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1.
J Cell Mol Med ; 28(7): e18219, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38509743

RESUMO

The present research focused on identifying necroptosis-related differentially expressed genes (NRDEGs) in spinal cord injury (SCI) to highlight potential therapeutic and prognostic target genes in clinical SCI. Three SCI-related datasets were downloaded, including GSE151371, GSE5296 and GSE47681. MSigDB and KEGG datasets were searched for necroptosis-related genes (NRGs). Differentially expressed genes (DEGs) and NRGs were intersected to obtain NRDEGs. The MCC algorithm was employed to select the first 10 genes as hub genes. A protein-protein interaction (PPI) network related to NRDEGs was developed utilizing STRING. Several databases were searched to predict interactions between hub genes and miRNAs, transcription factors, potential drugs, and small molecules. Immunoassays were performed to identify DEGs using CIBERSORTx. Additionally, qRT-PCR was carried out to verify NRDEGs in an animal model of SCI. Combined analysis of all datasets identified 15 co-expressed DEGs and NRGs. GO and KEGG pathway analyses highlighted DEGs mostly belonged to pathways associated with necroptosis and apoptosis. Hub gene expression analysis showed high accuracy in SCI diagnosis was associated with the expression of CHMP7 and FADD. A total of two hub genes, i.e. CHMP7, FADD, were considered potential targets for SCI therapy.


Assuntos
MicroRNAs , Traumatismos da Medula Espinal , Animais , Necroptose/genética , Biologia Computacional , Perfilação da Expressão Gênica , MicroRNAs/genética , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/genética
2.
Neural Regen Res ; 19(11): 2499-2512, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38526286

RESUMO

JOURNAL/nrgr/04.03/01300535-202419110-00030/figure1/v/2024-03-08T184507Z/r/image-tiff The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.

3.
J Biomed Res ; 37(5): 394-400, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37750309

RESUMO

The current study aims to ascertain the anatomical feasibility of transferring the contralateral S1 ventral root (VR) to the ipsilateral L5 VR for treating unilateral spastic lower limb paralysis. Six formalin-fixed (three males and three females) cadavers were used. The VR of the contralateral S1 was transferred to the VR of the ipsilateral L5. The sural nerve was selected as a bridge between the donor and recipient nerve. The number of axons, the cross-sectional areas and the pertinent distances between the donor and recipient nerves were measured. The extradural S1 VR and L5 VR could be separated based on anatomical markers of the dorsal root ganglion. The gross distance between the S1 nerve root and L5 nerve root was 31.31 (± 3.23) mm in the six cadavers, while that on the diffusion tensor imaging was 47.51 (± 3.23) mm in 60 patients without spinal diseases, and both distances were seperately greater than that between the outlet of S1 from the spinal cord and the ganglion. The numbers of axons in the S1 VRs and L5 VRs were 13414.20 (± 2890.30) and 10613.20 (± 2135.58), respectively. The cross-sectional areas of the S1 VR and L5 VR were 1.68 (± 0.26) mm 2 and 1.08 (± 0.26) mm 2, respectively. In conclusion, transfer of the contralateral S1 VR to the ipsilateral L5 VR may be an anatomically feasible treatment option for unilateral spastic lower limb paralysis.

4.
Talanta ; 252: 123867, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36041317

RESUMO

Accurate discriminating nerve fibers is a prerequisite for right suturing nerves in nerve transfer operation. Various methods have been developed for identification of motor and sensory fibers, but no simple method meets the requirements in clinic. In this study, a surface-enhanced Raman scattering (SERS) lever strategy is designed and developed to detect Acetylcholinesterase (AchE) ultrasensitively, in which using produced thiocholine with weak intrinsic Raman activity (four ounces) to adjust absorbance of Rhodamine B with strong intrinsic Raman activity (thousand catties) on SERS-active substrates is to increase the sensitivity. Employing a miniaturized SERS substrate, SERS-active microneedles, is to decrease the volume of enzymolysis systems. Adopting an internal reference is to increase the repeatability of collected signal. The ultrasensitive AchE detection method discriminate samples with four times of difference in enzyme activity between 1-1 × 10-4 U/mL in about 10 min of enzymolysis time. AchE amounts in 2-mm-long segments of ventral and dorsal roots were about 0.00025-0.001 U and 0.01-0.02 U, respectively. The developed method would be a reliable method met the requirements of identifying motor and sensory fibers in clinic.


