ABSTRACT
The adipose-derived stem cells (ASCs) are a valuable resource for regenerative medicine and essential materials for research in fat deposition. However, the isolation procedure of ASCs has not been standardized and needs to be harmonized; differences in proliferation and adipogenic differentiation of ASCs obtained from different fat depots have not been well characterized. In the present study, we compared the efficiency of ASCs isolation by enzymatic treatment and explant culture methods and the proliferation ability and adipogenic differentiation potential of ASCs isolated from subcutaneous and visceral fat depots. The explant culture method was simple and with no need for expensive enzymes while the enzymatic treatment method was complex, time consuming and costly. By the explant culture method, a larger number of ASCs were isolated from subcutaneous and visceral fat depots. By contrast, fewer ASCs were obtained by the enzymatic treatment method, especially from visceral adipose. ASCs isolated by the explant culture method performed well in cell proliferation and adipogenic differentiation, though they were slightly lower than those by the enzymatic treatment method. ASCs isolated from visceral depot demonstrated higher proliferation ability and adipogenic differentiation potential. In total, the explant culture method is simpler, more efficient, and lower cost than the enzymatic treatment method for ASCs isolation; compared with visceral adipose, subcutaneous adipose is easier to isolate ASCs; however, the visceral ASCs are superior to subcutaneous ASCs in proliferation and adipogenic differentiation.
Subject(s)
Adipogenesis , Subcutaneous Fat , Animals , Cattle , Cell Differentiation , Stem Cells , Cell Proliferation , Adipose Tissue , Cells, CulturedABSTRACT
BACKGROUND: Abnormal platelet activation is a key factor in the occurrence and development of thrombotic diseases. However, the physiological mechanisms that underlie platelet homeostasis remain unclear. Oleic acid, one of the most abundant lipids in the human diet, has potential antithrombotic effects. This study aimed to investigate the effects of oleic acid on platelet activation and thrombosis. METHODS: Platelet aggregation, ATP release, and fibrinogen spread were evaluated to determine the role of oleic acid in platelet activation. A ferric chloride-induced carotid injury model was used to establish the effect of oleic acid on thrombus formation in vivo. Western blotting analysis and transfection experiments were performed to determine the mechanisms involved in this process. RESULTS: Oleic acid inhibited platelet aggregation, granule release, and calcium mobilization. Furthermore, it inhibited the spread of platelets on fibrinogen. We also found that oleic acid delayed arterial thrombosis in mice, as demonstrated in a murine model of ferric chloride-induced carotid artery thrombosis. The molecular mechanism of its inhibition of platelet activity may be through the Syk-PLCγ2 and CaMKKß/AMPKα/VASP pathways. In addition, we demonstrated that the phosphorylation of AMPK at Ser496 was an important mechanism of platelet activation. CONCLUSIONS: Our study showed that oleic acid inhibits platelet activation and reduces thrombogenesis by inhibiting the phosphorylation of multiple signaling molecules, offering new insights into the research and development of antiplatelet drugs. Video Abstract.
Subject(s)
Oleic Acid , Thrombosis , Humans , Mice , Animals , Oleic Acid/pharmacology , Oleic Acid/metabolism , Platelet Activation , Blood Platelets , Thrombosis/metabolism , Phosphorylation , Collagen/metabolism , Fibrinogen/metabolism , Fibrinogen/pharmacologyABSTRACT
Intramuscular fat (IMF) content is one of the most significant factors influencing beef quality in terms of tenderness, flavor, and juiciness. Thus, internal factors affecting IMF deposition have received considerable attention for decades. In this study, we demonstrated a long non-coding RNA, lnc210, promoted adipogenic differentiation of buffalo intramuscular adipocytes. lnc210 was rich in adipose tissue and showed increased expression with the adipogenic differentiation of buffalo intramuscular adipocytes. lnc210 was mainly expressed in the nucleus of adipocytes. Full-length lnc210 was obtained by rapid amplification of cDNA ends technology. lnc210 overexpression promoted lipid accumulation by upregulating the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) and CCAAT enhancer binding protein alpha (C/EBPα) in buffalo intramuscular adipocytes. These results provide a basis for an in-depth analysis of the role of lnc210 in accelerating IMF deposition in buffaloes.
