We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past. These T1D SC-β cells express β-cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of β-cell stress. Using these assays, we find no major differences in T1D SC-β cells compared with SC-β cells derived from non-diabetic patients. These results show that T1D SC-β cells could potentially be used for the treatment of diabetes, drug screening and the study of β-cell biology.

Pyroptosis is a type of proinflammatory programmed cell death mediated by caspase 1 activity and occurs in several types of eukaryotic tumor cells, including gliomas. MicroRNAs (miRNAs), small endogenous noncoding RNAs, have been demonstrated to be advantageous in glioma therapy. However, the question of whether miRNAs regulate pyroptosis in glioma remains unknown. The current study found that caspase 1 expression was substantially increased in both glioma tissues and glioma cell lines, U87 and T98G, while miR-214 expression was significantly downregulated. Luciferase reporter assay recognized caspase 1 as a target gene of miR-214. These findings demonstrate that miR-214 could inhibit cell proliferation and migration through the regulation of pyroptosis intermediated by caspase 1 in glioma U87 and T98G cells and may suggest a novel therapeutic for the intervention of glioma.

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Our study for the first time demonstrated a significant correlation between HS ILAE types and long-term postoperative seizure outcome in patients with MTLE due to HS. Therefore, HS ILAE types have predictive value in long-term seizure outcome following epilepsy surgery.

Lecithin-cholesterol acyltransferase deficiency is frequently associated with hypertriglyceridemia (HTG) in animal models and humans. We investigated the mechanism of HTG in the ldlr؊/؊ ؋ lcat؊/؊ (double knockout (dko)) mice using the ldlr؊/؊ ؋ lcat؉/؉ (knock-out (ko)) littermates as control. Mean fasting triglyceride (TG) levels in the dko mice were elevated 1.75-fold compared with their controls (p < 0.002). Both the very low density lipoprotein and the low density lipoprotein/intermediate density lipoprotein fractions separated by fast protein liquid chromatography were TG-enriched in the dko mice. In vitro lipolysis assay revealed that the dko mouse very low density lipoprotein (d < 1.019 g/ml) fraction separated by ultracentrifugation was a more efficient substrate for lipolysis by exogenous bovine lipoprotein lipase. Post-heparin lipoprotein lipase activity was reduced by 61% in the dko mice. Hepatic TG production rate, determined after intravenous Triton WR1339 injection, was increased 8-fold in the dko mice. Hepatic mRNA levels of sterol regulatory element binding protein-1 (srebp-1) and its target genes acetyl-CoA carboxylase-1 (acc-1), fatty acid synthase (fas), and stearoyl-CoA desaturase-1 (scd-1) were significantly elevated in the dko mice compared with the ko control. The hepatic mRNA levels of LXR␣ (lxr␣) and its target genes including angiopoietin-like protein 3 (angptl-3) in the dko mice were unchanged. Fasting glucose and insulin levels were reduced by 31 and 42%, respectively in the dko mice, in conjunction with a 49% reduction in hepatic pepck-1 mRNA (p ‫؍‬ 0.014). Both the HTG and the improved fasting glucose phenotype seen in the dko mice are at least in part attributable to an up-regulation of the hepatic srebp-1c gene.

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Glioblastoma multiform is one of the most common and most aggressive brain tumors in humans. The molecular and cellular mechanisms responsible for the onset and progression of GBM are elusive and controversial. The function of tumor suppressor candidate 3 (TUSC3) has not been previously characterized in GBM. TUSC3 was originally identified as part of an enzyme complex involved in N-glycosylation of proteins, but was recently implicated as a potential tumor suppressor gene in a variety of cancer types. In this study, we demonstrated that the expression levels of TUSC3 were downregulated in both GBM tissues and cells, and also found that overexpression of TUSC3 inhibits GBM cell proliferation and invasion. In addition, the effects of increased levels of methylation on the TUSC3 promoter were responsible for decreased expression of TUSC3 in GBM. Finally, we determined that TUSC3 regulates proliferation and invasion of GBM cells by inhibiting the activity of the Akt signaling pathway.

BackgroundTo investigate the clinical characteristics and treatment outcomes in necrotizing fasciitis (NF) patients in a reconstructive unit in northeastern China.MethodsMedical records of patients diagnosed with and treated for NF in the extremities from November 2013 to December 2016 were retrospectively reviewed. Demographic data, clinical presentation, duration of signs and symptoms, location of infection, predisposing factors, causative microbiological organisms, laboratory risk indicator for necrotizing fasciitis (LRINEC) score, number of surgical debridements, length of hospital stay, treatments, and outcomes were recorded.ResultsA total of 39 consecutive patients were treated for severe NF (32 male and 7 female). Diabetes mellitus and blunt trauma were the most common risk factors (13 and 9 cases, respectively). The positive predictive value of the LRINEC score in NF diagnosis was 46.2%. Mean duration of signs and symptoms was 4.6 days. Staphylococcus aureus was the most commonly isolated bacteria (20 cases). All patients underwent their first debridement within 12 h of presentation (mean, 4.6 h). Mean number of surgical treatments was 2.8 (range, 2–5) per patient, including debridements. All patients survived, and mean length of hospital stay was 30.81 (range, 21–43) days. Three patients underwent limb amputation.ConclusionsIn our clinical experience, early detection and aggressive debridement are the cornerstones of NF treatment. Antibiotic therapy and intensive care support is essential in severe cases of NF. Anaerobic tissue culture and frozen section biopsy could be adopted as routine tests for diagnosis and decision-making in NF. These findings should inform clinical decisions about the treatment of individual patients with NF.