Pancreas Cancer

Phytoconstituents and their Therapeutic Potential in Precision Medicine

Spices and herbs have been an integral part of Indian cuisine since ancient times. They are not only cherished for improving the flavor and taste of Indian food but also confer their health benefits. Instant herbal remedies prepared from spices and herbs found in the kitchens of Indian homes have been used to treat many ailments and infections in a natural way. Most of the spices and herbs have high nutritional and antioxidant properties responsible for their medicinal effects. This is because of the presence of phytochemicals in the plants. The emphasis of the current article is to provide an overview of the therapeutic potentials elucidating the phytochemical compositions of the key Indian plants. Many such plant products are used mainly as spices in Indian cuisine. In this review, we aim to highlight the chemical constituents and active factors of some of these spices and their pharmacological potential. We believe that in-depth molecular characterization of these spices for all their chemical constituents and their impact on cells, organs, and different organelles will provide a wealth of information useful for human health. These findings may further be chiseled in the form of personalized medicine.

Medical Biotechnology - Approaches to become an Entrepreneur in Medical Biotechnology

Medical biotechnology is one of its branches which involves the application of medicine and biotechnology resources. Entrepreneurship is said to be the development of a new business making profits where innovation and creditability are considered as the backbone for its expansion. In the field of medical biotechnology, the innovation of new medicines, methods for the identification and analysis of new diseases, discovery of new solutions for a complex problem by satisfying the specific needs, etc., are involved. In this chapter, various approaches and ideas for becoming an entrepreneur in the field of medical biotechnology are discussed briefly.

Anti-Obesity Potential of Seaweeds

An excessive buildup of body fat is a sign of the metabolic disease known as obesity. The primary etiological factor for obesity is thought to be an imbalance between energy intake and expenditure, where genetic factors can also play a significant role. The rise in obesity rates over the past few years has encouraged a focus on adipose tissue biology and the precise processes behind adipocyte differentiation and adipogenesis. Due to the advent of several in vitro cell models and molecular biology tools, adipocyte commitment and differentiation have become complicated processes that may be studied to gain a better knowledge of adipogenesis and adipocyte malfunction related to obesity. As the available anti-obesity drugs and surgical interventions cause adverse effects, it is important to rely on natural-based therapeutics in order to manage obesity and its associated complications. Seaweeds are a rich source of natural bioactive compounds that exhibit human beneficial effects. Fucoxanthin, phlorotannins, fucoidan, and alginate are some of the bioactive compounds present in seaweeds exhibiting anti-obesity potential mainly via the inhibition of digestive enzymes and adipocyte differentiation. Therefore, this chapter mainly focuses on the anti-obesity potential of seaweeds proved by many animal and human cell culture models using in vitro and in vivo mechanisms.

Molecular Basis of Hepatitis B

Hepatitis B virus (HBV) is a serious global health problem affecting millions worldwide. Chronic HBV infection can lead to liver cirrhosis and hepatocellular carcinoma, making it a major cause of morbidity and mortality. The molecular basis of HBV infection and pathogenesis is complex and involves multiple interactions between the virus and the host immune system. HBV is a partially doublestranded DNA virus replicating through reverse RNA intermediate transcription. The virus has several proteins, including the envelope protein (HBsAg), core protein (HBcAg), and polymerase (HBp), that play critical roles in virus entry, replication, and assembly. The viral genome is organized into four overlapping open reading frames (ORFs), each encoding a different viral protein. During HBV infection, the virus initially binds to heparan sulfate proteoglycans on the cell surface, followed by binding to specific receptors, such as the sodium taurocholate co-transporting polypeptide (NTCP). The virus then enters the cell through endocytosis, where it is uncoated and releases the viral DNA into the nucleus. The viral DNA is then transcribed by the host RNA polymerase II, producing viral mRNAs translated into viral proteins. One key factor determining the outcome of HBV infection is the host's immune response. The innate immune response plays an important role in controlling the initial phase of HBV infection, while the adaptive immune response, particularly the CD8+ T cell response, is critical for the clearance of the virus. However, in some cases, the immune response cannot clear the virus, leading to chronic infection. Understanding the molecular basis of HBV infection and pathogenesis is critical for developing effective treatments and vaccines. Current treatments for chronic HBV infection include nucleoside/nucleotide analogs and interferon-based therapies, which can suppress viral replication and reduce liver damage. However, these treatments are not curative and can have significant side effects. Vaccination against HBV is highly effective in preventing infection and is recommended for all individuals at risk of HBV infection.

Utilizing in silico Methods in New Drug Design

The current chapter offers a highly informative and enlightening overview of the practical implementation of molecular docking in the field of biotechnology, with a specific focus on drug discovery for a variety of ailments. Molecular docking, an incredibly powerful computational methodology, has increasingly been utilized as an essential instrument in the elucidation of drug-receptor interactions, providing invaluable insights into the process of designing drugs. This chapter delves into the fundamentals of molecular docking algorithms, offering a comprehensive understanding of their theoretical underpinnings, methodologies, and typical applications. Furthermore, this chapter elaborates on how this method is used to predict the binding affinity and orientation of potential small-molecule therapeutics to their protein targets, emphasizing the crucial role that molecular docking plays in the quest for new medications to treat various diseases. By presenting case studies across a range of diseases, this chapter effectively demonstrates the remarkable versatility of molecular docking in advancing our knowledge of disease pathogenesis and therapeutic interventions. In addition, specific diseases and their corresponding drugs are carefully examined, along with an in-depth review of molecular docking studies performed on these drugs. This detailed exploration serves as a robust foundation for researchers seeking to understand the utility of molecular docking in the development of more effective, targeted therapeutics. This chapter thus positions molecular docking as an indispensable tool in the field of biotechnology, propelling drug discovery into a new era of precision and efficiency. Overall, this chapter presents a comprehensive and informative overview of the diverse applications of molecular docking in biotechnology, providing an essential resource for researchers in the field.

Role of Gut Microbiota in Neuroinflammation and Neurological Disorders

The prevalence of neurological diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Multiple sclerosis (MS) are growing in the world, but their pathogenesis is unclear and effective treatment does not exist. Neuroinflammation is associated with many neurodegenerative mechanisms involved in neurodegenerative diseases. The human gut microbiota is an aggregate of microorganisms that live in the gastrointestinal tract (GIT) that plays a crucial role in maintaining human health and the pathogenesis disease condition. The microbiota can affect neuronal function through neurotransmitters, vitamins, and neuroactive microbial metabolites like shortchain fatty acids. The change in gut microbiota architecture causes increased permeability of the intestine and immune system activation, contributing to systemic inflammation, neurological injury, and eventually neurodegeneration. Available data suggest that the microbiota send signals to the central nervous system (CNS) by activating afferent neurons of the vagus nerve via neuroendocrine and neuroimmune pathways. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring gut homeostasis and proper digestion. Evidence suggests that dysfunction of the gut-brain axis could be a significant factor leading to many disorders of CNS. In this chapter, we explore how the gut microbiome may affect brain function and the development of neurological disorders. In addition, we are also trying to highlight the recent advances in improving neurological disease by supplemental probiotics and faecal microbiota transplantation via the concept of the gut-brain axis to combat brain-related dysfunction.

Applications of Biosurfactants in Various Cancer Therapies

Biosurfactants are the naturally-occurring surface-active biomolecules produced by microorganisms having a wide range of applications. Because of their unique characteristics like low toxicity, specificity, biodegradability and relative ease of preparation, these surface active molecules have attracted a wide interest recently. The effective and side-effect-free treatment of cancer remains a top priority for researchers despite various advancements in cancer therapy. To go beyond the drawbacks of chemotherapy, it is necessary to investigate anticancer medications derived from natural sources. Since a wide variety of these compounds have revealed the capacity to elicit cytotoxicity against numerous cancer cell lines, hence modulating cancer growth pathways, biosurfactants have recently come to light as prospective agents for cancer therapy. In this context, microbial biosurfactants offer a potential replacement for existing cancer treatments as well as anti-cancer drug delivery methods. The synthesis, structure, and studies of several cancer cell lines, including breast cancer, cervical cancer, lung cancer, pancreatic cancer, and prostate cancer, are all covered in this chapter, which summarizes the state of the art on microbial surfactants with anti-cancer potential.

Natural Biomaterials: An Essential Element for in vitro Disease Modeling

In-depth analysis of human diseases, specifically emergent noncommunicable ones, needs to be carried out to understand the molecular mechanism and develop sustainable therapeutics. Animals such as small rodents and canines are frequently used as models for clinical trials. However, recent evidence suggests the inappropriateness of such in vivo models for human diseases. A new class of humanrelevant platforms needs to be established to resolve the issues surrounding the failure of potential drug candidates over the last decades. The development of human-relevant in vitro models must abide by the 3R’s principles for biomedical research. Modeling diseased tissue requires appropriate matrices such as scaffold, hydrogel, electrospinning mats, and others to mimic the strength and mechanics of the tissue in question. Biodegradable biomaterials from natural sources such as plants and animals are already used widely for tissue engineering, and regenerative medicines can be repurposed to develop a human-relevant disease model. Here we will discuss the current status of such in vitro models for a few highly fatal non-communicable diseases like cardiomyopathy, cancer, neuropathy, and others.

Promising Pharmaceutical Compounds of Marine Bryozoans: Their Chemistry and Therapeutic Applications

This chapter deals with the pharmaceutically important marine bryozoans, their promising secondary metabolites, and bioactivities. All the bioactive compounds of this marine invertebrate group are dealt with as per their chemical classes.

An Update on Biological, Pharmaceutical, and Biotechnological Investigations in Pterocarpus marsupium Roxb.

Pterocarpus marsupium Roxb. is one of the important plants of the Fabaceae family and is present in different regions of the world. It is greatly valued for its medicinal properties and has often been used for medical purposes. It was observed that P. marsupium contains numerous phytochemical components, such as glycosides, proteins, cardiac glycosides, terpenoids, alkaloids, carbohydrates, and flavonoids. Due to overexploitation, the natural population of P. marsupium is declining steadily, because of which it is required to be cultivated on a larger scale. The conventional propagation methods of P. marsupium are time-consuming processes, and the plant is not easy to propagate through seeds because of its low germination percentage. Hence, to overcome the problem related to conventional propagation and to reduce the destruction of plants in wild habitats, tissue culture functions as an important tool to conserve the plant. The tissue culture practice is extremely useful to meet the rising demands of the people because it gives a significant number of elite genotype progenies within a limited time and without seasonal dependence.

Autoimmune Diseases in Animals

Autoimmune diseases, known as immune-mediated diseases, occur when the immune system targets and attacks its own cells. In the field of medicine, there is a wide range of autoimmune conditions, including insulin-dependent Type 1 Diabetes Mellitus T1DM, Type 2 Diabetes Mellitus T2DM, Rheumatoid Arthritis RA, and Thyroiditis. These diseases can either be primary, with no clearly defined cause, or secondary, triggered by factors such as medications, infections, or malignancies. Animal models have proven invaluable for gaining insights into the underlying pathologies, causes, and specific signaling pathways associated with human autoimmune diseases. This is because these animal models share physiological similarities with humans and have shorter lifespans, allowing researchers to observe the entire disease progression. To replicate the complexity of autoimmune diseases in experimental models, researchers utilize various animal species, including monkeys, rabbits, rats, and mice. These methods can be broadly categorized into three strategies: immunization with autoantigens, transfer of autoimmunity, and induction through environmental factors. Numerous studies have been conducted using animal models to investigate the immunological pathophysiology of RA and assess the effectiveness of anti-rheumatic medications. There are several mouse models designed to mimic RAlike disease, each focusing on specific aspects of the condition. While animal models come with limitations, such as incomplete disease manifestations and limited genetic similarity to humans due to human genetic diversity, they remain an essential tool for understanding the pathogenesis of autoimmune diseases. Among the various animal models used in research, mice and other rodents like rats and hamsters account for over 90% of the total number of animals employed in these studies.

Animal Models for Cancer

Cancer is a complex multifactorial disease that affects many people worldwide. Animal models play an important role in deciphering cancer biology and developing new therapies. The animal models widely used in cancer research include tumor xenografts, genetically engineered mice, chemically induced models, and spontaneous tumor models. These models provide a controlled environment to study cancer progression, the interaction of cancer and the immune system, and the effectiveness of new therapies. Although animal models have several advantages, it is important to identify their limitations and use them in conjunction with other preclinical models, such as in-vitro cell culture and patient-derived xenografts, to ensure that results are transferable to humans. In this chapter, we discuss the importance of animal models in cancer research, the different types of animal models, and their advantages and disadvantages. We also provide some examples of animal models used in cancer research. Collectively, animal models have been invaluable in advancing our understanding of cancer and will continue to be important tools in the development of new therapies.

