Effects of high-quality protein supplementation on cardiovascular risk factors in individuals with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. METHODS: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. RESULTS: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. CONCLUSION: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders.

Foxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasis.

The liver plays a crucial role in maintaining systemic iron homeostasis by secreting hepcidin, which is essential for coordinating iron levels in the body. Imbalances in iron homeostasis are associated with various clinical disorders related to iron deficiency or iron overload. Despite the clinical significance, the mechanisms underlying how hepatocytes sense extracellular iron levels to regulate hepcidin synthesis and iron storage are not fully understood. In this study, we identified Foxo1, a well-known regulator of macronutrient metabolism, that translocates to the nucleus of hepatocytes in response to high-iron feeding, holo-transferrin, and BMP6 treatment. Furthermore, Foxo1 plays a crucial role in mediating hepcidin induction in response to both iron and BMP signals by directly interacting with evolutionally conserved Foxo binding sites within the hepcidin promoter region. These binding sites were found to colocalize with Smad-binding sites. To investigate the physiological relevance of Foxo1 in iron metabolism, we generated mice with hepatocyte-specific deletion of Foxo1. These mice exhibited reduced hepatic hepcidin expression and serum hepcidin levels, accompanied by elevated serum iron and liver non-heme iron concentrations. Moreover, high-iron diet further exacerbated these abnormalities in iron metabolism in mice lacking hepatic Foxo1. Conversely, hepatocyte-specific Foxo1 overexpression increased hepatic hepcidin expression and serum hepcidin levels, thereby ameliorating iron overload in a murine model of hereditary hemochromatosis (Hfe-/- mice). In summary, our study identifies Foxo1 is a critical regulator of hepcidin and systemic iron homeostasis. Targeting Foxo1 may offer therapeutic opportunities for managing conditions associated with aberrant iron metabolism.

Ameliorative Effect of Coenzyme Q10 on Phenotypic Transformation in Human Smooth Muscle Cells with FBN1 Knockdown.

Mutations of the FBN1 gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is currently no effective treatment for MFS. Here, we studied the role of mitochondrial dysfunction in the phenotypic transformation of human smooth muscle cells (SMCs) and whether a mitochondrial boosting strategy can be a potential treatment. We knocked down FBN1 in SMCs to create an MFS cell model and used rotenone to induce mitochondrial dysfunction. Furthermore, we incubated the shFBN1 SMCs with Coenzyme Q10 (CoQ10) to assess whether restoring mitochondrial function can reverse the phenotypic transformation. The results showed that shFBN1 SMCs had decreased TFAM (mitochondrial transcription factor A), mtDNA levels and mitochondrial mass, lost their contractile capacity and had increased synthetic phenotype markers. Inhibiting the mitochondrial function of SMCs can decrease the expression of contractile markers and increase the expression of synthetic genes. Imposing mitochondrial stress causes a double-hit effect on the TFAM level, oxidative phosphorylation and phenotypic transformation of FBN1-knockdown SMCs while restoring mitochondrial metabolism with CoQ10 can rapidly reverse the synthetic phenotype. Our results suggest that mitochondria function is a potential therapeutic target for the phenotypic transformation of SMCs in MFS.

Antioxidant Minerals Modified the Association between Iron and Type 2 Diabetes in a Chinese Population.

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case-control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

NEW PREDICTIVE BIOMARKERS FOR SCREENING COVID-19 PATIENTS WITH RHABDOMYOLYSIS IN COMBINATION WITH CYSTATIN C.

ABSTRACT: Purpose: Cystatin C (CysC) has been linked to the prognosis of corona virus disease 2019 (COVID-19). The study aims to investigate a predictor correlated with CysC screening for poor prognosis in COVID-19 patients combined with skeletal muscle (SKM) impairment and rhabdomyolysis (RM). Methods: A single-center retrospective cohort analysis was carried out. Demographic information, clinical data, laboratory test results, and clinical outcome data were gathered and analyzed. Results: According to the inclusion and exclusion criteria, 382 patients were included in this study. The subjects were divided into three groups based on CysC tertiles. Multivariate analysis revealed that SaO 2 (hazard ratio [HR], 0.946; 95% confidence interval [CI], 0.906-0.987; P = 0.011), CysC (HR, 2.124; 95% CI, 1.223-3.689; P = 0.008), aspartate aminotransferase (AST) (HR, 1.009; 95% CI, 1.000-1.018; P = 0.041), and hypersensitive C-reactive protein (HR, 1.005; 95% CI, 1.000-1.010; P = 0.045) were significantly associated with survivals. The area under curve (AUC) in the model characterized by RM incidence was 0.819 (0.698-0.941), as shown by CysC receiver operating characteristic curves. LDH*CysC and AST*CysC had better predictive values than CysC and the best prediction for RM, with an AUC of 0.880 (0.796,0.964) for LDH*CysC ( P < 0.05, vs CysC) and 0.925 (0.878,0.972) for AST*CysC ( P < 0.05, vs CysC). Conclusion: CysC is an essential evaluation indicator for COVID-19 patients' prognosis. AST*CysC and LDH*CysC have superior predictive value to CysC for SKM, RM, and death, and optimal classification for RM.

