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1.
FASEB J ; 38(10): e23646, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38795328

RESUMO

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.


Assuntos
Autofagia Mediada por Chaperonas , Glicogênio Sintase Quinase 3 beta , Inflamação , Proteína 2 de Membrana Associada ao Lisossomo , Células-Tronco Mesenquimais , Osteogênese , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , beta Catenina , Animais , Osteogênese/fisiologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , beta Catenina/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/genética , Transdução de Sinais , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Diferenciação Celular , Osteoclastos/metabolismo
2.
Cell Tissue Res ; 396(2): 269-281, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38470494

RESUMO

Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-ß-catenin and phospho-GSK3ß (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3ß/ß-catenin signaling pathway.


Assuntos
Diferenciação Celular , Glicogênio Sintase Quinase 3 beta , Células-Tronco Mesenquimais , Osteogênese , beta Catenina , Animais , Camundongos , beta Catenina/metabolismo , Células da Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Transdução de Sinais
3.
Phys Chem Chem Phys ; 26(25): 17549-17560, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38884195

RESUMO

In this paper, we combine an energy decomposition analysis (EDA) scheme with many-body expansion (MBE) to develop a MB-EDA method to study the cooperative and anti-cooperative effects in molecular cluster systems. Based on the target state optimization self-consistent field (TSO-SCF) method, the intermolecular interaction energy can be decomposed into five chemically meaningful terms, i.e., electrostatic, exchange, polarization, charge transfer and dispersion interaction energies. MB-EDA can decompose each of these terms in MBE. This MB-EDA has been applied to 3 different cluster systems: water clusters, ionic liquid clusters, and acetonitrile-methane clusters. This reveals that electrostatic, exchange, and dispersion interactions are highly pairwise additive in all systems. In water and ionic liquid clusters, the many-body effects are significant in both polarization and charge transfer interactions, but are cooperative and anti-cooperative, respectively. For acetonitrile-methane clusters, which do not involve hydrogen bonds or charge-charge Coulombic interactions, the many-body effects are quite small. The chemical origins of different many-body effects are deeply analyzed. The MB-EDA method has been implemented in Qbics (https://qbics.info) and can be a useful tool for understanding the many-body behavior in molecular aggregates at the quantum chemical level of theory.

4.
Psychol Med ; 53(1): 267-273, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34376264

RESUMO

BACKGROUND: It has long been hypothesized that personality plays a causative role in incidence and outcome of breast cancer (BC), but epidemiological evidence of association between personality and BC is inconsistent. METHOD: We used two-sample Mendelian randomization analysis to estimate the impact of personality on the risk and survival of BC. In total, 109 single nucleotide polymorphisms (SNPs) were utilized as instruments of neuroticism from a large-scale Genome-Wide Association Studies (GWAS), and five SNPs were utilized as instruments of extraversion from Genetic of Personality Consortium and 23andMe. Genetic association with the risk and survival of overall and individual subtype BC were obtained from the Breast Cancer Association Consortium. RESULT: Neuroticism is significantly associated with the risk of overall BC [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.11; p = 0.015] and the risk of luminal A BC (OR 1.09; 95% CI 1.03-1.16; p = 0.004). Extraversion is not associated with the risk of BC. None of neuroticism or extraversion is associated with the survival of BC. CONCLUSION: Neuroticism was associated with a modest increased risk of BC and particularly luminal A BC.


Assuntos
Neoplasias da Mama , Estudo de Associação Genômica Ampla , Humanos , Feminino , Neoplasias da Mama/genética , Análise da Randomização Mendeliana , Personalidade/genética , Neuroticismo , Polimorfismo de Nucleotídeo Único
5.
Med Sci Monit ; 29: e937933, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37032522

