BackgroundHyperglycemia is a significant risk factor for diabetic retinopathy and induces increased inflammatory responses and retinal leukostasis, as well as vascular damage. Although there is an increasing amount of evidence that miRNA may be involved in the regulation in the pathology of diabetic retinopathy, the mechanisms by which miRNA mediate cellular responses to control onset and progression of diabetic retinopathy are still unclear. The purpose of our study was to investigate the hypothesis that miR-15a/16 inhibit pro-inflammatory signaling to reduce retinal leukostasis.MethodsWe generated conditional knockout mice in which miR-15a/16 are eliminated in vascular endothelial cells. For the in vitro work, human retinal endothelial cells (REC) were cultured in normal (5 mM) glucose or transferred to high glucose medium (25 mM) for 3 days. Transfection was performed on REC in high glucose with miRNA mimic (hsa-miR-15a-5p, hsa-miR-16-5p). Statistical analyses were done using unpaired Student t test with two-tailed p value. p < 0.05 was considered significant. Data are presented as mean ± SEM.ResultsWe demonstrated that high glucose conditions decreased expression of miR-15a/16 in cultured REC. Overexpression of miR-15a/16 with the mimic significantly decreased pro-inflammatory signaling of IL-1β, TNFα, and NF-κB in REC. In vivo data demonstrated that the loss of miR-15a/16 in vascular cells led to increased retinal leukostasis and CD45 levels, together with upregulated levels of IL-1β, TNFα, and NF-κB.ConclusionsThe data indicate that miR-15a/16 play significant roles in reducing retinal leukostasis, potentially through inhibition of inflammatory cellular signaling. Therefore, we suggest that miR-15a/16 offer a novel potential target for the inhibition of inflammatory mediators in diabetic retinopathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0771-8) contains supplementary material, which is available to authorized users.
INTRODUCTION: HCC is the most common primary liver cancer and five-year survival of HCC depends on the extent of disease and liver reserve. The objective of this study was to determine the impact of racial disparity in identification, treatment and outcome in HCC patients seen in a predominately African American (AA) population. METHODS: From a database of HCC patients diagnosed between 2009 and 2017, 227 patients had a sufficient number of visits to identify treatment and outcomes. Date of diagnosis was defined by definitive imaging or biopsy. Tumor size (small = < 5 cm) was used as a surrogate for calculating Child’s-Pugh score in these predominately Hepatitis C cirrhotic patients. Outcomes was determined as death or transfer to hospice, while survival was defined by death only. Patients being sent to transplant (9 AA and 1 Non-AA ) were excluded from the analysis since transplant was at a different institution. RESULTS: There were 194 AA and 33 non-AA patients and hepatitis C was the dominant risk factor (n = 192; 85%). Only 29 patients (13%) were diagnosed under even a minimal surveillance protocol defined as a normal ultrasound within 6-12 months prior to diagnosis. AA patients were more likely to have a large tumor burden as compared to non-AA (AA = 74% and Non-AA = 51 %; P < 0.01). A variety of treatments for the HCC were use in the 61% of patients who received treatment. The remaining 39% of patients either died in the hospital prior to treatment or were sent to hospice for palliative care. Median outcome was better for patients with a small tumor at diagnosis, treated patients and for non-HCV patients (Table 1). When survival was evaluated, results were similar (44 months for small tumors vs 10 months for large tumors P < 0.001). Race did not have a major impact on overall outcome (AA = 16 months vs Non-AA = 20 months, P = 0.33) or survival (20 months vs 34 months P = 0.35). CONCLUSION: Most patients diagnosed with HCC in this urban medical center presented with large tumors with AA patients likelier to have large tumor burden. Outcome was better for patients with small tumors or who were treated regardless of tumor size. However, overall outcome was similar regardless of race. Our study reaffirms the potential importance of surveillance of high-risk individuals to identify early HCC tumors and thus increase survival in our AA population. Moreover, addressing the major risk factor of HCV by treatment with highly effective DAA would also impact the development of HCC especially in our AA population.
Conclusion: These data suggest that the sequence of developing HIV infection and IBD may influence the clinical course. While progressive immune depletion in HIV infection may diminish the clinical severity of established IBD, its de novo development in an HIV-infected patient may lead to serious disease with significant disease-related morbidity. We hypothesize that the development of IBD in an HIVinfected patient may be a mirror image of the remission hypothesis; prospective studies are needed for confirmation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.