Comparative efficacy on outcomes of C-CABG, OPCAB, and ONBEAT in coronary heart disease: a systematic review and network meta-analysis of randomized controlled trials.

IMPORTANCE: Coronary artery bypass grafting (CABG) remains the gold standard for the treatment of multivessel and left main coronary heart disease. However, the current evidence about the optimal surgical revascularization strategy is inconsistent and is not sufficient to allow for definite conclusions. Thus, this topic needs to be extensively discussed. OBJECTIVE: The aim of this present study was to compare the clinical outcomes of off-pump CABG (OPCAB), conventional on-pump CABG (C-CABG), and on-pump beating heart (ONBEAT) CABG via an updated systematic review and network meta-analysis of randomized controlled trials. DATA SOURCES: PubMed, Web of Science, and the Cochrane Central Registry were searched for relevant randomized controlled trials that were published in English before 1 December 2021. STUDY SELECTION: Published trials that included patients who received OPCAB, C-CABG, and ONBEAT CABG were selected. DATA EXTRACTION AND SYNTHESIS: Two authors independently screened the search results, assessed the full texts to identify eligible studies and the risk of bias of the included studies, and extracted data. All processes followed the Preferred Reporting Items for Systematic Review and Meta-analysis of Individual Participant Data. MAIN OUTCOMES AND MEASURES: The primary outcome was postoperative mortality in patients who underwent C-CABG, OPCAB, or ONBEAT CABG. The secondary outcomes were postoperative myocardial infarction, stroke, and renal impairment in the three groups. The time point for analysis of outcomes was all time periods during the postoperative follow-up. RESULTS: A total of 39 385 patients (83 496.2 person-years) in 65 studies who fulfilled the prespecified criteria were included. In the network meta-analysis, OPCAB was associated with an increase of 12% in the risk of all-cause mortality when compared with C-CABG [odds ratio (OR): 1.12; 95% CI: 1.04-1.21], a reduction of 49% in the risk of myocardial infarction when compared with ONBEAT (OR: 0.51; 95% CI: 0.26-0.99), a reduction of 16% in the risk of stroke when compared with C-CABG (OR: 0.84; 95% CI: 0.72-0.99) and a similar risk of renal impairment when compared with C-CABG and ONBEAT. CONCLUSIONS AND RELEVANCE: OPCAB was associated with higher all-cause mortality but lower postoperative stroke compared with C-CABG. OPCAB was associated with a lower postoperative myocardial infarction than that of ONBEAT. Early mortality was comparable among OPCAB, ONBEAT, and C-CABG.

Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells.

Cervical cancer is one of the leading causes of cancer death in women. Mitochondrial-mediated ferroptosis (MMF) is a recently discovered form of cancer cell death. However, the role and the underlying mechanism of MMF in cervical cancer remain elusive. Here, using an unbiased screening for mitochondrial transmembrane candidates, we identified mitochondrial carrier 1 (MTCH1) as a central mediator of MMF in cervical cancers. MTCH1-deficiency disrupted mitochondrial oxidative phosphorylation while elevated mitochondrial reactive oxygen species (ROS) by decreasing NAD+ levels. This mitochondrial autonomous event initiated a mitochondria-to-nucleus retrograde signaling involving reduced FoxO1 nuclear translocation and subsequently downregulation of the transcription and activity of a key anti-ferroptosis enzyme glutathione peroxidase 4 (GPX4), thereby elevating ROS and ultimately triggering ferroptosis. Strikingly, targeting MTCH1 in combination with Sorafenib effectively and synergistically inhibited the growth of cervical cancer in a nude mouse xenograft model by actively inducing ferroptosis. In conclusion, these findings enriched our understanding of the mechanisms of MMF in which MTCH1 governed ferroptosis though retrograde signaling to FoxO1-GPX4 axis, and provided a potential therapeutic target for treating cervical cancer.

Food groups and urologic cancers risk: a systematic review and meta-analysis of prospective studies.

