Spironolactone inhibits apoptosis in rat mesangial cells under hyperglycaemic conditions via the Wnt signalling pathway

Mesangial cells (MCs) play a crucial role in maintaining structure and function of glomerular tufts, providing structural support for capillary loops and modulating glomerular filtration by their contractility. MCs apoptosis occurs in experimental diabetic nephropathy, and this correlates with worsening albuminuria. Accumulating evidence suggests that mineralocorticoid receptor (MR) blockade effectively reduces proteinuria in diabetic nephropathy; however, it is rarely known whether spironolactone (SPI), a nonspecific MR antagonist, inhibits apoptosis in MCs under hyperglycaemic conditions. The objectives of this study are to determine the relationship between SPI and apoptosis, and investigate the cell signalling pathway by which SPI inhibits apoptosis. Rat MCs were treated with 30 mM d-glucose and 10^?8, 10^?7 or 10^?6 M aldosterone (ALD) for 24 h. In some experiments, MCs were pretreated with 10^?7 M SPI or 10 mM LiCl for 1 h. Apoptosis was evaluated by cell nucleus staining and flow cytometric analyses, and caspase-3 activity was assayed. Gene and protein expression were quantified using quantitative real-time PCR and Western blotting, respectively. SPI directly inhibited high glucose and ALD-induced MCs apoptosis in a caspase-dependent manner. Importantly, SPI inhibited MCs apoptosis via the Wnt signalling pathway. SPI promoted activation of the Wnt signalling pathway in MCs, leading to upregulation of Wnt4 and Wnt5a mRNA expression, decreased GSK-3β protein expression and increased β-catenin protein expression. As a conclusion, this study suggests that SPI may inhibit apoptosis in MCs during hyperglycaemic conditions via the Wnt signalling pathway. Blockade of the ALD system may represent a novel therapeutic strategy to prevent MCs injury under hyperglycaemic conditions.     

Hypobaria and hypoxia affects phytochemical production, gas exchange, and growth of lettuce

Hypobaria (low total atmospheric pressure) is essential in sustainable, energy-efficient plant production systems for long-term space exploration and human habitation on the Moon and Mars. There are also critical engineering, safety, and materials handling advantages of growing plants under hypobaria, including reduced atmospheric leakage from extraterrestrial base environments. The potential for producing crops under hypobaria and manipulating hypoxia (low oxygen stress) to increase health-promoting bioactive compounds is not well characterized. Here we showed that hypobaric-grown lettuce plants (25 kPa ≈ 25% of normal pressure) exposed to hypoxia (6 kPa pO₂ ≈ 29% of normal pO₂) during the final 3 d of the production cycle had enhanced antioxidant activity, increased synthesis of anthocyananins, phenolics, and carotenoids without reduction of photosynthesis or plant biomass. Net photosynthetic rate (P _N) was not affected by total pressure. However, 10 d of hypoxia reduced P _N, dark respiration rate (R _D), P _N/R _D ratio, and plant biomass. Growing plants under hypobaria and manipulating hypoxia during crop production to enhance health-promoting bioactive compounds is important for the health and well-being of astronauts exposed to space radiation and other stresses during long-term habitation.     

Molecular character of a phosphatase 2C (PP2C) gene relation to stress tolerance in Arabidopsis thaliana

Protein phosphatases type 2C (PP2Cs) from group A, which includes the ABI1/HAB1 and PP2CA branches, are key negative regulators of ABA signaling. HAI-1 gene had been shown to affect both seed and vegetative responses to ABA, which is one of PP2Cs clade A in Arabidopsis thaliana. Transgenic plants containing pHAI-1::GUS (β-glucuronidase) displayed GUS activity existing in the vascular system of leave veins, stems and petioles. Green fluorescent protein fused HAI-1 (HAI-1-GFP) was found in the nucleus through transient transformation assays with onion epidermal cells. The water-loss assays indicated the loss-of-function mutants did not show symptoms of wilting and they had still turgid green rosette leaves. The assays of seed germination by exogenous ABA and NaCl manifested that the loss-of-function mutants displayed higher insensitivity than wild-type plants. Taken together, the final results suggest that the HAI-1 (AT5G59220) encoded a nuclear protein and it can be highly induced by ABA and wound in Arabidposis, the stress-tolerance phenotype showed a slightly improvement when HAI-1 gene was disrupted.     

