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1.
FASEB J ; 35(10): e21851, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34547121

RESUMO

It has been known that moderate mechanical loading, like that caused by exercise, promotes bone formation. However, its underlying mechanisms remain elusive. Here we showed that moderate running dramatically improved trabecular bone in mice tibias with an increase in bone volume fraction and trabecular number and a decrease in trabecular pattern factor. Results of immunohistochemical and histochemical staining revealed that moderate running mainly increased the number of osteoblasts but had no effect on osteoclasts. In addition, we observed a dramatic increase in the number of colony forming unit-fibroblast in endosteal bone marrow and the percentage of CD45- Leptin receptor+ (CD45- LepR+ ) endosteal mesenchymal progenitors. Bioinformatics analysis of the transcriptional data from gene expression omnibus (GEO) database identified chemokine c-c-motif ligands (CCL2) as a critical candidate induced by mechanical loading. Interestingly, we found that CCL2 was up-regulated mainly in osteoblastic cells in the tibia of mice after moderate running. Further, we found that mechanical loading up-regulated the expression of CCL2 by activating ERK1/2 pathway, thereby stimulating migration of endosteal progenitors. Finally, neutralizing CCL2 abolished the recruitment of endosteal progenitors and the increased bone formation in mice after 4 weeks running. These results therefore uncover an unknown connection between osteoblasts and endosteal progenitors recruited in the increased bone formation induced by mechanical loading.


Assuntos
Osso Esponjoso/citologia , Quimiocina CCL2/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteogênese , Condicionamento Físico Animal , Animais , Osso Esponjoso/metabolismo , Movimento Celular , Quimiocina CCL2/genética , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo
2.
J Immunol Res ; 2021: 4634505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575360

RESUMO

Background: Currently, both clavicular bacterial osteomyelitis (BO) and nonbacterial osteitis (NBO) remain not well understood owing to their much lower incidences. This study is aimed at summarizing similarities and differences between clavicular BO and NBO based on comparisons of literature-reported cases. Methods: We searched the PubMed and Embase databases to identify English published literature between January 1st, 1980, and December 31st, 2018. Inclusion criteria were studies evaluating clinical features, diagnosis, and treatment of clavicular BO and NBO, with eligible data for synthesis analysis. Results: Altogether, 129 studies with 327 patients were included. Compared with BO, clavicular NBO favored females (P < 0.001) and age below 20 years (P < 0.001) and mostly presented in a chronic phase (disease term exceeding 2 months) (P < 0.001). Although local pain and swelling were the top two symptoms for both disorders, fever, erythema, and a sinus tract were more frequently found in BO patients (P < 0.01). Although they both favored the medial side, lesions in the clavicular lateral side mostly occurred in BO patients (P = 0.002). However, no significant differences were identified regarding the serological levels of white blood cell count (P = 0.06), erythrocyte sedimentation rate (P = 0.27), or C-reactive protein (P = 0.33) between BO and NBO patients before therapy. Overall, the BO patients achieved a statistically higher cure rate than that of the NBO patients (P = 0.018). Conclusions: Females, age below 20 years, and a long duration of clavicular pain and swelling may imply NBO. While the occurrence of a sinus tract and lesions in the lateral side may be clues of BO, inflammatory biomarkers revealed limited values for differential diagnosis. BO patients could achieve a better efficacy than the NBO patients based on current evidence.


Assuntos
Infecções Bacterianas/diagnóstico , Osteíte/diagnóstico , Osteomielite/diagnóstico , Adulto , Infecções Bacterianas/microbiologia , Biomarcadores , Diagnóstico Diferencial , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteíte/etiologia , Osteomielite/etiologia , Avaliação de Sintomas , Adulto Jovem
3.
J Orthop Translat ; 24: 12-22, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32518750