Subject(s)
Buffaloes , RNA, Long Noncoding , Cattle , Animals , Buffaloes/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Adipocytes/physiology , Adipogenesis/genetics , Adipose Tissue , Cell Differentiation/geneticsABSTRACT
Fat deposition is a significant economic trait in livestock animals. Adipose tissues (ATs) developed in subcutaneous and visceral depots are considered waste whereas those within muscle are highly valued. In river buffaloes, lipogenesis is highly active in subcutaneous (especially in the sternum subcutaneous) and visceral depots but not in muscle tissue. Revealing the features and functions of ATs in different depots is significant for the regulation of their development. Here, we characterize the cell size, composition, and function of six AT depots in river buffaloes. Our data support that the subcutaneous AT depots have a larger cell size than visceral AT depots, and the subcutaneous AT depots, especially the sternum subcutaneous AT, are mainly associated with the extracellular matrix whereas the visceral AT depots are mainly associated with immunity. We found that sternum subcutaneous AT is significantly different from ATs in other depots, due to the high unsaturated fatty acid content and the significant association with metabolic protection. The perirenal AT is more active in FA oxidation for energy supply. In addition, the expression of HOX paralogs supports the variable origins of ATs in different depots, indicating that the development of ATs in different depots is mediated by their progenitor cells. The present study enhances our understanding of the cellular and molecular features, metabolism, and origin of AT depots in buffaloes, which is significant for the regulation of fat deposition and provides new insights into the features of AT depots in multiple discrete locations.
Subject(s)
Buffaloes , Subcutaneous Fat , Animals , Subcutaneous Fat/metabolism , Rivers , Obesity/metabolism , Adipose Tissue/metabolism , Intra-Abdominal Fat/metabolismABSTRACT
Atherosclerosis, which is characterized by chronic inflammation in the arterial wall, is driven by immune cells and cytokines. Recent evidence indicated that interleukin (IL)-27 showed pleiotropic properties in immune diseases. However, precise mechanisms of IL-27, especially in atherosclerosis remains unknown. In our research, we examined the influence of the administration of IL-27 and an anti-IL-27p28 antibody (anti-IL-27p28-Ab) on both the initiation and the progression of atherosclerosis. In the groups (both the initiation and the progression) receiving recombinant IL-27 administration, the formation of atherosclerotic plaques was suspended, and the percentage of regulatory T cells (LAP+ or Foxp3+) in the spleen and peripheral blood was increased. Meanwhile, the number of T helper 1 (Th1) and T helper 17 (Th17) cells was decreased. In the peripheral blood plasma, TGF-ß and IL-10 expression were increased, while the levels of IFN-γ and IL-17 were reduced. As for lesions, the mRNA expression of Foxp3, TGF-ß, and IL-10 was increased, while that of IFN-γ and IL-17 was reduced. In the anti-IL-27p28 antibody groups, we obtained opposite results. We also observed that DCs treated with IL-27 display a tolerogenic phenotype and that IL-27-treated tolerogenic DCs (tDCs) are likely to play a protective role during atherosclerosis. Our study indicates that IL-27 or adoptive transfer of IL-27 loaded tDCs may be a new therapeutic approach in atherosclerosis.
