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Project description:synthetic construct submission portal test
| PRJNA940821 | ENA
Project description:Epigenetic changes deregulate gene expression to drive oncogenesis. The reversible nature of these changes enables therapeutic targeting, as in cutaneous T-cell lymphoma (MF/SS), Histone deacetylase inhibitors (HDACi), which alter epigenetic modifications, are effective in ~30% of MF/SS patients. However, there are no markers that predict MF/SS progression or therapy resistance. We hypothesized that epigenetic alterations drive MF/SS progression and promote HDACi drug resistance. Therefore, we profiled the epigenomes and transcriptomes of malignant T cell purified from skin biopsies and peripheral blood from MF/SS patients (N=21) before and after treatment with HDACi, as well as in vitro HDACi-treated CD4+ T cells from healthy donors. Here we report for the first time the epigenome-wide map of acetylation changes in MF/SS patients treated with HDACi, and define the significant differences in regulatory element activity and corresponding transcriptional changes in HDACi-sensitive versus resistant tumors. Our studies identified genes not previously associated with MF/SS, nor with disease progression or HDACi resistance, and were enriched in pathways that regulate apoptosis (BIRC5), cell cycle (RRM2), and chromosome cohesion (CENPH). We also identified a striking number of genes whose products are involved in cell adhesion and migration, including CCR6, LAIR2, VCAM1, and EPCAM. The mRNA of LAIR2, which encodes a receptor protein secreted by activated T cells that binds collagen and prevents binding of the inhibitory receptor LAIR1, was significantly upregulated in MF/SS tumors that were resistant to HDACi therapy and manifested in both skin and peripheral blood. We also detected elevated levels of LAIR2 protein in the plasma of MF/SS patients with progressive disease. Taken together, these studies defined the first epigenome-wide acetylation landscape of HDACi responsive and resistant MF/SS tumors, identified significantly altered patterns of epigenetic regulation and corresponding gene expression in HDACi resistant MF/SS tumors, and connected them to novel pathways of disease progression, particularly in cell adhesion and migration. These findings may represent novel predictive markers for MF/SS progression that are also targets for future therapeutic development.
2019-08-09 | GSE132053 | GEO
Project description:ImportanceThe 21st Century Cures Act Final Rule mandates the immediate electronic availability of test results to patients, likely empowering them to better manage their health. Concerns remain about unintended effects of releasing abnormal test results to patients.ObjectiveTo assess patient and caregiver attitudes and preferences related to receiving immediately released test results through an online patient portal.Design, setting, and participantsThis large, multisite survey study was conducted at 4 geographically distributed academic medical centers in the US using an instrument adapted from validated surveys. The survey was delivered in May 2022 to adult patients and care partners who had accessed test results via an online patient portal account between April 5, 2021, and April 4, 2022.ExposuresAccess to test results via a patient portal between April 5, 2021, and April 4, 2022.Main outcomes and measuresResponses to questions related to demographics, test type and result, reaction to result, notification experience and future preferences, and effect on health and well-being were aggregated. To evaluate characteristics associated with patient worry, logistic regression and pooled random-effects models were used to assess level of worry as a function of whether test results were perceived by patients as normal or not normal and whether patients were precounseled.ResultsOf 43 380 surveys delivered, there were 8139 respondents (18.8%). Most respondents were female (5129 [63.0%]) and spoke English as their primary language (7690 [94.5%]). The median age was 64 years (IQR, 50-72 years). Most respondents (7520 of 7859 [95.7%]), including 2337 of 2453 individuals (95.3%) who received nonnormal results, preferred to immediately receive test results through the portal. Few respondents (411 of 5473 [7.5%]) reported that reviewing results before they were contacted by a health care practitioner increased worry, though increased worry was more common among respondents who received abnormal results (403 of 2442 [16.5%]) than those whose results were normal (294 of 5918 [5.0%]). The result of the pooled model for worry as a function of test result normality was statistically significant (odds ratio [OR], 2.71; 99% CI, 1.96-3.74), suggesting an association between worry and nonnormal results. The result of the pooled model evaluating the association between worry and precounseling was not significant (OR, 0.70; 99% CI, 0.31-1.59).Conclusions and relevanceIn this multisite survey study of patient attitudes and preferences toward receiving immediately released test results via a patient portal, most respondents preferred to receive test results via the patient portal despite viewing results prior to discussion with a health care professional. This preference persisted among patients with nonnormal results.
| S-EPMC10028486 | biostudies-literature
Project description:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression. The aim of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans.
