Investigating the presence of dioxins in drinking water: implications for public health.

The presence of highly toxic dioxins, specifically polychlorinated dibenzo-p-dioxins (PCDDs), in drinking water is a matter of great concern due to their long-lasting nature and harmful effects. In this study, we detected three out of the five dioxin congeners: 2, 3, 7, 8-tetrachlorodibenzodioxin (TCDD), 1, 2, 3, 7, 8-pentachlorodibenzo-p-dioxin (PeCDD), and octachlorodibenzo-p-dioxin (OCDD). The investigation revealed that three dioxins were present in water samples of winter season, while TCDD and OCDD were found in the summer season. The geometric mean concentrations of PCDDs were 229.9 ng/L (winter) and 108.4 ng/L (summer), exceeded the maximum contaminant level of 30 pg/L set by the USEPA in surface water. The estimated daily intake of PCDDs for residents through drinking water was 273.97 ng-WHO2005-TEQ/kg/days during winter and 78.875 ng-WHO2005-TEQ/kg/days during summer. Our study emphasizes the urgent need for further research on persistent organic pollutants in drinking water to safeguard public health and community well-being.

Antibiotic disposal challenges in India: investigating causes and effects.

Antibiotic resistance has become a global problem and India emerges as a key battlefield in the fight against it. While inappropriate use of antibiotics is well known, the review article deliberates a less recognized yet equally perilous facet of the crisis i.e. improper antibiotic disposal. An investigation of the sources of antibiotic pollution in Indian water bodies identifies discharge of pharmaceutical effluents, hospital waste, and agricultural runoff as major contributing factors. Furthermore, it discusses the repercussions of antibiotic pollution including those relating to human health, aquatic ecosystems, and antibiotic resistance. Reviewing the causes and consequences of improper antibiotic disposal practices emphasizes the necessity of rethinking antibiotic waste management practices. The review highlights the need for stringent rules and increased awareness, while also discussing the emerging technologies and strategies to mitigate the risks of antibiotic disposal in India.

Unveiling the future of metabolic medicine: omics technologies driving personalized solutions for precision treatment of metabolic disorders.

Metabolic disorders are increasingly prevalent worldwide, leading to high rates of morbidity and mortality. The variety of metabolic illnesses can be addressed through personalized medicine. The goal of personalized medicine is to give doctors the ability to anticipate the best course of treatment for patients with metabolic problems. By analyzing a patient's metabolomic, proteomic, genetic profile, and clinical data, physicians can identify relevant diagnostic, and predictive biomarkers and develop treatment plans and therapy for acute and chronic metabolic diseases. To achieve this goal, real-time modeling of clinical data and multiple omics is essential to pinpoint underlying biological mechanisms, risk factors, and possibly useful data to promote early diagnosis and prevention of complex diseases. Incorporating cutting-edge technologies like artificial intelligence and machine learning is crucial for consolidating diverse forms of data, examining multiple variables, establishing databases of clinical indicators to aid decision-making, and formulating ethical protocols to address concerns. This review article aims to explore the potential of personalized medicine utilizing omics approaches for the treatment of metabolic disorders. It focuses on the recent advancements in genomics, epigenomics, proteomics, metabolomics, and nutrigenomics, emphasizing their role in revolutionizing personalized medicine.

Recent advances in bioengineered scaffold for in vitro meat production.

In vitro meat production via stem cell technology and tissue engineering provides hypothetically elevated resource efficiency which involves the differentiation of muscle cells from pluripotent stem cells. By applying the tissue engineering technique, muscle cells are cultivated and grown onto a scaffold, resulting in the development of muscle tissue. The studies related to in vitro meat production are advancing with a seamless pace, and scientists are trying to develop various approaches to mimic the natural meat. The formulation and fabrication of biodegradable and cost-effective edible scaffold is the key to the successful development of downstream culture and meat production. Non-mammalian biopolymers such as gelatin and alginate or plant-derived proteins namely soy protein and decellularized leaves have been suggested as potential scaffold materials for in vitro meat production. Thus, this article is aimed to furnish recent updates on bioengineered scaffolds, covering their formulation, fabrication, features, and the mode of utilization.

