Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Clin Exp Med ; 19(4): 571-576, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31598794

RESUMO

Interleukin (IL)-8 has been reported to be associated with the progression of sepsis. Recent studies have explored the relationship between the IL-8 - 251 A/T polymorphism and sepsis risk. This study evaluated the association between the IL-8 - 251 A/T polymorphism and sepsis susceptibility in a Chinese Han population. We designed a case-control study with 254 sepsis cases and 322 controls. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. SPSS 20.0 software was used for all statistical analysis (SPSS Inc., Chicago, USA). This study showed that the IL-8 - 251 A/T polymorphism was associated with a decreased risk of sepsis. Stratified analyses found that this association held true in females, non-smokers, and older individuals (age > 60 years). The IL-8 - 251 A/T polymorphism was also related to the severity and 28-day mortality of sepsis. The IL-8 - 251 A/T polymorphism is associated with a decreased risk of sepsis.

2.
ACS Appl Mater Interfaces ; 11(42): 39116-39124, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31569941

RESUMO

Selective catalytic hydrogenation of substituted nitro compounds (NCs) of hydrophobic nature in aqueous solution using transition-metal-based catalysts is highly desirable yet fairly challenging. Herein, we propose the idea of amphiphilic mesoporous catalysts for selective hydrogenation of hydrophobic NCs in aqueous solution. The amphiphilic catalyst Co@Co-N-C@SBA-15 with a sandwich-like structure is constructed by a one-step solvent-free melting coating method. The catalyst has an external hydrophilic silica support that facilitates catalyst dispersion in water. It has unique Co-N-C catalytic layers uniformly coated in the inner mesopore surfaces of the silica support, which enhance the selective adsorption and activation of hydrophobic NCs. It has a high surface area (448.2 m2/g) and a uniform mesopore size (∼7.0 nm) for fast mass transportation. It possesses ultrafine metallic Co nanoparticles uniformly anchored within the N-doped carbon (N-C) layers for easy magnetic separation. These features make the catalyst excellent for the selective hydrogenation of 4-nitrostyrene to form 4-aminostyrene, with a high conversion of 98.0% in 1.0 h, a superior selectivity of 98.8%, and a good stability under mild conditions. A comprehensive study confirms the excellence of the amphiphilic mesoporous catalysts compared with other control catalysts. The Co-N sites are the intrinsic active sites. They can selectively adsorb and activate the nitro groups other than the vinyl groups, leading to superior selectivity. Water as the solvent results in the best performance compared with typical organic solvents probably because of an enhanced water-mediated hydrogen spillover and transfer.

3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(8): 949-952, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31537217

RESUMO

OBJECTIVE: To explore the effect of intensive insulin therapy (IIT) on high mobility group box-1/nuclear factor-ΚB (HMGB1/NF-ΚB) signaling pathway in severe traumatic brain injury (sTBI) patient with stress hyperglycemia. METHODS: Sixty-one sTBI patients with stress hyperglycemia [Glasgow coma scale (GCS) ≤ 8, three times of random blood glucose levels > 11.1 mmoL/L, glycosylated hemoglobin (HbA1c) < 0.065] admitted to the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from July 2015 to October 2017 were enrolled. Patients were divided into IIT group (29 cases, keeping blood glucose at 4.4-7.8 mmol/L) and conventional glycemic therapy (CGT) group (32 cases, keeping blood glucose at 7.8-12.2 mmo/L) according to the random number table method. Before treatment and 1, 7 and 14 days after treatment, the levels of plasma HMGB1 and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA); C-reactive protein (CRP) was determined by automatic biochemical analyzer, and NF-ΚB p65 gene expression in peripheral blood mononuclear cells was detected by real-time quantitative polymerase chain reaction (PCR). RESULTS: Nine patients were withdrawn from the observation because the 4 consecutive blood glucose monitoring did not reach the target value, combined with severe infection, or abandoned the treatment with serious brain damage. Finally, 52 patients were enrolled in the analysis, including 28 in CGT group and 24 in IIT group. The levels of plasma HMGB1, TNF-α, CRP and the expression of NF-ΚB gene in monocytes of the two groups at 1 day after treatment were significantly higher than those before treatment, and reached the peak value, then gradually decreased. After 7 days of treatment, they were significantly lower than 1 day. The levels of plasma CRP and TNF-α in the IIT group were significantly lower than those in the CGT group [CRP (mg/L): 36.7±4.4 vs. 45.1±6.1, TNF-α (ng/L): 42.4±9.7 vs. 53.2±9.1, both P < 0.05], the level of HMGB1 in plasma and the expression of NF-ΚB p65 in monocytes were significantly lower than those in the CGT group after 14 days of treatment [HMGB1 (µg/L): 60.1±8.7 vs. 80.5±9.1, NF-ΚB p65 (ΔCt): 35.8±8.5 vs. 53.5±7.3, both P < 0.05]. CONCLUSIONS: IIT inhibits the inflammatory response in sTBI patients with stress hyperglycemia through HMGB1/NF-ΚB pathway.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Proteína HMGB1/metabolismo , Hiperglicemia/metabolismo , Insulina/uso terapêutico , NF-kappa B/metabolismo , Glicemia , Automonitorização da Glicemia , Humanos , Leucócitos Mononucleares , Fator de Necrose Tumoral alfa
4.
J Colloid Interface Sci ; 556: 529-540, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31473542

