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Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells

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bone research 2018年第4期6卷 393-407页

作者： Wenjia Liu Liqiang Zhang Kun Xuan Chenghu Hu Shiyu Liu Li Liao Bei Li Fang Jin Songtao Shi Yan Jin MS-State Key Laboratory & National Clinical research center for Oral diseases & Shaanxi International joint research center for Oral diseases Center for Tissue EngineeringSchool of StomatologyFourth Military Medical UniversityXi’anChina Xi’an Institute of Tissue Engineering and Regenerative Medicine Xi’anChina Department of Anatomy and Cell Biology School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA

Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous *** results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.

关键词： Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells ATP

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Therapeutic effect of neohesperidin on TNF-α-stimulated human rheumatoid arthritis fibroblast-like synoviocytes

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Chinese Journal of Natural Medicines 2021年第10期19卷 741-749页

作者： WANG Xiao-He DAI Ce WANG Jun LIU Rui LI Lei YIN Zong-Sheng Department of bone and joint Surgery Institute of Orthopedic Diseasesthe First Affiliated HospitalJinan UniversityGuangzhou 510000China Department of Orthopedics the First Affiliated Hospital of Anhui Medical UniversityHefei 230000China

During the pathogensis of rheumatoid arthritis(RA),activated RA fibroblast-like synoviocytes(RA-FLSs)combines similar proliferative features as tumor and inflammatory features as osteoarthritis,which eventually leads to joint ***,it is imperative to research and develop new compounds,which can effectively inhibit abnormal activation of RA-FLSs and retard RA ***(Neo)is a major active component of flavonoid compounds with anti-inflammation and anti-oxidant *** this study,the anti-inflammation,anti-migration,anti-invasion,anti-oxidant and apoptosis-induced effects of Neo on RAFLSs were explored to investigate the underlying *** results suggested that Neo decreased the levels of interleukin IL-1β,IL-6,IL-8,TNF-α,MMP-3,MMP-9 and MMP-13 in ***,Neo blocked the activation of the MAPK signaling ***,treatment with Neo induced the apoptosis of FLSs,and inhibited the migration of *** was also found that Neo reduced the accumulation of reactive oxygen species(ROS)induced by TNF-α.Taken together,our results highlighted that Neo may act as a potential and promising therapeutic drug for the management of RA.

关键词： Neohesperidin Rheumatoid-arthritis Fibroblast-like synoviocytes Inflammatory Oxidative stress MAPK

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Transmission Risks of Mountain-Type Zoonotic Visceral Leishmaniasis—Six Endemic Provincial-Level Administrative Divisions,China,2015–2020

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China CDC weekly 2022年第8期4卷 148-152页

作者： Xinyi Wang Shang Xia Jingbo Xue Zhengbin Zhou Yuanyuan Li Zelin Zhu Yi Zhang Qiang Wang Shizhu Li National Institute of Parasitic diseases Chinese Center for Disease Control and Prevention(Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector BiologyWHO Collaborating Centre for Tropical DiseasesNational Center for International Research on Tropical DiseasesShanghaiChina School of Global Health Chinese Center for Tropical Diseases ResearchShanghai Jiao Tong University School of MedicineShanghaiChina

Summary What is already known about this topic?Mountain-type zoonotic visceral leishmaniasis(MTZVL)cases in China have increased significantly between 2015 and 2020.A total of 25 regions had reemerged yielding 88 MT-ZVL indigenous cases,while the total number of visceral leishmaniasis cases *** is added by this report?The transmission risk of MT-ZVL showed a trend of patchy dissemination centered on major endemic areas and medium-high risk occurrence areas of Phlebotomus chinensis with discrete ***-point re-emergence and local outbreaks of MT-ZVL were trending in historically endemic *** are the implications for public health practice?Risk identification and early warnings of MT-ZVL are essential in formulating precise prevention and control strategies in *** frequent monitoring,establishing a mechanism of joint prevention and control,and highlighting health education are recommended.

