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1.
Proc Natl Acad Sci U S A ; 121(24): e2404383121, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38843184

RESUMEN

Transcription is extremely important for cellular processes but can be hindered by RNA polymerase II (RNAPII) pausing and stalling. Cockayne syndrome protein B (CSB) promotes the progression of paused RNAPII or initiates transcription-coupled nucleotide excision repair (TC-NER) to remove stalled RNAPII. However, the specific mechanism by which CSB initiates TC-NER upon damage remains unclear. In this study, we identified the indispensable role of the ARK2N-CK2 complex in the CSB-mediated initiation of TC-NER. The ARK2N-CK2 complex is recruited to damage sites through CSB and then phosphorylates CSB. Phosphorylation of CSB enhances its binding to stalled RNAPII, prolonging the association of CSB with chromatin and promoting CSA-mediated ubiquitination of stalled RNAPII. Consistent with this finding, Ark2n-/- mice exhibit a phenotype resembling Cockayne syndrome. These findings shed light on the pivotal role of the ARK2N-CK2 complex in governing the fate of RNAPII through CSB, bridging a critical gap necessary for initiating TC-NER.


Asunto(s)
Síndrome de Cockayne , ADN Helicasas , Enzimas Reparadoras del ADN , Reparación del ADN , Proteínas de Unión a Poli-ADP-Ribosa , ARN Polimerasa II , Enzimas Reparadoras del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , ARN Polimerasa II/metabolismo , ARN Polimerasa II/genética , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/genética , Humanos , Animales , Ratones , ADN Helicasas/metabolismo , ADN Helicasas/genética , Síndrome de Cockayne/genética , Síndrome de Cockayne/metabolismo , Transcripción Genética , Fosforilación , Quinasa de la Caseína II/metabolismo , Quinasa de la Caseína II/genética , Ratones Noqueados , Daño del ADN , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , ATPasas Asociadas con Actividades Celulares Diversas/genética , Cromatina/metabolismo , Ubiquitinación , Reparación por Escisión
2.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33500348

RESUMEN

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin-dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs.


Asunto(s)
Alelos , Impresión Genómica , Proteínas Represoras/genética , Animales , Metilación de ADN/genética , Embrión de Mamíferos/metabolismo , Femenino , Ratones , RNA-Seq , Receptores Notch/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal/genética
3.
Mol Med ; 28(1): 76, 2022 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-35768768

RESUMEN

BACKGROUND: Axonal regeneration following peripheral nerve injury (PNI) depends on the complex interaction between Schwann cells (SCs) and macrophages, but the mechanisms underlying macrophage recruitment and activation in axonal regeneration remain unclear. METHODS: RNA sequencing (RNA-seq) was conducted to identify differentially expressed long noncoding RNAs (DElncRNAs) between crushed sciatic nerves and intact contralateral nerves. The putative role of lncRNAs in nerve regeneration was analyzed in vitro and in vivo. RESULTS: An lncRNA, called axon regeneration-associated transcript (lncARAT), was upregulated in SCs and SC-derived exosomes (SCs-Exo) after sciatic nerve injury. LncARAT contributed to axonal regeneration and improved motor function recovery. Mechanistically, lncARAT epigenetically activated C-C motif ligand 2 (CCL2) expression by recruiting KMT2A to CCL2 promoter, resulting in increased histone 3 lysine 4 trimethylation (H3K4me3) and CCL2 transcription in SCs. CCL2 facilitated the infiltration of macrophages into the injured nerves. Meanwhile, lncARAT-enriched exosomes were released from SCs and incorporated into macrophages. LncARAT functioned as an endogenous sponge to adsorb miRNA-329-5p in macrophages, resulting in increased suppressor of cytokine signaling (SOCS) 2 expression, which induced a proregenerative function of macrophages through a signal transducer and activator of transcription (STAT) 1/6-dependent pathway. CONCLUSIONS: LncARAT may represent a promising therapeutic avenue for peripheral nerve repair.


