Role of non-coding RNAs and exosomal non-coding RNAs in retinoblastoma progression.

Retinoblastoma (RB) is a rare aggressive intraocular malignancy of childhood that has the potential to affect vision, and can even be fatal in some children. While the tumor can be controlled efficiently at early stages, metastatic tumors lead to high mortality. Non-coding RNAs (ncRNAs) are implicated in a number of physiological cellular process, including differentiation, proliferation, migration, and invasion, The deregulation of ncRNAs is correlated with several diseases, particularly cancer. ncRNAs are categorized into two main groups based on their length, i.e. short and long ncRNAs. Moreover, ncRNA deregulation has been demonstrated to play a role in the pathogenesis and development of RB. Several ncRNAs, such as miR-491-3p, miR-613,and SUSD2 have been found to act as tumor suppressor genes in RB, but other ncRNAs, such as circ-E2F3, NEAT1, and TUG1 act as tumor promoter genes. Understanding the regulatory mechanisms of ncRNAs can provide new opportunities for RB therapy. In the present review, we discuss the functional roles of the most important ncRNAs in RB, their interaction with the genes responsible for RB initiation and progression, and possible future clinical applications as diagnostic and prognostic tools or as therapeutic targets.

Albendazole ameliorates inflammatory response in a rat model of acute mesenteric ischemia reperfusion injury.

BACKGROUND: Acute mesenteric ischemia is known as a life threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. METHODS: Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 min followed by 120 min of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. RESULTS: Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. CONCLUSION: Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. More studies would clarify existing causality in this phenomenon.

New epigenetic players in stroke pathogenesis: From non-coding RNAs to exosomal non-coding RNAs.

Non-coding RNAs (ncRNAs) have critical role in the pathophysiology as well as recovery after ischemic stroke. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are critical for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. Moreover, exosomes have been considered as nanocarriers capable of transferring various cargos, such as lncRNAs and miRNAs to recipient cells, with prominent inter-cellular roles in the mediation of neuro-restorative events following strokes and neural injuries. In this review, we summarize the pathogenic role of ncRNAs and exosomal ncRNAs in the stroke.

Clinical outcome and determinants of amputation in a large cohort of Iranian patients with diabetic foot ulcers.

OBJECTIVE: Determining the predictive factors of diabetes foot ulcer (DFU) development and lower extremity amputations (LEA) in patients with diabetes mellitus (DM) is of great importance to compose risk stratification models. The aim of this study is to investigate the outcome and predictors of LEA in patients with DFU in large sample of Iranian patients. METHODS: This prospective cohort study was conducted during a 2-year period from 2014 to 2016, in Shiraz, southern Iran. All the patients with type 1 and 2 DM and DFU were included in the cohort and were followed for 2 years at least. They were visited in the clinic on a monthly basis and development of new DFU and LEA were recorded. The two-year free-DFU survival and predictors of the DFU development and LEA were recorded. Multivariate regression models were used to determine the factors. RESULTS: A total number of 432 patients with mean age of 56.8 ± 13.3 years were included. The two-year DFU-free survival rate was 0.826. The two-year DFU-free survival was associated with male gender (p = 0.005), foot deformity (p = 0.002), history of prior DFU (p < 0.001), cigarette smoking (p = 0.032), nephropathy (p = 0.005), retinopathy (p = 0.007), ischemic heart disease (p = 0.043), and neuropathy (p < 0.001). CONCLUSION: Development of new DFU is associated with higher age, longer duration of disease, and type I diabetes. LEA was associated with increased white blood cell (WBC), Creatinine and ulcer history for major amputation and ulcer history, fasting blood sugar (FBS), infection, revascularization history, and foot deformity, for minor amputation.