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1.
Artigo em Inglês | MEDLINE | ID: mdl-31621035

RESUMO

Diastolic dysfunction is common in various cardiovascular diseases, which could be affected by adiponectin (APN). Nevertheless, the effects of APN on diastolic dysfunction in pressure overload model induced by transverse aorta constriction (TAC) remain to be further elucidated. Here, we demonstrated that treatment of APN attenuated diastolic dysfunction and cardiac hypertrophy in TAC mice. Notably, APN also improved active relaxation of adult cardiomyocytes, increased N2BA/N2B ratios of titin isoform, and reduced collagen type I to type III ratio and lysyl oxidase (Lox) expressions in the myocardial tissue. Moreover, APN supplementation suppressed TAC-induced oxidative stress. In vitro, inhibition of AMPK by compound C (Cpc) abrogated the effect of APN on modulation of titin isoform shift and the anti-hypertrophic effect of APN on cardiomyocytes induced by AngII. In summary, our findings indicate that APN could attenuate diastolic dysfunction in TAC mice, which are at least partially mediated by AMPK pathway.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31502193

RESUMO

Endothelial cell apoptosis and renin-angiotensin-aldosterone system (RAAS) activation are the major pathological mechanisms for cardiovascular disease and heart failure; however, the interaction and mechanism between them remain unclear. Investigating the role of PTP1B in angiotensin II (Ang II)-induced apoptosis of primary cardiac microvascular endothelial cells (CMECs) may provide direct evidence of the link between endothelial cell apoptosis and RAAS. Isolated rat CMECs were treated with different concentrations of Ang II to induce apoptosis, and an Ang II concentration of 4 nM was selected as the effective dose for the subsequent studies. The CMECs were cultured for 48 h with or without Ang II (4 nM) in the absence or presence of the PTP1B inhibitor TCS 401 (8 µM) and the PI3K inhibitor LY294002 (10 µM). The level of CMEC apoptosis was assessed by TUNEL staining and caspase-3 activity. The protein expressions of PTP1B, PI3K, Akt, p-Akt, Bcl-2, Bax, caspase-3, and cleaved caspase-3 were determined by Western blot (WB). The results showed that Ang II increased apoptosis of CMECs, upregulated PTP1B expression, and inhibited the PI3K/Akt pathway. Furthermore, cotreatment with PTP1B inhibitor significantly decreased the number of apoptotic CMECs induced by Ang II, along with increased PI3K expression, phosphorylation of Akt and the ratio of Bcl-2/Bax, decreased caspase-3 activity, and a cleaved caspase-3/caspase-3 ratio, while treatment with LY294002 partly inhibited the anti-apoptotic effect of the PTP1B inhibitor. Ang II induces apoptosis of primary rat CMECs via regulating the PTP1B/PI3K/Akt pathway.

3.
N Engl J Med ; 381(17): 1609-1620, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31475794

RESUMO

BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).


Assuntos
Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Neprilisina/antagonistas & inibidores , Tetrazóis/administração & dosagem , Valsartana/administração & dosagem , Idoso , Aminobutiratos/efeitos adversos , Angioedema/induzido quimicamente , Antagonistas de Receptores de Angiotensina/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores Sexuais , Método Simples-Cego , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos
4.
Mol Med Rep ; 20(2): 1418-1428, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173238

