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1.
J Orthop Surg Res ; 19(1): 55, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217013

RESUMO

OBJECTIVE: To explore the applicability of bone reamer and trephine for foraminoscopy in percutaneous endoscopic lumbar discectomy (PELD), and to provide a theoretical basis for foraminoplasty options in clinical practice. METHODS: This study was a prospective cohort study. Sixty-three consecutive patients who underwent PELD for lumbar disc herniation between May 2021 and July 2022 were analysed. Foraminoplasty were performed by bone reamer or trephine. The amount of bone removed and the foramen area enlarged during foraminoplasty by both tools were measured by 3D slicer and Digimizer software, and the numbers of fluoroscopic views were recorded. RESULTS: The bone reamer removed less bone in the Superior Articular Process (SAP) than the trephine (t = 17.507, P < 0.001), and the area enlarged by the bone reamer was smaller than that of the trephine (t = 10.042, P = 0.002). The overall numbers of fluoroscopic views were significantly more in the bone reamer group than in the trephine group (t = 19.003, P < 0.001). In the bone reamer group, when the area of preoperative (FPZ) was no less than 54.55 mm2, the mean number of fluoroscopic views significantly decreased (t = 14.443, P = 0.001). CONCLUSION: Bone reamer was safer and trephine was more efficient for foraminoscopy in PELD. An area of preoperative (FPZ) of 54.55 mm2 can be used as a critical value: bone reamer reduced the risk for cases above the value, while trephine improved the efficiency for cases less than the value.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Endoscopia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos
2.
EFORT Open Rev ; 8(12): 906-918, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38038386

RESUMO

Purpose: Transforaminal lumbar interbody fusion (TLIF) is a classic surgical procedure for posterior lumbar fusion. This study aims to analyze the TLIF field by bibliometric method and comprehensively summarize the research status and trends. Methods: All TLIF-related articles were retrieved from the Web of Science. The data were analyzed using R software and SPSS to calculate corresponding indicators. Visualizations were drawn using VOSviewer and Scimago Graphica, including country, institution, journal, author, and keywords. Results: A total of 919 articles were included. The annual publication volume of TLIF-related articles presented an exponential growth. North America, Europe, and Asia were the main sources of articles, with the USA and China being the main contributors and the USA being the global research center for TLIF. The level of the national economy was an important factor affecting TLIF-related research. The highest number of contributions in this field was made by Kern Singh among authors and by Rush University among institutions. The European Spine Journal was the most influential journal. The research focus has gradually shifted from perfecting the TLIF technique toward emphasizing the patient level. The improvement of minimally invasive techniques and how to improve clinical outcomes as well as accelerate postoperative rehabilitation of patients may be the hot spot of future research. Conclusions: With the advancement of medical technology and the popularization of minimally invasive concepts in recent years, TLIF and its derivative technologies have attracted increasing attention. Patient-centered minimally invasive surgery is a hot research topic in the field of TLIF currently and will continue to be so into the future.

3.
Front Endocrinol (Lausanne) ; 14: 1252968, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37955003

RESUMO

Background: Observational studies have suggested associations between serum urate levels and sarcopenia, but the causality underlying this correlation remains uncertain. The principal objective of this study is to investigate a causal relationship of serum urate levels with sarcopenia-related traits (hand grip strength, lean mass, walking pace) using bidirectional two-sample Mendelian randomization (MR) approach. The utilization of MR methodology serves to minimize bias caused by reverse causality and confounding factors from observational studies. Methods: The summary statistics of serum urate levels were derived from a cohort consisting of 288,659 individuals participating in CKDGen study. The parameters of right-hand grip strength (N=461,089), left-hand grip strength (N=461,026), appendicular lean mass (ALM) (N=450,243), whole-body lean mass(N=454,850),right-leg fat-free mass(FFM;N=454,835),left-leg FFM(N=454,805), right-arm FFM(N=454,753),left-arm FFM(N=454,672) and walking pace (N=459,915)were sourced from the UK Biobank. MR analysis was conducted utilizing inverse variance weighted (IVW), weighted median, and MR-Egger to evaluate causality. Sensitivity analysis was performed using Cochran's Q test, MR-Egger intercept test, leave-one-out analysis and the funnel plot. Results: IVW estimates demonstrated that serum urate levels exhibited no causal association with sarcopenia-related traits. In the inverse MR investigation, we had exclusively discerned an inverse correlation between walking pace and serum urate levels. No compelling evidence had surfaced to substantiate any association of other sarcopenia-related traits with serum urate. Supplemental MR methods consistently validated the findings obtained from the primary analysis. Sensitivity analysis demonstrated the robustness of findings. Conclusion: Our MR study revealed the absence of the bidirectional causal relationship between serum urate levels and sarcopenia. It is imperative to acknowledge that advanced age and an individual's health status are pivotal determinants influencing urate level and the initiation and advancement of sarcopenia. However, it is worth underscoring that these aspects remain unexamined within the purview of this study. Thus, future investigations should delve deeper into these intricate facets.