Promising Nano-Carriers-Based Targeted Drug Delivery Approaches for the Effective Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is an attained disorder of cognitive and behavioral impingement with progressive symptoms over time. It is mostly witnessed in elderly people, and as per the World Health Organization (WHO), it has affected more than 35 million people worldwide, and this figure is presumed to double by the year 2050. The most commonly believed cause of AD is the accumulation of beta-amyloid, which forms extracellular plaques. Presently conventional therapy for treating cognitive impairments in AD relies on a neurotransmitter or enzyme modulation strategy. Conventional approved drugs, such as acetylcholinesterase inhibitors (memantine, tacrine), are widely available for the treatment of mild to moderate AD, but due to their lower bioavailability, poor solubility, and ineffective capability to surpass the blood brain barrier (BBB), they often fail to produce the desired effect. The potency of conventional AD drugs is highly dependent on various physiological aspects such as BBB; blood-cerebrospinal fluid barrier and drug efflux by P-glycoprotein, which all hampers the capabilities of AD drugs to grasp the central nervous system (CNS). So, in order to conquer the hurdle and these existing limitations faced by CNS drugs to cross the BBB, innovative pathways in drug development have become the need of the hour. Various nanocarriers based approaches profitably meet this demand by improving the efficacy as well as facilitating the sustained release of the entrapped AD drug via targeted drug delivery. The blood-brain barrier offers protection to the central nervous system and also limits the entry of therapeutic molecules to the CNS. On the other hand, nanotechnology offers the possibility to deliver small molecules against CNS disorders across BBB due to their enormous properties, such as small surface area, controllable physicochemical properties, higher drug payload, and better drug circulation time. Plenty of nanocarriers and nanoparticle prodrugs have been reported to have inconsequential cytotoxicity in preclinical studies, and these advancements have proclaimed a new juncture for the development of new classes of nano carriers’ based potent drug formulations for the treatment of AD. A plethora of nanotechnology-based approaches such as polymers, emulsions, lipo-carriers, solid lipid carriers, carbon nanotubes, and metal-based carriers have been redefined over time, and they have been successfully focusing on both neuroprotective and neurogenerative techniques for treating AD. Many researchers also reported that nanotechnological-based techniques can improve the early diagnosis of AD and enhance the therapeutic efficacy and bioavailability of drugs.

TMP21 in Alzheimer’s Disease: An Important Target For Effective Treatment Approach

Alzheimer's disease (AD) is the most prevalent form of dementia, and it is considered a dynamic cognitive decline. Neurofibrillary tangles and nerve cell injury are important neuropharmacological symptoms for one AD brain. TMP21 is an important molecule in cellular protein trafficking. TMP21, a protein involved in the production of neurotic plaques, appears to be dysregulated in AD. As a result, we want to look into TMP21 dysregulation in Alzheimer's disease, as well as the involvement of TMP21 in neurotic plaque development and the underlying mechanisms. TMP21's significance in the creation of neurofibrillary tangles, synaptic disbalance, and nerve cell death is also explored. It will shed light on the therapeutic potential of regulating TMP21 as a treatment for AD.

Recombinant DNA Techniques

Following the success of the human genome project with 99.99% sequence accuracy, with no gaps, biotechnology has been revolutionized. Recombinant DNA technology comprises a battery of experimental procedures to isolate (clone) pieces of DNA containing specific genes. The usage of restriction enzymes for manipulating DNA and producing recombinant DNA along with advances in gene editing technology has paved way for diagnosing the candidate disease genes and treating human genetic disorders by restoring functional genes through the modification of the mutant gene or by introduction of a functional gene by Gene therapy. Array technology helps in the validation of recognized sequences, proteins, other biomolecules, drugs, etc. on a miniaturized platform. Quality management in the lab along with lab safety plans for biomedical labs requires adherence to various governmental regulations for protecting health and safety of lab employees and for the maintenance of safe working environment.

Genome analysis is carried out by genome mapping. Genetic maps can be linkage, cytogenetic or physical maps. Gene expression can be analyzed by genomics and proteomics Microarrays are emerging as useful closed systems for genomic (DNA microarray) and proteome (protein chip) analysis.

Biosynthesis and Function of Glycoconjugates

Investigations to ascertain the physiological roles of carbohydrates in biological systems are being given more importance each day. Basically, carbohydrates are biomolecules with a wide range of biological functions, although they represent the primary energy source for metabolic processes. Carbohydrates are found as structural components in connective tissue in animal organisms. They also act as structural elements in both plant and bacterial cell walls. In the cell, they bind to lipids and proteins to form glycoconjugates called glycolipids, glycopeptides, glycoproteins and peptidoglycans. By binding to lipids and proteins on the cell surface, they perform as molecules that support intercellular adhesion and intercellular communication. Glycobiology is the science that investigates the structure, biosynthesis, and impacts of glycans on biological functions. In biology, glycoconjugates serve a variety of key roles. In mammalian cells, the majority of proteins are glycosylated, and this explains how proteins perform their various functions. In the future, these techniques will be crucial for the identification and treatment of specific diseases. The most major area of progress in glycobiology is the development of carbohydrate-based medicines.
Some diseases, including cancer, can be diagnosed via altered cell surface glycosylation pathways as a biomarker. Therefore, regulating glycosylation mechanisms and understanding the phenotypic characteristics of glycoconjugates are crucial steps in the design of novel strategies.
This chapter discusses the biosynthesis of glycoconjugates, their wide range of biological functions, and their significance for therapy

Photodynamic Therapy and Applications in Cancer

The idea of using light as a therapeutic tool has been popular for thousands of years. Scientific discoveries in line with technological innovations have contributed to the advancement of photodynamic therapy as a therapeutic modality. Photodynamic therapy is based on the generation of highly reactive species that alter the molecular systematics of cells through interactions between light, photosensitizer, and molecular oxygen. It has a minimally invasive protocol that can be combined with other clinical methods or can be stand-alone. The development of photosensitizers with the integration of nanotechnological approaches has provided favorable results over the years in malignant and non-malignant diseases by facilitating target-site action, selectivity, and controllable drug release. This chapter presents a review of photodynamic therapy with its important aspects; history, mechanism of action, cellular effects, integration into nanoscale drug delivery systems, and combinational therapeutic approaches in cancer.

Nanoscience for Nucleotide Delivery in Diabetes

The convergence of nanoscience and nucleotide delivery holds tremendous promise in revolutionizing diabetes treatment. Nucleotide delivery emerged as a promising tool to modulate gene expression and cellular function in diabetes. Integration of nanoscience and nucleotide delivery in diabetes treatment opens avenues for efficient therapies. This approach has the potential to significantly improve glucose regulation and mitigate long-term complications associated with the disease. This chapter discussed DNA and RNA delivery approaches in diabetes treatment and the future and challenges of nucleotide delivery in diabetes.

Nanoscience for Drug Delivery in Diabetes

Current conventional diabetes mellitus (DM) therapies are inadequate and have poor patient compliance. Subsequently, it is necessary to explore nanomedicine in managing diabetes. In recent years, several nanocarrier systems have been proven effective in various aspects of diabetes treatment, increasing drug stability, overcoming different biological barriers, and in enhancing bioavailability. Nanomedicine can potentially improve the therapeutic effect of drug substances to gain the patient’s belief and impart a greater level of acceptability. In the present scientific spectrum, nanomedicines promise to provide sustained and targeted delivery with potential physical stability for a prolonged period, rendering a safe and effective therapy for diabetes. This chapter comprehensively elaborates on trends in the drug delivery system in treating diabetes for improved delivery of different classes of antidiabetic agents compared to contemporary therapies.

Biological Functions of d- and f- Block Elements

Biological Functions of Elements of Main Groups

Incorporate Artificial Intelligence into the Fitness Field to Curb Diabetes in Malaysia: Current and Future

With the rapid technological change, most people are living an unhealthy lifestyle and consuming processed food. Additionally, most people spend time on their mobile phones instead of working on other activities such as exercise. Beginners should have at least 2 to 3 days of working out per week, and the intermediate should have 3 to 4 days of strength training. A set of stretching exercises is required after each workout. Approximately 3.9 million people aged 18 and above are diagnosed with diabetes in Malaysia. This means that 1 in 5 adults will be diagnosed with diabetes. The prevalence rate has increased from 13.4% in 2015 to 18.3% in 2019. Some of the main factors that can cause a person to acquire diabetes are obesity and consuming excessive amounts of food with high sugar levels. The two types of diabetes are type 1 diabetes and type 2 diabetes. Type 1 diabetes results in the body not producing insulin, whereas type 2 diabetes causes the body to not respond to insulin even though it produces insulin.

Management of Children with Systemic Diseases

Significant oral problems are associated with many medical disorders. Close cooperation and consultation between the dentist and the child’s physician are essential to render optimum medical care. Prevention of oral disease is the primary consideration for these children. Medically compromised children can be challenging to treat and affect dental care [30]. To treat medically compromised patients safely, it is essential to Obtain a relevant and thorough medical history and understand the possible implications of the illness on dental treatment and the potential importance of the condition on treatment planning and the caries risk associated with the medical condition. With advances in medical treatment, significantly more children survive longer with more complex medical needs, and these children will present to the general dentist for dental treatment.

Hepatotoxicity

The largest organ in the human body is the liver which captures 2 to 3% of the human body weight, located on the right side of the anterior quadrant in the abdomen and below the anterior hemidiaphragm ribcage. It performs various important functions such as digestion of food, protein production, fluid production, detoxification of waste, etc. Liver injury known as liver trauma can be categorized into four types: hepatocellular, autoimmune, cholestatic and infiltrative. Drug-induced liver injury can match with any form of acute or chronic liver injury. Acute injury to the liver is mainly due to the action of cytochrome P450, which disintegrates drugs into electrophiles or free radicals; these reactive metabolites can covalently act on protein and unsaturated fatty acids for induction of lipid peroxidation which leads to calcium homeostasis or death. Toxicology of the liver is a complex concept that entails either concurrent as well as sequential events. These events determine the pathways, severity and effects of liver injury. Pharmacogenetics has made great progress in current years which indicates the creation of refined algorithms that take drug, host and environmental risk variables into account, allowing for the selection of better medicine based on accurate risk-benefit ratio calculations. In this chapter, we will discuss the anatomy, functions of the liver, types of liver injury, risk factors, and various treatment strategies for the treatment of liver diseases.

Recent Development and Advancement in Microneedle-Assisted Drug Delivery System Used in the Treatment of Cancer

Cancer is one of the most common and distressing diseases. Cancer-related mortality and prevalence have both grown in the last 50 years. Due to its intricacy and progressive nature, cancer remains one of the most debilitating diseases in humans, and clinical care for this lethal disease remains a challenge in the twenty-first century. New and better cancer medicines are constantly needed. Due to the rising global incidence of cancer, the development of novel alternatives to traditional medicines is unavoidable to overcome constraints, such as limited efficacy, comorbidities and high cost. Microneedle arrays (MNs) have just been introduced as an innovative, low-cost, and minimally invasive technique. MNs can safely and precisely deliver micromolecular and macromolecular pharmaceuticals, as well as nanoparticles (NPs), to tumor tissue. However, only a few lipophilic pharmacological compounds with low molecular weight and a rational Log P value were able to pass the skin barrier. Microneedles (MNs) can circumvent these constraints by piercing the body's outermost skin layer and delivering a variety of medications into the dermal layer. MN patches have been made with a variety of materials and application methods. Recently, three-dimensional (3D) printing “A touch button approach” gives the prototyping and manufacturing methods the flexibility to produce the MN patches in a one-step manner with high levels of shape complexity and duplicability.

