SB203580 attenuates acute lung injury and inflammation in rats with acute pancreatitis in pregnancy.

Acute pancreatitis in pregnancy (APIP) can lead to multiple maternal and fetal organ injury and mitogen-activated protein kinase (MAPK) signaling pathway may be involved in it; however, whether APIP can result in acute lung injury and P38MAPK signaling pathway is involved in the pathogenesis has not been elucidated. The present study was undertaken to investigate the participation of P38MAPK signaling pathway and the protective effect of SB203580, an inhibitor of P38MAPK on acute lung injury induced by APIP. Twenty-four late-gestation SD rats were randomly assigned to four groups: Sham operation (SO) group, SB302580 (SB) group, APIP group, and SB + APIP group. All the rats were killed 6 h after modeling. The severity of pancreatitis was evaluated by serum amylase (AMY) and lipase (LIPA) and histopathological changes. Histological assessment of the lung and inflammatory cell infiltration was performed by H&E and immunofluorescence assay. The lung wet/dry (W/D) weight ratio was determined, and the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the protein expression of phosphorylated and total P38, tumor necrosis factor (TNF)-α, and intercellular adhesion molecules 1 (ICAM-1) in lung tissues. Obvious pathological changes existed in pancreas and lung after the induction of APIP, and their pathological scores were significantly higher than that of control group. The results showed that the phosphorylation of P38MAPK was elevated in the lung of APIP rats. Compared with APIP group, the intervention of SB203580 alleviated the pathological injury of the pancreas and lungs, decreased serum AMY and LIPA, attenuated the secretion of TNF-α, IL-1ß, and IL-6 in lung, reduced the inflammatory cells' infiltration and lung W/D ratio and inhibited the activation of P38MAPK signaling pathway. These results suggest that APIP can lead to acute lung injury and inflammation and SB203580 can inhibit the lung injury by inhibiting the P38MAPK signaling pathway and blocking the inflammatory responses.

IRE1α-JNK pathway-mediated autophagy promotes cell survival in response to endoplasmic reticulum stress during the initial phase of hepatic steatosis.

AIMS: It has been widely reported that autophagy and inositol-requiring enzyme-1α (IRE1α)-c-Jun N-terminal kinase (JNK) pathway was involved in cell survival under endoplasmic reticulum (ER) stress, but their specific roles in hepatic steatosis remain unclear. This study aimed to determine the interaction between autophagy and IRE1α-JNK pathway on cell survival in response to ER stress during the initial phase of hepatic steatosis. METHODS: Hepatic steatosis was induced in HepG2 cells by supplementing oleic acid (OA). Lipid accumulation was evaluated by BODIPY493/503 staining. ER stress and IRE1α-JNK signaling were investigated by western blot. Autophagy was monitored by western blot, GFP-LC3 plasmid and immunofluorescence staining, while apoptosis was determined by western blotting, Annexin-V-FITC/PI staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. KEY FINDINGS: Aggravated lipid accumulation was found under increased ER stress during the initial phase of hepatic steatosis. Meanwhile, an increase of autophagy and no alteration of apoptosis were observed under increased ER stress. Interestingly, autophagy was induced by ER stress, while autophagy suppression led to an increase of apoptosis in response to ER stress Moreover, further study showed that IRE1α-JNK pathway was activated after ER stress and consequently induced autophagy, which promoted cell survival in the initial phase of hepatic steatosis. SIGNIFICANCE: We conclude that IRE1α-JNK pathway was activated during ER stress in the initial phase of hepatic steatosis and promoted cell survival by enhancing autophagy. Targeting IRE1α-JNK-autophagy signaling may provide new insight into preventive strategies for hepatic steatosis.

Green tea polyphenols attenuate hepatic steatosis, and reduce insulin resistance and inflammation in high-fat diet-induced rats.

Non­alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and inflammation; however, the exact pathogenesis of NAFLD is not fully understood. Green tea polyphenols (GTP) exhibit beneficial effects against metabolic syndrome. However, the effect of GTP on NAFLD remains largely unknown. The aim of the present study was to investigate the effects of GTP on NAFLD in high­fat diet (HFD)­induced rats. The NAFLD rat model was induced with a HFD for 8 weeks. A total of 30 adult male Sprague Dawley rats were randomly divided into three groups: i) Normal control group; ii) HFD group; and iii) HFD with GTP group. Hematoxylin and eosin and Oil Red O analyses were performed. The levels of alanine aminotransferase (ALT), aspartate amino-transferase (AST) and inflammatory cytokines in the serum, as well as oxidative stress markers and hepatic lipids in the liver were measured. In addition, parameters associated with glucose metabolism were also assessed. Western blotting and RT­qPCR were used to determine the expression levels of 5' adenosine monophosphate­activated protein kinase (AMPK). HFD­induced rats exhibited features associated with NAFLD. GTP intervention significantly reduced serum ALT and AST levels. Fasting serum glucose, insulin resistance and hepatic lipid levels were all decreased in the GTP­treated rats. GTP also significantly decreased the levels of TNF­α, IL­6 and malondialdehyde. In contrast, superoxide dismutase levels were increased in the liver. Furthermore, GTP also significantly increased phosphorylation of AMPK and attenuated histopathological changes indicative of injury in liver tissue. GTP has a protective effect on HFD­induced hepatic steatosis, insulin resistance and inflammation, and the underlying mechanism may involve the AMPK pathway.

Association of MTHFR C677T gene polymorphism with metabolic syndrome in a Chinese population: a case-control study.

Objective To investigate the association of the MTHFR C677T gene polymorphism with metabolic syndrome (MetS) in people in Hubei Province, China. Methods A case-control study was conducted with 651 subjects with MetS (MetS group) and 727 healthy controls (control group) at Renmin Hospital of Wuhan University between January and December 2016. The MTHFR C677T genotype was detected by the gene chip technique and clinical data were collected. Results Body mass index, waist circumference, the waist-hip-ratio, systolic and diastolic blood pressure, fasting blood glucose, fasting insulin, triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and homocysteine levels, and the homeostasis model assessment of insulin resistance were higher in the MetS group than in controls. The risk of MetS was higher for the TT genotype and T allele carriers than for the CC genotype and C allele carriers. With MetS, the TT genotype increased the risk of elevated blood pressure, fasting glucose levels, and triglyceride levels. Patients with MetS and the TT genotype showed more severe abdominal obesity, dyslipidaemia, insulin resistance, elevated blood pressure, elevated fasting glucose levels, and hyperhomocysteinaemia compared with those with the CC genotype. Conclusions In this population, MTHFR C677T gene polymorphism may be a risk factor for MetS.