RESUMO

The fast and scalable spray-drying-assisted evaporation-induced self-assembly (EISA) synthesis of hierarchically porous SBA-15-type silica microparticles from a water-based system is demonstrated. The SBA-15-type silica microparticles has bowl-like shapes, uniform micro-sizes (∼90 µm), large ordered mesopores (∼9.5 nm), hierarchical meso-/macropores (20-100 nm) and open surfaces. In the synthesis, soft- and hard-templating approaches are combined in a single rapid drying process with a non-ionic tri-block copolymer (F127) and a water-insoluble polymer colloid (Eudragit RS, 120 nm) as the co-templates. The RS polymer colloid plays three important roles. First, the RS nanoparticles can be partially dissolved by in-situ generated ethanol to form RS polymer chains. The RS chains swell and modulate the hydrophilic-hydrophobic balance of F127 micelles to allow the formation of an ordered mesostructure with large mesopore sizes. Without RS, only worm-like mesostructure with much smaller mesopore sizes can be formed. Second, part of the RS nanoparticles plays a role in templating the hierarchical pores distributed throughout the microparticles. Third, part of the RS polymer forms surface "skins" and "bumps", which can be removed by calcination to enable a more open surface structure to overcome the low pore accessibility issue of spray-dried porous microparticles. The obtained materials have high surface areas (315-510 m2 g-1) and large pore volumes (0.64-1.0 cm3 g-1), which are dependent on RS concentration, HCl concentration, silica precursor hydrolysis time and drying temperature. The representative materials are promising for the adsorption of lysozyme. The adsorption occurs at a >three-fold faster rate, in a five-fold larger capacity (an increase from 20 to 100 mg g-1) and without pore blockage compared with the adsorption of lysozyme onto spray-dried microparticles of similar physicochemical properties obtained without the use of RS.

5.
Stem Cell Res Ther ; 10(1): 247, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399039

RESUMO

BACKGROUND: Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating skin wounds. However, the exact effects of hAMSCs on the healing of thermal burn skin wounds and their potential mechanisms are not explored. METHODS: hAMSCs were isolated from amniotic membrane and characterized by RT-PCR, flow cytometry, immunofluorescence, and tumorigenicity test. We assessed the effects of hAMSCs and hAMSC conditional medium (CM) on wound healing in a deep second-degree burn injury model of mice. We then investigated the biological effects of hAMSCs and hAMSC-CM on the apoptosis and proliferation of heat stress-injured human keratinocytes HaCAT and dermal fibroblasts (DFL) both in vivo and in vitro. Next, we explored the underlying mechanisms by assessing PI3K/AKT and GSK3ß/ß-catenin signaling pathways in heat injured HaCAT and DFL cells after hAMSCs and hAMSC-CM treatments using PI3K inhibitor LY294002 and ß-catenin inhibitor ICG001. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may activate PI3K/AKT signaling pathway. RESULTS: Our results showed that hAMSCs expressed various markers of embryonic stem cells and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAMSC and hAMSC-CM transplantation significantly promoted thermal burn wound healing by accelerating re-epithelialization with increased expression of CK19 and PCNA in vivo. hAMSCs and hAMSC-CM markedly inhibited heat stress-induced apoptosis in HaCAT and DFL cells in vitro through activation of PI3K/AKT signaling and promoted their proliferation by activating GSK3ß/ß-catenin signaling. Furthermore, we demonstrated that hAMSC-mediated activation of GSK3ß/ß-catenin signaling was dependent on PI3K/AKT signaling pathway. Antibody array assay showed that a panel of cytokines including PAI-1, C-GSF, periostin, and TIMP-1 delivered from hAMSCs may contribute to the improvement of the wound healing through activating PI3K/AKT signaling pathway. CONCLUSION: Our results demonstrated that hAMSCs and hAMSC-CM efficiently cure heat stress-induced skin injury by inhibiting apoptosis of skin cells and promoting their proliferation through activating PI3K/AKT signaling pathway, suggesting that hAMSCs and hAMSC-CM may provide an alternative therapeutic approach for the treatment of skin injury.

