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关键词： Cardiovascular Physiology  

摘要： IL-12 is a heterodimeric proinflammatory cytokine composed of IL-12α and IL-12β subunits and is mainly produced by monocytes/macrophages, dendritic cells, and B cells. IL-12β plays an important role in modulating inflammatory responses by activating the proliferation and differentiation of natural killer cells and T cells to produce interferon-gamma and enhance their anti-tumor and anti-microbial activity. However, the role of IL-12β on heart failure (HF) development and HF progression is unknown. Here, we investigated the effect of IL-12β on cardiac inflammation, hypertrophy, dysfunction, and HF progression in response to chronic pressure overload produced by transverse aortic constriction (TAC) by using wild-type (WT) and IL-12β gene knockout (IL-12β KO) mice of both genders. Interestingly, IL-12β KO significantly attenuated chronic pressure overload-induced HF development as evidenced by significantly less reduction in ejection fraction and fractional shortening in both genders. In addition, IL-12β KO also significantly ameliorated the TAC-induced increase of LV weight, LA weight, lung weight, RV weight, and their ratios to body weight or tibial length. Furthermore, IL-12β KO significantly attenuated TAC-induced LV inflammation, cardiomyocyte hypertrophy, fibrosis, and lung inflammation and remodeling. Moreover, RNA sequencing data from the LV tissues of the TAC group showed significant downregulation of genes related to fibrosis and inflammation in IL-12β KO mice compared to WT mice. Taken together, these findings indicate that IL-12β KO effectively attenuates pressure overload-induced cardiac inflammation, hypertrophy, and dysfunction and promotes the transition from LV failure to lung remodeling and RV hypertrophy. This research is funded by NIH grants R01HL161085, R01HL139797, P20GM104357, and P30GM149404. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The

关键词： Knee osteoarthritis   Sodium hyaluronate   Platelet-rich plasma   Physical therapy   Inflammation  

摘要： The occurrence of osteoarthritis in the knee joint is regulated by a complex network, and there is currently no specific therapeutic drug available. Functional exercises and treatments targeting inflammatory factors have shown the potential to alleviate knee osteoarthritis to some extent. Therefore, the aim of this study was to assess the intra-articular injection (IAI) of autologous platelet-rich plasma (PRP) combined with physical therapy (PT) in treating knee osteoarthritis. A total of 128 patients with knee osteoarthritis were included in the study, including 64 males and 64 females. A total of 128 patients were divided into sodium hyaluronate group (HA group), PRP group, PRP + PT group, and PT group, with 32 cases in each group. Visual analog scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Japanese Orthopaedic Association (JOA) were employed to evaluate the recovery of patients from pain and osteoarthritis. Color Doppler ultrasound imaging technology was utilized to assess joint effusion, synovial membrane thickness, and articular cartilage thickness in patients with knee osteoarthritis. Enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of interleukin-1 beta (IL-1 beta), transforming growth factor-beta 1 (TGF-beta 1), and matrix metallopeptidase 3 (MMP-3) in the synovial fluid. Compared to the HA group, the PT group, PRP group, and PRP combined with PT (PRP + PT) group all showed reduced VAS and WOMAC scores, increased JOA scores, decreased joint effusion, synovial membrane thickness, and articular cartilage thickness in the knee joint. Additionally, levels of IL-1 beta and MMP-3 in the synovial fluid decreased, while TGF-beta 1 levels increased (P < 0.05). Compared with the PT group, the VAS and WOMAC scores of the knee joint in the PRP group decreased, JOA scores increased, joint effusion, synovial thickness, and articular cartilage thickness decreased, but there was no statistically significant

关键词： CD   Crohn’s disease   FC   fecal calprotectin   IBD   inflammatory bowel disease   IC   indeterminate colitis   SD   standard deviation   TNF   tumor necrosis factor   UC   ulcerative colitis   UPA   upadacitinib  

摘要： Upadacitinib (UPA) is an oral selective inhibitor for Janus kinase 1 approved for the treatment of tumor necrosis factor (TNF)-alpha–experienced patients with inflammatory bowel disease (IBD). Phase III trials of UPA showed remission rates approac...

关键词： Cognitive dysfunction   Methamphetamine   Cytokines   Tumor necrosis factor-alpha   Interleukin-1 beta   Interleukin-6  

摘要： Objective: To investigate the cognitive impairment and peripheral inflammation induced by methamphetamine (METH) and their association in METH abusers. Methods: The cross-sectional study included 100 METH-dependent patients and 100 healthy controls. Cognitive screening was conducted using the Thai version of the Montreal Cognitive Assessment (MoCA-T). Thirty normal controls and 30 METH-dependent patients were randomly selected for blood collection to measure inflammatory markers, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1(3, and IL-6, using a quantitative enzyme-linked immunosorbent assay method. Results: METH-dependent patients had significantly poorer MoCA-T scores and higher levels of blood inflammatory markers compared to healthy controls. Demographic characteristics, METH use patterns, and proinflammatory cytokines were associated with cognitive impairment. The MoCA-T score was negatively associated with plasma TNF-alpha and IL-6 levels. Conclusion: METH-associated cognitive decline is correlated with elevated plasma levels of TNF-alpha and IL-6 cytokines, indicating the involvement of specific neuroinflammatory pathways in neurocognitive dysfunction. These insights could pave the way for novel therapeutic strategies aimed at mitigating neuroinflammation, potentially improving outcomes for individuals with METH addiction.

关键词： Serum amyloid P component   Porcine epidemic diarrhea virus   Toll-like receptor 4   Interferon regulatory factors 3   Type I IFN  

摘要： Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus that causes significant economic losses in many Asian and European countries. It is characterized by lethal watery diarrhea and high mortality rate in piglets. Serum amyloid P component (SAP), a member of acute response phase protein (APP) family, has been reported to play a crucial role in innate immune response against various microbial pathogens. However, its antiviral activities are little known. In this study, the antiviral activity of SAP during PEDV infection was investigated. In virus-infected IPEC cells, it was found that SAP expression was significantly upregulated. To study the role of SAP in PEDV replication, the expression of SAP was regulated in cells using eukaryotic expression plasmids expressing the SAP protein and sgRNA. PEDV replication was then assessed through realtime PCR, Western blotting, and TCID50 assays. The result showed that PEDV replication was inhibited in cells overexpressing SAP and promoted in cells with SAP knocking out. To further investigate the mechanism by which SAP inhibits PEDV replication, Interferon Beta (IFN-(3) and its related signaling pathway proteins were detected. The results demonstrated that SAP activates the promoter of (IFN-(3) and IFN regulatory factor 3 (IRF3) mediated by Toll-Like Receptor 4 (TLR4) signaling. During PEDV infection, SAP enhances TLR4-mediated IFN-(3 signaling, leading to increased IFN-(3 expression, which subsequently suppresses PEDV replication. By using TBK1/IKBKE inhibitor MRT67307 in PEDV-infected cells, the antiviral activity of SAP was inhibited. This suggests that the antiviral effect of SAP may rely on the activation of the TBK1/IKBKE signaling pathway, which is critical for the induction of type I interferons and other antiviral responses. Moreover, the interaction between SAP and PEDV N protein and the functional domain of SAP were investigated. From the results of this study, it can be concluded that the