RESUMO

Background: Abnormal bone formation in subchondral bone resulting from uncoupled bone remodeling is considered a central feature in osteoarthritis (OA) pathogenesis. H-type vessels can couple angiogenesis and osteogenesis. We previously revealed that elevated H-type vessels in subchondral bone were correlated with OA and focal adhesion kinase (FAK) in MSCs is critical for H-type vessel formation in osteoporosis. The aim of this study was to explore the correlation between H-type vessels and MSCs in OA pathogenesis through regulation of H-type vessel formation using defactinib (an FAK inhibitor). Methods: In vivo: 3-month-old male C57BL/6J (WT) mice were randomly divided into three groups: sham controls, vehicle-treated ACLT mice, and defactinib-treated ACLT mice (25 mg/kg, intraperitoneally weekly). In vitro: we explored the role of conditioned medium (CM) of MSCs from subchondral bone of different groups on the angiogenesis of endothelial cells (ECs). Flow cytometry, Western blotting, ELISA, real time (RT)-PCR, immunostaining, CT-based microangiography, and bone micro-CT (µCT) were used to detect changes in relative cells and tissues. Results: This study demonstrated that inhibition of H-type vessels with defactinib alleviated OA by inhibiting H-type vessel-linked MSCs in subchondral bone. During OA pathogenesis, H-type vessels and MSCs formed a positive feedback loop contributing to abnormal bone formation in subchondral bone. Elevated H-type vessels provided indispensable MSCs for abnormal bone formation in subchondral bone. Flow cytometry and immunostaining results confirmed that the amount of MSCs in subchondral bone was obviously higher in vehicle-treated ACLT mice than that in sham controls and defactinib-treated ACLT mice. In vitro, p-FAK in MSCs from subchondral bone of vehicle-treated ALCT mice increased significantly relative to other groups. Further, the CM from MSCs of vehicle-treated ACLT mice enhanced angiogenesis of ECs through FAK-Grb2-MAPK-linked VEGF expression. Conclusions: Our results demonstrate that defactinib inhibits OA by suppressing the positive feedback loop between H-type vessels and MSCs in subchondral bone. The translational potential of this article: Our results provide a mechanistic rationale for the use of defactinib as an effective candidate for OA treatment.

4.
Cell Microbiol ; 22(10): e13240, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32584493

RESUMO

Internalisation of Staphylococcus aureus in osteoblasts plays a critical role in the persistence and recurrence of osteomyelitis, the mechanisms involved in this process remain largely unknown. In the present study, evidence of internalised S. aureus in osteoblasts was found in long bone of haematogenous osteomyelitis in mice after 2 weeks of infection. Meanwhile, eliminating extracellular S. aureus by gentamicin can partially rescue bone loss, whereas the remaining intracellular S. aureus in osteoblasts may be associated with continuous bone destruction. In osteoblastic MC3T3 cells, intracellular S. aureus was detectable as early as 15 min after infection, and the internalisation rates increased with the extension of infection time. Additionally, S. aureus invasion stimulated the expression of phosphor-focal adhesion kinase (FAK), phosphor-epidermal growth factor receptor (EGFR) and phosphor-c-Src in a time-dependent way, and blocking EGFR/FAK or c-Src signalling significantly reduced the internalisation rate of S. aureus in osteoblasts. Our findings provide new insights into the mechanism of S. aureus internalisation in osteoblast and raise the potential of targeting EGFR/FAK and c-Src as adjunctive therapeutics for treating chronic S. aureus osteomyelitis.


Assuntos
Receptores ErbB/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Osteoblastos/microbiologia , Osteomielite/microbiologia , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Animais , Linhagem Celular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Staphylococcus aureus/metabolismo
5.
J Cell Physiol ; 235(11): 8653-8666, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32324278

RESUMO

Osteoarthritis (OA), a disease of the entire joint, is characterized by abnormal bone remodeling and coalescent degradation of articular cartilage. We have previously found that elevated levels of H-type vessels in subchondral bone correlate with OA and that focal adhesion kinase (FAK) is critical for H-type vessel formation in osteoporosis. However, the potential role of FAK in OA remains unexplored. Here, we demonstrate that the p-FAK level was dramatically elevated in subchondral bone following anterior cruciate ligament transection (ACLT) in rats. Specific inhibition of FAK signaling with Y15 in subchondral bone resulted in the suppression of subchondral bone deterioration and this effect was mediated by H-type vessel-induced ectopic bone formation. Further, articular cartilage degeneration was also alleviated after Y15 treatment. In vitro, the p-FAK level was significantly elevated in mesenchymal stem cells (MSCs) from vehicle-treated ACLT rats as compared to that in MSCs from sham controls and Y15-treated ACLT rats. Elevated p-FAK level in MSCs promoted vascular endothelial growth factor (VEGF) expression, as demonstrated from the high VEGF level in the blood, subchondral bone, and conditioned medium (CM) of MSCs from vehicle-treated ACLT rats. The CM of MSCs from vehicle-treated ACLT rats might promote the angiogenesis of endothelial cells and the catabolic response of chondrocytes through the FAK-growth factor receptor-bound protein 2-mitogen-activated protein kinase-mediated expression of VEGF. The effect of the CM from MSCs of Y15-treated ACLT rats or that treated with a VEGF-neutralizing antibody on vessel formation and the catabolic response was lowered. Thus, the specific inhibition of FAK signaling may be a promising avenue for the prevention or early treatment of OA.


