A novel GJA5 variant associated with increased risk of essential hypertension.

OBJECTIVES: Gap junction protein alpha 5 (GJA5), also termed connexin 40 (Cx40), exerts a pivotal role in the mediation of vascular wall tone and two closely-linked polymorphisms in the GJA5 promoter (-44G>A and +71A>G) have been associated with enhanced susceptibility to essential hypertension (EH) in men. The present investigation aimed to ascertain whether a novel common polymorphism within the upstream regulatory region of GJA5 (transcript 1B), -26A>G (rs10465885), confers an increased risk of EH. METHODS: For this investigation, 380 unrelated patients with EH and 396 unrelated normotensive individuals employed as control persons were enrolled from the Chinese Han-ethnicity population, and their GJA5 genotypes and plasma renin concentrations were determined by Sanger sequencing and an automated chemiluminescent immunoassay, respectively. The functional effect of the GJA5 variant was explored in cultured murine cardiomyocytes by dual-light reporter gene analysis. RESULTS: The GJA5 variant conferred a significantly increased risk for EH (OR: 2.156; 95% CL: 1.661-2.797, P < 0.0001), and significantly increased plasma renin levels were measured in patients with EH in comparison with control individuals (46.3±7.2 vs 37.4±6.9, P < 0.0001). A promoter-luciferase analysis revealed significantly diminished activity of the promoter harboring the minor allele for this variation in comparison with its wild-type counterpart (165.67±16.85 vs 61.53±8.67, P = 0.0007). CONCLUSIONS: These findings indicate that the novel variant upstream of the GJA5 gene (-26A>G) confers a significantly increased vulnerability of EH in humans, suggesting potential clinical implications for precisive prophylaxis and treatment of EH.

Characterization of diketopiperazine heterodimers as potential chemical markers for discrimination of two dominant black aspergilli, Aspergillus niger and Aspergillus tubingensis.

Black aspergilli are distributed worldwide and represent one of the most prolific sources of metabolites with biomedical and agrochemical interests. However, due to their similar morphological characteristics and insufficient molecular identification, the taxonomic classification of black aspergilli remains ill-defined. The production of specialised metabolites is often unique for species among black aspergilli and could be used as diagnostic chemical markers for species identification. In this study, chemical investigation of Aspergillus tubingensis OUCMBIII 143291 led to the discovery of the diagnostic chemical marker asperazine, a complex diketopiperazine heterodimer, as well as two previously undescribed analogues, asperazine B and C. In addition, an undescribed 2-benzylpyridin-4(1H)-one-containing amide, pestalamide D, along with four known related metabolites were isolated. Their chemical structures, including their absolute configurations, were established on the basis of comprehensive spectral analysis and chiral HPLC analysis of the acidic hydrolysates. Asperazines B and C can serve as potential chemical markers for distinguishing A. tubingensis from A. niger, two representative species of black aspergilli that are usually incorrectly identified. Moreover, the isolated compounds were evaluated for their antifungal activity against eight phytopathogenic fungi including Alternaria alternata, A. brassicae, Botrytis cinerea, Colletotrichum lagenarium, Fusarium oxysporum, Gaeumannomyces graminis, Penicillium digitatum, and Valsa mali. Pestalamide D exhibited significant activities against B. cinerea, C. lagenarium, and V. mali, with MIC values of 4, 8, and 8 µg/mL, respectively, compared with the positive controls carbendazim (MICs = 8, 4, and 4 µg/mL) and prochloraz (MICs = 8, 8, and 4 µg/mL). The results of this study reveal two additional chemical markers and provide a powerful tool for the rapid identification of black aspergilli.

Prenylated Diphenyl Ethers from the Marine Algal-Derived Endophytic Fungus Aspergillus tennesseensis.

Considerable attention has been paid to marine derived endophytic fungi, owing to their capacity to produce novel secondary metabolites with potent bioactivities. In this study, two new compounds with a prenylated diphenyl ether structure-diorcinol L (1) and (R)-diorcinol B (2)-were isolated from the marine algal-derived endophytic fungus Aspergillus tennesseensis, along with seven known compounds: (S)-diorcinol B (3), 9-acetyldiorcinol B (4), diorcinol C (5), diorcinol D (6), diorcinol E (7), diorcinol J (8), and a dihydrobenzofuran derivative 9. Their structures were elucidated by extensive NMR spectroscopy studies. Compound 2 represents the first example of an R-configuration in the prenylated moiety. All these isolated compounds were examined for antimicrobial and cytotoxic activities. Compounds 1⁻9 exhibited antimicrobial activities against some human- and plant-pathogenic microbes with MIC values ranging from 2 to 64 µg/mL. Moreover, compound 9 displayed considerable inhibitory activity against the THP-1 cell line in vitro, with an IC50 value of 7.0 µg/mL.

[Effects of megsin gene transfection on the expressions of MCP-1 and ICAM-1 in mouse glomerular mesangial cells].

AIM: To observe the effects of megsin gene transfection on the expressions of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1(ICAM-1). METHODS: Mouse glomerular mesangial cells were cultured in high glucose medium, and then cell proliferation was measured by MTT assay at 12, 24 and 48 h respectively. The expressions of megsin, MCP-1 and ICAM-1 in mesangial cells were detected by immunocytochemical staining and Western blotting. The concentration of type IV collagen in the culture supernatant of mesangial cells was measured by ELISA. RESULTS: Under high glucose concentration, the expressions of megsin, MCP-1 and ICAM-1 increased; the concentration of type IV collagen in the cell supernatant was elevated as well; and mesangial cell proliferation was enhanced. After megsin gene transfection, the above changes were more significant, but were abated following megsin shRNA/transfection. CONCLUSION: Megsin gene can up-regulate the expressions of MCP-1 and ICAM-1, promote mesangial cell proliferation and mesangial extracellular matrix accumulation.