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1.
Biomed Pharmacother ; 122: 109777, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918261

RESUMO

Sepsis is a critical illness that contributes a high mortality, while Xijiao Dihuang decoction (XJDHT) has been used in treatment against sepsis for many years by clinical doctors. Clinical studies confirmed a good efficacy of XJDHT against sepsis. The aim of this study is to observe the efficacy of XJDHT in sepsis model rats and macrophages activated by LPS, and to verify the underlying mechanisms. The key components of XJDHT and its targets against sepsis were analyzed and selected by network pharmacology. The potential mechanisms that XJDHT regulates the progress of sepsis were verified in sepsis rats and NR8383 cell lines. XJDHT at a dose of 25 mg/kg was administrated to rats which endured cecal ligation and perforation (CLP). After MTT assay, XJDHT at a dose of 4 mg/mL was selected to treat NR8383 cell lines activated by LPS. In vivo experiment, the survival of the rats was assessed. The content of cytokine in serum were assessed by Enzyme-linked immunosorbent assays (ELISA). Contents of cytokine and key molecules in relative signaling pathway were assessed by immunohistochemical method. The pathway protein expressions were detected by Western blotting. In vitro experiment, immunofluorescence was used to assess the content of cytokine and signaling pathway. A total of 42 targets of XJDHT against sepsis were identified by network pharmacology. After eliminating overlapping compounds and proteins, there were 8 compounds in XJDHT that associating with the 42 sepsis-related targets. NF-κB and HIF-1α signaling pathway were recognized to play important role for XJDHT against sepsis. XJDHT improved survival rate in the XJDHT group compared with the model group. The contents of IL-6 increased in the model group compared with the control group with ELISA and immunohistochemistry, while XJDHT reduced the content of IL-6. The expressions of p65 and HIF-1α reduced significantly in the XJDHT group compared with the model group. In vitro study, the content of IL-6 elevated significantly after LPS stimulation, while XJDHT reduced this increase. Furthermore, expressions of protein of p65 and HIF-1α decreased significantly compared with the LPS group. To conclude, our study demonstrated that XJDHT at a dose of 25 g/kg is capable of improving the survival of sepsis via regulating the NF-κB and HIF-1α signaling pathway.

2.
J Colloid Interface Sci ; 566: 11-20, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31986305

RESUMO

Functional separator, which bridges anode, electrolyte and cathode together, has the potential to offer a good solution for efficient polysulfide diffusion inhibition and anode protection of Li-S battery. Herein, a novel ultra-thin multifunctional separator is prepared by a facile coating of colloidal dispersion of Nb2O5/reduced graphene oxide nanocomposites (rGO) onto porous polypropylene (PP) matrix. Benefiting from the physical blocking effect of rGO layer and chemisorption of Nb2O5, the shuttle of polysulfides has been greatly suppressed. Meanwhile, the rGO layer functioning as a conductive upper current collector can improve the sulfur utilization, while the Nb2O5 with high activity promotes the transformation of sulfur-containing species. With the assistant of Nb2O5-rGO function layer, the sulfur cathode shows significantly improved electrochemical performance with a high specific capacity of 1328 mAh g-1 at 0.2C and 754 mAh g-1 retained after 200 cycles. The sulfur cathode also exhibits excellent rate capability and stable Coulombic efficiency of 91% without the addition of LiNO3 in the electrolyte. Moreover, the presence of thin Nb2O5-rGO layer also prevents the lithium surface corrosion and the dendrite growth in the lithium anode.

3.
Kaohsiung J Med Sci ; 35(9): 550-558, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31162822

RESUMO

This work was to investigate potential roles of HMGB1-mediated ERK pathway in the healing process of bone fracture. Rat tibial fracture models were established and divided into control (rats with normal saline), HMGB1 (rats with HMGB1), and HMGB1+ PD98059 groups (rats with HMGB1 and 1 mg/kg of ERK1/2 inhibitor PD98059) with 30 rats per each. The healing of rats' fracture was observed by X-ray films, the morphological changes of bone fractures by HE staining, the callus formation by micro-CT and biomechanical test, and the expression of osteogenesis-related genes, HMGB1 and ERK-related proteins by qRT-PCR and Western blot. Rats in the HMGB1 group was increased in X-ray scores, peak torque, torsional stiffness, and the bone volume fraction (bone volume/total volume, BV/TV); meanwhile, those rats presented elevations in osteogenesis-related genes and HMGB1 expressions, as well as p-ERK/ERK ratio. However, rats in the HMGB1+ PD98059 group was significantly reduced in X-ray score, peak torque, torsional stiffness, and BV/TV, as well as the expression of osteogenesis-related genes and the ratio of p-ERK/ERK, as compared to those from HMGB1 group. HMGB1 could promote the expressions of osteogenesis-related genes and accelerate the healing process of fracture via activation of the ERK signaling pathway.

