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1.
Int J Biol Macromol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32057858

RESUMO

CRISPR/Cas9 technology is an efficient genome editing tool for producing genetically modified animals. Carotenoids color the world around us and their accumulation in animals could be used to culture colorful new verities in animal breeding. ß, ß-carotene 9', 10'-oxygenase (BCO2) is an important enzyme during ß-carotene metabolism. In this research, one full-length cDNA sequence encoding BCO2 (named EcBCO2) were obtained from Exopalaemon carinicauda. The genomic structure analysis showed that EcBCO2 gene was composed of 9 exons and 8 introns. Then, the CRISPR/Cas9-mediated deletion of EcBCO2 gene was generated by co-microinjection of Cas9 mRNA and EcBCO2 sgRNA into one-cell stage embryos of E. carinicauda. Subsequently, the phenotype of EcBCO2-KO prawns was compared with that of wild-type prawns, which showed that EcBCO2-KO resulted in the color change in the hepatopancreas of prawns. In addition, the EcBCO2-KO prawns had a higher survival rate than wild-type prawns when the prawns were challenged with Vibrio parahaemolyticus or Aeromonas hydrophila. These results indicate that BCO2 gene could be used as a candidate gene in molecular marker-assistant breeding of prawns.

2.
J Phys Chem A ; 124(4): 618-624, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31894987

RESUMO

It is important to study nonlinear dynamical systems showing pH and temperature oscillations simultaneously. Here, we systematically investigated the bromate-sulfite reaction in its coupled system. Large-amplitude temperature oscillations could be measured accompanied by the pH oscillations with or without permanganate and manganese(II) ions. The modulation effects on the oscillatory dynamics of the bromate-sulfite reaction system produced by permanganate and manganese(II) ions were investigated in detail. On the one hand, with permanganate, an additional negative pH feedback process between permanganate and bisulfite occurs, leading to weakening the pH positive feedback. The above opposite effects make the period length change unmonotonically when adjusting the permanganate concentration and flow rate. On the other hand, with Mn2+ as the feedback agent, the nonmonotonic change of period was not obvious because it only contained one feedback loop, which can only reinforce negative feedback without affecting positive feedback.

3.
Gastrointest Endosc ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911077

RESUMO

BACKGROUND AND AIMS: Prediction models for esophageal squamous cell carcinoma are not common, and no model, which targets a clinical population, has previously been developed and validated. We aimed to develop a prediction model for estimating the risk of high-grade esophageal lesions for application in clinical settings, and to validate the performance of this model in an external population. METHODS: This model was developed based on results of endoscopic evaluation of 5,624 outpatients in one hospital in a high-risk region in northern China, and was validated using 5,765 outpatients who had undergone endoscopy in another hospital in a non-high-risk region in southern China. Predictors were selected with unconditional logistic regression analysis. The Akaike information criterion was used to determine the final model structure. Discrimination was estimated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed using a calibration plot with an intercept and slope. RESULTS: The final prediction model contained 5 variables, including age, smoking, BMI, dysphagia, and retrosternal pain. This model generated an AUC of 0.871 (95%CI, 0.842-0.946) in the development set, with an AUC of 0.862 after bootstrapping. The 5-variable model was superior to a single age model. In the validation population, the AUC was 0.843 (95% CI, 0.793-0.894). This model successfully stratified the clinical population into 3 risk groups and showed high ability for identifying concentrated groups of cases. CONCLUSIONS: Our model for esophageal high-grade lesions has a high predictive value. It has the potential for application in clinical opportunistic screening to aid decision-making for both healthcare professionals and individuals.

