Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the...Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model.The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this molecule.Methods:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of <15 mL/min/1.73 m2).The RE+BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD(intradialytic exercise).RE repetitions included concentric and eccentric lifting phases(each lasting 2 s) and were supervised by a strength and conditioning specialist.Results:Several variables were associated with elevated levels of D-dimer,including higher blood glucose,citrate use,recent cardiovascular events,recent intercurrents,higher inflammatory status,catheter as vascular access,older patients(>70 years old),and HD vintage.Furthermore,RE+BFR significantly increases D-dimer after 4 h.Patients with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.展开更多
Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine mode...Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.展开更多
Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl do...Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for th...BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.展开更多
Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis wh...Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.展开更多
The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrop...The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.展开更多
Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of...Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.展开更多
Energy restriction is defined as reducing nutrient intake without dragging the organism into malnutrition. Energy restriction is preferred because it is a non-genetic intervention that increases life expectancy. Nicot...Energy restriction is defined as reducing nutrient intake without dragging the organism into malnutrition. Energy restriction is preferred because it is a non-genetic intervention that increases life expectancy. Nicotinamide adenine dinucleotide(NAD~+)and adenosine monophosphate(AMP)levels, which are the indicators of intracellular energy deficiency, increase with energy restriction. The increase in NAD~+ level stimulates sirtuin(SIRT)enzymes, and the increase in AMP level stimulates AMP-activated protein kinase(AMPK). Various mechanisms are regulated by stimulating these enzymes. By Forkhead box O(FoxO)transcription factors, the ability of resistance to oxidative stress increases, and antioxidant genes, DNA repair, and autophagy genes are stimulated. Apoptosis is induced by stimulation of the p53 protein, and tumor growth is suppressed by the disruption of aging cells. The suppression of phosphoinositide 3-kinase(PI3K)-/-Akt, and therefore mTOR signal stimulates autophagy and mitophagia, and cleanses damaged cells and organelles. Mitochondrial biogenesis is stimulated, antioxidant capacity increases, and inflammatory response decreases. Adipose tissue and lipid metabolism are regulated by the regulation of fatty acid synthesis and oxidation. As a consequence, the effects of caloric restriction on cellular metabolism are regulated through the genetic pathways.展开更多
Objective:To explore the combinatorial effect of epigallocatechin-3-gallate(EGCG)and calorie restriction on activation of nuclear factor erythroid 2-related factor 2(Nrf2),a transcription factor involved in the antiox...Objective:To explore the combinatorial effect of epigallocatechin-3-gallate(EGCG)and calorie restriction on activation of nuclear factor erythroid 2-related factor 2(Nrf2),a transcription factor involved in the antioxidant defense system of aged rats.Methods:Aged male Wistar rats were calorie-restricted and treated with EGCG orally for 45 days.The initial body weight of aged rats was recorded,and the final body weight was measured at the end of the experimental period.Serum lipid and lipoprotein status,oxidative stress markers such as free radicals and malondialdehyde levels,and reduced glutathione were assessed.In addition,RT-PCR and Western blotting analyses were performed.Results:Calorie restriction potentiated the effect of EGCG on enhancing antioxidant status,improving the levels of serum lipid and lipoproteins,upregulating Nrf2 and Bcl2,and downregulating Keap1,cullin3,Bax and cytochrome c in aged rats.Conclusions:Calorie restriction can promote EGCG-mediated Nrf2 activation in aged rats.This preliminary finding paves the way for a combinatory approach to replenishing the antioxidant status during aging,thereby reducing the risk for age-associated degenerative diseases.展开更多
Introduction: Their efficacy in preventing thrombotic and embolic events has been proven in numerous studies, but their narrow therapeutic index requires particular vigilance, especially in terms of biology. In additi...Introduction: Their efficacy in preventing thrombotic and embolic events has been proven in numerous studies, but their narrow therapeutic index requires particular vigilance, especially in terms of biology. In addition, treatment-related hemorrhagic complications are not uncommon. This study explores the influence of dietary vitamin K restriction on the efficacy of antivitamin K treatment at the University Cardiology Clinic of CNHU-HKM. Methods: Cross-sectional and descriptive study that took place from 25 April to 29 August 2019. Patients’ dietary behaviors and successive INR values were collected. Information on dietary intake was obtained by 2 non-consecutive 24-hour recalls. The effectiveness of VKA treatment was assessed by the “Time in Therapeutic Range” (TTR) of the INR. VKA treatment was considered effective for a TTR greater than 65%. Results: At the end of this study, 40 patients were surveyed. The mean age of the participants was 58.05 years ± 13.32 years, with a sex ratio of 1.35. Complete arrhythmia due to atrial fibrillation was the main indication for VKA treatment (37.50%) and fluindione was the most commonly prescribed drug (77.50%). The duration of treatment was less than or equal to 2 years in 47.5% of the subjects surveyed. Before starting treatment, 85% of patients received advice on restricting vitamin K-rich foods, and 45% of patients reported “food burnout” after a period of compliance with the restriction. The majority of respondents (97.50%) complied with the restriction on vitamin K-rich foods. All respondents had high energy intakes and a poor distribution of macronutrients, with a predominance of carbohydrates and proteins. 