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1.
Medicine (Baltimore) ; 100(39): e27362, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596148

RESUMO

BACKGROUND: Individual randomized trials are not powered to assess the relationship between use of sodium-glucose transporter 2 inhibitors and risk of stroke. We sought to explore this issue by a meta-analysis incorporating relevant trials including several latest trials. METHODS: Cardiovascular outcome trials of gliflozins were included. Primary outcome was stroke, while secondary outcome was major adverse cardiovascular events (MACE), which was a composite of stroke, myocardial infarction, or cardiovascular death. Meta-analysis was conducted stratified by with/without chronic kidney disease (CKD), with/without heart failure (HF), and with/without atherosclerotic cardiovascular disease (ASCVD), and stratified by different gliflozins. RESULTS: We included 9 trials in this meta-analysis. Compared with placebo, gliflozins significantly lowered stroke (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.55-0.84) and MACE (HR 0.77, 95% CI 0.69-0.86) in type 2 diabetes (T2D) patients with CKD, but did not significantly affect stroke (HR 1.00, 95% CI 0.86-1.16) and MACE (HR 0.94, 95% CI 0.86-1.02) in T2D patients without CKD. Gliflozins had no significant effects on the stroke risk (HR 0.94, 95% CI 0.82-1.07) in T2D patients regardless of HF status (Psubgroup = .684) and ASCVD status (Psubgroup = .915), but significantly lowered MACE (HR 0.89, 95% CI 0.83-0.96) in T2D patients regardless of HF status (Psubgroup = .428) and ASCVD status (Psubgroup = .423). Canagliflozin (HR 0.84, 95% CI 0.69-1.01) showed the trend of a reduction in the stroke risk versus placebo, and sotagliflozin (HR 0.73, 95% CI 0.54-0.98) significantly lowered the stroke risk; whereas the other 3 gliflozins did not significantly affect that risk. Ertugliflozin (HR 0.97, 95% CI 0.85-1.11) had no significant effects on the MACE risk, whereas the other 4 gliflozins significantly lowered that risk. CONCLUSIONS: Gliflozins, especially canagliflozin and sotagliflozin, should be recommended in T2D patients with CKD to prevent stroke. Most gliflozins lower the risk of MACE in T2D patients regardless of HF status and ASCVD status, whereas ertugliflozin is not observed to lower that risk.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/complicações , Humanos , Metanálise como Assunto , Insuficiência Renal Crônica/complicações
2.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575973

RESUMO

Radiation damages many cellular components and disrupts cellular functions, and was previously reported to impair locomotion in the model organism Caenorhabditis elegans. However, the response to even higher doses is not clear. First, to investigate the effects of high-dose radiation on the locomotion of C. elegans, we investigated the dose range that reduces whole-body locomotion or leads to death. Irradiation was performed in the range of 0-6 kGy. In the crawling analysis, motility decreased after irradiation in a dose-dependent manner. Exposure to 6 kGy of radiation affected crawling on agar immediately and caused the complete loss of motility. Both γ-rays and carbon-ion beams significantly reduced crawling motility at 3 kGy. Next, swimming in buffer was measured as a motility index to assess the response over time after irradiation and motility similarly decreased. However, swimming partially recovered 6 h after irradiation with 3 kGy of γ-rays. To examine the possibility of a recovery mechanism, in situ GFP reporter assay of the autophagy-related gene lgg-1 was performed. The fluorescence intensity was stronger in the anterior half of the body 7 h after irradiation with 3 kGy of γ-rays. GFP::LGG-1 induction was observed in the pharynx, neurons along the body, and the intestine. Furthermore, worms were exposed to region-specific radiation with carbon-ion microbeams and the trajectory of crawling was measured by image processing. Motility was lower after anterior-half body irradiation than after posterior-half body irradiation. This further supported that the anterior half of the body is important in the locomotory response to radiation.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34491893

