Incidence and trends of type 1 diabetes before and after 2000 in the Western Pacific Region: A systematic review and meta-analysis.

OBJECTIVES: To undertake a systematic review of publications describing Type 1 diabetes (T1DM) incidence, trends over time and associated factors in the Western Pacific Region (WPR). METHODS: As per the PROSPERO-registered (CRD42019122646) protocol English (MEDLINE, Embase, Global Health) and Chinese data-bases (China National Knowledge Infrastructure, VIP, Wanfang) from onset to 31/12/2019 were searched for T1DM incidence in the WPR. Country level data extracted included annual crude incidence rates by sex, number of new cases per annum (p.a.) and cumulatively, and the population at-risk. A meta-analysis for T1DM incidence was performed (by region and narrow age-bands, where possible) with subgroup analyses by time and by region. FINDINGS: Forty-five population-based studies (21 from China), published 1973-2017, estimated T1DM incidence, mostly in youth, in 11 WPR countries. After 2000, mean annual T1DM incidence/100,000 person years aged 0-14 years ranged from 0.9 (95 % confidence intervals (CI), 0.6-1.3) in Fiji to 23.2 (95 % CI, 21.3-25.2) in Australia. The mean annual increase over time ranged from 2.8 % in Australia (1990-2002) to 14.2 % in Shanghai (1997-2011). T1DM incidence increased most in China (2.7-fold over 30-years) then Thailand (2-fold over 15-years). Most studies documented increasing incidence with age, though only two studies included people aged ≥ 20 years. Many, but not all studies reported significantly higher T1DM incidence in females vs. males. CONCLUSION: T1DM incidence in the WPR is generally increasing, varying by age, sex, time and country. Results increase understanding of regional T1DM incidence and inform research and healthcare strategies.

Stellate ganglion block relieves acute lung injury induced by severe acute pancreatitis via the miR-155-5p/SOCS5/JAK2/STAT3 axis.

Acute lung injury (ALI), a prevalent complication of severe acute pancreatitis (SAP), is also a leading contributor to respiratory failure and even death of SAP patients. Here, we intended to investigate the function and mechanism of stellate ganglion block (SGB) in ameliorating SAP-induced ALI (SAP-ALI). We engineered an SAP-ALI model in rats and treated them with SGB. HE staining and the dry and wet method were implemented to evaluate pathological alterations in the tissues and pulmonary edema. The rats serum changes of the profiles of TNF-α, IL-6, IL-1ß, and IL-10 were examined. The profiles of miR-155-5p and SOCS5/JAK2/STAT3 were detected. Functional assays were performed for confirming the role of miR-155-5p in modulating the SOCS5/JAK2/STAT3 pathway in pulmonary epithelial cells. Our findings revealed that SGB vigorously alleviated SAP rat lung tissue damage and lung edema and lessened the generation of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. SGB enhanced SOCS5 expression, hampered miR-155-5p, and suppressed JAK2/STAT3 pathway activation. As evidenced by mechanism studies, miR-155-5p targeted the 3'UTR of SOCS5 and repressed its expression, hence resulting in JAK2/STAT3 pathway activation. During animal trials, we discovered that SGB ameliorated SAP-ALI, boosted SOCS5 expression, and mitigated the levels of pro-inflammatory factors and miR-155-5p in the plasma. In vitro, miR-155-5p overexpression substantially facilitated pulmonary epithelial cell apoptosis, inflammation, and JAK2/STAT3 pathway activation and restrained SOCS5 expression. All in all, our work hinted that SGB could modulate the miR-155-5p/SOCS5/JAK2/STAT3 axis to alleviate SAP-ALI.

Ras-AKT signaling represses the phosphorylation of histone H1.5 at threonine 10 via GSK3 to promote the progression of glioma.

Background: Histone H1.5 has been considered as a novel cancer marker as its expression is associated with various human cancers. The objective of this study was to explore the effects of H1.5 phosphorylation in Ras-driven growth and migration of glioma cells. Methods: The plasmids for expression of wide-type of Ras or RasG12V/Y40C were transfected into A172 cells. The expression levels of phosphorylated AKT and H1.5T10ph were tested by Western blot. The effects of H1.5T10ph on A172 cells growth and migration were determined by MTT, soft-agar colony formation, and transwell assay. qRT-PCR and ChIP assay were utilized to assess the role of H1.5T10ph in the transcription of Ras downstream genes. Besides, qRT-PCR and Western blot analysis were carried out to reveal the enzymes which were responsible for phosphorylating H1.5. Results: H1.5T10ph was down-regulated by Ras mutation, which accompanied by the activation of AKT signaling. Ras-driven A172 cells growth and migration were inhibited when H1.5T10ph was overexpressed. Additionally, H1.5T10ph was able to regulate the transcription of Ras downstream genes, including CYR61, IGFBP3, WNT16B, NT5E, GDF15, and CARD16. Further experiments revealed that Ras-AKT signaling repressed H1.5T10ph expression through degradation of GSK3, and the degradation was dependent on MDM2 mediation. Conclusion: Ras-AKT signaling driven the growth and migration of glioma cells possibly through repressing the phosphorylation of H1.5 at threonine 10. Ras-AKT activation repressed H1.5T10ph through MDM2-dependent degradation of GSK3. The findings provide a better understanding of Ras's oncogenic functions which further suggest Ras as a therapeutic target for glioma.

Zurampic Protects Pancreatic ß-Cells from High Uric Acid Induced-Damage by Inhibiting URAT1 and Inactivating the ROS/AMPK/ERK Pathways.

BACKGROUND/AIMS: Zurampic is a US FDA approved drug for treatment of gout. However, the influence of Zurampic on pancreatic ß-cells remains unclear. The study aimed to evaluate the effects of Zurampic on high uric acid-induced damage of pancreatic ß-cells and the possible underlying mechanisms. METHODS: INS-1 cells and primary rat islets were stimulated with Zurampic and the mRNA expression of urate transporter 1 (URAT1) was assessed by qRT-PCR. Cells were stimulated with uric acid or uric acid plus Zurampic, and cell viability, apoptosis and ROS release were measured by MTT and flow cytometry assays. Western blot analysis was performed to evaluate the expressions of active Caspase-3 and phosphorylation of AMPK and ERK. Finally, cells were stimulated with uric acid or uric acid plus Zurampic at low/high level of glucose (2.8/16.7 mM glucose), and the insulin release was assessed by ELISA. RESULTS: mRNA expression of URAT1 was decreased by Zurampic in a dose-dependent manner. Uric acid decreased cell viability, promoted cell apoptosis and induced ROS release. Uric acid-induced alterations could be reversed by Zurampic. Activation of Caspase-3 and phosphorylation of AMPK and ERK were enhanced by uric acid, and the enhancements were reversed by Zurampic. Decreased phosphorylation of AMPK and ERK, induced by Zurampic, was further reduced by adding inhibitor of AMPK or ERK. Besides, uric acid inhibited high glucose-induced insulin secretion and the inhibition was rescued by Zurampic. CONCLUSIONS: Zurampic has a protective effect on pancreatic ß-cells against uric acid induced-damage by inhibiting URAT1 and inactivating the ROS/AMPK/ERK pathway.

MicroRNA-215 enhances invasion and migration by targeting retinoblastoma tumor suppressor gene 1 in high-grade glioma.

OBJECTIVE: To elucidate the molecular mechanism of microRNA-215 (miR-215) in the migration and invasion of high grade glioma. RESULTS: 42 Patients were analysed for clinicopathological characteristics. qRT-PCR showed that miR-215 was up-regulated in glioma tissues compared with non-neoplastic brain tissues (P < 0.05). The up-regulated miR-215 was closely associated with high grade glioma (P < 0.01) and poor overall survival (P < 0.01). Transwell assay showed that re-expression of miR-215 enhanced migration and invasion of glioma cells. miR-215 also down-regulated retinoblastoma tumor suppressor gene 1 (RB1) expression by targeting its 3'-UTR. Reversely, re-expression of RB1 inhibited partial effect of miR-215 on migration and invasion in vitro. CONCLUSIONS: Re-expression of miR-215 promoted cell migration and invasion of glioma by targeting RB1. miR-215 can thus be used as a biomarker for tumor progression and prognosis in human high grade glioma.