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Occurrence of antibiotic-resistant E. coli and antibiotic resistance genes from culturable bacteria in drinking water sources along the Upper Mahaweli River, Sri Lanka.

Antibiotic-resistant Escherichia coli (AR-E. coli) and antibiotic resistance genes (ARGs) in aquatic environments pose a serious threat to public health. However, their presence in river water in South Asian countries is not well established. The present study investigated AR-E. coli and ARGs from culturable bacteria in drinking water sources from 14 drinking water treatment plants situated along the Upper Mahaweli River, a tropical central hill-country river system in Sri Lanka. A total of 167 E. coli isolates were tested against ten antibiotics using the Kirby-Bauer method, and genomic DNA from culturable bacteria in 45 water samples were screened for 11 ARGs using PCR. Overall, 60.48% E. coli isolates exhibited resistance to at least one antibiotic and multidrug resistance was detected in 27.54%. Highest resistance was for amoxicillin (47.31%), tetracycline (26.95%), and co-trimoxazole (24.55%) and four antibiotics showed seasonal variation. ARGs, dominated by blaTEM (80.0%), tetA (66.67%), and tetM and qnrS (62.22%) were detected in 42.42% PCR assays (n = 210). Multiple antibiotic resistance index varied from 0.00 to 0.80, with 44.91% exceeding the 0.2 threshold value, and the antibiotic resistance index varied from 0.00 to 0.32, with eight above the threshold (≥ 0.2). Hierarchical cluster analysis grouped majority of drinking water sources into the intermediate category while few were categorized under low (Kotagala and Thalawakelle-Galkanda) and high (Haragama, Paradeka, and Nawalapitiya), reflecting the variability of anthropogenic interference. Results highlight the risk associated with AR-E. coli and ARGs from culturable bacteria in one of Sri Lanka's key drinking water sources. Proactive interventions ensuring long-term safety of drinking water sources are urgently needed to safeguard public health.

Sri Lanka↗

The Impact of Oncological Treatments on Return to Work, Work Ability, and Sickness Absence in Breast Cancer Survivors: A Systematic Review.

PURPOSE: Returning to work and maintaining an adequate ability to work serve as key indicators of quality of life, psychological well-being and psychosocial adjustment. Therefore, this study aims to analyze the impact of breast cancer treatments on return to work (RTW), work ability (WA), and sick leave (SL) among breast cancer survivors. METHODS: A systematic review was conducted according to the PRISMA guidelines. The sample consisted of 26 studies published between 2016 and 2025, including prospective multicenter cohorts and national registries from fifteen countries across four continents, with more than 25,000 participants. A methodological quality assessment and a narrative synthesis were performed to synthesize the results. RESULTS: Chemotherapy is the most consistent predictor of prolonged SL, delayed RTW, and significantly reduced WA. Radical surgery and axillary lymph node dissection (ALND) are associated with a significantly delayed RTW due to physical sequelae. While outcomes showed strong relationship with clinical factors, certain psychosocial variables such as depression, anxiety, and low self-efficacy seemed to act as important secondary factors that can further complicate the process. CONCLUSION: The findings suggest that more invasive or aggressive treatments (chemotherapy, ALND, and radical surgery) were associated with poorer outcomes on RTW, WA, and SL. Furthermore, the clinical recovery associated with treatment completion did not necessarily equate to a functional recovery in WA that facilitated a successful RTW. Thus, it is necessary to explore in depth the impact of cancer treatments on WA, alongside psychosocial variables, to design multidisciplinary interventions that enable sustainable occupational reintegration. REGISTRATION: PROSPERO 2026 (CRD420261322638).