RESUMO

Cells of bacterial strains G9T and 7MK23T, isolated from forest soil samples collected from the Dinghushan Biosphere Reserve, Guangdong Province, PR China, were Gram-stain-negative, aerobic and rod-shaped. Strain G9T was motile with single polar flagellum and grew at 12-37 °C (optimum, 28 °C), pH 4.5-8.0 (optimum, pH 6.0-7.5) and in the presence of 0-3.5 % NaCl (optimum, 1.5%, w/v); while strain 7MK23T was non-motile and grew at 12-42 °C (optimum, 28-33 °C), pH 2.5-8.5 (optimum, pH 4.5-6.5) and NaCl levels of 0-1.0 % (optimum, 0-0.5 %, w/v). Phylogenetic analysis based on 16S rRNA gene sequences revealed that both isolates fell within the cluster of the genus Dyella. The closely related species (with a 16S rRNA gene sequence similarity >98.65%) of strain G9T were Dyella terrae JS14-6T (99.0 %), D. kyungheensis THG-B117T (98.8 %) and D. amyloliquefaciens DHC06T (98.7 %) while that of strain 7MK23T were D. mobilis DHON07T (99.2 %) and D. flava DHOC52T (99.1 %), but the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strains G9T, 7MK23T and the closely related Dyella species listed above were in the ranges of 77.5-83.8 % and 22.0-27.0 %, much lower than the species demarcation lines of 95.5 and 70 %, respectively. Phylogenomic analyses using UBCG and Phylophlan also supported that these two strains represent two novel species of Dyella. The major fatty acids of strain G9T were iso-C15 : 0, iso-C17 : 1 ω9c and iso-C17 : 0 while that of strain 7MK23T were iso-C15 : 0 and anteiso-C15 : 0. Ubiquinone-8 was the only respiratory quinone detected in both strains. The polar lipids of strain G9T consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and several unknown phospholipids, aminophospholipids, aminolipids and lipid while strain 7MK23T contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and several unknown phospholipids and aminophospholipids. The DNA G+C contents of strains G9T and 7MK23T were 64.7 and 63.4 mol%, respectively. On the basis of 16S rRNA gene sequence phylogenetic and phylogenomic analyses as well as phenotypic data obtained, we propose that strains G9T and 7MK23T represent two novel species of the genus Dyella, for which the names Dyella telluris sp. nov. (type strain G9T=KACC 21725T=GDMCC 1.2132T) and Dyella acidiphila sp. nov. (type strain 7MK23T=KCTC 62739T=GDMCC 1.1446T) are proposed.


Assuntos
Florestas , Gammaproteobacteria/classificação , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Gammaproteobacteria/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
4.
Brain Behav ; : e32366, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520636

RESUMO

BACKGROUND: Sleep disorders are highly prevalent among stroke survivors and impede stroke recovery. It is well established that melatonin has neuroprotective effects in animal models of ischemic stroke. However, as a modulator of endogenous physiological circadian rhythms, the effects of melatonin on poststroke sleep disorders remain unclear. In the present study, we investigated how melatonin delivered intraperitoneally once daily in the subacute phase after stroke onset, influencing neuronal survival, motor recovery, and sleep-wake profiles in rats. METHODS: Transient ischemic stroke in male Sprague-Dawley rats was induced with 30 min occlusion of the middle cerebral artery. Melatonin or vehicle was delivered intraperitoneally once daily in the subacute phase, from 2 to 7 days after stroke. Electroencephalogram and electromyogram recordings were obtained simultaneously. RESULTS: Compared to the effects observed in the vehicle-treated ischemic group, after 6 daily consecutive treatment of melatonin at 10 mg/kg starting at ischemic/reperfusion day 2, the infarct volume was significantly decreased (from 39.6 to 26.2%), and the degeneration of axons in the ipsilateral striatum and the contralateral corpus callosum were significantly alleviated. Sensorimotor performances were obviously improved as evidenced by significant increases in the latency to falling off the wire and in the use of the impaired forelimb. In addition to those predictable results of reducing brain tissue damage and mitigating behavioral deficits, repeated melatonin treatment during the subacute phase of stroke also alleviated sleep fragmentation through reducing sleep-wake stage transitions and stage bouts, together with increasing stage durations. Furthermore, daily administration of melatonin at 9 a.m. significantly increased the nonrapid eye movement sleep delta power during both the light and dark periods and decreased the degree of reduction of the circadian index. CONCLUSIONS: Melatonin promptly reversed ischemia-induced sleep disturbances. The neuroprotective effects of melatonin on ischemic injury may be partially associated with its role in sleep modulation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34494310