RESUMO

An increasing body of evidence has demonstrated that microRNA (miR) deregulation serves pivotal roles in tumor progression and metastasis. However, the function of miR­379 in lung cancer remains understudied, particularly in non­small cell lung cancer (NSCLC). Bioinformatics and luciferase reporter analyses confirmed that conserved helix­loop­helix ubiquitous kinase (CHUK) is a target of miR­379, which may directly bind to the 3'­untranslated region of CHUK and significantly downregulate its expression in NSCLC cells. Transwell assays were used to evaluate the role of miR­379 in cell migration and invasion, and western blotting was used to address the association between miR­379 and epithelial­mesenchymal markers, including E­cadherin, cytokeratin and Vimentin. In the present study, miR­379 expression in NSCLC tissues and cell lines was downregulated, which may be associated with the poor survival of patients with NSCLC. miR­379 may act as a tumor suppressor in NSCLC, potentially by suppressing cell growth and proliferation, delaying G1­S transition, enhancing cell apoptosis and suppressing NSCLC cell migration and invasion. Furthermore, it was also observed that CHUK may function as an oncogene, and downregulation of CHUK induced by miR­379 may partially rescue the malignant characteristics of tumors, indicating that miR­379 may be suppressed in tumorigenesis. The overexpression of miR­379 may prevent the growth of NSCLC tumors via CHUK suppression and the downstream nuclear factor­κB pathway. The results of the present study demonstrated that miR­379 may act as a tumor suppressor, and may constitute a potential biomarker and a promising therapeutic agent for the treatment for NSCLC.

5.
Int J Mol Med ; 44(1): 196-206, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115480

RESUMO

The prognosis for patients with metastatic bladder cancer (BCa) is poor, and has not been improved by current treatment methods. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including bladder cancer. However, the role of zinc finger E­box­binding homeobox 1­antisense 1 (ZEB1­AS1) in BCa progression and metastasis remains unclear. The present study determined the expression level of ZEB1­AS1 in BCa and additionally investigated the functional role of ZEB1­AS1 in BCa metastasis. Reverse transcription quantitative polymerase chain reaction analysis showed that ZEB1­AS1 was upregulated in BCa cells compared with normal epithelial cells. Functionally, knockdown of ZEB1­AS1 suppressed BCa cell migration and invasion in vitro, and metastasis in vivo. Mechanistic investigations revealed that ZEB1­AS1 bound to heterogenous nuclear ribonucleoprotein D0 (AUF1), thereby activating the translation of ZEB1 mRNA without affecting its mRNA level. In addition, ZEB1­AS1 was significantly upregulated in BCa tissues and muscle­invasive BCa cases. ROC curve analysis demonstrated that ZEB1­AS1 expression was associated with metastasis in patients with BCa. In conclusion, the data from the present study demonstrated that ZEB1­AS1 induced BCa metastasis via an AUF1­mediated translation activation of ZEB1 mRNA mechanism. ZEB1­AS1 may serve as a promising target for clinical intervention in advanced BCa.

6.
Sci China Life Sci ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30519877

RESUMO

Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock, with mortality rates as high as 50%-70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial (NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time, we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes (i) mechanical life support (applications of mechanical respirators and circulatory support systems, including intraaortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO)), (ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and (iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis.

7.
Cancer Biol Ther ; : 1-18, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30461333

RESUMO

We aimed at investigating effects of long non-coding RNA maternally expressed 3 (MEG3) on the proliferation, cell cycle and apoptosis of bladder urothelial carcinoma cells and regulatory relationships among lncRNA MEG3, miR-96 and α-tropomyosin 1 (TPM1). Human clinical data from The Cancer Genome Atlas (TCGA) which contains bladder urothelial carcinoma tissues and adjacent tissues were used for analysis. The expression profiles of MEG3, miR-96, TPM1, cell cycle-related genes and apoptosis-related genes were examined by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Regulating relationship among MEG3, miR-96 and TPM1 was confirmed by dual luciferase reporter assay. MTT assay and flow cytometry were performed to observe cell proliferation, cell cycle and apoptosis. The effects of lncRNA MEG3 on bladder urothelial carcinoma were confirmed both in vivo and in vitro. The mRNA expression and protein expression of MEG3, TPM1 were down-regulated in carcinoma tissues, whereas miR-96 expression was up-regulated. MEG3 overexpression resulted in miR-96 downregulation along with TPM1 upregulation, which inhibited cell proliferation and cell cycle but promoted cell apoptosis of bladder urothelial carcinoma cells in vitro, and at the same time inhibited tumor growth in vivo. In this process, expressions of apoptosis-related protein BCL2 associated X (Bax), cleaved-caspase 3 was up-regulated, whereas apoptosis regulator protein (Bcl-2) expression was suppressed when MEG3 was overexpressed, and cell cycle-related protein Cyclin D1 was down-regulated. LncRNA MEG3 low-expression promotes the proliferation and inhibits apoptosis of bladder urothelial carcinoma cells by regulating miR-96 along with TPM1.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30315930

