Phage therapy: an alternative treatment modality for MDR bacterial infections.

The increasing global incidence of multidrug-resistant (MDR) bacterial infections threatens public health and compromises various aspects of modern medicine. Recognising the urgency of this issue, the World Health Organisation has prioritised the development of novel antimicrobials to combat ESKAPEE pathogens. Comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli, such pathogens represent a spectrum of high to critical drug resistance, accounting for a significant proportion of hospital-acquired infections worldwide. In response to the waning efficacy of antibiotics against these resilient pathogens, phage therapy (PT) has emerged as a promising therapeutic strategy. This review provides a comprehensive summary of clinical research on PT and explores the translational journey of phages from laboratory settings to clinical applications. It examines recent advancements in pre-clinical and clinical developments, highlighting the potential of phages and their proteins, alone or in combination with antibiotics. Furthermore, this review underlines the importance of establishing safe and approved routes of phage administration to patients. In conclusion, the evolving landscape of phage therapy offers a beacon of hope in the fight against MDR bacterial infections, emphasising the imperative for continued research, innovation and regulatory diligence to realise its full potential in clinical practice.

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.

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.

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.

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.

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.

Molecular surveillance of dengue virus in field-collected Aedes mosquitoes from Bhopal, central India: evidence of circulation of a new lineage of serotype 2.

Introduction: Dengue fever is hyperendemic in several Southeast and South Asian countries, including India, with all four serotypes (DENV 1-4) circulating at different periods and in different locations. Sustainable and improved virological and entomological surveillance is the only tool to prevent dengue and other vector-borne diseases. Objectives: The present study has been carried out to detect and characterize the circulating dengue virus (DENV) in field-collected Aedes mosquitoes in Bhopal, Central India. Methods: Aedes mosquitoes were collected from 29 localities within Bhopal city during October 2020 to September 2022. DENV infection was assessed in the individual head and thorax regions of Aedes mosquitoes using reverse transcriptase PCR. Positive samples were sequenced, and the circulating serotypes and genotypes were determined using phylogenetic analysis. Results: DENV RNA was detected in 7 Aedes aegypti and 1 Aedes albopictus, with infection rates of 0.59 and 0.14%, respectively. Phylogenetic analysis revealed all the isolates belonged to DENV serotype 2 and distinctly clustered with the non-Indian lineage (cosmopolitan genotype 4a), which was not recorded from the study area earlier. The time to most common recent ancestor (TMRCA) of these sequences was 7.4 years old, with the highest posterior density (HPD) of 3.5-12.2 years, indicating that this new lineage emerged during the year 2014. This is the first report on the DENV incrimination in both Ae. aegypti and Ae. albopictus mosquitoes collected from Bhopal, Central India. Conclusion: The observed emergence of the non-Indian lineage of DENV-2 in Bhopal, which again is a first report from the area, coincides with the gradual increase in DENV cases in Bhopal since 2014. This study emphasizes the importance of DENV surveillance and risk assessment in this strategically important part of the country to decipher its outbreak and severe disease-causing potential.

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.

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.

Dexamethasone induces cancer mitigation and irreversible senescence in lung cancer cells via damaging cortical actin and sustained hyperphosphorylation of pRb.

Activation of the glucocorticoid receptors by its cognate ligand, dexamethasone (DEX) is commonly used as an adjuvant treatment in solid tumors. However, its direct effect on cancerous phenotype is not fully understood. We explored the effect and molecular mechanisms of DEX action in lung cancer. In in vitro experiments, DEX treatment causes decrease in migration, invasion and colony formation ability of A549 cells even at lower doses. DEX also decreased adhesion of A549 cells by reducing the formation of cortical actin. Treatment with RU486, a GR antagonist, indicated that these effects are partially mediated through GR. Further; DEX induces G0/G1 arrest of A549 cells. Mechanistically, DEX induces expression of both CDK inhibitors (p21Cip1, p27Kip1) and cyclin-dependent kinases (CDK4, CDK6). Due to this compensatory activation of CDKs and CDKIs, DEX induces the hyper phosphorylation state of Rb protein (pRb) leading to irreversible senescence as confirmed by ß-gal staining. Next, in clinical dataset of NSCLC (Non-small cell lung cancer), GR was lowly expressed in cancer patients as compared to the normal group, where higher expression of GR led to higher overall survival of NSCLC indicating for a protective role of GR. Interestingly, when combined with chemotherapeutic agents, DEX can modulate the drug-sensitivity of cells. Taken together, these data indicate that DEX through GR activation may suppress tumor growth by decreasing proliferation and inducing irreversible senescence and combination of standard chemotherapy and DEX can be a potential treatment for NSCLC.

