Conclusion: The progress of developing a cancer treatment that may successfully and efficiently target mutant p53 is on the verge of development. Mutant p53 proteins not only initiate oncogenesis but also cause resistance in cancer cells to certain chemo or radiotherapies, further endorse cancer cell survival and promote migration as well as metastasis of cancerous cells. With this regard, many mutant p53 inhibitors have been developed, some of which are currently being evaluated at the pre-clinical level and have been identified and discussed. To date, APR-246 is the most prominent one that has progressed to the Phase III clinical trial.

Methods: Via bioinformatics approaches, we identified the target miRNA. Subsequently, CCK-8, cell cycle analysis, and flow cytometry were used to check the biological influences of miR-29c-3p on ESCA cells. TransmiR, mirDIP, miRPathDB, and miRDB databases were used as tools for the prediction of upstream transcription factors and downstream genes of miR-29c-3p. The targeting relationship of genes was detected via RNA immunoprecipitation and chromatin immunoprecipitation, which was further validated by dual-luciferase assay. Finally, in vitro experiments revealed the way E2F1/miR-29c-3p/COL11A1 affected sorafenib’s sensitivity, and in vivo experiments were used to verify the way E2F1 and sorafenib impacted ESCA tumor growth.

Results: miR-29c-3p, downregulated in ESCA, could suppress ESCA cell viability, arrest the cell cycle in the G0/G1 phase, and impel apoptosis. E2F1 was found to be upregulated in ESCA and it could abate the transcriptional activity of miR-29c-3p. COL11A1 was found to be a downstream target of miR-29c-3p to enhance cell viability, induce cell cycle arrest in S phase, and constrain apoptosis. Cellular and animal experiments together demonstrated that E2F1 abated the sorafenib’s sensitivity of ESCA cells via miR-29c-3p/COL11A1.

Conclusion: E2F1 affected the viability, cell cycle, and apoptosis of ESCA cells by modulating miR-29c-3p/COL11A1, and it attenuated the sensitivity of ESCA cells to sorafenib, shedding new light on the treatment of ESCA.

Objective: This study aimed to determine the capability of ultrasonography (US)-based radiomics for presurgical prediction of metastasis in LN-prRLNs in PTC.

Methods: Patients were retrospectively enrolled and pathologically confirmed as LN-prRLN metastasis with PTC after surgery. Radiomic analysis based on preoperative US images with manual segmentation of targets was used to develop a radiomics model. US features described in ACR TI-RADS were collected to construct a clinical model. The Radiomics model, a combined model integrating radiomics and clinical model, were also developed for the presurgical prediction of metastasis in LN-prRLNs.

Results: A total of 570 patients, including 488 patients with non-LN-prRLN metastasis and 82 with LN-prRLN metastasis, were assessed. The 15 topperforming features finally remained significant for constructing the radiomics model. The combined model showed that US measured tumor size (OR: 1.036, P = 0.044), US suspected lateral lymph node metastasis (OR: 2.247, P = 0.009), multifocality (OR: 1.920, P = 0.021), Delphian lymph node metastasis (DLNM) (OR: 2.300, P = 0.039), VIa compartment metastasis (OR: 5.357, P = 0.000), the radiomics score (OR: 1.003, P = 0.001) were significant risk factors for predicting LN-prRLN metastasis. The combined model achieved a higher AUC of 0.849 than that of the clinical model (AUC: 0.826) and radiomics model (AUC: 0.759).

Conclusion: The US-based radiomics combined model can more effectively predict LN-prRLN metastasis in PTCs patients preoperatively. This approach had the potential to assist surgeons in decision-making regarding LN-prRLN dissection.

Case presentation: We presented a case of a 72-year-old female who was admitted to our hospital for chest pain and hematemesis within several minutes after chewing betel nut. Gastroscopy showed two longitudinal ridge-like mucosal eminences in the esophagus located 20 cm from the incisors down to the gastric cardia, which was similar to varices. At last, a CT scan showed concentric-circle thickening of the esophagus wall, suggesting hematomas. Our treatment included fasting, inhibiting gastric acid and maintaining blood volume. After one week of medical treatment, rechecked gastroscopy showed that esophageal hematomas were gradually absorbed, with the formation of multiple shallow ulcers.

Conclusion: The acute toxicity of chewing betel nut can be easily overlooked. Patients who experience chest pain or hematemesis after chewing betel nut products,especially those who take aspirin at the same time, need to be alert to esophageal hematoma.

Methods: To ensure a thorough search of the literature for relevant English studies published before July 2023, several databases were searched, including PubMed, Web of Science, ProQuest, Cochrane Library, and Google Scholar. The study evaluated the impact of lncRNA SNHG5 on the overall survival (OS) of cancer by calculating the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). To further confirm the accuracy of the findings, the study investigated the expression profile and prognostic significance of lncRNA SNHG5 through the use of GenomicScape, OncoLnc, Kaplan-Meier plotter, and GEPIA databases.

Results: In this study, 995 patients were examined across a total of fourteen original studies. The findings indicated that there was a significant relationship between heightened lncRNA SNHG5 expression and reduced OS, as evidenced by both univariate and multivariate analyses (HR = 1.89; 95% CI, 1.44-2.49; p < 0.001; HR = 3.97; 95% CI, 1.80-8.73; p < 0.001, respectively). Pooled OR analysis showed a significant association between over-expression of lncRNA SNHG5 with advanced histological grade (OR = 0.28; 95% CI, 0.11-0.71; p = 0.007), present lymph node metastasis (LNM; OR = 4.28; 95% CI, 2.47-7.43; p < 0.001), and smoking history (OR = 0.27; 95% CI, 0.15-0.49; p < 0.001). Bioinformatic databases confirmed that elevated SNHG5 expression was significantly linked to poor prognosis in cancer patients, including colorectal cancer (CRC), acute myeloid leukemia (AML), and esophageal adenocarcinoma (ESAD), and a longer OS in patients with uterine corpus endometrial carcinoma (UCEC).

