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1.
Plant Cell ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32358072

RESUMO

Chromatin remodeling and histone modifications are important for development and floral transition in plants. However, it is largely unknown whether and how these two epigenetic regulators coordinately regulate the important biological processes. Here, we identified three types of ISWI chromatin remodeling complexes in Arabidopsis thaliana. We found that ARID5, a subunit of a plant-specific ISWI complex, can regulate development and floral transition. The ARID-PHD dual domain cassette of ARID5 recognizes both the H3K4me3 histone mark and AT-rich DNA. We determined the ternary complex structure of the ARID5 ARID-PHD cassette with an H3K4me3 peptide and an AT-containing DNA. The H3K4me3 peptide is combinatorially recognized by the PHD and ARID domains, while the DNA is specifically recognized by the ARID domain. Both PHD and ARID domains are necessary for the association of ARID5 with chromatin. The results suggest that the dual recognition of AT-rich DNA and H3K4me3 by the ARID5 ARID-PHD cassette may facilitate the association of the ISWI complex with specific chromatin regions to regulate development and floral transition.

2.
Infect Dis Poverty ; 9(1): 50, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381098

RESUMO

BACKGROUND: China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0-73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. RESULTS: One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02-0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02-0.31; χ2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21-0.12; χ2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. CONCLUSIONS: No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT02313610.

3.
Int J Mol Sci ; 21(9)2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32403414

RESUMO

Combined androgen blockade using bicalutamide (Bic) is a therapeutic choice for treating prostate cancer (PCa). However, even at regular clinical dosages, Bic frequently shows adverse effects associated with cardiovascular and renal damage. Previously, we found that Bic selectively damaged mesangial cells compared to tubular cells and in an in vivo rat model, we also found renal damage caused by Bic. In the present study, a rat mesangial cell model was used to further the investigation. Results indicated that Bic enhanced lactate dehydrogenase release, reactive oxygen species (ROS) production, lysosome population and kidney injury molecule-1 and decreased N-cadherin. Bic elicited mitochondrial swelling and reduced the mitochondrial potential, resulting in severe suppression of the oxygen consumption rate (OCR), maximum respiration and ATP production. The hypoxia-inducible factor (HIF)-1 transcriptional activity and messenger RNA were significantly upregulated in dose-dependent manners. The HIF-1 protein reached a peak value at 24 h then rapidly decayed. BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 and cleaved caspase-3 were dose-dependently upregulated by Bic (60 M) and that eventually led to cell apoptosis. It is suggested that Bic induces renal damage via ROS and modulates HIF-1 pathway and clinically, some protective agents like antioxidants are recommended for co-treatment.

4.
Int J Mol Sci ; 21(9)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365658

RESUMO

Nifedipine (NF) is reported to have many beneficial effects in antihypertensive therapy. Recently, we found that NF induced lipid accumulation in renal tubular cells. Palmitic acid-induced renal lipotoxicity was found to be partially mediated by endoplasmic reticular (ER) stress, while it can also be elicited by NF in kidney cells; we examined the induction of suspected pathways in both in vitro and in vivo models. NRK52E cells cultured in high-glucose medium were treated with NF (30 µM) for 24-48 h. ER stress-induced lipotoxicity was explored by staining with thioflavin T and Nile red, transmission electron microscopy, terminal uridine nick-end labeling, and Western blotting. ER stress was also investigated in rats with induced chronic kidney disease (CKD) fed NF for four weeks. NF induced the production of unfolded protein aggregates, resulting in ER stress, as evidenced by the upregulation of glucose-regulated protein, 78 kDa (GRP78), activating transcription factor 6α (ATF6α), C/EBP-homologous protein (CHOP), and caspases-12, -3, and -7. In vitro early apoptosis was more predominant than late apoptosis. Most importantly, ATF6α was confirmed to play a unique role in NF-induced ER stress in both models. CKD patients with hypertension should not undergo NF therapy. In cases where it is required, alleviation of ER stress should be considered to avoid further damaging the kidneys.

