Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
J Biol Chem ; 299(2): 102889, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36634847

RESUMEN

Osteoporosis is a chronic skeletal condition characterized by low bone mass and deteriorated microarchitecture of bone tissue and puts tens of millions of people at high risk of fractures. New therapeutic agents like i-bodies, a class of next-generation single-domain antibodies, are needed to overcome some limitations of conventional treatments. An i-body is a human immunoglobulin scaffold with two long binding loops that mimic the shape and position of those found in shark antibodies, the variable new antigen receptors of sharks. Its small size (∼12 kDa) and long binding loops provide access to drug targets, which are considered undruggable by traditional monoclonal antibodies. Here, we have successfully identified a human receptor activator of nuclear factor-κB ligand (RANKL) i-body, ADR3, which demonstrates a high binding affinity to human RANKL (hRANKL) with no adverse effect on the survival or proliferation of bone marrow-derived macrophages. Differential scanning fluorimetry suggested that ADR3 is stable and able to tolerate a wide range of physical environments (including both temperature and pH). In addition, in vitro studies showed a dose-dependent inhibitory effect of ADR3 on osteoclast differentiation, podosome belt formation, and bone resorption activity. Further investigation on the mechanism of action of ADR3 revealed that it can inhibit hRANKL-mediated signaling pathways, supporting the in vitro functional observations. These clues collectively indicate that hRANKL antagonist ADR3 attenuates osteoclast differentiation and bone resorption, with the potential to serve as a novel therapeutic to protect against bone loss.


Asunto(s)
Resorción Ósea , Osteoclastos , Ligando RANK , Anticuerpos de Dominio Único , Humanos , Resorción Ósea/genética , Resorción Ósea/metabolismo , Diferenciación Celular/genética , Macrófagos/citología , Macrófagos/metabolismo , Osteoclastos/citología , Ligando RANK/metabolismo , Transducción de Señal , Anticuerpos de Dominio Único/metabolismo
2.
Int Wound J ; 21(4): e14607, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38155433

RESUMEN

Surgical site infection (SSI) is one of the most common complications of posterior cervical surgery. It is difficult to diagnose in the early stage and may lead to severe consequences such as wound dehiscence and central nervous system infection. This retrospective study included patients who underwent posterior cervical surgery at The Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University from September 2018 to June 2022. We employed several machine learning methods, such as the gradient boosting (GB), random forests (RF), artificial neural network (ANN) and other popular machine learning models. To minimize the variability introduced by random splitting, the results underwent 10-fold cross-validation repeated 10 times. Five measurements were averaged across 10 repetitions with 10-fold cross-validation, the RF model achieved the highest AUROC (0.9916), specificity (0.9890) and precision (0.9759). The GB model achieved the highest sensitivity (0.9535) and the KNN achieved the highest sensitivity (0.9958). The application of machine learning techniques facilitated the development of a precise model for predicting SSI after posterior cervical surgery. This dynamic model can be served as a valuable tool for clinicians and patients to assess SSI risk and prevent it in clinical practice.


Asunto(s)
Aprendizaje Automático , Infección de la Herida Quirúrgica , Niño , Humanos , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/etiología , Estudios Retrospectivos , Proyectos de Investigación
3.
J Cell Physiol ; 236(6): 4369-4386, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33164235

RESUMEN

The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H2 S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H2 S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H2 S in the pathogenesis of OA and its protective effects on interleukin (IL)-1ß-induced chondrocytes were identified. Our data revealed decreased H2 S expression in both human degenerative OA cartilage tissue and IL-1ß-induced chondrocytes. Pretreatment with the H2 S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1ß-induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway-mediated inhibition of nuclear factor kappa B (NF-κB). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1ß-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1ß-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H2 S may antagonize IL-1ß-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.


