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Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
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Mice , Animals , Butyric Acid/metabolism , Ketone Bodies/metabolism , Liver/metabolism , Hydroxybutyrates/metabolism , Down-Regulation , Sirtuins/metabolism , Hydroxymethylglutaryl-CoA Synthase/metabolismABSTRACT
The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice [uncoupling protein 1 (Ucp1)-CreER-p65f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in cristae density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.
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Background:Malnutrition is common in patients with cancer, whichadversely affectsthesurvival and quality of life ofcancer patients.However, there is no national data on the prevalence of malnutrition inChinese cancer patients. Thisstudy aims to evaluate the prevalenceof malnutrition and quality of life(QOL)ofChinese patients with localregional, recurrentor metastatic cancer,to address the prognostic value of nutritional status and QOLon the survival of cancer patients in China and to validate the patient-generated subjective global assessment (PG-SGA) questionnaire in Chinese cancer patients.Methods:Thisisanobservational,multi-centered,and hospital-based prospective cohort study.We aimed to recruit 50,000 cancer patients (age 18and above)overan 8-year period.Data collection will occur within 48hrafter patientsare admitted to hospital, 30-days after hospital admission, and the follow-up will be conducted1-8years after enrolment. The primary outcomeisoverall survival, and secondaryoutcomes arelength of hospital stay and hospital costs. Factors measured are demographic characteristics, tumor characteristics, anthropometry measurements,hematological measurement, body composition, PG-SGAscores,Karnofsky performance status scores,and QLQ C30 scores. This protocol wasapproved by local ethical committees of all the participant hospitals.Conclusions: This multi-centered, large-scale, long-time follow-up prospective study will help diagnose malnutrition in cancer patients in China, and identify the related risk factors associated with the negative outcomes. The anticipated results will highlight the need for a truly scientific appraisal of nutrition therapy, and help to improve outcomes among cancer patients in China.Trial Registration: The trial has been registered with the Chinese Clinical Trial Registry, ChiCTR1800020329. Registered on 19 December 2018
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@#Objective To explore the relationship between serum uric acid and in-hospital mortality in patients with acute cerebral infarction. Methods The clinical data of 260 patients with acute ischemic stroke were retrospectively reviewed. The data obtained covered the period from December 2016 to December 2019.χ2-test was used to compare clinical differences between patients with or without hyperuricemia. Survival was evaluated with Kaplan-Meier’s curve. A log-rank univariate analysis was used to determine the prognostic factors related to the in-hospital death. The Cox model multivariate analysis was used to identify independent prognostic factors. Results In the overall sample，hyperuricemia was associated with an increased risk of in-hospital mortality（P=0.003）. Log-rank univariate analysis showed that the significant factors were age（P=0.000），Non-valvular atrial fibrillation（P=0.003），NIHSS（P=0.000），and SUA（P=0.007）. Cox regression analysis revealed that NIHSS was the prognostic factor（P=0.000）. In the subpopulation with normal renal function，the relationship between hyperuricemia and increased stroke mortality was not confirmed（P=0.557）. Log-rank univariate analysis showed that the significant factors were age（P=0.046） and NIHSS（P=0.003）. Cox regression analysis revealed that NIHSS was the prognostic factor（P=0.020）. In the subpopulation with renal dysfunction，hyperuricemia was associated to an increased risk of in-hospital mortality（P=0.008）. Log-rank univariate analysis showed that the significant factors were age（P=0.012），Non-valvular atrial fibrillation（P=0.035），NIHSS（P=0.001），and SUA（P=0.019）. Cox regression analysis revealed that NIHSS（P=0.002） and SUA（P=0.031） were the prognostic factors. Conclusion In the overall sample，hyperuricemia was associated to an increased risk of in-hospital mortality. This effect was stronger in patients with renal dysfunction.
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In recent years,along with social economic development and population aging,more and more fracture patients have received internal fixation and artificial joint replacement.Postoperative infection related to orthopedic implants is a catastrophic complication which imposes serious psychological,physiological and economic burdens on the patients.Therefore,it is necessary to be able to make an early diagnosis of the infection.However,diagnosis of implant-related infection is always a clinical problem for orthopedists.Currently,it is thought to be a valuable way to judge orthopedic implant infection by monitoring inflammatory cytokines.This article will offer an overview on the progress in research of diagnosis values of different inflammatory cytokines in postoperative infection related to orthopedic implants.
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Purpose To investigate the topological structure differences between the migraine patients group and the normal control group by using resting-state brain complex networks constructed based on graph theory. Materials and Methods Resting-state functional magnetic resonance imaging dataset were obtained from 22 migraine patients and 22 normal subjects. The functional complex networks of the two groups were constructed, and parameters including average clustering coefficient, characteristic path length, small worldness, assortativity, and betweenness of the two groups were respectively calculated. Results When compared with the parameters of normal control group, average clustering coefficient of migraine patients group was larger, small worldness and assortativity were also changed. The characteristic path length of the caudate nucleus and putamen areas presented abnormal in the migraine patients group. Betweenness centrality of the thalamus, inferior occipital gyrus and occipital gyrus increased in the migraine patients group. Conclusion The abnormal brain regions in the migraine patients group were mainly associated with pain processing, visual processing and sensory information relay. This study may contribute to better understanding and interpreting corresponding clinical condition of migraine.
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0.5 or close to 1.0,suggesting marker retained many parts of the sigmoid colon and rectum,FOOC possibility.Normal group,constipation group colon 48,72 hour markers district retention contrast,have significant differences.TI as the STC's kinetic parameters can be used as the difference between STC and the simple and reliable indicators FOOC.17 cases in this group(accounting for 68%)FC children with TI in 48 h,72 h were 0.5,in line with the characteristics of FOOC.Conclusion The results of this study showed that colonic transit time checks can be more accurately reflect the normal function of colonic transit may be the evaluation of patients with functional constipation colonic transit weaken the seriousness of the correct and reasonable to carry out sub-type of clinical treatment of important guiding significance.
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Objective To investigate the effects of selenium-and zinc-enriched probiotics on the content of selenium and zinc in blood,antioxidation function and intestinal microflora in canine.Method Eight 18-month native canines,female and male in half,were randomly divided into the control and treatment groups on average.The control group received basal diet,the treatment group received basal diet supplemented with 2.0g selenium-and zinc-enriched probiotics everyday.To determine the experimental indices,the samples were collected on D0,D15 and D30,respectively.Results Compared with the control group,on D15,the content of selenium and zinc in blood,blood GPX,serum SOD,T-AOC and the amount of Lactobacillus in the experimental group were significantly increased,while the amount of Escherichia coli significantly decreased,but the serum MDA and the amount of Bifidobacterium,Staphylococcus and Enterococcus had no significant change.On D30,the content of selenium in blood,serum SOD,T-AOC and the amount of Lactobacillus were very significantly increased,while the content of zinc in blood,blood GPX and the amount of Bifidobacterium significantly increased;but serum MDA and the amount of Escherichia coli,Staphylococcus and Enterococcus very significantly decreased.Conclusion Selenium-and zinc-enriched probiotics could increase content of selenium and zinc in blood,enhance antioxidation function,improve and regulate the intestinal microflora.