Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease(KBD).We also analyzed the i...Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease(KBD).We also analyzed the interaction between the CpGs methylations and CpG-SNPs.Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects.Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF-MS).The CpGs methylation levels were compared between samples from KBD patients and healthy subjects.The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes.Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls(P<0.05).The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls(P<0.05).The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls.The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype(P<0.05).Conclusion The methylation level of DIO2 increases in KBD patients.Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.展开更多
Grape crops are a great source of income for farmers.The yield and quality of grapes can be improved by preventing and treating diseases.The farmer’s yield will be dramatically impacted if diseases are found on grape...Grape crops are a great source of income for farmers.The yield and quality of grapes can be improved by preventing and treating diseases.The farmer’s yield will be dramatically impacted if diseases are found on grape leaves.Automatic detection can reduce the chances of leaf diseases affecting other healthy plants.Several studies have been conducted to detect grape leaf diseases,but most fail to engage with end users and integrate the model with real-time mobile applications.This study developed a mobile-based grape leaf disease detection(GLDD)application to identify infected leaves,Grape Guard,based on a TensorFlow Lite(TFLite)model generated from the You Only Look Once(YOLO)v8 model.A public grape leaf disease dataset containing four classes was used to train the model.The results of this study were relied on the YOLO architecture,specifically YOLOv5 and YOLOv8.After extensive experiments with different image sizes,YOLOv8 performed better than YOLOv5.YOLOv8 achieved 99.9%precision,100%recall,99.5%mean average precision(mAP),and 88%mAP50-95 for all classes to detect grape leaf diseases.The Grape Guard android mobile application can accurately detect the grape leaf disease by capturing images from grape vines.展开更多
Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels....Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.展开更多
Emerging evidence supports that sleep disorders are the main risk factor for sporadic Alzheimer's disease(AD),and iron dysregulation may be the link between them.Our previous studies have confirmed that ketogenic ...Emerging evidence supports that sleep disorders are the main risk factor for sporadic Alzheimer's disease(AD),and iron dysregulation may be the link between them.Our previous studies have confirmed that ketogenic diet(KD)can prevent chronic sleep deprivation-induced AD.However,it is uncertain whether exogenous ketones supplements(EKS),as an alternative intervention,have the same effects as KD.Thus,we investigated the prophylactic efficiency of EKS on chronic sleep deprivation-induced AD and reveal the underlying mechanism focus on iron metabolism.We observed that the prophylactic efficacy of EKS against chronic sleep deprivation-induced AD was comparable to that of KD.Meanwhile,our results suggest that both EKS and KD inhibited iron metabolism disorder through regulation of iron metabolism-related proteins.Moreover,we found that both EKS and KD reduced hippocampal mitochondrial dysfunction and iron-mediated lipid peroxides.Furthermore,EX527(silent information regulator 1(Sirt1)inhibitor),mostly abrogated these above protections of EKS,suggesting that the prophylactic effect of EKS on AD is partly dependent on Sirt1.Our findings provide novel evidence that EKS can be developed as functional foods to prevent or delay the development of AD,particularly in individuals with sleep disorders.展开更多
Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Er...Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.展开更多
Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide.Gut microbiota and its metabolites alteration are closely related to NAFLD.Nootkatone is an edible flavorant derived f...Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide.Gut microbiota and its metabolites alteration are closely related to NAFLD.Nootkatone is an edible flavorant derived from grapefruit which has a variety of biological activities.However,the precise mechanisms of nootkatone on NAFLD remains to be defined.Our results showed that nootkatone prevented body weight gain and decreased serum lipid level,hepatic lipogenesis,hepatic proinflammatory cytokines secretion in NAFLD mice.Also,nootkatone attenuated inflammatory response via inhibiting TLR4/NF-κB/NLRP3 pathway.Moreover,nootkatone restored intestinal barrier damage through increasing tight junction proteins and short chain fatty acids contents.Further 16S rRNA sequencing of colonic content suggested that nootkatone recovered the disturbed gut microbiota to improve NAFLD.Spearman correlation analysis between gut microbiota and NAFLD related parameters indicated that nootkatone regulated lipid metabolism and immunity via altering the gut microbiota.In conclusion,these findings revealed that nootkatone alleviated hepatic lipid homeostasis and inflammatory response in NAFLD mice,which associated with intestinal barrier integrity and the regulation of gut microbiota.This study provides new perspectives that nootkatone has efficacy on NAFLD via“gut-liver axis”,and nootkatone is expected to be developed as a functional food additive.展开更多