RESUMO

Previous evidence has indicated a beneficial role for aldehyde dehydrogenase 2 (ALDH2) in suppressing atherosclerotic plaque progression and instability. However, the underlying mechanism remains somewhat elusive. This study was designed to examine the effect of ALDH2 deficiency on high-cholesterol diet-induced atherosclerotic plaque progression and plaque vulnerability in atherosclerosis-prone ApoE knockout (ApoE-/-) mice with a focus on foam cell formation in macrophages and senescence of vascular smooth muscle cells (VSMCs). Serum lipid profile, plaque progression, and plaque vulnerability were examined in ApoE-/- and ALDH2/ApoE double knockout (ALDH2-/-ApoE-/-) mice after high-cholesterol diet intake for 8 weeks. ALDH2 deficiency increased the serum levels of triglycerides while it decreased levels of total cholesterol and high-density lipoprotein cholesterol. Unexpectedly, ALDH2 deficiency reduced the plaque area by 58.9% and 37.5% in aorta and aortic sinus, respectively. Plaque instability was aggravated by ALDH2 deficiency along with the increased necrotic core size, decreased collagen content, thinner fibrous cap area, decreased VSMC content, and increased macrophage content. In atherosclerotic lesions, ALDH2 protein was located in both macrophages and VSMCs. Further results revealed downregulated ALDH2 expression in aorta of aged ApoE-/- mice compared with young mice. However, in vitro study suggested that ALDH2 expression was upregulated in bone marrow-derived macrophages (BMDMs) with an opposite effect in VSMCs following 80 µg/ml oxidized low-density lipoprotein (oxLDL) treatment. Interestingly, ALDH2 deficiency displayed little effect in oxLDL-induced foam cell formation from BMDMs, while ALDH2 knockdown by siRNA and ALDH2 overexpression by lentivirus infection promoted and retarded oxLDL-induced VSMC senescence, respectively. Mechanistically, ALDH2 mitigated oxLDL-induced overproduction of mitochondrial reactive oxygen species (mROS) and activation of downstream p53/p21/p16 pathway. Clearance of mROS by mitoTEMPO significantly reversed the promotive effect of ALDH2 knockdown on VSMC senescence. Taken together, our data revealed that ALDH2 deficiency suppressed atherosclerotic plaque area while facilitating plaque instability possibly through accelerating mROS-mediated VSMC senescence. This article is part of a Special Issue entitled: Genetic and epigenetic regulation of aging and longevity edited by Jun Ren & Megan Yingmei Zhang.

9.
Clin Sci (Lond) ; 132(16): 1855-1874, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30072448

RESUMO

By employing a proteomic analysis on supernatant of mechanically stretched cardiomyocytes, we found that stretch induced a significantly high level of ß-2 microglobulin (ß2M), a non-glycosylated protein, which is related to inflammatory diseases but rarely known in cardiovascular diseases. The present data showed that serum ß2M level was increased in patients with hypertension and further increased in patients with chronic heart failure (HF) as compared with control group, and the high level of serum ß2M level correlated to cardiac dysfunction in these patients. In pressure overload mice model by transverse aortic constriction (TAC), ß2M levels in serum and heart tissue increased progressively in a time-dependent manner. Exogenous ß2M showed pro-fibrotic effects in cultured cardiac fibroblasts but few effects in cardiomyocytes. Adeno-associated virus 9 (AAV9)-mediated knockdown of ß2M significantly reduced cardiac ß2M level and inhibited myocardial fibrosis and cardiac dysfunction but not cardiac hypertrophy at 4 weeks after TAC. In vitro, mechanical stretch induced the rapid secretion of ß2M mainly from cardiomyocytes by activation of extracellular-regulated protein kinase (ERK). Conditional medium (CM) from mechanically stretched cardiomyocytes activated cultured cardiac fibroblasts, and the effect was partly abolished by CM from ß2M-knockdown cardiomyocytes. In vivo, knockdown of ß2M inhibited the increase in phosphorylation of epidermal growth factor receptor (EGFR) induced by TAC. In cultured cardiac fibroblasts, inhibition of EGFR significantly attenuated the ß2M-induced the activation of EGFR and pro-fibrotic responses. The present study suggests that ß2M is a paracrine pro-fibrotic mediator and associated with cardiac dysfunction in response to pressure overload.

