RESUMEN
BACKGROUND/AIMS: The adverse effects of obesity on male fertility have been widely reported. In recent years, the relationship between the differential expression of proteins and long non-coding RNAs with male reproductive disease has been reported. However, the exact mechanism in underlying obesity-induced decreased male fertility remains unclear. METHODS: We used isobaric tags for relative and absolute quantification to identify differential protein expression patterns in the testis of rats fed a high-fat diet and normal diet. A microarray-based gene expression analysis protocol was used to compare the differences in long non-coding RNAs in high-fat diet-fed and normal diet-fed rats. Five obviously upregulated or downregulated proteins were examined using western blot to verify the accuracy of their expression. Then, we carried out functional enrichment analysis of the differentially expressed proteins using gene ontology and pathway analysis. Finally, the metabolic Gene Ontology terms and pathways involved in the differential metabolites were analyzed using the MetaboAnalyst 2.0 software to explore the co-expression relationship between long non-coding RNAs and proteins. RESULTS: We found 107 proteins and 263 long non-coding RNAs differentially expressed between rats fed a high-fat diet and normal diet. The Gene Ontology term enrichment analysis showed that the protein function most highly enriched was related to negative regulation of reproductive processes. We also found five Gene Ontology terms and two metabolic pathways upregulated or downregulated for both proteins and long non-coding RNAs. CONCLUSION: The study revealed different expression levels for both proteins and long non-coding RNAs and showed that the function and metabolic pathways of differently expressed proteins were related to reproductive processes. The Gene Ontology terms and metabolic pathways upregulated or downregulated in both proteins and long non-coding RNAs may provide new candidates to explore the mechanisms of obesity-induced male infertility for both protein and epigenetic pathways.
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Dieta Alta en Grasa/efectos adversos , Perfilación de la Expresión Génica , Obesidad/etiología , Obesidad/genética , Testículo/metabolismo , Animales , Peso Corporal , Ontología de Genes , Glucolípidos/genética , Glucolípidos/metabolismo , Masculino , Redes y Vías Metabólicas , Obesidad/metabolismo , Proteínas/genética , Proteínas/metabolismo , Proteómica , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratas , Ratas Sprague-Dawley , Semen/metabolismo , Testículo/ultraestructuraRESUMEN
In this study, complex enzymes combined with ultrasonic extraction technologyï¼MCï¼ were used, to select optimal extraction combinations by single factor and orthogonal test, with Hedysarum polysaccharides yield and content as the comprehensive indexes. The components, physicochemical properties and antioxidant activity of Hedysarum polysaccharides from complex enzyme combined with ultrasonic extractionï¼HPS-MCï¼and the Hedysarum polysaccharides from hot water extractionï¼HPS-Rï¼were analyzed. The results showed thatï¼complex enzymes had significant effect on the yield and content of Hedysarum polysaccharides, and the ultrasonic power could significantly improve the content of Hedysarum polysaccharides. The optimum technological parameters were as follows: complex enzyme ratio 1:1, ultrasonic power 105 W, ultrasonic time 60 min, and enzymatic hydrolysis pH 5, achieving ï¼14.01±0.64ï¼% and ï¼92.45±1.47ï¼% respectively for the yield and content of Polysaccharides. As compared with HPS-R, the molecular weight, absolute viscosity and protein content of HPS-MC were decreased, while the content of uronic acid was increased. In the antioxidant system, the concentration of polysaccharide was within the range of 1-7 g·L⻹; the antioxidant activity of HPS-MC was higher than that of HPS-R, and HPS-MC (80%) with the lowest molecular weight showed a significant dose effect relationship with the increase of the experimental concentration. In conclusion, MC is a simple, convenient, economical and environmentally friendly extraction technology, and the Hedysarum polysaccharides extracted by this method have obvious antioxidant activity.
