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1.
Zhen Ci Yan Jiu ; 49(6): 594-603, 2024 Jun 25.
Article in English, Chinese | MEDLINE | ID: mdl-38897803

ABSTRACT

OBJECTIVES: To observe the effect of electroacupuncture (EA) on behavior and hippocampal protein phosphorylation in rats with chronic fatigue syndrome (CFS), so as to explore its mechanisms underlying improvement of CFS. METHODS: Male SD rats were randomly divided into control, model and EA groups (n=12 rats in each group). The CFS model was established by chronic multifactor combined with stress stimulation (treadmill training + restraint stress + sleep disturbance + crowded environment). For rats of the EA group, EA (1 mA, frequency of 10 Hz) was applied to "Shenting" (GV24) (with an acupuncture needle penetrated from GV24 to "Baihui" ï¼»GV20ï¼½) and "Dazhui" (GV14) for 15 min, once daily for 28 days. After treatment, the body weight, food intake and water intake of rats in each group were observed. The fatigue degree of rats was evaluated by Semi-quantitative score observation table of the general condition of experimental rats.The open field test (OFT) was used to assess the rats'anxiety severity by detecting the total number of grid-crossing and the times of the central area entered in 5 min, and Morris water maze test was employed to assess the rats' learning-memory ability by detecting the escape latency in 1 min, and the times of the original platform quadrant crossing in 1 min. The hippocampaus was taken for phosphorylated Label-free quantitative proteomics analysis by using Maxquant technology based on full scan mode to calculate the integral of each peptide signal of liquid chromatography-mass spectrometry(LC-MS). The differentially-expressed proteins (>1.5 folds for up-regulation or <0.67 folds for down-regulation) were evaluated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: Compared with the control group, the body weight, food intake, and the times of original-platform quadrant crossing of spatial exploring of Morris water maze test were significantly decreased (P<0.01, P<0.05) , and the score of general conditions, times of grid-crossing and center area-entering of OFT, and the escape latency of navigation task were apparently increased (P<0.01) in rats of the model group. After EA intervention, the decreased original-platform quadrant crossing, and the increased score of general conditions, times of grid-crossing and the escape latency of navigation task were all reversed (P<0.01, P<0.05). Outcomes of proteomics analysis indicated that compared with the model group, there were 297 differentially expressed peptide (48 up-regulated and 249 down-regulated) segments in the control group, and there were 245 differentially expressed peptide (185 up-regulated and 60 down-regulated) segments in the EA group, in which, 25 overlapping peptide segments were reversed after EA treatment, corresponding to 24 proteins, mainly involving cytoskeletal structure. GO function annotation analysis showed that the top three differentially expressed phosphorylated proteins involved in the effect of EA intervention were the actin filament polymerization, protein depolymerization and cytoskeletal tissue in the biological process, the actin binding, structural molecular activity and cytoskeletal protein binding in the molecular function, and the cytoskeleton, dendrites and dendritic trees in the cellular component, respectively. The KEGG pathway annotation analysis for differentially expressed phosphorylated proteins showed that theinsulin secretion, axon guidance, phosphatidylinositol signaling system and lysine biosynthesis, etc. were involved in the effect of EA intervention. CONCLUSIONS: EA of GV24-GV20 and GV14 can improve the general state, anxiety and learning-memory ability of CFS model rats, which may be related to its functions in regulating the hippocampal protein phosphorylation level, and repairing the structure and function of synapses in hippocampus.


Subject(s)
Electroacupuncture , Fatigue Syndrome, Chronic , Hippocampus , Rats, Sprague-Dawley , Animals , Male , Rats , Hippocampus/metabolism , Fatigue Syndrome, Chronic/therapy , Fatigue Syndrome, Chronic/metabolism , Phosphorylation , Humans , Acupuncture Points , Disease Models, Animal
2.
Immun Inflamm Dis ; 12(6): e1321, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888451