Breast cancer survivors↗

Proteomic regulation of anti-proliferative and anti-migratory activity by potent phytochemicals from Pistacia integerrima J.L. Steward Ex Brandis via PI3K, AKT1, and KRAS for Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of mortality worldwide and remains a major therapeutic challenge due to high metastasis, drug resistance and limited treatments. Pistacia integerrima J.L. Steward Ex Brandis (PI) consists of flavonoids, steroids, terpenoids and phenolic compounds reported for pharmacological activities. The efficacy of potent bioactives from P. integerrima may be ascertained employing cytotoxic, antiproliferative, anti-migratory, and anti-metastatic evaluations in A549 NSCLC cells with proteomic profiling, molecular docking, and dynamics simulation study. METHODS AND RESULTS: PI EtAc produced significant dose-dependent cytotoxicity in A549 cells (100&#xa0;&#xb5;g/mL, p&#x2009;<&#x2009;0.0001 in the MTT assay. There was a pronounced decrease in colony formation after treatment with EtAc, with 18.41% (p&#x2009;<&#x2009;0.002), and markedly. Furthermore. PI EtAC markedly inhibited cell migration emphasized by wound healing and Transwell migration (p&#x2009;<&#x2009;0.01) assays, indicating reduced metastatic migratory potential. Proteomic analysis demonstrated significant downregulation of Endoglin (CD105), KLK5 and MMP-2, indicating suppression of angiogenic and metastatic signalling pathways in the Human XL Oncology protein array. The interaction of major PI phytochemicals with key NSCLC-associated targets was recorded in Molecular docking, revealing favourable binding affinities of kaempferol, &#x3b2;- sitosterol, luteolin, and quercetin towards several oncogenic targets, including AKT1(-&#x2009;7.6&#xa0;kcal/mol), PI3K(-&#x2009;9.4&#xa0;kcal/mol), KRAS (-&#x2009;8.5&#xa0;kcal/mol) and MMP9 (-&#x2009;8.1&#xa0;kcal/mol). Molecular dynamics simulation confirmed the structural stability of the kaempferol -AKT1 complex throughout the 100 ns simulation. CONCLUSION: Pistacia integerrima bioactives exhibited significant anti-proliferative, anti-migratory, and anti-metastatic activities in vitro, which may provide scientific rationale identifying newer promising candidates for NSCLC.

Humans↗

Molecular insights and therapeutic innovations in low-risk human papillomavirus-associated cutaneous wart.

Human papillomavirus (HPV) is a DNA virus that belongs to the Papillomaviridae family. Among the various types, high-risk strains are associated to malignancy, whereas low-risk types cause benign skin warts due to persistent infection. Unlike high-risk HPVs, low-risk HPV genomes remain in an episomal state while expressing E6/E7 proteins. These proteins exhibit a reduced ability to degrade pRb and p53, which finally leads to controlled epithelial hyperplasia instead of developing malignancy. Infection with low-risk HPV activates distinct host signaling pathways, ultimately promoting the proliferation of keratinocytes and formation of warts. Simultaneously, it triggers host innate and adaptive immune responses that often clear the lesion. This review focuses on low-risk types that cause skin warts by analyzing the molecular pathways, particularly the integrin-FAK-PI3K/AKT, Hippo-YAP/TAZ pathway along with MAPK-ERK pathways that promotes cutaneous benign wart formation. This article further studies clinical management strategies for HPV associated warts, including primary destructive treatment (cryotherapy, keratolytics, excision), immunotherapies (imiquimod, interferon injections or intralesional antigen), and novel adjunctive therapies with clinical evidence including photodynamic therapy, intralesional chemotherapeutics, and emerging HPV vaccination strategies. Among these, for benign skin warts, intralesional immunotherapy, particularly Candida antigen, and intralesional HPV vaccination have shown encouraging responses clinically. But extensive controlled clinical studies are necessary to establish their efficacy and clinical value as a standard medicine. This review therefore, generates a comprehensive overview of papilloma virus mediated skin warts and their management for both clinicians and researchers.