Asunto(s)
Axones , Macrófagos , Traumatismos de los Nervios Periféricos , ARN Largo no Codificante , Células de Schwann , Axones/metabolismo , Axones/fisiología , Humanos , Macrófagos/citología , Macrófagos/metabolismo , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos/genética , Traumatismos de los Nervios Periféricos/terapia , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células de Schwann/citología , Células de Schwann/metabolismo , Nervio Ciático/lesiones , Regulación hacia Arriba
4.
Lab Invest ; 101(9): 1238-1253, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34059758

RESUMEN

Spinal cord injury (SCI) is one common neurological condition which involves primary injury and secondary injury. Neuron inflammation and apoptosis after SCI is the most important pathological process of this disease. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. First, by re-analysis of Gene Expression Omnibus dataset (accession GSE19890), miR-182 was selected for further study because of its suppressive effects on the inflammatory response in the various types of injuries. Functional experiments demonstrated that miR-182 overexpression promoted functional recovery, reduced histopathological changes, and alleviated spinal cord edema in mice. It was also observed that miR-182 overexpression reduced apoptosis and attenuated the inflammatory response in spinal cord tissue, as evidenced by the reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, and the induction of IL-10. Using a lipopolysaccharide (LPS)-induced SCI model in BV-2 cells, we found that miR-182 was downregulated in the BV-2 cells following LPS stimulation, and upregulation of miR-182 improved LPS-induced cell damage, as reflected by the inhibition of apoptosis and the inflammatory response. IκB kinase ß (IKKß), an upstream target of the NF-κB pathway, was directly targeted by miR-182 and miR-182 suppressed its translation. Further experiments revealed that overexpression of IKKß reversed the anti-apoptosis and anti-inflammatory effects of miR-182 in LPS stimulated BV-2 cells. Finally, we found that miR-182 overexpression blocked the activation of the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the downregulation of phosphorylated (p­) IκB-α and nuclear p-p65. Taken together, these data indicate that miR-182 improved SCI-induced secondary injury through inhibiting apoptosis and the inflammatory response by blocking the IKKß/NF-κB pathway. Our findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI.


Asunto(s)
Apoptosis/efectos de los fármacos , Inflamación/metabolismo , MicroARNs/farmacología , Traumatismos de la Médula Espinal/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Quinasa I-kappa B/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos
5.
J Orthop Sci ; 26(3): 409-414, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32354577

RESUMEN

BACKGROUND: Comminuted patellar fractures are not rare, and the ideal treatment method remains controversial. The present study was conducted to evaluate effects and compare complications of two different methods used to treat comminuted patellar fractures. METHODS: From March 2010 to August 2016, 102 cases of 34-C2 or 34-C3 comminuted patellar fractures were treated at our hospital, wherein patients received two different treatments: titanium cable tension band with cerclage method (group A) and intrafragmentary screws with X-shaped plating technique (group B). At follow-ups, articular step-off, range of motion (ROM), Lysholm scores, time of union, and complications were recorded and analyzed. Radiographic and clinical data as well as rate of complications were statistically analyzed. RESULTS: In total, 87 patients were included in the final analysis (n = 47 in group A and n = 40 in group B). No significant differences were noted in terms of cost of implant, age, gender, rate of 34-C3 fractures, rate of layered inferior pole fractures, postoperative articular step-off and union time. At 2-year follow-up, average Lysholm scores, ROM and rate of complications were (89.0 ± 4.5), (122°±12°) and (27.7%) in group A and (90.2 ± 3.9), (124°±11°) and (17.5%) in group B, respectively, with no significant differences (p > 0.05). The mean time of surgery in group B was shorter than that in group A with significant difference (p < 0.05). CONCLUSIONS: Treatment using the intrafragmentary screws and plate method for amenable comminuted patellar fractures achieved similar complication rate and favorable functional outcomes at the 2-year follow-up, which was comparable to the titanium cable tension band with cerclage method. Thus, the intrafragmentary screws and plate method is effective, safe and convenient for 34-C2/C3 comminuted patellar fractures, especially appropriate for patients with layered fragments.


