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1.
BMC Musculoskelet Disord ; 25(1): 445, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844933

RESUMEN

BACKGROUND: T2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI. METHODS: A total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations. RESULTS: A total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p<0.001). At short-term follow-up, the combined group presented a higher JOARR than the posterior group (posterior group: 50.7%±46.6%, combined group: 70.4%±20.3%, p = 0.024), while no significant difference in JOARR was observed between the groups at long-term follow-up (posterior group: 49.2%±48.5%, combined group: 59.6%±47.6%, p = 0.136). No significant difference was found in the overall complication and reoperation rates. CONCLUSIONS: For MDCM patients with ISI, both posterior and one-stage posteroanterior approaches could achieve considerable neurological alleviations in short-term and long-term follow-up. With greater surgical trauma, the combined group presented better short-term JOARR but did not show higher efficacy in long-term neurological function preservation in patients with comparable preoperative conditions.


Asunto(s)
Vértebras Cervicales , Descompresión Quirúrgica , Puntaje de Propensión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Estudios Retrospectivos , Anciano , Estudios de Seguimiento , Resultado del Tratamiento , Descompresión Quirúrgica/métodos , Imagen por Resonancia Magnética , Enfermedades de la Médula Espinal/cirugía , Enfermedades de la Médula Espinal/diagnóstico por imagen , Recuperación de la Función , Evaluación de la Discapacidad
2.
Mol Biol Rep ; 48(1): 595-600, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33394235

RESUMEN

We previously reported that Numb, a protein localized to clathrin-coated vesicles, regulates the membrane expression of metabotropic glutamate receptor 5 (mGluR5) and is critical to social behaviors. However, the distinct actions of Numb isoforms on mGluR5 have not been investigated. Here, we showed that the expression patterns of Numb-p72 and Numb-p65, two important isoforms of Numb, were distinct in HEK293T cells. Numb-p72, but not Numb-p65, bound to mGluR5α, and enhanced mGluR5 membrane expression by inhibiting its internalization. Our results suggest that a complete structure is required for Numb to bind to mGluR5 and to modulate mGluR5 trafficking.


Asunto(s)
Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Transporte de Proteínas/genética , Receptor del Glutamato Metabotropico 5/genética , Movimiento Celular/genética , Células HEK293 , Hipocampo/metabolismo , Humanos , Neuronas/metabolismo , Unión Proteica/genética , Isoformas de Proteínas/genética
3.
Rev Cardiovasc Med ; 25(9): 347, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39355579

RESUMEN

Background: Thoracic aortic endovascular repair (TEVAR) is the primary treatment for Stanford type B aortic dissection (type B AD). However, patients often encounter significant difficulties post-TEVAR that endanger their safety when transitioning from hospital- to home-based care. Moreover, information on the ideal transitional care for patients with type B AD post-TEVAR is scarce in China. This single-masked randomized clinical trial aimed to assess the effectiveness of the Assess, Advise, Agree, Assist, and Arrange (5As) model-based transitional care in improving discharge preparation level and transitional care quality post-TEVAR among patients with type B AD in China. Methods: This study was conducted at a hospital in China between January 2021 and October 2021. Patients with type B AD were randomly divided into intervention and control groups. Participants in the intervention group received the 5As model-based transitional nursing care. The 5As model is an evidence-based intervention strategy comprising: (1) Assess: assessing the preoperative cardiovascular risk behavior of patients with AD. (2) Advise: making suggestions according to the risk behaviors of the patients. (3) Agree: reaching a consensus on goals and action plans by making decisions with the patients and their families. (4) Assist: assisting patients in solving obstacles to implementing health plans. (5) Arrange: arranging follow-up visits according to the actual situation of the patients and guiding them in adhering to a schedule. The control group received the usual nursing care for the same duration and number of follow-up visits. A trained research nurse collected all the baseline data of the patients on admission, assessed discharge readiness level (using the Readiness for Hospital Discharge Scale) on the day of discharge, and collected transitional quality of care (by the Care Transition Measure-15) data on day 30 after discharge. Results: Overall, 72 patients with type B AD were recruited. Discharge readiness level and transitional care quality in the intervention group were significantly superior to those in the control group. Conclusions: This study showed that the 5As model-based transitional care program can effectively promote discharge readiness and transitional care quality of patients with type B AD post-TEVAR. Clinical Trial Registration: The Chinese Clinical Trial Registry Center: ChiCTR2200060797 (https://www.chictr.org.cn/showproj.html?proj=167403).

