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Abstract Context A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D–related diseases. Objective Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry. Design, Setting, Participants In a cross-sectional study within the Multi-Ethnic Study of Atherosclerosis (MESA), we compared a comprehensive panel of vitamin D metabolism markers across self-reported racial/ethnic groups of Black (N = 1759), White (N = 2507), Chinese (N = 788), and Hispanic (N = 1411). We evaluated associations of proportion African and European ancestry with this panel of markers in Black and Hispanic participants using ancestry informative markers. Latent class analysis evaluated associations between patterns of vitamin D measurements with race/ethnicity. Results Compared with Black participants, White participants had significantly higher serum concentrations of 25-hydroxyvitamin D and fibroblast growth factor-23; lower concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D; circulating vitamin D metabolite ratios suggesting lower CYP27B1 and higher CYP24A1 activity; higher urinary concentrations of calcium and phosphorus with higher urinary fractional excretion of phosphorus; and differences in vitamin D binding globulin haplotypes. Higher percent European ancestry was associated with higher 25-hydroxyvitamin D and lower parathyroid hormone concentrations among Black and Hispanic participants. Latent classes defined by vitamin D measurements reflected these patterns and differed significantly by race/ethnicity and ancestry. Conclusions Markers of vitamin D metabolism vary significantly by race/ethnicity, may serve to maintain bone and mineral homeostasis across ranges of 25-hydroxyvitamin D production, and be attributable, at least partly, to genetic ancestry.

Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and represents the main underlying cause of graft dysfunction and liver failure post-transplantation. To date, ischemia-reperfusion injury is an unsolved problem in clinical practice. In this context, inflammasome activation, recently described during ischemia-reperfusion injury, might be a potential therapeutic target to mitigate the clinical problems associated with liver transplantation and hepatic resections. The present review aims to summarize the current knowledge in inflammasome-mediated inflammation, describing the experimental models used to understand the molecular mechanisms of inflammasome in liver ischemia-reperfusion injury. In addition, a clear distinction between steatotic and non-steatotic livers and between warm and cold ischemia-reperfusion injury will be discussed. Finally, the most updated therapeutic strategies, as well as some of the scientific controversies in the field will be described. Such information may be useful to guide the design of better experimental models, as well as the effective therapeutic strategies in liver surgery and transplantation that can succeed in achieving its clinical application.

Aromatase inhibitors, which inhibit the conversion of androgens to estrogens, have had extensive use for more than 40 years to treat postmenopausal breast cancer as well as used in clinical studies for endometrial, ovarian cancers, and endometriosis. [...]showing the importance of targeting estrogen formation and metabolism in cancer treatment, sulfatase inhibitors that target the enzyme responsible for the hydrolysis of inactive estrogen-sulfates have entered clinical trials for the treatment of breast, endometrial cancers, and endometriosis, primarily demonstrating effects in breast cancer. Deficiency in BH4 leads to various symptoms in the peripheral and central nervous systems. [...]an ideal therapeutic approach would involve blocking excessive BH4 production while preventing BH4 depletion. [...]the current Research Topic included an original article that presented the role of cyclic nucleotides, specifically 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP), in fundamental brain functions, including learning and memory.Yanai et al.demonstrated that phosphodiesterase 3 (PDE3) regulated the cellular content of cAMP and cGMP, which is in agreement with previous studies showing that long-term administration of cilostazol, a PDE3 inhibitor, improved memory performance in aging mice.

Seascape genomics facilitates integrative research on eco‐evolutionary forces, such as migration and natural selection, which shape genomic connectivity and structure and provide critical insights for conservation strategies. The green abalone (Haliotis fulgens) is distributed from California, United States, to Baja California Sur, Mexico, and exposed to a latitudinal environmental gradient in the California Current System. This study aimed to investigate genomic population structure and potential local adaptations of green abalone across its distribution. The green abalone exhibits a distinctive neutral genetic structuring influenced by geographic distance and marine currents rather than local adaptations. Analyses using 9100 neutral and 17 outlier SNPs revealed three distinct populations: the North group (California to Ensenada, Baja California), a population on Guadalupe Island, and the South group (coastal locations of the Baja California peninsula). The research underscores the significance of life history traits and larval dispersal in shaping genetic connectivity. Connectivity appears to be influenced by geographic distance on neutral genetic structure, overshadowing natural selection's role. Furthermore, no genome–environment associations to sea surface temperature values were found. Future research should integrate genetic data with ocean circulation modeling to better understand the mechanisms and outcomes of larval dispersal and genetic connectivity. This study emphasizes the importance of both local and binational (USA‐Mexico) conservation efforts, suggesting the development of SNP marker panels for traceability and management. Collaborative strategies could serve as models for binational conservation initiatives in other ecoregions, promoting sustainable management and conservation of green abalone populations and other exploited species across national borders. The green abalone exhibits a distinctive neutral genetic structuring influenced by geographic distance and marine currents rather than local adaptations. Analyses using 1900 neutral and 17 putative outlier SNPs revealed three distinct populations: the North group (California to Ensenada, Baja California), a population on Guadalupe Island, and the South group (coastal locations of the Baja California peninsula). Connectivity appears to be influenced by geographic distance on neutral genetic structure, overshadowing natural selection role.