Humans↗

Overcoming cancer resistance in pancreatic cancer: toward dynamic precision oncology.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, largely because of its profound and evolving therapeutic resistance. Resistance is not determined by a single molecular alteration but arises from interconnected mechanisms, including intrinsic resistance, treatment-induced adaptive resistance, acquired resistance, genomic evolution, clonal selection, cancer stemness, phenotypic plasticity, metabolic adaptation, and tumor microenvironment-mediated effects. Emerging therapeutic approaches targeting KRAS/RAS signaling, stromal and immune components, metabolic dependencies, and DNA damage repair pathways offer opportunities to address these mechanisms, although durable efficacy remains limited by biological heterogeneity and adaptive responses. In this review, we examine therapeutic resistance as an evolutionary and multidimensional process and summarize emerging strategies for overcoming resistance. We further propose a Dynamic Precision Oncology (DPO) framework that extends conventional precision oncology beyond baseline molecular profiling by integrating longitudinal assessment of tumor genomics, circulating tumor DNA, CA19-9, imaging, radiomics, and clinical characteristics. This framework emphasizes iterative detection and characterization of emerging resistance, mechanism-informed treatment adaptation, and subsequent reassessment rather than automatic treatment modification based on a single biomarker. DPO may provide a conceptual framework for integrating evolving tumor biology into treatment decision-making, while prospective studies are needed to validate biomarkers, define actionable thresholds, and determine whether longitudinal resistance-guided strategies improve clinical outcomes in PDAC.

Humans↗

Risk governance of transgenic plants: bridging science, policy, and public trust.

Transgenic plants and genome editing technologies are revolutionizing agriculture through sustainable approaches to food security, pest management, and adaptation to climate change; but their widespread use is hampered by regulatory systems that are fragmented, ethics considerations, and an ongoing lack of trust from the general public. In contrast to other literature that evaluates regulation processes and public acceptance separately, our review paper introduces a new, holistic approach that includes both technical risk assessment from a scientific perspective, and Codex Alimentarius and OECD standards, and the socio-legal and judicial environment of how the national policy decisions are actually made. The paper provides a comparative, historical analysis of the key difference between product- and process-based risk governance in the USA, the EU, and India. Through the use of case studies with global significance like MON810 maize, Bt Brinjal, and the April 2024 Philippine Court of Appeals' order for cease-and-desist of Golden Rice, we discuss the increasing tension between administrative scientific approvals and precautionary judicial orders. We further explore the emerging exemptions to regulation of Site-Directed Nuclease (SDN-1 and SDN-2) genome edited crops which led to India's revolutionary 2025 commercialization of climate-resilient rice crops. Our review ends with a forward-looking approach to biotechnology regulation policy, making an appeal to shift from static historical dichotomies towards flexible risk-proportionate and internationally coordinated regulatory systems. Finally, we show that global success of agricultural biotechnology is not just about safety verification, but rather about establishment of transparent and communicable institutions that can transform scientific risk assessments into legitimate risk management decisions.

Plants, Genetically Modified↗

Phytoplasma-plant interactions: effector-mediated host reprogramming, hormonal crosstalk, metabolic alterations and plant-mediated vector manipulation.

Phytoplasmas are wall-less, phloem-restricted bacterial pathogens that infect over 1,000 plant species, causing substantial losses in agriculture, horticulture, and forestry worldwide. Despite their reduced genomes and limited metabolic autonomy, these obligate parasites colonize diverse hosts through secreted effector proteins that extensively reprogram plant development, metabolism, immune signalling, and vector interactions. Advances in genomics, transcriptomics, proteomics, metabolomics, and functional studies have substantially clarified the molecular basis of phytoplasma pathogenicity and symptom development. This review synthesizes current understanding of phytoplasma-plant interactions, covering phytoplasma biology, genome evolution, and the infection cycle across plant and insect vector hosts. We examine the molecular functions of key effectors, SAP11, SAP54/PHYL1, SAP05, TENGU, SWP1, and recently identified virulence factors, focusing on how they target host transcription factors, phytohormone networks, protein degradation pathways, and immune responses to promote colonization and disease progression. We further discuss how phytoplasma infection disrupts phytohormone signalling, primary and secondary metabolism, and developmental programs to produce characteristic disease symptoms, with particular attention to pathogen-induced changes in host volatiles and nutritional quality that alter vector behaviour and enhance transmission. Finally, we summarize insights from multi-omics studies and emerging management strategies, including CRISPR-based genome editing, RNAi, rapid molecular diagnostics, resistant cultivars, microbiome-based approaches, and sustainable vector control, and highlight key knowledge gaps and priorities for developing effective, environmentally sustainable phytoplasma disease management.

