Metformin and risk of hematological cancers in patients with diabetes: a systematic review and meta-analysis.

FUNDING: No external funding.

The effects of replacing ghee with rapeseed oil on liver steatosis and enzymes, lipid profile, insulin resistance and anthropometric measurements in patients with non-alcoholic fatty liver disease: a randomised controlled clinical trial.

Non-alcoholic fatty liver disease (NAFLD), which is a prevalent hepatic condition worldwide, is expected to develop into the leading reason for end-stage fatty liver in the forthcoming decades. Incorporating rapeseed oil into a balanced diet may be beneficial in improving NAFLD. The goal of this trial was to evaluate the impact of substituting ghee with rapeseed oil on primary outcomes such as fatty liver and liver enzymes, as well as on secondary outcomes including glycaemic variables, lipid profile and anthropometric measurements in individuals with NAFLD. Over 12 weeks, 110 patients (seventy men and forty women; BMI (mean) 28·2 (sd 1·6 kg/m2); mean age 42 (sd 9·6) years), who daily consumed ghee, were assigned to the intervention or control group through random allocation. The intervention group was advised to substitute ghee with rapeseed oil in the same amount. The control group continued the consumption of ghee and was instructed to adhere to a healthy diet. Results showed a significant reduction in the steatosis in the intervention group in comparison with the control group (P < 0·001). However, a significant change in the levels of alanine aminotransferase (­14·4 µg/l), γ-glutamyl transferase (­1·8 µg/l), TAG (­39·7 mg/dl), total cholesterol (­17·2 mg/dl), LDL (­7·5 mg/dl), fasting blood glucose (­7·5 mg/dl), insulin (­3·05 mU/l), Homeostatic Model Assessment for Insulin Resistance (­0·9), Quantitative Insulin-Sensitivity Check Index (+0·01), weight (­4·3 kg), BMI (­0·04 kg/m2), waist (­5·6 cm) and waist:height ratio (­0·04) was seen in the intervention group. The consumption of rapeseed oil instead of ghee caused improvements in liver steatosis and enzymes, glycaemic variables and anthropometric measurements among individuals with NAFLD.

Effects of the nutrition education intervention on food security, anthropometry, and body composition in women: A randomized controlled trial.

BACKGROUND: Food insecurity as a social determinant of health is associated with adverse physical health outcomes such as obesity. AIM: This study aimed to evaluate the effects of nutrition education intervention based on the transtheoretical model (TTM) on food security, anthropometry, and body composition status. METHODS: In this randomized controlled trial, an intervention was conducted over months (five weeks) using the TTM among 160 women aged 19-64 years. Food security status, anthropometry, and body composition were determined three times: at baseline, three months, and six months after the intervention. RESULTS: In the intervention group, food insecurity significantly decreased before, immediately after, and six months after the intervention, these changes were significant in follow-up time and treatment effect. After six months of follow-up, the intervention group significantly decreased weight (-1.29 kg), body mass index (-0.54), and waist circumference (-3.48 cm). Although differences between the two groups were not statistically significant except in the interaction between follow-up time and intervention groups. Also, the mean of fat mass and total body water decreased in the intervention group and differences between the two groups were statistically significant in follow-up time (p < 0.001 and p = 0.01, respectively) and interaction between follow-up time and intervention group (p < 0.001 and p = 0.005, respectively). CONCLUSION: In the current study, the findings of a six-month TTM-based intervention among women were positive that revealed to be a strategy that may improve anthropometric and nutritional status. Therefore, government programs that offer nutrition counseling should be prioritized to help the population to improve their eating habits.

Carboxymethyl cellulose@multi wall carbon nanotubes functionalized with Ugi reaction as a new curcumin carrier.

