Jie-Geng-Tang(JGT),a traditional formula,is employed in the treatment of sore throat and cough and comprises Platycodonis Radix and Glycyrrhizae Radix et Rhizoma in the ratio 1:2.Our previous study demonstrated that J...Jie-Geng-Tang(JGT),a traditional formula,is employed in the treatment of sore throat and cough and comprises Platycodonis Radix and Glycyrrhizae Radix et Rhizoma in the ratio 1:2.Our previous study demonstrated that JGT protected mice from S.aureus-induced acute lung injury(ALI).Five constituents of JGT showed antibacterial activities against S.aureus in vitro.However,the potential effective constituents of JGT in vivo were still unclear.In this study,the chemical constituents of JGT were identified by liquid chromatography with quadrupole time-of-flight spectrometry(LC-Q-TOF-MS).A total of 96 constituents were identified or assumed,including seven organic acids,45 flavonoids,36 triterpene saponins,and eight compounds of other types.The structures of 31 of the constituents were confirmed by comparing them with corresponding authentic standards.Moreover,15 prototypes and 49 metabolites were deduced in the serums of mice,24 prototypes and 47 metabolites were deduced in the lungs of mice after the oral administration of JGT.Three types of constituents,namely organic acids,flavonoids,and triterpene saponins,could be absorbed into the blood.Moreover,flavonoids and triterpene saponins were more likely distributed in the lung than in the blood.To the best of our knowledge,this is the first report on the systematic metabolites profile of JGT in vivo.The results reported were beneficial to the elucidation of the effective material basis of JGT.展开更多
Raman spectroscopy was used to distinguish the serums from lung cancer patients and healthy people, through spectral pretreatment method combined with pattern recognition methods including principal component analysis...Raman spectroscopy was used to distinguish the serums from lung cancer patients and healthy people, through spectral pretreatment method combined with pattern recognition methods including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), un-correlated linear discriminant analysis (ULDA), etc. Through the comparisons of the results, it can be found that ULDA and LDA combined with multiple scatter correction (MSC) pretreatment method successfully distinguish the patients of lung cancer and healthy people. The method has academic significance and promising clinical application value.展开更多
Dear Editor,Psoriasis,a chronic inflammatory cutaneous condition,is characterized by the development of red plaques with silvery scales,significantly affecting patients'quality of life and mental health[1].This co...Dear Editor,Psoriasis,a chronic inflammatory cutaneous condition,is characterized by the development of red plaques with silvery scales,significantly affecting patients'quality of life and mental health[1].This condition is thought to affect approximately 2%of the Western population,with diagnosis peaking in early adulthood[2].Vitamin D,a fat-soluble vitamin,is essential for phospho-calcium metabolism,calcium homeostasis,and bone health.展开更多
Activation of neutrophil membrane receptors initiates intracellular signal transduction cascades that orchestrate the cell's effector functions,including phagocytosis,production of reactive oxygen and halogen spec...Activation of neutrophil membrane receptors initiates intracellular signal transduction cascades that orchestrate the cell's effector functions,including phagocytosis,production of reactive oxygen and halogen species,degranulation,and NETosis(formation of neutrophil extracellular traps[NETs]).NETs,which contain antimicrobial compounds such as myeloperoxidase(MPO),represent a strategy to combat infection.However,excessive production of NETs promotes thrombosis,diabetes mellitus,and other diseases.Therefore,investigations into the mechanisms of NETosis and the identification of modulators of this process are critical for developing strategies to address NETosis-related disorders.Here,we identified a novel NETosis inducer,human serum albumin(HSA)modified by the MPO product hypochlorous acid(HSAHOCl),whose accumulation in vivo was correlated with inflammatory processes.Using human blood neutrophils,we investigated HSAHOCl-induced NETosis and detected NET formation by flow cytometry.The results showed that the mechanism of HSAHOClinduced NETosis involved MPO,NADPH oxidase,and phosphatidylinositol 3-kinases(PI3Ks),and that HSAHOCl activated a reactive oxygen species-dependent suicidal type of NETosis.Moreover,HSAHOCl-induced NETosis was inhibited by an anti-HSAHOCl monoclonal antibody.Thus,our findings may facilitate the development of strategies to modulate NETosis in inflammation associated with elevated MPO activity.展开更多
Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrat...Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.展开更多
Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva a...Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.展开更多
The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to r...The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.展开更多
BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to...BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to the intensive care unit(ICU).METHODS:Baseline data of adult patients with CA who were admitted to the ICU from 2008 to 2019 were collected from the Medical Information Mart for Intensive Care(MIMIC)-IV.Patients were divided into survivor and non-survivor groups according to the 28-day prognosis.Serum concentrations of sodium,potassium,glucose,and urea nitrogen on the fi rst day of ICU admission were used to determine serum osmolarity.The primary endpoint of this study was 28-day all-cause mortality.Propensity score matching(PSM)analysis was performed to reduce bias between the survivor and nonsurvivor groups.RESULTS:Among the 798 included CA patients,the high osmolarity on the first day of ICU admission remained significantly associated with increased 28-day mortality(62.0%vs.35.5%,P<0.001)and reduced cumulative survival(log-rank P<0.05)after PSM.Cox regression identifi ed the high osmolarity on the fi rst day of ICU admission as an independent predictor.High serum osmolarity on the fi rst day of ICU admission eff ectively predicted 1-,3-,7-,and 28-day all-cause mortality,with the strongest predictive performance for 1-day mortality both before and after PSM(all P<0.05).CONCLUSION:In this study,elevated serum osmolarity on the first day of ICU admission was independently associated with increased 28-day mortality in CA patients and could serve as a prognostic marker.展开更多
Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of arti...Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of artificial liver support therapy in patients with acute liver injury(ALF)remains unclear.Methods:Bioinformatics analyses were performed to identify HMGB1-interacting proteins and associated inflammatory signaling pathways.Peripheral blood samples were collected from ALF patients before and after artificial liver support therapy,and serum HMGB1 concentrations were quantified using ELISA.Primary mouse hepatocytes were stimulated with lipopolysaccharide(LPS)in vitro and HMGB1 expression was verified by western blot.Results:Single-cell transcriptomic profiling showed that HMGB1 is widely expressed across tissues and predominantly localized in the nucleus.In the liver,HMGB1 was primarily expressed in hepatocytes and hepatic stellate cells.STRING database analysis revealed that human HMGB1 interacts with multiple proteins,including TLR4,TP53,and BECN1.The constructed interaction network comprised 11 nodes with an average local clustering coefficient of 0.888,and the protein–protein interaction enrichment P-value was 1.42×10^(-5),indicating significant enrichment.Gene Ontology and KEGG pathway enrichment analyses demonstrated that HMGB1 is closely linked to inflammatory and injury-related signaling pathways,including the TLR and NLR pathways.Metabolomic profiling revealed significant metabolic alterations between patients with ALF and healthy controls under both positive and negative ion modes and functional analysis showed necroptosis was activated.The cell viability gradually decreased with time and dose under LPS treatment and extracellular HMGB1 was upregulated in LPS induced ALF model and patients(P<0.05).Serum HMGB1/RIPK3/MLKL levels were markedly elevated in ALF patients compared with controls(P<0.05)and progressively declined following artificial liver support therapy.Furthermore,elevated HMGB1 concentrations were positively correlated with unfavorable clinical outcomes.Conclusion:Peripheral blood HMGB1 levels are significantly increased in patients with acute liver failure,decrease following artificial liver support therapy,and are positively associated with poor clinical prognosis.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)r...Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)remain unclear.To explore the influence of photoperiod on basal metabolism and substrate metabolism in Zebra Finches,basal metabolic rate(BMR),body mass,cellular metabolic activities,and substrate metabolism were investigated under different photoperiods.After one week of exposure to a short photoperiod,Zebra Finches exhibited a temporary decrease in BMR,gross energy intake,digestible energy intake,and digestibility,although body mass remained unchanged throughout the experiment.After four weeks of acclimation,no significant differences were observed among different groups in state 4 respiration,cytochrome c oxidase activity,citrate synthase activity,avian uncoupling protein expression,or circulating triiodothyronine and thyroxine hormone levels.In terms of substrate metabolism,short photoperiod-exposed finches showed increased pectoral muscle glycogen content and elevated serum triglyceride and free fatty acid levels,accompanied by a decrease in body fat.No differences were detected in serum glucose levels or in the activity and mRNA levels of carnitine palmityltransferase-1 andβ-hydroxyacyl Co-A dehydrogenase.These findings suggest that changes in photoperiod may serve as signals for substrate metabolism remodeling,while having only transient effects on basal metabolism in Zebra Finches.展开更多
Interactions between platinum complexes and human serum albumin(HSA)play crucial roles in the bioavailability and toxicology of platinum-based anticancer drugs.Platinum-intercalator hybrid pharmacophores are a novel c...Interactions between platinum complexes and human serum albumin(HSA)play crucial roles in the bioavailability and toxicology of platinum-based anticancer drugs.Platinum-intercalator hybrid pharmacophores are a novel class of DNA-targeted cytotoxic agents that show potent activity across a broad range of solid tumor cell lines.In this study,the interactions of a cytotoxic Pt-benzoxazole hybrid agent,[PtLCl]Cl(1,where L=N-(4-(benzo[d]oxazol-2-yl)phenyl)-2-(bis(2-ethylthioethyl)amino)acetamide)and its tridentate chelating platinum unit,[PtL′Cl]Cl(2,where L′=bis(2-ethylthioethyl)amine),with HSA were investigated by multiple spectroscopic methods.The results revealed that both complexes exhibited moderate HSA binding affinity(1>2),triggering conformation and microenvironmental changes of the protein and suppressing its intrinsic fluorescence via static quenching pathways.The thermodynamic parameters(ΔG°,ΔH°,ΔS°)calculated from fluorescence data at different temperatures suggested that the binding reaction between the complexes and HSA was a spontaneous process dominated by hydrophobic interactions.The binding site number indicated 1∶1 stoichiometry for both complexes at a single primary binding site on HSA.Furthermore,site marker competition assays demonstrated that complexes 1 and 2 could bind to the drug binding sites I(bromophenol blue-binding domain)and site II(ibuprofen-binding domain)on HSA,respectively.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low pe...Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.展开更多
Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognost...Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.展开更多
Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarke...Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.展开更多
Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with...Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial...BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial curative benefits provided by surgical interventions for GC.Hence,the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community.AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery.METHODS This study included patients who underwent GC surgery from June 2022 to February 2024.The control group included 45 patients who received chemotherapy(oxaliplatin+calcium folinate+5-fluorouracil),whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group.Comparative analyses were conducted from the following perspectives:Gastrointestinal function(defecation time,intestinal gas discharge time,and hospitalization time),serum markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,and CA199],nutritional indicators total protein(TP)and transferrin(TRF),traditional Chinese medicine(TCM)syndrome score,and grades Ⅲ–Ⅳ adverse events(gastrointestinal reactions,renal/liver function impairment,and myelosuppression).RESULTS The two groups demonstrated similar defecation time(P>0.05),but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group(P<0.05).Further,the research group exhibited significant CEA,CA125,and CA199 reductions after treatment,which were lower compared to the control group,as well as notable increases in TP and TRF that were statistically higher than the control group(all P<0.05).Furthermore,the research group demonstrated an evident decrease in TCM syndrome scores in areas,such as poor appetite,epigastric distension and pain,fatigue and weakness(P<0.01),and abdominal distension after eating,which are notably lower than those in the control group(P<0.01),with a comparable incidence of grades Ⅲ-Ⅳ adverse events(P>0.05).CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA,CA125,and CA199 levels.展开更多
