The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

A Follow-Up Study of Ovarian Cancer (OOPS): A Study Protocol.

The ovarian cancer (OC) follow-up study (OOPS) is an on-going hospital-based large prospective longitudinal cohort study aimed to explore the relationship between pre/post-diagnostic biological, clinical, environmental, and lifestyle factors with focus on the diet and OC prognosis (including drug resistance, relapse, and mortality). Patients recruited during the baseline survey were between 18 and 79 years old, with histologically confirmed OC diagnosis. Their follow-up and medical treatment were conducted at the gynecological oncology ward at Shengjing Hospital of China Medical University, Shenyang, China after 2015. A total of 703 OC patients made up the final OOPS study population. The follow-up stage was conducted in both passive and active modes. In the passive mode, the follow-up was performed by linkage to the Liaoning Providence Center for Disease Control and Prevention every 6 months to obtain health outcome results. The status of lifestyle factors was re-estimated using the same measurements as those in the baseline survey. OC participants in the OOPS study completed a questionnaire and anthropometric examinations. In addition, biological specimens were collected during the baseline survey, which included blood, urine, and stool samples that were stored for further use. This article is intended to serve as an introduction to this project and to provide details for investigators who may be carry out related analysis.

Associations between Meat and Vegetable Intake, Cooking Methods, and Asthenozoospermia: A Hospital-Based Case-Control Study in China.

Background: The role of meat and vegetable intake in the development of asthenozoospermia has been controversial, and the role of cooking methods for meat and vegetables in the association has yet to be determined. The present study aimed to illuminate the relationship between the consumption and cooking methods of meat and vegetables and the risk of asthenozoospermia. Methods: In this hospital-based case-control study, we enrolled 552 patients with asthenozoospermia and 585 healthy controls. Dietary information was assessed using a validated self-administered food frequency questionnaire. Asthenozoospermia was diagnosed according to the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Results: Participants in the highest tertile of total meat and unprocessed meat intake had a 44% and 39% lower risk of asthenozoospermia than those in the lowest tertile (OR = 0.56, 95% CI: 0.37, 0.87 and OR = 0.61, 95% CI: 0.40, 0.93), respectively. Participants with the highest processed meat consumption showed higher risk (OR = 1.44, 95% CI: 1.01, 2.06). Raw vegetable consumption was negatively associated with the risk of asthenozoospermia (OR = 0.67, 95% CI: 0.45, 0.98). The stir-frying cooking method for meat was associated with increased risk of asthenozoospermia (OR = 1.58, 95% CI: 1.02, 2.46). Conclusions: Intake of total meat, unprocessed meat, and raw vegetable may reduce asthenozoospermia risk, while higher consumption of processed meat may increase the risk. Cooking methods may play a role in these associations. These findings need to be confirmed in large and prospective cohort studies.

Pre-diagnosis meat intake and cooking method and ovarian cancer survival: results from the Ovarian Cancer Follow-Up Study (OOPS).

Objectives: The relationships between pre-diagnosis meat intake and ovarian cancer (OC) survival were limited and controversial. To date, no study has taken account of cooking methods. Thus, we aimed to firstly clarify these associations based on the Ovarian Cancer Follow-Up Study. Methods: This prospective cohort study, including 853 OC patients between 2015 and 2020, was conducted to examine the aforementioned associations. All women completed a food frequency questionnaire. Deaths were ascertained up to March 31, 2021 via medical records and active follow-up. We used the Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During the median follow-up of 37.17 months, 130 women died. Pre-diagnosis fish and seafood intake was associated with better survival (HRT3 vs. T1 = 0.46, 95% CI = 0.26-0.82, p trend <0.05), whereas processed red meat (HR = 1.54, 95% CI = 1.04-2.26) and a high frequency of fried fish intake (HR = 1.49, 95% CI = 1.03-2.16) were associated with worse survival than consuming none. After considering the interaction of cooking methods, we found that compared with the lowest tertile of fish and seafood intake and almost no fried fish cooking, women with the highest tertile of intake and almost no fried fish cooking had better survival (HR = 0.35, 95% CI = 0.13-0.92). Additionally, compared with the lowest tertile of fish and seafood intake and almost no baked fish cooking, women with the lowest tertile of intake and consuming baked fish had worse survival (HR = 3.75, 95% CI = 1.53-9.15). Conclusions: Pre-diagnosis fish and seafood intake was associated with better OC survival, whereas processed red meat intake was associated with worse survival. Cooking methods, especially for fried or baked fish, may play interaction effects with fish intake on OC survival.

Cruciferous vegetable consumption and multiple health outcomes: an umbrella review of 41 systematic reviews and meta-analyses of 303 observational studies.