4.
Global Spine J ; : 21925682241265878, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39030762

RESUMEN

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: This study aimed to investigate the long-term outcomes of laminoplasty-alone (LP) and combined procedure (CP), consisting of laminoplasty and single-level anterior cervical discectomy and fusion, in comparable patients who had multilevel degenerative cervical myelopathy (MDCM) with concomitant anterior and posterior compression (CAPC). METHODS: Consecutive MDCM patients with CAPC underwent LP or CP between 2012 and 2015 from a same surgical group were enrolled and followed up for a minimum of 8 years. Preoperative demographic, radiological, and clinical variables were collected. Propensity score matching (PSM) analysis was performed to match patients with comparable conditions. The outcomes were evaluated by postoperative Japanese Orthopedic Association (JOA) score improvement, JOA recovery rate (JOARR) and complications. RESULTS: A total of 230 patients were included, of whom 146 underwent LP and 84 underwent CP. After PSM, 84 pairs of comparable patients were matched. The matched groups presented fair comparability in preoperative conditions. The CP group had significantly prolonged surgery time and greater blood loss. At the final follow-up, the postoperative JOA scores of LP and CP groups were 14.51 ± 1.79 and 15.47 ± 1.81 (P < 0.001) and the JOARR were 42.5% ± 53.3% and 68.5% ± 35.4%, respectively (P < 0.001). Three (3.6%) patients in the LP group underwent reoperations because of recurrent symptoms (P = 0.081). CONCLUSION: Both LP and CP demonstrated considerable long-term neurological recovery in patients with CAPC. The CP showed a significantly higher JOA improvement and JOARR. The combined decompression might be a safe and effective alternative in treating MDCM with CAPC in experienced hands.

5.
World J Orthop ; 15(6): 593-601, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38947265

RESUMEN

BACKGROUND: Mazabraud's syndrome (MS) is a rare and slowly progressive benign disease characterized by the concurrent presence of fibrous dysplasia of bone and intramuscular myxoma, and is thought to be associated with mutations of the GNAS gene. To date, only about 100 cases of MS have been reported in the literature, but its standard treatment strategy remains unclear. CASE SUMMARY: We report two cases of MS in young women who underwent different treatments based on their symptoms and disease manifestations. The first patient, aged 37, received internal fixation and intravenous bisphosphonate for a pathological fracture of the right femoral neck, excision of a right vastus medialis myxoma was subsequently performed for pain control, and asymptomatic psoas myxomas were monitored without surgery. Genetic testing confirmed a GNAS gene mutation in this patient. The second patient, aged 24, underwent right vastus intermedius muscle myxoma resection, and conservative treatment for fibrous dysplasia of the ilium. These patients were followed-up for 17 months and 3 years, respectively, and are now in a stable condition. CONCLUSION: Various treatments have been selected for MS patients who suffer different symptoms. The main treatment for myxomas is surgical resection, while fibrous dysplasia is selectively treated if the patient experiences pathological fracture or severe pain. However, given the documented instances of malignant transformation of fibrous dysplasia in individuals with MS, close follow-up is necessary.

