Corrigendum: Remarkable impacts of probiotics supplementation in enhancing of the antioxidant status: results of an umbrella meta-analysis.

[This corrects the article DOI: 10.3389/fnut.2023.1117387.].

Remarkable impacts of probiotics supplementation in enhancing of the antioxidant status: results of an umbrella meta-analysis.

Introduction: Numerous meta-analyses have demonstrated the beneficial effects of probiotics on oxidative stress biomarkers, although some studies have contradictory results. Therefore, the current research was conducted to obtain a precise and definite understanding on the impact of probiotics on oxidative stress biomarkers in adults. Methods: We conducted a comprehensive systematic search of results on Scopus, PubMed, Embase, Web of Science, and Google Scholar dating up to March 2022. Fifteen meta-analyses were included in this umbrella meta-analysis. The random-effects model was employed to obtain the overall effect size. Subgroup analyses were carried out based on supplementation dosage and duration, mean age, and study population. Results: Our results indicated that probiotics supplementation meaningfully decreased serum malondialdehyde (MDA) (ESWMD = -0.56, 95% CI: -0.72, -0.39; p < 0.001, and ESSMD = -0.50, 95% CI: -0.66, -0.34; p < 0.001). Moreover, the findings showed that probiotics resulted in a significant increase in total antioxidant capacity (TAC) (ESWMD = 29.18, 95% CI: 16.31, 42.04; p < 0.001, and ESSMD = 0.25, 95% CI: 0.02, 0.47; p = 0.032), total glutathione (GSH) (ESWMD: 30.65; 95% CI: 16.94, 44.35, p < 0.001), and nitric oxide (NO) (ESWMD: 1.48; 95% CI: 0.31, 2.65, p = 0.013; I2 = 51.7%, p = 0.043). Discussion: Probiotics could be considered a strong agent in the reinforcement of antioxidant status and preventing the incidence of chronic diseases.

Responsible enzymes for metabolizing vitamin D in patients with acute leukemia and the relationship with treatment outcomes: a case-control study.

Anti-cancer properties of vitamin D have been reported in studies. The aim of this study was to evaluate the expression of some key enzymes involved in vitamin D metabolism and the serum levels of related proteins. Fifty-four patients with acute myeloid leukemia (AML) and 55 eligible individuals were studied as the control group. The expression of VDR, CYP27B1, and CYP24A1 genes was measured. Serum levels of related proteins were quantified. The association between the studied variables and treatment outcomes: duration of fever and neutropenia, length of hospital stay, achievement of complete remission and overall survival has been investigated. Expression of CYP24A1 gene and serum levels of CYP27B1 and CYP24A1 proteins were significantly higher in the patient group. CYP24A1 gene expression, its blood concentrations and serum levels of CYP27B1 were significantly higher in the AML group. Vitamin D status and key enzymes did not show a strong change in AML patients neither did associate with treatment outcomes except CYP24A1.

Melatonin effectiveness in amelioration of oxidative stress and strengthening of antioxidant defense system: Findings from a systematic review and dose-response meta-analysis of controlled clinical trials.

BACKGROUND AND AIM: Oxidative stress is involved in the development of chronic diseases. It has been suggested that melatonin has a protective role against oxidative stress by activation of antioxidant enzymes and scavenging free-radicals. Present study aimed to investigate the effect of melatonin supplementation on oxidative stress and antioxidant biomarkers such as malondialdehyde (MDA), increased total antioxidant capacity (TAC), superoxide dismutase (SOD), and Glutathione peroxidase (GPx). METHODS: Systematic search was performed to identify relevant studies in PubMed/Medline, SCOPUS, Web of Science and Embase databases and Google Scholar up to September 2020. Meta-analysis was conducted using random-effect model. Subgroup analysis and meta-regression was used to identify sources of heterogeneity. The quality of studies was assessed using Cochrane Collaboration's tool. Publication bias was assessed by visual inspection of funnel plot. RESULTS: A total number of 16 eligible articles were included in the meta-analysis. The dosages of melatonin varied between 3 and 400 mg/day, with a duration range between 1.42 and 12 weeks. Melatonin supplementation significantly increased serum levels of TAC [SMD: 1.59; 95% CI: 0.89, 2.29; P < 0.001; (I2 = 93.53%, P < 0.001 No significant effects were observed on MDA [SMD: -3.09; 95% CI: -7.07, 0.89; P = 0.12; (I2 = 99.57%, P < 0.001)], GPx [SMD: 0.86; 95% CI: -3.46, 5.19; P = 0.61; (I2 = 98.17%, P < 0.001)] and SOD levels [SMD: 1.92; 95% CI: -3.57, 7.41; P = 0.35; (I2 = 98.27%, P < 0.001)]. CONCLUSION: Results of the current meta-analysis showed that melatonin supplementation had a significant impact on attenuating of oxidative stress and enhancing antioxidant performance. Melatonin supplementation could be suggested as a safe complementary approach in amelioration of the chronic diseases.

