Endocrine disrupting chemicals: gestational diabetes and beyond.

Gestational Diabetes Mellitus (GDM) has been on the rise for the last two decades along with the growing incidence of obesity. The ubiquitous use of Endocrine-Disrupting Chemicals (EDCs) worldwide has been associated with this increase in GDM incidence. Epigenetic modifications such as DNA methylation, histone acetylation, and methylation have been associated with prenatal exposure to EDCs. EDC exposure can also drive a sustained disruption of the hypothalamus-pituitary-thyroid axis and various other signaling pathways such as thyroid signaling, PPARγ signaling, PI3K-AKT signaling. This disruption leads to impaired glucose metabolism, insulin resistance as well as ß-cell dysfunction, which culminate into GDM. Persistent EDC exposure in pregnant women also increases adipogenesis, which results in gestational weight gain. Importantly, pregnant mothers transfer these EDCs to the fetus via the placenta, thus leading to other pregnancy-associated complications such as intrauterine growth restriction (IUGR), and large for gestational age neonates. Furthermore, this early EDC exposure of the fetus increases the susceptibility of the infant to metabolic diseases in early life. The transgenerational impact of EDCs is also associated with higher vascular tone, cognitive aberrations, and enhanced susceptibility to lifestyle disorders including reproductive health anomalies. The review focuses on the impact of environmental toxins in inducing epigenetic alterations and increasing the susceptibility to metabolic diseases during pregnancy needs to be extensively studied such that interventions can be developed to break this vicious cycle. Furthermore, the use of EDC-associated ExomiRs from the serum of patients can help in the early diagnosis of GDM, thereby leading to triaging of patients based on increasing risk factor of the clinicopathological condition.

Association of indoleamine 2,3 dioxygenase, brain derived neurotrophic factor and cellular senescence in type 2 diabetes mellitus with depression: a clinical approach.

BACKGROUND AND AIM: Type 2 diabetes mellitus (T2DM) and depression are often linked. Several studies have reported the role of molecular markers either in diabetes or depression. The present study aimed at molecular level profiling of Indoleamine-2,3-dioxygenase (IDO), brain-derived neurotrophic factor (BDNF) and cellular senescence in patients with type 2 diabetes with and without depression compared to individuals with healthy controls. METHODS: A total of 120 individuals diagnosed with T2DM were enlisted for the study, with a subset of participants with and without exhibiting depression. The gene expression analysis was done using quantitative real-time PCR. RESULTS: Indoleamine 2,3 dioxygenase (p < 0.001) and senescence genes (p < 0.001) were significantly upregulated, while brain derived neurotrophic factor (p < 0.01) was significantly downregulated in T2DM patients comorbid with and without depression when compared to healthy controls. CONCLUSION: Indoleamine 2,3 dioxygenase, Brain derived neurotrophic factor and cellular senescence may play a role in the progression of the disease. The aforementioned discoveries offer significant contributions to our understanding of the molecular mechanisms that underlie T2DM with depression, potentially aiding in the advancement of prediction and diagnostic methods for this particular ailment.

Exosomal microRNAs in breast cancer: towards theranostic applications.

Breast cancer is one of the top two reproductive cancers responsible for high rates of morbidity and mortality among women globally. Despite the advancements in the treatment of breast cancer, its early diagnosis remains a challenge. Recent evidence indicates that despite the adroit use of numerous strategies to facilitate rapid and precision-oriented screening of breast cancer at the community level through the use of mammograms, Fine-needle aspiration cytology (FNAC) and biomarker tracking, no strategy has been unequivocally accepted as a gold standard for facilitating rapid screening for disease. This necessitates the need to identify novel strategies for the detection and triage of breast cancer lesions at higher rates of specificity, and sensitivity, whilst taking into account the epidemiologic and social-demographic features of the patients. Recent shreds of evidence indicate that exosomes could be a robust source of biomaterial for the rapid screening of breast cancer due to their high stability and their presence in body fluids. Increasing evidence indicates that the Exosomal microRNAs- play a significant role in modifying the tumour microenvironment of breast cancers, thereby potentially aiding in the proliferation, invasion and metastasis of breast cancer. In this review, we summarize the role of ExomiRs in the tumour microenvironment in breast cancer. These ExomiRs can also be used as candidate biomarkers for facilitating rapid screening and triaging of breast cancer patients for clinical intervention.

