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Research on polycystic ovarian syndrome (PCOS) remains intense due to its evolving impact on metabolism, reproduction and cardiovascular function. Changes in metabolic pathways can also significantly impact renal function including the development of Focal Segmental Glomerulosclerosis (FSGS), one of the most highly investigated renal diseases. In FSGS, scarring of the glomerulus vascular tuft damages the kidneys. Onset of FSGS may either be congenital or due to other disorders that affect the metabolism and normal kidney function. Both PCOS and FSGS appear to be associated with Transforming Growth Factor-β (TGF-β) signalling. Over-expression of TGF-β may be due to the activation of the thrombospondin 1 (TSP1) gene, which increases the probability of developing renal disorders. Higher androgen levels in PCOS may also cause podocyte damage thus directly impacting development of FSGS. This article reviews the role of TGF-β's in PCOS and FSGS and explores the inter-relationship between these two disorders.

Fatty liver disease (FLD) is one of the largest burdens to human health worldwide and is associated with gut microbiome and metabolite stability. Engineered liver tissues have shown promise in restoring liver functions in non-alcoholic FLD (NAFLD), hepatitis and cirrhosis. Fatty liver, largely noted in obesity and hepatic cancer, is highly fatal and has led to a global increase in death rates. It is associated with complex metabolic reprogramming too. A standard approach to therapy in the newly diagnosed setting includes surgery or identification of biomarkers/ metabolites for therapeutic purposes, which ultimately focus on improvement of liver health in patients. As such there are no standard procedures for patient care, but depending on the severity, systemic therapy with either genomic, proteomic or metabolomic profiling form potential options. Better comparisons and study of underlying mechanisms in gut microbiome-based metabolic functions in obesity are urgently required. Today, an emerging field, focusing on metabolomic approaches and metabolic phenotyping, involved in high-throughput identification of metabolome in obesity and gut disorders, is involved in biomarker and metabolite identification. There are supporting technologies and approaches in NAFLD that throw light on the metabolites and gut microbiome, and also on the understanding of the risk factors of obesity along with liver cancer metabolic reaction networks. We discuss the current state of NAFLD metabolites, gut micro-environmental changes, and the further challenges in digital metabolomics profiling. Innovative clinical trial designs, with biomarker-enrichment strategies that are required to improve the outcome of NAFLD in patients are also discussed.

The pandemic of coronavirus disease 2019 (COVID-19) still remains on an upsurge trend. The second wave of this disease has led to panic in many countries, including India and some parts of the world suffering from the third wave. As there are no proper treatment options or remedies available for this deadly infection, supportive care equipment's such as oxygen cylinders, ventilators and heavy use of steroids play a vital role in the management of COVID-19. In the midst of this pandemic, the COVID-19 patients are acquiring secondary infections such as mucormycosis also known as black fungus disease. Mucormycosis is a serious, but rare opportunistic fungal infection that spreads rapidly, and hence prompt diagnosis and treatment are necessary to avoid high rate of mortality and morbidity rates. Mucormycosis is caused by the inhalation of its filamentous (hyphal form) fungi especially in the patients who are immunosuppressed. Recent studies have documented alarming number of COVID-19 patients with mucormycosis infection. Most of these patients had diabetes and were administered steroids for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and were consequently more prone to mucormycosis. Hence, the present review emphasizes mucormycosis and its related conditions, its mechanism in normal and COVID-19 affected individuals, influencing factors and challenges to overcome this black mold infection. Early identification and further investigation of this fungus will significantly reduce the severity of the disease and mortality rate in COVID-19 affected patients.

Doxorubicin is an extensively applied anti-cancerous drug since 1950′s and its usage is constrained because of its accumulation in a non-cancerous organ. Many studies have proven that doxorubicin causes reproductive toxicity depends on its dosage, particularly due to increased oxidative stress and apoptosis. A number of the researches have been carried out concerning its prevention. But there is a need to recognize the mechanism at the back of its toxicity to get better and improved method of treatment. To clarify the feasible mechanism of doxorubicin-mediated reproductive toxicity in rats, we have administrated doxorubicin at distinct dosages inclusive of low dosage (male rats that are at 230–250 g acquired cumulatively 1.5 mg/kg; ip; once per week for five weeks) and high dosage (male rats which are at 230–250 grams obtained cumulatively 15 mg/kg; ip; once every week for five weeks). Doxorubicin decreases antioxidant level such as GSH, Cu/Zn SOD, Mn SOD both in serum and testes. Increased oxidative stress is considered via elevated MDA level both in serum and testes. The level of ROS is measured via the DCFDA method in testes. Apoptosis become found through DNA fragmentation assay and quantification of Caspase 3, Caspase 9, Bcl2 and Cytochrome C. Doxorubicin mediated oxidative stress and apoptosis in testicular milieu is through deregulation of Nrf2, PGC-1α, AHR, ARNT, PXR, SUMO-1, UCP2, UCP3, ANX A5, Caspase 3, Caspase 9, Bcl2, Cytochrome C, GR, and GPX. In end, doxorubicin-mediated oxidative stress and apoptosis is through diverse transcriptional factors and genes with respect to decreased antioxidant level, augmented ROS level and Annexin A5 in the testicular milieu.