A comprehensive insight into the molecular and cellular mechanisms of the effects of Propolis on preserving renal function: a systematic review.

BACKGROUND: The present systematic review is conducted, focusing on the existing evidence of Propolis's effects due to its various health benefits, mainly antioxidant and anti-inflammatory properties on preserving renal function. METHODS: A systematic search of PubMed, Scopus, Embase, ProQuest, and Google Scholar was undertaken for relevant papers published from the start until January 2021. RESULTS: This review revealed that Propolis affects fasting blood sugar (FBS), postprandial blood glucose, advanced glycation end products (AGEs) concentrations, malondialdehyde (MDA) levels, urinary concentrations of reactive oxygen metabolites (Tbars), total oxidant status (TOS), oxidative stress index (OSI), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation favorably. The findings on hemoglobin A1C (HbA1C), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), ß-cell function (HOMA-ß), quantitative insulin sensitivity check index (QUICKI), and lipid profile were controversial. Moreover, a significant reduction in renal nuclear factor kappa B (NF-κB), serum immunoglobulins, renal ED-1+ cells, and urinary monocyte chemoattractant protein-1 (MCP-1) following Propolis supplementation has been reported, while the results on interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), nitric oxide (NO), nitric oxide synthetase (NOS), and high sensitivity C-reactive protein (hs-CRP) were controversial. Furthermore, included studies showed its anti- proteinuria and kidney restoring effects. CONCLUSION: In this review, both human and animal studies provide us evidences that Propolis could potentially improve the glycemic status, oxidative stress, renal tissue damage, and renal function. Further studies are needed to determine the underlying mechanisms.

Clinical efficacy of zinc supplementation in improving antioxidant defense system: A comprehensive systematic review and time-response meta-analysis of controlled clinical trials.

Oxidative stress is a contributing factor to many chronic diseases. It has been investigated that zinc (Zn) may enhance the antioxidant defense. The current dose-response and time-response meta-analysis aims to determine the efficacy of Zn supplementation in improving antioxidant defense. Scopus, PubMed/Medline, Web of Science, and Embase databases were searched systematically up to December 30, 2020. Meta-analysis was performed on human controlled clinical trials using random effects method. To find any source of heterogeneity, subgroup analysis and meta-regression were performed. Trim and fill analysis was used for adjusting the publication bias. To find any non-linear relationship between variables and effect size, dose-response and time-response analyses were performed. Cochrane Collaboration's tool was used for evaluating the quality assessment. A total of 23 controlled clinical trials were analyzed. The range of Zn supplementation duration in various studies was within 4-24 weeks. Zn supplementation did not have beneficial effects on glutathione peroxidase (GPx) activity (SMD = -0.34 U/g; 95% CI: -0.93, 0.25; P = 0.258). There were significant increasing effects of Zn supplementation on glutathione (GSH) (SMD = 1.28 µmol/l; 95% CI: 0.42, 2.14; P = 0.003) and total antioxidant capacity (TAC) levels (SMD = 1.39 mmol/l; 95% CI: 0.44, 2.35; P = 0.004). Zn had ameliorative effects on superoxide dismutase (SOD) activity after elimination of publication bias (SMD: 0.84 U/g; 95% CI: 0.12, 1.56, P < 0.05). Zn could also elevate GSH and TAC levels, plus SOD activity after modifying the publication bias. Finally, Zn had no significant effect on GPx activity.

Evaluation of iron overload by cardiac and liver T2* in ß-thalassemia: Correlation with serum ferritin, heart function and liver enzymes.

Introduction: In this study, we aimed to assess the relationship of cardiac and hepatic T2* magnetic resonance imaging (MRI) values as a gold standard for detecting iron overload with serum ferritin level, heart function, and liver enzymes as alternative diagnostic methods. Methods: A total 58 patients with beta-thalassemia major who were all transfusion dependent were evaluated for the study. T2* MRI of heart and liver, echocardiography, serum ferritin level, and liver enzymes measurement were performed. The relationship between T2* MRI findings and other assessments were examined. Cardiac and hepatic T2* findings were categorized as normal, mild, moderate, and severe iron overload. Results: 22% and 11% of the patients were suffering from severe iron overload in heart and liver, respectively. The echocardiographic findings were not significantly different among different iron load categories in heart or liver. ALT level was significantly higher in patient with severe iron overload than those with normal iron load in heart (P =0.005). Also, AST level was significantly lower in normal iron load group than mild, moderate, and severe iron load groups in liver (P <0.05). The serum ferritin level was significantly inversely correlated with cardiac T2* values (r = -0.34, P =0.035) and hepatic T2* values (r = -0.52, P =0.001). Conclusion: Cardiac and hepatic T2* MRI indicated significant correlation with serum ferritin level.

Spirulina supplementation and oxidative stress and pro-inflammatory biomarkers: A systematic review and meta-analysis of controlled clinical trials.