Assuntos
Força da Mão , Sarcopenia , Humanos , Análise da Randomização Mendeliana , Sarcopenia/genética , Ácido Úrico , Causalidade
4.
BMC Endocr Disord ; 23(1): 246, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37940909

RESUMO

OBJECTIVE: The association between segmental body composition and bone mineral density (BMD) remains uncertain. The primary aim of this cross-sectional investigation was to elucidate the connection between segmental body composition and BMD within the United States adult population. METHODS: We selected a cohort of 10,096 individuals from the National Health and Nutrition Examination Survey (NHANES) database, with a mean age of 39 years and a mean BMI of 28.5 kg/m². The parameter of segmental body composition was achieved by quantifying body fat and lean mass percentages across various anatomical regions, including the torso, Android, Gynoid, arms and legs. We conducted a weighted multivariate linear regression analysis to investigate the association between segmental body composition and total BMD. Additionally, subgroup analysis was performed based on age and gender. RESULTS: We found an inverse association between fat proportion in each anatomical region and total BMD, with the arm and leg regions demonstrating the most significant negative correlation. Conversely, a positive correlation was observed between lean mass and BMD across all anatomical regions. These associations remained consistent in subgroup analyses. CONCLUSION: Our investigation revealed a negative association between adipose levels in various anatomical regions and BMD among Americans aged 20 to 59. Importantly, higher fat proportion in the extremities exerted the most deleterious impact on BMD. Furthermore, an increase in lean mass within each anatomical region was ascertained to confer a positive effect on bone health. Consequently, the evaluation of segmental body composition is well-positioned to predict bone health status.


Assuntos
Composição Corporal , Densidade Óssea , Adulto , Humanos , Inquéritos Nutricionais , Estudos Transversais , Tecido Adiposo/metabolismo , Absorciometria de Fóton , Índice de Massa Corporal
5.
J Bone Oncol ; 41: 100494, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37575527

RESUMO

This study was designed to investigate the biological functions of LINC00482 in prostate cancer (PCa) with bone metastasis. TCGA dataset of PCa was applied for LINC00482 expression analysis and real time PCR was used to verify the expression level of LINC00482 in PCa tissues as well as PCa bone metastatic tissues. To detect the biological functions of LINC00482 in vitro, various assays were used including CCK-8, EdU, colony formation and transwell assays. The biological functions of LINC00482 were also identified in vivo by inoculating PCa cells into the left cardiac ventricle of mice, followed by evaluating the osteolytic lesions and osteolytic score. In addition, Starbase and Lncbase databases were applied for predicting the potential target miRNA of LINC00482, while TargetScan and Starbase databases were used for predicting the potential target of miRNA. The luciferase reporter assay was utilized to determine the interactions among these molecules and western blotting was employed to verified the targeted proteins. Results showed that high expression level of LINC00482 was observed in bone metastatic PCa tissues and associated with PCa progression. Silencing of LINC00482 inhibited cell proliferation, migration and invasion in PCa. Furthermore, LINC00482 was proved to act as a competing endogenous RNA by sponging miR-2467-3p to activate Wnt/ß-catenin signaling pathway, which may be a promising therapeutic target for PCa with bone metastasis.