10.
Cell Physiol Biochem ; 48(1): 371-384, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016766

RESUMO

BACKGROUND/AIMS: Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression. METHODS: RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance. The underlying mechanisms of TP73-AS1 in ccRCC were analyzed through in vitro functional assays. RESULTS: We found TP73-AS1 was upregulated in 40 ccRCC tissues compared with adjacent normal renal tissues and increased TP73-AS1 was correlated to aggressive clinicopathologic features and unfavorable prognosis. Knockdown of TP73-AS1 suppressed cell proliferation, invasion and induced cell apoptosis. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Knockdown of KISS1 partly reversed TP73-AS1 knockdown-induced inhibition of cell proliferation and promotion of apoptosis. We further determined that TP73-AS1 knockdown activated PI3K/Akt/mTOR signaling pathway, while overexpression of TP73-AS1 induced inhibition of PI3K/Akt/mTOR pathway and these effects could be partly abolished by overexpression of KISS1. CONCLUSION: In conclusion, we identified that TP73-AS1 as an oncogenic lncRNA in the development of ccRCC and a potential target for human renal carcinoma treatment.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Kisspeptinas/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Apoptose , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Kisspeptinas/genética , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Serina-Treonina Quinases TOR/metabolismo
11.
Circ Heart Fail ; 11(7): e004962, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29980595

RESUMO

BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), ß-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.

12.
J Cell Mol Med ; 22(5): 2791-2803, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29502357

RESUMO

Protection of cardiac microvascular endothelial cells (CMECs) against hypoxia injury is an important therapeutic strategy for treating ischaemic cardiovascular disease. In this study, we investigated the effects of qiliqiangxin (QL) on primary rat CMECs exposed to hypoxia and the underlying mechanisms. Rat CMECs were successfully isolated and passaged to the second generation. CMECs that were pre-treated with QL (0.5 mg/mL) and/or HIF-1α siRNA were cultured in a three-gas hypoxic incubator chamber (5% CO2 , 1% O2 , 94% N2 ) for 12 hours. Firstly, we demonstrated that compared with hypoxia group, QL effectively promoted the proliferation while attenuated the apoptosis, improved mitochondrial function and reduced ROS generation in hypoxic CMECs in a HIF-1α-dependent manner. Meanwhile, QL also promoted angiogenesis of CMECs via HIF-1α/VEGF signalling pathway. Moreover, QL improved glucose utilization and metabolism and increased ATP production by up-regulating HIF-1α and a series of glycolysis-relevant enzymes, including glucose transport 1 (GLUT1), hexokinase 2 (HK2), 6-phosphofructokinase 1 (PFK1), pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Our findings indicate that QL can protect CMECs against hypoxia injury via promoting glycolysis in a HIF-1α-dependent manner. Lastly, the results suggested that QL-dependent enhancement of HIF-1α protein expression in hypoxic CMECs was associated with the regulation of AMPK/mTOR/HIF-1α pathway, and we speculated that QL also improved HIF-1α stabilization through down-regulating prolyl hydroxylases 3 (PHD3) expression.

