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miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu Xiao-Jia Yang Qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina department of physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Jiangsu Clinical Medicine center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

Comparison of the effects of carbamyl-β-methylcholine chloride ad ministered by intravenous,intramuscular and intra-acupuncture point injections

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Journal of Traditional Chinese Medicine 2012年第1期32卷 93-98页

作者：王玉敏高俊虹逯波彭娟范斌崔晶晶王洪新马琰岩喻晓春 department of physiology Experimental Research CenterChina Academy of Chinese Medical Sciences department of physiology Institute of Acupuncture and MoxibustionChina Academy of Chinese Medical Sciences department of Pharmacology Liaoning Medical College

OBJECTIVE:To compare the effects of carbamylβ-methylcholine chloride(CMCC) administered by intra-acupuncture point injection(IAI),intramuscular injection(IMI),and intravenous injection(IVI),and to analyze the ***:In the IAI group,CMCC was injected into the Zusanli acupoint(ST 36) immediately after 30-min stimulation by electro-acupuncture(EA) at the acupoints,and into the femoral vein and skeletal muscle in IVI and IMI groups,***-gastric pressure was *** plasma concentration of CMCC was measured at various ***:The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other *** the IAI group,this effect was significantly stronger than that in the IMI group at 2 min and 15 min,but not significantly different between the two groups at 5 min and 30 *** concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min,but higher than that in the IMI *** concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5,15 and 30 min,indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI *** was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all ***:The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI,which correlated with the blood concentration of CMCC.

关键词： Acupuncture Intra-acupuncture point injection Synergistic effect Plasma concentration

Contribution of Water and Lipid Soluble Substances in the Relaxant Effects of Tymus Vulgaris Extract on Guinea Pig Tracheal Smooth muscle in Vitro

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Chinese Journal of Integrative Medicine 2016年第5期22卷 377-383页

作者： Rana Keyhanmanesh Mohammad Hossien Boskabady Mohammad Ali Ebrahimi Saadatloo Morteza Boskabady Drug Applied Research center Tabriz University of Medical Sciences Tuberculosis and Lung Research center Tabriz University of Medical Sciences department of physiology Tabriz University of Medical Sciences department of physiology School of MedicineMashhad University of Medical Sciences Neurogenic Inflammation Research center Mashhad University of Medical Sciences department of Basic sciences Islamic Azad University

Objective： To examine the relaxant effects of hydro-ethanolic, macerated aqueous （MA） and lipid- free macerated aqueous （LFMA） extract of Tymus vulgaris on tracheal chains of guinea pigs. Methods： The relaxant effects of five cumulative concentrations of each extract （0.4, 0.8, 1.2, 1.6 and 2.0 g/100 mL） were compared with saline as negative control and five cumulative concentrations of theophylline （0.1, 0.2, 0.4, 0.6 and 0.8 mmol/L） on precontracted tracheal smooth muscle of guinea pig with 60 mmol/L KCl （group 1） and 10 μmol/L methacholine （group 2, n=6 for each group）. Results： In group 1 all concentrations of theophylline, three higher concentrations of hydro-ethanolic, two concentrations of LFMA and last concentration of MA extracts showed significant relaxant effects compared with that of saline （P〈0.05 or P〈0.01）. Two lower concentrations of LFMA and all concentrations of MA except higher one caused contraction compared with saline （P〈0.05 or 0.01）. In group 2 experiments, all concentrations of theophylline, hydro-ethanolic, MA and LFMA extracts showed significant relaxant effects compared to that of saline （P〈0.05 or P〈0.01）. In both groups, the relaxant effect of all concentrations of hydro-ethanolic extract were significantly higher than most concentrations of others （P〈0.05 or P〈0.01）. The relaxant effect of different concentrations of three extracts were significantly greater in group 2 compared with group 1 experiments （all P〈0.01）. There were significantly positive correlations between the relaxant effects and concentrations for theophylline and all extracts in both groups （P〈0.05 or P〈0.01）. Conclusion： Hydro-ethanolic extract has a potent weaker relaxant effect for other extracts from Tymus vulgaris on tracheal chains of guinea pigs.

