RESUMO
OBJECTIVE: There is considerable evidence for relationship between gut microbiota and osteoarthritis (OA), but no studies have investigated their causal relationship. METHOD: This study utilized large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and OA risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for OA. Comprehensively sensitive analyses were performed to validate the robustness of results and novel multivariable MR analyses were further conducted to ensure the independence of causal association. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations. Finally, enrichment analyses were used to investigate the biofunction. RESULTS: After correction, three microbial taxa were identified to be causally associated with diverse joint OA (PFDR < 0.100), namely Methanobacteriaceae family for knee OA (PFDR = 0.043) and any OA (PFDR = 0.028), Desulfovibrionales order for knee OA (PFDR = 0.045) and Ruminiclostridium5 genus for knee OA (PFDR = 0.063). In addition, we also identified five suggestive microbial taxa that were significant with three different methods under the nominal significance (P < 0.05). Sensitive analysis excluded the influence of heterogeneity and horizontal pleiotropy and multivariable MR analysis ruled out the possibility of horizontal pleiotropy of BMI. GO enrichment analysis illustrates the protective mechanism of the identified taxa against OA. CONCLUSIONS: This study found that several microbial taxa were causally associated with diverse joint OA. The results enhanced our understanding of gut microbiota in the pathology of OA.
Assuntos
Microbioma Gastrointestinal , Osteoartrite/microbiologia , Causalidade , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Osteoartrite/genéticaRESUMO
Some studies assessed the association between lncRNA taurine-upregulated gene 1 (TUG1) and the survival in cancer. However, the results were inconclusive. Therefore, we performed a meta-analysis to determine this association. We used the following electronic databases to search for eligible literature: PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang. We used ORs and 95% CIs to measure the association between TUG1 and the survival of cancer. There was no significant association between TUG1 and OS of cancer (HR=1.26, 95% CI=0.97-1.64). In the subgroup analysis by cancer type, significant association could be find in osteosarcoma (HR=1.72, 95% CI=1.27-2.32) and digestive system's tumors (HR=1.66, 95% CI=1.04-2.66). In conclusion, this meta-analysis study indicated that TUG1 might associate with the OS of osteosarcoma and digestive system's tumors.
Assuntos
Neoplasias/genética , RNA Longo não Codificante/genética , Humanos , Prognóstico , Viés de Publicação , Análise de SobrevidaRESUMO
This study aimed to determine the relationship between changes in the serum levels of macrophage migratory inhibitory factor (MIF), interleukin (IL) 17, and IL-10 during chronic hepatitis B treatment via Baraclude(®) (Bristol-Meyers Squibb). Thirty-six patients with chronic hepatitis B and 24 healthy individuals were selected as the experimental and control groups, respectively, and the serum levels of MIF, IL-17, and IL-10 were measured during the period in which the experimental group was treated with oral Baraclude(®); meanwhile, the alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA, and HBV marker (M) levels were measured in the experimental group. In the experimental group, the ALT and HBV-DNA levels began to exhibit obvious decreases in week 4, and the MIF and IL-17 levels exhibited obvious increases in week 4 followed by gradual decreases; however, the IL-10 level exhibited an obvious decrease in week 12 and then increased gradually. These changes were significant when compared with the control group (P < 0.05). In conclusion, Baraclude(®) treatment not only actively suppressed HBV but also indirectly balanced the MIF, IL-17, and IL-10 levels and reduced the liver inflammatory response.
Assuntos
Antivirais/administração & dosagem , Guanina/análogos & derivados , Hepatite B Crônica/sangue , Interleucina-10/sangue , Interleucina-17/sangue , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Administração Oral , Adolescente , Adulto , Alanina Transaminase/sangue , Estudos de Casos e Controles , Feminino , Guanina/administração & dosagem , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Saccharum spontaneum L. is one of the most important germplasm resources for modern sugarcane breeding. Exploring the cold tolerance of S. spontaneum clones with different ploidy levels and screening for cold-tolerant material can be helpful in parent selection for breeding cold-tolerant sugarcane. Morphological indices, leaf ultrastructure and physiological indices were used to evaluate the cold tolerance of 36 S. spontaneum clones with different ploidy levels (2n = 40, 48, 54, 60, 64, 78, 80, 88, 92 and 96). The morphological indices of S. spontaneum clones with different ploidy levels were positively correlated with ploidy. Under low-temperature stress, the chloroplast and mitochondrial structures of the clones with high ploidy were more severely damaged than were those of clones with low ploidy. A comprehensive evaluation of the physiological indices showed that the 36 S. spontaneum clones could be divided into four categories: strongly cold tolerant, cold tolerant, moderately cold tolerant and cold sensitive. Correlation analysis of the morphological indices and cold tolerance revealed a significant negative correlation between cold tolerance and ploidy. On the basis of the morphological and physiological indices, optimal stepwise regression equations that can be used for the selection of cold-tolerant S. spontaneum resources were established. The S. spontaneum clones with low ploidy are more cold tolerant than those with high ploidy. Clones 12-37, 13-10 and 12-23 are strongly cold-tolerant germplasm resources, which suggests these germplasm sources have high potential for use in breeding cold-tolerant sugarcane.
