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BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/ Stat3 pathway in mesenchymal stem cells

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Genes & Diseases 2024年第3期11卷 468-483页

作者： Jie Zhang Jinhai Jiang Hang Liu Shiyu Wang Kaixin Ke Siyuan Liu Yue Jiang Lu Liu Xiang Gao Baicheng He Yuxi Su department of pharmacology School of PharmacyChongqing Medical UniversityChongqing 400016China Key Laboratory of Biochemistry and Molecular pharmacology of Chongqing Chongqing Medical UniversityChongqing 400016China department of Orthopedics Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China orthopedics department Children's Hospital of Chongqing Medical UniversityChongqing 400014China China International Science and Technology Cooperation Base of Child Development and Critical Disorders Jiangxi Hospital Affiliated Children's Hospital of Chongqing Medical UniversityJiangxi 330000China National Clinical Research Center for Child Health and Disorders China

Bone defects and non-union are prevalent in clinical orthopedy,and the outcomes of current treatments are often *** tissue engineering offers a promising approach to treating these conditions *** morphogenetic protein 9(BMP9)can commit mesenchymal stem cells to osteogenic lineage,and a knowledge of the underlying mechanisms may help advance the field of bone tissue ***-rich repeats con-taining G protein-coupled receptor 4(LGR4),a member of G protein-coupled receptors,is essential for modulating bone *** study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying *** marrow stromal cells from BMp9-knockout mice exhibited diminished LGR4 expression,and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal ***,LGR4 expression was increased by BMP9 in C3H10T1/2 ***4 augmented the benefits of BMP9-induced osteogenic markers and bone formation,whereas LGR4 inhibition restricted these ***,the BMP9-induced li-pogenic markers were increased by LGR4 *** protein levels of Raptor and p-Stat3 were elevated by *** knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by ***4 significantly reversed the blocking ef-fect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic *** interacts with p-Stat3,and p-Stat3 activates the LGR4 promoter *** conclusion,LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells,and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

关键词： BMP9 LGR4 mTORC1 Osteogenic differentiation Stat3

Geraniol alleviates cyclophosphamide-induced cardiotoxicity in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第10期14卷 427-435页

作者： Shahid Karim Rasheed A.Shaik department of Clinical pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of pharmacology and Toxicology Faculty of PharmacyKing Abdulaziz UniversityJeddahSaudi Arabia

Objective:To explore the effect of geraniol on cyclophosphamide-induced ***:Mice were divided into five groups:the control group,the cyclophosphamide group(200 mg/kg cyclophosphamide,*** day 7),the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14,along with a single dose of cyclophosphamide on day 7,and the geraniol alone group(200 mg/kg geraniol from day 1 to day 14).At the end of the study,animals were sacrificed,and blood and heart were collected and analyzed for biochemical,histopathological,and immunohistochemical ***:Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers,malondialdehyde,and inflammatory and apoptotic markers,while increasing antioxidant activities in mice with cyclophosphamide-induced ***,it remarkably alleviated histopathological aberrations in cardiac ***:Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant,anti-inflammatory,and antiapoptotic effects.

关键词： Geraniol Cardiotoxicity Natural product Cyclophosphamide Inflammation Apoptosis

Corneal and intraocular pressure changes associated to the circadian rhythms:a narrative review

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1921-1928页

作者： Laura Barberán-Bernardos MiguelÁngel Ariza-Gracia David P Piñero department of Optics Pharmacology and AnatomyUniversity of AlicanteSan Vicente del Raspeig 03690AlicanteSpain ARTORG Center for Biomedical Engineering Research University of BernBern 3008Switzerland department of Ophthalmology(IMQO-Oftalmar) Vithas Medimar International HospitalAlicante 03016Spain

AIM:To synthesize the current body of research regarding the diurnal variations in intraocular pressure(IOP)and corneal biomechanical and morphological parameters,highlighting their significance in various eye ***:A comprehensive review of studies on the diurnal variations of IOP and corneal parameters was *** findings from various studies were assessed,including the Goldmann applanation tonometry(GAT)and non-contact *** on the variations in central corneal thickness(CCT),corneal curvature,and corneal biomechanics measured by the Ocular Response Analyzer system across different population groups was extracted and ***:In both healthy subjects and those with Fuchs dystrophy,IOP and CCT demonstrate marked diurnal *** remains the gold standard for tonometry,with the highest ***,its measurements are influenced by *** patients and those with pseudoexfoliation showed significant diurnal variations in *** biomechanical parameters,especially corneal hysteresis(CH)and the corneal resistance factor(CRF),largely remain stable throughout the day for most of eye conditions,with some ***,the corneal morphology diurnal variation,particularly curvature,yielded mixed conclusions across ***:Circadian rhythms significantly influence various corneal parameters,most notably IOP and *** studies should emphasize standardized approaches larger sample sizes,and delve deeper into less-explored areas,such as the effects of orthokeratology lenses on diurnal biomechanical shifts.