Biomarkers as Tools for the Early Detection of Cancer

Every year, millions of people around the world lose their lives to different types of cancer, mostly in developing countries. The foremost challenge for the human race in to fight against cancer is its early detection, followed by the appropriate treatment. Currently, one of the most promising and dynamic strategies for early cancer diagnostics as well as for therapeutics, is the use of cancer biomarkers. Generally, biomarkers represent changes in the constituents or composition of cells, tissues, or body fluids, offering a means for comparable classification of diseases as well as the risk factor involved, and thereby providing information about the underlying pathogenesis of the disease. Similarly, a cancer biomarker (CB) is defined as a ‘molecular signature’ that can potentially provide valid information regarding staging as well as the mechanisms underlying the origin of cancer. Cancer biomarkers (CB) are biomolecules synthesized either by the cancer cells or by other cells of the body in response to cancer. Every cell type has its distinctive molecular signature and recognizable features, such as levels or activities of the myriad of genes, proteins, or other molecular characteristics; therefore, cancer biomarkers can facilitate the molecular definition of cancer. Endoscopy, X-rays, magnetic resonance imaging, computed tomography, invasive tissue biopsies, etc., are the traditional cancer diagnostic methods. However, the use of biomarkers as cancer screening tools have several advantages over these traditional approaches. The emergence of “omics” technologies, like metabolomics, genomics, epigenomics, proteomics, etc., has led to an increase in the number of potentially investigated biomarkers, such as DNA, RNA, miRNA, or other protein biomolecules. In this chapter, we have summarized the importance of biomarkers as powerful and dynamic tools for the early diagnosis of various types of cancers, the phases in the biomarker discovery, the criteria for the selection of biomarkers, the advantages of their preference over traditional methods, various categories of cancer biomarkers, examples of cancer biomarkers currently in use and the future prospectives.

Chemomodulatory Potential of Lutein Derived from Dietary Sources

The mortality rate from various types of cancer is unacceptably high till date. Although, there is a huge advancement in understanding the diverse mechanisms of carcinogenesis and the development of potential drug leads, still there are massive mortality rates. The consumption of various green/yellow vegetables and fruits can help in reducing the risk of cancer. There is a plethora of potential anticancer compounds present in green leafy vegetables, which have been extensively evaluated in cancer. Various anticancer leads include dietary agents in which carotenoids are very significant in combating cancer. Lutein is a yellow carotenoid present in vegetables and fruits. It is the second most prevalent carotenoid in human serum, and its consumption is beneficial for promoting good health. The nutritional value of lutein is very high, and besides this, it is reported to exert antiproliferative potential against various cancers such as cervical, skin, lung, breast and colon cancer. Lutein stimulates various genes involved in T-cell transformations that are activated by mitigens, cytokines and antigens, thereby acting as anti-cancer. Lutein can oxidize and degrade easily due to the presence of conjugated bonds in its isoprenoid polymeric structure. Various food processing techniques can also affect the integrity of lutein. Therefore, there has been development of novel drug delivery systems to enhance the absorption andbioavailability of lutein and also to prevent its chemical degradation. Therefore, it can be concluded that lutein can serve as an effective agent in chemoprevention to fight against various forms of cancer because of its nutritional value.

Molecular Mechanisms of Flavonoids Mediated Therapy and Chemoprevention of Cancer

Flavonoids derived from daily dietary source and plant products play a crucial role in the prevention and treatment of various degenerative diseases and cancer. Flavonoids are further subdivided into subclasses such as flavones, flavan-3- ols, flavonols, flavanones, isoflavones and anthocyanidins. There has been a resurgence in the research on flavonoids due to enhancement in the evidence that proves the health benefits of flavonoids. Several preclinical and epidemiological studies revealed that dietary intake of flavonoids may be found helpful in the reduction of risk of tumors like colon, breast, lung, pancreas and prostate. It also acts on the reactive oxygen species, and cellular signal transduction pathways associated with cellular proliferation, angiogenesis and apoptosis. Flavonoids are non-toxic in nature, so intensively studied the broad, vast aspect of their efficacy in biological activities that in turn promotes health benefits and also added to its availability in abundance in our daily diets, for instance, fruits, green leaves, tea, red wine and vegetables. Overall, the exciting data obtained so far elicit that dietary flavonoids have been considered a beneficial cancer preventive approach. This chapter unravels the molecular mechanisms involved in potential cancer preventive efficacy accomplished by the novel biological approach of flavonoids.

Chromosome 19

Gene is considered discrete coding units that contain the information for individual proteins. These lot of genes were combined and named DNA which is tightly coiled many times over the histone protein to form Chromosomes. Humans have got 23pairs of chromosomes, including the sex chromosome. The current study is about the major genes and their functions that are present in chromosome 19. There are approximately 1500 genes present in this chromosome, and changes in chromosome 19 are identified in many cancers. Dislocation of the chromosome, a mutation in genes that are present in a chromosome (rearrangements, deletions, or duplications) of DNA in the chromosome, epigenetic modification, and lifestyle changes are some of the chromosomal abnormalities that are responsible for cancer-causing. These changes will trigger the growth of normal cells and induce cancer cell proliferation, migration, invasion, angiogenesis, and metastasis. The signaling pathways like PI3K/AKT, JAK/STAT, NF-κB, and TGF-β are responsible for the various cellular functions with the result of autocrine, juxtacrine, intracrine, paracrine, or endocrine. When the dysregulation of these signaling pathways leads to cancer progression and metastasis. Prostate cancer, breast cancer, gastric cancer, pancreatic cancer, colon cancer, gastric cancer, lung cancer, leukemia, and cervical cancer are the major cancers that are caused because of mutation that occurs in chromosome 19.

Chromosome 16

Cancer is a heterogeneous disorder with invasive and metastatic potential. It is a deadly disorder affecting 1 in 6 people worldwide. Hence, it is important to eliminate the disease. Genetic alterations remain an underlying cause of cancer, and several gene mutations were involved in causing different types of cancer. Recently, researchers have been investigating the role of genetic mutations in causing cancer. For this reason, the genes associated with chromosome 16 were investigated for their role in causing cancer. This study revealed 70 genes associated with cancer. Of which, the cadherin genes (CDH11, CDH13, and CDH1), AXIN-1, ANKRD11, BANP, CYLD, CBFA2T3, IR8, MVP, MT1F, NQO1 and PYCARD was the tumor suppressor, and the gene MSLN is the potential oncogene. CBFB and MYH11 are well-known fusion genes associated with this chromosome. Loss of heterogeneity was noted in the q arm of this chromosome. The chromosome translocations, t (16;16) (16) (p13q22), t (16;21) (21) (p11;q22), t (12;16) (q13; p13; p11), t(16;21) (p11;q22) and t(7;16) (q33; p11) led to the development of acute myeloid leukemia, leukemia, and sarcoma. Several other genes associated with chromosome 16 responsible for cancer initiation and proliferation are summarized in this chapter. A novel insight into the genetic biomarkers and therapeutic targets has been provided to develop potential therapeutic strategies against cancer.

Chromosome 13

Chromosome 13 represents around 4 percent of the total cellular DNA with 115 million base pairs. It is home to various tumor suppressors and oncogenes, such as ADP ribosylation factors like GTPase-11 (ARL11), Retinoblastoma-1 (RB1), Ras-related protein Rap-2a (RAP2A), etc. Most of the somatic mutations in this chromosome lead to cancer development. Further, deletion in this chromosome has been reported to support the cancer of leukemias, lymphomas, etc. In this chapter, we have tried to list cancer-causing genes and their possible oncogenesis in cancer development.

Biosynthesis of Sterols, Carotenoids, and Polyprenols

Sterols are essential lipid components for the cell membrane. In addition to their structural roles, they are critical signaling molecules that regulate metabolism, development, and homeostasis. Due to the functions of sterols being concentrationdependent, the biosynthesis of sterols is tightly controlled. Here, we reviewed the biosynthesis processes of sterols (squalene, lanosterol, ergosterol, carotenoid, and polyprenols) and analyzed the key and limited enzymes in these processes. Although various sterols are identified in nature, their basic synthesis pathways appear to be conserved. Squalene is the key intermediate in the biosynthesis of sterols, and the cyclization of squalene into lanosterol (animals and fungi) or cycloartenol (plants), producing various types of terpenoids. In addition to the synthesis processes of sterols, how to enhance sterols production was also discussed, which provides the strategy for the industrial production of sterol products.

Sterols, Carotenoid and Polyprenols

Isoprenoid compounds are a family of compounds constructed with isoprene as the basic unit but with very different structures, including monoterpenes, diterpenes and polyterpenes. Isoprenoid compounds mainly include ergosterol, steroids, carotene, carotenoids, polyisoprene, and their structures range from relatively simple linear hydrocarbon chains to highly complex cyclic structures, in which the cyclic structure is cyclized by terpenoids. Enzymes, also known as terpene synthase catalyzed by them, are also called cyclic terpenes. Isoprenoids are widely distributed in archaea, bacteria, and eukaryotes, and a variety of isoprenoids are essential components of the biological mechanism of the organism. For example, in mammals, β-carotene (β-carotene) is the precursor substance of Vitamin A. β-carotene has the function of preventing oxidation reactions, and can inhibit and eliminate oxygen free radicals in the body, and has various effects such as slowing down aging and improving resistance. At the same time, carotenoids can be combined with protein. Astaxanthin and protein combine to form astaxanthin, which makes aquatic animals appear body color and has a certain protective effect. Therefore, ergosterol, steroids, carotene, carotenoids and polyisoprene, which are relatively large in terpenoids, are all important products with commercial value and have been widely used in food, medicine, and daily chemical products.

Destructive Effects of Steroidal Drug Abuse and their Immunological Impact

Steroidal drugs are synthetic in nature that are closely identical to naturally produced hormones in our body such as cortisol and testosterone. They are lifesavers for several threatening medical conditions. They are currently in wide use for the treatment of various inflammatory diseases since they are known to involve in suppressing the immune system resulting in a reduced inflammatory process. They are produced in different forms and do not cause any major side effects when consumed at low doses. However, occasionally they lead to perilous side effects when taken in appropriate doses that lead to mental health problems, high blood pressure, diabetes, osteoporosis, etc. Practices such as the uptake of illicit anabolic steroids and corticosteroid drugs without an appropriate prescription can potentially lead to fatal side effects. Anabolic steroids are performance and image-enhancing drugs that were once viewed as predicament associated with bodybuilders and have now become a widespread problem throughout our society including children. Dietary supplements which act as steroidal precursors also promote medical consequences that are similar to steroids and the absence of such awareness in our society leads to varied difficulties in our current lifestyle. The increasing concern about possible health hazards in association with abusive steroid drug uptake should be addressed with strict measures. It is important to educate our society about the hazardous effects of steroidal drug abuse and the precautions that need to be carried out while using them. This chapter highlights different types of steroid drugs that are currently in use and the deleterious side effects caused by their abusive use. Potential treatments for their withdrawal and preventive measures will also be addressed in detail.

A Comprehensive Overview of Estrogen: Physiological and Pathological Insights

Estrogens (estrone, estriol, and estradiol) are a class of steroidal hormones produced by developing ovarian follicles. These hormones induce various cyclic events in the uterine endothelium and vaginal epithelium and make the female body competent for conception and ultimately for motherly care. While estrogen is primarily produced by ovaries from cholesterol, the non-reproductive tissues including the brain, liver, and heart also produce a considerable amount of it. Apart from its important role in controlling sexual behavior and reproductive function, estrogen also functions in the regulation of various physiological functions including reproduction, skin physiology, cardiovascular health, skeletal homeostasis, bone integrity, electrolyte balance, cognition, and behavior. These biological functions are regulated by diffusion through the plasma membrane in vitro signaling through specific binding to nuclear receptors such as estrogen receptors (ERα and ERβ) or binding to cell membrane receptors such as GPR30 and ER-X. The signaling mechanism can be genomic (change in gene expression) or non-genomic (activation of various signaling cascades). Disruption in estrogen functioning has a pivotal role in the pathogenesis of many diseases such as osteoporosis, insulin resistance, neurodegenerative disease, obesity, and endometriosis. Also, dysregulation in the levels of estrogen has been linked to the development of many cancers such as breast cancer, etc. This chapter aims to summarize the complete insight of estrogen by providing a clear understanding of its synthesis, receptor binding, signaling, regulation of physiological functions, and role in various diseases.

Chromosome 12

Chromosome 12 spans about 134 million DNA building blocks and represents approximately 4.5 percent of the total cellular DNA. Gene dysregulation from chromosome 12 has triggered a cell to transform into a cancerous cell. Different types of genes are present in chromosome 12 that cause colon cancer, ovarian cancer, prostate cancer, ampulla of Vater cancer (Vater cancer), etc. These genes play their role in the development and the progression of cancer into metastasis, Epithelial to mesenchymal transition, and overall cancer growth. In this chapter, we have enlisted the genes responsible for cancer and their short introduction.

