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1.
BMC Complement Med Ther ; 24(1): 80, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38331805

ABSTRACT

BACKGROUND: Astragalus polysaccharides (APS) have been verified to have antioxidative and antiaging activities in the mouse liver and brain. However, the effect of APS on aortic endothelial senescence in old rats and its underlying mechanism are currently unclear. Here, we aimed to elucidate the effects of APS on rat aortic endothelial oxidative stress and senescence in vitro and in vivo and investigate the potential molecular targets. METHODS: Twenty-month-old natural aging male rats were treated with APS (200 mg/kg, 400 mg/kg, 800 mg/kg daily) for 3 months. Serum parameters were tested using corresponding assay kits. Aortic morphology was observed by staining with hematoxylin and eosin (H&E) and Verhoeff Van Gieson (VVG). Aging-related protein levels were evaluated using immunofluorescence and western blot analysis. Primary rat aortic endothelial cells (RAECs) were isolated by tissue explant method. RAEC mitochondrial function was evaluated by the mitochondrial membrane potential (MMP) measured with the fluorescent lipophilic cationic dye JC­1. Intracellular total antioxidant capacity (T-AOC) was detected by a commercial kit. Cellular senescence was assessed using senescence-associated-ß-galactosidase (SA-ß-Gal) staining. RESULTS: Treatment of APS for three months was found to lessen aortic wall thickness, renovate vascular elastic tissue, improve vascular endothelial function, and reduce oxidative stress levels in 20-month-old rats. Primary mechanism analysis showed that APS treatment enhanced Sirtuin 1 (SIRT-1) protein expression and decreased the levels of the aging marker proteins p53, p21 and p16 in rat aortic tissue. Furthermore, APS abated hydrogen peroxide (H2O2)-induced cell senescence and restored H2O2-induced impairment of the MMP and T-AOC in RAECs. Similarly, APS increased SIRT-1 and decreased p53, p21 and p16 protein levels in senescent RAECs isolated from old rats. Knockdown of SIRT-1 diminished the protective effect of APS against H2O2-induced RAEC senescence and T-AOC loss, increased the levels of the downstream proteins p53 and p21, and abolished the inhibitory effect of APS on the expression of these proteins in RAECs. CONCLUSION: APS may reduce rat aortic endothelial oxidative stress and senescence via the SIRT-1/p53 signaling pathway.


Subject(s)
Endothelial Cells , Sirtuin 1 , Mice , Male , Rats , Animals , Endothelial Cells/metabolism , Sirtuin 1/metabolism , Tumor Suppressor Protein p53/metabolism , Hydrogen Peroxide/pharmacology , Cellular Senescence/physiology , Antioxidants/pharmacology , Antioxidants/metabolism , Signal Transduction , Polysaccharides/pharmacology , Polysaccharides/metabolism
2.
Front Endocrinol (Lausanne) ; 14: 1191090, 2023.
Article in English | MEDLINE | ID: mdl-37424876

ABSTRACT

Background: The triglyceride glucose index (TyG index) has been regarded as a reliable surrogate marker of insulin resistance and an independent predictor of diabetes. However, few studies have reported the association between the TyG index and diabetes in the elderly population. Accordingly, this study aimed to investigate the association between the TyG index and diabetes progression in elderly Chinese. Methods: Baseline medical history, fasting plasma glucose (FPG), glucose levels during the oral glucose tolerance test (OGTT) after 1-hour (1h-PG) and 2-hour (2h-PG), and triglyceride (TG) were obtained from a cohort of 862 elderly (aged ≥ 60 years) Chinese in the Beijing urban area between 1998 and 1999. A follow-up visit was conducted between 1998 and 2019 to assess incident diabetes. TyG index was calculated by the following formula ln[TG (mg/dL) × FPG (mg(dL)/2]. The predictive values of TyG index, lipids, and glucose levels during OGTT were assessed alone and also in a clinical prediction model comprising traditional risk factors using concordance index (C-index). Areas under the receiver operating characteristics curves (AUC) and 95% CIs were calculated. Results: After 20 years of follow-up, there were 544 cases of incident type 2 diabetes mellitus (63.1% of incidence). The multivariable HRs (95% CI) for TyG index, FPG, 1h-PG and 2h-PG, high-density lipoprotein-cholesterol (HDL-c), and TG were 1.525 (1.290-1.804), 1.350 (1.181-1.544), 1.337 (1.282-1.395), 1.401 (1.327-1.480), 0.505 (0.375-0.681), and 1.120 (1.053-1.192), respectively. The corresponding C-index were 0.623, 0.617, 0.704, 0.694, 0.631, and 0.610, respectively. The AUC (95% CI) for the TyG index, FPG, 1h-PG, 2h-PG, HDL-c, and TG were 0.608 (0.569-0.647), 0.587 (0.548-0.625), 0.766 (0.734-0.797), 0.713 (0.679-0.747), 0.397 (0.358-0.435), and 0.588 (0.549-0.628). The AUC of the TyG index was higher than that of TG but did not differ with FPG and HDL-c. In addition, the AUCs of 1h-PG and 2h-PG were higher than that of the TyG index. Conclusions: Elevated TyG index is independently correlated with an increased risk of incident diabetes in the elderly male population, but it is not superior to OGTT 1h-PG and 2h-PG in predicting the risk of diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Glucose , Humans , Male , Aged , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Retrospective Studies , Triglycerides , Incidence , East Asian People , Models, Statistical , Blood Glucose , Prognosis , Cholesterol, HDL
3.
Cardiovasc Diabetol ; 21(1): 201, 2022 10 03.
Article in English | MEDLINE | ID: mdl-36192784

ABSTRACT

BACKGROUND: Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events. METHODS: A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice. RESULTS: Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was < 1.4 ng/mL and positive if the value was ≥ 1.4 ng/mL. These relationships remained significant after adjusting for hemoglobin A1c, insulin resistance index, and its interaction with C-peptide, even if the participants were stratified by glucose metabolism status or levels of insulin resistance index. Hazard ratios of cardiovascular events were first decreased and then increased with the increasing of baseline C-peptide levels, though these associations became unsignificant using the multivariate Cox regression model. Unlike the participants without previous T2DM, the associations of C-peptide with cardiovascular biomarkers and events were not significant in the patients with previous T2DM. CONCLUSIONS: The associations of C-peptide with cardiovascular biomarkers and events were different between the participants without previous T2DM and those with previous T2DM. The effect of C-peptide on cardiovascular risk may be bidirectional, play a benefit role at a low level, and play a harmful role at a high level in the nondiabetic adults and the patients with newly diagnosed T2DM.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Insulin Resistance , Adult , Biomarkers , C-Peptide , C-Reactive Protein/metabolism , Cardiovascular Diseases/diagnosis , Diabetes Mellitus, Type 2/diagnosis , Glucose , Glycated Hemoglobin/metabolism , Heart Disease Risk Factors , Humans , Retrospective Studies , Risk Factors , Troponin T
4.
Front Cardiovasc Med ; 9: 947292, 2022.
Article in English | MEDLINE | ID: mdl-36072872

ABSTRACT

Introduction: Elevated one-hour plasma glucose (1 h-PG) during oral glucose tolerance test predicts the development of type 2 diabetes mellitus and its complications. However, to date, there have been no studies investigating the predictive values of 1 h-PG for the risk of cardiovascular diseases (CVDs) and all-cause mortality in the elderly population in China. This study aimed to evaluate and compare the effectiveness of 1 h-PG and two-hour plasma glucose (2 h-PG) to predict the risk of CVD and all-cause mortality in the Chinese elderly population. Materials and methods: This retrospective and prospective cohort study was conducted using data obtained from the Chinese People's Liberation Army General Hospital. All the non-diabetic elderly participants, who had plasma glucose measured at 0, 1, and 2 h during an OGTT (75 g glucose), were followed for 20 years. The primary outcomes were all-cause mortality, myocardial infarction, unstable angina, and stroke. Multivariate-adjusted Cox proportional hazard regression models were performed to examine the association between risk factors and outcomes and to estimate the risk of CVD and all-cause mortality based on 1 h-PG levels. Results: A total of 862 non-diabetic male individuals were included. The median age was 74.0 (25th-75th percentile: 68.0-79.0) years. There were 480 CVD events and 191 deaths during 15,527 person-years of follow-up. The adjusted hazard ratio (HR) of 1 h-PG as a continuous variable was 1.097 (95% CI 1.027-1.172; P = 0.006) for CVD events and 1.196 (95% CI 1.115-1.281; P < 0.001) for higher risk of mortality. When compared with the lowest 1 h-PG tertile, the other tertiles were associated with CVD events (HR 1.464, 95% CI 1.031-2.080; P = 0.033 and HR 1.538, 95% CI 1.092-2.166; P = 0.014, for tertile 2 and tertile 3 compared with tertile 1, respectively), and the highest 1 h-PG tertile had a significantly higher risk of mortality (HR 2.384, 95% CI 1.631-3.485; P < 0.001) after full adjustment. Compared with 1 h-PG, 2 h-PG had similar abilities to predict all-cause mortality. However, 2 h-PG was less closely associated with CVD when examined in the fully adjusted model, neither as a continuous variable nor as a categorical variable. Conversely, 1 h-PG remained an independent predictor of CVD and all-cause mortality after adjusting for various traditional risk factors. Conclusion: Patients with higher 1 h-PG had a significantly increased risk of CVD and all-cause mortality regardless of prediabetes status or development of diabetes at follow-up. The 1 h-PG level might be a better predictor of cardiovascular risk than the 2 h-PG level for the Chinese elderly population.

5.
BMC Geriatr ; 22(1): 245, 2022 03 24.
Article in English | MEDLINE | ID: mdl-35331164

ABSTRACT

BACKGROUND: The association of vitamin D with all-cause mortality remains controversial and longitudinal evidence exploring the potential effects of change in vitamin D status is limited in the oldest old (aged ≥ 80 years old). We aimed to study the relationship between vitamin D change and all-cause mortality among older Chinese adults including the oldest old. METHODS: The data of Chinese Longitudinal and Health Longevity Study in 2012 and 2014 wave was used for baseline data. Mortality was assessed in the subsequent 2018 survey waves. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence interval (CI) of all-cause mortality related to vitamin D change, including maintaining deficiency or no deficiency, deficiency to no deficiency, and no deficiency to deficiency, using below 50 nmol/L as definition of deficiency. RESULTS: The mean age of the total 1362 participants was 84.4 ± 12.1(60-113) years. The prevalence of vitamin D deficiency was 67.5% and 68.4% in 2012 and 2014 wave respectively, and significantly differed by sex and age at baseline. Cox regression showed that participants with deficiency to no deficiency and maintaining no deficiency of vitamin D status had decreased HR for all-cause mortality, compared to the maintaining deficiency group. The HRs for mortality were 0.70(95%CI: 0.50-0.96, p = 0.028) and 0.47(95%CI: 0.33-0.68, p < 0.001) respectively in the adjusted model. Also, females and the oldest old had a greatest reduction in mortality risk. And no significant difference in mortality in the no deficiency to deficiency group. CONCLUSIONS: Not only maintaining no deficiency, but also the change from deficiency to no deficiency of vitamin D status were associated with lower risk of all-cause mortality, especially in the female and oldest-old participants initially with low vitamin D level.


Subject(s)
Vitamin D Deficiency , Vitamin D , Aged , Aged, 80 and over , China/epidemiology , Cohort Studies , Female , Humans , Middle Aged , Risk Factors , Vitamin D Deficiency/diagnosis , Vitamins
6.
Exp Gerontol ; 159: 111659, 2022 03.
Article in English | MEDLINE | ID: mdl-34921915

ABSTRACT

The prevalence of type 2 diabetes increases with age-associated increased susceptibility of islet ß-cells and altered dietary patterns, in part because of insufficient compensation of ß-cell functional mass in the face of increasing insulin resistance. However, the underlying mechanisms have not been fully elucidated. In the present study, we investigated the effects of a long-term calorie-restricted (CR) or high-fat (HF) diet compared to a normal ad libitum diet on ß-cell structure-function relationships and autophagy in the islets of 3- and 24-month-old Fischer 344 rats. Aging and the HF diet decreased the ß-cell-to-islet area ratio, disorganized the islet structure, and increased the expression of senescence markers. Aging and the long-term HF diet also decreased autophagy-related proteins, which suggests compromised autophagic function. These findings were further corroborated by increased p62 accumulation and polyubiquitin aggregates observed with aging and the HF diet intervention; these are cardinal markers of attenuated autophagic function. It is important to note that the 24-month-old rats maintained on the CR diet closely mimicked the 3-month-old rats, which indicates that a long-term CR diet can delay islet aging and prevent the decline in the autophagic function of islets during the aging process. Taken together, our results indicate an autophagy-dependent mechanism responsible for islet function in older people or those with altered dietary patterns and lay the foundations for future research leading to novel therapeutic strategies for treating diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Aging/physiology , Animals , Autophagy , Diet, High-Fat/adverse effects , Rats , Rats, Inbred F344
7.
Front Med (Lausanne) ; 8: 682116, 2021.
Article in English | MEDLINE | ID: mdl-34307412

ABSTRACT

Objective: It is currently unclear whether the Helicobacter pylori (H. pylori) infection leads to associated alterations in thyroid functions and thyroidal illnesses. This study aims to analyse this relationship in an elderly male cohort over a five-year period. Design: A case retrospective study. Methods: A longitudinal study was designed to collect subjects (≥65 years old) receiving both a thyroid examination and H. pylori infection status determined by 13C-urea breath test in 2013 at our unit. Subjects were followed every 1 to 2 years until December 2017 for laboratory results, visits to outpatient clinics/emergency departments etc. Blood tests and thyroid ultrasonography were performed to determine thyroid function and morphology. Results: 356 male subjects with mean age 78.5 ± 9.8 years were included. Active H. pylori infection was positive in 88 subjects (24.7%). Thyroid function tests and ultrasonography showed similar patterns between H. pylori positive and negative groups. Non-thyroidal-illness syndrome (NTIS) was diagnosed in 30/210 (14%) patients who experienced acute illnesses and hospitalization over five-year follow-up. Notably, NTIS demonstrated significantly higher prevalence in the H. pylori positive group compared to the negative group (17.1 vs. 5.6%, P = 0.001). Multivariate analysis showed that when age, APACHE II score and hemoglobin levels were adjusted, H. pylori status still has significant interrelationship with NTIS (OR = 3.497, P = 0.003). Conclusions: There is a positive association between chronic active H. pylori infection and NTIS prevalence in this elderly male cohort. Further studies are needed to elucidate the role of H. pylori infection on NTIS in elderly male patients.

8.
Diabetes Res Clin Pract ; 173: 108683, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33607161

ABSTRACT

AIM: There have been few reports regarding the association between 1 h-PG concentration and type 2 diabetes mellitus (T2DM) in the elderly. This study was performed to assess the efficacy of 1 h-PG and 2 h-PG values in predicting future risk of T2DM in elderly. METHODS: The study population consisted of 928 male volunteers ≥ 55 years old without diabetes who were involved in a retrospective-prospective cohort study over 20 years with a baseline fasting plasma glucose (FPG) and OGTT that included measurement of 1 h-PG and 2 h-PG. The predictive capabilities of FPG and 1 h-PG, 2 h-PG values obtained during OGTT alone and added to a clinical prediction model consisting of traditional diabetes risk factors were assessed. RESULTS: Overall, 577 of all the 928 study participants (62%) developed T2DM over the 20-year follow-up. 1 h-PG and 2 h-PG values predicted T2DM and remained independent predictors of T2DM after adjusting for various traditional risk factors [HR = 1.269 (95% CI = 1.214-1.327), P < 0.001; HR = 1.269 (95% CI = 1.179-1.366), P < 0.001, respectively]. C-statistics for 1-h PG (C-statistics 0.794 [95% CI 0.765-0.823]) was significantly greater than that for 2-h PG (C-statistic 0.747 [95% CI 0.716-0.779]) in models adjusting for various traditional risk factors. 1 h-PG had the greatest area under the ROC curve (AUC, 0.766), which was greater than that of 2 h-PG (0.719). CONCLUSIONS: 1 h-PG is useful as a predictor of future development of T2DM independently of traditional risk factors in an elderly Chinese male population.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Glucose Tolerance Test/methods , Aged , China , Humans , Male , Prognosis , Prospective Studies , Retrospective Studies , Risk Factors
9.
Exp Clin Endocrinol Diabetes ; 128(8): 540-547, 2020 Aug.
Article in English | MEDLINE | ID: mdl-30380573

ABSTRACT

BACKGROUND: Age-related bone deteriorations are the common endocrine disorders in the elderly population, leading to an increased risk of fractures. Therefore, effective treatment strategies provide a way to prevent bone loss and improve the quality of life in the elderly population. The present study aimed to investigate the anti-osteoporotic effects of doxercalciferol (DOX) in aging mice. METHODS: Bone metabolism-related markers were measured by ELISA assay. The expression of bone formation and resorption-related genes was performed by RT-qPCR analysis. Hematoxylin and eosin (H&E) and Safranin O staining were performed to analyze the trabecular bone and cartilage degeneration. RESULTS: Aging resulted in urine ca2+ excretion, a decrease in bone ca2+ content and reduction of biomechanical strength in mice. We also found that the level of PTH was increased in aging mice, while DOX administration markedly down-regulated serum PTH in aging mice. H&E and Safranin O staining showed that DOX protected against aging-induced bone loss and cartilage regeneration in the tibia from aging mice. Furthermore, DOX treatment resulted in an increase in Runx2, osterix and Col1a1 mRNA expression and a decrease in Ctsk, MMP-9 and CAII mRNA expression in the tibia from aging mice. CONCLUSION: These findings indicated that DOX had a beneficial effect on age-related bone deteriorations in aging mice by promoting osteoblast activity and cartilage regeneration and inhibiting osteoclast-specific genes expression.


Subject(s)
Cartilage Diseases/drug therapy , Cartilage/drug effects , Ergocalciferols/therapeutic use , Osteoporosis/drug therapy , Aging/drug effects , Aging/metabolism , Animals , Bone and Bones/drug effects , Bone and Bones/metabolism , Calcium/metabolism , Cartilage/pathology , Cartilage Diseases/blood , Cartilage Diseases/pathology , Cartilage Diseases/urine , Male , Mice , Mice, Inbred C57BL , Osteoblasts/drug effects , Osteoblasts/physiology , Osteoclasts/drug effects , Osteoclasts/physiology , Osteogenesis/drug effects , Osteoporosis/blood , Osteoporosis/pathology , Osteoporosis/urine
10.
Aging Male ; 22(1): 68-73, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30039993

ABSTRACT

OBJECTIVE: To investigate the relationship of testosterone and different glucose tolerance state, and its association with osteocalcin. METHODS: A cross-sectional study was conducted of 1176 males aged 60-97 years who were arranged for an annual regular checkup from March to May 2012 in Chinese PLA general hospital in Beijing. RESULTS: Individuals categorized as having prediabetes or diabetes were more likely to have lower osteocalcin, testosterone, and SHBG levels compared to those with normal glucose tolerance (p < .05 in males). In aging males, after adjusting for age, the negative association between osteocalcin and BMI, waist circumference, FPG, 2hPBG, or TG were significant. And serum TT was negatively associated with BMI, waist circumference, FPG, 2hPBG, or TG independent of age, ALP, Ca, P, VitD, and PTH. CONCLUSIONS: It showed that serum osteocalcin and TT were closely related with BMI, blood glucose, and TG, which supported the hypothesis that regulation of bone remodeling, energy metabolism, and reproduction are linked.


Subject(s)
Blood Glucose/analysis , Glucose Intolerance/blood , Osteocalcin/blood , Testosterone/blood , Aged , Aged, 80 and over , Biomarkers/blood , Body Mass Index , Cholesterol/blood , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Glucose Intolerance/classification , Humans , Linear Models , Male , Middle Aged , Waist Circumference
11.
Horm Metab Res ; 50(10): 747-753, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30312985

ABSTRACT

The incidence of vitamin D deficiency is high globally, and vitamin D supplementation draws particular attention. The objective of this study was to investigate the effects of stratified vitamin D supplementation in middle-aged and elderly individuals with vitamin D insufficiency in Beijing. A total of 448 subjects aged over 40 years old were selected from a community in Beijing. Among them, 100 middle-aged and elderly people with vitamin D insufficiency were randomly selected on a voluntary basis. They were further divided into control group and intervention group. The control group received health education and lifestyle guidance, and the intervention group received lifestyle guidance and vitamin D supplementation for nine months. The doses were stratified as follows: for vitamin D insufficiency, oral vitamin D3 supplement was given at 5000 IU/w; for mild vitamin D deficiency, oral vitamin D3 supplement was given at 10 000 IU/w; for severe vitamin D deficiency, oral vitamin D3 supplement was given at 15 000 IU/w. Safety evaluation was conducted after three-month treatment. The intervention group consisted of 8%, 62%, and 30% of cases who had vitamin D insufficiency, mild vitamin D deficiency, and severe vitamin D deficiency, respectively, which were similar with the control group. It showed that the blood 25(OH)D level increased significantly in the intervention group, from 14.30±4.30 ng/ml to 33.62±6.99 ng/ml (p<0.001), in contrast to insignificant change in the control group. Stratified vitamin D supplementation effectively increased the blood 25(OH)D level, as well as the number of cases with corrected vitamin D insufficiency or deficiency.


Subject(s)
Dietary Supplements , Vitamin D Deficiency/drug therapy , Vitamin D/therapeutic use , Aged , Female , Humans , Life Style , Male , Middle Aged , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood
12.
Mol Med Rep ; 18(5): 4675-4681, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30221655

ABSTRACT

Ursolic acid (UA) is a triterpenoid isolated from Chinese herbal medicine. It is extensively distributed in the plant kingdom in at least 63 Chinese herbal medicines of 26 families. UA has multiple bioactivities, including anti­viral hepatitis, antitumor, anti­oxidation, anti­bacterium and anti­inflammation. The aim of this in vitro study was to examine the effects of UA on diabetes­induced nephropathy and its possible mechanism. In mice with diabetes­induced nephropathy, UA increased the body weight, reduced kidney/body weight index, protected kidney cells, alleviated inflammation [tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL­6 and IL­18 levels] and kidney cell damage. It was also indicated that UA suppressed Toll­like receptor 4 (TLR4), myeloid differentiation factor 88 and nuclear factor­κB protein expression in mice with diabetes­induced nephropathy. The inhibition of TLR4 increased the anti­inflammation of UA on inflammation in rat with diabetes­induced nephropathy through the TLR4 signaling pathway. In conclusion, UA alleviates inflammation and inhibits diabetes­induced nephropathy through a TLR4­mediated inflammatory pathway. The present findings indicated that UA may be a possible therapeutic agent against diabetic nephropathy.


Subject(s)
Diabetic Nephropathies/drug therapy , Inflammation/drug therapy , Toll-Like Receptor 4/genetics , Triterpenes/administration & dosage , Animals , Diabetic Nephropathies/complications , Diabetic Nephropathies/genetics , Diabetic Nephropathies/pathology , Disease Models, Animal , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/chemistry , Gene Expression Regulation/drug effects , Humans , Inflammation/complications , Inflammation/genetics , Inflammation/pathology , Kidney/drug effects , Kidney/pathology , Mice , Myeloid Differentiation Factor 88/genetics , NF-kappa B/genetics , Oxidative Stress/drug effects , Rats , Signal Transduction/genetics , Triterpenes/chemistry , Tumor Necrosis Factor-alpha/genetics , Ursolic Acid
13.
FASEB J ; 32(9): 4627-4640, 2018 09.
Article in English | MEDLINE | ID: mdl-29565736

ABSTRACT

Testosterone is essential for spermatogenesis and the maintenance of secondary sexual characteristics in males. An important transcription factor, LIM-homeobox gene 9 (Lhx9) is indispensable for testis development and testosterone production; however, post-translational modifications of Lhx9 are largely unknown. Here, for the first time to our knowledge, we demonstrate that the level of Lhx9 protein increases in human chorionic gonadotropin-exposed Leydig cells and can be polyubiquitylated. We found that Smad ubiquitylation regulatory factor 1 (Smurf1), an E3 ubiquitin ligase, targets Lhx9 for ubiquitin-mediated proteasome degradation, thereby negatively modulating its function. Increasing Smurf1 decreases the level of Lhx9 and inhibits the Lhx9 transactivation capacity of steroidogenic factor 1 [nuclear receptor subfamily 5, group A, member 1 (NR5A1)]. In contrast, the depletion of Smurf1 leads to increased expression of Lhx9 protein and enhances testosterone biosynthesis-related gene transcripts [NR5A1, steroidogenic acute regulatory protein, CYP17A1, hydroxy-δ-5-steroid dehydrogenase, hydroxy-δ-5-steroid dehydrogenase isomerase 6, and hydroxysteroid (17-ß) dehydrogenase 3] and testosterone production in Leydig cells. Furthermore, we found that Smurf1 knockout mice exhibit higher levels of Lhx9 protein and steroidogenesis, which leads to increased serum testosterone concentration. These findings reveal that Smurf1 promotes Lhx9 ubiquitylation and is involved in testosterone production in Leydig cells directly. Our results provide new insights into the molecular events that play a role in the homeostasis of testosterone levels and may provide a new target for testosterone regulation.-Hu, F., Zhu, Q., Sun, B., Cui, C., Li, C., Zhang, L. Smad ubiquitylation regulatory factor 1 promotes LIM-homeobox gene 9 degradation and represses testosterone production in Leydig cells.


Subject(s)
LIM-Homeodomain Proteins/genetics , Leydig Cells/metabolism , Transcription Factors/genetics , Ubiquitin-Protein Ligases/genetics , Animals , Genes, Homeobox/genetics , Humans , Male , Mice, Knockout , Spermatogenesis/drug effects , Spermatogenesis/physiology , Testosterone/metabolism , Testosterone/pharmacology , Transcription Factors/metabolism
14.
Exp Gerontol ; 89: 87-92, 2017 03.
Article in English | MEDLINE | ID: mdl-28062371

ABSTRACT

OBJECTIVES: To assess the effect of baseline body mass index (BMI) status and weight change on mortality in older men with impaired glucose regulation (IGR). METHODS: Eight hundred eighty-five men with IGR aged 60 to 90 were included. Baseline and endpoint weight were measured. All-cause and cardiovascular mortality were observed during a median follow-up period of 10years. Multivariate Cox regressions were used to estimate associations between BMI, weight change and mortality. RESULTS: Relative to normal weight, overweight was associated with lower all-cause mortality (hazard ratios, HRs [95% confidence interval, 95% CI]: 0.57 [0.41, 0.78]) and cardiovascular mortality (0.52 [0.29, 0.93]), whereas obesity did not significantly decrease or increase the mortality risk. Furthermore, compared to weight stability, all types of weight change led to increased mortality risk, except small weight gain. Specifically, after adjustment for covariates and the initial weight, the HRs (95% CI) of large weight loss were 1.64 (1.15, 2.34) for all-cause mortality and 1.85 (1.10, 3.14) for cardiovascular mortality, and the HRs (95% CI) of large weight gain were 1.55 (1.01, 2.40) for all-cause mortality and 2.11 (1.04, 4.30) for cardiovascular mortality. Similar associations were observed when weight change was redefined in sensitivity analyses. CONCLUSIONS: Both BMI at baseline and weight change have independent U-shaped associations with all-cause and cardiovascular mortality among older men with IGR. The present study suggests that older men with IGR may ensure their best survival by being overweight at baseline or by maintaining their weight regardless of their baseline weight status.


Subject(s)
Body Mass Index , Body Weight , Cardiovascular Diseases/mortality , Glucose Intolerance/physiopathology , Aged , Aged, 80 and over , Blood Glucose/analysis , Body Weight Maintenance , China , Glucose Tolerance Test , Humans , Male , Middle Aged , Mortality , Multivariate Analysis , Obesity , Overweight , Proportional Hazards Models , Risk Factors
15.
Clin Exp Med ; 16(3): 437-42, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26055459

ABSTRACT

The aim of this study was to investigate the causes and influential factors of renal damage in elderly patients with type 2 diabetes mellitus (T2DM). Clinical data and pathological findings at autopsy of 161 elderly T2DM patients died between October 1994 and August 2011 were retrospectively reviewed. The mean age of these patients was 80.8 ± 8.3 years (range 60-105 years). The incidences of diabetic nephropathy (DN), non-diabetic renal diseases (NDRD), and DN complicated with NDRD were 31.1, 62.7, and 16.2 %, respectively. In patients with NDRD, the incidence of hypertensive renal damage (HRD) was 54.7 %. In the factors causing renal damage, DN and NDRD accounted for 1/3 and 2/3, respectively. HRD accounted for the largest proportion of NDRD. Blood pressure control may provide additional benefits for elderly T2DM patients by preventing and delaying the occurrence and development of renal disease.


Subject(s)
Diabetes Mellitus, Type 2/complications , Kidney Diseases/epidemiology , Kidney Diseases/pathology , Aged , Aged, 80 and over , Autopsy , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies
16.
Int J Clin Exp Med ; 8(8): 13790-6, 2015.
Article in English | MEDLINE | ID: mdl-26550327

ABSTRACT

Recent evidence indicates the potential role of vitamin D in the prevention of Metabolic syndrome (MetSyn). This is an analytical cross sectional study. A total of 3275 subjects were investigated. 25-hydroxyvitamin D(25[OH]D) was detected by electrochemiluminescence immunoassay (ECLIA) technology. Metabolic syndrome was defined according to the definition of International Diabetes Federation (IDF). Among the participants, the prevalence of the MetSyn was 6.0%. The prevalence of vitamin D deficiency and insufficiency was 50.1% and 25.0% respectively. Subjects with MetSyn presented with significantly lower 25(OH)Vit D serum levels compared with non-MetSyn group. The results shows that vitamin D deficiency is common in Chinese adults, and subjects with lower serum 25(OH)D have a higher risk of the MetSyn. The cut-off value of serum 25(OH)D that reflected MetSyn in Chinese adluts was 15.655 ng/mL.

17.
Int J Clin Exp Med ; 8(3): 3855-61, 2015.
Article in English | MEDLINE | ID: mdl-26064284

ABSTRACT

BACKGROUND: Osteoporosis is a significant cause of morbidity and mortality in the elderly and an important public health issue. Bisphosphonates are the primary treatment options for osteoporosis. The oral administration of bisphosphonates may result in poor patient compliance and thence reduced treatment efficacy. Intravenously administered bisphosphonates may therefore show better treatment efficacy. We have carried out a meta-analysis to evaluate the efficacy of zoledronic acid treatment for osteoporosis in both men and women with either vertebral or non-vertebral fracture. MATERIAL AND METHODS: Randomized controlled trials with zoledronic acid treatment for osteoporosis were retrieved from PubMed, EMBASE and clinicaltrials.gov. The risk ratio with 95% confidence interval (RR, 95% CI) was calculated to evaluate the effect of zoledronic acid treatment on incidence of fracture. Data on changes in bone mineral density (BMD) following zoledronic acid (ZOL) treatment was also extracted. STATA software was used for all the statistical analyses. RESULTS: Significant reduction in the incidence of both vertebral and nonvertebral fracture was observed following ZOL treatment, as seen from the values for RR with 95% CI (RR 0.24 and 95% CI 0.15 to 0.40 for vertebral fractures; RR 0.76 and 95% CI 0.67 to 0.86 for nonvertebral fractures). BMD was also seen to be increased after ZOL treatment. CONCLUSION: Ourmeta-analysis showed that zoledronic acid was effective in reducing the incidence of vertebral fractures as well as nonvertebral fractures, including hip fractures. Significant increase in bone mineral density (BMD) was also observed in patients administered ZOL as compared to placebo.