Arsenic is a ubiquitous metalloid compound commonly found in the environment, and it is usually found in combination with sulphur and metals. Arsenic is considered as a therapeutic as well as poisoning agent since ancient times. It causes toxic effects on different organs, mainly the liver. In this review, we focused on the molecular mechanism of arsenic-induced hepatotoxicity. Here we envisaged the bridge between arsenic and hepatotoxicity with particular focus on the level of hepatic enzymes such as ALT, AST, and ALP. Here, we attempted to elucidate the role of arsenic in redox imbalance on increased oxidative stress (elevated level of ROS, MDA and NO) and decreased antioxidant levels such as reduced GSH, catalase, and SOD. Oxidative stress induces mitochondrial dysfunction via apoptosis (AKT-PKB, MAPK, PI3/AKT, PKCδ-JNK, AKT/ERK, p53 pathways), fibrosis (TGF-β/Smad pathway), and necrosis and inflammation (TNF-α, NF-ĸB, IL-1, and IL-6). Along with that, arsenic activates caspases and Bax, decreases Bcl2 through mitochondrial dysfunction, and induces apoptosis regulatory mechanism. We believe the alteration of all these pathways leads to arsenic-induced hepatotoxicity.

Human coronaviruses, especially COVID-19, is an emerging pandemic infectious disease with high morbidity and mortality. Coronaviruses are associated with comorbidities, along with the symptoms of it. SARS-CoV-2 is one of the highly pathogenic coronaviruses that causes a high death rate compared to the SARS-CoV and MERS. In this review, we focused on the mechanism of coronavirus with comorbidities and impairment in multi-organ function. The main dysfunction upon coronavirus infection is damage to alveolar and acute respiratory failure. It is associated with the other organ damage such as cardiovascular risk via an increased level of hypertension through ACE2, gastrointestinal dysfunction, chronic kidney disease, diabetes mellitus, liver dysfunction, lung injury, CNS risk, ocular risks such as chemosis, conjunctivitis, and conjunctival hyperemia, cancer risk, venous thromboembolism, tuberculosis, aging, and cardiovascular dysfunction and reproductive risk. Along with this, we have discussed the immunopathology and coronaviruses at a molecular level and therapeutic approaches for the coronavirus infection. The comorbidities and multi-organ failure of COVID-19 have been explained at a molecular level along with the base of the SARS-CoV and MERS-CoV. This review would help us to understand the comorbidities associated with the coronaviruses with multi-organ damage., Graphical abstract Unlabelled Image

Adipose dysfunction is tightly associated with hepatic insulin resistance and steatosis condition. Doxorubicin would disturb the lipid metabolism both in adipose and liver. Here we projected that doxorubicin would impede lipogenesis and elevated lipolysis in adipose tissue would elevate the circulatory lipid profile and leads to insulin resistance. Further exacerbated lipid profile in circulation would impair the lipid metabolism in hepatic tissue which leads to fatty liver condition and consequently related disease during doxorubicin treatment. Doxorubicin impairs the lipogenesis through PPARγ and augments lipolysis and fatty acid oxidation through ATGL and PPARα in adipose tissue. Increased fatty acid level by adipose tissue in circulation would translocate into the liver and dysregulates AHR, PXR, PPARγ, ATGL and Apo B,which further develop insulin resistance and hepatic steatosis condition. The findings add to the mechanistic role of association between adipose tissue dysfunction and hepatic dysfunction.