Chromosome 7

Chromosome 7 consists of 159 million base pairs, and around 950 genes, representing at least 5 percent of the entire DNA in a cell. Various genes that regulate cell division and cellular growth are present in Chromosome 7. Aberrations in these genes can therefore lead to tumorigenesis. Lymphomas and Leukemia have been frequently correlated with abnormalities on chromosome 7. Aberrations in chromosome 7, such as aneusomy in prostate cancer, gene amplifications in gastric cancer, and chromosomal gain in glioblastoma, are some of the starkly real ramifications of genetic abnormalities on chromosome 7. Numerous essential genes from Chromosome 7, including ABCB5, BRAF, CDK6, EGFR, ETV1, EZH2, IL6, and TWIST1, involved in cancer have been explained in this chapter.

Chromosome 5

Chromosome 5 presents an extensive collection of genes, and includes several cancer-associated ones. The contribution of chromosome 5 in abnormalities is evident through somatic translocations, germline, somatic, and, in some instances, expression of genes. Various syndromes are associated with chromosome 5, such as 5q minus syndrome, leading to the development of acute myeloid leukemia, PDGFRBassociated chronic eosinophilic leukemia contributing to acute myeloid leukemia, and myelodysplastic syndromes. Studies propose that a few genes on chromosome 5 play important roles withinside the increase and department of cells. When chromosome segments are deleted, as in a few instances of AML and MDS, those crucial genes are missing. Without those genes, cells can develop and divide too speedy and in an out-o- -control way. Researchers are trying to perceive the genes on chromosome five that might be associated with AML and MDS.

Probiotics-based Anticancer Immunity in Pancreatic Cancer

Pancreatic cancer is still one of the malignancies with a very poor prognosis worldwide. In the recent past, the gut microbiota has been shown to have a role in pancreatic cancer patients’ survival and response to the therapy. Out of the possible mechanisms, the role of gut microbiota in shaping the microbial composition of pancreatic tumor and its effect on intra-tumor immune modulation has emerged as a potential therapeutic strategy. Modulation of gut microbiota for targeting pancreatic cancer initiation, progression and therapy could be achieved through different processes like treatment through faecal microbiota transplantation (FMT), antibiotics, prebiotics, probiotics, and synbiotics. In the recent past, various clinical and experimental pieces of evidence have demonstrated the efficacy of probiotics in cancer prevention, treatment and management. In this chapter, efforts have been directed towards summarizing the prospects and challenges associated with the use of probiotics and probiotics-derived products against pancreatic cancer.

Probiotics as Potential Remedy for Restoration of Gut Microbiome and Mitigation of Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorder currently plaguing women. There are many factors associated with high androgenicity in the female body. Dysbiosis of gut microbiota may be one of the primary reasons that initiate PCOS. Emerging evidence suggests that some plastics, pesticides, synthetic fertilizers, electronic waste, food additives, and artificial hormones that release endocrine-disrupting chemicals (EDCs) cause microbial Dysbiosis. It is reported that the permeability of the gut is increased due to an increase of some Gram-negative bacteria. It helps to promote the lipopolysaccharides (LPS) from the gut lumen to enter the systemic circulation resulting in inflammation. Due to inflammation, insulin receptors' impaired activity may result in insulin resistance (IR), which could be a possible pathogenic factor in PCOS development. Good bacteria produce short-chain fatty acids (SCFAs), and these SCFAs have been reported to increase the development of Mucin-2 (MUC-2) mucin in colonic mucosal cells and prevent the passage of bacteria. Probiotic supplementation for PCOS patients enhances many biochemical pathways with beneficial effects on changing the colonic bacterial balance. This way of applying probiotics in the modulation of the gut microbiome could be a potential therapy for PCOS.

Antidiabetic Activity Methods

Diabetes mellitus (DM) is a metabolic disease characterized by the destruction of pancreatic β cells or reduced insulin secretion and action, and is one of the most common health problems worldwide. Its incidence is increasing at a high rate, resulting in enormous social costs. Various drugs show their effectiveness by improving insulin sensitivity, and reducing glucose production in the liver or other tissues. Several preclinical studies on diabetes-induced in animals using surgical, pharmacological or genetic methods demonstrated the effectiveness of these drugs. The anti-diabetic activity of plants has been attributed to the occurrence of primary and secondary metabolites characterized by many beneficial effects with advantages over chemical treatments. A number of studies have demonstrated the potential health benefits of phytocomponents in treating DM by acting on multiple molecular targets. Therefore, it is important to test in vitro assays. This review includes methods for the evaluation of preclinical anti-diabetic activities and summarizes the potential of natural resources to prevent and/or treat diabetes. In addition, the database contains information including the plant name, useful plant parts, active compounds, and their mechanisms of action, in which in vitro and in vivo methods were studied.

Anticancer Delivery: Nanocarriers and Nanodrugs

Cancer is a disease in which cells grow uncontrollably and spread to different tissues. Existing treatment methods developed for cancer do not allow this disease to be completely cured, and these methods have various side effects. The search for effective cancer treatment has encouraged scientists to produce new ideas with nanotechnological methods. With the help of nanotechnological methods, which are becoming more popular day by day, the material is reduced to nano size, where it shows quantum effect, and gains unique physicochemical, mechanical, and biological properties. Thanks to the large surface area of the nanocarriers, more drug loading can be achieved on the unit surface, and their easy modification procedures enable these materials to be conjugated with biological molecules to become more specific structures. Due to the several advantages of nanocarriers, such as different synthesis methods, being open to modification, and relatively easy production, these materials can provide effective delivery of cancer drugs and even increase their efficacy. Moreover, there are also many nanodrugs approved for different routes of administration. Thanks to all these features, nanocarriers are promising ways to develop new drug formulations for cancer treatment. In this chapter, the anticancer activity of nanocarriers synthesized by different methods is clarified. Besides, the effects of the nanocarriers on different types of cancer, the targeting strategies of nanocarriers, and the effects of their size, surface charge, and shape, on their anticancer activity are summarized.

Antidiabetic Attributes of Mushrooms

Mushrooms are macrofungi, with distinct mycelia structure, and fruiting bodies, divided into stalk and cap that contains spores in most of the species. These mushrooms are edible with diverse therapeutic applications. Old civilizations from India, China, and Korea used these mushrooms to cure diseases, especially diabetes. Diabetes is now a newly emerging pandemic, affecting people worldwide, with special reference to developing countries. There are several medications available for the management of diabetes, but their permanent treatment is still to be explored. Due to synthetic medicines and their adverse effect, people are searching for natural therapeutic agents. Many mushroom species have shown their potential to control diabetes and its related complications, such as weight loss, lipidemia, hypertension, etc. In this chapter, we have discussed five different mushroom species, i.e., Auricularia auricula-judae, Agaricus bisporus, Ophiocordycep sinensis, Ganoderma lucidum, and Pleurotus species with their potential therapeutic application against diabetes and its related complications.

Potential Solutions for Nanotoxicology

Concerns regarding possible toxicological effects on human health and the environment have arisen as nanomaterials (NMs) result from various substances that have become more widely used in various sectors mainly industry, environment, and medicine. This chapter provides a thorough examination of nanotoxicology and nanosafety approaches concerning NMs upon their development and subsequent implementations. The importance of emerging toxicological strategies developed over the last few decades for the evaluation of NMs toxicity including cell culture studies (in vitro), living organisms (in vivo), and computational methods (in silico) following the advantages/disadvantages of each technique is addressed. A comprehensive overview to reduce the NMs toxicity and the most common approaches adopted up to now mostly focused on medical considerations are also presented here.

Natural Immunomodulators for Infections and Other Diseases

Infection is one of the most common occurring issues in an individual. Diseases caused by infections hamper the immune system of an individual. To modulate the immune system, immunomodulatory drugs work by either stimulating or suppressing the immune system. Several drugs like levamisole and azathioprine are available in the market today to overcome various infections. But an alternative is required to overcome the drug resistance and other side effects associated with these available drugs. To tackle these problems, many plant-based immunomodulators are being explored and have proven to be beneficial against these infections. This chapter focuses on the mechanism of action and application of natural immunomodulators like Curcumin, Resveratrol, and Genistein on various infections. The primary goal of this chapter is to understand the role of natural immunomodulators in the body for various infections and related disease conditions. With the help of findings, one can conclude that all-natural immunomodulators have areas that need attention, including their therapeutic risk-benefit ratio and their target binding affinity for various infections. However, further investigations into these drugs are necessary for a clear understanding to maximize their clinical applications

Plant Essential Oils in the Treatment of Gastrointestinal Cancer

Gastrointestinal malignancies are well-known terms in the pathogenesis of the alimentary canal. They have been prevalent in different organs of the gastrointestinal tract system. Gastric tumor is the second most common cause of death due to cancer in the world. The epidemiology of cancer has changed within the last few decades. A significant deal with such carcinomas is done using essential plant constituents like alkaloids, volatile oils, and glycosides. They involve various mechanisms for eliminating these carcinomas. Many plant essential oils, such as thymol, lemon oil, limonene, carvacrol, and lavender oils, have been investigated for their anti-inflammatory, anti-oxidant, and anti-carcinogenic properties been shown to modulate numerous immunological and cellular functions. Many types of research have proven that a large number of volatile oils and aromatic compounds present in various plants have important anti-cancer activities. They showed the anti-cancer effect on cell lines and cancer cells in animals. The use of various plant volatile oils may alter or affect the pathogenesis of several types of gastrointestinal cancer like liver cancer, esophageal cancer, gastric cancer, pancreatic cancer, etc. In this chapter, the anti-cancer activity of plant essential oil components against GIT cancers has been discussed, with a focus on their possible mechanism of action.

Saponins in the Treatment of Gastrointestinal Tract Cancer

The natural glycosides with triterpenoid or spirostaneaglycones are the saponins, which are associated with a wide range of therapeutic activities, inclusive of gastrointestinal anticancer activities. To promote research and development of novel cytotoxic agents against GIT cancer, this chapter focused on the anticancer potentia l of the naturally occurring triterpenoid and steroidal saponins. The in vitro assays and in vivo studies authenticated the anticancer potential of these compounds through antiangiogenic, anti-proliferative, anti-metastatic and anti-multidrug resistance activities. The protein targets and signaling cascades behind the anticancer effect of these compounds in GIT cancer are also discussed in this chapter.

Glycosides in the Treatment of Gastrointestinal Tract Cancer

Gastrointestinal (GI) carcinomas are tumors that impact the digestive system and its supporting organs. Esophageal, gastric and colorectal cancers are among the common cancers in the gastrointestinal tract. GI cancers are responsible for about 2.7 million deaths of the 8.2 million mortalities that occur from cancers every year around the globe. Chemoprevention is the method of intervening in this mechanism by essential dietary control or the addition of nutraceuticals to the daily nutritional intake. The initial stages of cancer growth, known as oncogenesis, have sparked a lot of emphasis on the function of dietary food. The intensity of the epidemiological studies attracted research scholars' interest in the mechanisms underlying the anti-proliferative activities; however, investigation has indeed discovered lots of new phytochemicals in vegetables and fruits which might prevent the development of carcinogenesis. In cancer treatment, drugs obtained from plant sources have a significant role in cancer treatment. The plant alkaloids isolated from Catharanthus roseus, such as vincristine and vinblastine, are clinically used to treat testicular carcinomas, leukemia, and breast cancer. Paclitaxel is isolated from Taxus brevifolia and is used in the management of lung cancer, breast cancer and ovarian cancer. In the 1960s, there has been initial proof of the in vitro cytotoxic impact of glycosides on human cancer cell lines and their in vivo anti-tumor activities. Cardiac glycosides are Na+/K+ATPase inhibitors and elevate the Ca+2 concentrations, which in turn leads to a positive inotropic effect and is thus used as cardio-tonic in the management of congestive heart failure. Cardiac glycosides have recently been documented to play roles in initiating, developing and metastasizing the tumor by controlling cell viability and mortality pathways. It has been reported that Na+/K+ATPase inhibitor causes cell death by inducing autophagy, apoptosis and synthesis of free radical species. Notwithstanding the advances in cancer treatments, the need for new medicinal products and treatments to enhance their effectiveness and to decrease the toxicity of existing regimes is strong and unequaled, although a broad objective is to improve the therapeutic results of GI cancers. This chapter briefly describes the glycosides, gastrointestinal malignancies and the diverse types of glycosi- des involved in the management of GI malignancies and the clinical trials under progress for the clinical efficacy.

