Triple-negative breast cancer (TNBC) is characterised by aggressive pathobiology and frequent chemoresistance, yet the mechanisms underpinning treatment failure remain incompletely understood. Chemotherapy-induced autophagy has been implicated in small extracellular vesicle (sEV) biogenesis and cargo remodelling; whether the exosomal microRNA (exomiR) landscape of TNBC is altered under autophagy-inducing chemotherapy has not been established. sEVs were isolated from MDA-MB-231 and MDA-MB-468 cells under doxorubicin-induced autophagy-inducing conditions (10 nM, 48 h) and from matched vehicle controls, and were confirmed by CD81 and CD63 immunoblotting with Calnexin as a negative purity control. Autophagy induction was confirmed by Beclin-1 upregulation, p62/SQSTM1 turnover and LC3 puncta formation. Small RNA sequencing (12 libraries; n = 3 biological replicates per condition; DESeq2, nominal p < 0.01 with |log₂FC| > 1) identified 10 differentially expressed exomiRs in MDA-MB-231 and 7 in MDA-MB-468, of which three per cell line additionally satisfied a Benjamini-Hochberg false discovery rate threshold (adj. p < 0.05). In-silico target analysis of these 17 exomiRs identified eight convergent autophagy and apoptosis pathway nodes, most prominently BECN1 (targeted by 6 of the 17). Exploratory qRT-PCR confirmed increased hsa-miR-1468-5p in MDA-MB-231 (23.97-fold; adjusted p = 0.007) but did not confirm the remaining five candidates, one of which changed significantly in the opposite direction. Doxorubicin treatment under autophagy-inducing conditions is associated with cell-line-specific remodelling of the sEV miRNA cargo of TNBC cells. The present data do not provide direct evidence that autophagy causes these changes; establishing causality will require pharmacological or genetic disruption of the autophagy pathway. These discovery-phase findings identify hsa-miR-1468-5p as the priority candidate for prospective functional and clinical validation, and indicate that the remaining candidates require methodological refinement before their biological relevance can be assessed.

Urolithiasis, a condition characterized by the formation of urinary tract calculi, affects millions of individuals worldwide, with a significant burden on countries like South Africa, where dietary and genetic factors majorly contribute to its prevalence, regardless of gender or age. This review highlights the therapeutic potential of Berberis vulgaris(B.vulgaris), a plant traditionally used in homeopathy and folk medicine across various regions, including South Asia, Europe, North Africa, and parts of South Africa. The bioactive compounds in B.vulgaris, particularly berberine, exhibit antioxidant and anti-inflammatory effects, inhibiting key lithogenic processes involved in stone formation, such as nucleation and aggregation. Furthermore, this plant enhances membrane integrity, reduces hyperoxaluria, and interacts with proteins involved in stone formation, offering a multifaceted approach to treating urolithiasis. This review underscores the natural, economic, and therapeutic benefits of B. vulgaris in addressing urolithiasis, supported by well-documented studies into its phytochemical composition, potential toxicity and clinical applications.

Breast cancer (BCa) is marked by uncontrolled cell division, causing the reactivation of the multi-unit ribonucleoprotein telomerase enzyme by expression of the catalytic telomerase reverse transcriptase (hTERT) subunit. Targeting hTERT can therefore offer an advantage in BCa management. Medicinal plants such as Hydrastis canadensis, used in homeopathy has therefore been explored for BCa treatment. Hydrastis canadensis mother tincture (MT) showed the presence of phytoactive components exhibiting anti-cancerous potential. The components were identified by GC-MS analysis and 34 phytochemicals were then screened using in-silico tools. The protein targets of the active components were predicted by submitting the Simplified Molecular Input Line Entry System (SMILES) of the compounds to SwissTargetPrediction, giving active components targeting the hTERT protein. Molecular docking studies were performed on AutoDock 4.2 and Molecular Dynamics (MD) simulation studies on GROningen MAchine for Chemical Simulations (GROMACS) 2023.2. The MM/PBSA calculations were performed with the gmxMMPBSA package. The data was then validated through wet lab experiments. Linoleic acid and Gadoleic acid, as modulators of human telomerase reverse transcriptase (hTERT) were identified, influencing cancer cell survival. The results highlighted the mechanistic role of Hydrastis canadensis to target the key oncogenic protein hTERT operative in breast cancer with potential therapeutic applications in cancer treatment.