Conclusion: These results suggest that lncRNA SNHG5 may serve as an adverse prognostic biomarker in several human cancers. Further investigations are needed to better understand the underlying mechanisms that link lncRNA SNHG5 to multiple malignancies.

Aim: To clarify the mechanism of HDW for esophageal adenocarcinoma (EAC), we utilized network pharmacology and weighted gene co-expression network analysis methods (WGCNA).

Methods: The gene modules that were linked with the clinical features of EAC were obtained through the WGCNA method. Then, the potential target genes were retrieved through the network pharmacology method in order to determine the targets of the active components. After enrichment analysis, a variety of signaling pathways with significant ratios of target genes were found, including regulation of trans-synaptic signaling, neuroactive ligand-receptor interaction and modulation of chemical synaptic transmission. By means of protein-protein interaction (PPI) network analysis, we have successfully identified the hub genes, which were AR, CNR1, GRIK1, MAPK10, MAPT, PGR and PIK3R1.

Result: Our study employed molecular docking simulations to evaluate the binding affinity of the active components with the hub gene. The identified active anticancer constituents in HDW are scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol.

Conclusion: Our findings shed light on the molecular underpinnings of HDW in the treatment of EAC and hold great promise for the identification of potential HDW compounds and biomarkers for EAC therapy.

Poor patient compliance and adherence are major issues with the conventional line of therapy. This burden may be more significant in resource-constrained settings, necessitating the creation of simple formulations that are both geriatric and child-friendly. An extensive literature survey has been conducted in this study using databases of Google Scholar, PubMed, and Research Gate, with a focus on specific research works on oro-dispersible films, tablets, and wafer technology loaded with anti-tuberculosis drugs from 2022 to 2010.

Mouth dissolving formulation technology is a very novel approach in the arena of tuberculosis therapy. This may pave the way for future researchers to develop different mouth dissolving formulations to treat both pulmonary and extra-tuberculosis. This review paper has summarized all the formulation approaches alongside the present state of the art in tuberculosis therapy using mouth dissolving formulations.

Methods: By setting the search terms correlated to PD-L1 and gastric cancer, a nearly comprehensive search was carried out in four major databases, and the deadline for searching was September 1, 2022. The retrieved documents were further screened by strict inclusion and exclusion criteria after removing the duplication. Next, the quality of the included studies was evaluated with the Newcastle-Ottawa Scale (NOS) scale. Finally, the STATA15.1 software was used to process data and draw plots, and the odds ratios (ORs) were adopted to assess the pooled effect size.

Results: A total of 85 works of literature were included in this study through screening strictly, and detailed data were extracted after evaluating the quality of the literature. The process of analysis was conducted in the whole population, Asia-Africa population, European and American population, and Asian population with CPS≥1, amd all found that the expression of PD-L1 in gastric cancer was correlated with age, tumor size, EBV infection, Her-2 expression and microsatellite status. However, the subgroup of the region also found some differences in Asian and Western regions, which was interesting and worth studying further. The included research of this study did not have significant publish bias.

Conclusion: After careful analysis, this study found that age (>60 years), tumor size (>5cm), EBV infection (+), Her-2 expression (+), microsatellite status (MSI), and mismatch repair status (dMMR) were risk factors for positive expression of PD-L1 in gastric cancer.

Objective: The study aimed to investigate the target gene of LJZD compatibility and the possible mechanism of action in the treatment of breast cancer by using network pharmacology and molecular docking.

Methods: Based on TCMSP, ETCM, and BATMAN database searching and screening to obtain the ingredients of LJZD, the related targets were obtained. Breast cancer-related targets were collected through GEO, Geencards, OMIM, and other databases, and drug-disease Venn diagrams were drawn by R. The PPI network map was constructed by using Cytoscape. The intersecting targets were imported into the STRING database, and the core targets were analyzed and screened. The intersected targets were analyzed by the DAVID database for GO and KEGG enrichment. AutoDock Vina and Gromacs were used for molecular docking and simulation of the core targets and active ingredients.

Results: 126 active ingredients of LJZD were obtained; 241 targets related to breast cancer were sought after screening, and 180 intersection targets were identified through Venn diagram analysis. The core targets were FOS and ESR1. KEGG enrichment analysis mainly involved PI3K/Akt, MAPK, and other signaling pathways.

Conclusion: This study has explored the possible targets and signaling pathways of LJZD in treating breast cancer through network pharmacology and bioinformatics analysis. Molecular docking and simulation have further validated the potential mechanism of action of LJZD in breast cancer treatment, providing essential experimental data for future studies.

Methods: In this study, we examined JNK2 expression in patient samples and performed experiments involving the knockdown and inhibition of the JNK2 in ESCC cell lines.

Results: Higher JNK2 expression was observed in tumor tissues compared to adjacent tissues. JNK2 overexpression was associated with advanced disease stages and poor prognosis. Furthermore, knockdown or inhibition of JNK2 in ESCC cell lines resulted in a decrease in cell proliferation and migration.

Conclusion: Additionally, a significant decrease in the expression of β-catenin and vimentin, along with an increase in the expression of Axin2, was observed upon downregulation of JNK2. Our study provides insight into the role of JNK2 in ESCC and its potential regulatory mechanism, offering a potential therapeutic strategy for ESCC patients with aberrant JNK2 expression.

Moreover, the current findings of the interplay between the oncogenic pathways and the lipid metabolic enzymes are elucidated briefly. The therapeutic implications of modulating these aberrations for the advancement of anti-cancer therapies are also discussed. Although the understanding of altered lipid metabolism in cancer initiation and progression is still in its infancy and somewhat obscure, its in-depth comprehension will open promising therapeutic opportunities for the development of novel and promising strategies for cancer treatment and management.

