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1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(2): 231-243, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38650448

ABSTRACT

MiRNAs are a class of small non-coding RNAs, which regulate gene expression post-transcriptionally by partial complementary base pairing. Aberrant miRNA expressions have been reported in tumor tissues and peripheral blood of cancer patients. In recent years, artificial intelligence algorithms such as machine learning and deep learning have been widely used in bioinformatic research. Compared to traditional bioinformatic tools, miRNA target prediction tools based on artificial intelligence algorithms have higher accuracy, and can successfully predict subcellular localization and redistribution of miRNAs to deepen our understanding. Additionally, the construction of clinical models based on artificial intelligence algorithms could significantly improve the mining efficiency of miRNA used as biomarkers. In this article, we summarize recent development of bioinformatic miRNA tools based on artificial intelligence algorithms, focusing on the potential of machine learning and deep learning in cancer-related miRNA research.


Subject(s)
Algorithms , Artificial Intelligence , Computational Biology , MicroRNAs , Neoplasms , MicroRNAs/genetics , Humans , Neoplasms/genetics , Computational Biology/methods , Machine Learning , Deep Learning
2.
Immun Inflamm Dis ; 12(1): e1165, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38270322

ABSTRACT

INTRODUCTION: Existing therapies of systemic lupus erythematosus (SLE) are efficacious only in certain patients. Developing new treatment methods is urgent. This meta-analysis aimed to evaluate the efficacy and safety of low-dose IL-2 (LD-IL-2). METHODS: According to published data from PubMed, Web of Science, Embase, ClinicalTrials.gov, MEDLINE, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, eight trials were included. RESULTS: After the LD-IL-2 treatment, 54.8% of patients had distinct clinical remission. The SRI-4 response rates were 0.819 (95% confidence interval [CI]: 0.745-0.894), and the SELENA-SLEDAI scores were significantly decreased (SMD = -2.109, 95% CI: [-3.271, -0.947], p < .001). Besides, the proportions of CD4+ T (SMD = 0.614, 95% CI: [0.250, 0.979], p = .001) and Treg cells (SMD = 1.096, 95% CI: [0.544, 1.649], p < .001) were increased dramatically after LD-IL-2 treatment, while there were no statistical differences in the proportions of CD8+ T cells, Th1 cells, Th2 cells, and Th17 cells (p > .05). Besides, the proportions of Th17 (SMD = 1.121, 95% CI: [0.709, 1.533], p < .001) and Treg (SMD = 0.655, 95% CI: [0.273, 1.038], p = .001) were significantly increased after receiving subcutaneously 0.5 million IU of LD-IL-2 treatment per day for 5 days, but there were no statistical differences in the proportions of Treg after receiving 1 million IU every other day subcutaneously of LD-IL-2 treatment. Injection site reaction and fever were common side effects of IL-2, which occurred in 33.1% and 14.4% of patients. No serious adverse events were reported. CONCLUSION: LD-IL-2 was promising and well-tolerated in treating SLE, which could promote Treg's proliferation and functional recovery. Injecting 0.5 million IU of IL-2 daily can better induce the differentiation of Treg cells and maintain immune homeostasis than injecting 1 million IU every other day.


Subject(s)
Interleukin-2 , Lupus Erythematosus, Systemic , Humans , CD8-Positive T-Lymphocytes , Cell Differentiation , Interleukin-2/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Lymphocyte Subsets
3.
Environ Manage ; 73(1): 81-101, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38078964

ABSTRACT

Hong Kong (HK), one of the world's most densely populated metropolises, is home to over 200 rivers and streams extending about 2500 km in length. During the 1970s-1990s, most of these rivers were converted into artificial canals, to which the local society pays little attention. Since the 2010s, the HK government has initiated river revitalization to enhance the social-environmental roles of rivers. This study employed a mixed research method, including literature and policy analysis, expert interviews, field visits, and a public survey, to identify key challenges in HK's Integrated River Basin Management (IRBM). The findings highlighted the lack of IRBM's institutional arrangements in HK, characterized by a fragmented 'one river, two systems' approach without both coordination and collaboration. The Water Supplies Department (WSD) impounds upland streams as reservoirs for securing the local water supply, while the Drainage Service Department (DSD) manages heavily channelized, culverted downstream serving as storm drains with diminished ecological functionality. One significant barrier to the implementation of IRBM in HK was the limited public participation, although our survey revealed a high level of public willingness to participate in river management. Presently, river revitalization efforts have achieved limited success, with ecological measures appearing mostly "cosmetic" and the conservation of freshwater biodiversity neglected. This further underscored the pressing need for the embracement of IRBM in HK to safeguard basin-wide freshwater ecosystems. Our survey also indicated low public awareness of river revitalization initiatives and widespread dissatisfaction with their outcomes. In conclusion, we proposed the development of IRBM in HK by instituting river basin coordination, prioritizing river ecosystem restoration in revitalization projects, and involving the public through tailored strategies.


