Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and combination therapy with gemcitabine was also evaluated. In cell culture, MYXV replication was robust in a broad range of pancreatic cancer cells and also showed increased oncolysis in combination with gemcitabine. In animal models, MYXV treatment conferred survival benefits over control or gemcitabine-treated cohorts regardless of the cell line or animal model used. MYXV monotherapy was most effective in an immunocompetent IPD model, and resulted in 60% long-term survivors. In Pan02 engrafted immunocompetent IPD models, sequential treatment in which MYXV was administered first, followed by gemcitabine, was the most effective and resulted in 100% long-term survivors. MYXV is an effective oncolytic virus for pancreatic cancer and can be combined with gemcitabine to enhance survival, particularly in the presence of an intact host immune system.
MicroRNAs (miRNAs), small non-coding RNAs, have been implicated in various diseases and cellular functions as microregulators of gene expression. Although the history of miRNA investigation in autoimmune Sjögren’s syndrome (SjS) is fairly short, a substantial amount of data has already been accumulated. These findings clearly indicate potential clinical implications of miRNAs, such as autoantigen expression and autoantibody production, viral miRNAs regulating the calcium signaling pathway, and aberrant immune cell regulation and cytokine production. Research endeavors in the field are currently underway to select disease-specific diagnostic and prognostic biomarkers by utilizing different types of tissues or biological specimens of SjS patients. Various techniques for miRNA analysis with different stringencies have been applied, with the most recent one being next-generation sequencing. This review compiles and highlights differentially-expressed miRNAs in various samples collected from SjS patients and their potential implications in the pathogenesis of SjS. To facilitate the development of miRNA-targeted personalized therapy in the future, we urge more follow-up studies that confirm these findings and elucidate the immunopathological roles of differentially-expressed miRNAs. Furthermore, improved diagnostic criteria for the disease itself will minimize sampling errors in patient recruitment, preventing the generation of inconsistent data.
Background Poor glycaemic control is associated with a greater risk of development of heart failure in diabetic patients. We aimed to study the prevalence of left ventricular (LV) systolic and diastolic dysfunction in asymptomatic patients with new-onset type 2 DM. We conducted a cross-sectional study including patients with newly diagnosed (within 1 year) type 2 DM; all patients were between the ages of 30 and 60 years, normotensive and clinically asymptomatic and attended the outpatient clinic of the endocrinology unit at a university hospital between March 2016 and June 2017. Demographic characteristics, clinical risk factors and waist-hip ratio (WHR) were assessed. Blood samples for laboratory analysis were obtained. Detailed echocardiography was performed to evaluate systolic and diastolic function. Results A total of 100 patients were included. Sixty-one percent had diastolic dysfunction with preserved ejection fraction. Left ventricular diastolic dysfunction (LVDD) was more prevalent in diabetic patients with HbA1c ≥ 8.1 (75%) Patients with LVDD had significant dyslipidaemia in comparison to those without LVDD. Multivariate logistic regression analysis showed that WHR and HbA1c levels are the only predictors of impaired diastolic function in patients with new-onset DM. Kaplan-Meier survival curves showed a significant correlation between the incidence of diastolic dysfunction and the duration of DM, with higher incidence with HbA1c ≥ 8.1. Conclusions Diastolic dysfunction is highly prevalent in patients with newly diagnosed DM and is positively correlated with HbA1c level, obesity, dyslipidaemia and the duration of diabetes.
External root resorption (ERR) is a silent destructive phenomenon detrimental to dental health. ERR may have multiple etiologies such as infection, inflammation, traumatic injuries, pressure, mechanical stimulations, neoplastic conditions, systemic disorders, or idiopathic causes. Often, if undiagnosed and untreated, ERR can lead to the loss of the tooth or multiple teeth. Traditionally, clinicians have relied on radiographs and cone beam computed tomography (CBCT) images for the diagnosis of ERR; however, these techniques are not often precise or definitive and may require exposure of patients to more ionizing radiation than necessary. To overcome these shortcomings, there is an immense need to develop non-invasive approaches such as biomarker screening methods for rapid and precise diagnosis for ERR. In this review, we performed a literature survey for potential salivary or gingival crevicular fluid (GCF) proteomic biomarkers associated with ERR and analyzed the potential pathways leading to ERR. To the best of our knowledge, this is the first proteomics biomarker survey that connects ERR to body biofluids which represents a novel approach to diagnose and even monitor treatment progress for ERR.
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