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1.
Ann Palliat Med ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34806394

RESUMO

BACKGROUND: Diabetes is an independent risk factor for COVID-19 patients, and SARS-CoV-2 infection may in turn induce hyperglycemia. In this work, we will map the trends of global research of COVID-19 and diabetes by using the method of bibliometric analysis, help researchers quickly understand the research hotspots and find meaningful research directions. METHODS: Documents related to COVID-19 and diabetes were obtained from the database of Science Citation Index Expanded of Web of Science. We then analysed the data by country/organization coauthorship analysis, sources/documents citation analysis, and keywords co-occurrence analysis. VOSviewer was applied to map the global research trends and hotspots in this field. RESULTS: A total of 1,206 articles were retrieved, including a total of 101 countries, 2,595 organizations, 526 journals, and 3,405 keywords. China had the highest total citations, followed by the United States, while these two countries were reversed in terms of the number of documents. Half of the top 10 highly cited organizations were from China, including Capital Medical University, which had the highest citations, and Huazhong University of Science and Technology, which had the largest number of documents. Diabetes Research and Clinical Practice was the most productive journal. Journal of Medical Virology was the most highly cited journal. Zhou et al.'s article (The Lancet, 2020) was the most representative and widely cited. The keywords mainly focused on 3 categories, namely risk factors & clinical outcomes, receptor ACE2 & cytokine storm, as well as clinical characteristics & epidemiology. Among them, hyperglycemia, obesity, outcomes, and cytokine storm are the hotspots of recent concern. CONCLUSIONS: This research mapped the global research trends in COVID-19 and diabetes, which may help researchers identify relevant collaborators and discover current hotspots and potential research directions.

2.
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
3.
Ann Palliat Med ; 10(4): 3726-3738, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33832287

RESUMO

BACKGROUND: Osteomyelitis is a difficult problem for orthopedic surgeons due to its great harm and complicated treatment. In this study, we aim to make a bibliometric analysis of the literature related to osteomyelitis and explore the research status, hotspots and frontiers in this field in recent 10 years. METHODS: Literature relating to osteomyelitis from 2010 to 2019 was retrieved from the database of Science Citation Index Expanded (SCIE) of Web of Science. CiteSpace was used to analyze country/institution, authors/cited authors, cited journals, cited references, and keywords. An analysis of counts and centrality was used to reveal publication outputs, countries/institutions, core journals, active authors, hot topics, and frontiers. RESULTS: A total of 6,421 valid literatures were retrieved. The most productive country and institution were the United States and Shanghai Jiao Tong University, respectively. Researchers and institutions from the United States, Germany, England, and France were the core research forces. There was a broad and close cooperation worldwide. Lipsky BA [24] was the most productive first author, and Lew DP [487] was the most frequently cited author. Lipsky et al.'s [2012] article (co-citation counts, 146) was the most representative and symbolic reference. Journal of Foot Ankle Surgery [111] was the most productive journal. Clin Infect Dis [2,275] was the most frequently co-cited journal. Staphylococcus aureus infection and the diagnosis, treatment and management strategy of osteomyelitis were the hot spots. Epidemiology, diabetic foot, treatment, especially antibiotics, biofilm and in vitro research were research frontiers. CONCLUSIONS: This study reveals the current research status and hot spots in the field of osteomyelitis in recent 10 years, which may help researchers to identify further potential perspectives on collaborators, research frontiers, and hot topics.


Assuntos
Bibliometria , Osteomielite , China , Inglaterra , França , Alemanha , Humanos , Estados Unidos
4.
Oncol Lett ; 20(4): 18, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32774491

RESUMO

Hepatitis B virus (HBV) infection is a critical factor for the initiation and progression of hepatocellular carcinoma (HCC). Gene expression profiles for HBV-associated HCC may provide valuable insight for the diagnosis and treatment of this type of HCC. The present study aimed to screen the differential genes in human HCC tissues based on high-throughput sequencing and to predict the potential therapeutic targets. Total mRNA was extracted from human HCC tissues and paracancerous tissues and sequenced using the Hiseq4000 sequencing platform. Differential gene expressions were screened and further analyzed using quantitative PCR and immunohistochemistry. A total of 2,386 differentially expressed genes were screened. Of these, 1119 were upregulated and 1,267 were downregulated in paracancerous tissues compared with tumor tissues. Gene Ontology term analysis demonstrated that differentially expressed genes were involved in carboxylic acid catabolism, monocarboxylic acid metabolic processes and α-amino acid metabolic processes. Molecular functional analysis revealed that the differentially expressed genes functioned in oxidoreductase activity, for example acting on CH-OH group of donors and permitting identical protein binding, anion binding, coenzyme binding and monocarxylic acid transporter activity. The Kyoto Encyclopedia of Genes and Genomes analysis reported that the differentially expressed genes were primarily concentrated in 20 signaling pathways, such as valine, leucine and leucine degradation, retinol metabolism and the cell cycle. Differential expression of proteins regulating the cell cycle, including stratifin, cyclin B1 and cyclin-dependent kinase 1, were significantly higher in tumor tissue compared with those in paracancerous tissue at both the mRNA and protein levels. These results were consistent with those obtained from high-throughput sequencing, indicating the reliability of the high-throughput sequencing. Together, these results identified differentially expressed genes and predicted the subsequent signaling pathways, which may be involved in the occurrence and development of HCC. Therefore, the present study may provide novel implications in the therapeutic and diagnosis of HCC.