Secure and privacy-preserving automated machine learning operations into end-to-end integrated IoT-edge-artificial intelligence-blockchain monitoring system for diabetes mellitus prediction.

Diabetes Mellitus, one of the leading causes of death worldwide, has no cure to date and can lead to severe health complications, such as retinopathy, limb amputation, cardiovascular diseases, and neuronal disease, if left untreated. Consequently, it becomes crucial to be able to monitor and predict the incidence of diabetes. Machine learning approaches have been proposed and evaluated in the literature for diabetes prediction. This paper proposes an IoT-edge-Artificial Intelligence (AI)-blockchain system for diabetes prediction based on risk factors. The proposed system is underpinned by blockchain to obtain a cohesive view of the risk factors data from patients across different hospitals and ensure security and privacy of the user's data. We provide a comparative analysis of different medical sensors, devices, and methods to measure and collect the risk factors values in the system. Numerical experiments and comparative analysis were carried out within our proposed system, using the most accurate random forest (RF) model, and the two most used state-of-the-art machine learning approaches, Logistic Regression (LR) and Support Vector Machine (SVM), using three real-life diabetes datasets. The results show that the proposed system predicts diabetes using RF with 4.57% more accuracy on average in comparison with the other models LR and SVM, with 2.87 times more execution time. Data balancing without feature selection does not show significant improvement. When using feature selection, the performance is improved by 1.14% for PIMA Indian and 0.02% for Sylhet datasets, while it is reduced by 0.89% for MIMIC III.

Hypothyroidism in acute coronary syndrome - A prospective Indian study.

BACKGROUND: Evidence suggests that hypothyroidism may be associated with an increased risk of acute coronary syndrome (ACS). The data regarding the influence of hypothyroidism on cardiovascular disease in the Asian population is conflicting. Therefore, we undertook this study to assess the overall prevalence of hypothyroidism in Acute Coronary Syndrome (ACS) patients and determine if there is a relationship between hypothyroidism, both sub-clinical and overt and other significant risk factors of ACS in an Indian population. METHODS: We studied 487 hospitalized patients between March 2018 and February 2021 with a diagnosis of ACS to determine the prevalence of hypothyroidism, both clinical and sub-clinical and their relationship with other known coronary risk factors. Thyroid function Tests - free T3, free T4 and TSH were collected from all the patients within 24 h of their admission to the coronary care unit (CCU) of 2 major hospitals in New Delhi and Imphal (Manipur). RESULTS: Subclinical hypothyroidism was prevalent in 44 (9 %), followed by overt hypothyroidism in 25 (5.2 %). Subclinical hypothyroidism was more common in females, whereas overt hypothyroidism was more common in males. ST Elevation Myocardial Infarction (STEMI) (52 %), followed by Non-ST-Elevation Myocardial Infarction (NSTEMI) (25 %), was the commonest diagnosis at presentation. Patients with overt hypothyroidism showed a higher proportion of increased triglyceride levels. Patients with hypothyroidism had no differences in the prevalence of concomitant diabetes hypertension and other coronary risk factors. CONCLUSIONS: Patients with ACS without known thyroid disorders should be screened for hypothyroidism since it is found frequently. There might be a case to treat their thyroid dysfunction appropriately.

Prevalence and correlates of multimorbidity among patients attending AYUSH primary care settings in Delhi-National Capital Region, India.