RESUMO

BACKGROUND This retrospective study from a single center aimed to evaluate 24 patients with coracoid process fractures of the scapula treated by baseplate three-column glenoid fixation of the 3 columns attached to the glenoid, or the scapula-glenoid construct, which includes the base of the coracoid, the scapular spine, and the lateral/scapular pillar. MATERIAL AND METHODS Twenty-four patients with 24 coracoid process fractures were treated from March 2018 to August 2020 in our hospital; 11 cases were treated with the modified technique and 13 with the conventional technique. The patients had comparable screw length, bone union time, fracture reduction, and Constant-Murley shoulder outcome scores. The significant differences between variables were tested using the t test and Fisher's exact test, while bone union and reduction position were confirmed with X-ray and CT scans. The average follow-up time was 12 months. RESULTS The mean Constant-Murley shoulder outcome score and fracture reduction did not differ significantly (P>0.05), and all patients returned to their previous occupations and levels of activity, with no loss of reduction or surgical revision at the last follow-up. Bone union time for the modified group was longer than that of the conventional group (P<0.05). However, 1 patient had a screw broken at 5 months from heavy manual labor and showed delayed union at 8 months. The lengths of the coracoid process screws in the modified group were longer than in the conventional group (P<0.01). CONCLUSIONS The findings from this retrospective study showed that baseplate three-column glenoid fixation of the coracoid process was a good surgical option for coracoid process fractures.


Assuntos
Fraturas Ósseas , Articulação do Ombro , Humanos , Processo Coracoide/cirurgia , Estudos Retrospectivos , Escápula/cirurgia , Fraturas Ósseas/cirurgia , Articulação do Ombro/cirurgia
6.
BMC Musculoskelet Disord ; 24(1): 937, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38044433

RESUMO

BACKGROUND: The treatment of Dubberley type B capitellar fractures, which are frequently complicated, is widely debated. This study aimed to investigate the prognostic factors and clinical outcomes of Dubberley type B capitellar fractures treated with Herbert screws combined with posterior buttress plates. METHODS: Seven men and nine women (aged 30-68 years) with Dubberley type B capitellar fractures were operated on with Herbert screws combined with posterior buttress plates. The patients were classified into Dubberley types IB (seven), IIB (four), and IIIB (five). Complications and bone union were observed, and functional outcomes were evaluated by the Mayo Elbow Performance Index (MEPI). RESULTS: All patients were followed up for a mean period of 23.5 months (12-30 months). All fractures healed in 8-14 weeks (mean, 10.5 weeks). No cases of non-union, elbow instability, or avascular necrosis occurred. Degenerative arthritis occurred in 7 (44%) and heterotopic ossification in 11 (69%) patients. The median MEPI score was 92.5 (interquartile range, 85-100) points, with 11 reporting excellent, 3 good, and 2 fair outcomes. The MEPI scores of type IIIB fractures were significantly lower than those of types IB and IIB fractures, while the MEPI scores of type IB and IIB fractures did not differ significantly. CONCLUSIONS: Dubberley type IIIB capitellar fractures with multiple articular fragments have a poorer prognosis than type IB and IIB fractures. However, Herbert screw fixation combined with posterior metacarpal locking plates is feasible, providing satisfactory recovery of elbow joint function.


Assuntos
Lesões no Cotovelo , Articulação do Cotovelo , Fraturas Cominutivas , Fraturas do Úmero , Instabilidade Articular , Ossos Metacarpais , Masculino , Humanos , Feminino , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/cirurgia , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Resultado do Tratamento , Fixação Interna de Fraturas/efeitos adversos , Amplitude de Movimento Articular , Estudos Retrospectivos , Fraturas Cominutivas/cirurgia , Placas Ósseas
7.
Int Orthop ; 46(12): 2727-2734, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36197460

RESUMO

OBJECTIVE: Infection and nonunion are the two most challenging issues for high-energy fractures. This study aimed to explore the clinical effect of benign inflammation-cultivated bone growth activity in the treatment of closed/small-sized open and high-energy fractures. METHODS: This study is a case series of closed/small-sized open and high-energy fractures of the lower limbs treated at our hospital from April 2009 to February 2017. All patients underwent debridement and external fixation in the early stage, followed by internal fixation in the second stage. After the operation, fracture healing was monitored by X-ray, and early-stage knee function training was initiated. Also, bone grafting was performed to stimulate the healing reaction, eliminating the atrophic nonunion factors. RESULTS: The operation in all 75 cases was carried out after the inflammatory responses completely subsided, leading to secondary wound healing. Bony union appeared in 71 patients who did not suffer from any pain and could stand up and walk without any restriction. Among them, 68 patients could flex their knee > 100°, and three patients had knee flexion ranging from 80 to 100°. No infections occurred after the second operation. CONCLUSION: This two-stage treatment for high-energy fractures could avoid the damage caused by excessive inflammatory responses that occurred following early-stage one-time internal fixation. This method protected benign inflammatory-callus reactions induced by the primary injury and utilized the advantages of closed reduction in AO fixation with open reduction, thereby avoiding potential infection and nonunion caused by one-time fixation during the early stage.


