Chemical Biology Letters https://pubs.thesciencein.org/journal/index.php/cbl <p>Chemical Biology Letters is a peer reviewed indexed international journal for publication of research and review articles from Medicinal Chemistry, BioChemistry, Chemical Biology, Drug Development and Drug Delivery related studies.</p> ScienceIn Publishing en-US Chemical Biology Letters 2347-9825 Clinical status of potential drugs used for COVID-19 treatment and recent advances in new therapeutics - A review https://pubs.thesciencein.org/journal/index.php/cbl/article/view/277 <p>COVID-19, a perilous disease caused by SARS-CoV-2, has brought a massive damage to humankind, and turned into a global catastrophe. It was first reported in Wuhan, China in December 2019 and since then has been a constant source of worry for the scientists and the medical world, due to the carnage it has caused globally. Extensive clinical studies are being carried to explore drug therapy and prophylaxis to combat this pestilence.&nbsp; It is still an excessively big challenge for the scientists and pharmacological industry to develop potential drugs for the treatment of this deadly virus. At present though no specific drug has been identified as a perfect cure for this zoonotic disease, medical practitioners are using the therapy of repurposing of drugs for the treatment. Systemic research was carried out through e-resources to identify drugs for the treatment of COVID-19. A recent proposal of 2-DG drug as a cure for COVID-19 has also been discussed in this review.</p> Kalpa Mandal Meenakshi Singh Charu Chandra Indraj Kumar Kumawat Copyright (c) 2021 ScienceIn Publishing 2021-09-21 2021-09-21 8 4 117 128 A comparative study of isothermal nucleic acid amplification methods for SARS-CoV-2 detection at point-of-care https://pubs.thesciencein.org/journal/index.php/cbl/article/view/274 <p>COVID-19, caused by the novel coronavirus SARS-CoV-2, has put most of the world under lockdown. Despite approved vaccines, COVID-19 cases, hospitalizations, and deaths have remained on the rise. Rapid diagnosis and necessary public health measures are still key parts to contain the pandemic. Here, the colorimetric isothermal nucleic acid amplification tests (iNAATs) for SARS-CoV-2 detection based on loop-mediated isothermal amplification (LAMP), cross-priming amplification (CPA), and polymerase spiral reaction (PSR) were designed and compared in performance for the first time. The findings showed that, for the detection of SARS-CoV-2 genomic-RNA, LAMP outperformed both CPA and PSR, exhibiting the limit of detection (LOD) of roughly 43.14 copies/reaction. The results can be read with the naked eye within 45 minutes, without cross-reactivity to closely related coronaviruses. The direct detection of SARS-CoV-2 RNA in simulated specimens by iNAATs was also successful. Additionally, the lyophilized reagents for LAMP reactions maintained the sensitivity and LOD of the liquid assays. The colorimetric LAMP assay was validated using clinical samples, showing 98.1% sensitivity and 100% specificity upon using extracted samples and 82.4% sensitivity and 86.2% specificity upon using unextracted specimens. The results indicate that the direct colorimetric LAMP assay developed is highly suitable for detecting SARS-CoV-2 at point-of-care.</p> Diem Hong Tran Hoang Quoc Cuong Hau Thi Tran Uyen Phuong Le Hoang Dang Khoa Do Le Minh Bui Nguyen Duc Hai Hoang Thuy Linh Nguyen Thi Thanh Thao Nguyen Hoang Anh Nguyen Trung Hieu Cao Minh Thang Van Van Vu Huong Thi Thu Phung Copyright (c) 2021 ScienceIn Publishing 2021-09-25 2021-09-25 8 4 106 116 Testosterone in the pathogenesis of tuberculosis https://pubs.thesciencein.org/journal/index.php/cbl/article/view/253 <p>Tuberculosis is a leading cause of death from infectious diseases worldwide with more than 1.5 million deaths occurring annually. Males have been known to be more susceptible to tuberculosis than females. Sex hormones could be an important factor governing this gender bias. Here, we discuss the evidence that testosterone may be a crucial factor in male susceptibility to tuberculosis considering that testosterone impairs important factors which have a significant bearing on the outcome of tuberculosis. We also discuss possible underlying mechanisms through which testosterone modulates the immune response that is necessary for host resistance to tuberculosis. We discuss various models that have helped to uncover the role of testosterone in the outcome of infection by <em>M. tuberculosis</em>. Studying the role of testosterone on the various components that constitute the immune response to the disease have provided valuable insights into the sexual dichotomy observed in male bias in tuberculosis morbidity.