Role of bacterial efflux pump proteins in antibiotic resistance across microbial species.

Efflux proteins are transporter molecules that actively pump out a variety of substrates, including antibiotics, from cells to the environment. They are found in both Gram-positive and Gram-negative bacteria and eukaryotic cells. Based on their protein sequence homology, energy source, and overall structure, efflux proteins can be divided into seven groups. Multidrug efflux pumps are transmembrane proteins produced by microbes to enhance their survival in harsh environments and contribute to antibiotic resistance. These pumps are present in all bacterial genomes studied, indicating their ancestral origins. Many bacterial genes encoding efflux pumps are involved in transport, a significant contributor to antibiotic resistance in microbes. Efflux pumps are widely implicated in the extrusion of clinically relevant antibiotics from cells to the extracellular environment and, as such, represent a significant challenge to antimicrobial therapy. This review aims to provide an overview of the structures and mechanisms of action, substrate profiles, regulation, and possible inhibition of clinically relevant efflux pumps. Additionally, recent advances in research and the pharmacological exploitation of efflux pump inhibitors as a promising intervention for combating drug resistance will be discussed.

Assessment of multidrug-resistant profile, multi-locus sequence typing and efflux pump activity in Salmonella Typhimurium isolated from hospital sewage.

Salmonella enterica serovar Typhimurium is becoming a leading cause of gastroenteritis and mortality. The use of antibiotics has increased natural resistance of S. Typhimurium to antibiotics. This study aims to isolate and characterize multi-drug-resistant (MDR) Salmonella strains from hospital sewage samples in Bhopal City, central India. The MDR isolates were characterized by molecular identification, antimicrobial resistance patterns, multi-locus sequence typing, and efflux pump activity. Specific genes (hilA, stn, invA, typh, and iroB) were used to confirm S. Typhimurium isolates. The Kirbey-Bauer method was employed to profile antimicrobial resistance using 20 antibiotics. Multi-locus sequence typing confirmed S. Typhimurium using seven housekeeping genes (aroC, dnaN, hemD, hisD, purE, sucA, and thr). Out of five strains, only four were confirmed as S. Typhimurium during MLST analysis. Efflux pump activity was determined using the ethidium bromide (EtBr) cartwheel test. Of the 160 isolates, 38 were presumptively confirmed as S. Typhimurium based on biochemical characterization, and only five MDR Salmonella strains were selected for their resistance against most antibiotics. Efflux pump activity revealed that five out of the four MDR isolates did not retain EtBr inside the cells, indicating pronounced efflux activity. Additionally, the isolated strains showed a specific correlation between the antimicrobial phenotypes and genotypes. The results of this study provide a better understanding of the characterization of S. Typhimurium serotype in Bhopal City. Future studies should focus on understanding changing antimicrobial resistance patterns, pathogenicity, and the genetic background of Salmonella serotypes. Further surveillance activities for antimicrobial-resistant Salmonella in different environmental sources should be prioritized.

From Cells to Environment: Exploring the Interplay between Factors Shaping Bone Health and Disease.

The skeletal system is an extraordinary structure that serves multiple purposes within the body, including providing support, facilitating movement, and safeguarding vital organs. Moreover, it acts as a reservoir for essential minerals crucial for overall bodily function. The intricate interplay of bone cells plays a critical role in maintaining bone homeostasis, ensuring a delicate balance. However, various factors, both intrinsic and extrinsic, can disrupt this vital physiological process. These factors encompass genetics, aging, dietary and lifestyle choices, the gut microbiome, environmental toxins, and more. They can interfere with bone health through several mechanisms, such as hormonal imbalances, disruptions in bone turnover, direct toxicity to osteoblasts, increased osteoclast activity, immune system aging, impaired inflammatory responses, and disturbances in the gut-bone axis. As a consequence, these disturbances can give rise to a range of bone disorders. The regulation of bone's physiological functions involves an intricate network of continuous processes known as bone remodeling, which is influenced by various intrinsic and extrinsic factors within the organism. However, our understanding of the precise cellular and molecular mechanisms governing the complex interactions between environmental factors and the host elements that affect bone health is still in its nascent stages. In light of this, this comprehensive review aims to explore emerging evidence surrounding bone homeostasis, potential risk factors influencing it, and prospective therapeutic interventions for future management of bone-related disorders.