6.
Sci Rep ; 13(1): 10682, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37393338

RESUMO

The relationship between the accumulation of fat in visceral or subcutaneous tissue and bone mineral density (BMD) remains unclear. Our primary objective in this study was to illuminate this relationship by conducting an investigation on a vast scale, encompassing a nationally representative population in the United States. A weighted multiple linear regression model was established to evaluate the relationship between visceral fat, subcutaneous fat, and BMD. Additionally, the exploration of the potential nonlinear relationship was conducted employing the methodology of smooth curve fitting. In order to determine potential inflection points, a two-stage linear regression model was utilized. A total of 10,455 participants between the ages of 20 and 59 were included in this study. Various weighted multiple linear regression models revealed a negative correlation between lumbar BMD and visceral mass index (VMI) and subcutaneous mass index (SMI). However, the association between VMI and lumbar BMD displayed a U-shaped pattern upon employing the smooth curve fitting, and the inflection point of 0.304 kg/m2was determined using a two-stage linear regression model. Our findings indicated a negative association between subcutaneous fat and BMD. A U-shaped relationship was observed between visceral fat and BMD.


Assuntos
Densidade Óssea , Gordura Subcutânea , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Estudos Transversais , Gordura Subcutânea/diagnóstico por imagem , Tela Subcutânea , Gordura Intra-Abdominal
7.
J Orthop Surg Res ; 18(1): 337, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37158874

RESUMO

BACKGROUND: Surgical site infection (SSI) is a common complication in spinal surgery that can significantly affect the patient's prognosis. Despite advances in surgical techniques and infection control measures, SSI remains a considerable concern for healthcare providers and patients alike. In recent years, there has been a steady increase in studies related to SSI in spine surgery, leading to the publication of numerous informative articles. However, the current state and trends of research in the field of spinal SSI remain unclear. This study aims to conduct a bibliometric analysis of SSI-related articles in spine surgery to identify research status and trends. Meanwhile, we identify the top 100 most cited articles for further analysis. METHODS: We searched for all articles related to spinal SSI in the Web of Science Core Collection, recording the publication year, country, journal, institution, keywords, and citation frequency for further analysis. In addition, we identified and analyzed the top 100 most cited articles. RESULTS: A total of 307 articles related to spinal SSI were identified. All of these articles were published between 2008 and 2022, with the number of publications showing an increasing trend over the years. The related articles originated from 37 countries, with the USA contributing the most (n = 138). The institution with the highest number of publications and citations was Johns Hopkins University (14 articles; 835 citations). Among the journals, Spine had the highest number of articles (n = 47). The prevention of spinal SSI has been a research hotspot in recent years. Among the top 100 most cited articles, the most common research theme was the risk factors associated with spinal SSI. CONCLUSIONS: In recent years, research related to spinal SSI has attracted the attention of numerous clinicians and scholars. As the first bibliometric analysis of spinal SSI, our study aims to provide pragmatic guidance for clinicians to learn the research status and trends in this field and improve their vigilance toward SSI.


Assuntos
Procedimentos Neurocirúrgicos , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Bibliometria , Pessoal de Saúde , Controle de Infecções
9.
J Mol Neurosci ; 72(12): 2507-2516, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36534294

RESUMO

Diabetic peripheral neuropathy (DPN) is a highly prevalent diabetic complication characterized at the molecular level by mitochondrial dysfunction and deleterious oxidative damage. No effective treatments for DPN are currently available. The present study was developed to examine the impact of exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) overexpressing sirtuin 1 (SIRT1) on DPN through antioxidant activity and the preservation of mitochondrial homeostasis. A DPN model was established using 20-week-old diabetic model mice (db/db). Exosomes were prepared from control BMSCs (exo-control) and BMSCs that had been transduced with a SIRT1 lentivirus (exo-SIRT1). Sensory and motor nerve conduction velocity values were measured to assess neurological function, and mechanical and thermal sensitivity were analyzed in these animals. Exo-SIRT1 preparations exhibited a high loading capacity and readily accumulated within peripheral nerves following intravenous administration, whereupon they were able to promote improved neurological recovery relative to exo-control treatment. DPN mice exhibited significantly improved nerve conduction velocity following exo-SIRT1 treatment. Relative to exo-control-treated mice, those that underwent exo-SIRT1 treatment exhibited significantly elevated TOMM20 and Nrf2/HO-1 expression, reduced MDA levels, increased GSH and SOD activity, and increased MMP. Together, these results revealed that both exo-control and exo-SIRT1 administration was sufficient to reduce the morphological and behavioral changes observed in DPN model mice, with exo-SIRT1 treatment exhibiting superior therapeutic efficacy. These data thus provide a foundation for future efforts to explore other combinations of gene therapy and exosome treatment in an effort to alleviate DPN.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Doenças do Sistema Nervoso Periférico , Animais , Camundongos , Medula Óssea/metabolismo , Exossomos/metabolismo , Exossomos/transplante , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 1/uso terapêutico
10.
J Orthop Surg Res ; 17(1): 460, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266695