Expression level of histone deacetylase 2 correlates with occurring of chronic obstructive pulmonary diseases

Chronic obstructive pulmonary disease (COPD) is associated with chronic severe airway inflammation and causes increasing global health problems. New biological markers for COPD prediction and prognosis are urgently necessary. Previous studies indicate that histone deacetylases (HDACs) play essential roles in COPD. This study is to investigate if HDAC2 levels can be used as a promising, easily detected biomarker of COPD. In this paper, 49 COPD patients were enrolled and 42 healthy individuals (smokers or non-smokers) were used as healthy controls. Human bronchial epithelial cells derived from non-smokers, smokers, or COPD patients were grown in primary cultures. Total proteins were harvested from lung tissues or bronchial epithelial cells and then subjected to immunoblot analyses of HDAC2, HDAC3, and HDAC5. Quantitative RT-PCR analysis of HDAC2, HDAC3, and HDAC5 mRNA levels in tissues or cells were also preformed. We found that among the three HDAC proteins, the mRNA and protein levels of HDAC2, but not HDAC3 and HDAC5, in the tissues or cultured cells from patients have a significant correlation with development and prognosis of COPD. These results suggested that HDAC2 levels may serve as a promising, easily detected biomarker of COPD.     

The hMLH1 promoter polymorphisms and cancer susceptibility in Asian populations: A meta-analysis

Background

A variety of studies have evaluated the associations between polymorphisms in the promoter regions of the hMLH1 and cancer risk. However, the results remain inconclusive. To better understand the roles of the hMLH1 polymorphisms and cancer risk, we conducted a comprehensive meta-analysis to investigate the association between the hMLH1 − 93G/A and 1151T/A (Val384Asp) polymorphisms and cancer risk in Asian population.

Methods

We performed a meta-analysis by conducting searches of the published studies in Pub Med, CNKI, CBM, ISI web of knowledge and Google scholar search databases. Finally, 12 studies were included into our meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between hMLH1 polymorphisms and cancer risk. Statistical analysis was performed with Review Manager 5.0.

Results

Twelve studies addressing two hMLH1 polymorphisms were analyzed among a total of 4128 cancer cases and 4678 controls. For hMLH1 − 93G/A, there was no evidence that the hMLH1 − 93G/A polymorphism was significantly associated with an increased cancer risk (P > 0.05) in Asian populations (heterozygote comparison: OR = 0.89 [95% CI (0.75, 1.060)] P = 0.20; dominant model comparison: OR = 0.98 [95% CI (0.83, 1.15)] P = 0.79). In subgroup analysis based on cancer types and the sources of control, no associations were found in colorectal cancer, gastric cancer and “other cancers” under the any gene model except for lung cancer (recessive model comparison: OR = 1.69 [95% CI (1.30, 2.19)] P < 0.0001). For hMLH1 1151T/A, the polymorphism significantly associated with an increased cancer risk in Asians: OR = 1.88 [95% CI (1.49, 2.25)], P < 0.0001, and OR = 1.87 [95% CI (1.49, 2.25)], P < 0.0001.

Conclusions

Our investigations demonstrated that the hMLH1 − 93G/A polymorphism is not a candidate for susceptibility to overall cancers, and that the hMLH1 1151T/A polymorphism is significantly associated with higher cancer risk in Asian populations. Further studies with large sample size for hMLH1 should be conducted.     

Antifouling substances of natural origin: Activity of benzoquinone compounds from Maesa Lanceolata against marine crustaceans

A screening of antifouling activity from plants extracts led to selection and further study of Maesa lanceolata Forssk. Two p‐benzoquinone compounds were isolated from the fruits and found to be active against Artemia salina. The anti‐crustacean activity of both p‐benzoquinones is reported for the first time.     

Dissipative particle dynamics simulation on the meso-scale structure of diblock copolymer under cylindrical confinement

The meso-scale structure of symmetric diblock copolymer under cylindrical confinement is studied by dissipative particle dynamics (DPD). The simulation results show that coiled cylindrical geometry is favored in the presence of larger cylinder radius (R/L ₀>～1.5), and the number of rings depends on the cylinder radius. Because of the cylinder wall's selectivity, each block can form the central core, but only the preferential block forms the outmost layer. An approximately linear relationship exists between structure transition point, which is approximately in proportion to the 3/5 exponential of chain length of copolymer and number of layers. As the cylinder radius is decreased, a helical morphology is found. Lamellae parallel to the underside of the cylinder appear when the cylinder radius is made smaller (R/L ₀ < ～1.1).