Arsenic is a natural metalloid found in abundance, in the environment. Exposure to arsenic can cause health issues due to its carcinogenic nature. The primary source of arsenic contact is drinking water. Exposure to arsenic in drinking water can cause reproductive dysfunction in males through a reduction in testes weight, accessory sex organ weight, viability, and motility of sperm, epididymal sperm count, decreased gonadotrophins level, decreased testosterone, and steroidogenesis disruption. This review focuses on the mechanisms by which arsenic impairs the quality of semen, based on epidemiological observations in humans, and experimental studies in different biological research models. Arsenic-mediated male reproductive toxicity can be induced by various mechanisms such as inhibition of spermatogenesis, testosterone pathway hinderance, oxidative stress, inflammation, genotoxic effects, activation of heat shock proteins, and activation of a signaling pathway in testes (ERK/AKT/NF-kB signaling pathway), among others. The interplay between the principal mechanisms involved needs to be elucidated further in future since an overall examination of arsenic-mediated male reproductive toxicity is still a deficit.

Exposure to arsenic in drinking water can stimulate a diverse number of diseases that originate from impaired lipid metabolism in adipose and glucose metabolism, leading to insulin resistance. Arsenic inhibits differentiation of adipocyte and mediates insulin resistance with diminutive information on arsenicosis on lipid storage and lipolysis. This review focused on different mechanisms and pathways involved in adipogenesis and lipolysis in adipose tissue during arsenic-induced diabetes. Though arsenic is known to cause type2 diabetes through different mechanisms, the role of adipose tissue in causing type2 diabetes is still unclear. With the existing literature, this review exhibits the effect of arsenic on adipose tissue and its signalling events such as SIRT3- FOXO3a signalling pathway, Ras -MAP -AP-1 cascade, PI(3)-K-Akt pathway, endoplasmic reticulum stress protein, C/EBP homologous protein (CHOP10) and GPCR pathway with role of adipokines. There is a need to elucidate the different types of adipokines which are involved in arsenic-induced diabetes. The exhibited information brings to light that arsenic has negative effects on a white adipose tissue (WAT) by decreasing adipogenesis and enhancing lipolysis. Some of the epidemiological studies show that arsenic would causes obesity. Few studies indicate that arsenic might induces lipodystrophy condition. Further research is needed to evaluate the mechanistic link between arsenic and adipose tissue dysfunction which leads to insulin resistance.

Background Epilepsy is one of the most prevalent neurological disorders. Around 50 million people worldwide suffer from Epilepsy, 85% of them are from the developing countries. It is a most significant as well as common brain disorder worldwide. Sodium channel alpha 1 subunit gene (SCN1A) is most commonly mutated the gene in different forms of epilepsy. Objective To screen the genomic damage and SCN1A gene mutation in patients with epilepsy. Methods To screen the genetic instability of SCN1A gene using Buccal micronucleus cytome (BMCyt) assay and molecular analysis with Single Strand Conformation Polymorphism (SSCP) technique was used to observe the variations in SCN1A gene. Results We found significant differences in buccal cells of patients than controls. So, we can interpret that BMCyt assay would be a minimally invasive biomarker to detect DNA damage and mutation screening in the SCN1A gene with SSCP technique showed no variation in epileptic patients. Conclusion These data confirmed that there is certainly DNA damage and no mutations in the SCN1A gene; hence the genetic instability has occurred in epileptic patients.

Diabetic cardiomyopathy is one of the life threatening complications of diabetes. A number of animal models are being used for studying diabetic cardiomyopathy. In laboratory animal models, induction of cardiomyopathy happens in two stages: first being the induction of diabetic condition and the second being the induction of cardiomyopathy by prolonging diabetic condition. It takes a longer time to develop diabetes with the limited success rate for development of cardiomyopathy. Adriamycin is an effective anti-cancer drug limited by its major side-effect cardiomyopathy. A number of features of Adriamycin treatment mimics diabetes. We postulate that Adriamycin-induced cardiomyopathy might be used as a model system to study diabetic cardiomyopathy in rodents since a number of features of both the cardiomyopathies overlap. Left ventricular hypertrophy, systolic and diastolic dysfunction, myofibrillar loss, and fibrosis are hallmarks of both of the cardiomyopathies. At the molecular level, calcium signaling, endoplasmic reticulum stress, advance glycation endproduct activation, mitochondrial dysfunction, inflammation, lipotoxicity and oxidative stress are similar in both the cardiomyopathies. The signature profile of both the cardiomyopathies shares commonalities. In conclusion, we suggest that Adriamycin induced cardiomyopathic animal model can be used for studying diabetic cardiomyopathy and would save time for researchers working on cardiomyopathy developed in rodent using the traditional method.

