Chagas disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a public health problem affecting 6 to 8 million people, mainly in Latin America. The role of microRNAs in the pathogenesis of Chagas disease has not been well described. Here, we investigate the role of microRNA-155 (miR-155), a proinflammatory host innate immune regulator responsible for T helper type 1 and type 17 (Th1 and Th17) development and macrophage responses during T. cruzi infection. For this, we compared the survival and parasite growth and distribution in miR-155−/− and wild-type (WT) C57BL/6 mice. The lack of miR-155 caused robust parasite infection and diminished survival of infected mice, while WT mice were resistant to infection. Immunological analysis of infected mice indicated that, in the absence of miR-155, there was decreased interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. In addition, we found that there was a significant reduction of CD8-positive (CD8+) T cells, natural killer (NK) cells, and NK-T cells and increased accumulation of neutrophils and inflammatory monocytes in miR-155−/− mice. Collectively, these data indicate that miR-155 is an important immune regulatory molecule critical for the control of T. cruzi infection.

Our findings show that oral Ibrutinib is highly effective for the treatment of VL caused by L. donovani and mediates its anti-leishmanial activity by promoting host immunity. Therefore, Ibrutinib could be a novel host-targeted drug for the treatment of VL.

Objectives: Patients experiencing functional constipation (FC) can participate in structured bowel management programs (BMPs) to manage constipation or fecal incontinence when standard management fails. We sought to evaluate the efficacy of BMPs for children with FC with and without neurodevelopmental disorders. Methods: We performed a retrospective review of children with FC who participated in our BMP from 2014 to 2021. Stool/urinary continence, bowel regimen, surgical history, parent-reported outcomes measures (PROMs: Cleveland Clinic Constipation Score, Baylor Continence Scale, Vancouver Symptom Score for Dysfunctional Elimination), and Pediatric Quality of Life Inventory (PedsQL) were assessed pre-and at least 9 months post-BMP. Results: The cohort included 156 patients with a median age of 9 years and follow-up of 627 days (IQR: 389-808 days). Two sub-cohorts included patients with FC only (69%) and FC plus a neurodevelopmental disorder (31%): 59% attention-deficit/hyperactivity disorder, 33% autism spectrum disorder, and 8% obsessive-compulsive disorder. Both groups had significantly improved follow-up bowel movement frequency and continence (39%-90% neurodevelopmental, 44%-82% FC only, P < 0.001) and urinary continence (65%-90% neurodevelopmental, 69%-91% FC only, P < 0.02). There was a significant improvement in most of the PROMs at follow-up. Both groups experienced a clinically meaningful improvement in overall PedsQL scores (pre-and postBMP difference of >4.5). Conclusions: Patients with FC with and without a neurodevelopmental disorder had significant improvement in stool and urinary continence after undergoing a BMP. Further studies are needed to see if this improvement is durable over a longer period of time in this challenging cohort.