ABSTRACT

BACKGROUND: For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the immunomodulatory capabilities of Succinate Coenzyme A ligase beta-like protein (SUCLA-ß) derived from Trichinella spiralis, a crucial excretory product of this parasite. OBJECTIVE: To explore the therapeutic potential of SUCLA-ß in alleviating and controlling ovalbumin (OVA)-induced allergic asthma, as well as its influence on host immune modulation. METHODS: In this research, we utilized the rTs-SUCLA-ß protein derived from T. spiralis to investigate its potential in mitigating airway inflammation in a murine model of asthma induced by OVA sensitization/stimulation, both pre- and post-challenge. The treatment's efficacy was assessed by quantifying the extent of inflammation in the lungs. RESULTS: Treatment with rTs-SUCLA-ß demonstrated efficacy in ameliorating OVA-induced airway inflammation, as evidenced by a reduction in eosinophil infiltration, levels of OVA-specific Immunoglobulin E, interferon-γ, interleukin (IL)-9, and IL-17A, along with an elevation in IL-10. The equilibrium between Th17 and Treg cells plays a pivotal role in modulating the abundance of inflammatory cells within the organism, thereby ameliorating inflammation and alleviating symptoms associated with allergic asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Our data revealed that T. spiralis-derived Ts-SUCLA-ß protein may inhibit the allergic airway inflammation by regulating host immune responses.


Subject(s)
Asthma , Helminth Proteins , Ovalbumin , Trichinella spiralis , Trichinella spiralis/immunology , Animals , Asthma/immunology , Asthma/drug therapy , Mice , Ovalbumin/immunology , Helminth Proteins/immunology , Helminth Proteins/pharmacology , Mice, Inbred BALB C , Disease Models, Animal , Female , Cytokines/metabolism , Cytokines/immunology , Immunoglobulin E/immunology , Lung/immunology , Lung/parasitology , Lung/pathology , T-Lymphocytes, Regulatory/immunology , Hypersensitivity/immunology , Hypersensitivity/drug therapy , Th17 Cells/immunology
3.
EBioMedicine ; 105: 105209, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38908099

ABSTRACT

BACKGROUND: Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. METHODS: This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. FINDINGS: Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%-10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%-49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%-95%) and 19% (95% CI: 11%-27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. INTERPRETATION: This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. FUNDING: This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the 'Pioneer' and 'Leading goose' R&D Program of Zhejiang.

4.
Food Sci Nutr ; 12(4): 2346-2363, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38628176

ABSTRACT

A safety evaluation was performed of Symbiota®, which is made by a proprietary anaerobic fermentation process of soybean with multistrains of probiotics and a yeast. The battery of genotoxicity studies showed that Symbiota® has no genotoxic effects. Safety and tolerability were further assessed by acute or repeated dose 28- and 90-day rodent studies, and no alterations in clinical observations, ophthalmological examination, blood chemistry, urinalysis, or hematology were observed between the control group and the different dosing groups (1.5, 5, and 15 mL/kg/day). There were no adverse effects on specific tissues or organs in terms of weight and histopathology. Importantly, the Symbiota® treatment did not perturb hormones and other endocrine-related endpoints. Of note, the No-Observed-Adverse-Effect-Level was determined to be 15 mL/kg/day in rats. Moreover, a randomized, double-blind, placebo-controlled clinical trial was recently conducted with healthy volunteers who consumed 8 mL/day of placebo or Symbiota® for 8 weeks. Only mild adverse events were reported in both groups, and the blood chemistry and blood cell profiles were also similar between the two groups. In summary, this study concluded that the oral consumption of Symbiota® at 8 mL/day by the general population does not pose any human health concerns.

5.
J Chem Phys ; 160(15)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38619457

ABSTRACT

In our recent publication, we have proposed a revised base excision repair pathway in which DNA polymerase ß (Polß) catalyzes Schiff base formation prior to the gap-filling DNA synthesis followed by ß-elimination. In addition, the polymerase activity of Polß employs the "three-metal ion mechanism" instead of the long-standing "two-metal ion mechanism" to catalyze phosphodiester bond formation based on the fact derived from time-resolved x-ray crystallography that a third Mg2+ was captured in the polymerase active site after the chemical reaction was initiated. In this study, we develop the models of the uncross-linked and cross-linked Polß complexes and investigate the "three-metal ion mechanism" vs the "two-metal ion mechanism" by using the quantum mechanics/molecular mechanics molecular dynamics simulations. Our results suggest that the presence of the third Mg2+ ion stabilizes the reaction-state structures, strengthens correct nucleotide binding, and accelerates phosphodiester bond formation. The improved understanding of Polß's catalytic mechanism provides valuable insights into DNA replication and damage repair.