Asunto(s)
Fracturas Conminutas , Rótula , Tornillos Óseos , Hilos Ortopédicos , Fijación Interna de Fracturas , Curación de Fractura , Fracturas Conminutas/diagnóstico por imagen , Fracturas Conminutas/cirugía , Humanos , Rótula/diagnóstico por imagen , Rótula/cirugía , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del Tratamiento
6.
Acta Biochim Biophys Sin (Shanghai) ; 51(12): 1198-1207, 2019 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-31748779

RESUMEN

Schwann cells are the main force in spontaneous regeneration after peripheral nerve injury. The neurotrophic factors could promote the regeneration, but clinical applications of these factors are limited by some constraints. Hence, searching for new substances to elevate the function of Schwann cells and facilitate the regeneration of nerve is urgently needed. Syringic acid (SA) is a natural product with neuroprotective activity in vivo, but the role of SA on Schwann cells remains unclear. In this study, we for the first time found that SA was able to promote the proliferation and migration of Schwann cells, two important abilities in the process of regeneration. Then, microRNA (miRNA) microarray analysis was performed and 26 differentially expressed miRNAs (22 down-regulated and 4 up-regulated) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses found that the target genes of these miRNAs were mainly enriched in cellular response to chemical stimulus and cancer-related pathways, respectively. Subsequently, the levels of top 6 down-regulated miRNAs were validated by RT-qPCR and miR-451-5p was shown to be the most down-regulated one. Further experiments demonstrated that inhibition of miR-451-5p significantly promoted the proliferation and migration of Schwann cells. These results suggested that SA promoted the proliferation and migration of Schwann cells via down-regulation of miR-451-5p, and SA could be developed into a promising nutritional supplement to assist peripheral nerve regeneration.


Asunto(s)
Ácido Gálico/análogos & derivados , MicroARNs/metabolismo , Células de Schwann/metabolismo , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ácido Gálico/farmacología , Regeneración Nerviosa , Nervios Periféricos/fisiología , Células de Schwann/citología
7.
Acta Neurochir (Wien) ; 161(2): 279-286, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30483983

RESUMEN

BACKGROUND: Sciatic nerve injuries cause significant disability. We propose here a novel reconstructive procedure of transferring the motor branches of the femoral nerve as donor nerves to reconstruct both the peroneal and tibial nerve function as a novel approach to treat high sciatic nerve injury. METHODS: The autopsies of donor nerves (vastus lateralis nerve branch (VLN), vastus medialis nerve branch (VMN), saphenous nerve (SAN)) and respective recipient nerves (deep peroneal nerve branch (DPN), medial gastrocnemius nerve branch (MGN), sural nerve (SN)) were conducted in six fresh-frozen lower limbs. The distance between the origin or bifurcation points of the nerves to the head of fibula and the diameter of the end at the coaptation site were measured. The feasibility of tensionless direct suturing or grafting between the donor nerves and the recipient was evaluated. Finally, the nerve end at the coaptation site was harvested for observation with toluidine blue staining and nerve fiber count. RESULTS: The mean diameter of the VMN, VLN, MGN, DPN, SAN, and SN nerves were 1.5 ± 0.1, 1.4 ± 0.1, 1.3 ± 0.1, 2.3 ± 0.1, 2.1 ± 0.3, and 1.3 ± 0.2 mm, respectively. Histological observation showed that the abovementioned six nerve bundles had a respective nerve fiber number of 392 ± 27, 205 ± 520, 219 ± 67, 394 ± 50, 308 ± 77, and 335 ± 49. A total of 5/6 specimens needed grafting for a length ranging from 5 to 15 cm to bridge the VMN-MGN, 6/6 needed a graft length of 10-20 cm for VLN-DPN bridging, and 2/6 needed a graft length of 0-4 cm for SAN-SN bridging. CONCLUSION: The study demonstrated the feasibility of the transferring femoral nerve branches to sciatic nerve branches to restore the function for sciatic injury.


Asunto(s)
Nervio Femoral/cirugía , Transferencia de Nervios/métodos , Traumatismos de los Nervios Periféricos/cirugía , Nervio Ciático/cirugía , Cadáver , Estudios de Factibilidad , Femenino , Humanos , Masculino
8.
Acta Neurochir (Wien) ; 161(2): 271-277, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30617632

RESUMEN

BACKGROUND: This study was performed to evaluate the clinical effect of translocating the soleus muscular branch of the tibial nerve to repair the deep peroneal nerve. METHODS: Eight patients were treated for high common peroneal nerve injury. The deep peroneal nerve was separated out from the common peroneal nerve if no injury occurred upon opening the epineurium of the common peroneal nerve. The soleus muscular branch of the tibial nerve was then translocated to the deep peroneal nerve. RESULTS: The average follow-up duration was 21.75 months. Electromyography revealed newly appearing electric potentials in the tibialis anterior, extensor hallucis longus, and extensor toe longus muscle at 8 to 10 months postoperatively. Four patients showed good functional recovery after surgery; functional recovery was poor in other patients. CONCLUSIONS: Translocation of the soleus muscle branch is a feasible method to treat high common peroneal nerve injuries. A full understanding of the indications for this operation is required.