5.
World Neurosurg ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32311555

RESUMO

OBJECTIVE: Currently, it remains controversial about the guidelines for the application of low molecular weight heparin (LMWH) in patients with acute ischemic stroke (AIS). Therefore, this meta-analysis was carried out aiming to systematically investigate the short-term and long-term safety and efficacy of LMWH in AIS patients. METHODS: Three electronic databases, including Pubmed, Embase database, and Cochrane library, were comprehensively retrieved by two investigators independently. Finally, a total of 19 randomized controlled trials (RCTs) were enrolled for analysis. The safety endpoints in this study included all-cause mortality, risk of bleeding (major, minor or cerebral hemorrhage), and the efficacy endpoints were the prevention of deep vein thrombosis (DVT)and recurrent stroke. RESULTS: The application of LMWH led to a decreased risk of DVT, and there was no significant association in all-cause mortality or recurrent stroke. According to age-stratified analyses, the risk of all-cause mortality increased by 39% (risk ratio, RR 1.39,1.03-1.88;I20%)in AIS patients aged over 70years who used LMWH for 14 days, and there was no significant effect on preventing DVT(RR 0.69,0.14-3.52;I226.4%) in patients aged below 70years within 3 months. Moreover, enoxaparin and danaparoid were more effective on preventing DVT, regardless of age. CONCLUSIONS: To sum up, based on the limited studies available currently, the early use of LMWH in AIS patients aged over 70 years should be cautious, since it may increase the risk of all-cause mortality. For patients aged below 70years, the early use of LMWH significantly reduces the short-term risk of DVT, but there is no significant relationship in the long-term. In terms of DVT prevention, enoxaparin and danaparoid are probably more effective. Nonetheless, more future RCTs are warranted to verify and support this conclusion.

6.
BMC Med Imaging ; 20(1): 30, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183731

RESUMO

BACKGROUND: Osteoporosis (OP) is a systemic metabolic bone disorder identified as an essential health issue worldwide. Orthopedic imaging approaches were commonly used with some limitations. Thus, our study aimed to investigate the diagnostic value of magnetic resonance spectroscopy (1-H MRS) and m-Dixon-Quant in OP. METHODS: A total of 76 subjects were enrolled in the study and bone mineral density (BMD) was measured using quantitative computed tomography (QCT). Then, the subjects were divided into three groups according to BMD: normal control group, osteopenia group and OP group. The following parameters were recorded for each patient: gender, age, height, body weight, waist circumference, and hip circumference. Further, the fat fraction percentage (FF%) values were determined by 1-H MRS and m-Dixon-Quant methods. RESULTS: In both 1-H MRS and magnetic resonance Imaging (MRI) m-Dixon-Quant, the FF% exhibited a negative correlation with BMD (P < 0.05). The FF% value of the OP group was significantly higher than that of the control group (P < 0.05). In addition, the FF% value in the m-Dixon scans was positively related to age, while BMD showed a negative linear relationship with age (P < 0.0001). Further, females had a significantly higher FF% value compared to males (P < 0.01), and height was correlated with BMD (P < 0.05) but not with FF% (P > 0.05). CONCLUSIONS: MRI investigations especially FF% value in the m-Dixon-Quant imaging system is correlated with OP. Its diagnostic value remains to be demonstrated on a large prospective cohort of patients. Besides, parameters such as age, gender, and height are important factors for predicting and diagnosing OP.

7.
EMBO J ; 39(7): e102008, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32115743

RESUMO

Deposition of H2A.Z in chromatin is known to be mediated by a conserved SWR1 chromatin-remodeling complex in eukaryotes. However, little is known about whether and how the SWR1 complex cooperates with other chromatin regulators. Using immunoprecipitation followed by mass spectrometry, we found all known components of the Arabidopsis thaliana SWR1 complex and additionally identified the following three classes of previously uncharacterized plant-specific SWR1 components: MBD9, a methyl-CpG-binding domain-containing protein; CHR11 and CHR17 (CHR11/17), ISWI chromatin remodelers responsible for nucleosome sliding; and TRA1a and TRA1b, accessory subunits of the conserved NuA4 histone acetyltransferase complex. MBD9 directly interacts with CHR11/17 and the SWR1 catalytic subunit PIE1, and is responsible for the association of CHR11/17 with the SWR1 complex. MBD9, TRA1a, and TRA1b function as canonical components of the SWR1 complex to mediate H2A.Z deposition. CHR11/17 are not only responsible for nucleosome sliding but also involved in H2A.Z deposition. These results indicate that the association of the SWR1 complex with CHR11/17 may facilitate the coupling of H2A.Z deposition with nucleosome sliding, thereby co-regulating gene expression, development, and flowering time.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31796985