Assuntos
Acetilcolinesterase , Análise Espectral Raman , Análise Espectral Raman/métodos , Tiocolina , Fibras Nervosas
5.
J Clin Med ; 11(23)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36498666

RESUMO

Robot-assisted orthopedic surgery has great application prospects, and the accuracy of the robot is the key to its overall performance. The aim of this study was to develop a new orthopedic surgical robot to assist in spinal surgeries and to compare its feasibility and accuracy with the existing orthopedic robot. A new type of high-precision orthopedic surgical robot (Tuoshou) was developed. A multicenter, randomized controlled trial was carried out to compare the Tuoshou with the TiRobot (TINAVI Medical Technologies Co., Ltd., Beijing) to evaluate the accuracy and safety of their navigation and positioning. A total of 112 patients were randomized, and 108 patients completed the study. The position deviation of the Kirschner wire placement in the Tuoshou group was smaller than that in the TiRobot group (p = 0.014). The Tuoshou group was better than the TiRobot group in terms of the pedicle screw insertion accuracy (p = 0.016) and entry point deviation (p < 0.001). No differences were observed in endpoint deviation (p = 0.170), axial deviation (p = 0.170), sagittal deviation (p = 0.324), and spatial deviation (p = 0.299). There was no difference in security indicators. The new orthopedic surgical robot was highly accurate and optimized for clinical practice, making it suitable for clinical application.

6.
Cell Transplant ; 31: 9636897221132502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278404

RESUMO

OBJECTIVE: To explore the method of eliminating donor-specific anti-HLA antibodies (DSA) in haploidentical stem cell transplantation (haplo-SCT). METHODS: We present a refractory B-cell acute lymphoblastic leukemia (ALL) patient who had strongly positive DSA, but had no human leukocyte antigen-matched donor. Although CD38 expression on leukemia cells was negative, daratumumab combined with etoposide and venetoclax therapy was chosen for her. RESULTS: She achieved a significant decrease in DSA levels and complete remission on the combination therapy with daratumumab. She then received a haplo-SCT from a daughter as a donor and had a successful engraftment of donor stem cell. In haplo-SCT, strongly positive DSA levels, directed against donor HLA antigens, could be significantly reduced by daratumumab therapy before transplantation and successfully bridge subsequent haplo-SCT. CONCLUSION: Although CD38 expression is negative in leukemia cells, refractory B-ALL patients may still benefit from combination therapy with daratumumab. We need further clinical observation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Feminino , Humanos , Etoposídeo , Antígenos de Histocompatibilidade , Antígenos HLA , Indução de Remissão
7.
Spine (Phila Pa 1976) ; 47(17): 1253-1258, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35853170

RESUMO

STUDY DESIGN: Eight cadavers were included in this anatomical study. OBJECTIVE: This study aimed to confirm the anatomical feasibility of extradural transfer of the contralateral T11 ventral root (VR) to the ipsilateral L2 level and the contralateral L1 VR to the ipsilateral L3 level to restore lower limb function in cases of paraplegia. SUMMARY OF BACKGROUND DATA: Motor dysfunction due to hemiplegia significantly affects the daily life of patients. To date, unlike in cases of upper limb dysfunction, there are few studies on the surgical management of lower limb movement dysfunction. MATERIALS AND METHODS: Eight cadavers were included in this study to confirm the feasibility of the nerve transfer. After separating the VR and dorsal root at each level, the VRs at the T11 and L1 levels were anastomosed with the VRs of L2 and L3, respectively. The length of the VRs of donor roots and the distance between the donor and recipient nerves were measured. H&E staining was performed to verify the number of axons and the cross-sectional area of the VRs. Lumbar x-rays of 60 healthy adults were used to measure the distance between the donor and recipient nerves. RESULTS: After exposing the bilateral extradural each root, the VRs could be easily isolated from the whole root. The distance between the VRs of T11 and L2, L1, and L3 was significantly longer than the length of the donor nerve. Therefore, the sural nerve was used for grafting. The measurements performed on the lumbar x-rays of the 60 healthy adults confirmed the results. The number of axons and cross-sectional area of the VRs were measured. CONCLUSION: Our study confirmed the anatomical feasibility of transferring the VRs of T11 to L2 and that of L1 to L3 to restore lower limb function in cases of hemiplegia. LEVEL OF EVIDENCE: 5.


Assuntos
Hemiplegia , Doenças Musculoesqueléticas , Adulto , Cadáver , Humanos , Extremidade Inferior/cirurgia , Paraplegia/cirurgia , Raízes Nervosas Espinhais/anatomia & histologia , Raízes Nervosas Espinhais/cirurgia
8.
Spine (Phila Pa 1976) ; 47(17): 1248-1252, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35867634

RESUMO

STUDY DESIGN: A total of 6 formalin-fixed cadavers were included in the cadaver feasibility study. OBJECTIVE: The aim was to ascertain the anatomical feasibility of extradural contralateral C7 ventral root transfer technique by cervical posterior. SUMMARY OF BACKGROUND DATA: Upper limb spastic hemiplegia is a common sequela after stroke. In our previous study, the authors established a method by transferring contralateral C7 dorsal and ventral roots to the corresponding C7 dorsal and ventral roots on the affected side in the cervical posterior. METHODS: In the present study, six formalin-fixed cadavers were dissected to confirm the anatomical feasibility. Experimental anastomosis in cadavers was conducted. The pertinent lengths of the extradural nerve roots were measured. The tissue structures surrounding regions between the extradural CC7 nerve roots and the vertebral artery were observed. The cervical magnetic resonance imaging scans of 60 adults were used to measure the distance between the donor and recipient nerves. RESULTS: Experimental anastomosis showed that the distance between the donor and recipient nerves was approximately 1 cm; the short segment of the sural nerve needed bridging. The distance between both exit sites of the exit of the extradural dura mater was 33.57±1.55 mm. The length of the extradural CC7 ventral root was 22.00±0.98 mm. The ventral distance (vd) and the dorsal distance (dd) in males were 23.98±1.72 mm and 30.85±2.22 mm ( P <0.05), while those in females were 23.28±1.51 mm and 30.03±2.16 mm, respectively. C7 vertebral transverse process, ligaments, and other soft tissues were observed between the vertebral artery and the extradural C7 nerve root. CONCLUSION: Under the premise of less trauma, our study shows that the extradural contralateral C7 ventral root transfer technique, in theory, yields better surgical results, including better recovery of motor function and complete preservation of sensory function. LEVEL OF EVIDENCE: 5.


Assuntos
Hemiplegia , Raízes Nervosas Espinhais , Adulto , Cadáver , Estudos de Viabilidade , Feminino , Formaldeído , Hemiplegia/cirurgia , Humanos , Masculino , Raízes Nervosas Espinhais/cirurgia , Extremidade Superior
9.
Cells ; 11(9)2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35563703

RESUMO

The recovery of lower-urinary-tract activity is a top priority for patients with spinal-cord injury. Historically, locomotor training improved micturition function in both patients with spinal cord injury and animal models. We explore whether training augments such as the supraspinal control of the external urethral sphincter results in enhanced coordination in detrusor-sphincter activity. We implemented a clinically relevant contusive spinal-cord injury at the 12th thoracic level in rats and administered forced wheel running exercise for 11 weeks. Awake rats then underwent bladder cystometrogram and sphincter electromyography recordings to examine the micturition reflex. Subsequently, pseudorabies-virus-encoding red fluorescent protein was injected into the sphincter to trans-synaptically trace the supraspinal innervation of Onuf's motoneurons. Training in the injury group reduced the occurrence of bladder nonvoiding contractions, decreased the voiding threshold and peak intravesical pressure, and shortened the latency of sphincter bursting during voiding, leading to enhanced voiding efficiency. Histological analysis demonstrated that the training increased the extent of spared spinal-cord tissue around the epicenter of lesions. Compared to the group of injury without exercise, training elicited denser 5-hydroxytryptamine-positive axon terminals in the vicinity of Onuf's motoneurons in the cord; more pseudorabies virus-labeled or c-fos expressing neurons were detected in the brainstem, suggesting the enhanced supraspinal control of sphincter activity. Thus, locomotor training promotes tissue sparing and axon innervation of spinal motoneurons to improve voiding function following contusive spinal-cord injury.


Assuntos
Contusões , Traumatismos da Medula Espinal , Animais , Humanos , Atividade Motora , Ratos , Traumatismos da Medula Espinal/patologia , Uretra/inervação , Uretra/fisiologia , Bexiga Urinária , Micção/fisiologia
10.
J Biomed Res ; 36(3): 208-214, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35635142

RESUMO

Osteoporotic vertebral compression fracture (OVCF) has become a major public health issue that becomes more pressing with increasing global aging. Percutaneous kyphoplasty (PKP) is an effective treatment for OVCF. Robot-assisted PKP has been utilized in recent years to improve accuracy and reduce complications. However, the effectiveness of robot-assisted PKP in the treatment of multi-segmental OVCF has yet to be proved. This study was designed to compare the efficacy of robot-assisted and conventional fluoroscopy-assisted multi-segmental PKP. A total of 30 cases with multi-segmental OVCF between April 2019 and April 2021 were included in this study. Fifteen cases were assigned to the robot-assisted PKP group (robot group) and 15 cases to the conventional fluoroscopy-assisted PKP group (conventional fluoroscopy group). The number of fluoroscopic exposures, fluoroscopic dose, operation time, cement leakage rate, visual analog scale (VAS) score, vertebral kyphosis angle (VKA), and height of fractured vertebral body (HFV) were compared between the 2 groups. The number of fluoroscopic exposures, fluoroscopic doses, and cement leakage rates in the robot group were lower than in the conventional fluoroscopy group ( P<0.05) while the operative time in the robot group was longer than in the conventional fluoroscopy group ( P<0.05). VAS score and VKA were decreased and HFV was increased after surgery in both groups ( P<0.05). Therefore, robot-assisted PKP for the treatment of multi-segmental OVCF can reduce the number of fluoroscopic exposures, fluoroscopic doses, and cement leakage compared to conventional treatment. As such, robot-assisted PKP has good application prospects and is potentially more effective in the treatment of multi-segmental OVCF.

11.
Spine (Phila Pa 1976) ; 46(20): 1363-1369, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34559748

RESUMO

STUDY DESIGN: Two fresh-frozen and six formalin-fixed cadavers were included in the study. OBJECTIVE: To ascertain whether transferring T9 or T11 ventral root (VR) to L2 VR and T10 or T12 VR to L3 VR in restoring lower limb function after spinal cord injury is anatomically feasible. SUMMARY OF BACKGROUND DATA: Lower limb paralysis impairs the quality of the life and places burden on the whole society. However, no significant improvement in this area was achieved during recent years. METHODS: In the present study, two fresh-frozen and six formalin-fixed cadavers were dissected to confirm the anatomical feasibility. A limited laminectomy was performed to expose the T9-L3 extradural nerve roots. T9 and T10 VR were anastomosed to L2 and L3 VR respectively, or T11 and T12 VR were anastomosed to L2 and L3 VR respectively. The pertinent distances between the donor and recipient nerves were measured and H&E staining was used to detect the axon number and cross-section area of each VR. RESULTS: The limited incision was performed to expose the T9-L3 nerve root. According to the anatomic landmark of dorsal root ganglion, each VR could be isolated from each extradural nerve root. The T9 or T11 VR needs sural nerve graft to be transferred to L2 VR, and T10 or T12 VR also needs a nerve bridge to connect to L3 VR. The nerve numbers of T9, T10, T11, T12, L2, and L3 VRs and the sural nerves were measured respectively. The cross-section areas of T9, T10, T11, T12, L2, and L3 VRs and sural nerves were measured respectively. CONCLUSION: Our study suggested that application of transferring T9 or T11 VR to L2 VR and T10 or T12 VR to L3 VR in restoring lower limb function is anatomically feasible.Level of Evidence: 5.


Assuntos
Traumatismos da Medula Espinal , Cadáver , Estudos de Viabilidade , Humanos , Extremidade Inferior/cirurgia , Raízes Nervosas Espinhais/cirurgia
12.
Cancer Immunol Immunother ; 70(12): 3501-3511, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33899130

RESUMO

The persistence or recurrence of minimal residual disease (MRD) after chemotherapy predicts relapse of B-cell acute lymphoblastic leukemia (B-ALL). CD19-directed chimeric antigen receptor T (CD19 CAR-T) cells have shown promising responses in B-ALL. However, their role in chemotherapy-refractory MRD-positive B-ALL remains unclear. Here we aimed to assess the effectiveness and safety of CD19 CAR-T cells in MRD-positive B-ALL patients. From January 2018, a total of 14 MRD-positive B-ALL patients received one or more infusions of autogenous CD19 CAR-T cells. Among them, 12 patients achieved MRD-negative remission after one cycle of CAR-T infusion. At a median follow-up time of 647 days (range 172-945 days), the 2-year event-free survival rate in MRD-positive patients was 61.2% ± 14.0% and the 2-year overall survival was 78.6 ± 11.0%, which were significantly higher than patients with active disease (blasts ≥ 5% or with extramedullary disease). Moreover, patients with MRD had a lower grade of cytokine release syndrome (CRS) than patients with active disease. However, the peak expansion of CAR-T cells in MRD positive patients showed no statistical difference compared to patients with active disease. Five patients received two or more CAR-T cell infusions and these patients showed a decreased peak expansion of CAR-T cell in subsequent infusions. In conclusion, pre-emptive CD19 CAR-T cell treatment is an effective and safe approach and may confer sustained remission in B-ALL patients with chemotherapy-refractory MRD. The trials were registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).


Assuntos
Antígenos CD19/imunologia , Linfoma de Células B/imunologia , Neoplasia Residual/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Imunoterapia Adotiva/métodos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Recidiva , Adulto Jovem
13.
J Biomed Res ; 34(5): 379-386, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32934191

RESUMO

Thoracolumbar fractures are usually treated by open posterior pedicle screw fixation. However, this procedure involves massive paraspinal muscle stripping, inflicting surgical trauma, and prolonged X-ray exposure. In this study, we observed 127 patients with single-segment injury thoracolumbar fractures. Thirty-six patients were treated by the modified Wiltse's paraspinal approach with minimally invasive channel system, while 91 patients were treated via traditional posterior approach. Operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, screw placement accuracy, visual analogue scale score, and Cobb's angle of two groups were compared. The X-ray exposure times were notably reduced (4.2±1.6) in the new approach group (P<0.05). The pedicle screw placement accuracy and Cobb's angle after surgery were similar in the two groups. We conclude that modified Wiltse's paraspinal approach with spinal minimally invasive channel system surgery can significantly reduce the X-ray exposure times and is an alternative therapy for the thoracolumbar fracture.

14.
J Pain Res ; 12: 2403-2410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534362

RESUMO

OBJECTIVE: To report a rare case of cervical intradural disc herniation (IDH) with Brown-Séquard syndrome and to review the related literature. METHODS: Pathogenesis, preoperative diagnosis, and the surgical technique are discussed, and previous literature reports are reviewed. RESULTS: A 44-year-old woman complained of weakness of the left upper and lower extremities and paresthesias in the right limbs after a bicycle ride 3 days earlier. She had a history of neck pain for 2 years prior. CT showed obvious ossification of the posterior longitudinal ligament (OPLL), and MRI revealed C3-7 disc herniations, with a positive "halo sign" around the herniated C4/5. We performed emergency decompression through anterior cervical corpectomy, and vertebrotomy decompression and fusion. At review 3 months after surgery, the patient's neck pain was markedly relieved, and motor strength in the limbs had improved. At 1 year after surgery, she had recovered completely. CONCLUSION: Cervical IDH is a rare condition that may be related to the traumatic inflammatory response and OPLL. Relatively rare imaging features such as the hawk-beak sign, halo sign, Y sign, and epidural gas sign could help in preoperative diagnosis. Prompt anterior cervical decompression is the preferred treatment for this condition.

15.
J Biomed Res ; 32(4): 298-304, 2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-29884775

RESUMO

The study aimed to demonstrate the feasibility of an extradural nerve anastomosis technique for the restoration of a C5 and C6 avulsion of the brachial plexus. Nine fresh frozen human cadavers were used. The diameters, sizes, and locations of the extradural spinal nerve roots were observed. The lengths of the extradural spinal nerve roots and the distance between the neighboring nerve root outlets were measured and compared in the cervical segments. In the spinal canal, the ventral and dorsal roots were separated by the dura and arachnoid. The ventral and dorsal roots of C7 had sufficient lengths to anastomose those of C6. The ventral and dorsal of C4 had enough length to be transferred to those of C5, respectively. The feasibility of this extradural nerve anastomosis technique for restoring C5 and C6 avulsion of the brachial plexus in human cadavers was demonstrated in our anatomical study.

