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Objective:To explore the protective effect and mechanism of scutellarin (Scu) on sepsis associated-acute kidney injury (SA-AKI).Methods:① In vivo experiment: 36 male C57BL/6 mice were divided into normal saline (NS) control group, lipopolysaccharide (LPS) induced SA-AKI model group (LPS group), 20 mg/kg Scu control group (Scu 20 control group), and 5, 10, 20 mg/kg Scu pretreatment groups by random number table with 6 mice in each group. The SA-AKI model was reproduced by intraperitoneal injection of 10 mg/kg LPS. The NS control group was injected with NS intraperitoneally. The Scu pretreatment groups were intraperitoneally injected with different doses of Scu every day before LPS injection for 1 week. Scu 20 control group was injected with 20 mg/kg Scu for 1 week. After 24 hours of LPS treatment, mice in each group were sacrificed, kidney tissues were collected, and kidney injury was detected by hematoxylin-eosin (HE) staining. Western blotting was used to detect the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway related molecules, apoptosis-related proteins and cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 (CCN1). ② In vitro experiment: human renal tubular epithelial cell line HK-2 was cultured in vitro and used for experiment when the cells fused to 80%. In the cells without LPS treatment and after 100 g/L LPS treatment, pcDNA3.1-CCN1 and small interfering RNA (siRNA) CCN1 sequence were transfected to overexpress and inhibit CCN1 expression, respectively, to observe whether CCN1 was involved in NF-κB signaling pathway activation and apoptosis. In addition, 100g/L LPS and 20 μmol/L Scu were added into HK-2 cells transfected with and without CCN1 siRNA to investigate the mechanism of protective effect of Scu on LPS-induced HK-2 cells injury. Results:① The results of in vivo experiment: the renal function of SA-AKI mice induced by LPS was significantly decreased, and had kidney histological damage and severely damaged renal tubules. Scu could alleviate renal function and histological damage in a dose-dependent manner. Western blotting results showed Scu could reduce the protein expression of NF-κB signaling pathway related molecules and CCN1 in the renal tissue, and had a significant alleviating effect on apoptosis, indicating that CCN1 was involved in NF-κB signaling pathway activation and apoptosis. ② The results of in vitro experiment: in HK-2 cells not treated with LPS, CCN1 overexpression had no effect on apoptosis related protein and pro-inflammatory factors of NF-κB signaling pathway. In HK-2 cells treated with LPS, overexpression of CCN1 significantly inhibited the mRNA expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), with significant differences as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 3.20±0.57 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 2.99±0.44 vs. 5.00±0.81, MCP-1 mRNA (2 -ΔΔCT): 2.81±0.50 vs. 5.41±0.75, all P < 0.05], and the apoptosis-related protein was significantly down-regulated. However, when siRNA was used to inhibit the expression of CCN1, the mRNA expressions of pro-inflammatory factors were significantly increased as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 6.01±1.13 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 5.15±0.86 vs. 5.00±0.81, all P < 0.05], and apoptosis-related protein was significantly up-regulated. In the LPS-induced HK-2 cells, the mRNA expressions of pro-inflammatory factors were significantly down-regulated after Scu treatment as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT) : 2.55±0.50 vs. 6.15±1.04, TNF-α mRNA (2 -ΔΔCT): 2.58±0.40 vs. 3.95±0.52, MCP-1 mRNA (2 -ΔΔCT): 2.64±0.44 vs. 6.21±0.96, all P < 0.05], and apoptosis-related protein was also significantly reduced. When the expression of CCN1 was inhibited by siRNA, the protective effect of Scu on cells was weakened, which showed that the mRNA expressions of pro-inflammatory factors in cells was significantly up-regulated compared with the cells without inhibition of CCN1 expression [IL-1β mRNA (2 -ΔΔCT): 5.34±0.76 vs. 2.55±0.50, TNF-α mRNA (2 -ΔΔCT): 3.66±0.54 vs. 2.58±0.40, MCP-1 mRNA (2 -ΔΔCT): 5.15±0.79 vs. 2.64±0.44, all P < 0.05], and the expression of apoptosis related protein was also significantly up-regulated. Conclusions:Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.