4.
Crit Care ; 23(1): 168, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088524

RESUMO

BACKGROUND: Catecholamines, especially norepinephrine, are the most frequently used vasopressors for treating patients with septic shock. During the recent decades, terlipressin, vasopressin V1A agonist, and even Ca2+ sensitizer were increasingly used by physicians. The aim of this study is to compare the efficacy of such different kinds of vasoactive medications on mortality among patients with septic shock. METHODS: Relevant randomized controlled trials were identified by searching PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials updated to February 22, 2018. A network meta-analysis was performed to evaluate the effect of different types of vasoactive medications. The primary outcome was 28-day mortality. Intensive care unit (ICU) mortality, hospital and ICU length of stay (LOS), and adverse events were also assessed. RESULTS: A total of 43 trials with 5767 patients assessing 17 treatment modalities were included. Treatments ranking based on surface under the cumulative ranking curve values from largest to smallest were NE/DB 85.9%, TP 75.1%, NE/EP 74.6%, PI 74.1%, EP 72.5%, VP 66.1%, NE 59.8%, PE 53.0%, DA 42.1%, DX 38.2%, SP 27.0%, PA 24.3%, EX 22.8%, LE 21.5%, and DB 13.3% for 28-day mortality. Treatments ranking for ICU mortality were TP/NE 86.4%, TP 80.3%, TP/DB/NE 65.7%, VP/NE 62.8%, NE 57.4%, VP 56.5%, PE 48.4%, DA 33.0%, PA 27.5%, LE 22.1%, and DB 9.9%. The incidence of myocardial infarction was reported with NE/EP 3.33% (n = 1 of 30), followed by EP 3.11% (n = 5 of 161), and then VP 3.10% (n = 19 of 613), NE 3.03% (n = 43 of 1417), DA 2.21% (n = 19 of 858), NE/DB 2.01% (n = 4 of 199), LE 1.16% (n = 3 of 258), and PA 0.39% (n = 1 of 257). The incidence of arrhythmia was reported with DA 26.01% (n = 258 of 992), followed by EP 22.98% (n = 37 of 161), and then NE/DB 20.60% (n = 41 of 199), NE/EP 20.0% (n = 6 of 30), NE 8.33% (n = 127 of 1525), LE 5.81% (n = 15 of 258), PA 2.33% (n = 6 of 257), and VP 1.67% (n = 10 of 600). CONCLUSIONS: The use of norepinephrine plus dobutamine was associated with lower 28-day mortality for septic shock, especially among patients with lower cardiac output.


Assuntos
Catecolaminas/normas , Choque Séptico/tratamento farmacológico , Catecolaminas/uso terapêutico , Dopamina/normas , Dopamina/uso terapêutico , Humanos , Mortalidade/tendências , Norepinefrina/normas , Norepinefrina/uso terapêutico , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Terlipressina/normas , Terlipressina/uso terapêutico , Vasopressinas/normas , Vasopressinas/uso terapêutico
5.
Biomed Pharmacother ; 115: 108971, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102910

RESUMO

Sepsis, as life-threatening organ dysfunction caused by a dysregulated host response to infection, is characterized by the extensive release of cytokines and other mediators. Sini decoction (SND), a traditional Chinese prescription medicine, has been used clinically for the treatment of sepsis. But its explicit mechanism of action is still unclear. The present study aims to evaluate the potential protective effects of SND on sepsis-induced acute lung injury (ALI). After SND intervention, the lung tissues of each experimental group were collected. H&E sections were used to observe the pathological changes of lung tissue, and alveolar lavage fluid was collected to detect the infiltration of inflammatory cells. Level of inflammatory factors in lung tissue were analyzed by qRT-PCR. The change of Renin angiotensin system (RAS), as well as downstream MAPK/NF-κB signaling pathways were measured by Western blot. For in vitro experiments, human umbilical vein endothelial cells (HUVECs) were pretreated with lipopolysaccharide (LPS) and treated with SND. Subsequently, the expression levels of RAS and MAPK/NF-κB signaling pathways were measured by Western blot. In vivo, we found that SND significantly attenuated sepsis-induced pathological injury in the lung. SND also inhibited LPS-mediated inflammatory cell infiltration, the expression of pro-apoptotic proteins and the production of IL-6, IL-1ß, TNF-α and MCP-1. In vitro, experiments using a co-culture of HUVECs with SND showed that there was a decrease in pro-apoptotic protein and pro-inflammatory mediator. In this research, we also found that SND protective action could be attributed to the regulation of renin-angiotensin system (RAS). MAPKs and NF-κB pathways. To conclude, our study demonstrated that SND ameliorates sepsis-induced-ALI via regulating ACE2-Ang (1-7)-Mas axis and inhibiting the MAPK signaling pathway.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Angiotensina I/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Sepse/prevenção & controle , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Células Endoteliais da Veia Umbilical Humana , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos ICR , Sepse/complicações , Sepse/metabolismo
6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(1): 73-80, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30707873