Chronic kidney disease (CKD) progresses over the years with a steady loss of renal function, often culminating in renal failure. While diabetes and hypertension are the major drivers, the exact underlying molecular mechanism for CKD remains only partially understood. Emerging research has revealed a new paradigm, linking microbiota imbalance or dysbiosis with CKD. Dysbiosis leads to the development of uremic toxins, which aggravate kidney damage, inflammation, and metabolic disruptions that accelerate disease progression. This review explores the complex interactions between dysbiosis, uremic toxins, and the major risk factors, namely, diabetes and hypertension. Microbiome-targeted interventions, such as dietary interventions, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), are discussed with an emphasis on their therapeutic relevance in influencing renal health. Additionally, the potential of genetic engineering, particularly CRISPR-based systems, to develop ‘smart bacteria’ designed to restore gut health is also examined. Future perspectives highlight the need for personalized therapies targeting the gut–kidney axis. Incorporating microbiome modulation into standard CKD treatments holds the potential to slow disease progression, enhance recovery, and improve the quality of life for patients.

Urolithiasis, or kidney stones, has emerged as a significant public health concern. Despite this, effective treatments targeting stone formation and recurrence are limited. This review delves into the molecular mechanisms underlying the condition. Investigating these molecular aspects can address existing gaps in treatment options. Future research can uncover new therapeutic strategies by targeting downstream pathways, and effector molecules. Cell signaling pathways offer potential targets, as they involve complex interactions that can be modulated to address multiple clinical symptoms. An imbalance in calcium and oxalate levels can lead to kidney stone formation which is characterized by oxidative stress, inflammation, and cell death. The interplay between key organelles like the endoplasmic reticulum and mitochondria triggers stress pathways, including oxidative stress and apoptosis. This review consolidates recent advances in understanding the pathophysiology and signaling events associated with kidney stones.

Oxidative stress is a key driver of inflammatory injury which predisposes renal cells to nephrolithiatic damage. Recurrent stone formation is associated with cellular dysfunction, oxidative stress, inflammation and renal epithelial cell death. Didymocarpus pedicellata is an important medicinal herb in the ayurvedic system for the treatment of renal afflictions. The phytochemicals present in medicinal plants like D. pedicellata show potential in mitigating these series of cellular responses. Bioactivity guided fractionation, crystallization assays, phytochemical screening and GCMS analysis were performed to assess secondary metabolites present in D. pedicellata. The cytoprotective potential of the extract was evaluated by assessing cell viability, reactive oxygen species (ROS) generation, analyzing cell death, and gene expression changes to determine the extent of damage caused by oxalate exposure. The crystal-cell interface, adhesion dynamics, and morphological alterations were characterized using histological analysis via hematoxylin and eosin staining and ultrastructural examination by scanning electron microscopy. Hyperoxaluric rat model was generated by treating the rats with ethylene glycol and ammonium chloride to induce nephrocalcinosis and the effects of treatment with D. pedicellata were evaluated using renal physiology biomarkers, microscopic analysis of urine and histological studies for crystal deposition and kidney tissue injury. Gene expression analysis of p38 Mitogen-activated protein kinase and Osteopontin was done to assess the expression levels due to hyperoxaluria and treatment with D. pedicellata extract. D. pedicellata extract showed cytoprotective potential through in vitro and in vivo studies. Antilithiatic efficacy was evaluated through crystallization assays which led to metabolic profiling through GCMS analysis exhibiting a wide range of secondary metabolites with antioxidant and anti-inflammatory properties. Our study demonstrated that oxalate injured NRK52-E renal epithelial cells when cotreated with ethanolic extract of D. pedicellata led to an overall increase in cell viability, reduced production of intracellular reactive oxygen species (ROS) which lowered oxidative damage in the cells and decreased apoptosis. Staining the tissues with H&E and SEM imaging revealed modulation of crystal structure and enhanced adhesion to renal epithelial cells. Further evaluation of calcium oxalate deposition in rat model revealed that D. pedicellata alleviated crystal deposition and kidney tissue injury as evaluated by urine analysis and histological studies and decreased expression of inflammatory markers p38MAPK and Osteopontin. This study demonstrates that D. pedicellata exerts cytoprotective effect against calcium oxalate induced nephrocalcinosis by reducing the production of reactive species, oxidative stress, lowering inflammation and apoptosis finally reducing renal injury.

