Engineered Probiotics for the Management of Congenital Metabolic Diseases: A Systematic Review.

Engineered probiotics (EPs) can be used to treat/manage chronic and congenital diseases. However, to the best of our knowledge, no systematic review has evaluated the effects of EPs on congenital metabolic disorders in murine models and human subjects. Thus, the present study systematically reviewed interventional studies that assessed the effects of EPs on congenital metabolic disorders. PubMed, Web of Science, and Scopus databases were searched up to February 2023 to retrieve related publications. Seventy-six articles were obtained in the primary step. After screening the titles/abstracts based on the inclusion and exclusion criteria, 11 papers were included. Finally, only seven articles were included after performing full-text evaluation. The included articles evaluated the effects of EPs on managing phenylketonuria (PKU, n=4) and hyperammonemia (n=3). Moreover, these studies examined mice and/or rats (n=6), monkeys (n=1), and humans (n=2). Studies on EPs and hyperammonemia revealed that some wild strains such as Lactobacillus plantarum have an innate ammonia-hyper-consuming potential; thus, there was no need to manipulate them. However, manipulation is needed to obtain a phenylalanine-metabolizing strain. In conclusion, EPs can be used to manage or treat congenital metabolic diseases including PKU.

The effect of L-carnitine supplementation on lipid profile in adults: an umbrella meta-analysis on interventional meta-analyses.

Introduction: Previous meta-analyses investigating the therapeutic effects of L-carnitine on lipid profiles have demonstrated inconsistent results. The present umbrella meta-analysis aimed to investigate the impact of efficacy of L-carnitine on lipid profiles in adults. Methods: Databases including PubMed, Scopus, and Embase, Web of Science, and Google Scholar were searched up to June 2023. Meta-analysis was performed using a random-effects model. Results: Our results from thirteen meta-analyses indicated that L-carnitine supplementation significantly total cholesterol (TC) (ES = -1.05 mg/dL, 95% CI: -1.71, -0.39; p = 0.002), triglycerides (TG) (ES = -2.51 mg/dL; 95% CI: -3.62, -1.39, p < 0.001), and low-density lipoprotein-cholesterol (LDL-C) (ES = -4.81 mg/dL; 95% CI: -6.04, -3.59; p < 0.001). It also increased high-density lipoprotein-cholesterol (HDL-C) (ES: 0.66 mg/dL, 95% CI: 0.20, 1.12, p = 0.005) levels. Conclusion: The present umbrella meta-analysis suggests supplementation with L-carnitine in a dosage of more than 2 g/day can improve lipid profile. Thus, L-carnitine supplementation can be recommended as an adjuvant anti-hyperlipidemic agent.

Artificial intelligence in cardiovascular medicine: An updated review of the literature.

Screening and early detection of cardiovascular disease (CVD) are crucial for managing progress and preventing related morbidity. In recent years, several studies have reported the important role of Artificial intelligence (AI) technology and its integration into various medical sectors. AI applications are able to deal with the massive amounts of data (medical records, ultrasounds, medications, and experimental results) generated in medicine and identify novel details that would otherwise be forgotten in the mass of healthcare data sets. Nowadays, AI algorithms are currently used to improve diagnosis of some CVDs including heart failure, atrial fibrillation, hypertrophic cardiomyopathy and pulmonary hypertension. This review summarized some AI concepts, critical execution requirements, obstacles, and new applications for CVDs.

Curcumin as a novel approach in improving lipid profile: An umbrella meta-analysis.

AIMS: Several meta-analyses exist supporting the beneficial effects of curcumin supplementation on lipid profile parameters; however, some studies' findings are inconsistent. Therefore, the current umbrella of meta-analysis of clinical trials was performed to evaluate the findings of multiple meta-analyses on the efficacy of curcumin on lipid profiles in adults. DATA SYNTHESIS: A comprehensive systematic search of PubMed/Medline, Scopus, Embase, Web of Science and Google Scholar were carried out up to May 2022 (in English only). Random-effects model was employed to conduct meta-analysis. The quality assessment of the selected meta-analyses was measured using a measurement tool to assess multiple systematic reviews (AMSTAR). From 101 articles returned in the literature search, 19 articles were met the qualified for inclusion in the umbrella meta-analysis. The results revealed that the curcumin supplementation was effective on reduction of total cholesterol (TC) (ES = -0.81 mg/dl; 95% CI: 1.39, -0.24, p = 0.006; I2 = 68.8%, p < 0.001), triglycerides (TG) (ES: 0.84 mg/dl, 95% CI: 1.42, -0.27, p = 0.004; I2 = 84.2%, p < 0.001), and low-density lipoprotein cholesterol (LDL-C) levels (ES: 0.49 mg/dl, 95%CI: 0.85, -0.13, p = 0.007; I2 = 51.9%, p = 0.004). Beyond that, Curcumin intake significantly increased high-density lipoprotein cholesterol (HDL-C) levels (ES: 1.34 mg/dl, 95% CI: 0.37, 2.31, p = 0.007; I2 = 97.8%, p < 0.001). CONCLUSION: Curcumin have ameliorating effects on TC, TG, LDL-c, and HDL-c levels. Overall, Curcumin could be recommended as an adjuvant anti-hyperlipidemic agent. REGISTRATION NUMBER: PROSPERO, CRD42021289500.