Subject(s)
Conservation of Natural Resources , Ecosystem , Hong Kong , Conservation of Natural Resources/methods , Rivers , Biodiversity
4.
Cancer Biol Med ; 20(11)2023 11 02.
Article in English | MEDLINE | ID: mdl-37921408

ABSTRACT

OBJECTIVE: Immature vasculature lacking pericyte coverage substantially contributes to tumor growth, drug resistance, and cancer cell dissemination. We previously demonstrated that tumor necrosis factor superfamily 15 (TNFSF15) is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis. The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b+ cells and further into pericytes. METHODS: A model of Lewis lung cancer was established in mice with red fluorescent bone marrow. After TNFSF15 treatment, CD11b+ myeloid cells and vascular pericytes in the tumors, and the co-localization of pericytes and vascular endothelial cells, were assessed. Additionally, CD11b+ cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells. RESULTS: We observed elevated percentages of bone marrow-derived CD11b+ myeloid cells and vascular pericytes in TNFSF15-treated tumors, and the latter cells co-localized with vascular endothelial cells. TNFSF15 protected against CD11b+ cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways. CONCLUSIONS: TNFSF15 facilitates the production of CD11b+ cells in the bone marrow and promotes the differentiation of these cells into pericytes, which may stabilize the tumor neovasculature.


Subject(s)
Neoplasms , Pericytes , Animals , Humans , Mice , Cell Differentiation , Endothelial Cells , Mice, Inbred C57BL , Myeloid Cells/metabolism , Neoplasms/metabolism , Pericytes/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 15/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 15/pharmacology , Tumor Necrosis Factors/metabolism , Tumor Necrosis Factors/pharmacology
5.
Entropy (Basel) ; 24(7)2022 Jul 13.
Article in English | MEDLINE | ID: mdl-35885194

ABSTRACT

Due to a colossal soccer market, soccer analysis has attracted considerable attention from industry and academia. In-game outcome prediction has great potential in various applications such as game broadcasting, tactical decision making, and betting. In some sports, the method of directly predicting in-game outcomes based on the ongoing game state is already being used as a statistical tool. However, soccer is a sport with low-scoring games and frequent draws, which makes in-game prediction challenging. Most existing studies focus on pre-game prediction instead. This paper, however, proposes a two-stage method for soccer in-game outcome prediction, namely in-game outcome prediction (IGSOP). When the full length of a soccer game is divided into sufficiently small time frames, the goal scored by each team in each time frame can be modeled as a random variable following the Bernoulli distribution. In the first stage, IGSOP adopts state-based machine learning to predict the probability of a scoring goal in each future time frame. In the second stage, IGSOP simulates the remainder of the game to estimate the outcome of a game. This two-stage approach effectively captures the dynamic situation after a goal and the uncertainty in the late phase of a game. Chinese Super League data have been used for algorithm training and evaluation, and the results demonstrate that IGSOP outperforms existing methods, especially in predicting draws and prediction during final moments of games. IGSOP provides a novel perspective to solve the problem of in-game outcome prediction in soccer, which has a potential ripple effect on related research.