Background: Epidemiological studies evaluating the associations between the consumption of cruciferous vegetables (CV) and diverse health outcomes have generated inconsistent findings. Therefore, we carried out an umbrella review to systematically summarize existing evidence on this topic. Methods: This study had been registered at PROSPERO (no. CRD42021262011). Relevant systematic reviews and meta-analyses of observational studies were identified by searching PubMed, Web of science, and Embase databases from inception up to March 15, 2021. Observational studies investigating the association between CV intake and multiple health outcomes in humans were eligible for inclusion. The validated AMSTAR (A Measurement Tool to Assess Systematic Reviews) instrument was utilized for assessing the methodological quality of the included systematic reviews. For each meta-analysis, we assessed the summary effect size by using fixed and random effects models, 95% prediction intervals, heterogeneity, evidence of small-study effects, and excess significance bias. Results: Our umbrella review included 41 meta-analyses of 303 individual studies involving 13 394 722 participants. Twenty-four health outcomes including cancers (n = 23), cardiovascular disease (n = 12), mortality (n = 5), and metabolic diseases (n = 1) were evaluated. The summary random effects estimates were significant at P < 0.05 in 24 meta-analyses - all of which reported decreased risks of health outcomes. All were of moderate methodological quality in our study. Of the 41 meta-analyses, we observed suggestive evidence for beneficial associations between gastric cancer, lung cancer, endometrial cancer, and all-cause mortality. Moreover, 16 associations were supported by weak evidence, including breast cancer, lung cancer, renal cell carcinoma, bladder cancer, prostate cancer, ovarian cancer, endometrial cancer, colon cancer, colorectal adenoma, colorectal neoplasm, non-Hodgkin lymphoma, and total cancer. Conclusions: It revealed that CV intake might be associated with beneficial effects on several health-related outcomes (gastric cancer, lung cancer, endometrial cancer, and all-cause mortality). Other associations could be genuine, but substantial uncertainty remains. Additional studies are needed to evaluate the relationship between the consumption of CV and various health outcomes as well as robust randomized controlled trials in the future.

Long-term PM2.5 exposure and various health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies.

Adverse effects from exposure to particulate matter <2.5 µm in diameter (PM2.5) on health-related outcomes have been found in a range of experimental and epidemiological studies. This study aimed to assess the significance, validity, and reliability of the relationship between long-term PM2.5 exposure and various health outcomes. The Embase, PubMed, Web of Science, CNKI, WANFANG, VIP, and SinoMed databases and reference lists of the retrieved review articles were searched to obtain meta-analysis and systematic reviews focusing on PM2.5-related outcomes as of August 31, 2021. Random-/fixed-effects models were applied to estimate summary effect size and 95% confidence intervals (CIs). The quality of included meta-analyses was evaluated based on the AMSTAR 2 tool. Small-study effect and excess significance bias studies were conducted to further assess the associations. Registered PROSPERO number: CRD42020200606. This included 24 articles involving 71 associations between PM2.5 exposure and the health outcomes. The evidence for the positive association of 10 µg/m3 increments of long-term exposure to PM2.5 and stroke incidence in Europe was convincing (effect size = 1.07, 95% CI: 1.05-1.10). There was evidence that was highly suggestive of a positive association between 10 µg/m3 increments of long-term exposure to PM2.5 and the following health-related outcomes: mortality of lung cancer (effect size = 1.11, 95% CI: 1.08-1.13) and Alzheimer's disease (effect size = 4.79, 95% CI: 2.79-8.21). There was highly suggestive evidence that chronic obstructive pulmonary disease risk is positively associated with higher long-term PM2.5 exposure versus lower long-term PM2.5 exposure (effect size = 2.32, 95% CI: 1.88-2.86). In conclusion, the positive association of long-term exposure to PM2.5 and stroke incidence in Europe was convincing. Given the validity of numerous associations of long-term exposure to PM2.5 and health-related outcomes is subject to biases, more robust evidence is urgently needed.

Dietary Carbohydrate and Diverse Health Outcomes: Umbrella Review of 30 Systematic Reviews and Meta-Analyses of 281 Observational Studies.

