Testicular Cancer

Recent Drugs Tested in Clinical Trials for Alzheimer´s and Parkinson´s Diseases Treatment: Current Approaches in Tracking New Drugs

Affecting more than 50 million people worldwide and with high global costs annually, neurological disorders such as Alzheimer's disease (AD) and Parkinson’s disease (PD) are a growing challenge all over the world. Globally, only in 2018, AD costs reached an astonishing $ 1 trillion and, since the annual costs of AD are rapidly increasing, the projections estimate that these numbers will double by 2030. Considering the industrial perspective, the costs related to the development of new drugs are extremely high when compared to the expected financial return. One of the aggravating factors is the exorbitant values for the synthesis of chemical compounds, hindering the process of searching for new drug candidates. In the last 10-year period, an average of 20 to 40 new drugs were approved per year, representing a success rate of less than 6%. However, the number of referrals for new drug orders and/or applications remained at approximately 700 each year, reinforcing the difficulty in the process of identifying and developing novel drugs. Regarding neurodegenerative diseases, the FDA (USA) approved 53 new therapies in 2019, including 48 new molecules and, from these, three are medicines and two are vaccines. The main drugs recommended for the treatment of these disorders are included in the following classes: Dopamine supplement (Levodopa), Monoamine oxidase (MAO) inhibitor (Selegiline, Rasagiline), Dopamine agonist (Apomorphine, Pramipexole), and Acetylcholinesterase inhibitor (Donepezil, Rivastigmine, Galantamine). Additionally, the current pharmacological treatments are not able to cure these patients and considering the etiological complexity and the prevalence of neurological disorders, scientists have a great challenge in exploring new therapies and new molecules to find an adequate and viable treatment for these diseases. Clinical trials are essential in this process and thus, this chapter describes the most important drugs that were targets of phase III and IV clinical studies in the last five years, associated with the most common neurological disorders worldwide, AD and PD. Information about mechanisms of action, experimental studies in other diseases that support their use, and chemical structure of the drugs are included in this chapter. Additionally, nature as a source of valuable chemical entities for PD and AD therapeutics was also revised, as well as future advances in the field regarding tracking new drugs to get successful results and critical opinions in the research and clinical investigation.

Hormoneal Therapy

Treatments that involve the use of hormones or their antagonists are commonly referred to as hormone therapy or hormonal therapy. Oncologic hormone therapy, hormone replacement therapy (HRT), androgen replacement therapy (ART), oral contraceptive pills and gender-affirming hormone therapy are the major classes of hormonal therapy in addition to a few others. Some hormonal therapies will be discussed in detail under different chapters including oncologic hormone therapy, glucocorticoids and mineralocorticoids and insulin under antineoplastic agents, antiinflammatory steroids and antidiabetic agents, respectively. After studying this chapter, students will be able to:

• Define and classify hormonal therapy and differentiate between hormonal therapy and treatment.

• Explain all types of hormone replacement therapy including menopausal, androgens, and oral contraceptives.

• Discuss the use of androgen replacement therapy (ART) in males with low levels of testosterone due to disease or aging.

• Describe gender-affirming hormone therapy such as feminizing hormone therapy and masculinizing hormone therapy. • Identify appropriate growth hormone therapy for growth hormone deficiency.

• Demonstrate understanding of thyroid hormone replacement in hypothyroidism and antithyroid therapy in hyperthyroidism.

• Demonstrate clear guidance to the use of oral contraceptive pills for various purposes including birth control.

Drugs Affecting Renin-Angiotensin System

This chapter presents a comprehensive account of the medicinal chemistry of drugs affecting the renin-angiotensin system (RAS). It provides the mechanism of drug action and details structure-activity relationships (SAR) of the drugs affecting RAS to give the knowledge base for pharmacists. After studying this chapter, students will be able to:

• Describe the historical background the RAS and drugs acting on this system.

• Explain RAS enzymes and hormones and their roles in blood pressure.

• Classify drugs acting on the RAS and their structures and binding.

• Discuss in detail the chemistry and SAR of the antagonists involved in RAS including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and renin inhibitors.

• Delineate the clinical significance and therapeutic evaluations of these classes of drugs by solving case studies.

• Explain the discovery process of ACEIs and ARBs.

Subject Index

Medicinal Plants: Traditional Trends to Modern Therapeutics

Medicinal plant therapies are becoming more common, as more people seek

natural cures and health approaches devoid of synthetic chemicals' adverse effects. The

biological and pharmacological potential of plants is studied and utilized all around the

globe for various purposes including the treatment of infections and diseases owing due

to bioactive compounds in plants produced as a result of secondary metabolism. The

study of medicinal plants is helpful in clinical trials to find pharmacologically useful

chemicals, and this method has produced thousands of valued medicines. Opium,

aspirin, quinine, and digoxin are some examples. Plants possess a large number of

bioactive compounds. On the basis of their chemical structure, they are divided into

four classes: alkaloids, flavonoids, tannins, and terpenes. Plants can now be turned into

“factories” that create therapeutic proteins, vaccines, and many more products for use

in the production of biotech pharmaceuticals, medications, and therapies. This chapter

discusses the diversity and importance of medicinal plants in various sectors as well as

highlights the successful drug products produced by the said entities and their future

trends.

Radiation from Mobile Phones and Cell Towers, Risks, and Protection

Modern life is strongly associated with new technologies such as telecommunication and wireless devices. These new technologies strongly affect the way people communicate, learn, train, think and solve their problems. Today, modern cell phones not only send and receive phone calls, but they also allow people to send and receive short messages, and e-mails, share photos and videos, write, edit and share documents, play games, listen to music, watch movies, surf the Internet, find an address using GPS (Global Positioning Systems) and use a wide range of applications. Given this consideration, excessive use of smartphones is associated with growing global concerns over the health effects of radiofrequency electromagnetic fields (RF-EMF) generated by these devices. As discussed by WHO, considering the very large number of people who use mobile phones, even a small increase in the risk of adverse health effects, either cancer or other health effects, could have key public health implications. WHO believes that research about these health effects is mostly focused on potential adverse effects of mobile phones, not their base stations, because the RF-EMF levels of mobile phones are 3 orders of magnitude higher than those of base stations. Therefore, in this chapter, due to the greater likelihood of adverse health effects of handsets, we mainly focused on reviewing the current scientific evidence on health risks associated with mobile phones. However, the health effects of RF-EMF exposure on people living in the proximity of mobile base stations are also reviewed.

Human Topoisomerases and Caspases: Important Targets in Cancer Therapy

Cancer has always remained a major challenge to humanity with its rising morbidity and mortality rate making it uncontrollable. Current treatments for cancer offer limited efficacy and suffer from serious side effects. With a focus on making treatment safer and more effective, there is a need to identify novel targets and potent drugs for these targets. Recent years have witnessed significant progress in the discovery of targeted cancer therapy. On-going research in this field suggests that human topoisomerases and caspases are important molecular drug targets for anti-cancer drug development. Topoisomerases are DNA processing enzymes essentially required to maintain DNA topology during transcription, replication, recombination and chromosomal decatenation. Several new chemical classes of topoisomerase inhibitors including natural product derivatives are in clinical trials for the treatment of various human cancers. Several topoisomerase inhibitors such as topotecan, irinotecan, camptothecin, teniposide and doxorubicin are clinically approved for various cancers such as colon cancer, lung cancer, breast cancer, and many more. However, many of these inhibitors have also been associated with serious side effects during chemotherapy. Emerging data in recent years also suggests the role of topoisomerase inhibition in immunogenic cell death and activating anticancer immune responses making them potential combinatorial modalities for cancer immunotherapy. Caspases [1-12] belong to the family of cysteine-aspartic proteases responsible for the execution of cell death in apoptotic cells. Caspases play an important role in various non-lethal biological processes like cell proliferation, cell differentiation, intercellular communication, and cell migration. The dysregulation of apoptotic signalling pathways is considered one of the hallmarks of cancer. Hence the focus of cancer therapy is correcting this aberrant behaviour. Natural products such as alkaloids, flavonoids, diterpenoids, sesquiterpenes, and polyphenolics have been reported with various anticancer properties. In this chapter, we have discussed topoisomerases and the regulation of caspase functions through direct or indirect methods for anticancer drug discovery.

Application of d- and f- Block Elements and Their Compounds in Medicine

In vitro and in vivo Methods used for the Evaluation of Anticancer Secondary Metabolites

Cancer is a large group of diseases that affect the human body at all ages and causes death worldwide. Important progresses have been made in early diagnosis, prevention measures and treatment. Widespread use of secondary metabolites derived from plants has been made for the production of various effective medicines. Various natural bioactive compounds derived from medicinal plants are used as anticancer mediators to remediate cancer syndrome, but they have toxicity and side effects, and hence there is a need to explore more plant-derived cytotoxic chemical agents. Consequently, an effort has been made to evaluate various in vitro and in vivo methods that are used for assessing the efficiency of the anticancer efficacy of natural bioactive compounds derived from medicinal plants. Anticancer secondary metabolites derived from plants are efficient candidates for in vivo and in vitro anticancer activity. This chapter provides detailed information on different plant explants and extracts and various methods used to evaluate anticancer activity.

Biomarkers for the Diagnosis and Surveillance of Cancer

Cancer remains one of the leading causes of death worldwide. Cancer management has been a daunting task for both health professionals and patients throughout the journey. Screening of cancer at the right time/stage remains the most critical part of the riddle. Certain molecules that characterize cancer, known as ‘biomarkers,’ come out to be the most useful in this journey. The National Institute of Health defines a biomarker as “a characteristic used to measure and evaluate objectively normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention”. These have proven to be often easily available agents employing minimally invasive methods. Biomarkers have played crucial roles in screening, asymptomatic and early-stage detection, monitoring of the treatment therapy and eventual follow-up to check upon a probable re-lapse or metastasis. A cancer biomarker can be any of the biomolecules such as protein, DNA, RNA, proteoglycans, immunological compounds, salivary biomarkers and endogenous peptides. With the refinement in high-throughput techniques, the list of the types of biomolecules and the number of potential biomarkers is only increasing, with volatile organic compounds from the breath (breath biopsy) adding to the list. In this chapter, we shall put effort into reviewing this otherwise very vast topic. The chapter will outline various types of biomarkers, the journey so far with clinically approved cancer biomarkers, the challenges being faced, and conclude with future perspectives.

