MicroRNA-512-3p mediates Trypanosoma cruzi-induced apoptosis during ex vivo infection of human placental explants.

INTRODUCTION: Upon infection, Trypanosoma cruzi, a protozoan parasite, crosses the placental barrier and causes congenital Chagas disease. Ex vivo infection of human placental explants (HPEs) with the parasite induces apoptotic cell death. This cellular process involves changes in gene expression, which are partially regulated by miRNAs. In this study, we investigated the role of miR-512-3p, a highly expressed miRNA in the placenta, in parasite-induced apoptosis. METHODS: HPE cells were transfected with antagomirs or mimics of miR-512-3p and subsequently challenged with the parasite. The expression levels of miR-512-3p, caspase 3, caspase 8, and Livin were measured using RT-qPCR, and apoptotic cell death was analyzed based on caspase activity and DNA fragmentation assays. RESULTS: Targeted inhibition of miR-512-3p effectively prevented parasite-induced expression and enzymatic activity of caspase 3 and caspase 8. However, it did not completely prevent DNA fragmentation, indicating the involvement of other factors in this process. Furthermore, the findings suggest that Livin may be regulated by miR-512-3p. DISCUSSION: Our findings suggest that miR-512-3p modulates parasite-induced apoptosis in the trophoblast. By understanding the mechanisms involved in this process, we can gain insights into the pathogenesis of congenital Chagas disease and develop targeted therapeutic strategies.

Genetic Variant HLA-DRB1*0403 and Therapeutic Response to Disease-Modifying Therapies in Multiple Sclerosis: A Case-Control Study.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, which leads to neurodegeneration and progressive disability. Approximately 30 to 50% of patients do not respond optimally to disease-modifying therapies (DMTs), and therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3) was used to classify the therapeutic response. Patients were classified as follows: (a) controls: patients who achieved NEDA-3; (b) cases: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA-DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were GG 50.5%, GA 34.3%, and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p = 0.6). We concluded that in Mexican patients with MS, HLA-DRB1*0403 was not associated with the therapeutic response to DMTs.

Differential microRNAs expression during ex vivo infection of canine and ovine placental explants with Trypanosoma cruzi and Toxoplasma gondii.

Trypanosoma cruzi and Toxoplasma gondii are two zoonotic parasites that constitute significant human and animal health threats, causing a significant economic burden worldwide. Both parasites can be transmitted congenitally, but transmission rates for T. gondii are high, contrary to what has been observed for T. cruzi. The probability of congenital transmission depends on complex interactions between the pathogen and the host, including the modulation of host cell gene expression by miRNAs. During ex vivo infection of canine and ovine placental explants, we evaluated the expression of 3 miRNAs (miR-30e-3p, miR-3074-5p, and miR-127-3p) previously associated with parasitic and placental diseases and modulated by both parasites. In addition, we identified the possible target genes of the miRNAs by using computational prediction tools and performed GO and KEGG enrichment analyses to identify the biological functions and associated pathologies. The three miRNAs are differentially expressed in the canine and ovine placenta in response to T. cruzi and T. gondii. We conclude that the observed differential expression and associated functions might explain, at least partially, the differences in transmission rates and susceptibility to parasite infection in different species.

MicroRNAs: master regulators in host-parasitic protist interactions.

MicroRNAs (miRNAs) are a group of small non-coding RNAs present in a wide diversity of organisms. MiRNAs regulate gene expression at a post-transcriptional level through their interaction with the 3' untranslated regions of target mRNAs, inducing translational inhibition or mRNA destabilization and degradation. Thus, miRNAs regulate key biological processes, such as cell death, signal transduction, development, cellular proliferation and differentiation. The dysregulation of miRNAs biogenesis and function is related to the pathogenesis of diseases, including parasite infection. Moreover, during host-parasite interactions, parasites and host miRNAs determine the probability of infection and progression of the disease. The present review is focused on the possible role of miRNAs in the pathogenesis of diseases of clinical interest caused by parasitic protists. In addition, the potential role of miRNAs as targets for the design of drugs and diagnostic and prognostic markers of parasitic diseases is also discussed.

Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation.

Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local placental defense against the parasite. Thus, Trypanosoma cruzi induces cellular proliferation, differentiation, and apoptotic cell death in the trophoblast, which are regulated, among other mechanisms, by small non-coding RNAs such as microRNAs. On the other hand, ex vivo infection of human placental explants induces a specific microRNA profile that includes microRNAs related to trophoblast differentiation such as miR-512-3p miR-515-5p, codified at the chromosome 19 microRNA cluster. Here we determined the expression validated target genes of miR-512-3p and miR-515-5p, specifically human glial cells missing 1 transcription factor and cellular FLICE-like inhibitory protein, as well as the expression of the main trophoblast differentiation marker human chorionic gonadotrophin during ex vivo infection of human placental explants, and examined how the inhibition or overexpression of both microRNAs affects parasite infection. We conclude that Trypanosoma cruzi-induced trophoblast epithelial turnover, particularly trophoblast differentiation, is at least partially mediated by placenta-specific miR-512-3p and miR-515-5p and that both miRNAs mediate placental susceptibility to ex vivo infection of human placental explants. Knowledge about the role of parasite-modulated microRNAs in the placenta might enable their use as biomarkers, as prognostic and therapeutic tools for congenital Chagas disease in the future.

microRNAs: Critical Players during Helminth Infections.

microRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression post-transcriptionally through their interaction with the 3' untranslated regions (3' UTR) of target mRNAs, affecting their stability and/or translation. Therefore, miRNAs regulate biological processes such as signal transduction, cell death, autophagy, metabolism, development, cellular proliferation, and differentiation. Dysregulated expression of microRNAs is associated with infectious diseases, where miRNAs modulate important aspects of the parasite-host interaction. Helminths are parasitic worms that cause various neglected tropical diseases affecting millions worldwide. These parasites have sophisticated mechanisms that give them a surprising immunomodulatory capacity favoring parasite persistence and establishment of infection. In this review, we analyze miRNAs in infections caused by helminths, emphasizing their role in immune regulation and its implication in diagnosis, prognosis, and the development of therapeutic strategies.

Enfermedad de Creutzfeldt-Jakob / Creutzfeldt-Jakob disease

Resumen: La enfermedad de Creutzfeldt-Jakob es una afección neuroselectiva y neurodegenerativa, de curso fatal, poco frecuente, que representa un desafío para el diagnóstico clínico. Se comunica el caso de un paciente de 52 años de edad con antecedente de ingesta de mamíferos silvestres durante su vida, con cuadro de disminución de la agudeza visual, demencia rápidamente progresiva, mioclonías, movimientos anormales y disfunción motora; con estudios auxiliares de diagnóstico diferencial dentro de parámetros normales y la determinación de la proteína TAU reactiva.

Abstract: Creutzfeldt-Jakob disease is a neuroselective and neurodegenerative illness, with fatal course, which is rare and represents a challenge for clinical diagnosis. This paper reports the case of a 52-year-old male with a history of ingestion of wild mam- mals during his life, with a picture of diminished visual acuity, rapidly progressive dementia, myoclonus, abnormal movements and motor dysfunction; with auxiliary studies of differential diagnosis within normal parameters and the determination of reactive TAU protein.

Effect of vildagliptin on glucose and insulin concentrations during a 24-hour period in type 2 diabetes patients with different ranges of baseline hemoglobin A1c levels.

BACKGROUND: Currently, it is still unknown whether differences in glycemic control have any effect on glucose and insulin kinetics after vildagliptin administration. The aim of this study was to evaluate the effect of vildagliptin on glucose and insulin concentrations during a 24-h period in type 2 diabetes patients with different ranges of baseline hemoglobin A1c (A1C) levels. PATIENTS AND METHODS: A randomized, double-blind, crossover, placebo-controlled clinical trial was carried out in 12 drug-naive adult volunteers with type 2 diabetes and overweight or obesity. Subjects had fasting glucose values between 7.2 and 13.3 mmol/L. Six patients had A1C between 7.0% and 8.4% (Group A), and the remaining subjects had A1C between 8.5% and 10.0% (Group B). Patients received oral administration of vildagliptin (50 mg twice daily) or placebo in a crossover manner for two consecutive days. Until the second day of the interventions, glucose and insulin concentrations were measured every hour during a 24-h period, and areas under the curve (AUCs) were calculated. Statistical analyses were evaluated with Wilcoxon and Mann-Whitney U tests. RESULTS: There were significant decreases in glucose concentrations after vildagliptin administration in both groups when comparing placebo in all measurements throughout the 24-h period and in the AUC. There were no significant changes in insulin concentration in both groups after vildagliptin administration when comparing placebo in all measurements throughout the 24-h period and in the AUC. CONCLUSIONS: Vildagliptin administration improved glucose control during a 24-h period in type 2 diabetes patients, independent of the basal A1C level, without changes in insulin levels.