Cardiovascular diseases, including vascular calcification (VC), cardiac hypertrophy, myocardial infarction and atherosclerosis, remain the leading causes of morbidity and mortality worldwide. Among these, VC involves the pathological deposition of calcium in arterial walls, leading to vascular stenosis and remodelling through the endothelial-to-mesenchymal transition (EndMT). This process mirrors biological bone formation, where osteoblasts and osteoclasts coordinate bone homeostasis. Notably, osteogenic markers identified in vascular tissues highlight the overlap between bone and vascular calcification. Recent advancements in next-generation sequencing (NGS) have revealed the pivotal role of noncoding RNAs(ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating biological and vascular calcification. These ncRNAs influence transcription, translation, and epigenetic modifications while modulating oxidative stress, inflammation, and endothelial dysfunction. This review elucidates the role of ncRNAs in modulating the pathophysiology of biological and vascular calcification, with a focus on the differential expression of ncRNAs and their implications for vascular and skeletal health. Figure created using Biorender.com.

Applied research in homeopathy has garnered the attention of the research fraternity, and there is a growing interest in investigating the mechanism of action of homeopathic medicines. The in vitro model systems being used rely mainly on isolated cells and cell lines. However, what has been seen from reviews of the published literature is the vast variation in the findings.[1] [2] [3] Treatment of cells reveals a clear role of homeopathic medicines in a majority of the studies, whereas some experiments yield no effects. This has led to controversies on the efficacy of homeopathic medicines at the cellular and molecular levels.[4]

The biological system contains a unique type of cell, which is capable of unlimited division and the ability to undergo differentiation into defined lineages and cell types. This ability of stem cells is responsible for maintaining the tissues so that they can carry out their functions. Aberration in the functioning of stem cells can lead to various diseases, and hence, these stem cells can be used as model systems that can contribute to research for expanding our knowledge of disease biology and ultimately offering avenues for the treatment of various diseases. However, the complexity of the pathways operative in these stem cells necessitates them to be robustly examined prior to their application. A key challenge for stem cell biologists is the vast amount of data being generated by scientists all over the world. Combining this plethora of resources and presentation of the knowledge in a single schema is useful for the overall understanding of complexities associated with stem cell biology. Integrative bioinformatic approaches hence provide a valuable platform for this purpose, and this chapter highlights the utility of systems biology to the advancement of our understanding of stem cells.

Nephrolithiasis often known as urolithiasis or kidney stone disease, is a painful and recurring condition that affects millions of people worldwide. It is a major public health concern owing to its rising prevalence, which is influenced by factors such as geography, diet, lifestyle, and gender. Traditional therapeutic approaches do exist; however, they are not completely efficient in preventing recurrence. Nanotechnology introduces a paradigm shift in kidney stone management by enabling the use of nanoparticles (NPs) for kidney stone management through improved therapy and diagnostic tools. This review delves into the various metal, carbon, silica, selenium, and polymer-based NPs for their application in the field of urolithiasis. However, continued research is needed to implement and improve nanoparticle-based therapies and imaging techniques which can overcome the current limitations, and ensure safe and efficient applications in the field of urolithiasis.