Asunto(s)
Transferencia de Nervios/métodos , Traumatismos de los Nervios Periféricos/cirugía , Neuropatías Peroneas/cirugía , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/inervación , Transferencia de Nervios/efectos adversos , Nervio Peroneo/cirugía , Complicaciones Posoperatorias/epidemiología , Recuperación de la Función , Nervio Tibial/cirugía
9.
J Orthop Sci ; 24(1): 142-146, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30316657

RESUMEN

BACKGROUND: Tension bands structures are widely used to treat transverse patellar fractures. However, many implants-related complications have been reported. The purpose of this study is to evaluate effects and compare complications of three methods used to treat transverse patellar fractures, including titanium cable tension bands, compression screws with titanium cable cerclage, and X-shaped plating technique. METHODS: From January 2010 to March 2016, 120 cases of transverse patellar fracture received open reduction and internal fixation with one of three methods: titanium cable tension band (group A), compression screws with titanium cable cerclage (group B), and X-shaped plating technique (group C). Of these, 108 cases were followed for >2 years. Clinical and radiographic data were retrospectively collected and statistically compared. RESULTS: Final analysis included 108 patients (n = 38 in group A, 36 in B, and 34 in C). Reduction was satisfactory in all patients after surgery. No significant differences were noted in age, gender, time from injury to surgery, postoperative articular step-off, Lysholm score, and range of motion at 24 months among all groups. At final follow-up, 12 (31.6%) symptomatic implant complications were encountered in group A, along with 6 (16.7%) and 2 (5.9%) in groups B and C, respectively (p < 0.05). CONCLUSION: All three methods could achieve the goal of rigid fixation and early functional rehabilitation. However, the X-plate technique had the lowest risk of symptomatic implant complications and could thus be a safe and effective alternative for internal fixation of transverse patellar fractures.


Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Traumatismos de la Rodilla/cirugía , Reducción Abierta/métodos , Rótula/lesiones , Placas Óseas , Tornillos Óseos , Hilos Ortopédicos , Femenino , Estudios de Seguimiento , Curación de Fractura , Fracturas Óseas/diagnóstico , Humanos , Traumatismos de la Rodilla/diagnóstico , Traumatismos de la Rodilla/fisiopatología , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Rótula/diagnóstico por imagen , Rótula/cirugía , Radiografía , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del Tratamiento
10.
Acta Neurochir (Wien) ; 160(7): 1385-1391, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29808458

RESUMEN

BACKGROUND: Quadriceps palsy is mainly caused by proximal lesions in the femoral nerve. The obturator nerve has been previously used to repair the femoral nerve, although only a few reports have described the procedure, and the outcomes have varied. In the present study, we aimed to confirm the feasibility and effectiveness of this treatment in a rodent model using the randomized control method. METHODS: Sixty Sprague-Dawley rats were randomized into two groups: the experimental group, wherein rats underwent femoral neurectomy and obturator nerve transfer to the femoral nerve motor branch; and the control group, wherein rats underwent femoral neurectomy without nerve transfer. Functional outcomes were measured using the BBB score, muscle mass, and histological assessment. RESULTS: At 12 and 16 weeks postoperatively, the rats in the experimental group exhibited recovery to a stronger stretch force of the knee and higher BBB score, as compared to the control group (p < 0.05). The muscle mass and myofiber cross-sectional area of the quadriceps were heavier and larger than those in the control group (p < 0.05). A regenerated nerve with myelinated and unmyelinated fibers was observed in the experimental group. No significant differences were observed between groups at 8 weeks postoperatively (p > 0.05). CONCLUSIONS: Obturator nerve transfer for repairing femoral nerve injury was feasible and effective in a rat model, and can hence be considered as an option for the treatment of femoral nerve injury.