Phytoplasma↗

Robotic surgery for gastric gastrointestinal stromal tumors: a systematic review.

Robotic surgery is used for selected gastric gastrointestinal stromal tumours (GISTs), particularly when location makes conventional wedge resection difficult. We synthesised technical, perioperative, pathological, functional and oncological outcomes. PubMed/MEDLINE, Scopus and the Cochrane Library were searched from inception to 14 August 2026. Primary reports with at least three eligible robotic gastric-GIST patients were included. Two reviewers independently selected studies, extracted data and completed design-specific JBI appraisal. Because outcome definitions, denominators and reporting were heterogeneous, findings were synthesised narratively in accordance with SWiM guidance rather than pooled. Twenty-three studies, including six comparative cohorts, were included. Institutional robotic cohorts contained 3-45 eligible patients; one national registry included 1,567 robotic cases. Tumour size ranged from 2.68&#x2009;&#xb1;&#x2009;1.55 to 7.9&#x2009;&#xb1;&#x2009;1.8&#xa0;cm among studies reporting means. Most institutional reports described R0 resection in all eligible patients; exceptions were 23/24 and 24/25, while the registry reported 1,425/1,567 R0 resections. Grade III morbidity occurred in 2/25 patients in one function-preserving series. Registry 30- and 90-day mortality after robotic resection were 0.5% and 0.8%, respectively. Comparative studies did not demonstrate superior postoperative or oncological outcomes with robotic surgery. Robotic gastric-GIST resection appears feasible in selected patients and may facilitate organ-preserving surgery at anatomically challenging sites. Current observational evidence does not establish comparative functional, oncological or economic superiority.

Humans↗

Integrated &#xb9;H-NMR Metabolomics and Growth Kinetics Uncover Three Distinct Metabolic Scenarios in Lactiplantibacillus pentosus P7 Fermentation of Plant-Derived Prebiotics.

Lactic acid bacteria (LAB) drive a broad range of food and biotechnological fermentations, the outcomes of which depend not only on the bacterial genotype but also on the chemical composition of the fermentation substrate. To resolve how a single strain reorganises chemically distinct plant matrices, we profiled fermentations of Lactiplantibacillus pentosus P7 (GenBank JBLMKZ000000000) on garlic, onion, and kiwifruit extracts prepared in water and 70% ethanol, using growth kinetics combined with solvent-suppressed 500-MHz proton nuclear magnetic resonance metabolomics over 48&#xa0;h, and integrated the data with whole-genome pathway annotations. Three substrate-specific metabolic scenarios emerged. On garlic, P7 grew vigorously, with the water extract exceeding the de Man-Rogosa-Sharpe reference medium at every time point (peak &#x394;OD&#x2086;&#x2080;&#x2080; of 9.38 versus 8.52 at 24&#xa0;h) and accumulating sorbose, rhamnose, and the aromatic amino acids phenylalanine and tryptophan (3.04- to 3.70-fold increases), providing first metabolic evidence consistent with the strain's four-copy aroE shikimate-dehydrogenase expansion. On onion, the lowest cell density coincided with the highest lactate output of the dataset (5.21-fold rise at 48&#xa0;h), transient 5-hydroxymethylfurfural reduction, and accumulation of acetoin and 1,3-propanediol, mapping onto a redundant set of pyridine-nucleotide-dependent oxidoreductases and a pdu-independent diol pathway. On kiwifruit, citrate accumulated 8.9-fold at 16&#xa0;h and then declined, consistent with an intact citCDEFG citrate-lyase operon paired with absence of canonical oxidative tricarboxylic acid enzymes. The optimal extraction solvent was substrate-dependent, water for garlic and ethanol for onion and kiwifruit. Overall, these results show that substrate chemistry, rather than strain identity, dictates which genome-encoded pathways P7 engages, establishing P7 as a versatile, substrate-tunable platform for the functional fermentation and biorefining of furanic-rich substrate streams. Raw NMR data and ISA-Tab metadata are available via MetaboLights with identifier MTBLS14463.