关键词： Tymus vulgaris hydro-ethanolic extract macerated aqueous extract lipid-free macerated aqueous extract relaxant effect guinea pig tracheal

Going nuclear: Molecular adaptations to exercise mediated by myonuclei

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Sports Medicine and Health Science 2023年第1期5卷 2-9页

作者： Pieter J.Koopmans Kevin A.Zwetsloot Kevin A.Murach Molecular muscle Mass Regulation Laboratory Exercise Science Research CenterDepartment of HealthHuman Performanceand RecreationUniversity of ArkansasFayettevilleARUSA Cell and Molecular biology Program University of ArkansasFayettevilleARUSA Integrated muscle physiology Laboratory Appalachian State UniversityBooneNCUSA department of Public Health and Exercise Science Appalachian State UniversityBooneNCUSA department of biology Appalachian State UniversityBooneNCUSA

muscle fibers are multinucleated,and muscle fiber nuclei(myonuclei)are believed to be post-mitotic and are typically situated near the periphery of the *** to the unique organization of muscle fibers and their nuclei,the cellular and molecular mechanisms regulating myofiber homeostasis in unstressed and stressed conditions(e.g.,exercise)are unique.A key role myonuclei play in regulating muscle during exercise is gene *** recently have investigators had the capability to identify molecular changes at high resolution exclusively in myonuclei in response to perturbations in *** purpose of this review is to describe how myonuclei modulate their transcriptome,epigenetic status,mobility and shape,and microRNA expression in response to exercise in *** the relative paucity of high-fidelity information on myonucleus-specific contributions to exercise adaptation,we identify specific gaps in knowledge and provide perspectives on future directions of research.

关键词： Skeletal muscle Epigenetics muscle memory Transcription myomiR

Antifibrogenic effects of vitamin D derivatives on mouse pancreatic stellate cells

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World Journal of Gastroenterology 2018年第2期24卷 170-178页

作者： Peter Wallbaum Sarah Rohde Luise Ehlers Falko Lange Alexander Hohn Carina Bergner Sarah Marie Schwarzenbock Bernd Joachim Krause Robert Jaster department of MedicineⅡ Division of GastroenterologyRostock University Medical CenterRostock 18057Germany Oscar-Langendorff-Institute of physiology Rostock University Medical CenterRostock 18057Germany department of Nuclear Medicine Rostock University Medical CenterRostock 18057Germany

AIM To study the molecular effects of three different D-vitamins, vitamin D2, vitamin D3 and calcipotriol, in pancreatic stellate cells(PSCs).METHODS Quiescent PSCs were isolated from mouse pancreas and activated in vitro by seeding on plastic surfaces. The cells were exposed to D-vitamins as primary cultures(early-activated PSCs) and upon re-culturing(fullyactivated cells). Exhibition of vitamin A-containing lipid droplets was visualized by oil-red staining. Expression of α-smooth muscle actin(α-SMA), a marker of PSC activation, was monitored by immunofluorescence and immunoblot analysis. The rate of DNA synthesis was quantified by 5-bromo-2'-deoxyuridine(Brd U) incorporation assays. Real-time PCR was employed to monitor gene expression, and protein levels of interleukin-6(IL-6) were measured by ELISA. Uptake of proline was determined using 18 *** Sustained culture of originally quiescent PSCs inducedcell proliferation, loss of lipid droplets and exhibition of stress fibers, indicating cell activation. When added to PSCs in primary culture, all three D-vitamins diminished expression of α-SMA(to 32%-39% of the level of control cells; P < 0.05) and increased the storage of lipids(scores from 1.97-2.15 on a scale from 0-3; controls: 1.49; P < 0.05). No such effects were observed when D-vitamins were added to fully-activated cells, while incorporation of Brd U remained unaffected under both experimental conditions. Treatment of re-cultured PSCs with D-vitamins was associated with lower expression of IL-6(-42% to-49%; P < 0.05; also confirmed at the protein level) and increased expression of the vitamin D receptor gene(209%-321% vs controls; P < 0.05). There was no effect of D-vitamins on the expression of transforming growth factor-β1 and collagen type 1(chain α1). The lowest uptake of proline, a main component of collagen, was observed in calcipotriol-treated *** The three D-vitamins inhibit, with similar efficiencies, activation of PSCs in v