Assuntos
Cartilagem Articular/metabolismo , Quinase 1 de Adesão Focal/antagonistas & inibidores , Proteína-Tirosina Quinases de Adesão Focal/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Osteoartrite/tratamento farmacológico , Alendronato/farmacologia , Animais , Ligamento Cruzado Anterior/patologia , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Osso e Ossos/patologia , Condrócitos/metabolismo , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Masculino , Osteoartrite/patologia , Ratos Sprague-Dawley
6.
J Biomater Appl ; 35(1): 97-107, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32233720

RESUMO

Fabrication of osteoconductive scaffold with osteoinductive capability and appropriate resorption rate is of great significance for treating bone defects. To achieve this aim, strontium-substituted calcium sulfate hemihydrate (Sr-CSH) and hydroxyapatite (HA) were mixed to develop a novel composite. Sr-CSH containing 5% and 10% strontium was mixed with HA at the weight ratio of 6:4, respectively. Female Sprague-Dawley rats underwent bone defect surgery in left tibia were randomly assigned to three different treatment groups filled with CSH/HA, 5% and 10% Sr-CSH/HA. Micro-CT analysis showed increased new bone formation in 10% Sr-CSH/HA group compared to CSH/HA group. In addition, histological analysis showed large amounts of chondrocytes and osteoblasts within the pores of Sr-CSH/HA composites as a result of the CSH resorption. Further, CFU-F assay demonstrated the increased amount of bone marrow mesenchymal stromal cells (BMSCs) colonies in 10% Sr-CSH/HA group. In primary BMSCs, extraction from Sr-CSH/HA composite significantly increased the migration of cells, up-regulated the expression of osteoblastic marker genes, and increased the area of mineralized nodules. Together, Sr-CSH/HA may promote bone formation by recruiting and stimulating osteogenic differentiation of BMSCs. Therefore, this composite may be proposed as an ideal substitute to repair bone defects.


Assuntos
Regeneração Óssea , Sulfato de Cálcio/química , Hidroxiapatitas/química , Células-Tronco Mesenquimais/citologia , Estrôncio/química , Tecidos Suporte/química , Animais , Regeneração Óssea/efeitos dos fármacos , Sulfato de Cálcio/farmacologia , Proliferação de Células/efeitos dos fármacos , Feminino , Hidroxiapatitas/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Estrôncio/farmacologia
7.
Stem Cell Res Ther ; 11(1): 131, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197645

RESUMO

BACKGROUND: Hypercholesterolemia increases the risk of tendon pain and tendon rupture. Tendon-derived stem cells (TDSCs) play a vital role in the development of tendinopathy. Our previous research found that high cholesterol inhibits tendon-related gene expression in TDSCs. Whether high cholesterol has other biological effects on TDSCs remains unknown. METHODS: TDSCs isolated from female SD rats were exposed to 10 mg/dL cholesterol for 24 h. Then, cell apoptosis was assessed using flow cytometry and fluorescence microscope. RFP-GFP-LC3 adenovirus transfection was used for measuring autophagy. Signaling transduction was measured by immunofluorescence and immunoblotting. In addition, Achilles tendons from ApoE -/- mice fed with a high-fat diet were histologically assessed using HE staining and immunohistochemistry. RESULTS: In this work, we verified that 10 mg/dL cholesterol suppressed cell proliferation and migration and induced G0/G1 phase arrest. Additionally, cholesterol induced apoptosis and autophagy simultaneously in TDSCs. Apoptosis induction was related to increased expression of cleaved caspase-3 and BAX and decreased expression of Bcl-xL. The occurrence of autophagic flux and accumulation of LC3-II demonstrated the induction of autophagy by cholesterol. Compared with the effects of cholesterol treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) enhanced apoptosis, while the apoptosis inhibitor Z-VAD-FMK diminished cholesterol-induced autophagy. Moreover, cholesterol triggered reactive oxygen species (ROS) generation and activated the AKT/FOXO1 pathway, while the ROS scavenger NAC blocked cholesterol-induced activation of the AKT/FOXO1 pathway. NAC and the FOXO1 inhibitor AS1842856 rescued the apoptosis and autophagy induced by cholesterol. Finally, high cholesterol elevated the expression of cleaved caspase-3, Bax, LC3-II, and FOXO1 in vivo. CONCLUSION: The present study indicated that high cholesterol induced apoptosis and autophagy through ROS-activated AKT/FOXO1 signaling in TDSCs, providing new insights into the mechanism of hypercholesterolemia-induced tendinopathy. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.