Asunto(s)
Antirreumáticos/farmacología , Apoptosis/efectos de los fármacos , Condrocitos/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , Mediadores de Inflamación/metabolismo , Interleucina-1beta/toxicidad , Articulaciones/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Osteoartritis/tratamiento farmacológico , Sulfuros/farmacología , Anciano , Animales , Antirreumáticos/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Condrocitos/inmunología , Condrocitos/metabolismo , Condrocitos/patología , Modelos Animales de Enfermedad , Femenino , Humanos , Sulfuro de Hidrógeno/metabolismo , Articulaciones/inmunología , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Mitocondrias/inmunología , Mitocondrias/metabolismo , Mitocondrias/patología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Osteoartritis/inmunología , Osteoartritis/metabolismo , Osteoartritis/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Sulfuros/metabolismo
4.
Phytother Res ; 35(10): 5754-5766, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34431562

RESUMEN

Spinal cord injury (SCI) is a devastating neurological occurrence that usually leads to a loss of motor and sensory function in patients. Axon regeneration has been reported to be crucial for recovery after trauma to the nervous system. Morin, a natural bioflavonoid obtained from the Moraceae family, has previously been reported to exert neuroprotective effects. In our study, we investigated the protective effects of morin on PC12 cells and primary neurons treated with oxygen-glucose deprivation (OGD) and its function in an SCI model. In vitro experiments showed that treating neuronal cells with morin enhanced axonal regeneration after OGD treatment by regulating microtubule stabilization and protecting mitochondrial function. Mechanistically, morin protected neuronal cells exposed to OGD by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. An in vivo study illustrated that oral morin administration improved microtubule stability and promoted axon regeneration in SCI rats. Taken together, this study showed that treatment with morin improves functional recovery after SCI and that morin may serve as a potential agent for treating SCI.


Asunto(s)
Hemo-Oxigenasa 1 , Traumatismos de la Médula Espinal , Animales , Axones , Flavonoides/farmacología , Humanos , Factor 2 Relacionado con NF-E2 , Regeneración Nerviosa , Ratas , Ratas Sprague-Dawley , Médula Espinal , Traumatismos de la Médula Espinal/tratamiento farmacológico
5.
Phytother Res ; 35(10): 5694-5707, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34423505

RESUMEN

Morin is a natural compound isolated from moraceae family members and has been reported to possess a range of pharmacological activities. However, the effects of morin on bone-associated disorders and the potential mechanism remain unknown. In this study, we investigated the anti-osteoclastogenic effect of morin in vitro and the potential therapeutic effects on ovariectomy (OVX)-induced osteoporosis in vivo. In vitro, by using a bone marrow macrophage-derived osteoclast culture system, we determined that morin attenuated receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclast formation via the inhibition of the mitogen-activated protein kinase (MAPK), NF-κB and calcium pathways. In addition, the subsequent expression of nuclear factor of activated T cells c1 (NFATc1) and c-fos was significantly suppressed by morin. In addition, NFATc1 downregulation led to the reduced expression of osteoclastogenesis-related marker genes, such as V-ATPase-d2 and Integrin ß3. In vivo, results provided that morin could effectively attenuate OVX-induced bone loss in C57BL/6 mice. In conclusion, our results demonstrated that morin suppressed RANKL-induced osteoclastogenesis via the NF-κB, MAPK and calcium pathways, in addition, its function of preventing OVX-induced bone loss in vivo, which suggested that morin may be a potential therapeutic agent for postmenopausal osteoporosis treatment.


Asunto(s)
Resorción Ósea , Osteoclastos , Animales , Calcio , Diferenciación Celular , Femenino , Flavonoides , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos , FN-kappa B , Factores de Transcripción NFATC , Osteogénesis , Ligando RANK
6.
J Cell Mol Med ; 23(12): 8355-8368, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31603626

RESUMEN

Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti-inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, V-ATPase-d2 and integrin ß3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca2+ oscillations and the NF-κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.


Asunto(s)
Resorción Ósea/prevención & control , Flavonoles/farmacología , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ligando RANK/farmacología , Animales , Células Cultivadas , Medicamentos Herbarios Chinos/farmacología , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Integrina beta3/genética , Integrina beta3/metabolismo , Ratones , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Osteogénesis/genética , Ovariectomía , Fitoterapia/métodos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Células RAW 264.7 , Fosfatasa Ácida Tartratorresistente/genética , Fosfatasa Ácida Tartratorresistente/metabolismo
7.
J Cell Mol Med ; 23(1): 522-534, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30451360