Levels of evidence for the association between different food groups/items consumption and the risk of various cancer sites: an umbrella review.

This study aimed to determine the level of evidence on the association between food groups/items consumption and the risk of different cancer sites from the meta-analyses/pooled analyses of observational studies. A systematic search was executed in Scopus, PubMed/MEDLINE, and Web of Science. The criteria from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Expert Report were adopted for evidence grading. In summary, there was convincing evidence for the association between fibre intake and decreased risk of colon and breast cancer. Also, consumption of dairy products, milk, fruits, and fibre was associated with a probable decreased risk of breast cancer. Consumption of whole grains, dairy products, milk, fruits, vegetables, and fibre had a probable inverse association with the incidence risk of gastrointestinal tract cancers. More qualified studies are needed to find reliable findings on the association between various food groups/items consumption and the risk of different cancer sites.

The engineered probiotics for the treatment of chronic diseases: A systematic review.

Engineered probiotics (EPs) are a group of probiotics whose proteome is manipulated by biotechnological techniques. EPs have attracted a lot of attention in recent researches for preventing and treating chronic diseases. The current study has been conducted to provide an overview regarding the EPs application in the treatment of chronic disease by a comprehensive systematic review of the published articles up to January 2022. To retrieve the related publications, three databases (PubMed/MEDLINE, Web of Sciences, and Scopus) were searched systematically. Finally, all human (n = 2) and animal (n = 37) studies were included. The included articles evaluated the effects of EPs on treatment of arthritis (n = 3), cancer (n = 2), autoimmune encephalomyelitis (EAE; n = 6), Parkinson disease (PD; n = 1), Alzheimer diseases (AD; n = 1), colitis (n = 11), celiac disease (n = 1), diabetes (n = 8) and cardiovascular disease (CVD; n = 6). Induction of oral tolerance (OT) is the most important mechanism of EPs action in the treatment of chronic disease. Providing oral vaccine and bioactive compounds are the other mechanisms of EPs action. PRACTICAL APPLICATIONS: The current systematic review gathered evidence about the application of EPs in the treatment of chronic diseases. Evidence suggests that EPs have very broad and potent effects in the treatment of chronic and even genetic diseases.

Is collagen supplementation friend or foe in rheumatoid arthritis and osteoarthritis? A comprehensive systematic review.

Rheumatoid arthritis (RA) and osteoarthritis (OA) both are chronic diseases affecting joints. Immune response against collagen in both diseases may have a role in the initiation and progression of the disease. There is a hypothesis that suppression of immune response vs collagen could be a therapeutic approach in RA and OA. Exposure of gut immune system to collagen is a way to suppress immune response against collagen in the joints. So, the current systematic review is aimed to evaluate the effects of collagen supplementation in OA and RA patients. In the current systematic review, online electronic databases including PubMed/MEDLINE, Web of Sciences and Scopus were searched and finally 19 articles were included. The enrolled articles evaluated the effects of collagen supplementation on treatment of OA (n = 9) and RA (n = 10). Intact (n = 4) and hydrolyzed (n = 5) collagen were used to treat OA. All of the studies on RA used intact and type II collagen in their intervention. The last trials on collagen supplementation in RA and OA patients were performed in 2011 and 2016, respectively. High adverse effects of collagen supplementation and its low efficiency compared to routine treatments were reported by several included studies. Also, risk of bias assessment showed that most of the studies had poor quality. Therefore, it is not possible to definitely decide on the beneficial or detrimental effects of collagen supplementation on OA and RA patients. Further studies are needed to reach a final decision.

Resveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis of randomized controlled trials.

We perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify the effect of resveratrol supplementation on endothelial function. A comprehensive search was performed in electronic databases including PubMed, Scopus, Web of Science, and Cochrane Library up to February 2021 with no limitation in time and language. A meta-analysis of eligible studies was performed using a random-effects model to estimate the pooled effect size of flow-mediated dilation (FMD), intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). In total, 21 arms from 17 studies were included. The meta-analysis results showed that resveratrol significantly change the concentrations of FMD (WMD: 1.43%; 95% CI: 0.98 to 1.88, p < .001) and ICAM-1 (WMD: -7.09 ng/ml, 95% CI: -7.45 to -6.73, p < .001). However, VCAM-1, fibrinogen, and PAI-1 did not change significantly after resveratrol supplementation. In conclusion, the results of this study suggest that resveratrol supplementation can improve endothelial function which could be important, especially in patients with cardiovascular diseases.

The association of a body shape index and visceral adiposity index with neurotrophic, hormonal and metabolic factors among apparently healthy women: a cross-sectional analysis.

Purpose: A body shape index (ABSI) and visceral; adiposity index (VAI) can reflect some cardio-metabolic risk factors in the population. To the best of our knowledge, there are no previous studies conducted on the assessment of the association between neurotrophic factors, Ghrelin and Obestatin with ABSI and VAI. We aimed to investigate this association among apparently healthy women. Methods: Ninety apparently healthy women were recruited in the present study. All participants were in need of dietary intervention for weight loss and participated in the study before receiving any intervention. Dietary, anthropometric, physical activity, stress level and biochemical assessments, as well as blood pressure measurements were done for all participants. Results: Women in the highest tertile of ABSI had significantly lower SBP compared to the lowest ABSI tertile. Women who were in the highest tertile of VAI had significantly lower serum Obestatin levels compared to the first and second tertiles in both crude and adjusted comparisons. Serum NGF, Obestatin and Ghrelin levels were significantly lower in the highest tertile of VAI compared to the lowest tertile in both crude and adjusted comparisons. HOMA-IR, serum insulin, LDL-C, TG and TC were significantly higher in the highest tertile of VAI compared to the lowest tertile. QUICKI in the highest tertiles were significantly lower than the first tertile in adjusted model. Conclusion: This evidence can be useful for researchers in applying appropriate anthropometric indices regarding different populations with multifactorial metabolic complications. The current findings need approving by prospective population study and also clinical trial researches.

Sodium selenite and Se-enriched yeast supplementation in atherosclerotic patients: Effects on the expression of pyroptosis-related genes and oxidative stress status.

BACKGROUND AND AIMS: Atherosclerosis as a chronic inflammatory disorder of the arterial wall is the main leading cause of the cardiovascular disease (CVD). Caspase-dependent pyroptosis plays a pivotal role in the pathogenesis of CVD. Selenium (Se) is an important component of the antioxidant defense and plays a crucial role in cardiovascular health. This study aimed to investigate the effects of daily consumption of sodium selenite and Se-enriched yeast on the expression of pyroptosis-related genes, and biomarkers of oxidative stress in patients with atherosclerosis. METHODS AND RESULTS: In this randomized, double-blinded, placebo-controlled clinical trial, 60 patients with atherosclerosis were recruited. Participants received 200 µg/day of sodium selenite, Se-enriched yeast, or placebo for 8 following weeks. The pyroptosis-related genes' mRNA expression in peripheral blood mononuclear cells (PBMCs) was assessed before and after the intervention. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidases (GPX) were measured at baseline and following the intervention. Following sodium selenite and Se-enriched yeast supplementation, the relative expression levels of TLR4, ASC, NLRP3, and NF-κB1 were significantly downregulated (p < 0.05). Furthermore, the changes in GPX were significantly increased after selenite and yeast supplementation (p < 0.05). Also, selenite and yeast consumption caused a statistically significant decrease in the change of MDA level (p < 0.05). CONCLUSION: In summary, these findings showed that Se supplementation may reduce inflammation through down-regulation of some pro-inflammatory genes, improving antioxidant defenses in atherosclerosis patients. Further research is required to come to a definite conclusion of selenium supplementation on the CVD risk. This study was registered on the Iranian Registry of Clinical Trials website (identifier: RCT20110123005670N28; https://www.irct.ir/).

Dairy-originated digestion-resistant and bioactive peptides increase the risk of hypertension: Tehran Lipid and Glucose Study.