RESUMO

Yaks display unique properties of the lung and heart, enabling their adaptation to high-altitude environments, but the underlying molecular mechanisms are still largely unknown. In the present study, the proteome differences in lung and heart tissues were compared between yak (Bos grunniens) and three cattle strains (Bos taurus, Holstein, Sanjiang and Tibetan cattle) using the sequential window acquisition of all theoretical mass spectra/data-independent acquisition (SWATH/DIA) proteomic method. In total, 51,755 peptides and 7215 proteins were identified. In the lung tissue, there were 162, 310 and 118 differential abundance proteins (DAPs) in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. In the heart tissue, there were 71, 57 and 78 DAPs in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DAPs were enriched for the retinol metabolism and toll-like receptor categories in lung tissue. The changes in these two pathways may regulate hypoxia-induced factor and immune function in yaks. Moreover, DAPs in heart tissues were enriched for cardiac muscle contraction, Huntington's disease, chemical carcinogenesis and drug metabolism-cytochrome P450. Further exploration indicated that yaks may alter cardiac function through regulation of type 2 ryanodine receptor (RyR2) and Ca2+ -release channels. The present results are useful to further develop an understanding of the mechanisms underlying adaptation of animals to high-altitude conditions.

7.
Pharmacol Res ; 172: 105796, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34343656

RESUMO

Restoring immune balance by targeting macrophage polarization is a potentially valuable therapeutic strategy for ulcerative colitis (UC). Dioscin is a steroidal saponin with potent anti-inflammatory, immunoregulatory, and hypolipidemic effects. This study examined the protective effect of Dioscin on UC in mice and explored the underlying mechanisms. Mice were induced colitis by dextran sulfate sodium (DSS) and concurrently treated with Dioscin oral administration. RAW264.7 cells were skewed to M1 macrophage polarization by lipopolysaccharide (LPS) and interferon-γ (INF-γ) in vitro, and received Dioscin treatment. The results showed that Dioscin ameliorated colitis in mice, reduced macrophage M1 polarization, but markedly promoted M2 polarization in mice colon. Dioscin inhibited mammalian target rapamycin complex 1 (mTORC1)/hypoxia-inducible factor-1α (HIF-1α) signaling and restrained glycolysis in RAW264.7; however, it activated mammalian target rapamycin complex 2 (mTORC2)/peroxisome proliferator-activated receptor-γ (PPAR-γ) signal and facilitated fatty acid oxidation (FAO). The modulation of mTORs signaling may inhibit M1, but promote M2 polarization. Furthermore, the effect of Dioscin on M2 polarization was neutralized by the FAO inhibitor Etomoxir and the mTORC2 inhibitor JR-AB2-011. In parallel, the inhibitory effect of Dioscin on M1 polarization was mitigated by the mTORC1 agonist L-leucine. Both JR-AB2-011 and L-leucine blocked the therapeutic effect of Dioscin in mice with UC. Therefore, Dioscin ameliorated UC in mice, possibly by restraining M1, while skewing M2 polarization of macrophages. Regulation of mTORC1/HIF-1α and mTORC2/PPAR-γ signals is a possible mechanism by which Dioscin inhibited aerobic glycolysis and promoted FAO of macrophages. In summary, Dioscin protected mice against DSS-induced UC by regulating mTOR signaling, thereby adjusting macrophage metabolism and polarization.