13.
Medicine (Baltimore) ; 97(1): e9316, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29505513

RESUMO

BACKGROUND: Conflict findings of the impact of inhalational anesthetics on postoperative cognitive function are reported. No systematic review has been performed to solve the problem. The aim of the study was to assess the effect of different inhalational anesthetics on postoperative cognitive function in a network meta-analysis. METHODS: We will search MEDLINE, EMBASE, the Central Register of Controlled Trials in the Cochrane library, and CINAHL for randomized controlled trials or cohort studies assessing the short-term or long-term cognitive function of elderly patients (over 60 years) receiving major surgeries and inhalational anesthetics (desflurane, isoflurane, sevoflurane, halothane, and nitrous oxide) during surgery. Two reviewers will independently screen study eligibility, extract information from eligible studies, and appraise study quality. The impact of inhalational anesthetics will be assessed through: incidence of postoperative cognitive dysfunction at 1 week, 3 months, 1 year, and over 1 year after surgery; incidence of post-operative delirium; test of postoperative cognitive function. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: To our knowledge, this systematic review will be the first to evaluate existing research on the incidence of postoperative cognitive function after inhalational anesthetics. Our study will assess the effect of different inhalational anesthetics on postoperative cognitive function. ETHICS AND DISSEMINATION: The review will be finished in December 2017, and the result will be published in a peer-reviewed journal or disseminated through conference posters or abstracts. REVIEW REGISTRATION NUMBER: CRD42017056675 (www.crd.york.ac.uk/PROSPERO).


Assuntos
Anestésicos Inalatórios/efeitos adversos , Cognição/efeitos dos fármacos , Humanos , Revisão Sistemática como Assunto
14.
Chin J Integr Med ; 24(5): 336-342, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29435729

RESUMO

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).


Assuntos
Aerossóis/uso terapêutico , Angina Pectoris/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Aerossóis/efeitos adversos , Estudos de Casos e Controles , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
15.
Int J Mol Med ; 41(3): 1584-1594, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328372

RESUMO

MicroRNAs (miRNAs/miRs) serve a role as important regulators in cardiac hypertrophy. The present study aimed to reveal the differential expression profile of miRNAs between young and aging spontaneously hypertensive rats (SHRs) and studied the functional annotation of predicted targets. Briefly, 3­month­old and 12­month­old SHRs (n=3/group) were subjected to echocardiography, histopathological analysis and dihydroethidium staining. Subsequently, small RNA sequencing and data processing was conducted to identify the differentially expressed miRNAs between these two groups. Eight significantly upregulated miRNAs were validated by reverse transcription­quantitative polymerase chain reaction (RT­qPCR), followed by in silico target gene prediction. Functional annotation analysis of the predicted targets was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. As a result, significantly impaired left ventricular diastolic function was detected in the 12­month­old SHRs, alongside increased myocyte cross­sectional area and percentage area of fibrosis, elevated reactive oxygen species production and reduced microvessel density (P<0.05). Compared with the 3­month­old SHRs, 21 miRNAs were significantly upregulated and five miRNAs were downregulated in 12­month­old rats (P<0.05). Eight upregulated, remodeling­associated miRNAs, including rno­miR­132­3p, rno­miR­182, rno­miR­208b­3p, rno­miR­212­3p, rno­miR­214­3p, rno­miR­218a­5p, rno­miR­221­3p and rno­miR­222­3p, underwent bioinformatics analysis. The target genes were significantly enriched in 688 GO terms and 39 KEGG pathways, including regulation of peptidyl­tyrosine phosphorylation, regulation of protein serine/threonine kinase activity, adrenergic signaling in cardiomyocytes, ErbB signaling pathway, mTOR signaling pathway, FoxO signaling pathway, Ras signaling pathway, insulin secretion, adipocytokine signaling pathway, HIF­1 signaling pathway, Rap1 signaling pathway, VEGF signaling pathway and TNF signaling pathway. Collectively, the present study identified a dysregulated miRNA profile in aging SHRs, which targeted numerous signaling pathways associated with cardiac hypertrophy, autophagy, insulin metabolism, angiogenesis and inflammatory response.