Subject Index

Chromosome Y

Sex chromosome constitution vary genetically in both genders, such as XY in male and XX in female. Even though the chromosomes X and Y advanced from the autosomal pair of the same ancestor, male-specific genes were harbored by the Y chromosome. This Y chromosome plays a crucial role in germ cell differentiation, sex determination in males, and numerous tissue masculinization. Translocations or deletions of SRY, the sex-determining gene of the Y chromosome, enable sex development disorders with dysgenic gonads. Gonadal improvement failure outturns not only in infertility but also in the highest possibilities of GCT (Germ Cell Tumour), like various kinds of testicular GCT and gonad blastoma. Studies have shown that selected somatic cancers are closely related to both losses of Y chromosome genes, ectopic expression, or Y chromosome. These observations remark that genes of the Y chromosome are associated with male diseases and health more than attic turns out not only in infertility but also in the highest possibilities of GCT (Germ Cell Tumour) like various kindspated. Even though only a compact amount of protein-coding genes are seen in Y chromosomes male-specific region, the effects of those Y chromosomal genes on human disease are still predominantly unknown. In this part, we can find the participation of selected genes of the Y chromosome in cancer growth in men.

Chromosome X

X Chromosome is the sex chromosome that is found in many organisms. Both males and females, including mammalians, have X Chromosomes. Females have XX sets of chromosomes, and males have XY sets of chromosomes. X Chromosome aids in identifying the sex of the organism. The Human X chromosome contains approximately 1500 genes. These genes may undergo some genetic alterations and eventually lead to complex diseases. Genetic mutations in some of the genes of the X chromosome are associated with cancer. Some specific mutations are observed in human cancer cells. This chapter specifically relayed on X chromosomal genes that are associated with different types of cancer and gave information on the location of the gene in the X chromosome. Moreover, the function of the specific gene and information regarding how many types of cancers were associated with a particular gene, has also been provided.

Chromosome 21

The significance of human chromosome 21 is that the trisomy of human chromosome 21 causes Down syndrome in children. There are about 235 protein-coding genes on chromosome 21. Mutations like translocation in human chromosome 21 cause different conditions such as partial monosomy 21, core binding factor acute myeloid leukemia, ring chromosome 21, and other types of cancers such as acute lymphoblastic leukemia. Mutation in the DSCAM gene causes mental retardation and facial deformities in down syndrome. The human chromosome 21 also comprises the APP gene, where the expression of the gene causes Alzheimer's disease. The genes that are involved in causing Down syndrome and Alzheimer's diseases are also involved in cancer. This chapter discusses 63 genes of human chromosome 21 that are involved in different types of cancer.

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 18

Cancer is an abnormal or unusual growth of cells in the body with invasive and migrating potential. It leads to loss of function, weakens the immune system, and is the second leading cause of death worldwide. This makes it important to eliminate the disease. Genetic predisposition imposes a high relative risk for several kinds of cancer. Inherited genetic mutations are responsible for causing 5 to 10 percent of all cancers. Scientists have investigated mutations in specific genes with more than 50 hereditary cancer syndromes. For this, chromosome 18 was explored for its genes associated with cancer and this study unveiled 30 genes involved in causing cancer. Of these, the genes DCC, EPB41L3, MBD1 PHLPP1, and RBBP8 were the potential tumor suppressors. This chromosome consists of the target genes of the transforming growth factor-beta (TGF-β) signaling pathway. The SMAD family genes (SMAD4, SMAD7, and SMAD2) are encoded by this chromosome, of which SMAD4 acts as a tumor suppressor. SERPINB5 and TCF-4 were the potential oncogenes. The enzyme coded by TYMS was a potential therapeutic target for chemotherapy. Several fusion genes of this chromosome (SS18-SSX2B, SS18-SSX2, and SS18-SSX4) have been identified to cause cancer. Therefore, this chapter provides a summary of the genes in chromosome 18 that are involved in the initiation and proliferation of cancer and provides an insight into the potential biomarkers and therapeutic targets for clinical application to develop a cancer-free world.

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 15

The genomic alteration at chromosome 15 has been widely recognized as the utmost significant and prevalent alteration in several cancers, including non-small-cell lung cancer, breast cancer, ovarian cancer, prostate cancer, gastrointestinal cancer, acute lymphoblastic leukemia, colorectal carcinoma, hepatocellular carcinoma, myeloma, pituitary adenomas, etc. Emerging reports suggest that the abnormalities of prime genes in chromosome 15 have drastic effects on tumor development and progression, and can be candidate biomarkers of disease prognosis, disease progression, and response to treatment. The translocations involving chromosome 15 and other chromosomes have been found in tumors, including mucoepidermoid carcinomas, mixed-lineage leukemia, colorectal cancer, pancreatic cancer, sarcoma, lung adenocarcinoma, melanoma, brain cancer, cholangiocarcinoma, spitz tumor, congenital mesoblastic nephroma, papillary thyroid cancer, pontine glioma tumors, and acute promyelocytic leukemia. The tumor suppressor genes such as C15orf65, CSK, CRABP1, DAPK2, FES, GREM1, KNSTRN, NEDD4-1, NTRK3, PML, SPRED1, TPM1, and TCF12 under chromosome 15 play a crucial role by enhancing cellular growth, proliferation, migration, invasion, metastasis, cellular differentiation, and development in various cancer, including colorectal cancer, acute promyelocytic leukemia, myeloid leukemia, breast cancer, thyroid carcinoma, glioblastoma, intrahepatic cholangiocarcinoma, chondrosarcoma, cartilaginous cancer, Squamous cell carcinoma, non- small-cell lung carcinomas, mucosal melanoma, and oral squamous cell carcinoma. Chapter 15 discusses the significance of each important gene under chromosome 15 in mediating oncogenesis. The elevated or attenuated expression levels of these cardinal genes can either act as an oncogene or a tumor suppressor. Thus, shedding light on these genes would be a game changer in the field of cancer genetics and theragnostic.

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.

Chromosome 10

Chromosome 10 contains various genes that are significantly involved in tumorigenesis. These genes described herein that play roles in cancer comprise receptor tyrosine kinases (FGFR2), proto-oncogenes (FRAT1, RET), tumor suppressor genes (PTEN, KLF6), and also genes involved in signal transduction (MAPK8), gene fusions (CCDC6, KIF5B, VTI1A), developmental processes (GATA3, NODAL), Epithelial- Mesenchymal transition (ZEB1, VIM) and epigenetic regulation (MLLT10). This chapter provides a compilation of many such genes from Chromosome 10 that are associated with cancer, with vivid delineations of the underlying molecular mechanisms of each gene in its contribution to cancer initiation, progression and metastasis. Genes that are insufficiently investigated but implicated in tumorigenesis have also been described in this chapter.

Chromosome 8

Chromosome 8 spans more than 146 million DNA base pairs, and represents between 4.5 and 5 percent of the total DNA in cells. Sixteen percent of these genes and their mutations have been identified to play a role in cancer development. Cancer is a genetic disease at the somatic cell level. Multiple gene mutations usually precede them throughout one’s life. Oncogenes such as Myc, Lyn, Atad2, etc., from chromosome 8 promoted cancer cell proliferation, invasion, and migration. The increased expression of these proteins can transform a normal cell into a cancer cell. Chromosome 8 also houses multiple tumor suppressor genes, such as Dlc1, E2f5, Gata4, Ido1, etc. These proteins, when expressed, reduce the chances of tumor initiation within cells. Thus, mutations leading to the reduced expression of these genes are associated with multiple cancers. Mutation of other functional genes like Ank1, Ctsb, Ext1, Il7, etc., has also been implicated in various cancers for their role in increasing the invasive nature of cancers by regulating angiogenesis and facilitating cancer metastasis. Cancers can also stem from the translocational mutations of genes in chromosome 8. This chapter explains essential cancer genes, genetic mutations, and gene variations that can cause an increased risk of cancer and its progression.

Chromosome 6

Chromosome 6 is among the 23 pairs of chromosomes in humans and it spans about 170 million base pairs. Several cancer genes have been identified to have a role in cancer development. Cancer is also a genetic disease caused due to changes in the genes that control cell function, such as cell division and cell growth. Most of these cancer genes either act as tumor suppressors or possess an oncogenic potential. Oncogenes like ROS1, MYB, HMGA1, etc., induce tumorigenesis by playing a role in DNA repair, replication, transcriptional regulation, and mRNA splicing. When these genes are highly expressed, they result in the transformation of normal cells to malignant cells; on the other side, tumor suppressor genes like IGF2R, AIM1, IRF4, etc., reduce tumorigenicity and invasive potential. Thus, reduced expression of these genes due to loss of heterozygosity, deletion or any epigenetic modifications can induce tumor formation. Also, some genes can either suppress or induce tumor formation given the cellular location and condition, such as CCN2, TNF, etc. Along with these, different types of structural abnormalities can be observed on chromosome 6, such as chromosomal translocation, deletion, duplication, and inversion. These abnormalities on both p and q arms have been known to contribute to the growth and spread of cancer by impacting the expression of cancer genes. Aberrant expression of the genes can also be influenced by fusions, missense mutations, non-missense mutations, silent mutations, frame-shift deletions, and insertion at the molecular level. Some genes can maintain stem-cell-like properties by regulating the expression of cell surface markers like Oct4, Nanog, Sox4, etc. This chapter explains important cancer genes, genetic mutations, and gene variations that can influence the risk of having cancer and induces cancer formation.