4.
Arch Orthop Trauma Surg ; 140(1): 11-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31127408

RESUMO

OBJECTIVE: To compare the clinical effect of 3D-printed template technology with X-ray fluoroscopy in assisting surgery for sacroiliac screws placement. DESIGN: Institutional review board-approved retrospective analysis. PATIENTS: The clinical data of 31 cases of sacroiliac complex injury between January 2015 and December 2016 were analyzed. There were 16 patients, males 11 and females 5, who underwent surgery assisted by 3D-printed template in template group, and that of contemporaneous 15 patients, males 11 and females 4, who underwent traditional surgery were gathered as fluoroscopy group. All those patients were followed up for more than 6 months. MAIN OUTCOME MEASURES: The operation time and X-ray fluoroscopy times for each screw placement, and the Matta and Majeed score were analyzed and the difference between the two group was tested. RESULTS: All cases were followed up for 6-20 months, average 11.4 ± 0.6 months. In template group, 19 screws were implanted. Each screw spent 25-38 min, average 27.2 ± 5.3 min, and need 2-5 times fluoroscopy, average 2.7 ± 0.5. The fracture reduction quality was evaluated by Matta score scale: excellent 10, well 4, fair 2, good rate 87.5%; and pelvic function were evaluated by Majeed score scale: excellent 11, well 3, fair 2, and good rate 87.5%. In fluoroscopy group, 17 screws were implanted. Each screw spent 45-70 min, average 60.3 ± 5.8 min, and needs 11-23 times fluoroscopy, average 15.4 ± 3.5. The fracture reduction quality was evaluated by Matta score scale: excellent 7, well 6, fair 2, and good rate 86.7%; and pelvic function was evaluated by Majeed score scale: excellent 6, well 6, fair 3, and good rate 80.0%. The difference in operation time, X-ray fluoroscopy times between template group and fluoroscopy group had statistical significance. But the Matta and Majeed score had no difference between two groups. CONCLUSION: Compared with traditional surgery, 3D-printed template technology-assisted surgery for sacroiliac screws placement in sacroiliac complex injury patients possesses advantage such as shortened operation time and reduced X-ray exposure times. This technology improves the safety profile of this operation and should be further studied in future clinical applications.

5.
Fish Shellfish Immunol ; 97: 421-431, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31846777

RESUMO

During the immune defense reaction of invertebrate, a plenty of reactive oxygen species (ROS) could be induced to product. Though ROS can kill foreign invaders, the accumulation of these reactive molecules in animals will cause serious cell damage. Carotenoids could function as scavengers of oxygen radicals. In this research, cDNA and genomic DNA of one carotenoid isomerooxygenase gene (named EcNinaB-X1) were cloned from Exopalaemon carinicauda. EcNinaB-X1 gene was composed of 12 exons and 11 introns. EcNinaB-X1 knock-out (KO) prawns were produced via CRISPR/Cas9 technology and the change of their phenotypes were analyzed. Of the 400 injected one-cell stage embryos with cas9 mRNA and one sgRNA targeting the first exon of EcNinaB-X1 gene, 26 EcNinaB-X1-KO prawns were generated and the mutant rate reached 6.5% after embryo injection. The EcNinaB-X1-KO prawns had significant lower mortality than those in wild-type group when the prawns were challenged with Vibrio parahaemolyticus or Aeromonas hydrophila. In conclusion, we first demonstrate the function of the carotenoid isomerooxygenase gene in immune defense of E. carinicauda by performing directed, heritable gene mutagenesis.

6.
Mol Cell Biol ; 40(5)2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31871129

RESUMO

Osteomyelitis, an infection of the bone and bone marrow, imposes a heavy burden on public health care systems owing to its progressive bone destruction and sequestration. Human bone mesenchymal stem cells (hBMSCs) play a key role in the process of bone formation, and mounting evidence has confirmed that long noncoding RNAs (lncRNAs) are involved in hBMSC osteogenic differentiation. Nevertheless, the exact function and molecular mechanism of lncRNAs in osteogenic differentiation during osteomyelitis development remain to be explored. In this study, hBMSCs were treated with staphylococcal protein A (SpA) during osteogenic differentiation induction to mimic osteomyelitis in vitro The results of lncRNA microarray analysis revealed that FAM83H-AS1 presented the lowest expression among the significantly downregulated lncRNAs. Functionally, ectopic expression of FAM83H-AS1 contributed to osteogenic differentiation of SpA-induced hBMSCs. Additionally, our findings revealed that FAM83H-AS1 negatively regulated microRNA 541-3p (miR-541-3p), and WNT3A was validated as a target gene of miR-541-3p. Mechanically, FAM83H-AS1 elevated WNT3A expression by competitively binding with miR-541-3p. Lastly, it was demonstrated that FAM83H-AS1/miR-541-3p/WNT3A ameliorated SpA-mediated inhibition of the osteogenic differentiation of hBMSCs, which provided a novel therapeutic strategy for patients with osteomyelitis.

