Highly Pathogenic Avian Influenza (HPAI) viruses, particularly IAV (H5N1), continue to pose a major global threat due to their widespread circulation and high mortality rates in birds. Management of HPAI is complicated by challenges in conserving migratory bird populations, sustaining poultry production, and uncertainties in disease dynamics. Structured decision-making frameworks, such as those based on the PrOACT model, are recommended to improve outbreak response and guide critical actions, especially when HPAI virus (HPAIV) detections occur in sensitive areas like wildlife refuges. Surveillance data from late 2024 to early 2025 show persistent HPAI activity, with 743 detections across 22 European countries and beyond, and notable outbreaks in poultry in nations like Hungary, Iceland, and the UK. The proximity of poultry farms to water sources increases environmental contamination risks. Meanwhile, HPAI A(IAV (H5N1)) and other H5Nx viruses have been detected in a wide range of mammalian species globally, raising concerns about mammalian adaptation due to mutations like E627K and D701N in the PB2 protein. Human infections with IAV (H5N1) have also been reported, with recent cases in North America highlighting zoonotic transmission risks. Molecular studies emphasize the importance of monitoring genetic variations associated with increased virulence and antiviral resistance. Preventive strategies focus on biosafety, personal protective measures, and vaccine development for both avian and human populations. Ongoing genetic characterization and vigilant surveillance remain critical to managing the evolving threat posed by HPAI viruses.

The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk.

Osteomyelitis is a bacterial infection of the bone that affects millions globally. Due to problems in drug delivery, bacterial resistance through biofilm formation, adverse effects of the medications in use, etc, the scientists are searching for novel antimicrobial agents. As drug repurposing is an excellent method to develop new antimicrobials, this study evaluates the antibacterial and antibiofilm effects of the antidepressant paroxetine, combined with hydroxyapatite (HA), against drug-resistant, biofilm-forming Staphylococcus aureus . The antibacterial activity of paroxetine was assessed using the agar diffusion assay, and the minimum inhibitory concentration (MIC) was determined by the microdilution method. The antibiofilm potential of paroxetine was quantified through the crystal violet assay and further examined using scanning electron microscopy and confocal laser scanning microscopy. The bacterial load on drug-loaded hydroxyapatite was determined using the viable colony count method. The expression of bacterial adhesion genes following paroxetine treatment was analyzed using real-time polymerase chain reaction. Molecular docking studies were performed to evaluate the binding affinity of paroxetine to bacterial adhesion proteins and penicillin-binding proteins. The study demonstrated promising antibacterial properties of the drug and the drug-HA combination against S aureus with a MIC of 18.75 µg/mL. Paroxetine prevented the biofilms formation by S aureus , and could eradicate mature biofilms, with 83%, 86%, and 89% efficacy after 1X MIC, and 2X treatment. The antibiofilm effect was further confirmed by in silico, in vitro methods, wherein a strong affinity was noted for biofilm adhesion protein and paroxetine. Paroxetine treatment revealed downregulation of biofilm-adhering genes, like icaA, clfA, cna, fnbpA, and fib, using RT-PCR. When combined with HA, paroxetine displayed synergistic activity, and this was visualized using confocal laser scanning microscopy, which showed 81% and 19% dead/live cells after treatment, respectively. Furthermore, the scanning electron microscopy analysis displayed the impact of the drug paroxetine on S aureus cell morphology, which showed remarkable damage to the bacterial cells. In silico docking revealed that paroxetine’s mode of action was mediated through binding with proteins and penicillin-binding protein, thereby inducing cell death. These results suggest that the paroxetine–HA combination may serve as a promising adjunctive strategy for treating biofilm-associated infections caused by S aureus .

Aim: Healthcare-associated infections (HAIs), especially when multidrug-resistant bacteria cause them, pose serious challenges resulting in higher healthcare expenses, increased morbidity, and higher mortality, and thus, there is a need for new antimicrobial agents. Repurposing an old drug for new applications is an important trend, and in the present study, an anti-breast cancer drug, Tamoxifen, has been screened alone and in combination with silver nanoparticles (AgNPs) synthesized using Abutilon indicum Linn. against Enterococcus faecalis, Escherichia coli, and Staphylococcus aureus, which are involved in HAIs. Methods: The drug and the combination were subjected to antimicrobial potential analysis and the determination of minimum inhibitory concentrations (MICs) by agar diffusion and microdilution methods. Biofilm formation assays were performed using the crystal violet method to understand biofilm prevention and eradication efficiencies. The synergism in the activities of the drug and the combination with selected antibiotics was studied using checkerboard assay, and the cytotoxic effects of the drug and the combination on L929 cells were analyzed using MTT assay. Results: Tamoxifen and the AgNPs showed promising antibacterial activities, and the MICs of the drug were found to be 62.5 µg/mL (E. coli), 31 µg/mL (S. aureus), and 125 µg/mL (E. faecalis). When combined with AgNPs, Tamoxifen showed a 4-fold reduction in the MIC. The drug also displayed promising antibiofilm activities as it reduced mature S. aureus biofilms by 91%, E. faecalis biofilms by 88%, and E. coli biofilms by 73%. AgNPs alone reduced 91%, 91%, and 81% of biofilms by S. aureus, E. faecalis, and E. coli, respectively, and the combination treatment revealed 92% of S. aureus, 94% of E. faecalis, and 82% of E. coli biofilm eradication at their MICs. Tamoxifen also showed synergism when combined with antibiotics—ampicillin and rifampicin and the AgNPs in combination with Tamoxifen revealed no cytotoxic effect on L929 cells at their MICs. Conclusions: All the mentioned studies suggest that Tamoxifen alone and in combination with AgNPs has promising antibacterial and anti-biofilm activities, and it can be developed for better treatment options against HAIs as they are safe for eukaryotic cells.