Cardiovascular diseases(CVD)are the leading cause of death in the world and one of the most common diseases in the elderly,with high prevalence and poor prognosis,which seriously affect the health of the elder patient...Cardiovascular diseases(CVD)are the leading cause of death in the world and one of the most common diseases in the elderly,with high prevalence and poor prognosis,which seriously affect the health of the elder patients.One report showed that global deaths from CVD increased from 12.4 million in 1990 to 19.8 million in 2022,reflecting the global population growth and aging,as well as the impact of metabolic,environmental,and behavioral risks.[1]With the progress of aging population,the burden of CVD in the elderly in China has increased year by year,and factors including multiple complications,organ function decline,and high complication rate have made the interventional treatment of CVD in the elderly one of the difficulties and focuses in the field of cardiology in China.展开更多
Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Alt...Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.展开更多
Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)an...Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)and two-dimensional carbide and nitride(MXene)with high gas sensitivity and photo responsiveness were formulated using a self-assembly strategy.A light-activated virtual sensor array(LAVSA)based on BP/Ti_(3)C_(2)Tx was prepared under photomodulation and further assembled into an instant gas sensing platform(IGSP).In addition,a machine learning(ML)algorithm was introduced to help the IGSP detect and recognize the signals of breath samples to diagnose CHD.Due to the synergistic effect of BP and Ti_(3)C_(2)Tx as well as photo excitation,the synthesized heterostructured complexes exhibited higher performance than pristine Ti_(3)C_(2)Tx,with a response value 26%higher than that of pristine Ti_(3)C_(2)Tx.In addition,with the help of a pattern recognition algorithm,LAVSA successfully detected and identified 15 odor molecules affiliated with alcohols,ketones,aldehydes,esters,and acids.Meanwhile,with the assistance of ML,the IGSP achieved 69.2%accuracy in detecting the breath odor of 45 volunteers from healthy people and CHD patients.In conclusion,an immediate,low-cost,and accurate prototype was designed and fabricated for the noninvasive diagnosis of CHD,which provided a generalized solution for diagnosing other diseases and other more complex application scenarios.展开更多
Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the ser...Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.展开更多
BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to ex...BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.展开更多
Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease...Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease(CKD).Methods:In the present study,we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018.Standard time-series regression models and random-effects Meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span,respectively.Results:A total of 768,129 hospitalizations for CKD was recorded during the study period.The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD,especially in sub-tropical cities.With a 1℃ increase in daily mean temperature,the cumulative relative risks(RR)over lag 0-7 d were 1.008[95% confidence interval(CI)1.003-1.012]for nationwide.The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%.Stronger associations were observed among younger patients and those with obstructive nephropathy.Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days(RR=1.116,95%CI 1.069-1.166)above the effect of daily mean temperature.Conclusions:Short-term heat exposure may increase the risk of hospitalization for CKD.Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.展开更多
Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammat...Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammation and anti-oxidation functions,and improving mitochondrial quality.Chronic diseases as non-communicable diseases are mainly caused by multiple factors,such as physiological decline and dysfunction in the body,and have become a significant challenge on public health worldwide.It is worth noting that chronic diseases such as Alzheimer's disease(AD),Parkinson's disease(PD),muscle atrophy,cardiovascular disease,obesity,and cancer are accompanied by abnormal mitochondrial function.Therefore,targeted regulation of mitochondria may be a meaningful way to prevent and treat chronic diseases.Increasing evidence has confirmed that RSV is actively involved in regulating mitochondria,and it has become an essential consideration to prevent and treat chronic diseases through targeting mitochondria and improving corresponding functions.In this article,current studies on RSV to optimize mitochondrial quality for preventing and alleviating chronic disease are systematically summarized,which can provide a theoretical reference for the development of functional foods or drugs to combat chronic diseases.展开更多
