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OBJECTIVE: To identify potential mutation of human androgen receptor (AR) gene in a patient with complete androgen insensitivity syndrome (CAIS). METHODS: DNA sequences of 8 exons and exon/intron boundaries of the AR gene were amplified with PCR and directly sequenced. RESULTS: DNA sequencing has revealed a frameshift mutation due to deletion of nucleotide C at position 3507 in exon 6, which gave rise to a stop codon resulting premature termination for translation. CONCLUSION: A novel frameshift mutation in exon 6 of AR gene probably underlies the disease in our patient.
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Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/genética , Mutação da Fase de Leitura , Receptores Androgênicos/genética , Sequência de Bases , Éxons , Humanos , Masculino , Fenótipo , Adulto JovemRESUMO
Previous studies showed a controversial result on the relationship between probiotics treatment duration and blood pressure (BP). The present meta-analysis is performed to summarize the effects of long-term (≥8 weeks) use of probiotics on office and ambulatory BP using combined evidence from randomized, controlled trials. We searched PubMed, Embase, Cochrane library, and the ClinicalTrials.gov till January, 2021 to identify eligible articles. Primary outcomes were changes in office BP. In the presence of heterogeneity, a random-effects model was used to calculate the combined treatment effect. Begg's funnel plots and Egger's regression test were used to assess the publication bias. Meta-analysis of 26 trials in 1624 participants demonstrated that probiotic consumption significantly decreased office systolic BP by 2.18 mmHg (95% confidence interval [CI], -3.41 to -0.94 mmHg) and diastolic BP by 1.07 mmHg (95% CI, -1.72 to -0.41 mmHg). The analysis on ambulatory BP from three trials showed a similar reduction by -2.35/-1.61 mmHg (p ≤ .052). Subgroup analysis in hypertensive and diabetic patients showed a significant reduction in systolic and diastolic BP (p ≤ .02). The reductions in diabetic and hypertensive patients were comparatively larger than nondiabetic and normotensive patients (p ≥ .052). With the increase of age, baseline body mass index (BMI), treatment duration, and systolic BP, the effects of probiotics on BP did not increase significantly (p trend ≥ .18). The present meta-analysis suggests a beneficial effect of probiotics on BP by a modest degree, especially in the diabetes mellitus and hypertension. Prolonging the treatment duration could not improve the antihypertensive effect.
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OBJECTIVE: In a substudy of a randomized controlled trial, we investigated the effects of the valsartan/amlodipine single-pill combination and nifedipine gastrointestinal therapeutic system (GITS) monotherapy on brachial pulse pressure (bPP) and radial augmentation index (rAI) in patients with previously uncontrolled hypertension. METHODS: We performed measurements of clinic blood pressure (BP) and pulse rate and rAI (n = 63) and ambulatory BP monitoring (n = 42) at baseline and 12-week of follow-up. Analysis of covariance was performed to calculate the least square mean change from baseline and between-group differences [95% confidence interval (CI)]. Correlation analysis was performed to study the interrelationship between the changes in bPP and rAI and in pulse rate. RESULTS: After 12-week treatment, clinic and ambulatory SBP/DBP and pulse rate were not differently changed between the valsartan/amlodipine (n = 29) and nifedipine GITS groups (n = 34, P ≥ 0.06) except daytime SBP (P = 0.01). The reductions in 24-h and daytime ambulatory bPP were significantly greater in the former than the latter group (P ≤ 0.04). rAI increased slightly by 3.5% (P = 0.20) and 5.2% (P = 0.06) in the valsartan/amlodipine and nifedipine groups, respectively, with a between-group difference of -1.7% (95% CI -9.6 to 6.1%, P = 0.66). In the two groups combined, the changes in clinic and ambulatory bPP were not or weakly associated with that in clinic or ambulatory pulse rate (r = -0.14 to 0.36, P = 0.02-0.95), while the changes in rAI were more strongly or significantly associated with that in clinic or ambulatory pulse rate (r = -0.39 to -0.23, P = 0.02-0.16). CONCLUSIONS: Antihypertensive drug-induced changes in rAI but not bPP were dependent on pulse rate.