Subject(s)
Atherosclerosis , Interleukin-27 , Mice , Animals , T-Lymphocytes, Regulatory/metabolism , Interleukin-10/metabolism , Interleukin-27/metabolism , Interleukin-17/metabolism , Apolipoproteins E/genetics , Atherosclerosis/drug therapy , Interleukins/metabolism , Transforming Growth Factor beta/metabolism , Immunologic Factors/therapeutic use , Forkhead Transcription Factors/metabolism , Dendritic Cells/metabolismABSTRACT
Real-time quantitative PCR (RT-qPCR) is widely used to measure and evaluate gene expression. The precision and reliability of RT-qPCR are critically dependent on the selection of suitable reference genes (RGs). In this study, an effort was made to identify the optimal RGs for RT-qPCR analysis of adipose and the longissimus dorsi muscle (LM) in buffaloes. RNA sequencing data were firstly analyzed to obtain 10 candidate genes (FKBP1A, C25H16orf72, PNRC2, IQGAP1, ATP5PD, RPL6, NDUFB4, TRA2A, CAPRIN1, and METAP2) that with high and stable expression across adipose tissues. Four other identified RGs (GAPDH, ACTB, TOP2B, and UXT) were selected as well. The expression stability of the candidate RGs was evaluated by three algorithms (geNorm, NormFinder, and BestKeeper) and then further validated by adipocyte and myocyte markers. Our results showed that UXT and TOP2B were the optimal RGs for RT-qPCR analysis across adipose tissues in buffaloes; three RGs, RPL6, UXT, and TOP2B, were the optimal RGs for RT-qPCR analysis across adipose and the LM tissues in buffaloes. This study provides significant information for improving the accuracy of gene expression in research on intramuscular fat deposition in buffaloes.
Subject(s)
Adipose Tissue , Buffaloes , Adipose Tissue/metabolism , Animals , Buffaloes/genetics , Gene Expression Profiling/veterinary , Muscle, Skeletal/metabolism , Real-Time Polymerase Chain Reaction/methods , Real-Time Polymerase Chain Reaction/veterinary , Reproducibility of ResultsABSTRACT
Lipid accumulation in mammals has been widely studied for decades due to its significant association with obesity in humans and meat quality in livestock animals. Fatty acid transport 1 (FATP1) is an evolutionarily conserved protein that localizes to the plasma membrane to enhance the transportation of fatty acids (FAs). In line with this function, FATP1 is involved in the metabolism of FAs, including their esterification and oxidation. In addition, the expression of FATP1 can be regulated by several energy-related factors, such as insulin and PPAR activators and transcription factors. These events connect FATP1 with cellular lipid accumulation. Recently, several studies have suggested that FATP1 acts as a facilitator in cellular lipid accumulation, whereas others hold a contrary view. Here, we will review these data and probe the possibility that FATP1 acts as a regulator in lipid accumulation, which will provide effective information for studies on the relationship between FATP1 and obesity in humans and meat quality in livestock animals.
Subject(s)
Fatty Acid Transport Proteins/metabolism , Fatty Acids/metabolism , Lipid Metabolism , Livestock/metabolism , Animals , HumansABSTRACT
Water contamination by mercury ions (Hg2+) causes irreversible and serious effect on the ambient environment, ecological systems, and human health, necessitating further improvement of Hg2+ monitoring at low concentrations. Here, we proposed a novel surface plasmon resonance (SPR) sensor for Hg2+ detection with desirable advantages of high sensitivity, simple operation, label-free, and low cost, in which the chitosan/poly (vinyl alcohol)/SnO2 composite film was modified on sensing surface as the active layer for sensitivity enhancement. Benefiting from the relatively high refractive index of SnO2 nanoparticles, the evanescent field generated at the metal-solution interface can be significantly enhanced, which results in a 5 times improvement of sensitivity. Through appropriate optimization in the aspects of componential constitutions, the sensor exhibits excellent sensitivity of 25.713 nm/µg/L and ultra-low calculated detection limit of 6.61 ng/L(32.95 pM). Such detection limit is strikingly lower than the limitation (10 nM) in drinking water set by the US Environmental Protection Agency. In addition, the as-prepared sensor presents relatively high selectivity for Hg2+, attributing to plenty of binding sites for specific adsorption produced by functionalized chitosan/poly (vinyl alcohol) composites, which have been furtherly verified by characterization of FTIR and XPS spectra. The proposed sensor also exhibits great repeatability and good time stability for 15 days. This work provides a promising strategy for developing high-performance SPR sensor for Hg2+ detection and a prospective application in environmental monitoring.
