BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Objective: to study the relationship between TCM constitution type and TCM syndrome differentiation of knee arthritis. Methods: a total of 100 patients with knee osteoarthritis collected in our department from April 2...Objective: to study the relationship between TCM constitution type and TCM syndrome differentiation of knee arthritis. Methods: a total of 100 patients with knee osteoarthritis collected in our department from April 2019 to April 2020 were selected for in-depth analysis of the distribution of TCM constitution types and TCM syndrome differentiation and classification, and the correlation was analyzed. Results: (1) in the dialectical classification of TCM, the deficiency of liver and kidney was correlated with the constitution types of Yang deficiency, Qi deficiency and Yin deficiency. (2) In the syndrome differentiation and classification of TCM, the syndrome of cold and dampness obstruction is correlated with the constitution type of TCM, which is Qi deficiency. (3) In the syndrome differentiation and classification of TCM, the syndrome of weakness of Qi and blood is correlated with the constitution types of TCM including Qi deficiency, Yang deficiency and Yin deficiency. (4) In TCM syndrome differentiation and classification, the syndrome of Qi stagnation and blood stasis is correlated with the constitution type of Yang deficiency. Conclusion: There is a certain correlation between TCM syndrome differentiation and TCM constitution type. Based on this, further exploration of the correlation between diseases and TCM constitution can provide corresponding diagnostic basis for prevention, diagnosis and treatment.展开更多
Macrocycle-based glycoclusters, on account of their promising anti-adhesive properties against bacteria,are potential therapeutic alternatives to classic antibiotics through the much less explored anti-adhesive strate...Macrocycle-based glycoclusters, on account of their promising anti-adhesive properties against bacteria,are potential therapeutic alternatives to classic antibiotics through the much less explored anti-adhesive strategy. In this study, a series of constitutionally-pure pentavalent glycoclusters was prepared by conjugating assorted azido-carbohydrates onto a penta-propargyl rim-differentiated pillar[5]arene(RD-P[5])scaffold through Cu(I)-catalyzed azide–alkyne cycloaddition “click” reactions. Their binding towards therapeutically relevant bacterial lectins, such as Lec A and Lec B from Pseudomonas aeruginosa and concanavalin A(Con A), were evaluated subsequently by isothermal titration calorimetric studies. Most of these isomerfree RD-P[5] pentavalent glycoclusters, except the fucosylated ones, display good affinities to lectins.Nonetheless, the dissociation constants observed are similar to those displayed by an analogous pentavalent glycocluster consisting of four P[5] constitutional isomers, in which the RD-P[5] component merely accounts for 7% in the mixture. Our results revealed that high constitutional purity is not essential for achieving effective multivalent interactions between P[5]-based glycoclusters and lectins, presumably as a result of the conformationally labile nature of the P[5] scaffold. This information provides valuable design principles for low-cost and facile syntheses of glycosylated P[5]s for biomedical applications.展开更多
OBJECTIVE:To investigate the difference in gut microbiota between population with damp-heat constitution(DHC)and balanced constitution(BC).METHODS:A multi-centered cross-sectional casecontrol study was conducted,which...OBJECTIVE:To investigate the difference in gut microbiota between population with damp-heat constitution(DHC)and balanced constitution(BC).METHODS:A multi-centered cross-sectional casecontrol study was conducted,which included 249 participants with damp-heat constitution or balanced constitution.Baseline information of participants was collected,and stool samples were collected for gut microbiota analysis.Principal coordinate analysis,linear discriminant analysis effect size analysis,receiver operating characteristic,random forest model,and phylogenetic investigation of communities by reconstruction of unobserved states methods were used to reveal the relationship between gut microbiota and the damp-heat constitution.RESULTS:Compared to those in the BC group,the richness and diversity of the microbiota,specifically those of several short-chain fatty acid producing genera such as Barnesiella,Coprobacter,and Butyricimonas,were significantly decreased in the DHC group.Regarding biological functions,flavonoid biosynthesis,propanoate metabolism,and nucleotide sugar metabolism were suppressed,while arachidonic acid metabolism and glutathione metabolism were enriched in the DHC group.Finally,a classifier based on the microbiota was constructed to discriminate between the DHC and BC populations.CONCLUSION:The gut microbiota of the DHC population exhibits significantly reduced diversity and is closely related to inflammation,metabolic disorders,and liver steatosis,which is consistent with clinical observations,thus serving as a potential diagnostic tool for traditional Chinese medicine constitution discrimination.展开更多
Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was dimini...Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.展开更多
The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with t...The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with the advantage of being environmental-friendly.As one of the organic acids produced by biological metabolism,citric acid was used to leach REEs and explore the performance and process.The results demonstrate that citric acid exhibits higher leaching efficiency(96.00%)for REEs at a relatively low concentration of 0.01 mol/L compared with(NH_(4))_(2)SO_(4)(84.29%,0.1 mol/L)and MgSO_(4)(83.99%,0.1 mol/L).Citric acid shows a preference for leaching heavy rare earth elements,with 99%leaching efficiency in IAREO,which shows higher capacity than(NH_(4))_(2)SO_(4)and MgSO_(4)(as inorganic leaching agents).Kinetic analysis indicates that the leaching process of REEs with citric acid is controlled by both the internal diffusion kinetics and chemical reaction kinetics,which is different from inorganic leaching agents.Visual Minteq calculations confirm that RE-Citrate is the main constituent of the extract solution in the leaching process of the IAREO,thereby enhancing the leaching efficiency of REEs from the IAREO.It suggests that citric acid may be used as a promising organic leaching agent for the environmentalfriendly extraction of REEs from IAREO.展开更多
