Ultraviolet-A (UVA, 320-380 nm) radiation is an oxidative stress that strongly induces heme oxygenase 1 (HO-1) expression in cultured human primary skin fibroblasts (FEK4). In this study, we show that NF-E2-related factor 2 (Nrf2) protein accumulates and HO-1 is strongly induced following UVA irradiation of FEK4 cells. Down-regulation of Nrf2 with specific short interfering RNA (siRNA) against Nrf2 (siNrf2) largely abolished the induction of HO-1 following either UVA irradiation or hemin treatment, suggesting that Nrf2 activation mediated modulation of HO-1 by both these agents. Furthermore, a reduction of free heme levels led to a strong decrease in UVA-induced Nrf2 and HO-1 protein levels confirming a clear role for heme in the UV-mediated stress response. Knock-down of Nrf2 protein enhanced membrane damage induced by UVA irradiation, indicating that Nrf2 has a crucial protective role in these cells.
In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells (tol-DCs) with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various tol-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.
Retinal fundus photography provides a non-invasive approach for identifying early microcirculatory alterations of chronic diseases prior to the onset of overt clinical complications. Here, we developed neural network models to predict hypertension, hyperglycemia, dyslipidemia, and a range of risk factors from retinal fundus images obtained from a cross-sectional study of chronic diseases in rural areas of Xinxiang County, Henan, in central China. 1222 high-quality retinal images and over 50 measurements of anthropometry and biochemical parameters were generated from 625 subjects. The models in this study achieved an area under the ROC curve (AUC) of 0.880 in predicting hyperglycemia, of 0.766 in predicting hypertension, and of 0.703 in predicting dyslipidemia. In addition, these models can predict with AUC>0.7 several blood test erythrocyte parameters, including hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and a cluster of cardiovascular disease (CVD) risk factors. Taken together, deep learning approaches are feasible for predicting hypertension, dyslipidemia, diabetes, and risks of other chronic diseases.
SummaryBone marrow mesenchymal stem cells (BMSCs) inhibit immune cell responsiveness, and especially of T lymphocytes. We showed that BMSCs markedly inhibited the proliferation and cytokine production by
BackgroundCognitive impairment may increase the risk of all‐cause and cardiovascular disease (CVD) mortality. This study examined the association between cognitive function and risk of all‐cause and CVD mortality among the elderly in Beijing, China.Methods and ResultsA total of 1996 participants aged ≥55 years at baseline were enrolled from the BLSA (Beijing Longitudinal Study of Aging). Cognitive function was assessed using the Mini‐Mental State Examination (MMSE), and participants were categorized as: <18, 18 to 23, 24 to 27, and 28 to 30. Cox proportional hazard models were used to estimate the association. Hazard ratio (HR) and 95% confidence interval (CI) were reported. During a 20‐year follow‐up, 1122 (56.21%) participants died, 478 (42.60%) of whom died of CVD. Compared with MMSE scores of 28 to 30, participants with MMSE scores of <18 were independently associated with all‐cause mortality (hazard ratio, 2.14; 95% confidence interval, 1.59–2.87; P<0.001) and CVD mortality (hazard ratio, 4.52; 95% confidence interval, 2.80–7.30, P<0.001). Each 5‐point decrease in MMSE score was associated with a 34% increased risk of all‐cause mortality and a 56% increased risk of CVD mortality. This relationship remained statistically significant after using the competing risk model to consider non‐CVD death as a competing risk event.ConclusionCognitive impairment measured by MMSE score was associated with elevated risk of all‐cause and CVD mortality among the elderly in Beijing, China.
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