</p> Parul Shrivastava Tamishraha Bagchi Copyright (c) 2021 ScienceIn Publishing 2021-09-25 2021-09-25 8 4 238 247 Resistin and visfatin: ‘connecting threads’ of immunity, energy modulations and male reproduction https://pubs.thesciencein.org/journal/index.php/cbl/article/view/273 <p>Adipokines, mostly produced by white adipose tissues, have been established to be endocrine factors which are also essential in energy homeostasis. More recently, their contribution in fertility regulation has been recommended. Resistin as well as visfatin are unique adipocyte-derived signaling chemicals whose expressions enhance in advanced obesity and are implicated in insulin resistance as well as type-2 diabetes. They are also found to be immune modulators and may participate in aggravating inflammatory responses which may partly explain obesity-mediated systemic inflammation. They are yet much less explored adipokines with potential to regulate metabolic rate, immune homeostasis as well as fertility. These adipokines are shown to be expressed in the hypothalamus in an area in charge of energy balance. Evidence suggest that they can potentially affect the hypothalamo-pituitary-gonadal (HPG) axis thereby modulating reproductive functions. They are also found to be expressed highly by the testes. In rodents, resistin and visfatin may positively modulate Leydig cell number and steroidogenesis. Additionally, visfatin exists in the human spermatozoa and may play role in the sperm maturation. However, reports on the impact of resistin and visfatin on human male fertility are inconsistent. In this article, we review the available literature on the role resistin and visfatin on male reproduction and integrate the mechanisms to discuss if they act as sensor for body energy dyshomeostatis and modulate male reproductive functions as per the metabolic status.</p> Sulagna Dutta Pallav Sengupta Ravindran Jegasothy Roland Eghoghosoa Akhigbe Copyright (c) 2021 ScienceIn Publishing 2021-09-22 2021-09-22 8 4 192 201 Immunoendocrine regulation of energy homeostasis and male reproduction https://pubs.thesciencein.org/journal/index.php/cbl/article/view/272 <p>Human reproductive system involve a number of intricate complex interconnected physiological metabolic pathways and metabolites with involvement of overall health of different body organs. Overall health alterations mediated physiological conditions such as obesity, diabetes etc. bring about additional variations in expression and presence of metabolic constituents including kinases, hormones, proteins, peptides. The detailed analysis of various molecules like endocrine hormones, neuropeptides, immunity and inflammation associated kinases and proteins that have an end effect in cells and tissues, and might be playing a role in impacting male reproduction have been deliberated here. A deliberative collection of obesity and infertility related molecules including endocrine hormones, cytokines, adipokines, adiponectin, resistin, visfatin, ghrelin, orexins, leptin, adropin, chemerin, along with diabetes and age related physiological impact analysis on male reproductive system have been included in this selective compilation. An in-depth understanding of changes and introduction of new intermediate molecules for regulation of physiological phenomena like energy homeostasis in obesity regulation and their interlinked associated impact on the male fertility potential would provide a reflection for possible development of new therapeutics.</p> Sulagna Dutta Pallav Sengupta BS Chhikara Copyright (c) 2021 ScienceIn Publishing 2021-09-24 2021-09-24 8 4 141 143 Adiponectin: ‘a metabolic ballcock’ modulating immune responses and male reproduction https://pubs.thesciencein.org/journal/index.php/cbl/article/view/271 <p>One of the most prevalent serum adipokines, adiponectin, is well-known for its function in regulating insulin sensitivity and preventing the metabolic syndrome from developing. Adiponectin is expressed in numerous components of the testis and studies claim that adiponectin may have positive paracrine effects on testicular functions. Adiponectin, on the other hand, inhibits hypothalamic-pituitary-gonadal (HPG) axis thereby that may affect testicular testosterone production. It is a strong anti-inflammatory and antioxidant molecule that may have beneficial effects on male reproductive in addition to its metabolic functions. In obese men, reduction in adiponectin levels may partly decipher the multitudinous pathways linking obesity-mediated metabolic disturbances, inflammation, and male infertility or subfertility. This article provides an overview of the actions of adipokines in energy homeostasis, metabolic balance, inflammation, and male reproduction, hence drawing a connexon between obesity-mediated dyshomeostasis in metabolism and immune functions and male reproductive disruptions.