16.
Anticancer Drugs ; 29(7): 646-651, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29878900

RESUMO

STAT5 is an important transcription factor that is constitutively activated in various types of malignancies, including chronic myelogenous leukemia (CML). Whether the antitumor effects of resveratrol (RES) are linked to its capability to inhibit STAT5 activation in CML cells was investigated. We found that RES inhibited STAT5 activation in K562 and KU812 cell lines; RES also reduced the STAT5 concentration in the nucleus of K562 and KU812 cells. Protein tyrosine phosphatase (PTP) inhibitor, sodium pervanadate, reversed the RES-induced downregulation of STAT5, suggesting the involvement of a PTP. Indeed, we observed that RES decreased the expression of tyrosine phosphatase SHP-1 and SHP-2; moreover, the deletion of SHP-1 and SHP-2 genes by siRNA abolished the ability of RES to inhibit STAT5 activation, which suggested the critical role of both SHP-1 and SHP-2 in its possible mechanism of action. RES downregulated the expression of STAT5-regulated gene products such as Bcl-xL, Bcl-2, Cyclin D1, and Mcl-1, and increased the expression of Bax. This correlated with the suppression of proliferation and induction of apoptosis. Overall, our results suggest that RES is a blocker of STAT5 activation and thus may be potentially useful for the treatment of CML.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva , Proteína Tirosina Fosfatase não Receptora Tipo 11/biossíntese , Proteína Tirosina Fosfatase não Receptora Tipo 6/biossíntese , Resveratrol/farmacologia , Fator de Transcrição STAT5/antagonistas & inibidores , Proteínas Supressoras de Tumor/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Transdução de Sinais
17.
Spine (Phila Pa 1976) ; 43(18): E1046-E1052, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29470276

RESUMO

STUDY DESIGN: Anatomic study in six formalin-fixed cadavers. OBJECTIVE: To determine the anatomical feasibility of transferring the S2 and S3 ventral roots (VRs) to S1 VR as a method for restoring bladder dysfunction in spinal cord injury. SUMMARY OF BACKGROUND DATA: A large quantity of researches of neuroanastomosis methods have been used for treating the bladder dysfunction in spinal cord injury. However, some limitations retard the development of those studies. METHODS: In this study, six formalin-fixed cadavers (four males, two females) were dissected. The feasibility of exposing the S1, S2, and S3 extradural nerve roots by the limited laminectomy, isolating the VR and dorsal roots from each extradural nerve root and transferring the S2,S3 VRs to the S1 VR were assessed. The pertinent distances and the nerve cross-sectional areas in each specimen were measured. The morphology of each nerve root was observed by hematoxylin-eosin staining. RESULTS: The limited laminectomy was performed to expose the S1 to S3 extradural nerve roots. The VRs could be isolated from each extradural nerve root at the location of the dorsal root ganglion and the hematoxylin-eosin staining showed that there were some connective tissues separating the VRs from the corresponding dorsal root ganglion. The S2 and S3 VRs have sufficient lengths to be transferred to S1 VR without grafting. The mean cross-sectional area of the S1 VR was 2.60 ±â€Š0.17 mm, and that was 1.02 ±â€Š0.32 mm and 0.51 ±â€Š0.21 mm of the S2 and S3 VRs, respectively. CONCLUSION: This study demonstrated that use of the S2 and S3 VRs for extradural transfer to S1 VR for restoring bladder dysfunction is surgically feasible. LEVEL OF EVIDENCE: 5.