Lactiplantibacillus pentosus↗

Endodermal Organoids Along Two Axes: Single-Organ Fidelity, Inter-Organ Reconstruction, and the Unbuilt Gut-Lung Frontier.

Three-dimensional organoids of the gut, liver, and lung have become mainstream models of human development, disease, and therapy. These organs share an embryonic endodermal origin, yet the field measures their progress inconsistently because the word "maturity" carries two unrelated meanings. Herein, we review the organoid work across all three organs and propose that the two orthogonal axes of advancement be analyzed separately. The first axis is single-organ fidelity. Adult stem cell organoids are faithful but partial, reproducing the adult epithelium of their source tissue with genomic stability yet lacking stromal, vascular, immune, and neural compartments. Human pluripotent stem cell organoids are complete but immature, co-emerging with multiple lineages yet arrested in a fetal-like state. The cost of each limitation is organ-dependent, smallest in the intestine, largest for hepatic drug metabolism, and most spatially defined across the proximal and distal lungs. The second axis is inter-organ reconstruction, where progress is strongly asymmetric. The gut-liver axis is comparatively advanced and sustained by linked organoid and microphysiological systems. The gut-lung axis, by contrast, remains the least-developed frontier, and no such linked organoid has yet been built. We therefore frame it as a proposal, using in vivo and correlative evidence to outline the design principles for such a model. Four bottlenecks recur across both axes: limited vascularization; batch-to-batch variability; organ-skewed immune, microbial, and stromal microenvironments; and unidirectional signaling. We argue that benchmarking models against single-cell developmental atlases and prioritizing construction of the gut-lung frontier should guide the field over the next decade.

Intestines↗

Comprehensive Clinicopathologic, Immunohistochemical, and Genomic Profiling of Sporadic Ampullary Somatostatin-producing D-cell Neuroendocrine Tumors Identifies Recurrent HRAS Hotspot Mutations.

Ampullary somatostatin-producing D-cell neuroendocrine tumors are rare neoplasms that may be associated with type 1 neurofibromatosis. The molecular features of sporadic ampullary somatostatin-producing D-cell neuroendocrine tumors (SAMSOM-NETs) remain poorly characterized. We performed an integrated morphological, immunohistochemical, and genomic analysis of a multicenter series of SAMSOM-NETs. Eleven cases were included (73% male; median age: 63&#xa0;years). All six patients who underwent lymphadenectomy were staged as pN1, and liver metastases were found in three cases; however, no tumor-related deaths occurred (median follow-up: 104&#xa0;months). Common histologic features that can pose diagnostic challenges in the differential diagnosis with adenocarcinoma included a tubulo-glandular architecture (100%), periodic Acid-Schiff (PAS)-positive intraluminal mucin (73%), MUC1 expression (100%), and carcinoembryonic antigen (45%) expression. All tumors exhibited dot-like cytoplasmic reactivity for cytokeratins (CK) CAM5.2 or CK AE1/AE3, and 82% were CK7-positive. ISL1 and PDX1 were diffusely expressed in all cases, while CDX2 was positive in 54% and ARX showed only focal expression in four tumors. Genomic profiling revealed microsatellite stability and low tumor mutational burden. Alterations in the RAS pathway, including HRAS mutations (4 cases, 36%), a KRAS mutation (1 case), and NF1 alterations (one case), were identified in 54% of cases and in all tumors with liver metastases. Additional molecular findings included a CDK12 splice-site alteration and an NTRK3::PRDM4 fusion. Potentially actionable alterations affecting kinase-related pathways were detected in 64% of tumors. Our findings support SAMSOM-NET as a peculiar neuroendocrine tumor subtype showing distinctive histologic and molecular characteristics with potential diagnostic and therapeutic implications.

Humans↗

Divergent c-MYC Expression Patterns in NET and NEC: Insights from a Multicentre Cohort of 1380 Neuroendocrine Neoplasms.