OBJECTIVE:Yang-deficiency constitution(YADC)is a common unbalanced constitution that predisposes individuals to certain diseases.However,not all people with YADC manifest develop diseases.This calls for delineation of...OBJECTIVE:Yang-deficiency constitution(YADC)is a common unbalanced constitution that predisposes individuals to certain diseases.However,not all people with YADC manifest develop diseases.This calls for delineation of the underlying molecular mechanisms.Previous studies suggested that the gut microbiota and gene differential expression should be considered.METHODS:In the present study,we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution(BC)counterparts,based on 16 S r RNA gene sequence analysis.Furthermore,YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis,functional clustering and pathway enrichment analyses.RESULTS:The levels of harmful gut microbiota(Prevotellaceae,LDA score>4.0,P=0.0141)and beneficial gut microbiota(Ruminococcaceae,LDA score>4.0,P=0.0025,Faecalibacterium,LDA score>4.0,P=0.0484)were both elevated in healthy YADC individuals.Also,we found that the specific metabolic pathway with 2,6-Dichloro-p-hydroquinone 1,2-Dioxygenase(Pcp A)as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon substances.CONCLUSIONS:Both beneficial and harmful factors had been detected in healthy YADC individuals,functionally,they may have triggered homeostasis to maintain the health of individuals with YADC.The homeostasis may be maintained by beneficial and harmful factors from gut flora and genes.Future studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.展开更多
Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infr...Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.展开更多
Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,...The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.展开更多
Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characteri...Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characterized by the loss of oligodendrocytes(OLs)and the disintegration of myelin sheaths,leading to impaired neural connectivity and motor dysfunction.Neural stem cells(NSCs)represent a promising regenerative source for replenishing lost OLs;however,conventional twodimensional(2D)in vitro culture systems lack the three-dimensional(3D)physiological microenvironment.Microfluidic chip technology has emerged as a powerful tool to overcome this limitation by enabling precise spatial and temporal control over 3D microenvironmental conditions,including the establishment of stable concentration gradients of bioactive molecules.Catalpol,an iridoid glycoside derived from traditional medicinal plants,exhibits dual antioxidant and anti-apoptotic properties.Despite its therapeutic potential,the capacity of catalpol to drive NSC differentiation toward OLs under biomimetic 3D conditions,as well as the underlying molecular mechanisms,remains poorly understood.This study aims to develop a microfluidic-based 3D biomimetic platform to systematically investigate the concentration-dependent effects of catalpol on promoting NSCs-to-OLs differentiation and to elucidate the role of the caveolin-1(Cav-1)signaling pathway in this process.Methods We developed a novel multiplexed microfluidic device featuring parallel microchannels with integrated gradient generators capable of establishing and maintaining precise linear concentration gradients(0-3 g/L catalpol)across 3D NSCs cultures.This platform facilitated the continuous perfusion culture of NSC-derived 3D spheroids,mimicking the dynamic in vivo microenvironment.Real-time cell viability was assessed using Calcein-AM/propidium iodide(PI)dual staining,with fluorescence imaging quantifying live/dead cell ratios.Oligodendrocyte differentiation was evaluated through quantitative reverse transcription polymerase chain reaction(qRT-PCR)for MBP and SOX10 gene expression,complemented by immunofluorescence staining to visualize corresponding protein changes.To dissect the molecular mechanism,the Cav-1-specific pharmacological inhibitor methyl‑β‑cyclodextrin(MCD)was employed to perturb the pathway,and its effects on differentiation markers were analyzed.Results Catalpol demonstrated excellent biocompatibility,with cell viability exceeding 96%across the entire tested concentration range(0-3 g/L),confirming its non-cytotoxic nature.At the optimal concentration of 0-3 g/L,catalpol significantly upregulated both MBP and SOX10 expression(P<0.05,P<0.01),indicating robust promotion of oligodendroglial differentiation.Intriguingly,Cav-1 mRNA expression was progressively downregulated during NSC differentiation into OLs.Further inhibition of Cav-1 with MCD further enhanced this effect,leading to a statistically significant increase in OL-specific gene expression(P<0.05,P<0.01),suggesting Cav-1 acts as a negative regulator of OLs differentiation.Conclusion This study established an integrated microfluidic gradient chip-3D NSC spheroid culture system,which combines the advantages of precise chemical gradient control with physiologically relevant 3D cell culture.The findings demonstrate that 3 g/L catalpol effectively suppresses Cav-1 signaling to drive NSC differentiation into functional OLs.This work not only provides novel insights into the Cav-1-dependent mechanisms of myelination but also delivers a scalable technological platform for future research on remyelination therapies,with potential applications in cerebral palsy and other white matter disorders.The platform’s modular design permits adaptation for screening other neurogenic compounds or investigating additional signaling pathways involved in OLs maturation.展开更多
