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1.
Biomed Chromatogr ; 38(8): e5923, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38837461

RESUMO

Carboxyamidotriazole (CAI) was previously recognized as a well-tolerated anticancer drug. It has also demonstrated significant anti-inflammatory effects in various cell and animal model experiments, prompting its investigation as a potential treatment for rheumatoid arthritis. In this study, the potential biotransformation metabolites of CAI were identified both in vitro and in vivo. A sensitive, specific, and accurate LC-MS method was developed for the quantitative analysis of CAI and its major metabolite, CAI-OH, in rat plasma. CAI, CAI-OH, and telmisartan (used as an internal standard) were separated using a Zorbax SB C18 column. The mobile phase consisted of water (phase A, containing 0.1% formic acid) and acetonitrile (phase B, containing 0.1% formic acid) at a flow rate of 0.2 mL/min. The analytes were examined using a high-resolution mass spectrometer, with detected mass-to-charge ratios of m/z 424.01293 for CAI, m/z 440.00785 for CAI-OH, and m/z 515.24415 for telmisartan. Good linearity was observed within the range of 10-5000 ng/mL. Both inter- and intra-batch precision (relative standard deviation, %) were below 6%, and the accuracy ranged from 94.9% to 106.1%. The analytes remained stable throughout the entire experimental period. This method was successfully applied in a pharmacokinetic study of CAI following oral administration in rats.


Assuntos
Espectrometria de Massas , Ratos Sprague-Dawley , Triazóis , Animais , Ratos , Triazóis/sangue , Triazóis/farmacocinética , Triazóis/química , Masculino , Reprodutibilidade dos Testes , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Modelos Lineares , Antirreumáticos/sangue , Antirreumáticos/farmacocinética , Limite de Detecção , Sensibilidade e Especificidade , Espectrometria de Massa com Cromatografia Líquida
2.
J Integr Neurosci ; 23(8): 157, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39207068

RESUMO

BACKGROUND: Peripheral nerve injury is a challenging orthopedic issue in clinical management that often leads to limb dysfunction or even disability in severe cases. A thorough exploration of the repair process of peripheral nerve injury and the underlying mechanism contributes to formulate more effective therapeutic strategies. METHODS: In the present study, we established a sciatic nerve transection injury model in Sprague-Dawley (SD) rats. A 12-week compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis was then performed via sleeve jointing the proximal common peroneal nerve to the distal tibial nerve and common peroneal nerve, with a 2 mm interval. Compensatory repair via small gap amplification was observed via gross observation of nerve specimen, osmic acid staining, and electrophysiological stimulation of sciatic nerve branches of the tibial and common peroneal nerve. Rat limbs were observed, and the functional recovery of effector muscles of the gastrocnemius and tibialis anterior muscles was assessed through weighing the muscle wet weight, Hematoxylin and Eosin (H&E) staining, and muscle strength detection. H&E staining, Masson staining, and toluidine blue staining were performed to observe the morphological changes of the dorsal root ganglion. Positive expressions of key proteins involved in the Phosphatase and tensin homologue deleted on chromosome ten (PTEN)-protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, including PTEN, AKT, mTOR, Toll-like receptor 4 (TLR4), and Caspase9 in the dorsal root ganglion during compensatory repair of sciatic nerve after injury via small gap amplification, were detected by immunohistochemical staining. RESULTS: It is found that the compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing effectively restored the continuity, number of myelinated nerve fibers, and nerve conduction velocity. It promoted toe abduction recovery, improved muscle fiber morphology and increased the wet weight and muscle strength of the gastrocnemius muscle and tibialis anterior muscle. Moreover, it increased the number of neurons and nerve fibers, and improved their morphology. Downregulated PTEN, TLR4, and Caspase9 in the dorsal root ganglia and upregulated AKT and mTOR were observed after small gap amplification than those of the transection injury group, which were closer to those of the control group. CONCLUSIONS: Compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing can restore the morphology and function of the sciatic nerve, effector muscles, and corresponding dorsal root ganglia by activating the PTEN-AKT/mTOR signaling pathway in the dorsal root ganglia. Our findings provide novel therapeutic targets for peripheral nerve injuries.