In recent years, the fabrication of new drug delivery systems (DDSs) based on functionalization by multi-component reactions (MCRs) has received special attention. In this regard, to obtain a new oral administration system for colon-specific cancer treatment, the CMC@MWCNTs@FCA carrier was designed and prepared from the functionalization of the CMC@MWCNTs as a biocompatible raw material with carboxamide group by the Ugi reaction. FT-IR analysis confirmed the successful synthesis of the product through the change in the functional groups of reagents. Additionally, the crystalline structure and porosity of the samples were studied by XRD and BET techniques. After a detailed characterization, the curcumin (CUR) was loaded on CMC@MWCNTs and CMC@MWCNTs@FCA, respectively, about 29 % and 38 %. In vitro drug release behavior studies for CUR-loaded CMC@MWCNTs@FCA showed the controlled release for it, so 11.6 % and 76.5 % of CUR, respectively were released at pH 1.2 and pH 7.4. Toxicological analysis displayed the IC50 of CMC@MWCNTs@FCA@CUR is 752 µg/mL. In conclusion, the obtained findings display that the fabricated system can be proposed as a biocompatible carrier for specific colon cancer treatment.

Intricate role of sleep deprivation in modulating depression: focusing on BDNF, VEGF, serotonin, cortisol, and TNF-α.

In this review article, we aimed to discuss intricate roles of SD in modulating depression in preclinical and clinical studies. Decades of research have shown the inconsistent effects of SD on depression, focusing on SD duration. However, inconsistent role of SD seems to be more complicated, and SD duration cannot be the only one factor. Regarding this issue, we chose some important factors involved in the effects of SD on cognitive functions and mood including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), serotonin, cortisol, and tumor necrosis factor-alpha (TNF-α). It was concluded that SD has a wide-range of inconsistent effects on BDNF, VEGF, serotonin, and cortisol levels. It was noted that BDNF diurnal rhythm is significantly involved in the modulatory role of SD in depression. Furthermore, the important role of VEGF in blood-brain barrier permeability which is involved in modulating depression was discussed. It was also noted that there is a negative correlation between cortisol and BDNF that modulates depression. Eventually, it was concluded that TNF-α regulates sleep/wake cycle and is involved in the vulnerability to cognitive and behavioral impairments following SD. TNF-α also increases the permeability of the blood-brain barrier which is accompanied by depressive behavior. In sum, it was suggested that future studies should focus on these mechanisms/factors to better investigate the reasons behind intricate roles of SD in modulating depression.

Efficacy of nigella sativa oil on endothelial function and atherogenic indices in patients with coronary artery diseases: A randomized, double-blind, placebo-control clinical trial.

A therapeutic compound with antioxidant and anti-inflammatory effects might be a practical approach in endothelial dysfunction caused by oxidation and inflammation associated with atherosclerosis. Therefore, we aim to examine the efficacy of Nigella sativa (NS) oil supplementation on endothelial function and atherogenic indices in coronary artery disease (CAD) patients. Sixty individuals aged between 35 to 65 years old were recruited and divided into two groups, receiving either 2 g/daily of NS oil or sunflower oil as the placebo for 8 weeks. Serum levels of adhesion molecules, oxidative markers, and atherogenic parameters were evaluated at the starting point and the end of supplementation. Serum levels of vascular cell adhesion protein 1 (sVCAM-1) [-264.44 95% C, (156.83, 372.04)], intercellular adhesion molecule 1 (sICAM-1) [-132.38 95% C, (40.64, 224.1)], and malondialdehyde (MDA) [-0.21 95% C, (0.03, 0.40)] declined significantly following NS supplementation, while total antioxidant capacity increased [0.03 95% C, (0.03, 0.16)]. NS oil supplementation demonstrated a potential beneficial effect on endothelial function by reducing ICAM-1, VCAM-1 levels and affecting oxidative markers. However, further studies are necessary to elucidate NS oil as a therapeutic agent and complementary therapy in patients with stable CAD.

Garlic essential oil-based nanoemulsion carrier: Release and stability kinetics of volatile components.