9.
Carbohydr Polym ; 226: 115302, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582049

RESUMO

Hydrogels could be promising wound healing dressings that maintain a moist environment in the wound site and accelerate wound healing. However, the lack of antibacterial effect, suitable mechanical property and adhesiveness limits their applications. Here, we designed a quaternized chitosan-Matrigel-polyacrylamide (QCS-M-PAM) hydrogel with multi-functions. The morphology, swelling ratio, mechanical test, antimicrobial property, hemostatic performance and biocompatibility of the hybrid hydrogel were investigated in vitro and vivo. The hybrid hydrogel showed a three-dimensional (3D) microporous structure, high swelling ratio, excellent stretchable and compressive property, similar modulus to human skin, good adhesiveness, and low cytotoxicity. The results of histology and molecular testing in vivo demonstrated that the hybrid hydrogel could significantly enhance wound healing, collagen deposition, and induce skin adnexal regeneration by upregulating anti-inflammatory factors, and downregulating proinflammatory factors. Together, the present antibacterial hydrogels with hemostatic and adhesive properties are considered to have promising potential used as wound dressings for full-thickness skin defect.

10.
Carcinogenesis ; 40(12): 1445-1451, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31570939

RESUMO

The clonal evolution which drives esophageal squamous cell carcinoma (ESCC) from initiation in normal cell to primary carcinoma and metastases is poorly understood. In this study, multi-region whole-exome sequencing (WES) (284X) and whole-genome single nucleotide polymorphism genotyping were performed on a total of 109 samples of ESCC from 10 patients. This included 42 apparently normal samples of esophageal mucosa at increasing distances from the upper or lower boundaries of the primary tumor to the surgical margins of resection, 43 spatially separated tissue samples within primary tumor and 24 regional lymph node metastases. Phylogenetic analysis was performed to reconstruct ancestor-descendant relationships of clones and the clonal composition of multi-region samples. Mutations of cancer-related genes were validated by deep targeted sequencing (1,168X). Both inter- and intra-tumoral genetic heterogeneity were obvious across multi-region samples among ESCC patients. Clones varying in number from one to seven were discovered within each regional tumor or metastatic sample. Phylogenetic analysis demonstrated complex clonal evolution patterns. Regional lymph node metastases had characteristics of early initiation and polyclonal spreading, and could be derived from carcinoma in situ (CIS) directly. TP53 was the only gene harboring non-silent mutations identified across all multi-region tumor samples of all ten patients. Mutations of TP53 were also found in histologically normal mucosa in sites away from primary tumor.

11.
Chin J Cancer Res ; 31(4): 699-706, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31564812

RESUMO

Objective: To evaluate the accuracy of identifying cancer patients by use of medical claims data in a health insurance system in China, and provide the basis for establishing the claims-based cancer surveillance system in China. Methods: We chose Hua County, Henan Province as the study site, and randomly selected 300 and 1,200 qualified inpatient electronic medical records (EMRs) as well as the New Rural Cooperative Medical Scheme (NCMS) claims records for cancer patients in Hua County People's Hospital (HCPH) and Anyang Cancer Hospital (ACH) in 2017. Diagnostic information for NCMS claims was evaluated on an individual level, and sensitivity and positive predictive value (PPV) were calculated taking the EMRs as the gold standard. Results: The sensitivity of NCMS was 95.2% (93.8%-96.3%) and 92.0% (88.3%-94.8%) in ACH and HCPH, respectively. The PPV of the NCMS was 97.8% (96.7%-98.5%) in ACH and 89.0% (84.9%-92.3%) in HCPH. Overall, the weighted and combined sensitivity and PPV of NCMS in Hua County was 93.1% and 92.1%, respectively. Significantly higher sensitivity and PPV in identifying patients with common cancers than non-common cancers were detected in HCPH and ACH separately (P<0.01). Conclusions: Identification of cancer patients by use of the NCMS is accurate on individual level, and it is therefore feasible to conduct claims-based cancer surveillance in areas not covered by cancer registries in China.