RESUMO

Current studies have shown that fibrauretine can be used in the treatment of cardiovascular diseases; however, the protective mechanism of fibrauretine in cardiovascular diseases is unclear. The aim of this study was to investigate the effect and mechanism of fibrauretine in acute myocardial ischemia-reperfusion injury. We investigated the effects of glucocorticoid receptor/oestrogen receptor (GR/ER)-mediated Akt phosphorylation, extracellular regulated protein kinase (ERK1/2) activation and nitric oxide (NO) on the treatment of acute myocardial ischemia-reperfusion injury by fibrauretine. Myocardial ischemia-reperfusion (I/R) injury models were established in rats and gene-knockout mice, and the infarct size was measured. We detected the expression and phosphorylation of phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor, oestrogen receptor, lactate dehydrogenase (LDH), creatine phosphokinase (CK-MB), stress-activated protein kinase (JNK), P38 protein kinase (P38 MAPK) and nitric oxide synthase (NOS) with or without the inhibitors to investigate the protective effect of fibrauretine on the heart. The results showed that fibrauretine can significantly reduce the myocardial infarction area in myocardial I/R injury, inhibit the activities of LDH and CK-MB in the serum, and increase the content of NO. However, the effects of fibrauretine on the reduction of the myocardial infarction area were eliminated by the PI3K inhibitor LY294002, Akt inhibitor IV, GR inhibitor RU468, ER inhibitor tamoxifen, eNOS inhibitor L-NAME and ERK1/2 inhibitor U0126. Moreover, in the case of WT mice and gene-knockout eNOS and iNOS mice, fibrauretine was able to significantly reduce the myocardial infarction area in iNOS-/- and wild type mice. However, there was no significant protective effect of fibrauretine in eNOS-/- mice. It is suggested that eNOS plays an important role in the protective effect of fibrauretine on the heart. Therefore, the results of this study show that the protective effect of fibrauretine on myocardial I/R injury is closely associated with eNOS expression, GR/ER-induced Akt phosphorylation and ERK1/2 activation.

9.
Life Sci ; 239: 116935, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610203

RESUMO

BACKGROUND: The protective effects of gastrodin and rhynchophylline in ischaemic injury have been reported. However, the underlying mechanism and the effect of the combination of these two drugs in ischaemic injury remain unclear. Herein, we aimed to explore the effects of the combination of gastrodin and rhynchophylline on ischaemia-induced inflammasome activation as well as the underlying mechanism. METHODS: Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD)-treated BV2 cells were used as in vivo and in vitro models of ischaemia, respectively. Cerebral injury was determined by TTC staining, H&E staining and neurological deficit scores. The effects of the combination of gastrodin and rhynchophylline on inflammasome activation were measured by the MTT assay, Western blotting and ELISA. The expression of miR-21-5p and miR-331-5p was measured by qRT-PCR. The potential binding between miR-21-5p and TXNIP and between miR-331-5p and TRAF6 was analysed with Targetscan and a luciferase assay. RESULTS: MCAO-induced tissue infarction, neurological deficits, inflammasome activation, and downregulation of miR-21-5p and miR-331-5p were all mitigated by the combination of gastrodin and rhynchophylline. In OGD-treated BV2 cells, the combination of gastrodin and rhynchophylline also alleviated inflammasome activation and restored the expression of miR-21-5p and miR-331-5p. TXNIP and TRAF6 were confirmed to be targets of miR-21-5p and miR-331-5p, respectively. Moreover, OGD-induced inflammasome activation was attenuated by the overexpression of either miR-331-5p or miR-21-5p and was further attenuated by the overexpression of both. Finally, we demonstrated that a miR-21-5p inhibitor and/or a miR-331-5p inhibitor counteracted the protective effects of gastrodin and/or rhynchophylline. CONCLUSIONS: The combination of gastrodin and rhynchophylline exerts neuroprotective effects by preventing ischaemia-induced inflammasome activation via upregulating miR-21-5p and miR-331-5p.