Background and Aims: The associations between dietary carbohydrate and diverse health outcomes remain controversial and confusing. To summarize the existing evidence of the association between dietary carbohydrate intake and diverse health outcomes and to evaluate the credibility of these sources of evidence. We performed this umbrella review of evidence from meta-analyses of observational studies. Methods: PubMed, Embase, Web of Science databases, and manual screening of references up to July 2020 were searched. Systematic reviews with meta-analyses of observational studies in humans investigating the association between dietary carbohydrate intake and multiple health outcomes were identified. We assessed the evidence levels by using summary effect sizes, 95% prediction intervals, between-study heterogeneity, evidence of small-study effects, and evidence of excess significance bias for each meta-analysis. Results: We included 43 meta-analyses of observational research studies with 23 health outcomes, including cancer (n = 26), mortality (n = 4), metabolic diseases (n = 4), digestive system outcomes (n = 3), and other outcomes [coronary heart disease (n = 2), stroke (n = 1), Parkinson's disease (n = 1), and bone fracture (n = 2)]. This umbrella review summarized 281 individual studies with 13,164,365 participants. Highly suggestive evidence of an association between dietary carbohydrate intake and metabolic syndrome was observed with adjusted summary odds ratio of 1.25 [95% confidence interval (CI) 1.15-1.37]. The suggestive evidences were observed in associations of carbohydrate consumption with esophageal adenocarcinoma (0.57, 95% CI = 0.42-0.78) and all-cause mortality (adjusted summary hazard ratio 1.19, 95% CI = 1.09-1.30). Conclusions: Despite the fact that numerous systematic reviews and meta-analyses have explored the relationship between carbohydrate intake and diverse health outcomes, there is no convincing evidence of a clear role of carbohydrate intake. However, there is highly suggestive evidence suggested carbohydrate intake is associated with high risk of metabolic syndrome, suggestive evidence found its association with increased risk of all-cause mortality and decreased risk of esophageal adenocarcinoma. Systematic Review Registration: CRD42020197424.

Environmental Risk Factors and Congenital Heart Disease: An Umbrella Review of 165 Systematic Reviews and Meta-Analyses With More Than 120 Million Participants.

Background: The etiology of congenital heart disease (CHD) has been extensively studied in the past decades. Therefore, it is critical to clarify clear hierarchies of evidence between types of environmental factors and CHD. Methods: Electronic searches in PubMed, Embase, Web of Science, Cochrane database were conducted from inception to April 20, 2020 for meta-analyses investigating the aforementioned topic. Results: Overall, 41 studies including a total of 165 meta-analyses of different environmental factors and CHD were examined, covering a wide range of risk factors. The summary random effects estimates were significant at P < 0.05 in 63 meta-analyses (38%), and 15 associations (9%) were significant at P < 10-6. Of these meta-analyses, eventually one risk factor (severe obesity; relative risk: 1.38, 95% confidence interval: 1.30-1.47) had significant summary associations at P < 10-6, included more than 1,000 cases, had 95% prediction intervals excluding the null value, and were not suggestive of large heterogeneity (I 2 < 50%), small-study effects (P-value for Egger's test > 0.10), or excess significance (P > 0.10). Eight associations (5%) (including maternal lithium exposure, maternal obesity, maternal alcohol consumption, and maternal fever) had results that were significant at P < 10-6, included more than 1,000 cases, and had 95% prediction intervals excluding the null value (highly suggestive). Conclusion: This umbrella review shows that many environmental factors have substantial evidence in relation to the risk of developing CHD. More and better-designed studies are needed to establish robust evidence between environmental factors and CHD. Systematic Review Registration: [PROSPERO], identifier [CRD42020193381].

Adherence to Cancer Prevention Guidelines and Endometrial Cancer Risk: Evidence from a Systematic Review and Dose-Response Meta-analysis of Prospective Studies.

PURPOSE: The evidence of adherence to cancer prevention guidelines and endometrial cancer (EC) risk has been limited and controversial. This study summarizes and quantifies the relationship between adherence to cancer prevention guidelines and EC risk. MATERIALS AND METHODS: The online databases PubMed, Web of Science, and EMBASE were searched for relevant publications up to June 2, 2020. This study had been registered at PROSPERO. The registration number is CRD42020149966. Study quality evaluation was performed based on the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity among studies. Egger's and Begg's tests assessed potential publication bias. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between adherence to cancer prevention guidelines score was assigned to participants by summarizing individual scores for each lifestyle-related factor. The scores ranged from least healthy (0) to most healthy (20) and the EC risk was calculated using a randomeffects model. RESULTS: Five prospective studies (four cohort studies and one case­cohort study) consisted of 4,470 EC cases, where 597,047 participants were included. Four studies had a low bias risk and one study had a high bias risk. Summary EC HR for the highest vs. lowest score of adherence to cancer prevention guidelines was 0.54 (95% CI, 0.40 to 0.73) and had a high heterogeneity (I2=86.1%). For the dose-response analysis, an increment of 1 significantly reduced the risk of EC by 6%. No significant publication bias was detected. CONCLUSION: This study suggested that adherence to cancer prevention guidelines was negatively related to EC risk.