Chromosome 2

The human chromosome 2 was formed by a head-to-head fusion mutation caused by two chromosomes of our ancestors. The gorilla and chimpanzee contain 48 chromosomes in contrast to 46 chromosomes in humans. Ten million years ago, the two chromosomes of apes underwent telomere-to-telomere fusion that gave rise to human chromosome 2. Apart from the exciting history, the human chromosome 2 is involved in various genetic conditions caused due to chromosomal deletions and duplications, leading to SATB2 (Special AT-rich sequence-binding protein 2)-associated syndrome, MBD5 (Methyl-CpG-binding domain 5)-associated neurodevelopmental disorder, 2q37 deletion syndrome, partial trisomy 2, myelodysplastic syndrome as well as cancer. These mutations cause different human abnormalities, such as craniofacial anomalies, cleft palate, genitourinary tract anomalies, microcephaly, hypotonia, heart defects, anemia, and myeloid malignancies. This chapter discusses 50 genes of human chromosome 2 involved in various cancer types.

Subject Index

Cytotoxic Activity Methods

Natural products have formed the basis of traditional medicine systems throughout human history. Today, drug discovery studies from natural origins continue rapidly and efficiently with modern methods. Among the many activities, cytotoxic activity is related to the behaviour of test material on cell viability and cellular growth. Cytotoxicity methods, used as a screening test or initial test for guiding other activities, provide useful information for biocompatibility studies for medical devices or materials, drug discovery and development processes, toxicity evaluation of cosmetics, research of disease mechanisms and treatments, and determination of chemopreventive agents. In vitro cytotoxicity analyses have emerged as an alternative to in vivo studies and have become preferable due to their ease of application, standardization, rapid, low cost, and compatibility with data from in vivo studies. With cell-based cytotoxicity studies, basic information about the cytostatic and cytotoxic effects of the tested substance is obtained. In studies dealing with natural products, the most appropriate cytotoxic method should be selected according to the properties and chemical structures of natural compounds, the ultimate goal of the study, cell types, etc. Although there are many cytotoxicity methods, this chapter is an introductory overview of the most commonly used assay methods to estimate the cytotoxic activity in natural products.

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.

Advances in Nanopharmacology: Focus on Reproduction, Endocrinology, Developmental Alterations, and Next Generational Effects

To date, the application of a wide range of nanostructured materials (NSMs), such as carbon nanotubes, silica compounds, metallic nanoparticles, nanovesicles (liposomes and exosomes), nanohydrogels (NHGs), nanohydroxyapatite (NHAPs), chitosans, and graphenes, has gained interest for various applications in biomedical sciences. These nanoparticles presented outstanding biological and mechanical features. Although the biocompatibility of NSMs is highly investigated, their interaction with the reproductive system is less exploited. On the other hand, recently, NSMs-mediated drug delivery presents a competent method in reproduction biology. Emerging evidence from the literature supports the considerable progress in nanopharmacology, which has transformed the theory of targeted biological delivery, permitting the engineering of complex biocompatible organic/inorganic platforms with a vast loading capacity, highly selective affinity, stability, and capacity for multiple, simultaneous usages; all within the nanometer scale. In this chapter, first, the potential application of NSMs in the field of reproduction is highlighted. Then, the possible effects of these materials on reproduction, endocrinology, developmental alterations, and next-generation impact will be discussed. The data presented in this chapter could provide insight into the effect of NSMs on the reproductive system and development and lead to better risk assessment of these materials or synthesis of safe nano-drug delivery systems to the reproductive organs.

Natural vs. Synthetic Immunomodulators

Immunomodulators are key components in deciding immunity status and development in an individual. The topic has been under more emphasis, especially during and after the COVID-19 pandemic phase. Several plants with medicinal potentials are appreciated in traditional medicines for their healing perspective and have been technically examined for their immunomodulation potential. A number of plant-based bioactive compounds have been extracted and purified with such bioactivities that can rationalise their usage in conventional medication in the past and can stimulate further research in the future as well. Synthetic immunomodulators are significant for generating remedial or prophylactic formulations with defined chemical ingredients from regulatory perspectives. The review highlights the key immunomodulators, both synthetic and natural, until 2020. It also emphasises on market potential and commercial aspects of these. We have explained and listed several plants and their active scaffolds having immunomodulation activities along with synthetic compounds with similar bioactivity. We envisage the review to be an organised compilation and comparison of natural and synthetic immunomodulators and also focus on new chemical immunomodulator scaffolds.

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.

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.

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.

Subject Index

Biosensor Application

In Chapter 5, we want to focus on biosensors application in different fields and Focus on various newest research related to electrochemical biosensors in the fields of medical diagnosis, environmental monitoring, and food quality. In the medical diagnosis section,, the research done on HIV-1 is examined. Then hepatitis B, hepatitis A, Ebola, Zika, murine norovirus, influenza A, dengue serotype 2, adenovirus, enterovirus 71, Epstein-Barr virus, the apple steam pitting virus, papillomavirus, and phinovirus, are examined, respectively. In addition, in the monitoring environment section, research conducted on heavy water and pesticides is reviewed. In the food quality analysis section, research conducted on food toxicity and Antibiotic residues are reviewed.

Implication of Biosensors For Cancer Diagnosis And Therapeutics

“Caution is the parent of Safety”. Early-stage diagnosis of Cancer can provide better medicinal therapeutic responses. Currently, a majority of cancer is diagnosed after having metastasized throughout the body. This led to the urgent requirement for potent and precise cancer detection methods for clinical diagnosis. Over the last several decades, the majority of researchers have concentrated their efforts on developing a potential rapid detection technique based on Biosensor technology for a variety of frightening human health-related disorders, such as cardiovascular disease, cancer, diabetes, and others. Significant advances were made in a wide range of fields attributed to the designed techniques having enhanced sensitivity, specificity, and repeatability. The development of diagnostic treatments in medicine was aided by noteworthy advancements in other scientific fields, including genetics, chemistry, micro-electrical engineering, and computational biology. As a result, efficient, accurate, rapid, and steady sensing platforms have been successfully developed for specific and ultrasensitive biomarker-based disease diagnostics. Biosensors are analytical devices designed to detect biological analytes by converting biological entities’ responses (DNA, RNA, Protein) into potent electrical signals. The biosensor device combines a biological component with a physiochemical detector for sensing an analyte (biological samples). The discovery of the Biosensor boosted the potential clinical diagnosis of cancer at a large scale. Biosensors can be designed to detect emerging cancer biomarkers and determine drug efficacy at various target sites. Biosensor technology has the potential to be used as a diagnostic tool for accurate and impressive cancer cell imaging, tracking cancer cell angiogenesis and metastasis, and evaluating the efficacy of treatment for the disease. This chapter will provide a quick overview of the challenges facing the early diagnosis of cancer, get through the depth of how biosensor technology may be used as a reliable diagnostic tool, and highlight potential uses for biosensor technology in the future.

Taurine as an Anti-aging Compound: Focus on Mitochondria-related Mechanisms

It has been well-established that mitochondria play a crucial role in aging. Thus, targeting mitochondria is a leading approach for anti-aging pharmacological interventions. On the other hand, the anti-aging effect of taurine (TAU) is an exciting feature of this amino acid. Effects of TAU on mitochondria-facilitated oxidative stress as well as mitochondria-mediated cell death, seem to play a pivotal role in its antiaging properties. The current chapter will discuss a good body of investigations that have converged at a consensus regarding mitochondria (dynamics and functionality) and oxidative stress as essential mechanisms involved in the aging process. In each part, the potential antiaging properties of TAU and its mechanisms of action are also highlighted. Finally, in the last section of this chapter, we described the possible role of recently-discovered signaling pathways (i.e., aryl hydrocarbon receptors; AhR) on mitochondria and their relevance to senescence.

Subject Index

miRNAs as Epigenetic Cancer Biomarker

Despite the fact that the mortality rate of many types of cancer has decreased in the last decades, cancer remains one of the most challenging diseases in the world. The number of newly diagnosed cases with advanced stages in different types of cancer is still high because available tests are not efficient enough to be used for screening. In addition, the available diagnostic tests failed to diagnose certain types of cancer until late presentation. Furthermore, therapeutic agents currently in clinical use to treat a certain type of malignant tumours still show a high rate of resistance in some patients. Many types of available cancer biomarkers failed to manage and resolve this problem because of the lack of both sensitivity and specificity of these markers. Advanced researches in epigenetics highlight the importance of certain non-coding genes in diagnosing and follow-up of patients with different types of cancer. One of these substances is microRNAs (miRNAs) which showed high sensitivity and specificity as cancer biomarkers. miRNAs are highly stable and expressed in different types of human body samples; some of them are tissue specific. These features make them available as cancer biomarkers, and they are started to be in clinical use recently.

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.

Tumour Markers in Clinical Use

Despite ever-growing experimental evidence for the utility of a wide range of tumour markers, only a handful are understood to be useful in clinical applications. Tumour markers are useful for screening and diagnosis of cancers, prognostication, guiding treatment pathways and post-treatment surveillance studies. The tumour makers play a significant role in cancer care and the markers included in the current treatment guidelines will be discussed in detail in this chapter. The utility of the tumour markers in the management of colorectal, breast, thyroid, hepatobiliary, pancreatic, ovarian, testicular, neuroendocrine and prostate cancer are detailed herein to provide an update on the current use of tumour markers in the clinical settings.

Hazards of Using Antibiotic Growth Promoters in the Poultry Industry

The poultry industry is one of the significant hubs of the livestock industry and the world's largest food industry. In the last 50 years, it has become common to observe poultry antibiotic feeding to treat disease and growth. Antibiotics inhibit the growth of toxic and beneficial microorganisms. They are used as growth promoters when given in adjunctive therapy. The Centers for Disease Control and Prevention (CDC) estimates that fifty million pounds of antibiotics will be produced each year in the USA. Forty percent of the total antibiotics produced will be used in agriculture. 11 million pounds are used for the poultry sector and 24 million for domestic and wild animals. Ciprofloxacin, chloramphenicol, enrofloxacin, oxytetracycline, tylosin, tetracycline, virginiamycin, tilmicos, nitrofuran and sulfamids are used as growth promoters in the poultry industry globally. Antibacterial residues are found in various parts of poultry birds, e.g., kidney, heart, gizzard, liver, chest, thigh muscles, albumin and egg yolk. These residues may directly or indirectly produce many health concerns in human beings, such as toxic effects in the liver, brain, bone marrow, kidney, allergic reaction, mutagenicity, reproductive abnormalities and gastrointestinal tract leading to indigestion. In addition, resistant strains of pathogenic microbes pose an indirect threat to antibacterial residues that can spread to humans and contaminate residual fertilizers used as plant fertilizers. This chapter describes the benefits and contraindications of antibiotics used as growth promoters and the toxic effects of antimicrobial residues in poultry and humans.