9.
Kaohsiung J Med Sci ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34431595

RESUMO

Sepsis is characterized by a severe inflammatory response throughout the whole body and can induce acute kidney injury (AKI). This research aimed to investigate the regulatory mechanisms underlying miR-155-5p in sepsis-induced AKI. CLP-treated mice were used as an in vivo model of sepsis-induced AKI, and LPS-treated HK-2 and TCMK-1 cells were used as in vitro models. Bioinformatics analyses and mechanistic assays were utilized to reveal the relationships between molecules. H&E staining was used to reveal morphological changes in kidney tissues. ELISAs were conducted to detect the concentrations of proinflammatory cytokines. We discovered that miR-155-5p was prominently upregulated in sepsis-induced AKI in vivo and in vitro. MiR-155-5p inhibition alleviated kidney injury in mice. Moreover, WWC1 served as a direct target of miR-155-5p and was negatively regulated by miR-155-5p. WWC1 upregulation inhibited the productions of inflammatory cytokines and suppressed apoptosis in vivo and in vitro. In addition, rescue assays demonstrated that WWC1 knockdown counteracted the inhibitory effect of anti-miR-155-5p on inflammation and apoptosis. Moreover, miR-155-5p could bind to XIST. XIST expression was downregulated in LPS-stimulated HK-2 and TCMK-1 cells. XIST could negatively regulate miR-155-5p expression and positively regulate WWC1 expression. Rescue assays revealed that miR-155-5p overexpression significantly reversed the suppressive effects of XIST upregulation on inflammation and apoptosis. In conclusion, our study revealed that the XIST/miR-155-5p/WWC1 axis modulated sepsis-induced AKI progression, providing promising insight into therapeutic targets for sepsis-induced AKI.

10.
Medicine (Baltimore) ; 100(28): e26561, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260534

RESUMO

BACKGROUND: The factors affecting the efficacy of gliflozins in patients with heart failure (HF) are not clear. We aimed to evaluate the effects of 11 important factors on the efficacy of gliflozins in HF patients. METHODS: Randomized trials assessing gliflozins in HF patients were included. The outcome of interest was composite HF outcome, a composite of cardiovascular death, or hospitalization for HF. Meta-analysis was done according to 11 factors: status of type 2 diabetes, sex, use of angiotensin receptor-neprilysin inhibitor, age, history of hospitalization for HF, estimated glomerular filtration rate, body mass index, New York Heart Association (NYHA) class, race, region, and left ventricular ejection fraction. RESULTS: Compared with placebo, gliflozins reduced the risk of composite HF outcome by 14% in the subgroup of patients with NYHA class III or IV (hazard ratios [HR] 0.86, 95% confidence intervals [CI] 0.75-0.99), by 34% in the subgroup of patients with NYHA class II (HR 0.66, 95% CI 0.59-0.74), and by 85% in the subgroup of patients with NYHA class I (HR 0.15, 95% CI 0.03-0.73). This between-group difference was approximate to statistical significance (Psubgroup = .06). The benefit of gliflozins in HF patients was not affected by the other 10 factors (Psubgroup ≥ .123). CONCLUSIONS: Gliflozins are applicable for a broad population of HF patients as for preventing HF events, while gliflozins may lead to greater benefits in patients with mild HF than in those with moderate to severe HF.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Fatores Etários , Índice de Massa Corporal , Grupos de Populações Continentais , Diabetes Mellitus Tipo 2/epidemiologia , Taxa de Filtração Glomerular , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Volume Sistólico
11.
Artigo em Inglês | MEDLINE | ID: mdl-34231123

RESUMO

BACKGROUND: The relative efficacy of different sodium-glucose transporter 2 inhibitors (SGLT2i) on cardiorenal outcomes is unclear. METHODS: We included cardiovascular outcome trials (CVOTs) of SGLT2i. The eight endpoints of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, cardiovascular death (CVD), CVD or hospitalization for heart failure (HHF), HHF, kidney function progression (KFP), and all-cause death (ACD). We conducted a Bayesian network meta-analysis and calculated the surface under the cumulative ranking curve (SUCRA) probability to rank treatments. RESULTS: We included ten CVOTs involving five SGLT2i. Canagliflozin (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.53-0.77), dapagliflozin (HR 0.70; 95% CI 0.62-0.79), empagliflozin (HR 0.68; 95% CI 0.59-0.78), ertugliflozin (HR 0.70; 95% CI 0.54-0.90), and sotagliflozin (HR 0.66; 95% CI 0.56-0.77) versus placebo reduced HHF, whereas none reduced MI and stroke. Empagliflozin reduced CVD or HHF (HR 0.81; 95% CI 0.67-0.99) and KFP (HR 0.65; 95% CI 0.45-0.93), and dapagliflozin reduced KFP (HR 0.69; 95% CI 0.52-0.92), versus ertugliflozin. Canagliflozin had the greatest SUCRA values for the reduction of MACE, stroke, and HHF, whereas empagliflozin had the greatest SUCRA values for the reduction of MI, CVD, CVD or HHF, KFP, and ACD. CONCLUSIONS: Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin versus placebo reduce HHF but none reduces MI and stroke. Canagliflozin is most effective in reducing MACE and HHF, and empagliflozin is most effective in reducing CVD, CVD or HHF, KFP, and ACD. These findings will guide the use of specific SGLT2i in the prevention of different cardiorenal events.