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.

Objective: The efficacy and safety profile of concurrent (chemo) radiotherapy combined with nimotuzumab in elderly patients with ESCC were investigated.

Methods: Eligible elderly (≥70 years) patients with locally advanced ESCC were enrolled in this prospective, real-world pragmatic study and received concurrent chemoradiotherapy or radiotherapy combined with nimotuzumab. The primary endpoint was overall survival (OS). Secondary endpoints were objective response rate, disease control rate, progression-free survival (PFS), and adverse drug reactions.

Results: Fifty-three elderly patients were enrolled. Thirty-two (60.4%) were treated with radiotherapy combined with nimotuzumab (RT+N), and 21 (39.6%) with concurrent chemoradiotherapy combined with nimotuzumab (CRT+N). The median age was 75.8 years. Fourteen (56.0%) patients achieved a partial response, and 11 (44.0%) patients achieved stable disease at 3 months. The median follow-up duration was 24.4 (95%CI, 21.6-26.7) months. Median OS (mOS) was 27.0 (95%CI, 14.8-48.4) months. Median PFS (mPFS) was 22.6 (95%CI, 12.4-not reached) months. Higher mPFS (not reached vs. 12.0 months; p=0.022) and mOS (48.4 vs. 15.3 months; p=0.009) were observed in the CRT+N group compared with the RT+N group. Most adverse reactions were grade 1-2 (46, 86.8%).

Conclusions: Concurrent chemoradiotherapy or radiotherapy combined with nimotuzumab was safe and well-tolerated in elderly patients with locally advanced ESCC. ESCC patients treated with CRT+N could live longer.

Objectives: NRs are associated with the progression of many cancers, including EC. Some NRs, such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs in EC is helpful for further understanding the development of EC. Preclinical research and development of small molecule compound drugs targeting NRs have provided new ideas for the potential targeted therapy of EC.

Methods: This review summarizes the studies on NRs in EC in recent years, mainly including in vitro cell experiments and in vivo animal experiments.

Results: NRs influence EC progress in a variety of ways. They mainly affect the proliferation, migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of NRs will become a potential therapeutic regimen for EC.

Conclusion: The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseases.

Aims: This study aimed to comparatively investigate in vitro anti-cancer and in vivo anti-angiogenic effects of TRPC blockers Pyr-3 and SKF-96365.

Methods: For anti-cancer effects, four cancer cell lines (MDA-MB-231, A549, PC-3, and HCT-116) were used. In vivo anti-angiogenic effects were investigated by employing in vivo CAM assay of fertilized hen eggs.

Results: Pyr-3 affected cell viability in a dose-dependent manner, all concentrations of SKF-96365 significantly reduced cell viability in all cell lines. Pyr-3 and SKF-96365 at concentrations of 2.5 μg/pellet and 50 μg/pellet, respectively inhibited in vivo angiogenesis significantly.

Conclusion: The concentration of 2.5 μg/pellet caused no irritation, whereas 50 μg/pellet produced some slight irritation. Apart from their anti-cancer effects, our findings indicate that Pyr-3 and SKF-96365 may be promising anti-angiogenic agents for the treatment of angiogenesis-related disorders.

Objective: This review reveals the changes and roles of WDFY3-AS2 in many tumors and cancers. The change of WDFY3-AS2 can be used as a cancer biomarker and plays an important role in improving tumor growth, migration and invasion. WDFY3-AS2 is unique because it can be considered a prognostic marker for many tumors and is of great significance for clinical diagnosis and treatment. WDFY3-AS2 shows the potential prognostic value and the prospect of therapeutic targets in various tumors.

Methods: PubMed reviewed the related literature to analyze and summarize the regulatory molecular mechanism of WDFY3-AS2 in various tumors and its value as a prognostic indicator.

Results: The abnormal expression of LncRNA WDFY3-AS2 in many cancers was connected with the poor prognosis of cancer patients, including diffuse glioma, hepatocellular carcinoma, ovarian cancer, esophageal cancer, triple-negative breast cancer, Clear Cell Renal Carcinoma, Esophageal squamous cell carcinoma, Lung adenocarcinoma, which participated in the recovery of orthodontic teeth. WDFY3-AS2 has revealed the cellular process of cancer cell growth, migration, and invasion.

Conclusion: The molecular mechanism of LncRNA WDFY3-AS2 regulating tumor specifically proves that WDFY3-AS2 has a good prospect in the biological index of prognosis or clinical treatment target of cancer patients.

Objective: In this study, six lead pyrazoline hybrids were synthesized by cyclization of chalcones and characterized by various spectroscopic and elemental analyses. All synthesized compounds were screened for anti-inflammatory and anti-microbial activity by computational tools and biological evaluation.

Methods: Synthesized pyrazoline analogues were characterized by various spectroscopic techniques and evaluated for prediction of pharmacokinetics, physicochemical properties and Molecular docking studies of various targeted enzymes on microbial and inflammatory mediators. Those compounds were screened by anti-microbial and anti-inflammatory activities by several in-vitro and in-vivo methods.

Results: The synthesized compounds (A1-A6) were screened for anti-inflammatory activity in which compound A2 produced effective percentage inhibition (45.8 %) potent activity compared with that of standard indomethacin (49.7 %) in the carrageenan paw edema method were observed. The anti-microbial activity was screened on synthesized compounds, among which A3 [2-(1,3- diphenyl-4,5-dihydro-1H-pyrazol-5-yl) phenol, A2 [5-(4-chlorophenyl)-1,3-diphenyl-4,5-dihydro- 1H-pyrazole] produced potential percentage zone of inhibition between 80 - 70 % for bacterial strains and 94 - 89 % for fungal strains were observed. The minimum inhibitory concentration values of those compounds were 1.56 to 6.25 μg/ml for bacterial strains, and 1.56 to 12.5 μg/ml for fungal strains were noted compared with the standard gatifloxacin and clotrimazole, respectively. The molecular docking, pharmacokinetics and toxicity predictions on those compounds were supported further for developing potent anti-infective agents.

