In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented...In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented product FGPA-G 2-H on Aβ25-35-induced PC 12 cells were explored.The structure of GPA-G 2-H was determined by means of zeta potential analysis,FTIR,HPLC,XRD,GC-MS and NMR.The backbone of GPA-G 2-H was mainly composed of→4)-α-D-Glcp-(1→with branches substituted at O-3.Notably,GPA-G 2-H was degraded by intestinal microbiota in vitro with total sugar content and pH value decreasing,and short-chain fatty acids(SCFAs)increasing.Moreover,GPA-G 2-H significantly promoted the proliferation of Lactobacillus,Muribaculaceae and Weissella,thereby making positive alterations in intestinal microbiota composition.Additionally,FGPA-G 2-H activated the Nrf 2/HO-1 signaling pathway,enhanced HO-1,NQO 1,SOD and GSH-Px,while inhabited Keap 1,MDA and LDH,which alleviated Aβ-induced oxidative stress in PC 12 cells.These provide a solid theoretical basis for the further development of ginseng polysaccharides as functional food and antioxidant drugs.展开更多
As a key component of shale oil,petroleum fractions,and chemical products,the oxidative pyrolysis behavior of paraffin directly influences energy conversion efficiency and the direction of process optimization.A deep ...As a key component of shale oil,petroleum fractions,and chemical products,the oxidative pyrolysis behavior of paraffin directly influences energy conversion efficiency and the direction of process optimization.A deep understanding of its oxidative pyrolysis mechanism is crucial for addressing wax deposition in oil and gas extraction,enhancing product selectivity in cracking processes,and advancing novel clean fuel technologies.Traditional experimental methods face challenges in capturing transient free-radical reaction pathways at high temperatures,whereas molecular dynamics simulations offer a powerful approach to bridge the research gap in elucidating atomic-scale dynamic mechanisms.This database is constructed based on high-precision molecular dynamics simulations,comprising oxidative pyrolysis trajectory data for three paraffin models featuring different straight-chain hydrocarbon distributions within the temperature range of 2100-2500 K.The COMPASS force field was employed to optimize the initial structures,and the ReaxFF reactive force field was used to simulate the oxidative pyrolysis process.The database includes atomic trajectories,species evolution information,and reaction network analysis results for both heating and isothermal cracking processes,with a total data volume of approximately 141 GB(including 150000 atomic configuration frames).The data is stored in a hierarchical directory structure,supporting multi-scale oxidative pyrolysis mechanism studies and providing atomic-scale dynamic evidence for revealing carbon chain length effects and temperature sensitivity.展开更多
Typhoon Bebinca in 2024 experienced a nearshore outbreak(a rapid intensification(RI)near the coast),making accurate forecasting of unpredictable tracks and intensities highly challenging.The AI model is superior to th...Typhoon Bebinca in 2024 experienced a nearshore outbreak(a rapid intensification(RI)near the coast),making accurate forecasting of unpredictable tracks and intensities highly challenging.The AI model is superior to the numerical model for typhoon track prediction but performs worse for intensity forecasting.Vortex initialization is an effective approach to further improve numerical prediction via cycle assimilation,accounting for multiple relocating TC centers and adjusting the typhoon initial structure.In addition,by integrating numerical runs with an AI weather model through real-time dynamic weight correction of the forecast,the predictive skill is further improved.For example,it can reduce the deviation of 72-h track forecasting by 25%compared with the numerical model and decrease the intensity deviation by 2%and 56%relative to the numerical run and AI forecasts,respectively.On the basis of the best-performing forecasting,the inner-core convective burst(CB)characteristics are illuminated.The attributions of the nearshore outbreak and RI of Typhoon Bebinca are examined.From the viewpoint of bottom-up convection growth,the CB is associated with the energy supply from the high-boundarylayer CAPE,the following upward-developing secondary circulation,and accompanying latent heat release of hydrometeors.The contracted radius of maximum winds(RMW)and increased inertial stability within the inner core region effectively prevent the escape of the high-energy atmosphere and favor rapid intensification and maintenance of the offshore burst of a typhoon.The intensifying secondary circulation further promotes the primary circulation of the TC and RI processes through the gradient wind balance.展开更多
In molybdenum chemistry,the oxidative addition of o-quinone or 1,2-dicarbonyl compounds to molybdenum has been widely used in Mo-catalyzed C—C bond construction.The carbonyl oxidative addition to Mo(0)or Mo(Ⅱ)is the...In molybdenum chemistry,the oxidative addition of o-quinone or 1,2-dicarbonyl compounds to molybdenum has been widely used in Mo-catalyzed C—C bond construction.The carbonyl oxidative addition to Mo(0)or Mo(Ⅱ)is the critical elementary reaction of molybdenum catalysis.However,the relevant density functional theory(DFT)studies are relatively scarce,especially regarding the rational selection of functionals.In this work,14 functionals were employed to investigate the Mo-catalyzed carbonyl oxidative addition step.A benchmark study was carried out to evaluate their performance in structure optimization and energy calculation.Analyses of mean absolute error(MAE)and mean squared error(MSE)indicated that the B3LYP-D3(BJ),TPSSh,and ωB97X-D functionals exhibited superior performance in structure optimization.Using the DLPNO-CCSD(T)functional as the reference,the M06,M06-L,and MN15-L functionals exhibited good performance for energy calculation based on the structures optimized using the B3LYP-D3(BJ)functional.In particular,MN15-L provided the best performance with the smallest MAE and MSE.展开更多
By using carbohydrates as the biomass carbon sources,Se/C materials could be easily prepared.The materials could catalyze the oxidative deoximation reactions,which are significant transformations in both pharmaceutica...By using carbohydrates as the biomass carbon sources,Se/C materials could be easily prepared.The materials could catalyze the oxidative deoximation reactions,which are significant transformations in both pharmaceutical industry and fine chemical production.Compared with the reported organoseleniumcatalyzed ionic reactions,the Se/C-catalyzed deoximation reactions occurred via unique free radical mechanisms,endowing the Se species high catalytic reactivity.The Se/C catalysts were recyclable and their turnover numbers(TONs)were high(>10^(4)),making the reactions practical for industrial grade preparation.The unique free radical mechanisms of the reaction and green and practical features of the catalysts are the characteristics and advantages of the work.展开更多