12.
Nat Biomed Eng ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611679

RESUMO

Implanted bioengineered livers have not exceeded three days of continuous perfusion. Here we show that decellularized whole porcine livers revascularized with human umbilical vein endothelial cells and implanted heterotopically into immunosuppressed pigs whose spleens had been removed can sustain perfusion for up to 15 days. We identified peak glucose consumption rate as a main predictor of the patency of the revascularized bioengineered livers (rBELs). Heterotopic implantation of rBELs into pigs in the absence of anticoagulation therapy led to sustained perfusion for three days, followed by a pronounced immune responses directed against the human endothelial cells. A 10 day steroid-based immunosuppression protocol and a splenectomy at the time of rBEL implantation reduced the immune responses and resulted in continuous perfusion of the rBELs for over two weeks. We also show that the human endothelial cells in the perfused rBELs colonize the liver sinusoids and express sinusoidal endothelial markers similar to those in normal liver tissue. Revascularized liver scaffolds that can maintain blood perfusion at physiological pressures might eventually help to overcome the chronic shortage of transplantable human livers.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31518715

RESUMO

BACKGROUND & AIMS: Chromoendoscopy with iodine staining is used to identify esophageal squamous dysplasia and esophageal squamous cell carcinomas (ESCCs)-absence of staining indicates suspicious regions of dysplasia. However, screening detects precancerous lesions (mild and moderate dysplasia) that do not require immediate treatment; it is a challenge to which lesions are at risk for progression. We investigated the association between absence of iodine staining at chromoendoscopy screening and lesion progression using 6 years of follow-up data from a population-based randomized controlled trial in China. We then constructed and validated a model to calculate risk of progression to severe dysplasia, carcinoma in situ, or ESCC. METHODS: We collected data from 1468 participants (45-69 years old) who were either negative for iodine staining at a baseline chromoendoscopy or found to have mild or moderate dysplasia in histologic analysis of biopsies in the Endoscopic Screening for Esophageal Cancer study in China, from January 2012 through September 2016; 788 of these participants were re-examined by endoscopy after a median interval of 4.2 years (development cohort). We investigated the association between absence of iodine staining and progression of esophageal lesions using Cox prediction models, considering corresponding baseline pathology findings and patient answers to a comprehensive questionnaire. Patients who did not receive a follow-up examination (n = 680) was used as the validation cohort; outcome events in these patients were identified by annual door to door active interviews or linkage with local electronic registry data. The primary outcome was incident esophageal severe dysplasia, carcinoma in situ, or ESCC. RESULTS: In the development cohort, 11 lesions that did not stain with iodine but were classified as not dysplastic in the histology analysis were found to be severe dysplasia, carcinoma in situ, or ESCC at the follow-up evaluation. These lesions accounted for 39.3% of all progressed lesions (n = 28). In the validation cohort, 6 patients with lesions did not stain with iodine but were classified as not dysplastic by histology had a later diagnosis of ESCC, determined from medical records; these patients accounted for 50.0% of all patients with lesion progression (n = 12) until the closing date of this study. We developed a model based on patient age, body mass index, pathology findings, and baseline iodine staining to calculate risk for severe dysplasia, carcinoma in situ, or ESCC. It identified patients for severe dysplasia, carcinoma in situ, or ESCC in the development set with an area under the curve of 0.868 (95% CI, 0.817-0.920) and in the validation set with an area under the curve of 0.850 (95% CI, 0.748-0.952). Almost no cases would be missed if subjects determined to be high or intermediate-high risk subjects by the model were included in surveillance. CONCLUSIONS: Absence of iodine staining at baseline chromoendoscopy identifies esophageal lesions at risk of progression with a high level of sensitivity. A model that combines results of iodine chromoendoscopy with other patient features identifies patients at risk of lesion progression with greater accuracy than histologic analysis of baseline biopsies.