Catheter-associated urinary tract infections (CAUTIs) cause serious complications among hospitalized patients due to biofilm-forming microorganisms which make treatment ineffective by forming antibiotic-resistant strains. As most CAUTI-causing bacterial pathogens have already developed multidrug resistance, there is an urgent need for alternative antibacterial agents to prevent biofilms on catheter surfaces. As a trial to find out such a potential agent of natural origin, the bark of Tamarix ericoides Rottl., a little-known plant from the Tamaricaceae family, was examined for its antibacterial and antibiofilm activities against one of the major, virulent, CAUTI-causing bacterial pathogens: Enterococcus faecalis. The methanolic T. ericoides bark extract was analyzed for its antibacterial activity using the well diffusion method and microdilution method. Killing kinetics were calculated using time–kill assay, and the ability of biofilm formation and its eradication upon treatment with the T. ericoides bark extract was studied by crystal violet assay. GC-MS analysis was performed to understand the phytochemical presence in the extract. A in vitro bladder model study was performed using extract-coated catheters against E. faecalis, and the effect was visualized using CLSM. The changes in the cell morphology of the bacterium after treatment with the T. ericoides bark extract were observed using SEM. The biocompatibility of the extract towards L₉₂₉ cells was studied by MTT assay. The anti-E. faecalis activity of the extract-coated catheter tube was quantified by viable cell count method, which exposed 20% of growth after five days of contact with E. faecalis. The anti-adhesive property of the T. ericoides bark extract was studied using CLSM. The extract showed potential antibacterial activity, and the lowest inhibitory concentration needed to inhibit the growth of E. faecalis was found to be 2 mg/mL. The GC-MS analysis of the methanolic fractions of the T. ericoides bark extract revealed the presence of major phytochemicals, such as diethyl phthalate, pentadecanoic acid, methyl 6,11-octadecadienoate, cyclopropaneoctanoic acid, 2-[(2-pentylcyclopropyl) methyl]-, methyl ester, erythro-7,8-bromochlorodisparlure, etc., that could be responsible for the antibacterial activity against E. faecalis. The killing kinetics of the extract against E. faecalis was calculated and the extract showed promising antibiofilm activity on polystyrene surfaces. The T. ericoides bark extract effectively reduced the E. faecalis mature biofilms by 75%, 82%, and 83% after treatment with 1X MIC (2 mg/mL), 2X MIC (4 mg/mL), and 3X MIC (6 mg/mL) concentrations, respectively, which was further confirmed by SEM analysis. The anti-adhesive property of the T. ericoides bark extract studied using CLSM revealed a reduction in the biofilm thickness, and the FDA and PI combination revealed the death of 80% of the cells on the extract-coated catheter tube. In addition, SEM analysis showed extensive damage to the E. faecalis cells after the T. ericoides bark extract treatment, and it was not cytotoxic. Hence, after further studies, T. ericoides bark extract with potential antibacterial, antibiofilm, and anti-adhesive activities can be developed as an alternative agent for treating CAUTIs.

The gut-brain axis (GBA) is a two-way communication system that connects neural, endocrine, immune, and metabolic pathways to coordinate the functions of the gastrointestinal tract and central nervous system (CNS). Most human microbes are found in the gastrointestinal tract, and their metabolic activity and roles in immune regulation are vital for overall body balance, cognitive functions, mood regulation, and neuroprotection. Growing evidence points to the vagus nerve as a main pathway for microbiota brain signaling, with germ free mice showing reduced vagal activity that is restored when microbes colonize the gut. Important microbial metabolites such as short chain fatty acids (SCFAs), bile acids, indoles, and neurotransmitter precursors stimulate vagal afferents, modulate neuroimmune responses, and affect microglial development and synaptic function. Disruption of the microbial community, known as dysbiosis (see Section 1.2.3), It is now recognized as a contributing factor in numerous neurological and psychiatric disorders. Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) show distinct microbial changes, chronic neuroinflammation, and impaired gut and blood brain barrier integrity. For example- PD patients consistently have higher levels of Enterobacteriaceae and lower levels of Prevotellaceae. Dysbiosis also affects mood disorders by disrupting the microbial production of GABA, serotonin, and tryptophan metabolites. Although microbial biomarkers differ across studies due to disease heterogeneity, integrative multi omics approaches are beginning to identify shared metabolic patterns and potential therapeutic targets. Microbiota derived metabolites like butyrate have neuroprotective and anti-inflammatory effects, while fecal microbiota transplantation (FMT), prebiotics, probiotics, and next-generation probiotics (NGPs) are emerging as promising modulators of the gut brain axis (GBA). Progress in metagenomics, metabolomics, and using machine learning to profile patients is helping us create more personalized, microbiome-based treatments for brain-related disorders.