12.
Ginekol Pol ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263920

RESUMO

OBJECTIVES: This article aimed to explore the relationship between hepatitis B virus infection (HBV) and intrahepatic cholestasis in pregnancy (ICP). MATERIAL AND METHODS: We conducted a retrospective study at the Beijing Youan Hospital in China between January 1, 2010 and November 31, 2016. In total, 217 pregnancies were identified and retrospectively studied. Characteristics, pregnant outcomes and the rate of mother-to-child transmission (MTCT) of HBV were compared between groups. RESULTS: Elevate of total bile acid occurred mainly during the second and third trimester among HBV with ICP (HBV + ICP) patients. The rate of preterm birth occurred more frequently in HBV + ICP patients than both ICP and HBV patients (p < 0.05). Furthermore HBV + ICP patients had a higher percentage of cesarean section, postpartum hemorrhage Apgar < 7 at 1/5 min, AFIII and LBWI rate than HBV patients (p > 0.05) but did not have an increased incidence of fetal loss or birth defect when compared with that in HBV and ICP patients (p > 0.05). CONCLUSIONS: HBV + ICP patients have adverse pregnant outcomes and as a high occurrence in the second and third trimesters of pregnancy monitoring should be enhanced at this time.

14.
Int J Mol Sci ; 22(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069068

RESUMO

MADS-box genes are involved in various developmental processes including vegetative development, flower architecture, flowering, pollen formation, seed and fruit development. However, the function of most MADS-box genes and their regulation mechanism are still unclear in woody plants compared with model plants. In this study, a MADS-box gene (CiMADS43) was identified in citrus. Phylogenetic and sequence analysis showed that CiMADS43 is a GOA-like Bsister MADS-box gene. It was localized in the nucleus and as a transcriptional activator. Overexpression of CiMADS43 promoted early flowering and leaves curling in transgenic Arabidopsis. Besides, overexpression or knockout of CiMADS43 also showed leaf curl phenotype in citrus similar to that of CiMADS43 overexpressed in Arabidopsis. Protein-protein interaction found that a SEPALLATA (SEP)-like protein (CiAGL9) interacted with CiMADS43 protein. Interestingly, CiAGL9 also can bind to the CiMADS43 promoter and promote its transcription. Expression analysis also showed that these two genes were closely related to seasonal flowering and the development of the leaf in citrus. Our findings revealed the multifunctional roles of CiMADS43 in the vegetative and reproductive development of citrus. These results will facilitate our understanding of the evolution and molecular mechanisms of MADS-box genes in citrus.


Assuntos
Citrus/crescimento & desenvolvimento , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Domínios e Motivos de Interação entre Proteínas , Sequência de Aminoácidos , Citrus/genética , Citrus/metabolismo , Flores/genética , Flores/metabolismo , Proteínas de Domínio MADS/genética , Fenótipo , Filogenia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Homologia de Sequência
15.
Medicine (Baltimore) ; 100(25): e26251, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160388

RESUMO

BACKGROUND: Several randomized controlled trials (RCTs) have evaluated the efficacy of complete vs culprit-only revascularization for treatment of ST-segment elevation myocardial infarction (STEMI) with multivessel disease. However, the efficacy of complete revascularization vs culprit-only revascularization in some STEMI patient subgroups remains unclear. METHODS: We searched PubMed and Embase for related RCTs from the start date of databases to January 3, 2020. The endpoint assessed in this meta-analysis was major adverse cardiac events (MACE). Random-effects meta-analysis was conducted stratified by each of the 5 factors of interest (i.e., sex, age, history of diabetes, ECG infarct location, and the number of arteries with stenosis) to estimate pooled hazard ratio and 95% confidence interval. Random-effects meta-regression was conducted to assess subgroup differences. We examined publication bias by drawing funnel plots and performing Egger test. This meta-analysis is reported according to the PRISMA statement. RESULTS: Six RCTs were included for pooled analysis. Compared with culprit-only revascularization, complete revascularization significantly reduced the risk of MACE (hazard ratio 0.48, 95% confidence interval 0.42-0.55; I2 = 0%; P for relative effect < .001). This significant reduction in the risk of MACE exhibited by complete revascularization was observed in most of the subgroups of interest. All of the subgroup effects based on the 5 factors of interest were not statistically significant (Psubgroup ranged from 0.198 to 0.556). Publication bias was not suggested by funnel plots and Egger test. CONCLUSIONS: Compared with culprit-only revascularization, complete revascularization significantly reduces the MACE risk in patients with STEMI and multivessel disease, which is independent of sex, age, history of diabetes, ECG infarct location, and the number of arteries with stenosis.