6.
J Colloid Interface Sci ; 551: 164-176, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31078098

RESUMO

In this paper, we demonstrate the facile and general synthesis of alkaline-earth metal manganites, denoted as A(Mg, Ca, Ba)MnxOy, for efficient degradation of high-concentration phenolic compounds via catalytic ozonation. The representative CaMnxOy oxides show a hierarchical spherical structure constructed by crystalline nanorods and numerous macropores. They possess mixed Mn4+/Mn3+ chemical valences and abundant surface hydroxyl (OH) groups. The ozone (O3) decomposition rate on the CaMnxOy catalysts is greatly accelerated and follows the first-order law. These catalysts are promising for the degradation of phenolic compounds via catalytic ozonation, exhibiting rapid pseudofirst-order degradation kinetics, a high total organic carbon (TOC) removal efficiency and an excellent stability. Under optimized conditions (a low O3 dosage of 1.5 mg/min and a catalyst dosage of 7.5 g/L), for the treatment of concentrated phenol (50-240 mg/L), the CaMnxOy catalysts show 100% degradation and 50-70% mineralization within 1.0 h. The Ca2+ ions are essential to create redox Mn4+/Mn3+ couples and to significantly reduce manganese leaching. High surface ratios of Mn4+/Mn3+ and OH/lattice oxygen (Olat) are beneficial for enhancing the catalytic performance. Superoxide anion free radicals (O2-) and singlet oxygen (1O2) are the predominant reactive species for the oxidation degradation. The O2- reaction pathway is proposed. Specifically, the surface OH sites activate O3, displaying highly enhanced decomposition rates. The generated O2- and 1O2 play a role in oxidation. The redox Mn4+/Mn3+ and the Olat/oxygen vacancy (Olat/Ovac) couples play important roles in electron transfer. The proposed mechanism is supported by active site probing, radical scavenging, spectroscopic studies, and the results in the degradation of substituted phenols.

7.
J Clin Gastroenterol ; 53(7): e276-e283, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29912754

RESUMO

BACKGROUND: Computed tomography-measured visceral adipose tissue (VAT) and the distribution of VAT are highly correlated with the severity and prognosis of acute pancreatitis (AP). To date, all available data are from the overall AP patient population; no subgroup analysis has been conducted to evaluate patients with moderately severe AP or patients with hyperlipidemia acute pancreatitis (HLAP) as independent populations. Currently, studies on the relationship between VAT and HLAP are lacking. MATERIALS AND METHODS: A total of 235 patients with moderately severe AP or severe acute pancreatitis were divided into 2 groups according to whether hyperlipidemia was present: the HLAP group and the non-HLAP group. The general inpatient information was collected, and computed tomography was used to measure VAT, subcutaneous adipose tissue (SAT), total adipose tissue, and VAT/SAT (V/S). The data were subjected to t test, χ test, matrix scatter plot, logistic regression, and receiver operating characteristic analyses to evaluate the relationship between VAT and HLAP severity. RESULTS: Significant differences were observed in VAT, SAT, total adipose tissue, and triglycerides (TGs) between the HLAP group and the non-HLAP group (P<0.001). Significant correlations were observed between VAT and body mass index (r=0.425, P=0.017) and between VAT and TG (r=0.367, P=0.042). In the HLAP group, VAT, V/S, TG, and local complications may have significant effects on disease severity. The receiver operating characteristic curves showed that VAT and V/S were more reliable than TGs in evaluating disease severity [area under the curve (AUC) of VAT: 0.819, P<0.001; AUC of V/S: 0.855, P<0.001; AUC of TG: 0.671, P=0.04]. Disease severity was reliably evaluated at 139 cm, the cut-off value of VAT. The cut-off value of V/S was 1.145; high V/S was associated with extended intensive care unit stay. VAT and its distribution had no significant effects on mortality. CONCLUSIONS: For patients with moderately severe to severe HLAP, VAT was correlated with body mass index and TG. VAT and V/S were valuable factors for evaluating disease severity and prognosis. However, VAT had no effect on mortality, and VAT could not be used to evaluate patients with moderately severe to severe non-HLAP.