Association between maternal antenatal depression and neonatal Apgar score: A systematic review and meta-analysis of prospective cohort studies.

INTRODUCTION: Antenatal depression is common, but most women with the condition choose to remain untreated. The Apgar score, an important indicator of newborn health, has been reported to be influenced by antenatal depression; thus, maternal antenatal depression, as reflected by a poor Apgar score, may harm children's health. AIM: To conduct a systematic review and meta-analysis to explore whether maternal antenatal depression is associated with the neonatal Apgar score. METHODS: We registered the protocol for this study with PROSPERO (CRD42019137585). We searched PubMed, Embase, Web of Science, and the Cochrane Library for published papers that reported the association between depression and Apgar score from inception to December 4, 2019. Two reviewers independently screened and selected the studies according to the inclusion and exclusion criteria, and extracted data according to the predesigned table. Stata version 12.0 software was used to analyze data. RESULTS: We finally identified 13 studies for inclusion, including a total of 12017 women. We did not find an association between antenatal depression and the 1 min Apgar score of neonates (mean difference= -0.03, 95% CI= -0.15-0.09) or the risk of a low Apgar score (OR=1.82, 95% CI=0.51 to 3.13). We found that antenatal depression increased the risk of a low Apgar score at 5 min (OR= 1.91, 95% CI= 1.23-2.59), but the association between the 5 min Apgar score and antenatal depression was not significant (mean difference= -0.001, 95% CI= -0.07-0.07). The results of the subgroup analyses also indicated that there was no association between the 5 min Apgar score and antenatal depression. CONCLUSIONS: Antenatal depression increased the risk of a low 5 min Apgar score; however, we did not find a difference in the mean and distribution of neonatal Apgar scores of mothers with depression and mothers without depression.

Relationship between Maternal Central Obesity and the Risk of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Cohort Studies.

OBJECTIVE: Nowadays, body mass index (BMI) is used to evaluate the risk stratification of obesity-related pregnancy complications in clinics. However, BMI cannot reflect fat distribution or the proportion of adipose to nonadipose tissue. The objective of this study is to evaluate the association of maternal first or second trimester central obesity with the risk of GDM. Research Design and Methods. We searched in PubMed, Embase, and Web of Science for English-language medical literature published up to 12 May 2019. Cohort studies were only included in the search. Abdominal subcutaneous fat thickness, waist circumference, waist-hip ratio or body fat distribution were elected as measures of maternal central obesity, and all diagnostic criteria for GDM were accepted. The random effect meta-analysis was performed to evaluate the relationship between central obesity and the risk of GDM. RESULTS: A total of 11 cohort studies with an overall sample size of 27,675 women and 2,226 patients with GDM were included in the analysis. The summary estimate of GDM risk in the central obesity pregnant women was 2.76 (95% confidence interval [CI]: 2.35-3.26) using the adjusted odds ratio (OR). The degree of heterogeneity among the studies was low (I 2 = 14.4, P = 0.307). The subgroup analyses showed that heterogeneity was affected by selected study characteristics (methods of exposure and trimesters). After adjusting for potential confounds, the OR of adjusted BMI was significant (OR = 3.07, 95% CI: 2.35-4.00). CONCLUSIONS: Our findings indicate that the risk of GDM was positively associated with maternal central obesity.

The association between glycemic index, glycemic load, and metabolic syndrome: a systematic review and dose-response meta-analysis of observational studies.

PURPOSE: The association of glycemic index (GI) and glycemic load (GL) with metabolic syndrome (MetS) is controversial. Therefore, we conducted this first systematic review and dose-response meta-analysis of observational studies to quantify these associations. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies up to 1 April 2019. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated by a random-effects model. This study was registered with PROSPERO (CRD42019131788). RESULTS: We included eight high-quality (n = 5) or medium-quality (n = 3) cross-sectional studies in the final meta-analysis, comprising 6058 MetS events and 28,998 participants. The summary ORs of MetS for the highest versus lowest categories were 1.23 (95% CI 1.10-1.38, I2 = 0, tau2 = 0, n = 5) for dietary GI, 1.06 (95% CI 0.89-1.25, I2 = 36.2%, tau2 = 0.0151, n = 6) for dietary GL. The summary OR was 1.12 (95% CI 1.00-1.26, I2 = 0, tau2 = 0, n = 3) per 5 GI units, 0.96 (95% CI 0.83-1.10, I2 = 33.4%, tau2 = 0.0059, n = 2) per 20 GL units. CONCLUSIONS: Dietary GI was positively associated with the prevalence of MetS. However, no significant association was found between dietary GL and the prevalence of MetS. Further studies with prospective design are needed to establish potential causal relationship between dietary GI and the MetS.

