Harnessing the physiochemical properties and enzymatic activities of nanozymes will provide new insights for disease theranostics. Herein, a novel carbon dot (C‐dot) superoxide dismutase (SOD) ...nanozyme that exhibits red fluorescence with emission wavelength of 683 nm and shows high SOD‐like activity of >4000 U mg−1 is reported, which presents the great potential for imaging the biodistribution of nanozyme itself in vivo and ameliorating acute lung injury. Through surface modifications, the mechanism of C‐dot SOD nanozyme activity is revealed to be relied on their surface functional groups which bind with superoxide radicals, promote the electron transfer between C‐dots and superoxide radicals, and finally accelerate the dismutation of superoxide radicals. The absolute quantum yield of ≈14% of red fluorescence C‐dot nanozyme endow it bioimaging in vitro and in vivo. Moreover, the C‐dot nanozyme effectively enters the cells, accumulates at mitochondria, and protects living cells from oxidative damage by scavenging reactive oxygen species (ROS) and reducing the levels of pro‐inflammatory factors. Importantly, in vivo animal experiments demonstrate the accumulation of C‐dots in injure lung and therapeutic effect of C‐dot nanozyme toward acute lung injury in mice. The red fluorescent C‐dot SOD nanozyme shows great potential for in vivo bioimaging and management of ROS‐related diseases.
Red emissive carbon dot nanozyme with high superoxide dismutase (SOD)‐like activity over 4000 U mg−1 is developed. The SOD nanozyme activity is revealed to be relied on their surface functional groups which capture O2•– and then promote the electron transfer between O2•– and π‐system of carbon dot. The C‐dot SOD nanozyme shows great potential in bioimaging and ameliorating acute lung injury.
IMPORTANCE: Understanding population-wide trends in prevalence and control of diabetes is critical to planning public health approaches for prevention and management of the disease. OBJECTIVE: To ...determine trends in prevalence of diabetes and control of risk factors in diabetes among US adults between 1999-2000 and 2017-2018. DESIGN, SETTING, AND PARTICIPANTS: Ten cycles of cross-sectional National Health and Nutrition Examination Survey (NHANES) data between 1999-2000 and 2017-2018 were included. The study samples were weighted to be representative of the noninstitutionalized civilian resident US population. Adults aged 18 years or older were included, except pregnant women. EXPOSURES: Survey cycle. MAIN OUTCOMES AND MEASURES: Diabetes was defined by self-report of diabetes diagnosis, fasting plasma glucose level of 126 mg/dL or more, or hemoglobin A1c (HbA1c) level of 6.5% or more. Three risk factor control goals were individualized HbA1c targets, blood pressure less than 130/80 mm Hg, and low-density lipoprotein cholesterol level less than 100 mg/dL. Prevalence of diabetes and proportion of adults with diagnosed diabetes who achieved risk factor control goals, overall and by sociodemographic variables, were estimated. RESULTS: Among the 28 143 participants included (weighted mean age, 48.2 years; 49.3% men), the estimated age-standardized prevalence of diabetes increased significantly from 9.8% (95% CI, 8.6%-11.1%) in 1999-2000 to 14.3% (95% CI, 12.9%-15.8%) in 2017-2018 (P for trend < .001). From 1999-2002 to 2015-2018, the estimated age-standardized proportion of adults with diagnosed diabetes who achieved blood pressure less than 130/80 mm Hg (P for trend = .007) and low-density lipoprotein cholesterol level less than 100 mg/dL (P for trend < .001) increased significantly, but not individualized HbA1c targets (P for trend = .51). In 2015-2018, 66.8% (95% CI, 63.2%-70.4%), 48.2% (95% CI, 44.6%-51.8%), and 59.7% (95% CI, 54.2%-65.2%) of adults with diagnosed diabetes achieved individualized HbA1c targets, blood pressure less than 130/80 mm Hg, and low-density lipoprotein cholesterol level less than 100 mg/dL, respectively. Only 21.2% of these adults (95% CI, 15.5%-26.8%) achieved all 3. During the entire study period, these 3 goals were significantly less likely to be achieved among young adults aged 18 to 44 years (vs older adults ≥65 years: estimated proportion, 7.4% vs 21.7%; adjusted odds ratio, 0.32 95% CI, 0.16-0.63), non-Hispanic Black adults (vs non-Hispanic White adults: estimated age-standardized proportion, 12.5% vs 20.6%; adjusted odds ratio, 0.60 95% CI, 0.40-0.90), and Mexican American adults (vs non-Hispanic White adults: estimated age-standardized proportion, 10.9% vs 20.6%; adjusted odds ratio, 0.48 95% CI, 0.31-0.77). CONCLUSIONS AND RELEVANCE: Based on NHANES data from US adults, the estimated prevalence of diabetes increased significantly between 1999-2000 and 2017-2018. Only an estimated 21% of adults with diagnosed diabetes achieved all 3 risk factor control goals in 2015-2018.