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Objective To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) at admission for mortality risk during hospitalization in patients with acute ischemic stroke (AIS). Methods Patients with AIS admitted to the Department of Neurology, the First Affiliated Hospital of China Medical University from January 2017 to December 2018 were enrolled retrospectively. The demographic data and all baseline clinical data were collected, and compared between the in-hospital death group and survival group. Multivariate logistic regression analysis was used to determine independent influencing factors for in-hospital death in patients with AIS. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of NLR for death during hospitalization. Results A total of 266 patients with AIS were enrolled, with an average age of 65 years, 168 were males (63.2% ), 98 were females (36.8% ), 52 died in hospital (19.5% ), and 214 (80.5% ) survived. The NLR of the death group was significantly higher than that of the survival group (median [ interquartile range]: 7.6 [4.6-14.0] vs. 2.4 [1.8-4.0]; Z=7.727, P<0.001). Multivariate logistic regression analysis showed that advanced age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.14; P=0.009), previous history of stroke or transient ischemic attack (OR 9.06, 95% CI 2.06-39.88; P=0.004), high NIHSS score (OR 1.13, 95% CI 1.04-1.24; P=0.004), and high NLR (OR 1.23, 95% CI 1.02-1.48; P=0.024) were the independent risk factors for death during hospitalization in patients with AIS. ROC curve analysis showed that the area under the curve of NLR predicting death during hospitalization for patients with AIS was 0.846 (95% CI 0.786-0.905; P<0.001). When the cut-off value of NLR was 4.52, the sensitivity and specificity were 76.9% and 80.8% respectively. The positive predictive value was 49.4% , and the negative predictive value was 93.5% . Conclusions The increased NLR level at admission had certain predictive value for the death of patients with AIS during hospitalization.
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OBJECTIVE: To study the association between superior mesenteric artery hemodynamic indexes and scores of lower gastrointestinal symptoms rating scales(LGSRS) in patients with type 2 diabetic mellitus. METHODS: Totally 142 inpatients with type 2 diabetes with average age of 58.76±12.32 yrs were enrolled, who were treated from August 2016 to March 2018. The history, gender, age,course and BMI were recorded, and fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), 2-hour postprandial blood glucose(PBG), total cholesterol(TC), triglyceride(TG), urine ACR and LGSRS were determined. Ultrasonic scanning of mesenteric artery was performed for hemodynamic indexes, including artery inner diameter(ID), peak systolic velocity(PSV), end-diastolic velocity(EDV), and resistance index(RI)at starting part,first level branch, and second level branch from root of the superior mesenteric artery(SMA).Patients were divided into 2 groups according to their LGSRS, 74 patients with LGSRS≥6 were in positive group, and 68 patients with LGSRS0.05), but the age and DD were significantly higher in positive group than in control group(P0.05). 3. There were no significant difference between positive group and control group in ID at starting part and first level branch of SMA, while ID at second level branch was significantly increased in positive group compared with control group [(3.83±0.85)mm vs.(3.53±0.90)mm, P<0.05)].4. RI at first(0.816±0.059 vs 0.842±0.063,P<0.05) and second level branch(0.813±0.076 vs 0.845±0.073, P<0.05) and PSV at first level branch[(110.89±46.89)cm/s vs(95.72±36.59)cm/s,P<0.05] were significantly high in positive group; there were no difference in other hemodynamic indexes between the groups. 5.Adjusted by age,DD,glycemic and lipidemic profile,Logistic regression showed that ID at first(RR=2.092,95%CI 1.080-4.050,P=0.029) and second level branch(RR=0.491,95%CI 0.252-0.955,P=0.36) and EDV at second level branch(RR=0.897,95%CI 0.824-0.976,P=0.012) were independent factors influencing LGSRS(P<0.05). CONCLUSION: Ultrosonic hemodynamic abnormalities in the superior mesenteric artery might be important factor in development of lower gastrointestinal tract symptoms in patients with type 2 diabetes.