The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic fu...The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic functions in the unit ball by radial derivative.Then we extend the Sharma's results.展开更多
Objective:The concept of constitution in traditional Chinese medicine(TCM)has been increasingly recognized as a crucial factor in both the prevention and treatment of insomnia.However,rigorous statistical evidence on ...Objective:The concept of constitution in traditional Chinese medicine(TCM)has been increasingly recognized as a crucial factor in both the prevention and treatment of insomnia.However,rigorous statistical evidence on the correlation between TCM constitutions—particularly mixed constitutions—and insomnia disorder remains limited.This study aimed to investigate the association between specific TCM constitutions and insomnia disorder.Methods:A cross-sectional study was conducted at the Department of Preventive Medicine,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai,from November 2022 to December 2023.TCM constitutions were assessed using the Constitution in Chinese Medicine Questionnaire.Insomnia disorder was diagnosed by experienced internal medicine physicians according to the criteria of the International Classification of Sleep Disorders,Third Edition.A total of 1065 eligible participants(242 with insomnia disorder and 823 controls)were included in the final analysis.Results:Among the participants,862(80.94%)exhibited biased constitutions,with 75.30%of these having mixed constitutions.Logistic regression analysis revealed a negative association between the gentleness constitution and insomnia disorder,whereas qi-deficiency,yang-deficiency,phlegm-dampness and qidepression constitutions were positively associated with insomnia disorder.These associations remained significant after adjusting for potential confounders and were further validated through sensitivity analysis using propensity score matching.Conclusion:Significant associations between TCM constitutions and insomnia disorder were demonstrated.Future research should further investigate these relationships and explore the underlying mechanisms through rigorous longitudinal and interventional studies to improve understanding and clinical applications.展开更多
Objective:To study the relationship between qi stagnation constitution and suboptimal health status(SHS)or lifestyle.Methods:From 2012 to 2013,we conducted a cross-sectional survey of 24159 Chinese individuals aged 12...Objective:To study the relationship between qi stagnation constitution and suboptimal health status(SHS)or lifestyle.Methods:From 2012 to 2013,we conducted a cross-sectional survey of 24159 Chinese individuals aged 12-80 years.The qi stagnation constitution was assessed using the Constitution in Chinese Medicine Questionnaire.Health status was evaluated through medical records and the Subhealth Measurement Scale V1.0(SHMS V1.0).Health-promoting lifestyles were measured using the Health-Promoting Lifestyle Profile Ⅱ(HPLP-Ⅱ).Results:Of the 24159 participants,16.1%and 15.2%were classified as“always”and“sometimes”having the qi stagnation constitution,respectively.Those classified as“rarely”having the qi stagnation constitution scored higher on both the HPLP-Ⅱ and SHMS V1.0.The participants classified as“always”having the qi stagnation constitution showed a significant association with SHS or disease compared to other imbalanced constitutions.Those in the“always”category were approximately 21 times more likely to be classified as having SHS(odds ratio[OR]:21.17,95%confidence interval[CI]:15.74-28.45),whereas those in the“sometimes”category were approximately six times more likely(OR:5.89,95%CI:5.04-6.90).Accordingly,the qi stagnation constitution score was significantly associated with the diagnosis of SHS,with an area under the curve of 0.77(P<.001).A score of 18.75 yielded the highest Youden Index(0.407),with a sensitivity of 60.5%and a specificity of 80.3%.Significant associations were observed between health-promoting lifestyles and qi stagnation constitution severity in an ordinal regression analysis(P<.001).Protective factors included stress management(OR:1.59),self-actualization(OR:1.57),and exercise(OR:1.36).In contrast,poorer interpersonal relationships(OR:0.79),greater health responsibilities(OR:0.86),and poorer nutrition(OR:0.91)were associated with increased severity.Conclusion:Modulating the qi stagnation constitution through lifestyle interventions may help prevent the progression of SHS to disease,which aligns with core preventive principles in traditional Chinese medicine.展开更多
It is well known that Traditional Chinese Medicine(TCM)has two outstanding academic characteristics:the holistic concept comes from Huang Di Nei Jing,and the syndrome differentiation and treatment comes from Shang Han...It is well known that Traditional Chinese Medicine(TCM)has two outstanding academic characteristics:the holistic concept comes from Huang Di Nei Jing,and the syndrome differentiation and treatment comes from Shang Han Lun.These two characteristics denote the two major academic systems of TCM:one is the medical system of Huang Di Nei Jing,also named syndrome differentiation and treatment system of Zang-Fu organs and meridians,focuses on theoretical exploration,which highlights functional connection and emphasizes philosophical thinking.The treatment in this system is based on physiological functions by taking Zang-Fu organs as the main body,Qi,blood,essence,and body fluid as the auxiliary body,and the meridians and collaterals as the connection channels.The other is the syndrome differentiation and treatment system of the six meridians,which emphasizes clinical practice.It encompasses the idea that the six meridians govern various diseases,emphasizes the disease sites and divisional treatment,and pays attention to the precision and appropriateness of prescription-syndrome differentiation.These two academic systems,with mutual influences and relations,are both the essence and pearl of TCM,nevertheless,there are obvious differences between the two in clinical application,so they should be distinguished.This paper will elaborate on the connection and difference between them,and how to organically combine the two systems for better application in clinical practice of TCM.展开更多