Milk-protein-derived bioactive peptides (BPs) have been proposed as modulators of different regulatory processes involved in blood pressure regulation. Studies on the long-term effects of BPs on blood pressure have not yet been conducted. We aimed to investigate the association of dairy-originated BPs with the risk of hypertension (HTN) in the Tehran Lipid and Glucose Cohort Study (TLGS). In this cohort study, 4378 subjects with a mean follow-up period of 3.1 years were included in the final analysis. Dietary intake, physical activity, demographic, and anthropometric data and blood pressure measurements were obtained for all participants. Various types of dairy-originated BPs were determined by an in silico method. High intake of total digestion-resistant and bioactive peptides (OR: 1.31, CI 95%: 1.01-1.70), dipeptides (OR: 1.33, CI 95%: 1.03-1.73), peptides with more than seven residues (OR: 1.32, CI 95%: 1.01-1.71), glycosylated residues (OR: 1.39, CI 95%: 1.07-1.80), highly hydrophilic peptides (OR: 1.32, CI 95%: 1.01-1.71), and low hydrophobic peptides (OR: 1.32, CI 95%: 1.01-1.71) was associated with an increased risk of HTN in the adjusted model. In addition, subjects in the higher tertile of anti-HTN peptide (OR: 1.33, CI 95%: 1.02-1.72) and antidiabetic peptide (OR: 1.35, CI 95%: 1.04-1.76) intake had a higher risk of HTN than those in the lower tertile. No significant association emerged between calcium intake from dairy and incident risk of HTN. Our results showed that the intake of some forms of digestion-resistant and BPs, such as anti-HTN peptides, dipeptides, and peptides with more than seven residues, can increase the risk of HTN in the TLGS population.

The interplay between fasting, gut microbiota, and lipid profile.

BACKGROUND: This study aimed to investigate the consequence of Ramadan fasting on gut bacterium (Bacteroides and Firmicutes), serum concentration for butyrate, and lipid profile. METHODS: Thirty healthy subjects were enlisted and investigated two times (before and at the end of Ramadan). Fasting blood samples were obtained for measuring fasting blood sugar (FBS) and lipid profile and serum butyrate concentration. Anthropometrics variables were measured before and after Ramadan for all 30 subjects. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, targeting the genome of Bacteroides and Firmicutes was performed to determine its presence in the stool samples. Food intake was assessed by a 3-day food record before and after Ramadan. Statistical analysis was performed by SPSS ver.13 and Minitab ver.17. P < 0.05 considered the level of significance. RESULTS: The study results showed that serum levels of butyrate significantly increase during the month from 0.23 ± 0.02 mM to 0.46 ± 0.03 mM (P < 0.05). The gut Bacteroides and Firmicutes increased by 21 and 13 percent after Ramadan compared to before (P < 0.05). The increment in Bacteroides occurred in both sexes, but Firmicutes significantly increased only in women. Food intake was decreased during Ramadan. Ramadan fasting caused significant reduction in BMI from 25.72 ± 0.58 kg/m2to 25.25 ± 0.55 kg/m2 (P < 0.05). Serum levels of LDL, HDL, LDL/HDL ratio, and total cholesterol significantly decreased during Ramadan (P < 0.05). However, the decrease in FBS and TG level were not statistically significant (P > 0.05). CONCLUSION: It can be stated that the promotion of Bacteroides and Firmicutes in the gut might play a crucial role in health promotion. However, more research is needed to achieve a definite conclusion.

Role of Butyrate, a Gut Microbiota Derived Metabolite, in Cardiovascular Diseases: A comprehensive narrative review.

Cardiovascular diseases (CVD) are major causes of death worldwide. Recently, new roles for intestinal microbiota in pathology and treatment of CVD have been proposed. Butyrate, a bacterial metabolite, is synthesized in the gut and performs most of its functions in there. However, researchers have discovered that butyrate could enter to portal vein and interact with various organs. Butyrate exhibits a broad range of pharmacological activities, including microbiome modulator, anti-inflammatory, anti-obesity, metabolic pathways regulator, anti-angiogenesis, and antioxidant. In this article we review evidence supporting a potentially therapeutic role for butyrate in CVD and the mechanisms and pathways involved in the cardio-protective effects of butyrate from the gut and circulation to the nervous system. In summary, although butyrate exhibits a wide variety of biological activities in different pathways including energy homeostasis, glucose and lipid metabolism, inflammation, oxidative stress, neural signaling, and epigenetic modulation in experimental settings, it remains unclear whether these findings are clinically relevant and whether the molecular pathways are activated by butyrate in humans.