Hantaviruses are rodent-borne zoonotic pathogens responsible for two major clinical syndromes: Hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome/cardiopulmonary syndrome. Although significant progress has been achieved in hantavirus research over recent decades, major challenges remain in surveillance, diagnostics, therapeutics, and vaccine development. This review comprehensively synthesizes current evidence on hantavirus virology, taxonomy, reservoir ecology, transmission dynamics, global epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, prevention, and One Health surveillance strategies. Particular emphasis is placed on the immunopathological mechanisms underlying endothelial dysfunction and vascular hyperpermeability, the hallmark features of severe disease. The review further explores how climate variability, land-use change, biodiversity loss, and rodent population dynamics shape spillover risk and geographic expansion. Current diagnostic approaches, including serology, RT-PCR, and next-generation sequencing, are critically evaluated alongside emerging point-of-care technologies. Therapeutic limitations are highlighted, particularly the absence of universally effective antivirals and globally approved vaccines. Key research gaps identified include inadequate surveillance in South Asia and Africa, insufficient understanding of Andes virus human-to-human transmission, limited validation of rapid diagnostics, and unresolved mechanisms of immune-mediated pathology. Adopting a One Health perspective, this review proposes priority research and public health directions to strengthen global preparedness, improve outbreak prediction, and accelerate development of effective diagnostics, therapeutics, and vaccines against hantavirus disease.

Classical swine fever remains a major threat to global pig production systems, despite decades of sustained control endeavours. Its causative agent classical swine fever virus (CSFV) employs a highly coordinated set of immune evasion mechanisms to weaken host antiviral defences and permit extensive viral replication. A central focus of this strategy is the antigen-presentation machinery, where CSFV disrupts both major histocompatibility complex class (MHC)-Ⅰ and MHC-Ⅱ pathways in macrophages and dendritic cells, which are its primary immune cell reservoirs. By suppressing interferon signaling, dysregulating NF-κB activation, and impairing the maturation of antigen-presenting cells, CSFV compromises peptide processing, co-stimulatory signaling, and T-cell priming. These defects propagate through the adaptive immune system, leading to delayed cytotoxic responses, inadequate CD4⁺ T-cell help, and impaired humoral immunity. CSFV simultaneously reshapes macrophage polarization, drives profound dendritic cell dysfunction, induces lymphoid apoptosis, and modulates γδ T-cell activity in a manner that correlates with viral virulence. In addition, viral remodeling of intracellular organelles further limits antigen presentation and exacerbates immunopathology. Together, these interconnected mechanisms create a permissive cellular environment that facilitates viral persistence and amplifies disease severity. Understanding how CSFV manipulates antigen-presentation pathways provides crucial insights for the design of next-generation vaccines and therapeutic strategies capable of restoring robust antiviral immunity.

Objective: To explore whether gomisin D, a lignan derived from Schisandra chinensis, protects against podocyte injury in diabetic kidney disease and to elucidate its underlying mechanisms. Methods: Network pharmacology was employed to analyze the potential interactions between gomisin D and podocyte injury-related targets in diabetic nephropathy. A high glucose-induced injury model of mouse podocyte MPC5 cells was established, and the effect of gomisin D on podocyte injury was subsequently evaluated by measurement of reactive oxygen species levels and biochemical markers and Western blotting. Molecular docking and further molecular biology assays were conducted to explore the interaction between gomisin D and the target protein. Results: Gomisin D inhibited high glucose-induced oxidative stress, improved cell viability, and preserved the expression of podocin and synaptopodin. Network pharmacology identified glycogen synthase kinase-3β (GSK3β) as a key target. Molecular docking predicted a potential interaction between gomisin D and GSK3β, which was further validated by drug affinity responsive target stability and cellular thermal shift assay, confirming direct binding in live cells. Mechanistically, gomisin D enhanced the phosphorylation of GSK3β at Ser9, promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), and upregulated levels of downstream antioxidant proteins heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. Furthermore, forced expression of the constitutively active GSK3β mutant S9A decreased GSK3β (Ser9) phosphorylation and reversed gomisin D-induced upregulation of these antioxidant markers. Conclusions: Gomisin D mitigates high glucose-induced podocyte injury in vitro by inhibiting oxidative stress via activation of the GSK3β(Ser9)/Nrf2/ARE signaling pathway.

Objective: To investigate the inhibitory effects of Ishige okamurae extract (IOE) against osteoclastogenesis in vitro and in vivo. Methods: The effects of IOE on osteoclast differentiation were examined in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated bone marrow macrophages. Cell viability was examined using an MTT assay, while osteoclast formation and differentiation were determined by tartrate-resistant acid phosphatase (TRAP) staining kit. Protein expression levels of osteoclast-related factors, transcriptional factors, and signaling molecules involved in osteoclastogenesis were analyzed by Western blotting. The effect of IOE was examined in the ovariectomy (OVX) mouse model following oral administration, and osteoclast-related parameters were analyzed using 3D X-ray microscopy. Results: IOE significantly reduced RANKL-induced osteoclast formation and differentiation without causing cytotoxic effects on bone marrow macrophages. It suppressed the formation of TRAP-positive multinuclear osteoclasts and downregulated the expression of osteoclast-related factors, such as TRAP (ACP5), matrix metalloproteinase-9, calcitonin receptor, and cathepsin K. Furthermore, IOE significantly inhibited the expression of key transcriptional factors, such as nuclear factor of activated T cells, cytoplasmic 1, and c-Fos. Mechanistically, IOE attenuated the activation of upstream extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-κB (NF-κB) cascades. In OVX mice, administration of IOE significantly improved bone microstructural parameters such as trabecular thickness, number, volume, and separation. Conclusions: The present findings demonstrate that IOE inhibits osteoclastogenesis via blockage of ERK, JNK, and NF-κB signaling pathways in vitro. Furthermore, IOE administration reduces bone loss in OVX mice. These results show that IOE has the potential to be a functional food for the prevention of osteoporosis.