ABSTRACT
Excessive immune-mediated inflammatory reaction plays a deleterious role in ventricular remodelling after myocardial infarction (MI). Interleukin (IL)-38 is a newly characterized cytokine of the IL-1 family and has been reported to exert a protective effect in some autoimmune diseases. However, its role in cardiac remodelling post-MI remains unknown. In this study, we found that the expression of IL-38 was increased in infarcted heart after MI induced in C57BL/6 mice by permanent ligation of the left anterior descending artery. In addition, our data showed that ventricular remodelling after MI was significantly ameliorated after recombinant IL-38 injection in mice. This amelioration was demonstrated by better cardiac function, restricted inflammatory response, attenuated myocardial injury and decreased myocardial fibrosis. Our results in vitro revealed that IL-38 affects the phenotype of dendritic cells (DCs) and IL-38 plus troponin I (TNI)-treated tolerogenic DCs dampened adaptive immune response when co-cultured with CD4+ T cells. In conclusion, IL-38 plays a protective effect in ventricular remodelling post-MI, one possibility by influencing DCs to attenuate inflammatory response. Therefore, targeting IL-38 may hold a new therapeutic potential in treating MI.
Subject(s)
Interleukin-1/metabolism , Myocardial Infarction/physiopathology , Ventricular Remodeling , Animals , Apoptosis/drug effects , Dendritic Cells/drug effects , Dendritic Cells/immunology , Fibrosis , Immune Tolerance/drug effects , Inflammation/pathology , Interleukin-1/genetics , Interleukin-1/pharmacology , Male , Mice, Inbred C57BL , Myocardial Infarction/genetics , Myocardial Infarction/immunology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Phenotype , RNA, Messenger/genetics , RNA, Messenger/metabolism , Survival Analysis , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Troponin I/metabolism , Ventricular Remodeling/drug effectsABSTRACT
BACKGROUND: In China, although buffaloes are abundant, beef is mainly obtained from cattle, and this preference is mainly attributed to the low intramuscular fat (IMF) content of buffalo. Genetic factors are an important driver that affects IMF deposition. RESULTS: To reveal the intrinsic factors responsible for the low IMF content of buffalo, mRNA expression patterns in muscle and adipose tissue between buffalo and cattle were characterized by RNA sequencing analysis. The IMF content in Nanyang cattle was higher than that in Xinyang buffalo. A total of 1566 mRNAs expressed in adipose tissue showed differential expression between the longissimus dorsi muscles of buffalo and cattle. Functional annotation suggested a difference in the glycolysis/gluconeogenesis pathway between the two species. The results of RT-qPCR analysis and gain-of-function experiments confirmed the positive association between the IMF content and phosphoenolpyruvate carboxykinase 1 (PCK1) expression in buffalo. In both mouse C2C12 cells and cultured bovine myocytes, the activity of the PCK1 promoter in buffalo is lower than that in cattle. However, in mouse 3T3-L1 adipocytes and cultured bovine adipocytes, the activity of PCK1 in buffalo promoter is higher than that in cattle. CONCLUSIONS: These results indicate the important role of PCK1 in buffalo IMF deposition and illustrate the differences between buffalo and cattle promoter activity that drive PCK1 expression. This research helps to establish a foundation for further studies investigating IMF deposition in buffalo.
Subject(s)
Adipose Tissue , Buffaloes , Phosphoenolpyruvate Carboxykinase (GTP) , Transcriptome , Adipose Tissue/metabolism , Animals , Buffaloes/genetics , Cattle , Cells, Cultured , China , Gene Expression Profiling , Mice , Muscle, Skeletal/metabolism , Phosphoenolpyruvate Carboxykinase (GTP)/geneticsABSTRACT
Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) play an important role in the regulation of the immune system and inflammatory responses; however, their role in acute liver failure (ALF) and related pathological conditions is unclear. In this study, we found that hUCMSC-EXOs can reduce the expression of the NLRP3 inflammasome and downstream inflammatory factors in acute liver failure. Western blot and ELISA results showed that hUCMSC-EXOs decreased the expression of NLRP3, caspase-1, IL-1ß and IL-6 in LPS-stimulated RAW 264.7 macrophages. In vivo, the hUCMSC-EXOs repaired damaged liver tissue and decreased the expression of the NLRP3 inflammasome and the levels of ALT and AST in a mouse ALF model. The results of this study provide a new strategy for the application of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of ALF.
