Identification of BAF60b as a chromatin remodeling checkpoint of diet-induced fatty liver disease.

Overnutrition has gradually become the primary causative factor of nonalcoholic fatty liver disease (NAFLD). However, how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression remains poorly understood. Here, we identified hepatic BAF60b as a lipid-sensitive subunit of the switch/sucrose-nonfermentable (SWI/SNF) chromatin-remodeling complex and is negatively associated with liver steatosis in mice and humans. Hepatic BAF60b deficiency promotes high-fat diet (HFD)-induced liver steatosis in mice, while transgenic expression of BAF60b in the liver attenuates HFD-induced obesity and NAFLD, both accompanied by a marked regulation of PPARγ expression. Mechanistically, through motif analysis of liver ATAC-Seq and multiple validation experiments, we identified CCAAT/enhancer-binding protein ß (C/EBPß) as the transcription factor that interacts with BAF60b to suppress PPARγ gene expression, thereby controlling hepatic lipid accumulation and NAFLD progression. This work uncovers hepatic BAF60b as a negative regulator of liver steatosis through C/EBPß dependent chromatin remodeling.

Lentinan improves intestinal inflammation and gut dysbiosis in antibiotics-induced mice.

Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of recovery of intestinal inflammation on broad-spectrum antibiotic-driven gut microbial dysbiosis in mice. Gut microbiota was elucidated by the Illumina MiSeq platform. Gas chromatography/mass spectrometry was used to investigate short-chain fatty acid content. Colon histology, expression of tight-junction associated proteins and pro-inflammatory cytokines levels were evaluated. The results showed that the gut microbiota of diversity and richness were reduced and various taxonomic levels of the gut microbiota were perturbed after antibiotics gavage. The abundance of Firmicutes and Bacteroidetes shifted to Proteobacteria and increased the relative abundance of harmful microbiota (Parabacteroides and Klebsiella) post-antibiotics, whereas lentinan administration reversed the dysbiosis and increased beneficial microbiota, including S24-7, Lactobacillus, Oscillospira, Ruminococcus and Allobaculum. The concentrations of propionic acid and butyric acid were significantly increased by treatment with lentinan. And lentinan improved colon tissue morphology and reduced pro-inflammatory cytokines via altering NF-κB signaling pathway in antibiotic-driven gut microbial dysbiosis mice. Taken together, the results proved that lentinan can be used as a prebiotic and the result provided a theoretical basis for improving the clinical treatment of broad-spectrum antibiotics side effects.

The Metabolites of Lactobacillus fermentum F-B9-1 Relieved Dextran Sulfate Sodium-Induced Experimental Ulcerative Colitis in Mice.

Because of the increased incidence and prevalence, ulcerative colitis (UC) has become a global health issue in the world. Current therapies for UC are not totally effective which result in persistent and recurrent symptom of many patients. Lactobacillus with anti-inflammatory effects might be beneficial to the prevention or treatment for UC. Here, we examined the ameliorative effects of the metabolites of Lactobacillus fermentum F-B9-1 (MLF) in Caco-2 cells and dextran sodium sulfate (DSS)-induced UC model mice. MLF displayed intestinal barrier-protective activities in Caco-2 cells by increasing the expression of Occludin and ZO-1. They also showed anti-inflammatory potential in interleukin (IL)-1ß and IL-6. In order to further examine the in vivo anti-inflammatory effect of MLF, the MLF was gavaged in the DSS-induced UC model mice. The intragastric administration of MLF effectively alleviated colitis symptoms of weight loss, diarrhea, colon shortening, and histopathological scores, protected intestinal barrier function by increasing Occludin and ZO-1, and attenuated colonic and systemic inflammation by suppressing production of IL-1ß and IL-6. Finally, the use of MLF remodeled the diversity of the gut microbiota and increased the number of beneficial microorganisms. Overall, the results demonstrated that MLF relieved DSS-induced UC in mice. And MLF might be an effective therapy method to UC in the clinic in the future.

Cistanche promotes the adipogenesis of 3T3-L1 preadipocytes.