Flavonoids in the Treatment of Gastrointestinal Tract Cancer

Globally, cancer is a leading cause of death next to cardiovascular disease. Gastrointestinal malignancies (GI) are extremely widespread malignancies, but their prevalence varies significantly amongst nations and communities. Existing cancer treatments are primarily concerned with low tissue availability, adverse drug reactions related to the demand for larger dose levels and non-specificity of the medicine. Phytochemicals have been important resources of preventive and curative entities for a variety of diseases, such as cancer. To a certain extent, enough investigation has been made over the last few decades to investigate natural compounds that possess anticancer properties. Phytochemicals used in the management of malignancies appear to be obligatory, serving as the cornerstone for the latest medicine as well as a rich reserve of novel medicines. Flavonoids are plant-derived secondary metabolites, which are readily available and considered safe, depicting perfect agents for cancer therapy or as adjunctive options in clinical practice. Flavonoids have already received increasing attention as anti-cancer entities, with promising findings as cytotoxic anti-cancer entities that induce apoptotic cell death in malignant cells. Flavonoids, such as kaempferol, Quercetin, Curcumin, myricetin, apigenin, luteolin and silymarin, are among the phytochemicals that have been revealed to be potential agents for the prevention and treatment of malignancies. Flavonoids like Kaempferol and luteolin are reported as potential therapeutic agents for the management of ovarian and GI malignancies. Flavonoid metabolism in major areas of the hepatic and colon cells, unveils reasonably considerable variations in the anti-cancer potential, presumably as a result of exposure to multiple metabolites with multiple functions. Luteolin and apigenin have a real insight into cervical cancer. Flavonoids are now explored to have an inhibitory action on cell cycle development at the G1/S or G2/M stages of the cell cycle via modifying several regulatory proteins of the cell cycle. This chapter is designed to provide comprehensive knowledge about flavonoids, their targeted mechanism of action in the management of GI cancer, clinical findings of flavonoids, synergistic effect with other anti-cancer medicines and future prospects of flavonoids in treating GI carcinoma.

Phytonutrients as a Therapeutic Modality: An Overview

Phytonutrients in plants play a great role in their protection against certain bacteria, viruses, and fungi resulting from certain detoxification processes within the plant. There are many recommendations to increase the intake of high amounts of fresh colored vegetables and fruits, besides whole grains (cereals) and beans, which contain phytoconstituents to lower the risk of certain cancers, diabetes and hypertension, in addition to certain heart diseases. The effect of phytonutrients differs according to their chemical class and amount. They may act as antioxidants which prevent the effect of carcinogens on the healthy body. The sources constituents and mechanisms of the phytonutrients are summarized in this chapter.

Pathophysiology of Gastrointestinal Tract Cancers and Therapeutic Status

Cancers of the gastrointestinal tract (GIT) are the most common human malignancies. The prevalence of esophageal Cancer, pancreatic ductal adenocarcinoma, gastric Cancer, hepatocellular carcinoma, colorectal Cancer and gallbladder Cancer are on the rise now a days. Despite advances in cancer treatment, increasing reports are focusing on finding novel therapies with lower side effects and higher potency. From the mechanistic point of view, several dysregulated factors are behind the pathophysiology of GIT cancers. Multiple studies have shown molecular targeted therapies in various GIT cancers, including epidermal growth factor receptor pathway (EGFR), vascular endothelial growth factor pathway (VEGF), Wnt/β-catenin pathway, and insulin-like growth factor receptor (IGFR).The aforementioned mediators are the critical targets of the existence of monoclonal antibodies and small molecules in treating GIT cancers. Accordingly, providing the exact dysregulated mechanisms behind GIT cancers could pave the road in the treatment of cancers. This chapter reveals dysregulated signaling pathways and potential therapeutic agents in the treatment of GIT cancer.

Subject Index

Cancer Surveillance

Surveillance against tumors is governed by both intrinsic (non-immune) and extrinsic (immune) surveillance. While research on non-immune surveillance started as early as the 1960s when it was demonstrated that cell environment within and around can induce tumor-suppressing mechanisms, a major part of the progress is missing compared to immune surveillance. Part of the reason could be due to the fact that immune surveillance is seen to have more potential in therapeutic application in curing cancerous tumors compared to non-immune surveillance mechanisms. Many of the non-immune mechanisms are still under investigation as theories, although a few studies have shown their possibility. Contrary to this, there is a plethora of studies on immune surveillance. The immune system has been proven to have a role in the surveillance against tumors, thus conferring a certain degree of protection. However, not all tumor cells are successfully detected by innate immunity, and many of them have developed strategic ways of escaping adaptive immunity. The immunosurveillance in both animal models and humans shows overwhelmingly that cells with immunodeficiencies are more susceptible to tumor development. However, it is confounding that even immune-competent individuals develop tumors, and thus a significant process is responsible. Thus, immunoediting was proposed as a theory to explain why tumors can escape immunosurveillance. This chapter provides detailed evidence from animal and human tumors and analyses the mechanisms, pathways, and components implicated in tumor immune surveillance. The findings suggest that while immune surveillance could be the key to promoting immune function against the development of tumors, there is more research and understanding needed in the various mechanisms and cells implicated. This is because most, if not all, of the therapeutic studies using immune effectors have proved to be poor in preventing, treating, or regulating the development of tumors.

Treatment of Cancer

Surgery, the oldest cancer treatment, is a mainstay in the cure and control of most cancers. Indeed, for many patients, surgery, usually in combination with chemotherapy, is the only hope for long-term survival or cure. But surgery can do more than treat cancer; it can also diagnose cancer (diagnostic surgery), investigate cancer further (staging surgery), debulk tumors (debulking surgery), relieve pain (palliative surgery), prevent cancer from occurring in the first place (preventative surgery), restore the appearance or function of the body after cancer surgery (reconstructive surgery) and help medical staff to administer chemotherapy (access surgery). This chapter looks at each of these purposes of cancer surgery in detail.

Diagnosis of Cancer

Cancer has a higher chance of being cured when it is diagnosed, detected, and treated early. Diagnosis of cancer in its early stages also results in the highest chance of survival with the improvement of lifestyle of cancer patients. A comprehensive physical exam and a full family medical history are needed before a cancer diagnosis can be made. Self-examination or other screening procedures will normally detect visible forms of cancers, such as melanoma and breast cancer, before the condition progresses. However, several forms of other types of cancer are discovered and diagnosed after disease development and severe signs have already occurred. This chapter discusses the diagnostic approaches that are often utilized to aid in the diagnosis of cancer.

Cancer Types

Normally, to replace damaged cells or for the purpose of growth, healthy cells can divide according to the proliferation potency, in a systematic and controlled manner. When this mechanism is interfered with in such a way that the cell multiplies beyond the control system, a neoplasm may originate. The name (neoplasm) comes from the ancient Greek words neo, which means “new,” and plasma, which means “creation, formation.”. Even after the underlying trigger is removed, a neoplasm's growth is disorganized with that of the healthy surrounding tissue, and it continues to grow abnormally. When this abnormal neoplastic growth creates a mass, it is referred to as a ” tumor”. There are four primary types of neoplasms (tumor): benign (noncancerous), in situ, malignant (cancerous), and neoplasms of unclear or unidentified behaviour, which follow the pattern of cell development. Oncology is concerned with malignant neoplasms, which are commonly known as malignancies or cancers. In Oncology, many cancer classifications emerged, however, the most notable of which is based on the nomenclature by the type of tissue from which it arises, or by the primary site in the body where it originally appeared. Herein, this chapter will go over the definition of cancer, classifications as well as the key differences between the types of cancers. This chapter will also cover the pathophysiology and epidemiology of the many types of cancers.

Epigenetic and Genetics Factors

Despite variations in the morphology and behaviors of human body cells, every single cell in our body is composed of identical DNA material. The variation in cell phenotypes is a result of a specific regulatory mechanism known as epigenetics, by which gene expression undergoes some modifications without the actual nucleotide sequence being affected [1]. This phenomenon is accomplished through several mechanisms, such as cytosine residue methylation, modifications of histone units, and RNA interference. Therefore, epigenetics performs a key function in embryonic growth and development, cellular RNA expression, gene imprinting, and silencing of females’ X chromosomes [2]. Any impairment in these mechanisms may cause various human disorders, including cancer [3]. In carcinogenesis, defective epigenetic machinery at several distinct levels results in abnormal cellular functions [4]. This chapter highlights epigenetics' importance in cancer development and its potential applications for cancer treatment.

Cancer Traits; Present and Future

This chapter on “Cancer Traits; Present and Future” begins with a description of the process of carcinogenesis and, finally, the abnormal process leading to carcinogenesis.
Cancer is a multi-step mechanism in which cells undergo biochemical and behavioral changes, causing them to proliferate in an unnecessary and untimely manner. These changes occur from modifications in mechanisms that regulate cell proliferation and longevity, relationships with neighboring cells, and the ability to escape the immune system. Modifications that contribute to cancer require genetic modifications that alter the DNA sequence. Another way to alter the program of cells is to adjust the conformation of chromatin, the matrix that bundles up DNA and controls its access through DNA reading, copying and repair machinery. These modifications are called “epigenetic. The abnormal process that leads to carcinogenesis includes early mutational events in carcinogenesis, microRNAs in human cancer and cancer stem cell hypothesis, Contact inhibition of proliferation, autophagy, necroptosis, signaling pathways, telomere deregulation, microenvironment, growth suppressors evasion, resisting cell death and sustained cell survival, enabling replicative immortality through activation of telomeres, inducing angiogenesis, ability to oppose apoptosis, and activating invasion and metastasis. Intensive research efforts during the last several decades have increased our understanding of carcinogenesis and have identified a genetic basis for the multi-step process of cancer development. Recognition and understating of the prevalent applicability of cancer cell characterization will increasingly affect the development of new means to treat human cancer.

SPR-Based Biosensors in the Diagnostics and Therapeutics

To analyze the physio-chemical measures of the cellular environment and display them in digital units, transducing methods are applied in biosensors. The labelfree biosensors employ biophysical characteristics such as spectroscopic methods, crystallization, and Surface plasmonic resonance (SPR) to determine the availability or concentration of substances. SPR is a method to elucidate interaction among biomolecules exhibiting affinity binding, structural changes, or alteration in pathological conditions. SPR methods are now employed in conjunction with a variety of transducer topologies, including optical fibers, nanoparticle-based SPR, immobilized or localized SPR (LSPR), long-range SPR, image SPR, immune-assay-based SPR, and phase sensing SPR biosensors' versatile configuration allows for the early detection of several illnesses, such as COVID-19, dengue, non-invasive cancer, biomarker-based fetuses identification, therapeutic antibody characterization, drug monitoring, etc. SPR system is leading in diagnostics and therapeutics with various advantages, such as their portable size, cost-effectiveness, quick result, and easy-to-handle method, but at extension, this technique needs development to ensure high sensitivity, averting background effect and evolution of label-free direct detector to quantify real sample. This chapter reviews the model’s instrumentation and bioassay of clinical samples from SPR and its associated biosensor.

Taurine and the Liver: A Focus on Mitochondria-related Liver Disease

Although the liver is the leading site for taurine (TAU) synthesis, the level of this amino acid in hepatic tissue is relatively low. It is well-known that TAU is efficiently redistributed from hepatocytes to the circulation. However, the human body’s capacity for TAU synthesis is negligible, and we receive a very high percentage of our body TAU from exogenous sources. Plasma TAU is taken up by several tissues, such as the skeletal muscle and the heart. The roles of TAU in liver function are the subject of many investigations. It has been found that TAU could have beneficial effects against xenobiotics-induced liver injury, alcoholism-associated hepatic damage, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or even viral hepatitis infections. The inhibition of cytochrome P450, alleviation of oxidative stress, inhibition of inflammatory reactions, and the mitigation of tissue fibrosis are fundamental mechanisms proposed for the hepatoprotective properties of TAU. On the other hand, many studies indicate that hepatocytes’ mitochondria are essential targets for the cytoprotective properties of TAU. The current chapter reviews the beneficial role of TAU on the most common liver disorders, focusing on the effects of this amino acid on mitochondrial function and energy metabolism.