Subject(s)
Exosomes/transplantation , Inflammasomes/metabolism , Liver Failure, Acute/metabolism , Liver Failure, Acute/therapy , Macrophages/metabolism , Mesenchymal Stem Cells/cytology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Umbilical Cord/cytology , Animals , Disease Models, Animal , Humans , Infant, Newborn , Lipopolysaccharides , Male , Mice , Mice, Inbred C57BL , RAW 264.7 CellsABSTRACT
BACKGROUND: Interleukin-37 (IL-37) acts as an inhibitor of innate and adaptive immunity. However, the exact role of IL-37 in the patients with acute coronary syndrome (ACS) remains to be elucidated. METHODS: Patients were classified into 4 groups: normal coronary artery (NCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). The circulating Treg, Th1, and Th17 frequencies were measured. The effect of IL-37 on stimulated peripheral blood mononuclear cells (PBMCs) and the influence of IL-37 on DCs were explored. In addition, the role of IL-37-treated tDCs on Treg cell expansion and the stability of these tDCs were also tested. RESULTS: Our results showed that the circulating Treg frequencies were decreased, while Th1 and Th17 frequencies were increased in ACS patients, and that IL-37 expanded Tregs but suppressed Th1 and Th17 cells in activated PBMCs derived from ACS patients. Of note, IL-37-treated human DCs obtained a tolerogenic phenotype, and such tDCs promoted expansion of Tregs and decreased the Th1 and Th17 populations when cocultured with CD4+ T cells. Interestingly, IL-37-treated DCs from patients with ACS are phenotypically and functionally comparable to IL-37-treated DCs from NCA patients, and tolerogenic properties of IL-37-treated DCs were highly stable. CONCLUSION: In conclusion, our results reveal a beneficial role of IL-37 in the patients with ACS and suggest that autologous IL-37-treated tDCs may be a novel therapeutic strategy for the patients with ACS.
Subject(s)
Acute Coronary Syndrome/metabolism , Interleukin-1/pharmacology , Angina, Stable/metabolism , Angina, Unstable/metabolism , CD4-Positive T-Lymphocytes/metabolism , Cells, Cultured , Flow Cytometry , Humans , Interleukin-17/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , T-Lymphocytes, Regulatory/metabolism , Th17 Cells/metabolismABSTRACT
Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4+ T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4+ CD25+ GARP+ regulatory T (Treg) cells in DCM. Forty-five DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral T helper type 1 (Th1) and Th17 number and their related cytokines [interferon-γ (IFN-γ), interleukin (IL-17)], and an obvious decrease in Treg number, transforming growth factor-ß1 (TGF-ß1 ) levels and the expression of forkhead box P3 (FOXP3) and GARP in patients with DCM compared with controls. In addition, the suppressive function of CD4+ CD25+ GARP+ Treg cells was impaired in DCM patients upon T-cell receptor stimulation detected using CFSE dye. Lower level of TGF-ß1 and higher levels of IFN-γ and IL-17 detected using ELISA were found in supernatants of the cultured CD4+ CD25+ GARP+ Treg cells in DCM patients compared with controls. Together, our results indicate that CD4+ CD25+ GARP+ Treg cells are defective in DCM patients and GARP seems to be a better molecular definition of the regulatory phenotype. Therefore, it might be an attractive stategy to pay more attention to GARP in DCM patients.