关键词： Pancreatic stellate cells Fibrosis Vitamin D2 Vitamin D3 Calcipotriol

The HDAC3 enzymatic activity regulates skeletal muscle fuel metabolism

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Journal of Molecular Cell biology 2019年第2期11卷 133-143页

作者： Shiyan Song Yefei Wen Hui Tong Emanuele Loro Yingyun Gong Jidong Liu Sungguan Hong Lei Li Tejvir S.Khurana Maoping Chu Zheng Sun Children's Heart center The Second Affiliated Hospital and Yuying Children's Hospital Institute of Cardiovascular Development and Translational MedicineWenzhou 325027 China Division of Endocrinology Diabetes and Metabolism Department of Medicine Baylor College of Medicine Houston TX 77030 USA department of physiology and Pennsylvania muscle Institute Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA department of Chemistry Chung-Ang University Seoul Korea department of Molecular and Cellular biology Baylor College of Medicine Houston TX 77030 USA

Histone deacetylase 3 (HDAC3) is a major HDAC, whose enzymatic activity is targeted by small molecule inhibitors for treating a variety of conditions. However, its enzymatic activity is largely dispensable for its function in embryonic development and hepatic lipid ***3 plays a pivotal role in regulating muscle fuel metabolism and contractile function. Here, we address whether these muscular functions of HDAC3 require its enzymatic activity. By mutating the NCoR/SMRT corepressors in a knock - in mouse model named NS-DADm, we ablated the enzymatic activity of HDAC3 without affecting its protein levels. Compared to the control mice, skeletal muscles from NS-DADm mice showed lower force generation, enhanced fatigue resistance, enhanced fatty acid oxidation, reduced glucose uptake during exercise, upregulated expression of metabolic genes involved in branchedchain amino acids catabolism, and reduced muscle mass during aging, without changes in the muscle fiber-type composition or mitochondrial protein content. These muscular phenotypes are similar to those observed in the HDAC3-depleted skeletal muscles, which demonstrates that, unlike that in the liver or embryonic development, the metabolic function of HDAC3 in skeletal muscles requires its enzymatic activity. These results suggest that drugs specifically targeting HDAC3 enzyme activity could be developed and tested to modulate muscle energy metabolism and exercise performance.

关键词： HDAC muscle metabolism nuclear receptor corepressor histone deacetylation

Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells

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Acta Pharmacologica Sinica 2004年第3期25卷 87-92页

作者： Lin CHANG2,3,Jian-xin XU4,Jing ZHAO5,Yong-zheng PANG2,3,Chao-shu TANG2,3,Yong-fen QI5,6 2Institute of Cardiovascular Diseases,the FirstHospital,Peking University,Beijing 100034 3Institute of Cardiovascular Diseases,Peking University,Beijing 100083 4Instituteof biophysics,Chinese Academy of Sciences,Beijing 100101 5department of physiology,Health Science center,Peking University,Beijing 100083,China Institute of Cardiovascular Diseases the First Hospital Peking University 北京 100034 Institute of biophysics Chinese Academy of Sciences 北京 100101 department of physiology Health Science Center Peking University 北京 100083

AIM: To observe protective effects of taurine on reactive oxygen species generation induced by homocysteine in rat vascular smooth muscle cells (VSMC). METHODS: Rat VSMC was incubated with various concentrations of homocysteine and taurine. The lactate dehydrogenase (LDH) activity which released into culture medium was elevated as an indicator for VSMC injury. The reactive oxygen species (ROS) — hydrogen peroxide (H2O2) and superoxide anion (O2ˉ· )were measured with luminol or lucigenin chemiluminescences method, and the mitochondria Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) were also measured in treated VSMC. RESULTS: LDH leakage from cultured VSMC treated with homocystenie, was increased (P0.05 vs control). In this study, the superoxide anion in VSMC was not detectable by chemiluminent method. In addition, treatment of VSMC with taurine increased mitochondria Mn-SOD and CAT activity in a concentration dependent manner (P<0.05), but homocysteine decreased mitochondria Mn-SOD and CAT activity (P<0.01 vs control). In addition, co-administration of taurine markedly ameliorated homocysteine-induced inhibition of Mn-SOD and CAT activity in VSMC (P<0.01 vs homocysteine alone group). CONCLUSION: Taurine antagonized the effects of homocysteine on ROS generation and anti-oxidant enzyme activities in rat VSMC in vitro.