Assuntos
Álcoois Benzílicos/farmacologia , Glucosídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , MicroRNAs/metabolismo , Oxindois/farmacologia , Animais , Isquemia Encefálica/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Inflamassomos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Fármacos Neuroprotetores , Ativação Transcricional/efeitos dos fármacos
10.
Diabetes Metab Syndr Obes ; 12: 1705-1716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564938

RESUMO

Objective: To investigate the effect of gross saponins of Tribulus terrestris (GSTT) on erectile function in rats resulting from type 2 diabetes mellitus (T2DMED). Methods: The T2DMED model was constructed by high-fat and high-sugar feeding and streptozotocin injection. After 4 weeks of GSTT intervention. Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured in each group. The level of nitric oxide (NO) in the cavernous tissue was detected using the nitrate reductase method. The production of reactive oxygen species (ROS) was detected using DHE fluorescent probe detection. Cyclic adenosine monophosphate (cGMP) level was detected by enzyme-linked immunosorbent assay, and endothelial nitric oxide synthase (eNOS) was detected using immunohistochemistry. Masson staining was used to detect the cavernosal smooth muscle/collagen ratio. Apoptosis in endothelial cells was measured using TUNEL. Western blotting method to detect the protein expression level of eNOS, TIMP-1, cleaved caspase 3, and cleaved caspase 9. Results: After treatment, the ICP and ICP/MAP values of the GSTT were significantly higher than those of the T2DMED group (P<0.05). Unlike the T2DMED group, the GSTT group showed significantly increased NO levels (P<0.05) and decreased ROS levels (P<0.05). There was no significant difference between the GSTT group and the sildenafil group in increasing cGMP levels (P>0.05), and the mixed group had higher levels than these two groups (P<0.05). Immunohistochemistry and Western blotting showed that the expression of eNOS in the GSTT was significantly higher than that in the T2DMED groups (P<0.05). Masson staining showed that the smooth muscle/collagen ratio of the GSTT group was significantly higher than that of the T2DMED groups (P<0.05), the expression of TIMP-1 was lower than that of T2DMED group (P<0.05). TUNEL assay showed that the apoptotic index and cleaved caspase 3 and cleaved caspase 9 expression level of GSTT group were lower than that of the T2DMED group (P<0.05). Conclusion: GSTT can protect T2DMED rats' erectile function by improving penile endothelial function and inhibiting cavernosum fibrosis, inhibiting apoptosis, and is synergistic with sildenafil.

11.
Ecotoxicol Environ Saf ; 184: 109640, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31499448

RESUMO

Altering Cd chemical form is one of the mechanisms to alleviate Cd toxicity in rice plant. Field experiments were carried out in this study to investigate the potential of rice vegetative organs in altering Cd into insoluble chemical forms in the natural environment. Experimental results showed that more than 80% of Cd in rice roots existed in the insoluble forms. Uppermost nodes altered Cd into insoluble form preferentially and generally had higher content of insoluble Cd than other organs. Rachises displayed a slow increasing trend in soluble Cd when total Cd in roots was less than 1.8 mg kg-1. However, when Cd content in roots exceeded 2.8 mg kg-1, the ratio of insoluble to soluble Cd remained stable at 85:15 in rachises and roots, and at 75:25 in uppermost nodes and flag leaves. Cd concentration in grains was greatly lower than that in vegetative organs, and closely correlated with the content of soluble Cd in rachises (r = 0.991**) as well as in uppermost nodes. Soluble Cd in the uppermost nodes displayed a much lower mobility than that in other organs. Accumulation of soluble Cd was always companied by decrease of Ca and increase of Mn in roots, uppermost nodes and rachises. A small increase of soluble Cd from 0.05 to 0.1 mg kg-1 caused a sharp decline of Ca:Mn ratio in roots and rachises. Roots and nodes had much higher Ca:Mn ratio than rachises when soluble Cd was less than 0.5 mg kg-1 in them. These results indicate that vegetative organs have a great potential to alter more than 75% Cd into insoluble forms and increasing Ca:Mn ratio may be another way to alleviate Cd toxicity by establishing new ionic homeostasis in rice plants.


