Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway.

Lung ischemia-reperfusion injury (LIRI) is a prevalent occurrence in various pulmonary diseases and surgical procedures, including lung resections and transplantation. LIRI can result in systemic hypoxemia and multi-organ failure. Hydroxycitric acid (HCA), the primary acid present in the peel of Garcinia cambogia, exhibits anti-inflammatory, antioxidant, and anticancer properties. However, the effects of HCA on LIRI remain unknown. To investigate the impact of HCA on LIRI in mice, the mice were randomly divided into four groups: the control group, the I/R model group, and the I/R + low- or high-dose HCA groups. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia for 12 h followed by reoxygenation for 6 h to simulate in vitro LIRI. The results demonstrated that administration of HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion. Moreover, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels while decreasing iron content and increasing superoxide dismutase (SOD) levels after ischemia-reperfusion insult. Mechanistically, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro. We found that HCA could also alleviate endothelial barrier damage in H/R-induced HUVECs in a concentration-dependent manner. In addition, overexpression of Hif-1α counteracted HCA-mediated inhibition of H/R-induced endothelial cell ferroptosis. In summary, these results indicate that HCA alleviated LIRI by inhibiting oxidative stress and ferroptosis through the Hif-1α pathway.

Association between spicy foods consumption and cardiovascular disease risk factors: Guangzhou Biobank Cohort Study.

BACKGROUND: Evidence regarding the association of spicy foods intake with cardiovascular disease (CVD) risk factors was less clear, especially in those with diabetes. We hereby examined the association of spicy foods intake with CVD risk factors in older Chinese. METHODS: Thirty thousand three hundred twenty-five participants (72.34% women) aged 50+ years were recruited in the Guangzhou Biobank Cohort Study from 2003 to 2008. Information of spicy foods intake and disease history was collected by face-to-face interview. CVD risk factors were measured and treated as continuous variables. Diabetes was defined by a fasting plasma glucose (FPG) ≥7.0 mmol/L and/or self-reported physician-diagnosed diabetes. RESULTS: Of 30,325 participants, 12.9% consumed spicy foods regularly. After adjusting for multiple confounders, participants who consumed spicy foods of 5-7 days/week, versus none, had higher body mass index (1.18, 95% confidence interval (CI) 0.95 to 1.42 kg/m2), waist circumference (2.80, 95% CI 2.18-3.41 cm), waist-to-hip ratio (0.010, 95% CI 0.006 to 0.015), systolic blood pressure (2.44, 95% CI 0.92 to 3.97 mmHg), diastolic blood pressure (1.94, 95% CI 1.14 to 2.73 mmHg), FPG (0.310, 95% CI 0.188 to 0.432 mmol/L), triglycerides (0.185, 95% CI 0.096 to 0.273 mmol/L), and lower high-`density lipoprotein cholesterol (- 0.040, 95% CI - 0.069 to - 0.012 mmol/L). Similar results were found for the associations of spicy foods strength with CVD risk factors. The results attenuated slightly but not substantially across diabetes groups. CONCLUSIONS: Our study showed that higher frequency and strength of spicy foods intake were associated with unfavorable cardiovascular disease risk profile in older people, and such associations did not vary by diabetes status. Whether the results were causal needs to be determined in further studies.

CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in acute lung injury induced by sepsis through modulating miR-21.

Acute lung injury (ALI) induced by sepsis is characterized by an inflammatory process related to the up-regulation of inflammatory cytokines and chemokines. In the present study, we explored the role of circC3P1 in sepsis-induced ALI in vitro and in vivo. The caecal ligation and puncture (CLP)-induced sepsis model was established through CLP surgery. Forty adult male C57BL/6 mice were randomly assigned into sham, CLP, CLP + vector and CLP + circC3P1 (each n = 10). Primary murine pulmonary microvascular endothelial cells (MPVECs) were transfected with circC3P1 or empty vector 24 hours prior to LPS treatment via Lipofectamine 2000. The expressions of circC3P1, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß were evaluated after 6-h LPS treatment. Cell apoptosis was evaluated via flow cytometry. The CLP group demonstrated pulmonary morphological abnormalities, increased concentrations of TNF-α, IL-6 and IL-1ß in the lung tissue, compared with the sham group. MPVECs treated with LPS significantly elevated TNF-α, IL-6 and IL-1ß levels and increased cell apoptosis than that in the control group. The circC3P1 overexpression in sepsis-induced ALI mice attenuated pulmonary injury, inflammation and apoptosis. Besides, circC3P1 revealed anti-inflammatory and anti-apoptotic effect in MPVEC-treated LPS. CircC3P1 overexpression reduced cell apoptosis and pro-inflammatory cytokines levels via down-regulating miR-21. CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in ALI induced by sepsis through modulating miR-21, indicating that circC3P1 is a promising therapeutic biomarker for sepsis-induced ALI.

