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Single-cell transcriptomic profiling reveals ZEB1-mediated regulation in microglial subtypes and the impact of exercise on neuroinflammatory responses

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Traditional medicine Research 2025年第2期10卷 55-64页

作者： Jin-Fang Wu Yi-Sheng Chen Yu-Chun Xie department of Rehabilitation medicine Jiangsu Province Geriatric HospitalNanjing 210024China Fujian Key Laboratory of Toxicant and Drug Toxicology Medical CollegeNingde Normal UniversityNingde 352100China Central Laboratory Jiangsu Province Geriatric HospitalNanjing 210024China

Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise ***:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker *** visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and ***,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular ***:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius *** showed a significant presence of Olfm3+ganglion ***1 gene knockout revealed changes in SMAD family gene expression,which regulate *** stress levels were also ***:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological *** may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.

关键词： single-cell transcriptomics brain tissue cellular subtypes biomarker expression neuronal diversity

Magnetic iron oxide nanoparticles carrying PTEN gene to reverse cisplatin-resistance of A549/CDDP cell lines

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Journal of Central South University 2012年第2期19卷 331-339页

作者：闵凌峰何玲玲陈琼俞巧谢明萱 department of geriatric medicine Department of RespiratoryXiangya Hospital of Central South University

To evaluate the feasibility of using magnetic iron oxide nanoparticle as wild PTEN gene carrier for transfection in vitro to reverse cisplatin-resistance of A549/CDDP cells, A549/CDDP cells were transfected with the wild PTEN gene expression plasmid (pGFP-PTEN) by magnetic iron nanoparticle and lipo2000. The transfection efficiency was detected by fluorescence microscope and flow cytometer. The expression levels of PTEN mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry analysis. The effect of PTEN transfection on cell cycle enhances the sensitivity of A549/CDDP to cisplatin and nanoparticle-mediated transfection has a higher efficiency than that of the liposome-mediated group. The apoptosis level was up-regulated in PTEN transfection group. The magnetic iron oxide nanoparticle could be used as one of the ideal gene carriers for PTEN gene delivery in vitro. PTEN can be an effective target for reversing cisplatin-resistance in lung cancer.

关键词： magnetic iron oxide nanoparticle liposome transfection lung cancer PTEN cisplatin-resistance

Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

Differential Expression of Three Hypoxia-inducible Factor-α Subunits in Pulmonary Arteries of Rat with Hypoxia-induced Hypertension

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Acta Biochimica et Biophysica Sinica 2005年第10期37卷 665-672页

作者： Qi-Fang LI Ai-Guo DAI department of respiratory medicine,Human Institute of Gerontology,Human Province geriatric Hospital,Changsha 410001,China department of Anesthesiology.Renji Hospital,Shanghai Second Medical University,Shanghai,China department of respiratory medicine Hunan Institute of Gerontology Hunan Province Geriatric HospitalChangsha 410001 China

Hypoxia inducible transcription factor (HIF)-1α plays an important role in the development ofhypoxic pulmonary hypertension,but little is known about HIF-2α and HIF-3α with respect to transcriptionalregulation by *** examine the expression patterns of all HIF-α subunits (HIF-α,HIF-2α andHIF-3α) in pulmonary arteries of rats undergoing systemic hypoxia,five groups of healthy male Wistarrats were exposed to normoxia (N) and hypoxia for 3 (H),7 (H),14 (Hand 21 (*** arterial pressure (mPAP),vessel morphometry and right ventricular hypertrophy index *** were inflation fixed for immunohistochemistry and in situ hybridization,and homogenizedfor Western blot. mPAP increased significantly after 7 d of hypoxia [(18.4±0.4) vs. (14.4±0.4) mmHg,Hvs.N],reached its peak after 14 d of hypoxia,then remained *** artery remodeling and rightventricular hypertrophy developed significantly after 14 d of *** normoxia,HIF-1α and HIF-3αstaining were slightly positive regarding mRNA levels.A substantial alteration of HIF-1α and HIF-3α stainingoccurred in puhnonary arteries after 14 d and 7 d of hypoxia,respectively,but HIF-2α staining showed aninversed trend after 14 d of *** levels of all HIF-α subunits except HIF-3α showed a markedincrease corresponding to the duration of hypoxia,which was obtained by Western *** study foundthat HIF-1α. HIF-2α and HIF-3α may not only confer different target genes,but also play key pathogeneticroles in hypoxic-induced pulmonary hypertension.

