Purpose The main purpose of this study was to examine the effect of the cumulative exposure of blood lipid parameters on type 2 diabetes mellitus (T2DM). Another purpose was to explore whether the cumulative burden of blood lipid parameters plays a certain role in the pathogenesis of diet affecting T2DM. Patients and Methods A total of 63 cases of diabetes occurred from 2017 to 2020, with an incidence density of 3.71 person-years. The dietary intake of the residents was obtained by using a dietary frequency questionnaire (FFQ). Cumulative lipid parameter burden was calculated according to the number of years (2016–2020) multiplied by total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG). A Cox proportional hazard model was used to estimate the effect of cumulative lipid burden on T2DM. A mediating analysis of accelerated failure time (AFT) was used to investigate the mediating effects of certain foods, the cumulative lipid parameter burden and T2DM. Results A higher cumulative TG load corresponded to a higher risk of T2DM onset ( P trend =0.021). After adjusting for covariates, the highest quartile cumulative TG burden had a 3.462 times higher risk of T2DM than that in the lowest quartile ( HR =3.462, 95% CI : 1.297–9.243). Moreover, a higher cumulative HDL load corresponded to a lower risk of T2DM onset ( P trend =0.006). After adjusting for covariates, the risk of T2DM was 0.314-fold lower in the highest quartile of cumulative HDL burden than that in the lowest quartile ( HR =0.314, 95% CI : 0.131–0.753). Cumulative TG burden partially mediated the association between red meat and T2DM. Conclusion The increase in cumulative HDL burden and the decrease in cumulative HDL burden are related to the incidence of T2DM. Cumulative TG burden was shown to play a partial mediating role in the pathogenesis of red meat and diabetes.
Purpose Corticosteroid insensitivity has become a major barrier in the treatment of chronic obstructive pulmonary disease (COPD). It is known that oxidative stress reduces the expression and activity of histone deacetylase (HDAC)-2 by activating phosphoinositide-3-kinase-δ(PI3Kδ)/Akt pathway, which is a common mechanism. The aim of this study was to investigate whether cryptotanshinone (CPT) can improve corticosteroid sensitivity and to investigate the molecular mechanisms by which this occurs. Patients and Methods Corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) collected from COPD patients, or in human monocytic U937 monocytic cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α (TNFα)–induced interleukin 8 (IL-8) production in the presence or absence of cryptotanshinone. PI3K/Akt activity (measured as the relative ratio of phosphorylated Akt at Ser-473 to total Akt) and HDAC2 expression levels were determined by western blotting. HDAC activity was evaluated by a Fluo-Lys HDAC activity assay kit in U937 monocytic cells. Results Both PBMCs in patients with COPD and U937 cells exposed to CSE were found to be insensitive to dexamethasone, accompanied by increased phosphorylated Akt (pAkt) and decreased HDAC2 protein expression. The pretreatment of cryptotanshinone restored their sensitivity to dexamethasone, and simultaneously downregulated the level of phosphorylated Akt and upregulated the level of HDAC2 protein. Pretreatment with cryptotanshinone or IC87114 reversed the decrease in HDAC activity in CSE-stimulated U937 cells. Conclusion Cryptotanshinone restores corticosteroid sensitivity induced by oxidative stress via inhibition of PI3Kδ and is a potential treatment for corticosteroid-insensitive diseases such as COPD.
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