Subject(s)
DNA Polymerase beta , Catalysis , DNA Replication , Magnesium , Molecular Dynamics Simulation , Biocatalysis
6.
Org Lett ; 26(15): 3235-3240, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38557113

ABSTRACT

Catalytic asymmetric 1,2-allylation of aurone-derived azadienes is very difficult to achieve due to the driving force for aromatization and the greater steric hindrance of 1,2-addition compared with 1,4-addition. By taking advantage of the ability of nitrogen ligated metal complexes, we successfully demonstrated the first example of copper-catalyzed 1,2-allylation of azadienes with allylboronates for the highly enantioselective synthesis of homoallylic amines. Meanwhile, the enantioenriched 1,4-addition products could also be obtained through a subsequent 3,3-sigmatropic rearrangement of the 1,2-addition products. Extensive DFT calculations were carried out to elucidate the origins of high regioselectivity (1,2- vs 1,4-) and enantioselectivity.

7.
Curr Med Sci ; 44(2): 333-345, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38622424

ABSTRACT

OBJECTIVE: Peritoneal fibrosis (PF) is the main cause of declining efficiency and ultrafiltration failure of the peritoneum, which restricts the long-term application of peritoneal dialysis (PD). This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes (BMSC-Exos) on PF in response to PD. METHODS: Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing. C57BL/6J mice were infused with 4.25% glucose-based peritoneal dialysis fluid (PDF) for 6 consecutive weeks to establish a PF model. A total of 36 mice were randomly divided into 6 groups: control group, 1.5% PDF group, 2.5% PDF group, 4.25% PDF group, BMSC-Exos treatment group, and BMSC-Exos+TP53 treatment group. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF. HE and Masson staining were performed to evaluate the extent of PF. The therapeutic potential of BMSC-Exos for PF was examined through pathological examination, RT-qPCR, Western blotting, and peritoneal function analyses. Epithelial-mesenchymal transition (EMT) of HMrSV5 was induced with 4.25% PDF. Cells were divided into control group, 4.25% PDF group, BMSC-Exos treatment group, and BMSC-Exos+TP53 treatment group. Cell Counting Kit-8 assay was used to measure cell viability, and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells. RESULTS: Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs. The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos, but decreased in PD mice. We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice. Compared with the control mice, the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of α-SMA, collagen-I, fibronectin, and ECM1. The mice with PD showed decreased miR-27a-3p. Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment, while PF and mesothelial damage were significantly ameliorated. Additionally, markers of fibrosis (α-SMA, collagen-I, fibronectin, ECM1) and profibrotic cytokines (TGF-ß1, PDGF) were downregulated at the mRNA and protein levels after BMSC-Exos treatment. In HMrSV5 cells, BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF. Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin (epithelial marker) and decreased expression of α-SMA, Snail, and vimentin (mesenchymal markers) compared to those of the 4.25% PDF-treated cells. Importantly, a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p. TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos. CONCLUSION: The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.


Subject(s)
Exosomes , MicroRNAs , Peritoneal Dialysis , Peritoneal Fibrosis , Mice , Animals , Peritoneal Fibrosis/genetics , Peritoneal Fibrosis/therapy , Fibronectins , Exosomes/metabolism , Mice, Inbred C57BL , Peritoneal Dialysis/adverse effects , MicroRNAs/genetics , MicroRNAs/metabolism , Glucose , Collagen
8.
Sci Rep ; 14(1): 5582, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38448540

ABSTRACT

This study presents a data-driven assisted real-time optimization model which is an innovative approach to address the challenges posed by integrating Submerged Arc Furnace (SAF) systems with renewable energy sources, specifically photovoltaic (PV) and wind power, with modern intelligent energy terminals. Specifically, the proposed method is divided into two stages. The first stage is related to data-driven prediction for addressing local time-varying renewable energy and electricity market prices with predicted information, and the second stage uses an optimization model for real-time SAF dispatch. Connections between intelligent energy terminals, demand-side devices, and load management systems are established to enhance local renewable resource utilization. Additionally, mathematical formulations of the operating resistance in SAF are explored, and deep neuron networks are employed and modified for dynamic uncertainty prediction. The proposed approach is validated through a case study involving an intelligent energy terminal with a 12.5 MVA SAF system and 12 MW capacity renewable generators in an electricity market with fluctuating prices. The findings of this research underscore the efficacy of the proposed optimization model in reducing operational costs and enhancing the utilization of localized renewable energy generation. By integrating four distinct dissatisfaction coefficients into the optimization framework, we demonstrate the model's adaptability and efficiency. The application of the optimization strategy delineated herein results in the SAF system's profitability oscillating between $111 and $416 across various time intervals, contingent upon the coefficient settings. Remarkably, an aggregate daily loss recovery amounting to $1,906.84 can be realized during the optimization period. Such outcomes not only signify considerable economic advantages but also contribute to grid stability and the diminution of renewable energy curtailment, thereby underscoring the dual benefits of economic efficiency and sustainability in energy management practices.