14.
J Orthop Surg Res ; 14(1): 248, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387611

RESUMO

BACKGROUND: Tennis elbow or lateral epicondylitis is a common source of pain among craftsmen. Although it cannot be completely resolved, extracorporeal shock wave therapy (ESWT) and ultrasonics (US) have been found to be effective for tennis elbow as highlighted in previously published randomized controlled trials (RCTs) and reviews. However, the efficacy of these two therapies in treating tennis elbow is unknown. This meta-analysis compares the effectiveness of ESWT and US in relieving pain and restoring the functions of tennis elbow following tendinopathy. METHODS: RCTs published in the PubMed, Embase, Cochrane Library, and SpringerLink databases comparing ESWT and US in treating tennis elbow were identified by a software and manual search. The risk of bias and clinical relevance of the included studies were assessed. Publication bias was explored using funnel plot and statistical tests (Egger's test and Begg's test). The major outcomes of the studies were analyzed using the Review Manager 5.3. RESULTS: Five RCTs comprising five patients were included in the present meta-analysis. The results revealed a significantly lower VAS score of pain in the ESWT group (1 month: MD = 4.47, p = 0.0001; 3 months: MD = 20.32, p < 0.00001; and 6 months: MD = 4.32, p < 0.0001) compared to US. Besides, the grip strength was markedly higher 3 months after the intervention in ESWT (MD = 8.87, p < 0.00001) than in the US group. Although no significant difference was observed in the scores of the elbow function after 3 months of treatment (SMD = 1.51, p = 0.13), the subjective scores of elbow functions were found to be better in the ESWT group (SMD = 3.34; p = 0.0008) compared to the US group. CONCLUSIONS: Although there was no significant difference in the elbow function evaluation scores between ESWT and US, the superiority of the ESWT group in the VAS of pain (both at 1 month, 3 months, and 6 months follow-ups) raised grip strength in ESWT group and the scores for subjective evaluation of efficacy indicated that ESWT offers more effective therapy for lateral epicondylitis than US therapy.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Cotovelo de Tenista/terapia , Ondas Ultrassônicas , Tratamento por Ondas de Choque Extracorpóreas/normas , Seguimentos , Humanos , Manejo da Dor/métodos , Manejo da Dor/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Cotovelo de Tenista/diagnóstico , Resultado do Tratamento , Terapia por Ultrassom/métodos , Terapia por Ultrassom/normas
15.
Mater Sci Eng C Mater Biol Appl ; 103: 109711, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349489

RESUMO

Tendon calcification is a common but intractable problem leading to pain and activity limitation when injury or tendinopathy progresses into the late stage. This is because tendon stem/progenitor cells (TSPCs) can undergo aberrant osteogenic differentiation under inflammatory conditions. This study aims to investigate the effect of curcumin, a natural anti-inflammatory agent, on regulating the differentiation of TSPCs in tendon calcification. With inflammatory stimulation, TSPCs showed higher alkaline phosphatase activity and more frequent formation of mineralized nodules which were verified in the culture system; however, curcumin significantly alleviated these pathological changes. In in vivo function analysis, chitosan microsphere-encapsulated curcumin was delivered to injured sites of rat tendon ectopic calcification model. The inflammation in the tendon tissues of the curcumin group was significantly relieved. Controlled-release curcumin partially rescued tendon calcification and enhanced tendon regeneration in animal model. This study demonstrates that controlled-release curcumin can manipulate the fate decision of TSPCs, and that it promotes the tenogenesis and inhibits the osteogenesis of TSPCs in a pathological microenvironment, which provides a possible new therapeutic strategy for tendon disease.


Assuntos
Tendão do Calcâneo/metabolismo , Calcinose/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Curcumina/farmacologia , Células-Tronco/metabolismo , Tendão do Calcâneo/patologia , Animais , Calcinose/metabolismo , Calcinose/patologia , Curcumina/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Camundongos , Ratos , Células-Tronco/patologia
16.
Mol Ther Nucleic Acids ; 17: 223-234, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31272072

RESUMO

Patients who sustain a traumatic brain injury (TBI) are known to have a significantly quicker fracture healing time than patients with isolated fractures, but the underlying mechanism has yet to be identified. In this study, we found that the upregulation of miRNA-26a-5p induced by TBI correlated with a decrease in phosphatase and tensin homolog (PTEN) in callus formation. In vitro, overexpressing miRNA-26a-5p inhibited PTEN expression and accelerated osteoblast differentiation, whereas silencing of miRNA-26a-5p inhibited osteoblast activity. Reduction of PTEN facilitated osteoblast differentiation via the PI3K/AKT signaling pathway. Through luciferase assays, we found evidence that PTEN is a miRNA-26a-5p target gene that negatively regulates the differentiation of osteoblasts. Moreover, the present study confirmed that preinjection of agomiR-26a-5p leads to increased bone formation. Collectively, these results indicate that miRNA-26a-5p overexpression may be a key factor governing the improved fracture healing observed in TBI patients after the downregulation of PTEN and PI3K/AKT signaling. Upregulation of miRNA-26a-5p may therefore be a promising therapeutic strategy for promoting fracture healing.

