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Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui Zhang Kuileung Tong Ningning Chen Shaoyu Liu Shenzhen Key Laboratory of bone Tissue Repair and Translational Research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina department of Orthopedic surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina department of Orthopedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina department of Orthopedic surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of Orthopedic surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

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PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

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Neural Regeneration Research 2025年第10期20卷 2758-2775页

作者： Tianlong Liu Xiaolin Li Xiaowei Zhou Wei Chen Aidong Wen Minna Liu Yi Ding department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina department of Pharmacy The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina department of Pharmacy The 944 Hospital of Joint Logistics Support Forces of Chinese PLAJiuquanGansu ProvinceChina department of Nephrology The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic *** a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from *** article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling *** key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic *** investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

关键词： apoptosis autophagy inflammation ischemic stroke neuroprotection oxidative stress pathogenesis phosphatidylinositol 3-kinase protein kinase B therapeutics

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Temporal changes in the spinal cord transcriptome after peripheral nerve injury

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Neural Regeneration Research 2020年第7期15卷 1360-1367页

作者： Jian Weng Dong-Dong Li Bao-Guo Jiang Xiao-Feng Yin department of Orthopedics and Trauma Peking University People's HospitalBeijingChina department of bone&joint surgery Peking University Shenzhen HospitalShenzhenGuangdong ProvinceChina department of surgery the 517th Hospital of the People's Liberation ArmyXinzhouShanxi ProvinceChina

Peripheral nerve injury may trigger changes in mRNA levels in the spinal *** key mRNAs is important for improving repair after nerve *** study aimed to investigate changes in mRNAs in the spinal cord following sciatic nerve injury by transcriptomic *** left sciatic nerve denervation model was established in C57 BL/6 *** left L4–6 spinal cord segment was obtained at 0,1,2,4 and 8 weeks after severing the sciatic *** expression profiles were generated by RNA *** sequencing results of spinal cord mRNA at 1,2,4,and 8 weeks after severing the sciatic nerve were compared with those at 0 weeks by bioinformatic *** identified 1915 differentially expressed mRNAs in the spinal cord,of which 4,1909,and 2 were differentially expressed at 1,4,and 8 weeks after sciatic nerve injury,*** results indicated that the number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve *** mRNAs were associated with the cellular response to lipid,ATP metabolism,energy coupled proton transmembrane transport,nuclear transcription factor complex,vacuolar proton-transporting V-type ATPase complex,inner mitochondrial membrane protein complex,tau protein binding,NADH dehydrogenase activity and hydrogen ion transmembrane transporter *** these mRNAs,Sgk1,Neurturin and Gpnmb took part in cell growth and *** analysis showed that these mRNAs were mainly involved in aldosterone-regulated sodium reabsorption,oxidative phosphorylation and collecting duct acid *** assessment indicated that these mRNAs were associated with inflammation and cell morphology *** findings show that the number and type of spinal cord mRNAs involved in changes at different time points after peripheral nerve injury were *** number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve *** results

关键词： deep sequencing expression profile gene therapy mRNAs nerve regeneration peripheral nerve injury RNA sequencing sciatic nerve injury spinal cord transcriptome

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Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

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World Journal of Stem Cells 2019年第6期11卷 322-336页

作者： Hui Li Bing Yue department of bone and joint surgery Renji Hospital Shanghai Jiaotong University School of Medicine

Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also related to the course and prognosis of bone and joint infections. The multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) is essential for tissue repair after local injury, which is directly related to the recovery of bone, cartilage, and medullary adipose tissue. Our previous studies and the literature indicate that certain antimicrobial agents can regulate the differentiation potential of bone marrow-derived MSCs. Here, in order to systematically analyze the effects of various antimicrobial drugs on local tissue regeneration, we comprehensively review the studies on the effects of these drugs on MSC differentiation, and classify them according to the three differentiation directions (osteogenesis, chondrogenesis, and adipogenesis). Our review demonstrates the specific effects of different antimicrobial agents on bone marrow-derived MSCs and the range of concentrations at which they work, and provides a basis for drug selection at different sites of infection.