Relationship between legume consumption and metabolic syndrome: A systematic review and meta-analysis of observational studies.

AIMS: The prevalence of metabolic syndrome (MetS) has been increasing in recent years. Investigation of whether consumption of legumes as a part of healthy diet could reduce the odds of MetS has led to inconsistent conclusions. Here, we performed the first meta-analysis of observational studies to analyze the association between legume consumption and prevalence of MetS. DATA SYNTHESIS: PubMed, EMBASE, and Web of Science databases were searched to identify observational studies up to June 1, 2019. We extracted data from the studies included and performed quality assessments. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias and subgroup and sensitivity analyses were also performed. We finally included four cross-sectional studies, two cohort studies, and one case-control study involving 56,028 participants. The summary OR revealed no statistically significant association between legume consumption and odds of MetS (OR = 0.93, 95% CI = 0.76-1.12, I2 = 73.5%). Subgroup analysis of study characteristics and adjustment for confounding along with sensitivity analyses revealed no statistically significant differences. No evidence of publication bias was detected. CONCLUSION: Legume consumption is not associated with the odds of MetS. These findings require validation in well-designed cohort studies and randomized clinical trials with accurate measurement of legume intake and strict control of confounders. REGISTRATION: This study was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42019131777).

Association between the ferritin level and risk of gestational diabetes mellitus: A meta-analysis of observational studies.

AIMS/INTRODUCTION: The relationship between ferritin and the risk of gestational diabetes mellitus (GDM) has not been established. Thus, we carried out a meta-analysis based on the current literature. MATERIALS AND METHODS: We searched relevant databases on Embase, PubMed, Cochrane Library and Web of Science before 10 May 2019 to determine the relationship between ferritin and the risk of GDM. The relative risks and 95% confidence intervals of GDM risk were summarized using a random effects model. Studies using categories of ferritin as exposure were combined by dose-response analysis. We carried out both linear and non-linear trends. We also carried out subgroup analysis, whether or not the studies adjusted for potential confounders, and meta-regression analysis to explore the source of heterogeneity. Sensitivity analysis was carried out to explore the robustness of the meta-analysis results. RESULTS: A total of 10 studies involving 4,690 participants were identified. The summary relative risk comparing persons with the highest concentration categories of ferritin with the lowest concentration categories of ferritin was 1.87 (95% confidence interval 1.50-2.34; I2  = 20.1%). Linear dose-response showed that an increase in ferritin of 10 µg/L increased the risk of GDM by 8% (1.08, 95% confidence interval 1.05-1.13, I2  = 55.1%; n = 4). A non-linear dose-response relationship also showed a consistently increasing risk of GDM with increased ferritin. No evidence of publication bias was detected. CONCLUSIONS: The findings from this meta-analysis suggest that increased ferritin levels are associated with an increased risk of GDM; however, we require further prospective cohort studies to confirm the results, especially the dose-response relationship between ferritin and GDM.

Carbohydrate intake and risk of metabolic syndrome: A dose-response meta-analysis of observational studies.

BACKGROUND AND AIMS: Epidemiological association studies have reported inconsistent findings on the relationship between carbohydrate intake and risk of metabolic syndrome (MetS). Therefore, we aimed to conduct the first dose-response meta-analysis to investigate this effect. METHODS AND RESULTS: A systematic search in PubMed and Web of Science databases from their inception to June 01, 2019, together with relevant literature scrutiny, was performed to identify related studies for inclusion into the meta-analysis. We calculated the odds ratios (ORs) with 95% confidence intervals (CIs) using a random effects model. Furthermore, subgroup, sensitivity, heterogeneity, and publication bias analyses were performed. This meta-analysis included 14 cross-sectional and four cohort studies, totaling 284,638 participants and 69,554 MetS cases. The highest versus the lowest carbohydrate intake values were associated with an increased risk of MetS (OR: 1.253, 95% CI: 1.147-1.368), with moderate heterogeneity (I2 = 54.5%). Using dose-response analysis, we found a linear association between carbohydrate consumption and MetS risk with a corresponding OR of 1.026 (95% CI, 1.004-1.048) and with significant heterogeneity (I2 = 82.0%) at 5% energy intake from carbohydrates. We have found similar results using subgroup analyses for major study characteristics and adjustment for confounders. Sensitivity analysis further enhanced the robustness of the results, and no publication bias was detected. CONCLUSION: Carbohydrate intake is associated with an increased risk of developing MetS. Therefore, additional large prospective cohort studies are warranted to confirm our findings.