Assuntos
Cádmio/toxicidade , Cálcio/análise , Manganês/análise , Oryza/efeitos dos fármacos , Cádmio/química , Grão Comestível/química , Grão Comestível/efeitos dos fármacos , Modelos Teóricos , Oryza/química , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Raízes de Plantas/química , Raízes de Plantas/efeitos dos fármacos , Solubilidade
12.
Int J Nurs Sci ; 6(1): 24-30, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31406865

RESUMO

Objectives: Maker education is a dominant force in education reform and is viewed as a revolutionary way to learn. As innovative pedagogy is continuously explored in the field of nursing, the emerging role of maker education must be examined. This research aims to build a nursing bachelor education program based on maker education and to evaluate the effectiveness of this program. Methods: Forty volunteer junior students majoring in nursing from a college were the subjects for this quasi-experiment. The training program for nursing students based on maker education was developed and implemented as an additional class for a period of 12 weeks. Before and after the experiment, two measures including the "Williams Creative Scale" and "Current Status Questionnaire of Nursing Students' Learning" were adopted for investigation, and corresponding statistical methods were used for analysis. The degree of satisfaction with this training program was investigated after the experiment. Results: The average scores of creativity, learning interest, cooperative learning skill, scientific research ability, and information attainment of the nursing students after the implementation of maker education all improved. The differences in the above points before and after the experiment were all statistically significant (P < 0.05). Most of the students expressed satisfaction with this training program (72.5% were very satisfied, 15.0% were partially satisfied, and 12.5% were not satisfied). Conclusion: Implementing the training program based on maker education enhanced student creativity, learning interest, cooperative learning skill, scientific research ability, and information attainment. Comprehensive nursing talents were also cultivated. Our data suggested the importance of improving this program, adopting the method, and pursuing research in nursing education.

13.
J Cardiovasc Pharmacol ; 74(3): 255-265, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306366

RESUMO

A majority of existing studies have focused on the efficacy of inhaled long-acting bronchodilators (ILABs), such as long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs), and LABAs combined with LAMAs in treating chronic obstructive pulmonary disease (COPD). The current meta-analysis aimed to investigate the correlation of ILABs with specific cardiovascular adverse events (CAEs). Five electronic databases, including PubMed, Embase, Cochrane Library, Scopus, and Web of Science were systematically retrieved. Finally, 16 randomized controlled trials were enrolled into the current meta-analysis. Typically, the efficacy of 3 major classes of drugs (LABAs, LAMAs, and LABAs combined with LAMAs), and 7 specific drugs (including formoterol, glycopyrrolate, indacaterol, olodaterol, Salmeterol, tiotropium, and vilanterol) for 4 CAEs, including myocardial infarction, cardiac failure (CF), ischemic heart disease (IHD), and stroke in stable COPD patients, was examined. All the pooled results were analyzed through the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). The direct meta-analysis results suggested that LABAs could increase the risk of CF in patients with stable COPD compared with placebo controls (OR 1.70, 95% CI, 1.00-2.90). In addition, network meta-analysis results indicated that LAMAs combined with LABAs would result in an increased risk of CF in patients with stable COPD (OR 2.31, 95% CI, 1.10-5.09). According to the ILABs specific drug analysis, formoterol may potentially have protective effects on IHD compared with placebo controls (OR 0.45, 95% CI, 0.18-1.00). In conclusion, among these 3 kinds of ILABs, including LAMAs, LABAs, and LABAs/LAMAs, for stable COPD patients, LAMAs and LABAs are associated with the least possibility to induce myocardial infarction and stroke, respectively. However, the application of LABAs will probably increase the risk of CF; they should be used with caution for stable COPD patients with CF. In addition, in specific-drug analysis, the use of formoterol can reduce the risk of treatment-related IHD. Nevertheless, more studies on different drug doses are needed in the future to further validate this conclusion.