关键词： Antimicrobial agents bone marrow mesenchymal stem cells Osteogenesis Chondrogenesis Adipogenesis

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Fabrication of Novel Scaffolds Containing Collagen-I/Polylactic Acid/Nanohydroxyapatite via Co-electrospinning Methods

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Chemical Research in Chinese Universities 2010年第4期26卷 662-666页

作者： ZANG Jun-ting QI Xin LI Shu-qiang LI Dong-song GONG Yu-bao YANG Chen XU Feng LIU Jian-guo department of bone and joint surgery First Hospital of Jilin University Changchun 130021 P R. China

A novel scaffold containing collagen-I/polylactic acid（PLA）/nanohydroxyapatite（nHA） was prepared via co-electrospinning method. Different target substrates were used to improve the collection efficiency of this scaffold. The properties of the novel scaffold were compared with those of conventionally prepared ones. Compared to con- ventional method, the modified method was more efficient in producing the scaffold. Moreover, the porosity, thickness, and morphology of the novel scaffold were better than those of scaffolds prepared by conventional methods. The properties of collagen-I, collagen-I/PLA and collagen-I/PLA/nHA scaffolds were also compared. Diameters of the electrospun fibers ranged from 180 to 405 nm, and roughness was present on the surface of the fibers due to the deposition of crystals of nHA along the long axis of the fibers. The fibers of the collagen-I/PLA/nHA scaffold and the fibers of natural bone tissue had similar structure.

关键词： Electrospinning Collagen-I PLA Nanohydroxyapatite

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Controlled WISP-1 shRNA Delivery Using Thermosensitive Biodegradable Hydrogel in the Treatment of Osteoarthritis

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Journal of Bionic Engineering 2015年第2期12卷 285-293页

作者： Gong Yubao Ma Hecheng Liu Jianguo department of bone and joint First Hospital of Jilin University Changchun 130021 China

This paper presents a new method of delivering shRNA with biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for gene treatment of osteoarthritis （OA）. OA is a chronic debilitating disease. Without the proper treatment and prognosis, it may result in the loss of joint function in aged people. Currently, gene therapy targeted on WISP-1 has emerged as an alternative method for OA treatment. In order to constantly release shRNA at 37.0 ℃, we synthetized the hydrogels via ring-opening copolymerization of lactide （LA） and glycolide （GA） using Polyethylene glycol （PEG Mn = 1000） and stannous octoate （Sn（Oct）2, 95%） as the macroinitiator and catalyst. First, the PLGA-PEG-PLGA copolymer was mixed with WISP- 1 shRNA and PEI-Lys in distilled water at 4.0 ℃. Then, the WISP-lshRNA/PEI-Lys loaded hydrogel was formed after incubation of the mixed solution at 37.0 ℃. During tests, the plasmid was released from this hydrogel complex constantly, and enhanced the transfection efficiency of WISP-1 shRNA. In addition, silencing WISP-1 results to lower expression of MMP-3 and ADAMTS, and the accumulation of HBP 1 in synoviocytes. Therefore, the hydrogel containing WISP-1 shRNA is demonstrated an efficient way for the treatment of OA.

关键词： osteoarthritis biodegradable thermosensitive hydrogel PLGA-PEG-PLGA WISP-1

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Carcinosarcoma of the breast:Facing the challenge of a rare nosologic entity

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World Journal of Clinical Cases 2025年第2期13卷 14-20页

作者： Aikaterini Mastoraki Maria Tsamopoulou Foivos-Konstantinos Stamatis Alexios Strimpakos Ero Mouchtouri Christiana Panagi Evgenia Mela Sotiria Mastoraki Aristotelis Kechagias Dimitrios Schizas department of surgery National and Kapodistrian University of AthensLaikon General HospitalAthens 11527Greece department of surgery National and Kapodistrian University of AthensAthens 11527Greece department of Medical Oncology Hygeia HospitalAthens 15123Greece department of Radiology Henry Dunant Hospital CenterAthens 11526Greece department of surgery Athens Metropolitan HospitalAthens 15562Greece