5.
Chin J Integr Med ; 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32829446

RESUMO

OBJECTIVE: To explore the prescription patterns of different dosage forms of Chinese herbal medicines (CHMs) for the treatment of rheumatoid arthritis (RA) and their effects on immune-inflammatory indices. METHODS: Clinical data were collected from patients with RA in 4 hospitals (3 Class A comprehensive hospitals and 1 Class B comprehensive hospital) in Anhui Province, China, from August 2012 to June 2018 via the electronic medical record gathering system. Following extraction of prescription information, each prescribed herb was quantified and standardized according to the knowledge base to establish a database of RA treatment formulae. The medical records were divided into the granules group and decoction pieces group. Core herbs and their combination patterns were obtained from the two groups of cases using Liquorice software. Changes in immune-inflammatory and hepatic and renal function indices were compared between the two groups using SPSS 23.0 software. The Aprior module of SPSS Clementine 11.1 software was applied to analyse the correlation between CHMs and improvement in indices. Finally, the ORACLE 10 g tool was used to evaluate the random walk model of the immune-inflammatory indices between the two groups. RESULTS: (1) We retrospectively analysed 35,898 prescriptions for 6,829 patients with RA who received CHM treatment. There were 3,816 patients in the granules group and 3,013 in the decoction pieces group. (2) The core herbs were Pi (Spleen)-strengthening and dampness-resolving drugs, blood-activating and stasis-resolving drugs, wind/dampness-dispelling drugs and heat-clearing and detoxifying drugs. (3) Both dosage forms could improve immune-inflammatory indices in RA patients, with similar efficacy and no influence on hepatic or renal function. (4) Herba Siegesbeckiae and Oldenlandia had a stronger association with immune-inflammatory indices in the two groups. (5) The immune-inflammatory indices showed obvious improvement after treatment with granules and decoction pieces of CHMs, and there were long range correlations between the comprehensive evaluation indices and interventions. CONCLUSIONS: The principal CHM treatment methods for RA in four hospitals in Anhui Province are strengthening Pi and resolving dampness, activating blood and resolving stasis, dispelling wind/dampness and clearing heat. Granules and decoction pieces of CHMs have similar efficacy in improving immune-inflammatory indices in RA patients and could be used as treatment options for RA.

6.
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.

7.
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
8.
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.
Exp Ther Med ; 18(1): 154-162, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31258649

RESUMO

A colonoscopy is considered to be the standard diagnostic test used to detect early colorectal lesions. Detection rates are expected to improve with optimised visualisation. A systematic review and network meta-analysis was conducted to evaluate detection efficiency in several colonoscopic modalities. Relevant articles were identified in searches of the PubMed, EMBASE and Cochrane Library databases. The modalities, comprising of standard-definition white light (SDWL), high-definition white light (HDWL), narrow-band imaging (NBI), autofluorescence imaging (AFI), PENTAX image enhanced technology (i-SCAN), Fuji Intelligent Color Enhancement (FICE), dye-based chromoendoscopy and novel image enhanced systems, including blue laser imaging (BLI) and linked color imaging (LCI), were compared to identify the most efficient modalities that could be used to detect colorectal lesions. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. As a result, 40 studies fulfilled the inclusion criteria. Overall, in the network meta-analyses, NBI (OR, 1.29; 95% CI, 1.04-1.58), FICE (OR, 1.39; 95% CI, 1.11-1.77), chromoendoscopy (OR, 1.53; 95% CI, 1.22-1.93) and AFI (OR, 1.81; 95% CI, 1.07-2.87) were significantly better compared with SDWL at identifying adenoma in patients, and chromoendoscopy also proved significantly superior to HDWL (OR, 1.30; 95% CI, 1.06-1.60). In pairwise analyses, it was demonstrated that chromoendoscopy was significantly superior to HDWL at detecting the number of polyps (MD, -1.11; 95% CI, -1.46, -0.76) and flat lesions (MD, -0.30; 95% CI, -0.49, -0.10) per subject. Additionally, FICE detected a significantly greater number of subjects with polyps (OR, 0.78; 95% CI, 0.64-0.96) and NBI was significantly better at detecting the number of subjects with flat lesions (OR, 0.77; 95% CI, 0.60-0.99) compared with HDWL. Based on the meta-analysis, NBI, FICE and AFI were significantly better compared with SDWL at detecting patients with adenoma. Additionally, chromoendoscopy was significantly better than SDWL and HDWL at detecting the number of colorectal adenoma, however additional studies are needed to confirm these findings.