Subject(s)
Adaptive Immunity , Cardiomyopathy, Dilated/immunology , Cell Proliferation , Interleukin-2 Receptor alpha Subunit/immunology , Lymphocyte Activation , Membrane Proteins/immunology , T-Lymphocytes, Regulatory/immunology , Adult , CD4 Lymphocyte Count , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/metabolism , Case-Control Studies , Cell Communication , Cells, Cultured , Coculture Techniques , Cytokines/immunology , Cytokines/metabolism , Female , Forkhead Transcription Factors/immunology , Forkhead Transcription Factors/metabolism , Humans , Interleukin-2 Receptor alpha Subunit/metabolism , Male , Membrane Proteins/metabolism , Middle Aged , Phenotype , Signal Transduction , T-Lymphocytes, Regulatory/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Transforming Growth Factor beta1/immunology , Transforming Growth Factor beta1/metabolismABSTRACT
BACKGROUND: Accumulating evidence shows that the pathological autoreactive immune response is responsible for plaque rupture and the subsequent onset of acute coronary syndrome (ACS). Naturally occurring CD4(+)CD25(+)regulatory T cells (nTregs) are indispensable in suppressing the pathological autoreactive immune response and maintaining immune homeostasis. However, the number and the suppressive function of glycoprotein-A repetitions predominant (GARP) (+) CD4(+) CD25(+) activated nTregs were impaired in patients with ACS. Recent evidence suggests that heme oxygenase-1 (HO-1) can regulate the adaptive immune response by promoting the expression of Foxp3. We therefore hypothesized that HO-1 may enhance the function of GARP(+) CD4(+) CD25(+)Tregs in patients with ACS and thus regulate immune imbalance. METHODS: T lymphocytes were isolated from healthy volunteers (control, n=30) and patients with stable angina (SA, n=40) or ACS (n=51). Half of these cells were treated with an HO-1 inducer (hemin) for 48 h, and the other half were incubated with complete RPMI-1640 medium. The frequencies of T-helper 1 (Th1), Th2, Th17 and latency-associated peptide (LAP) (+)CD4(+) T cells and the expression of Foxp3 and GARP by CD4(+)CD25(+)T cells were then assessed by measuring flow cytometry after stimulation in vitro. The suppressive function of activated Tregs was measured by thymidine uptake. The levels of transforming growth factor-1 (TGF-ß1) in the plasma were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of the genes encoding these proteins were analyzed by real-time polymerase chain reaction. RESULTS: Patients with ACS exhibited an impaired number and suppressive function of GARP(+) CD4(+) CD25(+)Tregs and a mixed Th1/Th17-dominant T cell response when compared with the SA and control groups. The expression of LAP in T cells was also lower in patients with ACS compared to patients with SA and the control individuals. Treatment with an HO-1 inducer enhanced the biological activity of GARP(+) CD4(+) CD25(+)Tregs and resulted in increased expression of LAP and GARP by activated T cells. CONCLUSIONS: The reduced number and impaired suppressive function of GARP(+) CD4(+) CD25(+)Tregs result in excess effector T cell proliferation, leading to plaque instability and the onset of ACS. HO-1 can effectively restore impaired GARP(+) CD4(+) CD25(+)Tregs from patients with ACS by promoting LAP and GARP expression on activated T cells.
Subject(s)
Acute Coronary Syndrome/immunology , Angina, Stable/immunology , Heme Oxygenase-1/metabolism , T-Lymphocytes, Regulatory/immunology , Transforming Growth Factor beta1/metabolism , Cells, Cultured , Female , Forkhead Transcription Factors/metabolism , Hemin , Humans , Lymphocyte Activation , Male , Membrane Proteins/metabolism , Middle Aged , T-Lymphocytes, Regulatory/cytology , Up-RegulationABSTRACT
BACKGROUND: Recently, several studies suggest that galectin-9 (Gal-9) might play a pivotal role in the pathogenesis of autoimmune diseases. However, the exact role of Gal-9 in atherosclerosis remains to be elucidated. METHODS: Serum Gal-9, high-sensitivity C-reactive protein (hs-CRP), interferon- (IFN-) γ, interleukin- (IL-) 4, IL-17, and transforming growth factor- (TGF-) ß1 were measured. The effect of Gal-9 on peripheral blood mononuclear cells (PBMC) was investigated in patients with normal coronary artery (NCA). RESULTS: The lowest level of Gal-9 was found in the ST-segment elevation myocardial infarction (STEMI) group, followed by the non-ST-segment elevation ACS (NSTEACS), the NCA, and the stable angina pectoris (SAP) groups, respectively. Additionally, Gal-9 was found to be independently associated with hs-CRP, lipoprotein(a), and creatinine. Notably, Gal-9 was also noted to be an independent predictor of the Gensini score. Moreover, Gal-9 suppressed T-helper 17 (Th17) and expanded regulatory T cells (Tregs), resulting in decreased IL-17 production and increased secretion of TGF-ß1. CONCLUSIONS: Serum Gal-9 is associated with not only coronary artery disease (CAD), but also the severity of coronary arteries stenosis. Gal-9 can expand Tregs and suppress Th17 development in activated PBMC, implying that Gal-9 has the potential to dampen the development of atherosclerosis and may be a new therapy for CAD.