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Transcription factor EB(TFEB)is a member of the MiTF/TFE family and plays an important role in cell stress,metabolism,cancer and so on.There are relatively few studies on the role of TFEB in renal diseases.TFEB was initially found to be highly expressed in TFEB-fusion renal cell carcinoma and plays a key role in the development of re-nal cell carcinoma.Blocking the downstream signaling pathway activated by TFEB would be a promising treatment for TFEB-fusion renal cell carcinoma.On the contrary,the expression of TFEB in renal intrinsic cells is decreased in diabetic kidney disease,leading to a blockage in the autophagy-lysosome pathway.TFEB enhances the ability of cell stress and self-repair,and then delays the progress of diabetic kidney disease.In cystine nephropathy,TFEB expression is reduced in re-nal tubular epithelial cells and compensatory activation is insufficient as well.TFEB over-expression effectively eliminates intracellular cystine and repairs damaged lysosome,which is expected to alleviate or cure the Fanconi syndrome.In summa-ry,TFEB plays a key role in different kidney diseases,and targeted regulation of TFEB provides new hope for the treatment of kidney diseases.
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Objective To measure the serum levels of vitamin D,total immunoglobulin E (tIgE),interleukin-4 (IL-4) and IL-6 in patients with atopic dermatitis (AD),to evaluate the association between vitamin D and severity of AD,and to investigate the role of vitamin D in inflammatory and immunoregulatory processes during the occurrence of AD.Methods Peripheral blood samples were collected from 37 patients with AD (AD group) and 30 healthy controls (control group).The serum levels of vitamin D,tIgE,and IL-6 were measured by chemiluminescent sandwich enzyme immunoassay,and those of IL-4 by enzyme-linked immunosorbent assay.The severity of AD was assessed by the SCORing atopic dermatitis (SCORAD) score.The t test or Mann-Whitney U test was performed to assess the differences in vitamin D,tIgE,IL-4 and IL-6 levels between the AD group and control group,chi-square test to compare the proportion of patients with vitamin D deficiency,insufficiency and sufficiency,and Pearson's correlation analysis or Spearman's correlation analysis to evaluate the correlations between the SCORAD score and serum levels of vitamin D,tIgE,IL-4 and IL-6.Results Compared with the control group,the AD group showed significantly decreased serum levels of vitamin D (24.77 ± 9.29 vs.28.98 ± 6.87 μg/L,t =2.015,P =0.048),but significantly increased serum levels of tIgE (137.68 [37.59-414.53] vs.45.16 [14.56-112.12] IU/ml,Z =-3.399,P =0.001),IL-4 (8.86 ± 4.83 vs.4.78 ± 3.07 ng/L,t =4.147,P ＜ 0.001) and IL-6 (6.53 [3.99-15.30] vs.4.58[2.85-8.17] ng/L,Z =-2.173,P =0.030).Among patients with AD,the SCORAD score was negatively correlated with serum levels of vitamin D (r =-0.505,P =0.001),positively correlated with those of tIgE (r =0.531,P =0.001) and IL-4 (r =0.519,P =0.001),but uncorrelated with those of IL-6 (r =-0.139,P =0.411).There were significant differences in the proportion of patients with vitamin D deficiency,insufficiency and sufficiency between the AD group and control group (x2 =8.762,P =0.013).AD patients with vitamin D deficiency showed significantly increased serum levels of tIgE (2846.87 [319.02-7300.00] IU/ml) and IL-4 ([16.37-2.05] ng/L) compared with those with vitamin D insufficiency (110.07 [26.20-501.48] IU/ml,P =0.045;[8.28 ± 4.48] ng/L,P =0.011) and those with vitamin D sufficiency (123.93 [91.61-273.68] IU/ml,P =0.024;[8.00 ± 4.63] ng/L,P =0.041).In addition,serum levels of IL-6 were also higher in patients with vitamin D deficiency than in those with vitamin D sufficiency (15.10 [8.49-30.72] vs.6.22 [4.47-9.47] ng/L,P =0.011].Conclusions Vitamin D deficiency or insufficiency exists in patients with AD.Vitamin D deficiency is correlated with high serum levels of tIgE,IL-4 and IL-6,and the severity of AD is closely correlated with increased serum levels of tIgE and IL-6 as well as decreased serum levels of vitamin D.