Subject Index

Fertility Sparing Team

Cancer is a leading cause of death in the female population, accounting for 6.7 million of new diagnoses worldwide. Cancer and its treatment can often impair the chances of having children, and the fertility sparing issueis an emerging need. In fact, more often, women are delaying conception and therefore, an increasing number of women are diagnosed with malignancy before the desired completion of childbearing. The care of these patients is challenging, and complex, and there is a total lack of validated guidelines. The problem of fertility in a cancer patient encounters not only clinical and technical problems, but it raises many other queries about ethical and psychological perspectives. Since an international consensus statement should be produced, the need for a dedicated multidisciplinary approach is mandatory to offer a clinical range of treatment options. Cancer survivors and the medical community have acknowledged the importance of patient counseling and the pursuit of options for fertility preservation. In 2006, the American Society of Clinical Oncology published the first recommendations on fertility preservation; however, despite the increasing awareness regarding these recommendations, fertility preservation services are still underutilized. ASCO guidelines advised oncologists to discuss fertility risks and preservation strategies and make referrals to fertility specialists for interested patients as early as possible. There are some programmatic requirements to set up a fertility preservation service, the most significant of which is the availability of a multidisciplinary medical team. A treatment planning approach in which medical figures are experts in different specialties aims to deliver a global treatment tailored to the patient and its disease. A multidisciplinary approach to debating with fertility-sparing issue in oncological patients has mainly two objectives: firstly, to ensure the oncological safety and, in second place, the verification of the fertility preservation desire, that should be not only the intention of the patient but also compliant to “minimum requirements” and therefore a step-wise and careful selection of the women candidate to conservative treatment is necessary. Counseling of patients pursuing fertility preservation should include a discussion of all methods of fertility preservation as well as the alternatives. Because of the sensitive and urgent nature of fertility preservation, a team approach to patient counseling is recommended. Effective provision of fertility preservation options requires an ongoing collaborative relationship among medical and surgical oncologists, reproductive endocrinologists and other medical figures. Oncologists have the initial responsibility to discuss the reproductive risks of intended therapies with the patient and subsequently make referrals to experienced specialists to discuss available reproductive options, which have to be discussed both for surgical decisions and chemotherapy and/or radiotherapy administration. Multidisciplinary teams should include: oncologists, gynecologic oncologists, radiation therapy specialists, reproductive endocrinology and infertility specialists, andrologists, fertilitydedicated biologists, and nurses in the specialties of oncology and infertility, oncopsychologists and social workers. All of these are required to work together in order to achieve a successful collaborative approach

Subject Index

Immunomodulatory Potential of Bioactives from Selected Ayurvedic Plants

The history of usage of herbal medicine is as old as human civilization. Plant-based drugs have been an invaluable and incredible source for several medical treatments in the traditional system of medicine. With technological advances, it has become possible to get a clear understanding of active compounds behind the therapeutic effectiveness of these drugs. Plant-derived immunomodulators are one such class of compounds, considered safe alternatives than synthetic immunomodulators which cause serious side effects. These agents can increase the body’s immune responsiveness against pathogens by activating both the innate and adaptive immune systems. Phyto drugs have gained more interest due to their multi-pharmacological potential of being antioxidant, adaptogen, etc. along with immunomodulator. The current book chapter focuses on a few extensively scrutinized immunomodulatory phytocompounds from medicinal plants such as Tinospora cordifolia, Andrographis paniculata, Curcuma longa, Zingiber officinale, Allium sativum, Terminalia chebula, and Piper longum. Phytomedicines from these plants have displayed significant immunomodulatory potential in a variety of experimental (in vitro and in vivo) models, few compounds have exhibited good therapeutic potential in clinical trials also.

Potential Uses of Plant and Marine Derived Bioactive Compounds for Cancer Theragnostic

The evolution of novel strategies for application in all facets of cancer theragnostic has shown great progress in the past several decades. Bioactive compounds collected from plants and marine natural provenances have now been accredited as the crucial stepping stone to endow with fortification approach against several relentless ailments counting cancer. As per sundry investigations reports, the naturally occurring bioactive compounds possess an unprecedented molecular diversity with the potential to modulate several metabolic processes with high priority objectives such as low toxicity, targeting multiple drug resistance and heterogeneity of the tumor cells. These attributes with bioactive compounds can provide safe and high quality of healthy life achievable with easily available low-cost alternatives and nominal or no side effects. In topical quondam, numerous potent phytochemicals and marine molecules have been isolated, exemplified, identified, and are under disparate phases of clinical trials for human welfare. In this context, the chapter addresses recently discovered plant and marine originated natural compounds for cancer therapeutics concerning with more targeted and innoxious approach with future outlook. Moreover, an attempt to consolidate data on various bioactive compounds has been made which herald to aid in unrelenting research into potential use either solely or in combination with other widely employed therapies.

Emerging Water Pollutants from Pharmaceuticals and Personal Care Products

Pharmaceuticals and personal care products (PCPs) are chemically modified products mostly used for beauty, cleaning, or health, such as disinfectants, fragrances, insect repellents, ultraviolet (UV) filters, and others. Due to the contamination caused by these chemically amended PCPs, water pollution has appeared as a hazardous condition for the water treatment and supply sector. A recent concern is that when these chemical compounds combine with water, they act as water pollutants and harm aquatic lives and the survival of human lives. Nowadays, the concern of water pollution by these chemicals is confined to water treatment complexities this contamination is leaving adverse effects on the environment. Most of these water pollutants borne by sewage effluents through wastewater plants develop because of the insufficient removal from treatment plants. Therefore, the emerging water pollutants caused by PCPs are responsible for environmental pollution. Hence, this chapter emphasized the state-of-the-art global application of PCPs, the mechanism of water pollution by PCPs, possible biohazards, and negative impacts on the environment. Besides that, various types of PCPs, along with the most applied chemical compounds in PCPs, have been discussed in this chapter. To minimize the contamination, suitable removal methods to enhance the removal efficacy have been discussed. The chapter also presents a future perspective for reducing the PCP contamination of surface water with cutting-edge technologies and wastewater treatment.

Subject Index

DNA Methylation Biomarkers in Cancer: Current Clinical Utility and Future Perspectives

Epigenetic alterations are related to inherited but reversible changes in modifications that regulate gene activity beyond the DNA sequence. DNA methylation is the best characterized epigenetic modification, controlling DNA stability, DNA structure, transcription, and regulation, contributing to normal development and differentiation. In this section, we first discuss the cellular functions of DNA methylation and focus on how this fundamental biological process is impaired in cancer. Changes in DNA methylation status in cancer have been heralded as promising targets for the development of diagnostic, prognostic, and predictive biomarkers due to their noninvasive accessibility in bodily fluids (such as blood, urine, stool), reversibility, stability, and frequency. The absence of markers for definitive diagnosis of most types of cancer and, in some cases, DNA methylation biomarkers being more specific and sensitive than commonly used protein biomarkers indicate a strong need for continued research to expand DNA methylation markers. Although the information on changes in DNA methylation status in cancer and research on its clinical relevance is rapidly increasing, the number of DNA methylation biomarkers currently available as commercial tests is very small. Here, we focus on the importance of DNA methylation location and target genes likely to be developed in the future for the development of biomarkers in addition to existing commercial tests. Following a detailed study of possible target genes, we summarize the current clinical application status of the most studied and validated DNA methylation biomarkers, including SEPT9, SDC2, BMP3, NDRG4, SFRP2, TFPI2, VIM and MGMT.

Biomarkers in Urological Cancers

Urological tumours have become one of the most common cancers in the last decade. It is important to apply an approach that evaluates many factors related to the patient and the disease carefully to minimize cancer-associated morbidity and mortality. The clinical use of cancer biomarkers is a valuable part of the clinical management of urological cancers. These biomarkers may lead to optimized detection, treatment, and follow-up of urological cancers. With the development of molecular research, newly developed biomarkers and next-generation sequencing have also contributed to patient management. In this chapter, we will present biomarkers in the most common urological cancers under subheadings of bladder cancer, prostate cancer, kidney cancer, and testicular cancer. Additionally, due to the development that occurred in the next-generation sequencing (NGS), all the above-mentioned malignancies are evaluated with regard to NGS.

Biomarkers in Gynecologic Tumors

Gynecologic malignancies are one of the most frequent cancers amongst women. Biomarkers are crucial for the differential diagnosis of adnexal masses; however, their potential for diagnosis is limited. In the era of difficulty in ovarian cancer screening, novel biomarkers are defined, but CA125 still remains the most valuable one. Circulating tumor DNAs, DNA hypermethylation, metabolites, microRNAs, and kallikreins have recently turned out as ovarian cancer biomarkers and are being applied to clinical practice. For uterine cancer, genomic classification has now been described, it will be used as a prognostic tool. In this chapter, we describe ovarian, endometrial, and cervical cancer biomarkers in detail.

Subject Index

Specific Diagnoses and Management Principles of the Urinary and Genital Tract Diseases

Urinary tract infections (UTIs) and genital tract diseases (GTD) are among the most common infectious diseases with female predominance. On the other hand, acute epididymitis and orchitis are the most common GTDs which cause scrotal pain in adult males. Testicular torsion is a true medical emergency with vascular compromise and mandates immediate intervention to beware of serious complications. Although a majority are self-limiting diseases which can be treated easily, rapid diagnosis and management of certain UTIs and GTDs are a must to prevent grave outcomes. The infections may inflict the lower and/or the upper parts of urinary tract which also determines the severity of the disease. The urinary stone disease generally presents with ureteral colicky pain, blunt flank pain, nausea/vomiting, and hematuria with a male predominance. Most patients are managed easily in the acute setting but some are prone to deterioration with protracted urinary obstruction and resultant renal damage. The utilization of reliable, easy-to-use diagnostic tools with high accuracy is the key to expedient detection, identification and treatment. Ultrasound provides invaluable information in point-of-care diagnosis of most urinary tract diseases in both sexes. Management should be individualized in accord with the patients’ signs and symptoms, general status and outcome estimations.