6.
Front Cell Dev Biol ; 10: 862294, 2022.
Article in English | MEDLINE | ID: mdl-35557959

ABSTRACT

Background: The immunotherapy efficacy in gastric cancer (GC) is limited. Cancer-associated fibroblasts (CAFs) induce primary resistance to immunotherapy. However, CAF infiltration in tumors is difficult to evaluate due to the lack of validated and standardized quantified methods. This study aimed to investigate the impact of infiltrating CAFs alternatively using fibroblast-associated mutation scoring (FAMscore). Methods: In a GC cohort from Affiliated Hospital of Jiangsu University (AHJU), whole exon sequencing of genomic mutations, whole transcriptome sequencing of mRNA expression profiles, and immunofluorescence staining of tumor-infiltrating immune cells were performed. GC data from The Cancer Genome Atlas were used to identify genetic mutations which were associated with overall survival (OS) and impacted infiltrating CAF abundance determined by transcriptome-based estimation. FAMscore was then constructed through a least absolute shrinkage and selection operator Cox regression model and further validated in AHJU. The predictive role of FAMscore for immunotherapy outcomes was tested in 1 GC, one melanoma, and two non-small-cell lung cancer (NSCLC-1 and -2) cohorts wherein participants were treated by immune checkpoint inhibitors. Results: FAMscore was calculated based on a mutation signature consisting of 16 genes. In both TCGA and AHJU, a high FAMscore was an independent predictor for poor OS of GC patients. FAMscore was associated with immune-associated genome biomarkers, immune cell infiltration, and signaling pathways of abnormal immunity. Importantly, patients with high FAMscore presented inferiority in the objective response rate of immunotherapy compared to those with low FAMscore, with 14.6% vs. 66.7% (p<0.001) in GC, 19.6% vs. 68.2% (p<0.001) in NSCLC-1, 23.1% vs 75% (p = 0.007) in NSCLC-2, and 40.9% vs 75% (p = 0.037) in melanoma. For available survival data, a high FAMscore was also an independent predictor of poor progression-free survival in NSCLC-1 (HR = 2.55, 95% CI: 1.16-5.62, p = 0.02) and NSCLC-2 (HR = 5.0, 95% CI: 1.13-22.19, p = 0.034) and poor OS in melanoma (HR = 3.48, 95% CI: 1.27-9.55, p = 0.015). Conclusions: Alternative evaluation of CAF infiltration in GC by determining the FAMscore could independently predict prognosis and immunotherapy outcomes. The FAMscore may be used to optimize patient selection for immunotherapy.

7.
J Biol Chem ; 298(6): 102033, 2022 06.
Article in English | MEDLINE | ID: mdl-35595096

ABSTRACT

The human rhomboid-5 homolog-1 (RHBDF1) is a multi-transmembrane protein present mainly on the endoplasmic reticulum. RHBDF1 has been implicated in the activation of epidermal growth factor receptor (EGFR)-derived cell growth signals and other activities critical to cellular responses to stressful conditions, but details of this activation mechanism are unclear. Here, we report a RHBDF1 mRNA transcript alternative splicing variant X6 (RHBDF1 X6 or RHX6) that antagonizes RHBDF1 activities. We found that while the RHBDF1 gene is marginally expressed in breast tumor-adjacent normal tissues, it is markedly elevated in the tumor tissues. In sharp contrast, the RHX6 mRNA represents the primary RHBDF1 variant in normal breast epithelial cells and tumor-adjacent normal tissues but is diminished in breast cancer cells and tumors. We demonstrate that, functionally, RHX6 acts as an inhibitor of RHBDF1 activities. We show that artificially overexpressing RHX6 in breast cancer cells leads to retarded proliferation, migration, and decreased production of epithelial-mesenchymal transition-related adhesion molecules. Mechanically, RHX6 is able to inhibit the maturation of TACE, a protease that processes pro-TGFα, a pro-ligand of EGFR, and to prevent intracellular transportation of pro-TGFα to the cell surface. Additionally, we show that the production of RHX6 is under the control of the alternative splicing regulator RNA binding motif protein-4 (RBM4). Our findings suggest that differential splicing of the RHBDF1 gene transcript may have a regulatory role in the development of epithelial cell cancers.


Subject(s)
Alternative Splicing , Breast Neoplasms , ErbB Receptors , Membrane Proteins , Breast Neoplasms/genetics , Cell Line, Tumor , ErbB Receptors/metabolism , Female , Humans , Membrane Proteins/genetics , Membrane Proteins/metabolism , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , Transforming Growth Factor alpha/metabolism
8.
ACS Appl Mater Interfaces ; 14(15): 17763-17773, 2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35384643