RESUMEN

Postmenopausal osteoporosis (PMO) is a progressive bone disease characterized by the over-production and activation of osteoclasts in elderly women. In our study, we investigated the anti-osteoclastogenic effect of evodiamine (EVO) in vivo and in vitro, as well as the underlying mechanism. By using an in vitro bone marrow macrophage (BMM)-derived osteoclast culture system, we found that EVO inhibited osteoclast formation, hydroxyapatite resorption and receptor activator of NF-κB ligand (RANKL)-induced osteoclast marker gene and protein expression. Mechanistically, we found that EVO inhibited the degradation and RANKL-induced transcriptional activity of IκBα. RANKL-induced Ca2+ oscillations were also abrogated by EVO. In vivo, an ovariectomized (OVX) mouse model was established to mimic PMO, and OVX mice received oral administration of either EVO (10 mg/kg) or saline every other day. We found that EVO can attenuate bone loss in OVX mice by inhibiting osteoclastogenesis. Taken together, our findings suggest that EVO suppresses RANKL-induced osteoclastogenesis through NF-κB and calcium signalling pathways and has potential value as a therapeutic agent for PMO.

8.
J Cell Mol Med ; 23(5): 3214-3223, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30809946

RESUMEN

The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. For the irreversibility of primary injury, therapies of SCI mainly focus on secondary injury, whereas inflammation is considered to be a major target for secondary injury; however the regulation of inflammation in SCI is unclear and targeted therapies are still lacking. In this study, we found that the expression of BRD4 was correlated with pro-inflammatory cytokines after SCI in rats; in vitro study in microglia showed that BRD4 inhibition either by lentivirus or JQ1 may both suppress the MAPK and NF-κB signalling pathways, which are the two major signalling pathways involved in inflammatory response in microglia. BRD4 inhibition by JQ1 not only blocked microglial M1 polarization, but also repressed the level of pro-inflammatory cytokines in microglia in vitro and in vivo. Furthermore, BRD4 inhibition by JQ1 can improve functional recovery and structural disorder as well as reduce neuron loss in SCI rats. Overall, this study illustrates that microglial BRD4 level is increased after SCI and BRD4 inhibition is able to suppress M1 polarization and pro-inflammatory cytokine production in microglia which ultimately promotes functional recovery after SCI.


Asunto(s)
Azepinas/farmacología , Inflamación/tratamiento farmacológico , Proteínas Nucleares/genética , Traumatismos de la Médula Espinal/tratamiento farmacológico , Factores de Transcripción/genética , Triazoles/farmacología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/genética , Inflamación/fisiopatología , MAP Quinasa Quinasa 1/genética , Microglía/efectos de los fármacos , Microglía/patología , FN-kappa B , Proteínas Nucleares/antagonistas & inhibidores , Ratas , Recuperación de la Función/genética , Transducción de Señal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patología , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/fisiopatología , Factores de Transcripción/antagonistas & inhibidores
9.
J Cell Mol Med ; 23(1): 380-394, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30338925

RESUMEN

Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti-inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, ATP6V0D2/V-ATPase-d2, and integrin ß3). Furthermore, we examined the underlying mechanisms and found that MA represses osteoclastogenesis by blocking Ca2+ oscillations and the NF-κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, MA might be a potential candidate for treating osteolytic bone diseases.


Asunto(s)
Estrógenos/metabolismo , Osteogénesis/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Ligando RANK/metabolismo , Triterpenos/farmacología , Animales , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Línea Celular , Centella , Femenino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoporosis/metabolismo , Extractos Vegetales , Proteínas Proto-Oncogénicas c-fos/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Fosfatasa Ácida Tartratorresistente/metabolismo
10.
J Cell Mol Med ; 23(1): 177-193, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30353656

RESUMEN

Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose-dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3-methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX-527 suppressed melatonin-induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1-autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1-autophagy pathway regulation, which may help us better understand the association between melatonin and IDD.


Asunto(s)
Calcinosis/tratamiento farmacológico , Condrocitos/efectos de los fármacos , Melatonina/farmacología , Sirtuina 1/metabolismo , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Autofagia/fisiología , Calcinosis/metabolismo , Calcinosis/patología , Carbazoles/farmacología , Células Cultivadas , Condrocitos/patología , Modelos Animales de Enfermedad , Femenino , Degeneración del Disco Intervertebral/inducido químicamente , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Sirtuina 1/antagonistas & inhibidores , terc-Butilhidroperóxido/toxicidad
11.
Phytother Res ; 33(1): 107-116, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30346051