While the interaction between information and disease in static networks has been extensively investigated,many studies have ignored the characteristics of network evolution.In this study,we construct a new two-layer ...While the interaction between information and disease in static networks has been extensively investigated,many studies have ignored the characteristics of network evolution.In this study,we construct a new two-layer coupling model to explore the interactions between information and disease.The upper layer describes the diffusion of disease-related information,and the lower layer represents the disease transmission.We then use power-law distributions to examine the influence of asymmetric activity levels on dynamic propagation,revealing a mapping relationship characterizing the interconnected propagation of information and diseases among partial nodes within the network.Subsequently,we derive the disease outbreak threshold by using the microscopic Markov-chain approach(MMCA).Finally,we perform extensive Monte Carlo(MC)numerical simulations to verify the accuracy of our theoretical results.Our findings indicate that the activity levels of individuals in the disease transmission layer have a more significant influence on disease transmission compared with the individual activity levels in the information diffusion layer.Moreover,reducing the damping factor can delay disease outbreaks and suppress disease transmission,while improving individual quarantine measures can contribute positively to disease control.This study provides valuable insights into policymakers for developing outbreak prevention and control strategies.展开更多
Objective To identify cuproptosis-and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.Methods The gene expression dataset GSE89632 was retrieve...Objective To identify cuproptosis-and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.Methods The gene expression dataset GSE89632 was retrieved from the Gene Expression Omnibus database to identify differentially expressed genes(DEGs)between the non-alcoholic steatohepatitis(NASH)group and the healthy group using the'limma'package in R software and weighted gene co-expression network analysis.Gene ontology,kyoto encyclopedia of genes and genomes pathway,and single-sample gene set enrichment analyses were performed to identify functional enrichment of DEGs.Ferroptosis-and cuproptosis-related genes were obtained from the FerrDb V2 database and available literatures,respectively.A combined signature for cuproptosis-and ferroptosis-related genes,called CRF,was constructed using the STRING database.Hub genes were identified by overlapping DEGs,WGCNA-derived key genes,and combined signature CRF genes,and validated using the GSE109836 and GSE227714 datasets and real-time quantitative polymerase chain reaction.A nomogram of NASH diagnostic model was established utilizing the'rms'package in R software based on the hub genes,and the diagnostic value of hub genes was assessed using receiver operating characteristic curve analysis.In addition,immune cell infiltration in NASH versus healthy controls was examined using the CIBERSORT algorithm.The relationships among various infiltrated immune cells were explored with Spearman's correlation analysis.Results Analysis of GSE89632 identified 236 DEGs between the NASH group and the healthy group.WGCNA highlighted 8 significant modules and 11,095 pivotal genes,of which 330 genes constituted CRF.Intersection analysis identified IL6,IL1B,JUN,NR4A1,and PTGS2 as hub genes.The hub genes were all downregulated in the NASH group,and this result was further verified by the NASH validation dataset and real-time quantitative polymerase chain reaction.Receiver operating characteristic curve analysis confirmed the diagnostic efficacy of these hub genes with areas under the curve of 0.985,0.941,1.000,0.967,and 0.985,respectively.Immune infiltration assessment revealed that gamma delta T cells,M1 macrophages,M2 macrophages,and resting mast cells were predominantly implicated.Conclusion Our investigation underscores the significant association of cuproptosis-and ferroptosis-related genes,specifically IL6,IL1B,JUN,NR4A1,and PTGS2,with NASH.These findings offer novel insights into the pathogenesis of NASH,potentially guiding future diagnostic and therapeutic strategies.展开更多
Nowadays,inflammatory bowel disease(IBD)-patient therapies are mainly based on corticosteroid,thiopurine,and immunomodulator treatments.Patients with active disease,that do not respond to corticosteroid and/or thiopur...Nowadays,inflammatory bowel disease(IBD)-patient therapies are mainly based on corticosteroid,thiopurine,and immunomodulator treatments.Patients with active disease,that do not respond to corticosteroid and/or thiopurine treatment,can switch to the usage of the chimeric monoclonal antibody infliximab(IFX).However,to date,no treatment appeared to be conclusive in lowering the incidence of IBD relapses.With the aim to increase the effectiveness of IFX treatment,we combined it with an adjuvant purple corn supplementation enriched in anthocyanins.IBD-patients were enrolled before they underwent to the IFX-infusion,and they were allocated in 2 different study arms.Patients in the intervention-arm followed a dietary supplementation with purple corn water-soluble extract,whereas control patients had a daily consumption of red fruit tea.16S rDNA gene-sequencing and high-resolution mass-spectrometry metabo-lipidomics analyses were conducted on stool and sera samples,respectively.As a result,the experimental intervention mainly affected the serum metabolome of IBD-patients by decreasing the concentration of specific lipids.Focusing on IBD patient annotated taxa,a significant decrease in Lactobacillus and Bifi dobacterium relative abundances was found.As far as it concerns the ulcerative colitis patient subset,the experimental intervention led to a decrease in Alistipes and Erysipelotrichaceae UCG-003 genus abundances and a concomitant Parabacteroides increase.On the contrary,after treatment,Crohn’s disease patients did not exhibit metataxonomics differences at the genus level.At the end of the treatment that led to a reshaped microbiota community,the gathered data paves the way for the usage of a specifically designed probiotic supplementation as a valuable strategy for IBD-patients under IFX infusion.展开更多
