In the present work, the researchers aimed to conduct a revisional study on BPA's harmful effects on human health, focusing on its carcinogenic potential, discussing its mechanisms of action, as well as its analogs effects, and identifying if BPS and BPF are viable alternatives to BPA's substitution in plastic polymers' production.

Methods: In this review, articles published in the last 15 years related to the different aspects of conventional plastics and BPA were analyzed and revised with precision. The subjects ranged from conventional plastics and the problems related to their large-scale production, BPA, its negative aspects, and the feasibility of using its analogs (BPS and BPF) to replace the compound. The articles were extensively reviewed and concisely discussed.

Results: This study demonstrated that BPA has a high carcinogenic potential, with known mechanisms to trigger breast, ovarian, prostate, cervical, and lung cancers, thus elucidating that its analogs are also xenoestrogens, and they can exert similar effects to BPA and, therefore, cannot be considered viable alternatives for its replacement.

Conclusion: .This study suggests that new research should be carried out to develop such alternatives, allowing the substitution of plastic materials containing BPA in their composition, such as developing economically viable and sustainable biodegradable bioplastics for socioenvironmental well-being.

Ziziphi Spinosae Semen: A Natural Herb Resource for Treating Neurological Disorders

Neurological disorders generally have the characteristics of occult onset and progressive development, which can do some serious damage to the human body in the aging process. It is worth noting that traditional medicine can potentially prevent and treat such diseases. Ziziphi Spinosae Semen (ZSS), the seeds of Ziziphus jujuba var. spinosa, has a long clinical history for sleep regulation. In recent years, ZSS has been proved to exhibit various types of neuroprotective activity, such as sleep improvement, antidepressant, anti-anxiety, memory improvement, etc. It has become a popular natural product due to its many inherently available compounds that demonstrate medicinal and pharmacological importance. This paper reviews the main components and their metabolic transformation processes, highlights the various neurofunctional regulation activities and the mechanisms of ZSS, providing a theoretical basis for further research and clinical application of this natural medicine.

Bisphenol A as a Factor in the Mosaic of Autoimmunity

The population worldwide is largely exposed to bisphenol A (BPA), a commonly used plasticizer, that has a similar molecular structure to endogenous estrogens. Therefore, it is able to influence physiological processes in the human body, taking part in pathophysiology of various endocrinopathies, as well as, cardiovascular, neurological and oncological diseases. BPA has been found to affect the immune system, leading to the development of autoimmunity and allergies, too.

In the last few decades, the prevalence of autoimmune diseases has significantly increased that could be explained by a rising exposure of the population to environmental factors, such as BPA. BPA has been found to play a role in the pathogenesis of systemic autoimmune diseases and also organ-specific autoimmunity (thyroid autoimmunity, diabetes mellitus type 1, myocarditis, inflammatory bowel disease, multiple sclerosis, encephalomyelitis etc), but the results of some studies still remain controversial, so further research is needed.

The Putative Adverse Effects of Bisphenol A on Autoimmune Diseases

Bisphenol A (BPA) is a monomer that is widely used in the manufacturing of polycarbonate plastics (including storage plastics and baby bottles) and is considered to be one of the most widely used synthetic compounds in the manufacturing industry. Exposure to BPA mainly occurs after oral ingestion and results from leaks into food and water from plastic containers. According to epidemiological data, exposure is widespread and estimated to occur in 90% of individuals. BPA exhibits pleiotropic and estrogen-like effects; thus, it is considered an endocrine-disrupting chemical. A growing body of evidence highlights the role of BPA in modulating immune responses and signaling pathways, which results in a proinflammatory response by enhancing the differential polarization of immune cells and cytokine production profile to one that is consistent with proinflammation. Indeed, epidemiological studies have uncovered associations between several autoimmune diseases and BPA exposure. Data from animal models provided consistent evidence, which highlighted the role of BPA in the pathogenesis, exacerbation, and perpetuation of various autoimmune phenomena including neuroinflammation in the context of multiple sclerosis, colitis in inflammatory bowel disease, nephritis in systemic lupus erythematosus, and insulitis in type 1 diabetes mellitus. Owing to the widespread use of BPA and its effects on immune system dysregulation, a call for careful assessment of patients’ risks and public health measures are needed to limit exposure and subsequent deleterious effects. The purpose of this study is to explore the autoimmune triggering mechanisms and present the current literature supporting the role of BPA in the pathogenesis of autoimmune diseases.