Asunto(s)
Nervio Femoral/cirugía , Transferencia de Nervios/métodos , Nervio Obturador/cirugía , Traumatismos de los Nervios Periféricos/cirugía , Animales , Regeneración Nerviosa , Ratas , Ratas Sprague-Dawley
11.
Acta Neurochir (Wien) ; 157(1): 123-8, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25377383

RESUMEN

BACKGROUND: There is limited knowledge about accurate segmental motor innervation of the human lower extremity skeletal muscles. The aim of the present study was to explore the truth of segmental motor innervation of the lower extremity. METHODS: Included in this study were 20 patients with unilateral fracture of the sacrum and sacral nerve injury, who underwent internal fixation and decompression of the sacral nerve in our hospital between June 2009 and January 2014. L4-S4 nerve roots of the uninjured side were stimulated during operation. Motor innervation was determined by stimulating the spinal nerves with supramaximal intensity. RESULTS: We found the gluteus medius and the gluteus maximus were both mainly innervated by L5 and S1. In addition, the nerve fibres that innervated the extensor digitorum brevis, the abductor hallucis and the flexor digitorum brevis were mainly from S2 to S3. CONCLUSIONS: Our study provides the electrophysiological mapping of the segmental anatomy of the human lower extremity muscles, which should be clinically useful in helping the diagnosis and treatment of nerve injury and neuropathies.


Asunto(s)
Vías Eferentes/fisiología , Pierna/inervación , Plexo Lumbosacro/fisiología , Músculo Esquelético/inervación , Adulto , Estudios de Casos y Controles , Vías Eferentes/lesiones , Femenino , Humanos , Plexo Lumbosacro/lesiones , Masculino , Persona de Mediana Edad , Sacro/lesiones
12.
Clin Anat ; 27(5): 783-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24288352

RESUMEN

Nerve transfer is a valid surgical procedure for restoring lower-extremity function after lumbosacral plexus nerve root avulsion. We determined the anatomical feasibility of transferring the obturator and genitofemoral nerves for this purpose. The obturator, genitofemoral and femoral nerves, and the S1 and S2 nerve roots on both sides were exposed in 10 cadaver specimens. We traced all nerves to their origins. The lengths of the obturator and genitofemoral nerves were measured from their origins to their exits from the abdominal cavity. The transverse and longitudinal diameters of all nerves were measured. Specimens were obtained to determine the total number of myelinated fibers in each nerve. The proximal part of the left obturator nerve was anastomosed with the distal part of the right femoral nerve, between the vertebrae and the peritoneum, with an overlap of 2-3 cm. Similarly, the proximal parts of the right obturator and genitofemoral nerves were anastomosed with the ipsilateral S1 and S2 nerve roots, respectively, with an overlap of 2-4 cm. The obturator nerve contained approximately one-third of the number of fibers (4,300-7,800) presenting in the femoral nerve (13,500-21,000). Similarly, the number of fibers found in the S1 nerve root was in the range 5,200-8,900. The genitofemoral nerve contained approximately half the number of fibers (3,000-4,500) presenting in the S2 nerve root (4,600-8,400). The obturator and genitofemoral nerves could be suitable donor nerves for repairing lumbosacral plexus nerve root avulsion.


Asunto(s)
Nervio Femoral/cirugía , Plexo Lumbosacro/cirugía , Transferencia de Nervios/métodos , Nervio Obturador/cirugía , Radiculopatía/cirugía , Cadáver , Estudios de Factibilidad , Femenino , Nervio Femoral/anatomía & histología , Humanos , Plexo Lumbosacro/anatomía & histología , Masculino , Nervio Obturador/anatomía & histología , Radiculopatía/patología , Sacro/inervación
13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(5): 598-607, 2024 May 15.
Artículo en Zh | MEDLINE | ID: mdl-38752248