Assuntos
Fraturas Ósseas , Fraturas Expostas , Fraturas da Tíbia , Humanos , Resultado do Tratamento , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fixação de Fratura/efeitos adversos , Fixação de Fratura/métodos , Consolidação da Fratura , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Fraturas Expostas/cirurgia , Estudos Retrospectivos
8.
Cell Tissue Res ; 382(3): 457-462, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32803322

RESUMO

Mesenchymal stem cells (MSCs) hold enormous potential for the treatment of immune-related conditions and degenerative diseases, owing to their self-renewal and multilineage differentiation capabilities. Nevertheless, cellular senescence significantly impacts the quantity and quality of MSCs, limiting their clinical use. Mitochondria play essential roles in energy production by oxidative phosphorylation and metabolism of energy sources via the tricarboxylic acid cycle. Therefore, mitochondrial dysfunction is a primary cause of senescence in MSCs. Herein, we summarize the current knowledge regarding the mechanisms underlying mitochondrial dysfunction-associated cellular senescence. We also discuss potential methods to prevent or even reverse MSC senescence.


Assuntos
Senescência Celular/fisiologia , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/metabolismo , Animais , Diferenciação Celular , Humanos , Camundongos
9.
Foot Ankle Surg ; 26(3): 289-294, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027877

RESUMO

BACKGROUND: The purpose of the study is to investigatethe prevalence of posterior malleolus intercalary fragment (ICF) in adult ankle fractures; to analyze the morphological characteristics of ICF; and its mechanism. METHODS: Retrospectively, 247 cases of posterior malleolus fractures (PMF) were included in 369 cases of adult ankle fractures. The prevalence of ICF, relationship between type of ankle fracture, posterior malleolar fracture and the ICF was studied. RESULTS: Among 369 cases, the ICF was found in 43% of the PMF and 29% of the hospitalized unstable ankle fractures. Position of ICF is posterolateral in 68 (64%), mid posterior in 20 (19%) and posteromedial in 18 (17%) cases. The prevalence of ICF was 70% in Bartonícek classification type III fractures, which was significantly higher than type I, II and IV. CONCLUSIONS: The highest incidence occurs in Bartonícek III type fracture. The study helps in further understanding and treatment of the PMF. LEVEL OF EVIDENCE: Level IV, case series.


Assuntos
Fraturas do Tornozelo/cirurgia , Articulação do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fraturas do Tornozelo/diagnóstico , Articulação do Tornozelo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
10.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(5): 415-419, 2020 Oct 08.
Artigo em Zh | MEDLINE | ID: mdl-33047564

RESUMO

OBJECTIVE: To explore the integration method and technical realization of artificial intelligence bone age assessment system with the hospital RIS-PACS network and workflow. METHODS: Two sets of artificial intelligence based on bone age assessment systems (CHBoneAI 1.0/2.0) were developed. The intelligent system was further integrated with RIS-PACS based on the http protocol in Python flask web framework. RESULTS: The two sets of systems were successfully integrated into the local network and RIS-PACS in hospital. The deployment has been smoothly running for nearly 3 years. Within the current network setting, it takes less than 3 s to complete bone age assessment for a single patient. CONCLUSIONS: The artificial intelligence based bone age assessment system has been deployed in clinical RIS-PACS platform and the "running in parallel", which is marking a success of Stage-I and paving the way to Stage-II where the intelligent systems can evolve to become more powerful in particular of the system self-evolution and the "running alternatively".


Assuntos
Inteligência Artificial , Sistemas de Informação Hospitalar , Sistemas de Informação em Radiologia , Determinação da Idade pelo Esqueleto , Osso e Ossos , Hospitais , Humanos , Integração de Sistemas
11.
FASEB J ; 32(4): 2280-2291, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29242275