A series of new chiral amide ligands were prepared from natural amino acids and applied to the copper-catalyzed asymmetric oxidative homocoupling reaction of 3-hydroxy-2-naphthoates.By optimizing the reaction conditio...A series of new chiral amide ligands were prepared from natural amino acids and applied to the copper-catalyzed asymmetric oxidative homocoupling reaction of 3-hydroxy-2-naphthoates.By optimizing the reaction conditions,it was found that when using L3(5 mol%)as the ligand,CuCl(5 mol%)as the catalyst,dichloromethane as the solvent,2,2,6,6-tetramethylpiperidine 1-oxyl(TEMPO)/O2 as the oxidant,and under the reaction condition of 40℃,this method exhibited good substrate tolerance.Under these conditions,a series of chiral 1,1'-bi-2-naphthol(BINOL)derivatives were synthesized with yields of 45%~90%and enantioselectivities ranging from 50∶50 to 97∶3.展开更多
Background Heat stress(HS)can impair boar testicular function,leading to reproductive issues.However,chlorogenic acid(CGA)has been shown to mitigate HS-induced damage in various livestock and poultry species.Prepubert...Background Heat stress(HS)can impair boar testicular function,leading to reproductive issues.However,chlorogenic acid(CGA)has been shown to mitigate HS-induced damage in various livestock and poultry species.Prepuberty is an important stage of testicular development in boars after birth.However,the protective effect of CGA on testicular HS injury during prepuberty boars and the underlying mechanisms are still not fully understood.Results In vivo,a total of 30 healthy boars with similar body weights and ages were obtained and randomly divided into 3 groups,which were fed a basal diet supplemented with CGA 0(the ND_TN group),0(the ND_HS group)or 1,000(the CGA_HS group)mg/kg.After being fed for 28 d,all the groups,except the ND_TN group,were treated with high temperature for 7 d,after which samples were collected from the boars and analysed.The results showed that CGA significantly mitigated the HS-induced reduction in T-AOC content in testicular tissue and sperm density.Mechanistically,multiomics analysis revealed that the genes differentially expressed by CGA and HS were predominantly associated with the glutathione metabolism pathway.The combined analysis of transcriptomics and proteomics revealed that only BLVRA was affected by both HS and CGA when the mRNA and protein levels of a gene showed differential expression with the same trend.In vitro studies confirmed that CGA modulated GPX3 expression via BLVRA,affected GPx activity,and attenuated HS-induced ROS accumulation.Conclusions In conclusion,prepubertal HS impairs the spermatogenic capacity of boars.BLVRA may mediate the testicular protective effect of CGA,although in vivo validation of this pathway is needed.This study contributes to elucidating the mechanisms underlying the effects of HS on prepubertal boar testicular development using multiomics approaches,laying a foundation for the potential utilization of CGA in swine production.展开更多
The liver,a critical metabolic organ,is particularly vulnerable to damage upon aluminum exposure.However,the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated.Thi...The liver,a critical metabolic organ,is particularly vulnerable to damage upon aluminum exposure.However,the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated.This study aimed to investigate the adverse effects of aluminum exposure on mouse liver tissue.The results indicated that AlCl_(3) exposure induced significant liver dysfunction,characterized by reduced adenosine triphosphate levels,elevated plasma alanine aminotransferase and aspartate aminotransferase.Histopathological analysis of liver tissue revealed marked histological damage,accompanied by substantial iron deposition.Further examinations demonstrated elevated hepatic levels of malondialdehyde,4-hydroxynonenal,and reactive oxygen species,decreased levels of glutathione(GSH)and superoxide dismutase,increased levels of oxidized glutathione(GSSG),and a reduced GSH/GSSG ratio.The mRNA and protein expression of ferroptosis-related molecules,including downregulated glutathione peroxidase 4 and solute carrier family 7 member 11,were significantly downregulated,while acyl-CoA synthetase long-chain family member 4,ferritin heavy chain 1,and iron regulatory protein 1 levels were significantly upregulated.Treatment with Ferrostatin-1 markedly ameliorated liver dysfunction and histopathological damage,attenuating signs of ferroptosis.These findings highlight the potential of ferroptosis-targeted therapies as a viable treatment strategy for aluminum exposure-induced hepatocyte injury.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be el...Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.展开更多
Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The ...Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models.Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers(NRF2 and GCLC).EtOH metabolism was examined by measuring alchohol-metabolizing enzymes(alcohol dehydrogenase and aldehyde dehydrogenase)and cytochrome P450 enzymes.Furthermore,lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers(SREBP-1 and FAS).Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase,and performing histological analysis.Results:In hepatocytes and zebrafish,both CPs and chondroitin reduced oxidative stress,downregulated cytochrome P450 enzymes and lipogenic markers,and enhanced antioxidant defenses,with chondroitin showing the strongest hepatoprotection.In EtOH-fed mice,chondroitin significantly improved liver enzyme profiles,reduced hepatic lipid accumulation and inflammation,and restored antioxidant and metabolic homeostasis.Conclusions:Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress,EtOH metabolism,and lipid regulation.These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage.展开更多
