MicroRNAs (miRs) are master regulators of post-transcriptional gene expression, and they are often dysregulated in individuals suffering from diabetes. We investigated the roles of miR-101-3p and miR-204-5p, both of which negatively regulate insulin secretion and cell survival and are highly expressed in pancreatic β cells, in the context of type 1 diabetes (T1D) pathogenesis. Using quantitative real time PCR, we evaluated serum levels of miR-101-3p and miR-204-5p in four groups, including recent-onset T1D patients (T1D group;
n
= 50), individuals with normal glucose levels expressing one islet autoantibody (Ab) (single Ab group;
n
= 26) or multiple autoantibodies (multiple Ab group;
n
= 12), and healthy controls (control group;
n
= 43). An
in silico
analysis was performed to identify potential target genes of these miRNAs and to delineate enriched pathways. The relative expression of serum miR-101-3p was approximately three times higher in the multiple Ab and T1D groups than that in the single Ab and control groups (
p
< 0.0001). When considering all groups together, miR-101-3p expression was positively correlated with the level of islet autoantibodies GADA (
r
= 0.267;
p
= 0.0027) and IA-2A (
r
= 0.291;
p
= 0.001), and the expression of the miRNA was not correlated with levels of ZnT8A (
r
= 0.125;
p
= 0.183). miR-101-3p expression did not correlate with HbA1c (
r
= 0.178;
p
= 0.052) or glucose levels (
r
= 0.177;
p
= 0.051). No significant differences were observed in miR-204-5p expression among the analyzed groups. Computational analysis of the miR-101-3p target gene pathways indicated a potential activation of the HGF/c-Met, Ephrin receptor, and STAT3 signaling pathways. Our study demonstrated that the circulating levels of miR-101-3p are higher in T1D patients and in individuals with normal glucose levels, testing positive for multiple autoantibodies, indicating that miR-101-3p precedes loss of glucose homeostasis. The pathogenic role of miR-101-3p in T1D may involve multiple molecular pathways.
fThe intracellular protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion by T. cruzi and its intracellular replication are essential to the parasite's life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host's cyclooxygenase (COX) enzymes during T. cruzi invasion. Pharmacological antagonists for COX-1 (aspirin) and COX-2 (celecoxib) caused marked inhibition of T. cruzi infection when rat cardiac cells were pretreated with these nonsteroidal anti-inflammatory drugs (NSAIDs) for 60 min at 37°C before inoculation. This inhibition was associated with an increase in the production of NO and interleukin-1 and decreased production of transforming growth factor  (TGF-) by cells. Taken together, these results indicate that COX-1 more than COX-2 is involved in the regulation of anti-T. cruzi activity in cardiac cells, and they provide a better understanding of the influence of TGF--interfering therapies on the innate inflammatory response to T. cruzi infection and may represent a very pertinent target for new therapeutic treatments of Chagas disease.
The SaMi-Trop project is a cohort study conducted in 21 municipalities of endemic
areas of Chagas disease, including 1,959 patients with chronic Chagas
cardiomyopathy. In this article we updated the results of the project, adding
information from the second cohort visit.
Trypanosoma
cruzi-
seropositive patients were enrolled from the primary care
Telehealth service in Minas Gerais State, Brazil. The eligibility criterium for
the second visit was the participation in the baseline evaluation. Of 1,959
participants at the baseline assessment, 1,585 (79.9%) returned after two years
for the second evaluation. The mortality rate was 6.7%, but varied from 0.9% to
18.2% when it was stratified by certain clinical characteristics. A lower
age-adjusted NT-Pro-BNP level (less than 300) and a prior benznidazole treatment
were associated with lower mortality. There was an improvement in most quality
of life domain scores. Participants have also reported fewer signs and symptoms
and greater use of medication. The second follow-up visit will be complete in
Oct 2021.
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.