INTRODUCTION: India has a multifaceted healthcare system and recognizes complementary and alternative systems of medicine (AYUSH) that cater to the healthcare needs of people. Multimorbidity requires frequent visits to physicians and long-term use of medications, due to which people tend to prefer AYUSH systems as they provide holistic patient-centered treatment. Hence, we aimed to estimate the prevalence of multimorbidity and assess its correlates among patients attending AYUSH primary care clinics in Delhi. METHODS: A cross-sectional study was conducted among 943 patients aged ≥ 18 years attending various AYUSH primary care clinics in Delhi from September 2021 to February 2022, employing a stratified random sampling technique. Descriptive statistics such as frequency and proportion were used to report the prevalence of multimorbidity (two or more chronic conditions in an individual out of the 33 conditions listed as per the Multimorbidity Assessment Questionnaire for Primary Care). A multivariable logistic regression assessed the association between various socio-demographic characteristics and multimorbidity, presented as an adjusted odds ratio (AOR) with a 95% confidence interval (CI). RESULTS: The prevalence of diabetes (14.7%) was found to be the highest (out of all included chronic conditions) among the patients attending various AYUSH primary care settings. The overall prevalence of multimorbidity was observed to be around 39.4%. We observed a higher likelihood of having multimorbidity among participants aged ≥ 70 years [AOR: 9.19 (95% CI: 3.75-22.54)], females [AOR: 1.57 (95% CI: 1.04-2.37)], and middle class [AOR: 2.23 (95% CI: 1.45-3.43)]. CONCLUSION: Multimorbidity was evidently prevalent across AYUSH primary care settings, which cannot be overlooked. The results suggest behavioral change communication may be aimed at older individuals, females, and the middle class.

Shigella storm and men who have sex with men: A perspective on the Indian context.

Shigellosis is one of the driving factors for extrahepatic manifestations of sexually transmitted Hepatitis-C infection, which was previously thought to affect only men who have sex with men (MSM) who were human immunodeficiency virus (HIV)-positive. Highly infectious diseases like shigellosis which has been termed as the potent factor for creating "perfect storm" of disease transmission with the conjunction of specific sexual activities between men, and HIV status is something which needs attention. Strategies such as health communication and social marketing could be utilized to enhance MSM awareness of shigellosis, and these efforts should focus on giving answers to the sorts of queries respondents pose regarding shigellosis.

Bisphenol A accelerates the vascular complications in patients with Type 2 diabetes mellitus through vascular calcification-a molecular approach.

PURPOSE: Environmental pollutant Bisphenol A (BPA) strongly interacts with insulin resistance, which leads to type 2 diabetes mellitus (T2DM). Uncontrolled glucose levels in both blood and urine develops vascular complications in T2DM patients. However, glucose-controlled diabetic patients are also affected by vascular complications due to vascular calcification, and there is a lack of clinically relevant data on BPA levels available in patients with T2DM-associated vascular complications due to vascular calcification. Therefore, we measured BPA levels in T2DM-associated vascular complications and correlated systemic BPA levels with vascular calcification-related gene expression. METHODS: This study included 120 participants with T2DM and its associated vascular complications. Serum and urinary BPA were estimated using an ELISA kit, and gene expression of the study participants in peripheral blood mononuclear cells (PBMCs) was studied with quantitative real-time PCR. RESULTS: Serum and urinary BPA levels were higher in T2DM and its associated vascular complications with CVD and DN patients compared to control. Both Serum and urinary BPA had higher significance with Sirt1 (p < 0.001, p < 0.001), Runx2 (p < 0.01, p < 0.001) and IL-1beta (p < 0.001, p < 0.02) gene expression in the study groups, but, TNF-alpha significant with Serum BPA (p < 0.04), not urinary BPA (p < 0.31). CONCLUSION: BPA levels were positively correlated with lower Sirt1 and increased Runx2 in T2DM-associated vascular complications patients. Also, higher expression of IL-1beta and TNF-alpha was observed in T2DM-associated vascular complications patients. Our study is the first to associate BPA levels with vascular calcification in patients with T2DM and its associated vascular complications.

FGF4 alleviates hyperglycemia in diabetes and obesity conditions.

Increasing evidence suggests that the brain plays a key role in glucose homeostasis, making it a potential target for the treatment of type 2 diabetes (T2D). Sun et al. recently reported that intracerebroventricular (ICV) administration of a single dose of fibroblast growth factor 4 (FGF4) can induce sustained T2D remission in mouse models in the absence of any risk of hypoglycemia.

Knowledge, attitude, and practice of menstrual blood-derived mesenchymal stem cells among female healthcare workers in India.