The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease.Extra virgin olive oil(EVOO)is the typical sources of fat in the Mediterranean diet which...The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease.Extra virgin olive oil(EVOO)is the typical sources of fat in the Mediterranean diet which have been shown to have noteworthy nutritional value and positive impact on human health.It is worth noting that EVOO owes its superior nutritional value to its bioactive composition.The main component of EVOO is monounsaturated fatty acids(MUFAs)in the form of oleic acid.Oleic acid accounts for up to 70%-80%of EVOO.Secondly,EVOO contains approximately more than 30 phenolic compounds,of which HT is essential for the protection against cardiovascular diseases.In this review,we focused on the potential mechanisms of oleic acid and polyphenols combat cardiovascular diseases risk in terms of oxidative stress,inflammation,blood pressure,endothelial function and cholesterol.This review might provide a reference for the studies on cardiovascular protective effects of EVOO.展开更多
Caffeine intake during pregnancy is common,while its effect on gut microbiota composition of offspring and the relationship with susceptibility to adult diseases remains unclear.This study aimed to confirm the effects...Caffeine intake during pregnancy is common,while its effect on gut microbiota composition of offspring and the relationship with susceptibility to adult diseases remains unclear.This study aimed to confirm the effects of prenatal caffeine exposure(PCE)on the gut microbiota composition and its metabolites in female offspring rats,and to further elucidate its underlying mechanism and intervention targets in adult non-alcoholic fatty disease(NAFLD).The results showed that the gut microbiota of PCE female offspring at multiple time points from infancy to adolescence were significantly changed with depletion of butyric acid-producing bacteria,leading to a decrease in butyric acid in adulthood.It was also found that PCE female offspring rats were sensitive to NAFLD induced by a postnatal high-fat diet(HFD),which is mainly related to the enhancement of hepatic triglyceride synthesis function.Through mechanism exploration,we found that HFD further reduced the fecal and serum butyric acid levels in the PCE female offspring,which was significantly negatively correlated with hepatic SREBP-1c/FASN mRNA expression and triglyceride level.In vivo and in vitro experiments confirmed that sodium butyrate(NaB)supplementation could reduce hepatic lipid accumulation through MCT1/GPR109A-AMPK,thereby effectively decreasing the susceptibility to NAFLD in the PCE female offspring rats.展开更多
Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediati...Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.展开更多
The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A com...The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.展开更多
基金supported by the National Natural Science Foundation of China(82073494)Key Re-search and Development Program of Shaanxi Prov-ince(2020SF-076)+1 种基金Special R&D Program Proj-ect of Chinese Academy of Se-enriched Industry(2020FXZX0501)the Subject Innovation Team of Shaanxi University of Chinese Medicine(132041933).
文摘Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease(KBD).We also analyzed the interaction between the CpGs methylations and CpG-SNPs.Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects.Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF-MS).The CpGs methylation levels were compared between samples from KBD patients and healthy subjects.The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes.Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls(P<0.05).The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls(P<0.05).The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls.The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype(P<0.05).Conclusion The methylation level of DIO2 increases in KBD patients.Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.
文摘Grape crops are a great source of income for farmers.The yield and quality of grapes can be improved by preventing and treating diseases.The farmer’s yield will be dramatically impacted if diseases are found on grape leaves.Automatic detection can reduce the chances of leaf diseases affecting other healthy plants.Several studies have been conducted to detect grape leaf diseases,but most fail to engage with end users and integrate the model with real-time mobile applications.This study developed a mobile-based grape leaf disease detection(GLDD)application to identify infected leaves,Grape Guard,based on a TensorFlow Lite(TFLite)model generated from the You Only Look Once(YOLO)v8 model.A public grape leaf disease dataset containing four classes was used to train the model.The results of this study were relied on the YOLO architecture,specifically YOLOv5 and YOLOv8.After extensive experiments with different image sizes,YOLOv8 performed better than YOLOv5.YOLOv8 achieved 99.9%precision,100%recall,99.5%mean average precision(mAP),and 88%mAP50-95 for all classes to detect grape leaf diseases.The Grape Guard android mobile application can accurately detect the grape leaf disease by capturing images from grape vines.