Background: To assess the association between 12 food groups intake and the risk of urologic cancers. Methods: We scanned PubMed and Web of Science databases up to April 1st, 2023, and 73 publications met the inclusion criteria in the meta-analysis. We used a random effects model to estimate the summary risk ratios (RRs) and 95% confidence intervals (95% CI). Results: In the linear dose-response meta-analysis, an inverse association was found between each additional daily 100 g of fruits [RR: 0.89, 95%CI = (0.83, 0.97)], 100 g of vegetables [RR: 0.92, 95%CI = (0.85, 0.99)], 12 g of alcohol [RR: 0.91, 95%CI = (0.88, 0.94)] and 1 cup of coffee [RR: 0.95, 95%CI = (0.83, 0.97)] intake and the risk of renal cell carcinoma. Conversely, each additional daily 100 g of red meat intake was positively associated with renal cell carcinoma [RR: 1.41, 95%CI = (1.03, 2.10)]. Inverse associations were observed between each additional daily 50 g of egg [RR: 0.73, 95%CI = (0.62, 0.87)] and each additional daily 1 cup of tea consumption and bladder cancer risk [RR: 0.97, 95%CI = (0.94, 0.99)]. There were no significant associations for nonlinear dose-response relationships between 12 food groups and urological cancers. Conclusion: Our meta-analysis strengthens the evidence that appropriate intake of specific food groups, such as fruits, vegetables, alcohol, tea, and coffee, is associated with the risk of renal cell carcinoma or bladder cancer. More studies are required to fill the knowledge gap on the links between various food groups and urologic cancers because the evidence was less credible in this meta-analysis. Systematic Review Registration: This study was registered on PROSPERO (CRD42022340336).

Micronutrient Supplementation to Reduce Cardiovascular Risk.

BACKGROUND: Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified. OBJECTIVES: The goal of this study was to provide a comprehensive and most up-to-date evidence-based map that systematically quantifies the impact of micronutrients on CVD outcomes. METHODS: This study comprised a systematic review and meta-analysis of randomized controlled intervention trials of micronutrients on CVD risk factors and clinical events. RESULTS: A total of 884 randomized controlled intervention trials evaluating 27 types of micronutrients among 883,627 participants (4,895,544 person-years) were identified. Supplementation with n-3 fatty acid, n-6 fatty acid, l-arginine, l-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors. Specifically, n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR]: 0.93; 95% CI: 0.88-0.97), myocardial infarction (RR: 0.85; 95% CI: 0.78-0.92), and coronary heart disease events (RR: 0.86; 95% CI: 0.80-0.93). Folic acid supplementation decreased stroke risk (RR: 0.84; 95% CI: 0.72-0.97), and coenzyme Q10 supplementation decreased all-cause mortality events (RR: 0.68; 95% CI: 0.49-0.94). Vitamin C, vitamin D, vitamin E, and selenium showed no effect on CVD or type 2 diabetes risk. ß-carotene supplementation increased all-cause mortality (RR: 1.10; 95% CI: 1.05-1.15), CVD mortality events (RR: 1.12; 95% CI: 1.06-1.18), and stroke risk (RR: 1.09; 95% CI: 1.01-1.17). CONCLUSIONS: Supplementation of some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations. (Antioxidant Supplementation in the Prevention and Treatment of Cardiovascular Diseases; CRD42022315165).

Solvents effect on phenolics, iridoids, antioxidant activity, antibacterial activity, and pancreatic lipase inhibition activity of noni (Morinda citrifolia L.) fruit extract.

This study focused on the relationship between content levels of phytochemicals and the biological activities of noni (Morinda Citrifolia L.) fruit extracts (NFEs) prepared with traditional solvents and deep eutectic solvents (DESs). The results indicated the total phenolic content in Bet-Gly (Betaine: Glycerol) extracts (11.89 mg GAE/g DW) and total iridoid content in 70% ethanol extracts (26.38 mg CE/g DW) were the highest. A total of 17 compounds were identified and quantified in NFEs. Traditional solvent extracts, except ethyl acetate, exhibited higher antioxidant activities than DESs. Three DES extracts showed higher activities against pancreatic lipase than traditional solvent extracts. Multivariate analysis revealed that the type of extraction solvent exerts a significant influence on the phytochemical compositions and biological activities of NFEs. This study provided valuable information on the efficient extraction of phytochemicals from noni fruits and DESs are promising green solvent for the extraction of bioactive compounds from noni fruits.

Association of Serum Antioxidant Minerals and Type 2 Diabetes Mellitus in Chinese Urban Residents.

Antioxidant minerals including zinc, copper and selenium play critical roles in the maintenance of the redox balance in the body. However, their influences on type 2 diabetes mellitus (T2DM) are still inconclusive in Chinese populations. To elucidate the relationship between antioxidant minerals and T2DM, serum zinc, copper and selenium concentrations were measured in 1443 Chinese urban residents using a 1:2 matched case-control study. Conditional logistic regression models (CLR) were used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs), and restricted cubic splines (RCS) were used to examine their dose−response associations. Serum zinc (OR = 0.52 [0.35, 0.77]) and copper concentrations (OR = 0.25 [0.17, 0.37]) were negatively associated with T2DM in a fully adjusted model. An L-shaped zinc-T2DM association (Poverall association = 0.003, and Pnonlinearity = 0.005) and a negative linear copper-T2DM association (Poverall association < 0.0001, and Pnonlinearity = 0.395) were observed. No association was found between serum selenium and T2DM in fully adjusted CLR or RCS models. In addition, joint associations with T2DM were identified between serum zinc and copper and between serum selenium and copper. In conclusion, our study emphasizes the importance of an adequate intake of antioxidant minerals for T2DM prevention in the Chinese population.