Introduction: Mesenchymal stem cells (MSCs) are pluripotent progenitor cells that can be differentiated into a variety of specialized cell types. Menstrual blood, such as umbilical cord blood and bone marrow stem cells, is a rich source of MSCs with proliferative properties. This research was conducted to understand the knowledge, attitude, and practice of menstrual blood donation regarding menstrual blood-derived mesenchymal stem cells (MenSCs) among female healthcare workers in India. Methodology: A cross-sectional online and offline survey was conducted at the national level between 20 November 2021 and 10 March 2022. A self-constructed semi-structured questionnaire was distributed through Google Forms on various social media platforms. The questionnaire was self-administered, and data were collected using the purposive sampling technique. Results: A total of 499 respondents completed the questionnaire. Nearly 49% of the respondents had adequate knowledge, 54% showed a positive attitude, and 45% reported adequate practices regarding menstrual blood donation and the usage of related products. The educational background, occupational status, and monthly income of the participants were found to be significantly associated with their attitude toward MenSCs. Conclusion: There is a need to promote interactive sessions on MenSCs among healthcare professionals in order to bridge the gap between general populations and the healthcare setting. Enhancing knowledge and awareness regarding the potential benefits of MenSCs would help in dissipating the age-old myths associated with menstruation and will benefit society as a whole.

Prospecting of exosomal-miRNA signatures as prognostic marker for gestational diabetes mellitus and other adverse pregnancy outcomes.

Exosomal microRNA (ExomiRs) serves as potential cargo molecules responsible for post-translation of gene expression and intracellular communication playing a vital role in acting as clinically relevant prognostic biomarkers for identifying pregnancy-associated complications in patients. ExomiRs are associated with Gestational Diabetes Mellitus (GDM) as potential targets for understanding the pathophysiology of beta-cell dysfunction. ExomiRs (ExomiR 122, ExomiR 16-5p, ExomiR 215-5p, ExomiR 450b-3p, ExomiR 122-5p) aid to act as biomarkers and regulate the progression of diabetes and its related complication. These ExomiRshave been reported to interfere with the regulation of various genes such as ZEB2, IRS1, IRS2, GLUT1, GLUT4, etc. and inhibition of several pathways like PI3K/AKT, Wnt, and mTOR signaling pathways leading to the modulation in the development of GDM affecting the clinical and pathological features of women. These ExomiRs have also been associated with other pregnancy-associated complications, including preeclampsia, hypothyroidism, pregnancy loss, and ectopic pregnancies. On the other hand, overexpression of certain ExomiRs such as Exomir-515-5p, ExomiR-221, and ExomiR-96 serve a regulatory role in overcoming insulin resistance. Taken together, the current review focuses on the prospective capabilities of ExomiRs for diagnosis and clinical prognosis of GDM women with respect to pregnancy outcomes.

Prospecting the theragnostic potential of the psycho-neuro-endocrinological perturbation of the gut-brain-immune axis for improving cardiovascular diseases outcomes.

Biological derivatives and their effective influence on psychological parameters are increasingly being deciphered to better understand body-mind perspectives in health. Recent evidence suggests that the gut-brain immune axis is an attractive theragnostic target due to its innate capacity to excite the immune system by activating monocyte exosomes. These exosomes induce spontaneous alterations in the microRNAs within the brain endothelial cells, resulting in an acute inflammatory response with physiological and psychological sequelae, evidenced by anxiety and depression. Exploring the role of the stress models that influence anxiety and depression may reflect on the effect and role of exosomes, shedding light on various physiological responses that explain the contributing factors of cardiovascular disorders. The pathophysiological effects of gut-microbiome dysbiosis are further accentuated by alterations in the glucose metabolism, leading to type 2 diabetes, which is known to be a risk factor for cardiovascular disorders. Understanding the role of exosomes and their implications for cell-to-cell communication, inflammatory responses, and neuronal stress reactions can easily provide insight into the gut-brain immune axis and downstream cardiovascular sequelae.

Awareness and Utilization of Unani Medicine among the Adult Population from East Delhi: A cross Sectional Survey.