8.
J Colloid Interface Sci ; 537: 112-122, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30423485

RESUMO

Adsorption and catalytic conversion of nitrophenols (NPs) over carbon-based materials have attracted wide interest. Batch adsorption and catalytic reduction of NPs have been widely reported, but less attention has been paid to flow systems, which require high particle size uniformity and superior active site accessibility. Herein, uniform mesoporous carbon hollow microspheres with their surfaces enriched by Au nanoparticles (denoted as Au@UMCHMs) are synthesized. The surface-enriched Au nanoparticle loading is promoted by the unique feature, that is, relatively dense external layers and mesoporous inner shells, of the carbon microspheres and the simple impregnation-reduction method. The Au@UMCHMs possess uniform sizes of ∼82 µm, small shell thickness of ∼5.8 µm, high specific surface area (∼1587 m2/g), and uniform mesopores (2.1 and 5.8 nm). They show excellent performance for flow adsorption and catalytic reduction of 4-nitrophenol (4-NP), superior to that of conventional Au-loaded carbon materials. In flow adsorption of 4-NP, the Au@UMCHMs show a fast and complete removal efficiency with high adsorption capacities (∼223 mg/g at breakthrough). They show outstanding performance in flow catalytic reduction of 4-NP. 4-NP with high concentrations (up to 100 mg/L) can be ultrafast and completely catalytically reduced to 4-aminophenol (4-AP) under rapid flow rates (up to ∼25 mL/min).

9.
Stem Cell Res Ther ; 9(1): 321, 2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30463600

RESUMO

BACKGROUND: Hepatocyte transplantation has been proposed as an effective treatment for patients with acute liver failure (ALF), but its application is limited by a severe shortage of donor livers. Human pluripotent stem cells (hPSCs) have emerged as a potential cell source for regenerative medicine. Human amniotic epithelial stem cells (hAESCs) derived from amniotic membrane have multilineage differentiation potential which makes them suitable for possible application in hepatocyte regeneration and ALF treatment. METHODS: The pluripotent characteristics, immunogenicity, and tumorigenicity of hAESCs were studied by various methods. hAESCs were differentiated to hepatocyte-like cells (HLCs) using a non-transgenic and three-step induction protocol. ALB secretion, urea production, periodic acid-Schiff staining, and ICG uptake were performed to investigate the function of HLCs. The HLCs were transplanted into ALF NOD-SCID (nonobese diabetic severe combined immunodeficient) mouse, and the therapeutic effects were determined via liver function test, histopathology, and survival rate analysis. The ability of HLCs to engraft the damaged liver was evaluated by detecting the presence of GFP-positive cells. RESULTS: hAESCs expressed various markers of embryonic stem cells, epithelial stem cells, and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAESC-derived hepatocytes possess the similar functions of human primary hepatocytes (hPH) such as producing urea, secreting ALB, uptaking ICG, storing glycogen, and expressing CYP enzymes. HLC transplantation via the tail vein could engraft in live parenchymal, improve the liver function, and protect hepatic injury from CCl4-induced ALF in mice. More importantly, HLC transplantation was able to significantly prolong the survival of ALF mouse. CONCLUSION: We have established a rapid and efficient differentiation protocol that is able to successfully generate ample functional HLCs from hAESCs, in which the liver injuries and death rate of CCl4-induced ALF mouse can be significantly rescued by HLC transplantation. Therefore, our results may offer a superior approach for treating ALF.


Assuntos
Âmnio/citologia , Hepatócitos/transplante , Falência Hepática Aguda/terapia , Células-Tronco Pluripotentes/transplante , Animais , Tetracloreto de Carbono/farmacologia , Modelos Animais de Doenças , Células Epiteliais/citologia , Hepatócitos/citologia , Xenoenxertos , Humanos , Falência Hepática Aguda/induzido quimicamente , Camundongos , Camundongos Endogâmicos NOD , Cultura Primária de Células
10.
J Cell Biochem ; 2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30203508