RESUMO

BACKGROUND: Osteosarcoma (OS) is a common primary malignant bone tumor. This study aimed to explore the biological role of long on-coding RNA (lncRNA) CASC9 and its regulatory mechanism in OC. METHODS: The CASC9 expressions in OS cells and tissues were measured using qRT-PCR. The functional role of CASC9 in OC was studied using MTT assay, colony formation assay, transwell invasion assay, and xenograft tumor assay. In addition, the mechanism of CASC9 function was determined using luciferase reporter assay. Western blot was used to analyze protein expressions in our paper. RESULTS: LncRNA CASC9 was found to be up-regulated in OS. Knockdown of CASC9 inhibited the proliferation and invasion of OS cells. Besides, miR-874-3p was identified as the target of CASC9, and SOX12 acted as a potential target of miR-874-3p. The down-regulation of miR-874-3p recovered the reduction in cell invasion and proliferation in vitro which were induced by CASC9 knockdown and delayed the tumor progression in vivo. CONCLUSION: LncRNA CASC9 promotes cell proliferation and invasion in OS via miR-874-3p/SOX12 axis. Our study might provide novel biomarkers and potential therapeutic targets for OS treatment.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Fatores de Transcrição SOXC , Humanos , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Fatores de Transcrição SOXC/genética
11.
J Pain Res ; 15: 3137-3156, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311292

RESUMO

Study design: A bibliometric analysis. Objective: To identify and analyze the top 100 cited articles in anterior cervical discectomy and fusion. Summary of Background Data: Anterior cervical discectomy and fusion (ACDF) is one of the most routine surgical procedures in spine surgery. Many surgeons and academics have researched ACDF thoroughly and published numerous articles. However, there is no relevant bibliometric analysis. Therefore, our study aims to identify and analyze the top 100 cited articles in ACDF to identify the research trends. Methods: We searched the Web of Science (WOS) Core Collection database with restrictions and identified the top 100 cited publications in ACDF for analysis. Results: The citation counts of the top 100 cited publications ranged from 37 to 361 (mean 67.42). All studies were published between 2008 and 2019, with 2013 and 2015 the most prolific years. The journals Spine and Journal of Neurosurgery-Spine provided the majority of the articles. Overall, the 100 articles came from 12 countries, with the United States being the top producer, followed by China and South Korea. The most frequent keywords were "spine", "anterior cervical discectomy and fusion", "interbody fusion", 'arthrodesis', "follow-up", "decompression", and "ACDF". Conclusion: ACDF has been regarded as a classical gold standard in anterior cervical surgery, and the emergence of new surgical procedures has not affected its status. Cervical disc arthroplasty still needs further research and development. As the first bibliometric analysis of ACDF, this bibliometric study is meant to provide guidance for clinicians and scholars to research the development trend of this field.

