Adiponectin inhibits vascular smooth muscle cell calcification induced by beta-glycerophosphate through JAK2/STAT3 signaling pathway

Radioresistance is a material obstacle for effective treatment of colorectal cancer (CRC). Thus, the discovery of a novelbiomarker for determining the CRC radiosensitivity is necessary. Recent studies have confirmed that miR-183-3p regulatescell phenotypes and tumor growth in various cancers. However, the role and mechanism of this micro-ribonucleic acid inCRC radiosensitivity remains unclear. Here, the abundances of miR-183-5p and ATG5 mRNA were detected by a real-timequantitative reverse transcription polymerase chain reaction. Kaplan–Meier survival analysis was carried out to explore thecorrelation between miR-183-5p and patient prognosis. Cell viability was evaluated by the MTT assay. Survival fractionanalysis through colony formation was performed to assess the cell radiation response. Bioinformatic, luciferase andwestern blot assays were employed to verify the targeted interaction between miR-183-5p and ATG5. The results showedthat an elevated abundance of miR-183-5p and a reduced ATG5 level in CRC were associated with the poor prognosis. Theknockdown of miR-183-5p enhanced the sensitivity of CRC cells to radiation, inflected by the decreased cell viability andsurvival fraction. Mechanically, ATG5 was targeted by miR-183-5p. The addition of ATG5 conferred the radiosensitivity ofthe CRC cells, which was revered by miR-183-5p restoration. Furthermore, miR-183-5p knockdown hindered the tumorgrowth by repressing ATG5 in vivo after radiation treatment. In summary, the output data indicated that miR-183-5pheightened the radiation response of the CRC cells by targeting ATG5, promising a novel therapeutic target for CRCpatients with radioresistance.

Betatrophin Levels were Increased in Pregnant Women with or without Gestational Diabetes Mellitus and Associated with Beta Cell Function / Níveis de betatrofina aumentados em grávidas com ou sem diabetes mellitus gestacional e associados à função das células beta

Abstract Purpose betatrophin has been reported to boost β cell expansion in insulin resistant states. Pregnancy is a well-recognized physiological state of insulin resistance. Betatrophin levels in pregnant women and their relationships with metabolic variables remain to be elucidated. Methods A total of 49 pregnant women and 31 age-matched unpregnant women with normal glucose regulation (UP-NGR) were included. Among these subjects, according to results from 75 g oral glucose tolerance test (OGTT), 22 women were diagnosed as having gestational diabetes mellitus ( GDM ). Results Our study found that pregnant women, regardless of their glucose regulation status, had remarkably higher triglycerides (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β). However, GDM patients had much lower HOMA-β compared with those of pregnant women with normal glucose regulation (P-NGR). Participants of the P-NGR group had almost 4 times higher levels of betatrophin than those of the UP-NGR group. Although betatrophin levels were lower in the GDM group than those of the P-NGR group, the difference did not reach statistical significance. Spearman correlation analysis showed that betatrophin levels were positively and significantly associated with total cholesterol, triglycerides, highdensity lipoprotein cholesterol (HDL-c), FINS and HOMA-β. However, adjustments of TC, TG and HDL-c eliminated the association between HOMA-β and betatrophin. Conclusions Pregnant women have significantly higher betatrophin levels in comparison to unpregnant women. Betatrophin levels are positively and significantly associated with β cell function and lipid levels. Furthermore, lipids may contribute to the association between betatrophin and β cell function.

Resumo Introdução Betatrofina tem sido relacionada à expansão de células β em estado de resistência à insulina. A gravidez é um conhecido estado fisiológico de resistência à insulina. Níveis de betatrofina em gestantes e sua relação com variáveis metabólicas ainda precisam ser esclarecidas. Métodos Um total de 49 gestantes e 31 não gestantes de mesma idade com níveis normais de glicose (UP-NGR) foram incluídas. Dentre elas, de acordo com os resultados da curva glicêmica, base em 75 g, 22 mulheres foram diagnosticadas com diabetes mellitus gestational ( DMG ). Resultados Nosso estudo identificou que gestantes, independente de seus níveis de glicose, tiveram notáveis níveis elevados de triglicerídeos (TG), colesterol (TC), insulina em jejum (FINS), HOMA-IR e HOMA-β. Contudo, pacientes com DMG tiveram bem menos HOMA-β se comparadas às gestantes com níveis normais de glicose ( P-NGR ). Participantes do grupo P-NGR tiveram níveis de betatrofina quase quarto vezes maiores ao das participantes do grupo UP-NGR. Embora os níveis de betatrofina sejam menores no grupo DMG do que no P-NGR, a diferença não obteve significância estatística. Análise da correlação de Spearman demonstrou que os níveis de betatrofina foram positiva e significativamente associados ao TC, TG, HDL-c (high-density lipoprotein cholesterol), FINS e HOMA-β. Contudo, ajustes em TC, TG e HDL-c eliminaram a associação entre HOMA-β e betatrofina. Conclusões Gestantes têm níveis de betatrofina significativamente maiores do que não gestantes. Níveis de betatrofina são positive e significativamente associados às células β funcionais e níveis de lipídeos. Além disso, lipídeos podem contribuir na associação entre betatrofina e células β funcionais.