Identification and verification of circRNA biomarkers for coronary artery disease based on WGCNA and the LASSO algorithm.

BACKGROUND: The role of circular RNAs (circRNAs) as biomarkers of coronary artery disease (CAD) remains poorly explored. This study aimed to identify and validate potential circulating circRNAs as biomarkers for the diagnosis of CAD. METHODS: The expression profile of circRNAs associated with CAD was obtained from Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operation (LASSO) were employed to identify CAD-related hub circRNAs. The expression levels of these hub circRNAs were validated using qRT-PCR in blood samples from 100 CAD patients and 100 controls. The diagnostic performance of these circRNAs was evaluated through logistic regression analysis, receiver operator characteristic (ROC) analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Functional enrichment analyses were performed to predict the possible mechanisms of circRNAs in CAD. RESULTS: A total of ten CAD-related hub circRNAs were identified through WGCNA and LASSO analysis. Among them, hsa_circ_0069972 and hsa_circ_0021509 were highly expressed in blood samples of CAD patients, and they were identified as independent predictors after adjustment for relevant confounders. The area under the ROC curve for hsa_circ_0069972 and hsa_circ_0021509 was 0.760 and 0.717, respectively. The classification of patients was improved with the incorporation of circRNAs into the clinical model composed of conventional cardiovascular risk factors, showing an IDI of 0.131 and NRI of 0.170 for hsa_circ_0069972, and an IDI of 0.111 and NRI of 0.150 for hsa_circ_0021509. Functional enrichment analyses revealed that the hsa_circ_0069972-miRNA-mRNA network was enriched in TGF-ß、FoxO and Hippo signaling pathways, while the hsa_circ_0021509-miRNA-mRNA network was enriched in PI3K/Akt and MAPK signaling pathways. CONCLUSION: Hsa_circ_0069972 and hsa_circ_0021509 were identified by integrated analysis, and they are highly expressed in CAD patients. They may serve as novel biomarkers for CAD.

Coffee Consumption and Risk of Lung Cancer: A Meta-Analysis of Prospective Cohort Studies.

The association between coffee consumption and lung cancer risk remains inconsistent. To quantitatively assess this association, we conducted a meta-analysis of prospective cohort studies. We searched PubMed and Web of Science databases along with hand searches for eligible studies published up to July 2023. A total of 26 prospective studies, including 30,305 lung cancer cases and 1,795,158 participants, were included in the meta-analysis. The pooled RR for high vs. low coffee consumption was 1.30 (95% CI: 1.11-1.53) with significant heterogeneity (I2 = 72.0%, p < .001). For never smokers, however, the pooled RR was 1.18 (95% CI: 0.999-1.38) with no evidence of heterogeneity (I2 = 0.0%, p = .53). By adjustment for body mass index (BMI), there was no significant association between coffee consumption and lung cancer risk in studies that adjusted for BMI (RR = 1.06; 95% CI: 0.87-1.30) (Pdifference = .01). Further analysis of studies that adjusted for BMI in never smokers found that coffee consumption was not associated with lung cancer risk. In conclusion, the association of high coffee consumption with lung cancer risk was attenuated when the confounding effects caused by smoking and BMI were controlled. Our results, therefore, imply that coffee consumption does not seem to be a risk factor for lung cancer incidence.

Vitamin D Intake, Blood 25-Hydroxyvitamin D, and Risk of Ovarian Cancer: A Meta-Analysis of Observational Studies.

Background: In vitro research suggests that vitamin D may protect against the risk of ovarian cancer. However, ecological and epidemiologic evidence is still debatable. Materials and Methods: We searched eligible studies via MEDLINE and Web of Science databases, as well as a hand search to examine the association between vitamin D intake or blood 25(OH)D (25-hydroxyvitamin D) and ovarian cancer risk in a meta-analysis. The overall relative risk (RR) was determined using a random-effect model. Results: For ovarian cancer incidence, 15 observational studies were included [5,634 cases for vitamin D intake and 975 cases for blood 25(OH)D]. For overall vitamin D intake (from food and supplements), the pooled RR of ovarian cancer risk for the highest versus lowest groups was 0.92 (95% confidence interval [CI]: 0.74-1.14). For blood 25(OH)D levels, however, people with high blood 25(OH)D levels had 37% lower risk of ovarian cancer than those with low levels (pooled RR = 0.63; 95% CI: 0.42-0.93). By study design, the inverse association was stronger in case-control studies than in prospective studies. The dose-response meta-analysis also supports the inverse association between blood 25(OH)D levels and ovarian cancer risk. When the pooled RRs were restricted to studies that adjusted for body mass index (BMI), they tended to be stronger, but the difference by adjustment for BMI was not significant. Conclusion: Our findings suggest that having a high blood 25(OH)D level is associated with a lower risk of ovarian cancer. More well-designed prospective studies are needed to confirm the link between vitamin D status and ovarian cancer risk.