9.
World J Stem Cells ; 16(2): 176-190, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38455106

ABSTRACT

BACKGROUND: Cartilage defects are some of the most common causes of arthritis. Cartilage lesions caused by inflammation, trauma or degenerative disease normally result in osteochondral defects. Previous studies have shown that decellularized extracellular matrix (ECM) derived from autologous, allogenic, or xenogeneic mesenchymal stromal cells (MSCs) can effectively restore osteochondral integrity. AIM: To determine whether the decellularized ECM of antler reserve mesenchymal cells (RMCs), a xenogeneic material from antler stem cells, is superior to the currently available treatments for osteochondral defects. METHODS: We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70% confluence; 50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition. Decellularized sheets of adipocyte-derived MSCs (aMSCs) and antlerogenic periosteal cells (another type of antler stem cells) were used as the controls. Three weeks after ascorbic acid stimulation, the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints. RESULTS: The defects were successfully repaired by applying the ECM-sheets. The highest quality of repair was achieved in the RMC-ECM group both in vitro (including cell attachment and proliferation), and in vivo (including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues). Notably, the antler-stem-cell-derived ECM (xenogeneic) performed better than the aMSC-ECM (allogenic), while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells. CONCLUSION: Decellularized xenogeneic ECM derived from the antler stem cell, particularly the active form (RMC-ECM), can achieve high quality repair/reconstruction of osteochondral defects, suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

10.
Zhen Ci Yan Jiu ; 49(3): 274-282, 2024 Mar 25.
Article in English, Chinese | MEDLINE | ID: mdl-38500324

ABSTRACT

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.


Subject(s)
Electroacupuncture , Fatigue Syndrome, Chronic , Rats , Animals , Rats, Sprague-Dawley , Interleukin-10 , Fatigue Syndrome, Chronic/therapy , Interleukin-17/genetics , Transforming Growth Factor beta1/genetics , Hippocampus
11.
Food Sci Nutr ; 12(2): 1095-1104, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38370070

ABSTRACT

Three-spot seahorse (Hippocampus trimaculatus) has been consumed as traditional Chinese medicine in Asian society. This study was designed to analyze the bioactive compounds of the solvent extracts from cultured three-spot seahorse by high pressure liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI/MS/MS). Subsequently, their biological activities were evaluated and confirmed by cell modes and Western blot analysis. Experimental results indicated that taurine and arginine were the primary bioactive compounds identified and quantified without pre- or post-column derivatization within 20 min retention time. The analytical method was established and validated with intraday/interday RSD from 0.25% to 3.34% and with recovery from 87.8% to 91.2%. As compared to other extracts, water layer extract (WLE) contained the most taurine and arginine contents of 6.807 and 0.437 mg/g (dry basis), respectively. In the meanwhile, WLE also showed anti-inflammatory activity on LPS-induced NO production and inhibited the protein expression of TNF-α and COX-2 by Western blot analysis with better cell viability.

12.
Diabetes Metab J ; 48(2): 242-252, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38273790

ABSTRACT

BACKGRUOUND: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. METHODS: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. RESULTS: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. CONCLUSION: Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Diabetes Mellitus, Type 2/complications , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Cardiovascular Diseases/etiology , Glomerular Filtration Rate , Glucose/pharmacology , Sodium/pharmacology
13.
Glycobiology ; 34(1)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-37935390