Subject(s)
Coronary Artery Disease/etiology , Galectins/blood , Adult , Aged , C-Reactive Protein/analysis , Coronary Artery Disease/blood , Cytokines/blood , Female , Humans , Male , Middle Aged , Regression AnalysisABSTRACT
Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-ß. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-ß in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE-/- mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-ß1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells.
Subject(s)
Atherosclerosis/drug therapy , Atherosclerosis/immunology , Atorvastatin/therapeutic use , Membrane Proteins/metabolism , Animals , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Apoptosis/drug effects , Atherosclerosis/metabolism , Blotting, Western , Cells, Cultured , Flow Cytometry , Immunohistochemistry , Male , Membrane Proteins/genetics , Mice , T-Lymphocytes, RegulatoryABSTRACT
Intensifying variability in precipitation under a changing climate is projected to amplify fluctuation in terrestrial hydrological cycle, leading to more severe water-related disasters. The connections between interannual variability of hydrological components and factors influencing these connections have not been clearly defined yet. Based on terrestrial water budget from Climate Data Record, we identify dominant factors influencing partitioning interannual variability of precipitation (P) into that of evapotranspiration (E), runoff (Q), and water storage deviation (ΔS) across the globe by employing geographical detector model (GDM). Sensitivities of the variability partitioning to dominant factors are quantified for different hydroclimate regions by linear regression model and law of total differential. Results show that dominant factors influencing precipitation variability partitioning (VP) are different across distinct hydroclimate conditions. Comparing the statistical index (q value) of the GDM, it can be seen that surface air temperature (Ta), snow water equivalent (SWE) and water storage capacity (Smax) are dominant factors of VP in humid, semi-arid and arid regions, respectively. Changes in P variability largely can transfer into Q variability in humid region. The P variability partitioned into Q variability is dramatically reduced in semi-arid region with SWE decreasing, while P variability partitioned into ΔS variability increases with Smax increasing in arid region. Joint effects of Ta and coefficient of variation of precipitation (Pcv) are found to be the most important interaction in determining VP across the globe. Furthermore, warmer temperatures in humid region cause >90 % of the change in precipitation variability to be transferred to Q variability change. In semi-arid region with snowfall, decreased SWE has strong effect on changes in ΔS (30-40 %) and Q (20-40 %) variability. Our findings imply a changing VP and more severe impacts of hydrological extremes under future climate, where intensive changes in Ta, SWE and land cover are projected.