Assuntos
Gânglios Espinais , Regeneração Nervosa , Transdução de Sinais , Animais , Masculino , Ratos , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Neuropatia Ciática/metabolismo , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo
3.
Nutr Neurosci ; 25(3): 631-641, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33054687

RESUMO

Objectives Small-molecule polypeptide neutrophil peptide 1 (NP-1) was reported to promote the regeneration of the sciatic nerve after denervation, but the mechanisms underlying this effect of NP-1 are unclear. Here, we established a Sprague-Dawley rat model of crush injury to study the effect of a single intermuscular injection of NP-1 on the repair of injured peripheral nerves and elucidate the possible underlying mechanism.Methods 39 rats were randomly selected to join this study and divided into the blank control group (normal group, n=9), experimental group (NP-1 group, n=15), and negative control group (NS group, n=15). The dynamic expression of cytokines in different groups of nerve tissues during Wallerian degeneration was observed using protein chips at different time points after injury. Recovery of injured nerves was determined based on the general condition, local gross morphology of the nerve suture site, sciatic nerve function index, neuroelectrophysiology, and osmic acid staining at 6 weeks after the surgery. The recovery of effector function was determined based on wet weight, hematoxylin-eosin staining, modified Gomori staining, and nicotinamide adenine dinucleotide-tetrazolium reductase staining at 6 weeks after the surgery.Results It was found that a single topical administration of NP-1 promoted sciatic nerve regeneration after crush injury and affected the expression of proteins related to neurotrophy, inflammation, cell chemotaxis, and cell generation pathways.


Assuntos
Regeneração Nervosa , Nervo Isquiático , alfa-Defensinas , Animais , Citocinas/metabolismo , Regeneração Nervosa/fisiologia , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões
4.
Artigo em Inglês | MEDLINE | ID: mdl-33220409

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

5.
Beijing Da Xue Xue Bao Yi Xue Ban ; 46(5): 756-9, 2014 Oct 18.
Artigo em Zh | MEDLINE | ID: mdl-25331400

RESUMO

OBJECTIVE: To explore the protected effect of sensory baby-sitter in reverse end-to-side fashion on denervated muscle. METHODS: The tibial nerve of twelve female adult Sprague Dawley rats was transected. Six animals served as controls. In the other rats, the end of the sural nerve was connected to the side of the distal tibial nerve stump. After twelve weeks, the wet weight, cross-sectional area, motor endplate perimeter from gastrocnemius muscle were examined. RESULTS: The difference in wet weight between the experimental group and the control group was statistically significant (39.2% ± 6.8% vs. 19.5% ± 4.3%, P<0.05). Histological observation of the unprotected muscles displayed wide areas of atrophied fibers and considerable connective tissue hyperplasia, whereas the structure of the experimental rats was preserved and there was only a slight increase in connective tissue. The average cross-sectional area and motor endplate perimeter of muscle fibers were significantly larger in the experimental group than in the control group [(1 148.85 ± 547.18) µm² vs. (575.05 ± 140.51) µm², (102.84 ± 53.29) µm vs. (59.60 ± 26.71) µm, respectively]. CONCLUSION: Sensory baby-sitter in reverse end-to-side neurorrhaphy preserves the structure of denervated muscle in rats.


Assuntos
Denervação Muscular , Músculo Esquelético/anatomia & histologia , Procedimentos Neurocirúrgicos , Nervo Tibial/cirurgia , Animais , Feminino , Músculo Esquelético/inervação , Ratos , Ratos Sprague-Dawley , Procedimentos de Cirurgia Plástica
6.
Neural Regen Res ; 19(8): 1822-1827, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38103249

RESUMO

JOURNAL/nrgr/04.03/01300535-202408000-00036/figure1/v/2023-12-16T180322Z/r/image-tiff Macrophages play an important role in peripheral nerve regeneration, but the specific mechanism of regeneration is still unclear. Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration. However, the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear. This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury. The functions of RAW 264.7 cells were elucidated by Cell Counting Kit-8 assay, flow cytometry, migration assays, phagocytosis assays, immunohistochemistry and enzyme-linked immunosorbent assay. Axonal debris phagocytosis was observed using the CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) optical clearing technique during Wallerian degeneration. Macrophage inflammatory factor expression in different polarization states was detected using a protein chip. The results showed that neutrophil peptide 1 promoted the proliferation, migration and phagocytosis of macrophages, and CD206 expression on the surface of macrophages, indicating M2 polarization. The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention. Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α, -6, -12, and tumor necrosis factor-α in vivo and in vitro. Thus, the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration, which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

7.
Int J Biol Macromol ; 268(Pt 1): 131594, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38621568

RESUMO

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.