It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases ...It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.展开更多
[Objectives]To investigate differences in BMI and renal function across constitution types and influencing factors of blood pressure.[Methods]92 college student volunteers aged 18-25 from January 2023 to December 2024...[Objectives]To investigate differences in BMI and renal function across constitution types and influencing factors of blood pressure.[Methods]92 college student volunteers aged 18-25 from January 2023 to December 2024 were selected.BMI,blood pressure,and renal function markers—blood urea nitrogen(BUN),creatinine(Cr),uric acid(UA),were compared across constitution types.Multiple stepwise regression analysis was applied to identify the influencing factors of blood pressure.[Results]Among 92 healthy participants aged 18-25,Shar-predominant constitution accounted for 50%,Khii-predominant for 25%,and Badgan-predominant for 20.65%.Significant differences existed in mean systolic and diastolic blood pressure across constitution types(systolic:F=4.56,P=0.001;diastolic:F=3.78,P=0.005).Shar-predominant group showed significantly higher systolic blood pressure than other types(P<0.05),while Khii-predominant group had higher diastolic pressure.Shar-predominant constitution demonstrated significantly greater height,weight,and BMI compared to other types(P<0.05).Males exhibited significantly higher height,weight,and BMI than females(P<0.05).Shar-predominant group showed significantly elevated urea,uric acid,and creatinine levels compared to other constitution types(P<0.05).Males had significantly higher mean urea,uric acid,and creatinine levels than females(P<0.05).Correlation analysis revealed stronger associations between BMI,renal function,and blood pressure in Shar-predominant group(r>0.50,P<0.05).Multiple regression analysis identified BMI as the primary influencing factor for blood pressure,followed by urea and uric acid.In Shar-predominant group,BMI exerted the strongest effect on blood pressure(β=0.60-0.65,P<0.001).[Conclusions]This study provides important evidence for health management in populations with different constitution types.展开更多
The authors regret to report the following error made in“Spatiotemporal dynamics of neuron differentiation and migration in the developing human spinal cord;52(2025)-101283-1295;Doi:https://doi.org/10.1016/j.jgg.2025...The authors regret to report the following error made in“Spatiotemporal dynamics of neuron differentiation and migration in the developing human spinal cord;52(2025)-101283-1295;Doi:https://doi.org/10.1016/j.jgg.2025.08.004”.In Tables S1 and S2 in the supplementary materials of this paper,some items were written in Chinese.The corresponding pictures and tables were not uploaded in time.展开更多
Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachrono...Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.展开更多
Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Metho...Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Methods:Acoustic analysis and TCM constitution assessment were performed for all 620 participants using Praat software and the CCMQ,respectively.Results:For formant features,the speech duration of special constitution participants was shorter than that of neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency participants when pronuncing the vowels/a/,/i/,and/u/.Compare to Yang-deficiency,Qi-deficiency participants had a shorter speech duration when pronucing/i/.For/u/,blood-stasis participants exhibited a lower F1 value than neutral participants.For vocal features,special constitution participants showed higher local jitter than neutral,dampness-heat,and Yang-deficiency participants(for/a/,/i/,and/u/).Higher absolute local jitter than neutral or dampness-heat participants.Compared with neutral or Yang-deficiency participants,special participants owned a higher local shimmer(dB).Special participants had a lower harmonicity autocorrelation than neutral,dampness-heat,or Yang-deficiency participants.Conclusions:Formant features may effectively differentiate special constitution from neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency constitutions based on vowel duration measurements(/a/,/i/,/u/).For the vowel/u/,F1 values may help distinguish blood-stasis from neutral constitution.Vocal features appear particularly useful for distinguishing special constitution from neutral,dampness-heat,or Yang-deficiency constitution,with local jitter and harmonicity autocorrelation showing significant discriminatory power.展开更多
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
文摘Objective: to study the relationship between TCM constitution type and TCM syndrome differentiation of knee arthritis. Methods: a total of 100 patients with knee osteoarthritis collected in our department from April 2019 to April 2020 were selected for in-depth analysis of the distribution of TCM constitution types and TCM syndrome differentiation and classification, and the correlation was analyzed. Results: (1) in the dialectical classification of TCM, the deficiency of liver and kidney was correlated with the constitution types of Yang deficiency, Qi deficiency and Yin deficiency. (2) In the syndrome differentiation and classification of TCM, the syndrome of cold and dampness obstruction is correlated with the constitution type of TCM, which is Qi deficiency. (3) In the syndrome differentiation and classification of TCM, the syndrome of weakness of Qi and blood is correlated with the constitution types of TCM including Qi deficiency, Yang deficiency and Yin deficiency. (4) In TCM syndrome differentiation and classification, the syndrome of Qi stagnation and blood stasis is correlated with the constitution type of Yang deficiency. Conclusion: There is a certain correlation between TCM syndrome differentiation and TCM constitution type. Based on this, further exploration of the correlation between diseases and TCM constitution can provide corresponding diagnostic basis for prevention, diagnosis and treatment.