17.
J Clin Epidemiol ; 114: 141-149, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31226412

RESUMO

OBJECTIVES: The objective of this study was to establish an optimal population-level follow-up strategy for identifying incident cancers using health insurance reimbursement data in rural China. STUDY DESIGN AND SETTING: We compared active follow-up and passive linkage with claims data for identification of incident cancer cases. Claims data were derived from the New Rural Cooperative Medical Scheme (NCMS). Follow-up data from subject enrollment to December 31, 2016, regarding 33,948 subjects in a large-scale randomized controlled trial were used in this study. RESULTS: The overall sensitivity of passive linkage with NCMS claims data was significantly higher than that of active follow-up (95.6% vs. 54.9%, P < 0.001). Of 12 cases missed by the NCMS data set, seven were treated on an outpatient basis and there were therefore no records in the NCMS system, and five were diagnosed at primary (township-level) health facilities and excluded from the quality control process. Of the 123 cases missed by active follow-up, 54 were reported as negative, 69 were reported as positive but had inaccurate information regarding the site of cancer, or exceeded the 6-month limitation from the date of diagnosis. CONCLUSION: Passive linkage with NCMS claims data is an efficient approach for identifying incident cancers in areas without cancer registries in rural China.

18.
19.
Mayo Clin Proc ; 94(4): 714-726, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947834

RESUMO

Portal hypertension is a major complication of cirrhosis, and its consequences, including ascites, esophageal varices, hepatic encephalopathy, and hepatorenal syndrome, lead to substantial morbidity and mortality. The past several decades have seen major improvements in the clinical management of complications of portal hypertension, resulting in substantial gains in patient outcomes. However, important challenges remain. This review focuses on the pathophysiology and diagnosis of portal hypertension and discusses general approaches in the management of patients with ascites as a result of portal hypertension.


Assuntos
Hipertensão Portal/fisiopatologia , Hipertensão Portal/terapia , Ascite/etiologia , Gerenciamento Clínico , Hemorragia Gastrointestinal/etiologia , Encefalopatia Hepática/etiologia , Humanos , Hipertensão Portal/complicações , Cirrose Hepática/etiologia
20.
Med Sci Monit ; 25: 2246-2256, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30916045

RESUMO

BACKGROUND Rheumatoid arthritis (RA) has a high prevalence in the elderly population. The genes and pathways in the inflamed synovium in patients with RA are poorly understood. This study aimed to identify differentially expressed genes (DEGs) linked to the progression of synovial inflammation in RA using bioinformatics analysis. MATERIAL AND METHODS Gene expression profiles of datasets GSE55235 and GSE55457 were acquired from the Gene Expression Omnibus (GEO) database. DEGs were identified using Morpheus software, and co-expressed DEGs were identified with Venn diagrams. Protein-protein interaction (PPI) networks were assembled with Cytoscape software and separated into subnetworks using the Molecular Complex Detection (MCODE) algorithm. The functions of the top module were assessed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. RESULTS DEGs that were upregulated were significantly enhanced in protein binding, the cell cytosol, organization of the extracellular matrix (ECM), regulation of RNA transcription, and cell adhesion. DEGs that were downregulated were associated with control of the immune response, B-cell and T-cell receptor signaling pathway regulation. KEGG pathway analysis showed that upregulated DEGs enhanced pathways associated with the cell adherens junction, osteoclast differentiation, and hereditary cardiomyopathies. Downregulated DEGs were enriched in primary immunodeficiency, cell adhesion molecules (CAMs), cytokine-cytokine receptor interaction, and hematopoietic cell lineages. CONCLUSIONS The findings from this bioinformatics network analysis study identified molecular mechanisms and the key hub genes that may contribute to synovial inflammation in patients with RA.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Membrana Sinovial/fisiologia , Artrite Reumatoide/metabolismo , China , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Inflamação/metabolismo , Osteoartrite/genética , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas/genética , Transdução de Sinais , Software , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismo , Transcriptoma/genética
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