RESUMEN

Objective: To investigate the feasibility of selenium-methylselenocysteine (SMC) to promote peripheral nerve regeneration and its mechanism of action. Methods: Rat Schwann cells RSC96 cells were randomly divided into 5 groups, which were group A (without any treatment, control group), group B (adding 100 µmol/L H 2O 2), group C (adding 100 µmol/L H 2O 2+100 µmol/L SMC), group D (adding 100 µmol/L H 2O 2+200 µmol/L SMC), group E (adding 100 µmol/L H 2O 2+400 µmol/L SMC); the effect of SMC on cell proliferation was detected by MTT method, and the level of oxidative stress was detected by immunofluorescence for free radicals [reactive oxygen species (ROS)] after determining the appropriate dose group. Thirty-six 4-week-old male Sprague Dawley rats were randomly divided into 3 groups, namely, the sham operation group (Sham group), the sciatic nerve injury group (PNI group), and the SMC treatment group (SMC group), with 12 rats in each group; the rats in the PNI group were fed with food and water normally after modelling operation, and the rats in the SMC group were added 0.75 mg/kg SMC to the drinking water every day. At 4 weeks after operation, the sciatic nerves of rats in each group were sampled for neuroelectrophysiological detection of highest potential of compound muscle action potential (CMAP). The levels of inflammatory factors [interleukin 17 (IL-17), IL-6, IL-10 and oxidative stress factors catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA)] were detected by ELISA assay. The luxol fast blue (LFB) staining was used to observe the myelin density, fluorescence intensity of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) was observed by immunofluorescence staining, and myelin morphology was observed by transmission electron microscopy with measurement of axon diameter. Western blot was used to detect the protein expressions of p38 mitogen-activated protein kinases (p38MAPK), phosphorylated p38MAPK (p-p38MAPK), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Results: MTT assay showed that the addition of SMC significantly promoted the proliferation of RSC96 cells, and the low concentration could achieve an effective effect, so the treatment method of group C was selected for the subsequent experiments; ROS immunofluorescence test showed that group B showed a significant increase in the intensity of ROS fluorescence compared with that of group A, and group C showed a significant decrease in the intensity of ROS fluorescence compared with that of group B ( P<0.05). Neuroelectrophysiological tests showed that the highest potential of CMAP in SMC group was significantly higher than that in PNI and Sham groups ( P<0.05). ELISA assay showed that the levels of IL-6, IL-17, and MDA in PNI group were significantly higher than those in Sham group, and the levels of IL-10, SOD, and CAT were significantly lower; the levels of IL-6, IL-17, and MDA in SMC group were significantly lower than those in PNI group, and the levels of IL-10, SOD, and CAT were significantly higher ( P<0.05). LFB staining and transmission electron microscopy showed that the myelin density and the diameter of axons in the SMC group were significantly higher than those of the PNI group and the Sham group ( P<0.05). Immunofluorescence staining showed that the fluorescence intensity of GFAP and MBP in the SMC group were significantly stronger than those in the PNI group and Sham group ( P<0.05). Western blot showed that the relative expressions of Nrf2 and HO-1 proteins in the SMC group were significantly higher than those in the PNI group and Sham group, and the ratio of p-p38MAPK/p38MAPK proteins was significantly higher in the PNI group than that in the SMC group and Sham group ( P<0.05). Conclusion: SMC may inhibit oxidative stress and inflammation after nerve injury by up-regulating the Nrf2/HO-1 pathway, and then inhibit the phosphorylation of p38MAPK pathway to promote the proliferation of Schwann cells, which ultimately promotes the formation of myelin sheaths and accelerates the regeneration of peripheral nerves.


Asunto(s)
Regeneración Nerviosa , Estrés Oxidativo , Ratas Sprague-Dawley , Células de Schwann , Nervio Ciático , Selenio , Selenocisteína , Animales , Regeneración Nerviosa/efectos de los fármacos , Ratas , Masculino , Selenocisteína/análogos & derivados , Selenocisteína/farmacología , Células de Schwann/metabolismo , Células de Schwann/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Selenio/farmacología , Proliferación Celular/efectos de los fármacos , Traumatismos de los Nervios Periféricos/metabolismo
14.
J Orthop ; 57: 29-34, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38948501

