Inulin Inhibits the Inflammatory Response through Modulating Enteric Glial Cell Function in Type 2 Diabetic Mellitus Mice by Reshaping Intestinal Flora.

Inulin, a commonly used dietary fiber supplement, is capable of modulating the gut microbiome. Chronic inflammation resulting from metabolic abnormalities and gut flora dysfunction plays a significant role in the development of type 2 diabetes mellitus (T2DM). Our research has demonstrated that inulin administration effectively reduced colonic inflammation in T2DM mice by inducing changes in the gut microbiota and increasing the concentration of butyric acid, which in turn modulated the function of enteric glial cells (EGCs). Experiments conducted on T2DM mice revealed that inulin administration led to an increase in the Bacteroidetes/Firmicutes ratio and the concentration of butyric acid in the colon. The anti-inflammatory effects of altered gastrointestinal flora and its metabolites were further confirmed through fecal microbiota transplantation. Butyric acid was found to inhibit the activation of the κB inhibitor kinase ß/nuclear factor κB pathway, regulate the expression levels of interleukin-6 and tumor necrosis factor-α, suppress the abnormal activation of EGCs, and prevent the release of inflammatory factors by EGCs. Similar results were observed in vitro experiments with butyric acid. Our findings demonstrate that inulin, by influencing the intestinal flora, modifies the activity of EGCs to effectively reduce colonic inflammation in T2DM mice.

Polysaccharide of Lactobacillus casei SB27 reduced colon cancer cell prognosis through mitochondrial damage by upregulation of HINT2.

AIMS: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. This study aimed to explore the effects of Polysaccharide of Lactobacillus casei SB27 in colon cancer and its possible mechanisms. METHODS: Colon cancer was induced by giving dextran sulfate sodium and Azoxymethane. Uman Colon Cancer Cell Line (HCT)-116 cells were used to vitro model in this experiment. RESULTS: Polysaccharide of L. casei SB27 reduced colon cancer in azoxymethane-dextran sulfate sodium (AOM+DSS)-induced mice. Polysaccharide of L. casei SB27 reduced colon cancer prognosis in vitro model. Polysaccharide of L. casei SB27 reduced short chain fatty acids by Bacillus coli. Polysaccharide of L. casei promoted mitochondrial damage by Calcium ion entry. Polysaccharide of L. casei induced histidine nucleotide binding protein 2/mitochondrial calcium uniporter (HINT2/MCU) signaling pathway. Immunocoprecipitation (IP) showed that HINT2 protein interlinked MCU protein. Polysaccharide of L. casei suppressed HINT2 ubiquitination. The regulation of HINT2 affected the effects of L. casei polysaccharide on colon cancer prognosis and mitochondrial damage by Calcium ion entry in vitro model. CONCLUSION: In conclusion, the present report demonstrated that polysaccharide of L. casei SB27 reduced colon cancer cell prognosis through mitochondrial damage by upregulation of HINT2. Polysaccharide of L. casei SB27 might be used for colon cancer treatment and could be helpful for personalized treatment.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study.

BACKGROUND: The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE). AIM: To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction. METHODS: This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS). RESULTS: All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001). CONCLUSION: Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Molecular characterization of myostatin in black seabream, Acanthopagrus schlegelii.

Myostatin is a negative regulator of skeletal muscle growth and has a potential application in aquaculture. The black seabream myostatin gene was cloned and sequenced. It had three exons encoding a protein of 382 amino acids. A 90 bp 5'-untranslated region (UTR) and a 536 bp 3'-UTR were obtained by RACE. Four microsatellite sequences, a (CAG)9, a (TC)12, a (CA)16 repeat and an "imperfect" (CA)25 microsatellite, were found in the myostatin. Two introns were 329 and 742 bp in length, respectively. The deduced amino acid sequence of the myostatin had a putative amino terminal signal sequence, a TGF-beta propeptide domain, a RXXR proteolytic processing site, a TGF-beta domain, and 12 conserved cysteine residues. The myostatin gene was expressed in four of the examined ten tissues and organs. The expression of myostatin was the strongest in the skeletal muscle and brain, intermediate in the eye, and low in the heart.

Molecular cloning and characterization of the myostatin gene in croceine croaker, Pseudosciaena crocea.

Myostatin (MSTN) is a negative regulator of skeletal muscle mass and has a potential application in aquaculture. We reported the characterization of the myostatin gene and its expression in the croceine croaker, Pseudosciaena crocea. The myostatin gene had three exons encoding 376 amino acids. The cDNA was 1,906 bp long with a 5'-UTR and 3'-UTR of 108 bp and 667 bp, respectively. A microsatellite sequence, CA(30) and CA(26) separated by TA, existed in the 3'-UTR. Intron I and II were 343 bp and 758 bp in length, respectively. The deduced amino acid sequence was highly conserved, and had more than 90% identical to shi drum, gilthead seabream, striped sea-bass, white perch, and white bass proteins. The myostatin of croceine croaker had a putative amino terminal signal sequence (residues 1-22), a transforming growth factor-beta (TGF-beta) propeptide domain (residues 41-256), a RXXR proteolytic processing site (RARR, residues 264-267, matching the RXXR consensus site), and a TGF-beta domain (residues 282-376). There were 13 conserved cysteine residues in croceine croaker myostatin, nine of which are common to all TGF-beta superfamily members. The most conserved region of vertebrate myostatins is the TGF-beta domain, which was the mature bioactive domain of the myostatin protein. The myostatin gene was expressed not only in the skeletal muscle, but also in the other tissues.