An O/W nanoemulsion of garlic essential oil (GEO) at different oil-to-emulsion (O/E) ratios (5%, 10%, 15%, and 25%) was formulated to protect the volatile components of GEO. The effects of O/E ratios on the encapsulation efficiency (EE%) of volatile compounds and droplet size of nanoemulsions were studied. The results showed that with increasing in E/O ratio, droplet size increased while EE% decreased so that the droplet size was below 100 nm for all samples and the EE% was almost above 80% for most samples. The effects of various factors such as temperature (5°C-45°C), pH values (3-7), ionic strength (0-500 mM), and O/E ratios (5%-25%) on kinetic of nanoemulsions stability were studied. Reducing pH values and raising the temperature, ionic strength, and O/E ratios intensified the instability process and constant rate of instability in all nanoemulsions. The effects of temperature and O/E ratios on the release kinetics of volatile components were evaluated over time, and kinetic parameters such as release rate constant (k), Q10, and activation energy (Ea) were calculated in which results showed a zero-degree model to describe the release kinetic behavior of most nanoemulsions. Both temperature and O/E ratios factors as well as their interaction (which had a synergistic effect) had a significant effect on increasing the release rate of volatiles so that the degree of reaction rate was changed from zero to the first order at simultaneous high levels of both factors. FT-IR spectroscopy was carried out to study interactions among nanoemulsion ingredients. The presence of sulfur-containing functional groups of garlic oil (thiosulphate, diallyl trisulfide, etc.) in nanoemulsions was confirmed by FT-IR.

Association of High Dietary Acid Load With the Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

Objective: This study aimed to determine the relationship between the high dietary acid load (DAL) and the risk of cancer. Methods: Five databases of PubMed, Web of Sciences, Scopus, Cochrane Library, and Google Scholar was searched to elicit original studies on humans, up to June 2021. Quality of the articles, risk of bias, and heterogeneity were assessed. A random-effects meta-analysis model was applied to estimate pooled effect size with a 95% confidence interval. Sensitivity analysis was performed using a fixed-effects model. Subgroup analyses were carried out based on gender, age, type of cancer, and type of DAL assessment indicator. Results: Seventeen effect sizes from 10 articles were included in the analysis. Overall, individuals with the highest DAL were associated with a 66% increased risk of cancer compared to those with the lowest DAL (p < 0.001]. The risk of cancer increased 41% (p < 0.001) and 53% (p = 0.03) by high PRAL and NEAP, respectively. High DAL was associated with 32% (p < 0.001) and 79% (p < 0.001) increased risk of breast and colorectal cancers, respectively. High DAL was associated with 32% (p = 0.001) and 76% (p = 0.007) increased risk of cancer incident in women and men, respectively. The risk of cancer incident increased 35% (p < 0.001) and 49% (p < 0.001) at age ≤ and > of 50, respectively. Conclusion: High DAL may be associated with a higher risk of cancer incidence not only in the whole studied population but also across cancer types, both genders, both DAL assessment indicators, and also among both high- and low-risk age groups for cancer.

Impact of Melatonin and Branched-Chain Amino Acids Cosupplementation on Quality of Life, Fatigue, and Nutritional Status in Cachectic Heart Failure Patients: A Randomized Controlled Trial.

Background: Cardiac cachexia (CC) adversely affects the lifestyle of heart failure (HF) patients. The current study examined the impact of melatonin cosupplementation and branched-chain amino acids (BCAAs) on quality of life (QoL), fatigue, and nutritional status in cachectic HF patients. Methods: In this trial, 84 CC patients were randomized to melatonin, BCAAs, or coadministration (both) as intervention groups and a control group over 8 weeks. At baseline and postintervention, QoL, fatigue, and nutritional status were assessed. Results: After intervention, improvement in the overall and physical dimensions of QoL and appetite score were found to be statistically significant in the BCAAs (P < .001) and the melatonin+BCAAs (P < .001) groups compared with the placebo group. The emotional dimension score was significantly lower in the BCAAs group compared with the placebo group (P = .001). There was a statistically significant improvement in fatigue severity in all 3 intervention groups compared with the placebo group. The nutrition risk index (NRI) score increased significantly only in the melatonin group (P = .015), and there was no significant difference between the other groups (P = .804). Conclusions: Cosupplementation with BCAAs and melatonin improved QoL, fatigue status, and appetite in cachectic HF patients but did not affect NRI.

Carotenoids supplementation and inflammation: a systematic review and meta-analysis of randomized clinical trials.

