Targeted Metabolomics Analysis of Serum Amino Acids in T2DM Patients.

Purpose: Amino acids are the important metabolites in the body and play a crucial role in biological processes. The purpose of this study is to provide a profile of amino acids change in the serum of T2DM patients and identify potential biomarkers. Patients and Methods: In this study, we quantitatively determined the serum amino acid profiles of 30 T2DM patients and 30 healthy volunteers. T test and multivariate statistical analysis were used to identify candidate biomarkers with GraphPad Prism 9.5 software and MetaboAnalyst 5.0 on-line platform. Results: Thirty-four amino acids were quantified, and 19 amino acid levels differed significantly between T2DM and Healthy groups. Screened by the specific screening criteria (VIP>1.0; P<0.05; FC>1.5, or FC<0.67) in MetaboAnalyst 5.0 platform, 8 amino acids were identified as potential biomarkers. Pearson rank correlation test showed 14 differential amino acids were significantly correlated with T2DM-related physiological parameters. Conclusion: The results of this study provide theoretical basis for the subsequent development of dietary supplements for the prevention or treatment of T2DM and its complications.

Metformin alleviates adriamycin resistance of osteosarcoma by declining YY1 to inhibit MDR1 transcriptional activity.

Chemotherapy resistance hinders the successful treatment of osteosarcoma (OS) to some extent. Previous studies have confirmed that metformin (Met) enhances apoptosis induced by chemotherapeutic drugs, but the underlying mechanism remains unclear. To establish adriamycin (ADM)-resistant MG-63 (MG-63/ADM) cells, the dosage of ADM was progressively increased. The results of qRT-PCR and Western blotting demonstrated that the expression level of Yin Yang 1 (YY1) and multi-drug resistance-1 (MDR1) in MG-63/ADM cells were remarkably increased compared with those in MG-63 cells. Met dramatically enhanced ADM cytotoxicity and accelerated apoptosis of MG-63/ADM cells. Moreover, Met suppressed the expressions of YY1 and MDR1 in MG-63/ADM cells. YY1 promoted its transcriptional expression by directly binding to the MDR1 promoter. Furthermore, the effects of Met on ADM sensitivity in MG-63/ADM cells was reversed due to overexpression of YY1 or MDR1. Collectively, these findings suggested that Met inhibited YY1/MDR1 pathway to reverse ADM resistance in OS, providing a new insight into the mechanism of Met in ADM resistance of OS.

Evaluation of intervention effects of dietary coenzyme Q10 supplementation on oxidized fish oil-induced stress response in largemouth bass Micropterus salmoides.

The aim of this experiment was to investigate whether dietary coenzyme Q10 could alleviate stress response of Micropterus salmoides caused by oxidized fish oil. Four isonitrogenous and isoenergetic diets were formulated to contain 100% fresh fish oil (FFO), 50% fresh fish oil + 50% oxidized fish oil (BFO), 100% oxidized fish oil (OFO) and 100% oxidized fish oil + 0.1% coenzyme Q10 (QFO) and were fed to Micropterus salmoides (95 ± 0.60 g) for 70 days. Higher weight gain rate was recorded in fish fed diet supplemented with coenzyme Q10 (CoQ10). FFO and BFO significantly increased contents of fat and energy in whole-body, while protein and energy retention significantly decreased in fish fed OFO. Apparent digestibility of energy and fat showed a significant decrease trend with increased the proportion of dietary oxidized fish oil. Fish fed OFO significantly increased activities of superoxide dismutase and catalase, while CoQ10 supplementation significantly reduced activities of alanine aminotransferase and aspartate aminotransferase in plasma. Contents of n-3 polyunsaturated fatty acids and highly unsaturated fatty acids, especially EPA and DHA in liver and muscle significantly decreased in fish fed OFO. Transcriptome analysis indicated that a total of 1238, 1189 and 1773 differentially expressed genes (DEGs, |log2(fold change) | >= 1 and q-value<=0.001) were found in the three comparison groups (FFO vs. OFO, FFO vs. QFO, OFO vs. QFO), respectively. After KEGG enrichment, the main changed pathways in the two comparison groups (FFO vs. OFO, OFO vs. QFO) related to the immune system. Dietary OFO up-regulated the expression of immune-related genes and inflammatory factors, while dietary CoQ10 supplementation reduced these effects.