Chemotherapeutic antibiotic doxorubicin belongs to the anthracycline class, slaughters not only the cancer cells but also non-cancerous cells even in the non-targeted organs thereby resulting in the toxicity. The liver is primarily involved in the process of detoxification and this mini-review we focused mainly to investigate the molecular mechanisms heading hepatotoxicity caused due to doxorubicin administration. The alterations in the doxorubicin treated liver tissue include vacuolation of hepatocytes, degeneration of hepatocyte cords, bile duct hyperplasia and focal necrosis. About the literature conducted, hepatotoxicity caused by doxorubicin has been explained by estimating the levels of liver serum biomarkers, ROS production, antioxidant enzymes, lipid peroxidation, and mitochondrial dysfunction. The liver serum biomarkers such as ALT and AST, elated levels of free radicals inducing oxidative stress characterized by a surge in Nrf-2, FOXO-1 and HO-1 genes and diminution of anti-oxidant activity characterized by a decline in SOD, GPx, and CAT genes. The augmented levels of SGOT, SGPT, LDH, creatine kinase, direct and total bilirubin levels also reveal the toxicity in the hepatic tissue due to doxorubicin treatment. The molecular insight of hepatotoxicity is mainly due to the production of ROS, ameliorated oxidative stress and inflammation, deteriorated mitochondrial production and functioning, and enhanced apoptosis. Certain substances such as extracts from medicinal plants, natural products, and chemical substances have been shown to produce an alleviating effect against the doxorubicin-induced hepatotoxicity are also discussed.

Highlights • COVID-19 is associated with the comorbidities such as male reproductive dysfunction • COVID-19 patients connected with the male reproductive dysfunction have decreased spermatogenesis, attenuated levels of testosterone via altering the cytokines such as TNF-α, IL-4, IL-6, and IL-12. • Inflammation is one of the causes of COVID-19 linked to male reproductive dysfunction through TNF-α and interferon. • IL-4 activated by the Th2 cells would trigger the JAK-STAT signaling and Batf/Irf4, and Bach2/Batf pathway • Augmented Th2 cells by the COVID-19 alters the IL-4, JAK-STAT signaling, and leads to male reproductive dysfunction., COVID-19 is a present-day complex pandemic infection with unpredictable levels of morbidity and mortality in various global populations. COVID-19 is associated with the different comorbidities with its change in biological function such as causing heart dysfunction via deregulating ACE-2 receptor, gastrointestinal risk via causing vomiting, diarrhea, and abdominal pain, chronic kidney disease via proteinuria and hematuria, diabetes mellitus, liver injury via increasing ALT, AST and bilirubin level, lung injury, CNS risk, ocular risk, and cancer risk. In this, we are focused on the COVID-19 connected with male infertility. Some of the studies show that the patients of COVID-19 are associated with impaired spermatogenesis. Impaired spermatogenesis via COVID-19 decreases the level of testosterone by disturbing cytokines such as TNF-α, IL-4, IL-6, and IL-12 and further, attenuates the sperm count. COVID-19 is causing inflammation via TNF-α and interferons. IL-4 plays an eminent role in the activation of the JAK-STAT pathway and leads to the disturbing pro-inflammatory cytokine as well as further cause’s male infertility. Th2 activates the IL-4 through IgG and IgE and mediates apoptosis with the triggering of STAT signaling. The activated STAT signaling augments Batf/Irf4, and the Bach2/Batf pathway. On the other hand, SARS-CoV-2 is activating the level of Th2 cells. So, we hypothesized that the augmented Th2 cells would disturb the level of IL-4, JAK-STAT signaling, Batf/Irf4, and Bach2/Batf pathway. The disturbed IL-4 decreases the level of the ACE-2 with the inflammation. This further leads to male infertility in COVID-19 patients. So, in this hypothesis, we focused on the role of IL-4 in COVID-19 patients associated with male infertility via Th2 cells and JAK-STAT signaling.