14.
J Sports Sci Med ; 18(2): 213-222, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31191090

RESUMO

Exercise program has been associated with improved cardiovascular outcomes in patients sustaining coronary artery disease. However, little is known about the role of exercise after percutaneous coronary intervention (PCI). Published literature was searched from Embase, PubMed, Wanfang Data, Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure (CNKI) and Central Database. Exercise versus no exercise following PCI in the patients with coronary heart disease (CHD) was investigated in randomized trials. Left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), 6-minute walking distance (6MWD), cardiac death, myocardial infarction, coronary angioplasty, coronary artery bypass surgery (CABG), and angina pectoris or restenosis per randomized patients were analyzed by meta-analytic procedure to compare the curative effect of exercise program with exclusive exercise program after PCI. Ten randomized controlled trials including 1274 subjects (636 in exercise group and 638 in control group) were analyzed. The meta-analysis demonstrated that LVEF was significantly improved in exercise group (MD = 2.82, 95% CI [1.50, 4.14], p < 0.05). In contrast, the incidence rate of cardiac death (RR = 0.24, 95% CI [007, 0.76], p = 0.02), myocardial infarction (RR = 0.23, 95% CI [0.09, 0.57], p = 0.002), coronary angioplasty (RR = 0.47, 95% CI [0.26, 0.84], p = 0.01), angina pectoris (RR = 0.39, 95% CI [0.24, 0.64], p = 0.0002) and restenosis (RR = 0.36, 95% CI [0.16, 0.83], p = 0.02) were significantly lower in exercise group. LVEDD (MD = -2.01, 95% CI [-4.72, 0.70]), 6MWD (MD = 50.85, 95% CI [-13.24, 114.94]), and CABG (RD = -0.01, 95% CI [-0.05, 0.03]) were not significantly different in the patients with or without exercise (p = 0.71). Trial sequential analysis reflected traditional meta-analysis might generate a false positive conclusion for MI and cardiac death. There was no firm evidence to support the beneficial effects of exercise after PCI for the CHD patients to improve heart function or to reduce the incidence of adverse cardiovascular events.


Assuntos
Doença da Artéria Coronariana/terapia , Terapia por Exercício , Intervenção Coronária Percutânea , Angina Pectoris/complicações , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Reestenose Coronária/complicações , Teste de Esforço , Humanos , Infarto do Miocárdio/complicações , Revascularização Miocárdica , Ensaios Clínicos Controlados Aleatórios como Assunto , Função Ventricular Esquerda
15.
Emerg Microbes Infect ; 8(1): 724-733, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130075

RESUMO

Anti-HBs is a well-known marker of protective capability against HBV. However, little is known about the association between the qAnti-HBs determined by immunoassays and the neutralization activity (NAT) derived from functional assays. We developed an in vitro assay for direct measurement of the NAT of human sera. The new assay was highly sensitive, with an analytical sensitivity of 9.6 ± 1.3 mIU/mL for the HBIG standard. For serum detection, the maximum fold dilution required to produce ≥50% inhibition (MDF50) of HBV infection was used as the quantitative index. In vitro NAT evaluations were conducted for a cohort of 164 HBV-free healthy individuals. The results demonstrated that the NAT positively correlated with the qAnti-HBs (R2 = 0.473, p < 0.001). ROC analysis indicated that the optimal cutoff value of the qAnti-HBs to discriminate significant NAT (MDF50 ≥ 8) was 62.9 mIU/mL, with an AUROC of 0.920. Additionally, we found that the qAnti-HBc was another independent parameter positively associated with the NAT (R2 = 0.300, p < 0.001), which suggested that antibodies against other HBV proteins generated by previous HBV exposure possibly also contribute to the NAT. In summary, the new cell-based assay provides a robust tool to analyse the anti-HBV NAT. Abbreviations: HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; Anti-HBs: Hepatitis B surface antibody; HBeAg: Hepatitis B e antigen; Anti-HBc: Hepatitis B core antibody; qAnti-HBs: quantitative hepatitis B surface antibody; qAnti-HBc: quantitative hepatitis B core antibody; qHBeAg: quantitative hepatitis B e antigen; NAT: neutralization activity; HBIG: hepatitis B immune globulin; NTCP: Na+-taurocholate cotransporting polypeptide; IRES: internal ribosome entry site; ccHBV: cell culture derived hepatitis B virus; GE/cell: genome equivalent per cell; MOI: multiplicity of infection; Dpi: day post infection; HepG2-TetOn: a HepG2-derived cell line that expresses the doxycycline-regulated transactivator; ROC: receiver operating characteristic curve; AUROC: area under receiver operating characteristic curve; LLOQ: the lower limits of quantification; MDF50: the maximum fold dilution required to produce ≥50% inhibition; IC50: half maximal inhibitory concentration.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/imunologia , Testes de Neutralização/métodos , Soro/imunologia , Células Hep G2 , Humanos , Curva ROC , Sensibilidade e Especificidade
16.
World Neurosurg ; 127: 92-96, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30947013