The aim of this study was to perform a systematic review and meta-analysis on randomized controlled trials investigating the effects of carotenoids on selected inflammatory parameters. PubMed, SCOPUS, and Web of science were searched from inception until April 2021. The random-effect model was used to analyze data and the overall effect size was computed as weighted mean difference (WMD) and corresponding 95% of confidence interval (CI). A total of 26 trials with 35 effect sizes were included in this meta-analysis. The results indicated significant effects of carotenoids on C-reactive protein (CRP) (WMD: ‒0.54 mg/L, 95% CI: ‒0.71, ‒0.37, P < 0.001), and interleukin-6 (IL-6) (WMD: ‒0.54 pg/mL, 95% CI: ‒1.01, ‒0.06, P = 0.025), however the effect on tumor necrosis factor-alpha (TNF-α) was not significant (WMD: ‒0.97 pg/ml, 95% CI: ‒1.98, 0.03, P = 0.0.059). For the individual carotenoids, astaxanthin, (WMD: ‒0.30 mg/L, 95% CI: ‒0.51, ‒0.09, P = 0.005), lutein/zeaxanthin (WMD: ‒0.30 mg/L, 95% CI: ‒0.45, ‒0.15, P < 0.001), and ß-cryptoxanthin (WMD: ‒0.35 mg/L, 95% CI: ‒0.54, ‒0.15, P < 0.001) significantly decreased CRP level. Also, only lycopene (WMD: ‒1.08 pg/ml, 95%CI: ‒2.03, ‒0.12, P = 0.027) led to a significant decrease in IL-6. The overall results supported possible protective effects of carotenoids on inflammatory biomarkers.

Effects of Melatonin and/or Magnesium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.

Magnesium and melatonin are known to exert multiple beneficial effects including anti-inflammatory and antioxidant actions. This study was designed to determine the effects of magnesium and/or melatonin supplementation on metabolic profiles in women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was conducted among 84 subjects with PCOS aged 18-40 years old. Patients were randomly assigned based on the random block procedure to take magnesium, melatonin, magnesium plus melatonin, or placebo for 8 weeks. Fasting blood samples were taken at baseline and after the intervention to quantify related variables. After the 8-week intervention, an insignificant marginal difference was seen in waist circumference (WC) between groups (P = 0.085). Magnesium-melatonin co-supplementation resulted in more reductions in hirsutism compared with other groups (P < 0.001). Serum levels of tumor necrosis factor-α (TNF-α) declined significantly in the melatonin and co-supplementation groups compared to baseline (P < 0.05). Also, magnesium plus melatonin was associated with a more increase in total antioxidant capacity (TAC) levels, as compared to the other treatment groups (P = 0.001). Overall, we found a favorable effect of co-supplementation of magnesium and melatonin for 8 weeks in women with PCOS on hirsutism, serum TNF-α, and TAC levels. Furthermore, melatonin independently contributed to decreased serum values of TNF-α.Clinical trial registration number http://www.irct.ir : IRCT20191130045556N1, January 2020.

A comprehensive insight into effects of green tea extract in polycystic ovary syndrome: a systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS), as the most common endocrine disorder in reproductive-aged women, is characterized by oxidative stress and ovarian tissue inflammation. Green tea extract (GTE) potentially possesses therapeutic effects for PCOS because of the antioxidant and anti-inflammatory compounds. This systematic review evaluates the potential roles of GTE on metabolic variables, hormone levels, and ovarian function in PCOS. METHODS: A systematic review was conducted of published studies reporting the effects of GTE on PCOS. Several major databases, including PubMed, SCOPUS, and Google Scholar, were searched up from inception to April 2021. Clinical trials and animal studies that assessed the effects of GTE on PCOS were eligible for inclusion. RESULTS: Of 314 articles found in the search, four human studies and four animal studies were included. All studies in humans showed the effects of GTE on weight loss. GTE's effect on decreasing testosterone levels in humans and LH levels in animals were also reported. In addition, increases in FSH and progesterone levels in animal models were observed. Although GTE improved fasting blood sugar and insulin levels, the effect of GTE on inflammatory parameters, such as TNF-alpha and IL-6 and antioxidant status, was limited to animal studies. CONCLUSION: Therefore, this review suggests that GTE could be considered a potential agent to attenuate PCOS complications mainly due to its effect on weight loss and glycemic levels. However, more studies are needed to formulate conclusions about the effects and mechanisms of GTE in PCOS.