RESUMEN

Objective: Surgical intervention and fixation is the recognized measurement to treat pubic symphysis diastasis caused by high-energy trauma. The purpose of this retrospective study was to assess the clinical application of modified pedicle screw-rod fixation (modified PSRF) and open reduction plate fixation (ORPF) for treating pubic symphysis diastasis. Methods: The data of this retrospective analysis were collected from 32 patients with pubic symphysis diastasis managed with modified PSRF or ORPF from January 2012 to December 2017, with or without posterior fixation. Indicators of clinical assessments including operating time, intraoperative blood loss, relevant surgical complications as well as follow-up were recorded. Majeed scores were performed for functional evaluation, as well as Matta criteria were applied to evaluate the quality of reduction. Results: The average time from injury to operation was 2.9 days in modified PSRF group and 3.2 days in ORPF group. Significant differences regarding average operation time (41.8 min versus 64.3 min) and average intraoperative blood loss (46.6 ml versus 304.6 ml) were presented between modified PSRF groups and ORPF group. Neither Majeed scores nor Matta evaluation showed a significant difference between two groups. In ORPF group, the incision infection occurred in one patient and two patients developed loosening of screws. In modified PSRF group, loosening of screws was found in one patient during the operative procedure and one patient experienced femoral nerve palsy. Irritation to the lateral femoral cutaneous nerve (LFCN) was detected in two patients in modified PSRF group. Conclusions: Satisfactory clinical outcomes were provided with applications of both fixation methods for treating pubic symphysis diastasis. Modified PSRF, as a minimal invasive technique, could serve as an effective and reasonable option for treating pubic symphysis diastasis.Level of evidence: III: retrospective cohort study.Trial registration: researchregistry3906.

15.
Neural Regen Res ; 19(5): 1142-1149, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37862220

RESUMEN

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity, damaging the neurons. However, how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear. Herein, we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury. We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice. Lipid droplet accumulation could be induced by myelin debris in HT22 cells. Myelin debris degradation by phospholipase led to massive free fatty acid production, which increased lipid droplet synthesis, ß-oxidation, and oxidative phosphorylation. Excessive oxidative phosphorylation increased reactive oxygen species generation, which led to increased lipid peroxidation and HT22 cell apoptosis. Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway, thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells. Motor function, lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury. The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

16.
Aging Dis ; 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38502589

RESUMEN

Osteoporotic fractures are the most severe complications of osteoporosis, characterized by poor bone quality, difficult realignment and fixation, slow fracture healing, and a high risk of recurrence. Clinically managing these fractures is relatively challenging, and in the context of rapid aging, they pose significant social hazards. The rapid advancement of disciplines such as biophysics and biochemistry brings new opportunities for future medical diagnosis and treatment. However, there has been limited attention to precision diagnosis and treatment strategies for osteoporotic fractures both domestically and internationally. In response to this, the Chinese Medical Association Orthopaedic Branch Youth Osteoporosis Group, Chinese Geriatrics Society Geriatric Orthopaedics Committee, Chinese Medical Doctor Association Orthopaedic Physicians Branch Youth Committee Osteoporosis Group, and Shanghai Association of Integrated Traditional Chinese and Western Medicine Osteoporosis Professional Committee have collaborated to develop this consensus. It aims to elucidate emerging technologies that may play a pivotal role in both diagnosis and treatment, advocating for clinicians to embrace interdisciplinary approaches and incorporate these new technologies into their practice. Ultimately, the goal is to improve the prognosis and quality of life for elderly patients with osteoporotic fractures.

17.
Muscle Nerve ; 47(2): 241-5, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23168676

RESUMEN

INTRODUCTION: Neurogenic bladder dysfunction after spinal cord injury (SCI) is a major medical and social problem. In this study we assessed the effectiveness of neurogenic bladder reinnervation in patients with SCI using a normal S1 nerve root. METHODS: Nine patients with bladder dysfunction caused by injury to the low conus medullaris (S2-S5) underwent a novel surgical procedure in which the unilateral proximal end of the S1 ventral root (VR) was anastomosed to the distal end of the S2 and S3 VRs. RESULTS: Seven patients regained satisfactory bladder control within 8-12 months after VR microanastomosis. The average residual urine volume decreased from 186.0 ± 35.0 ml to 43.0 ± 10.0 ml, and no urinary infections occurred. CONCLUSIONS: These results suggest the effectiveness of bladder innervation by S1 nerve transfer, which could provide a new approach for the reconstruction of atonic bladder function caused by low conus medullaris injuries.