关键词： hypoxia inducible factor-α hypoxia hypertension lung

Differential and Reciprocal Regulation between Hypoxia-inducible Factor-αSubunits and Their Prolyl Hydroxylases in Pulmonary Arteries of Rat with Hypoxia-induced Hypertension

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Acta Biochimica et Biophysica Sinica 2006年第6期38卷 423-434页

作者： Yun-Rong CHEN~&,Ai-Guo DAI~*,Rui-Cheng HU,and Yong-Liang JIANGdepartment of respiratory medicine,Hunan Institute of Gerontology,Hunan Province geriatric Hospital,Changsha 410001,China department of respiratory medicine Hunan Institute of Gerontology Hunan Province Geriatric HospitalChangsha 410001 China

Hypoxia-inducible factor (HIF)-α subunits (HIF-1α,HIF-2α and HIF-3α),which play a pivotalrole during the development of hypoxia-induced pulmonary hypertension (HPH),are regulated through post-U’anslational hydroxylation by their three prolyl hydroxylase domain-containing proteins (PHD 1,PHD2 and PHD3).PHDs could also be regulated by *** differential and reciprocal regulation between HIF-α and PHDs duringthe development of HPH remains *** investigate this problem,a rat HPH model was *** arterial pressure increased significantly after 7 d of *** artery remodeling indexand right ventricular hypertrophy became evident after 14 d of ***-1α and HIF-2α mRNA increasedslightly after 7 d of hypoxia,but HIF-3α increased significantly after 3 d of *** protein expressionlevels of all three HIF-α were markedly upregulated after exposure to ***2 mRNA and proteinexpression levels were upregulated after 3 d of hypoxia;PHD 1 protein declined after 14 d of hypoxia withoutsignificant mRNA ***3 mRNA and protein were markedly upregulated after 3 d of hypoxia,then themRNA remained at a high level,but the protein declined after 14 d of *** hypoxic animals,HIF-lotproteins negatively correlated with PHD2 proteins,whereas HIF-2α and HIF-3α proteins showed negativecorrelations with PHD3 and PHD 1 proteins,*** three HIF-α proteins were positively correlatedwith PHD2 and PHD3 *** the present study,HIF-α subunits and PHDs showed differential andreciprocal regulation,and this might play a key pathogenesis role in hypoxia-induced pulmonary hypertension.

关键词： hypoxia-inducible factor prolyl hydroxylase hypertension pulmonary hydroxylation

Transforming Growth Factor-β1 Induces Transdifferentiation of Fibroblasts into Myofibroblasts in Hyp0Xic Pulmonary Vascular Remodeling

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Acta Biochimica et Biophysica Sinica 2006年第1期38卷 29-36页

作者： Yong-Liang JIANG Ai-Guo DAI Qi-Fang LI Rui-Cheng HU department of respiratory medicine,Hunan Institute of Gerontology,Hunan Province geriatric Hospital,Changsha 410001,China department of respiratory medicine Hunan Institute of Gerontology Hunan Province Geriatric Hospital Changsha 410001 China

The muscularization of non-muscular pulmonary arterioles is an important pathological featureof hypoxic pulmonary vascular ***,the origin of the cells involved in this process is stillnot well *** present study was undertaken to test the hypothesis that transforming growthfactor-β1 (TGF-β1) can induce transdifferentiation of fibroblasts into myofibroblasts,which might play akey role in the muscularization of non-muscular pulmonary *** was found that mean pulmonaryarterial pressure increased significantly after 7 d of *** artery remodeling index and rightventricular hypertrophy became evident after 14 d of *** distribution of nonmuscular,partiallymuscular,and muscular vessels was significantly different after 7 d of *** demonstrated that the expression of co-smooth muscle actin was increased in intra-acinar pulmonaryarteries with increasing hypoxic ***-β1 mRNA expression in pulmonary arterial walls was increasedsignificantly after 14 d of hypoxia,but showed no obvious changes after 3 or 7 d of *** pulmonarytunica adventitia and tunica media,TGF-β1 protein staining was poorly positive in control rats,but wasmarkedly enhanced after 3 d of hypoxia,reaching its peak after 7 d Of *** myofibroblast phenotypewas confirmed by electron microscopy,which revealed microfilaments and a well-developed rough endo-plasmic *** together,our results suggested that TGF-β1 induces transdifferentiation of fibro-blasts into myofibroblasts,which is important in hypoxic pulmonary vascular remodeling.

关键词： transforming growth factor-β1 fibroblast myofibroblast hypertension lung

Hypoxia Induces Transforming Growth Factor-β1 Gene Expression in the Pulmonary Artery of Rats via Hypoxia-inducible Factor-1α

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Acta Biochimica et Biophysica Sinica 2007年第1期39卷 73-80页

作者： Yongliang JIANG Aiguo DAI Qifang LI and Ruicheng HU Depoptment of respiratory medicine,Hunan Institute of Gerontology,Hunan Province geriatric Hospital,Changsha 410001,China department of respiratory medicine Hunan Institute of Gerontology Hunan Province Geriatric HospitalChangsha 410001 China