Immune-Endocrine Perspectives of Breast Cancer

Cancer is the consequence of the recalcitrant multiplication of the transformed cells. Cancer cells grow and proliferate at a fast pace and do not follow normal regulation of cell division. Breast cancer is a heterogeneous group of diseases, which is the second leading cause of death among women. Although androgen is primarily considered a male steroid hormone, it also has an important role in the female reproductive system. The literature evidence suggests the role of androgen receptors (AR) in the normal development of the breast. At puberty, the expression of AR is even more than ER, suggesting its importance during the process of sexual development; its activity maintains the ER-induced cell proliferation and normal development of the breast. Epidemiological studies have suggested a positive correlation between high endogenous androgens and the risk of breast cancer in both pre- and postmenopausal women. In both ER and PR-positive breast cancers, AR is expressed in 60-70% of the cases. AR is also reported to be co-expressed with ER in around 80-90% of breast cancer cases and is considered an independent prognostic factor of ER-positive breast cancers. Tumor-microenvironment has a complex role in tumor initiation, progression, and metastasis. Tumor-infiltrating and resident cells secretes a variety of inflammatory and anti-inflammatory cytokines, which in turn either inhibit or promote tumor growth. Immunosuppressive and immuno-inductive effects of androgen have been reported in various studies. Androgens have been reported to influence the adaptive immune system more than the innate immune system in many ways. Crosstalk of androgen and cytokine signaling has many effects in breast cancer epidemiology. So, in this chapter, we will discuss the various immune-endocrine perspectives of breast cancers.

Recent Advances in Synthesis and the Anticancer Activity of Benzothiazole Hybrids as Anticancer Agents

Cancer is known as a silent killer that wreaks havoc on our immune systems. Cancer is the leading cause of death in the majority of cases. Resistance to anticancer drugs is becoming more agile, which encourages researchers to develop more effective cancer therapies. Heterocyclic compounds have long been important in advanced medicinal chemistry. Among the various heterocyclic scaffolds, benzothiazole (BT) is one of the most privileged moieties with a diverse range of biological activities such as anticancer, antidiabetic, anti-inflammatory, antiviral, antifungal, and so on. A large number of novel benzothiazole derivatives have been synthesized. Some of the mechanisms used by BT to treat cancer include tyrosine-kinase inhibitors, topoisomerase II inhibitors, CYP450 enzyme inhibitors, Abl kinase inhibitors, tubulin polymerase inhibitors, and HSP90 inhibitors. In this chapter, we will discuss various benzothiazole-hybrid compounds that optimise potency as well as anticancer activity in a concise manner. The goal of this chapter is to highlight recent research on benzothiazole scaffolds and their anticancer activity against various biological targets. The chapter will also provide updates on benzothiazole-containing drugs that are currently in clinical trials as well as those that have recently been granted patents.

Subject Index

Phytoconstituents, Biological Properties, and Health Benefits of Basil (Ocimum basilicum L.)

Herbs have been an important part of Indian food since the times of Romans and are effectively used as a possible alternative for medicinal treatments. Basil (Ocimum basilicum) is one of such annual herbs cultivated for several millennia for its ornamental and therapeutic importance in Ayurveda and traditional Chinese medicine. This chapter distinguishes sweet basil O. basilicum from other species of genus Ocimum, providing a place of origin and botanical distribution along with historical significance. The culinary, cosmetic, and traditional medicinal uses of sweet basil are described, followed by the chemical composition of the different parts of the plant used. Different types of chemical constituents found in the plant include terpenoids, alkaloids, flavonoids, tannins, saponin glycosides, and ascorbic acid. Major compounds which have been observed to be present in higher amounts in essential oils or extracts from different parts of the plant include rosmarinic acid, linalool, eugenol, 1, 8- cineone, methyl eugenol, and anthocyanins. These compounds have been found mainly responsible for various bioactive properties such as antioxidant, anticancer, antimicrobial, antidiabetic, analgesic, anti-inflammatory, hepatoprotective, insecticidal activities, etc. This chapter has covered up-to-date information on pharmacological investigations of the herb and its health-related benefits.

Piperine: An Alkaloid from Piper Species with a Wide Range of Therapeutic Properties

Based on the usefulness and importance among the spices, black pepper (Piper nigrum L.) is commonly referred to as “The King of Spices”. It is valued for its flavor, aroma, nutritional, and medicinal uses. The value of pepper is owed to its pungency and flavor, which is attributed to the presence of a naturally occurring alkaloid known as piperine. The amount of piperine varies in plants belonging to the Piperaceae family; it constitutes 2% to 7.4% of both black pepper and white pepper. It has been confirmed from the scientific studies that piperine has many bioactive effects, such as antimicrobial action, as well as many physiological effects that can contribute to general human health, including immunomodulatory, hepatoprotective, antioxidant, antitumor, and many other activities. Clinical studies demonstrated remarkable antioxidant, antitumor, and drug availability-enhancing characteristics of this compound, together with immunomodulatory potential. All these properties showed the therapeutic potentials of piperine and the need to incorporate this compound into general health-enhancing medical formulations, as well as into those that would be used as adjunctive therapy in order to enhance the bioavailability of various therapeutic drugs. The present chapter accounts for an overview of the therapeutic properties of piperine, the bioactive constituent of pepper. It also focuses on methods used to extract piperine from pepper along with recent approaches for the enhancement of the bioavailability of piperine.

Subject Index

Introduction of Common Pediatric Diseases

Pediatric health has improved over the past decades and there is a decline in deaths caused by infectious diseases. Yet, the top three causes of disease in children younger than 10 years in 2019 include neonatal disorders, lower respiratory tract infections, and diarrheal diseases. While in the adolescence age group, the major causes are road injuries, headache disorders, and self-harm. Preterm birth complications, pneumonia, and birth asphyxia are the most leading cause of death in children under five years. While in the five to nine years of age group, injuries, including road traffic injuries, drowning, burns, and falls, are the leading causes of death.

A Review of the Impact of Testosterone on Brain and Aging-related Decline in Brain Behavioural Function

The hormone testosterone is known to affect a variety of functions in the

body, a number of which are related to behaviour, and preservation of brain neuronal

integrity. Along this line, certain experimental evidences suggest that testosterone

supplementation may be beneficial in the preservation of cognitive functions and

neuronal integrity in aging and may be a valuable addition to a growing arsenal of

medications that can be used to combat aging-related cognitive decline. However, some

other studies have suggested instances where testosterone supplementation may be

deleterious for the brain neurons, while under certain conditions, the likely effects of

testosterone supplement may not be clear. Some studies had even suggested that race

may be a major determinant of testosterone’s effects on the brain. In this review, salient

aspects of testosterone’s effects on the brain are discussed with emphasis on its

behavioural and morphological effects. The impacts of aging on the behavioural and

brain morphological effects of testosterone are also discussed, with emphasis on its

nootropic effects. The limitations to the clinical application of testosterone in

mitigating aging related cognitive decline are also considered.

Subject Index

Role of Virgin Coconut Oil as Multiple Health Promoting Functional Oil

Numerous scientific studies have confirmed the effectiveness of virgin

coconut oil (VCO) as having multiple health-giving properties, as demonstrated both in

vivo and in vitro findings. The functional properties of VCO as antimicrobial,

antiobesity, antiulcerogenic, antiinflammatory, antipyretic, analgesic effect,

antidiabetic, and antioxidants properties have been widely reported. The remedial

effect of VCO was due to the presence of medium-chain triacylglycerols,

micronutrients (Vitamin E, provitamin A, plants sterols, polyphenols), and

antioxidants. The partially hydrolysed VCO, also known as activated virgin coconut

oil, is more potent than VCO as it contains more free medium-chain fatty acids

(caprylic, capric, and lauric acids) and their corresponding monoglycerides

(monocaprylin, monocaprin, and monolaurin); it has a broad spectrum of antimicrobial

properties. In this review, we summarized the major research, which provided evidence

of multiple beneficial effects of VCO and the mechanisms of therapeutic effects

towards human health management.

Ga-PSMA PET/CT for Patients with Prostate Cancer with PSA Relapse

In Danish guidelines for imaging of patients with prostate cancer and PSA

relapse, PSMA PET/CT is the recommended restaging modality. A multicenter study

has been initiated to analyze findings of 68Ga-PSMA PET/CT scans for patients with

prostate cancer with PSA relapse. This report details preliminary findings of 779

patients in six cohorts from three continents. At the time of the restaging, the PSA

values were grossly similar between the six cohorts, with an important subgroup of the

patients having PSA values < 1 ng/ml. Patients who initially underwent radical

prostatectomy had lower PSA values at the restaging than patients who were initially

treated with external beam radiation therapy or brachytherapy. Even for patients with

restaging PSA values < 0.5 ng/ml, some patients had positive sites in extra pelvic

lymph nodes and bones. Patients were followed up to 7 years after the restaging PSMA

PET/CT. In multiple Cox regression analysis of 196 patients, only the number of

positive sites on 68Ga-PSMA PET/CT significantly predicted overall survival (p =

0.0001). The findings illustrate why restaging PSMA PET/CT change salvage

treatment for up to half of the patients with PSA relapse compared with planned

salvage treatment based on only conventional imaging modalities like CT and bone

scans.

Preclinical Findings for Targeted Nanotherapies to Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is considered a major ailment throughout

the world, and conventional therapies including chemo and combinational have suboptimal

responses with toxicity and adverse effects. The use of conventional methods

becomes challenging, especially when the tumor cells adapt resistance rapidly, which

further limits their use. Nanotherapeutics for HCC show their potential with minimal

toxicity and enhanced degree of targeted drug delivery, which has attracted researchers

across the world to explore the various benefits of nanotherapeutics. This chapter has

briefly covered the epidemiology and incidence of HCC, its causes, stages, different

ways to diagnose HCC, its pathology, and conventional treatment options. We have

explained various targeted nanotherapeutic preclinical approaches such as lipidic

nanoparticles, polymeric nanoparticles, and liposomes for HCC. Surface-modified

nanoparticles and liposomes can actively target a wide array of overexpressed receptors

on the tumor surface. It can be seen from the literature that the nanotherapeutic

approach for the management of HCC has a high potential to become the mainstream

treatment platform if explored and tweaked appropriately. In almost all the works,

promising results were seen. Maximum amount of drug was delivered at the tumor site,

drug release at unwanted sites were prevented and selectively caused cell necrosis in

the tumors, while not affecting the normal cells. These remarkable outcomes further

strengthen the nanotherapeutic platform, showcasing its true potential.

