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Engineered regeneration 2024年第2期5卷 186-198页

作者： Hao Meng Weicheng Zhong Kui Ma Jianlong Su Liqian Ma Yaying Hao Yufeng Jiang Xi Liu Xiaobing Fu Cuiping Zhang research center for tissue repair and regeneration affiliated to the medical innovation research department PLA General Hospital and PLA Medical CollegeBeijing 100048PR China PLA Key Laboratory of tissue repair and Regenerative Medicine Beijing 100048PR China Beijing Key research Laboratory of Skin Injury Repair and RegenerationBeijing 100048PR China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048PR China College of Graduate Tianjin Medical UniversityTianjin300070PR China department of tissue regeneration and Wound repair PLA General HospitalBeijingPR China

Persistent inflammatory responses often occur when bacteria and other microorganisms frequently invade and colonize open wounds and eventually result in the formation of chronic wounds.Therefore,achieving real-time detection of invasive bacteria accurately and promptly is essential for efficient wound management and accelerat-ing the healing process.Recently,flexible wearable sensors have garnered significant attention,especially those designed for monitoring real-time biophysical or biochemical signals in wound sites in a minimally invasive manner.They provide more precise and continuous monitoring data,making them as emerging tools for clinical diagnostics.In this review,we first discuss the species and community distribution of different types of bacteria in chronic wounds.Next,we introduce currently developed techniques for detecting bacteria at wound sites.Fol-lowing that,we discuss the recent progress and unresolved issues of various flexible wearable sensors in detecting bacteria at wound sites.We believe that this review can provide meaningful guidance for the development of flexible wearable sensors for bacteria detection.

关键词： Flexible wearable sensors Chronic wounds Bacterial infections Real-time detection

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In situ forming injectable MSC-loaded GelMA hydrogels combined with PD for vascularized sweat gland regeneration

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Military medical research 2024年第1期11卷 152-155页

作者： Enhe Jirigala Bin Yao Zhao Li Yi-Jie Zhang Chao Zhang Li-Ting Liang Fan-Liang Zhang Xing-Yu Yuan Xian-Lan Duan Wei Song Meng-De Zhang Yi Kong Xiao-Bing Fu Sha Huang research center for tissue repair and regeneration Medical Innovation Research DepartmentChinese PLA General Hospital and PLA Medical CollegeBeijing 100048China Institute of Basic medical research Inner Mongolia Medical UniversityHohhot 010110China Academy of medical Engineering and Translational Medicine Tianjin UniversityTianjin 300072China School of Medicine Nankai UniversityTianjin 300071China

Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).

关键词： Sweat gland GelMA In situ niche Cell differentiation tissue incorporation Vascularization

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Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

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Neural regeneration research 2024年第3期19卷 598-605页

作者： Yaowei Lv Xiangyun Yao Xiao Li Yuanming Ouyang Cunyi Fan Yun Qian department of Orthopedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Engineering research center for Orthopaedic Material innovation and tissue regeneration ShanghaiChina Youth Science and Technology innovation Studio of Shanghai Jiao Tong University School of Medicine ShanghaiChina College of Fisheries and Life Science Shanghai Ocean UniversityShanghaiChina

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

关键词： cell metabolism diabetic peripheral neuropathy peripheral nerve injury protein kinase C pathway reactive oxygen species.

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Role of CD36 in central nervous system diseases

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Neural regeneration research 2024年第3期19卷 512-518页

作者： Min Feng Qiang Zhou Huimin Xie Chang Liu Mengru Zheng Shuyu Zhang Songlin Zhou Jian Zhao School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina department of Orthopedic Oncology Second Affiliated Hospital of Naval Medical UniversityShanghaiChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsJiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury RepairCo-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina department of Stomatology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina medical College of Nantong University NantongJiangsu ProvinceChina

CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.

关键词： animal experiments antagonists CD36 antagonist central nervous system diseases clinical trial curcumin microRNA salvianolic acid B small-molecule drugs sulfosuccinimidyl oleate

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COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors

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World Journal of Clinical Cases 2024年第11期12卷 1929-1935页

作者： Zhuo-Fan Ye Yi-Han Hong Jian-Lin Yang Meng-Qing Tan Ju-Min Xie Zu-Cai Xu department of Neurology The Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Hubei Key Laboratory of Renal Disease Occurrence and Intervention Medical SchoolHubei Polytechnic UniversityHuangshi 435003Hubei ProvinceChina Psychological Children's Ward Mental Health Center of HuangshiHuangshi 435111Hubei ProvinceChina The Collaborative innovation center of tissue Damage repair and regeneration Medicine Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina

BACKGROUND Recently,a growing number of adolescents have been afflicted with mental disorders,with annual morbidity rates on the rise.This trend has been exacerbated by the global coronavirus disease 2019(COVID-19)pandemic,leading to a surge in suicide and self-harm rates among this demographic.AIM To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder(BD),along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents.METHODS A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians.Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders,international classification of diseases-11,and the National institute of mental health research domain criteria.Statistical analyses were performed using SPSS 26.0 software,with significance set at P<0.05.RESULTS A cohort of 171 adolescents diagnosed with BD between January 1,2018,and December 31,2022,was included in the analysis.The gender distribution was 2.8:1(female to male),with ages ranging from 11 to 18 years old.Major factors contributing to adolescent BDs included familial influences,academic stress,genetic predisposition and exposure to school-related violence.Notably,a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic.Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress,thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents.CONCLUSION The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD.This study underscores the urgent need for societal,familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention,diagnosis and treatment of ad

关键词： Adolescents Bipolar disorder COVID-19 Suicide Self-harm

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CRISPR,CAR-T,and NK:Current applications and future perspectives

