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Extensive apoptosis of pancreatic acinar cells frequently occurs in acute pancreatitis (AP), and has been identified to be closely associated with the decrease of pancreatic parenchymal cells and pancreatic damage. The present study aimed to investigate the possible effect of angiotensin (Ang)‑(1‑7) on caerulein (CAE)‑induced pancreatic acinar cell apoptosis. Mouse pancreatic acinar cancer cells (MPC‑83) were divided into 4 groups: Control group; CAE group; CAE + Ang‑(1‑7) group; and CAE + Ang‑(1‑7) antagonist (A779) group. The control group consisted of normal MPC‑83 cells without special treatment. The CAE group was stimulated with 10 nmol/l CAE and harvested at 2, 6, 12, 24 and 48 h. For the CAE + Ang‑(1‑7) group and CAE + A779 group, the CAE‑induced pancreatic acinar cells were mock pretreated or pretreated with different concentrations of Ang‑(1‑7) or A779 (10‑7, 10‑6 or 10‑5 mol/l) for 30 min. Caspase‑3 is a critical executioner of apoptosis, as it is either partly or completely responsible for the proteolytic cleavage of numerous key proteins including the nuclear enzyme poly (ADP‑ribose) polymerase. Activation of caspase‑3 requires proteolytic processing of its inactive zymogen into activated p17 and p12 fragments. Thus, the present study investigated the apoptotic markers, including cleaved caspase‑3, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑like protein 4 (Bax) and renin‑angiotensin system (RAS) pathway related proteins (ACE2 and Mas receptor). The results demonstrated that the cleaved caspase‑3 levels were increased in the CAE group (P<0.05), peaking at 24 h, and declined when incubated with Ang‑(1‑7). Following treatment with Ang‑(1‑7), levels of the anti‑apoptotic protein Bcl‑2 rose dramatically in a dose‑dependent manner. The ratio of the pro‑apoptotic protein Bax to the anti‑apoptotic protein Bcl‑2 dropped notably, which demonstrated a tendency towards curbing apoptosis. In addition, the cleaved caspase‑3 levels, and the ratio of Bax to Bcl‑2 in the CAE + A779 group presented a significant rise compared with the CAE group. It was concluded that Ang‑(1‑7) may possess an inhibitory effect on CAE‑induced pancreatic acinar cell apoptosis and that appropriate interventions in RAS may attenuate pancreatic injury during AP. [ABSTRACT FROM AUTHOR]

Increased fibronectin (FN) expression has an important role during liver fibrosis. The present study examined FN expression in rats subjected to carbon tetrachloride (CCl4)-induced liver fibrosis. In addition, the potential mechanisms underlying fibrogenesis were investigated by exposing hepatic stellate cells (HSCs) to transforming growth factor-β (TGF-β), which is a known inducer of myofibroblastic transformation of HSCs. Briefly, a rat model of liver fibrosis was created by administering intraperitoneal injections of CCl4. Furthermore, HSC-T6 cells were stimulated with increasing doses of recombinant TGF-β over 24 h. Hepatic fibrosis gradually increased following CCl4 administration in vivo. Western blotting and immunohistochemistry demonstrated that fibronectin (FN), TGF-β and α-smooth muscle actin (SMA) expression was increased following CCl4 injection, and the maximum expression levels were observed at 8 weeks. Once CCl4 treatment had been terminated, the expression levels of FN, TGF-β and α-SMA progressively declined to near baseline levels. Western blotting and quantitative polymerase chain reaction demonstrated that FN expression was gradually increased in response to TGF-β-stimulation of HSCs; maximum expression was achieved 12 h post-treatment (P<0.01 vs. the baseline). In conclusion, these findings indicated that FN expression is an early and progressive event that occurs during liver fibrogenesis in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Herbal compound 861 (Cpd 861) exerts an anti-fibrotic effect in patients with hepatic fibrosis; however, the anti-fibrotic mechanism has yet to be fully elucidated. The present study aimed to explore the mechanistic basis for the anti-fibrotic effect, with a focus on bone morphogenetic protein 7 (BMP-7)/Smad signaling in a bile duct ligation (BDL)-induced liver fibrosis rat model. Following the induction of hepatic fibrosis, rats induced by BDL were treated with 9 g/kg Cpd 861 daily or an equal volume of saline for 28 days. Serum samples were prepared for monitoring the levels of alanine transaminase, aspartate transaminase and total bilirubin, and direct bilirubin analyses and liver samples were used to investigate gene expression, protein localization and protein expression analysis using real-time quantitative polymerase chain reaction, immunohistochemistry and western blotting. The results revealed the attenuation of liver fibrosis by Cpd 861 in the histological and biochemical experiments. BMP-7 and phospho (p)-Smad1/5/8 were localized predominantly in the cytoplasm of hepatocytes. In comparison with the saline-treated BDL rats, Cpd 861 markedly upregulated the gene expression of BMP-7 and Smad5, as well as the protein expression of BMP-7 and Smad1/5. In addition, p-Smad1/5/8 protein expression was markedly increased by Cpd 861 in the BDL model. These results indicated that Cpd 861 alleviates hepatic fibrosis possibly via the upregulation and activation of BMP-7/Smad signaling in hepatic fibrotic rats. [ABSTRACT FROM AUTHOR]

were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to assess the levels of cardiac fibrosis. The protein contents of microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (P62) were evaluated using western blotting, and the mRNA expression of Beclin 1 was measured using RT-qPCR, in order to assess autophagy. The results revealed that, in the diabetic rats, cardiac fibrosis developed and cardiac systolic function was reduced. In the hearts of the diabetic rats, the mRNA expression levels of collagen type I and III, and Beclin1 were upregulated; the ratio of the protein level of LC3-II/LC3-I was increased and the content of P62 was decreased. All the changes were aggravated as time increased. The changes in autophagy were correlated with those of cardiac fibrosis, suggesting that autophagy may have a synergistic role in diabetic cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Inflammation is the predominant characteristic of pneumonia. The present study aimed to to identify a faster and more reliable novel inflammatory marker for the diagnosis of pneumonia. The expression of the S100A12 gene was analyzed by reverse transcription quantitative polymerase chain reaction in samples obtained from 46 patients with bacterial pneumonia and other infections, compared with samples from 20 healthy individuals, using the 2-ΔΔCt method. The expression levels of S100A12 were increased in 12 patients with bacterial pneumonia. Compared with clinical inflammatory data, a positive correlation was observed between the expression of the S100A12 gene and levels of white blood cells, C-reactive protein (CRP), thrombocytocrit, neutrophils, erythrocyte sedimentation and soterocytes, and an inverse correlation was observed with the width of red blood cell volume distribution and platelet distribution, monocytes and hemoglobin, using Pearson's product-moment correlation method. The P-value of CRP and erythrocyte sedimentation were revealed to be statistically significant (P<0.05). A sporadic distribution of S100A12 was observed in a heatmap among the patients with different infections and bacterial pneumonia. Furthermore, the expression of S100A12 occurred in parallel to the number of clumps of inflamed tissue observed in chest computed tomography and X-ray. The value of gene expression of S100A12 (>1.0) determined using the 2-ΔΔCt method was associated with more severe respiratory diseases in the patients compromised by bacterial pneumonia, sepsis and pancreatitis. These findings suggested that S100A12 is an effective marker for inflammatory diseases. [ABSTRACT FROM AUTHOR]