The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or...The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or hyperuricemia among US adults and to explore the mediating role of systemic inflammation in the associations.A total of 10,307 US adults were conducted to assess the associations of seven urinary hydroxy–PAH with SUA and hyperuricemia and evaluate the role of C-reactive protein(CRP),a biomarker of systemic inflammation,in such associations.Results showed that each 1-unit increase in ln-transformed 2-hydroxynaphthalene(2-OHNa),1-hydroxyphenanthrene(1-OHPh),2&3-hydroxyphenanthrene(2&3-OHPh)and total hydroxyphenanthrene(OHPh)was associated with a 1.68(95%confidence interval(CI):0.19 to 3.17),2.46(0.78 to 4.13),3.34(1.59 to 5.09),and 2.99(1.23 to 4.75)μmol/L increase in SUA,and a 8%(odds ratio(OR):1.08,1.02 to 1.15),9%(OR:1.09,1.02 to 1.18),13%(OR:1.13,1.05 to 1.22),and 12%(OR:1.12,95%CI:1.03,1.21)increase in hyperuricemia,respectively.Co-exposure of seven PAHs was positively associated with SUA and hyperuricemia,with 2&3-OHPh showing the highest weight(components weights:0.83 and 0.78,respectively).The CRP mediated 11.47%and 10.44%of the associations ofΣOHPh and 2&3-OHPh with SUA and mediated 8.60%and 8.62%in associations ofΣOHPh and 2&3-OHPh with hyperuricemia,respectively.In conclusion,internal levels of PAH metabolites were associated with elevated SUA levels and the increased risk of hyperuricemia among US adults,and CRP played a mediating role in the associations.展开更多
基金supported by the National Science and Technology Major Project of China(No.2019ZX.9201005)the Zhejiang Provincial Natural Science Foundation of China(No.LY17H280002)。
文摘Jie-Geng-Tang(JGT),a traditional formula,is employed in the treatment of sore throat and cough and comprises Platycodonis Radix and Glycyrrhizae Radix et Rhizoma in the ratio 1:2.Our previous study demonstrated that JGT protected mice from S.aureus-induced acute lung injury(ALI).Five constituents of JGT showed antibacterial activities against S.aureus in vitro.However,the potential effective constituents of JGT in vivo were still unclear.In this study,the chemical constituents of JGT were identified by liquid chromatography with quadrupole time-of-flight spectrometry(LC-Q-TOF-MS).A total of 96 constituents were identified or assumed,including seven organic acids,45 flavonoids,36 triterpene saponins,and eight compounds of other types.The structures of 31 of the constituents were confirmed by comparing them with corresponding authentic standards.Moreover,15 prototypes and 49 metabolites were deduced in the serums of mice,24 prototypes and 47 metabolites were deduced in the lungs of mice after the oral administration of JGT.Three types of constituents,namely organic acids,flavonoids,and triterpene saponins,could be absorbed into the blood.Moreover,flavonoids and triterpene saponins were more likely distributed in the lung than in the blood.To the best of our knowledge,this is the first report on the systematic metabolites profile of JGT in vivo.The results reported were beneficial to the elucidation of the effective material basis of JGT.
文摘Raman spectroscopy was used to distinguish the serums from lung cancer patients and healthy people, through spectral pretreatment method combined with pattern recognition methods including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), un-correlated linear discriminant analysis (ULDA), etc. Through the comparisons of the results, it can be found that ULDA and LDA combined with multiple scatter correction (MSC) pretreatment method successfully distinguish the patients of lung cancer and healthy people. The method has academic significance and promising clinical application value.
基金supported by the National Natural Science Foundation of China(Grant Nos.82573974 and 82373475)to Z.Y.
文摘Dear Editor,Psoriasis,a chronic inflammatory cutaneous condition,is characterized by the development of red plaques with silvery scales,significantly affecting patients'quality of life and mental health[1].This condition is thought to affect approximately 2%of the Western population,with diagnosis peaking in early adulthood[2].Vitamin D,a fat-soluble vitamin,is essential for phospho-calcium metabolism,calcium homeostasis,and bone health.