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The fruit of Pandanus tectorius (PTF) has a long history of use as a folk medicine to treat hyperlipidemia in Hainan province, South China. Our previous studies have shown that the n-butanol extract of PTF is rich in caffeoylquinic acids and has an adequate therapeutic effect on dyslipidemic animals induced by high-fat diet. In this work, seven caffeoylquinic acids isolated from PTF were screened for the lipid-lowering activity in HepG2 hepatoma cells. Oil-Red O staining, microscopy and intracellular triglyceride (TG) and total cholesterol (TC) quantification showed that 3-O-caffeoylquinic acid (3-CQA), 3, 5-di-O-caffeoylquinic acid (3,5-CQA), and 3,4,5-tri-O-caffeoylquinic acid (3,4,5-CQA) significantly inhibited lipid accumulation induced by oleic acid and decreased intracellular levels of TC and TG in a dose-dependent manner. These three caffeoylquinic acids showed no significant cytotoxicity at concentrations of 1 -50 μmol x L(-1) as determined by MTT assay. Realtime quantitative PCR revealed that 3-CQA and 3, 5-CQA significantly increased the expression of lipid oxidation-related genes PPARα, CPT-1 and ACOX1 while 3-CQA, 3, 5-CQA and 3,4,5-CQA decreased the expression of lipogenic genes SREBP-1c, SREBP-2, HMGR, ACC, FAS. Overall, 3-CQA, 3, 5-CQA and 3, 4, 5-CQA may be the principal hypolipidemic components in PTF which can decrease intracellular lipid accumulation through up-regulating the expression of lipid oxidative genes and down-regulating the expression of lipogenic genes.
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Humanos , Carcinoma Hepatocelular , Metabolismo , China , Colesterol , Metabolismo , Regulação da Expressão Gênica , Células Hep G2 , Metabolismo dos Lipídeos , Neoplasias Hepáticas , Metabolismo , Ácido Oleico , Pandanaceae , Química , Ácido Quínico , Química , Proteína de Ligação a Elemento Regulador de Esterol 1 , Triglicerídeos , MetabolismoRESUMO
The fruit of Pandanus tectorius (PTF) has a long history of use as a folk medicine to treat hyperlipidemia in Hainan province, South China. Our previous studies have shown that the n-butanol extract of PTF is rich in caffeoylquinic acids and has an adequate therapeutic effect on dyslipidemic animals induced by high-fat diet. In this work, seven caffeoylquinic acids isolated from PTF were screened for the lipid-lowering activity in HepG2 hepatoma cells. Oil-Red O staining, microscopy and intracellular triglyceride (TG) and total cholesterol (TC) quantification showed that 3-O-caffeoylquinic acid (3-CQA), 3, 5-di-O-caffeoylquinic acid (3,5-CQA), and 3,4,5-tri-O-caffeoylquinic acid (3,4,5-CQA) significantly inhibited lipid accumulation induced by oleic acid and decreased intracellular levels of TC and TG in a dose-dependent manner. These three caffeoylquinic acids showed no significant cytotoxicity at concentrations of 1 -50 μmol x L(-1) as determined by MTT assay. Realtime quantitative PCR revealed that 3-CQA and 3, 5-CQA significantly increased the expression of lipid oxidation-related genes PPARα, CPT-1 and ACOX1 while 3-CQA, 3, 5-CQA and 3,4,5-CQA decreased the expression of lipogenic genes SREBP-1c, SREBP-2, HMGR, ACC, FAS. Overall, 3-CQA, 3, 5-CQA and 3, 4, 5-CQA may be the principal hypolipidemic components in PTF which can decrease intracellular lipid accumulation through up-regulating the expression of lipid oxidative genes and down-regulating the expression of lipogenic genes.