文摘Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.
基金supported by Natural Science Foundation of Shandong province(ZR2021QH022,ZR2021QB198)National Natural Science Foundation of China(82001286)the Open Project of Liaocheng University Animal Husbandry Discipline(319462207-24)。
文摘Emerging evidence supports that sleep disorders are the main risk factor for sporadic Alzheimer's disease(AD),and iron dysregulation may be the link between them.Our previous studies have confirmed that ketogenic diet(KD)can prevent chronic sleep deprivation-induced AD.However,it is uncertain whether exogenous ketones supplements(EKS),as an alternative intervention,have the same effects as KD.Thus,we investigated the prophylactic efficiency of EKS on chronic sleep deprivation-induced AD and reveal the underlying mechanism focus on iron metabolism.We observed that the prophylactic efficacy of EKS against chronic sleep deprivation-induced AD was comparable to that of KD.Meanwhile,our results suggest that both EKS and KD inhibited iron metabolism disorder through regulation of iron metabolism-related proteins.Moreover,we found that both EKS and KD reduced hippocampal mitochondrial dysfunction and iron-mediated lipid peroxides.Furthermore,EX527(silent information regulator 1(Sirt1)inhibitor),mostly abrogated these above protections of EKS,suggesting that the prophylactic effect of EKS on AD is partly dependent on Sirt1.Our findings provide novel evidence that EKS can be developed as functional foods to prevent or delay the development of AD,particularly in individuals with sleep disorders.
基金supported by the National Natural Science Foundation of China(U22A20272,82173807,82170497)。
文摘Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.
基金supported by grants from National Natural Science Foundation of China(82072709,81902441)Natural Science Foundation of Tianjin Municipal(23JCYBJC00850)+1 种基金China Postdoctoral Science Foundation(2022M712374)Tianjin“131”Innovative Talent Team Project(201926)。
文摘Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide.Gut microbiota and its metabolites alteration are closely related to NAFLD.Nootkatone is an edible flavorant derived from grapefruit which has a variety of biological activities.However,the precise mechanisms of nootkatone on NAFLD remains to be defined.Our results showed that nootkatone prevented body weight gain and decreased serum lipid level,hepatic lipogenesis,hepatic proinflammatory cytokines secretion in NAFLD mice.Also,nootkatone attenuated inflammatory response via inhibiting TLR4/NF-κB/NLRP3 pathway.Moreover,nootkatone restored intestinal barrier damage through increasing tight junction proteins and short chain fatty acids contents.Further 16S rRNA sequencing of colonic content suggested that nootkatone recovered the disturbed gut microbiota to improve NAFLD.Spearman correlation analysis between gut microbiota and NAFLD related parameters indicated that nootkatone regulated lipid metabolism and immunity via altering the gut microbiota.In conclusion,these findings revealed that nootkatone alleviated hepatic lipid homeostasis and inflammatory response in NAFLD mice,which associated with intestinal barrier integrity and the regulation of gut microbiota.This study provides new perspectives that nootkatone has efficacy on NAFLD via“gut-liver axis”,and nootkatone is expected to be developed as a functional food additive.
文摘Cardiovascular diseases(CVD)are the leading cause of death in the world and one of the most common diseases in the elderly,with high prevalence and poor prognosis,which seriously affect the health of the elder patients.One report showed that global deaths from CVD increased from 12.4 million in 1990 to 19.8 million in 2022,reflecting the global population growth and aging,as well as the impact of metabolic,environmental,and behavioral risks.[1]With the progress of aging population,the burden of CVD in the elderly in China has increased year by year,and factors including multiple complications,organ function decline,and high complication rate have made the interventional treatment of CVD in the elderly one of the difficulties and focuses in the field of cardiology in China.
基金supported by the National Natural Science Foundation of China(52173143 and 82371108)Natural Science Foundation of Henan Province(232300421176)Basic Science Key Project of Henan Eye Hospital(20JCZD002 and 23JCZD003).