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.

Implication of Obesity and Gut Microbiome Dysbiosis in the Etiology of Colorectal Cancer.

The complexity and variety of gut microbiomes within and among individuals have been extensively studied in recent years in connection to human health and diseases. Our growing understanding of the bidirectional communication between metabolic diseases and the gut microbiome has also highlighted the significance of gut microbiome dysbiosis in the genesis and development of obesity-related cancers. Therefore, it is crucial to comprehend the possible role of the gut microbiota in the crosstalk between obesity and colorectal cancer (CRC). Through the induction of gut microbial dysbiosis, gut epithelial barrier impairment, metabolomic dysregulation, chronic inflammation, or dysregulation in energy harvesting, obesity may promote the development of colorectal tumors. It is well known that strategies for cancer prevention and treatment are most effective when combined with a healthy diet, physical activity, and active lifestyle choices. Recent studies also suggest that an improved understanding of the complex linkages between the gut microbiome and various cancers as well as metabolic diseases can potentially improve cancer treatments and overall outcomes. In this context, we herein review and summarize the clinical and experimental evidence supporting the functional role of the gut microbiome in the pathogenesis and progression of CRC concerning obesity and its metabolic correlates, which may pave the way for the development of novel prognostic tools for CRC prevention. Therapeutic approaches for restoring the microbiome homeostasis in conjunction with cancer treatments are also discussed herein.

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.

Derivation and Characterization of Novel Cytocompatible Decellularized Tissue Scaffold for Myoblast Growth and Differentiation.

The selection of an appropriate scaffold is imperative for the successful development of alternative animal protein in the form of cultured meat or lab-grown meat. Decellularized tissues have been suggested as a potential scaffold for cultured meat production owing to their capacity to support an optimal environment and niche conducive to cell proliferation and growth. This approach facilitates the systematic development of 3D tissues in the laboratory. Decellularized scaffold biomaterials have characteristics of high biocompatibility, biodegradation, and various bioactivities, which could potentially address the limitations associated with synthetic bio-scaffold materials. The present study involved the derivation and characterization of a decellularized scaffold from mushroom tissue following subsequent assessment of the scaffold's capacity to support myogenic differentiation. Mushroom sections were soaked in nuclease and detergent solution for 4 days. Furthermore, decellularization was confirmed by histology and DAPI staining, which showed the removal of cellular components and nuclei. Myoblast cells were seeded onto decellularized tissue, which exhibited excellent cytocompatibility and promoted myogenic growth and differentiation. The study's findings can serve as a foreground for the generation of an edible and natural scaffold for producing a safe and disease-free source of alternative animal protein, potentially reducing the burden on the health sector caused by conventional animal protein production and consumption.

Impact of Environmental Pollutants on Gut Microbiome and Mental Health via the Gut-Brain Axis.

Over the last few years, the microbiome has emerged as a high-priority research area to discover missing links between brain health and gut dysbiosis. Emerging evidence suggests that the commensal gut microbiome is an important regulator of the gut-brain axis and plays a critical role in brain physiology. Engaging microbiome-generated metabolites such as short-chain fatty acids, the immune system, the enteric nervous system, the endocrine system (including the HPA axis), tryptophan metabolism or the vagus nerve plays a crucial role in communication between the gut microbes and the brain. Humans are exposed to a wide range of pollutants in everyday life that impact our intestinal microbiota and manipulate the bidirectional communication between the gut and the brain, resulting in predisposition to psychiatric or neurological disorders. However, the interaction between xenobiotics, microbiota and neurotoxicity has yet to be completely investigated. Although research into the precise processes of the microbiota-gut-brain axis is growing rapidly, comprehending the implications of environmental contaminants remains challenging. In these milieus, we herein discuss how various environmental pollutants such as phthalates, heavy metals, Bisphenol A and particulate matter may alter the intricate microbiota-gut-brain axis thereby impacting our neurological and overall mental health.