Cardiovascular disease (CVD) and environmental degradation are leading global health problems of our time. Recent studies have linked exposure to heavy metals to the risks of CVD and diabetes, ...particularly in populations from low- and middle-income countries, where concomitant rapid development occurs. In this review, we 1) assessed the totality, quantity, and consistency of the available epidemiological studies, linking heavy metal exposures to the risk of CVD (including stroke and coronary heart disease); 2) discussed the potential biological mechanisms underlying some tantalizing observations in humans; and 3) identified gaps in our knowledge base that must be investigated in future work. An accumulating body of evidence from both experimental and observational studies implicates exposure to heavy metals, in a dose-response manner, in the increased risk of CVD. The limitations of most existing studies include insufficient statistical power, lack of comprehensive assessment of exposure, and cross-sectional design. Given the widespread exposure to heavy metals, an urgent need has emerged to investigate these putative associations of environmental exposures, either independently or jointly, with incident CVD outcomes prospectively in well-characterized cohorts of diverse populations, and to determine potential strategies to prevent and control the impacts of heavy metal exposure on the cardiometabolic health outcomes of individuals and populations.
The aim of this meta-analysis of longitudinal studies was to obtain a valid and cogent assessment of predictive value of central haemodynamic variables for cardiovascular outcomes and all-cause ...mortality. We searched for eligible articles using MEDLINE, CINAHL, EMBASE and Web of Science between 1 January 1969 and 31 December 2017. We finally included 24 prospective cohort studies, comprising 146,986 individuals for this analysis. Adjusted pooled hazard ratio of total cardiovascular events was 1.10 (95% confidence interval CI 1.04-1.16) for a 10 mmHg increase of central systolic pressure, 1.12 (95% CI 1.05-1.19) for a 10 mmHg increase of central pulse pressure and 1.18 (95% CI 1.09-1.27) for a 10% increase of central augmentation index. Furthermore, pooled hazard ratio of all-cause mortality was 1.22 (95% CI 1.14-1.31) for a 10 mmHg increase of central pulse pressure and 1.19 (95% CI 1.05-1.34) for a 10% increase of central augmentation index. Central haemodynamic variables are independent predictors of cardiovascular disease and all-cause mortality. This finding supports the notion that central pressure components and indices could be suitably implemented in clinical practice.