Bone Disruption and Environmental Pollutants

Background: Endocrine Disrupting Chemicals (EDCs) are ubiquitous and may significantly contribute to environmental pollution and contamination in humans and wildlife. Ecological pollutants could interfere with bone homeostasis through different mechanisms, including hormonal imbalance, direct osteoblast toxicity, and enhancement of osteoclasts activity, leading to either osteopenia or osteoporosis. Among these chemicals, bisphenols, dioxins, polycyclic aromatic hydrocarbons, polychlorobiphenyls, poly- and perfluoroalkyl, phthalates, parabens, organotins, and cadmium may play a role in the bone disruption.

Methods: Authors searched PubMed/MEDLINE, ISI-web of knowledge, and Google scholar databases for medical subject headings terms and free-text words related to the classes mentioned above of chemicals and bone metabolism and remodeling for better clarifying and understanding the main mechanisms of bone disruption.

Results: Several EDCs act as xeno-estrogens. Considering that estrogens play a significant role in regulating bone remodeling, most of these chemicals generate hormonal imbalance with possible detrimental consequences on bone tissue structure and its mechanical and non-mechanical properties.

Discussion: Much evidence about bone disruptors was obtained from in vitro studies or animal models with equivocal results. Besides, a few data have been acquired from humans, and most of these data focused on the impact of EDCs on bone mineral density without considering their influence on long-term fracture risk. Moreover, humans may be exposed to a mixture of EDCs, and the final effect on bone metabolism might be attributable to either synergistic or antagonist effects. Age of first exposure, cumulative exposure over time, and the usually observed non-monotonic dose-response curve for EDCs should be considered as other essential variables influencing bone metabolism's final effect.

Conclusion: Given these variables, observational studies are needed to analyze this issue for ecological purposes better and preserve bone health.

MEG8: An Indispensable Long Non-coding RNA in Multiple Cancers

Background: As a member of long non-coding RNAs (lncRNAs), maternally expressed gene 8 (MEG8) has been found involving in the progression of a variety of cancers and playing a regulatory role. Therefore, MEG8 may turn into a new therapeutic target for cancer in the future. The purpose of this review is to illustrate the molecular mechanism and physiological function of MEG8 in various cancers.

Methods: We retrieved and analyzed related articles about MEG8, lncRNAs, and cancers, and then summarize the pathophysiological mechanisms of MEG8 in cancer development.

Results: LncRNA MEG8 participates in various cancers progression, thus influencing the proliferation, migration, and invasion of cancers. However, the expression of MEG8 is abnormally upregulated in non-small cell lung cancer (NSCLC), pancreatic cancer (PC), liver cancer (HCC), pituitary adenoma (PA) and hemangioma (HA), and inhibited in colorectal cancer (CRC), ovarian cancer (OC) and giant cell tumor (GCT), suggesting its clinical value in cancer therapy.

Conclusion: LncRNA MEG8 is expected to be a new therapeutic target or biomarker for a wide range of cancers in the future.

MicroRNA-7 Regulates Insulin Signaling Pathway by Targeting IRS1, IRS2, and RAF1 Genes in Gestational Diabetes Mellitus

Background: Small non-coding micro RNAs (miRNAs) are indicated in various metabolic processes and play a critical role in disease pathology, including gestational diabetes mellitus (GDM).

Objective: The purpose of this study was to examine the altered expression of miRNAs and their target genes in placental tissue (PL), cord blood (CB), and maternal blood (MB) of matched non-glucose tolerant (NGT) and GDM mother.

Methods: In a case-control study, micro-RNA was quantified from forty-five serum (MB n = 15, CB n = 15, and PL n = 15) and matched placental tissue using stem-loop RT-qPCR followed by target prediction, network construction and functional and pathways enrichment analysis. Further, target genes were verified in-vitro through transfection and RT-qPCR.

Results: Five miRNAs, namely hsa-let 7a-5P, hsa-miR7-5P, hsa-miR9-5P, hsa-miR18a-5P, and hsamiR23a- 3P were significantly over-expressed (p < 0.05) in all three samples namely PL, CB, and MB of GDM patients. However, the sample-wise comparison reveals higher expression of miRNA 7 in MB while lowest in CB than control. Furthermore, a comparison of fold change expression of target genes discloses a lower expression of IRS1, IRS2, and RAF1 in MB while comparatively higher expression of NRAS in MB and CB. In-vitro validation reveals lower expression of IRS1/2 and RAF1 in response to overexpression of miR-7 and vice-versa. Thus it is evident that increased miRNA7 expression causes down-regulation of its target genes IRS1, IRS2, and RAF1 in GDM mother compared to control. Further, target prediction, pathway enrichment, and hormone analysis (significantly higher FSH & LH in MB of GDM compared to NGT) revealed insulin signaling, inflammatory and GnRH signaling as major pathways regulated by miRNA7.