Oxidative potential(OP)can be used as an indicator of the health risks of particulate matter in the air.To study the variation and sources of OP,we conducted an observation of PM_(2.5) in a megacity in southern China ...Oxidative potential(OP)can be used as an indicator of the health risks of particulate matter in the air.To study the variation and sources of OP,we conducted an observation of PM_(2.5) in a megacity in southern China in winter and spring of 2021.The results show that the average concentration of PM_(2.5) decreased by 47%from winter to spring,while volume-normalized and mass-normalized OP(i.e.,OP_(v) and OP_(m))increased by 6%and 69%,respectively.It suggests that the decline of PM_(2.5) may not necessarily decrease the health risks and the intrinsic toxicity of PM_(2.5).Variations of OP_(v) and OP_(m) among different periods were related to the different source contributions and environmental conditions.The positive matrix factorization model was used to identify the major sources of OP_(v).OP_(v) was mainly contributed by biomass burning/industrial emissions(29%),soil/road dust(20%),secondary sulfate(14%),and coal combustion(13%)in winter.Different major sources were resolved to be secondary sulfate(36%),biological sources(21%),and marine vessels(20%)in spring,presenting the substantial contribution of biological sources.The analysis shows strong associations between OP_(v) and both live and dead bacteria,further confirming the important contribution of bioaerosols to the enhancement of OP.This study highlights the importance of understanding OP in ambient PM_(2.5) in terms of public health impact and provides a new insight into the biological contribution to OP.展开更多
Background During the weaning phase,piglets are exposed to significant physiological and environmental stressors,which disrupt the balance of their intestinal microbiota and often lead to severe diarrhea.Previous stud...Background During the weaning phase,piglets are exposed to significant physiological and environmental stressors,which disrupt the balance of their intestinal microbiota and often lead to severe diarrhea.Previous studies have demonstrated that alfalfa fiber,derived from the stems and leaves of alfalfa,can effectively alleviate diarrhea in piglets.Additionally,multiple studies have highlighted the potential of fecal microbiota transplantation(FMT)in mitigating diarrhea in various models of intestinal diseases in young animals.However,the specific mechanisms by which FMT from targeted sources alleviates diarrhea in weaned piglets remain to be fully elucidated.Results In this study,FMT from donor piglets fed an alfalfa fiber-supplemented diet effectively alleviated diarrhea,improved intestinal morphology,and enhanced gut barrier function in weaned piglets.FMT further promoted the colonization of beneficial bacterial genera(including UCG-005,unclassified Lachnospiraceae,Lachnospiraceae AC2044 group,UCG-002,Candidatus Saccharimonas,and Lachnospiraceae ND3007 group)while inhibiting the detrimental genus Tyzzerella,consequently enhancing the production of short-chain fatty acids(SCFAs).Additionally,FMT upregulated riboflavin metabolism,leading to elevated flavin adenine dinucleotide(FAD)levels and increased glutathione reductase activity,thereby collectively attenuating lipopolysaccharide(LPS)-induced oxidative stress and contributing to intestinal health.Conclusions We found that FMT modulates the structure of the gut microbiota,enhances microbial diversity and composition,increases the production of SCFAs,and upregulates riboflavin metabolism to elevate FAD levels.These changes collectively enhance immune and antioxidant capacities,thereby alleviating diarrhea.展开更多
Background:Myocardial infarction(MI)remains a major global public health challenge.Although advances in reperfusion therapy have reduced acute mortality,post-infarction cardiac remodeling continues to pose a substanti...Background:Myocardial infarction(MI)remains a major global public health challenge.Although advances in reperfusion therapy have reduced acute mortality,post-infarction cardiac remodeling continues to pose a substantial threat to long-term cardiovascular health.Oxidative stress and the ensuing inflammatory response are key drivers of this pathological process,leading to cardiomyocyte death,myocardial fibrosis,and functional impairment.Among the regulatory pathways involved,the kelch-like ECH-associated protein 1(Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)axis has emerged as a critical therapeutic target for mitigating post-MI cardiac injury.Methods:A murine MI model was established by permanent ligation of the left anterior descending coronary artery.Mice received oral Tongxinbi formula(TXB)at low,medium,or high doses(9/18/36 g/kg)once daily for 28 days.Cardiac function was assessed by echocardiography;myocardial fibrosis by Masson’s trichrome;and endothelial integrity by CD31 immunofluorescence.Plasma markers of endothelial function and inflammation were quantified.In vitro,oxidative stress was induced by H2O2 in vascular endothelial cells and cardiomyocytes,followed by treatment with TXB drug-containing serum.Western blot and RT-qPCR were used to measure components of the Keap1/Nrf2 pathway;ELISA quantified oxidative stress and inflammatory indices.Conditioned-medium experiments evaluated endothelial cell–mediated paracrine protection of cardiomyocytes.Results:TXB significantly improved cardiac function and reduced myocardial fibrosis after MI,in association with preservation of microvascular structure and systemic attenuation of oxidative stress and inflammation.In vitro,TXB activated the endothelial Keap1/Nrf2 pathway,enhanced cellular antioxidant defenses,increased VEGF secretion,and,via endothelial cell-mediated paracrine signaling,alleviated cardiomyocyte injury under oxidative stress.Conclusion:TXB exerts anti-fibrotic and cardioprotective effects by activating Nrf2 signaling and engaging endothelial-mediated paracrine mechanisms,collectively mitigating oxidative stress and inflammation in the post-MI setting.展开更多
In order to reveal the signaling pathways triggered by elicitor in plant-microbe interactions, the mechanisms of hypersensitive necrosis responses in Nicotiana tabacum L. cv. Gexin III induced by palmin were studied a...In order to reveal the signaling pathways triggered by elicitor in plant-microbe interactions, the mechanisms of hypersensitive necrosis responses in Nicotiana tabacum L. cv. Gexin III induced by palmin were studied at molecular and cellular level. The burst of superoxide, intercellular diffusion of hydrogen peroxide and process of cell death induced by palmin were investigated in tobacco plants by biochemical methods and Confocal microscopy. The results showed that a large amount of O-2(.-) was rapidly generated in tobacco cell elicited by palmin as a result of activation of NADPH oxidase, and the O-2(.-) was dismutated into H2O2 immediately by superoxide dismutase (SOD). Accumulation and intercellular diffusion of H2O2 were shown to be a trigger for hypersensitive cell death; and Ca2+ and some specific protein kinase were also shown to be involved in the activation of oxidative burst in tobacco cell induced by palmin.展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