RESUMO

OBJECTIVE: To systematically review the effect of Qingre Jiedu and Liangxue Sanyu method in patients with sepsis, and to discuss its effect in the treatment of sepsis. METHODS: The randomized controlled trials (RCTs) on the treatment of Qingre Jiedu and Liangxue Sanyu method for sepsis published on PubMed, Embase, Web of Science, CNKI and Wanfang database from the construction to December 31st, 2017 were searched by electronical way. Conventional treatment measures for sepsis, such as fluid resuscitation, maintenance of hemodynamic stability, anti-infection, improvement of tissue perfusion, maintenance of organ function and nutritional support were used in the control group. While traditional Chinese medicine treatment based on Qingre Jiedu and Liangxue Sanyu method were applied in the experimental group besides the conventional treatment, including Chinese patent medicine or Chinese herbal medicine. The main outcome was 28-day mortality, and the second outcome was acute physiology and chronic health evaluation II (APACHE II), coagulation function, inflammatory mediators, procalcitonin (PCT), lactic acid (Lac), and the length of intensive care unit (ICU) stay. Two researchers independently searched literatures, collected data and evaluated risk bias. The statistical analysis was completed by RevMan 5.3 and STATA 13.0 software. The funnel plot and Egger test were used to evaluate the potential publication bias of the main outcomes. RESULTS: A total of 20 RCTs were enrolled in this Meta-analysis, including 1 347 patients, with 667 patients in the control group and 680 patients in the experimental group. Comprehensive risk bias assessment showed that the risk bias of 11 RCT items was unknown, and the risk bias of 9 RCT items was high. Meta-analysis results showed that compared with the control group, the 28-day mortality of the experimental group was significantly lowered [relative risk (RR) = 0.54, 95% confidence interval (95%CI) = 0.45-0.65, P < 0.000 01], the 7-day APACHE II score was significantly lowered [mean difference (MD) = -3.86, 95%CI = -4.82 to -2.90, P < 0.000 01], the 7-day prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly shortened (PT: MD = -1.72, 95%CI = -2.29 to -1.14, P < 0.000 01; APTT: MD = -4.36, 95%CI = -5.81 to -2.91, P < 0.000 01), the 7-day D-dimer was slightly improved (MD = -0.13, 95%CI = -0.37-0.11, P = 0.29), the 10-day interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly decreased (IL-6: MD = -40.33, 95%CI = -59.55 to -21.11, P < 0.000 1; TNF-α: MD = -7.26, 95%CI = -11.31 to -3.21, P = 0.000 4), the 7-day Lac was significantly declined (MD = -1.30, 95%CI = -1.91 to -0.68, P < 0.000 1), but no significance in PCT (MD = -1.57, 95%CI = -3.25-0.11, P = 0.07) or the length of ICU stay (MD = -4.02, 95%CI = -8.60-0.56, P = 0.09) was found. The results of publication bias assessment showed that 19 studies reported 28-day mortality were basically "funnel-shaped" distribution without potential publication bias (P = 0.336). CONCLUSIONS: The Meta-analysis showed that Qingre Jiedu and Liangxue Sanyu method may reduce the release of inflammatory mediators, improve the coagulation function, and reduce the 28-day mortality in patients with sepsis.


Assuntos
Sepse/terapia , APACHE , Humanos , Unidades de Terapia Intensiva , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Bioorg Med Chem Lett ; 28(23-24): 3726-3730, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30342957

RESUMO

Our group has previously reported a series of isoflavone derivatives with antidyslipidemic activity. With this background, a series of isoflavone analogs of GW4064 were designed, synthesized and evaluated the lipid-lowering activity of analogs. As a result, most of compounds significantly reduced the lipid accumulation in 3T3-L1 adipocytes and four of them (10a, 11, 15c and 15d) showed stronger inhibitory than GW4064. The most potent compound 15d exhibited promising agonistic activity for FXR in a cell-based luciferase reporter assay. Meanwhile, 15d up-regulated FXR, SHP and BSEP gene expression and down-regulated the mRNA expression of lipogenesis gene SREBP-1c. Besides, an improved safety profile of 15d was also observed in a HepG2 cytotoxicity assay compared with GW4064. The obtained biological results were further confirmed by a molecular docking study showing that 15d fitted well in the binding pocket of FXR and interacted with some key residues simultaneously.