Assuntos
Doença da Artéria Coronariana/cirurgia , Revascularização Miocárdica/métodos , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Fatores Etários , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Eletrocardiografia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Revascularização Miocárdica/estatística & dados numéricos , Intervenção Coronária Percutânea/estatística & dados numéricos , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento
16.
Endocr J ; 68(6): 739-742, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34024887

RESUMO

The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I2 = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I2 = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I2 = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I2 = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors.

18.
Diab Vasc Dis Res ; 18(2): 14791641211011016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33887983

RESUMO

There are no relevant meta-analyses that have assessed the safety of the sodium-glucose transporter 2 (SGLT2) inhibitors in different chronic diseases. We aimed at evaluating the safety of four SGLT2 inhibitors in three chronic diseases by meta-analysis of the large randomized trials of SGLT2 inhibitors. We performed random-effects meta-analysis and carried out subgroup analysis according to type of underlying diseases and type of SGLT2 inhibitors. SGLT2 inhibitors versus placebo significantly reduced the risk of acute kidney injury (RR 0.75, 95% CI 0.66-0.85), and showed the reduced trend in the risk of severe hypoglycemia (RR 0.86, 95% CI 0.71-1.03). SGLT2 inhibitors significantly increased the risks of diabetic ketoacidosis (RR 2.57), genital infection (RR 3.75), and volume depletion (RR 1.14); and showed the increased trends in the risks of fracture (RR 1.07), amputation (RR 1.21), and urinary tract infection (RR 1.07). These effects exhibited by SGLT2 inhibitors were consistent across three chronic diseases (i.e. type 2 diabetes, chronic heart failure, and chronic kidney disease) and four SGLT2 inhibitors (i.e. dapagliflozin, empagliflozin, ertugliflozin, and canagliflozin) (all Psubgroup > 0.05). These findings will guide that specific adverse events are monitored when SGLT2 inhibitors are used in clinical practice.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/prevenção & controle , Amputação , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Cetoacidose Diabética/epidemiologia , Fraturas Ósseas/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Segurança do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Infecções do Sistema Genital/epidemiologia , Medição de Risco , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento , Infecções Urinárias/epidemiologia
19.
Phytochemistry ; 187: 112780, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33915419

RESUMO

Whole plants of Gentianella turkestanorum are commonly used as a traditional Uighur medicine. A phytochemical investigation led to the isolation of eight undescribed gentianellane-type sesterterpenoids (18-epi-nitidasin, gentianelloids D-F, and 18-epi-gentianelloids C-F), one undescribed 11,12-seco-gentianellane (18-epi-alborosin), and three known analogs (nitidasin, gentianelloid C and alborosin) among which gentianelloid C was found for the first time from a natural source. The structures of these compounds were elucidated by extensive spectroscopic analyses (including 1D and 2D NMR, HRMS, IR, and specific rotation) and in the case of 18-epi-gentianelloid C by the single-crystal X-ray diffraction analysis. A putative biosynthetic route for these sesterterpenoids was proposed. The immunosuppressive activity of the isolated compounds was also evaluated by their ability to inhibit the proliferation of T cells and T cell cytokine IFN-γ production. Nitidasin suppressed IFN-γ production with an IC50 value of 16.50 µM, while gentianelloid F and alborosin inhibited the proliferation of and IFN-γ production in T cells with IC50 values of 12.40-14.66 µM.


Assuntos
Gentianella , Espectroscopia de Ressonância Magnética , Medicina Tradicional , Estrutura Molecular , Compostos Fitoquímicos
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