Carcinosarcoma(CS),also known as metaplastic breast carcinoma with mesenchymal differentiation,is one of the five distinct subtypes of metaplastic breast *** is considered as a mixed,biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition *** cellular origin of this neoplasm remains controversial,most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic *** recent research on the therapeutic strategies against CS neoplastic disorders,surgical resection appears the only potentially curative *** CS metastasize by the lymphatic route,axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always ***,the tumor also presents a hematogenous metastatic pattern including pleural,pulmonary,liver,brain and less commonly bone ***,surgical removal of breast CS does not necessarily ensure patient’s long-term ***,alternative therapies,such as radio-and chemotherapy proved insufficient and 5-year survival rate is ***,there is evidence that following surgery,the combination of radio and chemotherapy is associated with a better prognosis than either treatment *** aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological *** features,histogenesis,morphological and immunochemical findings are discussed,while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

关键词： Carcinosarcoma Breast Diagnostic approach Therapeutic management Prognostic parameters

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Approaches to promoting bone marrow mesenchymal stem cell osteogenesis on orthopedic implant surface

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World Journal of Stem Cells 2020年第7期12卷 545-561页

作者： Shi-Cheng Huo Bing Yue department of bone and joint surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

bone marrow-derived mesenchymal stem cells(BMSCs)play a critical role in the osseointegration of bone and orthopedic ***,osseointegration between the Ti-based implants and the surrounding bone tissue must be improved due to titanium’s inherent *** modification stands out as a versatile technique to create instructive biomaterials that can actively direct stem cell ***,we summarize the current approaches to promoting BMSC osteogenesis on the surface of titanium and its *** will highlight the utilization of the unique properties of titanium and its alloys in promoting tissue regeneration,and discuss recent advances in understanding their role in regenerative *** aim to provide a systematic and comprehensive review of approaches to promoting BMSC osteogenesis on the orthopedic implant surface.

关键词： bone marrow mesenchymal stem cells Osseointegration Orthopedic implant Biofunctionalization

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Recurrent aneurysmal bone cyst of talus resulted in tibiotalocalcaneal arthrodesis

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World Journal of Clinical Cases 2017年第9期5卷 364-367页

作者： Amir R Vosoughi Kamran Mozaffarian Mohammad A Erfani bone and joint Diseases Research Center Department of Orthopedic SurgeryShiraz University of Medical Sciences

Aneurysmal bone cyst(ABC), a locally benign aggressive lytic lesion of either primary or secondary origin, seldom involves the talus. Herein, we present a 25-year-old man with recurrent ABC of the talus after curettage and bone grafting, which was managed by total resection followed by filling the defect using fibular graft and finally tibiotalocalcaneal arthrodesis due to articular surface involvement. At 18 mo postoperatively, no recurrence was detected. Arthrodesis might be a good option in cases with recurrent ABC of the talus especially with articular surface involvement.

关键词： Aneurysmal bone cyst Tibiotalocalcaneal arthrodesis bone tumor Talus

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Potential Impact of Space Environments on Developmental and Maturational Programs Which Evolved to Meet the Boundary Conditions of Earth: Will Maturing Humans Be Able to Establish a Functional Biologic System Set Point under Non-Earth Conditions?

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Journal of Biomedical Science and Engineering 2019年第12期12卷 500-513页

作者： David A.Hart Faculty of Kinesiology CalgaryCanada McCaig Institute for bone&joint Health CalgaryCanada department of surgery University of CalgaryCalgaryCanada Alberta Health Services Bone&Joint Health Strategic Clinical NetworkEdmontonCanada

Mammalian development and maturation, particularly processes for humans have evolved in the context of the boundary conditions of Earth (i.e. 1 g gravity, geomagnetic field, background radiation) to yield functional individuals, although the process is not perfect and “errors” do occur. With the advent of spaceflight to low Earth orbit (the International Space Station), humans are now exposed to microgravity and increased exposure to radiation. However, thus far, only adult humans have served as astronauts, but this will likely change with plans to explore deep space and colonize planets. Thus, conception, fetal development, post-birth maturation, puberty and skeletal maturity will occur in the context of boundary conditions that did not shape human evolution and influence physiological and biomechanical systems designed to function within the Earth’s boundary conditions. Thus, processes utilizing the 1 g environment (i.e. walking upright) and the geomagnetic field (i.e. the electrical/biomagnetic basis of neural interactions) will have to adapt to new boundary conditions, providing opportunity for additional errors or alterations in processing during development which could impact functional outcomes at multiple levels. This review/perspective will discuss some of these issues and attempt to provide direction for addressing the potential issues to be encountered.

关键词： Development Maturation Humans Microgravity Geomagnetic Influences Space Environments

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