Current and Future Treatments of Iron Overload in Thalassemia Patients

Iron overload is a major complication among thalassemia patients. In these

patients, ineffective erythropoiesis decreases hepcidin production resulting in iron

dysregulation, which leads to a number of serious complications. Damage to organs

susceptible to iron overload could be prevented by effective iron chelation. Despite the

efficacy of iron chelators, limitations to their use are that they are only used after the

patients have suffered from iron overload, and they have also been associated with a

number of side effects. New therapeutic strategies for the treatment of thalassemia have

focused on addressing the pathophysiology of the disease. Drugs currently being

developed to improve ineffective erythropoiesis are aimed at increasing hemoglobin

levels and subsequently decreasing iron absorption. The new therapeutic drugs in this

class include pegylated erythropoietin, JAK 2 inhibitors, and TGF-β activin receptor

traps (sotatercept and luspatercept). Luspatercept is currently recognized as the most

promising drug in this class and has completed phase III of trials. With the aim of

improving iron dysregulation, these new therapeutic strategies focus on preventing the

absorption of iron in the gastrointestinal tract. These therapies involve hepcidin

agonists and specific derivatives, such as LJPC-401 and Rusfertide (formerly PTG-

300), certain ferroportin inhibitors, such as Vamifeport (formerly VIT-2763) and

transmembrane protease serine 6 (TMPRSS6) antisense oligonucleotides. Although the

therapeutic potential of these new treatments in thalassemia patients is promising,

ongoing clinical trials are needed. Importantly, these new treatment strategies may

provide a new, more effective paradigm of treatment in thalassemia patients.

Monitoring Therapeutic Response in Cancers: A Raman Spectroscopy Approach

Cancer is a multifactorial disease that is often asymptomatic and is thus

detected at an advanced stage. Late detection and resistance to treatment are two of the

major reasons for poor prognosis. The inherent limitations of conventional tools in

evaluating therapeutic responses, raise the need to monitor such responses during

treatment. Raman spectroscopy is a rapid, label-free, minimally invasive optical

vibrational spectroscopy technique that has been widely employed for cancer detection.

There is also significant literature on its applications in intraoperative surgical margin

assessment, chemotherapeutic drug monitoring, and prediction of radiation response.

However, most books and reviews focus on the diagnostic and screening applications

of Raman spectroscopy. This chapter describes the role of Raman spectroscopy in the

therapeutic monitoring of cancers and discusses its prospective applications. The

present work provides a brief introduction to the basic principles of Raman

spectroscopy, concise information on cancer aetiology, pathogenesis, diagnosis and

therapeutics, and applications of Raman spectroscopy in the therapeutic monitoring of

cancers. The role of Raman spectroscopy in monitoring conventional treatment

modalities such as surgery, radiotherapy, and chemotherapy, along with novel

treatment approaches such as immunotherapy and cold atmospheric plasma therapy, is

discussed in detail. The chapter concludes with a brief introduction to the emerging

field of Raman spectroscopy and artificial intelligence.

The Male Patient

This chapter considers the various causes of male infertility and the input of

the male into the overall process of fertility treatment. Fertility treatment is unique in

that it involves 2 patients at the same time and the role of these patients is equally

important to the overall success of the treatment. The male plays a critical role in

fertility treatment, and this role may be down-played by some fertility clinics to the

point at which the male feels disengaged from the treatment process. This is a bad

thing.

PDX Clinical Trial Design in Anti-Cancer Research

Animal models are useful tools for understanding cancer biology and genetics and serve as an essential platform for the preclinical development of anticancer therapeutics. In this context, cancer-bearing patient-derived xenograft (PDX) models, also called cancer avatars, have successfully replaced the traditional cell linederived models in recent years. PDX-based studies are now widely used for preclinical testing of novel treatments as well as tailoring personalized medicine. For anti-cancer research, however, the use of PDX models propagated from a unique patient does not fully represent the true therapeutic efficacy and toxicity of a drug. That is why many studies in this format later failed to show efficacy and safety in human clinical trials. Hence, the concepts of PDX clinical trials and co-clinical trials have gained importance and prospered in recent years. A PDX clinical trial implies investigation on a set of PDXs originated from multiple patients prior to an early phase human trial, whereas a co-clinical trial refers to drug response assays, in parallel and simultaneously with a human clinical trial, on a set of PDX models established from the same clinical trial participants. A carefully designed PDX- /co- clinical trial requires a meticulous calculation of the sample size, enrollment of pathologically and molecularly diverse patients, and selection of suitable endpoints and outcome measures. With a special focus on PDX clinical trial design in anti-cancer research, this chapter specifically addresses how to develop cancer-bearing PDX models, what to consider in characterizing them, how to track their fidelity to the parental tumor, how to estimate the number of animals included in a PDX trial, how to achieve greater power in the translation of final outcomes, what are the minimum endpoints to be considered, and what measures are preferred for evaluating the response to therapeutic interventions.

Developmental Toxicity of Aluminium and other Metals: Areas Unexplored

Reproduction and developmental damage has irreversible consequences compared to other body functions and may have adverse effects throughout life. In some circumstances, the damage passes from generation to generation. Many environmental agents contribute to developmental toxicities such as toxic metals, insecticides or pesticides, commercial or industrial pollutants, and air pollutants. Increased urbanization and industrialization have led to the accumulation of toxic metals in the environment. Widespread use of heavy metals in different fields such as agriculture, domestic, medical, industrial, and technological applications have resulted in increased exposure of heavy metals to the human population. Environmental exposure to heavy metals is extensively linked to toxic effects on mammalian embryos. Metals such as lead, cadmium, mercury and arsenic are known developmental toxicants that intensely affect fetal and embryonic development and cause certain malformations in developing embryo even at low concentrations. Other metals such as uranium, cobalt, lithium, Aluminium, manganese, and copper are also reported to induce developmental consequences, including neurobehavioral abnormalities, neural tube defects, fetal growth retardation, skeletal deformation, preterm or delayed birth, and still birth or postnatal death. Heavy metal developmental toxicity depends on different factors, including dose, duration, and route of exposure. Hence, heavy metals are known to be toxic to fetal and embryonic tissues and can produce serious teratogenicity in mammals; however, not much attention has been given to this topic. This chapter, therefore, summarizes the developmental toxicity of heavy metals on the mammalian system and their teratogenic mechanism in growing embryos.

Breast Cancer Vaccines: Current Status and Future Approach

Breast cancer, a heterogeneous disease, is the frequently diagnosed cancer and the leading cause of cancer-related deaths among women globally. Today, even if the survival rate of breast cancer patients is increased with combination therapies including chemotherapy, monoclonal antibodies, tyrosine kinase inhibitors or immune checkpoint blockade in the patients resistant to the therapies, the disease progression continues. Moreover, the clinical activity of the therapies is limited only to subsets of patients. These difficulties highlight the necessitate for the development of alternative treatment approaches. Vaccines that have protected humans against infectious diseases for centuries are increasingly being developed due to the cost-effective approach related to prevention, treatment, and eradication of cancer. In addition, vaccines confer long-term immune memory critical to prevent tumor recurrence. Breast cancer vaccines have been extensively tested in clinical trials, but no vaccine has been approved for either breast cancer treatment or prevention yet. In the past years, tumor self-antigens have been used in vaccine development. Tumor-specific antigens are not only present in the tumor cell but also in normal cells. Such developed vaccines cause immunological tolerance and cannot provide effective treatment. Currently, neoantigens are popular during vaccine development against breast cancer. Neoantigens formed by somatic mutations differ from self-tumor antigens and are specific to each individual patient. Another important vaccine target is the cancer stem cell that plays a key role in tumor development, dissemination, and resistance to therapy. Breast cancer vaccines targeting cancer stem cell and neoantigen can be used either single or combined with chemotherapy and immune checkpoint blockade and are also considered as an effective therapeutic strategy in breast cancer. In this chapter, the vaccination strategies in current clinical trials and possible future directions for vaccine development against breast cancer are portrayed and intensely discussed.

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Breast Surgery

At the end of week 4 of human embryonic development, paired thickenings appear in the ectoderm on the ventral aspect of the torso. Extending from the axilla to the inguinal region, they form the mammary ridges or “milk lines.” Subsequently they regress and leave a pair of primary mammary buds at the level of the fourth and fifth inter- costal spaces. The primary buds thicken into lens-shaped mammary placodes. Epithelial cells invade the underlying mesenchyme during weeks 7 and 8 to form the primitive mammary disk. In week 9, a surge of mesenchymal proliferation occurs, coincident with a thinning of the overlying epithelium. A dense mesenchymal stroma then coalesces around the bud. Between weeks 10 and 12, epithelial buds form, begin to branch, and extend into the epithelial–mesenchyme bound- ary. By the first half of the second trimester (weeks 13–20), there are 15–20 solid epithelial cords that converge at the nipples. Ramification processes continue to week 32, when the cords undergo apoptosis to establish tubules and alveoli. At birth, male and female mammary glands are equally formed. There are 20 lactiferous ducts draining into the dimple. In later stages of the final trimester, the mesoderm underlying the dimple changes it into a true nipple with an areola. Placental estrogens during the final weeks of gestation cause breast buds to enlarge to create a true breast nodule at birth, about 1 cm in size, in both genders.

Pediatric Malignancy

Cancer is the second leading cause of death in children after trauma and accounts for approximately 11% of all pediatric deaths in the United States. In the western countries, leukemia, central nervous system (CNS) tumors, lymphomas, neuroblastomas and nephroblastomas account for most pediatric malignancies. Neuroblastoma and nephroblastoma are among the more common solid abdominal tumors. The prognoses for these cancers have improved after numerous multicentre trials. The following description will be restricted to the most commonly encountered tumors in children.