关键词： prevention establishing precise

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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical research center for Otolaryngologic diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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LOXL3 Inhibits Autophagy of Chondrocytes by Activating Rheb in Osteoarthritis

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Current Medical Science 2023年第6期43卷 1195-1200页

作者： Guang-ping ZHENG Chen LIU Liang ZHANG Qiang ZHONG Yun ZHANG Zhong-ming HUANG Ganzhou Municipal Key Laboratory of bone and joint research The Affiliated Ganzhou Hospital of Nanchang UniversityGanzhou341000China research center of Translational Medicine Jinan Central Hospital Affiliated to Shandong First Medical UniversityJinan250013China

Objective This study aimed to investigate the potential mechanisms by which lysyl oxidase like 3(LOXL3)affects the autophagy in chondrocytes in osteoarthritis(OA),specifically through the activation of mammalian target of rapamycin complex 1(mTORC1).Methods To establish an OA model,rats underwent anterior cruciate ligament transection(ACLT).Chondrocytes were isolated from cartilage tissues and *** blotting was performed to assess the expression of LOXL3,Rheb,phosphorylation of p70S6K(p-p70S6K,a downstream marker of mTORC1),and autophagy *** autophagy of chondrocytes was observed using an immunofluorescence *** The expression levels of both LOXL3 and Rheb proteins were upregulated in chondrocytes isolated from the OA model cartilage,in comparison to those from the normal *** silencing of LOXL3 resulted in a decrease in the protein levels of Rheb and p-p70S6K,as well as an increase in the expression of autophagy-related ***,the effect of LOXL3 could be reversed through the silencing of *** results of the immunofluorescence assay confirmed the impact of LOXL3 and Rheb on chondrocyte *** LOXL3 inhibits chondrocyte autophagy by activating the Rheb and mTORC1 signaling pathways.

关键词： osteoarthritis LOXL3 Rheb mTORC1 chondrocyte autophagy

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Mitigated transmission and health impact of COVID-19 in Beijing,China during spring 2024:Comparison with the global trends

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Science Bulletin 2024年第20期69卷 3212-3215页

作者： Ying Shen Zhaomin Feng Daitao Zhang Xiaoli Wang Ying Sun Fu Li Li Zhang Jiaojiao Zhang Chunna Ma Peng Yang Quanyi Wang Beijing center for Disease Prevention and Control Beijing 100013China Beijing research center for Respiratory Infectious diseases Beijing 100013China

As the coronavirus disease 2019(COVID-19)pandemic enters its fifth year,a global decrease in the prevalence of COVID-19 has been *** waves of COVID-19 have occurred across most nations,each predominantly driven by a particular variant,without evident seasonal or regional patterns[1].However,during winter and spring,when the transmission risk of respiratory pathogens is high,the potential co-circulation of COVID-19 and other respiratory diseases poses significant health risks,potentially straining healthcare systems.

关键词： spring COV global

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Mechanical Sensitive Molecule MACF1 Promotes Osteoblast Differentiation

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医用生物力学 2019年第A1期34卷 71-72页

作者： Lifang Hu Chong Yin Zixiang Wu Zizhang Huang Peihong Su Yan Zhang Zhihao Chen Airong Qian Lab for bone Metabolism Key Lab for Space Biosciences and BiotechnologyResearch Center for Special Medicine and Health Systems EngineeringNPU-UAB Joint Laboratory for Bone MetabolismSchool of Life SciencesNorthwestern Polytechnical University

The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone *** previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity *** findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone *** verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)*** results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling ***,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further ***,we found that MACF1 sequesterd repressors of osteoblast differentiation in *** conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.