ABSTRACT

GM1 is a major brain ganglioside that exerts neurotrophic, neuroprotective and antineuroinflammatory effects. The aim of this study was to obtain insights into the antineuroinflammatory mechanisms of exogenous GM1 in lipopolysaccharide (LPS)-stimulated MG6 mouse transformed microglial cell line. First, we found that GM1 prevented the LPS-induced transformation of microglia into an amoeboid-like shape. GM1 treatment inhibited LPS-induced expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), and proinflammatory cytokines such as TNF-α, IL-1ß and IL-6 in MG6 cells. In LPS-treated mice, GM1 also reduced striatal microglia activation and attenuated COX-2 expression. Subsequent mechanistic studies showed that GM1 suppressed LPS-induced nuclear translocation of nuclear factor κB (NF-κB) and activator protein-1 (AP-1), two critical transcription factors responsible for the production of proinflammatory mediators. GM1 exhibited antineuroinflammatory properties by suppressing Akt/NF-κB signaling and the activation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Furthermore, GM1 suppressed LPS-induced activation of transforming growth factor-ß-activated kinase 1 (TAK1) and NADPH oxidase 2 (NOX2), upstream regulators of the IκBα/NF-κB and MAPK/AP-1 signaling pathways. GM1 also inhibited NOX-mediated reactive oxygen species (ROS) production and protected against LPS-induced MG6 cell death, suggesting an antioxidant role of GM1. In conclusion, GM1 exerts both antineuroinflammatory and antioxidative effects by inhibiting Akt, TAK1 and NOX2 activation.


Subject(s)
Microglia , NF-kappa B , Mice , Animals , NF-kappa B/metabolism , Microglia/metabolism , G(M1) Ganglioside/metabolism , Lipopolysaccharides/toxicity , Lipopolysaccharides/metabolism , Proto-Oncogene Proteins c-akt/metabolism , NADPH Oxidases/metabolism , NADPH Oxidases/pharmacology , Transcription Factor AP-1/metabolism , Transcription Factor AP-1/pharmacology , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/metabolism , Phosphorylation , Oxidative Stress
14.
J Vasc Surg ; 79(6): 1510-1524, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38122857

ABSTRACT

BACKGROUND: At present, open surgical aortic arch repair (OAR) and debranching hybrid surgical aortic arch repair (HAR) serve as significant therapeutic approaches for aortic arch aneurysm or dissection. It remains unclear which technique is preferable. Our study aimed to compare the short-term and long-term outcomes of these two procedures. METHODS: To identify comparison studies of debranching HAR and OAR, a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from January 2002 to April 2022. This study was registered on PROSPERO (CRD42020218080). RESULTS: Sixteen publications (1316 patients), including six propensity score-matching (PSM) analysis papers, were included in this study. Compared with the HAR group, the patients who underwent OAR were younger (OAR vs HAR: 67.53 ± 12.81 vs 71.29 ± 11.0; P < .00001), had less coronary artery disease (OAR vs HAR: 22.45% vs 32.6%; P = .007), less chronic obstructive pulmonary disease (OAR vs HAR: 16.16% vs 23.92%; P = .001), lower rates of previous stroke (OAR vs HAR: 12.46% vs 18.02%; P = .05), and a lower EuroSCORE (European System for Cardiac Operative Risk Evaluation) score (OAR vs HAR: 6.27 ± 1.04 vs 6.9 ± 3.76; P < .00001). HAR was associated with less postoperative blood transfusion (OAR vs HAR: 12.23% vs 7.91%; P = .04), shorter length of intensive care unit stays (OAR vs HAR: 5.92 ± 7.58 days vs 4.02 ± 6.60 days; P < .00001) and hospital stays (OAR vs HAR: 21.59 ± 17.54 days vs 16.49 ± 18.45 days; P < .0001), lower incidence of reoperation for bleeding complications (OAR vs HAR: 8.07% vs 3.96%; P = .01), fewer postoperative pulmonary complication (OAR vs HAR: 14.75% vs 5.02%; P < .0001), and acute renal failure (OAR vs HAR: 7.54% vs 5.17%; P = .03). In the PSM subgroup, the rates of spinal cord ischemic (OAR vs HAR: 5.75% vs 11.49%; P = .02), stroke (OAR vs HAR: 5.1% vs 17.35%; P = .01), and permanent paraplegia (OAR vs HAR: 2.79% vs 6.08%; P = .006) were lower in the OAR group than that in the HAR group. Although there was no statistically significant difference in 1-year survival rates (HAR vs OAR: hazard ratio [HR]: 1.54; P = .10), the 3-year and 5-year survivals were significantly higher in the OAR group than that in the HAR group (HAR vs OAR: HR: 1.69; P = .01; HAR vs OAR: HR: 1.68; P = .01). In the PSM subgroup, the OAR group was also significantly superior to the HAR group in terms of 3-year and 5-year survivals (HAR vs OAR: HR: 1.73; P = .04; HAR vs OAR: HR: 1.67; P = .04). The reintervention rate in the HAR group was significantly higher than that in the OAR group (OAR vs HAR: 8.24% vs 16.01%; P = .01). The most common reintervention was postoperative bleeding (8.07%) in the OAR group and endoleak (9.67%) in the HAR group. CONCLUSIONS: Our meta-analysis revealed that debranching HAR was associated with fewer perioperative complications than the OAR group, except for postoperative permanent paraplegia, reintervention, and stroke events. The OAR group demonstrated better 3-year and 5-year survivals than the debranching HAR group. However, patients in the OAR group had fewer comorbid factors and were younger than those in the HAR group. High-quality studies and well-powered randomized trials are needed to further evaluate this evolving field.