The present study was undertaken to investigate the dynamic expression of hypoxia induciblefactor-1 α (HIF-1α) and transforming growth factor-β1 (TGF-β1) in hypoxia-induced pulmonary hypertensionof *** was found that mean pulmonary arterial pressure (mPAP) increased significantly after 7 d *** artery remodeling index and right ventricular hypertrophy became evident after 14 d ***-1α mRNA staining was less positive in the control,hypoxia for 3 d and hypoxia for 7 d,butbegan to enhance significantly after 14 d of hypoxia,then remained *** of HIF-1 α protein inthe control was less positive,but was up-regulated in pulmonary arterial tunica intima of all hypoxic ***-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, butshowed no obvious changes after 3 or 7 d of *** pulmonary tunica adventitia and tunica media,TGF-β1 protein staining was less positive in control rats,but was markedly enhanced after 3 d of hypoxia,reaching its peak after 7 d of hypoxia,and then weakening after 14 and 21 d of *** blottingshowed that HIF- 1α protein levels increased significantly after 7 d of hypoxia and then remained at a highlevel. TGF-β1 protein level was markedly enhanced after 3 d of hypoxia,reaching its peak after 7 d ofhypoxia,and then decreasing after 14 and 21 d of *** correlation analysis showed that HIF-1αmRNA, TGF-β1 mRNA, TGF-β1 protein were positively correlated with mPAP,vessel morphometry andright ventricular hypertrophy ***-β1 protein (tunica adventitia) was negatively correlated withHIF-lα *** together,our results suggest that changes in HIF-lα and TGF-β1 expression afterhypoxia play an important role in hypoxia-induced pulmonary hypertension of rats.

关键词： hypoxia inducible factor-1α transforming growth factor-β1 hypertension lung hypoxia

Effects of Ligustrazine on Airway Inflammation in A Mouse Model of Neutrophilic Asthma

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Chinese Journal of Integrative medicine 2018年第5期24卷 353-358页

作者： LIU Xiao-ming1 WANG Yong-bin2 WU Qian2 BIAN Zhong-rui2 CHE Xiao-wen2 department of geriatric medicine the Affiliated Hospital of Shandong University of Traditional Chinese Medicine department of respiratory medicine the Second Hospital of Shandong University

Objective: To investigate the effects of ligustrazine(LTZ) on airway inflammation in a mouse model of neutrophilic asthma(NA). Methods: Forty healthy C57 BL/6 female mice were randomly divided into 4 groups using a random number table, including the normal control, NA, LTZ and dexamethasone(DXM) groups, with 10 rats in each group. The NA mice model was established by the method of ovalbumin combined with lipopolysaccharide sensitization. At 0.5 h before each challenge, LTZ and DXM groups were intraperitoneally injected with LTZ(80 mg/kg) or DXM(0.5 mg/kg) for 14 d, respectively, while the other two groups were given the equal volume of normal saline. After last challenge for 24 h, the aerosol inhalation of methacholine was performed and the airway reactivity was measured. The bronchoalveolar lavage fluid(BALF) was collected. The Wright-Giemsa staining was used for total white blood cells and differential counts. The levels of cytokines interleukin(IL)-17 and IL-10 were detected by enzyme-linked immunosorbent assay. The pathological change of lung tissue was observed by hematoxylin eosin staining. Results: The airway responsiveness of the NA group was significantly higher than the normal control group(P<0.05), while those in the LTZ and DXM groups were significantly lower than the NA group(P<0.05). The neutrophil and eosinophil counts in the LTZ and DXM groups were significantly lower than the NA group(P<0.05), and those in the LTZ group were significantly lower than the DXM group(P<0.05). There were a large number of peribronchiolar and perivascular inflammatory cells in filtration in the NA group. The airway inflammation in the LTZ and DXM groups were significantly alleviated than the NA group. The infiltration in the LTZ group was significantly reduced than the DXM group. Compared with the normal control group, the IL-17 level in BALF was significantly increased and the IL-10 level in BALF was significantly decreased in the NA group(P<0.05). LTZ and DXM treatment

关键词： ligustrazine neutrophilic asthma airway inflammation cytokine

Development and Validation of A Patient Reported Outcome Instrument for Chronic Obstructive Pulmonary Diseases

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Chinese Journal of Integrative medicine 2015年第9期21卷 667-675页

作者：李建生王明航余学庆李素云谢洋 geriatric department Henan University of Traditional Chinese Medicine department of respiratory The First Affiliated Hospital of Henan University of Traditional Chinese Medicine

Objective： To develop and validate a specific patient reported outcome （PRO） for chronic obstructive pulmonary disease （COPD） patients （COPD-PRO） at a set of standardized procedures. Methods： Literature analysis, interview and group discussion were performed to draft an initial model of COPD-PRO. Thereafter, 65 clinicians and experts throughout China reviewed the draft scale, Then cognitive debriefing interviews with 40 patients were conducted to assess respondent comprehension of the scale. After that, the revised scale was validated through pre-testing and field-testing. Finally, the psychometric properties of the COPD-PRO were evaluated by indicators such as validity, reliability and responsiveness based on the data from 230 patients. Results： The COPD-PRO contained 17 items in 3 domains： amelioration of clinical symptoms, satisfaction of health condition and satisfaction of treatment effect. The Cronbach＇s ~, Split-half coefficient and test-retest coefficient were 0.806, 0.744, 0.703, respectively; the correlation coefficients between domains and overall scale were 0.835-0.963; 5 factors were extracted according to the conceptual model. The differences of the scale scores before and after treatment were statistically significant （P=0.000）. Conclusions： The COPD- PRO has good validity, reliability and responsiveness. The COPD-PRO could provide patients＇ response to the treatments and then evaluate the effect of treatment in a standardized way.

关键词： lung disease obstructive Chinese medicine patient reported outcome reliability validity