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Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

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Neural Regeneration Research 2025年第2期20卷 533-547页

作者： Yanli Zhang Tian Li Jie Miao Zhina Zhang Mingxuan Yang Zhuoran Wang Bo Yang Jiawei Zhang Haiting Li Qiang Su Junhong Guo department of Neurology First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina department of Neurology Sixth Hospital of Shanxi Medical University(General Hospital of Tisco)TaiyuanShanxi ProvinceChina department of Physiology Key Laboratory of Cellular PhysiologyMinistry of EducationShanxi Medical UniversityTaiyuanShanxi ProvinceChina department of Hernia and Abdominal Wall surgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina department of Laboratory Medicine of Fenyang College Shanxi Medical UniversityFenyangShanxi ProvinceChina

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial ***,the functional role of GGT5 in the development of Alzheimer’s disease remains *** study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying *** observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse ***,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive ***,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 *** effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa *** findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 *** findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

关键词： Alzheimer’s disease amyloid-β APP/PS1 mice cerebrovascular endothelial cells cognitive deficits gamma-glutamyl transferase 5 neurovascular unit nuclear factor‐kappa B synaptic plasticity β-site APP cleaving enzyme 1

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng department of Orthopedics(Spine surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

Use of short stems in revision of standard femoral stem:A case report

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World Journal of Orthopedics 2020年第11期11卷 528-533页

作者： Francesco Roberto Evola Giuseppe Evola Giuseppe Sessa University of Catania Department of SurgeryClinic OrthopaedicCatania 95124Italy General and emergency surgery department Surgery ClinicCatania 95124Italy

BACKGROUND Short stems are usually uncemented prosthetics and are recommended in the treatment of traumatic or degenerative diseases of *** revision procedures for elderly patients with serious comorbidity,applying a short stem could reduce peri-and post-operative secondary surgical risks to femoral osteotomy,which are necessary for the removal of parts of the implant or acrylic cement from the medullary *** are no cases in the literature that apply a short stem for prosthetic revision by acrylic cement *** SUMMARY A male patient had a left hip replacement in 1995 due to *** the age of eighty the patient reported an accidental trauma and walked with pain in the left *** X-ray highlighted the stem breakage in the distal section without fracturing the femoral *** patient had various comorbidities(diabetes,anaemia,heart deficiency,and arrhythmia)presenting a high operation risk(ASA 4).During the revision procedure,the distal apex of the stem could not be removed from the femoral *** of the poor general health of the patient,the surgeon decided not to perform a Wagner femoral osteotomy to remove the distal section of the stem and decided to implant a short stem to avoid removing the stem section of the previous *** patient had his left femur X-rayed 15 d *** A field of application of short stem may be the development of a cemented short stem to reduce the complexity of the revision procedure.

关键词： Short stem Revision procedure Cementless implant Total hip replacement Prosthesis design Case report

Nanoparticles for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun department of Orthopedic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

Is it possible to foot reflexology for infants with sensorineural hearing loss?

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World Journal of Clinical Cases 2025年第2期13卷 1-4页

作者： Min Ai Hang-Hang Zhang Jun-Bang Feng Chuan-Ming Li Wen-Jing Wang Meng-Die Hu department of Anesthesiology Nanan District People's Hospital of ChongqingChongqing 400060China department of Breast and Thyroid surgery Chongqing Bishan District Maternal and Child Health Care HospitalChongqing 402760China department of Medical Imaging Chongqing University Central HospitalChongqing 400014China

Foot reflexology is a non-invasive and safe complementary therapy that works by massaging the reflex zones of the feet and exerts systemic or whole-body regulation through meridian nerve *** therapy is commonly used in the treatment of various conditions such as autism and Parkinson's ***,there is limited reporting on the use of foot reflexology therapy for infants with sensorineural hearing loss(SNHL).Currently,there is no definitive conclusion on how foot reflexology therapy can influence *** editorial holds some guiding significance regarding this clinical *** aim is to present physiological evidence of how foot reflexology therapy can impact infants with SNHL,thereby enhancing clinician’s awareness of foot reflexology in treating infants with SNHL.