ABSTRACT
Background: Patients with acute-on-chronic liver failure (ACLF) who take entecavir (ETV) and tenofovir disoproxil fumarate (TDF) experience a reduction in hepatic events and mortality. The effectiveness of tenofovir alafenamide (TAF) was not well investigated. This study was aim to compare the antiviral efficacy and mortality between TAF and ETV in patients with ACLF caused by the hepatitis B virus (HBV). Methods: One hundred and six patients with HBV-ACLF who received TAF (25 mg/day) and ETV (0.5 mg/day) for 12 weeks were analyzed. The primary endpoints were overall mortality and liver transplantation (LT) at week 12. Biochemical responses, virologic responses, mortality, drug safety, and side effects were evaluated. Results: At 4 and 12 weeks of TAF treatment, patients showed significantly higher HBV-DNA reduction (P < .001), higher HBV-DNA undetectability rates (P < .001), and lower HBV DNA levels (P < .001) in serum. Lower Child-Turcotte-Pugh (CTP) scores (P = .003) were observed at 4 weeks in the TAF group, although the CTP scores showed no difference between TAF group and ETV group at 12 weeks (P = 1.143). Lower alanine aminotransferase (ALT) levels of patients in the TAF group at week 4 and 12 were observed (P = .023 and P < .0001, separately). The mortality of TAF group was lower after 4 weeks of treatment (P = .038); however, the 2 groups had similar mortality rates at week 8 and 12. Among the causes of death in HBV-ACLF patients, we found the same incidence of liver-related problems in both groups (P > .05). Conclusions: This study showed that ACLF patients with chronic HBV infection treated with TAF had a rapid decline in HBV DNA, a higher rate of ALT reduction and improved CTP scores compared to the ETV group, thereby improving patient survival.
ABSTRACT
Listening to natural sounds, both live and recorded, in either a natural or built environment is considered natural sound exposure (NSE). Sound is closely related to daily life, and research on the restorative effects of natural sounds is expanding. However, there is a lack of quantitative and comprehensive analysis on the impact of NSE on health recovery. This study systematically reviewed and conducted a meta-analysis on the impact of NSE on health recovery. Fifteen studies (1285 participants) were selected for the meta-analysis out of the 1157 literatures about the recovery of the NSE, searched from the Web of Science and Science Direct. The results indicate that NSE has certain positive effects: (a) In terms of emotional changes, NSE significantly reduces anxiety as measured by both the Visual Analog Scale (VAS) -2.31 (95 % CI -2.83, -1.79) and the State Anxiety Inventory (SAI) -12.22 (95 % CI -22.46, -1.98). (b) In terms of physiological reaction, NSE resulted in reduced heart rate (HR) -5.46 (95 % CI -9.62, -1.31), systolic blood pressure (SBP) -11.74 (95 % CI -15.51, -7.97), diastolic blood pressure (DBP) -13.98 (95 % CI -24.96, -2.99) and respiratory rate (RR) -1.58 (95 % CI -3.06, -0.10). (c) While the potential for restoration of cognitive performance by NSE was found, no consistent conclusions have been reached yet. However, there was significant heterogeneity between studies, primarily attributed to variations in study populations and methodologies. Because of the limited literature, we did not conduct subgroup analysis and meta-regression analysis. It is recommended that future studies address this heterogeneity by including more and higher-quality literature and employing rigorous methodologies to establish a robust foundation for evidence-based medicine. This will be of great significance for the application natural sounds in landscape planning and medical rehabilitation environments, and has the potential to promote improvements in public health.
Subject(s)
Anxiety , Emotions , Sound , Humans , Public HealthABSTRACT
Circular RNAs (circRNA) are a kind of endogenous biological macromolecules that play significant roles in many biological processes, including adipogenesis, a precisely orchestrated process that is mediated by a large number of factors. Among them, peroxisome proliferator-activated receptor gamma (PPARG), is undoubtedly the most important regulator of adipocyte development in all types of adipose tissue. The formation of intramuscular fat (IMF), is a key factor that influences the meat quality in livestock animals. PPARG has been demonstrated to show a positive correlation with IMF deposition although the regulatory mechanism involved is not known. This study demonstrates that PPARG mediates IMF deposition by producing multiple exonic circRNAs (circPPARGs). Three circPPARGs promote adipogenic differentiation and inhibit the proliferation of intramuscular preadipocytes and these effects are conserved across several species including buffaloes, cattle and mice. Notably, circPPARG1 interacts with PPARG protein to inhibit the transcription of hormone sensitive lipase (HSL) involved in lipolysis. In addition, the positive effects of circPPARG1 on IMF deposition were identified in mice in vivo. Thus, PPARG drives IMF deposition, not only through the common transcription factor pathway, but also by producing circRNAs. This study provides new insights into our understanding of the regulatory mechanisms of PPARG in IMF deposition.