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Background: Physio-psycho-socioeconomical health comprehensively declines during aging, the complexity of which is challenging to measure. Among the complexity, multiple chronic disorders continuously cumulated during aging, further aggravating the challenge., Methods: A population-based survey on Comprehensive Ageing Health Assessment was conducted in older adults (age >  = 60) enrolled from hospital settings and community settings in 13 working centers in six subnational regions in China. Cross-sectional datasets of 8,093 older participants with approximately complete assessment results were collected for the present analysis. Individual's multi-disease or multi-symptom was respectively scored by summing coexistent multiple diseases or multiple symptoms by respective weighting efficient for Self-Rated Health (SRH). Individual's age-dependent health decline was further summed of four SRH-weighted scores for daily function (activity of daily life, ADL), physical mobility (an average of three metrics), cognitive function (mini mental state examination, MMSE) and mental being (geriatric depression scale, GDS) plus multi-disease score (MDS) and multi-symptom score (MSS).Multi-disease patten among 18 diseases or multi-symptom pattern among 15 symptoms was latent-clustered in the older adults, the optimal outcome of which was categorized into high, moderate or low aging-associated clusters, respectively. Percentage distribution was compared between overall health decline score and multi-disease pattern cluster or multi-symptom patten cluster. A new variable of difference between MDS and MSS (hereinafter terming DMM) that displayed linear variation with socioeconomic factors was further fitted using multilevel regression analyses by substantial adjustments on individual confounders (level-1) and subnational region variation (level-2)., Results: Consistent gradient distribution was shown between health decline and multimorbidity pattern cluster in the older adults. DMM was found linearly varied with personal education attainment and regional socioeconomic status. Using optimally fitted stratification of DMM (DMM interval = 0.02), an independent U-shaped interrelated tendency was shown between health decline, multi-disease and multi-symptom, which could be well explained by regional disparities in socioeconomic status., Conclusion: Newly developed metrics for age-dependent health decline and aging-associated multimorbidity patten were preliminarily validated from within. The new variable of optimally fitted categorization of DMM might function as a practical indicator aiding in improving the cost-effectiveness and reduce inequity of healthcare delivery for older adults in developing countries., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Endothelial-mesenchymal transition (EndMT) is an important source of myofibroblasts, but also contributes to the progression of diabetic nephropathy (DN). By several differential gene expression analyses from the Gene Expression Omnibus (GEO) database, the tissue factor pathway inhibitor 2 (TFPI2) gene, known as a tumor suppressor, was shown to be dysregulated in DN; however, the potential role and regulatory mechanism of TFPI2 in DN are unclear. Here, we found abnormal upregulation of TFPI2 in the renal cortex of diabetic mice, accompanied by impaired renal function. We also injected a single dose of adeno-associated virus (AAV)2 carrying shRNA targeting TFPI2 intravenously into these mice and found that knockdown of TFPI2 improved renal function and reduced renal fibrosis and cell apoptosis in experimental DN. Furthermore, hyperglycemia-induced EndMT was inhibited in the absence of TFPI2, as evidenced by increased expression of endothelial markers (VE-cadherin and CD31) and decreased expression of mesenchymal markers (α-SMA, desmin, and FSP-1). To further explore the mechanism in vitro, human renal glomerular endothelial cells (hRGECs) were incubated in the presence of high glucose or transforming growth factor beta (TGF-β)2. TFPI2 deficiency inhibited high glucose-induced cell apoptosis and TGF-β2-induced EndMT in hRGECs, while overexpression of TFPI2 had the opposite effects. Importantly, TGF-β2 is a crucial driver of EndMT, and we found that TFPI2 promoted TGF-β2/Smad signaling activation by interferring the interaction of TGF-β pathway regulators (SMURF2 with SMAD7). Our results show that TFPI2 regulates EndMT and the TGF-β2 signaling pathway and is a potential promoter of DN pathogenesis., Competing Interests: Conflict of interest The authors declare that they have no conflict of interests with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Vanadium is an ultratrace element. The transition metal vanadium, widely exists in the environment and exhibits various biological and physiological effects in the human body, yet with no presently known specific physiological function in mammals. Sodium orthovanadate (SOV) is a kind of vanadium compound. SOV has shown promising antineoplastic activity in several human cancers. But the effects of SOV on acute promyelocytic leukemia (APL) are still unknown. In the present study, for the first time, we found that SOV could inhibit proliferation, induce G2/M cell cycle arrest and apoptosis, and could inhibit autophagy of acute leukemia cell lines in vitro. Thus, our findings suggest that SOV could effectively suppress the growth of acute leukemia HL60 cells and HL60/A cells through the regulations of proliferation, cell cycle, apoptosis and autophagy, and thus may act as a potential therapeutic agent in APL treatment., (© 2020 The Author(s).)

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.

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.