Conclusion: The hypothesis of this research was correlated with the results of anti-inflammatory and anti-microbial activity. The binding interactions of respective enzymes coincided with a reduction of paw edema in the anti-inflammatory model and a zone of inhibition in anti-microbial activity.

Case Presentation: A 74-year-old woman with a previous history of oesophageal cancer was admitted to the hospital after having cough and sputum for 15 days. Despite the COVID-19 symptoms, this patient did not have a fever at the time of the onset. Results of routine blood tests were normal at first but then declined with persistent fever, and A whole-body C.T. examination ruled out the possibility of tumor-metastasis–related fever. This patient had no hepatosplenomegaly or regional lymphadenopathy, and there was no concrete evidence of haemophagocytic lymphohistiocytosis or lymphoma until bone marrow biopsy results confirmed the latter.

Conclusion: We describe an uncommon case of COVID-19 who was finally diagnosed with B-cell lymphoma. An awareness of persistent fever and declined routine blood tests caused by hematological malignancies instead of COVID-19 itself can aid in providing appropriate guidelines for management and treatment.

The current review explores in detail the various links leading to and /or facilitating oncogenesis, providing sound reasoning or a basis for its utilization as potential therapeutic targets. The present review emphasizes the existing knowledge of the microbiome in cancer and further elaborates on the factors, like genetic modifications, effects of dietary components, and environmental agents, that are considered to assess the direct and indirect effect of microbes in the process of oncogenesis and on the host’s health. Strategies modulating the microbiome and novel biotherapeutics are also discussed. Pharmacomicrobiomics is one such niche accounting for the interplay between the microbiome, xenobiotic, and host responses, which is also looked upon.

The literature search strategy for this review was conducted by following the methodology of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The method includes the collection of data from different search engines, like PubMed, ScienceDirect, SciFinder, etc., to get coverage of relevant literature for accumulating appropriate information regarding microbiome, cancer, and their linkages.

These considerations are made to expand the existing literature on the role of gut microbiota in the host's health, the interaction between host and microbiota, and the reciprocal relationship between the microbiome and modified neoplastic cells.

Potential therapeutic implications of cancer microbiomes that are yet unexplored and have rich therapeutic dividends improving human health are discussed in detail in this review.

Objective: This review paper provides updated information gathered on medicinal plants and isolated phytoconstituents used as anticancer agents and summarises the plant extracts and their isolated chemical constituents exhibiting anticancer potential on clinical trials.

Methods: An extensive bibliographic investigation was carried out by analysing worldwide established scientific databases like SCOPUS, PUBMED, SCIELO, ScienceDirect, Springerlink, Web of Science, Wiley, SciFinder and Google Scholar etc. In the next few decades, herbal medicine may become a new epoch of medical system.

Results: Many researches are going on medicinal plants for the treatment of cancer but it is a time to increase further experimental studies on plant extracts and their chemical constituents to find out their mechanism of action at molecular level.

Conclusion: The article may help many researchers to start off further experimentation that might lead to the drugs for the cancer treatment.

Objectives: The objective of the study was to highlight current therapy and novel techniques used in the treatment of peptic ulcer diseases.

Methods: An exhaustive literature search has been conducted across PubMed, Google, Scopus and Web of Science electronic databases to extract the crucial information from the relevant literature.

Results: In the present review, we have discussed PUD and its pathophysiology. The recent trends in PUD and possible treatments with novel techniques have also been discussed. The type and presence of ulcers cannot be predicted accurately based on symptoms. The available treatment approaches for peptic ulcers based on their clinical presentation and etiology are anti-secretory therapy, endoscopy to reveal ulcers, followed by drug therapy, and triple therapy for H. pylori infection.

Conclusion: Thus, the popular and effective methods are very beneficial in controlling PUD. The treatment based on diagnosis is the foremost requirement for ameliorating any disorder. In this article, the emerging techniques and advancements in the treatment and diagnosis of PUD have been reviewed.

Objective: This manuscript provides a critical overview of the use of CAM model in pharmaceutical and biological research, especially to test the toxicity of new drugs and formulations and the biodistribution and the efficacy of novel anticancer and antiinfective therapies, analyzing its advantages and disadvantages in comparison to animal models.

Conclusion: The chick chorioallantoic membrane model shows a great utility in several research areas, such as cancer, toxicology, biodistribution studies and anti-infective therapies. In fact, it has become an intermediate stage between in vitro experiments and animal studies, and, in the case of toxicological studies (skin and ocular toxicity), it has even replaced the animal models.

Objectives: With the following goals in mind, this review tries to describe significant recent advances in the medicinal chemistry of heterocycle-based compounds: (1) To shed light on recent literature focused on heterocyclic derivatives' anticancer potential; (2) To discuss recent advances in the medicinal chemistry of heterocyclic derivatives, as well as their biological implications for cancer eradication; (3) To summarise the comprehensive correlation of structure activity relationship (SAR) with pharmacological outcomes in cancer therapy.