AIM：To evaluate the phagocytic activity and neutrophil oxidative burst in liver cirrhosis.METHODS： In 45 patients with advanced postalcoholic liver cirrhosis （aged 45±14 years） and in 25 healthy volunteers （...AIM：To evaluate the phagocytic activity and neutrophil oxidative burst in liver cirrhosis.METHODS： In 45 patients with advanced postalcoholic liver cirrhosis （aged 45±14 years） and in 25 healthy volunteers （aged 38±5 years）, the percentage of phagocytizing cells after in vitro incubation with E. coli （Phagotest Kit）, phagocytic activity （mean intensity of fluorescence, MIF） and the percentage of neutrophil oxidative burst （Bursttest Kit）, and the level of free oxygen radical production （MIF of Rodamine 123） were analyzed by flow cytometry. The levels of soluble sICAM-1, sVCAM-1, sP-selectin, sE-selectin, sL-selectin, and TNF-α were determined in blood serum.RESISTS： The percentage of E. coli phagocytizing neutrophils in liver cirrhosis patients was comparable to that in healthy subjects. MIF of neutrophil - ingested E. coli was higher in patients with liver cirrhosis. The oxidative burst in E. coli phagocytizing neutrophils generated less amount of active oxygen compounds in liver cirrhosis pa- tients （MIF of R123：24.7±7.1 and 29.7±6.6 in healthy, P〈0.01）. Phorbol myristate acetate （PMA） - stimulated neutrophilsproduced less reactive oxidants in liver cirrhosis patients than in healthy subjects （MIF of R123： 42.7±14.6 vs 50.2±13.3, P〈0.01）. A negative correlation was observed between oxidative burst MIF of PMA-stimulated neutrophils and ALT and AST levels （r -0.35, P〈0.05; r-0.4, P〈0.03）. sVCAM-1, sICAM-1, sE-selectin concentrations correlated negatively with the oxygen free radical production （MIF of R123） in neutrophils after PMA stimulation in liver cirrhosis patients （r-0.45, P〈0.05, r-0.41, P〈0.05; r-0.39, P〈0.05, respectively）.CONCLUSION： Neutrophil metabolic activity diminishes together with the intensification of liver failure. The metabolic potential of phagocytizing neutrophils is significantly lower in liver cirrhosis patients, which can be one of the causes of immune mechanism damage. The evaluation of oxygen metabolism of E. coli-stimulated neutrophils reveals that the amount of released oxygen metabolites is smaller in liver cirrhosis patients than in healthy subjects.展开更多
Reactive oxygen species(ROS)are widely generated in various redox reactions in plants.In earlier studies.ROS were considered toxic byproducts of aerobic metabolism.In recent years,it has become clear that ROS act as p...Reactive oxygen species(ROS)are widely generated in various redox reactions in plants.In earlier studies.ROS were considered toxic byproducts of aerobic metabolism.In recent years,it has become clear that ROS act as plant signaling molecules that participate in various processes such as growth and development.Several studies have elucidated the roles of ROS from seed germination to senescence.However,there is much to discover about the diverse roles of ROS as signaling molecules and their mechanisms of sensing and response.ROS may provide possible benefits to plant physiological processes by supporting cellular proliferation in cells that maintain basal levels prior to oxidative effects.Although ROS are largely perceived as either negative by-products of aerobic metabolism or makers for plant stress,elucidating the range of functions that ROS play in growth and development still require attention.展开更多
Objective:To evaluate in vitro immunomodulating properties and potential cytotoxicity of six tropical medicinal herbs and food plants namely Antidesma madagascariense(Euphorbiaceae) (AM),Erylhroxylum macrocarpum(Eryth...Objective:To evaluate in vitro immunomodulating properties and potential cytotoxicity of six tropical medicinal herbs and food plants namely Antidesma madagascariense(Euphorbiaceae) (AM),Erylhroxylum macrocarpum(Erythroxylaceae)(EM),Faujasiopsis flexuosa(Asteraceae) (FF),Pittosporum senacia(Pittosporaceae)(PS),Momordica charantia(Cucurbitaceae)(MC) and Orimum tenuiflorum(Lamiaceae)(Of).Methods:Initially,the crude water and methanol extracts were probed for their capacity to trigger immune cells’ NADPH oxidase and MPO-dependent activities as measured by lucigenin- and luminol-amplified chemiluminescence,respectively; as compared to receptor-dependent(serum opsonised zymosan- OPZ) or receptor-independent phorbol myristerate acetate(PMA).Results:Preliminary screening on whole human blood oxidative buret activity showed significant and concentration-dependent immunomodulating properties of three plants AM,FF and OT.Further investigations of the fractions on isolated human polymorphonuclear cells(PMNs) and mice monocytes using two different pathways for activation of phagocytic oxidative burst showed that ethyl acetate fraction was the most potent extract. None of the active samples had cell-death effects on human PMNs,under the assay conditions as determined by the trypan-blue exclusion assay.Since PMA and OPZ NADPH oxidase complex is activated via different transduction pathways,these results suggest that AM,FF and OT does not affect a specific transductional pathway,but rather directly inhibit a final common biochemical target such as the NADPH oxidase enzyme and/or scavenges ROS.Conclusions:Our findings suggest that some of these plants extracts/fractions were able to modulate significantly immune response of phagocytes and monocytes at different steps,emphasizing their potential as a source of new natural alternative immunomodulatory agents.展开更多
基金Supported by the National Key Research and Development Program of Traditional Chinese Medicine Modernization Project,China(No.2023YFC3504000)the Science and Technology Development Project of Jilin Province,China(No.20240404043ZP)the Science and Technology Innovation Cooperation Project of Changchun Science and Technology Bureau and Chinese Academy of Sciences,China(No.23SH14)。
文摘In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented product FGPA-G 2-H on Aβ25-35-induced PC 12 cells were explored.The structure of GPA-G 2-H was determined by means of zeta potential analysis,FTIR,HPLC,XRD,GC-MS and NMR.The backbone of GPA-G 2-H was mainly composed of→4)-α-D-Glcp-(1→with branches substituted at O-3.Notably,GPA-G 2-H was degraded by intestinal microbiota in vitro with total sugar content and pH value decreasing,and short-chain fatty acids(SCFAs)increasing.Moreover,GPA-G 2-H significantly promoted the proliferation of Lactobacillus,Muribaculaceae and Weissella,thereby making positive alterations in intestinal microbiota composition.Additionally,FGPA-G 2-H activated the Nrf 2/HO-1 signaling pathway,enhanced HO-1,NQO 1,SOD and GSH-Px,while inhabited Keap 1,MDA and LDH,which alleviated Aβ-induced oxidative stress in PC 12 cells.These provide a solid theoretical basis for the further development of ginseng polysaccharides as functional food and antioxidant drugs.