Assuntos
Alginatos , Quitosana , Células Endoteliais da Veia Umbilical Humana , Regeneração Nervosa , Células de Schwann , Quitosana/química , Quitosana/farmacologia , Alginatos/química , Alginatos/farmacologia , Animais , Humanos , Ratos , Regeneração Nervosa/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Microgéis/química , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Traumatismos dos Nervos Periféricos/terapia , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Alicerces Teciduais/química , Metacrilatos/química , Metacrilatos/farmacologia , Movimento Celular/efeitos dos fármacos
8.
Int J Med Sci ; 10(2): 171-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23329889

RESUMO

Nerve regeneration and re-innervation are usually difficult after peripheral nerve injury. Epineurium neurorrhaphy to recover the nerve continuity is the traditional choice of peripheral nerve mutilation without nerve defects, whereas the functional recovery remains quite unsatisfactory. Based on previous research in SD rats and Rhesus Monkeys, a multiple centers clinical trial about biodegradable conduit small gap tubulization for peripheral nerve mutilation to substitute traditional epineurial neurorrhaphy was carried out. Herein, the authors reviewed the literature that focused on peripheral nerve injury and possible clinical application, and confirmed the clinical possibilities of biodegradable conduit small gap tubulization to substitute traditional epineurial neurorrhaphy for peripheral nerve mutilation. The biodegradable conduit small gap tubulization to substitute traditional epineurial neurorrhaphy for peripheral nerve mutilation may be a revolutionary innovation in peripheral nerve injury and repair field.


Assuntos
Implantes Absorvíveis , Traumatismos dos Nervos Periféricos/terapia , Nervos Periféricos/fisiopatologia , Animais , Humanos , Macaca mulatta , Regeneração Nervosa , Ratos , Recuperação de Função Fisiológica , Nervo Isquiático/lesões
9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(5): 807-14, 2013 Oct 18.
Artigo em Zh | MEDLINE | ID: mdl-24136284

RESUMO

OBJECTIVE: To generate peripheral nerve animal model of pure motor nerve fibers/pure sensory nerve fibers, and identify them. METHODS: The SPF SD rats were adopted in this study, and divided into 3 groups. In group A, we ablated L2-L4 ventral roots (VRs) to generate peripheral nerve animal model of pure sensory fibers. In group B, we ablated L2-L4 dorsal root ganglions (DRGs) to generate peripheral nerve animal model of pure motor fibers. Two time end-points were set as 2 weeks and 4 weeks. Neuron cells in lumbar spinal cords were detected by immunohistochemical staining with antibody of neuronal nuclei (NeuN). Motor neuron cells in lumbar spinal cords of pure motor fiber animal models and sensory neuron cells in lumbar spinal cords of pure sensory fiber animal models were counted respectively, and then compared to that of normal animals. Femoral nerves distal to the furcation were stained in osmium tetroxide, and then myelinated nerve fibers in the muscle branch and cutaneous branch of femoral nerve were counted respectively. RESULTS: The mean numbers of sensory neuron cells and motor neuron cells in normal lumbar spinal cords were 62.57 ± 1.02 and 29.73 ± 3.03 per 10 × 20 visual field respectively. For different end-points, the mean numbers of sensory neuron cells after ablating vental foots were 62.12 ± 1.77 (2 weeks), 62.15 ± 1.32 (4 weeks) per 10 × 20 visual field respectively; the mean numbers of motor neuron cells after ablating DRGs were 30.12 ± 0.44 (2 weeks), 30.00 ± 1.87 (4 weeks) per 10 × 20 visual field respectively. In group A, motor axons in muscle branch were degenerated as the sensory axons in muscle branch and cutaneous branch were not changed. The senory axons in femoral nerve for the two end-points were 1 558.17 ± 50.14 (2 weeks) and 1 544.00 ± 47.42 (4 weeks). In group B, sensory axons in muscle branch were degenerated as the motor axons were reserved. The motor axons in muscle branch for the two end-points were 387.67 ± 48.50 (2 weeks) and 393.50 ± 27.86 (4 weeks). There was no statistically significant difference in these mean numbers for the two end-points. The degenerating axons and myelin sheath had not been totally eliminated by the endpoint of 2 weeks. CONCLUSION: Peripheral nerve animal model of pure motor fibers can be generated by ablating L2-L4 DRGs; peripheral nerve animal model of pure sensory fibers can be generated by ablating L2-L4 ventral roots. The degenerating axons and myelin sheath have been totally eliminated by the end-point of 4 weeks. Ablating the ventral roots does not influence the survival of sensory neuron cells; and ablating the DRGs does not influence the survival of motor neuron cells.


