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ABSTRACT Purpose: To evaluate the ameliorative effect of mesenchymal stem cells (MSCs) on acetic acid colitis model via Nrf2/HO-1 pathway in rats. Methods: In this study, 30 rats were divided into three groups. Acute colitis was induced by rectal administration of 4% solution of acetic acid. MSCs were injected intraperitoneally in the treatment group. Results: Increased levels of tumor necrosis factor-α (TNF-α), pentraxin-3, and malondialdehyde (MDA) in colitis group were revealed biochemically. Increased level of TNF-α and decreased levels of Nrf2 and interleukin-10 (IL-10) were observed in rectum tissues. Increased fibrous tissue proliferation, vascularization and inflammatory cell infiltration were described in the colitis group. Significant improvement was observed in MSCs treated group histopathologically. Increased immunopositivity of TNF-α, vascular endothelial growth factor (VEGF) and CD68 markers was observed in the colitis group cells, and decreased level of this positivity was observed in MSCs treated group. Conclusions: Biochemical, histopathological and immunohistochemical results strongly support the ameliorative effect of MSCs against acetic induced colitis model via Nrf2/HO-1 pathway in rats.

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ABSTRACT Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

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ABSTRACT Purpose: Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI. Methods: MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation. Results: We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation. Conclusions: Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

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ABSTRACT Purpose: To explore the mechanism of jatrorrhizine on apoptosis and fibrosis induced by myocardial infarction (MI) in an animal model. Methods: The left anterior descending branch of coronary artery was surgically ligated to duplicate the mouse model of MI. The sham and infarcted mice were treated with normal saline once a day, while mice in experimental groups received low-dose (LD) and high-dose (HD) jatrorrhizine once a day respectively. Two weeks later, cardiac function was detected by echocardiography, and histopathological examination was performed using hematoxylin and eosin (H&E) and Masson staining. The expressions of p53, TGF-β1, Smad/2/3, Bax, Bcl-2, collagen I and collagen III were quantified using qRT-PCR and western blot assays. Results: Jatrorrhizine significantly improved left ventricular ejection fraction (LVEF) and left ventricle end-systolic (LVES) in mice. Histopathological, administration of jatrorrhizine weakened infiltration of inflammatory cells and cardiac fibrosis in myocardium of mice caused by MI. Additionally, jatrorrhizine suppressed cardiomyocyte apoptosis exhibited as its capability to reverse changes of Bax and Bcl-2 levels in myocardium caused by MI. Jatrorrhizine statistically significantly downregulated expression of collagen I and collagen III, as well as TGF-β1, Smad2/3 and p53. Conclusions: Jatrorrhizine reduce cardiomyocyte apoptosis and fibrosis through inhibiting p53/Bax/Bcl-2 and TGF-β1/Smad2/3 signaling pathways.

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ABSTRACT Purpose: Abnormal activation of NOD-like receptor protein 3 (NLRP3) inflammasome can lead to the occurrence and progression of acute pancreatitis. This study investigated the protective effect of MCC950 on pancreatitis mice. Methods: Eighteen mice were randomly divided into control group, severe acute pancreatitis (SAP) group and SAP+MCC950 group. Serum interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA. Hematoxylin and eosin (HE) staining was used to evaluate the pathological damage. Western blotting was used to detect the expression of NLRP3 inflammasome and tight junction proteins in the small intestine and pancreas. Results: MCC950 could reduce the levels of IL-6 and IL-1β in SAP mice. After treatment with MCC950, the expression levels of NLRP3 inflammasome in the pancreas of SAP mice were significantly reduced and the pathological damage to the pancreas and intestine was alleviated. Compared with the control group, the expression of tight junction protein (ZO-1,occludin and claudin-4) in the intestinal mucosa of SAP mice was decreased, and the expression of claudin-4 and occludin were upregulated after MCC950 treatment. Conclusions: MCC950 can inhibit NLRP3 inflammasome activation and significantly reduce the inflammatory response and delay the process of pancreatitis. It has therapeutic potential in the treatment of acute pancreatitis.

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ABSTRACT Purpose: To demonstrate through a controlled study whether the use of tranexamic acid in bariatric surgeries is effective for bleeding control. Methods: Prospective, comparative, and double-blind study performed with patients from 18 to 65 years old submitted to bariatric surgery. The selected patients received venous tranexamic acid (TXA) during the induction of anesthesia or not (CG). The anesthesia and thromboprophylaxis protocols were similar among the groups. For statistical analysis, the χ2 and analysis of variance tests were performed at a significance level of p < 0.05, using the statistical program SPSS 21.0®. Results: Sixty-one patients were included in the study, 31 in the control group and 30 in the TXA group (GTXA). In the intraoperative period, the bleeding volume was greater in the CG than in the GTXA. In the postoperative period, the tranexamic acid group had a higher value hematocrit, absence of surgical reoperations due to bleeding complications, and shorter hospitalization time than the control group. Conclusions: The use of tranexamic acid was effective in reducing bleeding rates and of hospital stay length, in addition to demonstrating the clinical safety of its use, for not having been associated with any thromboembolic events.