2.5% of respondents were on effective anti-vitamin K therapy with a TTR of over 65%. Conclusion: Restriction of vitamin K-rich foods is not conducive to effective treatment with vitamin K antagonists.展开更多
Introduction: Sleep is critical to human physiological function, cognitive performance, and emotional regulation. Healthcare personnel, especially physicians, are chronically exposed to long working hours, which are o...Introduction: Sleep is critical to human physiological function, cognitive performance, and emotional regulation. Healthcare personnel, especially physicians, are chronically exposed to long working hours, which are often accompanied by decreased sleep time. Clinical evidence indicates that these conditions affect their cognitive function and professional practice, but researchers in the field have not sufficiently explored the possible effects of reductions in sleep time on social cognition. Objective: The aim of this is to further explore the effects of sleep restriction among medical residents, the specific impairments in social cognition that it produces, and the effects of a sleep hygiene orientation on those impairments. Method: There were 124 medical residents (50 males, 74 females) who completed a daily sleep/work log, a battery of sleep tests/questionnaires, and neuropsychological evaluations. The participants then received a short course (8 hours) on basic concepts of sleep hygiene and sleep psychoeducation. Once the course was completed, participants filled out the questionnaires again. Results: The results indicate that sleep disturbances in medical residents were associated with severe neurocognitive and social cognition impairments. After the sleep hygiene intervention, neuropsychological function and sleep parameters improved, awareness increased, and social cognition performance significantly improved. Conclusion: Using sleep psychoeducation and sleep hygiene intervention in medical residents is a simple strategy to mitigate the effects of sleep restriction.展开更多
According to constitutional jurisprudence in China,Article 51 of the Constitution is an unenumerated restrictive clause.Such theoretical construction fails to justify the differentiated restrictions established in the...According to constitutional jurisprudence in China,Article 51 of the Constitution is an unenumerated restrictive clause.Such theoretical construction fails to justify the differentiated restrictions established in the Constitution and makes it difficult to explain the constitutional status of human dignity. Article 51 implies the possibility of other theoretical constructions. It is not an unenumerated restriction clause but an unenumerated rights clause. It aims to provide guarantees for general freedom of action not enumerated in the Constitution rather than restricting fundamental rights. The actual benefit of this kind of theoretical construction lies in that it can establish the basis of the constitutional text for general freedom of action and promote the people’s correct understanding of the model of restriction on fundamental rights established by the Constitution of PRC.展开更多
目的:基于CiteSpace和VOSviewer可视化软件对饮食限制(DR)调控炎症文献进行定量可视化分析,探索DR调控炎症领域的研究热点和趋势。方法:检索2010年1月1日至2022年9月29日Web of Science核心数据库中收录的DR调控炎症相关文献共1678篇,...目的:基于CiteSpace和VOSviewer可视化软件对饮食限制(DR)调控炎症文献进行定量可视化分析,探索DR调控炎症领域的研究热点和趋势。方法:检索2010年1月1日至2022年9月29日Web of Science核心数据库中收录的DR调控炎症相关文献共1678篇,经筛查最终获得1344篇,使用CiteSpace和VOSviewer可视化软件对检索到的文献数据进行年发文量、国家、机构、作者、被引频次和关键词的定量和可视化分析。结果:最终获得的1344篇文献年发文量总体呈上升趋势,文献最高被引频次为1676次,美国(481篇)是出产文献数量最多的国家,中国(181篇)位居第二。DR调控炎症领域研究热点集中在热量限制(CR)、生酮饮食、衰老、代谢性疾病、脂肪组织及肠道菌群等方面。结论:DR调控炎症愈来愈受到国际和国内研究者青睐,未来研究热点可能是CR模拟物(CRM)、肠道菌群、神经退行性疾病和心血管疾病,总体研究趋势为进一步明确DR的抗炎机制,寻找新的治疗靶点,将更多经过体外和动物模型证实的有效方案进行更严格的临床试验。展开更多
基金supported by a grant provided by the Coordenacao de Aperfeicoamento de Pessoal de Nível Superior-Brazil-Finance Code 001 and National Council for Scientific and Technological Developmentfinanced in part by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil--Finance Code 001funded by the Fundacao de Apoio à Pesquisa do Distrito Federal with grants from demanda espontanea-Edital 09/2022
文摘Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model.The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this molecule.Methods:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of <15 mL/min/1.73 m2).The RE+BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD(intradialytic exercise).RE repetitions included concentric and eccentric lifting phases(each lasting 2 s) and were supervised by a strength and conditioning specialist.Results:Several variables were associated with elevated levels of D-dimer,including higher blood glucose,citrate use,recent cardiovascular events,recent intercurrents,higher inflammatory status,catheter as vascular access,older patients(>70 years old),and HD vintage.Furthermore,RE+BFR significantly increases D-dimer after 4 h.Patients with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.
