To investigate the involvement of transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase 4 (TIMP-4) in influencing the severity of atrial fibrosis in rheumatic heart disease (RHD) patients with atrial fibrillation (AF). The degree of myocardial fibrosis was evaluated using Masson staining. The expression levels of TGF-β1, TIMP-4, matrix metalloproteinase-2 (MMP-2), type I collagen, and type III collagen were estimated by Western blot analysis. Additionally, TGF-β1 and TIMP-4 mRNA levels were quantified by qRT-PCR. The effect of TGF-β1 stimulation on TIMP-4 expression was assessed by in vitro stimulation of freshly isolated human atrial fibroblasts with recombinant human TGF-β1, followed by Western blot analysis to detect changes in TIMP-4 levels. Masson stain revealed that the left atrial diameter and collagen volume fraction were obviously increased in AF patients, compared to sinus rhythm (SR) controls (both P < 0.05). Western blot analysis showed significantly elevated levels of the AF markers MMP-2, type I collagen, and type III collagen in the AF group, in comparison to the SR controls (all P < 0.05). In the AF group, TGF-β1 expression was relatively higher, while TIMP-4 expression was apparently lower than the SR group (all P < 0.05). TIMP-4 expression level showed a negative association with TGF-β1 expression level (r = -0.98, P < 0.01) and TGF-β1 stimulation of atrial fibroblasts led to a sharp decrease in TIMP-4 protein level. Increased TGF-β1 expression and decreased TIMP-4 expression correlated with atrial fibrosis and ECM changes in the atria of RHD patients with AF. Notably, TGF-β1 suppressed TIMP-4 expression, suggesting that selective TGF-β1 inhibitors may be useful therapeutic agents.

Remote ischemic preconditioning (IPreC) is an effective strategy to defend against cerebral ischemia/reperfusion (IR) injury; however, its mechanisms remain to be elucidated. The aim of the present study was to investigate the effect of IPreC on brain tissue following cerebral ischemia, as well as the underlying mechanisms. Adult male Sprague-Dawley rats were treated with IPreC for 72 h prior to the induction of transient cerebral ischemia and reperfusion. The results demonstrated that IPreC reduced the area of cerebral infarction in the IR rats by 2,3,5-triphenyl-tetrazolium chloride staining. In addition, cell apoptosis was markedly suppressed by IPreC with an increased expression of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associatd X protein using Terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay and western blot analysis. IR induced a decrease in the level of superoxide dismutase, and IPreC significantly suppressed increased levels of malondialdehyde, lactate dehydrogenase and nitric oxide. The expression of CD11b and CD18 was markedly inhibited by IpreC unsing flow cytometry. Furthermore, IPreC markedly decreased the release of pro-inflammatory factors interleukin (IL)-6 and IL-1β, and enhanced the level of anti-inflammatory factors (IL-10 and IL-1 receptor antagonist) by ELISA assay. Finally, IPreC reduced the levels of transforming growth factor-β-activated kinase 1, phosphorylated-P65/P65, and tumor necrosis factor-α, indicating that the nuclear factor-κB pathway was involved in IPreC-mediated protection against cerebral ischemia. Taken together, the results suggested that IPreC decreased ischemic brain injury through alleviating free radical injury and the inflammatory response in cerebral IR rats.

Values of low density lipoprotein (LDL) and procalcitonin (PCT) levels in evaluating the condition and prognosis of patients with acute cerebral infarction (ACI) were investigated. According to the volume of cerebral infarction, 150 patients with ACI (observation group) were divided into the mild infarction group (n=50), moderate infarction group (n=50), and severe infarction group (n=50). Besides, another 50 healthy subjects were enrolled during the same period as the control group. The levels of serum LDL and PCT on admission and at the 1st, 3rd, 7th and 10th day after treatment were detected, which were compared with those in the control group. Ten days after treatment, patients were divided into two groups, the effective group and non-effective group, based on the clinical efficacy. The differences in LDL and PCT levels were compared between the two groups. After 1 month, the clinical efficacy was evaluated again, and the correlations of LDL and PCT levels with prognosis were analyzed. The levels of serum LDL and PCT in the observation group 1 day after admission were higher than those in the control group (P<0.05), which reached the peak at the 3rd day and continuously declined after the 7th day. The LDL and PCT levels had statistically significant differences between the effective group and non-effective group (P<0.05). Pearson's correlation analysis showed that the serum LDL and PCT levels in acute phase were negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score after 1 month of treatment (P<0.05). The dynamic monitoring of serum LDL and PCT levels in ACI patients can help evaluate the condition and prognosis of patients.