RESUMO

Insulin-like growth factor-binding protein 7 (IGFBP7), a low-affinity IGF binder, may play an important role in bone metabolism. However, its function in osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we investigated its effects on osteogenic differentiation. Overexpression of IGFBP7 enhanced the expression of osteo-specific genes and proteins, and IGFBP7 knockdown decreased osteogenesis-specific markers. More mineral deposits and higher alkaline phosphatase activity were observed after the up-regulation of IGFBP7. Moreover, ß-catenin levels were up-regulated by the overexpression of IGFBP7 or the addition of extracellular IGFBP7 protein and were reduced by the depletion of IGFBP7. The increase in osteogenic differentiation due to the overexpression of IGFBP7 was partially decreased by specific Wnt/ß-catenin signaling inhibitors. Using a rat tibial osteotomy model, a sheet of IGFBP7-overexpressing BMSCs improved bone healing, as demonstrated by imaging, biomechanical, and histologic analyses. Taken together, these findings indicate that IGFBP7 regulates the osteogenic differentiation of BMSCs partly via the Wnt/ß-catenin signaling pathway.-Zhang, W., Chen, E., Chen, M., Ye, C., Qi, Y., Ding, Q., Li, H., Xue, D., Gao, X., Pan, Z. IGFBP7 regulates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells via Wnt/ß-catenin signaling pathway.


Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Células-Tronco Mesenquimais/citologia , Osteogênese , Via de Sinalização Wnt , Animais , Regeneração Óssea , Células Cultivadas , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Masculino , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Ratos , Ratos Sprague-Dawley , Adulto Jovem
12.
FASEB J ; 32(9): 4917-4929, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29630408

RESUMO

Microenvironmental conditions can influence the differentiation and functional roles of mesenchymal stem cells (MSCs). Recent studies have suggested that an inflammatory microenvironment can significantly affect the osteogenic differentiation of MSCs. Here, we show, for the first time, that IL-10 has concentration-dependent, dual roles in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs). Low physiologic concentrations of IL-10 (0.01-1.0 ng/ml) activate the p38/MAPK signaling pathway to promote the osteogenesis of hBMSCs, but higher pathologic doses of IL-10 (10-100 ng/ml) inhibit p38/MAPK signaling by activating NF-κB, inhibiting osteogenesis. These results demonstrate that p38/MAPK and NF-κB signaling mediates the double-edged sword effect of IL-10 on hBMSCs. The osteogenic impairment was reversed at higher doses of IL-10 when cells were supplemented with the NF-κB inhibitor BAY11-7082. These data provide important insights into the regulatory effects of IL-10 on the biologic behavior of hBMSCs.-Chen, E., Liu, G., Zhou, X., Zhang, W., Wang, C., Hu, D., Xue, D., Pan, Z. Concentration-dependent, dual roles of IL-10 in the osteogenesis of human BMSCs via P38/MAPK and NF-κB signaling pathways.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Interleucina-10/farmacologia , Osteogênese/efeitos dos fármacos , Células da Medula Óssea/citologia , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Molecules ; 24(24)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817653

RESUMO

Sweet potato is the sixth most important crop widely cultivated around the world with abundant varieties. Different varieties gain different phenolic profiles which has drawn researchers' attention for its unique health benefits. Our study evaluated the phenolic profiles, total and cellular antioxidant activities, antiproliferative activities, and cytotoxicity in 10 cultivated varieties of sweet potato in different colours. Among fourteen metabolites detected in our study, hyperoside, ferulic acid and caffeic acid were considered as prominent in SPSRs. According to the principle component analysis, phytochemical composition of HX22, YS15 and YS7 was quite similar. The results also evidenced that purple-fleshed varieties, such as YS43, YZ7 and YY153, have higher total phenolics content and corresponding stronger total antioxidant capacities as well as cellular antiproliferative activities against human liver cancer HepG2 cells than other varieties. The extremely significant correlation between phenolics and total antioxidant activity was also revealed by Pearson correlation analysis (p < 0.05). However, no significant relevance was found between intracellular antioxidant activity and total phenolic content or flesh colour of sweet potatoes.


Assuntos
Antioxidantes/química , Ipomoea batatas/química , Fenóis/análise , Raízes de Plantas/química , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos
14.
BMC Musculoskelet Disord ; 19(1): 288, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30111311

