Diabetes mellitus has been identified as a major risk factor for cardiovascular diseases. High glucose-induced endothelial dysfunction and apoptosis is an important pathological feature of diabetic vasculopathy. Neferine, an alkaloid ingredient in lotus seed embryo has many biological actions such as anticancer and antioxidant. But little is known about whether Neferine protects endothelial cells against high glucose-induced oxidative stress and apoptosis. The present study was conducted to investigate the preventive effects of Neferine on hyperglycemia-induced injury of human umbilical vein endothelial cells (HUVECs). Our study showed that Neferine pretreatment effectively suppressed high glucose-induced HUVECs apoptosis. Also, Neferine pretreatment inhibited the augment of reactive oxygen species (ROS) in high glucose-treated HUVECs. The changes of SOD and MDA level in high glucose-treated HUVECs were also prevented by Neferine. Further study showed that Neferine did not affect the phosphorylation of JNK and p38 in high glucose-treated HUVECs. Interestingly, Neferine markedly inhibited high glucose-induced activation of PI3K/Akt pathway in HUVECs. High glucose-induced activation of NF-κB signal was also obviously suppressed by Neferine pretreatment. Collectively, we found that Neferine inhibited high glucose-induced endothelial apoptosis via blocking ROS/Akt/NF-κB pathway, which provides the evidence for using Neferine to treat diabetic vasculopathy.

The effect of irbesartan on the expression of connective tissue growth factor (CTGF) and α-smooth-muscle actin (α-SMA) in the renal tubulointerstitium of diabetic rats was investigated in our study. Diabetes was induced in male Wistar rats by intraperitoneal administration of streptozotocin (STZ), 60 mg·kg^–1 body weight. The rats were then randomized to a diabetic group (DM) and an irbesartan therapy group (DM + Irb). The normal group (non-DM) rats were administered only citrate buffer. At the end of the 16th week, blood glucose, kidney weight/body weight, urine albumin (UAlb) and creatinine clearance rate were determined. The renal histopathology was observed by light microscopy. Further biochemical analysis of CTGF and α-SMA was provided using real-time reverse transcription PCR, immunostaining and Western blotting techniques. Compared with the non-DM group, blood glucose, kidney weight/body weight, UAlb, creatinine clearance and interstitial fibrotic lesions were increased in the DM group (p < 0.01). Treatment with irbesartan improved these parameters except blood glucose. Compared with the non-DM group, expressions of CTGF and α-SMA in the renal tubulointerstitium were highly upregulated in the DM group (p < 0.01). Administration of irbesartan prevented the high expressions of CTGF and α-SMA in renal tissue of diabetic rats. These results indicated that irbesartan can protect the kidney of STZ-diabetic rats by reducing the expression of CTGF and α-SMA in the renal tubulointerstitium.

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Diabetes mellitus (DM) often causes vascular endothelial damage and alters vascular microRNA (miR) expression. miR‐448‐3p has been reported to be involved in the development of DM, but whether miR‐448‐3p regulates diabetic vascular endothelial dysfunction remains unclear. To investigate the molecular mechanism of diabetic vascular endothelial dysfunction and the role of miR‐448‐3p therein, Sprague‐Dawley rats were injected with streptozotocin (STZ) to establish diabetic animal model and the rat aortic endothelial cells were treated with high glucose to establish diabetic cell model. For the treatment group, after the induction of diabetes, the miR‐448‐3p levels in vivo and in vitro were upregulated by adeno‐associated virus serotype 2 (AAV2)‐miR‐448‐3p injection and miR‐448‐3p mimic transfection, respectively. Our results showed that AAV2‐miR‐448‐3p injection alleviated the body weight loss and blood glucose level elevation induced by STZ injection. The miR‐448‐3p level was significantly decreased and the dipeptidyl peptidase‐4 (DPP‐4) messenger RNA level was increased in diabetic animal and cell models, which was reversed by miR‐448‐3p treatment. Moreover, the diabetic rats exhibited endothelial damage and endothelial–mesenchymal transition (EndMT), while AAV2‐miR‐448‐3p injection relieved those situations. In vitro experiments demonstrated that miR‐448‐3p overexpression in endothelial cells alleviated endothelial damage by inhibiting EndMT through blocking the transforming growth factor‐β/Smad pathway. We further proved that miR‐448‐3p negatively regulated DPP‐4 by binding to its 3′‐untranslated region, and DPP‐4 overexpression reversed the effect of miR‐448‐3p overexpression on EndMT. Overall, we conclude that miR‐448‐3p overexpression inhibits EndMT via targeting DPP‐4 and further ameliorates diabetic vascular endothelial dysfunction, indicating that miR‐448‐3p may serve as a promising therapeutic target for diabetic endothelial dysfunction.

Aging-related health and functioning are difficult to quantify in humans and nonhuman primates. We constructed an observer-based scale for daily application in assessing the aging-related health and functioning of rhesus macaques. Ten items referring to an aging appearance, musculoskeletal aging and aging-related eating behavior were selected through a panel consensus. The Aging-related Health and Functioning Scale (AHFS) was constructed based on these scored items form 57 healthy rhesus macaques. High reliability of the AHFS was shown based on Cronbach’s alpha coefficient (0.877). The structure of the AHFS was validated by three exploratory factors. The largest factor, whose four components were dietary uptake, iliac muscle mass, hair condition and fragility, and sex, explained 50.5% of the variation in aging-related health and functioning scores. The second factor, involving age, tooth loss and tooth wear, explained 15.5% of the variation. The lowest-ranking factor comprised only facial redness and accounted for 10% of the variation. A hierarchical cluster analysis validated the good applicability of the scale in distinct samples. From these scale-scored results, complicated aging phenomena observed in humans, including the sex-survival paradox and the calorie-related health-survival paradox, were both demonstrated in rhesus macaques. Therefore, the AHFS provides a valuable approach for aging-related research.