The effects of Cuminum cyminum on glycemic parameters: A systematic review and meta-analysis of controlled clinical trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuminum Cyminum (CC) is a traditional herbal medicine using as an antiseptic, anti-carcinogenic, anti-mutagenic, anti-cancer, anti-hypertensive, anti-inflammatory, and antioxidant. Recently hypoglycemic characteristics of CC have been indicated. AIM OF THE STUDY: We intended to conduct a meta-analysis on the effect of CC supplementation on glycemic parameters in patients with different chronic diseases. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Scopus were searched until May 2021. Random effect model was conducted to perform the meta-analysis. Source of heterogeneity was explored using the meta-regression and subgroup analyses. The Cochrane Collaboration's tool was used to assess the quality of studies. The GRADE approach was used to assess the quality of evidence. RESULTS: Findings of eight studies showed that CC supplementation reduced FBS (SMD = -1.4 mg/dl; 95 % CI: -2.29, -0.51; P = 0.002), HbA1c (SMD = -1.71 %; 95 % CI: -3.24, -0.18; P = 0.028), and HOMA-ß (SMD = 0.46; 95 % CI: -0.62, 1.55; P = 0.404) significantly. Also, CC increased QUICKI level (SMD = 0.89; 95 % CI: 0.37, 1.4; P = 0.001. However, no significant effect of CC was observed on insulin (SMD = -0.70 µIU/dl; 95 % CI: -1.84, 0.45; P = 0.234) and HOMA-IR (SMD = 0.46; 95 % CI: -0.62, 1.55; P = 0.404). CONCLUSION: CC had an improving effect on FBS, HbA1C, HOMA-B, and QUICKI. The effect of CC on amending HOMA-IR was significant after sensitivity analysis. However, the insulin level was not changed significantly.

Effects of Nigella sativa oil supplementation on selected metabolic parameters and anthropometric indices in patients with coronary artery disease: A randomized, double-blind, placebo-controlled clinical trial.

Various metabolic parameters are risk factors related to the amplified risk of atherosclerotic cardiovascular disease. A wide variety of data exist on Nigella sativa (NS) and metabolic parameters. The current study is designed to examine NS supplementation on lipid profile, blood pressure, glycemic control, anthropometric indices, and insulin resistance in individuals with coronary artery disease (CAD). In a randomized, double-blind, placebo-controlled clinical trial, 60 patients with CAD received either 2 g of NS oil or sunflower oil as a placebo for 8 weeks. Biochemical and anthropometric measurements were assessed. NS significantly reduced weight (-1.82 Kg; 95% C, [2.72, 4.13]), body mass index (-0.67 kg/m2 ; 95% C, [0.33, 1.01]), waist circumference (-2.15 cm; 95% C, [1.06, 3.23]), hip circumference (-1.26 cm; 95% C, [0.61, 1.910]), waist-to-hip ratio (0.008; 95%C, [0.001, 0.01]), systolic (-9.52 mmHg; 95% C, [7.14, 11.9]), diastolic blood pressure (-8.26 mmHg; 95% C, [4.89, 11.62]), and fasting blood glucose (FBS) (-4.32 mg/dl; 95% C, [-0.51, 9.15]) as compared with the placebo group. The results indicate a potential beneficiary effect of NS on the metabolic parameters in CAD patients including improvements in anthropometric indices, blood pressure, and FBS.

Prognostic Potential of the Preoperative Controlling Nutritional Status (CONUT) Score in Predicting Survival of Patients with Cancer: A Systematic Review.