Assuntos
Procedimentos Neurocirúrgicos/métodos , Sacro/cirurgia , Traumatismos da Medula Espinal/cirurgia , Raízes Nervosas Espinhais/cirurgia , Bexiga Urinaria Neurogênica/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Sacro/diagnóstico por imagem , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Raízes Nervosas Espinhais/diagnóstico por imagem , Bexiga Urinaria Neurogênica/diagnóstico por imagem , Bexiga Urinaria Neurogênica/etiologia
18.
J Biomed Res ; 32(2): 123-129, 2018 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-28866657

RESUMO

This study was aimed to introduce a novel entry point for pedicle screw fixation in the thoracic spine and compare it with the traditional entry point. A novel entry point was found with the aim of improving accuracy, safety and stability of pedicle screw technique based on anatomical structures of the spine. A total of 76 pieces of normal thoracic CT images at the transverse plane and the thoracic pedicle anatomy of 6 cadaveric specimens were recruited. Transverse pedicle angle (TPA), screw length, screw placement accuracy rate and axial pullout strength of the two different entry point groups were compared. There were significant differences in the TPA, screw length, and the screw placement accuracy rate between the two groups (P<0.05). The maximum axial pullout strength of the novel entry point group was slightly larger than that of the traditional group. However, the difference was not significant (P>0.05). The novel entry point significantly improved the accuracy, stability and safety of pedicle screw placement. With reference to the advantages above, the new entry point can be used for spinal internal fixations in the thoracic spine.

19.
Neural Regen Res ; 12(4): 644-653, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28553347

RESUMO

Numerous studies have shown that topical application of mitomycin C after surgical decompression effectively reduces scar adhesion. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of mitomycin C on the proliferation and apoptosis of human epidural scar fibroblasts. Human epidural scar fibroblasts were treated with various concentrations of mitomycin C (1, 5, 10, 20, 40 µg/mL) for 12, 24 and 48 hours. Mitomycin C suppressed the growth of these cells in a dose- and time-dependent manner. Mitomycin C upregulated the expression levels of Fas, DR4, DR5, cleaved caspase-8/9, Bax, Bim and cleaved caspase-3 proteins, and it downregulated Bcl-2 and Bcl-xL expression. In addition, inhibitors of caspase-8 and caspase-9 (Z-IETD-FMK and Z-LEHD-FMK, respectively) did not fully inhibit mitomycin C-induced apoptosis. Furthermore, mitomycin C induced endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78, CAAT/enhancer-binding protein homologous protein (CHOP) and caspase-4 in a dose-dependent manner. Salubrinal significantly inhibited the mitomycin C-induced cell viability loss and apoptosis, and these effects were accompanied by a reduction in CHOP expression. Our results support the hypothesis that mitomycin C induces human epidural scar fibroblast apoptosis, at least in part, via the endoplasmic reticulum stress pathway.

20.
J Spinal Cord Med ; 39(6): 679-685, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27858587

RESUMO

OBJECTIVE: Intradural nerve anastomosis for bladder innervation has been demonstrated to be useful. However, its clinical application remains limited because of the complex surgery, its complications and extensive bony destruction. The purpose of the current study was to demonstrate the feasibility of extradural spinal root anastomosis for bladder innervation in canines. METHODS: Ten beagle dogs were used. The length of the extradural segment of the nerve root, upper nerve root outlet (the point at which it emerges from the spinal dura mater) to S2 (dS2), the S3 (dS3) nerve root outlet distance, and the diameters of the extradural spinal roots were measured. The numbers of nerve fibers from L6 to S3 ventral roots were calculated using immunohistochemical staining. RESULTS: The extradural spinal roots could be divided into a ventral root (VR) and a dorsal root (DR) before the ganglionic enlargement of the dorsal root, and the extradural motor nerve roots situate ventrally to their corresponding sensory nerve roots. The extradural nerve root lengths of S1 and parts of L7 were longer than the corresponding dS2. The numbers of nerve and motor nerve fibers, and the diameters of extradural nerve roots, were gradually descending from L6 to S3. CONCLUSION: The S1 VRs and parts of the L7 VRs can be extradurally anastomosed to the S2 nerves without tension. A nerve graft was needed for extradural anastomosis of L6 VRs and parts of L7 VRs to S2 VRs. This study demonstrated the feasibility of extradural spinal nerve anastomosis for treating neurogenic bladder in canines.


Assuntos
Procedimentos Neurocirúrgicos/métodos , Traumatismos da Medula Espinal/complicações , Raízes Nervosas Espinhais/cirurgia , Bexiga Urinaria Neurogênica/cirurgia , Bexiga Urinária/inervação , Animais , Cães , Estudos de Viabilidade , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Bexiga Urinaria Neurogênica/etiologia
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