Local kallikrein�Ckinin system is involved in podocyte apoptosis under diabetic conditions

The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10(-7) mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10(-8) mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.     

Association between Epstein-Barr virus infection and chemoresistance to docetaxel in gastric carcinoma

Epstein-Barr virus (EBV) is associated with human cancers such as nasopharyngeal carcinoma, Burkitt’s lymphoma, Hodgkin’s disease, and gastric carcinoma (GC). EBV is associated with about 10% of all GC cases globally. EBV-associated GC has distinct features from EBV-negative GC. However, it is still unclear if EBV infection has any effect on GC chemoresistance. Cell proliferation assay, cell cycle analysis, and active caspase Western blot revealed that the EBV-positive GC cell line (AGS-EBV) showed chemoresistance to docetaxel compared to the EBV-negative GC cell line (AGS). Docetaxel treatment increased expression of Bax similarly in AGS and AGS-EBV cell lines. However, Bcl-2 induction was markedly higher in AGS-EBV cells, after docetaxel treatment. Although docetaxel increased the expression of p53 to a similar extent in both cell lines, induction of p21 in AGS-EBV cells was lower than in AGS cells. Furthermore, expression of survivin was higher in AGS-EBV cells than in AGS cells following docetaxel treatment as well as at basal state. EBVlytic gene expression was induced by docetaxel treatment in AGS-EBV cells. The results suggest that EBV infection and lytic induction confers chemoresistance to GC, possibly by regulating cellular and EBV latent and lytic gene expression.     

Effects of siRNA-dependent knock-down of cardiolipin synthase and tafazzin on mitochondria and proliferation of glioma cells

The mitochondrial phospholipid cardiolipin (CL) has been implicated with mitochondrial morphology, function, and cell proliferation. Changes in CL are often paralleled by changes in the lipid environment of mitochondria that may contribute to mitochondrial function and proliferation. This study aimed to separate the effects of CL content and CL composition from cellular free fatty acid distribution on bioenergetics and proliferation in C6 glioma cells. To this end, cardiolipin synthase and the CL remodelling enzyme, tafazzin, were knocked-down by siRNA in C6 cells. After 72?h of cultivation, we analysed CL composition by means of LC/MS/MS, distribution of cellular fatty acids by means of gas chromatography, and determined oxygen consumption and proliferation. Knock-down of cardiolipin synthase affected the cellular CL content in the presence of linoleic acid (LA) in the culture medium. Knock-down of tafazzin had no consequence with respect to the pattern of cellular fatty acids but caused a decrease in cell proliferation. It significantly changed the distribution of molecular CL species, increased CL content, decreased oxygen consumption, and decreased cell proliferation when cultured in the presence of linoleic acid (LA). The addition of linoleic acid to the culture medium caused significant changes in the pattern of cellular fatty acids and the composition of molecular CL species. These data suggest that tafazzin is required for efficient bioenergetics and for proliferation of glioma cells. Supplementation of fatty acids can be a powerful tool to direct specific changes in these parameters.     

Two new species of Torymidae (Hymenoptera: Chalcidoidea) reared from flower heads of Echinops orientalis Trautvetter in south-eastern Turkey

Two new species of torymids, Pseudotorymus hasanberkayi sp. n. and Microdontomerus kahramanmarasensis sp. n. (Hymenoptera: Torymidae), were reared from flower heads of Echinops orientalis Trautvetter (Asteraceae) collected in Kahramanmara? province, south-eastern Turkey. The new species are described and their diagnostic characters are illustrated.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:848B4E9D-AE8A-4EF8-8072-1F28BE21ADA1     

Different fermentation strategies by Schizochytrium mangrovei strain pq6 to produce feedstock for exploitation of squalene and omega‐3 fatty acids

Schizochytrium mangrovei strain PQ 6 was investigated for coproduction of docosahexaenoic acid (C22: 6ω‐3, DHA ) and squalene using a 30‐L bioreactor with a working volume of 15 L under various batch and fed‐batch fermentation process regimes. The fed‐batch process was a more efficient cultivation strategy for achieving higher biomass production rich in DHA and squalene. The final biomass, total lipid, unsaponifiable lipid content, and DHA productivity were 105.25 g · L^?1, 43.40% of dry cell weight, 8.58% total lipid, and 61.66 mg · g^?1 · L^?1, respectively, after a 96 h fed‐batch fermentation. The squalene content was highest at 48 h after feeding glucose (98.07 mg · g^?1 of lipid). Differences in lipid accumulation during fermentation were correlated with changes in ultrastructure using transmission electron microscopy and Nile Red staining of cells. The results may be of relevance to industrial‐scale coproduction of DHA and squalene in heterotrophic marine microalgae such as Schizochytrium .     

Further sesquiterpenoids from the rhizomes of Homalomena occulta and their anti-inflammatory activity

The rhizomes of Homalomena occulta are called Qian-nian-jian in Traditional Chinese Medicine (TCM), which is widely consumed in China owing to its health benefits for the treatment of rheumatoid arthritis and for strengthening tendons and bones. A phytochemical investigation on this famous TCM yielded 19 sesquiterpenoids (1–19) with various carbocyclic skeletons including isodaucane (2, 8, and 9), guaiane (3), eudesmane (4 and 10–15), oppositane (5, 16, and 17), and aromadendrane (18 and 19) types. The structures of new compounds, Homalomenins A-E (1–5), were determined by diverse spectroscopic data. Compound 1 possessed a rare sesquiterpenoid skeleton and compound 5 represented the first example of 1,4-oxa-oppositane sesquiterpenoid. These isolates were evaluated for their inhibitory effects on COX-2 mRNA, COX-2 protein expression, and prostaglandin E2 (PGE2) production in Raw264.7 cells, which demonstrated that compounds 5, 18, 19 showed potent anti-inflammatory activity by suppressing LPS-induced COX-2 expression and PGE2 production in a dose-dependent manner.     

The Wag31 protein interacts with AccA3 and coordinates cell wall lipid permeability and lipophilic drug resistance in Mycobacterium smegmatis

Mycobacterium tuberculosis, especially drug resistant tuberculosis, is a serious threat to global human health. Compared with other bacterial pathogens, M. tuberculosis gains stronger natural drug resistance from its unusually lipid-rich cell wall. As a DivIVA homolog, Wag31 has been demonstrated to be closely involved in peptidoglycan synthesis, cell growth and cell division. Previous research rarely investigated the role of Wag31 in drug resistance. In this study, we found Wag31 knock-down in Mycobacterium smegmatis resulted in a co-decrease of the resistance to four lipophilic drugs (rifampicin, novobiocin, erythromycin and clofazimine) and an increase in the cell permeability to lipophilic molecules. Six proteins (AccA3, AccD4 and AccD5, Fas, InhA and MmpL3) that are involved in fatty acid and mycolic acid synthesis were identified in the Wag31 interactome through Co-Immunoprecipitation. The Wag31–AccA3 interaction was confirmed by the pull-down assay. AccA3 overexpression resulted in a decrease in lipid permeability and an increase in the resistance of rifampicin and novobiocin. It confirmed the close relationship of lipophilic drug resistance, lipid permeability and the Wag31–AccA3 interaction. These results demonstrated that Wag31 maintained the resistance to lipophilic drugs and that Wag31 could play a role in controlling the lipid permeability of the cell wall through the Wag31–AccA3 interaction.