RESUMO

Long noncoding RNAs (lncRNA) have been recognized as significant regulators in the progression of atherosclerosis (AS). Oxidized low-density lipoprotein (ox-LDL) can induce macrophage inflammation and oxidative stress, that serves important roles in AS. However, the exact function of lncRNA NEAT1 and its possible molecular mechanism in AS remain unclear. Here, we concentrated on the roles and molecular mechanisms of NEAT1 in AS development. In our current study, we observed that NEAT1 was elevated by ox-LDL in a dose-dependent and time-dependent manner. RAW264.7 cell survival was greatly enhanced, and cell apoptosis was significantly inhibited by LV-shNEAT1 transfection. In addition, knockdown of NEAT1 in RAW264.7 cells repressed CD36 expression and foam cell formation while NEAT1 overexpression shown an opposite process. Moreover, NEAT1 downregulation inhibited inflammation molecules including IL-6, IL-1ß, and TNF-α. Meanwhile, silencing of NEAT1 can also suppress reactive oxygen species (ROS) and malondialdehyde (MDA) levels with an enhancement of superoxide dismutase (SOD) activity in RAW264.7 cells. MicroRNAs are some short RNAs, and they can regulate multiple biological functions in many diseases including AS. Here, we found that miR-128 expression was remarkably decreased in ox-LDL-incubated RAW264.7 cells. Interestingly, miR-128 mimics was able to reverse AS-correlated events induced by overexpression of NEAT1. By using bioinformatics analysis, miR-128 was predicted as a target of NEAT1 and the correlation between them was validated in our study. Taken these together, it was implied that NEAT1 participated in ox-LDL-induced inflammation and oxidative stress in AS development through sponging miR-128.

11.
Cell Physiol Biochem ; 48(3): 1347-1354, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30048993

RESUMO

BACKGROUND/AIMS: Elabela (ELA) or Toddler is a recently identified hormone that plays a crucial role in embryonic development through the activation of the apelin receptor (APJ). Our previous study indicated that ELA is highly expressed in adult kidney and the ELA receptor signaling pathway is functional in mammalian systems. Whereas nothing is yet known regarding ELA and diabetic kidney disease (DKD). Here, we evaluated the relationship between serum ELA levels and albuminuria in patients with type 2 diabetes (T2D). METHODS: An observational study involving 80 patients divided into groups according to their baseline urinary albumin/creatinine ratio (ACR): Group 1 (ACR ≤ 29 mg/g), Group 2 (ACR = 30-299 mg/g), Group 3 (ACR ≥ 300 mg/g with normal serum creatinine), and Group 4 (ACR ≥ 300 mg/g with increased serum creatinine). The demographic, clinical, and biochemical variables including serum ELA were obtained or measured through disease history, physical examination, or laboratory evidence. RESULTS: The results showed that the serum ELA levels decreased gradually with the deterioration of DKD from the stages of normal albuminuria, microalbuminuria, macroalbuminuria, to macroalbuminuria and elevated serum creatinine. In addition, ELA had a significantly negative correlation with ACR (r = -0.561, P < 0.001), retinopathy (r = -0.424, P < 0.001), serum creatinine (r = -0.269, P = 0.016), SBP (r = -0.249, P = 0.026), DBP (r = -0.261, P = 0.020) and a positive correlation with eGFR (r = 0.318, P = 0.004). Furthermore, stepwise multiple linear regression analysis showed that ACR, retinopathy, and LDL-C were considered the most relevant variables to ELA, and ELA, retinopathy, eGFR, and age were important predictors for ACR (t = -4.546, P = 0.000). CONCLUSIONS: To our knowledge, this is the first study to explore the clinical relationship between ELA levels and CKD. Decreased serum ELA levels might be a significant clinical predictor in patients with DKD or even as a promising agent for treating CKD patients.


Assuntos
Albuminúria/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Hormônios Peptídicos/sangue , Adulto , Idoso , Albuminúria/complicações , Albuminúria/urina , Creatinina/sangue , Creatinina/urina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Int J Mol Med ; 41(5): 2977-2985, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29484377