Assuntos
Modelos Animais , Neurônios Motores/fisiologia , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/fisiopatologia , Células Receptoras Sensoriais/fisiologia , Técnicas de Ablação , Animais , Axônios/fisiologia , Contagem de Células , Gânglios Espinais/fisiologia , Gânglios Espinais/cirurgia , Masculino , Neurônios Motores/citologia , Fibras Nervosas/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/citologia , Raízes Nervosas Espinhais/fisiologia , Raízes Nervosas Espinhais/cirurgia
10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(5): 830-3, 2013 Oct 18.
Artigo em Zh | MEDLINE | ID: mdl-24136287

RESUMO

Treatment of peripheral nerve injury is a major challenge in clinical practice. With advances in molecular biology and development of microsurgical techniques and tissue engineering, peripheral nerve repair procedures have been greatly improved. In the last 10 decades, most treatments for peripheral nerve injury in animal models have achieved histological and functional recovery, the treatments in humans, however, produce insufficient recovery, especially for proximal nerve injury. Increasing attention has been paid to the Traditional Chinese Medicine (TCM) for promoting peripheral nerve regeneration, since these remedies often display effective clinical outcome, minor side effects and effectiveness for multiple targets. Although TCM has complex ingredients and the specific pharmacological mechanisms for their effectiveness are still unclear, an effective clinical outcome is welcomed by many clinicians. In the past 20 years, we have made a series of detailed studies including the toxicity tests, pharmacodynamic tests, pharmacological experiments etc, about a new traditional formula which mainly contains the Radix hedysari, Epimedium etc. RESULTS have shown that this formula is safe to be used in both animals and humans with no toxicity and adverse effect, and systemic administration of this formula could enhance the peripheral nerve regeneration.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fabaceae/química , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Epimedium/química , Humanos , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/fisiologia , Raízes de Plantas/química , Plantas Medicinais/química , Ratos
11.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(5): 675-8, 2013 Oct 18.
Artigo em Zh | MEDLINE | ID: mdl-24136256

RESUMO

OBJECTIVE: To explore the pain sensation recovery discipline of 2 mm small gap biological conduit tubulization and epineurial neurorrhaphy in rat sciatic nerve multilation model. METHODS: Based on the rat sciatic nerve multilation model, 2 mm small gap biological conduit tubulization and epineurial neurorrhaphy were applied and the 50% paw withdrawal threshold was observed after 2, 4, 5, 6, 8 and 12 weeks. The data were analyzed by two-way ANOVA and chi-square criterion. RESULTS: Obvious hyperalgesia was observed in week 2 in both experimental group and control group, and 50% paw withdrawal threshold was improved significantly even to 15 g. The 50% paw withdrawal threshold began to decline week 4 and the 50% paw withdrawal threshold of small gap tubulization group was obviously lower than that of control group, which may imply that the pain sensation recovery of small gap tubulization group was earlier than that of control group. The 50% paw withdrawal threshold of small gap tubulization group began to increase to the plateau period [week 5: (12.70 ± 5.64) g; week 6: (12.20 ± 3.26) g; week 8: (12.31 ± 4.19) g; week 12: (13.95 ± 2.58) g]. The 50% paw withdrawal threshold of control group declined gradually [week 5: (10.47 ± 7.02) g; week 6: (9.42 ± 6.86) g; week 8: (8.50 ± 7.15) g; week 12: (8.06 ± 5.93) g]. The difference was statistical significant between small gap tubulization group and control group in 12th week. CONCLUSION: Compared with the traditional epineurial neurorrhaphy for peripheral nerve multilation, 2 mm small gap biological conduit tubulization can improve the 50% paw withdrawal threshold during peripheral nerve regeneration process and reduce the pain incidence.