</p> Sulagna Dutta Pallav Sengupta Srikumar Chakravarthi Tulay Irez Gul Baktir Copyright (c) 2021 ScienceIn Publishing 2021-09-22 2021-09-22 8 4 171 182 Chemerin and male reproduction: ‘a tangled rope’ connecting metabolism and inflammation https://pubs.thesciencein.org/journal/index.php/cbl/article/view/270 <p>Adipokines are peptides produced mainly by the fat tissue adipocytes and their levels are sensitive to alterations in metabolic state. While there is little known about the impact of adipokines on male reproductive control, both animal-based experimental data and clinical research suggest that they can influence numerous male fertility indices. Chemerin is a newly found adipokine which is generally recognized&nbsp;as a&nbsp;chemoattractant and chemokine. Chemerin has been correlated with inflammatory reactions and metabolic imbalances, as seen in various metabolic syndromes. A sex dimorphic chemerin expression pattern has also been shown with greater&nbsp;levels in men in comparison to women. Chemerin&nbsp;can thus be offered as a potential new candidate in the connection among metabolic disorders, inflammation&nbsp;and male reproduction. The present article explores the multidimensional metabolic and inflammatory roles of chemerin and discusses its impact upon the male reproduction.</p> Fong Fong Liew Sulagna Dutta Pallav Sengupta Bhupender S. Chhikara Copyright (c) 2021 ScienceIn Publishing 2021-09-21 2021-09-21 8 4 224 237 Orexins: the ‘multitasking’ neuropeptides in the energy metabolism and immune regulation of male reproduction https://pubs.thesciencein.org/journal/index.php/cbl/article/view/269 <p>Orexins are hypothalamus-derived neuropeptides with versatile functions. The most explored domains of orexins’ functions are their influence on the central nervous system (CNS) implicated in the regulation of sleep/wakefulness cycle, food intake behavior, energy homeostasis, and cognitive processes. Orexins reportedly bear two isoforms, orexin-A (OXA) and orexin-B (OXB), that act via their specific G protein-coupled receptor (GPCR), OX1R and OX2R. These peptides also play vital roles in various other peripheral organs where they regulate metabolism, neuroendocrine functions, blood pressure, as well as reproductive functions. Interestingly orexins also exhibit immuno-regulatory, anti-inflammatory properties and facilitate the mechanism of obesity resistance. Recent research has also shed light on significant role of orexins, in particular orexin A, in regulating reproductive functions in male since the Leydig cells, Sertoli cells, germ cells in various stages of the development, and even the epididymis and penis, manifest the OXA receptor. It will be intriguing to explore the properties of the orexins in reversing obesity, downregulation of inflammatory responses and mediation of male reproductive functions. The present article thus reviews these multitudinous properties of orexins and comprehends the possible connection among the behavioral, metabolic, anti-inflammatory functions of orexins with their roles in male reproduction.</p> Pallav Sengupta Muhjah Falah Hasan Sulagna Dutta Ravindran Jegasothy Bhupender S. Chhikara Copyright (c) 2021 ScienceIn Publishing 2021-09-21 2021-09-21 8 4 202 212 Lactobacillus casei and Bifidobacterium bifidum reduces postprandial hyperglycaemia, inhibits α-glucosidase activity and improve histology of pancreatic islets in streptozotocin induced diabetic rats https://pubs.thesciencein.org/journal/index.php/cbl/article/view/268 <p><em>Lactobacillus</em>&nbsp;and&nbsp;<em>Bifidobacteria</em>&nbsp;are generally accredited as potential anti-diabetic agents, but the mechanism of action is still not clear. This study aimed to investigate the result of administration of&nbsp;<em>Lactobacillus casei and Bifidobacterium bifidum&nbsp;</em>on α-glucosidase enzyme, postprandial blood glucose level, and histological changes that occur in the pancreatic β-cells in streptozotocin (STZ (50 mg/kg body weight)) induced diabetic rats. The experimental diabetic rats were treated with a single dose of&nbsp;<em>L. casei</em>&nbsp;and&nbsp;<em>B. bifidum</em>&nbsp;alone and combination for 28 days. The diabetic animals of a positive control group were treated with the standard hypoglycaemic drug, acarbose (10mg/kg body weight). Maltose and starch tolerance tests were performed. Treatment demonstrated significant hypoglycemic activity, lower postprandial blood glucose levels induced by maltose and starch loading in diabetic rats. The results demonstrated that&nbsp;<em>L. casei</em>&nbsp;and&nbsp;<em>B. bifidum</em>&nbsp;had α-glucosidase inhibitory activity and can reduce blood glucose level observed from the maltose and starch tolerance test. Histological analysis showed treatment prevented the function of pancreatic islets and regenerate degenerated cells.