EBioMedicine
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2022
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IF 11.205
Xiaoqi Hong,Yujin Jian,Shenghao Ding,Jianpo Zhou,Xiaoli Zheng,Huimin Zhang,Butian Zhou,Canbin Zhuang,Jieqing Wan,Xiaoping Tong
Summary Background Stroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and disability rate, which severely affects people's health and diminishes the quality of life. However, there is no efficient treatment that can be considered curative and there are other less well-known theories of pathogenesis. Therefore, it is imperative to gain a full understanding of the pathophysiology of ischemia and to seek new therapeutic strategies. Methods We first examined Kir4.1 channel and myelin based protein (MBP) expression in brain tissues from acute ischemic patients by Western blotting. We then established a transient ischemic mouse model (tMCAO) to conduct molecular, cell biological, transmission electron microscopy and pharmacokinetic studies, as well as in Kir4.1 cKO mice. Finally, neuroimaging and behavioral analyses were used to examine whether activation of Kir4.1 channel by luteolin could contribute to neuronal functional recovery in ischemic stroke. Findings In acute ischemic stroke patients, we first demonstrated that Kir4.1 ion channels were greatly impaired and a severe demyelination of axons occurred in ischemic infarction area of cerebral cortex in these patients. Further evidence showed that the deficits of Kir4.1 channels in NG2 glia led to the myelin loss of axons in a transient ischemic mouse model (tMCAO). Treating ischemic mice with a natural botanical extract, luteolin augmented Kir4.1 channel currents in NG2 glia and consequently promoted remyelination of axons, alleviated the infarction area and ultimately improved motor function in a series of behavioral tests. Interpretation Targeting Kir4.1 ion channels expressed in NG2 glial cells by luteolin treatment highlights an effective therapeutic strategy for a prompt brain functional recovery in ischemic stroke. Funding This work was supported by grants from the Ministry of Science and Technology China Brain Initiative (2022ZD0204702, to X.T.), the National Natural Science Foundation of China ( 82271466 , 82171279 , 31970904 and 31571063 ), the Program for Professor of Special Appointment (Eastern Scholar for Dr. X.T.) at Shanghai Institutions for Higher Learning ( 1510000084 ), Shanghai Pujiang Talent Award ( 15PJ1404600 ), Shanghai Municipal Science and Technology Major Project ( 2018SHZDZX05 ) and Shanghai Science and Technology Project ( 17411954000 ).
研究领域:
神经科学
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药理学
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分子生物学
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临床医学
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DOI
PubMed
高影响因子
Neural Regeneration Research
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2022
·Vol. 18
·期 7
·1591
·
IF 6.058
Liu Yu-Tian,Xu Zhao,Liu Wei,Ren Sen,Xiong He-Wei,Jiang Tao,Chen Jing,Kang Yu,Li Qian-Yun,Wu Zi-Han,Machens Hans-GüNther,Yang Xiao-Fan,Chen Zhen-Bing
Circular RNAs (circRNAs) play a vital role in diabetic peripheral neuropathy . However, their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood. Here, we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls. Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group. Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation. A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs. circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy . Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin (PLLP) expression. Moreover, overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function. The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p, while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration. These findings suggest that the circ_0002538 /miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients, improving myelin sheath structure and nerve function. Thus, this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy .
研究领域:
神经科学
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分子生物学
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糖尿病研究
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Shuqin Xu,Xiaoli Tang,Maosen Wang,Zhuqun Wang,Rui Zhan,Jinghua Chen
Myelination is modulated by neuron-glial communication, which is an essential physiological process during nerve regeneration. However, available scaffold for myelination of oriented axons is still challenging and lack of sufficient attention in neural tissue engineering. Here, we fabricate an extracellular matrix-mimic hydrogel (GB-SH), which was composed of cellulose nanocrystal grafted with sulfated hyperbranched polyglycerols (SHC) and 3-aminophenylboronic acid modified GelMA (GMPB) for stimuli-responsive release of sodium Danshensu (DSS). SHC with a “lubricative coating” maintained the crystalline core with a uniform size and 17.27 % of sulfation degree. GMPB having a grafting ratio of 14.94 % displayed a glucose-responsive release of dye. GB-SH hydrogels displaying oriented microchannels with controllable pore sizes were constructed by combining directional freeze-casting and photo-crosslinking strategies, which performed improved strengths, high water contents and slow degradation. It also exhibited stimulus (glucose, pH, H 2 O 2 ) triggered release of DSS. In vitro studies revealed that DSS loaded GB-SH enhanced the cellular viability, proliferation and orientation on fibroblast and oligodendrocyte precursor cells (OPCs). This scaffold induced OPCs differentiated into matured oligodendrocytes, which myelinated the extensive axons of hippocampal neurons successfully. The multi-functional hydrogel is a promising platform for studying myelination in vitro and a potential neural transplant in treating traumatic nerve injury.
