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Background: High fat diet impact transcription of hepatic genes responsible for drug metabolism and pharmacokinetics. Until now, researches just focused on a couple specific genes without a global profile showing. Age-dependent manner was also not noted well. This study aims to investigate the high fat diet effect on transcriptome of drug metabolism and pharmacokinetic system in mouse livers and show the age-dependent evidence. Methods: C57BL/6 male mice were used in this experiment. High fat diet was used to treat mice for 16 and 38 weeks. Serum total cholesterol, low density lipoprotein cholesterol, aspartate transaminase, and alanine transaminaselevels were measured. Meanwhile, Histology, RNA-Seq, RT-PCR analysis and fourteen major hepatic bile acids quantification were performed for the liver tissues. Data was mined at levels of genes, drug metabolism and pharmacokinetic sysem, and genome wide. Results: Treatment with high fat diet for 38 weeks significantly increased levels of serum lipids as well as aspartate transaminase, and alanine transaminase. Meanwhile, lipid accumulation in livers was observed. At week 38 of the experiment, the profile of 612 genes involved in drug metabolism and pharmacokinetics was significantly changed, indicated by a heatmap visulization and a principal component analysis. In total 210 genes were significantly regulated. Cyp3a11, Cyp4a10, and Cyp4a14 were down-regulated by 10–35 folds, while these three genes also were highly expressed in the liver. High fat diet regulated 11% of genome-wide gene while 30% of genes involved in the hepatic drug metabolism and pharmacokinetic system. Genes, including Adh4, Aldh1b1, Cyp3a11, Cyp4a10, Cyp8b1, Fmo2, Gsta3, Nat8f1, Slc22a7, Slco1a4, Sult5a1, and Ugt1a9, were regulated by high fat diet as an aging-dependent manner. Bile acids homeostasis, in which many genes related to metabolism and transportation were enriched, was also changed by high fat diet with an aging-dependet manner. Expression of genes in drug metabolism and disposition system significantly correlated to serum lipid profiles, and frequently correlated with each other. Conclusions: High fat diet changed the global transcription profile of hepatic drug metabolism and pharmacokinetic system with a age-dependent manner. [ABSTRACT FROM AUTHOR]

The liver is the largest internal organ of the human body. It has a complex structure and function and plays a vital role in drug metabolism. In recent decades, extensive research has aimed to develop in vitro models that can simulate liver function to demonstrate changes in the physiological and pathological environment of the liver. Animal models and in vitro cell models are common, but the data obtained from animal models lack relevance when applied to humans, while cell models have limited predictive ability for metabolism and toxicity in humans. Recent advancements in tissue engineering, biomaterials, chip technology, and 3D bioprinting have provided opportunities for further research in in vitro models. Among them, liver-on-a-Chip (LOC) technology has made significant achievements in reproducing the in vivo behavior, physiological microenvironment, and metabolism of cells and organs. In this review, we discuss the development of LOC and its research progress in liver diseases, hepatotoxicity tests, and drug screening, as well as chip combinations. First, we review the structure and the physiological function of the liver. Then, we introduce the LOC technology, including general concepts, preparation materials, and methods. Finally, we review the application of LOC in disease modeling, hepatotoxicity tests, drug screening, and chip combinations, as well as the future challenges and directions of LOC. [ABSTRACT FROM AUTHOR]

Background: Polygonum Multiflorum Thunb(PMT) has multiple biological effects, such as anti-inflammatory, lipid-lowering, anti-aging and so on. Therefore, D-galactose-induced aging mice were used to study the effect of PMT on fatty acid metabolism and its underlying mechanism. Methods: C57BL/6 male mice were randomly divided into normal group, aging model group, PMT intragastrical administration group (high, Medium, low); model group and PMT intragastrical administration group Daily intraperitoneal injection D-galactose 800 mg·ml− 1·Kg− 1 to establish subacute aging model; PMT intragastrical administration group at the same time to intragastrical PMT extract (1 g·ml− 1·Kg− 1, 0.6 g·ml− 1·Kg− 1, 0.3 g·ml− 1·Kg− 1), normal group injection and intragastrical equivalent saline for 60 consecutive days. By detecting the oxidation index of liver to judge the efficacy of PMT, gas chromatography-mass spectrometry (GC-MS) analysis was used to quantitatively analyze the fatty acid content in liver. Results: Finally, we found that PMT improved the enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in aging mice, and reduce the enzyme activity of malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The content of fatty acids such as C18:1, C18:2, C18:3 N3, C20:2 and C20:3 N3 decreased significantly in senescent mice (P < 0.05) as evidenced by GC-MS analysis, whereas, these fatty acids increased significantly after treatment of PMT (P < 0.05). Conclusion: PMT improves the content of liver fatty acids in aging mice induced by D-galactose through, enhancing the activity of anti-oxidant enzymes. [ABSTRACT FROM AUTHOR]