6.
J Clin Med ; 12(4)2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36836078

RESUMEN

(1) Background: Topical non-steroidal anti-inflammatory drugs (NSAIDs) are one of the primary drugs for treating musculoskeletal pain. However, there are currently no evidence-based recommendations about drug selection, drug administration, drug interactions, and use in special populations or other pharmacology-related content of such medications. To this end, the Chinese Pharmaceutical Association Hospital Pharmacy Professional Committee developed multidisciplinary guidelines on using topical NSAIDs to treat musculoskeletal pain. (2) Methods: The guidelines development process followed the World Health Organization guideline development handbook, the GRADE methodology, and the statement of Reporting Items for Practice Guidelines in Healthcare. The guideline panel used the Delphi method to identify six clinical questions to be addressed in the guidelines. An independent systematic review team conducted a systematic search and integration of evidence. (3) Results: Based on the balance between the benefits and harms of an intervention, the quality of the evidence, patient preferences and values, and resource utilization, the guideline panel developed 11 recommendations and nine expert consensuses on using topical NSAIDs to treat acute and chronic musculoskeletal pain. (4) Conclusions: Based on the effectiveness and overall safety of topical NSAIDs, we recommend patients with musculoskeletal pain use topical NSAIDs and suggest high-risk patients use topical NSAIDs, such as those with other diseases or receiving other concurrent treatments. The evidenced-based guidelines on topical NSAIDs for musculoskeletal pain incorporated a pharmacist perspective. The guidelines have the potential to facilitate the rational use of topical NSAIDs. The guideline panel will monitor the relevant evidence and update the recommendations accordingly.

7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(7): 817-821, 2022 Jul 15.
Artículo en Zh | MEDLINE | ID: mdl-35848176

RESUMEN

Objective: To investigate the effectiveness of three-dimensional (3D) printed total scapula for reverse shoulder arthroplasty in the treatment of scapular tumors. Methods: Between November 2017 and December 2021, 5 patients with scapular tumors were treated by reverse shoulder arthroplasty with 3D printed total scapula. There was 1 male and 4 females. The age ranged from 44 to 59 years, with an average of 50.4 years. There were 2 cases of chondro sarcoma, 1 case of high-grade osteosarcoma, 1 case of lung cancer with scapular metastasis, and 1 case of ligamentoid fibromatosis recurrence. The disease duration was 4-8 months, with an average of 5.8 months. According to the Musculoskeletal Tumor Society (MSTS) scapular girdle classification criteria, 4 cases of tumors involved both S1 and S2 zones, and 1 case involved S2 zone. The tumor diameters ranged from 4.2 to 11.2 cm, with an average of 6.1 cm. The operation time, intraoperative blood loss, and blood transfusion were recorded. During follow-up, the MSTS score was used to evaluate the recovery of limb function of the patients. The sink depth of the affected shoulder, complications, and oncological outcomes were observed. The position of the prosthesis was reviewed by imaging. Results: The operation time ranged from 155 to 230 minutes, with an average of 189 minutes. The intraoperative blood loss was 100-1 500 mL, with a median of 600 mL. Two patients were received blood transfusion of 800 mL and 1 850 mL respectively during operation. All incisions healed by first intention, and no complications such as infection occurred. All patients were followed up 4-22 months, with an average of 13 months. Two patients died at 8 and 15 months after operation respectively due to multiple metastases and organ failure. At last follow-up, the MSTS score of all patients was 73%-83%, with an average of 77.4%. The affected shoulder was 2-4 cm lower than the contralateral side, with an average of 3 cm. Imaging examinations showed that no prosthesis loosening, dislocation, or fracture occurred during follow-up. Conclusion: Reverse shoulder arthroplasty with 3D printed total scapula can obtain good shoulder function and appearance. Patients have high acceptance and satisfaction with this surgical method.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Neoplasias Óseas , Impresión Tridimensional , Escápula , Adulto , Artroplastia , Pérdida de Sangre Quirúrgica , Neoplasias Óseas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Escápula/patología , Escápula/cirugía , Articulación del Hombro/cirugía , Resultado del Tratamiento
8.
Oncoimmunology ; 11(1): 2024941, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35036076