文摘Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.
基金supported by the National Natural Science Foundation of China(22278241)the National Key R&D Program of China(2018YFA0901700)+1 种基金a grant from the Institute Guo Qiang,Tsinghua University(2021GQG1016)Department of Chemical Engineering-iBHE Joint Cooperation Fund.
文摘Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)and two-dimensional carbide and nitride(MXene)with high gas sensitivity and photo responsiveness were formulated using a self-assembly strategy.A light-activated virtual sensor array(LAVSA)based on BP/Ti_(3)C_(2)Tx was prepared under photomodulation and further assembled into an instant gas sensing platform(IGSP).In addition,a machine learning(ML)algorithm was introduced to help the IGSP detect and recognize the signals of breath samples to diagnose CHD.Due to the synergistic effect of BP and Ti_(3)C_(2)Tx as well as photo excitation,the synthesized heterostructured complexes exhibited higher performance than pristine Ti_(3)C_(2)Tx,with a response value 26%higher than that of pristine Ti_(3)C_(2)Tx.In addition,with the help of a pattern recognition algorithm,LAVSA successfully detected and identified 15 odor molecules affiliated with alcohols,ketones,aldehydes,esters,and acids.Meanwhile,with the assistance of ML,the IGSP achieved 69.2%accuracy in detecting the breath odor of 45 volunteers from healthy people and CHD patients.In conclusion,an immediate,low-cost,and accurate prototype was designed and fabricated for the noninvasive diagnosis of CHD,which provided a generalized solution for diagnosing other diseases and other more complex application scenarios.
基金supported by the China Postdoctoral Science Foundation(2021M693870,2022M711395)the National Natural Science Foundation of China(32000426,31971335)Department of Education of Liaoning Province(1911520092).
文摘Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.
文摘BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.
基金This study was supported by the National Natural Science Foundation of China(82003529,72125009)the National Key Research and Development Program of the Ministry of Science and Technology of China(2019YFC2005000)+4 种基金the Chinese Scientific and Technical Innovation Project 2030(2018AAA0102100)the National High Level Hospital Clinical Research Funding(“Star of Outlook”Scientific Research Project of Peking University First Hospital,2022XW06)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-046)the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the PKU-Baidu Fund(2020BD004,2020BD005 and 2020BD032).
文摘Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease(CKD).Methods:In the present study,we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018.Standard time-series regression models and random-effects Meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span,respectively.Results:A total of 768,129 hospitalizations for CKD was recorded during the study period.The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD,especially in sub-tropical cities.With a 1℃ increase in daily mean temperature,the cumulative relative risks(RR)over lag 0-7 d were 1.008[95% confidence interval(CI)1.003-1.012]for nationwide.The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%.Stronger associations were observed among younger patients and those with obstructive nephropathy.Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days(RR=1.116,95%CI 1.069-1.166)above the effect of daily mean temperature.Conclusions:Short-term heat exposure may increase the risk of hospitalization for CKD.Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.
基金supported by the National Natural Science Foundation of China(No.32071176)the 14th Five-Year-Plan Advantageous and Characteristic Disciplines(Groups)of Colleges and Universities in Hubei Province for Exercise and Brain Science from Hubei Provincial Department of Education+1 种基金the Chutian Scholar ProgramInnovative Start-Up Foundation from Wuhan Sports University to Ning Chen。
文摘Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammation and anti-oxidation functions,and improving mitochondrial quality.Chronic diseases as non-communicable diseases are mainly caused by multiple factors,such as physiological decline and dysfunction in the body,and have become a significant challenge on public health worldwide.It is worth noting that chronic diseases such as Alzheimer's disease(AD),Parkinson's disease(PD),muscle atrophy,cardiovascular disease,obesity,and cancer are accompanied by abnormal mitochondrial function.Therefore,targeted regulation of mitochondria may be a meaningful way to prevent and treat chronic diseases.Increasing evidence has confirmed that RSV is actively involved in regulating mitochondria,and it has become an essential consideration to prevent and treat chronic diseases through targeting mitochondria and improving corresponding functions.In this article,current studies on RSV to optimize mitochondrial quality for preventing and alleviating chronic disease are systematically summarized,which can provide a theoretical reference for the development of functional foods or drugs to combat chronic diseases.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 72174121 and 71774111)the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learningthe Project for the Natural Science Foundation of Shanghai, China (Grant No. 21ZR1444100)
文摘While the interaction between information and disease in static networks has been extensively investigated,many studies have ignored the characteristics of network evolution.In this study,we construct a new two-layer coupling model to explore the interactions between information and disease.The upper layer describes the diffusion of disease-related information,and the lower layer represents the disease transmission.We then use power-law distributions to examine the influence of asymmetric activity levels on dynamic propagation,revealing a mapping relationship characterizing the interconnected propagation of information and diseases among partial nodes within the network.Subsequently,we derive the disease outbreak threshold by using the microscopic Markov-chain approach(MMCA).Finally,we perform extensive Monte Carlo(MC)numerical simulations to verify the accuracy of our theoretical results.Our findings indicate that the activity levels of individuals in the disease transmission layer have a more significant influence on disease transmission compared with the individual activity levels in the information diffusion layer.Moreover,reducing the damping factor can delay disease outbreaks and suppress disease transmission,while improving individual quarantine measures can contribute positively to disease control.This study provides valuable insights into policymakers for developing outbreak prevention and control strategies.
