Lansoprazole enhances the antidiabetic effect of dapagliflozin in fortified diet‐fed streptozotocin‐treated diabetic rats

Dapagliflozin (DAPA) is used for treating type 2 diabetes, whereas lansoprazole (LPZ) is used as a traditional antiulcer drug. The present study investigated the possible antidiabetic effects of LPZ on fortified diet‐fed streptozotocin (FDF/STZ)‐induced insulin‐resistant diabetic rats. On the basis of the current results, it can be concluded that LPZ could be used as an add‐on drug along with the conventional treatment for T2D as it showed beneficial effects in the current experimental model of insulin resistance.     

Akt Inhibition Promotes ABCA1-Mediated Cholesterol Efflux to ApoA-I through Suppressing mTORC1

ATP-binding cassette transporter A1 (ABCA1) plays an essential role in mediating cholesterol efflux to apolipoprotein A-I (apoA-I), a major housekeeping mechanism for cellular cholesterol homeostasis. After initial engagement with ABCA1, apoA-I directly interacts with the plasma membrane to acquire cholesterol. This apoA-I lipidation process is also known to require cellular signaling processes, presumably to support cholesterol trafficking to the plasma membrane. We report here that one of major signaling pathways in mammalian cells, Akt, is also involved. In several cell models that express ABCA1 including macrophages, pancreatic beta cells and hepatocytes, inhibition of Akt increases cholesterol efflux to apoA-I. Importantly, Akt inhibition has little effect on cells expressing non-functional mutant of ABCA1, implicating a specific role of Akt in ABCA1 function. Furthermore, we provide evidence that mTORC1, a major downstream target of Akt, is also a negative regulator of cholesterol efflux. In cells where mTORC1 is constitutively activated due to tuberous sclerosis complex 2 deletion, cholesterol efflux to apoA-I is no longer sensitive to Akt activity. This suggests that Akt suppresses cholesterol efflux through mTORC1 activation. Indeed, inhibition of mTORC1 by rapamycin or Torin-1 promotes cholesterol efflux. On the other hand, autophagy, one of the major pathways of cholesterol trafficking, is increased upon Akt inhibition. Furthermore, Akt inhibition disrupts lipid rafts, which is known to promote cholesterol efflux to apoA-I. We therefore conclude that Akt, through its downstream targets, mTORC1 and hence autophagy, negatively regulates cholesterol efflux to apoA-I.     

Selective synthesis and reactions of 6-substituted-2-beta-galactosyl-1,2,4-triazines of potential anticancer activity

Selective synthesis and reactions of different 6-substituted-2-beta-D-galactosyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-ones using the developed amino or aryl protecting group strategy were investigated. Primary human anticancer screening of twelve selected compounds (in vitro) resulted in an active compound against both MCF7 (Breast) and SF-268(CNS) cell lines.     

Intravascular detection of Giardia trophozoites in naturally infected mice. An electron microscopic study

During routine transmission electron microscopic (TEM) examination of mice naturally infected with Giardia muris, an intense infection with Giardia trophozoites was demonstrated within intestinal and renal tissues. Examination of randomly taken sections from these heavily infected tissues revealed marked deep affection with mixed pathology. Duodenal sections were found loaded with Giardia trophozoites in intimate contact with necrotic gut cells. Some of these trophozoites were detected within central lacteal of damaged villi and nearby blood vessels. Interestingly, and for the first time to be demonstrated, morphologically identical G. muris trophozoite was detected in a renal blood vessel. An intense cellular immune reaction was obviously demonstrated with remarkable interaction between giant macrophages and the trophozoites particulates. Involvement of deep tissues by Giardia trophozoites and their presence within vascular channels could open up questions about the possible invasive and disseminative behavior of G. muris, particularly in heavily and naturally infected hosts.     

3-Chloroacetylpyridine adenine dinucleotide phosphate, an alkylating analogue of NADP+.

An alkylating analogue of NADP+ the 3-chloroacetylpyridine adenine dinucleotide phosphate was prepared from 3-diazoacetylpyridine adenine dinucleotide phosphate which was obtained by enzymatic transglucosidation of NADP+. The 3-diazoacetylpyridine adenine dinucleotide phosphate proved to be more unstable when compared to the corresponding NAD+ analogue. The alkylation of several dehydrogenases using this alkylating analogue is mentioned.     

Characterization of protein–protein interactions between rice viruses and vector insects

Planthoppers are the most notorious rice pests, because they transmit various rice viruses in a persistent-propagative manner. Protein–protein interactions (PPIs) between virus and vector are crucial for virus transmission by vector insects. However, the number of known PPIs for pairs of rice viruses and planthoppers is restricted by low throughput research methods. In this study, we applied DeNovo, a virus-host sequence-based PPI predictor, to predict potential PPIs at a genome-wide scale between three planthoppers and five rice viruses. PPIs were identified at two different confidence thresholds, referred to as low and high modes. The number of PPIs for the five planthopper-virus pairs ranged from 506 to 1985 in the low mode and from 1254 to 4286 in the high mode. After eliminating the “one-too-many” redundant interacting information, the PPIs with unique planthopper proteins were reduced to 343–724 in the low mode and 758–1671 in the high mode. Homologous analysis showed that 11 sets and 31 sets of homologous planthopper proteins were shared by all planthopper-virus interactions in the two modes, indicating that they are potential conserved vector factors essential for transmission of rice viruses. Ten PPIs between small brown planthopper and rice stripe virus (RSV) were verified using glutathione-S-transferase (GST)/His-pull down or co-immunoprecipitation assay. Five of the ten PPIs were proven positive, and three of the five SBPH proteins were confirmed to interact with RSV. The predicted PPIs provide new clues for further studies of the complicated relationship between rice viruses and their vector insects.