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Neuroprotective and neuroregenerative potential of pharmacologically-induced hypothermia with D-alanine D-leucine enkephalin in brain injury

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Neural Regeneration Research 2018年第12期13卷 2029-2037页

作者： M.Grant Liska Marci G.Crowley Julian P.Tuazon Cesar V.Borlongan center of Excellence for aging and Brain Repair University of South Florida College of Medicine

Neurovascular disorders, such as traumatic brain injury and stroke, persist as leading causes of death and disability - thus, the search for novel therapeutic approaches for these disorders continues. Many hurdles have hindered the translation of effective therapies for traumatic brain injury and stroke primarily because of the inherent complexity of neuropathologies and an inability of current treatment approaches to adapt to the unique cell death pathways that accompany the disorder symptoms. Indeed, developing potent treatments for brain injury that incorporate dynamic and multiple disorder-engaging therapeutic targets are likely to produce more effective outcomes than traditional drugs. The therapeutic use of hypothermia presents a promising option which may fit these criteria. While regulated temperature reduction has displayed great promise in preclinical studies of brain injury, clinical trials have been far less consistent and associated with adverse effects, especially when hypothermia is pursued via systemic cooling. Accordingly, devising better methods of inducing hypothermia may facilitate the entry of this treatment modality into the clinic. The use of the delta opioid peptide D-alanine D-leucine enkephalin（DADLE） to pharmacologically induce temperature reduction may offer a potent alternative, as DADLE displays both the ability to cause temperature reduction and to confer a broad profile of other neuroprotective and neuroregenerative processes. This review explores the prospect of DADLE-mediated hypothermia to treat neurovascular brain injuries, emphasizing the translational steps necessary for its clinical translation.

关键词： stroke traumatic brian injury neurodegeneration temperature management regenerative medicine delta opioids metabolic suppression cerebrovascular disease neurovascular disease

Fabrication of physical and chemical crosslinked hydrogels for bone tissue engineering

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Bioactive Materials 2022年第6期7卷 327-339页

作者： Xu Xue Yan Hu Sicheng Wang Xiao Chen Yingying Jiang Jiacan Su School of Environmental and Chemical Engineering Shanghai UniversityShanghai200444China Institute of translational medicine Shanghai UniversityShanghai200444China Department of Orthopedics Trauma Shanghai Zhongye HospitalShanghai201900China Department of Orthopaedics Trauma Changhai HospitalSecond Military Medical UniversityShanghai200433China Shanghai Clinical Research center for aging and medicine Shanghai200040China

Bone tissue engineering has emerged as a significant research area that provides promising novel tools for the preparation of biomimetic hydrogels applied in bone-related diseases(e.g.,bone defects,cartilage damage,osteoarthritis,etc.).Herein,thermal sensitive polymers(e.g.,PNIPAAm,Soluplus,etc.)were introduced into main chains to fabricate biomimetic hydrogels with injectability and compatibility for those bone defect need minimally invasive surgery.Mineral ions(e.g.,calcium,copper,zinc,and magnesium),as an indispensable role in maintaining the balance of the organism,were linked with polymer chains to form functional hydrogels for accelerating bone regeneration.In the chemically triggered hydrogel section,advanced hydrogels crosslinked by different molecular agents(e.g.,genipin,dopamine,caffeic acid,and tannic acid)possess many advantages,including extensive selectivity,rapid gel-forming capacity and tunable mechanical property.Additionally,photo crosslinking hydrogel with rapid response and mild condition can be triggered by different photoinitiators(e.g.,I2959,LAP,eosin Y,riboflavin,etc.)under specific wavelength of light.Moreover,enzyme triggered hydrogels were also utilized in the tissue regeneration due to its rapid gel-forming capacity and excellent biocompatibility.Particularly,some key factors that can determine the therapy effect for bone tissue engineering were also mentioned.Finally,brief summaries and remaining issues on how to properly design clinical-oriented hydrogels were provided in this review.

关键词： Different crosslinking conditions Biomimetic hydrogel Bone tissue engineering

Artemisinin reverses glucocorticoid-induced injury in bone marrow derived mesenchymal stem cells through regulation of ERK1/2-CREB signaling pathway

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Artemisinin reverses glucocorticoid-induced injury in bone m...

For the sake of longevity:eating less and eating at the right time

世界中医药学会联合会老年医学专业委员会2021年学术年...