文摘Activation of neutrophil membrane receptors initiates intracellular signal transduction cascades that orchestrate the cell's effector functions,including phagocytosis,production of reactive oxygen and halogen species,degranulation,and NETosis(formation of neutrophil extracellular traps[NETs]).NETs,which contain antimicrobial compounds such as myeloperoxidase(MPO),represent a strategy to combat infection.However,excessive production of NETs promotes thrombosis,diabetes mellitus,and other diseases.Therefore,investigations into the mechanisms of NETosis and the identification of modulators of this process are critical for developing strategies to address NETosis-related disorders.Here,we identified a novel NETosis inducer,human serum albumin(HSA)modified by the MPO product hypochlorous acid(HSAHOCl),whose accumulation in vivo was correlated with inflammatory processes.Using human blood neutrophils,we investigated HSAHOCl-induced NETosis and detected NET formation by flow cytometry.The results showed that the mechanism of HSAHOClinduced NETosis involved MPO,NADPH oxidase,and phosphatidylinositol 3-kinases(PI3Ks),and that HSAHOCl activated a reactive oxygen species-dependent suicidal type of NETosis.Moreover,HSAHOCl-induced NETosis was inhibited by an anti-HSAHOCl monoclonal antibody.Thus,our findings may facilitate the development of strategies to modulate NETosis in inflammation associated with elevated MPO activity.
基金supported by the Natural Science Foundation of Hunan Province (2022JJ30987)the Key Research and Development Project of Hunan Province (2024JK2107),China。
文摘Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.
文摘Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.
基金supported by the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055)the National Natural Science Foundation of China(82471925)。
文摘The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.
基金funded by the Shenzhen Science and Technology Program(JCYJ20230807112007014 to PG)the Shenzhen Key Medical Discipline Construction Fund(SZXK046 to PG).
文摘BACKGROUND:Serum osmolality is a prognostic indicator in critically ill patients.This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest(CA)admitted to the intensive care unit(ICU).METHODS:Baseline data of adult patients with CA who were admitted to the ICU from 2008 to 2019 were collected from the Medical Information Mart for Intensive Care(MIMIC)-IV.Patients were divided into survivor and non-survivor groups according to the 28-day prognosis.Serum concentrations of sodium,potassium,glucose,and urea nitrogen on the fi rst day of ICU admission were used to determine serum osmolarity.The primary endpoint of this study was 28-day all-cause mortality.Propensity score matching(PSM)analysis was performed to reduce bias between the survivor and nonsurvivor groups.RESULTS:Among the 798 included CA patients,the high osmolarity on the first day of ICU admission remained significantly associated with increased 28-day mortality(62.0%vs.35.5%,P<0.001)and reduced cumulative survival(log-rank P<0.05)after PSM.Cox regression identifi ed the high osmolarity on the fi rst day of ICU admission as an independent predictor.High serum osmolarity on the fi rst day of ICU admission eff ectively predicted 1-,3-,7-,and 28-day all-cause mortality,with the strongest predictive performance for 1-day mortality both before and after PSM(all P<0.05).CONCLUSION:In this study,elevated serum osmolarity on the first day of ICU admission was independently associated with increased 28-day mortality in CA patients and could serve as a prognostic marker.
基金supported by the National Natural Science Foundation of China(No.82360120)the Kunming Medical University Joint Special Project on Applied Basic Research(202401AY070001-134),and project iGandanF-1082022-RGG049+2 种基金the Open Project of Yunnan Provincial Clinical Medical Center for Digestive System Diseases(2022LCZXXF-XH07/17)the 14th Undergraduate Scientific Research Project of Mudanjiang Medical University(2024057)Yunnan Provincial Key Laboratory of Clinical Virology(No.2023A4010403-04).