Assuntos
Adipócitos/efeitos dos fármacos , Isoflavonas/química , Isoflavonas/farmacologia , Isoxazóis/química , Isoxazóis/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Desenho de Drogas , Células Hep G2 , Humanos , Isoflavonas/síntese química , Isoxazóis/síntese química , Camundongos , Simulação de Acoplamento Molecular , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(6): 578-582, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30009735

RESUMO

OBJECTIVE: To investigate the effect of Qingfeihuayutongfu prescription on oxygenation and pulmonary fibrosis in patients with sepsis-associated acute respiratory distress syndrome (ARDS). METHODS: A prospective randomized controlled trial was performed. Patients with moderate to severe ARDS admitted to intensive care unit (ICU) of Affiliated Hospital of Nanjing University of Chinese Medicine from July 2015 to February 2017 were enrolled, and randomly divided into Qingfeihuayutongfu prescription group (observation group, 200 mL of Qingfeihuayutongfu prescription was given through nasal feeding on the first day after admission, one dose per day for 7 days) and placebo control group. Routine treatment of ARDS in both groups was the same. The oxygenation index (PaO2/FiO2), levels of serum procollagen III (PC III) and prolidase (PLD) were measured at 1, 3, 7, 14 and 28 days after treatment, duration of mechanical ventilation, the length of ICU stay and 60-day survival rate were recorded. RESULTS: A total of 32 patients with ARDS were selected, with 16 in each group, and their baseline data were balanced and comparable. As time went on, PaO2/FiO2 in both groups was decreased gradually, and serum levels of PC III and PLD were increased gradually. Compared with placebo control group, PaO2/FiO2 was significantly increased at 14 days and 28 days after treatment in observation group [mmHg (1 mmHg = 0.133 kPa): 185.81±65.07 vs. 137.19±55.72, 250.56±102.72 vs. 178.25±80.97, both P < 0.05], the levels of serum PC III were significantly decreased at 14 days and 28 days after treatment (µmol/L: 197.13±26.61 vs. 240.81±45.27, 169.06±36.34 vs. 234.75±46.30, both P < 0.01), the levels of serum PLD was significantly decreased at 28 days after treatment (U/L: 1 166.31±304.84 vs. 1 468.81±387.65, P < 0.05), duration of mechanical ventilation (days: 18.20±5.20 vs. 23.38±7.57) and the length of ICU stay (days: 23.7±5.7 vs. 31.0±7.9 ) were significantly shortened (both P < 0.05). Kaplan-Meier survival curve analysis showed that there was no significant difference in the 60-day survival rate between the observation group and placebo control group [81.25% (13/16) vs. 68.75% (11/16), χ2 = 0.667, P = 0.505]. CONCLUSIONS: The Qingfeihuayutongfu prescription may improve oxygenation of ARDS patients, reduce the levels of serum PC III and PLD, and inhibit pulmonary fibrosis, thus improve prognosis.


Assuntos
Sepse , Humanos , Estudos Prospectivos , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto , Método Simples-Cego
9.
J Surg Res ; 228: 314-321, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29907227

RESUMO

BACKGROUND: Sepsis is a major health care problem, which affects millions of people around the world. Glucose metabolic reprogramming of immune cells plays a crucial role during advancement of sepsis. However, the association between glucose metabolic reprogramming and mortality in patients with sepsis is unclear. Lactate dehydrogenase (LDH) catalyzes the last step of glycolysis. Investigating the relationship between LDH and mortality is important to understand the effect of metabolic reprogramming on prognosis of patients with sepsis. METHODS: A total of 192 patients with sepsis were included in our study. Data on characteristics of patients, biochemical variables, and inflammatory mediator were collected. Association between the level of serum LDH and 28-day mortality was also analyzed. The correlations between serum LDH, interleukin-1ß, creatinine, PaO2/FiO2, and lactate were also observed. The association between LDH and the risk of death was further analyzed. Moreover, receiver operating characteristic curve was depicted to compare the accuracy in prediction of LDH and other variables. RESULTS: There were statistic difference in 28-day mortality between elevated LDH group and normal LDH group (P = 0.021). Level of serum LDH was an independent risk factor for death of patients with sepsis (hazard ratio 1.005, 95% confidence interval 1.002-1.007, P = 0.001). There were significant correlations between LDH, interleukin-1ß (r = 0.514, P = 0.000), creatinine (r = 0.368, P = 0.000), PaO2/FiO2 (r = -0.304, P = 0.000), and lactate (r = 0.560, P = 0.000). The receiver operating characteristic curves showed that the area under the LDH curve for prediction for mortality was 0.783. CONCLUSIONS: Serum LDH is probably associated with 28-day mortality in patients with sepsis.