基金supported by the fund for the National 14th Five-Year Plan Key Research and Development Program(2021YFD1600702)XPCC Agricultural Science and Technology Innovation Project(NCG202232)the Top Talents Award Plan of Yangzhou University(2020)。
文摘Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.
基金This work was supported by Sichuan Provincial Science Fund for Distinguished Young Scholars(Grant No.2020JDJQ0041)CARS-35 and Sichuan Key Science and Technology Project(NO.2021ZDZX0009).
文摘Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.
文摘BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.
文摘Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.
基金supported by grants from the National Natural Science Foundation of China(81800245,81970228,82102306,81900779)the China Postdoctoral Science Foundation(2020M670030ZX)+1 种基金the Shaoguan Science and Technology Program(2019sn078)the Start-up Fund for RAPs under the Strategic Hiring Scheme(P0035913)。
文摘The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.
文摘Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.
文摘Energy restriction is defined as reducing nutrient intake without dragging the organism into malnutrition. Energy restriction is preferred because it is a non-genetic intervention that increases life expectancy. Nicotinamide adenine dinucleotide(NAD~+)and adenosine monophosphate(AMP)levels, which are the indicators of intracellular energy deficiency, increase with energy restriction. The increase in NAD~+ level stimulates sirtuin(SIRT)enzymes, and the increase in AMP level stimulates AMP-activated protein kinase(AMPK). Various mechanisms are regulated by stimulating these enzymes. By Forkhead box O(FoxO)transcription factors, the ability of resistance to oxidative stress increases, and antioxidant genes, DNA repair, and autophagy genes are stimulated. Apoptosis is induced by stimulation of the p53 protein, and tumor growth is suppressed by the disruption of aging cells. The suppression of phosphoinositide 3-kinase(PI3K)-/-Akt, and therefore mTOR signal stimulates autophagy and mitophagia, and cleanses damaged cells and organelles. Mitochondrial biogenesis is stimulated, antioxidant capacity increases, and inflammatory response decreases. Adipose tissue and lipid metabolism are regulated by the regulation of fatty acid synthesis and oxidation. As a consequence, the effects of caloric restriction on cellular metabolism are regulated through the genetic pathways.
基金The article was financially supported by UGC SAP Programme,University of Madras,Chennai,India.
文摘Objective:To explore the combinatorial effect of epigallocatechin-3-gallate(EGCG)and calorie restriction on activation of nuclear factor erythroid 2-related factor 2(Nrf2),a transcription factor involved in the antioxidant defense system of aged rats.Methods:Aged male Wistar rats were calorie-restricted and treated with EGCG orally for 45 days.The initial body weight of aged rats was recorded,and the final body weight was measured at the end of the experimental period.Serum lipid and lipoprotein status,oxidative stress markers such as free radicals and malondialdehyde levels,and reduced glutathione were assessed.In addition,RT-PCR and Western blotting analyses were performed.Results:Calorie restriction potentiated the effect of EGCG on enhancing antioxidant status,improving the levels of serum lipid and lipoproteins,upregulating Nrf2 and Bcl2,and downregulating Keap1,cullin3,Bax and cytochrome c in aged rats.Conclusions:Calorie restriction can promote EGCG-mediated Nrf2 activation in aged rats.This preliminary finding paves the way for a combinatory approach to replenishing the antioxidant status during aging,thereby reducing the risk for age-associated degenerative diseases.