Swellings of Orofacial Structures in Children

Orofacial swelling is clinically a common problem found in pediatric dental patients. The causes of these swellings are mostly diverse, and the knowledge about specific clinical as well as imaging manifestations along with the most affected sites of these swelling is needed for the formulation of a differential diagnosis. Mid-facial nonprogressive swelling is usually suggestive of a congenital defect (like a cephalocele, nasal glioma, epidermoid cyst or nasal dermoid). Swelling that is slowly progressive, may be indicative of a neurofibroma, hemangioma, vascular malformation, lymph angioma, pseudocyst or fibrous dysplasia. In cases of facial swellings that are rapidly progressive and associated with cranial nerve deficits, rhabdomyosarcoma, Ewing sarcoma, Langerhans cell histiocytosis, metastatic neuroblastoma and osteogenic sarcoma should also be included in the differential diagnosis.

Diabesity and the Kidney

Diabetes Mellitus and obesity, now coined as “Diabesity”, is a worldwide epidemic that imposes a huge burden on healthcare and society. Diabesity has been associated with poor outcomes and increased morbidity and mortality. The kidneys are a vulnerable target of diabesity. In this chapter, we discuss the epidemiology, pathophysiology, and treatment of diabesity–induced kidney disease. We specifically focus on the therapeutic targets and pharmacological management of diabesity-related kidney diseases.

Diabetes Type II: Should Aspartame be a Concern?

Blood sugar levels have to be controlled by individuals with type II diabetes (T2D) to preserve health and longevity. For such people, artificial sweeteners (including aspartame) are proposed sugar substitutes. In particular, the protection of aspartame has long been the point of discussion. Although it is such a problematic product, T2D patients are advised by many physicians to use it during a managed diet and as part of a treatment modality. Aspartame is 200 times sweeter than sugar and has a marginal effect on blood glucose levels. It is recommended for use so that T2D can regulate carbohydrate consumption and blood sugar levels. Previous studies, however, indicate that aspartame consumption may increase a person's risk of gaining weight instead of losing weight, resulting in intolerance to blood glucose in T2D. By increasing the levels of cortisol, aspartame can act as a biochemical stressor. It may cause systemic oxidative stress by creating excess free radicals, altering the gut's microbial activity, and interacting with the receptor N-methyl D-aspartate (NMDA), resulting in insulin deficiency or tolerance. Due to the lack of reliable evidence, aspartame and its derivatives are safe for T2D yet are still debatable. In the already stressful physiology of T2D, more research is needed to provide indications and raise concerns that aspartame may worsen the prevalence of pathological physiology.

Current Strategies of New Drugs for Diabetes Management

Several aspects need to be explored in drug therapy for diabetes patients. Some specific glucose-reducing medicines are present, while other medicines are associated with unintentional changes in hyperglycemia. Diabetes is a developing epidemic that has caused significant socioeconomic problems in several countries throughout the world. Despite scientific discoveries, greater healthcare services, and higher literacy rates, the disease continues to plague many industries, particularly developing countries. The current trends show an increase in premature mortality, which threatens world prosperity. Experimental and technical improvements have been made in sulphonylureas, alpha-glucosidase inhibitors, biguanides, and thiazolidinediones, all of which are beneficial in lowering glucose levels. The latest drug research techniques have led to the development of novel therapeutic groups such as amylin analogs, incretin mimetics, GIP analogs, active peroxisome proliferator receptors, and dipeptidyl peptidase-4 inhibitors as targets for future diabetes therapy medications. Furthermore, drug development and detection for diabetes treatment have been revolutionized by identifying and investigating bioactive compounds from herbs. This chapter discusses vital fields of clinical diabetology regarding opportunities for stem cells and nanotechnology as next-generation therapies, with an emphasis on evolving developments and reviews why plant-derived products are reliably common for treating and managing diabetes.

Future Prospective and Challenges in the Treatment of Cancer

Cancer is responsible for millions of deaths worldwide yearly. Many miles have been crossed towards the treatment of this deadly disease, however, there are still many more to explore about the occurrence, consequences, and, specifically, the accurate therapy to win over this deadly disease. Complex areas like cancer initiation, pathogenesis and the progression of cancer in the human body should be explored with better understanding to discover specific treatments against it. Currently, cancer treatments include radiation therapy, targeted therapy, surgery, chemotherapy, radiation therapy, immunotherapy, and some existing symptomatic treatments. However, the specific treatments of cancer are still a big puzzle to solve. The challenges faced in the treatment of cancer are mainly the heterogenicity of some cancers, drug resistance, late diagnosis, few treatment advances for early-stage cancer, non-selectivity of drugs towards cancer cells leading to side effects, and many more, which are still in the dark. Exploring the solution to this challenge, we need to understand the disease in totality, and understand the existing lacunas of the existing treatments too. Thus, in this chapter, we have discussed the current challenges faced in cancer therapy, followed by the future perspectives in the treatment of a wide variety of cancer.

Smartphone-Based Real-Time Monitoring and Forecasting of Drinking Water Quality using LSTM and GRU in IoT Environment

Water quality plays an important role in human health. Contamination of drinking water resources causes waterborne diseases like diarrhoea and even some deadly diseases like cancer, kidney problems, etc. The mortality rate of waterborne diseases is increasing every day and most school children get affected to a great extent. Real-time monitoring of water quality of drinking water is a tedious process and most of the existing systems are not automated and can work only with human intervention. The proposed system makes use of the Internet of Things (IoT) for measuring water quality parameters and recurrent neural networks for analysing the data. An IoT kit using raspberry pi is developed and connected with a GPS module and proper sensors for measuring pH, temperature, nitrate, turbidity, and dissolved oxygen. The measured water quality data can be sent directly from raspberry pi to the database server or through the mobile application by QR code scanning. Recurrent Neural Network algorithms namely Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) are used for forecasting water quality. Results show that analysis made using GRU is much faster than LSTM, whereas prediction of LSTM is slightly more accurate than GRU. The data is categorized as poor, moderate, or good for drinking and it can be accessed using smartphones through mobile application. In general, the proposed system produces accurate results and can be implemented in schools and other drinking water resources.

Medicinal Plants from the Himalayas Acting on Inflammatory and Oxidative Stress Pathways

Located between the Indian subcontinent and the Tibetan plateau, the Himalayas are home to a rich repertoire of medicinal resources. A wide range of communities from Asia and Africa prefer natural remedies, including medicinal plants, over prescription drugs. Since so many people use medicinal plants as their only source of healing, the plants are also an important source of income for the locals.. The plants found in the entire region of this snowy mountain range provide remedies ranging from bronchitis to cancer. We attempted to summarise the important medicinal plants of this region in this book chapter, specifically those that act and modulate the inflammatory and oxidative stress pathways, as these are the primary culprits behind many diseases and disorders. The current chapter will list the ethnobotanicals used, their active ingredients, and reported pharmacological properties, as well as potential mechanisms of action.

Hormones as Cancer Biomarkers

Among all the cancer biomarkers, hormones are less discussed despite having the ability to be used as potential biomarkers in the diagnosis and prognosis of various cancers. When a tissue, normally produces hormones in lesser quantity, produces a hormone in excess levels, then hormones can be used as tumour biomarkers. Sometimes it is also seen that a hormone is produced by the tissue, which is not normally associated with the secretion of that hormone. For example, calcitonin, a protein hormone produced by the thyroid gland, is reported to be increased in production in thyroid carcinoma. Another protein hormone, namely human chorionic gonadotropin (hCG), is used as a biomarker in choriocarcinoma, testicular tumors, etc. On the other hand, a lower level of testosterone hormone is found in prostate cancer, indicating its role in prostate cancer prognosis. There are other peptidase and steroid hormones, such as insulin, glucagon, estrogen and progesterone which significantly contribute to various tumours and are used as valuable biomarkers in the diagnosis and prognosis. Taken into consideration, in this chapter, we discuss the roles of multiple peptides and steroid hormones in the diagnosis and prognosis of various cancer types.

Glycoproteins and Cancer Biomarkers

Glycoproteins or glycosylated proteins are carbohydrates (oligosaccharide chains or glycan’s) linked proteins and execute important functions in the biological systems, such as embryonic development, cell-to-cell recognition, adhesion, pathogen identification and immune functions. It is evident that the alteration of glycoproteins in cells are associated with a number of human diseases, including cancer, rheumatoid arthritis, inflammatory diseases as well as immunodeficiency diseases. Recent advances in modern technologies in cancer treatment are promising. However, researchers and clinicians are still searching for appropriate biomarkers for the early detection and management of patients with cancer. Altered glycoprotein levels are associated with critical events in cancer pathogenesis and progression. Also, abnormal glycosylation of protein is a common regulatory event in carcinogenesis, therefore, aberrant glycosylation could act as a promising resource in identifying a cancer biomarker for diagnosis and monitoring of the progression of patients with cancers. This chapter summarizes the major clinically approved glycoproteins utilized for screening, diagnosis, and monitoring of the treatment response of patients with cancers.

Tumour DNA Sequencing

Cancer pathogenesis is a multistep process involving the accumulation of complex genetic and epigenetic alterations. The disease can be sporadic or familial in nature. The genes associated with much familial cancer or inherited cancer susceptible syndrome have already been identified. Thus, genetic testing for pathogenic variants of these genes could predict whether an individual has a high risk of developing cancer in their lifetime. Also, tumour DNA sequencing in patients with cancer can be used for therapy selection and to predict treatment outcomes. The recent development of high throughput sequencing enables the exploration of whole genome profiling, including mutations, structural variations, transcriptomes, splicing events, etc., in patients with cancer, thereby providing guidelines for personalized precision medicine in clinical practice. However, the translation of cancer genome sequencing information into the clinical treatment plan is highly complicated, needs multidisciplinary expert panels and is not cost-effective for mass application. Further development in sequencing analysis and data interpretation are imperative for point-of-care settings applications. This chapter outlines the clinical significance of tumour DNA testing and genomic sequencing in various cancers.

Phyto-nanotechnology: Enhancing Plant Based Chemical Constituent Mediated Anticancer Therapies

95% of anti-cancer agents were associated with the worst pharmaceutical and pharmacokinetic properties including poor targeted cellular uptake, shorter halflife, toxicity, and many more. In this regard, nanotechnology including nanomedicines, nano-carriers, and nanomaterials may emerge as a beneficial tool to facilitate an efficient delivery of therapeutic regimens by adapting active or passive targeting mechanisms. The nanotechnology-based delivery system of phytoconstituents can efficiently battle against recalcitrant TNBC. This chapter highlighted the nanotechnology-based therapeutic approach including smart nanoparticles, cell membrane-coated nanoparticles, and immunological cell-based nano-systems for the treatment of TNBC. Furthermore, the role of nano-soldiers in improving bioavailability and targeted drug delivery was highlighted. Nano conjugates of curcumin, anacardic acid, EGCG, betulinic acid, gambogic acid, and resveratrol were also evaluated to enhance the pharmacokinetic profile, distribution, and the release rate of respective compounds and ultimately their ability to target TNBC.

Some Aspects of Pathology and Pathogenesis of Coronavirus Infection

This chapter presents an overview of pathology and pathogenesis in coronavirus infections in humans and animals based on literary data and our own experience, illustrated by numerous original images.

Polyphenols and Flavonoids: Chemical, Pharmacological and Therapeutic Aspects

Polyphenols and flavonoids represent a group of compounds characterized by a large assortment of phenolic structures, which can be naturally found in vegetables, roots, stems, flowers, grains, and fruits. Thanks to their biological activities, molecules belonging to these classes of compounds, besides their nutritional role, have found applications in several fields such as pharmaceutical, cosmetic, and nutraceutical. In fact, like many natural derivatives from plants, they possess several therapeutic properties, including antitumor, anti-oxidative, anti-neurodegenerative, antimicrobial and anti-inflammatory effects. Nowadays, the growing interest in polyphenolics and flavonoids translates into constant research to better define their pharmacological mechanism of action. Extraction studies in order to obtain pure compounds with a more defined biological activity, as well as pharmacokinetic studies to understand the bioavailability, the involved metabolic pathways and the related active metabolites, are carried out. Molecular docking studies are also continuously in progress to expand the field of application. Moreover, toxicity experiments to clarify their safety and studies about the interaction with other compounds to understand their selectivity of action are continuously forwarded and deepened. Consequently, many recent studies are aimed at introducing polyphenols, more specifically flavonoids, and their semi-synthetic derivatives, in the prevention, management and treatment of several diseases.