12.
J Pain Res ; 15: 2373-2392, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003290

RESUMO

Background: With the aging population growth in the world, the prevalence of osteoporotic vertebral compression fracture (OVCF) is rapidly increasing and receiving widespread attention. Although there are numerous articles on the topic, the research status and hotspot analysis are unclear. Objective: The goal of this study is to identify trends in the OVCF field and to analyze the most highly cited original articles published in the Web of Science Index on OVCF using bibliometric analysis. Methods: All OVCF data were obtained from the Web of Science Core Collection, and the number of citations, institutions, journals, countries, and years of publication in this field were visually analyzed using VOSviewer, the bibliometrics online analysis platform, and Excel software. Simultaneously, the top 100 most cited articles were extracted and analyzed. Results: A total of 756 publications were related to OVCF were included from 1900 to 2022. In recent years, the number of articles on OVCF significantly increased. They are mainly from 41 countries/regions and 202 journals, led by China and the United States. Among all countries, China had the most significant contribution on OVCF (n = 363), and it also was cited most often (n = 3337). The institution with the most articles was Soochow University (n = 40). Osteoporosis International was the journal with most studies and has published 50 on this field. The journal of Spine was cited most often (n = 1968). The most productive periods were from 2016 to 2020, which received 294 articles and 4868 citations. After the analysis, the "vertebroplasty" and "kyphoplasty" of OVCF have been the most common research hotspots. Conclusion: This study represents an updated bibliometric analysis of OVCF. The aim is to identify current research hotspots and future trends to guide clinicians and researchers in this field.

14.
J Clin Lab Anal ; 35(11): e24032, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34606644

RESUMO

BACKGROUND: Gout is an inflammatory arthritis and is characterized by the accumulation of deposited monosodium urate (MSU) crystals in the joints. miRNAs may act as key regulators of gout pathogenesis. The aim of our study was to explore the underlying role and molecular mechanism of miR-3146 in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of gout. METHODS: The expression of miR-3146 and sirtuin 1 (SIRT1) was determined by real-time reverse transcription-polymerase chain reaction and Western blot, respectively. The luciferase reporter assay was performed to identify the targeting relationship between miR-3146 and SIRT1. Reactive oxygen species (ROS) production was detected by fluorescent staining. NETs formation was demonstrated via immunofluorescence staining and ELISA method. Gout model was induced in rats to verify the effects of miR-3146 inhibition on histopathological changes and NETs. RESULTS: Here, we found miR-3146 expression was dramatically increased in neutrophils of patients with gout, which was accompanied with the higher levels of NETs. MSU crystals significantly increased miR-3146 expression and ROS production in neutrophils. The NETs process was also triggered by MSU crystals. Furthermore, we verified the interaction between miR-3146 and SIRT1. Additionally, antagomir-3146-based therapy effectively inhibited the formation of NETs in rats with gout. CONCLUSION: Our findings indicated that miR-3146-mediated NETs formation may play a potential role in the pathogenesis of gout. These results suggested that miR-3146 could be used as a potential therapeutic target for the treatment of gout.


Assuntos
Armadilhas Extracelulares/metabolismo , Gota , MicroRNAs/metabolismo , Adulto , Idoso , Animais , Modelos Animais de Doenças , Gota/genética , Gota/metabolismo , Gota/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley
15.
Front Endocrinol (Lausanne) ; 12: 752176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35356148

RESUMO

Background: The overall survival (OS) of pancreatic cancer (PC) patients with bone metastasis (BM) is extremely low, and it is pretty hard to treat bone metastasis. However, there are currently no effective nomograms to predict the diagnosis and prognosis of pancreatic cancer with bone metastasis (PCBM). Therefore, it is of great significance to establish effective predictive models to guide clinical practice. Methods: We screened patients from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2016. The independent risk factors of PCBM were identified from univariable and multivariable logistic regression analyses, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors affecting the prognosis of PCBM. In addition, two nomograms were constructed to predict the risk and prognosis of PCBM. We used the area under the curve (AUC), C-index and calibration curve to determine the predictive accuracy and discriminability of nomograms. The decision curve analysis (DCA) and Kaplan-Meier(K-M) survival curves were employed to further confirm the clinical effectiveness of the nomogram. Results: Multivariable logistic regression analyses revealed that risk factors of PCBM included age, primary site, histological subtype, N stage, radiotherapy, surgery, brain metastasis, lung metastasis, and liver metastasis. Using Cox regression analyses, we found that independent prognostic factors of PCBM were age, race, grade, histological subtype, surgery, chemotherapy, and lung metastasis. We utilized nomograms to visually express data analysis results. The C-index of training cohort was 0.795 (95%CI: 0.758-0.832), whereas that of internal validation cohort was 0.800 (95%CI: 0.739-0.862), and the external validation cohort was 0.787 (95%CI: 0.746-0.828). Based on AUC of receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA), we concluded that the risk and prognosis model of PCBM exhibits excellent performance. Conclusion: Nomogram is sufficiently accurate to predict the risk and prognostic factors of PCBM, allowing for individualized clinical decisions for future clinical work.