Conclusion: Thus, an elevated level of miRNA7 may be associated with the progression of GDM by altering the multiple pathways like insulin, GnRH, and inflammatory signaling pathways via targeting IRS1, IRS2, and RAF1, implicating a new therapeutic target for GDM.

Meet the Editorial Board Member

Role of the Cytoskeleton in Steroidogenesis

Steroidogenesis in the adrenal cortex or gonads is a complicated process modulated by various elements either at the tissue or molecular level. The substrate cholesterol is first delivered to the outer membrane of mitochondria, undergoing a series of enzymatic reactions along with the material exchange between the mitochondria and the ER (endoplasmic reticulum) and ultimately yielding various steroids, such as aldosterone, cortisol, testosterone, and estrone. Several valves are set to adjust the amount of production as per the needs, e.g., StAR (steroidogenic acute regulator) controls the traffic of cholesterol from the outer membrane to the inner membrane of mitochondria which is a rate-limiting step. Moreover, the “need” is partly reflected by trophic signals, like ACTH, LH, and downstream pathways, such as the intracellular cAMP pathway, representing the endocrinal regulation of steroid synthesis.

The coordinated activities of these related factors are all associated with another crucial cellular constituent, the cytoskeleton, which plays a crucial role in cellular architecture and substrate trafficking. Though considerable studies have been performed regarding steroid synthesis, details regarding the upstream signaling pathways and mechanisms of the regulation by the cytoskeleton network still remain unclear. The metabolism and interplays of the pivotal cellular organelles with cytoskeleton are worth exploring as well. This review summarizes the research of different periods, describing the roles of specific cytoskeleton elements in steroidogenesis and related signaling pathways involved in steroid synthesis. In addition, we discuss the inner cytoskeletal network involved in steroidogenic processes, such as mitochondrial movement, organelle interactions, and cholesterol trafficking.

Heterocyclic Moieties as HDAC Inhibitors: Role in Cancer Therapeutics

‘Epigenetic’ regulation of genes via post-translational modulation of proteins is a wellexplored approach for disease therapies, particularly cancer chemotherapeutics. Histone deacetylases (HDACs) are one of the important epigenetic targets and are mainly responsible for balancing the acetylation/deacetylation of lysine amino acids on histone/nonhistone proteins along with histone acetyltransferase (HAT). HDAC inhibitors (HDACIs) have become important biologically active compounds for the treatment of cancers due to cell cycle arrest, differentiation, and apoptosis in tumor cells, thus leading to anticancer activity. Out of the four classes of HDAC, i.e., Class I, II, III, and IV, HDACIs act on Class IV (Zinc dependent HDAC), and various FDA-approved drugs belong to this category. The required canonical pharmacophore model (zinc-binding group, surface recognition cap, and appropriate linker) supported by HDACIs, various heterocyclic moieties containing compounds exhibiting HDAC inhibitory activity, and structure-activity relationship of different synthetic derivatives reported during the last twelve years have been summarized in this review.

Insights into Interactions of Human Cytochrome P450 17A1: A Review

Cytochrome P450s are a widespread and vast superfamily of hemeprotein monooxygenases that metabolize physiologically essential chemicals necessary for most species' survival, ranging from protists to plants to humans. They catalyze the synthesis of steroid hormones, cholesterol, bile acids, and arachidonate metabolites and the degradation of endogenous compounds, such as steroids, fatty acids, and other catabolizing compounds as an energy source and detoxifying xenobiotics, such as drugs, procarcinogens, and carcinogens. The human CYP17A1 is one of the cytochrome P450 genes located at the 10q chromosome. The gene expression occurs in the adrenals and gonads, with minor amounts in the brain, placenta, and heart. This P450c17 cytochrome gene is a critical steroidogenesis regulator which performs two distinct activities: 17 alpha-hydroxylase activity (converting pregnenolone to 17- hydroxypregnenolone and progesterone to 17-hydroxyprogesterone; these precursors are further processed to provide glucocorticoids and sex hormones) and 17, 20-lyase activity (which converts 17-hydroxypregnenolone to DHEA). Dozens of mutations within CYP17A1 are found to cause 17-alpha-hydroxylase and 17, 20-lyase deficiency. This condition affects the function of certain hormone-producing glands, resulting in high blood pressure levels (hypertension), abnormal sexual development, and other deficiency diseases. This review highlights the changes in CYP17A1 associated with gene-gene interaction, drug-gene interaction, chemical-gene interaction, and its biochemical reactions; they have some insights to correlate with the fascinating functional characteristics of this human steroidogenic gene. The findings of our theoretical results will be helpful to further the design of specific inhibitors of CYP17A1.