RESUMO

BACKGROUND: Basilar invagination (BI) is a developmental anomaly and commonly presents with neurologic findings. The incidence of BI associated with other osseous anomalies of the craniovertebral junction is high, including incomplete ring of C1 with spreading of the lateral masses, atlanto-occipital assimilation, hypoplasia of the atlas, basiocciput hypoplasia, and occipital condylar hypoplasia. However, BI combined with C1 prolapsing into the foramen magnum (FM) is an extremely rare condition. CASE DESCRIPTION: A previously healthy 6-year-old girl (case 1) presented with extremities numbness and left limb weakness over a period of 3 months. Radiograph and computed tomography (CT) scan demonstrated basilar invagination with C1 and dens upward into the FM and C2-3 congenital fusion. Magnetic resonance imaging (MRI) showed ventral brainstem and medulla compression, and the medulla-cervical angle was about 100°. The patient underwent transoral anterior decompression, reduction, and fusion by transoral atlantoaxial reduction plate surgery. The symptoms of extremities numbness and limb weakness were all alleviated after surgery. Postoperative MRI showed that the medulla-cervical angle improved from 100° to 143°. An 11-year-old boy (case 2) presented with a 2-month history of limbs numbness and weakness. CT scan and MRI demonstrated BI and compression of the spinal cord, with a craniospinal angle of only 63°. The 3-dimensional (3D) printed model showed that the anterior arch and lateral of C1 was 90° flipping and vertically upward prolapsing into the FM together with the dens, and the width of the atlas was greater than the maximum diameter of the FM, which resulted in structural incarceration. The patient received posterior occipitocervical fixation and fusion surgery with hyperextension skull traction. Postoperative CT scan revealed the craniospinal angle increased to 102°. CONCLUSIONS: We present 2 rare cases of BI combined with C1 prolapsing into the FM. We adopted different surgical strategies with satisfying outcome for these patients. We deem that the treatment of unique BI should be individualized according to the different image characteristics. The image-based modern rapid prototyping and 3D printed techniques can provide invaluable information in presurgical planning for complex craniovertebral junction anomalies.


Assuntos
Atlas Cervical/patologia , Forame Magno/patologia , Platibasia/patologia , Platibasia/cirurgia , Articulação Atlantoccipital/patologia , Criança , Descompressão Cirúrgica , Feminino , Humanos , Masculino , Resultado do Tratamento
17.
Int J Mol Sci ; 20(7)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934807

RESUMO

Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Rim/metabolismo , Lipogênese/efeitos dos fármacos , Nifedipino/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Transcrição Genética/efeitos dos fármacos , Animais , Vias Biossintéticas/efeitos dos fármacos , Antígenos CD36/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/metabolismo , Regulação para Baixo/efeitos dos fármacos , Espaço Intracelular/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/lesões , Modelos Biológicos , PPAR alfa/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
Sci Rep ; 9(1): 3392, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833616

RESUMO

Bicalutamide (Bic) is frequently used in androgen deprivation therapy (ADT) for treating prostate cancer. ADT-induced hypogonadism was reported to have the potential to lead to acute kidney injury (AKI). ADT was also shown to induce bladder fibrosis via induction of the transforming growth factor (TGF)-ß level. We hypothesized that Bic can likely induce renal fibrosis. To understand this, a cell model was used to explore expressions of relevant profibrotic proteins. Results indicated that Bic initiated multiple apoptotic and fibrotic pathways, including androgen deprivation, downregulation of the androgen receptor → phosphatidylinositol-3-kinase → Akt pathway, upregulation of the extrinsic apoptotic pathway- tumor necrosis factor α → nuclear factor κB → caspase-3, increased expressions of fibrosis-related proteins including platelet-derived growth factor ß, fibronectin and collagen IV, and enhanced cell migration. The endoplasmic reticular stress pathway and smooth muscle actin were unaffected by Bic. Co-treatment with testosterone was shown to have an anti-apoptotic effect against Bic, suggesting a better outcome of Bic therapy if administered with an appropriate testosterone intervention. However, since Bic was found to inhibit the membrane transport and consumption rates of testosterone, a slightly larger dose of testosterone is recommended. In conclusion, these pathways can be considered to be pharmaceutically relevant targets for drug development in treating the adverse effects of Bic.