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AMP-activated protein kinase (AMPK) is an energy sensor playing a key role in regulation of cellular metabolism. When activated by increased intracellular AMP/ATP ratio or by other factors, AMPK promotes the oxidation of fatty acid, increases energy production and improves glucose uptake and use. Meanwhile, it inhibits glycogen synthesis, gluconeogenesis and lipid synthesis, thus reducing energy consumption and keeping the balance of cell energy metabolism. There are many natural products with regulating lipid metabolism such as flavones, saponins, and alkaloids. Their mechanisms of regulating lipid metabolism are different. In recent years, many natural products with AMPK-activating activity have been identified. This paper reviews the research progress in the actions of natural products in regulating lipid metabolism through activation of AMPK.
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OBJECTIVE@#To study the influence of PD173074 on proliferation and apoptosis of nasopharyngeal carcinoma.@*METHOD@#With immunoblotting and RT-PCR, FGFR1 expression was detected in CNE, PONE1 and C666-1 cell lines. With MTT assay,the time-effect and dose-effect correlation between PD173074 and inhibition of CNE proliferation was evaluated. After PD173074 stimulation, the phosphorylation level of FGFR1 and AKT was detected with immunoblotting assay. Furthermore, influence of PD173074 on the activation of Caspase3 and Caspase9 was detected to study the underlying mechanism of why PD173074 could inhibit CNE proliferation.@*RESULT@#FGFR1 has the highest expression in CNE cell line. Under incubation of 10 nmol/L PD173074 stimulation for 36 hours to 72 hours, the phosphorylation of FGFR1 and AKT was impaired significantly, which further reduced the proliferation of CNE. Moreover, PD173074 can activate the intrinsic apoptotic pathway by stimulating Caspase9,which activated Caspase3 and induced the apoptosis.@*CONCLUSION@#PD173074 could inhibit proliferation of nasopharyngeal carcinoma cell through reducing the phosphorylation of FGFR1 and AKT. Additionally, PD173074 can induce CNE apoptosis by activating intrinsic apoptotic pathway via cleaving Caspase9 and Caspase3.
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Humanos , Antineoplásicos , Farmacologia , Apoptose , Carcinoma , Caspase 3 , Metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Tratamento Farmacológico , Patologia , Pirimidinas , FarmacologiaRESUMO
The efficacy and safety of uric-acid-lowering therapy (UALT) on slowing the progression of chronic kidney disease (CKD) accompanied by hyperuricemia were assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases up to November 15, 2012 for randomized controlled trials (RCTs) which compared the effect of UALT to control therapy in hyperuricemic patients secondary to CKD, and then performed quality evaluation and meta-analysis on the included studies. Seven RCTs involving 451 cases were included. UALT delayed the increase of serum creatinine (MD=-62.55 μmol/L, 95% CI: -98.10 to -26.99) and blood urea nitrogen (MD= -6.15 mmol/L, 95% CI: -8.17 to -4.13) as well as the decrease of glomerular filtration rate [MD=5.65 mL/(min·1.73 m2), 95% CI: 1.88 to 9.41], decreased systolic blood pressure (SBP) (MD= -6.08 mmHg, 95% CI: -11.67 to -0.49), and reduced the risk of the renal disease progression (RR=0.30, 95% CI: 0.19 to 0.46). However, there was no statistically significant difference in 24-h urinary protein quantity and diastolic blood pressure (P>0.05). We identified that UALT could delay the progression of CKD with secondary hyperuricemia. And this also indirectly proved that hyperuricemia was a risk factor for the CKD progression.