基金Supported by Natural Science Foundation of Shanxi Province (202203021221219)Research on the Construction of Scientific and Technological Innovation Think Tank of Shanxi Association for Science and Technology (KXKT202542)Planning Project under Commerce Statistical Society of China (2025STY122)。
文摘As a key component of shale oil,petroleum fractions,and chemical products,the oxidative pyrolysis behavior of paraffin directly influences energy conversion efficiency and the direction of process optimization.A deep understanding of its oxidative pyrolysis mechanism is crucial for addressing wax deposition in oil and gas extraction,enhancing product selectivity in cracking processes,and advancing novel clean fuel technologies.Traditional experimental methods face challenges in capturing transient free-radical reaction pathways at high temperatures,whereas molecular dynamics simulations offer a powerful approach to bridge the research gap in elucidating atomic-scale dynamic mechanisms.This database is constructed based on high-precision molecular dynamics simulations,comprising oxidative pyrolysis trajectory data for three paraffin models featuring different straight-chain hydrocarbon distributions within the temperature range of 2100-2500 K.The COMPASS force field was employed to optimize the initial structures,and the ReaxFF reactive force field was used to simulate the oxidative pyrolysis process.The database includes atomic trajectories,species evolution information,and reaction network analysis results for both heating and isothermal cracking processes,with a total data volume of approximately 141 GB(including 150000 atomic configuration frames).The data is stored in a hierarchical directory structure,supporting multi-scale oxidative pyrolysis mechanism studies and providing atomic-scale dynamic evidence for revealing carbon chain length effects and temperature sensitivity.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No.XDB0760300)the National Natural Science Foundation of China (Grant Nos.42175010 and 41875079)。
文摘Typhoon Bebinca in 2024 experienced a nearshore outbreak(a rapid intensification(RI)near the coast),making accurate forecasting of unpredictable tracks and intensities highly challenging.The AI model is superior to the numerical model for typhoon track prediction but performs worse for intensity forecasting.Vortex initialization is an effective approach to further improve numerical prediction via cycle assimilation,accounting for multiple relocating TC centers and adjusting the typhoon initial structure.In addition,by integrating numerical runs with an AI weather model through real-time dynamic weight correction of the forecast,the predictive skill is further improved.For example,it can reduce the deviation of 72-h track forecasting by 25%compared with the numerical model and decrease the intensity deviation by 2%and 56%relative to the numerical run and AI forecasts,respectively.On the basis of the best-performing forecasting,the inner-core convective burst(CB)characteristics are illuminated.The attributions of the nearshore outbreak and RI of Typhoon Bebinca are examined.From the viewpoint of bottom-up convection growth,the CB is associated with the energy supply from the high-boundarylayer CAPE,the following upward-developing secondary circulation,and accompanying latent heat release of hydrometeors.The contracted radius of maximum winds(RMW)and increased inertial stability within the inner core region effectively prevent the escape of the high-energy atmosphere and favor rapid intensification and maintenance of the offshore burst of a typhoon.The intensifying secondary circulation further promotes the primary circulation of the TC and RI processes through the gradient wind balance.
基金Project supported by the Fundamental Research Funds for the Central Universities(No.2042025kf0052)。
文摘In molybdenum chemistry,the oxidative addition of o-quinone or 1,2-dicarbonyl compounds to molybdenum has been widely used in Mo-catalyzed C—C bond construction.The carbonyl oxidative addition to Mo(0)or Mo(Ⅱ)is the critical elementary reaction of molybdenum catalysis.However,the relevant density functional theory(DFT)studies are relatively scarce,especially regarding the rational selection of functionals.In this work,14 functionals were employed to investigate the Mo-catalyzed carbonyl oxidative addition step.A benchmark study was carried out to evaluate their performance in structure optimization and energy calculation.Analyses of mean absolute error(MAE)and mean squared error(MSE)indicated that the B3LYP-D3(BJ),TPSSh,and ωB97X-D functionals exhibited superior performance in structure optimization.Using the DLPNO-CCSD(T)functional as the reference,the M06,M06-L,and MN15-L functionals exhibited good performance for energy calculation based on the structures optimized using the B3LYP-D3(BJ)functional.In particular,MN15-L provided the best performance with the smallest MAE and MSE.
基金financially supported by the Hospital University United Fund of the Second Affiliated Hospital,School of Medicine,The Chinese University of Hong Kong,Shenzhen(Nos.AIE2202,HUUF-ZD-202302)Longgang Medical Discipline Construction Fund+1 种基金Cooperation Project of Yangzhou City with Yangzhou University(No.YZ2023209)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)for financial support。
文摘By using carbohydrates as the biomass carbon sources,Se/C materials could be easily prepared.The materials could catalyze the oxidative deoximation reactions,which are significant transformations in both pharmaceutical industry and fine chemical production.Compared with the reported organoseleniumcatalyzed ionic reactions,the Se/C-catalyzed deoximation reactions occurred via unique free radical mechanisms,endowing the Se species high catalytic reactivity.The Se/C catalysts were recyclable and their turnover numbers(TONs)were high(>10^(4)),making the reactions practical for industrial grade preparation.The unique free radical mechanisms of the reaction and green and practical features of the catalysts are the characteristics and advantages of the work.