研究领域:
神经组织工程
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
Translational Pediatrics
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2021
·Vol. 10
·期 4
·860
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IF 2.488
Yang Shen,Jing Zhao,Ling Sun,Li Zeng,Zhi Chen,Mi Tian,Xingtao Zhou
Background The syndrome of monocular myelinated retinal nerve fibers (MRNF), myopia and amblyopia threatens visual development of infants and young children. The efficacy of part-time occlusion therapy remains controversial, and the long-term prognosis of the syndrome remains unclear. Methods Ten children (4.40±2.22 years, 4 boys and 6 girls) with monocular MRNF, myopia and amblyopia were recruited. Both the affected eyes (treatment group) and the fellow eyes (control group) underwent routine ophthalmic examinations, including AL, cycloplegic refraction, best-spectacles-corrected distance visual acuity (BSCDVA), cover test, simultaneous perception, corneal curvature, anterior segment and fundus examinations. Refractive error was corrected by either spectacles or rigid gas permeable (RGP) contact lenses. Part-time occlusion therapy was employed for amblyopia treatment. The retinal characteristics were examined only on the final visit with a Fourier-domain optical coherence tomography (FD-OCT). The speed of myopia progression and axial elongation were calculated. Statistical analysis was performed using SPSS 20 software. Cut-off P values were 0.05. Results On the final visit, six children had normal simultaneous perception but three had strabismus. The mean AL and spherical equivalent (SE) values of the affected eyes were 28.05±1.59 mm and −12.60±4.20 D, respectively, while those of the fellow eyes were 23.67±1.13 mm and −0.66±1.99 D, respectively. AL and SE were significantly different over time and between groups (P<0.0001), but no time*group interaction effect (P>0.05) was observed. The differences in the corneal curvature, mean speed of myopia progression, axial elongation, foveal thickness and parafoveal thickness between the two groups were not significant (P>0.05). However, the perifoveal thickness in the affected eyes was significantly higher than that of the control eyes (P=0.047). In the treatment group, the occlusion dosage positively correlated with the final BSCDVA (R=0.764, P=0.016) but did not correlate with the speed of myopia progression or axial elongation (both P values >0.05). Conclusions The affected eyes have longer AL, severer myopia and thicker perifoveal retina when compared with the fellow eyes. Both the affected and the fellow eyes have similar speed of myopia progression as well as that of axial elongation.
研究领域:
眼科
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小儿眼科学
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屈光学
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视觉发育
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影像学
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临床研究
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Xiaochen Su,Xunan Jing,Wanting Jiang,Meng Li,Kai Liu,Menghao Teng,Daquan Wang,Lingjie Meng,Yingang Zhang,Wenchen Ji
The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1β, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/β-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.
研究领域:
药理学
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神经科学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Xu Zhang,Tong Qi,Yu Sun,Xinran Chen,Pengxiang Yang,Shuai Wei,Xiyang Cheng,Xiu Dai
Nerve conduits have shown promise as alternatives to autologous nerves, but their repair effects need to be improved. The topographical guidance and functionalization of scaffolds are crucial in nerve repair. In this work, a chitosan-based nerve graft filled with guiding fibres modified by ZIF-8 nanoparticles (CS@ZIF-8) was fabricated for defective nerve repair. An in vitro study demonstrated that CS@ZIF-8 exhibited excellent cytocompatibility and could significantly promote Schwann cell proliferation. In vivo, nerve conduits filled with CS@ZIF-8 were observed to guide stronger axonal longitudinal elongation. Rats bridged with the conduit filled with CS@ZIF-8 showed significant morphological and functional improvements in terms of regenerated nerve density, the number of myelinated nerve fibres, the number of myelin layers, the thickness of myelin sheath, target muscle recovery and sensory function compared to those transplanted with the hollow conduit and the conduit filled with pure chitosan fibres. The repair effects achieved by using the conduit filled with CS@ZIF-8 were similar to those of autografts. Altogether, the data here show that nerve conduits filled with ZIF-8-loaded guide fibres provide a promising approach for repairing nerve defects.