关键词： homocysteine taurine vascular smooth muscle mitochondria reactive oxygen species

Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs

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Journal of Zhejiang University-Science B(biomedicine & biotechnology) 2011年第3期12卷 201-209页

作者： Mohammad-Hossein BOSKABADY Rana KEYHANMANESH Saeed KHAMENEH Yousef DOOSTDAR Mohammad-Reza KHAKZAD Pharmaceutical Research Centre Department of PhysiologySchool of MedicineMashhad University of Medical Sciences department of physiology Tabriz University of Medical Sciences Tuberculosis and Lung Research Centre Tabriz University of Medical Sciences Drug Applied Research Centre Tabriz University of Medical Sciences department of Pathology Islamic Azad University Zakaria Research center Islamic Azad University

Several different pharmacological effects have been described for Nigella sativa(Siah-Daneh) ,including an anti-inflammatory *** the present study,the effect of the extract of *** on lung pathology and blood interleukin-4(IL-4) and interferon-γ(IFN-γ) of sensitized guinea pigs was *** groups(n=8 for each group) of guinea pigs sensitized to ovalbumin(OA) were given drinking water alone,and drinking water containing low and high concentrations of the plant extract,*** animals of the control group(n=8) were treated with saline instead of OA and were given drinking *** pathological changes of the lung,including infiltration of eosinophils and lymphocytes,local epithelial necrosis,the presence of oedema,thickening of the basement membrane,smooth muscle layer hypertrophy,mucosal secretion,and the presence of mucosal plug,and blood IL-4 and IFN-γof sensi-tized guinea pigs were *** lungs of the sensitized group showed significant pathological changes(P<0.001) .Blood IL-4 and IFN-γwere increased in sensitized animals compared to the controls(P<0.01 and P<0.001,respectively) .Treatment of sensitized animals with the extract led to a significant decrease in pathological changes of the lung(P<0.01 to P<0.001) ,except for the oedema in the sensitized group treated with low concentration of the extract,but an increased IFN-γ.These results confirm a preventive effect of *** extract on lung inflammation of sensitized guinea pigs.

关键词： Nigella sativa Asthma Sensitization Inflammation Cytokine

Anti-diabetic properties and bioactive compounds of Teucrium polium L.

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Asian Pacific Journal of Tropical biomedicine 2020年第10期10卷 433-441页

作者： Ali Akbar Asghari Amin Mokhtari-Zaer Saeed Niazmand Kathleen Mc Entee Maryam Mahmoudabady department of physiology Faculty of MedicineMashhad University of Medical SciencesMashhadIran Laboratory of physiology Faculty of MedicineUniversitéLibre de BruxellesBrusselsBelgium Neurogenic Inflammation Research center Mashhad University of Medical SciencesMashhadIran

Diabetes mellitus is a common metabolic disease with considerable morbidity and mortality. Untreated or improperly-treated diabetes can be associated with several long-term complications that necessitate an effective way to manage diabetes. Due to the side effects of synthetic glucose-lowering agents, alternative therapeutic modalities such as medicinal plants have attracted notable attention. Teucrium polium L. is a medicinal herb with antioxidant, antinociceptive, anti-inflammatory, hypolipidemic, hepatoprotective, and hypoglycemic properties. In vitro and in vivo studies have been conducted to characterize the anti-diabetic properties of Teucrium polium L. and its bioactive compounds. We conducted a literature study using Scopus, Pub Med, and Google Scholar including the keywords "diabetes" and "Teucrium polium". We also scanned all the references cited by the retrieved articles. According to this review, Teucrium polium administration displayed anti-diabetic effects by targeting different mechanisms and pathways, such as enhancement of insulin secretion and insulin level, improvement of oxidative damage, regeneration of pancreatic β-cells, and promotion of glucose uptake in muscle tissues by increasing GLUT-4 translocation as well as inhibiting α-amylase activity. Although Teucrium polium has been widely regarded as a traditional method, the pharmacological studies on anti-diabetic effects are not sufficient, most studies are either in-vivo or in-vitro. The preclinical and clinical studies are further required to confirm the efficacy of Teucrium polium.

关键词： diabetic protective bioactive