ABSTRACT

This work presents the preparation and property characterization of a biomass gelatin (GA)-based aerogel. Halloysite nanotubes (HNTs) were used to improve the mechanical strength, pore size distribution, and thermal stability of the aerogel. Polyethyleneimine (PEI) and (3-glycidyloxypropyl)trimethoxysilane (GPTMS) were utilized to increase the interfacial interaction between HNTs and GA through chemical cross-linking. Green, sustainable, and low-cost composite aerogels were prepared by "cogel" and freeze-drying techniques. The experimental results show that the HNTs/GA composite aerogel has a low density (31.98-57.48 mg/cm3), a high porosity (>95%), a low thermal conductivity (31.85-40.16 mW m-1 K-1), and superior moldability. In addition, the mechanical strength and thermal insulation properties of the HNTs/GA composite aerogels with a "thorn"-like lamellar porous network structure are different in the axial direction versus the radial direction. The maximum compressive strength, maximum compressive modulus, and corresponding specific modulus in the axial direction were 1.81 MPa, 5.45 MPa, and 94.8 kN m kg-1, respectively. Therefore, the biomass/clay composite aerogel will be a sustainable and renewable functional material with high mechanical strength and thermal insulation properties, which is expected to further promote biomass and clay for high value utilization.

9.
J Colloid Interface Sci ; 612: 572-583, 2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35026566

ABSTRACT

In this study, FeMg-LDH loaded with bentonite (FeMg-LDH@bentonite) was prepared using the facile co-precipitating method in situ to remove heavy metals from water and then characterized using XRD, SEM, TEM, FTIR, BET, TGA, and XPS. Pb (II) and Cd (II) were selected as the representative heavy metals to evaluate the adsorption capability of the FeMg-LDH@bentonite. The batch adsorption method was adopted to test the effects of the contact time, pH, initial concentration, different cations, and temperatures. The kinetic study indicated that the adsorption of heavy metals onto FeMg-LDH@bentonite was well fitted by the pseudo-second-order method. Isotherms were effectively simulated based on the Langmuir model. The maximal adsorption capability of Cd (II) and Pb (II) can reach 510.2 mg/g and 1397.62 mg/g, exceeding those of conventional adsorbents. The adsorption mechanisms of FeMg-LDH@bentonite demonstrating that there may exist surface complexation, ion exchange, and chemical deposition between FeMg-LDH@bentonite and heavy metals. Moreover, FeMg-LDH@bentonite was found to have a promising application for practically treating wastewater with heavy metals and can be used for various environmental water pollution treatments. The material may be used for heavy metal contaminated soil in the future.


Subject(s)
Bentonite , Water Pollutants, Chemical , Adsorption , Cadmium , Hydrogen-Ion Concentration , Hydroxides , Kinetics , Lead , Water Pollutants, Chemical/analysis
10.
Nanotechnology ; 33(3)2021 Oct 29.
Article in English | MEDLINE | ID: mdl-34638108

ABSTRACT

Fluorescent carbon dots (CDs) have attracted considerable interest due to their superior optical properties and facile preparation. In this work, O-phenylenediamine and melamine were used as precursors for the one-step hydrothermal synthesis of novel orange emissive CDs (O-CDs) in an aqueous solution. The fluorescence intensity (580 nm) of the O-CDs exhibited a good linear relationship with Ag+in the range of 0.0-50.0µM with the detection limit of 0.289µM. Moreover, the O-CDs were successfully used to determine Ag+in biological samples (Hela cells) because of their low cytotoxicity, and good biocompatibility. Besides, the O-CDs-doped solid-phase detection materials (test paper and hydrogel) were employed to monitor Ag+qualitatively and quantitatively, indicated that the O-CDs had a great capacity for the detection of Ag+in biological and environmental areas. Based on their extraordinary fluorescence property, the O-CDs could also be used as security ink. Overall, based on their excellent fluorescent performance, the CDs in this study have significant potential for practical application toward solid-phase sensing and security ink.