Role of Medicinal Plants in Combating Anti-depressant Induced Male Infertility

Depression is a complex neurological disorder. More than two hundred million people are affected by depression. Anti-depressant drugs prescribed to alleviate the symptoms associated with depression can interact with the neuroendocrine system and alter the level of neurotransmitters in the CNS. Dopamine, serotonin, testosterone, and other hormones influence human reproductive functions and sexual behavior. Anti-depressant drugs induce multiple hormonal and neurochemical changes throughout the central and peripheral nervous system. They were found to impair male sexual function by altering the concentration of androgenic hormones. Moreover, they were found to deteriorate semen parameters and adversely affect the integrity of sperm DNA. The paper describes the role of anti-depressants in inducing male infertility and the potential of traditionally used medicinal plants in restoring male fertility, which is compromised by anti-depressants. Medicinal plants have been reported to restore testosterone, FSH, and LH level in patients who consume antidepressants. Although the studies could not provide a specific mechanism, it has been reported that the plants showed the ability to upregulated anti-oxidant pathways and counter the oxidative stress induced by anti-oxidants which inhibit sperm DNA damage and improve semen parameters.

Recent Applications of Artificial Intelligence in Early Cancer Detection

Cancer is a deadly disease that is often caused by the accumulation of various genetic mutations and pathological alterations. The death rate can only be reduced when it is detected in the early stages, because cancer treatment when the tumor has not metastasized in many regions of the body is more effective. However, early cancer detection is fraught with difficulties. Advances in artificial intelligence (AI) have developed a new scope for efficient and early detection of such a fatal disease. AI algorithms have a remarkable ability to perform well on a variety of tasks that are presented or fed to the system. Numerous studies have produced machine learning and deep learning-assisted cancer prediction models to detect cancer from previously accessible data with better accuracy, sensitivity, and specificity. It has been observed that the accuracy of prediction models in classifying fed data as benign, malignant, or normal is improved by implementing efficient image processing techniques and data segmentation augmentation methodologies, along with advanced algorithms. In this review, recent AI-based models for the diagnosis of the most prevalent cancers in the breast, lung, brain, and skin have been analysed. Available AI techniques, data preparation, modeling processes, and performance assessments have been included in the review.

The Innate Immune System and Fever under Redox Control: A Narrative Review

In living cells, redox potential is vitally important for normal physiological processes that are closely regulated by antioxidants, free amino acids, and proteins that either have reactive oxygen and nitrogen species capturing capability or can be compartmentalized. Although hundreds of experiments support the regulatory role of free radicals and their derivatives, several authors continue to claim that these perform only harmful and non-regulatory functions. In this paper, we demonstrate that countless intracellular and extracellular signal pathways are directly or indirectly linked to regulated redox processes. We also briefly discuss how artificial oxidative stress can have important therapeutic potential and the possible negative effects of popular antioxidant supplements.

Next, we present the argument supported by a large number of studies that many of the major components of innate immunity and fever are essentially associated with redox processes. Our goal is to point out that the production of excess or unregulated free radicals and reactive species can be secondary processes due to the perturbed cellular signal pathways. However, research on pharmacology should consider the important role of redox mechanisms in the innate immune system and fever.

Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality Versus Wishful Thinking?

Background: The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in treating neurologic disease. Vasoactive peptides have been shown in animal studies to transiently disrupt the blood-brain barrier and regadenoson is currently being studied in humans to determine if it can improve drug delivery to the brain. However, many other vasoactive peptides could potentially be used for this purpose.

Methods: We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the blood-brain barrier, we devised a four-tier classification system to organize the available evidence.

Results: We identified 32 vasoactive peptides with potential blood-brain barrier permeabilityaltering properties. To date, none of these are shown to open the blood-brain barrier in humans. Twelve vasoactive peptides increased blood-brain barrier permeability in rodents. The remaining 20 had favorable physiologic effects on blood vessels but lacked specific information on permeability changes to the blood-brain barrier.

Conclusion: Vasoactive peptides remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other neurologic diseases. Dozens of vasoactive peptides have yet to be formally evaluated for this important clinical effect. This narrative review summarizes the available data on vasoactive peptides, highlighting agents that deserve further in vitro and in vivo investigations.