作者： Xingan Xing Jiankang Fang Marta Silva Ruohong Lin Wenhua Zheng Centre of Reproduction Development and Aging Institute of Translational MedicineMoE Frontiers Science Center for Precision Oncology Faculty of Health SciencesUniversity of Macau

Glucocorticoids are the most common cause of secondary osteoporosis, which affects both women(pre-and post-menopausal) and men. In cases of prolonged treatment, glucocorticoids promote the loss and inactivation of the differentiational function of bone marrow mesenchymal stromal cells(BMSCs), risking the development of skeletal system diseases such as osteoporosis. This study reports for the first time the protective effect of the antimalarial artemisinin against glucocorticoid-induced insults on primary cultured rat BMSC. At clinically relevant concentrations, artemisinin treatment improved BMSCs survival by promoting a decline of reactive oxygen specias(ROS) production that correlated with the decrease of Caspase 3 activation, LDH release, Δψm loss and apoptosis induced by dexamethasone(DEXA). Additionally, artemisinin improved the osteogenic differentiation of DEXA-damaged cells. DEXA inhibited extracellular-signal-regulated kinase 1/2(ERK1/2) and c AMP response element binding protein(CREB) phosphorylation, and artemisinin treatment promoted their activation in a concentration-dependent manner. PD98059, the specific inhibitor of the ERK1/2 pathway, blocked ERK1/2 phosphorylation and artemisinin protection. Similarly, siCREB attenuated the protective effect of artemisinin, strongly suggesting the involvement of the ERK1/2-CREB pathway in the protective action of artemisinin against DEXA damage in BMSCs.

关键词： Artemisinin Dexamethasone BMSC ERK pathway

来源： cnki会议评论

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3616-3617页

作者： Fei Sun Si Wang Guang-Hui Liu Beijing Institute for Stem Cell and Regenerative medicine Beijing 100101China Department of Cell Biology Duke University Medical CenterDurhamNCUSA Advanced Innovation center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China The Fifth People’s Hospital of Chongqing Chongqing 400062China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

In a recent issue of Science,Acosta-Rodriguez et al.defined a feeding paradigm to maximize the effects of caloric restriction(CR)on lifespans.Aligning feeding with the circadian rhythm and imposing>12-hour fasting daily on caloric-restricted animals can optimally extend lifespans.While embracing the projection of our life expectancy in the last 100~150 years,we are facing aging,an all-new challenge in human evolution.aging-associated diseases have gradually replaced communicable diseases,becoming the top cause of death globally.The increasing social and medical burdens call for not only novel therapies for chronic diseases but also early interventions that mitigate the progression of aging and extend life and health spans.

关键词： life aging globally

National Research center for translational medicine· Shanghai——National Key Scientific Infrastructure for translational medicine

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Science China(Life Sciences) 2016年第10期59卷 1051-1054页

作者： Chao-Jun Wen Sai-Juan Chen Collaborative Innovation center of Systems Biomedicine National Research Center for Translational Medicine.Shanghai State Key Laboratory of Medical Genomics Shanghai Institute of Hematology Rui-Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine

In July 2013,the National Development and Reform Commission formally approved the'National Research center for translational medicine·Shanghai'(hereinafter'the center'),a piece of the national key scientific infrastruc-

关键词：基础设施医学转化上海科学国家发展基础结构共同管理

Neuroprotective effect of hydroxy-α-sanshool against β-amyloid-induced damage in differentiated PC12 cells

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Chinese Medical Journal 2023年第17期136卷 2140-2142页

作者： Shufang Shan Siquan Zhou Guochen Ma Xiaoyu Wang Jingyuan Xiong Guo Cheng Laboratory of Molecular translational medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationDepartment of PediatricsWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Healthy Food Evaluation Research center West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China

To the Editor:Alzheimer’s disease(AD)is a chronic neurodegenerative disorder that accounts for approximately 70%of global dementia cases and leads to cognitive and behavioral impairments.[1]Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of AD and are related to the accumulation of b-amyloid(Ab)peptides in cerebral tissues and cytoskeletal changes,which arise from the hyperphosphorylation of microtubule-associated tau proteins in neurons.Oxidative stress is among the earliest events in AD pathogenesis.The accumulation of Ab could promote the production of reactive oxygen species(ROS)and consequently lipid peroxidation,protein oxidation,and tau hyperphosphorylation,exerting toxic effects on synapses and neurons.In turn,oxidative stress could increase Ab production.Therefore,antioxidant therapy is becoming a popular strategy for treating AD.