Assuntos
Adaptação Fisiológica , Temperatura Baixa , Ploidias , Saccharum , Adaptação Fisiológica/genética , Cruzamento , Saccharum/anatomia & histologia , Saccharum/genéticaRESUMO
BACKGROUND: Prostate volume (PV) and its change rate are important for the progression of prostate disease, but studies on their estimates are inconsistent. OBJECTIVES: To investigate whether age, prostate-specific antigen (PSA), and other specific characteristics are associated with PV and its change rate. MATERIALS AND METHODS: A community-based cohort study was conducted in a rural area of China among male residents aged 40-80 years. PV was estimated at baseline and at 4 years of follow-up by trans-abdominal ultrasound. Annual PV change rate (PVCR) was calculated as change in volume divided by time interval. Baseline characteristics, including age, serum PSA, and hormones, were evaluated. And their relationships with PV or PVCR were assessed with Pearson correlation and multivariate linear regression analyses. RESULTS: Totally, 462 participants completed the follow-up with baseline PV (PV0 ) of 15.6 ± 5.5 ml. PV0 was highly correlated with age and PSA in pairwise correlations (Pearson r = 0.35 and 0.34, respectively, p < 0.01). Multivariate linear regression showed similar associations that PV0 tended to increase with age and PSA. The average PVCR was 0.7 ± 1.8 ml/year. In pairwise correlations, PVCR was inversely correlated with PV0 and positively correlated with PSA, while it was not significantly related to baseline age. Linear regression of PVCR on age and PSA in groups classified by PV0 quartile showed that age was not a significant estimator of PVCR, whereas PSA was. In each PV0 group, PVCR tended to increase with PSA. DISCUSSION AND CONCLUSION: PV was positively associated with age and PSA, and it tended to grow faster in men with smaller baseline PV and higher PSA. PSA can be a valuable parameter for estimating both the size and the growth speed of prostate. Although age is associated with prostate enlargement, it does not appear to be related to the longitudinal change rate of PV.
Assuntos
Antígeno Prostático Específico/sangue , Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
OBJECTIVE: The previous work has shown that Berberine and Hesperidin have beneficial effects on cardiovascular diseases. However, the underlying mechanisms remain unknown. This study aimed to investigate the effect of Berberine and Hesperidin on inflammatory cytokine secretion, proliferation, differentiation, and collagen synthesis of cardiac fibroblasts stimulated by the transforming growth factor-ß1 (TGF-ß1), and the potential of these drugs to regulate the Notch1 signaling pathway. PATIENTS AND METHODS: Neonatal rat primary cardiac fibroblasts were stimulated with 5 ng/mL TGF-ß1 as model (TGF) group. In the Berberine (TGF+B) group cells were given TGF-ß1, along with 1.25/2.5/5/10 mg/L Berberine, while the Hesperidin (TGF+H) group was treated with TGF-ß1 and 12.5/25/50/100 µmmol/L Hesperidin. Cellular proliferation, differentiation, and collagen synthesis were evaluated. The role of the Notch1 signaling pathway in the protective effects of Berberine and Hesperidin was analyzed by using γ-secretase inhibitor (DAPT) to block the Notch1 pathway. RESULTS: 5/10 mg/L Berberine intervention could noticeably decrease both TGF-ß1 and IL-1ß levels, 25/50/100 µmol/L Hesperidin could reduce IL-1ß secretion from TGF-ß1 stimulated cardiac fibroblasts. Both Berberine and Hesperidin decreased the expression of α-SMA and cell viability in a concentration-dependent manner; however, the apoptosis of cardiac fibroblasts was not influenced. 10 mg/L Berberine or at least 50 µmol/L Hesperidin could noticeably decrease MMP-1 expression, and at least 5 mg/L Berberine or 100 µmol/L Hesperidin could markedly reduce MMP-9 expression. Using DAPT to block Notch1 signaling could reverse the protective effects of Berberine and Hesperidin. CONCLUSIONS: Berberine and Hesperidin can reduce the secretion of inflammatory cytokines, differentiation, and proliferation, and increase the collagen synthesis of cardiac fibroblasts stimulated by TGF-ß1 via the Notch1 signaling pathway.
Assuntos
Berberina/farmacologia , Cardiotônicos/farmacologia , Fibroblastos/efeitos dos fármacos , Hesperidina/farmacologia , Miocárdio/citologia , Animais , Animais Recém-Nascidos , Berberina/uso terapêutico , Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/prevenção & controle , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Diaminas/farmacologia , Fibroblastos/imunologia , Fibroblastos/metabolismo , Hesperidina/uso terapêutico , Humanos , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Cultura Primária de Células , Ratos , Receptor Notch1/antagonistas & inibidores , Receptor Notch1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Tiazóis/farmacologia , Fator de Crescimento Transformador beta1/imunologiaRESUMO
The mitochondria pathway is regarded as a central component of some types of programmed cell death (PCD) in animal cells where specific signals cause the release of cytochrome c from mitochondria to trigger a proteolytic cascade involving caspases. However, plant cells lack canonical caspases, therefore a role for the mitochondria in programmed cell death in plant cells is not obvious. Using plant cells which terminally differentiate, we provide evidence supporting the involvement of mitochondria in PCD, however the release of cytochrome c is insufficient to trigger the PCD. Prior to execution of cellular autolysis initiated by the rupture of the large central vacuole to release sequestered hydrolases, mitochondria adopt a definable morphology, the inner membrane depolarizes prior to death, and cytochrome c is released from mitochondria. However, PCD can be blocked despite translocation of cytochrome c. These results suggest a role for the mitochondria in this PCD but do not support the current animal model for a causative role of cytochrome c in triggering PCD.