Gut Microbiota and Cardiovascular Disease: Symbiosis Versus Dysbiosis

The gut microbiome interacts with host physiology through various mechanisms, including the cardiovascular (CV) system. A healthy microbiome has the ability to process and digest complex carbohydrates into short-chain fatty acids (SCFA). These SCFA function as signaling molecules, immune-modulating molecules, and energy sources. However, when the microbiome is altered, it produces gut dysbiosis with overgrowth of certain bacteria that may lead to overproduction of trimethylamine-N-oxide (TMAO) from the metabolism of phosphatidylcholine, choline, and carnitine; dysbiosis also leads to increased intestinal permeability allowing the microbiome-derived lipopolysaccharide (LPS), a bacterial endotoxin, to enter the blood circulation, triggering inflammatory responses. An altered gastrointestinal (GI) tract environment and microbiome- derived metabolites are associated with CV events. Disrupted content and function of the microbiome leading to elevated TMAO and LPS levels, altered bile acid metabolism pathways, and SCFA production are associated with an increased risk of CV diseases (CVD), including atherosclerosis, myocardial infarction, thrombosis, arrhythmias, and stroke. Therapeutic interventions that may favorably influence a dysbiotic GI tract profile and promote a healthy microbiome may benefit the CV system and lead to a reduction of CVD incidence in certain situations. These issues are herein reviewed with a focus on the spectrum of microbiota-related CVD, the mechanisms involved, and the potential use of microbiome modification as a possible therapeutic intervention.

Nanoparticles Mediated Target-specific Drug Delivery in Prostate Cancer: An In-depth Review

Nanotechnology has been extensively exploited for its enormous therapeutic and diagnostic potential in the management of multiple disorders. It employs nanomaterials as drug carriers with enhanced efficacy and limited side effects on normal tissues. A lot of nanomaterials have been studied and produced, imminently reforming the treatment and diagnostics of numerous malignancies, including cancer. The purpose of the present study is to explore the role of nanotechnology-based devices/therapies that have a vital function in the therapeutics and diagnostics of cancer with potential impact at three levels: early detection, tumor imaging, and drug delivery methods. Concentrating on cancer, promising nanotechnology-based approaches have been planned to satisfy the need for targeted specificity of traditional agents of chemotherapeutics, in addition to early recognition of malignant and precancerous lesions. Prostate cancer is the fifth most wellknown cancer worldwide and the second most usually detected cancer in men. Therefore, there is a crucial need to improve therapeutic prospects for the diagnosis and treatment of prostate cancer via the exploitation of the potential of nanomaterials for cell-targeted specificity and improved primary diagnosis of precancerous tumors. The present review, therefore, focuses on summarizing all prospective applications of nanotechnology in the prognosis and diagnosis of prostate cancer, which would further help researchers to elucidate a more potent therapeutic approach for the better management of prostate cancer in the days ahead.

Polyphenols and Stem Cells for Neuroregeneration in Parkinson’s Disease and Amyotrophic Lateral Sclerosis

Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS) are neurological disorders pathologically characterized by chronic degeneration of dopaminergic neurons and motor neurons, respectively. There is still no cure or effective treatment against the disease progression and most of the treatments are symptomatic. The present review offers an overview of the different factors involved in the pathogenesis of these diseases. Subsequently, we focused on the recent advanced studies of dietary polyphenols and stem cell therapies, which have made it possible to slow down the progression of neurodegeneration. To date, stem cells and different polyphenols have been used for the directional induction of neural stem cells into dopaminergic neurons and motor neurons. We have also discussed their involvement in the modulation of different signal transduction pathways and growth factor levels in various in vivo and in vitro studies. Likewise stem cells, polyphenols also exhibit the potential of neuroprotection by their anti-apoptotic, anti-inflammatory, and anti-oxidant properties regulating the growth factors levels and molecular signaling events. Overall this review provides a detailed insight into recent strategies that promise the use of polyphenol with stem cell therapy for the possible treatment of PD and ALS.

Therapeutic Benefits of Piper nigrum: A Review

This manuscript aims to describe the various pharmacological activities of Piper nigrum. Pepper is a common spice of the plant which is used as spice in preparation of various foods. Pepper production is centered in Kerela, followed by Karnataka and Maharashtra in India. Other big pepper-producing countries include Indonesia, Malaysia, Brazil, Vietnam, and Sri Lanka. It has various pharmacological activities which is why it is used in the treatment of different diseases. The manuscript mainly describes the antituberculosis, anticonvulsant, analgesic, antipyretic, anti- inflammatory, antimicrobial, antioxidant, gastrointestinal and anticancer activities of Piper nigrum. The manuscript also describes the various studies related to the pharmacological activities of Piper nigrum. It is concluded from the manuscript that Piper nigrum has great efficacy in the treatment of various diseases.