553 research outputs found

    Galectin-1 is essential for efficient liver regeneration following hepatectomy

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    Galectin-1 (Gal1) is a known immune/inflammatory regulator which actsboth extracellularly and intracellularly, modulating innate and adaptive immuneresponses. Here, we explored the role of Gal1 in liver regeneration using 70% partial hepatectomy (PHx) of C57BL/6 wild type and Gal1-knockout (Gal1-KO, Lgals1-/-) mice. Gene or protein expression, in liver samples collected at time intervals from 2 to 168 hours post-operation, was tested by either RT-PCR or by immunoblotting and immunohistochemistry, respectively. We demonstrated that Gal1 transcript and protein expression was induced in the liver tissue of wild type mice upon PHx. Liver regeneration following PHx was significantly delayed in the Gal1-KO compared to the control liver. This delay was accompanied by a decreased Akt phosphorylation, and accumulation of the hepatocyte nuclear p21 protein in the Gal1-KO versus control livers at 24 and 48 hours following PHx. Transcripts of several known regulators of inflammation, cell cycle and cell signaling, including some known PHx-induced genes, were aberrantly expressed (mainly down-regulated) in Gal1-KO compared to control livers at 2, 6 and 24 hours post-PHx. Transient steatosis, which is imperative for liver regeneration following PHx, was significantly delayed and decreased in the Gal1- KO compared to the control liver and was accompanied by a significantly decreased expression in the mutant liver of several genes encoding lipid metabolism regulators.Our results demonstrate that Gal1 protein is essential for efficient liver regeneration following PHx through the regulation of liver inflammation, hepatic cell proliferation, and the control of lipid storage in the regenerating liver.Fil: Potikha, Tamara. Hadassah Hebrew University Medical Center; IsraelFil: Ella, Ezra. Hadassah Hebrew University Medical Center; IsraelFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mizrahi, Lina. Hadassah Hebrew University Medical Center; IsraelFil: Pappo, Orit. Hadassah Hebrew University Medical Center; IsraelFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Galun, Eithan. Hadassah Hebrew University Medical Center; IsraelFil: Goldenberg, Daniel S.. Hadassah Hebrew University Medical Center; Israe

    Testing transgenic regulatory elements through live mouse imaging

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    AbstractTo overcome positional and methylation effects on transgene expression, we developed a universal cloning cassette for in vivo assessment of regulatory elements using the luciferase reporter gene and the CCCD camera. Monitoring luciferase expression pattern in live mice enables screening of large numbers of transgenic founders quickly and inexpensively. We demonstrate that in the engineered transgenic mice, the chicken β-globin 5′HS4 insulator did not always provide the desirable expression pattern, and the Island Element, responsible for the demethylation of the surrounding DNA region, was not beneficial. Both tested liver-specific and developmentally regulated promoters exhibited the expected expression pattern in most transgenic founders

    Psychosocial Disparities Among Racial/Ethnic Minority Transgender Young Adults and Young Men Who Have Sex with Men Living in Detroit

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    Purpose: Transgender populations in the United States experience unique inequities in health and social well-being; however, they continue to be categorized with men who have sex with men (MSM) in HIV surveillance. To illustrate the differences in the lived realities of young MSM and transgender youth, we compare psychosocial outcomes across a sample of transgender and MSM youth from Detroit. Methods: Data for this study come from a community-based cross-sectional survey of young adults (ages 18?29) living in Detroit who identify as transgender and/or as cisgender young men who have sex with men (YMSM). Using participants' geographic location within the city of Detroit, we matched transgender participants (N=26) to YMSM (N=123) living in the same area, and compared the prevalence in risk and resilience indicators across the two groups. Results: Transgender participants were more likely than YMSM to experience socioeconomic vulnerability across several indicators, including lower educational attainment and workforce participation, greater residential instability, and higher lifetime experiences of transactional sex. Transgender participants were more likely than YMSM to report poorer health status, higher symptoms of depression and anxiety, and greater experiences of daily hassles and gender-related discrimination. Transgender participants did not differ from YMSM peers on health-promotive factors, including self-esteem, coping mastery, purpose in life, or social support. Conclusions: Our findings underscore the importance of addressing the social and economic inequities experienced by transgender young adults. Local- and national-level programmatic and policy interventions are recommended to alleviate the psychosocial vulnerability experienced by transgender young adults and to improve their health and social well-being.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140300/1/trgh.2016.0027.pd

    The common apolipoprotein A-1 polymorphism −75A>G is associated with ethnic differences in recurrent coronary events after recovery from an acute myocardial infarction

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    Since data regarding the relationship between a common polymorphism (SNP) of the apoA1 gene with apoA1 levels and risk of coronary artery disease are inconsistent, we hypothesized that its association with recurrent coronary events differs for White and Black individuals with diagnosed coronary heart disease. The apoA1 −75G>A SNP was genotyped in a cohort of 834 Black (n=129) and White (n=705) post-myocardial infarction patients. Recurrent coronary events (coronary-related death, non-fatal myocardial infarction, or unstable angina) were documented during an average follow-up of 28 months. Thirty percent of White and 21% of Black patients carried the SNP. Cox proportional-hazards regression analysis, adjusting for clinical and laboratory covariates, demonstrated that the SNP was not associated with recurrent events in the total cohort (HR=1.37, 95% CI 0.95–1.97; p= 0.09) but was the only variable associated with an increased risk of recurrent cardiac events in Blacks (HR=2.40, 95% CI 1.07–5.40; p= 0.034). Conversely in Whites, the SNP was not associated with recurrent events (HR=1.12, 95% CI 0.75–1.67; p= 0.59) whereas apoB (HR=1.78, 95% CI 1.20 −2.65; p= 0.0042) and calcium channel blocker use (HR=2.53, 95% CI 1.72–3.72; p<0.001) were associated; p= 0.0024 for interaction between ethnicity and the SNP. A common apoA1 SNP is associated with a significantly increased risk of recurrent cardiac events among Black, but not White, postmyocardial infarction patients. Relationships with lipoproteins may help explain this finding
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