Exploring the pathological relationships between adamantinomatous craniopharyngioma and contiguous structures with tumor origin.

PURPOSE: Identifying relationships between craniopharyngiomas (CPs) and contiguous structures, and tumor origin are crucial for treatments. This study attempted to explore the relationships and tumor origin. METHODS: CPs that underwent endoscopic surgeries were enrolled. The interfacial specimens of CPs attaching the hypothalamus, pituitary stalk (PS), pituitary grand (PG), optic chiasma (OC) and brain tissue (BT) were pathologically examined. Boundaries between CPs and these structures were observed during operations. Expression of ß-catenin and stem cell markers were analyzed to explore the tumor origin. Outcomes of patients were assessed. RESULTS: A total of 34 CPs were categorized into two groups based on the locations of finger-like protrusions (FP). Group A comprised 18 CPs with FP only present in the specimens attaching to hypothalamus. The surface of these CPs was fused with hypothalamus under endoscopic videos. However, the specimens attaching to the PS, PG, OC, and BT showed no FP. Clear boundaries was observed between these CPs and these structures. Group B comprised 16 CPs with FP only present in the specimens attaching to PS. The tumor surface was fused with PS. Specimens attaching to the hypothalamus, PG, OC and BT showed no FP. Clear boundary was observed among these CPs with these structures. These results implied CPs only invaded a certain part of hypothalamic-pituitary axis. ß-catenin and stem cells markers mainly distributed in the FP tissues of both groups. Patients in group B achieved better outcomes than group A. CONCLUSIONS: CPs only invade the hypothalamic-pituitary axis with FP and the FP would be the tumor origin.

The eagle sign: a new preoperative MRI-based tool for predicting topographic correlation between craniopharyngioma and hypothalamus.

PURPOSE: Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological-surgical-pathological-outcome analysis. MATERIALS AND METHODS: Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named "eagle sign" was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. RESULTS: A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of "eagle sign". Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical-pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of "eagle sign" were more than 90%. CONCLUSION: "Eagle sign" is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation.

Misdirected immunity gives rise to the autoimmune tissue inflammation of rheumatoid arthritis, in which excess production of the cytokine tumor necrosis factor (TNF) is a central pathogenic event. Mechanisms underlying the breakdown of self-tolerance are unclear, but T cells in the arthritic joint have a distinctive metabolic signature of ATPlo acetyl-CoAhi proinflammatory effector cells. Here we show that a deficiency in the production of mitochondrial aspartate is an important abnormality in these autoimmune T cells. Shortage of mitochondrial aspartate disrupted the regeneration of the metabolic cofactor nicotinamide adenine dinucleotide, causing ADP deribosylation of the endoplasmic reticulum (ER) sensor GRP78/BiP. As a result, ribosome-rich ER membranes expanded, promoting co-translational translocation and enhanced biogenesis of transmembrane TNF. ERrich T cells were the predominant TNF producers in the arthritic joint. Transfer of intact mitochondria into T cells, as well as supplementation of exogenous aspartate, rescued the mitochondria-instructed expansion of ER membranes and suppressed TNF release and rheumatoid tissue inflammation.

Dihydroberberine, an isoquinoline alkaloid, exhibits protective effect against dextran sulfate sodium-induced ulcerative colitis in mice.