11.
J Cell Mol Med ; 25(19): 9168-9182, 2021 10.
Article in English | MEDLINE | ID: mdl-34510715

ABSTRACT

Existing literature has highlighted the tumour suppressive capacity of microRNA-15a (miR-15a); however, its role in hepatocellular carcinoma (HCC) remains relatively unknown. This study aimed to investigate the role of miR-15a in HCC and the associated underlying mechanism. Initially, RT-qPCR was performed to detect the expression of miR-15a in HCC tissues and cells. Bioinformatics analysis, Pearson correlation coefficient, dual-luciferase reporter assay, and molecular approaches were all conducted to ascertain the interaction between miR-15a and O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). PUGNAc treatment and cycloheximide (CHX) assay were performed to evaluate O-GlcNAc and the stabilization of the enhancer of zeste homolog 2 (EZH2). Finally, gain- and loss-of-function studies were employed to elucidate the role of P53 and the miR-15a/OGT/EZH2 axis in the progression of HCC, followed by in vivo experiments based on tumour-bearing nude mice. Our results demonstrated that the miR-15a expression was decreased in the HCC tissues and cells. P53 upregulated miR-15a expression, which inhibited the proliferation, migration and invasion of HCC cells, while inducing apoptosis and triggering a G0/G1 cell cycle phase arrest. OGT stabilized EZH2 via catalysing O-GlcNAc, which reversed the effect of P53 and miR-15a. The results of our in vivo study provided evidence demonstrating that P53 could suppress the development of HCC via the miR-15a/OGT/EZH2 axis. P53 was found to inhibit the OGT expression by promoting the expression of miR-15a, which destabilized EZH2 and suppressed the development of HCC. The key findings of our study highlight a promising novel therapeutic strategy for the treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Enhancer of Zeste Homolog 2 Protein/metabolism , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , N-Acetylglucosaminyltransferases/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Biomarkers, Tumor , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Disease Models, Animal , Disease Progression , Gene Expression Profiling , Heterografts , Humans , Mice , Prognosis
12.
Phys Rev Lett ; 126(4): 048002, 2021 Jan 29.
Article in English | MEDLINE | ID: mdl-33576668

ABSTRACT

We perform combined x-ray tomography and shear force measurements on a cyclically sheared granular system with highly transient behaviors, and obtain the evolution of microscopic structures and macroscopic shear force during the shear cycle. We explain the macroscopic behaviors of the system based on microscopic processes, including particle level structural rearrangement and frictional contact variation. Specifically, we show how contact friction can induce large structural fluctuations and cause significant shear dilatancy effect for granular materials, and we also construct an empirical constitutive relationship for the macroscopic shear force.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 249: 119217, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33257243

ABSTRACT

Specifically, visually, and quantitatively monitor copper ion (Cu2+) is critical in the area of biological and environmental detection. Herein, a ratiometric fluorescent probe with benzoxazole appended xanthenes skeleton was constructed and further employed to monitor Cu2+ in Hela cells, real water samples, and test strips. An easily distinguishable colorimetric (colorless to red) and fluorescence (green to red) change could be observed by naked eye under the portable UV lamp (365 nm) and the changes could be recovered by adding S2-. Furthermore, electrospinning technique was employed to fabricate a probe composited fluorescent sensing film (PMMA) for realizing the visual and recyclable monitoring of Cu2+, indicating that the probe-composited fluorescent sensing film has great potential for on-site and naked-eye detection of Cu2+ in practical.


Subject(s)
Copper , Fluorescent Dyes , Colorimetry , HeLa Cells , Humans , Spectrometry, Fluorescence
14.
Cancer Gene Ther ; 28(5): 486-501, 2021 05.
Article in English | MEDLINE | ID: mdl-33277615

ABSTRACT

Recent studies have illustrated the role of aberrant regulatory interactions in the mediation of malignant phenotypes of cancer cells, which could potentially provide novel therapeutic targets to limit the destructive recurrence and metastasis of hepatocellular carcinoma (HCC). Herein, we clarify the oncogenic role of the long noncoding RNA (lncRNA) distal-less homeobox 6 antisense 1 (DLX6-AS1) in HCC in vivo and in vitro. To this end, we knocked down lncRNA DLX6-AS1 and manipulated the expression of miR-513c to characterize their effects in HCC cell viability, migration, invasion, and apoptosis. Furthermore, we probed the interactions with miR-513c's target gene Cullin4A (Cul4A) and the degradation of Annexin A10 (ANXA10) protein. Our data show that lncRNA DLX6-AS1 and Cul4A were highly expressed, while miR-513c and ANXA10 were poorly expressed in HCC tissues and cells. Moreover, the silencing of lncRNA DLX6-AS1 impeded the viability, invasion, and migration of HCC cells, while stimulating cell apoptosis. Further data indicated that lncRNA DLX6-AS1 targeted and repressed miR-513c expression, where the tumor-inhibiting effects of lncRNA DLX6-AS1 silencing was achieved by elevating miR-513c expression. Importantly, the lncRNA DLX6-AS1 upregulated the expression of Cul4A through sponging of miR-513c. The silencing of Cul4A restricted the malignant phenotypes of HCC cells by repressing the ubiquitination-mediated degradation of ANXA10. In vivo experiments verified that lncRNA DLX6-AS1 promoted the progression of HCC through the miR-513c/Cul4A/ANXA10 axis. Thus, the silencing of lncRNA DLX6-AS1 impaired miR-513c-dependent Cul4A inhibition and subsequently elevated ubiquitination-mediated degradation of ANXA10, thereby preventing the occurrence and development of HCC.