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Antioxidantes/farmacología , Fabaceae/química , Polisacáridos/farmacología , Enzimas , Hidrólisis , Peso Molecular , Extractos Vegetales , Ultrasonografía , AguaRESUMEN
Casein kinase 2 (CK2) is a highly pleiotropic serine-threonine kinase, which catalyzed phosphorylation of more than 300 proteins that are implicated in regulation of many cellular functions, such as signal transduction, transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is abnormally elevated in a variety of tumors, and is considered as a promising therapeutic target. The currently available ATP-competitive CK2 inhibitors, however, lack selectivity, which has impeded their development in cancer therapy. Because allosteric inhibitors can avoid the shortcomings of conventional kinase inhibitors, this study was aimed to discover a new allosteric site in CK2α and to investigate the effects of mutations in this site on the activity of CK2α. Using Allosite based on protein dynamics and structural alignment, we predicted a new allosteric site that was partly located in the αC helix of CK2α. Five residues exposed on the surface of this site were mutated to validate the prediction. Kinetic analyses were performed using a luminescent ADP detection assay by varying the concentrations of a peptide substrate, and the results showed that the mutations I78C and I78W decreased CK2α activity, whereas V31R, K75E, I82C and P109C increased CK2α activity. Potential allosteric pathways were identified using the Monte Carlo path generation approach, and the results of these predicted allosteric pathways were consistent with the mutation analysis. Multiple sequence alignments of CK2α with the other kinases in the family were conducted using the ClustalX method, which revealed the diversity of the residues in the site. In conclusion, we identified a new allosteric site in CK2α that can be altered to modulate the activity of the kinase. Because of the high diversity of the residues in the site, the site can be targeted using rational drug design of specific CK2α inhibitors for biological relevance.
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Biología Computacional , Algoritmos , Sitio Alostérico/efectos de los fármacos , Secuencia de Aminoácidos , Quinasa de la Caseína II/antagonistas & inhibidores , Quinasa de la Caseína II/química , Quinasa de la Caseína II/genética , Quinasa de la Caseína II/metabolismo , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Modelos Moleculares , Alineación de SecuenciaRESUMEN
A series of novel Heteroaryldihydropyrimidines (HAPs) derivatives were designed and synthesized as potent inhibitors of HBV capsid assembly. These compounds were prepared from efforts to optimize an earlier series of HAPs, and compounds Mo1, Mo7, Mo8, Mo10, Mo12, and Mo13 demonstrated potent inhibition of HBV DNA replication at submicromolar range.
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Antivirales/farmacología , Cápside/efectos de los fármacos , Virus de la Hepatitis B/efectos de los fármacos , Pirimidinas/farmacología , Antivirales/síntesis química , Antivirales/química , Cápside/metabolismo , Supervivencia Celular/efectos de los fármacos , ADN Viral/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Virus de la Hepatitis B/crecimiento & desarrollo , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Pirimidinas/síntesis química , Pirimidinas/química , Relación Estructura-Actividad , Replicación Viral/efectos de los fármacosRESUMEN
An efficient synthesis of enantiopure (R)-heteroarylpyrimidine analogs is described here, which involves introduction of a chiral group, formation and separation of diasteroisomers and final transformation of an amide to an ester. The absolute configuration of the enantiopure HAPs is confirmed by X-ray analysis of their intermediates.
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Pirimidinas/síntesis química , Cristalografía por Rayos X , Modelos Moleculares , Conformación Molecular , Pirimidinas/aislamiento & purificación , EstereoisomerismoRESUMEN
OBJECTIVE: To explore the clinical and laboratory characteristics of patients with lupus enteritis to provide rationales for clinical diagnosis and treatment. METHODS: A retrospective group control study was conducted for systemic lupus erythematosus (SLE) patients with complaints of acute abdominal pain from 2004 to 2011. They were divided into 2 groups: lupus enteritis (n = 66) and non-lupus related abdominal pain (n = 73). The associated factors included demographic, laboratory, clinical and radiographic data. RESULTS: Lupus enteritis (39.3%) was the most common cause of lupus patients with acute abdominal pain. There were no differences in autoantibody profiles, complement, erythrocyte sedimentation rate, C reactive protein and SLE disease activity index (SLEDAI) score between two groups. The level of D-dimer and European consensus lupus activity measurement (ECLAM) score were significantly higher in the group of lupus enteritis than those in non-lupus related gastrointestinal injury. Lupus enteritis had significantly higher percentage of complications with multiple serous cavity effusions and ascites. But after adjusting with logistic regression multivariate analysis, only the level of D-dimer, ECLAM and volume of ascites were associated with occurrence of lupus enteritis. CONCLUSION: Lupus enteritis is the most common cause of acute abdominal pain. D-dimer is an excellent predictor for lupus abdominal pain. As compared with SLEDAI, ECLAM may be more suitable for assessment in SLE patients with alimentary tract injury.