文摘Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of artificial liver support therapy in patients with acute liver injury(ALF)remains unclear.Methods:Bioinformatics analyses were performed to identify HMGB1-interacting proteins and associated inflammatory signaling pathways.Peripheral blood samples were collected from ALF patients before and after artificial liver support therapy,and serum HMGB1 concentrations were quantified using ELISA.Primary mouse hepatocytes were stimulated with lipopolysaccharide(LPS)in vitro and HMGB1 expression was verified by western blot.Results:Single-cell transcriptomic profiling showed that HMGB1 is widely expressed across tissues and predominantly localized in the nucleus.In the liver,HMGB1 was primarily expressed in hepatocytes and hepatic stellate cells.STRING database analysis revealed that human HMGB1 interacts with multiple proteins,including TLR4,TP53,and BECN1.The constructed interaction network comprised 11 nodes with an average local clustering coefficient of 0.888,and the protein–protein interaction enrichment P-value was 1.42×10^(-5),indicating significant enrichment.Gene Ontology and KEGG pathway enrichment analyses demonstrated that HMGB1 is closely linked to inflammatory and injury-related signaling pathways,including the TLR and NLR pathways.Metabolomic profiling revealed significant metabolic alterations between patients with ALF and healthy controls under both positive and negative ion modes and functional analysis showed necroptosis was activated.The cell viability gradually decreased with time and dose under LPS treatment and extracellular HMGB1 was upregulated in LPS induced ALF model and patients(P<0.05).Serum HMGB1/RIPK3/MLKL levels were markedly elevated in ALF patients compared with controls(P<0.05)and progressively declined following artificial liver support therapy.Furthermore,elevated HMGB1 concentrations were positively correlated with unfavorable clinical outcomes.Conclusion:Peripheral blood HMGB1 levels are significantly increased in patients with acute liver failure,decrease following artificial liver support therapy,and are positively associated with poor clinical prognosis.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
基金supported by the National Natural Science Foundation of China(Nos.32371573 and 32171497)。
文摘Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)remain unclear.To explore the influence of photoperiod on basal metabolism and substrate metabolism in Zebra Finches,basal metabolic rate(BMR),body mass,cellular metabolic activities,and substrate metabolism were investigated under different photoperiods.After one week of exposure to a short photoperiod,Zebra Finches exhibited a temporary decrease in BMR,gross energy intake,digestible energy intake,and digestibility,although body mass remained unchanged throughout the experiment.After four weeks of acclimation,no significant differences were observed among different groups in state 4 respiration,cytochrome c oxidase activity,citrate synthase activity,avian uncoupling protein expression,or circulating triiodothyronine and thyroxine hormone levels.In terms of substrate metabolism,short photoperiod-exposed finches showed increased pectoral muscle glycogen content and elevated serum triglyceride and free fatty acid levels,accompanied by a decrease in body fat.No differences were detected in serum glucose levels or in the activity and mRNA levels of carnitine palmityltransferase-1 andβ-hydroxyacyl Co-A dehydrogenase.These findings suggest that changes in photoperiod may serve as signals for substrate metabolism remodeling,while having only transient effects on basal metabolism in Zebra Finches.
基金Excellent Discipline Cultivation Project of Jianghan University (2023XKZ006)Four New Disciplines Special Project of Jianghan University(2022SXZX02)Jianghan University Research Projects(2023zd037,2024zd043,2024yb105)。
文摘Interactions between platinum complexes and human serum albumin(HSA)play crucial roles in the bioavailability and toxicology of platinum-based anticancer drugs.Platinum-intercalator hybrid pharmacophores are a novel class of DNA-targeted cytotoxic agents that show potent activity across a broad range of solid tumor cell lines.In this study,the interactions of a cytotoxic Pt-benzoxazole hybrid agent,[PtLCl]Cl(1,where L=N-(4-(benzo[d]oxazol-2-yl)phenyl)-2-(bis(2-ethylthioethyl)amino)acetamide)and its tridentate chelating platinum unit,[PtL′Cl]Cl(2,where L′=bis(2-ethylthioethyl)amine),with HSA were investigated by multiple spectroscopic methods.The results revealed that both complexes exhibited moderate HSA binding affinity(1>2),triggering conformation and microenvironmental changes of the protein and suppressing its intrinsic fluorescence via static quenching pathways.The thermodynamic parameters(ΔG°,ΔH°,ΔS°)calculated from fluorescence data at different temperatures suggested that the binding reaction between the complexes and HSA was a spontaneous process dominated by hydrophobic interactions.The binding site number indicated 1∶1 stoichiometry for both complexes at a single primary binding site on HSA.Furthermore,site marker competition assays demonstrated that complexes 1 and 2 could bind to the drug binding sites I(bromophenol blue-binding domain)and site II(ibuprofen-binding domain)on HSA,respectively.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
基金supported by the NIH RF1 grant NS119477 jointly funded by NINDS and NIA(to RM).