Subject(s)
Annexins/metabolism , Carcinoma, Hepatocellular/pathology , Cullin Proteins/metabolism , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Adult , Aged , Animals , Annexins/genetics , Apoptosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Proliferation , Cullin Proteins/genetics , Female , Homeodomain Proteins/genetics , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Prognosis , RNA, Antisense/genetics , Survival Rate , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
15.
Phytomedicine ; 59: 152782, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31005808

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Swertia bimaculata (Sieb. et Zucc.) Hook. Thoms.ex Clarke, a glabrous or procumbent perennial herb, is a traditional herb medicine. Swertiamarin, a secoiridoid glycoside, is a representative ingredient in this medical plant crude extract and shows antidiabetic and antihyperlipidaemic activities and protective effect against hepatic injury. PURPOSE: The present study aimed to determine whether swertiamarin can attenuate NAFLD in fructose-fed mice. METHODS: Healthy male mice freely drank water containing 10% fructose for 12 consecutive weeks, whereas animals in those swertiamarin tested groups received different doses of swertiamarin (25, 50 and 100 mg/kg) by intragastric administration once a day from the ninth week to the twelfth week. RESULTS: At the end of the experiment, fructose-fed mice administrated with swertiamarin showed low levels of serum glucose, triglycerides, uric acid, alanine aminotransferase and aspartate transaminase. Histological examinations suggested the alleviation of hepatic ballooning degeneration and steatosis by swertiamarin treatment. Moreover, swertiamarin administration mitigated hepatic oxidative stress along with decreases of hepatic pro-inflammation cytokines, which was associated with decrease of hepatic xanthine oxidase (XO) activity and enhancements of anti-oxidant defense system enzymes, as well as activation of nuclear factor E2-related factor 2 (Nrf2) in fructose-fed mice. In addition, swertiamarin down-regulated expression of sterol-regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1) in liver of fructose-fed mice. CONCLUSION: The present study demonstrates that swertiamarin alleviates NAFLD and metabolic alterations in fructose-fed mice.


Subject(s)
Fructose/adverse effects , Iridoid Glucosides/pharmacology , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Pyrones/pharmacology , Acetyl-CoA Carboxylase/metabolism , Alanine Transaminase/metabolism , Animals , Cytokines/metabolism , Fatty Acid Synthases/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Mice , NF-E2-Related Factor 2/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Oxidative Stress/drug effects , Sterol Regulatory Element Binding Protein 1/metabolism , Triglycerides/blood , Triglycerides/metabolism , Xanthine Oxidase/metabolism
16.
Int J Mol Sci ; 19(10)2018 Oct 17.
Article in English | MEDLINE | ID: mdl-30336596

ABSTRACT

Senna and its main components sennosides are well-known effective laxative drugs and are used in the treatment of intestinal constipation in the world. Their potential side effects have attracted more attention in clinics but have little scientific justification. In this study, senna extract (SE), sennosides (SS), and sennoside A (SA) were prepared and used to generate diarrhea rats. The diarrhea rats were investigated with behaviors, clinical signs, organ index, pathological examination, and gene expression on multiple aquaporins (Aqps) including Aqp1, Aqp2, Aqp3, Aqp4, Aqp5, Aqp6, Aqp7, Aqp8, Aqp9, and Aqp11. Using qRT-PCR, the Aqp expression profiles were constructed for six organs including colon, kidney, liver, spleen, lung, and stomach. The Aqp alteration profiles were characterized and was performed with Principle Component Analysis (PCA). The SE treatments on the rats resulted in a significant body weight loss (p < 0.001), significant increases (p < 0.001) on the kidney index (27.72%) and liver index (42.55%), and distinguished changes with up-regulation on Aqps expressions in the kidneys and livers. The SS treatments showed prominent laxative actions and down regulation on Aqps expression in the colons. The study results indicated that the SE had more influence/toxicity on the kidneys and livers. The SS showed more powerful actions on the colons. We suggest that the caution should be particularly exercised in the patients with kidney and liver diseases when chronic using senna-based products.