RESUMEN

The poor progress of immunotherapy on osteosarcoma patients requires deeper delineation of immune tolerance mechanisms in the osteosarcoma microenvironment and a new therapeutic strategy. Clearance of apoptotic cells by phagocytes, a process termed "efferocytosis," is ubiquitous in tumors and mediates the suppression of innate immune inflammatory response. Considering the massive infiltrated macrophages in osteosarcoma, efferocytosis probably serves as a potential target, but is rarely studied in osteosarcoma. Here, we verified M2 polarization and PD-L1 expression of macrophages following efferocytosis. Pharmacological inhibition and genetic knockdown were used to explore the underlying pathway. Moreover, tumor progression and immune landscape were evaluated following inhibition of efferocytosis in osteosarcoma model. Our study indicated that efferocytosis promoted PD-L1 expression and M2 polarization of macrophages. Ëfferocytosis was mediated by MerTK receptor in osteosarcoma and regulated the phenotypes of macrophages through the p38/STAT3 pathway. By establishing the murine osteosarcoma model, we emphasized that inhibition of MerTK suppressed tumor growth and enhanced the T cell cytotoxic function by increasing the infiltration of CD8+ T cells and decreasing their exhaustion. Our findings demonstrate that MerTK-mediated efferocytosis promotes osteosarcoma progression by enhancing M2 polarization of macrophages and PD-L1-induced immune tolerance, which were regulated through the p38/STAT3 pathway.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Animales , Antígeno B7-H1/genética , Neoplasias Óseas/genética , Linfocitos T CD8-positivos , Humanos , Tolerancia Inmunológica , Ratones , Osteosarcoma/genética , Microambiente Tumoral , Tirosina Quinasa c-Mer
9.
Elife ; 112022 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-35138249

RESUMEN

Dynamic microtubules play a critical role in cell structure and function. In nervous system, microtubules are the major route for cargo protein trafficking and they specially extend into and out of synapses to regulate synaptic development and plasticity. However, the detailed depolymerization mechanism that regulates dynamic microtubules in synapses and dendrites is still unclear. In this study, we find that KIF2C, a dynamic microtubule depolymerization protein without known function in the nervous system, plays a pivotal role in the structural and functional plasticity of synapses and regulates cognitive function in mice. Through its microtubule depolymerization capability, KIF2C regulates microtubule dynamics in dendrites, and regulates microtubule invasion of spines in neurons in a neuronal activity-dependent manner. Using RNAi knockdown and conditional knockout approaches, we showed that KIF2C regulates spine morphology and synaptic membrane expression of AMPA receptors. Moreover, KIF2C deficiency leads to impaired excitatory transmission, long-term potentiation, and altered cognitive behaviors in mice. Collectively, our study explores a novel function of KIF2C in the nervous system and provides an important regulatory mechanism on how activity-dependent microtubule dynamic regulates synaptic plasticity and cognition behaviors.


Asunto(s)
Cinesinas/metabolismo , Microtúbulos/metabolismo , Plasticidad Neuronal/genética , Receptores AMPA/metabolismo , Sinapsis/metabolismo , Animales , Cognición , Femenino , Células HEK293 , Humanos , Cinesinas/genética , Potenciación a Largo Plazo , Masculino , Ratones , Ratones Endogámicos C57BL , Microtúbulos/genética , Neuronas/metabolismo , Transporte de Proteínas
10.
Int J Surg ; 101: 106630, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35452847

RESUMEN

BACKGROUND: Tumor resection and prosthetic replacement have become the treatments of choice for malignant bone tumors. Infections are the leading cause of failure of limb salvage surgeries. Therefore, treating infections around prostheses after limb salvage is essential and challenging. Our research team designed a "domino" sequential treatment plan to treat postoperative infections around tumor prostheses and evaluated its efficacy. PURPOSE: To introduce the new domino sequential treatment plan for postoperative infections of tumor prostheses, and evaluate the technical points of the plan and prognosis in medium- and long-term follow-ups. METHODS: Between January 2015 and August 2021, 14 patients were treated with prosthesis-preserving domino sequential therapy for peripheral prosthesis infections after bone-tumor limb salvage. The sample included eight cases of distal femur tumor, two of proximal tibia tumor, three of pelvic tumor, and one of middle femur tumor. We evaluated routine blood test results, C-reactive protein level, the erythrocyte sedimentation rate, and other indicators. X-rays and CT scans of the surgical site were obtained and the Musculoskeletal Tumor Society (MSTS) score was calculated. Treatment involved debridement and lavage of the prosthesis, and systemic and local antibiotics. RESULTS: The positivity rate of microbial culture was 78.6%. There were three cases of Staphylococcus aureus, one of Staphylococcus epidermidis, two of methicillin-resistant Staphylococcus epidermidis, one of methicillin-resistant Staphylococcus aureus, two of Acinetobacter baumannii, one of Streptococcus lactis (group C), one of Streptococcus mitis, and three with negative cultures. In three cases, sequential treatment failed to control the infection. The operation success rate was 78.6% (11/14). One case eventually required amputation, and another required long-term wound dressings. To control the infection, a third had to be treated using antibiotic bone cement combined with the "intramedullary nail reverse double insertion" technique. The MSTS scores of patients before infection debridement and at the last follow-up showed statistically significant differences (t = 5.312, p = 0.02). CONCLUSIONS: The prosthesis-preserving domino sequential method has certain advantages for treating bone-tumor limb salvage infections around the prosthesis. LEVEL OF EVIDENCE: Level IV, therapeutic.