研究领域:
生物医学工程
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神经科学
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组织工程
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产品关联
DOI
高影响因子
Theranostics
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2020
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IF 8.579
Teng Ma,Yafeng Yang,Xin Quan,Lei Lu,Bing Xia,Jianbo Gao,Fengyu Qi,Shengyou Li,Laihe Zhao,Liangwei Mei,Yi Zheng,Yanbing Shen,Zhuojing Luo,Yan Jin,Jinghui Huang
Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury. Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo . The system was used to bridge large sciatic nerve defects in rats. Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro , enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery. Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.
研究领域:
组织工程
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神经科学
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生物材料
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再生医学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Zuoxiang Dong,Jihu Zhao,Wenshuai Deng,Congxiao Wang,Zhiguo Chen,Peng Sun
Spinal cord injury (SCI) often leads to severe and long-lasting disability, profoundly impacting both the physical and mental well-being of patients. While rehabilitation and regenerative medicine represent promising avenues for SCI recovery, their combined application remains underexplored. In this study, we developed a biodegradable, low-swelling, multi-ionic hydrogel composed of oxidized dextran (ODex), dopamine-grafted gelatin (DG), and a combination of essential ions (Ca 2+ , Mg 2+ , Zn 2+ , and Fe 3+ ). This hydrogel exhibits a suite of desirable properties, including optimal pore size, excellent biocompatibility, injectability, minimal swelling, strong adhesiveness, and notable antioxidative capacity. Functionally, the hydrogel can block calcium channels, reduce neuronal excitability, and alleviate muscle stiffness. At the cellular level, it supports neuronal growth and enhances antioxidative defense mechanisms. Behavioral assessments and electrophysiological studies in animals demonstrated that the multi-ionic hydrogel promotes the generation of new neurons, axonal regeneration, synaptogenesis of various neurotransmitters, and supports remyelination. The results showed significant functional recovery in rodents, particularly in motor and sensory functions, with remarkable improvement in urinary retention. This study suggests that multi-ionic hydrogels hold great potential as a strategy for spinal cord injury repair and neural regeneration, and may also provide hope for tissue regeneration in other medical conditions.
研究领域:
生物材料
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神经科学
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组织工程
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再生医学
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生物医学工程
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产品关联
DOI
高影响因子
Molecular Medicine Reports
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2017
·Vol. 16
·期 2
·1864-1870
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IF 1.692
Chao Weng,Man Ding,Shanghua Fan,Qian Cao,Zuneng Lu
Transcription factor 7 like 2 (TCF7L2, also termed TCF4), is a Wnt effector induced transiently in the oligodendroglial lineage. The current well accepted hypothesis is that TCF7L2 inhibits oligodendrocyte differentiation and remyelination through canonical Wnt/β‑catenin signaling. However, recent studies indicated that TCF7L2 activity is required during oligodendrocyte differentiation and remyelination. In order to clarify this, in situ hybridization, immunofluorescence and western blot analysis using in vivo TCF7L2 conditional knockout mice, were performed and it was found that TCF7L2 promotes oligodendrocyte differentiation during myelin formation and remyelination. Furthermore, it was established that TCF7L2 does not affect oligodendrocyte precursor cells during remyelination. These data are of important clinical significance to develop novel therapeutic targets to overcome multiple sclerosis and other demyelinating diseases.