Background: Cancer remains one of the major serious health issues in the world today. Cancer is a complex disease in which improperly altered cells proliferate at an uncontrolled, rapid, and severe rate. Variables such as poor dietary habits, high stress, age, and smoking, can all contribute to the development of cancer. Cancer can affect almost any organ or tissue, although the brain, breast, liver, and colon are the most frequently affected organs. For several years, surgical operations and irradiation have been in use along with chemotherapy as a primary treatment of cancer, but still, effective treatment of cancer remains a huge challenge. Chemotherapy is now considered one of the most effective strategies to eradicate cancer, although it has been shown to have a number of cytotoxic and unfavourable effects on normal cells. Despite all of these cancer treatments, there are several other targets for anticancer drugs. Cancer can be effectively eradicated by focusing on these targets, including cell-specific and receptor-specific targets such as tyrosine kinase receptors (TKIs). Heterocyclic scaffolds also have a variety of applications in drug development and are a common moiety in the pharmaceutical, agrochemical, and textile industries.

Methods: The association between structural activity relationship data of many powerful compounds and their anticancer potential in vitro and in vivo has been studied. SAR of powerful heterocyclic compounds can also be generated using molecular docking simulations, as reported in literature.

Conclusion: Heterocycles have a wide range of applications, from natural compounds to synthesised derivatives with powerful anticancer properties. To avoid cytotoxicity or unfavourable effects on normal mammalian cells due to a lack of selectivity towards the target site, as well as to reduce the occurrence of drug resistance, safer anticancer lead compounds with higher potency and lower cytotoxicity are needed. This review emphasizes on design and development of heterocyclic lead compounds with promising anticancer potential.

Methods: Volunteers with advanced-stage, histopathologically proven HNSCC, indicated to have radiotherapy/chemoradiotherapy, were evaluated for CT and PET/CT for radiotherapy planning. The attenuation and SUVmax of the primary lesion and the largest, possibly metastatic lymph node, and the round index and volume of the lymph node were calculated. The relationship between lymph node/primary lesion attenuation and SUVmax ratios was investigated. The differences in CT findings between the SUVmax < and ≥3 groups were examined.

Results: Thirty-two cases with adequate diagnostic quality were studied. There was a very strong positive correlation between the primary lesion and lymph node attenuation (r=0.817, p<0.001), a strong correlation between the lymph node volume and SUVmax (r=0.681, p<0.001), and a moderate negative correlation between lymph node/primary lesion SUVmax and attenuation (r=-0.503, p=0.004). In patients with ≥3 SUVmax, lymph node volume and lymph node/primary lesion SUVmax were significantly higher, and the attenuation ratio was close to 1 (PPV 94.1, 86.3%, respectively).

Conclusion: In HNSCC, the lymph node/primary lesion attenuation ratio can be used instead of SUVmax if supported by other conventional CT findings. Metastasis should be considered if lymph node attenuation is similar to primary mass attenuation and excluded if higher. CT attenuation rate can be used as a supportive finding if PET/CT cannot be performed or lymph node SUVmax is close to the acceptable cut-off for metastasis.

Methods: The ligands were screened for potential targets based on their shape similarity and pharmacophore model matching. The overlapping targets obtained from both methods were verified using the reverse docking approach and validated by docking analysis. MM/PBSA calculation was performed to predict binding affinities between ligand and confirmed targets.

Results: Interleukin-2 inducible T cell kinase [ITK] was confirmed as a potential target of calactin (Ki= -10.3 kcal/mol), calotropin (Ki= -8.7 kcal/mol) and calotoxin (Ki= -10.2 kcal/mol). The ligands interacted with hinge region residues such as Met438 and Asp500 which occupy the highly conserved ATP binding site. Binding energies of calactin (ΔEbind = -29.18 kJ/mol), calotropin (-28.57 kJ/mol) and calotoxin (-21.21 kJ/mol) with ITK were higher than (more negative) positive control sunitinib (-15.03 kJ/mol) and standard staurosporine (-21.09 kJ/mol). Besides this, Interstitial collagenase [MMP1] was confirmed as a potential target of calotoxin (Ki= -8.2 kcal/mol). However the binding energy (ΔEbind = -11.89 kJ/mol) was lower compared to positive control batimastat (-21.07 kJ/mol).

Conclusion: The results of this study confirmed ITK as a potential target for calactin, calotropin and calotoxin. These compounds can therefore be used as lead molecules for the development of novel ITK inhibitors, which may have immense therapeutic applications as immune-suppressants and as anticancer drugs.]]> https://www.benthamscience.comarticle/108415 https://www.benthamscience.comarticle/114843 https://www.benthamscience.comarticle/111555A significant percentage of costs in pharmaceutical markets is devoted to supplements due to the confidence of consumers in the beneficial effects of these products. Magnesium is one of the supplements with enduring and increasing popularity. According to what is reported online, this metal ion can cure or prevent almost all kinds of diseases. This review aims at illustrating a series of scientifically demonstrated cases in which magnesium was used in clinical practice. Except for its ordinary use as antacid and laxative, other ascertained uses, reported in scientific literature, consist of helping to treat several diseases such as nocturnal leg cramps, pre-eclampsia, diabetes, depression, Parkinson’s and Alzheimer’s disease, hypertension, some types of arrhythmias, asthma, migraine headaches, epilepsy, cerebral haemorrhage, and stroke.

However, many of these promising uses of magnesium require further studies to define the involved molecular mechanisms which should help establishing its uses in relation to the prolonged use of supplements.

Methods: Nine Corriedale sheep that had been monitored for 10 minutes during a basal stage underwent 5-minute myocardial ischemia, followed by 60-minute reperfusion. Seven of them were subjected to an induced heart failure through an overdose of halothane, two of which were treated with intra-aortic counterpulsation during the reperfusion stage. The remaining two animals were monitored during their ischemia-reperfusion stage.

Results: Data obtained in the 5 animals suffering from heart failure followed by myocardial ischemia showed that: a) heart failure induction determined decrease in cardiac output, cardiac index and systolic and diastolic aortic pressure (AoP) with respect to their basal values (p<0.05), b) myocardial ischemia decreased the WTF compared with basal and induced heart failure values (p<0.05), c) during the reperfusion stage accompanied by induced heart failure, WTF increased with respect to values observed during the ischemia induction stage (p<0.05); nevertheless, basal values were not recovered after reperfusion (p<0.05). During this 60-minute stage, systolic and diastolic AoP values were lower (p<0.05) than those at the basal stage.