Asunto(s)
Miembros Artificiales , Neoplasias Óseas , Staphylococcus aureus Resistente a Meticilina , Neoplasias Óseas/cirugía , Humanos , Recuperación del Miembro , Estudios Retrospectivos , Resultado del Tratamiento
11.
World J Clin Cases ; 9(2): 379-388, 2021 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-33521105

RESUMEN

BACKGROUND: Spinal metastases are common in patients with malignancies, but studies on those metastasized from unknown primaries are scarce due to the difficulty in treatment and the relatively poor prognosis. Knowledge of surgical complications, particularly perioperative mortality, in patients with spinal metastases from unidentified sources is still insufficient. CASE SUMMARY: A 54-year-old man with chest-back pain was diagnosed with spinal metastasis in the seventh thoracic vertebra (T7). Radiographic examinations, as well as needle biopsy and immunohistochemical tests were performed to verify the characteristics of the lesion, resulting in an inconclusive diagnosis of poorly differentiated cancer from an unknown primary lesion. Therefore, spinal surgery was performed using the posterior approach to relieve symptoms and verify the diagnosis. Postoperative histologic examination indicated that this poorly differentiated metastatic cancer was possibly sarcomatoid carcinoma. As the patient experienced unexpectedly fast progression of the disease and died 16 d after surgery, the origin of this metastasis was undetermined. We discuss this case with respect to reported perioperative mortality in similar cases. CONCLUSION: A comprehensive assessment prior to surgical decision-making is essential to reduce perioperative mortality risk in patients with spinal metastases from an unknown origin.

12.
Mol Med Rep ; 23(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33236155

RESUMEN

Matrix metalloproteinase 2 (MMP2) is a well­characterized protein that is indispensable for extracellular matrix remodeling and other pathological processes, such as tumor progression and skeletal dysplasia. Excessive activation of MMP2 promotes osteolytic metastasis and bone destruction in late­stage cancers, while its loss­of­function mutations result in the decreased bone mineralization and generalized osteolysis occurring progressively in skeletal developmental disorders, particularly in multicentric osteolysis, nodulosis and arthropathy (MONA). Either upregulation or downregulation of MMP2 activity can result in the same osteolytic effects. Thus, different functions of MMP2 have been recently identified that could explain this observation. While MMP2 can degrade bone matrix, facilitate osteoclastogenesis and amplify various signaling pathways that enhance osteolysis in bone metastasis, its role in maintaining the number of bone cells, supporting osteocytic canalicular network formation and suppressing leptin­mediated inhibition of bone formation has been implicated in osteolytic disorders caused by MMP2 deficiency. Furthermore, the proangiogenic activity of MMP2 is one of the potential mechanisms that are associated with both pathological situations. In the present article, the latest research on MMP2 in bone homeostasis is reviewed and the mechanisms underlying the role of this protein in skeletal metastasis and developmental osteolysis are discussed.