Inaccuracy of Self-reported Low Sodium Diet among Chinese: Findings from Baseline Survey for Shandong & Ministry of Health Action on Salt and Hypertension (SMASH) Project.

This study was aimed to evaluate the agreement between the self-reported sodium intake level and 24-h urine sodium excretion level in Chinese. The 24-h urine collection was conducted among 2112 adults aged 18-69 years randomly selected in Shandong Province, China. The subjects were asked whether their sodium intake was low, moderate, or high. The weighted kappa statistics was calculated to assess the agreement between 24-h urine sodium excretion level and self-reported sodium intake level. One third of the subjects reported low sodium intake level. About 70% of the subjects had mean 24-h sodium excretion>9 g/d, but reported low or moderate sodium intake. The agreement between self-reported sodium intake level and 24-h urine sodium excretion level was low in both normotensive subjects and hypertensive subjects. These findings suggested that many subjects who reported low sodium intake had actual urine sodium excretion>9 g/d. Sodium intake is often underestimated in both hypertensive and normotensive participants in China.

Prevalence of overweight and obesity and their associations with blood pressure among children and adolescents in Shandong, China.

BACKGROUND: Obesity and high blood pressure (BP) are public health problems all over the world. Some studies have reported a positive association between them in children and adolescents. The purpose of this study was to assess the prevalence of overweight and obesity and their associations with BP among school children and adolescents in Shandong, an important province in eastern China. METHODS: In 2011, we conducted a cross-sectional population-representative survey in Shandong, China. A total of 4 898 children and adolescents aged 6-17 years were randomly selected from 140 counties/districts using a multistage random cluster sampling. Weight, height and BP were measured by a trained physician or pediatrician, and information about age, gender and place of residence was obtained using questionnaires. Obesity and high BP were defined according to age- and gender-specific Chinese reference data for children. RESULTS: A total of 4 898 (100%) children and adolescents provided complete information. The prevalence of overweight, obesity and overweight plus obesity were 10.9%, 8.7% and 19.6%, respectively. Boys were more likely to be overweight or obese than girls (P < 0.05 for overweight; P < 0.001 for obesity). The prevalence of overweight plus obesity was highest among children aged 6-11 years (22.3%). BP and the prevalence of high BP increased with increasing body mass index (BMI). With age and sex adjusted, odds ratios (ORs) for high BP were [OR 2.2;95% CI 1.7-2.8) in overweight and [OR 3.6;95% CI 2.6-4.9] in obese children. CONCLUSION: The representative survey confirms high prevalence of overweight and obesity among children and adolescents in Shandong. Childhood obesity is a strong risk factor for high BP. Intervention programs should be implemented to combat the growing obesity epidemic.

Dietary sodium intake and its impact factors in adults of Shandong province.

Dietary sodium intake and its impact factors in 2 140 adults aged 18-69 years were analyzed. The mean daily sodium intake was 5745.0 (5427.6-6062.5) mg per day, which was higher in males than in females (P<0.01). After having been adjusted for gender, age and urban/city areas, the mean daily sodium intake was significantly higher in participants with a lower education level, drinkers and smokers than in those with a higher education level, nondrinkers and nonsmokers (P<0.01). The dietary sodium intake in adults of Shandong Province is higher than the recommended standards.

Mitochondrial quality control in human health and disease.

Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.

[Evaluation on the effectiveness of community intervention on hypertension related knowledge in mid-western rural area of Shandong province].