基金Financial supports from the National Natural Science Foundation of China (No. 21801184)the Tianjin Municipal Applied Basic and Key Research Scheme of China (No. 18JCQNJC06400)+3 种基金Xiamen University, Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study (No. SN-ZJU-SIAS-006)Université de Lyon, the French Agence Nationale de la Recherche (Dyna Sweet, ANR-08-BLAN-0305)Glyco@Alps (ANR-15-IDEX-02)Labex Arcane/CBH-EUR-GS (ANR-17-EURE-0003) are gratefully acknowledged。
文摘Macrocycle-based glycoclusters, on account of their promising anti-adhesive properties against bacteria,are potential therapeutic alternatives to classic antibiotics through the much less explored anti-adhesive strategy. In this study, a series of constitutionally-pure pentavalent glycoclusters was prepared by conjugating assorted azido-carbohydrates onto a penta-propargyl rim-differentiated pillar[5]arene(RD-P[5])scaffold through Cu(I)-catalyzed azide–alkyne cycloaddition “click” reactions. Their binding towards therapeutically relevant bacterial lectins, such as Lec A and Lec B from Pseudomonas aeruginosa and concanavalin A(Con A), were evaluated subsequently by isothermal titration calorimetric studies. Most of these isomerfree RD-P[5] pentavalent glycoclusters, except the fucosylated ones, display good affinities to lectins.Nonetheless, the dissociation constants observed are similar to those displayed by an analogous pentavalent glycocluster consisting of four P[5] constitutional isomers, in which the RD-P[5] component merely accounts for 7% in the mixture. Our results revealed that high constitutional purity is not essential for achieving effective multivalent interactions between P[5]-based glycoclusters and lectins, presumably as a result of the conformationally labile nature of the P[5] scaffold. This information provides valuable design principles for low-cost and facile syntheses of glycosylated P[5]s for biomedical applications.
基金National Nonprofit Institute Research Grant for the Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences:Mechanism of Regulating Phlegm-Dampness Constitution to Prevent Metabolic Diseases based on Gut Microbiota-host DNA Methylation(No.YZ-202151)。
文摘OBJECTIVE:To investigate the difference in gut microbiota between population with damp-heat constitution(DHC)and balanced constitution(BC).METHODS:A multi-centered cross-sectional casecontrol study was conducted,which included 249 participants with damp-heat constitution or balanced constitution.Baseline information of participants was collected,and stool samples were collected for gut microbiota analysis.Principal coordinate analysis,linear discriminant analysis effect size analysis,receiver operating characteristic,random forest model,and phylogenetic investigation of communities by reconstruction of unobserved states methods were used to reveal the relationship between gut microbiota and the damp-heat constitution.RESULTS:Compared to those in the BC group,the richness and diversity of the microbiota,specifically those of several short-chain fatty acid producing genera such as Barnesiella,Coprobacter,and Butyricimonas,were significantly decreased in the DHC group.Regarding biological functions,flavonoid biosynthesis,propanoate metabolism,and nucleotide sugar metabolism were suppressed,while arachidonic acid metabolism and glutathione metabolism were enriched in the DHC group.Finally,a classifier based on the microbiota was constructed to discriminate between the DHC and BC populations.CONCLUSION:The gut microbiota of the DHC population exhibits significantly reduced diversity and is closely related to inflammation,metabolic disorders,and liver steatosis,which is consistent with clinical observations,thus serving as a potential diagnostic tool for traditional Chinese medicine constitution discrimination.
基金supported by grants from National Natural Science Foundation of China(82272444,81972031,81972033)China Postdoctoral Science Foundation(2022M722382)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-032A)。
文摘Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.
基金Project supported by the Thousand Talents Program of Jiangxi Province,China(JXSQ2023201003)National Natural Science Foundation of China(42107254)+4 种基金Science and Technology Major Program of Ordos City(2022EEDSKJZDZX014-2)Technological Innovation Guidance Program of Jiangxi Province(20212BDH81029)Rare Earth Industry Fund(IAGM2020DB06)Selfdeployed Projects of Ganjiang Innovation Academy,Chinese Academy of Sciences(E055A01)the Key Research Program of the Chinese Academy of Sciences(ZDRW-CN-2021-3-3)。
文摘The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with the advantage of being environmental-friendly.As one of the organic acids produced by biological metabolism,citric acid was used to leach REEs and explore the performance and process.The results demonstrate that citric acid exhibits higher leaching efficiency(96.00%)for REEs at a relatively low concentration of 0.01 mol/L compared with(NH_(4))_(2)SO_(4)(84.29%,0.1 mol/L)and MgSO_(4)(83.99%,0.1 mol/L).Citric acid shows a preference for leaching heavy rare earth elements,with 99%leaching efficiency in IAREO,which shows higher capacity than(NH_(4))_(2)SO_(4)and MgSO_(4)(as inorganic leaching agents).Kinetic analysis indicates that the leaching process of REEs with citric acid is controlled by both the internal diffusion kinetics and chemical reaction kinetics,which is different from inorganic leaching agents.Visual Minteq calculations confirm that RE-Citrate is the main constituent of the extract solution in the leaching process of the IAREO,thereby enhancing the leaching efficiency of REEs from the IAREO.It suggests that citric acid may be used as a promising organic leaching agent for the environmentalfriendly extraction of REEs from IAREO.
