Glabridin Functions as a Quorum Sensing Inhibitor to Inhibit Biofilm Formation and Swarming Motility of Multidrug-Resistant Acinetobacter baumannii.

Objective: Acinetobacter baumannii is a hazardous bacterium that causes hospital-acquired nosocomial infections, and the advent of multidrug-resistant A. baumannii (MDR-AB) strains is concerning. Novel antibacterial therapeutic strategies must be developed. The biological effects of glabridin on MDR-AB were investigated in this study. Methods: The minimum inhibitory concentrations (MICs) of glabridin against eight clinical MDR-AB strains were determined using the broth microdilution technique. Crystal violet staining was used to assess biofilm development, which has significant contribution to bacterial resistance. Swarming motility was measured according to surface growth zone of MDR-AB on LB agar medium. qRT-PCR was used to evaluate the expression of quorum sensing genes abaI and abaR. Glabridin and routinely used therapeutic antimicrobial agents were tested for synergistic action using the checkerboard method. Results: According to our findings, glabridin suppressed MDR-AB growth at high doses (512-1024 µg/mL). The 1/4 MIC of glabridin significantly decreased MDR-AB biofilm formation by 19.98% (P < 0.05), inhibited MDR-AB motility by 44.27% (P < 0.05), whereas the 1/2 MIC of glabridin dramatically reduced MDR-AB biofilm development by 27.43% (P < 0.01), suppressed MDR-AB motility by 50.64% (P < 0.05). Mechanistically, glabridin substantially downregulated the expression of quorum sensing-related genes abaI and abaR by up to 39.12% (P < 0.001) and 25.19% (P < 0.01), respectively. However, no synergistic effect between glabridin and antibacterial drugs was found. Conclusion: Glabridin might be a quorum sensing inhibitor that inhibits MDR-AB biofilm development and swarming motility.

Whole exome sequencing and trio analysis to broaden the variant spectrum of genes in idiopathic hypogonadotropic hypogonadism.

Dozens of genes are associated with idiopathic hypogonadotropic hypogonadism (IHH) and an oligogenic etiology has been suggested. However, the associated genes may account for only approximately 50% cases. In addition, a genomic systematic pedigree analysis is still lacking. Here, we conducted whole exome sequencing (WES) on 18 unrelated men affected by IHH and their corresponding parents. Notably, one reported and 10 novel variants in eight known IHH causative genes (AXL, CCDC141, CHD7, DMXL2, FGFR1, PNPLA6, POLR3A, and PROKR2), nine variants in nine recently reported candidate genes (DCAF17, DCC, EGF, IGSF10, NOTCH1, PDE3A, RELN, SLIT2, and TRAPPC9), and four variants in four novel candidate genes for IHH (CCDC88C, CDON, GADL1, and SPRED3) were identified in 77.8% (14/18) of IHH cases. Among them, eight (8/18, 44.4%) cases carried more than one variant in IHH-related genes, supporting the oligogenic model. Interestingly, we found that those variants tended to be maternally inherited (maternal with n = 17 vs paternal with n = 7; P = 0.028). Our further retrospective investigation of published reports replicated the maternal bias (maternal with n = 46 vs paternal with n = 28; P = 0.024). Our study extended a variant spectrum for IHH and provided the first evidence that women are probably more tolerant to variants of IHH-related genes than men.

Prohibitin overexpression improves myocardial function in diabetic cardiomyopathy.

Prohibitin (PHB) is a highly conserved protein implicated in various cellular functions including proliferation, apoptosis, tumor suppression, transcription, and mitochondrial protein folding. However, its function in diabetic cardiomyopathy (DCM) is still unclear. In vivo, type 2 diabetic rat model was induced by using a high-fat diet and low-dose streptozotocin. Overexpression of the PHB protein in the model rats was achieved by injecting lentivirus carrying PHB cDNA via the jugular vein. Characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. Rats with DCM showed severe insulin resistance, left ventricular dysfunction, fibrosis and apoptosis. PHB overexpression ameliorated the disease. Cardiofibroblasts (CFs) and H9c2 cardiomyoblasts were used in vitro to investigate the mechanism of PHB in altered function. In CFs treated with HG, PHB overexpression decreased expression of collagen, matrix metalloproteinase activity, and proliferation. In H9c2 cardiomyoblasts, PHB overexpression inhibited apoptosis induced by HG. Furthermore, the increased phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was significantly decreased and the inhibited phosphorylation of Akt was restored in DCM. Therefore, PHB may be a new therapeutic target for human DCM.

[Two new phragmalin-type limonoid orthesters from Chukrasia tabularis var. velutina].

As a part of our ongoing research program to isolate novel phragmalin limonoids from the stem bark of Chukrasia tabularis var. velutina, two new phragmalin limonoids orthesters, tabularin Q (1) and tabulalide O (4), along with two known compounds tabularin C (2) and tabularin H (3) were isolated. Their structures were elucidated by means of extensive 1D and 2D spectroscopic analyses which included HSQC, HMBC, and ROESY experiments and HR-ESI-MS.