Subject(s)
Aquaporins/genetics , Diarrhea/chemically induced , Gene Expression Profiling , Senna Extract/adverse effects , Animals , Aquaporins/metabolism , Colon/parasitology , Diarrhea/genetics , Diarrhea/pathology , Gene Expression Regulation , Hypoxanthine Phosphoribosyltransferase/genetics , Hypoxanthine Phosphoribosyltransferase/metabolism , Organ Specificity , Principal Component Analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Sennosides , Weight Loss/drug effects
17.
Nat Commun ; 9(1): 2911, 2018 07 25.
Article in English | MEDLINE | ID: mdl-30046062

ABSTRACT

Upon mechanical loading, granular materials yield and undergo plastic deformation. The nature of plastic deformation is essential for the development of the macroscopic constitutive models and the understanding of shear band formation. However, we still do not fully understand the microscopic nature of plastic deformation in disordered granular materials. Here we used synchrotron X-ray tomography technique to track the structural evolutions of three-dimensional granular materials under shear. We establish that highly distorted coplanar tetrahedra are the structural defects responsible for microscopic plasticity in disordered granular packings. The elementary plastic events occur through flip events which correspond to a neighbor switching process among these coplanar tetrahedra (or equivalently as the rotation motion of 4-ring disclinations). These events are discrete in space and possess specific orientations with the principal stress direction.

18.
Phys Rev Lett ; 121(1): 018002, 2018 Jul 06.
Article in English | MEDLINE | ID: mdl-30028176

ABSTRACT

We use x-ray tomography to investigate the translational and rotational dynamical heterogeneities of a three dimensional hard ellipsoid granular packing driven by oscillatory shear. We find that particles which translate quickly form clusters with a size distribution given by a power law with an exponent that is independent of the strain amplitude. Identical behavior is found for particles that are translating slowly, rotating quickly, or rotating slowly. The geometrical properties of these four different types of clusters are the same as those of random clusters. Different cluster types are considerably correlated or anticorrelated, indicating a significant coupling between translational and rotational degrees of freedom. Surprisingly, these clusters are formed already at time scales that are much shorter than the α-relaxation time, in stark contrast to the behavior found in glass-forming systems.

19.
Nature ; 551(7680): 360-363, 2017 11 16.
Article in English | MEDLINE | ID: mdl-29088704

ABSTRACT

Granular materials such as sand, powders and foams are ubiquitous in daily life and in industrial and geotechnical applications. These disordered systems form stable structures when unperturbed, but in the presence of external influences such as tapping or shear they 'relax', becoming fluid in nature. It is often assumed that the relaxation dynamics of granular systems is similar to that of thermal glass-forming systems. However, so far it has not been possible to determine experimentally the dynamic properties of three-dimensional granular systems at the particle level. This lack of experimental data, combined with the fact that the motion of granular particles involves friction (whereas the motion of particles in thermal glass-forming systems does not), means that an accurate description of the relaxation dynamics of granular materials is lacking. Here we use X-ray tomography to determine the microscale relaxation dynamics of hard granular ellipsoids subject to an oscillatory shear. We find that the distribution of the displacements of the ellipsoids is well described by a Gumbel law (which is similar to a Gaussian distribution for small displacements but has a heavier tail for larger displacements), with a shape parameter that is independent of the amplitude of the shear strain and of the time. Despite this universality, the mean squared displacement of an individual ellipsoid follows a power law as a function of time, with an exponent that does depend on the strain amplitude and time. We argue that these results are related to microscale relaxation mechanisms that involve friction and memory effects (whereby the motion of an ellipsoid at a given point in time depends on its previous motion). Our observations demonstrate that, at the particle level, the dynamic behaviour of granular systems is qualitatively different from that of thermal glass-forming systems, and is instead more similar to that of complex fluids. We conclude that granular materials can relax even when the driving strain is weak.

20.
Phys Rev Lett ; 118(23): 238002, 2017 Jun 09.
Article in English | MEDLINE | ID: mdl-28644675

ABSTRACT

Recent diffraction experiments on metallic glasses have unveiled an unexpected noncubic scaling law between density and average interatomic distance, which led to the speculation of the presence of fractal glass order. Using x-ray tomography we identify here a similar noncubic scaling law in disordered granular packing of spherical particles. We find that the scaling law is directly related to the contact neighbors within the first nearest neighbor shell, and, therefore, is closely connected to the phenomenon of jamming. The seemingly universal scaling exponent around 2.5 arises due to the isostatic condition with a contact number around 6, and we argue that the exponent should not be universal.

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