Undescended Testis (Cryptorchidism)

This chapter will discuss common genital tract diseases in pediatric age group. These include undescended testis, testicular neoplasm, ovarian cyst, and ovarian neoplasm, and ambiguous genitalia. Undescended testis incidence is 30% in pre-term and 3% in full-term infants and it is associated with an increased risk of infertility and malignancy. Testicular neoplasm has different types; the most common type is yolk sac tumor. Ovarian cysts are quite common in childhood and adolescence age groups. Lastly, we will discuss ambiguous genitalia, which should address as a medical emergency condition during evaluation.

Stem Cell Therapy for COVID-19

Stem cells have long been a topic of interest around the globe. Now and then, stem cells are being studied for revealing their beneficial effects. Countries around the world are in a race in stem cell research. Stem cells possess some unique and considerable qualities that hardly any other cell to date has. The outbreak of novel coronavirus or coronavirus disease-19 (COVID-19) was located in Wuhan, China. After a few months, the episode was declared Pandemic by the World Health Organization (WHO) as it engulfed many countries worldwide. Since then, stem cells have gained more push in clinical as well as pre-clinical stage research studies. COVID-19 shares some molecular properties with other coronaviruses like severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). Stem cells surprisingly showed some good outcomes in many patients infected with COVID-19. A lot of laboratory evaluation is being carried out to check the feasibility of different stem cells to be used in COVID-19 infected patients. This chapter discusses and highlights the possible interventions in COVID-19 using different lineages and bio-cultured stem cells.

Role of Biochemistry in Tumor Detection

Learning objectives:

1. Enlist Specific Tumor markers for particular cancer.

2. Illustrate different oncogenes and their products.

3. Describe in detail Ectopic production of hormones.

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Cannabinoid-based Anti-cancer Strategies: Slowly Approaching the Bedside

Modulation of the endocannabinoid system has emerged as a potential therapeutic strategy for the treatment of diverse types of cancer and related pathologies. Thus far, the use of specific cannabinoids has been primarily approved for the management of chemotherapy-induced side effects. Palliative actions of cannabinoids include the control of nausea and vomiting, pain alleviation and appetite stimulation. Moreover, a growing body of research has exposed the anticarcinogenic potential of cannabinoids. In vitro and in vivo studies have shown that endogenous, plant-derived and synthetic cannabinoids can effectively modulate tumor growth in diverse cancer models. Although this has not yet reached the bedside, ongoing clinical trials and research efforts may approach cannabinoid-based antitumor therapies to cancer patients in the near future.

So far, studies on cannabinoids as antitumor agents have been mainly focused on understanding the mechanism of action of well-known phytocannabinoids such as Δ9-THC or CBD. However, novel cannabinoids with antitumor properties are also emerging in the literature. In this chapter, we aim to provide an updated overview of the therapeutic potential of cannabinoids in cancer. We will comprehensively summarize the diverse cannabinoid structures exerting antitumor properties analyzing the molecular basis of these actions. Recent and ongoing clinical trials will be considered to provide a deeper insight into the current scenario of cannabinoids in oncology.

Pharmacological Effects of Curcuma longa, Focused on Anti-inflammatory, Antioxidant and Immunomodulatory Effects

Curcuma longa (C. longa) or turmeric is a plant with a long history of use in traditional medicine, especially for treatment of inflammatory conditions. Also, pharmacological effects such as antioxidant and anti-microbial properties were described for this plant. This chapter reports the latest knowledge on antiinflammatory, antioxidant and immunomodulatory effects of C. longa based on a literature survey using various databases and appropriate keywords until the end of July 2020. Various studies showed anti-inflammatory effects of C. longa, including decreased total white blood cells (WBC), neutrophils and eosinophils, as well as its effects on serum levels of inflammatory mediators such as phospholipase A2 (PLA2) and total protein in different inflammatory conditions. The anti-toxin effects of C. longa were also reported in several studies. The plant extracts decreased malondialdehyde and nitric oxide levels but increased thiol, superoxide dismutase, and catalase levels in oxidative stress conditions. Treatment with C. longa improved the levels of IgE, pro-inflammatory cytokines including interleukin (IL)-4, transforming growth factor beta (TGF-β) and IL-17 as well as anti-inflammatory cytokines such as interferon gamma (IFN-γ) and forkhead box P3 (FOXP3) and T helper cells 1 Th1/Th2 ratio in various conditions with disturbed immune balance. The reviewed papers showed anti-inflammatory, antioxidant and immunomodulatory effects of C. longa, indicating potential therapeutic property of the plant for treatment of inflammatory, oxidative and immune-dysregulation diseases.

Clinical Presentation and Comorbidities

Presently, the whole world is going through a historic yet a troublesome situation following COVID-19 outbreak. The clinicians have observed a wide variety of respiratory and non-respiratory clinical manifestations in COVID-19 patients. Accumulating reports revealed that the clinical features of COVID-19 may include asymptomatic/mild symptoms, neurological, cardiovascular complications, severe pneumonia and mortality. The most common features noticed are fever, dry cough, sore throat, shortness of breath, sputum production, fatigue, and myalgia. Recently, US health protection agency has also reported repeated shaking along with chills, loss of taste and smell in new case studies as additional symptoms. In addition to this, COVID-19 patients may show clinical signs like persistent pressure and pain in the chest, blue lips or face, confusion and GIT disturbances (diarrhea, nausea, vomiting and abdominal discomfort). The current ongoing pandemic has remarkably affected almost every age group of humans, starting from infants less than 3 months, adults, elder and older patients. Furthermore, the clinical presentations in these groups of COVID-19 infected patients were found to show considerable inter-individual variations. The findings also suggested that the comorbid conditions (heart injury, hyperglycemia, hypertension, neurodegenerative diseases) in elder/older patients further complicate the health of COVID-19 patients.

In the present book chapter, the clinical presentation of COVID-19 in pediatric, adults and geriatric group of population will be emphasized along with the higher susceptibility of COVID-19 in comorbid patients.

Analysis of Banana Plant (Musa balbisiana Colla) Pseudo-Stem Juice

Materials and methods for the extraction and analysis of banana plant pseudo-stem juice have been discussed. The pseudo-stem consists of nearly 95% juice and less than 5% fibers. The juice is quite rich in potassium and oxalate, moderately rich in sodium and chloride. In addition, nitrate, phosphate and a couple of heavy metals in trace concentrations have been detected. Two important bioactive organic molecules, namely (E)-4- (4-methoxyphenyl) but-3-en-2-one and (1E,4E)-1, 5-bis- 4-methoxyphenyl)penta-1,4-dien-3-one, have been isolated from the juice, and characterized.

Melatonin as an Anti-cancer Agent

Cancer is a disease that causes a huge health burden for communities. Despite the great progress made in diagnostic tools for cancer and the advancement of treatment strategies, cancer is still one of the commonest causes of death in the world. Melatonin, a hormone produced mainly by the pineal gland, possesses an anti-cancer property. The discovery of this effect of melatonin on cancer cells was a breakthrough in the field of cancer research. Several lines of evidence support this property of melatonin, including in vitro and in vivo studies and clinical trials. This effect of melatonin was examined in various types of cancer, and a consensus has been reached with regard to its oncostatic/anti-cancer effect. Multiple mechanisms have been proposed for this effect of melatonin, among which are the anti-oxidant, antiinflammatory, anti-estrogen/androgen, anti-angiogenic, and pro-apoptotic actions of melatonin. This chapter presents an account on the anti-cancer effect of melatonin, focusing on mechanisms of action by presenting examples of cancer types, including the most common types of cancer in the world: cancers of the lung, prostate, breast, and colon, as well as ovarian cancer.

A Human Touch

This chapter describes the development and potential applications of manmade stem cells called induced pluripotent stem cells (iPSC). The technology involved and the possibilities for research and therapy are described.

Genetically Modified T-cells Affinity to Tumor Cells-Development of Adoptive T-cell Immunotherapy

T-cells play an essential role in the cell-mediated immune response to tumor cells, while tumor cells in tumor sites take many strategies to evade the host immune response, including creating many immune-suppressive factors from tumor microenvironment (TME) or decreasing expression of immunogenicity of target antigens. To resolve the evasion of tumor cells from T-cells attacking, some strategies such as genetically modified T-cells altering the specificity of the T-cell receptor (TCR) or introducing antibody-like recognition of chimeric antigen receptors (CARs) have made significant advances. The modified TCR T-cells or CAR T-cells have been administered to cure B-cell lymphoma or B-lymphocyte leukemia in clinical trials successfully. We have been going to study the specificity and safety of T-cell adoptive immunotherapy for more than 30 years so that our experiences to apply for genetically modified T-cell more focus on the specificity and safety of these therapies. Moreover, the strategies using genetically modified T-cell immunotherapy need face challenges for immunogenicity from different types of tumors. The chapter will introduce T-cell specific affinity between T-cell and tumor cells such as TCR and CAR T-cells, discuss challenges from the selection of antigen targets, and address safety issues to clinical development. All in all, T-cell adoptive immunology regarding TCR and CAR T-cell improves the clinical application.

Primary Cell Culture and T-cell Cloning - Fundamental of Adoptive T-cell Immunotherapy

Tumor-associated antigen (TAA) or tumor-specific antigen (TSA) is essential for the target of tumor-specific T-cells such as tumor-infiltrating T cells (TIL), specific T-cells, TCR T-cells and CAR-T-cells for adoptive T-cell immunotherapy. The tumor cells often accumulate hundreds of mutations and harbor several immunogenic neoantigens, and thus, the repertoire of mutation or neoantigen from patient tumor cells might need the screen to uncover for engineering these T-cells. To understand the Tcell screening and determining tumor antigen-based on primary tumor cells from an individual patient, this chapter, we focus on streamlining the process of ex vivo T-cell culture and primary tumor cell culture, T-cell cloning for tumor neoantigen-specific T cells, allowing the patient to the benefit of downstream T-cell targets. Because T-cell engineering cultures are very important methods for TIL, TCR and CAR T-cells, moreover, because using primary tumor cells isolation and cultures is very important for screening and identifying tumor antigen of patients, we first introduce primary cell culture techniques, including those developed from two-dimensional (2-D) tumor cell cultures, three-dimensional (3-D) tumor cell culture and multiple dimensional tumor cell culture (4-D cultures). These methodologies are increasingly supporting clinical oncologists to apply to tumor therapeutic agents and Ag targets for patients in the clinical laboratory. Besides, we also conclude some growth factors for T-cell cloning cultures. The chapter aims to present a foundation to adoptive T cell immunotherapy of clinical patients.