文摘Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.
基金The authors extend their appreciation to Taif University,Saudi Arabia,for supporting this work through project No.(TU-DSPP-2024-54).
文摘Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.
文摘Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.
文摘Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金Supported by Liaoning Provincial Science and Technology Plan Joint Plan,No.2023JH2/101700149。
文摘BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial curative benefits provided by surgical interventions for GC.Hence,the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community.AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery.METHODS This study included patients who underwent GC surgery from June 2022 to February 2024.The control group included 45 patients who received chemotherapy(oxaliplatin+calcium folinate+5-fluorouracil),whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group.Comparative analyses were conducted from the following perspectives:Gastrointestinal function(defecation time,intestinal gas discharge time,and hospitalization time),serum markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,and CA199],nutritional indicators total protein(TP)and transferrin(TRF),traditional Chinese medicine(TCM)syndrome score,and grades Ⅲ–Ⅳ adverse events(gastrointestinal reactions,renal/liver function impairment,and myelosuppression).RESULTS The two groups demonstrated similar defecation time(P>0.05),but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group(P<0.05).Further,the research group exhibited significant CEA,CA125,and CA199 reductions after treatment,which were lower compared to the control group,as well as notable increases in TP and TRF that were statistically higher than the control group(all P<0.05).Furthermore,the research group demonstrated an evident decrease in TCM syndrome scores in areas,such as poor appetite,epigastric distension and pain,fatigue and weakness(P<0.01),and abdominal distension after eating,which are notably lower than those in the control group(P<0.01),with a comparable incidence of grades Ⅲ-Ⅳ adverse events(P>0.05).CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA,CA125,and CA199 levels.
基金supported by the Key Program of National Natural Science Foundation of China(No.82241088)the Natural Science Foundation of Hubei Province(No.2022CFB813).
文摘The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or hyperuricemia among US adults and to explore the mediating role of systemic inflammation in the associations.A total of 10,307 US adults were conducted to assess the associations of seven urinary hydroxy–PAH with SUA and hyperuricemia and evaluate the role of C-reactive protein(CRP),a biomarker of systemic inflammation,in such associations.Results showed that each 1-unit increase in ln-transformed 2-hydroxynaphthalene(2-OHNa),1-hydroxyphenanthrene(1-OHPh),2&3-hydroxyphenanthrene(2&3-OHPh)and total hydroxyphenanthrene(OHPh)was associated with a 1.68(95%confidence interval(CI):0.19 to 3.17),2.46(0.78 to 4.13),3.34(1.59 to 5.09),and 2.99(1.23 to 4.75)μmol/L increase in SUA,and a 8%(odds ratio(OR):1.08,1.02 to 1.15),9%(OR:1.09,1.02 to 1.18),13%(OR:1.13,1.05 to 1.22),and 12%(OR:1.12,95%CI:1.03,1.21)increase in hyperuricemia,respectively.Co-exposure of seven PAHs was positively associated with SUA and hyperuricemia,with 2&3-OHPh showing the highest weight(components weights:0.83 and 0.78,respectively).The CRP mediated 11.47%and 10.44%of the associations ofΣOHPh and 2&3-OHPh with SUA and mediated 8.60%and 8.62%in associations ofΣOHPh and 2&3-OHPh with hyperuricemia,respectively.In conclusion,internal levels of PAH metabolites were associated with elevated SUA levels and the increased risk of hyperuricemia among US adults,and CRP played a mediating role in the associations.