Using ~60,000 SNPs selected for minimal linkage disequilibrium, we perform population structure analysis of 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n = 93), Cuba (n = 50), the Dominican Republic (n = 203), Mexico (n = 708), Puerto Rico (n = 192), and South America (n = 111). By projection of principal components (PCs) of ancestry to samples from the HapMap phase III and the Human Genome Diversity Panel (HGDP), we show the first two PCs quantify the Caucasian, African, and Native American origins, while the third and fourth PCs bring out an axis that aligns with known South-to-North geographic location of HGDP Native American samples and further separates MESA Mexican versus Central/South American samples along the same axis. Using k-means clustering computed from the first four PCs, we define four subgroups of the MESA Hispanic cohort that show close agreement with self-identification, labeling the clusters as primarily Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. To demonstrate our recommendations for genetic analysis in the MESA Hispanic cohort, we present pooled and stratified association analysis of triglycerides for selected SNPs in the LPL and TRIB1 gene regions, previously reported in GWAS of triglycerides in Caucasians but as yet unconfirmed in Hispanic populations. We report statistically significant evidence for genetic association in both genes, and we further demonstrate the importance of considering population substructure and genetic heterogeneity in genetic association studies performed in the United States Hispanic population.

Background The composition of organ preservation solutions is crucial for maintaining graft integrity and early graft function after transplantation. The aim of this study is to compare new organ preservation solution PERLA® with the gold standard preservation solution University of Wisconsin (UW) regarding oxidative stress and early graft injury. Methods In order to assess oxidative stress after cold storage, kidney grafts have been preserved for 18 h at 4° C in either UW solution or PERLA® solution and then assessed for oxidative stress injury (protocol 1). To assess kidney injuries and oxidative stress after reperfusion, rat kidneys were harvested, stored in cold UW or in PERLA® solutions for 18 h at 4 °C and then transplanted heterotopically for 6 h (protocol 2). PERLA® is a high Na + /low K +  solution including PEG-35 (1 g/L), trimetazidine (1 µM), carvedilol (10 µM) and tacrolimus (5 µM). Results Our results showed that preservation of kidneys in PERLA® solution significantly attenuates oxidative stress parameters after cold storage and reperfusion. We found a significant decrease in oxidative damage indicators (MDA, CD and CP) and a significant increase in antioxidant indicators (GPx, GSH, CAT, SOD and PSH). Moreover, PERLA® solution decreased kidney injury after reperfusion (creatinine, LDH and uric acid). Conclusion PERLA® solution was more effective than UW storage solution in preserving rat’s kidney grafts.

Women who decide to pursue a scientific career, focusing on gastroenterology, face many challenges, including funding of research, the time constraints to juggle a clinical and research career and the process of research itself including obtaining data protection clearance, data collection and statistical analysis of data and the publication process that can be lengthy. There has been extensive research in the development of non-invasive markers in patients with inflammatory bowel disease that reflect disease activity. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Despite numerous studies, the impact of each extended criteria donor variable on graft function or recipient survival is still under investigation because of contradictory results (9). [...]molecular aspects of the harmful effects of BD and CD are poorly described (2,10,11). Or, are the considerable mechanisms reported the result of the great diversity of experimental models used to study this pathological condition? The detrimental effect of various conditions on liver viability is also supported by other research included in this issue that describes several factors correlated with the patient and the surgery that directly influence the success of human hepatocyte isolation. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (2014)20:14455–62.10.3748/wjg.v20.i39.1445525339832 8.CannistràMRuggieroMZulloAGallelliGSerafiniSMariaM.Hepatic ischemia reperfusion injury: a systematic review of literature and the role of current drugs and biomarkers.Int J Surg.

Pentraxin-3 (PTX3) is an inflammatory marker thought to be more specific to vascular inflammation than C-reactive protein (CRP). Whether PTX3 is independently associated with adverse events among persons with stable coronary heart disease (CHD), independently of CRP, and whether kidney dysfunction influences these associations are not known. We evaluated the associations of baseline PTX3 levels with all-cause mortality, cardiovascular (CV) events (myocardial infarction, stroke, or CHD death), and incident heart failure (HF) during 37 months among ambulatory persons with stable CHD participating in the Heart and Soul Study. Cox proportional hazards models were adjusted for age, sex, race, hypertension, diabetes, smoking, and CRP. Among 986 persons with stable CHD, each 1 unit increase in log PTX3 at baseline was associated with an 80% increased risk of all-cause mortality (hazard ratio [HR] 1.8, 95% CI 1.5-2.1), a 50% increased risk of CV events (HR 1.5, 95% CI, 1.2-1.9), and an 80% greater risk of incident HF (HR 1.8, 95% CI, 1.3-2.5). Further adjustment for estimated glomerular filtration rate (eGFR) attenuated these associations to 1.6 (1.3-1.9) for mortality, 1.3 (1.0-1.6) for CV events and 1.5 (1.1-2.1) for incident HF. Stratification by eGFR >60 mL/min per 1.73m2 or <60 mL/min per 1.73m2 did not affect these associations (P interaction > .3 for all outcomes). Among persons with stable CHD, higher PTX3 concentrations were associated with increased risk for all-cause mortality, CV events, and incident HF independently of systemic inflammation. Adjustment for eGFR modestly attenuated these associations, suggesting that future studies of PTX3 should adjust for kidney function.