The nutritional status of a patient has prognostic potency concerning short- and long-term outcomes, including survival, in many diseases. The controlling nutritional status (CONUT) score is a method for assessing nutritional status and predicting outcomes of several diseases. This study sought to systematically identify the prognostic role of preoperative CONUT score on posttreatment overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) in patients with cancer. The PubMed, SCOPUS, and Google Scholar databases and Google were searched for all dates until December 2019. Original articles investigating the association of preoperative CONUT score with survival in cancer patients who underwent surgery were included. Duplicate and irrelevant reports were screened out and the remaining articles assessed for quality and data extracted during critical analysis. Results of multivariate analysis were used to evaluate the prognostic competence of CONUT score in predicting survival. The search method identified an initial 181 articles, of which 32 were included in the final analysis. Lower OS, CSS, and RFS rates were reported by 100%, 100%, and 87.0% of the included studies, respectively, in cancer patients with high CONUT scores. A prognostic role of the CONUT score for prediction of OS, CSS, and RFS in cancer patients was shown by 91.7%, 90.9%, and 52.6% of the studies, respectively. The receiver operating characteristic curve area under the curve (AUC) value of the CONUT score for predicting OS, CSS, and RFS was at an acceptable level (>0.5) in all studies with available AUC values (n = 19). Sixty percent (12 of 20) of the studies reported that high CONUT score was significantly related to lower BMI. The findings promote confidence that a high preoperative CONUT score is associated with poor survival rate and is an independent prognostic factor of OS and CSS in patients with various types of cancer. Evaluation of the preoperative CONUT score might help clinicians in decision-making with respect to surgical implications.

Novel multi-targeted nanoparticles for targeted co-delivery of nucleic acid and chemotherapeutic agents to breast cancer tissues.

Selective delivery of drugs to damaged tissues favorable to reduce the side effects while enhancing the therapeutic efficacy. The purpose of the present study was the design and synthesis of multi-targeted nanoparticles for co-delivery of both drug and nucleic acid to cancer cells. In this study biocompatible compounds such as chitosan, polyethylene glycol (PEG), polycaprolactone (PCL), folic acid (FA) and glucose (Glu) were used to synthesize the FA-PEG-Chitosan-PCL-Chitosan-PEG-FA (FPCP) and Glu-PEG-Chitosan-PCL-Chitosan-PEG-Glu (GPCP) copolymers. Then, paclitaxel (PTX), oleic acid-coated FeCO nanoparticles (FeCO-OA) and 6-carboxy-fluorescein phosphoramidate (FAM)-labeled siRNA (siRNA-FAM) were encapsulated into either FPCP or GPCP, or both FPCP and GPCP (GFPCP), using the solvent evaporation technique. In vitro and in vivo biocompatibility and drug delivery efficiency of FPCP/FeCO-OA/PTX, GPCP/FeCO-OA/PTX and GFPCP/FeCO-OA/PTX nanoparticles were determined by recording the MTT assay, weight loss and tumor volume respectively. In addition, the ability of FPCP/FeCO-OA/siRNA-FAM, GPCP/FeCO-OA/siRNA-FAM, and GFPCP/FeCO-OA/siRNA-FAM gene transfer was determined using flow cytometry analysis. Moreover, the effects of applying an external magnetic field to the tumor site on the efficiency of drug delivery using FPCP/FeCO-OA/siRNA-FAM/PTX (NPsA), GPCP/FeCO-OA/siRNA-FAM/PTX (NPsB) and GFPCP/FeCO-OA/siRNA-FAM/PTX (NPsAB) were also investigated in the present study. No significant toxicity was observed for the FPCP and GPCP copolymers. Meanwhile, PTX encapsulated FPCP, GPCP and GFPCP exhibited greater anticancer activities against MCF-7 cells. The in vivo and in vitro results showed that the nanoparticles targeted with both folic acid and glucose increased drug and RNA transfer efficiency compared to when folic acid or glucose alone used. Also, the efficiency of PTX and siRNA-FAM delivery to tumor tissues by nanoparticles increased significantly by applying an external magnetic field to the tumor area. The hydrophobic interactions between different amphipathic copolymers in appropriate is an efficient and easy technique to synthesize complex and multifunctional nanoparticles.

A comprehensive insight into potential roles of Nigella sativa on diseases by targeting AMP-activated protein kinase: a review.

OBJECTIVES: Nigella sativa (NS) is a known medicinal herb with numerous therapeutic effects such as antidiabetic, anti-proliferative, anti-inflammatory, and anti-cancer activities. It has been indicated that NS can regulate cellular metabolism by adjusting transduction signaling pathways. Adenosine monophosphate-activated protein kinase (AMPK) is one of the main physiological processes, such as energy hemostasis, cellular metabolism, and autophagy regulators. Herb-derived medicines have always been considered as one of the main AMPK activators, and surprisingly recent data has demonstrated that it can be a target for NS and its derivatives. EVIDENCE ACQUISITION: The literature search was conducted in PubMed, SCOPUS, Embase, ProQuest, and Google Scholar electronic resources. Published articles up to September 2020 were considered, and those of which investigated Nigella sativa effects on the AMPK pathway after meeting the inclusion criteria were included. RESULTS: The search was performed on several online databases such as PubMed, Scopus, Embase, ProQuest, and Google Scholar from inception until January 2020. Among the initial search, 245 studies were found. After removing duplicated data and meeting the inclusion criteria, only 14 studies were selected. They included the effects of NS and its bioactive compounds as anti-hyperglycemic (n = 5), on liver function (n = 4), cancers (n = 3), and on Neuroinflammation and Atherosclerosis (n = 2). Most of the included studies are animals or in-vitro investigations. CONCLUSION: In this review, we discuss the latest findings on the molecular mechanism of NS effecting the AMPK signaling pathway. We also focus on the therapeutic effects of NS, including the prevention and treatment of metabolic and pro-inflammatory disease by targeting the AMPK pathway.

The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials.

The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (- 0.52, 95% CI - 0.80, - 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose-response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.

Effect of flaxseed oil supplementation on the erythrocyte membrane fatty acid composition and endocannabinoid system modulation in patients with coronary artery disease: a double-blind randomized controlled trial.

BACKGROUND: The endocannabinoid system (ECS) overactivation, associated with increased inflammatory process, may act as a risk factor for coronary artery disease (CAD). Dietary fat may influence the ECS tone. The aim of the present study was to investigate the effect of flaxseed oil on the erythrocyte membrane fatty acid profile and ECS activity by the measurement of serum N-arachydonoil ethanolamine (AEA) and cannabinoid receptor type-1 (CB1), cannabinoid receptor type-2 (CB2), and fatty acid amide hydrolase (FAAH) mRNA expression. METHODS: This clinical trial was performed on 44 patients with CAD. The intervention group received 1.5% fat milk supplemented with flaxseed oil (containing 2.5 g α-linolenic acid or ALA), while the placebo group received 1.5% fat milk for 10 weeks. The fatty acid profile of erythrocyte membrane phospholipids was measured by gas chromatography. The AEA level was determined using an ELISA kit, and real-time PCR was performed to measure CB1, CB2, and FAAH mRNA expression pre- and post-intervention. RESULTS: Flaxseed oil supplementation resulted in a significant increase in the ALA content and a significant reduction in linoleic acid (LA) content of membrane phospholipids, compared to the placebo group (MD = - 0.35 and 2.89, respectively; P < 0.05). The within group analysis showed that flaxseed oil supplementation caused a significant reduction in both LA and arachidonic acid (MD = - 4.84 and - 4.03, respectively; P < 0.05) and an elevation in the ALA (MD = 0.37, P < 0.001) content of membrane phospholipids compared with the baseline. In the intervention group, a marked reduction was observed in the serum AEA level after 10 weeks of intervention, compared with the placebo group (MD = 0.64, P = 0.016). Changes in CB2 mRNA expression in the flaxseed oil group were significant (fold change = 1.30, P = 0.003), compared with the placebo group. CONCLUSION: Flaxseed oil supplementation could attenuate the ECS tone by decreasing the AEA level and increasing CB2 mRNA expression. Therefore, flaxseed oil may be considered a promising agent with cardioprotective properties.