RESUMEN

Laminectomy has been widely considered one of the most common treatments for lumbar disorders. Epidural fibrosis (EF) is a common complication after laminectomy, causing recurrent postoperative pain. Schisandrin B (Sch.B), the active ingredient extracted from Schisandra chinensis Fructus, has been found to have potent antiproliferative and antifibrotic effects on several cells. This study aimed to investigate the effects of Sch.B on the prevention of postlaminectomy EF formation. In vitro, we studied the effects of Sch.B on transforming growth factor beta 1 (TGF-ß1)-induced proliferation and extracellular matrix (ECM) production of primary fibroblasts, as well as its underlying mechanism. We found that Sch.B not only inhibited the proliferation of fibroblasts but also reduced ECM production, including that of connective tissue growth factor, fibronectin, and type I collagen, in a dose-dependent manner. Mechanistically, we found that Sch.B suppressed TGF-ß1-stimulated activation of the Smad2/3 and mitogen-activated protein kinase pathways. Moreover, the in vivo study demonstrated that Sch.B treatment attenuated the progression of EF in a postlaminectomy rat model via reducing the cell number and ECM production of scar tissue. Taken together, these data suggested that Sch.B possesses great potential value as a preventative agent for EF.


Asunto(s)
Matriz Extracelular/metabolismo , Fibroblastos/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Laminectomía/métodos , Lignanos/uso terapéutico , Compuestos Policíclicos/uso terapéutico , Animales , Proliferación Celular , Ciclooctanos/farmacología , Ciclooctanos/uso terapéutico , Lignanos/farmacología , Masculino , Compuestos Policíclicos/farmacología , Ratas , Ratas Sprague-Dawley
12.
Chemistry ; 23(15): 3631-3636, 2017 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-27981644

RESUMEN

A series of phenanthroline-based ligands have been synthesised and their influence as bidentate nitrogen ligands in heteroleptic [Cu(P^P)(N^N)]+ photosensitisers in light-driven water reduction has been studied. In this noble-metal-free Cu-Fe-based photocatalytic water reduction system, the structural effects of the nitrogen ligands have been explored, including the steric and electronic effects of substituents at the 2,9- and 4,7-positions of phenanthroline. Ligands were prepared that led to increased hydrogen generation, with turnover numbers (TONCu ) of up to 1388 being observed. All the new complexes were electrochemically and photophysically characterised. We demonstrate for the first time that the presence of fluorine in nitrogen ligands increases the efficacy of copper complexes in photocatalytic hydrogen production.

13.
Pharmacol Res ; 117: 357-369, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28087442

RESUMEN

It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)-1ß, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL-1ß-induced apoptosis in nucleus pulposus (NP) cells. Here, we found that the expression levels of cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE), two key enzymes in the generation of H2S, were significantly decreased in human degenerate NP tissues as well as in IL-1ß-treated NP cells. NaHS (H2S donor) administration showed a protective effect by inhibiting the endoplasmic reticulum (ER) stress response and mitochondrial dysfunction induced by IL-1ß stimulation in vitro, the effect was related to activation of the PI3K/Akt and ERK1/2 signaling pathways. Suppression of these pathways by specific inhibitors, LY294002 and PD98059, partially reduced the protective effect of NaHS. Moreover, in the percutaneous needle puncture disc degeneration rat tail model, disc degeneration was partially reversed by NaHS administration. Taken together, our results suggest that H2S plays a protective role in IVDD and the underlying mechanism involves PI3K/Akt and ERK1/2 signaling pathways-mediated suppression of ER stress and mitochondrial dysfunction in IL-1ß-induced NP cells.


Asunto(s)
Estrés del Retículo Endoplásmico/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , Degeneración del Disco Intervertebral/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Enfermedades Mitocondriales/tratamiento farmacológico , Núcleo Pulposo/efectos de los fármacos , Sustancias Protectoras/farmacología , Adolescente , Adulto , Anciano , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Niño , Citocinas/metabolismo , Femenino , Humanos , Degeneración del Disco Intervertebral/metabolismo , Masculino , Persona de Mediana Edad , Mitocondrias/metabolismo , Enfermedades Mitocondriales/metabolismo , Núcleo Pulposo/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Adulto Joven
14.
Eur Spine J ; 26(5): 1454-1462, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27388020