Assuntos
Implantes Absorvíveis , Medição da Dor , Traumatismos dos Nervos Periféricos/terapia , Nervo Isquiático/lesões , Animais , Materiais Biocompatíveis , Feminino , Hiperalgesia/fisiopatologia , Hiperalgesia/terapia , Masculino , Regeneração Nervosa , Procedimentos Neurocirúrgicos , Limiar da Dor , Traumatismos dos Nervos Periféricos/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/fisiopatologia , Técnicas de Sutura
12.
Theranostics ; 13(12): 4266-4286, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554270

RESUMO

Severe injuries or diseases affecting the peripheral and central nervous systems can result in impaired organ function and permanent paralysis. Conventional interventions, such as drug administration and cell-based therapy, exhibit limited effectiveness due to their inability to preserve post-implantation cell survival and impede the deterioration of adjacent tissues. Exosomes have recently emerged as powerful tools for tissue repair owing to their proteins and nucleic acids, as well as their unique phospholipid properties, which facilitate targeted delivery to recipient cells. Engineering exosomes, obtained by manipulating the parental cells or directly functionalizing exosomes, play critical roles in enhancing regenerative repair, reducing inflammation, and maintaining physiological homeostasis. Furthermore, exosomes have been shown to restore neurological function when used in combination with biomaterials. This paper primarily focuses on the engineering strategies and delivery routes of exosomes related to neural research and emphasizes the theranostic application of optimized exosomes in peripheral nerve, traumatic spinal cord, and brain injuries. Finally, the prospects of exosomes development and their combination with other approaches will be discussed to enhance our knowledge on their theranostic effectiveness in neurological diseases.


Assuntos
Exossomos , Tecido Nervoso , Exossomos/metabolismo , Medicina de Precisão , Terapia Baseada em Transplante de Células e Tecidos , Materiais Biocompatíveis , Engenharia Tecidual
13.
Front Biosci (Landmark Ed) ; 28(11): 298, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38062831

RESUMO

BACKGROUND: Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. An innovative approach to repairing severe peripheral nerve damage involves using conduit suturing for nerve transposition repair. Cylindrical nerve guides are typically unsuitable for nerve transposition repair. Moreover, postsurgical adjuvant treatment is essential to promote the development of axonal lateral sprouts, proximal growth, and the restoration of neurostructure and function. The purpose of this research is to assess the impact of chitosan-based conduits with varying inner diameters on nerve transposition repair when combined with modified formula Radix Hedysari (MFRH). METHODS: Using chitosan, we created conduits with varying inner diameters on both ends. These conduits were then utilized to repair the distal common peroneal and tibial nerves in SD rats using the proximal common peroneal nerve. Subsequently, MFRH was employed as a supplementary treatment. The assessment of the repair's effectiveness took place 16 weeks postsurgery, utilizing a range of techniques, including the neurological nerve function index, neuroelectrophysiological measurements, muscle wet weight, and examination of nerve and muscle histology. RESULTS: The outcomes of our study showed that following 16 weeks of postoperative treatment, MFRH had a significant positive impact on the recovery of neuromotor and nerve conduction abilities. Moreover, there was a significant increase in the ratio of wet weight of muscles, cross-sectional area of muscle fibers, quantity and structure of regenerated myelinated nerve fibers, and the count of neurons. CONCLUSIONS: A combination of chitosan-based chitin conduits possessing different inner diameters and MFRH can considerably promote the regeneration and functional recovery of damaged nerves, which in turn enhances nerve transposition repair efficacy.


Assuntos
Quitosana , Doenças do Sistema Nervoso Periférico , Ratos , Animais , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Nervo Isquiático/fisiologia , Ratos Sprague-Dawley , Nervo Tibial/cirurgia , Nervo Tibial/lesões , Nervo Tibial/fisiologia , Regeneração Nervosa/fisiologia
14.
J Funct Biomater ; 14(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37754856