Two Faces of Catechol-O-Methyltransferase Inhibitor on One-Carbon Metabolism in Parkinson's Disease: A Meta-Analysis.

Levodopa (L-dopa) and catechol-O-methyltransferase (COMT) inhibition are widely used therapeutics in Parkinson's disease (PD). Despite their therapeutic effects, it was raised that nutrients involved in one-carbon metabolism can be deteriorated by PD therapies. The aim of this meta-analysis was to investigate the impact of L-dopa and COMT inhibitors on levels of homocysteine (Hcy), vitamin B12 and folate in patients with PD. A total of 35 case-control studies from 14 different countries were selected through PubMed, MEDLINE and Google Scholar and were meta-analyzed. In the L-dopa group, the Hcy level was higher compared to the PD without L-dopa group (SMD: 5.11 µmol/L, 95% CI: 3.56 to 6.66). Moreover, vitamin B12 and folate levels in the L-dopa group were lower compared to the healthy control (SMD: -62.67 pg/mL, 95% CI: -86.53 to -38.81; SMD: -0.89 ng/mL, 95% CI: -1.44 to -0.33, respectively). The COMT inhibitor group showed lower levels of Hcy (SMD: -3.78 µmol/L, 95% CI: -5.27 to -2.29) and vitamin B12 (SMD: -51.01 pg/mL, 95% CI: -91.45 to -10.57), but higher folate levels (SMD: 1.78 ng/mL, 95% CI: -0.59 to 4.15) compared to the L-dopa group. COMT inhibitors may ameliorate L-dopa-induced hyper-homocysteine and folate deficiency but exacerbate vitamin B12 deficiency.

Nuts and legumes consumption and risk of colorectal cancer: a systematic review and meta-analysis.

Several case-control and prospective cohort studies have examined the association between the consumption of nuts and legumes and the risk of colorectal cancer. For the quantitative assessment of this association, we conducted a meta-analysis of observational studies. We searched PubMed and Web of Science databases along with hand searches for eligible studies published up to January 2022. A total of 13 studies (8 cohort studies and 5 case-control studies) on nuts consumption and 29 studies (16 cohort studies and 13 case-control studies) on legumes consumption were included in the meta-analysis. The pooled relative risks (RRs) of colorectal cancer for the highest versus lowest categories of nuts consumption and legumes consumption were 0.84 (95% CI: 0.71-0.99) and 0.90 (95% CI: 0.83-0.98), respectively. Based on the dose-response analysis, a 28 g/day (1 serving/day) increment of nut consumption was associated with a 33% lower risk of colorectal cancer, and 100 g/day (1 serving/day) increment of legumes consumption was associated with a 21% lower risk of colorectal cancer. By geographic region for nuts consumption, however, the inverse association for the highest versus lowest categories was only observed in Asia (RR = 0.44; 95% CI: 0.29-0.68) from 3 studies, and no association was found in America (RR = 1.01; 95% CI: 0.92-1.11) (Pdifference = 0.003) or Europe (RR = 1.02; 95% CI: 0.84-1.25) (Pdifference = 0.003). In addition, the associations tended to be weak when stratified by adjustment for confounders. Our findings suggest that the evidence for an association is currently weak, and thus further well-designed prospective studies are needed.

Dairy Consumption and Total Cancer and Cancer-Specific Mortality: A Meta-Analysis of Prospective Cohort Studies.

The association between dairy consumption and cancer mortality varies among studies and remains unclear. Thus, we conducted a comprehensive meta-analysis of prospective cohort studies to examine the association between dairy consumption and total cancer and cancer-specific mortality. We sought eligible studies in PubMed and Web of Science databases for all publications through March 2021, and pooled RRs and 95% CIs were calculated. We identified 34 prospective cohort studies including 3,171,186 participants and 88,545 deaths. Compared with low milk consumption, high milk consumption was associated with higher cancer mortality in females (RR: 1.10; 95% CI: 1.01, 1.21) and people consuming high/whole-fat milk (fat content ≥3.5%) (RR: 1.17; 95% CI: 1.07, 1.28). Increased risks of cancer-specific mortality were detected for liver (RR: 1.13; 95% CI: 1.02, 1.26), ovarian (RR: 1.32; 95% CI: 1.13, 1.55), and prostate (RR: 1.23; 95% CI: 1.02, 1.48) cancers. Also, females with high consumption of fermented milk had a lower cancer mortality risk (RR: 0.85; 95% CI: 0.77, 0.94). High cheese consumption was not associated with total cancer mortality but rather with higher colorectal cancer mortality (RR: 1.22; 95% CI: 1.02, 1.46). There was no association between butter (RR: 1.06; 95% CI: 0.70, 1.59) or total dairy product consumption (RR: 0.99; 95% CI: 0.95, 1.03) and cancer mortality. Our results imply that high milk consumption, especially high/whole-fat milk, was associated with higher cancer mortality, whereas fermented milk consumption was associated with lower cancer mortality, and this was particularly evident in females. Consequently, further studies are warranted.