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Feminino , Humanos , Masculino , Pressão Sanguínea , Creatinina , Sangue , Progressão da Doença , Taxa de Filtração Glomerular , Hiperuricemia , Sangue , Terapêutica , PubMed , Insuficiência Renal Crônica , Sangue , Terapêutica , Fatores de Risco , Ureia , Sangue , Ácido Úrico , SangueRESUMO
Studying on marine natural products is a vibrant research area in the world. Due to their prevention and treatment effects on malignant tumor,cardiovascular disease and other major human diseases,marine natural products have become an important guidance to find the primary drugs. Recently,beneficial effects of marine natural products on treatment of metabolic syndrome related diseases have been intensively explored. Therefore,numbers of novel active products were found out and new mechanisms were revealed. This article reviews the research literature published after 2010 and summarizes the effects of marine natural products in metabolic syndrome related diseases,such as central obesity,insulin resistance,hyperlipidemia,hypertension and inflammation.
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The efficacy and safety of uric-acid-lowering therapy (UALT) on slowing the progression of chronic kidney disease (CKD) accompanied by hyperuricemia were assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases up to November 15, 2012 for randomized controlled trials (RCTs) which compared the effect of UALT to control therapy in hyperuricemic patients secondary to CKD, and then performed quality evaluation and meta-analysis on the included studies. Seven RCTs involving 451 cases were included. UALT delayed the increase of serum creatinine (MD=-62.55 μmol/L, 95% CI: -98.10 to -26.99) and blood urea nitrogen (MD= -6.15 mmol/L, 95% CI: -8.17 to -4.13) as well as the decrease of glomerular filtration rate [MD=5.65 mL/(min·1.73 m2), 95% CI: 1.88 to 9.41], decreased systolic blood pressure (SBP) (MD= -6.08 mmHg, 95% CI: -11.67 to -0.49), and reduced the risk of the renal disease progression (RR=0.30, 95% CI: 0.19 to 0.46). However, there was no statistically significant difference in 24-h urinary protein quantity and diastolic blood pressure (P>0.05). We identified that UALT could delay the progression of CKD with secondary hyperuricemia. And this also indirectly proved that hyperuricemia was a risk factor for the CKD progression.
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The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated. Medline, Embase, the Cochrane Library, some databases of clinical trial registries, grey literatures, other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved. RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected. Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration's RevMan 4.2 software package. The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs. control: RD=0.03, 95% CI=-0.13-0.18, Z=0.34, P=0.73; ARBs vs. control: RD=-0.02, 95% CI=-0.07-0.03, Z=0.75, P=0.45). However, there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs. control: WMD=0.10, 95% CI=0.06-0.15, Z=4.64, P<0.00001; ARBs vs. control: WMD=-0.24, 95% CI=-0.37-0.11, Z=3.58, P=0.0003). The use of ACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients, however the serum potassium could be increased with use of ACEIs in HD patients. Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Angiotensina , Usos Terapêuticos , Inibidores da Enzima Conversora de Angiotensina , Usos Terapêuticos , Hiperpotassemia , Diálise RenalRESUMO
Objective To study the immune regulation of Galectin-9 on the active CD4+T cells and demonstrate the mechanisms.Methods Lymphocytes were harvested from wild-type C57BL/6 mouse,from which na(i)ve CD4+T cells were separated via MACS and then stimulated with anti-CD3 antibody(Ab) (2.5 μg/ml),anti-CD28 Ab(5 μg/ml) and IL-2(100 ng/ml) for 3 days.The active CD4+T cells were divided into 3 groups:Control group,Galectin-9 group and Galectin-9+α-lactose group.We detected the cell proliferation level by CFSE fluorescence intensity and then dynamically observed the cell morphological changes.The proportion of CD4+CD69+T cell,Th1,Th2 and Th17 cell was valued; Meanwhile,ELISA was used to detect the cytokine levels of IFN-γ,IL-4,IL-10,IL-12,IL-17A and TGF-β1 secreted by lymphocytes.Also Western blot was used to observe the changes of T cell differentiation regulatory protein such as T-bet,GATA-3 and ROR-γt.Results Compared with control group and Galectin-9+α-lactose group,in Galectin-9 group,the cell morphology began to change at 2 h.Moreover the proportions of CD4+CD69+ T cell,Th1 and Th17 cells decreased (P＜0.05),but no significant differences in Th2 cells.The level of IFN-γ,IL-12,IL-17A and TGF-β1 from the supernatant decreased (P＜0.05),while Th2-type cytokines IL-4 and IL-1O did not change.In addition,the expressions of T-bet and ROR-γt were significantly down-regulated (P＜0.05).Conclusion Galectin-9 inhibited Th1 and Th17-type immune response,while had no effect on Th2-type immune response.The mechanism of the immune regulation may be related to affect the expression of Th1 and Th17 specific transcription factors at transcription level.