Conclusion: AIx and WTF values calculated from synchronically recorded values of aortic pressure and left ventricular wall thickness during the reperfusion stage in all animals (n = 9) showed a negative correlation (p<0.05). Analysed data provided evidence of a negative relationship between a left ventricular index of myocardial function and an arterial index obtained from AoP waves.

Methods: Differentially expressed genes in GEO and TCGA databases were analyzed by bioinformatics. The expression levels of miR-375 and XPR1 mRNA were detected by qRT-PCR. Protein expression of XPR1 was detected by western blot. Bioinformatics analysis and dual luciferase assay were conducted to confirm the target relationship between miR-375 and XPR1. The viability, proliferation, migration and invasion of cells in each treatment group were detected by CCK-8, colony formation, wound healing and Transwell assays.

Results: Significantly down-regulated miR-375 and remarkably up-regulated XPR1 were observed in ESCC tissue and cells. Overexpression of miR-375 inhibited proliferation, invasion and migration of ESCC cells, and greatly reduced the promoting effect of XPR1 overexpression on cell proliferation, migration and invasion. Dual luciferase assay confirmed that miR-375 targeted and inhibited XPR1 expression in ESCC.

Conclusion: These results demonstrate the regulatory role of the miR-375/XPR1 axis in ESCC cells and provide a new potential target for the precise treatment of patients with ESCC.

Methods: Human esophageal carcinoma cell line KYSE150 was used for this study. CCK-8 assay was used to determine the cytotoxicity of QGF. The KYSE150 cells were treated with QGF to determine its effect on cell migration (cell scratch assay and imaging) and invasion (Transwell system based with Matrigel assay). Western blotting was used to investigate the effect of QGF on relevant molecules of signaling pathways. A mouse model of lung metastasis of esophageal cancer was established by injecting the KYSE150-Luc cells through the tail vein. A small animal imaging system was used to observe tumor metastasis in the mice.

Results: QGF reduced cell migration and invasion of KYSE150 cells. QGF significantly inhibited lung metastasis in nude mice. Further study revealed that the expression of Growth arrest-specific 6 (Gas6), Anexelekto (Axl), N-Nuclear factor-kappa B (NF-κB) and matrix metalloproteinase-9 (MMP-9) proteins were decreased both in vitro and in vivo upon treatment with QGF.

Conclusion: QGF could prevent invasion and metastasis of esophageal cancer by inhibiting the Gas6/Axl signaling pathway.

Objective: The present review aims to describe recent research and current observations about zonulin involvement in several diseases and the use of its inhibitor Larazotide for their treatment.

Methods: A systematic search was conducted on PubMed and Google Scholar, resulting in 209 publications obtained with the following search query: “Larazotide,” “Larazotide acetate,” “AT-1001,” “FZI/0” and “INN-202.” After careful examination, some publications were removed from consideration because they were either not in English or were not directly related to Larazotide.

Results: The obtained publications were subdivided according to Larazotide’s mechanism of action and different diseases: celiac disease, type 1 diabetes, other autoimmune diseases, inflammatory bowel disease, Kawasaki disease, respiratory (infective and/or non-infective) diseases, and other.

Conclusion: A substantial role of zonulin in many chronic and acute inflammatory diseases has been demonstrated in both in vivo and in vitro, indicating the possible efficacy of a Larazotide treatment. Moreover, new possible molecular targets for this molecule have also been demonstrated.

Objective: We analyzed the effects of deferasirox and eltrombopag in human osteosarcoma cells in an attempt to identify other therapeutic approaches for this tumor.

Methods: We cultured and treated with deferasirox and Eltrombopag, alone and in combination, two human osteosarcoma cell lines, MG63 and 143B. After 72h exposure, we performed RTqPCR, Western Blotting, Iron Assay and cytofluorimetric assays to evaluate the effect on viability, apoptosis, cell cycle progression and ROS production.

Results: The iron-chelating properties of the two compounds are also confirmed in osteosarcoma, but we did not observe any direct effect on tumor progression.

Discussion: We tested deferasirox and eltrombopag, alone and in combination, in human osteosarcoma cells for the first time and demonstrated that their iron-chelating activity does not influence biochemical pathways related to cancer progression and maintenance.

Conclusion: Although further investigations on possible effects mediated by cells of the tumor microenvironment could be of great interest, in vitro iron chelation in osteosarcoma does not impair tumor progression.

Objective/Methods: Therefore, in this study, we used a combined drug repurposing, virtual screening and per-Residue Energy Decomposition (PRED) to identify ZUFSP inhibitors with therapeutic potential. 3-bromo-6-{[4-hydroxy-1-3(3-phenylbutanoyl)piperidin-4-yl]methyl}-4H,5H,6H,7H-thieno[2,3- C]pyridine-7-one (BHPTP) which is an inhibitor of USP7 was repurposed to target ZUFSP. The rationale behind this is based on the similarity of the active between USP7 and ZUFSP.

Results: PRED of the binding between BHPTP and ZUFSP revealed Cys223, Arg408, Met410, Asn460, and Tyr465 as the crucial residues responsible for this interaction. The pharmacophoric moieties of BHPTP responsible for this binding along with other physiochemical properties were used as a filter to retrieve potential ligands. 799 compounds were retrieved, ZINC083241427, ZINC063648749, and ZINC063648753 were selected due to the binding energy they exhibited. Cheminformatics analysis revealed that the compounds possess high membrane permeability, however, BHPTP had a low membrane permeability. Furthermore, the compounds are drug like, having obeyed Lipinski’s rule of five.