基金Supported by the Applied Basic Research Foundation of Yunnan Province(202101AY070001-050,2019FE001(-026))the Open Foundation(2019KF003)of State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan,Yunnan University+1 种基金the National Natural Science Foundation of China(81860255,81760869)the Scientific Research Foundation of Yunnan Provincial Department of Education(2018JS159)。
文摘OBJECTIVE:Yang-deficiency constitution(YADC)is a common unbalanced constitution that predisposes individuals to certain diseases.However,not all people with YADC manifest develop diseases.This calls for delineation of the underlying molecular mechanisms.Previous studies suggested that the gut microbiota and gene differential expression should be considered.METHODS:In the present study,we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution(BC)counterparts,based on 16 S r RNA gene sequence analysis.Furthermore,YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis,functional clustering and pathway enrichment analyses.RESULTS:The levels of harmful gut microbiota(Prevotellaceae,LDA score>4.0,P=0.0141)and beneficial gut microbiota(Ruminococcaceae,LDA score>4.0,P=0.0025,Faecalibacterium,LDA score>4.0,P=0.0484)were both elevated in healthy YADC individuals.Also,we found that the specific metabolic pathway with 2,6-Dichloro-p-hydroquinone 1,2-Dioxygenase(Pcp A)as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon substances.CONCLUSIONS:Both beneficial and harmful factors had been detected in healthy YADC individuals,functionally,they may have triggered homeostasis to maintain the health of individuals with YADC.The homeostasis may be maintained by beneficial and harmful factors from gut flora and genes.Future studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.
基金supported by the National Research Foundation(NRF)S&F-Scarce Skills Postdoctoral Fellowship,No.120752(to AC)the Global Excellence and Stature,Fourth Industrial Revolution(GES 4.0)Postgraduate Scholarship(to MJR)the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa(SARChI/NRF-DST),No.146290(to DDS and HA).
文摘Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
基金supported by National Natural Science Foundation of China(grant numbers 82072523 to Zhiyong Hou)Postdoctoral program of Clinical medicine of Hebei Medical University(grant numbers PD2023012 to Sujuan Xu)+2 种基金Excellent postdoctoral research funding project of Hebei Province(grant numbers B2023005011 to Sujuan Xu)The 16th special grant of China Postdoctoral Science Foundation(grant numbers 2023T160182 to Sujuan Xu)Natural Science Foundation of Hebei Province,China(grant numbers H2023206230 to Yingchao Yin,H2024206186 to Sujuan Xu).
文摘The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.
基金supported by grants from the Liaoning Province Excellent Talent Program Project(XLYC1902031)Dalian Science and Technology Talent Innovation Plan Grant(2022RG18)Basic Research Project of the Department of Education of Liaoning Province(LJKQZ20222395)。
文摘Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characterized by the loss of oligodendrocytes(OLs)and the disintegration of myelin sheaths,leading to impaired neural connectivity and motor dysfunction.Neural stem cells(NSCs)represent a promising regenerative source for replenishing lost OLs;however,conventional twodimensional(2D)in vitro culture systems lack the three-dimensional(3D)physiological microenvironment.Microfluidic chip technology has emerged as a powerful tool to overcome this limitation by enabling precise spatial and temporal control over 3D microenvironmental conditions,including the establishment of stable concentration gradients of bioactive molecules.Catalpol,an iridoid glycoside derived from traditional medicinal plants,exhibits dual antioxidant and anti-apoptotic properties.Despite its therapeutic potential,the capacity of catalpol to drive NSC differentiation toward OLs under biomimetic 3D conditions,as well as the underlying molecular mechanisms,remains poorly understood.This study aims to develop a microfluidic-based 3D biomimetic platform to systematically investigate the concentration-dependent effects of catalpol on promoting NSCs-to-OLs differentiation and to elucidate the role of the caveolin-1(Cav-1)signaling pathway in this process.Methods We developed a novel multiplexed microfluidic device featuring parallel microchannels with integrated gradient generators capable of establishing and maintaining precise linear concentration gradients(0-3 g/L catalpol)across 3D NSCs cultures.This platform facilitated the continuous perfusion culture of NSC-derived 3D spheroids,mimicking the dynamic in vivo microenvironment.Real-time cell viability was assessed using Calcein-AM/propidium iodide(PI)dual staining,with fluorescence imaging quantifying live/dead cell ratios.Oligodendrocyte differentiation was evaluated through quantitative reverse transcription polymerase chain reaction(qRT-PCR)for MBP and SOX10 gene expression,complemented by immunofluorescence staining to visualize corresponding protein changes.To dissect the molecular mechanism,the Cav-1-specific pharmacological inhibitor methyl‑β‑cyclodextrin(MCD)was employed to perturb the pathway,and its effects on differentiation markers were analyzed.Results Catalpol demonstrated excellent biocompatibility,with cell viability exceeding 96%across the entire tested concentration range(0-3 g/L),confirming its non-cytotoxic nature.At the optimal concentration of 0-3 g/L,catalpol significantly upregulated both MBP and SOX10 expression(P<0.05,P<0.01),indicating robust promotion of oligodendroglial differentiation.Intriguingly,Cav-1 mRNA expression was progressively downregulated during NSC differentiation into OLs.Further inhibition of Cav-1 with MCD further enhanced this effect,leading to a statistically significant increase in OL-specific gene expression(P<0.05,P<0.01),suggesting Cav-1 acts as a negative regulator of OLs differentiation.Conclusion This study established an integrated microfluidic gradient chip-3D NSC spheroid culture system,which combines the advantages of precise chemical gradient control with physiologically relevant 3D cell culture.The findings demonstrate that 3 g/L catalpol effectively suppresses Cav-1 signaling to drive NSC differentiation into functional OLs.This work not only provides novel insights into the Cav-1-dependent mechanisms of myelination but also delivers a scalable technological platform for future research on remyelination therapies,with potential applications in cerebral palsy and other white matter disorders.The platform’s modular design permits adaptation for screening other neurogenic compounds or investigating additional signaling pathways involved in OLs maturation.