关键词： circadian rhythms intraocular pressure corneal thickness corneal biomechanics corneal curvature

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.Wolfe Computational Medicine Program and department of pharmacology University of North Carolina–Chapel HillChapel HillNCUSA department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

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Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu Linxi Li Yunxiang Ji Yezhong Wang Yingjia Li Yongyi Ye department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s *** perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory ***,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly *** this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s *** suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in ***,the neurotoxic effects were mitigated,which alleviated neuronal ***,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic *** further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α***,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关键词： metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases neuroinflammation oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry

Efficacy of intraovarian autologous platelet-rich plasma administration in women with low ovarian reserve: A systematic review and meta-analysis

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Asian pacific Journal of Reproduction 2024年第2期13卷 60-67页

作者： Yasmin Sabina Sa’diah Agung Dewanto Lukman A Chandra department of Obstetrics and Gynecology Faculty of MedicinePublic Health and NursingUniversitas Gadjah MadaYogyakartaIndonesia department of pharmacology and Therapy Faculty of MedicinePublic Health and NursingUniversitas Gadjah MadaYogyakartaIndonesia

Objective:To conduct a systematic examination and meta-analysis of the most reliable data from experimental studies evaluating the efficacy of autologous platelet-rich plasma(PRP)on low ovarian ***:A comprehensive search was performed utilizing pertinent search terms across electronic databases,including PubMed,Cochrane,and Google *** included studies that assigned infertile women with low ovarian reserve in experimental *** reserve parameters were measured before and after PRP injection into *** data of each study was retrieved and subsequently ***:Of 301 articles collected and reviewed,six studies were finally included in the *** PRP injection,infertile women showed a non-significant increase in anti-Mullerian hormone(AMH)level(MD=0.10;95%CI-0.04,0.23),a significant increase in antral follicular count(AFC)(MD=1.88;95%CI 0.47,3.29),and a non-significant reduction in follicle-stimulating hormone(FSH)level(MD=-0.22;95%CI-8.32,7.87).Conclusions:Autologous PRP may increase AFC,but not *** it is found beneficial in enhancing ovarian reserve(AFC),further research with strong evidence is still required.

关键词： Platelet-rich plasma Low ovarian reserve Ovarian rejuvenation

Remaking a connection:molecular players involved in post-injury synapse formation

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： Diogo Tomé Ramiro D.Almeida iBiMED-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-Center for neuroscience and Cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

具有快上转化速率的窄光谱蓝光多重共振发光材料

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Science China Materials 2024年第7期67卷 2311-2318页

作者：田杨苏蓉川刘俊杰雷搏文刘旻昊宾正杨 College of Chemistry Sichuan UniversityChengdu 610064China department of pharmacology North Sichuan Medical UniversityNanchong 637100China

如何提高蓝光多重共振发光材料的反隙间窜跃速率(kRISC),并维持较快的辐射跃迁速率(kR)是促进其进一步发展和应用的关键.本论文报道了一种简单且高效的“空间限制的受体-供体-受体(SCADA)”策略,旨在加速蓝色多重共振发光分子的上转化过... 详细信息

如何提高蓝光多重共振发光材料的反隙间窜跃速率(kRISC),并维持较快的辐射跃迁速率(kR)是促进其进一步发展和应用的关键.本论文报道了一种简单且高效的“空间限制的受体-供体-受体(SCADA)”策略,旨在加速蓝色多重共振发光分子的上转化过程.在多重共振中心骨架的最高占据轨道(HOMO)分布位点引入两个氰基苯受体,并在最低位占据轨道(LUMO)引入一个叔丁基咔唑给体,使发射波长蓝移的同时,减小发射的半峰宽(FWHM).此外,供体单元和受体单元呈现近距离的面对面取向,产生分子内给受体相互作用,进而增强自旋轨道耦合,加速反隙间窜跃过程.基于“SCADA”策略,本文成功开发出蓝光多重共振发光分子2DCNCz-BN,其FWHM仅为19 nm,并同时具有较快的kRISC(1.8×10^(6) s^(−1))和kR(2.0×10^(8) s^(−1)).以2DCNCz-BN为发光分子的OLED器件,最大外量子效率(EQEmax)为30.2%,并展现出较低的效率滚降,在1000 cd m^(−2)的亮度下,EQE可以维持22.3%.

关键词： multiple resonance emitter boron-nitrogen em-bedded framework fast radiative decay rate fast reverse inter-system crossing rate narrowband blue emission

m^(6)A reader YTHDF1 promotes cardiac fibrosis by enhancing AXL translation

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Frontiers of Medicine 2024年第3期18卷 499-515页

作者： Han Wu Weitao Jiang Ping Pang Wei Si Xue Kong Xinyue Zhang Yuting Xiong Chunlei Wang Feng Zhang Jinglun Song Yang Yang Linghua Zeng Kuiwu Liu Yingqiong Jia Zhuo Wang Jiaming Ju Hongtao Diao Yu Bian Baofeng Yang department of pharmacology(National Key Laboratory of Frigid Zone Cardiovascular Diseases the State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin150081China

Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction(MI)can lead to heart *** N6-methyladenosine(m^(6)A)methylation has been shown to play a pivotal role in the occurrence and development of many *** investigating the biological function of the m^(6)A reader YTHDF1 in cardiac fibrosis,adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts,and MI surgery in vivo and transforming growth factor-β(TGF-β)-activated cardiac fibroblasts in vitro were performed to establish fibrosis *** results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis,whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic ***,zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene ***1 augmented AXL translation and activated the TGF-β-Smad2/3 signaling pathway,thereby aggravating the occurrence and development of cardiac dysfunction and myocardial ***,our data indicated that YTHDF1 was involved in activation,proliferation,and migration to participate in cardiac fibrosis in *** results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.

关键词： cardiac fibrosis YTHDF1 AXL ZBED6 heart failure