关键词： protective amyloid peroxidation

Bone/cartilage targeted hydrogel: Strategies and applications

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生物活性材料(英文) 2023年第5期23卷 156-169页

作者： Hao Zhang Shunli Wu Weikai Chen Yan Hu Zhen Geng Jiacan Su Institute of translational medicine Shanghai UniversityShanghai200444China Musculoskeletal Organoid Research center Shanghai UniversityShanghai200444China School of medicine Shanghai UniversityShanghai200444China School of Environmental and Chemical Engineering Shanghai UniversityShanghai200444China

The skeletal system is responsible for weight-bearing,organ protection,and movement.Bone diseases caused by trauma,infection,and aging can seriously affect a patient’s quality of life.Bone targeted biomaterials are suitable for the treatment of bone diseases.Biomaterials with bone-targeted properties can improve drug utilization and reduce side effects.A large number of bone-targeted micro-nano materials have been developed.However,only a few studies addressed bone-targeted hydrogel.The large size of hydrogel makes it difficult to achieve systematic targeting.However,local targeted hydrogel still has significant prospects.Molecules in bone/cartilage extracellular matrix and bone cells provide binding sites for bone-targeted hydrogel.Drug delivery systems featuring microgels with targeting properties is a key construction strategy for bone-targeted hydrogel.Besides,injectable hydrogel drug depot carrying bone-targeted drugs is another strategy.In this review,we summarize the bone-targeted hydrogel through application environment,construction strategies and disease applications.We hope this article will provide a reference for the development of bone-targeted hydrogels.We also hope this article could increase awareness of bone-targeted materials.

关键词： Bone Cartilage Hydrogel Target therapy Bone disease

Macrophage RGS12 contributes to osteoarthritis pathogenesis through enhancing the ubiquitination

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Genes & Diseases 2022年第5期9卷 1357-1367页

作者： Gongsheng Yuan Shuting Yang Shuying Yang Department of Basic and translational Sciences School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Penn center for Musculoskeletal Disorders School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA center for Innovation&Precision Dentistry School of Dental MedicineSchool of Engineering and Applied SciencesUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Ubiquitination has important functions in osteoarthritis(OA),yet the mechanism remains unclear.Here,we identify the regulator of G protein signaling 12(RGS12)in macrophages,which promotes the association between ubiquitin and IκB during inflammation.We also find that RGS12 promotes the degradation of IκB through enhancing the ubiquitination whereas the process can be inhibited by MG132.Moreover,the increased ubiquitination further inhibits the expression of MTAP,which can indirectly activate the phosphorylation of IκB.Finally,due to the degradation of IκB,the NF-κB translocates into the nucleus and further promotes the gene expression of cytokines such as IL1β,IL6,and TNFαduring inflammation.Importantly,RGS12 deficiency prevents ubiquitination and inflammation in surgically or chemically induced OA.We conclude that the lack of RGS12 in macrophages interferes with the ubiquitination and degradation of IκB,thereby preventing inflammation and cartilage damage.Our results provide evidence for the relevance of RGS12 in promoting inflammation and regulating immune signaling.

关键词： IkB NF-kB Osteoarthritis RGS12 Ubiquitination

The Yin-Yang of osteopontin in nervous system diseases: damage versus repair

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Neural Regeneration Research 2021年第6期16卷 1131-1137页

作者： Giuseppe Cappellano Domizia Vecchio Luca Magistrelli Nausicaa Clemente Davide Raineri Camilla Barbero Mazzucca Eleonora Virgilio Umberto Dianzani Annalisa Chiocchetti Cristoforo Comi Department of Health Sciences Interdisciplinary Research Center of Autoimmune Diseases(IRCAD)University of Piemonte OrientaleNovaraItaly center for translational Research on Autoimmune and Allergic Disease-CAAD University of Piemonte OrientaleNovaraItaly Department of translational medicine Neurology UnitInterdisciplinary Research Center of Autoimmune Diseases(IRCAD)University of Piemonte OrientaleNovaraItaly PhD Program in Clinical and Experimental medicine and Medical Humanities University of InsubriaVareseItaly

Osteopontin is a broadly expressed pleiotropic protein,and is attracting increased attention because of its role in the pathophysiology of several inflammatory,degenerative,autoimmune,and oncologic diseases.In fact,in the last decade,several studies have shown that osteopontin contributes to tissue damage not only by recruiting harmful inflammatory cells to the site of lesion,but also increasing their survival.The detrimental role of osteopontin has been indeed well documented in the context of different neurological conditions(i.e.,multiple sclerosis,Parkinson’s,and Alzheimer’s diseases).Intriguingly,recent findings show that osteopontin is involved not only in promoting tissue damage(the Yin),but also in repair/regenerative mechanisms(the Yang),mostly triggered by the inflammatory response.These two apparently discordant roles are partly related to the presence of different functional domains in the osteopontin molecule,which are exposed after thrombin or metalloproteases cleavages.Such functional domains may in turn activate intracellular signaling pathways and mediate cell-cell and cell-matrix interactions.This review describes the current knowledge on the Yin and Yang features of osteopontin in nervous system diseases.Understanding the mechanisms behind the Yin/Yang would be relevant to develop highly specific tools targeting this multifunctional protein.

关键词： Alzheimer’s disease cytokine immunity microglia multiple sclerosis neuroinflammation neuroprotection neurotoxicity Parkinson’s disease Spp1 stroke