RESUMEN

PURPOSES: To discuss whether radiologic parameters are closely related to posterior ligamentous complex (PLC) injury identified by magnetic resonance imaging (MRI). METHODS: One hundred and five thoracolumbar fracture (T11-L2) patients were retrospectively analyzed in the study. The patients were divided into different groups by the status of the PLC on MRI: intact, incompletely ruptured and ruptured. The radiographic parameters included the anterior edge-inferior endplate angle (AEIEA), the anterior edge displacement (AED), the Cobb angle (CA), the region angle (RA), the sagittal index (SI), local kyphosis (LK), the anterior/posterior vertebral height ratio (A/P ratio), the anterior vertebral height ratio (AVH ratio), and bony fragment in front of the fractured vertebra (BFOFV). T test, Pearson's Chi-square and multivariate logistic regression were calculated for the variables. RESULTS: Supraspinous ligament (SSL) rupture versus intact was not only associated with the occurrence of AEIEA <70°, LK >25° and BFOFV, but also with increased AED (9.89 ± 3.12 mm and 9.34 ± 3.36 mm, P = 0.034), RA (9.52 ± 3.93° versus 7.91 ± 3.99°, P = 0.042), and LK (23.98 ± 5.88° versus 15.55 ± 5.28°, P = 0.021). The indications for interspinous ligament (ISL) injury included AEIEA <75°, AEIEA <70° (P = 0.004 and P < 0.001, respectively), increased AED (P = 0.010), LK >25° (P = 0.024), AVH (P < 0.001), and BFOFV (P < 0.001). Multivariate logistic regression analysis revealed that AEIEA <70° and BFOFV were high risk factors for SSL rupture [standard partial regression coefficients (betas) were 0.439 and 0.408, P = 0.003 and 0.001, respectively] and ISL rupture (betas were 0.548 and 0.494, P = 0.028 and 0.001, respectively). Increased AED and LK >25° were also related to either ISL rupture (P = 0.035 and 0.001, respectively) or SSL rupture (P = 0.014 and 0.008, respectively). CONCLUSION: Our data may prove useful in a preliminary assessment of the PLC integrity based on plain radiographic imaging. We show that radiologic indications, such as AEIEA <70°, BFOFV, LK >25°, and increased AED, are correlated with ISL or SSL rupture, while RA, CA, SI, A/P ratio, and AVH ratio are not.


Asunto(s)
Ligamentos Longitudinales/diagnóstico por imagen , Ligamentos Longitudinales/lesiones , Vértebras Lumbares/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagen , Adulto , Femenino , Humanos , Vértebras Lumbares/lesiones , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vértebras Torácicas/lesiones , Adulto Joven
15.
Eur Spine J ; 26(1): 221-227, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27832363

RESUMEN

PURPOSE: The aim of this study was to develop a novel method for observing the morphology of the blood vessels in the rabbit endplate. METHODS: Twenty 6-month-old rabbits were used in this study. The blood vessels in the L5 endplate in Group A were injected with iohexol and Group B with barium sulfate. Group C was the control group with saline. To optimize the study, Group B was divided into two subgroups: Group B-1 was injected with 100% (w/v) barium sulfate and Group B-2 with 50% (w/v). After injection, the L4-L5 vertebral body was excised and the cranial endplate of L5 was scanned using a micro-CT scanner. Models of the vertebral endplate and vessels were reconstructed using the 3D reconstruction software (Mimics 16.0) by calculating a bone threshold value, and then merged these two models to create a superimposed model. RESULTS: The 3D vessel models could not be created in Groups A and C, but they were clearly visualized in Group B. In the 3D model, the blood vessels extended from the subchondral bone to the endplate, and the density of the blood vessels in the area of the nucleus pulposus (NP) was higher than in the annulus fibrosus. CONCLUSIONS: The results of this study suggest that the blood vessels in the rabbit endplate can be clearly observed by the method described using barium sulfate [the 50% (w/v) gave better results compared with the 100% (w/v)]. The information from the 3D vessel structure could provide essential data to help us understand the nutrient pathways within the vertebral endplate.