研究领域:
神经科学
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分子生物学
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细胞生物学
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神经病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2023
·
IF 9.9
Xiao Li,Ning He,Xiaojing Li,Xu Wang,Lei Zhan,Wei-En Yuan,Jialin Song,Yuanming Ouyang
Graphdiyne (GDY) is a kind of nanomaterial from the graphene carbon family with excellent physical and chemical properties. Despite some applications in medical engineering, GDY has not been used as an electroactive scaffold for tissue regeneration because of its unclear in vitro and in vivo biosafety profiles. Here, a conductive GDY nanomaterial-loaded polycaprolactone (PCL) scaffold was prepared by electrospinning technique. For the first time, the biocompatibility of GDY-based scaffold was assessed at the cellular and animal levels in a peripheral nerve injury (PNI) model. The findings indicated that the conductive three-dimensional (3D) GDY/PCL nerve guide conduits (NGCs) could significantly improve the proliferation, adhesion and glial expression of Schwann cells (SCs). The conduits were implanted into a rat 10-mm sciatic nerve defect model for 3 months in vivo. The toxicity of scaffolds to the organs was negligible, while the GDY/PCL NGCs significantly promoted myelination and axonal growth by upregulating the expression levels of SC marker (S100 β protein), Myelin basic protein (MBP), and axon regeneration marker (β3-tubulin protein (Tuj1) and neurofilament protein 200 (NF200)). In addition, upregulation of vascular factor expression in GDY/PCL NGC group suggested the potential role in angiogenesis to improve nerve repair by GDY nanomaterials. Our findings provide new perspectives on biocompatibility and effectiveness of GDY nanomaterial scaffold in peripheral nerve regeneration for preclinical application.
研究领域:
生物医学工程
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组织工程
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纳米技术
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神经科学
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再生医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
·
IF 15.1
Junkai Zeng,Changjiang Gu,Yu Zhuang,Kaili Lin,Youzhuan Xie,Xiongsheng Chen
Spinal cord injury (SCI) is a devastating condition that results in sensory and motor dysfunctions below the injury site. Currently, there is no effective treatment. Extracellular vesicles (NEVs) derived from neural stem cells (NSCs) have shown promising potential in exerting neuroprotective effect. However, the limited yield and quality of NEVs restrict their further application. Melatonin, an indolamine hormone that is released from the pineal gland, was used in the present study to enhance the secretion and therapeutic effects of NEVs. Compared with original NEVs, NEVs derived from melatonin-pretreated NSCs (MNEVs) exhibited improved neuroregenerative and anti-inflammatory properties in vitro . Furthermore, to achieve prolonged retention in vivo, MNEVs were encapsulated in GelMA hydrogel microspheres ( [email protected] ). After encapsulation, MNEVs effectively accumulated at the site of injury over a 28-day period. The injection of [email protected] successfully improved motor function recovery in SCI model mice. Subsequently, [email protected] inhibited the uncontrollable inflammatory response after SCI by increasing M2 macrophage polarization; in addition, MNEVs released from [email protected] exerted neuroprotective effects by promoting axonal regeneration and remyelination. Collectively, these findings reveal a promising cell-free approach for suppressing inflammation and promoting neural regeneration to treat SCI.
研究领域:
神经科学
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再生医学
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药理学
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生物材料
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产品关联
DOI
高影响因子
ZOOLOGICAL RESEARCH
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2025
·Vol. 46
·期 4
·733
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IF 4.7
Bao-Guo Shen,Yuan Wen,Sheng-Jian Lu,Hong-Yuan Wei,Shu-Rui Huang,Guang-Ming Zhou,Wen-Tao Yan,Wen-Can Wu,Yi-Kui Zhang
In adult mammals, optic nerve injury leads to irreversible vision loss due to its extremely limited regenerative capacity. In contrast, adult zebrafish possess a robust capacity for spontaneous visual system regeneration, although the spatiotemporal coordination of recovery across the retina, optic nerve, and brain remains poorly understood. In the present study, the regenerative dynamics following optic nerve transection were systematically characterized in adult zebrafish over a 5 week period using hematoxylin-eosin staining, immunohistochemistry, transmission electron microscopy, single-cell RNA sequencing, and optokinetic response (OKR) behavioral assessments. At 1 week post-injury (1 wpi), retinal ganglion cell depletion was evident but showed significant recovery by 2 wpi. Concurrently, the injured optic nerve displayed a marked increase in diameter and cell number at 2 wpi, including widespread expression of proliferating cell nuclear antigen, consistent with heightened proliferative activity. Single-cell transcriptomic profiling at 2 wpi revealed five principal cell populations: fibroblasts, mural cells, immune cells, mature oligodendrocytes, and myelin-forming oligodendrocytes. By 4–5 wpi, remyelination within the optic nerve and re-establishment of synaptic architecture in the optic tectum were strongly correlated with functional restoration of OKR behavior. These findings provide a comprehensive spatiotemporal framework of visual pathway regeneration in zebrafish, establishing a valuable model for elucidating conserved mechanisms of neural repair with translational potential for human vision restoration.
研究领域:
神经再生
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发育生物学
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分子神经科学
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视觉系统
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转化医学研究
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）