Liensinine reduces acute lung injury brought on by lipopolysaccharide by inhibiting the activation of the NF-κB signaling pathway through modification of the Src/TRAF6/TAK1 axis.

ALI is characterized by macrophage-driven inflammation, causing severe lung damage. Currently, there are limited therapeutic options available for ALI. Liensinine (LIEN), with known anti-inflammatory properties, lacks extensive study in the ALI context. This study aimed to investigate the impact of LIEN on ALI and elucidate its molecular mechanisms. A total of thirty-six male BALB/c mice altogether were split into six groups: Control, LPS (10 mg/kg), Low (10 mg/kg LIEN + 10 mg/kg LPS), Middle (20 mg/kg LIEN + 10 mg/kg LPS), High (40 mg/kg LIEN + 10 mg/kg LPS), and DEX (2 mg/kg DEX + 10 mg/kg LPS). Lung tissue injury, pulmonary edema, and inflammatory factor levels were evaluated in lung tissues and LPS-stimulated bone marrow-derived macrophages (BMDM). TAK1 activation, TRAF6 ubiquitination, and their interactions were assessed to understand the involved molecular mechanisms. LIEN treatment ameliorated lung tissue injury and suppressed LPS-induced inflammatory factor levels in lung tissues and BMDM. Mechanistically, LIEN inhibited TAK1 activation by disrupting TRAF6-TAK1 interactions, limiting p65's nuclear translocation, and reducing the release of inflammatory factors. According to network pharmacology and molecular docking, LIEN most likely prevents inflammation by interfering directly with the Src. Overexpression of Src in BMDM abolished the regulation of TRAF6 by LIEN, supporting the involvement of the Src/TRAF6/TAK1 axis in its mechanism of action. Based on this study, LIEN treats ALI by modifying the Src/TRAF6/TAK1 axis and blocking the activation of the NF-κB pathway, regulating the release of inflammatory factors. These findings highlight the promise of LIEN as a prospective therapeutic option for the treatment of ALI.

Risk factors of acute ischemic stroke and the role of angiotensin I in predicting prognosis of patients undergoing endovascular thrombectomy.

Purpose: The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk factors of AIS and explore the role of serum indicators such as angiotensin I (Ang I) in the prognosis of patients undergoing endovascular thrombectomy (EVT). Patients and methods: Patients with AIS who underwent EVT and healthy controls were retrospectively enrolled in this study, and the patients were divided into a good or a poor prognosis group. We compared Ang I, blood routine indexes, biochemical indexes, electrolyte indexes, and coagulation indexes between patients and controls. We used univariate and multivariate logistic regression analyses to evaluate possible risk factors for AIS and the prognosis of patients undergoing EVT. Independent risk factors for the prognosis of patients undergoing EVT were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves (ROC). Results: Consistent with previous studies, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. In addition, Ang I levels are lower in AIS compared to the controls. The level of Ang I was higher in the good prognosis group. Furthermore, we developed a nomogram to evaluate its ability to predict the prognosis of AIS after EVT. The AUC value of the combined ROC model (Ang I and albumin-globulin ratio (AGR)) was 0.859. Conclusions: In conclusion, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. The combined Ang I and AGR model has a good predictive ability for the prognosis of AIS patients undergoing arterial thrombectomy.

[Construction of HA-1-DC nucleic-acid vaccine and induction of specific cytotoxic T lymphocytes].

The purpose of this study was to construct a HA-1-DC nucleic acid vaccine and to induce anti-leukemia effect after hematopoietic stem cell transplantation (HSCT). The dendritic cells (DCs) were generated from HSCT donors in vitro, and its immunologic activity was studied by using flow cytometry and mix lymphocyte reaction. HA-1 gene was electroporated into the cultured DCs to construct a DC nucleic acid vaccine. After transfecting for 48 hours, the expression of HA-1 protein was detected by Western blot. The DCs were cultured with isogenic lymphocytes to induce specific cytotoxic T lymphocytes (CTLs). The cytotoxicity of the CTLs was detected by LDH assay. The results showed that the DCs derived from peripheral blood monocytes (PBMCs) expressed the DC phenotype, and were effective in stimulating proliferation of the allogenic lymphocytes. After electroporating for 48 hours, HA-1 protein was detected by Western blot. The cytotoxity of inducing CTLs was higher than that in the control group. It is concluded that the minor histocompatibility antigen HA-1 can be considered as a target of immunotherapy against leukemia after HSCT.