Stem cells-derived in vitro meat: from petri dish to dinner plate.

Sustainable food supply to the world is possibly the greatest challenge that human civilization has ever faced. Among animal sourced foods, meat plays a starring role in human food chain. Traditional meat production necessitates high proportion of agricultural land, energy and clean water for rearing meat-producing animals; also massive emission of greenhouse gases from the unutilized nutrients of the digestive process into the environment is a major challenge to the world. Also, conventional meat production is associated with evolution and spread of superbugs and zoonotic infections. In vitro meat has the potential to provide a healthy alternative nutritious meal and to avoid the issues associated with animal slaughtering and environmental effects. Stem cell technology may provide a fascinating approach to produce meat in an animal-free environment. Theoretically, in vitro meat can supplement the meat produced by culling the animals and satisfy the global demand. This article highlights the necessity and potential of stem cell-derived in vitro meat as an alternative source of animal protein vis-a-vis the constraints of conventional approaches of meat production.

Role of air pollution in chronic kidney disease: an update on evidence, mechanisms and mitigation strategies.

Air pollution results from a variable and complex mixture of harmful gases and suspended particles and is the most worrisome of all environmental hazards. It is implicated in several non -communicable diseases and is recognized to be a public health problem. Though the initial exposure to air pollution is through the respiratory system, kidneys are thought to be exposed to higher concentrations owing to their filtration function. Chronic kidney disease is the insidious end result of several disease processes which cumulatively form a large healthcare burden, particularly in low- and middle-income countries. There is a growing body of evidence that air pollution may be a contributing factor that leads to CKD by not only its direct effects, but can also compound the effect of other factors/diseases causing kidney injury. PM2.5 exposure particularly has been implicated, although there is some evidence regarding other air pollutants as well. These pollutants are thought to act on kidneys through several interlinked systemic pathways and mechanisms which individually and collectively damage the nephrons. Long-term exposures seem to gradually diminish renal function and lead to end-stage renal disease. A thorough understanding of the mechanism of kidney injury is the key for formulating and implementing effective strategies for reducing this burden. Maintaining the air quality, promoting education, improving health quality and promotion of targeted nephroprotective measures through effective policy and research support are required in addressing this global public health problem.

Ti2C-TiO2 MXene Nanocomposite-Based High-Efficiency Non-Enzymatic Glucose Sensing Platform for Diabetes Monitoring.

Diabetes is a major health challenge, and it is linked to a number of serious health issues, including cardiovascular disease (heart attack and stroke), diabetic nephropathy (kidney damage or failure), and birth defects. The detection of glucose has a direct and significant clinical importance in the management of diabetes. Herein, we demonstrate the application of in-situ synthesized Ti2C-TiO2 MXene nanocomposite for high throughput non-enzymatic electrochemical sensing of glucose. The nanocomposite was synthesized by controlled oxidation of Ti2C-MXene nanosheets using H2O2 at room temperature. The oxidation results in the opening up of Ti2C-MXene nanosheets and the formation of TiO2 nanocrystals on their surfaces as revealed in microscopic and spectroscopic analysis. Nanocomposite exhibited considerably high electrochemical response than parent Ti2C MXene, and hence utilized as a novel electrode material for enzyme-free sensitive and specific detection of glucose. Developed nanocomposite-based non-enzymatic glucose sensor (NEGS) displays a wide linearity range (0.1 µM-200 µM, R2 = 0.992), high sensitivity of 75.32 µA mM-1 cm-2, a low limit of detection (0.12 µM) and a rapid response time (~3s). NEGS has further shown a high level of repeatability and selectivity for glucose in serum spiked samples. The unveiled excellent sensing performance of NEGS is credited to synergistically improved electrochemical response of Ti2C MXene and TiO2 nanoparticles. All of these attributes highlight the potential of MXene nanocomposite as a next-generation NEGS for on the spot mass screening of diabetic patients.