Assuntos
Nomogramas , Neoplasias Pancreáticas , Humanos , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Prognóstico , Programa de SEER
16.
Spine (Phila Pa 1976) ; 45(17): E1057-E1065, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32205703

RESUMO

STUDY DESIGN: Experimental analysis of the thoracic ligamentum flavum cell osteogenic differentiation process. OBJECTIVE: This study aimed to explore the role of miR-29a-5p and special AT-rich sequence-binding protein 2 (SATB2) in a pathological osteogenic process. SUMMARY OF BACKGROUND DATA: Thoracic ossification of the ligamentum flavum (TOLF) is an uncommon disease wherein ligaments within the spine undergo progressive ossification, resulting in stenosis of the spinal canal and myelopathy. MiR-29a-5p was found to be downregulated in ligament cells from ossified ligament tissue in a previous study. However, whether miR-29a-5p is involved in the process of TOLF has not been investigated. METHODS: The expression of miR-29a-5p in ligament tissues or in the context of TOLF osteogenic cell differentiation was measured via qRT-PCR. Alkaline phosphatase activity assay and Alizarin red staining were used to analyze cellular osteogenesis. The protein-level expression of SATB2, SIRT1, and Smad3 were measured via immunohistochemistry or western blotting. Dual luciferase reporter assays and western blotting were used to confirm that miR-29a targets SATB2. RESULTS: SATB2 was found to be upregulated and miR-29a-5p was downregulated in TOLF tissue. We additionally observed decreased miR-29a-5p expression during the process of TOLF osteogenic cell differentiation, and there was a marked reduction in the expression of key mediators of osteogenesis when miR-29a-5p was overexpressed. Consistent with this, when miR-29a-5p was inhibited this led to enhanced osteogenic cell differentiation of these cells. We further found miR-29a-5p to directly target and suppress the expression of SATB2. Knock-down of SATB2 was sufficient to reduce the ability of miR-29a-5p to inhibit osteogenesis, and this also led to decreased SIRT1 expression and Smad3 acetylation. CONCLUSION: Together our findings indicate that miR-29a-5p is able to prevent thoracic ligamentum flavum cell osteogenesis at least in part via targeting SATB2 and thereby suppressing the SIRT1/Smad3 deacetylation pathway. LEVEL OF EVIDENCE: N/A.


Assuntos
Ligamento Amarelo/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/biossíntese , MicroRNAs/biossíntese , Osteogênese/fisiologia , Sirtuína 1/biossíntese , Proteína Smad3/biossíntese , Fatores de Transcrição/biossíntese , Acetilação , Adulto , Idoso , Células Cultivadas , Feminino , Células HEK293 , Humanos , Ligamento Amarelo/patologia , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/antagonistas & inibidores , Pessoa de Meia-Idade , Transdução de Sinais/fisiologia , Sirtuína 1/antagonistas & inibidores , Proteína Smad3/antagonistas & inibidores , Vértebras Torácicas/metabolismo , Vértebras Torácicas/patologia , Fatores de Transcrição/antagonistas & inibidores
17.
Sci Adv ; 6(3): eaax7467, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31998838

RESUMO

Our nearest neighbor, Proxima Centauri, hosts a temperate terrestrial planet. We detected in radial velocities evidence of a possible second planet with minimum mass m c sin i c = 5.8 ± 1.9M ⊕ and orbital period P c = 5.21 - 0.22 + 0.26 years. The analysis of photometric data and spectro-scopic activity diagnostics does not explain the signal in terms of a stellar activity cycle, but follow-up is required in the coming years for confirming its planetary origin. We show that the existence of the planet can be ascertained, and its true mass can be determined with high accuracy, by combining Gaia astrometry and radial velocities. Proxima c could become a prime target for follow-up and characterization with next-generation direct imaging instrumentation due to the large maximum angular separation of ~1 arc second from the parent star. The candidate planet represents a challenge for the models of super-Earth formation and evolution.