Fruits have important bioactive and dietary components ingredients of our everyday life that plays a major role to cure diseases. Inadequate intake of antioxidant and improved reactive oxygen species is associated with diabetes mellitus. Many of the components were proved to be succeeding to treat several chronic diseases like cancer, cardiovascular, obesity, and diabetes. Fruits which have listed here have dietary fiber which reduces diabetes and cardiac and other diseases also. Fruits like Momordica cymbalaria, Pongamia pinnata, Diospyros peregrina, Xylopia aethiopica, Ficus deltoidea, Prunus avium, Trapa natans, Terminalia pallida and Punica granatum. The fruit aqueous extract of Momordica cymbalaria exposed significant antihyperlipidemic as well as antihyperglycemic administered orally at 0.5 g/kg for six weeks by alloxan-induced diabetic rats. In Pongamia pinnata fruits, compounds called pongamal and karanjin was administered using streptozotocin diabetic rats which decreases the blood glucose level at the dosage of 50 mg/kg for 11.7 and 12.8%, 20.7% at 100 mg/kg individually post oral administration of six hours. An edible fruit of Diospyros peregrina streptozotocin-nicotinamide induced type 2 diabetes was achieved in aqueous extract decreases the blood glucose level at the dosage of 50 and 100 mg/kg body weight for twenty-eight days. Xylopia aethiopica acetone fraction of ethanol extract was investigated for type 2 diabetes. Streptozotocin was induced by single intraperitoneal injection and animals were treated orally at the dosage of 150 or 300 mg/kg body weight for 4 weeks reduces blood glucose level. Ficus deltoidea fruit was carried out with crude aqueous extract and fractions were estimated for sugars, phenol, protein and flavonoid content. Antidiabetic activity was carried out in water fraction using alpha-glucosidase assay reveals the highest amount of protein 73.33 ± 4.99 μg/mg. Ethanol extract (200 mg/kg) of Prunus avium fruit was administered orally by single intraperitoneal injection using alloxan induced (120 mg/kg) rats which decrease blood glucose level. Trapa natans fruit peel of methanol extract was evaluated for antidiabetic activity by streptozotocin (100 and 200 mg/ kg body weight) induced a diabetic rat which decreases blood glucose level. Terminalia pallida ethanol fruit extract was given intraperitoneal injection using alloxan (150 mg/kg body weight) monohydrate induced for diabetic rats model. Blood glucose levels were significant to at the dosage of 0.5 g/kg body weight. The aqueous ethanol extract of Punica granatum juice sugar for diabetic rats for ten days. Significantly reduces the blood sugar level, total peroxide level, and peritoneal macrophages. The aim of this book chapter reveals that fruit is considered as one of the important dietary ingredients. It has a vital significant role to control and to treat type 1 and type 2 diabetes mellitus. Henceforth, encouraging adherence of mentioned fruits was considerable significance to public health.

Doxorubicin is utilized for anti-neoplastic treatment for several decades. The utility of this drug is limited due to its side effects. Generally, doxorubicin toxicity is originated from the myocardium and then other organs are also ruined. The mechanism of doxorubicin is intercalated with the DNA and inhibits topoisomerase 2. There are various signalling mechanisms involved in doxorubicin cardiotoxicity. First and foremost, the doxorubicin-induced cardiotoxicity is due to oxidative stress. Cardiac mitochondrial damage is supposed after few hours following the revelation of doxorubicin. This has led important new uses for the mechanism of doxorubicin-induced cardiotoxicity and novel avenues of investigation to determine better pharmacotherapies and interventions for the impediment of cardiotoxicity. The idea of this review is to bring up to date the recent findings of the mechanism of doxorubicin cardiomyopathies such as calcium dysregulation, endoplasmic reticulum stress, impairment of progenitor cells, activation of immune, ubiquitous system and some other parameters.

Many male infertility cases are because of genetic and environmental factors and most of them are idiopathic. About 10-20% of azoospermic patients are showing the microdeletion in Y-chromosome. The azoospermia factor or AZF region at the Yq11 position which consists of genes those are necessary for spermatogenesis. In Y chromosome microdeletion, deletion in AZFa region is very rare. The aim of our study is to find out the frequency of microdeletions in Y chromosome particularly in AZFa region in azoospermic men of Vellore cohort. For this study, we collected 10 azoospermic patient and 10 control men samples from the Sandhya hospital, Vellore. In this study, we mainly focused on AZFa region to analyze the frequency of microdeletions in Y chromosome using SY82 (264bp) and SY83 (275bp) STS markers. There was an absence of microdeletion in patient samples for SY82 and SY83 markers of AZFa region. We concluded that sample size should be increased to confirm our results.

Polycystic Ovarian syndrome (PCOS) is a major cause of infertility in females of reproducing age and is typified by oligo-anovulation, hyperandrogenism, hirsutism and polycystic ovaries. FSHR gene located on chromosome 2 p21 is responsible for the normal follicular development and any deletion or mutation in the gene affects the interaction of FSH with its receptor. Thus, it becomes the candidate gene for PCOS study. Inactivating mutation in FSHR gene limits the receptor's function by creating a complete block, changing the receptor-ligand complex or the basic hormone signal transduction.To screen the inactivating mutations in Exon 6 and Exon 10E of FSHR gene in women diagnosed with PCOS.PCR-RFLP analysis indicated that there were no inactivating mutations found in Exon 6 and Exon 10E. Variations in hormone levels were seen amongst the PCOS patients. There were no inactivating mutations found in FSHR gene of the women diagnosed with PCOS according to the Rotterdam criteria in Vellore population.