Background/Aims: Although it is widely acknowledged that atherosclerosis is mainly a chronic inflammatory process, in which both miR-29b and interleukin-6 (IL-6) play multifaceted roles, the ...association between miR-29b and IL-6 remains unknown. The aim of the present study was to explore the relationship between miR-29b and IL-6 and to test whether circulating levels of miR-29b and IL-6 could predict atherosclerosis. Methods: A total of 170 participants were divided into two groups according to carotid intima-media thickness (CIMT): study group (CIMT ≥ 0.9mm) and control group (CIMT < 0.9mm). Levels of circulating miR-29b and IL-6 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The association of miR-29b and IL-6 levels with CIMT was assessed using Spearman correlation analysis and multiple linear regression analysis. Results: The study group showed higher miR-29b levels (31.61 ± 3.05 vs. 27.91 ± 1.71 Ct, p < 0.001) and IL-6 levels (3.40 ± 0.67 vs. 2.99 ± 0.37 pg/ml, p < 0.001), compared with the control group. CIMT was positively correlated with miR-29b (r = 0.587, p < 0.001) and IL-6 (r = 0.410, p < 0.001), and miR-29b levels were also correlated with IL-6 (r = 0.242, p = 0.001). Multiple linear regression analysis also showed that CIMT was positively correlated with miR-29b and IL-6. After adjustment for age, body mass index, systolic blood pressure, total cholesterol and C-reactive protein, CIMT was still closely correlated with miR-29b and IL-6. The combination of miR-29b and IL-6 (AUC = 0.901, p < 0.001) offered a better predictive index for atherosclerosis than either miR-29b (AUC = 0.867, p < 0.001) or IL-6 (AUC = 0.747, p < 0.001) alone. Conclusion: Circulating levels of miR-29b and IL-6 may be independently correlated with subclinical atherosclerosis, and may serve as novel biomarkers for the identification of atherosclerosis.
The triglyceride-glucose (TyG) index could serve as a convenient substitute of insulin resistance (IR), but epidemiological evidence on its relationship with the long-term risk of mortality is ...limited.
Participants from the National Health and Nutrition Examination Survey during 1999-2014 were grouped according to TyG index (<8, 8-9, 9-10, >10). Cox regression was conducted to compute the hazard ratios (HRs) and 95% confidence interval (CI). Restricted cubic spline and piecewise linear regression were performed to detect the shape of the relationship between TyG index and mortality.
A total of 19,420 participants (48.9% men) were included. On average, participants were followed-up for 98.2 months, and 2,238 (11.5%) and 445 (2.3%) cases of mortality due to all-cause or cardiovascular disease were observed. After adjusting for confounders, TyG index was independently associated with an elevated risk of all-cause (HR, 1.10; 95% CI, 1.00-1.20) and cardiovascular death (HR, 1.29; 95% CI, 1.05-1.57). Spline analyses showed that the relationship of TyG index with mortality was non-linear (All non-linear
< 0.001), and the threshold value were 9.36 for all-cause and 9.52 for cardiovascular death, respectively. The HRs above the threshold point were 1.50 (95% CI, 1.29-1.75) and 2.35 (95% CI, 1.73-3.19) for all-cause and cardiovascular death. No significant difference was found below the threshold points (All
> 0.05).
Elevated TyG index reflected a more severe IR and was associated with mortality due to all-cause and cardiovascular disease in a non-linear manner.
Several reports indicate that melatonin alleviates bleomycin (BLM)-induced pulmonary fibrosis in rodent animals. Nevertheless, the exact mechanism remains obscure. The present study investigated the ...effects of melatonin on endoplasmic reticulum (ER) stress and epithelial-mesenchymal transition (EMT) during BLM-induced lung fibrosis. For the induction of pulmonary fibrosis, mice were intratracheally injected with a single dose of BLM (5.0 mg/kg). Some mice were intraperitoneally injected with melatonin (5 mg/kg) daily for a period of 3 wk. Twenty-one days after BLM injection, lung fibrosis was evaluated. As expected, melatonin significantly alleviated BLM-induced pulmonary fibrosis, as evidenced by Sirius red staining. Moreover, melatonin significantly attenuated BLM-induced EMT to myofibroblasts, as determined by its repression of α-SMA expression. Further analysis showed that melatonin markedly attenuated BLM-induced GRP78 up-regulation and elevation of the cleaved ATF6 in the lungs. Moreover, melatonin obviously attenuated BLM-induced activation of pulmonary eIF2α, a downstream target of the PERK pathway. Finally, melatonin repressed BLM-induced pulmonary IRE1α phosphorylation. Correspondingly, melatonin inhibited BLM-induced activation of XBP-1 and JNK, two downstream targets of the IRE1 pathway. Taken together, these results suggest that melatonin alleviates ER stress and ER stress-mediated EMT in the process of BLM-induced pulmonary fibrosis.