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Enteritis/etiología , Lupus Eritematoso Sistémico/complicaciones , Dolor Abdominal/etiología , Adulto , Autoanticuerpos/análisis , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Lupus Eritematoso Sistémico/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the modulation of RhoA/Rho kinase (ROCK), a small Rho GTPase, on migration, invasion and proliferation of fibroblast like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. METHODS: RA FLS were collected from active RA patients. And 10% fetal bovine serum (FBS) and interleukin-1ß (IL-1ß) were used as stimuli in migration and proliferation experiments respectively. RhoA activity was measured by pull down assay while ROCK activity by Western blot. FLS migration and invasion in vitro were measured by the Transwell chamber method. And thiazolyl blue tetrazolium bromide (MTT) test was used to detect cell proliferation. RESULTS: There were increased activities of RhoA and ROCK in ex vivo FLS from RA versus OA patients and healthy control. The migrated cell number of FBS-induced, C3-treated and Y27632-treated groups was 85 ± 14, 51 ± 15 and 42 ± 11 respectively. The Matrigel invading cell number of 3 groups was 64 ± 13, 39 ± 12 and 26 ± 9 respectively. Statistical differences existed in cell number between FBS-induced, C3-treated or Y27632-treated group (P < 0.05) in above migration and invasion experiments. Inhibition of RhoA and ROCK activity also suppressed the cytoskeletal reorganization and proliferation of RA FLS. CONCLUSION: Increased RhoA/ROCK activity may contribute to abnormal migration, invasion and proliferation of RA FLS. Thus inhibition of ROCK activity may be a new therapeutic target for RA.
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Artritis Reumatoide/metabolismo , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Artritis Reumatoide/patología , Movimiento Celular , Proliferación Celular , Células Cultivadas , Femenino , Fibroblastos/citología , Humanos , Masculino , Membrana Sinovial/citologíaRESUMEN
Moringa oleifera leaf (MLP) contains abundant complex nutrients with anti-osteoporosis potential. However, its efficacy and mechanisms against osteoporosis remain unknown. The purpose of this research is to investigate MLP's anti-osteoporotic effects and mechanisms. Animal experiments were used in this work to validate MLP's anti-osteoporotic efficacy. We investigated the mode of action of MLP, analyzed its impact on the gut microbiota, and predicted and validated its anti-osteoporosis-related molecular targets and pathways through network pharmacology, molecular docking, and western blotting. In an ovariectomized osteoporosis rat model, MLP significantly increased bone mineral density and improved bone metabolism-related indicators, bone microstructure, and lipid profile. Moreover, it improved gut microbiota composition and increased the expression of Occludin and Claudin-1 protein in the duodenum. Network pharmacology identified a total of 97 active ingredients and 478 core anti-osteoporosis targets. Of these, MAPK1 (also known as ERK2), MAPK3 (also known as ERK1), and MAPK8 (also known as JNK) were successfully docked with the active constituents of MLP. Interestingly, MLP increased ERK and VAV3 protein expression and decreased p-ERK and JNK protein expression in the femur. These findings confirm MLP's anti-osteoporotic efficacy, which could be mediated via regulation of gut microbiota and MAPK signaling.
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Microbioma Gastrointestinal , Moringa oleifera , Osteoporosis , Ratas , Animales , Moringa oleifera/química , Simulación del Acoplamiento Molecular , Osteoporosis/tratamiento farmacológico , Transducción de Señal , Hojas de la PlantaRESUMEN
OBJECTIVE: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). METHODS: Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. RESULTS: In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. CONCLUSION: The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.
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Artritis Reumatoide/complicaciones , Enfermedad de la Arteria Coronaria/complicaciones , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , China/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. METHODS: A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. RESULTS: In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). CONCLUSION: About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.
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Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Honorarios por Prescripción de Medicamentos/estadística & datos numéricos , Inhibidores del Factor de Necrosis Tumoral , Adulto , Anciano , Antiinflamatorios no Esteroideos/economía , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales/uso terapéutico , Artritis Reumatoide/economía , China , Etanercept , Femenino , Humanos , Inmunoglobulina G/economía , Inmunoglobulina G/uso terapéutico , Inmunosupresores/economía , Inmunosupresores/uso terapéutico , Infliximab , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect. METHODS: A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy. RESULTS: In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%). CONCLUSION: Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.