Nanosheets Based Approach to Elevate the Proliferative and Differentiation Efficacy of Human Wharton's Jelly Mesenchymal Stem Cells.

Mesenchymal stem cell (MSC)-based therapy and tissue repair necessitate the use of an ideal clinical biomaterial capable of increasing cell proliferation and differentiation. Recently, MXenes 2D nanomaterials have shown remarkable potential for improving the functional properties of MSCs. In the present study, we elucidated the potential of Ti2CTx MXene as a biomaterial through its primary biological response to human Wharton's Jelly MSCs (hWJ-MSCs). A Ti2CTx nanosheet was synthesized and thoroughly characterized using various microscopic and spectroscopic tools. Our findings suggest that Ti2CTx MXene nanosheet exposure does not alter the morphology of the hWJ-MSCs; however, it causes a dose-dependent (10-200 µg/mL) increase in cell proliferation, and upon using it with conditional media, it also enhanced its tri-lineage differentiation potential, which is a novel finding of our study. A two-fold increase in cell viability was also noticed at the highest tested dose of the nanosheet. The treated hWJ-MSCs showed no sign of cellular stress or toxicity. Taken together, these findings suggest that the Ti2CTx MXene nanosheet is capable of augmenting the proliferation and differentiation potential of the cells.

Purification and characterization of Cyclophilin: a protein associated with protein folding in Salmonella Typhimurium.

Salmonella Typhimurium (ST) is a Gram-negative zoonotic pathogenic bacterium that causes infectious disease in humans as well as in animals. It causes foodborne diarrheal or gastrointestinal illness and fever called salmonellosis, which is a leading cause of millions of deaths worldwide. Salmonellaenterica serovar Typhimurium (S. Typhimurium) during its pathogenesis take away the actin cytoskeleton of their host cells and this is the crucial step of its infection cycle. Cyclophilin A, a type of peptidyl-prolyl isomerase that's encoded by the ppiA gene in ST, plays pleiotropic roles in maintaining bacterial physiology. In this investigation, the proteomic characterization of the peptidyl-prolyl cis-trans isomerase- A (Cyclophilin A) from Salmonella Typhimurium is reported. Cyclophilin A (CypA) protein from Salmonella Typhimurium proved to be highly conserved and homologous protein sequence compared to other organisms. This protein was expressed in Escherichia coli followed by its purification in a recombinant form protein exhibited a characteristic PPIases activity (Vmax = 0.8752 ± 0.13892 µmoles/min, Km = 0.9315 ± 0.5670 µM) in comparison to control. The mass spectrometry analysis of Cyp A protein-peptide showed a highest sequence similarity with the cyclophilin protein of Salmonella. PPIases proteins (enzyme) data suggest that Ppi-A has roles in the protein folding that may be contributing to the virulence of Salmonella by isomerization of protein outline. These results suggest an active and vital role of this protein in protein folding along with regulation in Salmonella Typhimurium.

Establishment of Capra hircus somatic cells and induction of pluripotent stem-like cells.

Capra hircus (goat) induced pluripotent stem cells (giPSCs) harbor enormous scientific value and contribute to cellular agriculture, animal cloning, etc. Conventional approaches to giPSC generation suffer from complexity and low preparation efficiency. In the present study, we introduced the episomal vectors carrying the human pluripotent genes in goat somatic cells to generate the giPSC-like colonies. Initially, a simple non-enzymatic method was used to isolate the goat dermal fibroblast cells and, further, a cell line was established. Later, goat fibroblast cells were transfected with commercially available episomal vectors carrying the human pluripotent genes and successfully generated the iPSC-like colonies which exhibited the expression of goat endogenous pluripotent genes and positive staining with alkaline phosphatase. Moreover, giPS-like cells formed embryoid bodies (EBs)-like aggregates and weekly expressed the marker genes of two germ layers. Reprogramming of goat fibroblast using episomal vectors carrying human pluripotent genes could lead to the development of an efficient and time- and cost-effective approach to giPSC generation.