Assuntos
Mortalidade Hospitalar , L-Lactato Desidrogenase/sangue , Sepse/mortalidade , APACHE , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Sepse/sangue , Sepse/diagnóstico , Sepse/terapia , Análise de Sobrevida , Taxa de Sobrevida
10.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(2): 156-159, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29402366

RESUMO

OBJECTIVE: To investigate the value of bedside lung ultrasound B-line score in the diagnosis of acute heart failure (AHF). METHODS: A retrospectively analysis was conducted. The adult patients presenting with acute dyspnea in intensive care unit (ICU) of Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2016 to June 2017 were enrolled. An 8-zone lung ultrasound was performed and plasma B-type natriuretic peptide (BNP) level was tested in all patients. AHF was determined as the final diagnosis by two experienced ICU doctors according to the diagnostic criteria of AHF. Patients were divided into two groups: AHF group and non-AHF group. The levels of BNP and B-line score were compared between the two groups, and the diagnostic value of BNP and B-line score in AHF was evaluated. RESULTS: Fifty-six patients were included in this study, with 32 of men and 24 of women, and with an average age of 77.3±8.8. Thirty-six patients were diagnosed as AHF. The level of BNP and lung ultrasound B-line score in AHF group were higher than those in non-AHF group [BNP (ng/L): 1 640.4±1 078.4 vs. 236.9±124.9, B line score: 12.8±5.3 vs. 5.4±1.8, both P < 0.01]. There was a strong correlation between elevated BNP levels and an increased B-lines score (R2 = 0.712, P = 0.000). The receiver operating characteristic curve (ROC) showed that when the cut-off of lung ultrasound B-line score was 8.5, AHF could be discriminated from dyspnea caused by other diseases (sensitivity was 77.8%, specificity was 95%, positive likelihood ratio was 15.56, negative likelihood ratio was 0.23). The area under the ROC curve (AUC) of lung ultrasound B-line score was 0.917 [95% confidence interval (95%CI) = 0.847-0.987, P = 0.000], slightly lower than that of plasma BNP [0.979 (95%CI = 0.951-1.008)]. CONCLUSIONS: Lung ultrasound B-line score was highly specific, but moderately sensitive for identifying patients with AHF.


Assuntos
Insuficiência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Dispneia , Feminino , Humanos , Masculino , Peptídeo Natriurético Encefálico , Prognóstico , Curva ROC , Estudos Retrospectivos , Ultrassonografia
11.
J Affect Disord ; 227: 226-235, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29102837

RESUMO

BACKGROUND: Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. METHODS: Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. RESULTS: The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). LIMITATIONS: The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. CONCLUSIONS: We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Depressão/genética , Interação Gene-Ambiente , Predisposição Genética para Doença , Estresse Psicológico/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética
12.
Eur J Med Chem ; 139: 390-400, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28810190

RESUMO

2-methoxyestradiol is a novel agent showing both anti-angiogenic and vascular disrupting properties. In this study, a series of 11α-substituted 2-methoxyestradiol analogs have been designed and synthesized targeting dual ERα and microtubulin. Biological evaluation was performed on their anti-proliferative activities against 5 different cell lines. The results indicated that most compounds exhibited good activities, in which compound 24c and 30c showed the best activity with low micromolar IC50 (2.73 µM -7.75 µM) in all cell lines. The investigation of ER affinity showed that the majority of the compounds displayed good activity at the concentration of 50 µM. In further mechanism study, it was observed that 24c and 30c could induce G2/M cell cycle arrest as well as significant anti-estrogenic activity. In CAM assay, compound 24c and 30c presented significantly anti-angiogenesis activity comparable with 2-methoxyestradiol. Overall, based on biological activities data, 24c and 30c can be identified as a potential lead molecule which might be of therapeutic importance for cancer treatment.


Assuntos
Inibidores da Angiogênese/farmacologia , Desenho de Drogas , Estradiol/análogos & derivados , Moduladores de Receptor Estrogênico/farmacologia , 2-Metoxiestradiol , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estradiol/síntese química , Estradiol/química , Estradiol/farmacologia , Moduladores de Receptor Estrogênico/síntese química , Moduladores de Receptor Estrogênico/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Células MCF-7 , Estrutura Molecular , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Relação Estrutura-Atividade
13.
Artigo em Chinês | MEDLINE | ID: mdl-28459404

RESUMO

OBJECTIVE: To confirm the effects of statin therapy on mortality of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: PubMed/Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched for articles using the terms "acute lung injury", "ALI", "acute respiratory distress syndrome", "ARDS", "statin", "simvastatin" and "rosuvastatin" updated to November 17, 2015. Randomized controlled trial (RCT) or observational cohort studies investigating the effects of statin therapy on mortality in patients with ALI or ARDS were all identified, without date or language restriction. The control group was given conventional treatment, while the experimental group was treated with statins additionally. The primary outcome was in-hospital mortality. Meanwhile, ventilator-free day, intensive care unit (ICU)-free day, ICU length of stay (LOS) and ICU mortality were also analyzed. RevMan 5.2 and STATA 13 software were used for systematic review and Meta analysis, and funnel plot was used to analyze the publication bias. RESULTS: A total of five trials including three randomized controlled trials and two observational studies were included. Among 1 636 patients enrolled in the study, there were 739 patients in experimental group, and 897 in control group. It was shown by Meta analysis that there was no significant difference in in-hospital mortality between experimental group and control group [relative risk (RR) = 0.96, 95% confidence interval (95%CI) = 0.79-1.15, P = 0.63]. The subgroup analysis based on RCT and cohort study, or the subgroup analysis of different statins showed that there was no significant difference in in-hospital mortality between the experimental group and the control group (both P > 0.05). There were no significant differences in ventilator-free days [mean difference (MD) = 1.41, 95%CI = -0.32-3.13, P = 0.11], ICU-free days (MD = -0.23, 95%CI = -1.61-1.15, P = 0.75), ICU length of stay (MD = -1.03, 95%CI = -6.55-4.50, P = 0.72), or ICU mortality (RR = 0.88, 95%CI = 0.68-1.14, P = 0.33) between the experimental group and the control group. It was shown by funnel plot that there was no publication bias in in-hospital mortality. CONCLUSIONS: The systematic review and meta-analysis suggests that statin may not be associated with a significant reduction in mortality, ventilator-free day, ICU-free day and ICU length of stay in patients with ALI/ARDS.


Assuntos
Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório do Adulto , Estudos de Coortes , Mortalidade Hospitalar , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Unidades de Terapia Intensiva , Tempo de Internação , Respiração Artificial , Sinvastatina
14.
Bioorg Med Chem Lett ; 27(12): 2668-2673, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28460819

RESUMO

The estrogen receptor (ER) has played an important role in breast cancer development and progression and is a central target for anticancer drug discovery. In order to develop novel selective ERα modulators (SERMs), we designed and synthesized 18 novel 3-aryl-4-anilino-2H-chromen-2-one derivatives based on previously reported lead compounds. The biological results indicated that most of the compounds presented potent ERα binding affinity and possessed better anti-proliferative activities against MCF-7 and Ishikawa cell lines than the positive control tamoxifen. The piperidyl substituted compounds such as 16d and 18d demonstrated strong ERα binding affinities and excellent anti-proliferative activities respectively. Compound 18d displayed the most potent ERα binding affinity with RBA value of 2.83%, while 16d exhibited the best anti-proliferative activity against MCF-7 cells with IC50 value of 4.52±2.47µM. Further molecular docking studies were also carried out to investigate binding pattern of the newly synthesized compounds with ERα. All these results together with the structure-activity relationships (SARs) indicated that these 3-aryl-4-anilino-2H-chromen-2-one derivatives with basic side chain could serve as promising leads for further optimization as novel SERMs.


Assuntos
Antineoplásicos/farmacologia , Cromonas/farmacologia , Desenho de Drogas , Receptor alfa de Estrogênio/antagonistas & inibidores , Simulação de Acoplamento Molecular , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromonas/síntese química , Cromonas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptor alfa de Estrogênio/metabolismo , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade
15.
J Affect Disord ; 217: 295-298, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28448948

RESUMO

BACKGROUND: Recent studies suggest that vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder. The aim of this study is to investigate the interaction between vascular endothelial growth factor (VEGF) polymorphism (+405G/C, rs2010963) and negative life events in the pathogenesis of major depressive disorder (MDD). METHODS: DNA genotyping was performed on peripheral blood leukocytes in 274 patients with MDD and 273 age-and sex-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A logistics method was employed to assess the gene-environment interaction (G×E). RESULTS: Differences in rs2010963 genotype distributions were observed between MDD patients and controls. Significant G×E interactions between allelic variation of rs2010963 and negative life events were observed. Individuals carrying the C alleles were susceptible to MDD only when exposed to high-negative life events. CONCLUSIONS: These results indicate that interactions between the VEGF rs2010963 polymorphism and environment increases the risk of developing MDD.


Assuntos
Transtorno Depressivo Maior/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
16.
Neurosci Lett ; 650: 146-152, 2017 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28455102

RESUMO

Sleep disorders have previously been connected with the neurodegenerative pathology of Alzheimer's disease (AD) due to the aggregation of ß-amyloid(Aß)peptides and tau proteinsinduced by sleep deprivation (SD). However, the underlying mechanisms remain unclear. Therefore, this study was performed to clarify how Aß-related metabolism is regulated after SD. Three-month-old Sprague-Dawley rats (250-300g) were randomly divided into 5 groups: two SD groups(i.e.,SD-2d and SD-4d), two platform control groups(i.e.,PC-2d and PC-4d) and a home cage control group (CC). For the two SD groups, themodified multiple platform method (MMPM) was used to induce SD.Our experiments confirmed that SD impaired cognitive function and increased the levels of Aß peptides, a hallmark of AD. Additionally, we found that SD significantly increasedthe levels of the ß-site amyloid precursor protein (APP)-cleaving enzyme 1(BACE1, ß-secretase), but had little impacton the levels of Aß-degradationenzymes.This resultmay be the main cause of the over-expression of Aß1-42 and Aß1-40. Our results suggested that SD accelerates the progression of AD bymodulating Aß-related metabolism. This findinghasimportant implications for the diagnosis and prevention of AD.


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/metabolismo , Progressão da Doença , Privação do Sono/complicações , Privação do Sono/fisiopatologia , Doença de Alzheimer/diagnóstico , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Privação do Sono/diagnóstico
17.
Shock ; 48(1): 43-53, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28125527

RESUMO

PURPOSE: An open lung strategy (OLS) that includes positive end expiratory pressure and recruitment maneuvers during mechanical ventilation is probably an important treatment method in patients with acute respiratory distress syndrome (ARDS). However, the effect of OLS is unknown. We therefore hypothesized that patients with ARDS may benefit from OLS treatment. METHODS: We identified relevant randomized controlled trials by searching through PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials updated to May 22, 2016. We performed a systematic review and meta-analysis to evaluate the effect of OLS in patients with ARDS. The primary outcome was mortality. RESULTS: A total of 15 randomized controlled trials involving 1,563 patients in OLS group and 1,571 patients in control group were included. Pooled analysis showed that there was significant difference in hospital mortality (relative risk [RR], 0.88; 95% CI, 0.80-0.97; P = 0.009), 28-day mortality (RR, 0.83; 95% CI, 0.71-0.96; P = 0.010), and intensive care unit (ICU) mortality (RR, 0.77; 95% CI, 0.65-0.92; P = 0.003) between the OLS group and control group, with no substantial heterogeneity. There was no significant difference in ventilator-free days at 28-day (mean difference [MD]; 3.32 d; 95% CI, -0.49 to 7.12; P = 0.09) and ICU length of stay (MD; 1.60 d; 95% CI, -2.99 to 6.20; P = 0.49) between OLS group and control group. CONCLUSIONS: Results from this systematic review and meta-analysis suggest that OLS during mechanical ventilation significantly reduces mortality among patients with ARDS.


Assuntos
Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Adulto/terapia , Lesão Pulmonar Aguda/mortalidade , Lesão Pulmonar Aguda/terapia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Respiração com Pressão Positiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório do Adulto/mortalidade
18.
J Biomed Nanotechnol ; 13(1): 54-60, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29372988

RESUMO

Energy metabolism may alter pattern differences in acute lung injury (ALI) as one of the causes but the detailed features at single-cellular level remain unclear. Changes in intercellular temperature and adenosine triphosphate (ATP) concentration within the single cell may help to understand the role of energy metabolism in causing ALI. ALI in vitro models were established by treating mice lung epithelial (MLE-12) cells with lipopolysaccharide (LPS), hydrogen peroxide (H2O2), hydrochloric acid (HCl) and cobalt chloride (CoCl2, respectively. 100 nm micro thermocouple probe (TMP) was inserted into the cytosol by micromanipulation system and thermoelectric readings were recorded to calculate the intracellular temperature based on standard curve. The total ATP contents for the MLE-12 cells were evaluated at different time intervals after treatments. A significant increase of intracellular temperature was observed after 10 or 20 µg/L LPS and HCl treatments. The HCl increased the temperature in a dose-dependent manner. On the contrary, H2O2 induced a significant decline of intracellular temperature after treatment. No significant difference in intracellular temperature was observed after CoCl2 exposure. The intracellular ATP levels decreased in a time-dependent manner after treatment with H2O2 and HCl, while the LPS and CoCl2 had no significant effect on ATP levels. The intracellular temperature responses varied in different ALI models. The concentration of ATP in the MLE-12 cells played part in the intracellular temperature changes. No direct correlation was observed between the intracellular temperature and concentration of ATP in the MLE-12 cells.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Pulmão/metabolismo , Nanotecnologia/métodos , Análise de Célula Única/métodos , Termometria/métodos , Lesão Pulmonar Aguda/fisiopatologia , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Cobalto/efeitos adversos , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Ácido Clorídrico/efeitos adversos , Peróxido de Hidrogênio/efeitos adversos , Lipopolissacarídeos/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Camundongos , Temperatura Ambiente
19.
Arch Med Res ; 47(5): 356-364, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27751369