Dairy Consumption and Risk of Metabolic Syndrome: Results from Korean Population and Meta-Analysis.

Dairy consumption has been associated with decreased risk of metabolic syndrome (MetS) in previous studies, but the association may be different according to each type of dairy products and its subgroups. Thus, we conducted an updated meta-analysis of observational studies to examine the association between various dairy products and risk of MetS. The PubMed and Web of Science databases were searched for eligible studies published up to February 2021. In addition, we included unpublished results from Korea National Health and Nutrition Examination Survey, 2013-2018, including 23,319 Korean adults and the elderly. A total of 35 studies (12 cohort studies and 25 cross-sectional studies) with 398,877 subjects were included in the meta-analysis. The pooled relative risks (RR) of MetS for the highest versus lowest categories of dairy consumption was 0.80 [95% confidence interval (CI): 0.72-0.88]. For the type of dairy products, there were also significant inverse associations with milk (RR: 0.83; 95% CI: 0.78-0.89) and yogurt consumption (RR: 0.89; 95% CI: 0.83-0.95). For cheese consumption, however, no significant association was found (RR: 0.98; 95% CI: 0.86-1.11). Our findings suggest that milk and yogurt consumption is inversely associated with the risk of MetS, but not cheese consumption.

Dairy Consumption and Risk of Metabolic Syndrome in Korean Adults and Elderly People.

Background: To investigate the association of dairy consumption with metabolic syndrome (MetS) in a representative sample of Korean adult and elderly population. Methods: We used data from the Korea National Health and Nutrition Examination Survey, 2013-2018. A total of 18,206 adults (19-64 years) and 5113 elderly people (≥65 years) were included in the analysis. Dairy product consumption was assessed with a 24-hr dietary recall, and the subjects were divided into three groups based on their total dairy consumption (0, <1, ≥1 serving/day). The primary outcome, MetS, was defined according to the National Cholesterol Education Program Adult Treatment Panel III and the Korean Society for the Study of Obesity. Results: After adjusting for covariates, high dairy consumption was associated with 12% lower odds of MetS in adults compared with no dairy consumption [odds ratio (OR) 0.88, 95% confidence interval (CI) 0.78-0.998, P for trend = 0.048]. A similar inverse association was found in adult men (OR 0.84, 95% CI 0.71-0.99), but no significant association was found in adult women (OR 0.93, 95% CI 0.78-1.11). For the elderly, high dairy consumption was associated with 20% lower odds of MetS (OR 0.80, 95% CI 0.65-0.98, P for trend = 0.020); a significant inverse association was shown in elderly women (OR 0.72, 95% CI 0.56-0.94) but not in elderly men (OR 0.93, 95% CI 0.68-1.28). Conclusion: Our findings suggest that one or more servings/day of dairy products were associated with lower prevalence of MetS in Korean adult men and elderly women.

Dairy Consumption and Risks of Colorectal Cancer Incidence and Mortality: A Meta-analysis of Prospective Cohort Studies.

BACKGROUND: Previous studies of dairy consumption and colorectal cancer incidence have shown inconsistent results, and there was no meta-analysis of association of dairy consumption with colorectal cancer mortality. Thus, we conducted a comprehensive analysis of prospective cohort studies to investigate these associations. METHODS: PubMed and Web of Science databases were searched for eligible studies published up to July 2019, and a random effects model was used to estimate pooled RR. RESULTS: We identified 31 prospective cohort studies, which included 24,964 and 2,302 cases for colorectal cancer incidence and mortality, respectively. The pooled RR of colorectal cancer incidence for the highest versus lowest categories of total dairy consumption was 0.79 [95% confidence interval (CI), 0.74-0.85]. For milk consumption, there was also a significant inverse association (RR, 0.81; 95% CI, 0.76-0.86). For cheese and fermented milk consumption, overall no association was found, but studies conducted in Europe showed a significant inverse association for cheese (RR, 0.87; 95% CI, 0.78-0.97) and fermented milk consumption (RR, 0.91; 95% CI, 0.85-0.98). For colorectal cancer mortality, we found 29% lower risk of death from colorectal cancer in subjects with high dairy consumption compared with those with low intakes of dairy products (RR, 0.71; 95% CI, 0.54-0.93), but each type of dairy consumption did not show a significant association. CONCLUSIONS: High dairy consumption was associated with lower colorectal cancer incidence and mortality. IMPACT: Our findings suggest that high dairy consumption may be associated with lower colorectal cancer incidence and mortality, but further studies are warranted.