基金Supported by Natural Science Foundation of Guangdong Province in China(2018KTSCX161)。
文摘The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic functions in the unit ball by radial derivative.Then we extend the Sharma's results.
基金supported by the Special Clinical Research Project of the Health Industry by the Shanghai Municipal Health Commission(No.202240055)。
文摘Objective:The concept of constitution in traditional Chinese medicine(TCM)has been increasingly recognized as a crucial factor in both the prevention and treatment of insomnia.However,rigorous statistical evidence on the correlation between TCM constitutions—particularly mixed constitutions—and insomnia disorder remains limited.This study aimed to investigate the association between specific TCM constitutions and insomnia disorder.Methods:A cross-sectional study was conducted at the Department of Preventive Medicine,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai,from November 2022 to December 2023.TCM constitutions were assessed using the Constitution in Chinese Medicine Questionnaire.Insomnia disorder was diagnosed by experienced internal medicine physicians according to the criteria of the International Classification of Sleep Disorders,Third Edition.A total of 1065 eligible participants(242 with insomnia disorder and 823 controls)were included in the final analysis.Results:Among the participants,862(80.94%)exhibited biased constitutions,with 75.30%of these having mixed constitutions.Logistic regression analysis revealed a negative association between the gentleness constitution and insomnia disorder,whereas qi-deficiency,yang-deficiency,phlegm-dampness and qidepression constitutions were positively associated with insomnia disorder.These associations remained significant after adjusting for potential confounders and were further validated through sensitivity analysis using propensity score matching.Conclusion:Significant associations between TCM constitutions and insomnia disorder were demonstrated.Future research should further investigate these relationships and explore the underlying mechanisms through rigorous longitudinal and interventional studies to improve understanding and clinical applications.
基金supported by the National Natural Science Foundation of China(T2341019)NSFC-Guangdong Joint Fund(U1132001)+9 种基金General Program of the National Natural Science Foundation of China(82174243 and 82204948)Natural Science Foundation of Guangdong Province,China(2023A1515110757)Guangzhou Science and Technology Plan Project(2024B03J1343)Major Scientific and Technological Project of Guangzhou Municipal Health Commission(20252D003)Research Project of Traditional Chinese Medicine Bureau of Guangdong Province(20241208)General project of Beijing Natural Science Foundation(7242227)Fundamental Research Funds for the Central Universities(BZY-JMZY-2022-001 and 2023-JYB-JBZD-009)High-level Key Discipline of the National Administration of Traditional Chinese Medicine-Traditional Chinese Constitutional Medicine(zyyzdxk-2023251)Major Science and Technology Special Projects in Hubei Province(2023BCA005)the Chief Scientist Research Project of Hubei Shizhen Laboratory(HSL2024SX0002).
文摘Objective:To study the relationship between qi stagnation constitution and suboptimal health status(SHS)or lifestyle.Methods:From 2012 to 2013,we conducted a cross-sectional survey of 24159 Chinese individuals aged 12-80 years.The qi stagnation constitution was assessed using the Constitution in Chinese Medicine Questionnaire.Health status was evaluated through medical records and the Subhealth Measurement Scale V1.0(SHMS V1.0).Health-promoting lifestyles were measured using the Health-Promoting Lifestyle Profile Ⅱ(HPLP-Ⅱ).Results:Of the 24159 participants,16.1%and 15.2%were classified as“always”and“sometimes”having the qi stagnation constitution,respectively.Those classified as“rarely”having the qi stagnation constitution scored higher on both the HPLP-Ⅱ and SHMS V1.0.The participants classified as“always”having the qi stagnation constitution showed a significant association with SHS or disease compared to other imbalanced constitutions.Those in the“always”category were approximately 21 times more likely to be classified as having SHS(odds ratio[OR]:21.17,95%confidence interval[CI]:15.74-28.45),whereas those in the“sometimes”category were approximately six times more likely(OR:5.89,95%CI:5.04-6.90).Accordingly,the qi stagnation constitution score was significantly associated with the diagnosis of SHS,with an area under the curve of 0.77(P<.001).A score of 18.75 yielded the highest Youden Index(0.407),with a sensitivity of 60.5%and a specificity of 80.3%.Significant associations were observed between health-promoting lifestyles and qi stagnation constitution severity in an ordinal regression analysis(P<.001).Protective factors included stress management(OR:1.59),self-actualization(OR:1.57),and exercise(OR:1.36).In contrast,poorer interpersonal relationships(OR:0.79),greater health responsibilities(OR:0.86),and poorer nutrition(OR:0.91)were associated with increased severity.Conclusion:Modulating the qi stagnation constitution through lifestyle interventions may help prevent the progression of SHS to disease,which aligns with core preventive principles in traditional Chinese medicine.