Asunto(s)
Neoplasias Óseas , Huesos , Metaloproteinasa 2 de la Matriz , Proteínas de Neoplasias , Osteocondrodisplasias , Osteólisis , Animales , Neoplasias Óseas/enzimología , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Huesos/enzimología , Huesos/patología , Humanos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Osteocondrodisplasias/enzimología , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Osteólisis/enzimología , Osteólisis/genética , Osteólisis/patología
13.
Front Oncol ; 11: 722916, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34386431

RESUMEN

Tumor microenvironment (TME) formation is a major cause of immunosuppression. The TME consists of a considerable number of macrophages and stromal cells that have been identified in multiple tumor types. CCL2 is the strongest chemoattractant involved in macrophage recruitment and a powerful initiator of inflammation. Evidence indicates that CCL2 can attract other host cells in the TME and direct their differentiation in cooperation with other cytokines. Overall, CCL2 has an unfavorable effect on prognosis in tumor patients because of the accumulation of immunosuppressive cell subtypes. However, there is also evidence demonstrating that CCL2 enhances the anti-tumor capability of specific cell types such as inflammatory monocytes and neutrophils. The inflammation state of the tumor seems to have a bi-lateral role in tumor progression. Here, we review works focusing on the interactions between cancer cells and host cells, and on the biological role of CCL2 in these processes.

14.
Int Immunopharmacol ; 73: 203-211, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31103876

RESUMEN

The overproduction of proteolytic enzymes and dysregulation of extracellular matrix (ECM) metabolism have been shown to accelerate the degradation process of articular cartilage. The purpose of this study was to investigate the role of KIAA1199 and its association with the pathophysiology of osteoarthritis (OA). We found that the expression of KIAA1199 was significantly upregulated in OA cartilage compared with normal tissues. Serum levels of KIAA1199 were higher in OA patients than in non-OA patients. Furthermore, knockdown of KIAA1199 inhibited interleukin-1 beta (IL-1ß)-induced ECM metabolic imbalance by regulating the expression of A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 5; matrix metallopeptidase-13; aggrecan; and COL2A1. In addition, silencing of KIAA1199 significantly decreased the expression of inflammatory mediators such as prostaglandin E2, IL-6, and TNF-α. Mechanistic analyses further revealed that IL-1ß-induced activation of the Wnt/ß-catenin pathway was suppressed during KIAA1199 knockdown. Moreover, KIAA1199 expression was also upregulated in an in vivo rat OA model. Together, these results increase our understanding of the emerging role of KIAA1199 in the process of OA degeneration, and may lead to a novel molecular target to prevent cartilage degradation.


Asunto(s)
Cartílago Articular/metabolismo , Condrocitos/metabolismo , Hialuronoglucosaminidasa/metabolismo , Interleucina-1beta , Osteoartritis/metabolismo , Vía de Señalización Wnt , Animales , Células Cultivadas , Técnicas de Silenciamiento del Gen , Humanos , Hialuronoglucosaminidasa/sangre , Hialuronoglucosaminidasa/genética , Masculino , Ratas Sprague-Dawley , Regulación hacia Arriba
15.
Front Cell Neurosci ; 13: 518, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31849609

RESUMEN

Neuroligins (NLs) are a group of postsynaptic cell adhesion molecules that function in synaptogenesis and synaptic transmission. Genetic defects in neuroligin 3 (NL3), a member of the NL protein family, are associated with autism. Studies in rodents have revealed that mutations of NL3 gene lead to increased growth and complexity in dendrites in the central nervous system. However, the detailed mechanism is still unclear. In our study, we found that deficiency of NL3 led to morphological changes of the pyramidal neurons in layer II/III somatosensory cortex in mice, including enlarged somata, elongated dendritic length, and increased dendritic complexity. Knockdown of NL3 in cultured rat neurons upregulated Akt/mTOR signaling, resulting in both increased protein synthesis and dendritic growth. Treating neurons with either rapamycin to inhibit the mTOR or LY294002 to inhibit the PI3K/Akt activity rescued the morphological abnormalities resulting from either NL3 knockdown or knockout (KO). In addition, we found that the hyperactivated Akt/mTOR signaling associated with NL3 defects was mediated by a reduction in phosphatase and tensin (PTEN) expression, and that MAGI-2, a scaffold protein, interacted with both NL3 and PTEN and could be a linker between NL3 and Akt/mTOR signaling pathway. In conclusion, our results suggest that NL3 regulates neuronal morphology, especially dendritic outgrowth, by modulating the PTEN/Akt/mTOR signaling pathway, probably via MAGI-2. Thereby, this study provides a new link between NL3 and neuronal morphology.

