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Here we explored the impact of hydrogen sulfide (H2S) on biophysical properties of the primary human airway smooth muscle (ASM)–the end effector of acute airway narrowing in asthma. Using magnetic twisting cytometry (MTC), we measured dynamic changes in the stiffness of isolated ASM, at the single-cell level, in response to varying doses of GYY4137 (1–10 mM). GYY4137 slowly released appreciable levels of H2S in the range of 10–275 μM, and H2S released was long lived. In isolated human ASM cells, GYY4137 acutely decreased stiffness (i.e. an indicator of the single-cell relaxation) in a dose-dependent fashion, and stiffness decreases were sustained in culture for 24 h. Human ASM cells showed protein expressions of cystathionine-γ-lyase (CSE; a H2S synthesizing enzyme) and ATP-sensitive potassium (KATP) channels. The KATP channel opener pinacidil effectively relaxed isolated ASM cells. In addition, pinacidil-induced ASM relaxation was completely inhibited by the treatment of cells with the KATP channel blocker glibenclamide. Glibenclamide also markedly attenuated GYY4137-mediated relaxation of isolated human ASM cells. Taken together, our findings demonstrate that H2S causes the relaxation of human ASM and implicate as well the role for sarcolemmal KATP channels. Finally, given that ASM cells express intrinsic enzymatic machinery of generating H2S, we suggest thereby this class of gasotransmitter can be further exploited for potential therapy against obstructive lung disease.  相似文献   
3.
Polyomavirus BK (BKV) infection is an important cause of renal allograft failure. Viral microRNAs are known to play a crucial role in viral replication. This study investigated the expression of BKV-encoded microRNAs (miR-B1) in patients with polyomavirus-associated nephropathy (PVAN) and their role in viral replication. Following BKV infection in renal proximal tubular cells, the 3p and 5p miR-B1 levels were significantly increased. Cells transfected with the vector containing the miR-B1 precursor (the miR-B1 vector) showed a significant increase in expression of 3p and 5p miR-B1 and decrease in luciferase activity of a reporter containing the 3p and 5p miR-B1 binding sites, compared to cells transfected with the miR-B1-mutated vector. Transfection of the miR-B1 expression vector or the 3p and 5p miR-B1 oligonucleotides inhibited expression of TAg. TAg-enhanced promoter activity and BKV replication were inhibited by miR-B1. In contrast, inhibition of miR-B1 expression by addition of miR-B1 antagomirs or silencing of Dicer upregulated the expression of TAg and VP1 proteins in BKV-infected cells. Importantly, patients with PVAN had significantly higher levels of 3p and 5p miR-B1 compared to renal transplant patients without PVAN. In conclusion, we demonstrated that (1) miR-B1 expression was upregulated during BKV infection and (2) miR-B1 suppressed TAg-mediated autoregulation of BKV replication. Use of miR-B1 can be evaluated as a potential treatment strategy against BKV infection.  相似文献   
4.
Interleukin-33 is a newly described member of the interleukin-1 family. Recent research suggests that IL-33 is increased in lungs and plays a critical role in chronic airway inflammation in cigarette smoke-induced chronic obstructive pulmonary disease (COPD) mice. To determine the role of IL-33 in systemic inflammation, we induced COPD mice models by passive cigarette smoking and identified the IL-33 expression in bronchial endothelial cells and peripheral blood mononuclear cells (PBMCs) of them. After isolation, PBMCs were cultured and stimulated in vitro. We measured expressions of interleukin-6 and interleukin-8 in PBMCs in different groups. The expression of IL-33 in bronchial endothelial cells and PBMCs of COPD mice were highly expressed. Stimulated by cigarette smoke extract (CSE), the expression of IL-6 and IL-8 were induced and enhanced by IL-33. PBMCs of COPD mice produced more IL-6 and IL-8 stimulated by CSE and IL-33. Expression of IL-6 and IL-8 were decreased when stimulated by IL-33 together with soluble ST2. The mRNA production of ST2 in IL-33 stimulated PBMCs was increased. Being pretreated with several kinds of MAPK inhibitors, the secretions of IL-6 and IL-8 in PBMCs did not decrease except for the p38 MAPK inhibitor. We found that IL-33 could induce and enhance the expression of IL-6 and IL-8 in PBMCs of COPD mice via p38 MAPK pathway, and it is a promoter of the IL-6 and IL-8 production in systemic inflammation in COPD mice.  相似文献   
5.
A Gram-stain negative, motile, rod-shaped bacterium, designated strain WM-2T, was isolated from a forest soil in Sihui City, South China, and characterized by means of a polyphasic approach. Growth occurred with 0–5 % (w/v) NaCl (optimum 0–1 %) and at pH 5.0–10.5 (optimum pH 8.5) and 4–40 °C (optimum 30 °C) in Luria–Bertani medium. Comparative 16S rRNA gene sequence analyses showed that strain WM-2T is a member of the genus Pseudomonas and most closely related to P. guguanensis, P. oleovorans subsp. lubricantis, P. toyotomiensis, P. alcaliphila and P. mendocina with 97.1–96.6 % sequence similarities. In terms of gyrB and rpoB gene sequences, strain WM-2T showed the highest similarity with the type strains of the species P. toyotomiensis and P. alcaliphila. The DNA–DNA relatedness values of strain WM-2T with P. guguanensis and P. oleovorans subsp. lubricantis was 48.7 and 37.2 %, respectively. Chemotaxonomic characteristics (the main ubiquinone Q-9, major fatty acids C18:1 ω7c/C18:1 ω6c, C16:0 and C16:1 ω7c/C16:1 ω6c and DNA G+C content 65.2 ± 0.7 mol%) were similar to those of members of the genus Pseudomonas. Polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unknown aminophospholipid, an unknown phospholipid and five unknown lipids. According to the results of polyphasic analyses, strain WM-2T represents a novel species in the genus Pseudomonas, for which the name Pseudomonas sihuiensis sp. nov. is proposed. The type strain is WM-2T (=KCTC 32246T=CGMCC 1.12407T).  相似文献   
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7.
Reactive oxygen species (ROS) including hydrogen peroxide (H2O2) exhibit both pro-survival and pro-death signaling in leukemic cells. We examined the effect of exogenous H2O2 on Fas ligand (FasL) -induced apoptosis in Jurkat cells. H2O2 applied prior to (pre-conditioning) and during (post-conditioning) FasL stimulation attenuated early apoptosis through activation of EKR5. H2O2 increased the activated caspase-8 sequestered in the mitochondria thereby decreasing cell death through the extrinsic apoptotic pathway. In addition, inhibition of a protein tyrosine phosphatase likely explains the post-conditioning requirement for H2O2. Given that chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia are thought to work partly through production of ROS, a simultaneous inhibition of the ERK5 pathway may abrogate the ROS-initiated pro-survival signaling for an enhanced cell kill.  相似文献   
8.

Purpose

Congenital heart diseases (CHD) are among the most common birth defects in China. Environmental causes and folate metabolism changes may alter susceptibility to CHD. The aim of this study is to evaluate the relevant risk-factors of children with CHD and their mothers.

Methods

138 children with CHD and 207 normal children for controls were recruited. Their mothers were also enlisted in this study and interviewed following a questionnaire about their pregnant history and early pregnancy situation. Five single nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS) and cystathionine β-synthase (CBS) of mothers and children were genotyped.

Results

There were significant differences in the gender of children, occupation of mothers, family history with CHD, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHD group and control group ( P < 0.05). Logistic regression analyses showed that after adjustment for above factors, MTHFR rs1801131 were significantly associated with their offspring CHD risk in mothers. Compared with the mothers whose MTHFR were rs1801131 AA and AC genotypes, the mothers who got a mutation of MTHFR rs1801131 CC genotypes had a 267% increase in risk of given birth of a CHD children (OR=3.67,95%CI=1.12-12.05). Meanwhile, MTHFR rs1801131 were significantly associated with CHD susceptibility in children (OR = 1.42, 95% CI = 1.00-2.44 in additive model).

Conclusions

Besides mothers’ social and fertility characteristics, our results suggested that the genetic variants in folate metabolism pathway might be one of the most related risk-factors of CHD. MTHFR rs1801131 were identified as loci in Chinese population that were involved in CHD.  相似文献   
9.

Purpose

To investigate the predictors and treatment of the 6-Fr Perclose Proglide-related complications (PRC) in percutaneous endovascular aortic repair (pEVAR).

Methods

We retrospectively analyzed the PRC after pEVAR for the treatment of aortic aneurysm or dissection in our center from December 2012 to November 2013. Procedure success was defined as effective functioning of the two devices and local hemostasis. Access-related adverse events included vascular complications and device failures. Operative data and angiographic and computed tomography images were collected to assess the complications and treatment strategy.

Results

A total of 198 patients with 275 puncture sites underwent pEVAR with the 6-Fr Perclose Proglide. The procedure was successful in 178 patients (89.9%), whereas PRC occurred in 20 cases (10.1%), including 10 device failures and 10 vascular complications. An extra manual ancillary compression was conducted in 7 patients, one more device was used in 8 patients, and surgical repair of the femoral artery was performed in 5 patients. PRC had a tendency to occur in patients with body mass index (BMI)>30 kg/m2 (p = 0.021), thoracic stent grafts (p = 0.038), common femoral artery (CFA) calcification (p = 0.001), CFA depth>4 cm (p = 0.001), and sheath size>20Fr (p = 0.005). Device failure-related mortality was zero. None of the access sites had complications during the midterm follow-up.

Conclusions

The pre-close technique with 6-Fr Perclose Proglide devices for pEVAR appears to be safe and effective with low technical failure and complication rates. Careful patient selection and proficiency in device manipulation might reduce the device related complications.  相似文献   
10.
Because of its strong pollutant degradation ability, nanoscale zerovalent iron (NZVI) has been introduced to soils and groundwater for remediation purposes, but its impacts on plants are still not very clear. In this work, the effects of low concentration (10–320 μmol/L) NZVI particles on seed germination and growth of peanut plants were evaluated. The exposure of peanut seeds to NZVI at all the tested concentrations altered the seed germination activity, especially the development of seedlings. In comparison with the deionized water treated controls (CK), all of the NZVI treatments had significantly larger average lengths. Further investigations with transmission electron microscopy (TEM) and thermogravimetric analysis (TGA) suggested that NZVI particles may penetrate the peanut seed coats to increase the water uptake to stimulate seed germination. The growth experiments showed that although NZVI at a relatively high concentration (320μmol/L) showed phytotoxicity to the peanut plants, the lower concentrations of NZVI particles stimulated the growth and root development of the plants. At certain concentrations (e.g., 40 and 80 μmol/L), the NZVI treated samples were even better than the ethylenediaminetetraacetate-iron (EDTA-Fe) solution, a commonly used iron nutrient solution, in stimulating the plant growth. This positive effect was probably due to the uptake of NZVI by the plants, as indicated in the TEM analyses. Because low concentrations of NZVI particles stimulated both the seedling development and growth of peanut, they might be used to benefit the growth of peanuts in large-scale agricultural settings.  相似文献   
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