Asunto(s)
Disco Intervertebral/irrigación sanguínea , Vértebras Lumbares/irrigación sanguínea , Microtomografía por Rayos X , Animales , Medios de Contraste , Imagenología Tridimensional , Conejos
16.
Eur Spine J ; 25(12): 4199-4207, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27554355

RESUMEN

PURPOSE: To evaluate the feasibility of cortical bone trajectory (CBT) screws fixation via pedicle or pedicle rib unit in the cadaveric thoracic spine (T9-T12). METHODS: Computed tomography (CT) images of 100 patients are analyzed by multiplanar reconstruction. Ten cadaveric thoracic spines are used to insert 4.5 × 35.0 mm CBT screws at all levels from T9 to T12. RESULTS: Maximal screw length obtained by CT has a tendency to gradually increase from T9 (29.64 mm) to T12 (32.84 mm), and the difference reaches significant level at all levels except T9 versus T10 (P < 0.01). Maximal screw diameter increases from T9 (4.92 mm) to T12 (7.47 mm) and the difference reaches significant level among all levels (P < 0.01). Lateral angle increases from T9 (7.37°) to T12 (10.47°), and the difference reaches significant level among all levels except T11 versus T12. Cephalad angle from T9 to T12 are 19.03°, 22.10°, 25.62° and 27.50° (P < 0.01), respectively. The percentage of the inner and outer pedicle breakage are 2.5 and 22.5 %, respectively. The violation of lateral pedicle wall occurs at T9 and T10, especially for women at T9. CONCLUSIONS: Both radiographic and cadaveric studies establish the feasibility of CBT screws placement via pedicle or pedicle rib unit in the lower thoracic spine (T9-T12). Furthermore, our measurements are also useful for application of this technique.


Asunto(s)
Hueso Cortical/diagnóstico por imagen , Procedimientos Ortopédicos/métodos , Tornillos Pediculares , Vértebras Torácicas/cirugía , Adulto , Anciano , Cadáver , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Vértebras Torácicas/diagnóstico por imagen , Tomografía Computarizada por Rayos X
17.
Int Orthop ; 40(6): 1253-60, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27116190

RESUMEN

PURPOSE: Our aim was to evaluate the results of short-segment pedicle instrumentation with screw insertion in the fracture level and find factors predicting kyphosis recurrence in thoracolumbar burst fractures. METHODS: We retrospectively analysed 122 patients with thoracolumbar burst fracture who were divided into two groups: kyphosis recurrence and no kyphosis recurrence. Pre-operative radiographic data comprising Cobb angle (CA), regional angle, anterior vertebra height (AVH), upper intervertebral angle, vertebral wedge angle (VWA), pre-anteroposterior A/P approach, superior endplate fracture, load-sharing classification (LSC) score and clinical data including age, visual analogue scale (VAS) score, thoracolumbar injury classification and severity score were compared between groups. T test, Pearson's chi-square and multivariate logistic regression were calculated for variables. RESULTS: CA, VWA and AVH were significantly corrected after surgery. CA changed from 23.7 to 3.0 (p <0.001), VWA from 38.7 to 9.6 (p <0.001) and AVH from 48.8 % to 91.2 % (p <0.001). These parameters were well maintained during the follow-up period with a mild, tolerant loss of correction. Neurological function and pain were significantly improved without deterioration. Age, pre-A/P and pre-AVH < 50 % influenced kyphosis recurrence (p = 0.032, 0.026, 0.011, respectively). CONCLUSIONS: Short-segment pedicle instrumentation including the fractured vertebra was effective in treating thoracolumbar burst fractures. The loss of correction at follow-up after implant removal was associated with age, A/P ratio and anterior vertebral height < 50 %.


Asunto(s)
Tornillos Óseos/efectos adversos , Fijación Interna de Fracturas/métodos , Cifosis/cirugía , Vértebras Lumbares/cirugía , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Adulto , Anciano , Remoción de Dispositivos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo
18.
Front Cell Dev Biol ; 12: 1431566, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170917

RESUMEN

Lysosomes serve as catabolic centers and signaling hubs in cells, regulating a multitude of cellular processes such as intracellular environment homeostasis, macromolecule degradation, intracellular vesicle trafficking and autophagy. Alterations in lysosomal level and function are crucial for cellular adaptation to external stimuli, with lysosome dysfunction being implicated in the pathogenesis of numerous diseases. Osteoclasts (OCs), as multinucleated cells responsible for bone resorption and maintaining bone homeostasis, have a complex relationship with lysosomes that is not fully understood. Dysregulated function of OCs can disrupt bone homeostasis leading to the development of various bone disorders. The regulation of OC differentiation and bone resorption for the treatment of bone disease have received considerable attention in recent years, yet the role and regulation of lysosomes in OCs, as well as the potential therapeutic implications of intervening in lysosomal biologic behavior for the treatment of bone diseases, remain relatively understudied. This review aims to elucidate the mechanisms involved in lysosomal biogenesis and to discuss the functions of lysosomes in OCs, specifically in relation to differentiation, bone resorption, and autophagy. Finally, we explore the potential therapeutic implication of targeting lysosomes in the treatment of bone metabolic disorders.