Subject(s)
Aorta, Thoracic , Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Postoperative Complications , Humans , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Endovascular Procedures/methods , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/mortality , Aortic Aneurysm, Thoracic/diagnostic imaging , Treatment Outcome , Aorta, Thoracic/surgery , Aorta, Thoracic/diagnostic imaging , Postoperative Complications/etiology , Risk Factors , Aortic Dissection/surgery , Aortic Dissection/mortality , Aortic Dissection/diagnostic imaging , Time Factors , Risk Assessment , Female , Aged , Male , Middle Aged , Aged, 80 and over
15.
Small ; : e2307350, 2023 Dec 10.
Article in English | MEDLINE | ID: mdl-38072806

ABSTRACT

Hydrogen (H2 ), the most abundant element in the universe, has the potential to address the challenges of energy security and climate change. However, due to the lack of a safe and efficient method for storing and delivering hydrogen, its practical application is still in its infancy stages. To overcome this challenge, a promising solution is demonstrated in the form of on-demand production of H2 using nano-Silicon (Si) powders. The method offers instantaneous production of H2 , yielding a volume of 1.3 L per gram of Si at room temperature. Moreover, the H2 production yield and the rate can be effectively controlled by adjusting the reaction pH value and temperatures. Additionally, liquid-phase transmission electron microscopy (LPTEM) is utilized in situ to demonstrate the entire reaction in real-time, wherein H2 bubble formation is observed and illustrated the gradual conversion of crystalline Si particles into amorphous oxides. Moreover, it is confirmed that the purity of the generated gas is 99.5% using gas chromatography mass spectrometry (GC-MS). These findings suggest a viable option for instant H2 production in portable fuel cells using Si cartridges or pellets.

16.
Org Lett ; 25(46): 8344-8349, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37962415

ABSTRACT

A nickel-catalyzed three-component alkylarylation of alkenyl N-heteroarenes with α-bromocarboxylates and aryl boronic acids is reported. The protocol provides a new method to access a variety of N-heteroarene substituted diarylalkanes in moderate to good yields. It features mild reaction conditions, cheap nickel catalyst, readily available substrates, and broad substrate scope.

17.
Sci Rep ; 13(1): 20400, 2023 11 21.
Article in English | MEDLINE | ID: mdl-37990054

ABSTRACT

IGT family genes play essential roles in shaping plant architecture. However, limited amount of information is available about IGT family genes in peanuts (Arachis hypogaea). In the current study, 13 AhIGT genes were identified and classified into three groups based on their phylogenetic relationship. Gene structure, conserved domain analyses indicated all AhIGTs were observed to share a similar exon-intron distribution pattern. AhIGTs within the same subfamily maintained a consistent motif composition. Chromosomal localization and synteny analyses showed that AhIGTs were unevenly localized on 9 chromosomes and that segmental duplication and purifying selection may have played important roles in the evolution of AhIGT genes. The analysis of conserved motifs, GO annotation, and transcript profile suggested that AhLAZY1-3 may play roles in gravity sensing and shaping peanut plant architecture. Transcript profile analysis suggested that AhTAC1 could potentially be involved gynophore ('peg') penetration into the soil. The cis-element analysis revealed that the light-responsive elements accounted for most of all cis-acting elements. Furthermore, qRT-PCR analysis showed that the expression of several AhIGT genes, like AhTAC1-2/4, was light-dependent, indicating that these genes may regulate plant architecture in response to light signals. This study may facilitate functional studies of the IGT genes in peanut.