Potential Applications of Nitric Oxide Donors in Type 2 Diabetes

Nitric oxide (NO) donors are chemical agents that produce NO-related activity in biological systems, mimic endogenous NO-related responses, or compensate for NO deficiency. NO donors have been increasingly studied as promising therapeutic agents for insulin resistance and type 2 diabetes (T2D). Here, we provide evidence, which investigated the effects of the most frequently studied and implemented NOreleasing compounds, including sodium nitroprusside (SNP), S-nitrosothiols [RSNOs, i.e., S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-penicillamine, (SNAP)], and NDiazeniumdiolates (NONOates, i.e., spermine NONOate, diethylamine NONOate) on glucose and insulin homeostasis. Available evidence could not draw a clear conclusion regarding therapeutic applications of NO donors in T2D due to different methodological approaches (i.e., in vitro vs. in vivo) and different doses and formulations used to assess the potential effects of NO donors on carbohydrate metabolism. Considering key properties and different kinetic behaviors between various classes of NO donors, targeted compound selection, defining optimum doses, and appropriate use of NO-releasing platforms (topical vs. systemic delivery mode) seem to be critical issues that can accelerate the bench-to-beside translation of NO donors in T2D.

Bioactive Compounds from Algae: Potential Applications

Algae are ancient oxygen-producing photosynthetic organism that lives in water bodies all over the world. The algal biodiversity in the aquatic ecosystem represents a new field of product discovery with the potential to manage human ailments. They are untapped resources, and in recent years, algal culture technology has been a business-oriented field owing to its diverse applications. The consumption of algae is traditional in human diets and dates back thousand years ago. The recent increasing algal demand is due to its safety and functional benefits. Algae are an edible source of food with potential therapeutic activities of anti-oxidant, antiobesity, antidiabetic, anti-inflammatory, anti-cancer, anti-viral, antifungal, and antibacterial properties, which could be employed as medical ailments. Different types of algalderived bioactive compounds in a biological system are evidenced by in vitro and in vivo examinations. Raw algae or its compound are under a pipeline of market production due to their cultivable nature, which actually paves the way to generate larger business in the food and nutraceutical industry. This chapter summarizes several algal bioactive compounds with proven activities against metabolic disorders.

Probiotics in Poultry Nutrition as a Natural Alternative for Antibiotics

Since the early 1950s, antibiotics have been used in poultry for improving feed efficiency and growth performance. Nevertheless, various side effects have appeared, such as antibiotic resistance, antibiotic residues in eggs and meat, and imbalance of beneficial intestinal bacteria. Consequently, it is essential to find other alternatives that include probiotics that improve poultry production. Probiotics are live microorganisms administered in adequate doses and improve host health. Probiotics are available to be used as feed additives, increasing the availability of the nutrients for enhanced growth by digesting the feed properly. Immunity and meat and egg quality can be improved by supplementation of probiotics in poultry feed. Furthermore, the major reason for using probiotics as feed additives is that they can compete with various infectious diseases causing pathogens in poultry's gastrointestinal tract. Hence, this chapter focuses on the types and mechanisms of action of probiotics and their benefits, by feed supplementation, for poultry health and production.

Dandelion Herb: Chemical Composition and Use in Poultry Nutrition

Taraxacum officinale, also known as dandelion herb, is a popular medicinal and therapeutic herb used for many years and is mostly raised in Europe, Asia, North and South America. It contains several nutrients and bioactive substances, especially the leaves and roots of this herb, which are a rich source of fiber, lecithin, choline, and micronutrients such as minerals (potassium, magnesium, calcium, zinc, etc., iron) and vitamins (A, C, K, and B-complex). The root has been commonly used for digestive and liver problems due to its stimulatory effects on the production of bile and detoxification functions. The leaves of dandelion have stimulatory functions on the digestive system and possess diuretic effects. Furthermore, several studies have shown that dandelion leaves can enhance the growth and productivity of poultry. Various functions on the intestinal mucosa have been reported, including the effects on the architecture of villi, villus height/crypt depth ratio, and cellular infiltration. This herb also has various beneficial functions, such as immunomodulatory effects, stimulation of the digestive system and insulin activation, enhancing the metabolism of androgens, and acting as a probiotic, antiangiogenic, antineoplastic and demulcent. Moreover, the dandelion herb can treat indigestions and hepatitis B infection. Due to the lack of studies on the effects of dandelion, further research has to be conducted to exploit the medicinal properties of this herb for its beneficial health impact on humans, pet and livestock animals (e.g., poultry) nutrition.

Subject Index

Application of 21st Century Genetic Engineering Tools and CRISPR-Cas9 Technologies to Treat Most Advanced Cardiovascular Diseases of Humans

21st Century Genome-editing technologies have been rapidly emerging as the most powerful tool capable of creating genetically altered cells or organisms for explicit gene functions and mechanisms for causing several human ailments. While clinical gene therapy celebrates its first taste of success, with several products approved for clinical usage and several thousands of them awaiting stages in pipelines, unfortunately, there are no gene therapy treatment methods available for many cardiovascular diseases (CVD). Despite sustained medical advances over the last 50 years in CVD, the main cause of death is still uncertain in the developed world. The management of genetic expression by using small molecule RNA therapeutics and the development of accurate gene corrections may lead to several applications, such as cardiac revitalization after myocardial infarctions and gene corrections for the inherited cardiomyopathies but certainly with some limitations. CRISPR/Cas9 technology can be utilized to realign DNA modifications ranging from a single base pair to multiplepairs of mutations in both in vitro and in vivo models. This book chapter emphasizes various types of applications by CRISPR technologies in cardio-vascular research, and genome-editing novel therapies for future medicines.

Subject Index

Occupational Cancer

This chapter provides an up-to-date review of the occurrence and causes of occupational cancer based on epidemiologic studies and discusses the epidemiology of occupational cancer, the characteristics, research priorities, prevention, and surveillance. Epidemiologic methods have been very successful in documenting cancer risks associated with agents. Epidemiologic data is useful when an exposure-response relationship can be demonstrated. Examples of agents for which epidemiologic studies provide evidence of an exposure-response relationship include benzene and myelogenous leukemia. Vinyl chloride causes liver cancer which is an example of associations between single agents and rare histologic types of cancer. It is more difficult to conduct epidemiologic studies to identify cancer risks associated with complex mixtures. Studies of diesel exhaust, lung cancer, and metal machining oils are cited as having employed advanced industrial hygiene and epidemiologic methods for studies of complex mixtures. At present, less than 20 known occupational carcinogenic agents have been evaluated based on studies in humans and animals by the International Agent for Research on Cancer. Furthermore, exciting developments in epidemiologic and animal studies will contribute to identifying additional carcinogenic agents in the workplace. New biologic markers of exposure and cancer-related outcomes must be identified and integrated into epidemiologic studies. Because epidemiologic data regarding the carcinogenicity of many exposures are not available, research methods to evaluate and improve the predictive value of animal and in vitro systems must be developed. A complete understanding of occupational cancer trends will be required further to research occupational cancer risks and means of prevention.

Occupational Epidemiology

The development of occupational epidemiology has been steadily accelerating, regardingmethodology and the number of studies being conducted. This chapter reviews the general application of occupational epidemiology and illustrates some of the various studies reported in the literature to assist in the practical application of the epidemiologic approach. The epidemiologist uses analytic tools such as the case-control method to examine the complexity of variables to understand workplace exposures to disease. The analytic methods used to examine epidemiologic data have become more sophisticated over the past several decades as the focus of occupational epidemiology has shifted to the detection of early health effects associated with low-level exposures. In the future, epidemiologists need to collaborate more effectively with toxicologists, environmental scientists and biostatisticians to improve the collection of exposure data and develop more precise methods for estimating exposure that account for metabolism and excretion of toxic materials. Continuous improvement of epidemiologic analytic methods and prevention of occupational disease and surveillance are needed.

Green Synthesis Application in Diabetes Therapy

The use of medicinal plants and or medicinal plants-aided nanoparticles (NPs) in the management of diabetes mellitus has progressively received wider acceptance over the years due to the accompanying side effects with conventional therapy. The review explores the application of green-synthesized nanostructures in the control or management of diabetes as well as probable mechanism of NPs formation and possible toxicity. Information sourced from scientific databases including Science Direct, Google Scholar, PubMed, Web of Science, SciFinder, JSTOR revealed 58 medicinal plants explored in the synthesis of four (4) NS such as gold, silver, zinc oxide and platinum with established antidiabetic potential. The NS is characterized by varying microscopic and or spectroscopic instruments such as UV-Vis, SEM, EDS, FTIR and XRD commonly are stable, smaller-sized and mostly crystalline in nature. The functional groups responsible for the reduction and stabilization of the nanoparticles are predominantly C-O, C-H, COOH, N-H found in phenols, flavonoids, alkaloids, proteins and so on. The review identified and revealed 45% studies with less than 5% (mostly from India) conducted on animal models for antidiabetic and toxicity determinations, respectively with none for clinical studies, indicating the need for intensified efforts on research on these identified plants and unidentified species for drug development.

The Role of Plant Secondary Metabolites in Health Management

Plant secondary metabolites (PSM) are bioactive compounds produced by plants for protection against predatory organisms and to attract insects for pollination. Recently, greater attention is being focused on PSM due to their perceived ability to elicit pharmacological activities, including antihypertensive, antiarrhythmic, antimalarial, anticancer, analgesic, antispasmodic, antidiabetic, and antimicrobial effects. Therefore, many plant species are continually screened for PSM, such as alkaloids, flavonoids, terpenes, saponins, cardiac glycosides, fatty acids, steroids, and tannins with a view to exploiting them in the manufacture of drugs and pharmaceuticals. In this review, the pharmacological activities and possible mechanisms of action of selected PSM are discussed.

Bioactive Constituents and Anti-diabetic Activity of the Indian Medicinal Plant Hemidesmus indicus R. Br.: An Overview

Hemidesmus indicus R. Br. is a laticiferous, slender, and twining shrub, which is found over almost every part of India. Its roots (Anantmul - Sanskrit meaning: endless root) are particularly used extensively as a single drug and in formulations with other plants to treat several ailments. In view of the wide range of medicinal properties claimed in traditional medicine, significant efforts have been made to determine the efficacy of Hemidesmus indicus through pharmacological experiments in vitro and in vivo models. These include analgesic, anti-inflammatory, antipyretic, antioxidant, antiarthritic, hepatoprotective, antiepileptic, anticonvulsant, antiulcer, antivenom, antiacne, and antipsychotic activities. Recent studies have also established antidiabetic, anti-carcinogenic, anti-venom, and wound healing activities. Extensive phytochemical investigations have been carried out by several research groups. The present review provides an overview of the bioactive compounds of this Indian medicinal plant. Several classes of compounds, viz. triterpenoids, steroids, steroid glycosides, coumarin-lignoids, flavonoids in addition to many simpler compounds, have been isolated and characterised from different parts of H. indicus. These are listed, along with brief write-ups on isolation procedures, spectroscopical and chemical characterization, and their biological properties. Particular emphasis is given to the anti-diabetic properties associated with it, indicus root extracts, and the factors contributing to these properties

Plant Based Bioactive Molecules in Diabetes with Their Therapeutic Mechanism

Plant based bioactive compounds are the secondary metabolites that are produced by them to perform their non-essential functions. They provide an ample source of nutraceuticals and therapeutics for humans. The research on these compounds is on trend these days and most of the research suggests their importance as therapeutic agents and as prophylactic agents against many diseases. Easy accessibility, and better efficacy with lesser adverse effects of bioactive compounds have made their research trending. Diabetes is the oldest known metabolic disease which requires a multimodal treatment approach for its management. The available drugs and treatment options are still unable to control the complications and economic burden faced by the patients. Many plants have been used traditionally for the management of diabetes worldwide. Now it has been well established that the plants provide a rich reservoir of bioactive compounds which have the potential to modulate various pathways involved in the regulation of blood glucose. This chapter discusses the common groups of plant derived bioactive compounds, their sources, and their mechanistic antidiabetic role.

Understanding Promising Anticancer Targets for Heterocyclic Leads: An Introduction

With the second-highest cause of mortality in the world, cancer becomes a major threat around the globe. In the last few decades, heterocyclic compounds, obtained naturally or synthetically, have been developed as a potential scaffold for developing many anticancer drugs. Heterocyclic compounds due to heteroatoms such as oxygen, nitrogen and sulphur can be employed as hydrogen bond donors as well as acceptors. Thus, they can bind suitably to pharmacological targets and receptors via intermolecular H-bonds more effectively, giving pharmacological effects. They can also alter liposolubility, hence the aqueous solubility of drug molecules to achieve remarkable pharmacotherapeutic properties. These heterocyclic leads exert the anticancer activity by a distinctive mechanism such as inhibiting Bcl-2, Mcl-1 proteins (induce apoptosis), inhibiting PIM proteins (hinder the cellular process and signal transduction in cells), inhibiting DNA topoisomerase, inhibiting aromatase (inhibit replication and transcription), modulating epigenetic mechanisms (inhibit histone deacetylase/HDAC) and inhibiting cellular mitosis (tubulin inhibitors).The current chapter aims to describe these promising anticancer targets. The novel targets are also illustrated with a pictorial presentation to understand heterocyclic drugs action on various cancer targets. This chapter will facilitate researchers, pharmacologists, and medicinal chemists in the understanding mechanism of heterocyclic drugs, which can help develop new anticancer agents.