文摘Objective To identify cuproptosis-and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.Methods The gene expression dataset GSE89632 was retrieved from the Gene Expression Omnibus database to identify differentially expressed genes(DEGs)between the non-alcoholic steatohepatitis(NASH)group and the healthy group using the'limma'package in R software and weighted gene co-expression network analysis.Gene ontology,kyoto encyclopedia of genes and genomes pathway,and single-sample gene set enrichment analyses were performed to identify functional enrichment of DEGs.Ferroptosis-and cuproptosis-related genes were obtained from the FerrDb V2 database and available literatures,respectively.A combined signature for cuproptosis-and ferroptosis-related genes,called CRF,was constructed using the STRING database.Hub genes were identified by overlapping DEGs,WGCNA-derived key genes,and combined signature CRF genes,and validated using the GSE109836 and GSE227714 datasets and real-time quantitative polymerase chain reaction.A nomogram of NASH diagnostic model was established utilizing the'rms'package in R software based on the hub genes,and the diagnostic value of hub genes was assessed using receiver operating characteristic curve analysis.In addition,immune cell infiltration in NASH versus healthy controls was examined using the CIBERSORT algorithm.The relationships among various infiltrated immune cells were explored with Spearman's correlation analysis.Results Analysis of GSE89632 identified 236 DEGs between the NASH group and the healthy group.WGCNA highlighted 8 significant modules and 11,095 pivotal genes,of which 330 genes constituted CRF.Intersection analysis identified IL6,IL1B,JUN,NR4A1,and PTGS2 as hub genes.The hub genes were all downregulated in the NASH group,and this result was further verified by the NASH validation dataset and real-time quantitative polymerase chain reaction.Receiver operating characteristic curve analysis confirmed the diagnostic efficacy of these hub genes with areas under the curve of 0.985,0.941,1.000,0.967,and 0.985,respectively.Immune infiltration assessment revealed that gamma delta T cells,M1 macrophages,M2 macrophages,and resting mast cells were predominantly implicated.Conclusion Our investigation underscores the significant association of cuproptosis-and ferroptosis-related genes,specifically IL6,IL1B,JUN,NR4A1,and PTGS2,with NASH.These findings offer novel insights into the pathogenesis of NASH,potentially guiding future diagnostic and therapeutic strategies.
基金supported by the grant from Italian Ministry of Health Ricerca Corrente 2023 IRCCS“S.de Bellis”by the Apulia Region grant SiCURA“Soluzioni Innovative per la gestione del paziente e il follow up terapeutico della Colite UlceRosA”(KC3U5Y1).
文摘Nowadays,inflammatory bowel disease(IBD)-patient therapies are mainly based on corticosteroid,thiopurine,and immunomodulator treatments.Patients with active disease,that do not respond to corticosteroid and/or thiopurine treatment,can switch to the usage of the chimeric monoclonal antibody infliximab(IFX).However,to date,no treatment appeared to be conclusive in lowering the incidence of IBD relapses.With the aim to increase the effectiveness of IFX treatment,we combined it with an adjuvant purple corn supplementation enriched in anthocyanins.IBD-patients were enrolled before they underwent to the IFX-infusion,and they were allocated in 2 different study arms.Patients in the intervention-arm followed a dietary supplementation with purple corn water-soluble extract,whereas control patients had a daily consumption of red fruit tea.16S rDNA gene-sequencing and high-resolution mass-spectrometry metabo-lipidomics analyses were conducted on stool and sera samples,respectively.As a result,the experimental intervention mainly affected the serum metabolome of IBD-patients by decreasing the concentration of specific lipids.Focusing on IBD patient annotated taxa,a significant decrease in Lactobacillus and Bifi dobacterium relative abundances was found.As far as it concerns the ulcerative colitis patient subset,the experimental intervention led to a decrease in Alistipes and Erysipelotrichaceae UCG-003 genus abundances and a concomitant Parabacteroides increase.On the contrary,after treatment,Crohn’s disease patients did not exhibit metataxonomics differences at the genus level.At the end of the treatment that led to a reshaped microbiota community,the gathered data paves the way for the usage of a specifically designed probiotic supplementation as a valuable strategy for IBD-patients under IFX infusion.
基金supported by the CACMS Innovation Fund(CI2021A00914)the Beijing Novaprogram(Z211100002121062)+1 种基金the Opening Project of the Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province(2C32001)the National Natural Science Foundation of China(82004193)。
文摘The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease.Extra virgin olive oil(EVOO)is the typical sources of fat in the Mediterranean diet which have been shown to have noteworthy nutritional value and positive impact on human health.It is worth noting that EVOO owes its superior nutritional value to its bioactive composition.The main component of EVOO is monounsaturated fatty acids(MUFAs)in the form of oleic acid.Oleic acid accounts for up to 70%-80%of EVOO.Secondly,EVOO contains approximately more than 30 phenolic compounds,of which HT is essential for the protection against cardiovascular diseases.In this review,we focused on the potential mechanisms of oleic acid and polyphenols combat cardiovascular diseases risk in terms of oxidative stress,inflammation,blood pressure,endothelial function and cholesterol.This review might provide a reference for the studies on cardiovascular protective effects of EVOO.
基金funded by the National Natural Science Foundation of China (82030111, U23A20407)the National Key Research and Development Program of China (2020YFA0803900)+2 种基金the Major Technological Innovation Projects of Hubei Province (2019ACA140)Hubei Province's Outstanding Medical Academic Leader programthe Basic and Clinical Medical Research Joint Fund of Zhongnan Hospital, Wuhan University (ZNLH202208)
文摘Caffeine intake during pregnancy is common,while its effect on gut microbiota composition of offspring and the relationship with susceptibility to adult diseases remains unclear.This study aimed to confirm the effects of prenatal caffeine exposure(PCE)on the gut microbiota composition and its metabolites in female offspring rats,and to further elucidate its underlying mechanism and intervention targets in adult non-alcoholic fatty disease(NAFLD).The results showed that the gut microbiota of PCE female offspring at multiple time points from infancy to adolescence were significantly changed with depletion of butyric acid-producing bacteria,leading to a decrease in butyric acid in adulthood.It was also found that PCE female offspring rats were sensitive to NAFLD induced by a postnatal high-fat diet(HFD),which is mainly related to the enhancement of hepatic triglyceride synthesis function.Through mechanism exploration,we found that HFD further reduced the fecal and serum butyric acid levels in the PCE female offspring,which was significantly negatively correlated with hepatic SREBP-1c/FASN mRNA expression and triglyceride level.In vivo and in vitro experiments confirmed that sodium butyrate(NaB)supplementation could reduce hepatic lipid accumulation through MCT1/GPR109A-AMPK,thereby effectively decreasing the susceptibility to NAFLD in the PCE female offspring rats.
基金financially supported by the National Natural Science Foundation of China(82074131,81774170,82260926)the Guangdong Basic and Applied Basic Research Foundation(2018B030306012,2022A1515220179,2021A1515011667)+2 种基金the Outstanding Youth Development Scheme project of Southern Medical University(G621299870)the Young Elite Scientists Sponsorship Program by CACM(2021-QNRC2-B28)the China Postdoctoral Science Foundation(2022M721532).
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.
基金supported by National Natural Science Foundation of China(NSFC:82073538 and 81773433)by the 2018 Chinese Nutrition Society(CNS)Nutrition Research Foundation-DSM Research Fund(CNS-DSM2018A30)。
文摘The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.