基金Supported by Central Government Major Budget Adjustment Program(the Research on the Medicinal Properties of Brazilian Ginseng,Tonico,and Guarana,No.2060302)。
文摘It is well known that Traditional Chinese Medicine(TCM)has two outstanding academic characteristics:the holistic concept comes from Huang Di Nei Jing,and the syndrome differentiation and treatment comes from Shang Han Lun.These two characteristics denote the two major academic systems of TCM:one is the medical system of Huang Di Nei Jing,also named syndrome differentiation and treatment system of Zang-Fu organs and meridians,focuses on theoretical exploration,which highlights functional connection and emphasizes philosophical thinking.The treatment in this system is based on physiological functions by taking Zang-Fu organs as the main body,Qi,blood,essence,and body fluid as the auxiliary body,and the meridians and collaterals as the connection channels.The other is the syndrome differentiation and treatment system of the six meridians,which emphasizes clinical practice.It encompasses the idea that the six meridians govern various diseases,emphasizes the disease sites and divisional treatment,and pays attention to the precision and appropriateness of prescription-syndrome differentiation.These two academic systems,with mutual influences and relations,are both the essence and pearl of TCM,nevertheless,there are obvious differences between the two in clinical application,so they should be distinguished.This paper will elaborate on the connection and difference between them,and how to organically combine the two systems for better application in clinical practice of TCM.
基金supported by the Natural Science Foundation of Jiangsu Province of China,No.BK20211348(to SHQ)Xuzhou Basic Research Program,No.KC21030(to LYH)+1 种基金Leadership Program of Xuzhou Medical University,No.JBGS202203(to SHQ)Research Grant Council GRF of Hong Kong Special Administrative Region of China,No.17105220(to JGS)。
文摘It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.
基金Supported by Project of Science and Technology Department of Inner Mongolia Autonomous Region(2021GG0117).
文摘[Objectives]To investigate differences in BMI and renal function across constitution types and influencing factors of blood pressure.[Methods]92 college student volunteers aged 18-25 from January 2023 to December 2024 were selected.BMI,blood pressure,and renal function markers—blood urea nitrogen(BUN),creatinine(Cr),uric acid(UA),were compared across constitution types.Multiple stepwise regression analysis was applied to identify the influencing factors of blood pressure.[Results]Among 92 healthy participants aged 18-25,Shar-predominant constitution accounted for 50%,Khii-predominant for 25%,and Badgan-predominant for 20.65%.Significant differences existed in mean systolic and diastolic blood pressure across constitution types(systolic:F=4.56,P=0.001;diastolic:F=3.78,P=0.005).Shar-predominant group showed significantly higher systolic blood pressure than other types(P<0.05),while Khii-predominant group had higher diastolic pressure.Shar-predominant constitution demonstrated significantly greater height,weight,and BMI compared to other types(P<0.05).Males exhibited significantly higher height,weight,and BMI than females(P<0.05).Shar-predominant group showed significantly elevated urea,uric acid,and creatinine levels compared to other constitution types(P<0.05).Males had significantly higher mean urea,uric acid,and creatinine levels than females(P<0.05).Correlation analysis revealed stronger associations between BMI,renal function,and blood pressure in Shar-predominant group(r>0.50,P<0.05).Multiple regression analysis identified BMI as the primary influencing factor for blood pressure,followed by urea and uric acid.In Shar-predominant group,BMI exerted the strongest effect on blood pressure(β=0.60-0.65,P<0.001).[Conclusions]This study provides important evidence for health management in populations with different constitution types.
文摘The authors regret to report the following error made in“Spatiotemporal dynamics of neuron differentiation and migration in the developing human spinal cord;52(2025)-101283-1295;Doi:https://doi.org/10.1016/j.jgg.2025.08.004”.In Tables S1 and S2 in the supplementary materials of this paper,some items were written in Chinese.The corresponding pictures and tables were not uploaded in time.
基金Brazilian National Program of Genomics and Precision Health-Genomas Brasil,Grant/Award Number:MS-SECTICS-Decit/CNPq 16/2023São Paulo Research Foundation,Grant/Award Number:FAPESP-2021/07957-5+5 种基金Barretos Cancer Hospital,Grant/Award Number:13/2021National Oncology Care Support Program (PRONON),CNPq,Grant/Award Number:444217/2023-1Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer)Brazilian Ministry of Health (MoH)National Council for Scientific and Technological DevelopmentCNPq Productivity
文摘Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.
基金supported by the National Natural Science Foundation of China(Nos.81730107 and 81973883)the National Science&Technology Basic Research Project(No.2015FY111700)the Shanghai Pudong New District New Area Project(No.PW2022A-78(WQZ)).
文摘Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Methods:Acoustic analysis and TCM constitution assessment were performed for all 620 participants using Praat software and the CCMQ,respectively.Results:For formant features,the speech duration of special constitution participants was shorter than that of neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency participants when pronuncing the vowels/a/,/i/,and/u/.Compare to Yang-deficiency,Qi-deficiency participants had a shorter speech duration when pronucing/i/.For/u/,blood-stasis participants exhibited a lower F1 value than neutral participants.For vocal features,special constitution participants showed higher local jitter than neutral,dampness-heat,and Yang-deficiency participants(for/a/,/i/,and/u/).Higher absolute local jitter than neutral or dampness-heat participants.Compared with neutral or Yang-deficiency participants,special participants owned a higher local shimmer(dB).Special participants had a lower harmonicity autocorrelation than neutral,dampness-heat,or Yang-deficiency participants.Conclusions:Formant features may effectively differentiate special constitution from neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency constitutions based on vowel duration measurements(/a/,/i/,/u/).For the vowel/u/,F1 values may help distinguish blood-stasis from neutral constitution.Vocal features appear particularly useful for distinguishing special constitution from neutral,dampness-heat,or Yang-deficiency constitution,with local jitter and harmonicity autocorrelation showing significant discriminatory power.