OBJECTIVE: To evaluate the intervention effect of health education on hypertension knowledge in mid-western rural area of Shandong province. METHODS: A project was launched on chronic disease control in mid-western rural area of Shandong province from 2007 to 2010. The baseline survey was performed using multi-stage random sampling method in 8 counties of mid-western rural area of Shandong province in April, 2007. A total of 20 087 participants aged 25 and above were recruited in the survey to study the relationship between awareness of hypertension and diet, smoking, obesity. Health education focusing on balance diet, physical activity promotion and tobacco control was performed among intervention population. The final evaluation survey using same questionnaire was performed in 2010, classified in intervention (4071 participants) and control (2145 participants) group. Control group was selected from non-intervention town in same county. Intervention and control group shared the same baseline data in 2007 for evaluation. By comparing the changes of hypertension knowledge before and after intervention, the intervention effect was evaluated. RESULTS: Awareness of the relationship between hypertension and diet rose from 34.0% (6830/20 087) at baseline in 2007 to 69.3% (2821/4071) (χ(2) = 1757.30, P < 0.01) of intervention group and 44.8% (961/2145) (χ(2) = 99.30, P < 0.01) of control group in 2010. Awareness of hypertension associated to smoking rose from 25.6% (5142/20 087) at baseline in 2007 to 55.2% (2247/4071) (χ(2) = 1396.59, P < 0.01) in intervention group, 30.9% (662/2145) (χ(2) = 27.83, P < 0.01) in control group in 2010. Awareness of hypertension related to obesity rose from 37.2% (7472/20 087) of the baseline in 2007 to 68.3% (2780/4071) (χ(2) = 1339.27, P < 0.01) in intervention group, 45.1% (967/2145) (χ(2) = 51.14, P < 0.01) in control group in 2010. CONCLUSION: Community comprehensive intervention showed significant effects on hypertension related knowledge improvement in mid-western rural area of Shandong province.

[Combination effects of vitamin A and zinc on human's PMBC DNA damage in vitro].

OBJECTIVE: To study the combination effects of vitamin A (Vit. A) and zinc on human's PBMC DNA damage in vitro. Methods The PBMC from healthy volunteer was purification and cultured in the basic culture medium with Vit.A of 10(-4), 10(-5) and 10(-6) mol/L, or/and with Zn of 10(-6), 10(-5) 10(-4) and 10(-3) mol/L. The basic culture medium with K2Cr2O7 of 1 mmol/L was the male control. The damage of PBMC DNA was respectively examined by SCGE and the image analyzer measured the comet tail rate and length. The apoptosis of each group PBMC was detected by FCM. RESULTS: The overdose supplement of zinc and Vit. A can damage the PBMC DNA in vitro culture (P < 0.01), while the suitable supplement doesn't find. When the Vit. A supplement has been excessive, giving suitable zinc could repair the damage of DNA, but would expand the injured cell. While when the zinc supplement has been excessive, giving suitable Vit. A could protect the healthy cells, but would aggravate the damage degree of injured cell. CONCLUSION: In vitro culture, the overdose Vit. A and zinc supplement could damage the human's PBMC DNA significantly. This need more researches to provide.

[The status of awareness, treatment and control of hypertension in adult population in Shandong province in 2011].

OBJECTIVE: To identify the status of awareness, treatment and control of hypertension in adult population in Shandong province in China. METHODS: A total of 15 350 representative subjects aged 18 to 69 in Shandong province were selected with multistage stratified and clustered sampling design. Questionnaire investigation and physical examination including measurement of blood pressure, height and weight, were taken for all of them. The prevalence was estimated by weighted SURVEYFREQ model. RESULTS: In Shandong province, 34.5% of the hypertensive patients were aware of their high blood pressure (31.1% in male, 38.5% in female), 27.5% of them were taking antihypertensive medications (24.1% in male, 31.7% in female), and 14.9% of them (13.7% in male, 16.4% in female) were under control for their blood pressure (<140/90 mm Hg). CONCLUSION: The rates of awareness, treatment and control of hypertension in adult hypertensive population in Shandong province, China were low, and it is urgently needed to take steps for intervention and control for hypertension prevention, particularly in rural areas.

Dietary sodium intake: knowledge, attitudes and practices in Shandong Province, China, 2011.

OBJECTIVE: To investigate the knowledge, attitudes and practices (KAP) for dietary sodium intake among adult residents of Shandong Province, China. METHODS: In 2011, we conducted a cross sectional survey among a representative sample of 15,350 adults aged 18 to 69 years using a standardized questionnaire to assess their KAP for sodium. Variation in the KAPs by gender, and residence location were compared using the Chi-square tests. Predictors for the 'intention to' and 'currently taking action to' reduce sodium intake were determined by multivariate logistic regression with adjustment for confounding factors. RESULTS: KAPs for dietary sodium intake among urban residents was generally more favorable than among rural residents. Women were likely to have more favorable KAPs than men. About four fifth of subjects reported that they favored a low sodium diets. However, 31% reported that consumption of less sodium results in less physical strength. Overall, 70% indicated their intention to reduce sodium intake, although only 39 % reported that they had taken action to reduce sodium. Multiple logistic regression analyses indicated that favorable actions to dietary sodium reduction were more likely to occur among those who were aware of the link between sodium and hypertension, and less likely among those who had unfavorable attitudes towards dietary sodium reduction. CONCLUSION: Increasing knowledge levels about the benefits of sodium reduction will be a key success factor for effective sodium reduction initiatives and is linked to favorable behavioral change. Emphasis should be placed on the rural area.