关键词： MACF1 osteoblast cell differentiation β-catenin signaling

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Spreading of Human Babesiosis in China:Current Epidemiological Status and Future Challenges

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China CDC weekly 2020年第33期2卷 634-637页

作者： Muxin Chen Qin Liu Jingbo Xue Shaohong Chen Dana Huang Yingfang Yu Yuchun Cai Yan Lu Peng Song Renli Zhang Lin Ai Jiaxu Chen National Institute of Parasitic diseases Chinese Center for Disease Control and Prevention/Chinese Center for Tropical Diseases Research/Key Laboratory of Parasite and Vector BiologyMinistry of Health/National Center for International Research on Tropical DiseasesMinistry of Science and Technology/WHO Collaborating Center for Tropical DiseasesShanghaiChina Shenzhen center for Disease Control and Prevention ShenzhenChina National Institute of Parasitic diseases Chinese Center for Disease Control and Prevention-Shenzhen Center for Disease Control and Prevention Joint Laboratory for Imported Tropical Disease ControlShanghaiChina

Human babesiosis is an infection caused by intraerythrocytic protozoa of the genus Babesia and is a worldwide emerging tick-borne disease(1).Babesia is mainly parasitized in erythrocytes of human or other vertebrates and transmitted by the bite of ticks,blood transfusion,or organ transplantation(1).Humans are generally susceptible to Babesia,especially those who are immunocompromised with conditions such as splenectomy or splenic dysfunction,as well as those of old age,with infirmity,or with other severe diseases.

关键词： (1) Human transfusion

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Disturbed bone remodelling activity varies in different stages of experimental, gradually progressive apical periodontitis in rats

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International Journal of Oral Science 2019年第4期11卷 289-299页

作者： Ruoshi Xu Daimo Guo Xuedong Zhou Jianxun Sun Yachuan Zhou Yi Fan Xin Zhou Mian Wan Wei Du Liwei Zheng State Key Laboratory of Oral diseases National Clinical Research Center for Oral DiseasesDepartment of Cariology and EndodontologyWest China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral diseases National Clinical Research Center for Oral DiseasesDepartment of PediatricsWest China Hospital of StomatologySichuan UniversityChengduChina

bone remodelling keeps going through the lifespan of human by bone formation and bone *** the craniofacial region,mandibles act as the main force for biting and chewing,and also become susceptible to a common bone-loss disease,namely,apical periodontitis,once infected dental pulp is not treated timely,during which bone resorption occurs from the apical foramen to the apical bone *** conventional root canal treatment(RCT)can remove the most of the infection,chronical apical periodontitis due to incomplete removal of dental pulp and subsequent microleakage will become refractory and more challenging,and this process has scarcely been specifically studied as a bone remodelling issue in rat ***,to study chronical and refractory apical periodontitis owing to incomplete cleaning of infected dental pulp and microleackage in vivo,we establish a modified rat model of gradually progressive apical periodontitis by sealing residual necrotic dental pulp and introducing limited saliva,which simulates gradually progressive apical periodontitis,as observed in the clinical treatment of chronical and refractory apical *** show that bone-loss is inevitable and progressive in this case of apical periodontitis,which confirms again that complete and sound root canal treatment is crucial to halt the progression of chronical and refractory apical periodontitis and promote bone ***,bone remodelling was enhanced at the initial stage of apical periodontitis in this model while reduced with a high osteoblast number afterwards,as shown by the time course study of the modified *** that the pathological apical microenvironment reserve its hard tissue formation ability to some degree but in a disturbed ***,our findings can provide insights for future bone regenerative treatment for apical periodontitisassociated bone loss.

关键词： incomplete modelling progressive

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Magnesium promotes vascularization and osseointegration in diabetic states

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International Journal of Oral Science 2024年第1期16卷 122-133页

作者： Linfeng Liu Feiyu Wang Wei Song Danting Zhang Weimin Lin Qi Yin Qian Wang Hanwen Li Quan Yuan Shiwen Zhang State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical research center for Oral diseases&Department of Oral Implantology West China Hospital of StomatologySichuan UniversityChengduChina

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral *** has been proved to promote bone healing under normal ***,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic *** generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased *** then developed Mg-coating implants with hydrothermal *** implants successfully improved the vascularization and osseointegration in diabetic ***,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under ***,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.

关键词： healing diabetic impaired

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