Data collected from large-scale studies has shown that the incidence of prostate cancer globally is on the rise, which could be attributed to an overall increase in lifespan. So, the question is how has modern science with all its new technologies and clinical breakthroughs mitigated or managed this disease? The answer is not a simple one as prostate cancer exhibits various subtypes, each with its unique characteristics or signatures which creates challenges in treatment. To understand the complexity of prostate cancer these signatures must be deciphered. Molecular studies of prostate cancer samples have identified certain genetic and epigenetic alterations, which are instrumental in tumorigenesis. Some of these candidates include the androgen receptor (AR), various oncogenes, tumor suppressor genes, and the tumor microenvironment, which serve as major drivers that lead to cancer progression. These aberrant genes and their products can give an insight into prostate cancer development and progression by acting as potent markers to guide future therapeutic approaches. Thus, understanding the complexity of prostate cancer is crucial for targeting specific markers and tailoring treatments accordingly.

Objectives This is the first systematic review and meta-analysis of the prevalence of multimorbidity, its risk factors including socioeconomic factors, and the consequences of multimorbidity on health systems and broader society in India. Methods A systematic review of both published and grey literature from five databases (Medline, Embase, EBSCO, Scopus, and ProQuest) was conducted including original studies documenting prevalence or patient outcomes associated with multimorbidity among adults in India. We excluded studies that did not explicitly mention multimorbidity. Three independent reviewers did primary screening based on titles and abstracts followed by full-text review for potential eligibility. The risk of bias was independently assessed by two reviewers following the Appraisal Tool for Cross-Sectional Studies. We presented both qualitative and quantitative (through meta-analysis) summaries of the evidence. The protocol for this study was prospectively registered with PROSPERO (CRD42021257281). Results The review identified 5442 articles out of which 35 articles were finally included in this study. Twenty-three studies were based on the primary data while 12 used secondary data. Eleven studies were conducted in hospital/primary care setting while 24 were community-based. The pooled prevalence of multimorbidity based on (n=19) studies included for meta-analysis was 20% (95% CI: 19% to 20%). The most frequent outcomes were increased healthcare utilization, reduced health-related quality of life, physical and mental functioning. Conclusion We identified a wide variance in the magnitude of multimorbidity across age groups and regions with most of the studies from eastern India. Nation-wide studies, studies on vulnerable populations and interventions are warranted.

Objective: Acute undifferentiated febrile illness (AUFI) is a neglected topic in health care. It has considerable morbidity and mortality worldwide. Slum dwellers are at high risk due to poor living conditions. This longitudinal cohort study estimated the incidence of AUFI in urban slum dwellers in Delhi. Methods: This study was conducted on urban slum dwellers in Delhi. Data were collected using a structured interviewer-administered questionnaire over a period of 18 months. Adjusted incidence rates (IR) and incidence rate ratios (IRR) were calculated using Poisson regression models. Kaplan-Meier survival curves were used to estimate survival from fever. Results: A total of 1497 population were studied. Incidence rate of AUFI was 47.43 per 1000 person-months (95% CI: 44.88; 50.08). The incidence was highest among the 50–59 year age group (54.18 per 1000 person months; 95% CI: 43.19; 67.17). Significant seasonal variation was observed with IR high in winter (IR: 32.80 per 1000 person month; adjusted IRR: 1.44 (95% CI: 1.26; 1.66) and monsoon (IR:19.89 per 1000 person month; adjusted IRR: 0.44 (95% CI: 0.36; 0.53). Conclusion: This study has shown a high incidence rate of AUFI amongst the slum dwellers in Delhi. This calls for awareness about clinical investigation and management among patients and healthcare providers. The findings from this study may sensitize policymakers and healthcare stakeholders to draw a road map with insightful consideration of the environmental factors that bring health burdens to the slum population. Further, comparative studies between slum and non-slum dwellers may be undertaken to evaluate the incidence of AUFI.

BACKGROUND:Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells.METHODS:Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay.RESULTS:The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer.CONCLUSIONS:In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells.