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The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated. Medline, Embase, the Cochrane Library, some databases of clinical trial registries, grey literatures, other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved. RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected. Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration's RevMan 4.2 software package. The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs. control: RD=0.03, 95% CI=-0.13-0.18, Z=0.34, P=0.73; ARBs vs. control: RD=-0.02, 95% CI=-0.07-0.03, Z=0.75, P=0.45). However, there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs. control: WMD=0.10, 95% CI=0.06-0.15, Z=4.64, P<0.00001; ARBs vs. control: WMD=-0.24, 95% CI=-0.37-0.11, Z=3.58, P=0.0003). The use of ACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients, however the serum potassium could be increased with use of ACEIs in HD patients. Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.
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Objective To investigate the relationship between subclinical cervical HPV infection and recurrence of condyloma acuminatum (CA) in patients. Methods Cervical swabs were collected from 52 patients with frequently recurrent CA, 55 patients with infrequently recurrent CA, and 65 normal human controls. The Cenechip method was performed to detect the presence and type of HPV in cervical swabs followed by a statistical analysis. Results HPV was found in 67.3% (35/52) of swabs from patients with frequently recurrent CA, 5% (19/55) from patients with infrequently recurrent CA, and 4.6% (3/65) in the controls. There was a statistical difference among the three groups in the detection rate of HPV. Conclusion The subclinical cervical HPV infection may contribute to the recurrence of CA.
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The echolocating big brown bats (Eptesicus fuscus) emit trains of frequency-modulated (FM) biosonar signals with duration, amplitude, repetition rate, and sweep structure changing systematically during interception of their prey. In the present study, the sound stimuli of temporally patterned pulse trains at three different pulse repetition rates (PRRs) were used to mimic the sounds received during search, approach, and terminal stages of echolocation. Electrophysiological method was adopted in recordings from the inferior colliculus (IC) of midbrain. By means of iontophoretic application of bicuculline, the effect of GABAergic inhibition on the intensity sensitivity of IC neurons responding to three different PRRs of 10, 30 and 90 pulses per second (pps) was examined. The rate-intensity functions (RIFs) were acquired. The dynamic range (DR) of RIFs was considered as a criterion of intensity sensitivity. Comparing the average DR of RIFs at different PRRs, we found that the intensity sensitivity of some neurons improved, but that of other neurons decayed when repetition rate of stimulus trains increased from 10 to 30 and 90 pps. During application of bicuculline, the number of impulses responding to the different pulse trains increased under all stimulating conditions, while the DR differences of RIFs at different PRRs were abolished. The results indicate that GABAergic inhibition was involved in modulating the intensity sensitivity of IC neurons responding to pulse trains at different PRRs. Before and during bicuculline application, the percentage of changes in responses was maximal in lower stimulus intensity near to the minimum threshold (MT), and decreased gradually with the increment of stimulus intensity. This observation suggests that GABAergic inhibition contributes more effectively to the intensity sensitivity of the IC neurons responding to pulse trains at lower sound level.