文摘A series of new chiral amide ligands were prepared from natural amino acids and applied to the copper-catalyzed asymmetric oxidative homocoupling reaction of 3-hydroxy-2-naphthoates.By optimizing the reaction conditions,it was found that when using L3(5 mol%)as the ligand,CuCl(5 mol%)as the catalyst,dichloromethane as the solvent,2,2,6,6-tetramethylpiperidine 1-oxyl(TEMPO)/O2 as the oxidant,and under the reaction condition of 40℃,this method exhibited good substrate tolerance.Under these conditions,a series of chiral 1,1'-bi-2-naphthol(BINOL)derivatives were synthesized with yields of 45%~90%and enantioselectivities ranging from 50∶50 to 97∶3.
基金supported by The Program of Science and Technology Development Plan of Jilin Province(20230202066NC)Graduate Innovation Research Project of Jilin University(2024CX151)。
文摘Background Heat stress(HS)can impair boar testicular function,leading to reproductive issues.However,chlorogenic acid(CGA)has been shown to mitigate HS-induced damage in various livestock and poultry species.Prepuberty is an important stage of testicular development in boars after birth.However,the protective effect of CGA on testicular HS injury during prepuberty boars and the underlying mechanisms are still not fully understood.Results In vivo,a total of 30 healthy boars with similar body weights and ages were obtained and randomly divided into 3 groups,which were fed a basal diet supplemented with CGA 0(the ND_TN group),0(the ND_HS group)or 1,000(the CGA_HS group)mg/kg.After being fed for 28 d,all the groups,except the ND_TN group,were treated with high temperature for 7 d,after which samples were collected from the boars and analysed.The results showed that CGA significantly mitigated the HS-induced reduction in T-AOC content in testicular tissue and sperm density.Mechanistically,multiomics analysis revealed that the genes differentially expressed by CGA and HS were predominantly associated with the glutathione metabolism pathway.The combined analysis of transcriptomics and proteomics revealed that only BLVRA was affected by both HS and CGA when the mRNA and protein levels of a gene showed differential expression with the same trend.In vitro studies confirmed that CGA modulated GPX3 expression via BLVRA,affected GPx activity,and attenuated HS-induced ROS accumulation.Conclusions In conclusion,prepubertal HS impairs the spermatogenic capacity of boars.BLVRA may mediate the testicular protective effect of CGA,although in vivo validation of this pathway is needed.This study contributes to elucidating the mechanisms underlying the effects of HS on prepubertal boar testicular development using multiomics approaches,laying a foundation for the potential utilization of CGA in swine production.
基金supported by the Central Guided Local Development Fund Special Project(No.ZY23055039)the Natural Science Foundation of Guangxi Province(No.2025GXNSFHA069061)+5 种基金Baise City Scientific Research and Technology Development Plan Self-Funded Project(No.Encyclopedia 20241590)Baise City Scientific Research and Technol-ogy Development Plan Project(No.Encyclopedia 20232083)Guangxi Zhuang Autonomous Region Traditional Chinese Medicine Management Bureau Self-Funded Scientific Research Project(No.GZZC2020248)Guangxi Zhuang Autonomous Region Health Commission Self-Funded Scientific Research Project(No.Z20201416)2024 Innovation Project of Youjiang Medical University for Nationalities Graduate Education(No.YXCXJH2024004)the Natural Science Foundation of Guangxi Province(No.GUIKEAB24010060).
文摘The liver,a critical metabolic organ,is particularly vulnerable to damage upon aluminum exposure.However,the precise molecular mechanisms through which aluminum induces hepatotoxicity remain to be fully elucidated.This study aimed to investigate the adverse effects of aluminum exposure on mouse liver tissue.The results indicated that AlCl_(3) exposure induced significant liver dysfunction,characterized by reduced adenosine triphosphate levels,elevated plasma alanine aminotransferase and aspartate aminotransferase.Histopathological analysis of liver tissue revealed marked histological damage,accompanied by substantial iron deposition.Further examinations demonstrated elevated hepatic levels of malondialdehyde,4-hydroxynonenal,and reactive oxygen species,decreased levels of glutathione(GSH)and superoxide dismutase,increased levels of oxidized glutathione(GSSG),and a reduced GSH/GSSG ratio.The mRNA and protein expression of ferroptosis-related molecules,including downregulated glutathione peroxidase 4 and solute carrier family 7 member 11,were significantly downregulated,while acyl-CoA synthetase long-chain family member 4,ferritin heavy chain 1,and iron regulatory protein 1 levels were significantly upregulated.Treatment with Ferrostatin-1 markedly ameliorated liver dysfunction and histopathological damage,attenuating signs of ferroptosis.These findings highlight the potential of ferroptosis-targeted therapies as a viable treatment strategy for aluminum exposure-induced hepatocyte injury.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金funded by research grant from National Natural Science Foundation of China(32171135).
文摘Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.
基金supported by the National Research Foundation of Korea grant funded by the Korean government(Grant no.:RS-2022-NR070862).
文摘Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models.Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers(NRF2 and GCLC).EtOH metabolism was examined by measuring alchohol-metabolizing enzymes(alcohol dehydrogenase and aldehyde dehydrogenase)and cytochrome P450 enzymes.Furthermore,lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers(SREBP-1 and FAS).Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase,and performing histological analysis.Results:In hepatocytes and zebrafish,both CPs and chondroitin reduced oxidative stress,downregulated cytochrome P450 enzymes and lipogenic markers,and enhanced antioxidant defenses,with chondroitin showing the strongest hepatoprotection.In EtOH-fed mice,chondroitin significantly improved liver enzyme profiles,reduced hepatic lipid accumulation and inflammation,and restored antioxidant and metabolic homeostasis.Conclusions:Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress,EtOH metabolism,and lipid regulation.These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage.