Assuntos
Hipercolesterolemia , Proteínas Proto-Oncogênicas c-akt , Animais , Apoptose , Autofagia , Linhagem Celular Tumoral , Colesterol , Feminino , Proteína Forkhead Box O1 , Camundongos , Proteínas do Tecido Nervoso , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Células-Tronco , Tendões
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 24-28, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027248

RESUMO

OBJECTIVE: To investigate the clinical manifestations and laboratory features of B-ALL patients with EP300-ZNF384 fusion gene positive, so as to improve the understanding of this subtype disease. METHODS: The clinical data of 3 B-ALL patients with EP300-ZNF384 fusion gene positive admitted in Department of Hematology, the first medical center of Chinese PLA general hospital from February 2017 to February 2018 were collected and analyzed retrospectively. The clinical and laboratory characteristics as well as the therapentic outcome in B-ALL patients with EP300-ZNF384 fusion gene positive were analyzed. RESULTS: The fusion gene of EP300-ZNF384 was detected in 8.1%(3/37) of B-ALL patients. All cases showed the normal karyotype and aberrant CD13 and/or CD33 expression for immunophenotype. 3 patients were sensitive to traditional chemotherapy. CONCLUSION: The B-ALL with EEP300-ZNF384 fusion gene positive may be a subgroup of B-ALL with a uniqe clinical characteristis and laboatorial features. EP300-ZNF384 positive patients show a good response to conventional chemotherapy, suggesting a favorable prognosis.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteína p300 Associada a E1A , Humanos , Proteínas de Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos Retrospectivos , Transativadores , Fatores de Transcrição
9.
Drug Des Devel Ther ; 13: 3529-3538, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631977

RESUMO

Objective: Chondrocyte apoptosis has also been strongly correlated with the severity of cartilage damage and matrix depletion in an osteoarthritis (OA) joint. Therefore, pharmacological inhibitors of apoptosis may provide a novel treatment option for patients with OA. Aucubin, a natural compound isolated from Eucommia ulmoides, has been proved to possess antioxidative and anti-apoptotic properties. However, anti-osteoarthritis effect of aucubin in animal model and anti-apoptotic response of aucubin in OA chondrocytes remain unclear. This study aimed to determine whether aucubin could slow progression of OA in a mouse model and inhibit the IL-1ß-induced chondrocyte apoptosis. Methods: OA severity and articular cartilage degradation were evaluated by Safranin-O staining, Hematoxylin-eosin (H&E) staining, and Osteoarthritis Research Society International (OARSI) standards. Chondrocyte viability was observed by Cell Counting Kit-8 (CCK8) and live/dead cells assay; the apoptotic rate of chondrocytes was evaluated by flow cytometry (FCM) with Annexin V-FITC/PI kit. Mediators of apoptosis were tested by Western blot of Bax, caspase-3, caspase-9, and Bcl-2 expression. The intracellular levels of Reactive oxygen species (ROS) were assessed by the probe of 2,7-Dichlorofluorescin diacetate (DCFH-DA). Results: The articular cartilage in the limb with destabilization of the medial meniscus (DMM) exhibited early OA-like manifestations characterized by proteoglycan loss, cartilage fibrillation, and erosion, with lower OARSI score. Oral administration of aucubin remarkably attenuated the loss of proteoglycan and the articular cartilage erosion and decreased the OARSI scores underwent DMM surgery. Aucubin treatment significantly reverses IL-1ß-induced cytotoxicity and attenuated the IL-1ß-induced chondrocyte apoptosis. In addition, aucubin can significantly inhibit mediators of apoptosis in rat primary chondrocytes. Furthermore, aucubin remarkably attenuated the IL-1ß-induced intracellular ROS production. Conclusion: Our findings suggest that aucubin has a protective effect on articular cartilage and slowing progression of OA in a mouse model. This protective effect may result from inhibiting chondrocyte apoptosis and excessive ROS production.


Assuntos
Apoptose/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Glucosídeos Iridoides/farmacologia , Osteoartrite/tratamento farmacológico , Substâncias Protetoras/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/metabolismo , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoartrite/metabolismo , Osteoartrite/patologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 995-1000, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418347

RESUMO

OBJECTIVE: To retrospectively analyze the clinical manifestation, laboratorial test features and prognosis of patients with CML in myeloid blast crisis. METHODS: The clinical data of 10 patients with CML in myeloid blast crisis admitted in Chinese PLA General Hospital from June 2011 to May 2018 were collected, and their clinical features, laboratorial data and long-term survival were analyzed. RESULTS: The median age of these 10 cases was 32.5 (23-73) years old. Nine cases had chronic phase history. The median chronic phase was 17(4-84) months. All the 10 cases had splenomegaly; B-ultrasonography showed that the median spleen size was 5.2 (4-7.8) cm in thickness, and 14.6 (11.4-19.8) in length. When chronic myeloid leukemia was in blast crisis, the median WBC count was 41.705(11.9-344.41)×109 /L and the median platelet count was 159 (13-2326) ×109 /L. The Ph+ chromosome and BCR-ABL1 fusion gene coulld be detected in all the cases. The chromosome karyotyping showed that additional chromosome abnormalities were found in 5 cases. One case was of low diploid, and two cases were with complex karyotype. ABL1 mutation was detected in 6 out of these 10 cases. ABL1 T315I mutation was detected in 2 of them and one was with deletion of combined P53 in genetic tests. The median follow-up time was 10.5(0.2-78) months. There were 5 cases treated sequentially by chemotheraphy with or without TKI and allo-HSCT. Three cases reached CP2 before transplantation. Among them, two cases still survived without progression for 67 months and 69 months after the transplantation respectively. One case died of transplantation-related mortality (suffered from cerebral hemorrhage 7 months after the transplantation). Two cases were NR before the transplantation, and both died of disease relapse or progression at the time points of one or three months after the transplantation. Five cases treated by TKI ± chemotheraphy and without HSCT succumbed to disease progression. The median time was 6(0.2-22) months. CONCLUSION: CML patients in myeloid blast crisis treated by chemotheraphy combined with TKI gain CP2, the survival time of patients treated by sequential allo-HSCT is prolonged.


Assuntos
Crise Blástica , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adulto , Idoso , Aberrações Cromossômicas , Proteínas de Fusão bcr-abl , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
Bone ; 125: 140-150, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31108241

RESUMO

Crosstalk between subchondral bone and articular cartilage is considered a central feature of osteoarthritis (OA) initiation and progression, but its underlying molecular mechanism remains elusive. Meanwhile, specific administration of drugs in subchondral bone is also a great challenge during investigation of the process. We here explore the role of stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis in the crosstalk between subchondral bone and articular cartilage in OA pathogenesis, using osmotic infusion pumps implanted in tibial subchondral bone directly to ensure quantitative, continuous and steady drug delivery over the entire experiment. We found that increased SDF-1 in subchondral bone firstly induced subchondral bone deterioration by erroneous Mesenchymal Stem Cells (MSCs) recruitment and excessive bone resorption in anterior cruciate ligament transection (ACLT) mice. Deterioration of subchondral bone then led to the traverse of SDF-1 from subchondral bone to overlying cartilage. Finally, SDF-1 from underlying subchondral bone combined with CXCR4 in chondrocytes to induce articular cartilage degradation by promoting the shift of transforming growth factor-ß receptor type I (TßRI) in chondrocytes from activin receptor-like kinase 5 (ALK5) to activin receptor-like kinase 1 (ALK1). More importantly, specific inhibition of SDF-1/CXCR4 axis in ACLT rats attenuated OA by stabilizing subchondral bone microarchitecture, reducing SDF-1 in cartilage and abrogating the shift of TßRI in chondrocytes. Our data demonstrate that the SDF-1/CXCR4 axis may coordinate the crosstalk between subchondral bone and articular cartilage in OA pathogenesis. Therefore, specific inhibition of SDF-1/CXCR4 axis in subchondral bone or intervention in SDF-1 traverse may be therapeutic targets for OA.


Assuntos
Cartilagem Articular/citologia , Cartilagem Articular/metabolismo , Quimiocina CXCL12/metabolismo , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Receptores CXCR4/metabolismo , Animais , Western Blotting , Cartilagem Articular/patologia , Quimiocina CXCL12/genética , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Receptores CXCR4/genética
12.
Biomed Res Int ; 2019: 7483537, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949508

RESUMO

Background: Previous studies had indicated that interleukin-1 beta (IL-1ß) gene single nucleotide polymorphisms (SNPs) associate with different inflammatory diseases. However, potential links between these polymorphisms and susceptibility to extremity chronic osteomyelitis (COM) remain unclear. This study aimed to investigate relationships between IL-1ß gene polymorphisms (rs16944, rs1143627, rs1143634, and rs2853550) and risks of developing extremity COM in Chinese Han population. Methods: Altogether 233 extremity COM patients and 200 healthy controls were genotyped for the four tag SNPs of the IL-1ß gene using the SNapShot genotyping method. Comparisons were performed regarding genotype distribution, mutant allele frequency, and four genetic models (dominant, recessive, homozygous, and heterozygous models) of the four SNPs between the two groups. Results: Significant associations were identified between rs16944 polymorphism and the risk of developing COM by dominant model (P = 0.026, OR = 1.698, 95% CI 1.065-2.707) and heterozygous model (P = 0.030, OR = 1.733, 95% CI 1.055-2.847). Although no statistical differences were found of rs1143627 polymorphism between the two groups, there existed a trend that rs1143627 may be linked to an elevated risk of developing COM by outcomes of dominant (P = 0.061), homozygous (P = 0.080) and heterozygous (P = 0.095) models. However, no statistical correlations were found between rs1143634 and rs2853550 polymorphisms and susceptibility to COM in Chinese Han population. Conclusions: To our knowledge, we reported for the first time that IL-1ß gene rs16944 polymorphism may contribute to the increased susceptibility to extremity COM in Chinese Han population, with genotype of AG as a risk factor.


Assuntos
Grupo com Ancestrais do Continente Asiático , Frequência do Gene , Predisposição Genética para Doença , Interleucina-1beta/genética , Osteomielite , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , China/etnologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/etnologia , Osteomielite/genética
13.
J Cell Physiol ; 234(10): 17946-17958, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30834523

RESUMO

To identify the effects of running on articular cartilage and subchondral bone remodeling, C57BL/6 mice were randomly divided into three groups: control, moderate-, and strenuous running. Magnetic resonance imaging showed bone marrow lesions in the knee subchondral bone in the strenuous-running group in contrast with the other two groups. The microcomputed tomography analysis showed promoted bone formation in the subchondral bone in mice subjected to strenuous running. Histological and immunohistochemistry results indicated that terminal differentiation of chondrocytes and degeneration of articular cartilage were enhanced but, synthesis of platelet-derived growth factor-AA (PDGF-AA) in the subchondral bone was suppressed after strenuous running. In vitro, excessive mechanical treatments suppressed the expression of PDGF-AA in osteoblasts, and the condition medium from mechanical-treated osteoblasts stimulated maturation and terminal differentiation of chondrocytes. These results indicate that strenuous running suppresses the synthesis of PDGF-AA in subchondral bone, leading to downregulated PDGF/Akt signal in articular cartilage and thus cartilage degeneration.


Assuntos
Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Fêmur/metabolismo , Osteoblastos/metabolismo , Osteogênese , Esforço Físico , Fator de Crescimento Derivado de Plaquetas/metabolismo , Corrida , Tíbia/metabolismo , Animais , Cartilagem Articular/patologia , Diferenciação Celular , Células Cultivadas , Condrócitos/patologia , Regulação para Baixo , Feminino , Fêmur/diagnóstico por imagem , Camundongos Endogâmicos C57BL , Fator de Crescimento Derivado de Plaquetas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Tíbia/diagnóstico por imagem
14.
J Shoulder Elbow Surg ; 28(7): 1411-1421, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30826202

RESUMO

BACKGROUND: It is usually difficult to diagnose clavicular osteomyelitis (OM), and treatment is delayed because of its rarity. This study aimed to summarize clinical characteristics and treatment of this disease. METHODS: We searched the PubMed and Embase databases to identify English studies that reported on clavicular OM from January 1980 through December 2016. Effective data were pooled for analysis. RESULTS: In total, 111 studies comprising 294 cases (bacterial OM, 146; nonbacterial OM, 148) were included, with a sex ratio of 1.89:1 indicating female predilection. Overall, the median age at diagnosis was 16 years. The acute to chronic phase ratio was 0.30, with a median symptom duration of 4 months. The most frequently reported symptom was pain (192 cases), followed by swelling (151 cases) and fever (52 cases). Altogether, 86.94% cases of single-site involvement were reported, with the medial side being the most common site (69.95%). The erythrocyte sedimentation rate achieved the highest positive rate (74.44%) before treatment. The total positive rate of culture for bacterial OM was 81.82%, with Staphylococcus aureus being the most frequently detected pathogen (44.70%). The average cure rate was 83.52%, with no significant difference between surgical (89.70%) and nonsurgical (79.63%) cases (P = .079). CONCLUSIONS: Clavicular OM, predominant in female patients and young people, usually occurred at a chronic stage. Pain was the most frequent symptom, with the medial side being the most involved site. The erythrocyte sedimentation rate may be a helpful indicator for diagnosis. Regardless of surgery or nonsurgery, most patients achieved a favorable prognosis.


Assuntos
Clavícula , Osteomielite/diagnóstico , Sedimentação Sanguínea , Edema/etiologia , Febre/etiologia , Humanos , Osteomielite/etiologia , Osteomielite/terapia , Dor/etiologia , Infecções Estafilocócicas , Staphylococcus aureus
15.
Per Med ; 15(5): 395-401, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30259788

RESUMO

AIM: This study aims to investigate the link between TNF-α gene SNPs and patients with extremity chronic osteomyelitis in China. METHODOLOGY: Our study included 433 subjects, composed of 233 extremity chronic osteomyelitis patients and 200 controls. Six single-nucleotide polymorphisms (rs1799964, rs1800630, rs1799724, rs1800750, rs1800629 and rs361525) in TNF-α gene were detected by the SNaPshot genotyping method. RESULTS: Significant genotype distribution of rs1799964 was identified between patients and healthy controls (p = 0.045). In addition, statistical difference was found between rs1799964 SNP and the susceptibility to extremity chronic osteomyelitis (p = 0.044). CONCLUSION: We reported for the first time that TNF-α gene SNP rs1799964 contributes to the elevated venture of extremity chronic osteomyelitis in China.


Assuntos
Osteomielite/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Doença Crônica , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Orthop Surg ; 10(3): 218-226, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30152611

RESUMO

OBJECTIVE: Iatrogenic radial nerve injury is a great challenge for orthopaedic surgeons who deal with distal-third diaphyseal humerus fractures. Conventional open reduction and internal fixation (ORIF) remains the gold standard, but complications such as nonunion and iatrogenic radial nerve injury still occur. We fixed the fractures with a lateral locking compression plate (LCP) subcutaneously after small incision reduction to protect the radial nerve. This study reports the clinical and radiographic outcomes of our modified method. METHODS: Thirty-eight patients with distal-third diaphyseal humerus fractures were treated with lateral subcutaneous LCP and small incision reduction at our department between September 2013 and August 2016. There were 33 males and 5 females, with an average age of 30.3 years (range, 17 to 49 years). All the cases were types A or B (AO/OTA classification, type A, 24 cases; type B, 14 cases). Among them, 6 cases were combined with preoperative radial nerve palsy. All patients were diagnosed with closed humeral fractures after X-ray examination, and had typical upper limb pain, swelling, and movement disorders. The operations were performed by a single surgeons' team. Union time, range of motion (ROM), University of California, Los Angeles (UCLA) shoulder rating scale, and Mayo Elbow Performance Index (MEPI) scores were assessed to evaluate the postoperative results. RESULTS: All patients were followed up for an average of 11.4 months (range, 3 to 36 months). The average operation time was 75.5 min (range, 60 to 150 min) and average intraoperative radiation exposure was 10.5 s (range, 8 to 18 s). Bony union was achieved in all cases after an average of 16.2 weeks (range, 12 to 25 weeks). No complications such as infection or screw and plate fracture occurred, and no iatrogenic radial nerve injury was observed. According to the UCLA shoulder rating scale, the average score was 33.7 (range, 31 to 35), with 33 excellent (86.8%) and 5 good cases (13.2%). They were all excellent according to their MEPI scores (ranging, 94 to 100, with an average of 97.4). The average operation time for secondary removal of the plate was 15.2 min (range, 10 to 20 min), and no complications such as infection or secondary radial nerve injury occurred. CONCLUSIONS: Lateral subcutaneous LCP and small incision reduction may reduce the risk of iatrogenic radial nerve injury significantly in the treatment of distal-third diaphyseal humerus fractures. It also leads to solid fixation, good postoperative function, and convenient removal of the plate without injuring the radial nerve.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Adolescente , Adulto , Diáfises/diagnóstico por imagem , Diáfises/cirurgia , Articulação do Cotovelo/fisiopatologia , Feminino , Seguimentos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Consolidação da Fratura , Humanos , Fraturas do Úmero/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias , Período Pós-Operatório , Nervo Radial/lesões , Neuropatia Radial/etiologia , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos , Articulação do Ombro/fisiopatologia , Adulto Jovem
17.
Front Microbiol ; 9: 1093, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887852

RESUMO

Osteomyelitis (OM) is a complicated and serious disease and its underlying molecular signatures of disease initiation and progression remain unclear. Staphylococcus aureus (S. aureus) is the most common causative agent of OM. Previous study of Banchereau et al. has established a link between whole blood transcription profiles and clinical manifestations in patients infected with S. aureus. However, the differentially expressed genes (DEGs) in OM induced by S. aureus infection have not been intensively investigated. In this study, we downloaded the gene expression profile dataset GSE30119 from Gene Expression Omnibus, and performed bioinformatic analysis to identify DEGs in S. aureus infection induced OM from the transcriptional level. The study consisted of 143 whole blood samples, including 44 healthy controls, 42 OM-free, and 57 OM infection patients. A total of 209 S. aureus infection-related genes (SARGs) and 377 OM-related genes (OMRGs) were identified. The SARGs were primarily involved in the immune response by GO functional and pathway enrichment analysis. Several proteins adhere to neutrophil extracellular traps may be critical for the immune response to the process of S. aureus infection. By contrast, the OMRGs differ from the SARGs. The OMRGs were enriched in transmembrane signaling receptor and calcium channel activity, cilium morphogenesis, chromatin silencing, even multicellular organism development. Several key proteins, including PHLPP2 and EGF, were hub nodes in protein-protein interaction network of the OMRGs. In addition, alcoholism, systemic lupus erythematosus and proteoglycans in cancer were the top pathways influenced by the OMRGs associated with OM. Thus, this study has further explored the DEGs and their biological functions associated with S. aureus infection and OM, comparing with the previous study, and may light the further insight into the underlying molecular mechanisms and the potential critical biomarkers in OM development.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 684-690, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950204

RESUMO

OBJECTIVE: To investigate the safety and efficacy of high dose tigecycline for treatment of fibric neutrope-nia in acute leukemia patients after ineffectiveness of carbapenems chemotherapy of acute leukemia. METHODS: The clinical data of 41 acute leukemia patients with febrile ncutropenia received high dose tigecycline (100 mg q12h), who showed ineffectiveness of treatment with carbapenems, from 20151.30-2017.1. 29 in our hospital were collected and analyzed retrospectively. The temperature, inflammatory indicators as well as hepatic and renal function before and after treatment with tigecycline were compared. RESULTS: Among 41 patients treated with tigecycline due to ineffectiveness of treatment with carbapenems, the infection had been controled in 34 cases, 7 patients died due to ineffectiveness of anti-infective treatment, these patients all were patients with relapse/refractory leukemia. 41 patients were examined etialogically, as a result, 22 patients showed possitive, among them the gram-negative bacill was found in 11(11/22) cases. The average deferves counce time of tigecycline was 28.2±12.0 hours. The temperature of patients treated with tigecycline for 48 hours decreased significantly (P<0.05). There were no significant differences in calcitonin and C-reactive protein levels after treatment with tigecycline (P>0.05), but cacitonin level displayed decrease tread. There was no hepatic and renal impairment after treatment with tigecycline, but levels of as partate aminotransferase, total bilirubin and blood area nitrogen in blood significantly increased as compared with levels before treatment with tigecycline (P<0.05). CONCLUSION: The application of high dose tigecycline for treatment of febrile neutropenia is safety and effective. The high dose tigecycline can decrease the temperature, calcitonin and C-reactive protein levels, and can control infection without the hepatic and renal impairment, but it needs to be confimed by more prospective studies.


Assuntos
Neutropenia Febril , Antibacterianos , Carbapenêmicos , Humanos , Minociclina/análogos & derivados , Estudos Retrospectivos , Tigeciclina
19.
Oncotarget ; 8(32): 53654-53663, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28881839

RESUMO

In this study, we first initiated a multicenter, single-arm, phase-II clinical trial using decitabine (DAC) (20mg/m2 for five days) based chemotherapy, followed by haploidentical lymphocyte infusion (HLI) that was applied as induction therapy for elderly patients with AML. Furthermore, the role of HLI infusion was explored in a mouse model. The clinical trial included 29 elderly patients (median age: 64, range 57-77) with AML. Sixteen cases achieved complete remission (CR) and 9 cases achieved partial remission (PR) after the first treatment cycle. Of the patients with PR, 5 subjects achieved remission after the second induction, which brings the overall CR rate to 72.4%. The 2-year overall survival (OS) and disease-free survival (DFS) was 59.6% and 36.9% respectively. The treatment regimen was well tolerated with only one patient died of severe pneumonia one month after the first treatment. In the mouse experiment, we found that DAC/HLI significantly enhanced the survival of leukemic mice. These results suggested that DAC-based chemotherapy combined with HLI is an alternative first line induction therapy for elderly patients with AML. This trial is registered at ClinicalTrials.gov (NCT01690507).

20.
Biomark Med ; 11(8): 597-605, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28770614

RESUMO

AIM: This study aimed to investigate the values of preoperative serum levels of white blood cell, erythrocyte sedimentation rate (ESR), C-reactive protein, procalcitonin, IL-6, TNF-α and serum amyloid A for diagnosis of chronic osteomyelitis (COM) in Chinese patients. METHODS: All 586 eligible patients were included for analysis. RESULTS: Outcomes revealed that positive ratios of TNF-α, ESR and IL-6 lied in top three. Taken predicted probability and detection cost into consideration, combination of ESR, IL-6 and TNF-α might be the optimal model due to its high predicted probability for COM (91.02%) with an acceptable cost (CN¥161). CONCLUSION: Combination of preoperative serum TNF-α, ESR and IL-6 can help a reliable predication of COM.

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