RESUMO

Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. Innovative techniques, such as nerve transposition repair with conduit suturing, can be employed to successfully treat severe peripheral nerve damage. However, cylindrical nerve guides are typically unsuitable for nerve transposition repair. Furthermore, angiogenic and neurotrophic factors are necessary to stimulate the emergence of axonal lateral sprouts, proximal growth, and the rehabilitation of neuron structures and functions. In the current study, we used chitosan to make chitin conduits with different inner diameters at both ends, combined with gelatin methacrylate hydrogels that can continuously release dual growth factors, namely, the vascular endothelial growth factor (VEGF) and the nerve growth factor (NGF), and evaluated its impact on nerve transposition repair in rats. At 16 weeks after the operation, our findings showed that the conduit combined with the dual growth factor hydrogel significantly improved the restoration of both motor and conduction functions of the nerve. In addition, histological analysis showed significant recovery of nerve fibers, target muscles, and neurons. In conclusion, the combination of chitin conduits with different inner diameters and dual growth factor hydrogels can significantly improve the effect of nerve transposition repair, which has important potential clinical value.

15.
Cell Reprogram ; 25(3): 99-108, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37184657

RESUMO

Severe osteoporotic fracture occurring in sites with inadequate blood supply can cause irreversible damage to cells, particularly osteoblasts, with current drug and surgical interventions exhibiting limitations for elderly individuals. As participants mediating intercellular communication, extracellular vesicles (EVs) are rarely reported to play functional roles in osteoblasts under hypoxia. Our study mainly investigated the effects of bone marrow mesenchymal stem cells-derived EVs (BMSCs-EVs) on apoptosis and differentiation of osteoblasts treated with CoCl2. Primary rat BMSCs and osteoblasts were extracted as required for the following experiments. Cell counting kit 8 assay was used to explore the concentration of CoCl2 for treating osteoblasts, and we found that 100 µM CoCl2 was appropriate to treat osteoblasts for 48 hours. The analysis of flow cytometer showed that CoCl2-treated osteoblasts apoptosis can be ameliorated when cocultured with BMSCs-EVs. Further findings revealed that reactive oxygen species (ROS) was related to CoCl2-induced apoptosis. In addition, our results demonstrated that EVs exerted an important role in increasing expression levels of ALP, BMP-2, OCN, and OSTERIX under hypoxia. Similarly, the functional effects of BMSCs-EVs were observed on the osteoblasts mineralization. In summary, these findings provide insight that BMSCs-EVs might decrease the effect of CoCl2-induced apoptosis through inhibiting ROS, and promote osteogenic differentiation under hypoxia.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Ratos , Animais , Espécies Reativas de Oxigênio , Osteogênese , Diferenciação Celular , Células Cultivadas , Apoptose , Osteoblastos , Células da Medula Óssea , Hipóxia
16.
Artigo em Inglês | MEDLINE | ID: mdl-22384852

RESUMO

During the process of peripheral nerve regeneration, a single neuron can regenerate and maintain more than one collateral in a regenerative distal stump. Furthermore, some of the new shoots can mature gradually through remyelination and grow into the remote target organ to play a physiological function. Our study found that when neonatal nerve fibers are subjected to a second injury, the regenerative distal stump can regenerate and maintain more than one collateral in the second regenerative distal stump. The neonatal nerve contributed to the functional recovery of the nerve, but the restoration of nerve function was not complete.


Assuntos
Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervo Fibular/lesões , Nervo Fibular/fisiopatologia , Nervo Tibial/lesões , Nervo Tibial/fisiopatologia , Animais , Animais Recém-Nascidos , Masculino , Músculos/inervação , Músculos/patologia , Bainha de Mielina/fisiologia , Fibras Nervosas/patologia , Traumatismos dos Nervos Periféricos/patologia , Nervo Fibular/patologia , Ratos , Ratos Sprague-Dawley , Nervo Tibial/patologia
17.
Chin J Traumatol ; 15(5): 268-72, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23069096