Background: Lotus corniculatus is a widely distributed perennial legume whose great adaptability to different environments and resistance to barrenness make it an excellent forage and ecological restoration plant. However, its molecular genetics and genomic relationships among populations are yet to be uncovered. Result: Here we report on a genomic variation map from worldwide 272 L. corniculatus accessions by genome resequencing. Our analysis suggests that L. corniculatus accessions have high genetic diversity and could be further divided into three subgroups, with the genetic diversity centers were located in Transcaucasia. Several candidate genes and SNP site associated with CNglcs content and growth traits were identified by genome-wide associated study (GWAS). A non-synonymous in LjMTR was responsible for the decreased expression of CNglcs synthesis genes and LjZCD was verified to positively regulate CNglcs synthesis gene CYP79D3. The LjZCB and an SNP in LjZCA promoter were confirmed to be involved in plant growth. Conclusion: This study provided a large number of genomic resources and described genetic relationship and population structure among different accessions. Moreover, we attempt to provide insights into the molecular studies and breeding of CNglcs and growth traits in L. corniculatus. [ABSTRACT FROM AUTHOR]

Backgrounds: The incidence of gastric cardiac cancer (GCC) has obviously increased recently with poor prognosis. It's necessary to compare GCC prognosis with other gastric sites carcinoma and set up an effective prognostic model based on a neural network to predict the survival of GCC patients. Methods: In the population-based cohort study, we first enrolled the clinical features from the Surveillance, Epidemiology and End Results (SEER) data (n = 31,397) as well as the public Chinese data from different hospitals (n = 1049). Then according to the diagnostic time, the SEER data were then divided into two cohorts, the train cohort (patients were diagnosed as GCC in 2010–2014, n = 4414) and the test cohort (diagnosed in 2015, n = 957). Age, sex, pathology, tumor, node, and metastasis (TNM) stage, tumor size, surgery or not, radiotherapy or not, chemotherapy or not and history of malignancy were chosen as the predictive clinical features. The train cohort was utilized to conduct the neural network-based prognostic predictive model which validated by itself and the test cohort. Area under the receiver operating characteristics curve (AUC) was used to evaluate model performance. Results: The prognosis of GCC patients in SEER database was worse than that of non GCC (NGCC) patients, while it was not worse in the Chinese data. The total of 5371 patients were used to conduct the model, following inclusion and exclusion criteria. Neural network-based prognostic predictive model had a satisfactory performance for GCC overall survival (OS) prediction, which owned 0.7431 AUC in the train cohort (95% confidence intervals, CI, 0.7423–0.7439) and 0.7419 in the test cohort (95% CI, 0.7411–0.7428). Conclusions: GCC patients indeed have different survival time compared with non GCC patients. And the neural network-based prognostic predictive tool developed in this study is a novel and promising software for the clinical outcome analysis of GCC patients. [ABSTRACT FROM AUTHOR]