Application of Biomarkers in the Diagnostic Distinction of Bacterial and Viral Infections

Infectious diseases, which pose a great threat worldwide, have a significant impact on public health and the world economy. It contributes to increased healthcare costs, unnecessary drug-related side effects, and increased antimicrobial resistance. It is not always easy to distinguish the etiological differentiation of diseases that can develop with bacteria and viruses. Therefore, one of the biggest challenges in medicine is how to correctly distinguish between the different causes of these infections and how to manage the patient. Because bacterial and viral infections often present similar symptoms. The real decision is whether the infection is caused by bacteria or viruses and whether to treat the patient with antibiotics. There are many different methodological approaches to diagnosing infections. Biomarkers have been used in the diagnosis of diseases and other conditions for many years. Biomarkers are molecules found in blood and body fluids in measurable amounts, which can evaluate biological and pathological processes. These key indicators can provide vital information in determining disease prognosis, predicting response to treatments, adverse events and drug interactions, and identifying key risks. An effective biomarker is extremely important for the early diagnosis of various diseases. The explosion of interest in biomarker research is driving the development of new predictive, diagnostic, and prognostic products in modern medical practice. The purpose of this review is to demonstrate the use and diagnostic potential of current and investigational biomarkers in the distinction between bacterial and viral infections.

Clinical Application of Circulating MicroRNAs as Novel Biomarkers for Different Diseases

Biomarker research has become increasingly interesting in many areas nowadays. Biomarkers are indicators of the biological process that can show changes in disease and health status and reveal pathological conditions. There is always a need for markers that divide patients into risk categories that can help in early diagnosis, detect complications ahead of time, guide treatment, and predict adverse outcomes in a chronic complex and certain diseases such as cancer. microRNAs (miRNAs) are ~ 22 nt long npcRNAs involved in post-transcriptional arrangements. miRNAs regulate messenger RNAs (mRNA), especially through negative regulation of gene expression. The fact that miRNAs have come to the fore in many disease mechanisms brings up their use as biomarkers in the early stage. The purpose of this review is to gather the latest information on this subject by bringing together recent articles and reviews to contribute to understanding the role of miRNAs, which act as biomarkers in different ways in vital processes, in the formation, early diagnosis, and treatment of diseases. miRNAs have an important potential to become a next-generation biomarker and therapeutic. But, each miRNA molecule can bind to a large number of different mRNAs, and different miRNAs in each mRNA. Therefore, new findings are needed to determine the expression activities and targets of miRNAs.

Biomarkers in Liver Disease

Symptoms and signs of liver diseases are highly variable depending on the etiology, disease stage, and type of liver involvement. There are different types of liver diseases; causes of liver diseases may be viral, toxic, metabolic, or autoimmune. However, in some cases, liver disease can develop as a result of diseases of other organs or systems. It is almost impossible to differentiate all of these solely on the basis of clinical symptoms and findings. Furthermore, the early stages of liver disease may be completely asymptomatic, or in some cases, the disease may progress with only subtle and non-specific symptoms. Therefore, biomarkers have a critical role in screening, diagnosis, staging, and evaluation of therapeutic response to treatment in liver diseases.

Biomarkers and their Clinical Applications in Pediatrics

Biomarker studies are becoming increasingly interesting for many fields of medicine. The use of biomarkers in medicine is involved in detecting diseases and supporting diagnosis and treatment decisions. New research and new discoveries on the molecular basis of the disease show that there may be a number of promising new biomarkers for use in daily clinical practice. Clinical trials in children lag behind adult research both in quality and quantity. The number of biomarkers validated to optimize pediatric patient management is limited. In the pathogenesis of many diseases, it should not be extrapolated to the pediatric clinical setting, taking into account that biomarkers that are effective in adults are clearly different in children and that ontogeny directly affects disease development and therapeutic response in children. The search for ideal biomarkers or markers that can make an early and definitive diagnosis in neonatal sepsis is still ongoing. The ideal biomarker for pediatric diseases should be costeffective, noninvasive, applicable to pediatric specific diseases, and its results should correspond to age-related physiological changes. Lactate, troponin and B-type natriuretic peptide are valuable biomarkers in the evaluation and management of critically ill children with cardiac disease. Tumor markers in children are biochemical substances used in the clinical treatment of pediatric tumors and to detect the presence of cancer (regression or progression). In this chapter, current and brief information about biomarkers and their clinical applications used in the diagnosis and monitoring of pediatric diseases is presented.

A Pathophysiological Approach To Current Biomarkers

Biomarkers are necessary for screening and diagnosing numerous diseases, predicting the prognosis of patients, and following-up treatment and the course of the patient. Everyday new biomarkers are being used in clinics for these purposes. This section will discuss the physiological roles of the various current biomarkers in a healthy person and the pathophysiological mechanisms underlying the release of these biomarkers. This chapter aims to gain a new perspective for evaluating and interpreting the most current biomarkers.

Applications of Biomarkers in Cancer Surgery

The most problematic and difficult cases of general surgery applications are cancers. Cancer can be diagnosed in many ways, including the presence of some symptoms and signs, screening tests, and imaging methods. The diagnosis of cancer is confirmed anatomically by microscopic examination of tissue samples. Biomarker research has become increasingly interesting for many medical fields today. Biomarkers are indicators of the biological process that can show changes in disease and health status and reveal pathological conditions. The sensitivity of markers used for early and painless diagnosis is weak in all types of cancer, including thyroid, breast, stomach, pancreatic, and colorectal cancers. Biochemical and molecular markers have been found to be of great importance in cancer research in recent years in the formation mechanisms and treatment steps of cancer. Several biomarkers have been studied in the circulating body fluids and tissue of preoperative, intraoperative, and postoperative patients. The main use of tumor markers is the follow-up of the response to treatment and early detection of recurrences in patients diagnosed with cancer. Tumor markers correctly selected will guide the patient's monitoring and treatment planning. But, still, the field of cancer surgery needs new biomarkers.

Circulating Biomarkers in the Management of Breast Cancer

Circulating biomarkers have become a promising modality in the management of many cancers. Similarly, in breast cancer, circulatory biomarkers are useful, non-invasive methods in the diagnosis, prognostication, and evaluation of response to treatment. Invasive surgical biopsies can be potentially replaced by “liquid biopsy,” which involves analysing circulatory biomarkers that may reveal features of primary and metastatic disease. Therefore, providing an insight into the cancer biology can be utilised to monitor treatment response, treatment-induced adaptation and tumour and disease progression through non-invasive means. The objective of this review is to provide an overview of the current status of the circulating biomarkers highlighting their promising impact on the management of patients with breast cancer.

Circulating Biomarkers in Predicting Pathological Response to Neoadjuvant Therapy for Colorectal Cancer

Circulating biomarkers show promise in the management of many cancers. They have become the novel non-invasive approach to complement the current strategies in colorectal cancer (CRC) management. Their ability in guiding diagnosis, evaluating response to treatment, screening and prognosis is phenomenal, especially when it comes to their minimally invasive nature. These “liquid biopsies,” which show potential for replacing invasive surgical biopsies, provide useful information on the primary and metastatic disease by providing an insight into cancer biology. Analysis of blood and body fluids for circulating tumour DNA (ctDNA), carcinoembryonic antigen (CEA), circulating tumour cells (CTC), or circulating micro RNA (miRNA) shows potential for improving CRC management. Recognizing a predictive model to assess response to neoadjuvant chemotherapy would help in better patient selection. This review was conducted with the aim of outlining the use of circulatory biomarkers in current practice and their effectiveness in the management of patients having CRC with a focus on response to neoadjuvant therapy.

Circulating Biomarkers in Thyroid Cancer

Thyroid cancer is the most important endocrine cancer with increasing incidence. While thyroid cancers, especially papillary thyroid cancers, are known to exhibit generally a favorable outcome with excellent survival rates, some thyroid cancers are more aggressive with a poor prognosis. Several different biomarkers have been introduced for the diagnosis of disease, identification of tumor load, assessment of therapy response, and the detection of recurrence during follow-up of the thyroid cancer patients. This chapter gives a brief overview of the circulating biomarkers used in thyroid cancer patients.

Special Groups and Abdominal Pain

Specific patient groups have inherent characteristics when they suffer from diseases, including those of the digestive system and other causes of abdominal pain. Both diagnostic features and treatment measures differ regarding the patient’s age, sex, previous medical / surgical history, and comorbid diseases. Pregnancy has its unique features in both anatomy and physiology of the woman which result in substantial variation in physical examination finding, radiological and laboratory adjuncts (e.g., the location of the appendix is shifted away from its usual site and computed tomography is hardly ever used to diagnose etiologies of abdominal pain in pregnant women). Likewise, children have many differences in presentation, examination findings, work up and treatment principles, complicating the management process. In addition, the pandemic disease has caused a paradigm shift in the evaluation of almost all diseases, including those with abdominal pain. Many data suggest a close relationship between COVID-19 and the digestive system. Patients with COVID-19 carry a high risk of digestive symptomatology including abdominal pain, nausea and vomiting, diarrhea and others. HIV (+) patients exhibit various GI symptoms such as diarrhea, abdominal pain and proctitis. Healthcare providers should have robust knowledge of various forms of presentations and characteristics of special subgroups with abdominal pain in this regard, to prevent misdiagnoses and treatment errors in those patients.

Specific Diagnoses and Management Principles of the Hepatobiliary and Pancreatic Diseases

Hepatobiliary and pancreatic diseases are among common illnesses which cause major morbidity and mortality in the middle-aged and elderly patients and some specific subpopulations. Some geographic predispositions also exist for some diseases. For example, pain, fever, jaundice, and hepatomegaly can be noted in hydatic cyst disease which may cause allergic reaction and portal hypertension in the Southeast Europe and the Middle East. Of note, hepatobiliary and pancreatic diseases are commonly confused with each other, which may complicate diagnostic and therapeutic processes. A patient with biliary stones may be asymptomatic or suffer from acute or chronic cholecystitis, biliary colic, obstructive jaundice, cholangitis, mucocele, empyema, acute pancreatitis, gallstone ileus, and carcinoma. Cholecystitis and cholangitis are among diseases with high morbidity especially in the elderly and thus need to be ruled out in any patient with abdominal pain evaluated in acute and primary care setting. Some diagnostic clues are extremely helpful, such as Charcot triad which suggest severe cholecystitis (right upper quadrant AP, jaundice and fever) or cholangitis when complicated by altered mental status and hemodynamic instability. Acute pancreatitis refers to acute response to injury of the pancreas is referred to. Chronic pancreatitis, on the contrary, results from permanent damage to the endocrine and exocrine functions of the gland. Ultrasound, computed tomography and magnetic resonance imaging are among invaluable tools in diagnosing these diseases, together with specific laboratory adjuncts such as serum lipase for pancreatitis and bilirubin for obstructive jaundice. Definitive treatment encompasses surgical procedures, mostly in patients with acute abdomen due to gallstones or pancreatic necrosis.

Specific Diagnoses and Management Principles of the Upper Digestive Canal

Acute abdominal conditions which frequently necessitate emergency interventions and/or surgery include visceral perforations i.e., gastric and duodenal ulcer, bleeding and rarely, ingested foreign bodies causing tissue damage, e.g., button batteries. However, the differential diagnosis (DD) of patients presenting with acute abdominal pain is much broader than this, including many benign conditions as well. Acute gastroenteritis, acute gastritis and peptic ulcer disease are benign and mostly temporary diseases which may be relieved with simple treatments and follow-up. Gastrointestinal bleeding (with or without esophageal varices) may cause hemorrhagic shock unless expedient management is pursued. Ingested foreign bodies can constitute emergency conditions with tissue damage, especially when lodged in a specific site. The most important thing about button batteries is the prevention of their ingestion. Complications increase in direct proportion to time wasted.