19.
J Agric Food Chem ; 72(37): 20383-20395, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39238071

RESUMEN

Postmenopausal osteoporosis (PMOP) arises from the disruption in bone remodeling caused by estrogen deficiency, leading to a heightened susceptibility to osteoporotic fractures in aging women. Tetrahydroberberine (THB) is a chemical compound extracted from Corydalis yanhusuo, a member of the traditional Chinese medicine series "Zhejiang eight taste", possessing a variety of pharmacological functions such as lowering lipids and preventing muscle atrophy. However, the impact of THB on PMOP has not been systematically explored. In vitro experiments supported that THB suppresses osteoclast formation and resorption of bone concentration-dependently. Further experiments confirmed that these inhibitory effects of THB were related to inhibition on expressions of osteoclast-specific genes, the mitogen-activated protein kinase (MAPK) pathway, and the nuclear factor kappa-B (NF-κB) pathway and an increased apoptosis level in mature osteoclasts. Additionally, THB treatment mitigated the ovariectomy-induced bone loss and improved the skeletal microarchitecture in vivo. In conclusion, THB has such potential to improve the PMOP status.


Asunto(s)
Apoptosis , FN-kappa B , Osteoclastos , Osteogénesis , Ovariectomía , Ligando RANK , Animales , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Apoptosis/efectos de los fármacos , Femenino , Ligando RANK/metabolismo , Ligando RANK/genética , Ovariectomía/efectos adversos , Ratones , Osteogénesis/efectos de los fármacos , Humanos , FN-kappa B/metabolismo , FN-kappa B/genética , Osteoporosis Posmenopáusica/prevención & control , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/fisiopatología , Osteoporosis Posmenopáusica/genética , Osteoporosis Posmenopáusica/tratamiento farmacológico , Alcaloides de Berberina/farmacología , Ratones Endogámicos C57BL , Resorción Ósea/prevención & control , Resorción Ósea/tratamiento farmacológico , Células RAW 264.7
20.
Int J Biol Macromol ; 260(Pt 2): 129357, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38216011

RESUMEN

Osteoporosis is a prevalent systemic skeletal disorder, particularly affecting postmenopausal women, primarily due to excessive production and activation of osteoclasts. However, the current anti-osteoporotic drugs utilized in clinical practice may lead to certain side effects. Therefore, it is necessary to further unravel the potential mechanisms regulating the osteoclast differentiation and to identify novel targets for osteoporosis treatment. This study revealed the most significant decline in VSIG4 expression among the VSIG family members. VSIG4 overexpression significantly inhibited RANKL-induced osteoclastogenesis and bone resorption function. Mechanistically, both western blot and immunofluorescence assay results demonstrated that VSIG4 overexpression attenuated the expression of osteoclast marker genes and dampened the activation of MAPK and NF-κB signaling pathways. Furthermore, VSIG4 overexpression could inhibit the generation of reactive oxygen species (ROS) and stimulate the expression of Nrf2 along with its downstream antioxidant enzymes via interaction with Keap1. Notably, a potent Nrf2 inhibitor, ML385, could reverse the inhibitory effect of VSIG4 on osteoclast differentiation. In line with these findings, VSIG4 overexpression also mitigated bone loss induced by OVX and attenuated the activation of osteoclasts in vivo. In conclusion, our results suggest that VSIG4 holds promise as a novel target for addressing postmenopausal osteoporosis. This is achieved by suppressing osteoclast formation via enhancing Nrf2-dependent antioxidant response against reactive oxygen species production.


Asunto(s)
Osteogénesis , Osteoporosis , Femenino , Humanos , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Osteoclastos , FN-kappa B/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Diferenciación Celular , Receptores de Complemento/metabolismo , Receptores de Complemento/uso terapéutico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA