Adverse outcomes of intrinsic capacity in older adults: A scoping review.

Background and Purpose Intrinsic capacity (IC) has been shown to have the greatest impact on an individual's health status and health trajectory and can independently predict adverse outcomes such as mortality and care dependency in older adults. However, the current understanding of adverse outcomes associated with IC is incomplete. Methods A scoping review of the literature from PubMed, Web of Science (WOS), The Cochrane Library, CINAHL, and Embase databases was conducted from January 2015 to March 2023 to identify articles related to the adverse outcomes associated with IC in older adults. Results 711 studies met screening criteria, and 25 studies met inclusion criteria. These studies reported a total of 17 adverse outcomes related to IC across four domains. (1) Adverse outcomes in the physiological function domains included frailty, pneumonia onset, memory impairment, polypharmacy, incontinence, and poor/fair self-rated health. (2) Clinical outcomes domains included IADL disability, ADL disability, mortality, falls, autonomy decline, and incident dependence. (3) The resource utilization domains included hospitalization, nursing home stays, polypharmacy healthcare costs, and emergency department visits. (4) The other domains mainly included poor quality of life. Conclusion It is evident that IC decline in older adults is associated with a broad spectrum of adverse outcomes spanning cognitive function, activity ability, sensory perception, physical and mental health and living standards. Future studies should further deepen the exploration of IC.

The digestive tract histology and geographical distribution of gastrointestinal microbiota in yellow-feather broilers.

Exhaustive understanding of intestinal physiological characteristics is the critical precondition for the improvement of intestinal health and growth performance of yellow-feather broilers (YFB). As a vital part of gastrointestinal tract, the symbiotic, complex, and variable microbiota have a profound effect on the nutrition, immunity, health, and production of broilers. Hence, the development status of proventriculus, jejunum, and cecum, and spatial heterogeneity of bacterial community in crop, proventriculus, gizzard, jejunum, cecum, and rectum of adult YFB were detected in our study. The results revealed that proventriculus, jejunum, and cecum of broilers are well-developed based on morphological observation. The Chao and Shannon indexes in cecum and rectum are notably higher than other sections and their microbiota structure is also distinct from foregut. Firmicutes and Lactobacillus are the predominant phylum and genus in all gastrointestinal sections, respectively. As feature species of crop, Lactobacillus spp. mainly settle in foregut, whereas some Clostridia species (unclassified Lachnospiraceae, Faecalibacterium, Romboutsia and so on) are characteristic and more abundant in cecum and rectum. Interestingly, there are 2 Ruminococcus torques strains positively and negatively correlated with cecum development, respectively. In a whole, our findings reveal the specialized digestive physiology and regional distribution of intestinal microbiota in YFB, which provides a reference for the future study on the improvement of growth performance and intestinal development through microbiota manipulation in yellow-feather broilers.

The integrated analysis of digestive physiology and gastrointestinal microbiota structure in Changle goose.

Changle goose in Fujian, China is a rare genetic resource and in urgent need to be protected. Understanding the characteristics of digestive physiology and spatial variation of gastrointestinal microbiota is crucial for developing nutritional intervention strategies to improve intestinal health and production performance of goose. Hence, histomorphological assay was used for observing development status of proventriculus, jejunum, and cecum in 70-day-old Changle geese, whereas digesta from 6 alimentary canal locations (crop, proventriculus, gizzard, jejunum, cecum, and rectum) were collected for 16S rRNA gene sequencing and short chain fatty acids (SCFAs) quantitative analysis. The histomorphological observation indicated that the jejunum and cecum of Changle goose were well developed. The alpha diversity analysis revealed that, except rectum, microbiota in other noncecum sections were in high diversity as cecum. The Nonmetric MultiDimensional Scaling (NMDS) analysis showed that microbial community of proventriculus, gizzard, and jejunum formed a cluster, which distinctly discrete with the microbiota of the other gastrointestinal locations. Additionally, the proportions of Proteobacteria, Bacteroidota, and Campilobacterota at the phylum level and Lactobacillus, Streptococcus, Helicobacter, and Subdoligranulum at the genus level exhibited tremendous alternations among different gastrointestinal locations. The characteristic bacterial composition in each section was further disclosed by analyzing the core and feature Amplicon Sequence Variants (ASVs) and SCFAs pattern. Importantly, 7 body-weight-associated ASVs and 2 cecum-development-related ASVs were identified via correlation analysis. In a whole, our findings provided the first insights into the specialized digestive physiology of Changle geese and distinctive regional distribution of gastrointestinal microbiota, which laid the important foundation for improving growth performance through microbiota manipulation in geese.

The association of neutrophil to lymphocyte ratio, mean platelet volume, and platelet distribution width with diabetic retinopathy and nephropathy: a meta-analysis.

The aim of the present study was to investigate the correlation of neutrophil to lymphocyte ratio (NLR), mean platelet volume (MPV), and platelet distribution width (PDW) with diabetic nephropathy (DN) and diabetic retinopathy (DR). We searched for eligible studies from PubMed, Embase, Web of Science, and CNKI up to 1 December 2017. Standardized mean difference (SMD) was calculated with a confidence interval (CI) of 95%. A total of 48 studies were included in our meta-analysis. Compared with patients with type Ⅱ diabetes mellitus (T2DM) and without DR, NLR, MPV, and PDW were higher in patients with DR (SMD = 0.77; 95% CI: 0.49-1.05; P<0.001; SMD = 0.68; 95% CI: 0.36-0.99; P<0.001; SMD = 0.52; 95% CI: 0.28-0.76; P<0.01). Compared with patients with T2DM and without DN, NLR, MPV, and PDW were higher in patients with DN (SMD = 0.63; 95% CI: 0.43-0.83; P<0.001; SMD = 0.81; 95% CI: 0.36-1.25; P<0.001; SMD = 0.70; 95% CI: 0.50-0.90; P<0.001). We also found that MPV was strongly associated with the severity of DR, and NLR was closely related to the degree of DN. Our findings indicated that NLR, MPV, and PDW could be recommended as inexpensive diagnostic biomarkers for DN and DR. However, considering several limitations in the present study, further high-quality clinical studies should be performed to investigate the relationship of NLR, MPV, and PDW to DN and DR.

Angiotensin II receptor blocker valsartan ameliorates cardiac fibrosis partly by inhibiting miR-21 expression in diabetic nephropathy mice.

Cardiac fibrosis with diabetic nephropathy (DN) is one of major diabetic complications. miR-21 and MMP-9 were closely associated with fibrosis diseases. Angiotensin II receptor blockers (ARB) have cardioprotective effects. However, it remains unclear whether miR-21 was involved in the mechanism of cardiac fibrosis with DN by target MMP-9 and ARB ameliorates cardiac fibrosis partly by inhibiting miR-21 expression. In this study, In Situ Hybridization(ISH), RT-PCR, cell transfection, western blotting and laser confocal telescope were used, respectively. ISH showed that miR-21, concentrated in cytoplasmic foci in the proximity of the nucleus, was mainly localized in cardiac fibroblasts and at relatively low levels in cardiomyocytes within cardiac tissue with DN. RT-PCR showed that miR-21 expression was significantly enhanced in cardiac tissue with DN, accompanied by the increase of col-IV, FN, CVF, PVCA, LVMI, HWI and NT-pro-BNP (p < 0.05). Bioinformatics analysis and Luciferase reporter gene assays showed that MMP-9 was a validated target of miR-21. Furthermore, cell transfection experiments showed that miR-21 overexpression directly decreased MMP-9 expression. Interestingly, miR-21 levels in cardiac tissue was positively correlated with ACR (r = -0.870, P = 0.003), whereas, uncorrelated with SBP, HbA1C and T-Cho (p > 0.05). More importantly, ARB can significantly decrease miR-21 expression in cardiac tissue, cardiac fibroblasts and serum. Overall, our results suggested that miR-21 may contribute to the pathogenesis of cardiac fibrosis with DN by target MMP-9, and that miR-21 may be a new possible therapeutic target for ARB in cardiac fibrosis with DN.

Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model.

Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-ß/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-ß1/smads expression. In this study, high-fat diet rats with IR model and IR-skeletal muscle L6 cells (L6-SMCs) model were established, insulin sensitive index (ISI) and Homeostasis model assessment of IR (HOMA-IR) were applied, miR-21 and TGF-ß1/smads mRNA expression were examined by RT-PCR, smad3 and smad7 protein were detected by western-blotting and laser scanning confocal microscopy (LSCM), the valid target of miR-21 was detected by luciferase reporter gene assay. Here, we found that metformin dose-dependently decreased miR-21 expression, accompanied by the decrease of HOMA-IR and the increase of HOMA-ISI. Luciferase report gene assay showed that smad7 was an effective target of miR-21. miR-21 overexpression directly downregulated smad7 and indirectly upregulated smad3 expression. Interestingly, miR-21 expression positively correlated with HOMA-IR and negatively correlated with HOMA-ISI. In conclusion, our results demonstrated that metformin improved IRSM by inhibiting miR-21 expression, and that miR-21 may be one of the therapeutic targets for IR.

Palmitate induces VSMC apoptosis via toll like receptor (TLR)4/ROS/p53 pathway.

BACKGROUND AND AIMS: Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. METHODS: VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. RESULTS: Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. CONCLUSIONS: Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis.

The Association Between Endocan Levels and Subclinical Atherosclerosis in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Proinflammatory conditions induced by circulating factors in diabetes play a pivotal role in endothelial dysfunction and related vascular complications. Endothelial cell-specific molecule-1 or endocan is a dermatan sulfate proteoglycan secreted primarily by the vascular endothelium. Although endocan has been shown to be a potential biomarker in coronary heart disease, its role in the pathogenesis of atherosclerosis (AS) in diabetes remains unclear. In this study, we investigated the correlation between serum endocan levels and subclinical AS in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Patients (n = 69) with T2DM were included. All the patients were stratified based on the absence (n = 42) or presence (n = 27) of subclinical AS. Healthy subjects (n = 28) served as controls. Serum levels of endocan, fasting blood glucose, glycosylated hemoglobin A1, high-sensitivity C-reactive protein and carotid intima-media thickness (cIMT) were measured. RESULTS: Endocan levels were significantly elevated in both the T2DM (0.89 ± 0.28ng/mL) and T2DM with subclinical AS (1.20 ± 0.33ng/mL) groups relative to the control group (0.68 ± 0.24ng/mL) (P < 0.05 for all). Endocan levels were also positively correlated with glycosylated hemoglobin A1, fasting blood glucose and cIMT (r = 0.292, P = 0.004; r = 0.224, P = 0.027 and r = 0.496, P < 0.001, respectively). In addition, endocan levels were independently associated with cIMT (ß = 0.220, t = 5.816, P = 0.000) and were a significant risk factor for T2DM with subclinical AS (odds ratio = 1.98, 95% CI: 1.43-2.73, P < 0.001). CONCLUSIONS: These findings suggest that serum endocan levels may be a useful biomarker for the early diagnosis of subclinical AS in patients with T2DM.

Are home visits an effective method for diabetes management? A quantitative systematic review and meta-analysis.

AIMS/INTRODUCTION: Previous reviews have revealed uncertainty regarding the effectiveness of home visit interventions for managing diabetes. Therefore, we carried out a quantitative systematic review and meta-analysis to evaluate the effects of home visit interventions among patients with diabetes. MATERIALS AND METHODS: We searched various electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL, Wanfang and Chinese scientific full-text databases) from their inception until March 2016. We included randomized controlled trials that included patients with diabetes, and evaluated the effects of home visit programs on glycated hemoglobin concentrations. Two reviewers independently used the Cochrane Collaboration methods to assess the included studies' risk of bias and quality. RESULTS: We included seven randomized controlled trials with 686 participants. Compared with the usual care, the home visit group showed a greater reduction in glycated hemoglobin concentrations (mean difference -0.79% [-9 mmol/mol], 95% confidence interval [CI]: -0.93 to -0.25% [11 to -3 mmol/mol]; P < 0.05; I2  = 0%), systolic blood pressure (mean difference -5.94 mmHg, 95% confidence interval -11.34 to -0.54 mmHg) and diastolic blood pressure (mean difference -6.32 mmHg, 95% confidence interval -12.00 to -0.65 mmHg). Furthermore, home visits improved quality of life, high-density lipoprotein, low-density lipoprotein, total triglycerides and self-management. However, there were no significant differences between the two groups in their bodyweight, total cholesterol, body mass index and self-efficacy. CONCLUSION: Home visits were associated with improved glycemic control and reduced cardiovascular risk factors, which shows that it is an effective method for diabetes management.

Reduced serum milk fat globule-epidermal growth factor 8 (MFG-E8) concentrations are associated with an increased risk of microvascular complications in patients with type 2 diabetes.

BACKGROUND: The association between serum milk fat globule-epidermal growth factor 8 (MFG-E8) concentrations and vascular complications in T2DM remains unclear. METHODS: A total of 149 patients with T2DM were included. The serum concentrations of MFG-E8, glycosylated hemoglobin (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured. RESULTS: There was no significant difference in serum MFG-E8 concentrations between the T2DM group and the T2DM with subclinical atherosclerosis (AS) group (615.49±143.54 vs. 596.22±79.46ng/ml, P=0.365), while the serum concentrations of MFG-E8 in the T2DM with microvascular complications group (446.70±61.53ng/ml) and the T2DM with subclinical AS and microvascular complications group (200.87±38.86ng/ml) were significantly lower than those in the T2DM group (P=0.000 for both). In addition, hs-CRP and HbAlc concentrations were independently associated with serum MFG-E8 concentrations (P=0.024 and P=0.01, respectively), and low serum MFG-E8 concentrations were significantly associated with an increased risk of microvascular complications in T2DM patients. CONCLUSIONS: Serum concentrations of MFG-E8 were negatively associated with the risk of microvascular complications in patients with T2DM. Thus, it might be a potential candidate biomarker for diabetic microvascular complications.

Protection effect of endomorphins on advanced glycation end products induced injury in endothelial cells.

Endomorphins (EMs) have a very important bridge-function in cardiovascular, endocrinological, and neurological systems. This study is to investigate the effects of EMs on the synthesis and secretion of vasoactive substances induced by advanced glycation end products in primary cultured human umbilical vein endothelial cells (HUVECs). Firstly, HUVECs were stimulated with AGEs-bovine serum albumin (AGEs-BSA), bovine serum albumin (BSA), or both AGEs-BSA and EMs together, respectively. Then, HUVEC survival rate was calculated by MTT assay, the levels of NO, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were detected by colorimetric analysis, and the contents of endothelin-1 (ET-1) were detected by ELISA. The mRNA levels of eNOS and ET-1 were measured by RT-PCR. The expression of p38 mitogen-activated protein kinase (p38 MAPK) was detected by immunofluorescence assay. The results showed that the mRNA expression and secretion of eNOS were significantly enhanced after incubation with EMs compared to those with AGEs-BSA, while the secretion of NO and iNOS, mRNA expression, and secretion of ET-1 had opposite changes. The fluorescence intensity of p38MAPK in nuclear was decreased after pretreatment with EMs compared to incubation with AGEs-BSA. Conclusion. The present study suggests that EMs have certain protection effect on AGEs-BSA-induced injury in HUVEC.

Effects of endomorphins on human umbilical vein endothelial cells under high glucose.

The endomorphin-1 (EM1) and endomorphin-2 (EM2) are endogenous opioid peptides, which modulate extensive bioactivities such as pain, cardiovascular responses, immunological responses and so on. The present study was undertaken to investigate the effects of EM1/EM2 on the primary cultured human umbilical vein endothelial cells (HUVECs) damaged by high glucose. PI AnnexinV-FITC detection was performed to evaluate the apoptosis rate. Levels of nitric oxide (NO) and nitric oxide synthase (NOS) activity were measured by the Griess reaction and the conversion of 3H-arginine to 3H-citrulline, respectively. Endothelin-1 (ET-1) was evaluated by the enzyme-linked immunosorbent assay (ELISA). Cell proliferation was determined by the MTT viability assay. mRNA expression of endothelial nitric oxide synthase (eNOS) and ET-1 were measured by real-time PCR. Our data showed that EM1/EM2 inhibited cell apoptosis. The high glucose induced increase in expression of NO, NOS and ET-1 were significantly attenuated by pretreatment with EM1/EM2 in a dose dependent manner. In addition, EM1/EM2 suppressed the mRNA eNOS and mRNA ET-1 expression in HUVECs under high glucose conditions. Naloxone, the nonselective opioid receptor antagonist, did not influence the mRNA eNOS expression when it was administrated on its own; but it could significantly antagonize the effects induced by EM1/EM2. Furthermore, in all assay systems, EM1 was more potent than EM2. The results suggest that EM1/EM2 have a beneficial effect in protecting against the endothelial dysfunction by high glucose in vitro, and these effects were mediated by the opioid receptors in HUVECs.