Conclusion: Taken together, findings from this study put ZINC083241427, ZINC063648749, and ZINC063648753 as potential ZUFSP inhibitor, however, more experimental validation is required to unravel the mechanism of actions of these compounds.

Objective: The main objective of this research was to prepare and evaluate more target specific formulation for the treatment of colorectal cancer. PLGA and PEG-based polymeric nanoparticles are capable of preventing opsonization via the reticuloendothelial system. Hence, prepared polymeric nanoparticles are capable of higher cellular uptake.

Methods: The Poly(d,1-lactide-co-glycolide) (PLGA) and Polyethylene Glycol (PEG) were combined utilizing the ring-opening polymerization method. The presence of PEG prevents opsonization and distinguished blood concentration along with enhanced targeting. The presence of PLGA benefits in the sustained release of polymeric formulations. The optimized formulation (5-FU-PLGA- PEG-NP) was lyophilized using 4% trehalose (cryoprotectants) and conjugated with Anti- EGFR mAb on its surface to produce Anti-EGFR-5-FU-PLGA-PEG-NP; the final formulation, which increases target specificity and drug delivery system of nanoparticles.

Results: The spherical shaped optimized formulation, 5-FU-PLGA-PEG-NP-3 was found to have higher percentage drug entrapment efficacy (71.23%), higher percentage drug content (1.98 ± 0.34%) with minimum particles size (252.3nm) and anionic zeta potential (-31.23mV). The IC₅₀ value of Anti-EGFR-5-FU-PLGA-PEG-NP was 1.01μg/mL after 48 hours incubation period in the HCT 116 cell line, indicating higher anticancer effects of the final formulation.

Conclusion: From the outcomes of various experiments, it was concluded that Anti-EGFR-5-FUPLGA- PEG-NP has biphasic drug release kinetics, higher cellular uptake and higher cytotoxicity. Therefore, anti-EGFR-5-FU-PLGA-PEG-NP holds excellent potential for drug delivery to EGFR positive colorectal cancer cells.

Objective: To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents.

Methods: A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed Central, and Google scholar for the implication of curcumin in cancer management, along with a special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com, and www.freshpatents.com.

Result: Recent studies based on cancer cells have proven that curcumin has potential effects against cancer cells as it prevents the growth of cancer and acts as a cancer therapeutic agent. Besides, curcumin exerted anti-cancer effects by inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion, and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells.

Conclusion: Accumulating evidences suggest that curcumin has the potential to inhibit cancer growth, induce apoptosis, and modulate various cell signaling pathway molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy, and safe dose in the management of various cancers.

Objective: Our study employed a novel data-driven approach to classifying the normal samples and different types of gastrointestinal cancer samples, to find potential biomarkers for effective diagnosis and prognosis assessment of gastrointestinal cancer patients.

Methods: Different feature selection methods were used, and the diagnostic performance of the proposed biosignatures was benchmarked using support vector machine (SVM) and random forest (RF) models.

Results: All models showed satisfactory performance in which Multilabel-RF appeared to be the best. The accuracy of the Multilabel-RF based model was 83.12%, with precision, recall, F1, and Hamming- Loss of 79.70%, 68.31%, 0.7357 and 0.1688, respectively. Moreover, proposed biomarker signatures were highly associated with multifaceted hallmarks in cancer. Functional enrichment analysis and impact of the biomarker candidates in the prognosis of the patients were also examined.

Conclusion: We successfully introduced a solid workflow based on multi-label learning with High- Throughput Omics for diagnosis of cancer and identification of novel biomarkers. Novel transcriptome biosignatures that may improve the diagnostic accuracy in gastrointestinal cancer are introduced for further validations in various clinical settings.

Methodology: In this present review, we explored the anticancer drugs with curcumin-based drugs under pre-clinical and clinical studies with critical examination. Based on the strong scientific reports of patentable and non-patented literature survey, we have investigated the mode of the interactions of curcumin-based molecules with the target molecules.

Results: Advanced studies have added new dimensions of the molecular response of cancer cells to curcumin at the genomic level. However, poor bioavailability of the molecule seems to be the major limitation of the curcumin. Several researchers have been involved to improve the curcumin derivatives to overcome this limitation. Sufficient data of clinical trials to various cancers that include multiple myeloma, pancreatic cancer and colon cancer, have also been discussed.

Conclusion: The detailed analysis of the structure-activity relationship (SAR) and common synthesis of curcumin-based derivatives have been discussed in the review. Utilising the predictions of in silico coupled with validation reports of in vitro and in vivo studies have concluded many targets for curcumin. Among them, cancer-related inflammation genes regulating curcumin-based molecules are a very promising target to overcome hurdles in the multimodality therapy of cancer.

Methods: The current review tries to present a brief framework of angiogenesis and tumor progression phenomenon along with the latest therapeutic interventions against VEGFR-2 and its future directions.

Results: The tumor angiogenic pathways functioning in diverse mechanisms via sprouting angiogenesis, intussusceptive angiogenesis, vascular co-option, vascular mimicry, and glomeruloid angiogenesis are normally activated by varied angiogenic stimulators and their receptors are interrelated to give rise to specialized signaling pathways. Amongst these receptors, VEGFR-2 is found as one of the key, critical mediators in tumor angiogenesis and is seen as a major therapeutic target for combating angiogenesis. Though a number of anti-angiogenic drugs like Ramucirumab, Sunitinib, Axitinib, Sorafenib, etc. showing good survival rates have been developed and approved by FDA against VEGFR-2, but these have also been found to be associated with serious health effects and adverse reactions.

Conclusion: An improved or alternative treatment is needed shortly that has a higher survival rate with the least side effects. Innovative strategies, including personalized medicine, nano-medicine, and cancer immunotherapy have also been outlined as an alternative treatment with a discussion on advancements and improvements required for their implementation methods.