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Hipertensão , Nifedipino , Anlodipino , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Humanos , Hipertensão/tratamento farmacológico , Nifedipino/farmacologia , Tetrazóis , Resultado do Tratamento , Valsartana/farmacologiaRESUMO
OBJECTIVE: Although growing evidences have showed that long non-coding RNA (lncRNAs) plasmacytoma variant translocation 1 (PVT1) plays a critical role in the progression of non-small cell lung cancer (NSCLC), there are still many unsolved mysteries remains to be deeply elucidated. This study aimed to find a new underlying mechanism of PVT1 in regulating the tumorigenesis and development of NSCLC. MATERIALS AND METHODS: In this experimental study, Quantitative reverse transcription polymerase chain reaction (qRTPCR) was used to profile the expression of PVT1 in NSCLC tissues and cells. The effects of PVT1 on cell growth, migration and invasion were detected by colony formation assay, Matrigel-free transwell and Matrigel transwell assays, respectively. Changes of the key protein expression in Hippo and NOTCH signaling pathways, as well as epithelialmesenchymal transition (EMT) markers, were analyzed using western blot. Interaction of PVT1 with enhancer of zeste homolog 2 (EZH2) was verified by RNA pull-down, and their binding to the downstream targets was detected by Chromatin Immunoprecipitation (ChIP) assays. RESULTS: These results showed that PVT1 was up-regulated in NSCLC tissue and cell lines, promoting NSCLC cell proliferation, migration and invasion. Knockdown of PVT1 inhibited the expression of Yes-associated protein 1 (YAP1) and NOTCH1 signaling activation. Further, we have confirmed that PVT1 regulated expression of YAP1 through EZH2-mediated miR-497 promoter methylation resulting in the inhibition of miR-497 transcription and its target YAP1 upregulation, and finally NOTCH signaling pathway was activated, which promoted EMT and invasion and metastasis. CONCLUSION: These results suggested that lncRNA PVT1 promotes NSCLC metastasis through EZH2-mediated activation of Hippo/NOTCH1 signaling pathways. This study provides a new opportunity to advance our understanding in the potential mechanism of NSCLC development.
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BACKGROUND: MicroRNAs (miRNAs) are crucial regulators in the pathological processes and drug resistance of lung cancer. In this study, we investigated the role of miR-497-5p in modulating the function of non-small cell lung cancer (NSCLC). METHODS: MiR-497-5p expression in lung cancer tissues and cells was evaluated by qRT-PCR. Cell proliferation was evaluated by CCK-8 assay and colony-formation assay. Cell cycle and cell apoptosis were detected by flow cytometry. The effect of miR-497-5p on the expression of Yes-associated protein 1 (YAP1) and TEA domain family member 1 (TEAD1) was analyzed by qRT-PCR, Western blot and luciferase activity assay. RESULTS: The expression of miR-497-5p was significantly downregulated in lung cancer tissues and cells compared with paired normal tissues and cells. Overexpression of miR-497-5p induced growth retardation and apoptosis of A549 lung cancer cells. Mechanistically, YAP1 and TEAD1 were targeted and downregulated by miR-497-5p. Finally, we found that miR-497-5p increased cisplatin chemosensitivity in A549 cells. CONCLUSIONS: MiR-497-5p suppresses cell proliferation and resistance to cisplatin in NSCLC by downregulating the expression of YAP1 and TEAD1.
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A complexation of non-fluorescent phenformin hydrochloride (PFH) with cucurbit [7]uril (CB [7]) in aqueous solution was investigated using the fluorescent probe of palmatine (PAL) coupled with CB [7]. The fluorescent probe of CB [7]-PAL exhibited strong fluorescence in aqueous solution, which was quenched gradually with the increase of PFH. This effect is observed because when PFH was added to the host-guest system of CB [7]-PAL, PFH and PAL competed to occupy the CB [7] cavity. Portions of the PAL molecule were expelled from the CB [7] cavity owing to the introduction of PFH. Based on the significant quenching of the supramolecular complex fluorescence intensity, a fluorescence method of high sensitivity and selectivity was developed to determine PFH with good precision and accuracy for the first time. The linear range of the method was 0.005-1.9 µg mL(-1) with a detection limit of 0.003 µg mL(-1). In this work, association constants (K) of PFH with CB [7] were also determined. KCB [7]-PFH=(2.52±0.05)×10(5) L mol(-1). The ability of PFH to bind with CB [7] is stronger than that of PAL. The results of a density functional theory calculation authenticated that the moiety of PFH was embedded in the hydrophobic cavity of CB [7] tightly, and the nitrogen atom is located in the vicinity of a carbonyl-laced portal in the energy-minimized structure. The molecular modelling of the interaction between PFH and CB [7] was also confirmed by (1)H NMR spectra (Bruker 600 MHz).
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Hidrocarbonetos Aromáticos com Pontes/química , Corantes Fluorescentes/química , Imidazóis/química , Modelos Químicos , Fenformin/análise , Fenformin/química , Espectroscopia de Ressonância MagnéticaRESUMO
With 319 rice varieties as test objects, this paper studied the effects of cadmium on their seed germination. The results showed that after treated with 10 mg x L(-1) of Cd2+, seed germination rate was less affected, but root growth was restrained evidently. Cadmium had more serious impact on root than on sprout. Different rice varieties had different germination responses to Cd2+, with the sequence of conventional rice (Japonica rice) > hybrid rice (Indianica rice) > conventional rice (Indianica rice). The root length and number of two-line sterilities were restrained more strongly than those of three-line sterilities. Based on their responses to Cd2+, the test 319 varieties were clustered into 3 types, i.e., endurant type, medium type, and sensitive type.