17.
PLoS One ; 10(10): e0140031, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26460488

RESUMEN

OBJECTIVE: The optimal surgical treatment for multilevel cervical spondylotic myelopathy (MCSM) remains controversial. This study compared the outcomes of three surgical approaches for MSCM treatment, focusing on the efficacy and safety of a combined approach. METHODS: This retrospective study included 153 consecutive MCSM patients (100 men, 53 women; mean age ± standard deviation, 55.7 ± 9.4 years) undergoing operations involving ≥3 intervertebral segments. The patients were divided into three groups according to surgical approach: anterior (n = 19), posterior (n = 76), and combined (n = 58). We assessed demographic variables, perioperative parameters, and clinical outcomes ≥12 months after surgery (20.5 ± 7.6 months), including Japanese Orthopaedic Association (JOA) score, improvement, recovery rate, and complications. RESULTS: The anterior group had the most favorable preoperative conditions, including the highest preoperative JOA score (12.95 ± 1.86, p = 0.046). In contrast, the combined group had the highest occupancy ratio (48.0% ± 11.6%, p = 0.002). All groups showed significant neurological improvement at final follow-ups, with JOA recovery rates of 59.7%, 54.6%, and 68.9% in the anterior, posterior, and combined groups, respectively (p = 0.163). After multivariable adjustments, the groups did not have significantly different clinical outcomes (postoperative JOA score, p = 0.424; improvement, p = 0.424; recovery rate, p = 0.080). Further, subgroup analyses of patients with occupancy ratios ≥50% showed similar functional outcomes following the posterior and combined approaches. Overall complication rates did not differ significantly among the three approaches (p = 0.600). Occupancy ratios did not have a significant negative influence on postoperative recovery following the posterior approach. CONCLUSIONS: If applied appropriately, all three approaches are effective for treating MCSM. All three approaches had equivalent neurological outcomes, even in subgroups with high occupancy ratios. Further investigations of surgical approaches to MCSM are needed, particularly prospective multicenter studies with long-term follow-up.


Asunto(s)
Vértebras Cervicales/cirugía , Espondilosis/cirugía , Vértebras Cervicales/fisiopatología , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Cuidados Preoperatorios , Estudios Retrospectivos , Espondilosis/fisiopatología , Resultado del Tratamiento
18.
Sci Rep ; 3: 2842, 2013 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-24100262

RESUMEN

PICK1 (protein interacting with C-kinase 1) is a peripheral membrane protein with high expression in brain, testis, pancreas and other neuroendocrine tissues. Male Pick1 knockout mice are completely infertile, with a phenotype resembling the human disease globozoospermia. Since PICK1 is expressed in both testis and neuroendocrine tissues, infertility of Pick1 knockout mice may be due to either impaired neuroendocrine function or abnormal spermatogenesis. To distinguish these two possibilities, we restored PICK1's expression in the testis by seminiferous tubule microinjection of PICK1-containing lentivirus. By examining the testis-specific Pick1 transgenic mice, we found that PICK1's expression in testis rescued the spermatogenic abnormalities and male infertility in Pick1 knockout mice. Our results indicate that the infertility is caused by the lack of PICK1 in the testis rather than in other organs. In addition, we found that seminiferous tubule microinjection of lentivirus has a strong preference to produce testis-specific transgenic mice.


Asunto(s)
Proteínas Portadoras/genética , Infertilidad Masculina/genética , Proteínas Nucleares/genética , Testículo/metabolismo , Animales , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular , Expresión Génica , Orden Génico , Genes Reporteros , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Proteínas Fluorescentes Verdes/genética , Humanos , Lentivirus/genética , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , Microinyecciones , Proteínas Nucleares/metabolismo , Especificidad de Órganos/genética , Túbulos Seminíferos/metabolismo , Transducción Genética
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