2016-01-01 | GSE69670 | GEO
Project description: Not available
| S-EPMC10690577 | biostudies-literature
Project description:Background. The Dahl salt-sensitive (SS) rat is an established model of salt-sensitive hypertension and renal damage. Recently, sodium-independent dietary effects were shown to be important in the development of the SS hypertensive phenotype. Compared to Dahl SS/JrHsdMcwi (SS/MCW) rats fed a purified diet (AIN-76A), grain-fed Dahl SS/JrHsdMcwiCrl rats (SS/CRL; Teklad 5L2F) were less susceptible to salt-induced hypertension and renal damage. Methods. With the known role of the immune system in hypertension, the present study characterized the immune cells infiltrating SS/MCW and SS/CRL kidneys. To further identify distinct molecular pathways between SS/MCW and SS/CRL, transcriptomic analysis was performed via RNA sequencing in T-cells isolated from the blood and kidneys of low and high salt-fed rats. Results. Following a 3-week high salt (4.0% NaCl) challenge, SS/CRL rats were protected from salt-induced hypertension (116.5±1.2 vs 141.9±14.4 mmHg) and albuminuria (21.7±3.5 vs 162.9±22.2 mg/day) compared to SS/MCW. Additionally, the absolute number of immune cells infiltrating the kidney was significantly reduced in SS/CRL. RNA-seq revealed >50% of all annotated genes in the entire transcriptome to be significantly differentially expressed in T-cells isolated from blood versus kidney. Pathway analysis of significant differentially expressed genes between SS/MCW and SS/CRL renal and circulating T-cells demonstrated salt-induced changes in genes related to inflammation in SS/MCW compared to metabolism-related pathways in SS/CRL. Conclusions. These functional and transcriptomic T-cell differences between SS/MCW and SS/CRL show that sodium-independent dietary effects may influence the immune response and infiltration of immune cells into the kidney, ultimately impacting susceptibility to salt-induced hypertension and renal damage.
2019-08-26 | GSE127000 | GEO
Project description:IntroductionDespite advances in perioperative management and surgical technique, postoperative liver failure remains a feared complication after hepatic resection. Various supportive treatment options are under current discussion, but lack of structured evaluation. We therefore established a porcine model of major liver resection to study regeneration after partial hepatectomy in a reliable and well-defined pre-clinical setting.MethodsMajor hepatectomy was performed on seven minipigs with the intention to set up a non-lethal but relevant transient impairment of liver function. For steady postoperative vascular access (e.g. for blood withdrawal, measurement of venous pressure), permanent catheters were implanted into the internal jugular and portal veins, respectively. Animals were followed up for 30 days; clinical and laboratory results were recorded in detail. Monitoring was enhanced by non-invasive determination of the maximum liver function capacity (LiMAx test).Results and conclusionsThe established porcine model appeared suitable for evaluation of postoperative liver regeneration. Clinical characteristics and progression of liver function impairment as well as subsequent recovery were comparable to courses known from surgery in humans. Laboratory parameters (e.g. liver enzymes, bilirubin, INR, coagulation factor II) showed relevant derangements during postoperative days (POD) 0 to 3 followed by normalization until POD 7. Application of the LiMAx test was feasible in minipigs, again showing values comparable to humans and kinetics in line with obtained laboratory parameters. The exteriorized portal vein catheters enabled intra- and postoperative monitoring of portal venous pressures as well as easy access for blood withdrawal without relevant risk of postoperative complications.
| S-EPMC6544243 | biostudies-literature
Project description:The current study aimed to investigate whether bovine non-coding RNA play a role in regulating E. coli O157 shedding through studying miRNAomes of the whole gastrointestinal tract including duodenum, proximal jejunum, distal jejunum, cecum, spiral colon, descending colon and rectum. The number of miRNAs detected in each intestinal region ranged from 390 ± 13 to 413 ± 49. Compared between SS and NS, the number of differentially expressed (DE) miRNAs ranged from one to eight, and through the whole gut, seven miRNAs were up-regulated and seven were down-regulated in SS. The distal jejunum and rectum were the regions where the most DE miRNAs were identified (8 and 7, respectively). Functional analysis indicated that the bta-miR-378b, bta-miR-2284j and bta-miR-2284d which were down-regulated in both distal jejunum and rectum of SS, the bta-miR-2887 which was down-regulated in rectum of SS, as well as the bta-miR-211 and bta-miR-29d-3p which were up-regulated in rectum of SS were potentially regulatory to host immune functions, including hematological system development and immune cell trafficking. Our findings suggest that the alternation of miRNA expression in the gut of SS may lead to differential regulation in immune functions involved in E. coli O157 super-shedding in cattle.
2018-12-01 | GSE96973 | GEO
Project description:The current study aimed to investigate whether bovine non-coding RNA play a role in regulating E. coli O157 shedding through studying miRNAomes of the whole gastrointestinal tract including duodenum, proximal jejunum, distal jejunum, cecum, spiral colon, descending colon and rectum. The number of miRNAs detected in each intestinal region ranged from 390 ± 13 to 413 ± 49. Compared between SS and NS, the number of differentially expressed (DE) miRNAs ranged from one to eight, and through the whole gut, seven miRNAs were up-regulated and seven were down-regulated in SS. The distal jejunum and rectum were the regions where the most DE miRNAs were identified (8 and 7, respectively). Functional analysis indicated that the bta-miR-378b, bta-miR-2284j and bta-miR-2284d which were down-regulated in both distal jejunum and rectum of SS, the bta-miR-2887 which was down-regulated in rectum of SS, as well as the bta-miR-211 and bta-miR-29d-3p which were up-regulated in rectum of SS were potentially regulatory to host immune functions, including hematological system development and immune cell trafficking. Our findings suggest that the alternation of miRNA expression in the gut of SS may lead to differential regulation in immune functions involved in E. coli O157 super-shedding in cattle.
2018-10-30 | GSE121916 | GEO