18.
Aging Male ; 18(1): 27-33, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25657081

ABSTRACT

OBJECTIVE: This single-centre cross-sectional study aimed to investigate the metabolic and gonadal risk factors of vascular diseases in elderly males. METHODS: After screening, 337 subjects aged 60-90 were found to be qualified. Odds ratios (ORs) in cross-table analyses and exp(B) in logistic regression analyses were used to evaluate the vascular risk of dependent factors. R(2) of logistic regression equation was used to estimate the goodness-of-fit of vascular diseases logistic regression models. RESULTS: Hypertension increased the risk of cardiovascular disease (CAVD) in elderly men approximately 3-fold. The number of metabolic diseases also correlated with incremental risks of CAVD; presence of one abnormality approximately increases the risk approximately 62%. Cerebrovascular disease (CEVD) development was closely associated with both metabolic syndrome and sex hormone levels; their explanation effects of single action and combined action were 13.2%, 12.55% and 28.5%. C-peptide might be the underlying mechanism of the metabolic syndrome's effect on CEVD. C-peptide = 2.43 U/L and FE(2) = 0.66 were the tangent points in receiver operating characteristic (ROC) analyses. CONCLUSIONS: Metabolic diseases and sex hormones play different roles in the development of CAVD and CEVD, the methods for vascular protection in elderly men should be promoted differently according to the their risks of CAVD and CEVD.


Subject(s)
Cardiovascular Diseases/etiology , Cerebrovascular Disorders/etiology , Gonadal Steroid Hormones/blood , Metabolic Syndrome/complications , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cerebrovascular Disorders/epidemiology , Cross-Sectional Studies , Humans , Male , Middle Aged , Risk Factors
19.
Zhonghua Yi Xue Za Zhi ; 94(33): 2597-601, 2014 Sep 09.
Article in Chinese | MEDLINE | ID: mdl-25511492

ABSTRACT

OBJECTIVE: To explore the mortality risks of elders with and without type 2 diabetes mellitus (T2DM) during a fellow-up period of 17 years. METHODS: The subjects were elderly patients (>60 years old) undergoing annual health examinations at our hospital. And the incidence and risk factors were analyzed by Kaplan-Meier method and COX's proportional hazard. RESULTS: A total of 2 142 subjects were divided into T2DM group (DM, n = 746) and non-T2DM group (N-DM, n = 1 396). During a 17-year follow-up, the mortality rate of all causes was 50.9% in DM group versus 32.45% in N-DM group (P < 0.01). The major mortality causes were malignant tumor, respiratory disease and cardiovascular disease. Kaplan-Meier analysis revealed that the accumulative mortality of all causes and cardiovascular with DM was significantly above that of N-DM. The independent mortality risk factors of elders was T2DM (P < 0.01, HR = 1.36, 95% CI: 1.192-1.558) and cardiovascular disease (P < 0.01, HR = 3.26, 95% CI: 2.887-3.690) based upon the COX's proportional hazard analysis. CONCLUSION: Type 2 diabetes mellitus is an independent risk factor for elders with increased mortality risk.


Subject(s)
Diabetes Mellitus, Type 2 , Aged , Cardiovascular Diseases , Cohort Studies , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Proportional Hazards Models , Risk Factors
20.
Int J Clin Exp Med ; 7(10): 3800-7, 2014.
Article in English | MEDLINE | ID: mdl-25419435

ABSTRACT

Type 2 diabetes mellitus (T2DM) accounts for the majority of diabetes cases and affects a significant proportion of the adult population worldwide. Calpain-10 has been implicated in the development of type 2 diabetes, and some polymorphisms in the CAPN10 gene have been associated with an increased risk of developing this disease. Several molecular epidemiological studies were conducted in recent years to evaluate the association between the CAPN10 rs2975760 polymorphism and T2DM risk in diverse populations. However, the results remain conflicting rather than conclusive. We performed a meta-analysis of 8 case-control studies that included 2758 T2DM cases and 2762 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confi dence intervals (CIs). Overall, this meta-analysis showed that the CAPN10 rs2975760 polymorphism was not associated with a significantly type 2 diabetes risk in three genetic models. However, after excluding two study for its heterogeneity, a significantly increased risk was found in all comparisons (for C vs T: OR=1.14, 95% CI=1.03-1.27, I (2)=0, P heterpgeneity=0.420, P b=0.012; for TC vs TT: OR=1.15, 95% CI=1.01-1.30, I (2)=3.8%, P heterpgeneity=0.392, P b=0.030; for CC+TC vs TT: OR=1.16, 95% CI=1.03-1.31, I (2)=3.7%, P heterpgeneity=0.393, P b=0.015). No publication bias was found in the present study. This meta-analysis suggests that the C allele of the CAPN10 rs2975760 polymorphism is associated with an increased T2DM risk. Further large and well-designed studies are needed to confi rm this association.

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