RESUMO

The present study aimed to investigate the mechanism of glucagon­like peptide­1 receptor (GLP­1R) agonists in the progression of diabetic peripheral neuropathy (DPN) in streptozotocin (STZ)­induced diabetic rats, through inflammatory signaling pathways. The DPN rat model was generated by intraperitoneal injection of STZ and then treated with the GLP­1R agonist liraglutide or saline for 8 weeks. These animals were randomly divided into 4 groups (10 rats in each): The normal control + saline group, the normal control + liraglutide group, the diabetic + saline (DM) group and the diabetic + liraglutide (DML) group. The nerve conduction velocity (NCV) in the sciatic nerves of the rats was monitored over a period of 8 weeks. Peripheral serum was obtained for the measurement of blood glucose, tumor necrosis factor­α (TNF­α), interleukin­6 (IL­6) and IL­1ß level. The protein levels of phosphorylated (p­) and total extracellular signal­regulated kinase, c­Jun NH2­terminal kinases, p38 mitogen­activated protein kinases (MAPK), and nuclear and cytoplasmic nuclear factor­κB (NF­κB) were measured through western blot analysis. Sciatic nerve mRNA expression levels of proinflammatory chemokines (TNF­α, IL­6 and IL­1ß), chemokines [monocyte chemoattractant protein­1 (MCP­1)], adhesion molecules [intercellular adhesion molecule 1 (ICAM­1)], neurotrophic factors [neuritin, nerve growth factor (NGF) and neuron­specific enolase (NSE)] and NADPH oxidase 4 (NOX4) were evaluated by reverse transcription-quantitative polymerase chain reaction. Subsequent to 8 weeks of treatment with liraglutide, the density of myelin nerve fibers was partially restored in the DML group. The delayed motor NCV and sensory NCV in the DML group were improved. The IOD value of NOX4 staining in the DML group (24.43±9.01) was reduced compared with that in the DM group (56.60±6.91). The levels of TNF­α, IL­1ß and IL­6 in the peripheral serum of the DML group were significantly suppressed compared with those of the DM group. It was also observed that the mRNA expression levels of TNF­α, IL­6, IL­1ß, MCP­1, ICAM­1 and NOX4 in the sciatic nerve were attenuated in the DML group. The mRNA expression of neuritin and NGF was significantly increased in the DML group compared with that of the DM group; NSE was reduced in the sciatic nerves of the DML group compared with that of the DM group. Additionally, the protein expression of p­p38 MAPK and NF­κB in the DML group was significantly suppressed. These data demonstrated that GLP­1R agonists may prevent nerve dysfunction in the sciatic nerves of diabetic rats via p38 MAPK/NF­κB signaling pathways independent of glycemic control. GLP­1R agonists may be a useful therapeutic strategy for slowing the progression of DPN.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , NF-kappa B/imunologia , Nervo Isquiático/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/imunologia , Neuropatias Diabéticas/fisiopatologia , Receptor do Peptídeo Semelhante ao Glucagon 1/imunologia , Inflamação/complicações , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/imunologia , Nervo Isquiático/fisiopatologia , Transdução de Sinais/efeitos dos fármacos
13.
Kidney Blood Press Res ; 42(5): 894-904, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29241180

RESUMO

BACKGROUND/AIMS: High mobility group box 1 (HMGB1) is an important mediator of the inflammatory response. It has been implicated in the pathogenesis of autoimmune diseases, atherosclerosis, and obesity. However, the effects of HMGB1 on diabetic nephropathy remain unclear. Here, we investigated the potential roles and mechanisms of an HMGB1 inhibitor, glycyrrhizic acid (GA), in renal injury with the streptozotocin (STZ)-induced rat model. METHODS: The diabetic rat was generated by intraperitoneal injection of STZ and then treated with the HMGB1 inhibitor GA or saline for 8 weeks. Rats were randomly divided into three groups: the normal control and saline group (Control), the diabetic rats with saline group (Diabetic) and the diabetic rats plus GA group (Diabetic+GA). Peripheral blood was obtained for measurements of blood glucose, TNF-a, IL-6 and IL-1ß. The mRNA levels of proinflammatory cytokines (TNF-a, IL-6 and IL-1ß), chemokines (MCP-1), intercellular adhesion molecules (ICAM-1) and TGF-ß1 in the kidneys were evaluated by quantitative real-time PCR. The protein levels of phosphorylated(p) and total(t) p38 MAPK, JNK, ERK, and NF-κB were measured by western blot. RESULTS: We found that diabetic rats showed obvious renal lesions, an elevated urinary albumin/creatinine ratio (UACR) and increased expression levels of TGF-ß1 and Col-IV in the kidneys, accompanied by significantly enhanced expression levels of HMGB1, receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR-4) in the kidney tissue. Furthermore, the GA treatment significantly reduced the UAC levels, ameliorated renal injury, and decreased the TNF-α, 1L-6, IL-1ß, MCP-1, ICAM-1, TGF-ß1 and Col-IV levels. Importantly, the expression levels of HMGBI, RAGE and TLR4 in the kidney tissues of the diabetic rats were also inhibited by the GA treatment. Furthermore, the GA treatment significantly reduced the phosphorylation levels of ERK and p38 MAPK and suppressed NF-κB translocation from the cytoplasm to the nucleus. CONCLUSION: Our findings indicate that the HMGB1 inhibitor GA may improve renal injury and inflammatory responses in diabetic rats by regulating RAGE/TLR4-related ERK and p38 MAPK/NF-κB activation.