Multimorbidity has become a significant challenge for the health-care systems to combat. A person suffers from more than one disease due to several reasons. Apart from age itself, environmental factors, social factors, and behavioral factors such as unhealthy lifestyle, physical inactivity, and mental stress are other reasons. Multimorbidity, polypharmacy, and antimicrobial resistance are the three biggest challenges in present-day conventional care. Here, the Ayush system (Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa Rigpa, and Homeopathy) can have a potential role in their management. A comprehensive search of the literature was conducted to enlist evidence of Ayush systems of medicine for multimorbidity. Data sources include PubMed, Google Scholar, Scopus, and EBSCOhost. All types of evidence such as case reports, case series, and cohort studies were included. No studies reported multimorbidity management in Ayurveda, Unani, and Siddha systems, whereas, in homeopathy, one cohort study and four case reports are identified with an insight of improvement in symptoms, overall well-being, and management of multimorbidity. These hypothesis-generating studies are a lead for further research. In yoga, two RCTs (one a study protocol and the other about trial feasibility) were reported. The current evidence precludes drawing any firm conclusions about the role of Ayush systems in multimorbidity management, but its scope cannot be overlooked. Future research should focus on well-designed, randomized trials as well as pragmatic comparative effectiveness trials.

Stem cell-based tissue engineering is an emerging tool for developing functional tissues of choice. To understand pluripotency and hepatic differentiation of mouse embryonic stem cells (mESCs) on a three-dimensional (3D) scaffold, we established an efficient approach for generating hepatocyte-like cells (HLCs) from hepatoblast cells. We developed porous and biodegradable scaffold, which was stimulated with exogenous growth factors and investigated stemness and differentiation capacity of mESCs into HLCs on the scaffold in-vitro. In animal studies, we had cultured mESCs-derived hepatoblast-like cells on the scaffold and then, transplanted them into the partially hepatectomized C57BL/6 male mice model to evaluate the effect of gelatin scaffold on hepatic regeneration. The 3D culture system allowed maintenance of stemness properties in mESCs. The step-wise induction of mESCs with differentiation factors leads to the formation of HLCs and expressed liver-specific genes, including albumin, hepatocyte nucleic factor 4 alpha, and cytokeratin 18. In addition, cells also expressed Ki67, indicating cells are proliferating. The secretome showed expression of albumin, urea, creatinine, alanine transaminase, and aspartate aminotransferase. However, the volume of the excised liver which aids regeneration has not been studied. Our results indicate that hepatoblast cells on the scaffold implanted in PH mouse indicates that these cells efficiently differentiate into HLCs and cholangiocytes, forming hepatic lobules with central and portal veins, and bile duct-like structures with neovascularization. The gelatin scaffold provides an efficient microenvironment for liver differentiation and regeneration both in-vitro and in-vivo. These hepatoblasts cells would be a valuable source for 3D liver tissue engineering/transplantation in liver diseases.

Abstract 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.

BACKGROUND:Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in females worldwide. Schleichera oleosa (kusum tree) belongs to the Sapindaceae family commonly found in many states of India. This plant is traditionally being used in various pathological conditions.METHODS:In vitro studies were performed using seed extract of Schleichera oleosa. Different concentrations of seed extracts were treated on MCF-7 breast cancer cell line and its effect on migration and colony formation were observed. BRCA1 and p16 gene expression was analyzed by real-time PCR and Western blotting.RESULTS:We have analyzed anticancer and anti-metastatic effects of seed extract in breast cancer and IC50 was 140µg/ml concentration. Further, its inhibitory role in cell migration and colony formation was at 140µg/ml (P<0.0001) concentration and reduced significantly growth of sphere at 140 µg (P<0.0031) and 150µg (P<0.0010) concentration after 5 days of treatment. The apoptosis study was shown a significant increase at 140 µg (P<0.0001) in apoptotic cells. Expression of BRCA1 and p16 were found to be over-expressed as 1.4 and 1.7 fold, respectively, at 140µg/ml concentration after 24 h of treatment at the transcription level. BRCA1 protein was up-regulated but p16 expression down-regulated at 140 to 150µg/ml (One-Way ANOVA, P<0.0001) concentration.CONCLUSION:In this study, we found a significant role of S. Oleosa seed extract has an anti-cancer as well as anti-metastatic via up-regulation of BRCA1 and p16 genes in breast cancer cells.