http://www.nexuspt.org/ Nexus of Pathophysiology & Therapeutics Journal (NPT) en daily 1 Sat, 25 Apr 2026 00:00:00 +0330 Sat, 25 Apr 2026 00:00:00 +0330 http://www.nexuspt.org/article_242955.html Biomedical science has achieved unprecedented resolution, mapping disease at molecular and cellular scales. Yet, understanding mechanisms does not consistently translate into effective treatment. This reflects a structural challenge: mechanistic insights often remain clinically isolated, while therapeutic advances may precede biological rationale. Nexus of Pathophysiology and Therapeutics Journal (NPT) addresses this tension by focusing on the explicit relationship between disease mechanisms and interventions. The journal prioritizes studies that clarify how biological understanding informs therapy and how therapeutic outcomes refine mechanistic reasoning. Cross-disease biology, such as chronic inflammation, dysregulated repair, and immunometabolic imbalance, is emphasized to reveal conserved programs and transferable strategies. NPT values rigor, relevance, and clarity: mechanistic depth must align with therapeutic significance, and claims must be proportionate to evidence. By bridging explanation and intervention, the journal seeks to integrate descriptive, experimental, computational, and clinical research into a coherent framework, guiding precision medicine and shaping the future of translational science. http://www.nexuspt.org/article_243351.html Hantaviruses are zoonotic RNA viruses that cause a spectrum of diseases, including hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Although clinical manifestations vary among hantavirus species, increasing evidence suggests that disease severity is driven primarily by dysregulated host immune responses and vascular dysfunction rather than direct viral cytopathic effects alone. Hantaviruses exhibit a marked tropism for endothelial and immune cells, where infection alters inflammatory signaling pathways and disrupts vascular homeostasis. Increased endothelial permeability and capillary leakage are central features of severe disease and are associated with cytokine amplification, leukocyte recruitment, and endothelial barrier dysregulation. Multiple mediators, including tumor necrosis factor-α, interleukin-6, interferon-γ, vascular endothelial growth factor, and bradykinin-related pathways, have been implicated in the pathogenesis of tissue edema and vascular instability. Current evidence further suggests that endothelial injury in hantavirus infection is predominantly functional rather than structurally destructive, reflecting complex interactions between viral persistence, host inflammatory responses, and vascular signaling networks. This review summarizes current understanding of the molecular and immunopathogenic mechanisms underlying hantavirus-associated vascular disease, with particular emphasis on endothelial dysregulation, cytokine-mediated injury, and permeability signaling pathways. http://www.nexuspt.org/article_243698.html Background: Preeclampsia is a pregnancy-specific disorder characterized by multisystem involvement and significant maternal–fetal morbidity. Emerging evidence suggests that hematological indices may reflect underlying pathophysiological mechanisms, including inflammation, oxidative stress, and impaired erythropoiesis.Methods: This case–control study was conducted on 130 pregnant women (65 cases and 65 controls) referred to Shahid Rahimi Hospital between 2023 and 2024. Participants were matched based on maternal age and gestational age. Demographic characteristics and hematological parameters, including hemoglobin (Hb), hematocrit (HCT), red blood cell (RBC) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW), were extracted from medical records. Independent t-tests and analysis of covariance (ANCOVA) were used for statistical analysis, adjusting for age, body mass index (BMI), education level, and parity.Results: Significant differences were observed in MCV, MCHC, and RDW between the two groups. MCV and MCHC were significantly lower in the preeclampsia group, while RDW was significantly higher (P = 0.001 for all). These associations remained statistically significant after adjustment for confounding variables. No significant differences were observed in Hb, HCT, RBC count, or MCH.Conclusion: Alterations in RBC indices, particularly RDW, MCV, and MCHC, are associated with preeclampsia and may reflect underlying biological processes such as oxidative stress, inflammation, and impaired erythropoiesis. These routinely available hematological parameters may have potential translational value as accessible biomarkers for clinical assessment and risk stratification in preeclampsia, although further mechanistic and prospective studies are warranted.Mechanistic and Translational Relevance: These hematological indices may reflect underlying