Holistic One Health Surveillance Framework: Synergizing Environmental, Animal, and Human Determinants for Enhanced Infectious Disease Management.

Recent pandemics, including the COVID-19 outbreak, have brought up growing concerns about transmission of zoonotic diseases from animals to humans. This highlights the requirement for a novel approach to discern and address the escalating health threats. The One Health paradigm has been developed as a responsive strategy to confront forthcoming outbreaks through early warning, highlighting the interconnectedness of humans, animals, and their environment. The system employs several innovative methods such as the use of advanced technology, global collaboration, and data-driven decision-making to come up with an extraordinary solution for improving worldwide disease responses. This Review deliberates environmental, animal, and human factors that influence disease risk, analyzes the challenges and advantages inherent in using the One Health surveillance system, and demonstrates how these can be empowered by Big Data and Artificial Intelligence. The Holistic One Health Surveillance Framework presented herein holds the potential to revolutionize our capacity to monitor, understand, and mitigate the impact of infectious diseases on global populations.

Spatiotemporal Epidemiology of Malaria in India from 2007 to 2022.

India is a major contributor to the global burden of malaria, especially Plasmodium vivax infection. Understanding the spatiotemporal trends of malaria across India over the last two decades may assist in targeted intervention. The population-normalized spatiotemporal trends of malaria epidemiology in India from 2007 to 2022 were analyzed using a geographic information system with the publicly available "malaria situation" report of the National Vector Borne Disease Control Program (NVBDCP). The NVBDCP data showed malaria cases to have steeply declined from 1.17 million in 2015 to 0.18 million cases in 2022; this is 10.1 and 18.7 fold lower than the WHO's estimate of 11.93 million and 3.38 million cases in 2015 and 2022, respectively. From 2007 to 2022, Mizoram, Meghalaya, Tripura, Odisha, Chhattisgarh, and Jharkhand consistently reported high caseloads of Plasmodium falciparum. In the same period, the P. vivax caseload was high in Arunachal Pradesh, Mizoram, Nagaland, Jharkhand, Odisha, Chhattisgarh, Goa, Daman and Diu, Dadra and Nagar Haveli, and Andaman and Nicobar Islands. The distribution of forest cover, annual rainfall, and proportion of the Scheduled Tribe population (the most underprivileged in Indian society) spatially correlated with malaria cases and deaths. Mizoram is the only state where cases were higher in 2022 than in 2007. Overall, India has made tremendous progress in controlling malaria and malaria-related deaths in the last decade. The decline could be attributed to the effective vector and parasite control strategies implemented across the country.

Deciphering the complex interplay of risk factors in type 2 diabetes mellitus: A comprehensive review.

The complex and multidimensional landscape of type 2 diabetes mellitus (T2D) is a major global concern. Despite several years of extensive research, the precise underlying causes of T2D remain elusive, but evidence suggests that it is influenced by a myriad of interconnected risk factors such as epigenetics, genetics, gut microbiome, environmental factors, organelle stress, and dietary habits. The number of factors influencing the pathogenesis is increasing day by day which worsens the scenario; meanwhile, the interconnections shoot up the frame. By gaining deeper insights into the contributing factors, we may pave the way for the development of personalized medicine, which could unlock more precise and impactful treatment pathways for individuals with T2D. This review summarizes the state of knowledge about T2D pathogenesis, focusing on the interplay between various risk factors and their implications for future therapeutic strategies. Understanding these factors could lead to tailored treatments targeting specific risk factors and inform prevention efforts on a population level, ultimately improving outcomes for individuals with T2D and reducing its burden globally.

Spatio-temporal epidemiology and associated indicators of COVID-19 (wave-I and II) in India.