</p> Sumiran Srivastava Mansi Shrivastava Poonam Sharma Rambir Singh Copyright (c) 2021 ScienceIn Publishing 2021-09-20 2021-09-20 8 4 88 93 Leptin in Energy homeostasis, Male reproduction, and Immune regulation https://pubs.thesciencein.org/journal/index.php/cbl/article/view/266 <p>Discovery of leptin has changed the view of adipose tissue from energy storehouse to active neuroendocrine and immune organ. Adipokineleptin is a16 kDa amino acid protein, encoded by LEP gene, secreted by adipose tissue, and acts through leptin receptor which is a cytokine receptor. Leptin is a central regulator of energy homeostasis by regulating food intake, appetite, satiety and basal metabolism. Leptin acts at each level of hypothalamus pituitary gonadal axis (HPG) and has a key role in initiation, progression of pubertal events and sexual maturation. Leptin acts directly at testicular level and affects the spermatogenesis, sperm quality and capacitation thus have important role in male reproduction and fertility. Leptin receptors are present on every cell involved in innate and adaptive immunity and regulate the functions of these cells. Leptin acts as common link between energy homeostasis, reproduction, stress responses and immune system by modulating common complex neuronal circuits. Leptin is implicated in pathogenesis of multiple disorders like obesity, type 2 diabetes mellitus, Systemic Lupus Erythematosis, osteoarthritis, rheumatoid arthritis, male infertility and other chronic inflammatory disorders. Therapies based on modulating the functions of leptin can be the key area of research in future for treatment of these chronic disorders.</p> Kush Dev Singh Jarial Ritu Mahajan Nisha Kapoor Copyright (c) 2021 ScienceIn Publishing 2021-09-20 2021-09-20 8 4 183 191 In silico analysis of the role of hsa-miR-155-5p in cervical cancer https://pubs.thesciencein.org/journal/index.php/cbl/article/view/264 <p>Numerous studies have established a critical role of micro-RNAs in the transcriptional regulation of multiple genes during cancer pathogenesis. Several micro-RNAs are associated with the poor prognosis and outcome of cervical cancer implicating their potential role in therapeutic intervention. The aim of this study was to determine the role of miR-155-5p in cervical cancer by performing a meta-analysis on its expression and identifying its molecular targets and pathways based on Gene Expression Omnibus (GEO) dataset, The Cancer Genome Atlas (TCGA) dataset, and literature review. Meta-analysis confirmed the upregulation of miR-155-5p expression in cervical cancer that significantly correlated with the numbers of tumour purity and histopathological grades. By using integrated bioinformatics approach, this study demonstrates that miR-155-5p could promote cervical cancer progression through targeting the expression of <em>Sp1, EGFR, UBR4 </em>and<em> PIk3R1</em> genes. Importantly, these four genes play a crucial role in estrogen signaling pathway and choline metabolism. This study may provide future insights in revealing the mechanisms underlying pathogenesis of cervical cancer.</p> Mehreen Aftab Maryam Ghufran Dhruv Kumar Bhudev.C. Das Copyright (c) 2021 ScienceIn Publishing 2021-09-07 2021-09-07 8 4 94 105 Immune and endocrine aspects of the testis and its relation to male infertility https://pubs.thesciencein.org/journal/index.php/cbl/article/view/262 <p>Spermatogenesis and steroidogenesis are the two important functions of the testis which are controlled by the hypothalamo-pituitary-gonadal axis of the body. Presence of blood-testis barrier (BTB) in the seminiferous tubules as well as the immune components of the interstitial space also maintains remarkable immune privileged microenvironment in the testis. This helps the sperm autoantigens to escape from the immune attack. The testis also has its own innate immune defensive mechanism to combat against male reproductive tract infection. There are many local immune modulators which maintain the immune privilege and regulate the innate immune mechanism of the testis. Factors like Infection and inflammatory conditions, endocrine disruptors, heat stress, Reactive Oxygen Species, Reactive Nitrogen Species may have impact on the BTB integrity and may finally lead to immunologic infertility. An insight into biomolecules associated with spermatozoal immune mechanism may generate inputs to develop diagnostic tools and modulate fertility.