Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 22, Issue 11, 2022

Endocrine disruptors are natural or man-made chemicals that interfere with the body’s endocrine system leading to hormone synthesis and production defects. These chemicals are categorized as plasticizers and cosmetic chemicals, heavy metals, phytoestrogens, pesticides, detergents, surfactants, and flame retardants. Some of the most common endocrine disruptors are dioxins, bisphenol A, phthalates, perchlorate, perfluoroalkyl, and poly-fluoroalkyl substances (PFAs), phytoestrogens, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCB), triclosan, atrazine, lead, arsenic, mercury, organophosphate pesticides, and glycol ethers. Epigenetic alterations such as DNA methylation, histone modification, and miRNA regulation have been observed to play a major role in many diseases such as cancer, neurodegenerative diseases, PCOS, cardiovascular diseases, and various other disorders. In recent times, there has been a focus on endocrine-disrupting chemicals in epigenetic alterations. This review concentrates on estrogen and androgen disrupting effects, placental, and fetal effects, thyroid disrupting effects, and transgenerational effects of endocrine disruptors.

Cancer of the female reproductive system involves abnormal cell growth that can potentially invade the peritoneal cavity resulting in malignancy and disease severity. Ovarian cancer is the most common type of gynecological cancer, which often remains undiagnosed until the later stages of the disease or until cancer has metastasized towards the peritoneum and omentum, compelling it to be a deadly disease complicating the prognosis and therapeutics. Environmental, genetics and microbial factors are the common mainsprings to the disease. Moreover, human beings harbor rich microbial diversity in various organs (gut, respiratory tract, reproductive tract, etc.) as a microbiome, crucially impacting health. Any dysbiosis in the microbial diversity or richness of the reproductive tract and gut can contribute to preconditions to develop/progress various diseases, including ovarian carcinoma. The microbiome may have a casual or associate role in ovarian cancer development, with Proteobacteria being the most dominant taxa in cancer patients and Firmicutes being the most dominant in a normal healthy adult female. A healthy estrogen-gut axis has an essential role in estrogen metabolism and utilization. However, estrobolome (Bacteriodete, Firmicutes, Actinobacteria, and Proteobacteria) dysbiosis has an indirect association with ovarian carcinoma. Microbes associated with sexually transmitted diseases also impact the induction and progression of ovarian malignancies. Altogether, the microbes and their metabolites are incidental to the risk of developing ovarian carcinoma.

The COVID-19 illness is a highly contagious disease presently affecting more than 200 countries caused by the SARS-CoV-2 coronavirus (Severe Acute Respiratory Syndrome Coronavirus-2). Persons with diabetes mellitus (DM), severe obesity, cardiovascular disease, and hypertension are more likely to be infected with COVID-19 and are at a higher risk of death. The COVID-19 pandemic is overlapping the preexisting diabetes pandemic to produce fast and very vulnerable groups of COVID-19 and diabetes patients. Evidence relating to COVID-19 and diabetes is less but continues to emerge. In this context, we present evidence identified through rapid reviews. The current manuscript aims to provide information on diabetic patients suffering from COVID-19. Consequently, diabetic people have a higher susceptibility to severe SARS-CoV- 2 infections since defects in the glucose metabolism exacerbate the COVID-19 pathogenesis. After an extensive literature survey, it can come to an end that specific care is required for diabetes patients suffering from the COVID-19 virus. COVID-19 infection in diabetic patients may lead to loss of life if immediate care is not taken. This paper gives insight into the COVID-19 disease complications relevant to diabetes and emphasizes the current information and emerging concepts for SARS-CoV-2 infections in patients with DM.

Breast cancer, even today, can cause death. Therefore, prevention and early detection are fundamental factors. The mechanisms that favour it are genetic and epigenetic, and seem to play a significant role; also, the microbiota can change estrogen levels and can induce chronic inflammation in the neoplastic site, alternating the balance between proliferation and cell death. Activated steroid hormone receptors induce transcription of genes that encode for proteins involved in cell proliferation and activate another transduction pathway, inducing cell cycle progression and cell migration. These important studies have allowed to develop therapies with selective modulators of estrogen receptors (SERMs), able to block their proliferative and pro-tumorigenic action. Of fundamental importance is also the role played by the microbiota in regulating the metabolism of estrogens and their levels in the blood. There are microbial populations that are able to promote the development of breast cancer, through the production of enzymes responsible for the deconjugation of estrogens, the increase of these in the intestine, subsequent circulation and migration to other locations, such as the udder. Other microbial populations are, instead, able to synthesize estrogen compounds or mimic estrogenic action, and interfere with the metabolism of drugs, affecting the outcome of therapies. The microbial composition of the intestine and hormonal metabolism depend largely on eating habits; the consumption of fats and proteins favours the increase of estrogen in the blood, unlike a diet rich in fiber. Therefore, in-depth knowledge of the microbiota present in the intestine-breast axis could, in the future, encourage the development of new diagnostic and therapeutic approaches to breast cancers.

Background: Non-alcoholic fatty liver disease is a common chronic liver injury disease, and its incidence is rapidly increasing across the globe, thus becoming a serious threat to human health. So far, the clinical prevention and treatment of non-alcoholic fatty liver disease mainly include single-targeted drug therapy, surgical treatment and lifestyle changes. However, these treatments cannot completely address the complex pathogenesis of non-alcoholic fatty liver disease and have various side effects. Recent studies reveal that many herbal extracts are found to have potential anti-non-alcoholic fatty liver disease activities. Objective: This paper presents a review on herbal extracts used for the treatment of non-alcoholic fatty liver disease in experimental studies to provide a theoretical basis for their clinical application in the treatment of non-alcoholic fatty liver disease and for new drug development. Methods: Scientific papers were retrieved by searching the PubMed database up to Feb 2021 using the following keywords: ‘non-alcoholic fatty liver disease’, ‘herbal extracts’ (‘flavonoids’, ‘saponins’, ‘quinones’, ‘phenolic compounds’, ‘alkaloids’, ‘polysaccharides’, ‘ginkgolide B’, ‘schizandrin B’, ‘ursolic acid’) and ‘mechanism’. Results: The pharmacological effects and mechanisms of many herbal extracts can reverse the adverse health effects of non-alcoholic fatty liver disease. Conclusion: In vitro and in vivo experimental studies indicated that herbal extracts can improve the symptoms of non-alcoholic fatty liver disease by inhibiting inflammation, antioxidant stress, improvement of lipid metabolism and insulin sensitivity and regulating intestinal bacteria flora. However, there needs to be sufficient data from human clinical trials to prove their efficacy and safety.