The authors performed a meta‐analysis to assess the efficacy of non‐atenolol β‐blockers as add‐on to monotherapy or as a component of combination antihypertensive therapy in patients with ...hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β‐blockers with diuretics, calcium channel blockers (CCBs), angiotensin‐converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β‐blockers add‐on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non‐β‐blocker monotherapy (weighted mean difference in mm Hg 95% confidence interval: −4.1 −6.0, −2.2 and −3.7 −4.6, −2.8, respectively). These results were consistent across the comparisons with diuretics (systolic pressure, −10.2 −14.2, −6.2; diastolic pressure, −5.4 −8.2, −2.6), CCBs (systolic pressure, −4.1 −7.1, −1.0; diastolic pressure, −2.8 −4.1, −1.5), and ACEIs/ARBs (systolic pressure, −2.9 −4.3, −1.5; diastolic pressure, −4.2 −5.0, −3.4). There was no significant difference in blood pressure lowering effects between combinations with and without a β‐blocker (systolic pressure, −1.3 mm Hg −5.8, 3.2; diastolic pressure, −.3 mm Hg −2.7, 2.1). Metoprolol add‐on or combination therapy had a significantly greater blood pressure reduction than non‐β‐blocker therapy (systolic pressure, −3.6 mm Hg −5.9, −1.3; diastolic pressure, −2.1 mm Hg −3.5, −.7). In conclusion, non‐atenolol β‐blockers are effective in lowering blood pressure as add‐on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β‐blockers can and should be used in combination with other antihypertensive drugs.
Angiotensin‐receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin‐receptor blockers may be more effective than the older ones. A ...network meta‐analysis was performed to compare the efficacy of various angiotensin‐receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin‐receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6‐12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20‐80 mg), irbesartan (300 mg), olmesartan (20‐40 mg), telmisartan (80 mg), and valsartan (160‐320 mg), but not candesartan (8‐16 mg), losartan (50‐100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24‐hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin‐receptor blockers had different blood pressure lowering efficacy. The newest angiotensin‐receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.
We performed a network meta‐analysis of 34 studies on the office or ambulatory blood pressure lowering efficacy of various angiotensin‐receptor blockers. We found that these drugs had different blood pressure lowering efficacy. The newest one, azilsartan medoxomil, at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.
Background
Distinct populations differ in LVH prevalence and impaired LV geometry. Currently, the prevalence of and risk factors for LV geometric patterns in Chinese hypertensives administered ...irbesartan have not been specifically addressed in large studies.
Methods
Totally 10,883 patients (6623 men and 4260 women) completed the survey, including 1181 hypertensives administered irbesartan (488 males and 693 females) that were finally enrolled. Based on LVMI and RWT derived from comprehensive echocardiography, the LV geometric patterns of irbesartan‐treated hypertensive individuals were classified into four types, including the normal, concentric remodeling, and concentric and eccentric hypertrophy groups. Logistic regression analysis was applied in males and females, respectively, for determining odds ratios (ORs) and 95% confidence intervals (CIs) for various potential risk factors for abnormal LV geometrical patterns in irbesartan‐treated hypertensives.
Results
The clinical and echocardiographic data differed significantly between males and females. The prevalence rates of concentric remodeling, concentric hypertrophy, and eccentric hypertrophy were 36.3%, 15.4%, and 6.1% in males, respectively, and 23.5%, 20.3%, and 23.8% in females, accordingly. Gender, daily dose of irbesartan, BMI, SBP, WtHR, and neck‐circumference were significantly associated with LV geometric patterns. After adjustment for confounding factors, risk factors for LVH and impaired LV geometry included SBP, WtHR in males, and MAU‐Cr and WtHR in females.
Conclusions
LVH and impaired LV geometric patterns are more prevalent in females (67.7%) compared with that in males (57.8%) among hypertensives upon irbesartan administration. For such population, risk factors beyond elevated blood pressure may be involved in the progression of LVH and impaired LV geometric patterns in both genders.
Prevalence of and risk factors for abnormal left ventricular geometrical patterns in hypertensive subjects with irbesartan treatment.
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