RESUMO

BACKGROUND: The use of bone graft for the radial head fractures has been previously described and occasionally used by other authors.This is the first paper, to my knowledge, dealing with the relevant issue about the importance that the use of an autologous bone graft can have on the radial head fractures. METHODS: From July 2010 to July 2014, 20 consecutive patients who underwent open reduction and internal fixation for a closed Mason type II radial head fracture were retrospectively reviewed. Patients with Mason type I, III, simple type II, and comminuted type II fractures treated without bone grafting were excluded. A clinical examination and radiographic evaluation were performed. The overall functional result was evaluated using the Mayo Elbow Performance Score (MEPS). The Broberg and Morrey classification was used to evaluate traumatic arthritis. RESULTS: The average follow-up duration was 31 months (range, 24-50 months). Bone union of the radial head fracture was achieved in all patients at an average of 13.5 weeks (range, 12-17 weeks). Postoperative radiographs showed no cases of postsurgical ligamentous instability, necrosis of the radial head, or internal fixation failure. The mean range of motion of the affected elbow was 128° ± 8.4° in flexion, 14.5° ± 11.1° in extension, 68.7° ± 14.1° in pronation, and 65.2° ± 18.2° in supination. The mean MEPS was 92 ± 7.9 points (range, 80-100); the outcome was excellent (90-100 points) in 13 patients and good (75-89 points) in 7 patients. The MEPS tended to be higher in patients with an isolated fracture (p = 0.016). Based on the Broberg and Morrey classification for radiographic assessment of post-traumatic arthritis, 15 elbows had no evidence of degenerative changes (grade 0), and 5 elbows had grade 1 changes. CONCLUSION: Although radial head fractures may not be amenable to internal fixation, our findings suggest that open reduction and internal fixation with an autogenous bone graft from the lateral epicondyle of the humerus provides satisfactory elbow function in patients with comminuted Mason type II radial head fractures.


Assuntos
Transplante Ósseo/métodos , Fixação Interna de Fraturas , Fraturas Cominutivas/cirurgia , Úmero/transplante , Redução Aberta , Fraturas do Rádio/cirurgia , Rádio (Anatomia)/cirurgia , Adulto , Idoso , Transplante Ósseo/efeitos adversos , Feminino , Fixação Interna de Fraturas/efeitos adversos , Consolidação da Fratura , Fraturas Cominutivas/diagnóstico por imagem , Fraturas Cominutivas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Redução Aberta/efeitos adversos , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/fisiopatologia , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/fisiopatologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
15.
Growth Factors ; 33(5-6): 356-65, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26607681

RESUMO

Increasing evidence indicates that the osteogenic differentiation of mesenchymal stem cells (MSCs) is related to bone formation, heterotopic ossification, and even vascular calcification. Therefore, it is essential to understand the microenvironment that regulates these processes. The Klotho gene plays an important role in tissue mineralization, and its secreted protein functions as a hormone. We investigated the effects of secreted Klotho protein on the osteogenesis of human bone marrow MSC (hBMSCs). To this end, the cells received osteogenic medium with or without Klotho protein. The results showed that osteoblast-specific gene expression and mineral deposition were decreased when MSCs were incubated with Klotho. Klotho reduced the expression of fibroblast growth factor receptor 1 (FGFR1) and phosphorylated extracellular signal-regulated kinase 1/2. However, both MEK and FGFR1 inhibitors delayed bone mineral formation more than Klotho. These data suggest that secreted Klotho protein attenuates the osteogenic differentiation of hBMSCs in vitro through FGFR1/ERK signaling.


Assuntos
Diferenciação Celular/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glucuronidase/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Células-Tronco Mesenquimais/citologia , Osteogênese/fisiologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Fosfatase Alcalina/metabolismo , Células da Medula Óssea/citologia , Calcificação Fisiológica/genética , Calcificação Fisiológica/fisiologia , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Flavonoides/farmacologia , Humanos , Proteínas Klotho , Osteogênese/genética , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores
16.
J Chem Phys ; 142(21): 212419, 2015 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-26049439

RESUMO

The 2D Raman-THz spectrum of the MgCl2 solution was simulated using the molecular dynamics simulation and the stability matrix method and compared with that of the pure water. The 2D Raman-THz signal provides more information on the ion effects on the collective water motion than the conventional 1D signal. The presence of MgCl2 suppresses the cross peak of water between the hydrogen bond bending and the other intermolecular vibrational mode, which clearly illustrates that the water hydrogen bending motion is affected by the confining effect of the ions. Our theoretical work thus demonstrates that the 2D Raman-THz technique can become a valuable nonlinear vibrational probe for the molecular dynamics in the ionic solutions.