RESUMO

BACKGROUND AND AIMS: Continuous renal replacement therapy (CRRT) is an important treatment in the intensive care unit (ICU). Nevertheless, the outcome of CRRT remains unclear. It is important to find a useful and easy indicator to predict the prognosis in patients on CRRT treatment. We undertook this study to observe the association between serum D-dimer level and mortality of ICU patients in the treatment of CRRT. METHODS: A total of 149 patients who received CRRT were enrolled in our study. We observed the correlation of D-dimer with the information of biochemical parameters, acute physiology and chronic health evaluation II (APACHE II) score. We analyzed the association between serum D-dimer level before CRRT and 28-d mortality retrospectively. Furthermore, we used Cox regression analysis to assess whether D-dimer could be the independent risk factor for mortality. RESULTS: There were significant correlations between D-dimer and C-reaction protein (r2 = 0.033, p = 0.026), creatinine (r2 = 0.066, p = 0.002) and APACHE II (r2 = 0.036, p = 0.021). The difference in 28-d mortality risk between elevated D-dimer group and normal D-dimer group was significant (HR 2.872, 95% CI 1.563-5.278, p = 0.001), and the elevated D-dimer level was an independent risk factor for 28-d mortality (HR 2.067, 95% CI 1.104-3.872, p = 0.023). The difference in 28-d mortality was significant between groups (p <0.001). ROC curves showed that the area under the curve (AUC) of D-dimer was 0.763. CONCLUSION: The present study demonstrates that serum D-dimer could be a useful and easy prognostic variable of 28-d mortality in critically ill patients who received CRRT.


Assuntos
Lesão Renal Aguda/terapia , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Terapia de Substituição Renal , APACHE , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/mortalidade , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Creatinina/sangue , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Análise de Regressão , Estudos Retrospectivos
20.
J Surg Res ; 202(2): 389-97, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27229114

RESUMO

BACKGROUND: The Surviving Sepsis Campaign has recommended early goal-directed therapy (EGDT) as an essential strategy to decrease mortality among patients with severe sepsis and septic shock. However, three latest multicenter trials failed to show its benefit in the patients with severe sepsis and septic shock. This article was to evaluate the effect of EGDT on the mortality of patients with severe sepsis and septic shock. METHODS: Relevant studies from PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were identified from January 1, 2001 to June 13, 2015. With both randomized controlled trials (RCTs) and non-RCTs selected, a meta-analysis on the effects of EGDT on all identified trials was performed. The primary outcome was the inhospital mortality. In subgroup, RCTs and non-RCTs were analyzed, respectively. RESULTS: A total of five RCTs and 10 non-RCTs involving 3285 patients in EGDT group and 3233 patients in the control group were identified. Pooled analyses of all studies showed significant difference in the inhospital mortality between the EGDT group and the control group (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.74-0.94; P = 0.003) with substantial heterogeneity (χ2 = 24.93, P = 0.04, I(2) = 44%). In subgroup analysis, there were no significant difference in inhospital mortality between the EGDT group and the control group (RR, 0.95; 95% CI, 0.83-1.10; P = 0.51) with no significant difference in heterogeneity (χ2 = 6.62, P = 0.16, I(2) = 40%) in RCTs. In non-RCTs, EGDT significantly reduced inhospital mortality (RR, 0.75; 95% CI, 0.65-0.88; P = 0.0003) with no significant difference in heterogeneity (χ2 = 11.96, P = 0.22, I(2) = 25%). CONCLUSIONS: This meta-analysis suggests that EGDT can significantly reduce the mortality among patients with severe sepsis and septic shock.


Assuntos
Protocolos Clínicos , Mortalidade Hospitalar , Ressuscitação/métodos , Choque Séptico/terapia , Metas , Humanos , Modelos Estatísticos , Choque Séptico/mortalidade , Resultado do Tratamento
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