RESUMO

OBJECTIVE: To evaluate the effect of autograft bone, allograft bone, calcium sulfate bone cement, and calcium phosphate bone cement on the repair of tibial plateau defect in rabbits. METHODS: We used autograft bone, allograft bone, calcium sulfate bone cement, and calcium phosphate bone cement to repair tibial plateau defect in rabbits. Gross and histologic observations, X-ray examination, and biomechanical test were conducted at 1, 2, 4, 8 weeks after operation. RESULTS: X-ray examination found that the bone density was evidently reduced in calcium sulfate group at 8 weeks after operation; there were no marked changes in other groups. The maximal load measurements showed that autograft and allograft groups were greater than calcium sulfate and calcium phosphate groups at 1 and 2 weeks after operation. However at 4 and 8 weeks after operation, no significant difference was found among the four groups. In autograft and allograft groups, there was no significant difference in biomechanical intensity at 2, 4, and 8 weeks, but it was significantly higher than that at 1 week. In calcium sulfate and calcium phosphate groups, the outcome was ranked in descending order as 1 week less than 2 week less than 4 week equal to 8 week. Histologic examination found a great amount of new bones at 8 week in both autograft and allograft groups. In calcium sulfate group, calcium sulfate was almost absorbed and there were numerous bone trabeculations. There was a large amount of unabsorbed calcium phosphate in calcium phosphate group. CONCLUSION: At 1-2 weeks postoperatively, the biomechanical intensity is higher in autograft and allograft groups than calcium sulfate and calcium phosphate groups, but after 4-8 weeks, there is no significant difference among groups. At 1-2 weeks, the biomechanical intensity in all groups is increased, but at 4-8 weeks, there is no significant increase. The rates of absorption and bone formation are quicker in calcium sulfate group than calcium phosphate group.


Assuntos
Cimentos Ósseos , Transplante Ósseo , Animais , Fenômenos Biomecânicos , Articulação do Joelho , Tíbia , Transplante Autólogo
18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 44(6): 831-7, 2012 Dec 18.
Artigo em Zh | MEDLINE | ID: mdl-23247440

RESUMO

OBJECTIVE: To establish a stable animal model for studying the effect of traumatic brain injury on bone fracture healing. METHODS: Eighty adult male Sprague-Dawley rats were randomly divided into fracture combined brain injury group (A) and simple fracture group (B). Animals of the two groups were killed 6 hours, 1 week, 2 weeks, 1 month and 2 months after trauma, respectively. Their brain histopathology changes were observed and neurological severity scores (NSS, 0 through 25 from no injury to severe injury) determined to measure the brain injury after head trauma, and fracture-healing was assessed by measuring callus volume and X ray examination at the scheduled time points after trauma. The callus volumes were compared between the groups using independent-samples t test 1 week, 2 weeks, 1 month and 2 months after trauma respectively. A value of P<0.05 was considered statistically significant. RESULTS: Ninety percent of the rats of group A presented with hemiplegia and the mortality rate was 10% (4/40) . The survived rats developed decorticated flexion deformity of the forelimbs, with behavioral depression, and lost some reflexes and muscle tone. The NSS were 10.83±1.94, 9.33±0.82, 8.17±1.17, 7.83±0.75 and 8.07±0.82 with 6 hours, 1 week, 2 weeks, 1 month and 2 months after trauma, respectively. It showed that the animals received moderate head injury, which tended to be stable from 2 weeks after trauma. Brain pathology showed that blood brain barrier was destroyed, and neurons were degenerative and necrotic at and around the trauma sites. The callus volumes(unit: mm(3)) of the two groups 1 week, 2 weeks, 1 month and 2 months after trauma were 60.03±28.05 and 32.80±11.04, 78.54±15.16 and 51.36±23.02, 93.01±10.65 and 72.38±20.38, 115.26±40.00 and 60.30±13.34, respectively. The callus volumes of the two groups 2 weeks, 1 month and 2 months after trauma were statistically and significantly different (P values were 0.036, 0.006 and 0.01 respectively), and there was no difference 1 week after trauma (P=0.065). CONCLUSION: This model is capable of producing accurately quantified brain injury. The animal model is credible, stable and reproducible, so it is an effective platform for studying the effect of traumatic brain injury on fracture.


