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CURATOR
A pinboard by
Xiaoyu Zhang

PhD student, East China Normal University

PINBOARD SUMMARY

Immune system is a miraculous creation; it is a complex system made of many diverse cells each working to maintain the life and protect from viral or bacterial infections. It’s fantastic for me to find out the mystery of immunity. Now, my research interest is consistent with my desire, we focus on G protein-coupled receptors and signal transduction in the regulation of inflammation. On one hand, we demonstrated that Gpr97 is dispensable for inflammation in development of asthma (PLoS One, 2015), as well as the chronic metabolic inflammation (Scientific Report, 2016). On the other hand, we found that toll-like receptor-triggered calcium mobilization protects mice against bacterial infection through extracellular ATP release (Infection and Immunity, 2014), as well TLR induced UDP play an important role in protecting infection via P2Y6 (The Journal of Immunology, 2016). Furthermore, extracellular ATP is easily degraded in plasma, so we do a lot research on its secondary product, ADP. Our results show that Pathogen-associated molecular patterns induced ADP facilitates monocyte recruitment through P2Y12/13 receptors in bacterial infection (Cellular &Molecular Immunology, 2016), and ADP also plays a key role in development of local inflammation in RA. I hope that our findings can make sense for further investigation of GPCR-based drugs.

5 ITEMS PINNED

Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran.

Abstract: The use of anti-retroviral therapy has been effective in controlling the spread of HIV-1, and has prolonged life expectancy, but this success can be affected by the emergence of drug resistance. The main goal of this study was to investigate drug resistance in the reverse transcriptase (RT), and protease (PR) genes among HIV-1 infected individuals. We systematically selected 59 HIV-1 infected individuals from Shiraz Voluntary Counseling and Testing Center (29 treatment- naïve and 30 treated). In this study intravenous drug users older than 18 were included in this study. Using specific primers, nested RT-PCR was performed on RNA extracted from patient samples. The genes targeted for RT and PCR were successfully amplified and sequenced. The sequences of these two genes were compared with mutations related to drug resistance against nucleotide reverse transcriptase inhibitors (NRTI), non-nucleotide reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) using the latest database from the International AIDS society - USA, Stanford University, and the patterns were recorded. Among treatment-naïve, the detected NRTI and NNRTI resistance mutations were V179T, V75 M and E138A. V179T causes high level resistance to Efavirenze and Nevirapin. V75 M causes intermediate resistance to Stavudine. Regarding NRTI and NNRTI resistance mutations among treated patients, the most frequent mutation (7%) was M184 V, which causes high level resistance to zidovudin and emtricitabine. The interesting result from this study was the detection of NRTI and NNRTI resistance mutations before the initiation of treatment, which signifies the transmission of resistant strains of virus between individuals. This mutation highlights the importance of drug resistance HIV-1 genotyping before commencing treatment.

Pub.: 08 Oct '17, Pinned: 10 Oct '17

Invasive breast carcinomas with ATM gene variants of uncertain significance share distinct histopathologic features.

Abstract: The increasing availability of next-generation sequencing for clinical research dramatically improved our understanding of breast cancer genetics and resulted in detection of new mutation variants. Cancer risk data relating to some of these variants are insufficient, prompting the designation of variants of uncertain significance (VUS). The histopathologic characteristics of these variants have not been previously described. We propose to depict these characteristics and determine if invasive carcinomas with similar VUS genes share similar histomorphologic features. In total, 28 invasive breast cancers with VUS were retrospectively identified. Tumor sections were reviewed and a predefined set of histopathologic characteristics were documented and compared. Nine of the 28 cases were variants in the ATM gene and were found to share similar histologic characteristics; all had tumor cells with low nuclear grade, absent tumor infiltrating lymphocytes, as well as a marked desmoplastic response. A subset of the above findings were identified in variants of other genes but none had all findings collectively. Furthermore, variants of ATM gene had smaller tumor size, lower pathologic T stage at presentation, and more favorable surrogate molecular subtype compared to variants of other genes. These findings could potentially be used to reclassify VUS and predict which patients may harbor ATM mutations, and hence could have implications in triaging toward ATM variant identification for potential future targeted therapy.

Pub.: 08 Oct '17, Pinned: 10 Oct '17

Early indications of ANIT-induced cholestatic liver injury: Alteration of hepatocyte polarization and bile acid homeostasis.

Abstract: Hepatocyte polarization is essential for biliary secretion, and loss of polarity causes bile secretory failure and hepatotoxicity. Here, we showed that alpha-naphthyl isothiocyanate (ANIT)-induced liver injury was accompanied by the dynamic interruption of bile acid homeostasis in rat plasma, liver and bile, which was characterized by the redistribution of bile acids in plasma and bile and a small range of fluctuations in the liver. Molecular mechanism studies indicated that these factors are dynamically mediated by the disruption of bile acid transporters and hepatic tight junctions. Dynamic changes in tight junction (TJ) permeability were observed by hepatobiliary barrier function assessment. Hepatocyte polarization was disrupted by ANIT before the development of cholestatic hepatotoxicity and alteration of bile acid metabolic profiles, which were assayed by high-performance liquid chromatography-tandem mass spectrometry, further verifying TJ deficiency. S1PR1 activation with SEW2871 reduced ANIT-induced liver injury by reducing the total serum bile acid concentration, liver functional enzyme activity and inflammation. Our data suggest that hepatocyte polarization plays an important role in maintaining bile acid homeostasis before the development of cholestatic hepatotoxicity and that TJs were more prominent in the early stage of cholestasis. S1PR1 may be a potential target for the prevention of drug-induced cholestatic liver injury.

Pub.: 08 Oct '17, Pinned: 10 Oct '17