Effect of bone marrow mesenchymal stem cells-derived exosomes on diabetes-induced retinal injury: Implication of Wnt/ b-catenin signaling pathway.

BACKGROUND: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Mesenchymal stem cells are currently studied as therapeutic strategy for management of DR. Exosomes, considered as a promising cell-free therapy option, display biological functions similar to those of their parent cells. In retinal development, Wnt/b-catenin signaling provides key cues for functional progression. The present study aimed to evaluate the potential efficacy of bone marrow-derived mesenchymal stem cell-derived exosomes (BM-MSCs-Ex) in diabetes-induced retinal injury via modulation of the Wnt/ b-catenin signaling pathway. METHODS: Eighty-one rats were allocated into 6 groups (control, DR, DR + DKK1, DR + exosomes, DR + Wnt3a and DR + exosomes+Wnt3a). Evaluation of each group was via histopathological examination, assessment of gene and/or protein expression concerned with oxidative stress (SOD1, SOD2, Nox2, Nox4, iNOS), inflammation (TNF-α, ICAM-1, NF-κB) and angiogenesis (VEGF, VE-cadherin). RESULTS: Results demonstrated that exosomes blocked the wnt/b-catenin pathway in diabetic retina concomitant with significant reduction of features of DR as shown by downregulation of retinal oxidants, upregulation of antioxidant enzymes, suppression of retinal inflammatory and angiogenic markers. These results were further confirmed by histopathological results, fundus examination and optical coherence tomography. Additionally, exosomes ameliorative effects abrogated wnt3a-triggered retinal injury in DR. CONCLUSION: Collectively, these data demonstrated that exosomes ameliorated diabetes-induced retinal injury via suppressing Wnt/ b-catenin signaling with subsequent reduction of oxidative stress, inflammation and angiogenesis

Common surgical procedures in pilonidal sinus disease: A meta-analysis, merged data analysis, and comprehensive study on recurrence

Abstract We systematically searched available databases. We reviewed 6,143 studies published from 1833 to 2017. Reports in English, French, German, Italian, and Spanish were considered, as were publications in other languages if definitive treatment and recurrence at specific follow-up times were described in an English abstract. We assessed data in the manner of a meta-analysis of RCTs; further we assessed non-RCTs in the manner of a merged data analysis. In the RCT analysis including 11,730 patients, Limberg & Dufourmentel operations were associated with low recurrence of 0.6% (95%CI 0.3–0.9%) 12 months and 1.8% (95%CI 1.1–2.4%) respectively 24 months postoperatively. Analysing 89,583 patients from RCTs and non-RCTs, the Karydakis & Bascom approaches were associated with recurrence of only 0.2% (95%CI 0.1–0.3%) 12 months and 0.6% (95%CI 0.5–0.8%) 24 months postoperatively. Primary midline closure exhibited long-term recurrence up to 67.9% (95%CI 53.3–82.4%) 240 months post-surgery. For most procedures, only a few RCTs without long term follow up data exist, but substitute data from numerous non-RCTs are available. Recurrence in PSD is highly dependent on surgical procedure and by follow-up time; both must be considered when drawing conclusions regarding the efficacy of a procedure