The beneficial effects of Ganoderic acid A (GAA) from Ganoderma lucidum on alcoholic liver injury and intestinal microbial disorder in mice exposed to excessive alcohol intake.

DDIT4 is a mitochondrial and tumor-related protein involved in anti-tumor therapy resistance, proliferation, and invasion, etc. Its expression level increases under the stress such as chemotherapy, hypoxia, and DNA damage. A number of clinical studies have confirmed that DDIT4 can change the behavior of tumor cells and the prognosis of patients with cancer. However, the role of DDIT4 in promoting or suppressing cancer is still inconclusive. This article summarized the four characteristics of DDIT4 including a mitochondria-related protein, interactions with various protein molecules, immune and metabolic cell related proteins and participator in the oxygen sensing pathway, which may be related to the progress of cancer.

Selenium-enriched probiotics have attracted much attention due to the physiological activities of both probiotics and selenium (organic selenium). In this study, we investigated the mitigating effect of selenium-enriched Lactobacillus rhamnosus GG (LGG@Se) and its pathway on alcohol-induced liver injury (ALI) in mice. The results showed that LGG@Se was superior to LGG and sodium selenite in alleviating ALI. Oral LGG@Se effectively prevented lipid metabolism disorders and liver oxidative damage in mice caused by excessive alcohol intake. 16S amplicon sequencing showed that LGG@Se intervention increased the abundance of beneficial bacteria and suppressed the growth of harmful bacteria in the intestinal tract of over-drinking mice, and thus effectively modulated the homeostasis of intestinal flora, which were highly correlated with the improvement of liver function. Liver metabolomics analysis indicated that LGG@Se intervention altered liver metabolic profiling, and the characteristic biomarkers were mainly involved in amino acid metabolism, including alanine, aspartate and glutamate metabolism, arginine biosynthesis, etc. In addition, LGG@Se intervention modulated the expression of genes and proteins related to lipid metabolism and oxidative stress in liver of over-drinking mice. Western blot analysis revealed that LGG@Se intervention up-regulated the expression of intestinal barrier function-related proteins, thereby ameliorating alcohol-induced intestinal barrier damage. Collectively, these findings provide scientific evidence that LGG@Se possesses the biological activity of improving alcohol-induced lipid metabolism and intestinal microbiota disorder.

Acute pancreatitis (AP)‑associated lung injury (ALI) is a critical complication of AP. Adropin is a regulatory protein of immune metabolism. The present study aimed to explore the immunomodulatory effects of adropin on AP‑ALI. For this purpose, serum samples of patients with AP were collected and the expression levels of serum adropin were detected using ELISA. Animal models of AP and adropin knockout (Adro‑KO) were constructed, and adropin expression in serum and lung tissues was investigated. The levels of fibrosis and apoptosis were evaluated using hematoxylin and eosin staining, Masson's staining and immunohistochemistry of in lung tissue. M1/M2 type macrophages in the lungs were detected using immunofluorescence staining, western blot analysis and reverse transcription‑quantitative PCR. As shown by the results, adropin expression was decreased in AP. In the Adro‑KO + L‑arginine (L‑Arg) group, macrophage infiltration, fibrosis and apoptosis were increased. The expression of peroxisome proliferator‑ activated receptor γ (PPARγ) was downregulated, and the macrophages exhibited a trend towards M1 polarization in the Adro‑KO + L‑Arg group. Adropin exogenous supplement attenuated the levels of fibrosis and apoptosis in the model of AP. Adropin exogenous supplement also increased PPARγ expression by the regulation of the phosphorylation levels, which was associated with M2 macrophage polarization. On the whole, the findings of the present study suggest that adropin promotes the M2 polarization of lung macrophages and reduces the severity of AP‑ALI by regulating the function of PPARγ through the regulation of its phosphorylation level.

Pancreatic cancer is one of the most common malignancies worldwide. This study is aimed at searching the possible genetic mutations and the value of novel gene mutation in the DNA damage-inducible transcript 4 (DDIT4) and signaling pathway in pancreatic cancer. Polymerase chain reaction (PCR) was performed to amplify the DNA sequences of DDIT4 from patients with pancreatic ductal adenocarcinoma. In addition, we used IHC to detect the expression level of DDIT4 in patients with pancreatic cancer in different types of gene mutation. Double-labeled immunofluorescence was employed to explore the expression levels of DDIT4/LC3 and their potential correlation. Our work indicated the two novel stable gene mutations in DDIT4 mRNA 3-untranslated region (m.990 U>A and m.1246 C>U). Thirteen samples were found to have mutation in the DDIT4 3-untranslated regions (UTR). To further verify the influence of gene mutation on protein expression, we performed immunohistochemistry on different gene mutation types, and we found a correlation between DDIT4 expression and gene mutation, which is accompanied by nuclear staining deepening. In order to further discuss the clinical value of DDIT4 gene mutation, immunofluorescence suggested that the expression of DDIT4 colocated with LC3; thus, we speculated that DDIT4 mutation may be involved in autophagy in pancreatic cancer cell. In this study, we found mutation in the 3-UTR region of DDIT4, which may be associated with DDIT4 expression and tumor autophagy in pancreatic cancer tissues.