</p> Silpi Acharyya Copyright (c) 2021 ScienceIn Publishing 2021-09-13 2021-09-13 8 4 144 161 Protective effect of hydroethanolic leaf extract of Parquetina nigrescens against D-galactose-induced neurotoxicity in male Wistar rats https://pubs.thesciencein.org/journal/index.php/cbl/article/view/257 <p>This study investigated the effect of hydroethanolic leaf extract of <em>Parquetina nigrescens</em> (HELEPN) on D-galactose induced neurotoxicity in male Wistar rats. Brain damage was induced by the administration of 300mg/kg b.w of D-galactose subcutaneously for six weeks while HELEPN treatments (250mg and 500 mg/kg b.w) were given orally for four weeks. After the study, rats were sacrificed and brain tissues collected for biochemical analysis. The concentrations of Advanced Glycation end products (AGEs), Tumour Necrosis Factor α (TNF-α), 8-dehydroyxguanosine (8-OHDG) and Caspase 3 activity was done using Enzyme linked immunosorbent assay (ELISA) kits.&nbsp; Levels of malondialdehyde (MDA), glutathione, Nitric oxide and activities of Acetycholinestrease (AChE), Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx) as well as DNA fragmentation index (DFI) were determined using standard techniques. HELEPN administration attenuated D-galactose-induced brain alterations through decreased MDA level and increased activities of SOD, CAT as well as elevated glutathione concentration. HELEPN also improved the activities of brain caspase 3-dependent apoptosis and AChE, TNF-α and DNA fragmentation index. The administration of HELEPN provided neuroprotection against D-galactose-induced brain damage through anti-oxidative, anti-inflammatory as well as anti-apoptotic mechanisms and these protective effects could be as a result of a profile of phytochemicals present in the plant leaves.</p> Lydia Oluwatoyin Ajayi Ademola Olabode Ayeleso Temitope Adenike Oyedepo Copyright (c) 2021 ScienceIn Publishing 2021-07-25 2021-07-25 8 4 79 87 Adropin in immune and energy balance: ‘a molecule of interest’ in male reproduction https://pubs.thesciencein.org/journal/index.php/cbl/article/view/255 <p>Adropin is a novel peptide hormone with multidimensional functionalities awaiting to be unveiled completely. This hormone is encoded by the ‘energy homeostasis-associated’ (<em>Enho</em>) gene. It is primarily produced by the liver, while to some extent by the brain, circulatory system and numerous other peripheral tissues. In the twelve years of its discovery, studies have established that adropin has essential role in body weight management, glucose and lipid balance, and is salubrious in a variety of illnesses. Exploring the potential of adropin in male infertility studies will be fascinating. Metabolic disorders, inflammation, and oxidative stress (OS) are among the main underlying mechanisms of male infertility. Since this molecule reduces body adiposity, possesses anti-inflammatory as well as antioxidant properties, it may have potential role in restoration of male fertility. In this review, we amalgamate the evidence available on physiological, metabolic, and immune functions of adropin and thereafter address the possible role of adropin in male reproduction.</p> Roland Akhigbe Sulagna Dutta Pallav Sengupta Bhupender S. Chhikara Copyright (c) 2021 ScienceIn Publishing 2021-09-22 2021-09-22 8 4 213 223 Obesity and Male Infertility: Energy Imbalance to Inflammation https://pubs.thesciencein.org/journal/index.php/cbl/article/view/254 <p>Obesity is an important health problem with an increasing frequency in the world. In recent years, obesity has been shown to be closely related to infertility in addition to causing many important additional and systemic health problems. The relationship between obesity and infertility is evaluated based on many complex mechanisms, such as inflammatory cellular response, endocrine factors released from adipose tissue, and epigenetic changes, as well as other known factors including increased scrotal temperature and hormonal imbalance. While increasing BMI negatively affects the known reproductive hormonal mechanism, on the other hand, adipose tissue acts as an endocrine organ and secretes several hormones called adipokines. These hormones affect spermatogenesis both central and testicular ways. Moreover, increased adipose tissue and BMI cause to rising scrotal temperature, and result in sperm DNA damage. Therefore, sperm DNA damage caused by both the negative effect of adipokines, increased scrotal temperature, and increased inflammatory response impairs sperm functional structure. In addition to all these factors, sexual dysfunction which develops due to hormonal imbalance as a result of excess weight and psychologic factors caused by a distorted body image, constitute an important obstacle to a healthy sexual life. As a result, obesity should be considered as a health problem that plays a role in male infertility with its multi-faceted interaction.</p> Mehmet Murad Basar A. Egemen Avci Copyright (c) 2021 ScienceIn Publishing 2021-09-13 2021-09-13 8 4 162 170