Cistanche deserticola Ma (cistanche) is a traditional herb with a wide range of therapeutic properties. However, no evidence of cistanche's effect on adipogenesis has been found. The effect of cistanche that promotes the adipogenesis of 3T3-L1 preadipocytes was proved by using MTT spectrophotometry, Nile Red staining, Oil Red O staining and transcriptome sequencing technology. The mRNA level of key transcription factors for adipogenesis such as PPAR, AP2 and LPL were examined by RT-PCR. The results showed that the intracellular lipid content in cistanche treated cells were notably increased when compared with the non-treated cells. Between the differentiation and cistanche treated groups, the expression of adipogenesis related genes such as grow hormone releasing hormone (Ghrp), BCL2/adenovirus E1B interacting protein 3 (Bnip3) and Gastric inhibitory polypeptide receptor (Gipr) were significantly increased. Our findings also verified that cistanche promoted adipogenesis, which was accompanied by up-regulated level of Bnip3 and PPAR. This study could uncover new signaling pathways involved in adipogenesis regulation.

Weilan gum oligosaccharide ameliorates dextran sulfate sodium­induced experimental ulcerative colitis.

Ulcerative colitis (UC) is a global disease, characterized by periods of relapse that seriously affects the quality of life of patients. Oligosaccharides are considered to be a prospective strategy to alleviate the symptoms of UC. The present study aimed to evaluate the effect of weilan gum oligosaccharide (WLGO) on a mouse UC model induced by dextran sulfate sodium (DSS). WLGO structural physical properties were characterized by electrospray mass spectrometry and fourier tansform infrared spectroscopy. MTT assays were performed to evaluate the non­toxic concentration of WLGO. RT­qPCR and ELISAs were conducted to determine the levels of inflammatory factors. The clinical symptoms and mucosal integrity of the DSS­induced UC model were assessed by DAI and histological assessment. LPS­induced Caco­2 cells and DSS­induced UC mice were used to explore the effects of WLGO on UC. Treatment of the mice with 4.48 g/kg/day WLGO via gavage for 7 days significantly relieved the symptoms of DSS­induced UC model mice, whereas significant effects were not observed for all symptoms of DSS­induced UC in the WLGO­low group. The disease activity index score was decreased and the loss of body weight was reduced in DSS­induced UC model mice treated with WLGO. Moreover, colonic damage and abnormally short colon length shortenings were relieved following WLGO treatment. WLGO treatment also reduced the concentration and mRNA expression levels of proinflammatory cytokines, including interleukin­1ß, interleukin­6 and tumor necrosis factor α, in DSS­induced UC model mice and lipopolysaccharide­treated Caco­2 cells. These results indicated that WLGO may be an effective strategy for UC treatment.

Ideal Anatomical Landmark Points for Thoracic Esophagus Segmentation in the Chinese Population.

Introduction: The standards of esophagus segmentation remain different between the Japan Esophageal Society (JES) guideline and the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) guideline. This study aimed to present variations in the location of intrathoracic esophageal adjacent anatomical landmarks (EAALs) and determine an appropriate method for segmenting the thoracic esophagus based on the relatively fixed EAALs. Patients and Methods: The distances from the upper incisors to the upper border of the esophageal hiatus, lower border of the inferior pulmonary vein (LPV), tracheal bifurcation, lower border of the azygous vein (LAV), and thoracic inlet were measured in the patients undergoing thoracic surgery. The median distances between the EAALs and the specified starting points, as well as reference value ranges and ratios, were obtained. The variation coefficients of distances and ratios from certain starting points to different EAALs were calculated and compared to determine the relatively fixed landmarks. Results: This study included 305 patients. The average distance from the upper incisors to the upper border of the cardia, the midpoint between the tracheal bifurcation and esophageal hiatus (MTBEH), LPV, LAV, tracheal bifurcation, and thoracic inlet were 41.6, 35.3, 34.8, 29.4, 29.5, and 20.3 cm, respectively. The distances from the upper incisors or thoracic inlet to any intrathoracic EAALs in men were higher than in women. In addition, the height, weight, and body mass index (BMI) were correlated with the distances. The ratio of the distance between the upper incisors and tracheal bifurcation to the distance between the upper incisors and upper border of the cardia and the ratio of the distance between the thoracic inlet and tracheal bifurcation to the distance between the thoracic inlet and upper border of the cardia possessed relatively smaller coefficients of variation. Conclusion: The distances from the EAALs to the upper incisors vary with height, weight, BMI, and gender. Compared with distance, the ratios are more suitable for esophagus segmentation. Tracheal bifurcation and MTBEH are ideal EAALs for thoracic esophagus segmentation, and this is consistent with the JES guideline recommendation.