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Environmental and Human Health Issues in Campania Region Italy

Waste generation rates continue to grow around the world, creating a need for more comprehensive waste management strategies to meet sustainability needs. Uncontrolled disposal generates complex and challenging situation that involves the entire population. In particular, the illegal dumping and burning of toxic waste in Campania (Italy) has caused immense environmental damage and an increase in cancer rate among the population. Different epidemiological studies were commissioned by the Ministry of Health to assess the magnitude of contamination under an illegal dump in Campania and to evaluate the population health impact. The data and other available evidence testify the dramatic situation in Caserta and Naples provinces about the severe impairment of the environmental conditions in several places and increase of cancer incidence. For this reason, the Campania region is known, such as Triangle of Death” and “Land of Fires” (LoF) (or Terra dei fuochi-TdF), as reported both in academic publications and the national press. This chapter is aimed to provide the findings regarding human health and environmental contamination in this region.

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Potential Natural Products For Prostate Cancer Management: Prospects For Castration-Resistant Patients

Prostate Cancer (PCa) is a major global health burden with alarming epidemiological indices. Research advances in this area have revealed complex molecular aspects associated with the disease, thus necessitating the novel development of diagnostic methods and therapeutic strategies. The main molecular target is the androgen receptor (AR), which is involved in both normal development and malignant transformation. However, many patients become resistant to conventional treatments, and the disease progresses to a castration-resistant stage (CRPC) in which tumor aggressiveness is driven by a constitutive activation of AR signaling. Tremendous effort has been made for elucidating CRPC and chemoresistance. In fact, multiple signaling pathways are related to the insurgence and maintenance of CRPC, highlighting the need for continuously updating such a complex scenario. Different drugs have been tested and used for CRPC treatment, facing unfavorable heterogeneity and leading to substantial morbidity and mortality. Thus, the clinical impact of advanced PCa with poorer outcomes still underscores the need for new compounds. The discovery and current use of natural products has given way to promising possibilities, offering alternative tools that aim to control the disease and to better manage patients. These natural products are versatile and effective molecules with different mechanisms of action and structures. In the present chapter, we explore the challenges of PCa and describe recent scientific contributions in this field, with special attention devoted to CRPC. We also discuss and suggest natural products as potential novel anti-tumor agents to overcome clinical limits and to treat and cure CRPC patients.

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Recent Progress of Phenazines as Anticancer Agents

Phenazines are nitrogen-containing heterocycles which possess a wide range of biological activities and in particular, cytotoxic effects. Moreover, various phenazines have been prepared having alkyl, amide, carboxylic acid, aldehyde, and pyrano groups. These synthetic phenazines possess significant anticancer effects towards various cancers. On the other hand, only a few natural phenazines have been reported with anticancer effects. This chapter presents a comprehensive overview of the most recent patents related to the phenazines as anticancer agents.

Saffron: The Golden Spice

Saffron, as one of the most expensive spices in the world, is obtained from the stigma of Crocus sativus. Crocus sativus L. belongs to the Iridaceae family, and has been widely used as an herbal medicine, spice, food coloring, and a flavoring agent since ancient times. Saffron is one of the most famous plants cultivated in Iran, and this country now accounts for approximately 90% of the world production of saffron. Saffron has a long history in Islamic Traditional Medicine (ITM). It has been used for the treatment of several diseases such as urogenital, ocular, and respiratory disorders. Moreover, it has oxytocic, anti-depressant, aphrodisiac, cardioprotective, anticarcinogenic, and anti-inflammatory properties. There are several studies on pharmacological activities of saffron in vitro, in vivo, and clinical trials which not only confirm the application of saffron in traditional medicine, but also introduce some new medicinal aspects. In this chapter, we aim to present a comprehensive review on traditional and ethnomedicinal uses of saffron in different systems of traditional medicine, especially ITM. Then, we will discuss pharmacological activities reported for saffron in modern medicine as in vitro, in vivo, and clinical trial studies. Finally, we will compare the properties reported for saffron in traditional medicine with the activities in modern medicine to reveal the potential of this valuable herb for treatment of various diseases.

An Introduction to the Recent Perspectives of Marine Pollution

Marine ecosystem covers two-thirds of the earth’s surface, and is characterized by its rich biodiversity and endemism of marine life. However, like many other ecosystems, it has been subject to diverse anthropogenic pressures, such as climate change, pollution, and biodiversity losses. In the first part of the book, we discussed the pollution dynamics of the inorganic pollutants (heavy metals, metalloids) and organic pollutants including persistent organic pollutants (POPs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), microplastics, nutrients, and algal blooms in the marine environment. Marine pollutants can have a wide range of pollution sources that are able to cause deleterious effects on marine flora and fauna. The second section of the book specifically elucidates the toxicity assessment by using marine model organisms. It provides extensive new insight into screening biomarker genes combined with advanced gene editing applications. In the last section of the book, various remedial techniques, such as bioremediation and phytoremediation, were discussed whether it could be beneficial to deal with the challenges of marine pollution.

Subcellular Localization and Physiological Roles of Androgen Receptor

Androgens, such as testosterone and Dihydrotestosterone (DHT), exert their actions through the Androgen Receptor (AR), a ligand-dependent nuclear transcription factor that belongs to the steroid hormone nuclear receptor superfamily. The actions of androgens can be mediated through the AR in a DNA binding-dependent manner to modulate the transcription of target genes, or in a manner independent of DNA binding, to trigger rapid cellular events such as the activation of the second messenger signaling pathway. The AR is expressed ubiquitously and it has a wide variety of biological actions comprising significant roles in the development and maintenance of the reproductive, skeletal muscle, cardiovascular, immune, neural and haemopoietic systems, exerting a diversity of roles in many physiological and pathological processes. Studies with AR Knockout (ARKO) mouse models, specifically the cell type- or tissue-specific ARKO models, have revealed many cell type- or tissue-specific pathophysiological roles of AR in mice. Because of the huge amount of information about androgens and the AR, this chapter is not presented as an extensive review of all of it, but rather as an overview of the expression and biological function of AR as well as its significant role in clinical medicine.

Glioblastoma Multiforme; Drug Resistance & Combination Therapy

Brain tumors are most aggressive lethal types of cancer and have been reported to have poor prognosis. Patients diagnosed with glioblastoma multiforme (GBM) have an aggressive, tough and resistant brain tumor with average survival 12 to 16 months. The most common age for diagnosis of GBM is reported to be in between 45 and 70 years. GBM arises from glial cells which are glue like supportive cells of the brain that help to maintain and protect the neurons of central and peripheral nervous system from any damage. GBM is usually treated with surgery and radiation followed by chemotherapy where temozolomide (TMZ) is a part of therapy. TMZ is an alkaline agent that destroys the glioblastoma cells by forming O6-methylgunine in DNA. TMZ is an anticancer drug popularly used sometimes along with ionizing radiation. However, one of the downsides of chemotherapy is the development of resistance against the drug which results in the failure of the treatment and hence poor prognosis. The alternate treatment strategies are being explored to prolong the survival of GBM. The treatment of GBM by using HDACi (histone deacetylase inhibitors), MGMT (O6-methylguanine DNA methyltransferase) inhibitors, beta blockers, statins, antimetabolites, and some phytotherapeutics in synergistic combinations may be beneficial for outcome. A number of drugs are being investigated in synergistic combination and will offer a substantial survival advantage in GBM patients. The present chapter discusses the synergistic combinations of mainly TMZ with various other anti-cancer or FDA approved drugs for other indications that can enhance different molecular mechanisms, increase cell death, reduce drug resistance or decrease the drug toxicity in glioblastomas.

The Role of ncRNAs in Human Cancer and its Related Patents

The development of the new sequencing technologies has unveiled a new world of regulatory non-coding RNAs (ncRNAs) that is revolutionizing our understanding of the RNA world. New transcripts with non-coding functions are being identified from most of the human genome. Although we have just started to study these ncRNAs, the broad list of regulatory functions assigned to them has assured a prominent role in the regulation of the molecular processes involved in human cancer. This chapter presents a review of the state of the art in the study of ncRNAs and their relationship with human cancer, summarizing the origin, structure and function of the most relevant new classes of ncRNAs. In addition, a selection of recent patents related to ncRNAs and human cancer is included here, analyzing their promising potential in the diagnosis and treatment of human cancer.

Anticancer Properties of Apiaceae

The aim of this book chapter was to highlight the great importance of plants from Apiaceae family as functional food products, focusing on its anticancer properties. The plants that will be discussed for their anticancer properties include: caraway (Carum carvi L.), dill (Anethum graveolens L.), anise (Pimpinella anisum L.), fennel (Foeniculum vulgare Mill.), coriander (Coriandrum sativum L.), celery and celeriac (Apium graveolens L.), lovage (Levisticum officinale Koch.), carrot (Daucus carota L.), parsley (Petroselinum crispum L.), parsnip (Pastinaca sativa L.), angelica (Angelica archangelica L.), cumin (Cuminum cyminum L.), chervil (Anthriscus sp.) and eryngo (Eryngium campestre L.). Leaves, roots and seeds of these plants are widely used as spices, flavoring agents and dietary supplements in the folk medicine and pharmaceutical industry. Furthermore, roots and leaves of these plants are valuable sources of phytochemicals used on a daily basis as food with nutraceutical potential. Their essential oils have characteristic aroma and have potent antioxidant and antimicrobial properties, which contribute to their ability to serve as natural food conservatives. Additionally, due to their anticancer, hypoglycemic, hypolipidemic, hepatoprotective and other activities these plants are widely used as alternative and healthy food for the prevention and treatment of many disorders.