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Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Sulfasalazina/administración & dosificación , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Antirreumáticos/uso terapéutico , China , Estudios Transversales , Quimioterapia Combinada , Femenino , Humanos , Isoxazoles/administración & dosificación , Leflunamida , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Sulfasalazina/efectos adversos , Encuestas y CuestionariosRESUMEN
PURPOSE: To evaluate the effect of naringenin on improving PCOS and explore the mechanism. METHODS: Firstly, we carried out differential gene expression analysis from transcriptome sequencing data of human oocyte to screen the KEGG pathway, then the PCOS-like rat model was induced by letrozole. They were randomly divided into four groups: Normal group (N), PCOS group (P), Diane-35 group (D), and Naringenin group (Nar). The changes of estrus cycle, body weight, ovarian function, serum hormone levels, glucose metabolism, along with the expression of SIRT1, PGC-1É, claudin-1 and occludin of the ovary and colon were investigated. Furthermore, the composition of the gut microbiome of fecal was tested. RESULTS: By searching the KEGG pathway in target genes, we found that at least 15 KEGG pathways are significantly enriched in the ovarian function, such as AMPK signaling pathway, insulin secretion, and ovarian steroidogenesis. Interestingly, naringenin supplementation significantly reduced body weight, ameliorated hormone levels, improved insulin resistance, and mitigated pathological changes in ovarian tissue, up-regulated the expression of PGC-1É, SIRT1, occludin and claudin-1 in colon. In addition, we also found that the abundance of Prevotella and Gemella was down-regulated, while the abundance of Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus, Streptococcus, Coprococcus was up-regulated. CONCLUSION: Our data suggest that naringenin exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota and SIRT1/PGC-1É signaling pathway. Our research may provide a new perspective for the treatment of PCOS and related diseases.
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Microbioma Gastrointestinal , Síndrome del Ovario Poliquístico , Animales , Peso Corporal , Claudina-1/genética , Claudina-1/farmacología , Femenino , Flavanonas , Hormonas , Humanos , Letrozol/efectos adversos , Ocludina , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genética , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Sirtuina 1/metabolismoRESUMEN
OBJECTIVE: To analyze the relationship between the radiological progression and quality of life in ankylosing spondylitis (AS) patients using etanercept/methotrexate (MTX) combination therapy. METHODS: A total of 153 AS cases fulfilling the 1984 modified New York diagnostic criteria were reviewed. All patients received radiological evolution at baseline and during a follow-up period. Radiological progression, clinical remission and life quality were recorded and analyzed for their relations. RESULTS: The radiological assessments of mSASSS (modified Stoke ankylosing spondylitis spine score) were recorded at baseline, 3, 6 & 12 months after treatment. Life quality assessments were recorded with SF (short-form)-36 simultaneously. No significant radiological improvement was observed at the end points. However, most patients reported a significant improvement of life quality after a combination therapy of etanercept/MTX. BASDAI (Bath ankylosing spondylitis disease activity index), C-reactive protein and erythrocyte sedimentation rate demonstrated similar trends. With no relevance with mSASSS, life quality was significantly correlated with disease activity and pain control. CONCLUSION: The combination therapy of etanercept/MTX greatly improves life quality in AS patients. Yet clinical remission and pain control offer no hint of a suspension of radiological progression. Routine radiological assessment is required throughout the follow-up period of AS even if life quality index reaches a high level.