Asunto(s)
Transferencia de Nervios/métodos , Traumatismos de la Médula Espinal/cirugía , Raíces Nerviosas Espinales/cirugía , Vejiga Urinaria Neurogénica/cirugía , Vejiga Urinaria/cirugía , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/fisiopatología , Resultado del Tratamiento , Vejiga Urinaria/fisiopatología , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Neurogénica/fisiopatología
18.
J Reconstr Microsurg ; 29(5): 325-30, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23599214

RESUMEN

The aim of this study was to evaluate the feasibility and effectiveness of transferring the contralateral C7 root to repair avulsed C7 nerve root. Thirty rats were randomized into three groups. In group A, rats underwent whole-root avulsion of the left brachial plexus and contralateral C7 root transfer to the avulsed C7 nerve root. In group B, rats underwent whole-root avulsion and contralateral C7 root transfer to the radial nerve. In group C, rats underwent whole-root avulsion of the left brachial plexus without nerve transfer. Functional outcomes were measured by electrophysiological studies, muscle tetanus contraction force, muscle mass, and histology. Six months postoperatively, increased amplitude and shortened latency of compound muscle action potentials, larger maximum tetanic contractile tension, heavier muscle mass, and larger cross-sectional area of the muscle fibers were observed in the triceps, extensor carpi radialis brevis, and extensor digitorum in groups A and B when compared with group C (p < 0.01). There were no significant differences between group A and B (p > 0.05). Contralateral C7 nerve transfer to repair avulsed C7 nerve root was feasible and effective in this rat model. It should be considered as an option for the treatment of brachial plexus injuries.


Asunto(s)
Plexo Braquial/lesiones , Plexo Braquial/cirugía , Transferencia de Nervios/métodos , Radiculopatía/cirugía , Raíces Nerviosas Espinales/lesiones , Raíces Nerviosas Espinales/cirugía , Animales , Modelos Animales de Enfermedad , Electrofisiología , Estudios de Factibilidad , Masculino , Contracción Muscular , Ratas , Ratas Sprague-Dawley
19.
Front Cell Neurosci ; 17: 1228282, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37545880

RESUMEN

Peripheral nerve injury (PNI) is associated with delayed repair of the injured nerves in elderly patients, resulting in loss of nerve function, chronic pain, muscle atrophy, and permanent disability. Therefore, the mechanism underlying the delayed repair of peripheral nerves in aging patients should be investigated. Schwann cells (SCs) play a crucial role in repairing PNI and regulating various nerve-repair genes after injury. SCs also promote peripheral nerve repair through various modalities, including mediating nerve demyelination, secreting neurotrophic factors, establishing Büngner bands, clearing axon and myelin debris, and promoting axon remyelination. However, aged SCs undergo structural and functional changes, leading to demyelination and dedifferentiation disorders, decreased secretion of neurotrophic factors, impaired clearance of axonal and myelin debris, and reduced capacity for axon remyelination. As a result, aged SCs may result in delayed repair of nerves after injury. This review article aimed to examine the mechanism underlying the diminished neural repair ability of aging SCs.

20.
Orthop Surg ; 15(8): 2152-2156, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36349872

RESUMEN

OBJECTIVE: Implant failure is a disastrous complication of the operative treatment of midshaft clavicle fractures, and improving the osteosynthesis plate is a strategy for preventing this. We aimed to investigate whether canceling the notch and adding screw-hole inserts enhanced the mechanical properties of the plate. METHODS: A clavicle model was generated based on the CT images of six adult volunteers (age range, 20-40 years; three males and three females; height range 160-175) using dedicated software, and a midshaft fracture model was created. The domestically made seven-hole locking plate commonly used for midshaft clavicle fractures was simulated (Model I); modifications were made to the plate (Model II). Using 3D finite element analysis, we simulated the fracture construct under three different load conditions-downward cantilever bending, axial compression, and axial torsion-and compared the stress distribution. RESULTS: We found that under axial compression, Model II experienced its maximum stress on the plate at 551.9MPa, which was less than that in Model I (790.4 MPa). Moreover, a greater stress concentration at the fracture site was observed under axial torsion, despite the maximum stress of both the models being similar. CONCLUSION: Canceling the notch and filling the screw holes near the fracture can ameliorate stress concentration on the internal fixation construct and enhance its reliability under axial compression. This improvement has substantial effects on the mechanical properties of implants and potentially prevents implant failure. Modern osteosynthesis anatomical implants need to be improved.


Asunto(s)
Clavícula , Fracturas Óseas , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Clavícula/cirugía , Análisis de Elementos Finitos , Reproducibilidad de los Resultados , Fenómenos Biomecánicos , Fijación Interna de Fracturas/métodos , Placas Óseas , Fracturas Óseas/cirugía
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