文摘Introduction: Their efficacy in preventing thrombotic and embolic events has been proven in numerous studies, but their narrow therapeutic index requires particular vigilance, especially in terms of biology. In addition, treatment-related hemorrhagic complications are not uncommon. This study explores the influence of dietary vitamin K restriction on the efficacy of antivitamin K treatment at the University Cardiology Clinic of CNHU-HKM. Methods: Cross-sectional and descriptive study that took place from 25 April to 29 August 2019. Patients’ dietary behaviors and successive INR values were collected. Information on dietary intake was obtained by 2 non-consecutive 24-hour recalls. The effectiveness of VKA treatment was assessed by the “Time in Therapeutic Range” (TTR) of the INR. VKA treatment was considered effective for a TTR greater than 65%. Results: At the end of this study, 40 patients were surveyed. The mean age of the participants was 58.05 years ± 13.32 years, with a sex ratio of 1.35. Complete arrhythmia due to atrial fibrillation was the main indication for VKA treatment (37.50%) and fluindione was the most commonly prescribed drug (77.50%). The duration of treatment was less than or equal to 2 years in 47.5% of the subjects surveyed. Before starting treatment, 85% of patients received advice on restricting vitamin K-rich foods, and 45% of patients reported “food burnout” after a period of compliance with the restriction. The majority of respondents (97.50%) complied with the restriction on vitamin K-rich foods. All respondents had high energy intakes and a poor distribution of macronutrients, with a predominance of carbohydrates and proteins. 2.5% of respondents were on effective anti-vitamin K therapy with a TTR of over 65%. Conclusion: Restriction of vitamin K-rich foods is not conducive to effective treatment with vitamin K antagonists.
文摘Introduction: Sleep is critical to human physiological function, cognitive performance, and emotional regulation. Healthcare personnel, especially physicians, are chronically exposed to long working hours, which are often accompanied by decreased sleep time. Clinical evidence indicates that these conditions affect their cognitive function and professional practice, but researchers in the field have not sufficiently explored the possible effects of reductions in sleep time on social cognition. Objective: The aim of this is to further explore the effects of sleep restriction among medical residents, the specific impairments in social cognition that it produces, and the effects of a sleep hygiene orientation on those impairments. Method: There were 124 medical residents (50 males, 74 females) who completed a daily sleep/work log, a battery of sleep tests/questionnaires, and neuropsychological evaluations. The participants then received a short course (8 hours) on basic concepts of sleep hygiene and sleep psychoeducation. Once the course was completed, participants filled out the questionnaires again. Results: The results indicate that sleep disturbances in medical residents were associated with severe neurocognitive and social cognition impairments. After the sleep hygiene intervention, neuropsychological function and sleep parameters improved, awareness increased, and social cognition performance significantly improved. Conclusion: Using sleep psychoeducation and sleep hygiene intervention in medical residents is a simple strategy to mitigate the effects of sleep restriction.
基金a phased achievement of Constitutional Interpretation in Line with Law and Its Practical Research,a General Project of Humanities and Social Sciences Research of the Ministry of Education for 2019 (Approval No. 19YJA820008)。
文摘According to constitutional jurisprudence in China,Article 51 of the Constitution is an unenumerated restrictive clause.Such theoretical construction fails to justify the differentiated restrictions established in the Constitution and makes it difficult to explain the constitutional status of human dignity. Article 51 implies the possibility of other theoretical constructions. It is not an unenumerated restriction clause but an unenumerated rights clause. It aims to provide guarantees for general freedom of action not enumerated in the Constitution rather than restricting fundamental rights. The actual benefit of this kind of theoretical construction lies in that it can establish the basis of the constitutional text for general freedom of action and promote the people’s correct understanding of the model of restriction on fundamental rights established by the Constitution of PRC.
文摘目的:基于CiteSpace和VOSviewer可视化软件对饮食限制(DR)调控炎症文献进行定量可视化分析,探索DR调控炎症领域的研究热点和趋势。方法:检索2010年1月1日至2022年9月29日Web of Science核心数据库中收录的DR调控炎症相关文献共1678篇,经筛查最终获得1344篇,使用CiteSpace和VOSviewer可视化软件对检索到的文献数据进行年发文量、国家、机构、作者、被引频次和关键词的定量和可视化分析。结果:最终获得的1344篇文献年发文量总体呈上升趋势,文献最高被引频次为1676次,美国(481篇)是出产文献数量最多的国家,中国(181篇)位居第二。DR调控炎症领域研究热点集中在热量限制(CR)、生酮饮食、衰老、代谢性疾病、脂肪组织及肠道菌群等方面。结论:DR调控炎症愈来愈受到国际和国内研究者青睐,未来研究热点可能是CR模拟物(CRM)、肠道菌群、神经退行性疾病和心血管疾病,总体研究趋势为进一步明确DR的抗炎机制,寻找新的治疗靶点,将更多经过体外和动物模型证实的有效方案进行更严格的临床试验。