The spatio-temporal distribution of COVID-19 across India's states and union territories is not uniform, and the reasons for the heterogeneous spread are unclear. Identifying the space-time trends and underlying indicators influencing COVID-19 epidemiology at micro-administrative units (districts) will help guide public health strategies. The district-wise daily COVID-19 data of cases and deaths from February 2020 to August 2021 (COVID-19 waves-I and II) for the entire country were downloaded and curated from public databases. The COVID-19 data normalized with the projected population (2020) and used for space-time trend analysis shows the states/districts in southern India are the worst hit. Coastal districts and districts adjoining large urban regions of Mumbai, Chennai, Bengaluru, Goa, and New Delhi experienced > 50,001 cases per million population. Negative binomial regression analysis with 21 independent variables (identified through multicollinearity analysis, with VIF < 10) covering demography, socio-economic status, environment, and health was carried out for wave-I, wave-II, and total (wave-I and wave-II) cases and deaths. It shows wealth index, derived from household amenities datasets, has a high positive risk ratio (RR) with COVID-19 cases (RR: 3.577; 95% CI: 2.062-6.205) and deaths (RR: 2.477; 95% CI: 1.361-4.506) across the districts. Furthermore, socio-economic factors such as literacy rate, health services, other workers' rate, alcohol use in men, tobacco use in women, overweight/obese women, and rainfall have a positive RR and are significantly associated with COVID-19 cases/deaths at the district level. These positively associated variables are highly interconnected in COVID-19 hotspot districts. Among these, the wealth index, literacy rate, and health services, the key indices of socio-economic development within a state, are some of the significant indicators associated with COVID-19 epidemiology in India. The identification of district-level space-time trends and indicators associated with COVID-19 would help policymakers devise strategies and guidelines during public health emergencies.

Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics.

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS.

Seroprevalence of scrub typhus and other rickettsial diseases among the household rodents of Mizoram, North-East India.

In the last decade, scrub typhus, a zoonotic disease has emerged as a major health concern in Mizoram, a North-East Indian state that shares international borders with Myanmar and Bangladesh. Mizoram is a biodiversity hotspot and >85% of the state is under forest cover, which provides an ideal ecological niche for the rodents and mites to transmit scrub typhus and other rickettsial infections. Using the Weil-Felix test, a serosurvey of household rodents from 41 villages spread across all the 11 districts in Mizoram was undertaken to gather important insights on their role in disease transmission. Furthermore, the chigger and flea indexes were calculated from the captured rodents. The 163 rodents captured belonged to five species; the highest numbers were from Rattus tanezumi (87), followed by Rattus rattus (41), Mus musculus (17), Suncus murinus (16), and Bandicota bengalensis (2). The rickettsial seropositivity of the captured rodents was 66.26% (108 out of 163 were positive). Among the 163 rodents, sera of 75 (46.01%), 61 (37.42%), and 73 (44.78%) were reactive to OXK, OX19, and OX2 antigens, respectively. The chigger and flea index were 17.92 and 0.16, respectively. Overall, the study has given important insights into the risk of multiple rickettsial infections that household rodents could transmit in Mizoram. These findings indicate the need for the urgent implementation of effective rodent control strategies in Mizoram.

Recent trends and advances in type 1 diabetes therapeutics: A comprehensive review.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic ß-cells, leading to insulin deficiency. Insulin replacement therapy is the current standard of care for T1D, but it has significant limitations. However, stem cell-based replacement therapy has the potential to restore ß-cell function and achieve glycaemic control eradicating the necessity for drugs or injecting insulin externally. While significant progress has been made in preclinical studies, the clinical translation of stem cell therapy for T1D is still in its early stages. In continuation, further research is essentially required to determine the safety and efficacy of stem cell therapies and to develop strategies to prevent immune rejection of stem cell-derived ß-cells. The current review highlights the current state of cellular therapies for T1D including, different types of stem cell therapies, gene therapy, immunotherapy, artificial pancreas, and cell encapsulation being investigated, and their potential for clinical translation.