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Antirreumáticos/uso terapéutico , Inmunoglobulina G/uso terapéutico , Metotrexato/uso terapéutico , Calidad de Vida , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Adolescente , Adulto , Quimioterapia Combinada , Etanercept , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Espondilitis Anquilosante/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the modulation of RhoA/Rho kinase (ROCK) signaling pathway, a small Rho GTPase that is considered as an important modulator in inflammatory responses, on Toll-like receptor-2 mediated chemokine secretion in fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. METHODS: The RhoA activity was measured by a pull-down assay. And the ROCK activity was assessed by Western blot. The secretion of chemokines was measured by ELISA (enzyme-linked immunosorbent assay). MTT test was used to detect the cellular viability. RESULTS: The stimulation of peptidoglycan (PG, 5 mg/L) increased the levels of IL-8 (interleukin-8), RANTES (regulated upon activation normal T cell expressed & secreted) and MCP-2 (monocyte chemotactic protein-2) and boosted the activities of RhoA and ROCK versus the unstimulated RA FLS. And these effects of PG were suppressed by anti-TLR-2 monoclonal antibody. Inhibition of RhoA and ROCK with a specific inhibitor inhibited the secretion of IL-8, RANTES and MCP-2 in PG-induced RA FLS. CONCLUSION: The present study provides novel evidence that the RhoA/ROCK signal pathway modulates the TLR-2-mediated secretion of chemokines in RA FLS. It suggests that the inhibition of RhoA/ROCK may be a new therapeutic approach for RA.
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Artritis Reumatoide/metabolismo , Transducción de Señal , Membrana Sinovial/metabolismo , Receptor Toll-Like 2/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Células Cultivadas , Quimiocina CCL5/metabolismo , Quimiocina CCL8/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Interleucina-8/metabolismo , Masculino , Líquido Sinovial/citología , Membrana Sinovial/citologíaRESUMEN
OBJECTIVE: To assess the therapeutic efficacy and safety of Kunxian Capsule (KXC) in treatment of rheumatoid arthritis (RA). METHODS: Randomized positive parallel controlled and multi-center open test method was adopted. 240 RA patients of mild/moderate degree were randomly assigned to three groups equally, i.e., KXC group (who took KXC), the methotrexate (MTX) group (who took MTX), and the KXC + MTX group (who took KXC and MTX simultaneously), respectively. The therapeutic course for them all was 12 weeks. The effect of the treatment was assessed in items of DAS28, ACR20, and ACR50; number of joints with pain and swelling; VAS score of pain, tiredness, and general condition; time of morning stiffness; bilateral grip strength; HAQ score, as well as blood levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP antibody, and platelet count. RESULTS: By the end of the 4th week, the improvement of ACR20, ACR50, DAS28 efficacy judgment, and DAS28 score in the KXC + MTX group were much better than those in the other two groups, with statistical difference (P<0.05). The total effective rate was 88. 6% and the markedly effective rate was 51.8% in the KXC + MTX group at the 12 th week. The Improvement was more obviously shown in all groups after treatment (all P<0.05). Better effects in reducing VAS scores of pain and tiredness were shown in the KXC group and the KXC + MTX group. The effects of KXC + MTX were superior to the other two groups in terms of swollen joint numbers, pain joints, grip strength (assessed by researcher), as well as VAS score of general condition and HAQ score (assessed by both patients and researcher, P<0.05). But the differences among groups in improving morning stiffness and the incidence rate of adverse events were in- significant. CONCLUSIONS: KXC could relieve symptoms, improve joint functions, physical signs, and laboratory indices of RA patients with less adverse reaction. It was synergistic with MTX.
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Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Adulto , Antirreumáticos/uso terapéutico , Sinergismo Farmacológico , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the effects of the quinoa diet on glycolipid metabolism and endoplasmic reticulum (ER) stress in an obese mouse model. METHODS: Six-week-old C57BL/6J female mice have received a high-fat diet (HFD) to induce obesity and subsequently were treated with a quinoa diet for 12 weeks. During this period, fasting blood glucose, body fat and insulin resistance were measured regularly. At the end of the experiment, mouse serum and liver tissue were collected. The differences in glucose and lipid metabolism were analyzed, and liver tissue pathological morphology, liver endoplasmic reticulum stress-related mRNA and protein levels, and serum oxidative stress levels were measured. RESULTS: Quinoa diet could significantly reduce the level of blood glucose, triglyceride, cholesterol, low-density lipoprotein, improve glucose tolerance, as well as improve histological changes of liver tissues in obese mice (P < 0.05 or < 0.01). Besides, quinoa could improve oxidative stress indicators such as GSH, and MDA (P < 0.05 or < 0.01). Furthermore, quinoa can down-regulate mRNA expression of ER stress markers eIF2α, GRP78, and CHOP in the liver of obese mice (P < 0.05 or < 0.01). CONCLUSIONS: Quinoa supplementation can improve glycolipid metabolism, regulate ER stress, and alleviate obesity in HFD-induced mice.