Neuroendocrine neoplasms (NEN) comprise well-differentiated neuroendocrine tumours (NET) and neuroendocrine carcinomas (NEC), whose distinction is clinically critical. Although c-MYC alterations have been implicated in NEC pathogenesis, c-MYC expression across NEC subtypes and anatomical sites, as well as in NET, remains incompletely defined. We analysed c-MYC immunohistochemically in 1380 resected NEN using the Immunoreactive Score (IRS: negative 0-1, weak 2-3, moderate 4-8, strong 9-12). Overall, c-MYC positivity (IRS&#x2009;&#x2265;&#x2009;2) was observed in 13.3% of NEN. Expression was detected in 43% of NEC (164/381), including strong staining in 19.4%, whereas it was rare in NET and pulmonary carcinoids (20/999; 2%; p&#x2009;&#x2264;&#x2009;0.001). Within NEC, c-MYC expression was enriched in LCNEC and MiNEN compared with SCNEC and Merkel cell carcinoma (p&#x2009;&#x2264;&#x2009;0.001) and occurred more often in gastroenteropancreatic than in pulmonary NEC (57.6% vs. 37.3%; p&#x2009;&#x2264;&#x2009;0.001). Among NET, G3 tumours showed the highest positivity rate (6/35; 17.1%), although this was significantly lower than in NEC (p&#x2009;&#x2264;&#x2009;0.001), with strong expression observed in only one NET G3 (2.9%). No association between c-MYC expression and survival was identified in either NEC or NET. Our study confirms c-MYC expression as a common event in NEC and highlights differences across histological subtypes and anatomical sites, while demonstrating its absence in most low-proliferative NET. A subset of NET G3 tumours exhibits weak to moderate c-MYC expression at levels far below those seen in NEC, suggesting that strong c-MYC positivity may support a NEC classification in borderline cases but does not represent a definitive discriminatory marker.

Humans↗

Mitochondrial Function-Related Genes in Sleep Disorders: A Multi-Omics Mendelian Randomization Study.

Mitochondrial dysfunction is linked to sleep disorders in previous report, but the potential roles of specific genes remain unclear. This study aimed to dissect different subtype-specific genetic associations and their underlying mechanisms. A multi-omics Summary-data-based Mendelian Randomization (SMR) approach was performed to identify potential causal links between mitochondrial function-related genes and sleep disorders. We integrated GWAS data from FinnGen database (the discovery set), independent GWAS datasets (covering different sleep-disorder subtypes and used for validation), and cis-QTLs (including mQTLs, eQTLs, and pQTLs) to perform systematic exploration. Specially, we performed targeted validation of tissue-specific effects, leveraging gene expression data from disease-relevant brain regions within the GTEx database. Our SMR analysis identified mitochondrial function-related genes potentially modulating sleep disorders across biological layers, initially identifying 102 genes at the methylation level, 48 at the gene expression level, and 6 at the protein abundance level. Integrative analysis subsequently prioritized DCXR and ACADVL and revealed their distinct, subtype-specific associations. DCXR exhibited a protective role in sleep apnea while ACADVL showed a paradoxical risk conferring role in daytime sleepiness. In addition, the analysis identified an epigenetic regulatory mechanism for DCXR in which its expression and protein levels are modulated by DNA methylation. Finally, validation in brain-hypothalamus tissue confirmed DCXR as a significant potential protective factor (OR&#x2009;=&#x2009;0.929, 95% CI: 0.887-0.973, P_HEIDI&#x2009;=&#x2009;0.999, FDR&#x2009;=&#x2009;0.2449). Our findings implicate key mitochondrial genes, particularly DCXR and ACADVL, in the pathophysiology of specific sleep disorder subtypes, highlighting potential avenues for precision medicine. Clinical trial number: Not applicable.

Humans↗

Genomic Insights Into the Probiotic and Safety Attributes of Pediococcus acidilactici BC-7 for its Potential Application in Livestock Health.