Assuntos
Lesões Encefálicas/complicações , Modelos Animais de Doenças , Consolidação da Fratura/fisiologia , Fraturas Ósseas/complicações , Animais , Lesões Encefálicas/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley
19.
Beijing Da Xue Xue Bao Yi Xue Ban ; 44(6): 842-6, 2012 Dec 18.
Artigo em Zh | MEDLINE | ID: mdl-23247442

RESUMO

OBJECTIVE: To observe the clinical effect of biodegradable conduit small gap tublization to repair peripheral nerve injury. METHODS: In the study, 30 cases of fresh peripheral nerve injury in the upper extremities were recruited. After formally informed and obtaining the consent, the recruited patients were divided into the degradable chitin conduit tublization group (experimental group: 15 cases) and traditional epineurial neurorrhaphy group (control group: 15 cases). Their nerve functional recovery conditions were clinically observed according to the standard score methods provided by SHEN Ning-jiang and British Medical Research Council. The excellent and good rates of the overall nerve functional recovery were calculated. The electrophysiologic study was carried out after 6 months. RESULTS: Of the total 30 cases, 28 were followed up, and there were 14 cases in the degradable chitin conduit tublization group and traditional epineurial neurorrhaphy group. The operation procedure was very simple, and the mean suture time [(8.0±0.8) min] was 20% shorter than that of the traditional epineurial neurorrhaphy group [(10.0±0.6) min]. All the wounds in the degradable chitin conduit tublization group healed as expected without rejection, hypersensitive reaction or anomalous draining. Electrophysiology examination results after 6 months displayed that the sensory nerves conduction velocity recovery rate was 77.37% of the normal value, and motor nerve conduction velocity recovery rate was 70.09% in the degradable chitin conduit tublization group. The sensory nerves conduction velocity recovery rate was 61.69% of the normal value, and motor nerve conduction velocity recovery rate was 56.15% in the traditional epineurial neurorrhaphy group. The exact propability methods was applied in the comparison of sensory and motor nerve conduction velocity recovery rate, and there was no statistically significant of two groups(sensory nerve conduction velocity recovery rate P=0.678;motor nerve conduction velocity recovery rate P=0.695). The combinated functional recovery excellent and good rates after repair in the degradable chitin conduit tublization group were 78.57%, while 28.57% in the traditional epineurial neurorrhaphy group. The Fisher's exact probabilistic method was applied in the comparison of combinated functional recovery excellent and good rates, and there was statistically significant of two groups(P=0.021). CONCLUSION: The operation procedure of the degradable chitin conduit tublization is very simple and the clinical recovery effect is much better than that of the traditional epineurial neurorrhaphy. The biodegradable conduit small gap tublization methods to repair peripheral nerve injury has the possibility to substitute the traditional epineurial neurorrhaphy.


Assuntos
Implantes Absorvíveis , Nervo Mediano/lesões , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Adolescente , Adulto , Idoso , Materiais Biocompatíveis , Quitina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Nervo Ulnar/lesões , Adulto Jovem
20.
ANZ J Surg ; 92(11): 2849-2858, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35785463

RESUMO

BACKGROUND: To evaluate outcomes following percutaneous vertebroplasty with high viscosity cement (PVP-HVC) and percutaneous kyphoplasty (PKP) with normal-viscosity cement in patients with osteoporotic vertebral compression fractures (OVCFs). METHODS: Pertinent studies were retrieved by searching five electronic databases up to July 2021. Additional records were identified via hand-searching of related references. Risk ratio (RR) and weighted mean difference (WMD), with their 95% confidence intervals (CIs), were calculated. A trial sequential analysis (TSA) was done for cement leakage. RESULTS: Twelve studies, embracing 1050 patients with OVCFs, were included. PVP-HVC was superior to PKP with normal-viscosity cement regarding risk of cement leakage (RR: 0.67, 95% CI: 0.54-0.83, I2 : 45.1%) and operation time (WMD: -11.26, 95% CI: -14.78 to -8.34, I2 : 88.8%). However, TSA revealed that a sufficient level of evidence for leakage reduction may have yet to be reached. PKP groups had a significant decrease in Cobb's angles postoperatively (within 1 month, WMD: 2.68, 95% CI: 1.85-3.48, I2 : 0%; after 1 year, WMD: 2.68, 95% CI: 1.35-4.01, I2 : 0%). There are no significant differences between the two procedures pertaining to injected cement volume, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and risk of adjacent vertebral fractures. CONCLUSION: PVP-HVC and PKP with normal-viscosity cement are safe and effective treatments for the management of OVCF, but the former is superior to the latter in terms of procedure time. The potential of PVP-HVC in reducing cement leaks remains to be validated by more well-designed studies.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Cimentos Ósseos/uso terapêutico , Fraturas por Compressão/cirurgia , Cifoplastia/métodos , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento , Viscosidade
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