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Animais , Estimulação Acústica , Bicuculina , Farmacologia , Quirópteros , Ecolocação , Fenômenos Eletrofisiológicos , Antagonistas de Receptores de GABA-A , Farmacologia , Colículos Inferiores , Biologia Celular , Neurônios , Biologia CelularRESUMO
Temporal features of sound convey information vital for behaviors as diverse as speech recognition by human and echolocation by bats. However, auditory stimuli presented in temporal proximity might interfere with each other. Although much progress has been made in the description of this phenomenon from psychophysical studies, the neural mechanism responsible for its formation at central auditory structures especially at the inferior colliculus (IC), a midbrain auditory nucleus which practically receives massive bilateral projections from all the major auditory structures in the brainstem, remains unclear. This study was designed to investigate it in vivo by using electrophysiological recording from the inferior collicular neurons of the big brown bat, Eptesicus fuscus. In our results, the responses of 12 (38%, n= 31) neurons to the test sound (leading sound) were obviously inhibited by the masker (lagging sound). The inhibitory effects in these neurons were correlated with the inter-stimulus level difference (SLD) and the inter-stimulus onset asynchrony (SOA) interval. The strength of backward masking increased with the masker intensity increasing, the test sound intensity decreasing and the SOA interval shortening. There were no obvious effects of backward masking on the responses of many other neurons (52%, 16/31), and yet in a part of these neurons, the neural inhibition of responses to the test sound was observed at the special SLD and the special SOA intervals. Moreover, few of the 31 sampled IC neurons (10%, 3/31) displayed facilitating responses to the test sound at the special SLD and the special SOA intervals. These data demonstrate that a lot of IC neurons are involved in the generation of the backward masking of acoustical perception. It is conjectured that the temporal dynamic integration between the leading inhibitory inputs evoked by the masker sound and the excitatory inputs evoked by the test sound might play a key role in shaping the acoustical response characteristics of the IC neurons.
Assuntos
Animais , Masculino , Estimulação Acústica , Percepção Auditiva , Fisiologia , Quirópteros , Fisiologia , Ecolocação , Fisiologia , Potenciais Evocados Auditivos , Colículos Inferiores , Biologia Celular , Fisiologia , Neurônios , Fisiologia , Mascaramento Perceptivo , FisiologiaRESUMO
<p><b>AIM</b>To screen swimming-fatigue related genes in mice and lay theoretic basis for researching the molecular mechanism of fatigue.</p><p><b>METHODS</b>30 male BALB/c mice (20 +/- 2g) were divided into control group, dipping in water group and swimming-fatigue group respectively. After fatigue for swimming in swimming-fatigue group, with control group and dipping in water group, liver tissues in mice were collected. With improved silver staining mRNA differential display method, the differentially expressed genes in mice livers were screened and evaluated by reversed Northern blot. The positive segments were analyzed homology by BLAST.</p><p><b>RESULTS</b>7 of DD-ESTs were gained. Two of them only expressed in swimming-fatigue group, two down-regulated expressed, and three up-regulated. One of them was a novel gene and was accepted by GenBank, AY615302.</p><p><b>CONCLUSION</b>Seven DD-ESTs in swimming-fatigue mice were gained by silver staining mRNA differential display method.</p>
Assuntos
Animais , Masculino , Camundongos , Fadiga , Metabolismo , Perfilação da Expressão Gênica , Métodos , Fígado , Metabolismo , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Métodos , RNA Mensageiro , Genética , Coloração pela Prata , NataçãoRESUMO
Objective To observe the expressions of vascular endothelial growth factor(VEGF) and cyclooxygenase-2(COX-2) in the cerebral tissue following hypoxic-ischemic encephalopathy(HIE) in newborn rats and explore the machanism of inosine in protecting against hypoxic-ischemic brain damage(HIBD).Methods Sixty-six newborn rats aged 7 days were divided into sham,control and experimental groups.HIE models were made by clamping the right cervical artery and making hypoxia for 2 hours.The rats in experimental group began injecting inosine,at 1 day before experiment,and the rats in the sham and control groups saline solution with same dose.The samples were made at the given time,and expressions of VEGF and COX-2 were investigated by immunohistochemical technique.Results The cerebral tissue had no expression of VEGF and COX-2 in sham group.From 2 hours on cortex and striatum after HIE in control and experimental groups,expressions of VEGF and COX-2 increased rapidly,peaking at 12-24 hours,and then decreased gradually.Expressions of VEGF and COX-2 were higher in experimental group(All P