11.
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
12.
Oncol Rep ; 41(4): 2471-2481, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816466

RESUMO

Gastric cancer (GC) is an aggressive and highly lethal gastrointestinal cancer, with an exceedingly poor prognosis. In the present study, the carcinogenic mechanism of human GC and the role of cell division cycle­associated 3 (CDCA3) were investigated. The expression levels of CDCA3 were investigated in GC samples and matched, peritumoral tissues by reverse transcription­quantitative polymerase chain reaction and immunohistochemical analysis. The effects of CDCA3 on cell proliferation were explored by Cell Counting Kit­8, colony formation, flow cytometric analysis and western blotting in vitro, and in vivo tumorigenesis in nude mice. The results demonstrated that CDCA3 expression was increased in human GC tissues compared with those in adjacent non­tumor tissues. Evaluation of the clinicopathological significance indicated that CDCA3 was closely associated with features of GC and patients with unfavorable overall survival times. CDCA3 overexpression resulted in the stimulation of cell growth and colony formation in vitro and xenograft tumors in vivo. Conversely, knockdown of CDCA3 inhibited these effects. Furthermore, the ectopic expression of CDCA3 in SGC7901 cells consistently promoted the cell cycle transition from the G0/G1 phase to the S phase; whereas knockdown of CDCA3 in BGC823 cells blocked the transition from the G0/G1 phase. Additionally, the present study revealed that the Ras signaling pathway was involved in CDCA3­mediated regulation of GC cell proliferation. CDCA3 activated the Ras signaling pathway to promote cell proliferation in vitro and in vivo in GC cells. Levels of CDCA3 greatly accelerated the progression of human GC. CDCA3 served as an oncogene, and may be a significant prognostic predictor and a novel therapeutic target for patients with GC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/patologia , Animais , Biomarcadores Tumorais/genética , Carcinogênese/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Seguimentos , Gastrectomia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Oncogenes/genética , Prognóstico , RNA Interferente Pequeno/metabolismo , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Mol Med Rep ; 18(6): 5044-5052, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30320384

RESUMO

Tendon repair follows a slow course of early inflammatory, proliferative and remodeling phases, which commonly results in the failure and loss of normal biomechanical properties. Previous studies have demonstrated that tendon­derived stem cells (TDSCs) are vital healing cells and that mRNA expression of anti­inflammatory cytokine interleukin (IL)­10 is significantly upregulated at the late inflammatory phase. To explore how IL­10 may impact tendon healing, the present study investigated the in vitro effects of IL­10 on TDSCs isolated from rat Achilles tendons. Cellular activities of TDSCs and the expression levels of tendon cell markers were measured treatment with IL­10 and subsequent performance of wound healing assays, reverse transcription­quantitative polymerase chain reaction and western blot analyses. The results demonstrated that IL­10 treatment markedly increased the proliferative capacity of TDSCs. In addition, IL­10 significantly enhanced cell migration when compared with the control cells. Furthermore, IL­10 treatment significantly activated the JAK/Stat3 signaling pathway and inhibited the protein expression of tendon cell markers, including scleraxis and tenomodulin. Notably, IL­10 treatment also reduced the gene expression levels of type 1 collagen, type 3 collagen, lumican and fibromodulin in TDSCs. These findings indicated that IL­10 enhanced cell proliferation and migration, and inhibited tenogenic differentiation in TDSCs in vitro. Reducing the negative effects whilst enhancing the positive effects of IL­10 may be a potential therapeutic target in tendon repair.


Assuntos
Diferenciação Celular , Interleucina-10/metabolismo , Janus Quinases/metabolismo , Fator de Transcrição STAT3/metabolismo , Células-Tronco/metabolismo , Tendões/citologia , Animais , Ciclo Celular , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Interleucina-10/farmacologia , Ratos , Cicatrização
14.
Biochem Biophys Res Commun ; 505(2): 346-352, 2018 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-30249393

RESUMO

Circular RNAs(circRNAs) are a class of non-coding RNAs that are widely expressed in a variety of cell species. The role they play in cancers is poorly understood, especially in colorectal cancer (CRC). Hsa_circRNA_103809 (hsa_circ_0072088, circZFR)has been demonstrated to be lowly expressed in colorectal cancer tissues and is associated with stage and lymph node metastasis of cancer tissues. Real-time quantitative PCR (qRT-PCR) was used to verify the relationship of hsa_circRNA_103809 between colorectal cancer and paired adjacent tissue in clinical tissue samples. Then, the proliferative capacity, migration ability, cell cycle, and apoptosis were measured using wound-healing assay, CCK8, transwell assay, flow cytometry, and the like, when hsa_circRNA_103809 expression in SW620 and COCA-2. The qRT-PCR, western bolt and other experiments verify that the expression of hsa_circRNA_103809 can regulate the expression of miR-532-3P and FOXO4. Hsa_circRNA_103809 was found to be significantly down regulated in CRC tissues and cell lines and compared with paired adjacent non-tumorous tissues and normal FHC cells. Hsa_circRNA_103809 participates in the regulation of biological functions through the miR-532-3P/FOXO4 axis in the CRC. Hsa_circRNA_103809 may be a potential novel gene target for the diagnosis and treatment of CRC.


Assuntos
Neoplasias Colorretais/patologia , MicroRNAs/metabolismo , RNA/genética , Fatores de Transcrição/metabolismo , Apoptose , Proteínas de Ciclo Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fatores de Transcrição Forkhead , Humanos , Metástase Linfática , Estadiamento de Neoplasias , RNA Circular
15.
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.

16.
Hum Pathol ; 72: 107-116, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29208564

RESUMO

Nectin-4, a member of the Nectin family that includes 4 Ca+-independent immunoglobulin-like cell adhesion molecules, plays a carcinogenic role in multiple cancers. However, Nectin-4 expression and its biological role in gastric cancer (GC) remain largely unknown. In this study, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to evaluate the expression patterns of Nectin-4 in GC specimens and cell lines. We observed that high expression of Nectin-4 in GC patients was associated with TNM stage and lymph node metastasis status, and poor prognosis. In addition, cell proliferation and cell migration assays in vitro and tumorigenicity in vivo were performed to observe the effects of up-regulation and down-regulation of Nectin-4 expression on GC cell phenotypes. In further studies, the PI3K/AKT signaling pathway was revealed to be involved in Nectin-4-mediated GC progression. These results demonstrated that Nectin-4 had a promoter effect on human GC cell growth and motility, indicating that Nectin-4 may serve as an effective therapeutic target in GC.


Assuntos
Moléculas de Adesão Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Gástricas/patologia , Idoso , Animais , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Metástase Linfática/genética , Masculino , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Estômago/patologia , Neoplasias Gástricas/genética
17.
Int J Clin Exp Pathol ; 10(8): 8633-8639, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966720

RESUMO

AIM: To investigate the expression of NIBP and its clinical significance in early colorectal cancer. PATIENTS AND METHODS: With immunohistochemistry, the expression of NIBP was detected in 23 patients of early colorectal cancer tissues, 102 patients of invasive colorectal cancer tissues, 32 patients of adenoma and 20 patients of normal tissues. The relationship between NIBP expression and clinicopathological characteristic of colorectal cancer were also analyzed. RESULT: We found that the positive rates of NIBP was higher in early colorectal cancer tissues (82.6%, 19/23) than those in adenomas and normal tissues (x2=29.07, P<0.05), but not significant than those in invasive colorectal cancer (x2=1.79, P>0.05). Positivity for T1N0M0, T2N0M0, II, III and IV was 82.6% (19/23), 80.0% (4/5), 78.0% (32/41), 63.6% (21/33), 56.5% (13/23), respectively. With the increase in TNM stage, the positive rate of NIBP decreased, the positive rate of T1N0M0 is highest than other TNM stages, but no statistically significant (P>0.05). CONCLUSION: These results suggested that NIBP is highly expressed in human early colorectal cancer tissues. NIBP might involve in the tumorigenesis and probably serve as a new marker for human early colorectal cancer.

18.
Biochem Biophys Res Commun ; 482(4): 870-876, 2017 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-27889608

RESUMO

SPOCK1 encodes a Ca2+-binding matricellular glycoprotein which plays an oncogenic role in cancer cells. However, the role of SPOCK1 in the pathogenesis of colorectal cancer (CRC) has not been determined. Here, SPOCK1 was found higher expressed in CRC tissues than that of adjacent normal tissues. Furthermore, up-regulated expression of SPOCK1 in CRC patients was associated with tumor size and TNM stage. In addition, we observed that the depletion of SPOCK1 inhibited proliferation in vitro and tumorigenicity in vivo and promoted apoptosis in cell culture. Our data suggest that inactivation of PI3K/Akt signaling pathway was involved in down-regulation of SPOCK1-mediated suppression of tumor cell proliferation. These results suggest that SPOCK1 expression is correlated with malignant features of CRC and may serve as potential therapeutic and preventive strategies for CRC.


Assuntos
Colo/patologia , Neoplasias Colorretais/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteoglicanas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reto/patologia , Regulação para Cima , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Colo/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteoglicanas/análise , Proteoglicanas/metabolismo , Reto/metabolismo , Transdução de Sinais
19.
Oncotarget ; 7(24): 36645-36654, 2016 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-27153560

RESUMO

BACKGROUND: Circulating tumor cells (CTC) are prognostic and predictive for several cancer types. Only limited data exist regarding prognostic or predictive impact of CTC on gastrointestinal stromal tumor (GIST) patients. The aim of our study was to elucidate the role of CTC in GIST patients. RESULTS: A total of 121 GIST patients and 54 non-GIST samples were enrolled in the study. The cutoff value for ANO1 positive was 3*10-5 and 65 (54%) GIST patients were defined as ANO1 positive. ANO1s were more frequently detected in unresectable patients. Tumor size, mitotic count and risk level were associated with ANO1 detection in resectable GIST patients. The presence of ANO1 significantly correlated with poor disease-free survival (15.3 versus 19.6 months, p = 0.038). Most patients turned ANO1-negative after surgery and inversely, all 21 patients with recurrence turned ANO1-positive with high ANO1 expression levels. Moreover, in the neoadjuvant setting, decline of ANO1 expression level correlated with the response of imatinib. METHODS: Cells from peripheral blood mononuclear cells tested positive for anoctamin 1, calcium activated chloride channel, ANO1 (DOG1) were considered as tumor CTC of GISTs. The expression levels of ANO1 were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The highest level of ANO1 expression in non-GIST samples was used as the "cutoff" value. CONCLUSION: ANO1 detection by qRT-PCR in peripheral blood is of clinical potential for monitoring recurrence and evaluating therapeutic efficacy of imatinib for GIST patients.


Assuntos
Anoctamina-1/genética , Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Proteínas de Neoplasias/genética , Células Neoplásicas Circulantes/metabolismo , Anoctamina-1/sangue , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/cirurgia , Regulação Neoplásica da Expressão Gênica , Humanos , Mesilato de Imatinib/uso terapêutico , Estimativa de Kaplan-Meier , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Recidiva Local de Neoplasia , Prognóstico , Estudos Prospectivos
20.
Biotechnol Prog ; 26(6): 1741-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20818654

RESUMO

Current strategies to repair fractures rely on orthopaedic surgeons harvesting bone from one area of the body, typically pelvis and transferring it to the fracture site. The amount of tissue available is therefore limited, requiring a second surgical procedure and often causing the patient long term pain. An alternative approach is utilise therapeutic cells contained within bone marrow aspirate during the primary procedure. The number of therapeutic cells within a fresh aspirate is insufficient to provide clinically acceptable bone healing in a timescale that is satisfactory to the surgeon and the patient. Therefore methods to efficiently concentrate bone marrow in the clinical setting are required. Centrifugation is the current method of choice but has limitations in that it requires large capital equipment, servicing and there are potential issues of tissue contamination. We have developed a novel, acoustically-assisted filtration device that addresses these limitations, delivering a concentrated bone marrow in a point of care, single use, fully disposable, compact device. An additional advantage is that the level of concentration required can be specified by the end user. The resulting bone marrow concentrate has been characterised in terms of cell number, viability and osteogenic potential using flow cytometry and alkaline phosphatase assay. When compared to recent clinical studies using bone marrow to repair non-union fractures, the findings from our work suggest that the bone marrow concentrate is likely to be highly therapeutic and clinically efficacious as a bone fracture repair strategy. A product concept for use in the clinical setting is presented.


Assuntos
Células da Medula Óssea/citologia , Filtração/métodos , Filtração/instrumentação , Humanos , Membranas Artificiais , Porosidade , Propriedades de Superfície , Vácuo
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