Assuntos
Envelhecimento/genética , Biologia Computacional , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , MicroRNAs/genética , Envelhecimento/sangue , Animais , Análise por Conglomerados , Regulação para Baixo/genética , Eletrocardiografia , Ontologia Genética , Ventrículos do Coração/anatomia & histologia , Sequenciamento de Nucleotídeos em Larga Escala , Inflamação/genética , Masculino , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Peptídeo Natriurético Encefálico/sangue , Tamanho do Órgão , Fragmentos de Peptídeos/sangue , Ratos Endogâmicos SHR , Espécies Reativas de Oxigênio/metabolismo , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Estatística como Assunto , Regulação para Cima/genética
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 39(4): 568-572, 2017 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-28877837

RESUMO

Objective To summarize our experiences in the clinical diagnosis and treatment of male breast cancer(MBC).Methods The clinical date of 24 MBC patients treated in our hospital from January 2006 to December 2012 were retrospective analyzed.Results The average age of these 24 patients was(55.7±2.1) years.All the patients received surgical treatment,and the surgical procedures were simple excision of breast lesion in 6 patients,breast resection alone in 5 patients,and modified radical mastectomy in 13 patients(bilateral in 1 case).The pathological diagnoses included invasive ductal carcinoma in 18 cases,papillary carcinoma in 4 cases,mucinous adenocarcinoma in 1 case,and malignant solitary fibrous tumor in 1 case.Twenty patients received chemotherapy,7 received radiotherapy,and 15 received endocrine therapy after operation.The 5-year survival rate was 54.2%.Conclusions The incidence of MBC is low.This malignancy is mainly seen in elderly individuals,with relatively long disease course,poor prognosis,and high risk of metastasis.MBC is mainly treated by surgery,and adjuvant chemotherapy,radiotherapy,and endocrine therapy may be applied,if appropriate,after the operation.

17.
Artigo em Inglês | MEDLINE | ID: mdl-28706558

RESUMO

Cardiac diastolic dysfunction has emerged as a growing type of heart failure. The present study aims to explore whether Qiliqiangxin (QL) can benefit cardiac diastolic function in spontaneously hypertensive rat (SHR) through enhancement of cardiac glucose metabolism. Fifteen 12-month-old male SHRs were randomly divided into QL-treated, olmesartan-treated, and saline-treated groups. Age-matched WKY rats served as normal controls. Echocardiography and histological analysis were performed. Myocardial glucose uptake was determined by 18F-FDG using small-animal PET imaging. Expressions of several crucial proteins and key enzymes related to glucose metabolism were also evaluated. As a result, QL improved cardiac diastolic function in SHRs, as evidenced by increased E'/A'and decreased E/E' (P < 0.01). Meanwhile, QL alleviated myocardial hypertrophy, collagen deposits, and apoptosis (P < 0.01). An even higher myocardial glucose uptake was illustrated in QL-treated SHR group (P < 0.01). Moreover, an increased CS activity and ATP production was observed in QL-treated SHRs (P < 0.05). QL enhanced cardiac glucose utilization and oxidative phosphorylation in SHRs by upregulating AMPK/PGC-1α axis, promoting GLUT-4 expression, and regulating key enzymes related to glucose aerobic oxidation such as HK2, PDK4, and CS (P < 0.01). Our data suggests that QL improves cardiac diastolic function in SHRs, which may be associated with enhancement of myocardial glucose metabolism.

18.
Biochim Biophys Acta Mol Basis Dis ; 1863(8): 1919-1932, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28347844