inflammation, oxidative stress, and impaired erythropoiesis in preeclampsia. They may serve as accessible, low-cost biomarkers of systemic involvement and could support adjunctive clinical assessment and risk stratification, particularly in resource-limited settings. http://www.nexuspt.org/article_243712.html Hantavirus infections are primarily acquired through inhalation of aerosolized particles originating from rodent excreta and lead to severe pulmonary and renal syndromes. Although clinical features are well characterized, tissue-level mechanisms remain unclear. Histopathology consistently shows endothelial swelling, edema, and immune cell infiltration, indicating combined viral and host immune contributions to disease pathogenesis. The lungs and kidneys are the principal target organs, where microvascular dysfunction drives the most severe clinical manifestations. Hantaviruses preferentially infect endothelial cells of the microvasculature in these organs through integrin-mediated entry. Following infection, viral replication proceeds without marked cytopathic effects; instead, disruption of endothelial junctional proteins and cytoskeletal remodeling leads to progressive loss of barrier integrity. This results in increased vascular permeability, plasma leakage, and tissue edema. Activation of signaling pathways such as VEGF and RhoA/ROCK further amplifies endothelial dysfunction, contributing to pulmonary edema and renal impairment. In parallel, immune-mediated mechanisms play a central role in tissue injury. Recruitment of macrophages and cytotoxic T cells, together with elevated levels of proinflammatory cytokines including TNF-α and IL-6, intensifies vascular leakage and exacerbates organ damage. Disease severity appears to correlate more strongly with the magnitude of the host immune response than with direct viral cytotoxicity, emphasizing the importance of immunopathology in disease progression. From a mechanistic and translational perspective, hantavirus disease represents a paradigm of combined endothelial and immune-driven injury. The disruption of vascular integrity identifies potential therapeutic targets aimed at stabilizing endothelial junctions and modulating permeability-related signaling pathways such as VEGF and RhoA/ROCK. In addition, strategies that selectively attenuate excessive cytokine responses without inducing broad immunosuppression may reduce tissue damage and improve clinical outcomes. Histopathological features including endothelial swelling, tubular necrosis, and interstitial hemorrhage further provide measurable biomarkers for evaluating disease severity and therapeutic efficacy, bridging mechanistic insights with clinical application and supporting the development of targeted interventions. http://www.nexuspt.org/article_243713.html Inflammation is a conserved biological response essential for host defense; however, its dysregulation contributes to a broad spectrum of chronic diseases, including autoimmune, cardiovascular, metabolic, neurodegenerative, and malignant disorders. Over recent decades, advances in molecular immunology have shifted the conceptual framework of inflammation from a linear cascade to a complex, network-based regulatory system, in which therapeutic efficacy depends on precise modulation of interconnected signaling pathways rather than broad immunosuppression. Despite the clinical success of biologics targeting tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as small-molecule inhibitors such as Janus kinase (JAK) inhibitors, long-term disease control remains limited due to cytokine redundancy, compensatory signaling, and underlying disease heterogeneity. Intracellular signaling hubs such as nuclear factor-κB (NF-κB) and innate immune complexes including the NLRP3 inflammasome further illustrate the challenge of targeting central regulatory nodes that are simultaneously essential for physiological immune homeostasis. This commentary emphasizes that inflammatory diseases should be understood as emergent properties of adaptive immune networks rather than isolated molecular events. Mechanistic and translational relevance of this perspective lies in integrating cytokine signaling, intracellular pathways, and inflammasome biology within a systems-level framework that explains both therapeutic success and failure of current interventions. Such an integrated view highlights the limitations of single-target strategies and supports a shift toward network-informed and patient-specific approaches. Future therapeutic development will likely depend on causal network modeling, multi-omics integration, and biomarker-guided stratification to enable precision immunomodulation. This paradigm shift from pathway-centric inhibition to dynamic regulation of immune networks may provide more durable and mechanistically grounded strategies for the treatment of chronic inflammatory diseases.