RESUMEN
OBJECTIVE: To evaluate the inhibitory effect of blockade of Rho kinase upon mediating the secretion of proinflammatory cytokine in monocytic cells from rheumatoid arthritis (RA) patients. METHODS: Synovial fluid (SF) monocytic cells and peripheral blood monocytes (PB) from active RA patients were treated with TNFalpha or LPS respectively in the presence or absence of a specific ROK inhibitor, Y27632. ROK activity was assessed by Western blot and cytokine secretion measured by ELISA. RESULTS: Elevated ROK activity was found in synovial fluid monocytic cells from active RA patients. ROK activity was correlated with DAS, an index of disease activity of RA patients. ROK inhibitor Y27632 reduced the secretion of TNFalpha, IL-1beta and IL-6 in RA SF monocytic cells, but had no effect upon the secretion of IL-10, an anti-inflammatory cytokine. CONCLUSION: The present study provides novel evidence that ROK mediates the secretion of proinflammatory cytokines in monocytic cells from RA synovial fluids, suggesting a critical role of ROK in macrophage-mediated synovial inflammation of RA. Thus inhibition of ROK may be a new therapeutic target for RA.
Asunto(s)
Artritis Reumatoide/metabolismo , Macrófagos/efectos de los fármacos , Monocitos/efectos de los fármacos , Quinasas Asociadas a rho/antagonistas & inhibidores , Amidas/farmacología , Citocinas/metabolismo , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Masculino , Monocitos/metabolismo , Piridinas/farmacología , Membrana Sinovial/citología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To evaluate the side effects of non-steroidal anti-inflammatory drugs (NSAID) on gastric mucosa, and to study the preventive effects of teprenone in patients. METHODS: 108 patients taking NSAID for more than 3 months with no infection of helicobacter pylori (Hp) were collected. All patients were screened by endoscopy and their upper gastrointestinal symptoms were evaluated. Then, 16 patients with ulcers were excluded and 92 patients were randomly divided into intervention group with teprenone and control group. After follow-up for 3 months, patients were screened again by endoscopy and their upper gastrointestinal symptoms were also evaluated. Specimens of gastric mucosa were studied by PAS dyeing, and Cyclooxygenase (COX) level were evaluated by immunohistochemical technique. RESULTS: Of patients taking NSAIDs, the erosion was found in 48 (44.4%) patients while 16 (14.8%) were found with peptic ulcers. The damages were improved significantly (Z = -4.96, P = 0.000) in the intervention group with teprenone (n = 45) as compared with control group (n = 47) after follow-up for 3 months. Both the cox-1 level [31.1% (14/45) vs 6.7% (3/45), P = 0.003] and mucus thickness [66.7% (30/45) vs 13.3% (6/45), P= 0.000] also increased in the intervention group as compared with control group. No significant difference was found on COX-2 level between these two groups [28.9% (13/45) vs 31.1% (14/45), P = 0.82]. CONCLUSION: Long-term use of NSAID caused severe damages on gastric and duodenal mucosa; teprenone improved NSAID-related gastric side effects and increased the COX-1 level and mucus thickness.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Diterpenos/farmacología , Mucosa Gástrica/efectos de los fármacos , Adulto , Anciano , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Femenino , Estudios de Seguimiento , Mucosa Gástrica/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: To investigate the efficacy and safety of Infliximab (IFX) plus methotrexate (MTX) combination therapy in patients with rheumatoid arthritis (RA). METHODS: Prospectively observe refractory RA patients who were treated with combination therapy of MTX and IFX. IFX was infused at the dosage of 3 mg/kg, in week 0, 2, 6, and then every 8 weeks. During treatment, clinical variables, disease activity and adverse effects were evaluated. RESULTS: After treatment, 69.8%, 52.4%, 29.5% and 7.2% RA patients achieved ACR20, ACR50, ACR70 and ACR90 respectively. There were significant statistical differences in the changes of swollen joint counts, tender joint counts, VAS scale, patient' s global assessment, and physician's global assessment before and after therapy. CONCLUSION: Infliximab plus MTX achieved significant efficacy and safety in refractory RA patients.