Subject(s)
Arachis , Multigene Family , Arachis/genetics , Arachis/metabolism , Phylogeny , Plants/metabolism , Synteny/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant
18.
Cardiovasc Diabetol ; 22(1): 290, 2023 10 27.
Article in English | MEDLINE | ID: mdl-37891550

ABSTRACT

BACKGROUND: A comprehensive network meta-analysis comparing the effects of individual sodium-glucose cotransporter 2 (SGLT2) inhibitors on patients with and without comorbidities including diabetes mellitus (DM), heart failure (HF), and chronic kidney disease (CKD) has not been previously conducted. METHODS: We searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for randomized controlled trials up to March 28, 2023. Network meta-analysis using a random-effects model was conducted to calculate risk ratios (RRs). Risk of Bias tool 2.0 was used to assess bias, and CINeMA to assess the certainty of evidence. In the subgroup analysis, the SGLT2 inhibitors were classified into highly (dapagliflozin, empagliflozin, and ertugliflozin) and less selective SGLT2 inhibitors (canagliflozin and sotagliflozin). RESULTS: A total of fourteen trials with 75,334 patients were analyzed. Among these, 40,956 had taken SGLT2 inhibitors and 34,378 had not. One of the main results with particular findings was empagliflozin users had a significantly lower risk of all-cause death compared to dapagliflozin users in DM population (RR: 0.81, 95% CI 0.69-0.96). In HF population, sotagliflozin users had a borderline significantly lower risk of CV death or hospitalization for HF (HHF) than dapagliflozin users (RR: 0.90, 95% CI 0.80-1.01). In non-HF population, those who used canagliflozin had a significantly lower risk of CV death or HHF compared with those who used dapagliflozin (RR: 0.75, 95% CI 0.58-0.98). At last, for HF patients, those who used less selective SGLT2 inhibitors had a significantly lower risk of MACEs compared to those who used highly selective SGLT2 inhibitors (RR: 0.75, 95% CI 0.62-0.90). CONCLUSIONS: Our network meta-analysis revealed that empagliflozin users with diabetes experienced a lower risk of dying from any cause than those using dapagliflozin. Additionally, canagliflozin users demonstrated a reduced risk of cardiovascular death or HHF compared to dapagliflozin users in those without HF. In HF patients, less selective SGLT2 inhibitors showed superior CV composite outcomes, even surpassing the performance of highly selective SGLT2 inhibitors. TRIAL REGISTRATION: PROSPERO [CRD42022361906].


Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Canagliflozin/adverse effects , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hypoglycemic Agents/adverse effects , Network Meta-Analysis , Heart Failure/diagnosis , Heart Failure/drug therapy , Heart Failure/epidemiology
19.
J Epidemiol ; 2023 Oct 07.
Article in English | MEDLINE | ID: mdl-37813622

ABSTRACT

BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.

20.
Angew Chem Int Ed Engl ; 62(44): e202306759, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37710396

ABSTRACT

To synthesize high molecular weight poly(phenolic ester) via a living ring-opening polymerization (ROP) of cyclic phenolic ester monomers remains a critical challenge due to serious transesterification and back-biting reactions. Both phenolic ester bonds in monomer and polymer chains are highly active, and it is difficult so far to distinguish them. In this work, an unprecedented selectively bifunctional catalytic system of tetra-n-butylammonium chloride (TBACl) was discovered to mediate the syntheses of high molecular weight salicylic acid-based copolyesters via a living ROP of salicylate cyclic esters (for poly(salicylic methyl glycolide) (PSMG), Mn =361.8 kg/mol, Ð<1.30). Compared to previous catalysis systems, the side reactions were suppressed remarkably in this catalysis system because phenolic ester bond in monomer can be selectively cleaved over that in polymer chains during ROP progress. Mechanistic studies reveal that the halide anion and alkyl-quaternaryammonium cation work synergistically, where the alkyl-quaternaryammonium cation moiety interacts with the carbonyl group of substrates via non-classical hydrogen bonding. Moreover, these salicylic acid-based copolyesters can be recycled to dimeric monomer under solution condition, and can be recycled to original monomeric monomers without catalyst under sublimation condition.

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