Objective: (i) Select and identify strains that can degrade biogenic amines, (ii) overexpress enzyme from Enterococcus spp., (iii) measure gene expression and probe amine-degradation differences among strains (native, E. coli DH5α, and L. delbruckii), and (iv) examine the biochemical properties of recombinant multicopper oxidase, (v) apply the recombinant enzyme into smoked horsemeat sausage.

Methods: Reverse transcription PCR and high-performance liquid chromatography were performed to examine gene expression and amine degradation rate.

Results: The results demonstrated that target enzymes were successfully overexpressed, accompanied by increased amine-degrading activity (P <0.05). Gene from E. faecalis M5B was expressed in L. delbrueckii resulted in degradation rates for phenylethylamine, putrescine, histamine and tyramine of 54%, 52%, 70% and 40%, respectively, significantly higher than achieved by other recombinant strains.

Conclusion: In this work, gene expression levels were higher in recombinant M5B than recombinant M2B, regardless of host. E. coli is more stable to express multicopper oxidase. Besides, the amine-degrading ability was markedly increased in the two recombinant strains. After prolonged incubation, the recombinant enzyme could degrade three amines, and it displayed high alkali resistance and thermostability.

Methods: Sprague Dawley rats' heart and myocardial cells I/R model were established in vivo and vitro, then 100 mg/kg and 10 μmol/l baicalin were administrated, respectively. The experiment was randomly divided into 4 groups (n=10): Control; I/R; IR+DMEM; and I/R+baicalin groups. Postoperation, the Left Ventricular (LV) End-Diastolic Pressure (LVEDP), the maximum velocity of LV contraction (dP/dtmax) and the maximum velocity of LV diastole (dP/dtmin) were recorded by the transthoracic echocardiography; the myocardial apoptosis percentage was analyzed by Annexin VFITC/ PI and TUNEL staining, and the apoptosis gene and protein were detected by RT-PCR and western blot. Furthermore, the protein expression of the calcium-sensing receptor (CaSR) and ERK1/2 phosphorylation were observed by western blot and Fura-2-acetoxymethyl ester. Moreover, primary rats’ cardiomyocytes were cultured and ERK1/2 specific inhibitor PD98059 was added to the culture medium. The cell survival rate, vitality and apoptosis were detected by MTT, lactate dehydrogenase (LDH) and TUNEL staining assay Kit, respectively.

Results: Our present study showed that baicalin significantly improved LV hemodynamic parameters and myocardial apoptosis in myocardial I/R injury rats. Furthermore, we found that baicalin could down-regulate the protein expression of CaSR, but up-regulate the protein expression of ERK1/2. Furthermore, when the cells were pretreated with ERK1/2 inhibitor PD98059, the cells survival rate significantly decreased, but LDH activity and apoptosis significantly increased. The results indicated that the effect of baicalin on myocardial I/R injury could be inhibited by ERK1/2 inhibitor.

Conclusion: In conclusion, our data suggests that baicalin attenuates I/R-induced myocardial injury maybe through the suppression of the CaSR/ERK1/2 signaling pathway.

Objective: This study aims to examine the phytochemistry of the whole crude extract of T. coadunata for the first time with evaluation of antibacterial, antioxidant and anticancer activity.

Methods: High Resolution Liquid Chromatography Mass Spectrometry analysis (HR-LCMS) was performed for confirming the presence of biologically active constituents in the extract of T. coadunata followed by antibacterial, antioxidant and anticancer activity.

Results: With the detailed Mass spectra data, absorbance spectra and retention times, chemical composition of T. coadunata holds a diverse group of bioactive/chemical components such as sugars, sugar alcohol, flavonoids, terpenoids and phenolics. The results for antioxidant activity showed that T. coadunata crude extract had higher scavenging potential against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals than H2O2 molecules, which was followed by positive antibacterial activity against several pathogenic bacteria like Shigella flexneri, Staphylococcus aureus and Salmonella typhi.

Discussion: The ethanolic extract of T. coadunata showed favorable antiproliferation activity against three leukemic (KG1, MOLT-3 and K-562) cells in a dose dependent manner, especially for KG1 42.850±1.24μg/ml.

Conclusion: This study has provided a better understanding of the presence of biologically active phytochemical constituents in the extract of T. coadunata, which can be the reason for its bioactive potential. Moreover, T. coadunata has significant anticancer activities against human leukemic cancer cell lines, indicating it as a potential anticancer agent.

Objective: In a prospective study, the influence of CYP1A1*2C and CYP2D6*4 gene polymorphisms on the susceptibility to chronic myelocytic leukaemia (CML) were investigated.

Methods: Prevalence of CYP1A1*2C and CYP2D6*4 was detected in blood specimens from three hundred participants - two hundred patients and a hundred healthy individuals as a control group, using PCR-RFLP.

Results: CYP1A1 Ile/Val and Val/Val genotype frequency in our study population was 82% & 15% in CML patients and 55% & 8% in controls, respectively. This suggests that carriers had an elevated risk (OR=18.38, 95% CI=7.364-45.913, p value; =0.000 and OR=23.125,95 % CI=7.228-73.980, p value=0.000, respectively). Individuals carrying the CYP2D6 heterozygous genotype (IM) were notably fewer in number within the CML group at 43.5%, as opposed to 93% of the controls. This suggests that the IM genotype may have a prophylactic function in lowering CML risk (OR=0.036, 95% CI=0.005-0.271, p value =0.001). In spite of the distribution of the homozygous mutant (PM) genotype being higher in cases with CML (87% as opposed to 6% in the control), this difference was deemed non-significant (OR=0.558, 95% CI=0.064-4.845, p value =0.597).

Conclusion: These findings indicate that polymorphic CYP1A1 and CYP2D6 genes affect the susceptibility to CML.