17.
Nutrients ; 16(8)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38674860

RESUMO

Silymarin, salvianolic acids B, and puerarin were considered healthy food agents with tremendous potential to ameliorate non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which they interact with gut microbiota to exert benefits are largely unknown. After 8 weeks of NAFLD modeling, C57BL/6J mice were randomly divided into five groups and fed a normal diet, high-fat diet (HFD), or HFD supplemented with a medium or high dose of Silybum marianum extract contained silymarin or polyherbal extract contained silymarin, salvianolic acids B, and puerarin for 16 weeks, respectively. The untargeted metabolomics and 16S rRNA sequencing were used for molecular mechanisms exploration. The intervention of silymarin and polyherbal extract significantly improved liver steatosis and recovered liver function in the mice, accompanied by an increase in probiotics like Akkermansia and Blautia, and suppressed Clostridium, which related to changes in the bile acids profile in feces and serum. Fecal microbiome transplantation confirmed that this alteration of microbiota and its metabolites were responsible for the improvement in NAFLD. The present study substantiated that alterations of the gut microbiota upon silymarin and polyherbal extract intervention have beneficial effects on HFD-induced hepatic steatosis and suggested the pivotal role of gut microbiota and its metabolites in the amelioration of NAFLD.


Assuntos
Depsídeos , Dieta Hiperlipídica , Suplementos Nutricionais , Microbioma Gastrointestinal , Isoflavonas , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Silimarina , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Isoflavonas/farmacologia , Masculino , Camundongos , Silimarina/farmacologia , Benzofuranos/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Modelos Animais de Doenças , Ácidos e Sais Biliares/metabolismo , Extratos Vegetais/farmacologia
18.
Nutrients ; 16(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38613119

RESUMO

Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.


Assuntos
Microbioma Gastrointestinal , Hiperuricemia , Animais , Camundongos , Hiperuricemia/tratamento farmacológico , Resveratrol/farmacologia , Ácido Úrico , Túbulos Renais , Inflamação
19.
Eur Spine J ; 22(1): 79-86, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23161420

RESUMO

PURPOSE: This study describes a percutaneous technique for C2 transpedicular screw fixation and evaluates its safety and efficacy in the treatment of patients with hangman's fracture. METHODS: Ten patients with hangman's fracture were treated by percutaneous C2 transpedicular screw fixation. There are six males and four females, who were, based on the classification of Levine and Edwards, sorted as follows: type I fracture, three cases; type II, five cases; type IIa, two cases. The causes of injury were road traffic accident in six patients and falling injury in four patients. Other associated lesions included rib fractures (7 patients), head injuries (4 patients), and fractures of extremities (6 patients). RESULTS: The new technique was performed successfully in all cases. The average operation time was 98 min (range 60-130 min) and the estimated blood loss was 25 ml (range 15-40 ml). No complications such as vascular or neural structures injuries were found intraoperatively. Postoperative CT scans demonstrated that 17 (85 %) of 20 screws were placed satisfactorily, and 3 (15 %) screws showed perforations of the pedicle wall (<2 mm). These patients were asymptomatic and no further intervention was required postoperatively. After 8-25 months follow-up (mean 15.3 months), solid fusion was demonstrated by computed tomography. All cases got well-sagittal alignment and no angulation or dislocation was found at the segment of C2-C3. There was no loss of fixation. Clinical examination showed a full range of motion in the neck in all patients. CONCLUSIONS: The fluoroscopically assisted percutaneous C2 transpedicular screw fixation method is a technically feasible and minimally invasive technique for hangman's fracture.


Assuntos
Fraturas da Coluna Vertebral/cirurgia , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Adulto , Idoso , Parafusos Ósseos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Front Surg ; 10: 1103952, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36911604

RESUMO

Background: The purpose of the present study is to examine the possible correlation between standing plain x-rays and supine magnetic resonance imaging (MRI) for evaluating spinal sagittal alignment in degenerative lumbar disease (DLD). Methods: The characteristics and images of 64 patients with DLD were reviewed retrospectively. The thoracolumbar junction kyphosis (TJK), lumbar lordosis (LL) and sacral slope (SS) were measured on lateral plain x-rays and by MRI. Inter- and intra-observer reliability was tested using intra-class correlation coefficients. Results: The results suggested that TJK measurements obtained from MRI tended to underestimate the radiographic measures by 2°, whereas SS measurements obtained from MRI tended to overestimate the radiographic measures by 2°. The LL measurements obtained from MRI were approximately equal to the radiographic measures, and the x-ray and MRI measurements were linearly related. Conclusions: In conclusion, supine MRI can be directly translated into sagittal alignment angle measurements obtained from standing x-rays with an acceptable degree of accuracy. This can avoid the impaired view caused by the overlapping ilium, while reducing the patient's exposure to radiation.

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