Pediococcus acidilactici is widely recognized for its health-beneficial aspects and has gained increasing interest for use in livestock industry. It shows strong probiotic efficacy, antimicrobial activity, cholesterol-lowering potential, immune modulation, and other therapeutic attributes. The novel strain from indigenous habitats mainly depicted potent probiotic efficacy and high adaptability. In this study, we evaluated the probiotic characteristics and genomic features of strain BC-7 obtained from a Nili - Ravi buffalo calf raised under domestic conditions using phenotypic assessment, genomic analysis and in vivo studies. The strain BC-7 exhibited key probiotic traits i.e., gut tolerance (70.43% - 97.5%), auto-aggregation (85.24%), co-aggregation (14.33% - 25.88%), hydrophobicity (78.33% - 88%), antioxidant potential (54%), and antibacterial activity (16.47-18&#xa0;mm). The safety analysis revealed that BC-7 exhibited susceptibility and resistance to various antimicrobial agents and showed no &#x3b2; hemolytic activity. BC-7 was taxonomically classified as Pediococcus acidilactici by 16&#xa0;S rRNA gene sequencing. Whole genome sequence (WGS) analysis showed that P. acidilactici BC-7 contains a 1.9&#xa0;Mb genome with 42% GC content. Pediococccus acidilactici BC-7 harbored 1900 genes, which were mainly associated with metabolism and genetic processes. Based on genomic comparison, BC-7 shared 99% average nucleotide identity and strong genomic collinearity with P. acidilactici NARCC1 which is a TYPE strain having potent probiotic potential. Probiotic strain BC-7 shared 1,664 core genes with reference strains and 69 unique genes specific for metabolism and genetic processes. The BC-7 strain contained unique bacteriocins-associated genes and defense-related CAzymes, it harbors only vancomycin resistance genes and lacked true virulence determinants. In vivo trial showed that BC-7 treated mice showed increased growth rate, improved immune modulation, and membrane integrity. These significant findings revealed that BC-7 emerging as a potential probiotic strain with strong functionality and efficacy. Thus, our strain BC-7 could be used as a promising candidate for applications in the animal health industry.

Gastrointestinal tract↗

Evaluation of Indigenous Bacillus Strains from Asian Fermented Foods for Probiotic Properties.

Bacillus species hold particular importance due to their versatile enzymatic repertoire and ability to synthesize diverse bioactive metabolites. In this study, two fermented food-derived strains, Bacillus siamensis BB3 (from douchi) and Bacillus velezensis TMA10 (from tapai) were evaluated for their probiotic, anti-microbial and functional potentials. Both strains exhibited desirable probiotic characteristics, including desirable tolerance to simulated gastric and intestinal conditions, with BB3 showing greater acid tolerance than TMA10. Safety assessments confirmed the absence of hemolytic activity, virulence factors and antibiotic resistance genes. Whole genome sequencing showed that the strains harbored genomic sequences for a wide range of metabolites, including non-ribosomal peptides and polyketides. Ethyl acetate (EtOAc) extracts from both strains demonstrated broad-spectrum anti-microbial activity against several indicator microorganisms, including Listeria grayi, Bacillus cereus, Serratia marcescens, Escherichia coli, and Pseudomonas aeruginosa, with TMA10 additionally inhibiting MRSA and Streptococcus mutans. Liquid Chromatography-Mass Spectrometry profiling identified key anti-microbial compounds, namely surfactins, macrolactins, bacillaene from BB3 and TMA10. In addition, difficidins were also detected from TMA10. Genomic analysis further indicated diverse carbohydrate utilization capacities; both strains encoded pathways for sucrose, raffinose-family oligosaccharides and lactose metabolism, while TMA10 possessed pathways for trehalose, glucomannan and arabinoxylan degradation. Both strains also showed anti-oxidant activity, with enhanced effects observed in their cell-free supernatants and heat-killed preparations. Overall, these findings highlight BB3 and TMA10 as promising candidates for the development of fermented food-derived Bacillus probiotics and functional cultures with anti-microbial, anti-oxidant, and broad carbohydrate-utilization capabilities.

Bacillus↗

GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid&#xae; platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I2 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings.

Journal Article↗

Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To summarise the literature regarding the safety of short-term use of the non-steroidal anti-inflammatory drug&#xa0;(NSAID) celecoxib. STUDY DESIGN: Systematic review with meta-analysis of randomised trials. Participants comprised individuals of all ages with acute non-cancer pain. Interventions included celecoxib at 200-400 mg/day for up to 10 days. The comparators were placebo, other NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDS [nsNSAIDS]), or opioids. DATA SOURCES: Five databases were searched from inception to April 2025: Embase, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus. Additionally, a registry was searched: ClinicalTrials.gov. DATA SYNTHESIS: Meta-analyses using Mantel-Haenszel and random-effects model were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for severe cardiovascular, respiratory, and gastrointestinal adverse events and secondary outcomes. The Cochrane Risk of Bias Tool for randomised trials (RoB-2) was used to assess bias risk. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) was conducted to assess the certainty of evidence of each reported outcome. RESULTS: Title/abstract and full text screening comprised 3976 and 273 studies, respectively. Fifty studies were included with 10,693 participants. The RRs for adverse events were no different between celecoxib and placebo for severe events (3 studies) (RR 0.44 [95% CI 0.10-2.03]), cardiovascular (3 studies) (RR 0.84 [95% CI 0.24-2.92]), respiratory (4 studies) (RR 1.23 [95% CI 0.29-5.26]), and gastrointestinal events (33 studies) (RR 0.96 [95% CI 0.64-1.43]). There was no difference between celecoxib and NSAIDS for gastrointestinal adverse events, RR 0.89 (95% CI 0.68-1.17). Celecoxib had a lower risk compared to opioids for gastrointestinal events, RR 0.34 (95% CI 0.14-0.86), and showed a lower risk of nausea compared with placebo, RR 0.75 (95% CI 0.60-0.93), and nsNSAIDS, RR 0.80 (95% CI 0.64-0.99). Most studies had some risk of bias concerns, and the overall certainty of evidence for most outcomes was very low. Celecoxib appears to be safe for acute non-cancer pain when compared to placebo, NSAIDS, and opioids. It had a lower risk compared to opioids for gastrointestinal adverse events in general, nausea and vomiting, as well as a lower risk for nausea adverse events when compared to placebo and nsNSAIDS. REGISTRATION: PROSPERO-CRD42025642152.

Journal Article↗

Optimising Exercise Prescription: A Meta-Analysis Examining the Dose Response of Exercise Duration on Cardiorespiratory Fitness Following HIIT and MICT.

BACKGROUND: High-intensity interval training (HIIT) is often promoted as a time-efficient alternative to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness, yet the duration of HIIT sessions varies considerably across studies. OBJECTIVE: We aimed to characterise the dose-response relationship between exercise session duration and the improvement in cardiorespiratory fitness for HIIT and MICT. METHODS: A dose-response meta-analysis of randomised controlled trials comparing exercise duration in HIIT and MICT, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (CRD42022335590). Effect sizes were calculated using a random-effects meta-analysis. The primary outcome was maximal oxygen uptake (VO2max). Secondary outcomes included blood pressure, lipid profiles, glucose metabolism markers and body composition measures. A one-stage random-effects dose-response meta-analysis was performed to examine the relationship between exercise duration and adaptations. We searched PubMed and Google Scholar; eligibility criteria for selecting studies were randomised controlled trials in humans, published in English and exercise interventions lasting at least 4&#xa0;weeks. RESULTS: We identified 69 randomised controlled trials (2387 participants). High-intensity interval training elicited greater improvements in VO2max than MICT (d = 0.38, 95% confidence interval 0.27-0.49, p < 0.001). High-intensity interval training demonstrated a non-linear dose-response relationship between exercise session duration and VO2max, with 80% of maximal effect (changes in VO2max = 3.45&#xa0;mL/kg/min) achieved with only ~11&#xa0;min/session (95% confidence interval 9.5-40.2). Moderate-intensity interval training showed a linear dose-response relationship between exercise session duration and VO2max, requiring ~52&#xa0;min/session to achieve 80% of the&#xa0;maximal observed&#xa0;effect (95% confidence interval 30.4-55.8). The dose-response relationship was consistent across populations. High-intensity interval training and MICT had comparable effects in improving cardiometabolic risk factors. CONCLUSIONS: High-intensity interval training demonstrated a non-linear dose response, with 80% of maximal effect on VO2max in ~11&#xa0;min/session, whilst MICT required four to five times longer to reach similar responses. The different types of training had comparable effects on cardiometabolic risk factors.

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