Objectives: To assess the awareness, practice, and utilization pattern of Unani medicine among the general population of Trilokpuri, East Delhi. Materials and Methods: A cross-sectional, observational descriptive survey was conducted in New Delhi using pretested, predesigned, and structured questionnaire to assess the awareness and utilization pattern of Unani medicine on a sample size of 100 subjects. Result: Out of 100 subjects, 60% were males and 40% were females with mean age 38.96 ± 9.12 years, ranged between 18 and 65 years. The awareness about Unani medicine was found in 67% of adopted population, while 57% population among them preferred Unani system of medicine as a mode of treatment. Unani is preferred because of minimal side effects associated as reported by 47% users. On the other hand, among nonuser (n = 29), 48% population do not prefer Unani medicine because of its slow action. Very few (2.6%) users adopted Unani medicine exclusively, while most of them preferred Unani as an adjuvant with allopathic. Unani medicine is preferred mainly for the management of musculoskeletal disorders (35%), followed by GIT disorders (19%) and their related disorders. Conclusion: The awareness level regarding Unani medicine is good rather utilization of is relatively lower as compared to modern system of medicine. There is a need and scope for promotion of health education as well as improvement in the people's attitude towards Unani system of medicine.

Exosomes as Theranostic Targets: Implications for the Clinical Prognosis of Aggressive Cancers.

Exosomes are extracellular vesicles produced by various cell types and extensively distributed in physiological fluids. Because of their significant role in cancer progression, they have been a focal point for the novel cancer therapy approach. Exosomes are highly efficient at transporting proteins, RNAs, and small drugs into cancer cells for therapeutic purposes. In addition to their prominent role as potential biomarkers for transporting targeted information from their progenitor cells, exosomes have also emerged as a new avenue for developing more effective clinical diagnostics and therapeutic techniques, also known as exosome theranostics. Lipids, proteins, and nucleic acids transported by exosomes were investigated as potential biomarkers for cancer diagnosis, prognosis, and future cancer treatment targets. The unique mechanism of exosomes and their therapeutic as well as diagnostic uses, also known as theranostic applications of exosomes in malignancies, are discussed in this review.

Urinary concentration of endocrine-disrupting phthalates and breast cancer risk in Indian women: A case-control study with a focus on mutations in phthalate-responsive genes.

BACKGROUND: Phthalates are known endocrine-disrupting chemicals used indiscriminately as constituents in consumer products including food processing, and packaging, cosmetics, personal care and household items. Although, few studies have assessed the risk of breast cancer on exposure to phthalates, their association with breast cancer risk in Indian women have not yet been evaluated. METHODS: We conducted a case-control study involving 171 participants. Urinary concentrations of six phthalate dieters; DMP (Dimethyl phthalate), DEP (Diethyl phthalate), DBP (Dibutyl phthalate), BBP (benzyl butyl phthalate), DEHP (Di-2-ethyl-hexyl phthalate), DINOP (Di-n-octyl phthalate) were estimated by GC-MS and geometric means were calculated. Univariate and multivariable logistic regression was performed to assess breast cancer risk on exposure to phthalates. Genes responsive to phthalates were identified through literature search and matched with NGS data, and gene-enrichment analysis was performed. RESULTS: Significant associations were observed between urinary phthalate concentrations and increased risk of breast cancer for di-butyl phthalate (OR=1.5, 95% CI; 1.06, 2.11, p = 0.002) and di-2-ethyl-hexyl phthalate (>median vs ≤ median; OR=2.97, 95% CI; 1.18, 7.47, p = 0.005) in multivariable analyses. We also found several phthalate-responsive gene mutations in paired breast tumor tissues, which include PTPRD (76.19%), AR (42.86%), CYP1A1 (42.86%), CYP19A1 (23.81%), AHRR (19.05%), PIK3CA (19.05%), CYP1B1 (9.52%), RB1 (9.52%) and MMP9 (9.52%). Gene-enrichment analysis revealed that these genes form a major part of ER/PR, PPAR and HIF-1α-TGF-ß signaling cascades involved in breast cancer CONCLUSION: Although the sample size is small, in this first case-control study from India, DBP and DEHP were found to be associated with increased risk of invasive breast cancer and tumor tissues revealed mutations in several phthalate-responsive genes. It is, therefore suggested that human biomonitoring in India and larger studies evaluating the early life genetic and epigenetic alterations on phthalates exposure are required to establish their role in breast carcinogenesis.