19.
Plant Physiol ; 179(2): 656-670, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30567970

RESUMO

Plant roots rely on inorganic orthophosphate (Pi) transporters to acquire soluble Pi from soil solutions that exists at micromolar levels in natural ecosystems. Here, we functionally characterized a rice (Oryza sativa) Pi transporter, Os Phosphate Transporter-1;3 (OsPHT1;3), that mediates Pi uptake, translocation, and remobilization. OsPHT1;3 was directly regulated by Os Phosphate Starvation Response-2 and, in response to Pi starvation, showed enhanced expression in young leaf blades and shoot basal regions and even more so in roots and old leaf blades. OsPHT1;3 was able to complement a yeast mutant strain defective in five Pi transporters and mediate Pi influx in Xenopus laevis oocytes. Overexpression of OsPHT1;3 led to increased Pi concentration both in roots and shoots. However, unlike that reported for other known OsPHT1 members that facilitate Pi uptake at relatively higher Pi levels, mutation of OsPHT1;3 impaired Pi uptake and root-to-shoot Pi translocation only when external Pi concentration was below 5 µm Moreover, in basal nodes, the expression of OsPHT1;3 was restricted to the phloem of regular vascular bundles and enlarged vascular bundles. An isotope labeling experiment with 32P showed that ospht1;3 mutant lines were impaired in remobilization of Pi from source to sink leaves. Furthermore, overexpression and mutation of OsPHT1;3 led to reciprocal alteration in the expression of OsPHT1;2 and several other OsPHT1 genes. Yeast-two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays all demonstrated a physical interaction between OsPHT1;3 and OsPHT1;2. Taken together, our results indicate that OsPHT1;3 acts as a crucial factor for Pi acquisition, root-to-shoot Pi translocation, and redistribution of phosphorus in plants growing in environments with extremely low Pi levels.


Assuntos
Oryza/metabolismo , Proteínas de Transporte de Fosfato/metabolismo , Fosfatos/metabolismo , Proteínas de Plantas/metabolismo , Animais , Transporte Biológico , Feminino , Regulação da Expressão Gênica de Plantas , Mutação , Oócitos/metabolismo , Oryza/genética , Floema/genética , Floema/metabolismo , Proteínas de Transporte de Fosfato/genética , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Plantas Geneticamente Modificadas , Mapas de Interação de Proteínas , Técnicas do Sistema de Duplo-Híbrido , Xenopus laevis
20.
Front Microbiol ; 9: 1870, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233502

RESUMO

Bacillus cereus was isolated from ready-to-serve brine goose, identified by 16S rRNA gene sequencing analysis and treated with a commercial microwave sterilization condition (a power of 1,800 W at 85°C for 5 min). The influence of microwaves on the morphology, the permeability of membrane and the expression of total bacterial proteins was observed. Microwave induced the clean of bacterial nuclear chromatin, increased the permeability and disrupted the integrity of membrane. Twenty-three proteins including 18 expressed down-regulated proteins and 5 expressed up-regulated proteins were identified by HPLC-MS/MS in the samples treated with microwave. The frequencies of proteins changed after microwaves treatment were labeled as 39.13% (synthesis and metabolism of amino acid or proteins), 21.74% (carbohydrate metabolism), 8.70% (anti-oxidant and acetyl Co-A synthesis), and 4.35% (the catalyst of catabolism of bacterial acetoin, ethanol metabolism, glyoxylate pathway, butyrate synthesis and detoxification activity), respectively. This study indicates that microwaves result in the inactivation of Bacillus cereus by cleaning nuclear chromatin, disrupting cell membrane and disordering the expression of proteins.

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