Cytokine & Growth Factor Reviews最新文献

Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease, with inflammation and fibrosis serving as pivotal drivers of disease progression. Chronic hyperglycemia induces oxidative stress, activates immune pathways, and promotes extracellular matrix (ECM) accumulation, leading to irreversible kidney damage. Inflammatory cytokines contribute to DN progression, such as tumor necrosis factor-a (TNF-a), interleukin-1 (IL-1), IL-6, and IL-17. Moreover, chemokines, their receptors, and adhesion molecules are critically involved in the progression of inflammation during the development of DN. On the other hand, several renal cell types contribute to the fibrotic process of DN by either producing ECM components directly or secreting profibrotic mediators that stimulate fibroblast activation. Fibroblasts, immune cells, and endothelial cells play pivotal roles in mediating fibrosis. Emerging evidence highlights the critical role of inflammatory and fibrotic signaling pathways in DN progression. The activation of the NF-κB, JAK-STAT, and NLRP3 inflammasome pathways contributes to sustained inflammation by promoting proinflammatory cytokine release and immune cell infiltration. Simultaneously, the TGF-β/Smad, Wnt/β-catenin, PI3K/Akt, and MAPK signaling pathways drive fibrosis by inducing ECM deposition and epithelialmesenchymal transition (EMT). Understanding these interconnected pathways provides insights into potential therapeutic targets for mitigating DN progression. In this review, we explore the molecular mechanisms that link inflammation and fibrotic responses to the progression of DN, focusing on signaling pathways, cellular mediators and therapeutic targets.

Long COVID is a chronic condition that arises after SARS-CoV-2 infection and is characterized by persistent and often debilitating symptoms, such as fatigue, cognitive dysfunction ("brain fog"), dyspnea, and autonomic disturbances. Increasing evidence suggests that Long COVID shares key immunopathological mechanisms with autoimmune diseases, primarily sustained immune dysregulation. In individuals with genetic or immunological susceptibility, SARS-CoV-2 infection can trigger the production of autoantibodies targeting cytokines, membrane receptors, and components of the autonomic nervous system (ANS), thereby disrupting neuroimmune homeostasis. This immune imbalance may impair anti-inflammatory regulatory pathways, such as the cholinergic anti-inflammatory pathway (CAP), and may contribute to a chronic state of inflammation and autoimmunity. One proposed contributor to this process is inflammaging - a chronic, low-grade inflammation associated with aging - which may not only predispose individuals to Long COVID but may also be amplified by the persistent immune activation seen in this condition. In this perspective, we propose a conceptual framework in which inflammaging, immune-tolerance breakdown, and autonomic dysfunctions interact to sustain the pathophysiology of Long COVID. We discuss emerging biomarkers across these axes, including inflammatory cytokines, circulating autoantibodies, immune cell phenotypes, epigenetic modifications, and heart rate variability. Advances in inflammaging-related biomarkers and biological clocks may support early identification of individuals at higher risk for persistent immune and autonomic dysregulation, ultimately informing more precise diagnostic and therapeutic strategies for Long COVID.