RESUMO

Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a cascade of biological processes including aging. A number of autophagy regulators have been identified. Here we demonstrated that mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme with the most common single point mutation in humans, governs cardiac aging through regulation of autophagy. Myocardial mechanical and autophagy properties were examined in young (4months) and old (26-28months) wild-type (WT) and global ALDH2 transgenic mice. ALDH2 overexpression shortened lifespan by 7.7% without affecting aging-associated changes in plasma metabolic profiles. Myocardial function was compromised with aging associated with cardiac hypertrophy, the effects were accentuated by ALDH2. Aging overtly suppressed autophagy and compromised autophagy flux, the effects were exacerbated by ALDH2. Aging dampened phosphorylation of JNK, Bcl-2, IKKß, AMPK and TSC2 while promoting phosphorylation of mTOR, the effects of which were exaggerated by ALDH2. Co-immunoprecipitation revealed increased dissociation between Bcl-2 and Beclin-1 (result of decreased Bcl-2 phosphorylation) in aging, the effect of which was exacerbated with ALDH2. Chronic treatment of the autophagy inducer rapamycin alleviated aging-induced cardiac dysfunction in both WT and ALDH2 mice. Moreover, activation of JNK and inhibition of either Bcl-2 or IKKß overtly attenuated ALDH2 activation-induced accentuation of cardiomyocyte aging. Examination of the otherwise elderly individuals revealed a positive correlation between cardiac function/geometry and ALDH2 gene mutation. Taken together, our data revealed that ALDH2 enzyme may suppress myocardial autophagy possibly through a complex JNK-Bcl-2 and IKKß-AMPK-dependent mechanism en route to accentuation of myocardial remodeling and contractile dysfunction in aging. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.


Assuntos
Aldeído-Desidrogenase Mitocondrial/metabolismo , Autofagia , Longevidade , Miocárdio/enzimologia , Aldeído-Desidrogenase Mitocondrial/genética , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Miocárdio/patologia
19.
Zhongguo Fei Ai Za Zhi ; 20(3): 192-198, 2017 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-28302222

RESUMO

Small cell lung cancer (SCLC) is a highly malignant tumor. The initial treatment of radiotherapy and chemotherapy are more sensitive, high remission rate, but susceptible to drug resistance and relapse after treatment. Although the treatment of lung cancer has undergone enormous changes in recent years, treatment for relapsed SCLC is still a difficult problem in clinical field. In view of the serious resistance of recurrent SCLC to the existing chemotherapeutic drugs, the research on recurrent SCLC around the world is focused on the clinical trial of new drug development, optimization of chemotherapy regimen and target drug development. This paper summarize and estimate studies and literature reports of chemotherapy and precision therapy for relapsed SCLC, hopefully it could help clinicians treat relapsed SCLC and give us clinical research direction for relapsed SCLC in the future.


Assuntos
Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/tratamento farmacológico , Medicina de Precisão , Recidiva , Carcinoma de Pequenas Células do Pulmão/irrigação sanguínea , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
20.
J Cell Mol Med ; 21(9): 1905-1914, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28271613

RESUMO

Cardiac microvascular endothelial cells (CMECs) are important angiogenic components and are injured rapidly after cardiac ischaemia and anoxia. Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, have been displayed recently. This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague-Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary-like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase-3 activity. Neuregulin-1 (NRG-1) siRNA and LY294002 were administrated to block NRG-1/ErbB and PI3K/Akt signalling, respectively. As a result, anoxia inhibited cell migration, capillary-like tube formation and angiogenesis, and increased cell apoptosis. QL significantly reversed these anoxia-induced injuries and up-regulated expressions of NRG-1, phospho-ErbB2, phospho-ErbB4, phospho-Akt, phospho-mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in CMECs, while NRG-1 knockdown abolished the protective effects of QL with suppressed NRG-1, phospho-ErbB2, phospho-ErbB4, phospho-Akt, phospho-mTOR, HIF-1α and VEGF expressions. Similarly, LY294002 interrupted the beneficial effects of QL with down-regulated phospho-Akt, phospho-mTOR, HIF-1α and VEGF expressions. However, it had no impact on NRG-1/ErbB signalling. Our data indicated that QL could attenuate anoxia-induced injuries in CMECs via NRG-1/ErbB signalling which was most probably dependent on PI3K/Akt/mTOR pathway.


Assuntos
Cardiotônicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/metabolismo , Microvasos/patologia , Miocárdio/patologia , Transdução de Sinais/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Hipóxia Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Separação Celular , Células Cultivadas , Cromonas/farmacologia , Células Endoteliais/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Masculino , Morfolinas/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Neuregulina-1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos Sprague-Dawley , Receptor ErbB-2/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacos
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