Assuntos
Ácido Glicirrízico/uso terapêutico , Proteína HMGB1/antagonistas & inibidores , Rim/lesões , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Ratos , Receptor para Produtos Finais de Glicação Avançada , Estreptozocina , Receptor 4 Toll-Like , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Saudi Pharm J ; 25(4): 666-670, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28579909

RESUMO

For patients who have sepsis, acute lung injury (ALI) causes most of death. Metformin (Met) is an anti-hyperglycemic agent and it has extensive pharmacological properties. This study aimed to analyze the influence of Met on lipopolysaccharide (LPS) -induced ALI. Met (1, 2, and 4 mg/kg) were injected and LPS was injected 30 min later. The data suggested Met can reduce release of inflammatory cytokines and bronchoalveolar lavage fluid (BALF) protein expression, reduce lung wet/dry ratio, and significantly improve LPS-induced lung destruction during ALI. In addition, Met inhibits LPS-induced neutrophil and macrophage infiltration, reduces MPO activity, and promotes AMPK-α1 expression in lung tissues. Our data suggested that metformin alleviates capillary injury during ALI via AMPK-α1.

15.
ChemSusChem ; 9(19): 2841-2848, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27552078

RESUMO

A facile two-step strategy was used to prepare black of hydrogenated/nitrogen-doped TiO2 nanoplates (NHTA) with a flower-like hierarchical architecture. In situ nitriding and self-assembly was realized by hydrothermal synthesis using tripolycyanamide as a N source and as a structure-directing agent. After thorough characterization, it was found that the hydrogenation treatment did not damage the flower-like architecture but distorted the anatase crystal structure and significantly changed the band structure of NHTA owing to the increased concentration of oxygen vacancies, hydroxyl groups, and Ti3+ cations. Under AM 1.5 illumination, the photocatalytic H2 evolution rate on the black NHTA was approximately 1500 µmol g-1 h-1 , which was much better than the N-doped TiO2 nanoplates (≈690 µmol g-1 h-1 ). This improvement in the hydrogen evolution rate was attributed to a reduced bandgap, enhanced separation of the photogenerated charge carriers, and an increase in the surface-active sites.


Assuntos
Hidrogênio/química , Nanoestruturas/química , Nitrogênio/química , Titânio/química , Catálise , Espectroscopia de Ressonância de Spin Eletrônica , Microscopia Eletrônica de Varredura , Processos Fotoquímicos , Espectrofotometria Ultravioleta , Análise Espectral Raman , Difração de Raios X
16.
Adv Mater ; 28(7): 1477-81, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26661886

RESUMO

The fabrication of novel superhydrophobic electrodes is described, which have an air-liquid-solid three-phase interface, where oxygen is sufficient and constant. Oxygen is an effective natural electron acceptor for oxidase, and plays a key role in the development of reliable bioassays. Such an electrode allows detection of glucose concentration, linearly from 50 × 10(-9) m to 156 × 10(-3) m with good sensitivity and accuracy without analyte dilution. This strategy offers a unique route to address the gas-deficit problem of many reaction systems.


Assuntos
Técnicas Biossensoriais/instrumentação , Enzimas Imobilizadas/química , Interações Hidrofóbicas e Hidrofílicas , Oxigênio/química , Ar , Eletroquímica , Eletrodos , Enzimas Imobilizadas/metabolismo , Glucose/análise , Glucose/química , Glucose Oxidase/química , Glucose Oxidase/metabolismo
17.
Pak J Pharm Sci ; 29(6 Spec): 2179-2183, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28412677

RESUMO

To investigate the difference in clinical efficacy and safety of different meropenem regimens on patients with serious infection in ICU. Then, 228 patients with serious infection in ICU were divided by random into control group (intermittent administration in 1000mg/30min single dose) and research group (continuous administration in 200mg/10min +800mg/180min), respectively. The blood concentration of meropenem were recorded in two groups at different time points, and difference in treatment effectiveness, iconographic effectiveness, bacterial eradication rate, 28-day survival rate and many other clinical scoring indices (SOFA, APACHEII, CPIS, and SIRS) were compared between two groups. There were 212 patients completing the whole research, including 104 patients in research group and 108 patients in control group. The difference in treatment effectiveness (77.8% vs 53.7%), iconographic effectiveness (51.0% vs 18.5%), and 28-day survival rate (86.5% vs 64.8%) between two groups performed statistical significance (P<0.05). However, the difference in bacterial eradication rate (48.0% vs 46.3%) performed no statistical significance. Eight hours later, the difference in average blood concentration between two groups (9.61±3.63µg/ml vs 1.5±0.51µg/ml) showed statistical significance. Moreover, the difference in clinical scoring indices except APACHE II score between two groups performed statistical significance. It was helpful to maintain the blood concentration of meropenem by extending the transfusion time. Therefore, it could increase the clinical cure rate and 28-day survival of patients with serious infection in ICU, improve clinical indices, and reduce the usage amount of antibiotics.