基金supported by the National Natural Science Foundation of China(No.41975156)and the Fundamental Research Funds for the Central Universities.
文摘Oxidative potential(OP)can be used as an indicator of the health risks of particulate matter in the air.To study the variation and sources of OP,we conducted an observation of PM_(2.5) in a megacity in southern China in winter and spring of 2021.The results show that the average concentration of PM_(2.5) decreased by 47%from winter to spring,while volume-normalized and mass-normalized OP(i.e.,OP_(v) and OP_(m))increased by 6%and 69%,respectively.It suggests that the decline of PM_(2.5) may not necessarily decrease the health risks and the intrinsic toxicity of PM_(2.5).Variations of OP_(v) and OP_(m) among different periods were related to the different source contributions and environmental conditions.The positive matrix factorization model was used to identify the major sources of OP_(v).OP_(v) was mainly contributed by biomass burning/industrial emissions(29%),soil/road dust(20%),secondary sulfate(14%),and coal combustion(13%)in winter.Different major sources were resolved to be secondary sulfate(36%),biological sources(21%),and marine vessels(20%)in spring,presenting the substantial contribution of biological sources.The analysis shows strong associations between OP_(v) and both live and dead bacteria,further confirming the important contribution of bioaerosols to the enhancement of OP.This study highlights the importance of understanding OP in ambient PM_(2.5) in terms of public health impact and provides a new insight into the biological contribution to OP.
基金Financial support for this research was provided by Modern Agro-industry Technology Research System of China(CARS-34)the Science and Technology Innovation Leading Talent in Central Plains(No.244200510010)the Outstanding Talents of Henan Agricultural University(No.30500636)。
文摘Background During the weaning phase,piglets are exposed to significant physiological and environmental stressors,which disrupt the balance of their intestinal microbiota and often lead to severe diarrhea.Previous studies have demonstrated that alfalfa fiber,derived from the stems and leaves of alfalfa,can effectively alleviate diarrhea in piglets.Additionally,multiple studies have highlighted the potential of fecal microbiota transplantation(FMT)in mitigating diarrhea in various models of intestinal diseases in young animals.However,the specific mechanisms by which FMT from targeted sources alleviates diarrhea in weaned piglets remain to be fully elucidated.Results In this study,FMT from donor piglets fed an alfalfa fiber-supplemented diet effectively alleviated diarrhea,improved intestinal morphology,and enhanced gut barrier function in weaned piglets.FMT further promoted the colonization of beneficial bacterial genera(including UCG-005,unclassified Lachnospiraceae,Lachnospiraceae AC2044 group,UCG-002,Candidatus Saccharimonas,and Lachnospiraceae ND3007 group)while inhibiting the detrimental genus Tyzzerella,consequently enhancing the production of short-chain fatty acids(SCFAs).Additionally,FMT upregulated riboflavin metabolism,leading to elevated flavin adenine dinucleotide(FAD)levels and increased glutathione reductase activity,thereby collectively attenuating lipopolysaccharide(LPS)-induced oxidative stress and contributing to intestinal health.Conclusions We found that FMT modulates the structure of the gut microbiota,enhances microbial diversity and composition,increases the production of SCFAs,and upregulates riboflavin metabolism to elevate FAD levels.These changes collectively enhance immune and antioxidant capacities,thereby alleviating diarrhea.
基金the Major Special Project of Jiangsu Administration of Traditional Chinese Medicine(Project No.ZT202116)the Key R&D Project of Jiangsu Province(Project No.BE2020727)+2 种基金the Yangzhou Science and Technology Program(Project No.YZ2021062,YZ2024143 and YZ2024194)the Third Batch of Academic Mentorship Program for Senior TCM Experts in Jiangsu Province(Project No.2019028)the 2023 Jiangsu Pharmaceutical Association–Aosaikang Hospital Pharmacy Research Project(Project No.A202333).
文摘Background:Myocardial infarction(MI)remains a major global public health challenge.Although advances in reperfusion therapy have reduced acute mortality,post-infarction cardiac remodeling continues to pose a substantial threat to long-term cardiovascular health.Oxidative stress and the ensuing inflammatory response are key drivers of this pathological process,leading to cardiomyocyte death,myocardial fibrosis,and functional impairment.Among the regulatory pathways involved,the kelch-like ECH-associated protein 1(Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)axis has emerged as a critical therapeutic target for mitigating post-MI cardiac injury.Methods:A murine MI model was established by permanent ligation of the left anterior descending coronary artery.Mice received oral Tongxinbi formula(TXB)at low,medium,or high doses(9/18/36 g/kg)once daily for 28 days.Cardiac function was assessed by echocardiography;myocardial fibrosis by Masson’s trichrome;and endothelial integrity by CD31 immunofluorescence.Plasma markers of endothelial function and inflammation were quantified.In vitro,oxidative stress was induced by H2O2 in vascular endothelial cells and cardiomyocytes,followed by treatment with TXB drug-containing serum.Western blot and RT-qPCR were used to measure components of the Keap1/Nrf2 pathway;ELISA quantified oxidative stress and inflammatory indices.Conditioned-medium experiments evaluated endothelial cell–mediated paracrine protection of cardiomyocytes.Results:TXB significantly improved cardiac function and reduced myocardial fibrosis after MI,in association with preservation of microvascular structure and systemic attenuation of oxidative stress and inflammation.In vitro,TXB activated the endothelial Keap1/Nrf2 pathway,enhanced cellular antioxidant defenses,increased VEGF secretion,and,via endothelial cell-mediated paracrine signaling,alleviated cardiomyocyte injury under oxidative stress.Conclusion:TXB exerts anti-fibrotic and cardioprotective effects by activating Nrf2 signaling and engaging endothelial-mediated paracrine mechanisms,collectively mitigating oxidative stress and inflammation in the post-MI setting.
文摘In order to reveal the signaling pathways triggered by elicitor in plant-microbe interactions, the mechanisms of hypersensitive necrosis responses in Nicotiana tabacum L. cv. Gexin III induced by palmin were studied at molecular and cellular level. The burst of superoxide, intercellular diffusion of hydrogen peroxide and process of cell death induced by palmin were investigated in tobacco plants by biochemical methods and Confocal microscopy. The results showed that a large amount of O-2(.-) was rapidly generated in tobacco cell elicited by palmin as a result of activation of NADPH oxidase, and the O-2(.-) was dismutated into H2O2 immediately by superoxide dismutase (SOD). Accumulation and intercellular diffusion of H2O2 were shown to be a trigger for hypersensitive cell death; and Ca2+ and some specific protein kinase were also shown to be involved in the activation of oxidative burst in tobacco cell induced by palmin.
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
文摘AIM：To evaluate the phagocytic activity and neutrophil oxidative burst in liver cirrhosis.METHODS： In 45 patients with advanced postalcoholic liver cirrhosis （aged 45±14 years） and in 25 healthy volunteers （aged 38±5 years）, the percentage of phagocytizing cells after in vitro incubation with E. coli （Phagotest Kit）, phagocytic activity （mean intensity of fluorescence, MIF） and the percentage of neutrophil oxidative burst （Bursttest Kit）, and the level of free oxygen radical production （MIF of Rodamine 123） were analyzed by flow cytometry. The levels of soluble sICAM-1, sVCAM-1, sP-selectin, sE-selectin, sL-selectin, and TNF-α were determined in blood serum.RESISTS： The percentage of E. coli phagocytizing neutrophils in liver cirrhosis patients was comparable to that in healthy subjects. MIF of neutrophil - ingested E. coli was higher in patients with liver cirrhosis. The oxidative burst in E. coli phagocytizing neutrophils generated less amount of active oxygen compounds in liver cirrhosis pa- tients （MIF of R123：24.7±7.1 and 29.7±6.6 in healthy, P〈0.01）. Phorbol myristate acetate （PMA） - stimulated neutrophilsproduced less reactive oxidants in liver cirrhosis patients than in healthy subjects （MIF of R123： 42.7±14.6 vs 50.2±13.3, P〈0.01）. A negative correlation was observed between oxidative burst MIF of PMA-stimulated neutrophils and ALT and AST levels （r -0.35, P〈0.05; r-0.4, P〈0.03）. sVCAM-1, sICAM-1, sE-selectin concentrations correlated negatively with the oxygen free radical production （MIF of R123） in neutrophils after PMA stimulation in liver cirrhosis patients （r-0.45, P〈0.05, r-0.41, P〈0.05; r-0.39, P〈0.05, respectively）.CONCLUSION： Neutrophil metabolic activity diminishes together with the intensification of liver failure. The metabolic potential of phagocytizing neutrophils is significantly lower in liver cirrhosis patients, which can be one of the causes of immune mechanism damage. The evaluation of oxygen metabolism of E. coli-stimulated neutrophils reveals that the amount of released oxygen metabolites is smaller in liver cirrhosis patients than in healthy subjects.
文摘Reactive oxygen species(ROS)are widely generated in various redox reactions in plants.In earlier studies.ROS were considered toxic byproducts of aerobic metabolism.In recent years,it has become clear that ROS act as plant signaling molecules that participate in various processes such as growth and development.Several studies have elucidated the roles of ROS from seed germination to senescence.However,there is much to discover about the diverse roles of ROS as signaling molecules and their mechanisms of sensing and response.ROS may provide possible benefits to plant physiological processes by supporting cellular proliferation in cells that maintain basal levels prior to oxidative effects.Although ROS are largely perceived as either negative by-products of aerobic metabolism or makers for plant stress,elucidating the range of functions that ROS play in growth and development still require attention.
基金the Tertiary Education Commission,the University of Mauritius,H.E.J.Research Institute of Chemistry,ICCBS,and Dr Panjwani Center for Molecular Medicines and Drug Research,University of Karachi,Pakistan,for financial support
文摘Objective:To evaluate in vitro immunomodulating properties and potential cytotoxicity of six tropical medicinal herbs and food plants namely Antidesma madagascariense(Euphorbiaceae) (AM),Erylhroxylum macrocarpum(Erythroxylaceae)(EM),Faujasiopsis flexuosa(Asteraceae) (FF),Pittosporum senacia(Pittosporaceae)(PS),Momordica charantia(Cucurbitaceae)(MC) and Orimum tenuiflorum(Lamiaceae)(Of).Methods:Initially,the crude water and methanol extracts were probed for their capacity to trigger immune cells’ NADPH oxidase and MPO-dependent activities as measured by lucigenin- and luminol-amplified chemiluminescence,respectively; as compared to receptor-dependent(serum opsonised zymosan- OPZ) or receptor-independent phorbol myristerate acetate(PMA).Results:Preliminary screening on whole human blood oxidative buret activity showed significant and concentration-dependent immunomodulating properties of three plants AM,FF and OT.Further investigations of the fractions on isolated human polymorphonuclear cells(PMNs) and mice monocytes using two different pathways for activation of phagocytic oxidative burst showed that ethyl acetate fraction was the most potent extract. None of the active samples had cell-death effects on human PMNs,under the assay conditions as determined by the trypan-blue exclusion assay.Since PMA and OPZ NADPH oxidase complex is activated via different transduction pathways,these results suggest that AM,FF and OT does not affect a specific transductional pathway,but rather directly inhibit a final common biochemical target such as the NADPH oxidase enzyme and/or scavenges ROS.Conclusions:Our findings suggest that some of these plants extracts/fractions were able to modulate significantly immune response of phagocytes and monocytes at different steps,emphasizing their potential as a source of new natural alternative immunomodulatory agents.