Introduction: The Gelao people are a unique minority in Southwest China with a unique culture for the utilization of edible plants, including a large number of medicinal plants. They believe that at least 61 species are edible and have medicinal value. Ethnobotany research can reveal the local knowledge of the Gelao people regarding the traditional use of plants and the relationship between this minority and their living environment to help retain and pass on this traditional knowledge forever. Methods: Edible wild plants and their applied ethnic knowledge were investigated in three counties in northern Guizhou. Gelao residents were the main informants, and literature search, village interviews, participatory observation and quantitative ethnobotany evaluation were used. Results: A total of 151 species of wild plants in 67 families are collected and eaten by Gelao residents, among which 61 species were considered to have medicinal value, accounting for 40.4% of the total, and 43 were listed in the Chinese Pharmacopoeia. There were 57 plant species with fruits as their edible parts, which are consumed as snacks, followed by 54 species whose young seedlings and leaves are the edible parts, most of which are consumed cold or stir-fried. Other edible parts included roots or rhizomes (bulbs), flowers, whole plants, seeds, fruiting bodies and stems. There were two consumption modes: raw and cooked. Raw foods were mainly consumed as snacks, which mainly comprise fruits. Cooked foods were mainly vegetables consumed cold or stir-fried. Some plants were used as seasonings, infused wines, condiments and grains. The main medicinal functions were nourishing and reducing heatiness. Nourishing plants were mainly "shen" plants and Liliaceae, while plants able to reduce heatiness were mainly Asteraceae. Others functions included anti-hangover, anticancer and insecticidal. There were 38 species of important edible wild plants (CFSI > 500) in northern Guizhou, which had a high utilization rate. Houttuynia cordata Thunb. and Mentha suaveolens Ehrh. were the most representative edible wild plants in this area. The species, edible parts, edible categories, consumption modes and medicinal functions of edible wild plants in this area are diverse, and the traditional knowledge on their uses is rich. However, the number of wild plant species eaten by the informants and their related knowledge were positively correlated with age, which indicates that the rich traditional knowledge in this area is gradually disappearing with urbanization. Conclusions: The Gelao have a rich history of consuming wild plants. With the development of the social economy, the traditional knowledge passed from older generations is gradually being lost and its inheritance is facing great risks. This study collects, sorts and spreads this precious traditional knowledge, which is of great value to its protection and inheritance and fully demonstrates the value and importance of our work. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests that gut microbiota plays a predominant role in Crohn's disease (CD). However, the microbiome alterations in the early stage of CD patients still remain unclear. The present study aimed to identify dysbacteriosis in patients with early CD and explore specific gut bacteria related to the progression of CD. Methods: This study was nested within a longitudinal prospective Chinese CD cohort, and it included 18 early CD patients, 22 advanced CD patients and 30 healthy controls. The microbiota communities were investigated using high-throughput Illumina HiSeq sequencing targeting the V3–V4 region of 16S ribosomal DNA (rDNA) gene. The relationship between the gut microbiota and clinical characteristics of CD was analyzed. Results: Differential microbiota compositions were observed in CD samples (including early and advanced CD samples) and healthy controls samples. Notably, Lachnospiracea_incertae_sedis and Parabacteroides were enriched in the early CD patients, Escherichia/Shigella, Enterococcus and Proteus were enriched in the advanced CD patients, and Roseburia, Gemmiger, Coprococcus, Ruminococcus 2, Butyricicoccus, Dorea, Fusicatenibacter, Anaerostipes, Clostridium IV were enriched in the healthy controls [LDA score (log10) > 2]. Furthermore, Kruskal–Wallis Rank sum test results showed that Blautia, Clostridium IV, Coprococcus, Dorea, Fusicatenibacter continued to significantly decrease in early and advanced CD patients, and Escherichia/Shigella and Proteus continued to significantly increase compared with healthy controls (P < 0.05). The PICRUSt analysis identified 16 remarkably different metabolic pathways [LDA score (log10) > 2]. Some genera were significantly correlated with various clinical parameters, such as fecal calprotectin, erythrocyte sedimentation rate, C-reactive protein, gland reduce, goblet cells decreased, clinical symptoms (P < 0.05). Conclusions: Dysbacteriosis occurs in the early stage of CD and is associated with the progression of CD. This data provides a foundation that furthers the understanding of the role of gut microbiota in CD's pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The development of diabetes vascular calcification (VC) is tightly associated with the inhibition of vascular smooth muscle cell (VSMC) autophagy. Previously, our team found that miR-32-5p (miR-32) promotes macrophage activation, and miR-32 is expressed at higher level in the plasma of patients with coronary calcification. However, whether miR-32 mediates the function of macrophages in type 2 diabetes (T2D) VC is still unclear.Methods: Wild-type (WT) and miR-32-/- mice were used in this study. qRT-PCR and western blotting were used to analyze gene expression. Flow cytometry was used to analyze the influence of glucose concentration on macrophage polarization. Nanoparticle tracking analysis (NTA), transmission electron microscopy, and confocal microscopy were used to identify macrophage extracellular vehicles (EVs). Immunofluorescence, in situ hybridization (ISH), immunohistochemistry, and alizarin red staining were used to analyze the influence of macrophage EVs on autophagy and calcification of the aorta of miR-32-/- mice. A luciferase assay was used to analyze the effect of miR-32 on myocyte enhancer factor 2D (Mef2d) expression. Co-IP combined with mass spectrometry (MS) and transcriptome sequencing was used to analyze the signalling pathway by which Mef2d acts in VSMC autophagy.Results: We found that high glucose conditions upregulate miR-32 expression in macrophages and their EVs. Importantly, macrophages and their EVs promote VSMC osteogenic differentiation and upregulate miR-32 expression in VSMCs. Moreover, miR-32 mimics transfection promoted osteogenic differentiation and inhibited autophagy in VSMCs. In vitro and in vivo experiments showed that Mef2d is the key target gene of miR-32 that inhibits VSMC autophagy. Furthermore, MS and transcriptome sequencing found that cGMP-PKG is an important signalling pathway by which Mef2d regulates VSMC autophagy. In addition, after T2D miR-32-/- mice were injected with macrophage EVs via the caudal vein, miR-32 was detected in aortic VSMCs of miR-32-/- mice. Moreover, autophagy was significantly inhibited, and calcification was significantly enhanced in aorta cells.Conclusions: These results reveal that EVs are the key pathway by which macrophages promote T2D VC, and that EVs miR-32 is a key cause of autophagy inhibition in VSMCs. [ABSTRACT FROM AUTHOR]

Background: We report a unique case of a superficial esophageal cancer arising in a single diverticulum, diagnosed with magnifying image-enhanced endoscopy and then successfully treated by endoscopic submucosal dissection (ESD).Case Presentation: A 66-year-old man with alcohol-related liver injury visited our hospital for endoscopy for investigation of varix. Esophagogastroduodenoscopy showed no varix but a large epiphrenic diverticulum with an area of fainted redness just above the esophagogastric junction. Narrow band imaging revealed a sharply demarcated brownish dotted area, and dilated intra-epithelial papillary capillary loops (IPCL) were subsequently seen after magnification. Chromoendoscopy with 1% Lugol's iodine solution demonstrated a well-demarcated unstained area, approximately 20 mm in diameter. Endoscopic biopsy revealed a squamous cell carcinoma (SCC).Conclusion: The tumor was completely resected by ESD without perforation. Histologically, it was an intraepithelial SCC without lympho-vascular invasion of cancer cells. No local recurrence or metastasis was detected at the last follow-up of 42 months. [ABSTRACT FROM AUTHOR]