[Estimation on the mortality and disease burden attributed to selected risk factors in Shandong province].

OBJECTIVE: To determine the major health related risk factors and provide evidence for policy-making, using health burden analysis on selected factors among general population from Shandong province. METHODS: Based on data derived from the Third Death of Cause Sampling Survey in Shandong, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) were calculated according to the GBD methodology. Deaths and DALYs attributed to the selected risk factors were than estimated together with the PAF data from GBD 2001 study. The indirect method was employed to estimate the YLDs. RESULTS: 51.09% of the total deaths and 31.83% of the total DALYs from the Shandong population were resulted from the 19 selected risk factors. High blood pressure, smoking, low fruit and vegetable intake, alcohol consumption, indoor smoke from solid fuels, high cholesterol, urban air pollution, physical inactivity, overweight and obesity and unsafe injections in health care settings were identified as the top 10 risk factors for mortality which together caused 50.21% of the total deaths. Alcohol use, smoking, high blood pressure, low fruit and vegetable intake, indoor smoke from solid fuels, overweight and obesity, high cholesterol, physical inactivity, urban air pollution and iron-deficiency anemia were proved as the top 10 risk factors related to disease burden and were responsible for 29.04% of the total DALYs. CONCLUSION: Alcohol use, smoking and high blood pressure were determined as the major risk factors which influencing the health of residents in Shandong. The mortality and burden of disease could be reduced significantly if these major factors were effectively under control.

[Estimation of disability weights on malignant neoplasms in Shandong province].

OBJECTIVE: To determine stage-specific and average disability weights (DWs) of malignant neoplasm and provide support and evidence for study on burden of cancer and policy development in Shandong province. METHODS: Health status of each cancer patient identified during the cancer prevalence survey in Shandong, 2007 was investigated. In line with the GBD methodology in estimating DWs, the disability extent of every case was classified and evaluated according to the Six-class Disability Classification version and then the stage-specific weights and average DWs with their 95% confidence intervals were calculated, using SAS software. RESULTS: A total of 11 757 cancer cases were investigated and evaluated. DWs of specific stage of therapy, remission, metastasis and terminal of all cancers were 0.310, 0.218, 0.450 and 0.653 respectively. The average DW of all cancers was 0.317 (95%CI: 0.312 - 0.321). Weights of different stage and different cancer varied significantly, while no significant differences were found between males and females. DWs were found higher (> 0.4) for liver cancer, bone cancer, lymphoma and pancreas cancer. Lower DWs (< 0.3) were found for breast cancer, cervix uteri, corpus uteri, ovarian cancer, larynx cancer, mouth and oropharynx cancer. CONCLUSION: Stage-specific and average DWs for various cancers were estimated based on a large sample size survey. The average DWs of 0.317 for all cancers indicated that 1/3 healthy year lost for each survived life year of them. The difference of DWs between different cancer and stage provide scientific evidence for cancer prevention strategy development.

[Changes of mortality and causes of death from 1970 to 2005 and decomposition analysis in Shandong province].

OBJECTIVE: To describe the trend of overall mortality and major causes of death in Shandong population from 1970 to 2005, and to quantitatively estimate the influential factors. METHODS: Trends of overall mortality and major causes of death were described using indicators such as mortality rates and age-adjusted death rates by comparing three large-scale mortality surveys in Shandong province. Difference decomposing method was applied to estimate the contribution of demographic and non-demographic factors for the change of mortality. RESULTS: The total mortality had had a slight change since 1970s, but had increased since 1990s. However, both the mortality rates of age-adjusted and age-specific decreased significantly. The mortality of Group I diseases including infectious diseases as well maternal and perinatal diseases decreased drastically. By contrast, the mortality of non-communicable chronic diseases (NCDs) including cardiovascular diseases (CVDs), cancer and injuries increased. The sustentation of recent overall mortality was caused by the interaction of demographic and non-demographic factors which worked oppositely. Non-demographic factors were responsible for the decrease of Group I disease and the increase of injuries. With respect to the increase of NCDs as a whole, demographic factors might take the full responsibility and the non-demographic factors were the opposite force to reduce the mortality. Nevertheless, for the increase of some leading NCD diseases as CVDs and cancer, the increase was mainly due to non-demographic rather than demographic factors. CONCLUSION: Through the interaction of the aggravation of ageing population and the enhancement of non-demographic effect, the overall mortality in Shandong would maintain a balance or slightly rise in the coming years. Group I diseases in Shandong had been effectively under control. Strategies focusing on disease control and prevention should be transferred to chronic diseases, especially leading NCDs, such as CVDs and cancer.