关键词： Foot reflexology Sensorineural Hearing Loss Future perspectives Limitations Neural conduction

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

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Asian Journal of Andrology 2016年第5期18卷 803-808页

作者： Wei-Yuan Kong Li-Quan Tong Hai-Jun Zhang Yong-Gang Cao Gong-Chen Wang Jin-Zhi Zhu Feng Zhang Xue-Ying Sun Tie-Hui Zhang Lin-Lin Zhang department of emergency surgery The Daqing Oilfield General Hospital Daqing China department of General surgery The Fifth Affiliated Hospital of Harbin Medical University Daqing China department of emergency surgery The Fourth Hospital of Jilin University Changchun China department of Pharmacology Daqing Campus of Harbin Medical University Daqing China department of Urologic surgery The Fifth Affiliated Hospital of Harbin Medical University Daqing China The Hepatosplenic surgery Center Department of General Surgery The First Affiliated Hospital of Harbin Medical University Harbin China School of Nursing Daqing Campus of Harbin Medical University Daqing China

Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor （CaSR） is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin （STZ, 40 mg kg-1） in Wistar rats. Animals then received GdCl3 （an agonist of CaSR, 8.67 mg kg-1）, NPS-2390 （an antagonist of CaSR, 0.20 g kg-~）, or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde （MDA）, lower superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase （JNK）, p38, and extracellular signaling-regulated kinase （ERK） 1/2. The above parameters could be further increased or aggravated by the administration of GdCI3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

关键词： apoptosis calcium-sensing receptor diabetes testicular damage

Advances and challenges in diagnosing and managing adult autoimmune enteropathy

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World Journal of Gastroenterology 2025年第2期31卷 128-131页

作者： Grigorios Christodoulidis Sara E Agko Marina N Kouliou Konstantinos E Koumarelas Dimitris Zacharoulis department of General surgery University Hospital of LarissaLarissa 41110Greece department of Intensive Care Unit Asklepios Paulinen Clinic WiesbadenWiesbaden 65197Germany department of emergency Medicine General Hospital of LarissaLarissa 41221Greece department of surgery University Hospital of LarissaLarissa 41334Greece

Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous *** has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac *** diagnostic criteria for AIE include small bowel villous atrophy,lack of response to dietary restrictions,presence of anti-enterocyte antibodies,and predisposition to autoimmunity without severe *** criteria emphasize characteristic histological findings and exclusion of other causes of villous *** is associated with various autoimmune disorders and can present with overlapping features with Celiac disease,including villous atrophy but without significant intraepithelial *** primarily involves immunosuppression using corticosteroids,calcineurin inhibitors,and anti-tumor necrosis factor therapy,alongside nutri-tional *** the challenges,understanding AIE’s diverse manifest-ations and improving diagnostic criteria are essential for effective management and improved patient *** research is needed to elucidate the pathogenesis,disease progression and long-term outcomes of AIE.

关键词： Autoimmune enteropathy Diagnosis Prognosis Adult autoimmune enter-opathy and challenges Autoimmune enteropathy and treatment Autoimmune enteropathy and diagnostic criteria Pathophysiology of autoimmune enteropathy

Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

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World Journal of Clinical Oncology 2025年第1期16卷 43-52页

作者： Zhi-Jian Tang Yuan-Ming Pan Wei Li Rui-Qiong Ma Jian-Liu Wang department of Obstetrics and Gynecology Peking University People’s HospitalBeijing 100044China Cancer Research Center Beijing Chest HospitalBeijing 101149China department of Thoracic surgery Sichuan Provincial People's HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment *** To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural *** Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression *** genes were sourced from the MitoCarta3.0 *** discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation *** the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were *** In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy *** average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation *** average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation *** The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

关键词： Ovarian cancer Mitochondria Prognosis Immunotherapy Neural network

A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

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Neural Regeneration Research 2025年第7期20卷 2029-2037页

作者： Xiao Liang Xingping Quan Xiaorui Geng Yujing Huang Yonghua Zhao Lei Xi Zhen Yuan Ping Wang Bin Liu Faculty of Health Sciences University of MacaoMacao Special Administrative RegionChina Center for Cognitive and Brain Sciences University of MacaoMacao Special Administrative RegionChina department of Biomedical Engineering Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina department of emergency Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral ***,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly *** this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed *** observed the molding process in mice of different ages and presented age-dependent vascular embolism ***,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a *** imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

关键词： age-dependent cerebral cortex ischemic stroke mouse model optical coherence tomography angiography photoacoustic microscopy photothrombosis vascular imaging