BACKGROUND: As a chronic inflammatory disease, ulcerative colitis (UC) is relevant to a rising risk of colorectal cancer. Dihydroberberine (DHBB), a natural occurring isoquinoline alkaloid with various bioactivities, was found in many plants including Coptis chinensis Franch. (Ranunculaceae), Phellodendron chinense Schneid. (Rutaceae), and Chelidonium majus L. (Papaveraceae). However, its protective effect on UC is sparsely dissected out. PURPOSE: To explore the protective role and underlying mechanism of DHBB on a model of colitis. METHODS: Acute colitis model was established by gavage with 3% dextran sulfate sodium (DSS) for 8 days. Influence of DHBB on DSS-induced clinical symptoms and disease activity index (DAI) was monitored and analyzed. Pathological injury of colon tissues was examined by hematoxylin-eosin and Alcian blue staining. The expression of intestinal mucosal barrier function proteins, immune-inflammation related biomarkers and signal pathway key targets were determined by ELISA kit, Western blot, immunohistochemistry and qRT-PCR. RESULTS: DHBB treatment effectively alleviated DSS-induced UC by relieving clinical manifestations, DAI scores and pathological damage, which exerted similar beneficial effect to azathioprine (AZA), and better than berberine (BBR). In addition, DHBB significantly improved the gut barrier function through up-regulating the levels of tight junction proteins and mucins. Furthermore, DHBB dramatically ameliorated colonic immune-inflammation state, which was related to the decrease of colonic pro-inflammatory cytokines and immunoglobulin through blocking TLR4/MyD88/NF-κB signal pathway. CONCLUSION: These results demonstrated that DHBB exerted a significant protective effect on DSS-induced experimental UC, at least partly through suppressing immune-inflammatory response and maintaining gut barrier function.

Natural-Derived Polysaccharides From Plants, Mushrooms, and Seaweeds for the Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease impairing the gastrointestinal tract, and its incidence and prevalence have been increasing over time worldwide. IBD greatly reduces peoples' quality of life and results in several life-threatening complications, including polyp, toxic colonic dilatation, intestinal perforation, gastrointestinal bleeding, and cancerization. The current therapies for IBD mainly include drugs for noncritical patients and operation for critical patients. However, continuous use of these drugs causes serious side effects and increased drug resistance, and the demand of effective and affordable drugs with minimal side effects for IBD sufferers is urgent. Natural-derived polysaccharides are becoming a research hotspot for their therapeutic effects on IBD. This study focuses on the research progress of various natural polysaccharides from plants, seaweeds, and mushrooms for the treatment of IBD during recent 20 years. Regulation of oxidative stress, inflammatory status, gut microbiota, and immune system and protection of the intestinal epithelial barrier function are the underlying mechanisms for the natural-derived polysaccharides to treat IBD. The excellent efficacy and safety of polysaccharides make them promising candidates for IBD therapy.

[Research on regularity of traditional Chinese medicine in treatment of Alzheimer's disease based on data mining].

To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.

Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines.

Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day). We observed c-Myc oncoprotein and oncofetal RNA-binding protein Lin28B overexpressions accompanied by cancer progenitor-like cell formation in the liver by AAI exposure. Meanwhile, we found that forkhead box O1 (FOXO1) was robustly phosphorylated, thereby shuttling into the cytoplasm of hepatocytes. Furthermore, utilizing microarray and qRT-PCR analysis, we confirmed that microRNA expression significantly dysregulated in the liver treated with AAI. Among them, we particularly focused on the members in let-7 miRNAs and miR-23a clusters, the downstream of c-Myc and IL6 receptor (IL6R) signaling pathway linking the premalignant alteration. Strikingly, when IL6 was added in vitro, IL6R/NF-κB signaling activation contributed to the increase of FOXO1 phosphorylation by the let-7b inhibitor. Therefore, it highlights the new insight into the interplay of the network in hepatic tumorigenesis by AAI exposure, and also suggests that anti-premalignant therapy may be crucial for preventing AAI-induced hepatocarcinogenesis.