18.
Biomed Pharmacother ; 71: 240-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25960243

RESUMO

Our previous study suggests that heme oxygenase-1 (HO-1) may play an important role in the metastasis of gastric cancer. Zinc protoporphyrin IX (ZnPPIX) is a special HO-1 inhibitor that inhibits the angiogenesis of pancreatic and lung cancer. In this study, we employed ZnPPIX to investigate the role of HO-1 in peritoneal metastasis of gastric cancer (PMGC) and explored the potential mechanism. We established animal model of PMGC by orthotopic implantation into nude mice of human gastric cancer cell line GC9811-P with high peritoneal metastasis potential. The mice were injected intraperitoneally with saline, CTX or ZnPPIX. Tumor microvessel density (MVD) in peritoneal metastatic nodules was determined by immunohistochemistry, and vascular endothelial growth factor (VEGF) level was determined by ELISA. We found that the number, volume, weight of peritoneal metastatic nodules and volume of seroperitoneum in ZnPPIX (4 mg/kg) group decreased remarkably compared with control group. MVD value and VEGF level of peritoneal metastatic tumor in ZnPPIX (4 mg/kg) group also decreased significantly, while the survival rate and survival time of the mice were higher than control group. ZnPPIX dose-dependently suppressed VEGF and GC9811-P induced angiogenesis. Furthermore, ZnPPIX suppressed VEGF induced reactive oxygen species production and ERK phosphorylation in human umbilical vein endothelial cells. In conclusion, our results suggest that HO-1 plays an important role in PMGC and ZnPPIX is an effective antitumor and antiangiogenic agent for PMGC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Protoporfirinas/uso terapêutico , Neoplasias Gástricas/patologia , Inibidores da Angiogênese/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Galinhas , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Estimativa de Kaplan-Meier , Camundongos Nus , Fosforilação/efeitos dos fármacos , Protoporfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Kidney Blood Press Res ; 35(6): 483-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22687869

RESUMO

AIMS: It was reported that exenatide ameliorated renal injury in diabetic rats. The present study was carried out to evaluate the effect of exenatide on 24-hour urinary albumin, urinary transforming growth factor-ß(1) (TGF-ß(1)) and type IV collagen excretion in patients with type 2 diabetes and microalbuminuria. METHODS: 31 type 2 diabetic patients with microalbuminuria were randomly allocated to receive exenatide (group Exe, n = 13) or glimepiride treatment (group Glm, n = 18) for 16 weeks. Body mass index (BMI), fasting plasma glucose, 2-hour postprandial plasma glucose, glycated hemoglobin A(1c), systolic blood pressure, diastolic blood pressure, 24-hour urinary albumin, urinary TGF-ß(1) and type IV collagen concentration were analyzed between the two treatment groups. 20 age- and BMI-matched healthy subjects were chosen as the normal control group (group NC, n = 20). RESULTS: After 16 weeks of treatment, 24-hour urinary albumin, urinary TGF-ß(1) and type IV collagen in group Exe were significantly lower than those of group Glm (p < 0.01), while glycemic control had no statistical difference between the two groups. CONCLUSIONS: Our results indicate that exenatide reduces urinary TGF-ß(1) and type IV collagen excretion in patients with type 2 diabetes and microalbuminuria, which may be partly contributory to its directly renoprotective role.


Assuntos
Albuminúria/urina , Colágeno Tipo IV/urina , Diabetes Mellitus Tipo 2/urina , Hipoglicemiantes/uso terapêutico , Peptídeos/uso terapêutico , Fator de Crescimento Transformador beta1/urina , Peçonhas/uso terapêutico , Adulto , Idoso , Albuminúria/tratamento farmacológico , Albuminúria/epidemiologia , Biomarcadores/urina , Colágeno Tipo IV/antagonistas & inibidores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Exenatida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta1/antagonistas & inibidores
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA