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Objective: To investigate the effect of Schizandrin B on lung injury in rats with acute pancreatitis (AP) via Toll-like receptor 4 (TLR4) /nuclear factor-κB (NF-κB) signaling pathway. Methods: SD rats were taken and induced the establishment of AP lung injury model by retrograde injection of 5% sodium taurocholate into the bile duct. According to random number table method, they were divided into model group, schisandrin B group, TLR4 overexpression vector group, TLR4 empty group, schisandrin B+ TLR4 overexpression vector group, 12 rats per group. Twelve SD rats only flipped the intestines without injecting 5% sodium taurocholate, as the sham operation group. After intervening rats in groups with drugs, pulmonary function of rats in each group, the amount of ascites and lung tissue wet weight/dry weight (W/D) of rats in each group were measured; HE staining was used to detect pathological morphology of lung tissue and score; levels of arterial blood gas indexes of rats in each group were detected by fully automatic biochemical analyser; levels of serum amylase and inflammatory cytokines IL-6 and IL-18 were measured by ELISA; Western blotting was used to detect protein expression of TLR4/NF-κB signaling pathway in lung tissue; expression of TLR4 protein in lung tissue of rat in each group was detected by immunohistochemical staining. Results: Compared with sham operation group, lung tissue of rats in model group showed pathological changes, MV, PEF, PaO2 and OI of model group were significantly reduced (P<0.05), while Ri, ascites volume, W/D, PaCO2, Holfbauer score, serum amylase, IL-6 and IL-18 levels, lung tissue proportion of TLR4 positive cells, expressions of TLR4 and MYD88 protein, p-NF-κB p65/NF-κB p65 level were significantly increased (P<0.05) . Compared with model group and schisandrin B+TLR4 overexpression vector group, respectively, pathological changes of lung tissue of rats in schisandrin B group were reduced, MV, PEF, PaO2 and OI were all increased (P<0.05), while Ri, ascites volume, W/D, PaCO2, Holfbauer score, serum amylase, IL-6 and IL-18 levels, lung tissue proportion of TLR4 positive cells, expressions of TLR4 and MYD88 protein, p-NF-κB p65/NF-κB p65 levels were decreased (P<0.05); in TLR4 overexpression vector group, degree of pathological damage in lung tissue of rats was aggravated, MV, PEF, PaO2 and OI were all decreased (P<0.05), while Ri, ascites volume, W/D, PaCO2, Holfbauer score, serum amylase, IL-6 and IL-18 levels, lung tissue proportion of TLR4 positive cells, expressions of TLR4 and MYD88 protein, p-NF-κB p65/NF-κB p65 level were increased (P<0.05) . Compared with model group, rats in TLR4 empty group showed no significant difference (P>0.05). Conclusion: Schizandrin B can down-regulate TLR4/NF-κB signaling pathway to inhibit inflammation, reduce lung injury in AP rats, and repair lung function. [ABSTRACT FROM AUTHOR]

Liver cirrhosis can cause disturbances in blood circulation in the liver, resulting in impaired portal blood flow and ultimately increasing portal venous pressure. Portal hypertension induces portal-systemic collateral formation and fatal complications. Extrahepatic angiogenesis plays a crucial role in the development of portal hypertension. Curcumol is a sesquiterpenoid derived from the rhizome of Curcumae Rhizoma and has been confirmed to alleviate liver fibrosis by inhibiting angiogenesis. Therefore, our study was designed to explore the effects of curcumol on extrahepatic angiogenesis and portal hypertension. To induce cirrhosis, Sprague Dawley rats underwent bile duct ligation (BDL) surgery. Rats received oral administration with curcumol (30 mg/kg/d) or vehicle (distilled water) starting on day 15 following surgery, when BDL-induced liver fibrosis had developed. The effect of curcumol was assessed on day 28, which is the typical time of BDL-induced cirrhosis. The results showed that curcumol markedly reduced portal pressure in cirrhotic rats. Curcumol inhibited abnormal splanchnic inflow, mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting in cirrhotic rats. These protective effects were partially attributed to the inhibition on mesenteric angiogenesis by curcumol. Mechanically, curcumol partially reversed the BDL-induced activation of the JAK2/STAT3 signaling pathway in cirrhotic rats. Collectively, curcumol attenuates portal hypertension in liver cirrhosis by suppressing extrahepatic angiogenesis through inhibiting the JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R. [ABSTRACT FROM AUTHOR]