Hem Chandra Jha

Objective Disruption of the intestinal epithelial barrier by pathogens such as Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV) have been well-documented in recent years. However, the combined effects of these two common infections remain poorly understood. This study aimed to determine how H. pylori-EBV coinfection alters epithelial integrity and propagates barrier dysfunction along the gut-brain axis.Design Gastric epithelial cells were coinfected with H. pylori and EBV to assess junctional integrity. The coinfection-derived secretome collected from gastric cells was applied to brain endothelial cells (HBEC-5i) to evaluate blood-brain barrier (BBB)-mediated junctional modulations. This was also checked in a transwell model where HBEC-5i (in upper transwell) were cultured with astrocytes and neurons (U87-MG and IMR-32, in bottom transwell) to further assess neural molecular changes. In vivo, secretome was administered intraperitoneally to examine systemic inflammation and neurobehavioural outcomes.Results Gastric epithelial cells showed coinfection-mediated mislocalisation of tight and adherens junction proteins (Zonula occludens‐1 and E-cadherin). Furthermore, exposure of brain endothelial cells to coinfection-derived gastric secretome resulted in alterations of junctional markers and barrier-associated properties in BBB model. This was accompanied by junctional marker disruption in BBB-like model. In vivo exposure of secretome triggered systemic inflammation and neurobehavioural modulations.Conclusion These findings demonstrate that coinfection-derived gastric secretome can influence barrier-associated processes along the gut-brain axis, highlighting a potential mechanism by which peripheral infections may modulate cerebral homeostasis.

Orthobunyaviruses are linked to a broad spectrum of neurological disorders. However, the molecular determinants governing bunyavirus neuropathogenesis remain poorly understood, precluding the identification of drugs able to alleviate virus-induced neuronal dysfunctions. Here, we show that the prevalent, yet neglected, orthobunyavirus Ťahyňa virus (TAHV) disrupts neuronal integrity and proteostasis in human cerebral organoids (hCO), significantly decreasing synaptic protein expression and density. Moreover, TAHV-induced synaptic remodeling is associated with perturbed local field potential in organotypic cultures of human post-mortem adult brain explants (OPAB) and higher expression of the metabotropic Glutamate receptor 1 (mGluR1) in mice in the absence of overt neurological disease or neuroinflammation. Using proteome-based network medicine, we identified gabapentin as a therapeutic candidate that restores neurotransmitter receptor levels back to baseline in mice, and prevents TAHV-induced hyperexcitability in OPAB. Together, our data highlights the underappreciated neuropathological potential of a neglected orthobunyavirus, that interferes with neural integrity and neurotransmission, while neuromodulatory interventions may help to preserve cerebral functions.

Small peptides exhibit remarkable antimicrobial and biological functions, yet their translation into biomaterials often requires chemical modifications that can compromise their native functionalities. Physically cross-linked hydrogels involving noncovalent interactions can retain pristine biomolecules, enabling their functional integration. Here, we present a facile strategy for constructing all-biomolecular hydrogels through the noncovalent integration of glutathione and guanosine monophosphate. The spontaneous formation of transparent, robust, and physically cross-linked hydrogels occurs via G-quadruplex assembly, preserving inherent biomolecular functionality. These hydrogels demonstrate good mechanical strength, broad pH stability, and self-healing behavior. Morphological analysis reveals protocell-like spherical intermediates, eventually yielding helical fibrillar networks. The supramolecular fibers exhibit dose-dependent cytocompatibility with selective bioactivities, suitable for biomedical applications. In vitro studies confirmed pronounced antiviral efficacy against Epstein–Barr virus and SARS-CoV-2, alongside broad-spectrum antibacterial efficacy. Additionally, the fibers induced apoptosis in gastric cancer cells. The viscoelastic and shape-sustaining behavior of these hydrogels holds potential scope to develop antimicrobial coating materials.

Neurological disorders are increasingly linked to dysfunction of key cellular organelles, including mitochondria, endoplasmic reticulum (ER), lysosomes, endosomes, and peroxisomes. These organelles coordinate essential neuronal processes via tightly regulated crosstalk. Disruption in one organelle can propagate dysfunction across others, amplifying neurodegenerative cascades. Emerging evidence suggests that neurological diseases can result not only from disturbances in brain homeostasis but also from imbalances in gut homeostasis, highlighting the significant role of the gut-brain axis in maintaining neurological health. Helicobacter pylori, a gut pathogen contribute to the progression of neurological modalities by its secretome comprising Vac A, CagA, urease, and outer membrane vesicles via perturbing organelle function. These virulence factors induce mitochondrial fragmentation, ER stress, lysosomal dysfunction, and impaired mitophagy, disrupting organelle networks and promoting synaptic loss and neuronal death. Understanding how pathogen-induced organelle stress contributes to neurodegeneration offers novel insights into infection-driven brain disorders.