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Genes & Diseases 2024年第4期11卷 246-257页

作者： Mohadeseh Khoshandam Hossein Soltaninejad Amir Ali Hamidieh Saman Hosseinkhani department of Reproductive Biology Academic Center for EducationCultureand Research(ACECR)Qom branch***Iran National Institute of Genetic Engineering and Biotechnology(NIGEB) Tehran 14965/161Iran department of stem cells technology and tissue regeneration Faculty of Interdisciplinary Science and TechnologiesTarbiat Modares UniversityTehran 15614Iran Pediatric Cell Therapy and Gene Therapy research center GeneCell&Tissue Research InstituteTehran University of Medical SciencesTehran ***Iran department of Biochemistry Faculty of Biological SciencesTarbiat Modares UniversityTehran 15614Iran

Chimeric antigen receptor T(CAR-T)cell therapy represents a breakthrough in personalized cancer treatments.In this regard,synthetic receptors comprised of antigen recognition domains,signaling,and stimulatory domains are used to reprogram T-cells to target tum or cells and destroy them.Despite the success of this approach in refractory B-cell malignancies,the optimal potency of CAR T-cell therapy for many other cancers,particularly solid tumors,has not been validated.Natural killer cells are powerful cytotoxic lymphocytes specialized in recognizing and dispensing the tumor cells in coordination with other anti-tumor immunity cells.Based on these studies,many investigations are focused on the accurate designing of CAR T-cells with clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system or other novel gene editing tools that can induce hereditary changes with or without the presence of a double-stranded break into the genome.These methodologies can be specifically focused on negative controllers of T-cells,induce modifications to a particular gene,and produce reproducible,safe,and powerful allogeneic CAR T-cells for on-demand cancer immunotherapy.The improvement of the CRISPR/Cas9 innovation offers an adaptable and proficient gene-editing capability in activating different pathways to help natural killer cells interact with novel CARs to particularly target tumor cells.Novel achievements and future challenges of combining next-generation CRISPR-Cas9 gene editing tools to optimize CAR T-cell and natural killer cell treatment for future clinical trials toward the foundation of modern cancer treatments have been assessed inthis review.

关键词： Cancer CAR T-cell CRISPR Gene editing Immunotherapy NK cell

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Brain circuits for retching-like behavior

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National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State Key Laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science Laboratory National Institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+neurons.These Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

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Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation

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Neural regeneration research 2024年第1期19卷 190-195页

作者： Miao Gu Xiao Cheng Di Zhang Weiyan Wu Yi Cao Jianghong He Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina School of Basic medical Sciences Hebei Key Laboratory of Nerve Injury and RepairChengde Medical UniversityChengdeHebei ProvinceChina

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.

关键词： axon elongation bioinformatic analysis cell migration cell proliferation dorsal root ganglia peripheral nerve regeneration peripheral nerve trauma platelet factor 4 rat sciatic nerve Schwann cells

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Elevated peripheral levels of receptor-interacting protein kinase 1(RIPK1)and IL-8 as biomarkers of human amyotrophic lateral sclerosis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 271-278页

作者： Jun Wei Min Li Zhi Ye Xinqian Hu Xiaoyan He Jia Wang Gaofeng Chen Chengyu Zou Daichao Xu Hongbing Zhang Junying Yuan Yunhong Zha Institute of Neural regeneration and repair and department of Neurology The First College of Clinical Medical ScienceYichang Central HospitalCollege of Basic Medical ScienceChina Three Gorges UniversityHubei Province Clinical Medical Research Center for Rare Diseases of Nervous SystemYichang 443000China Interdisciplinary research center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai Key Laboratory of Aging StudiesShanghai 201210China State Key Laboratory of Common Mechanism research for Major Diseases Haihe Laboratory of Cell EcosystemDepartment of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Amyotrophic lateral sclerosis(ALS)is a devastating fatal neurodegenerative disease with no cure.Receptor-interacting protein kinase 1(RIPK1)has been proposed to mediate pathogenesis of ALS.Primidone has been identified as an old drug that can also inhibit RIPK1 kinase.We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients.SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance.One-hundred-sixty-two ALS participants dosed daily with primidone(62.5 mg)completed 24-week follow-up.A significant reduction was showed in serum levels of RIPK1 and IL-8,which were significantly higher in ALS patients than that of healthy controls(P<0.0001).Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms(P<0.05).Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients.Repurposing primidone may provide a promising therapeutic strategy for ALS.The effect of primidone for the treatment of other inflammatory diseases may also be considered,since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome(CRS).(ChiCTR2200060149).

关键词： RIPK1 diseases Serum

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Development of Chinese herbal medicine for sensorineural hearing loss

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Acta Pharmaceutica Sinica B 2024年第2期14卷 455-467页

作者： Yunhao Wu Jingwen Zhang Qiuping Liu Zhuang Miao Renjie Chai Wenyong Chen State Key Laboratory of Bioelectronics Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province HighTech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China department of Otolaryngology-Head and Neck the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China department of Otolaryngology-Head and Neck Surgery Affiliated Hospital of Jiangnan UniversityWuxi 214000China department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610000China Co-innovation center of Neuroregeneration Nantong UniversityNantong 226001China Institute for Stem Cell and regeneration Chinese Academy of ScienceBeijing 100085China Beijing Key Laboratory of Neural regeneration and repair Capital Medical UniversityBeijing 100069China

According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national economies.Sensorineural hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial dysfunction.Though recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for SNHL.Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine.Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.

关键词： Sensorineural hearing loss Chinese herbal medicine Molecular mechanism Active ingredients Prescriptions Ototoxic drugs Noise Hair cells

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