18.
Biochem Biophys Res Commun ; 522(1): 14-20, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31735337

RESUMO

Diabetes mellitus is a metabolic disease characterized by an increase in blood glucose levels due to lack of insulin secretion. Previous studies have confirmed that PICK1 is critical for both ß-cell function and glucose homeostasis. The aim of this study was to investigate the role of PICK1 in response to high glucose-induced ß-cell dysfunction and the molecular mechanism of regulation of PICK1. We found that overexpression of PICK1 in db/db diabetic mice significantly improved glucose tolerance and increased insulin release. High glucose treatment of Min6 cells inhibited PICK1 expression, and overexpression of PICK1 protected against high glucose-induced pancreatic cell dysfunction. Activation of the PI3K/Akt pathway by PICK1 in Min6 cells resulted in increased GLUT2 expression and this increase was abolished by treatment with a PI3K-specific inhibitor. Further, we showed that expression of PICK1 is negatively regulated by miR-139-5p through directly targeting its 3'UTR. These data suggested that PICK1 may participate in the functional protection of pancreatic ß-cells through PI3K/Akt signaling, promote insulin secretion, and delay the progression of diabetes, and is negatively regulated by miR-139-5p, further clarifying the regulation of pancreatic ß-cell function.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Morte Celular , Glucose/metabolismo , Células Secretoras de Insulina/citologia , MicroRNAs/genética , Transdução de Sinais , Animais , Linhagem Celular , Dieta Hiperlipídica , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 2/metabolismo , Homeostase , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
19.
Biosci Rep ; 39(7)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31221817

RESUMO

Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. A high glucose niche-mediated disc cell apoptosis is an implicate causative factor for the spine degenerative diseases related with DM. However, the effects of a high glucose niche on disc annulus fibrosus (AF) cell apoptosis and the potential signaling transduction pathway is unclear. The present study is to investigate the effects of high glucose on disc AF cell apoptosis and the role of two potential signaling pathways in this process. Rat AF cells were cultured in baseline medium or medium with different concentrations (0.1 and 0.2 M) of glucose for 3 days. Flow cytometry was used to assess the degree of apoptosis. Activity of caspase 3/9 was evaluated by chemical kit. Expression of pro-apoptotic and anti-apoptotic molecules was analyzed by real-time polymerase chain reaction and Western blot. In addition, activity of the C-Jun NH2-terminal kinases (JNK) pathway and p38 mitogen-activated protein kinase (MAPK) pathway was evaluated by Western blot. Compared with the control group, high glucose culture increased cell apoptosis ratio and caspase-3/9 activity, up-regulated expression of bax, caspase-3, cleaved caspase-3 and cleaved PARP, and down-regulated expression of bcl-2 in a glucose concentration-dependent manner. Additionally, high glucose culture increased expression of the p-JNK and p-p38 MAPK in a concentration-dependent manner. Further results showed that inhibition of the JNK or p38 MAPK pathway attenuated the effects of high glucose on AF cell apoptosis. Together, high glucose promoted disc AF cell apoptosis through regulating the JNK pathway and p38 MAPK pathway in a glucose concentration-dependent manner.


Assuntos
Complicações do Diabetes/genética , Diabetes Mellitus/genética , Glucose/efeitos adversos , Degeneração do Disco Intervertebral/genética , Animais , Anel Fibroso/metabolismo , Anel Fibroso/patologia , Apoptose/efeitos dos fármacos , Complicações do Diabetes/patologia , Diabetes Mellitus/patologia , Modelos Animais de Doenças , Glucose/farmacologia , Humanos , Degeneração do Disco Intervertebral/induzido quimicamente , Degeneração do Disco Intervertebral/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ratos , Fatores de Risco , Proteínas Quinases p38 Ativadas por Mitógeno/genética
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