Studies investigating the effects of spirulina on inflammation and oxidative stress status are controversial. Therefore, the current systematic review and meta-analysis aimed to evaluate the impacts of spirulina supplementation on oxidative stress indicators and inflammatory markers. PubMed-Medline, SCOPUS, Web of Science, Embase databases and Google Scholar were searched up to 1 October 2020. Random-effect analysis was applied to perform meta-analysis. Subgroup analyses and multivariate meta-regression were performed to find heterogeneity sources. Quality assessment was conducted using Cochrane Collaboration's tool. A total of 11 studies that enrolled 465 subjects were included in our meta-analysis. Pooled results demonstrated a significant increase in interleukin-2 (IL-2) concentrations [Standardized mean difference (SMD = 2.69 pg/mL; 95% CI: 0.26, 5.11; P = .03)]; however this result changed to insignificant (SMD = 0.54 pg/mL; 95% CI: -1.29, 2.27; P > .05) when sensitivity analysis performed. A marginal decreasing effect were also found on interleukin-6 (IL-6) (SMD = -0.72 mg/dL; 95% CI: -1.50, 0.07; P = .073) and thiobarbituric acid reactive substances (TBARS) levels (SMD = -0.65; 95% CI: -1.37, 0.08; P = .08). In addition, results of subgroup analysis revealed a significant reduction in IL-6 and TBARS concentrations when the baseline body mass index (BMI) of participants was lower than 25 kg/m2 . Moreover, spirulina had no significant effect on tumour necrosis factor-α (TNF-α) (SMD = -0.07 mg/dL; 95% CI: -0.33, 0.18; P = .56) and malondialdehyde (MDA) concentrations (SMD = -0.42; 95% CI: -0.98, 0.14; P = .14). Spirulina consumption contributed to a significant increase in IL-2 concentrations changing to insignificant after sensitivity analysis and marginal decreasing effects on IL-6 and TBARS levels. No considerable impacts were observed on TNF-α and MDA concentrations.

Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer.

BACKGROUND: Paclitaxel induced peripheral neuropathy (PIPN) is a major debilitating side effect of paclitaxel in patients with breast cancer with no fully known mechanisms. The aim of the study was to find out the possible risk factors for PIPN. METHODS: Eligible patients with node positive breast cancer undergoing chemotherapy with paclitaxel were assessed. They belonged to an initial randomized controlled trial in which the effectiveness of omega-3 fatty acids in preventing and reducing severity of PIPN was evaluated (protocol ID: NCT01049295). Reduced total neuropathy score (r-TNS) was used for measuring PIPN. All analyses were performed adjusting for intervention effect. The association between age, BMI, BSA, pathological grade, molecular biomarkers and PIPN was evaluated. RESULTS: Fifty-seven patients with breast cancer were investigated. Age was significantly associated with risk of PIPN (RR:1.50, P value = .024). Body mass index and BSA had significant association with severity of PIPN (B:1.28, P = .025; and B: 3.88, P = .010 respectively). Also, BSA showed a significant association with the risk of PIPN (RR: 2.28, P = .035; B: 3.88, P = .035). Incidence and severity of PIPN were much more pronounced in progesterone receptor positive (PR+) patients (RR:1.88, P = .015 and B:1.54, P = .012). Multivariate analysis showed that age and the status of PR+ were independent risk factor for incidence and the status of PR+ was the only independent risk factor for severity of PIPN. CONCLUSION: Age, BSA and the status of PR+, should be considered as the risk factors for PIPN before commencement of chemotherapy with paclitaxel in patients with breast cancer. Older patients, those with greater BSA and PR+ patients may need closer follow up and more medical attention due to greater incidence and severity of PIPN.

A new score for screening of malnutrition in patients with inoperable gastric adenocarcinoma.

BACKGROUND: Malnutrition is common in patients with gastric cancer. Early identification of malnourished patients results in improving quality of life. We aimed to assess the nutritional status of patients with inoperable gastric adenocarcinoma (IGA) and finding a precise malnutrition screening score for these patients before the onset of chemotherapy. METHODS: Nutritional status was assessed using patient generated subjective global assessment (PG-SGA), visceral proteins, and high-sensitivity C reactive protein. Tumor markers of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125) and CA 19-9 and their association with nutritional status were assessed. Then a new score for malnutrition screening was defined. RESULTS: Seventy-one patients with IGA completed the study. Malnourished and well-nourished patients (based on PG-SGA) were statistically different regarding albumin, prealbumin and CA-125. The best cut-off value for prealbumin for prediction of malnutrition was determined at 0.20 mg/dl and using known cut-off values for albumin (3.5 g/dl) and CA-125 (35 U/ml), a new score was defined for malnutrition screening named MS-score. According to MS-score, 92% of the patients had malnutrition and it could predict malnutrition with 96.8% sensitivity, 50% specificity and accuracy of 91.4%. CONCLUSION: MS-score has been suggested as an available and easy-to-use tool for malnutrition screening in patients with IGA.

The effect of n-3 polyunsaturated fatty acids on incidence and severity of oxaliplatin induced peripheral neuropathy: a randomized controlled trial.

BACKGROUND: Oxaliplatin induced peripheral neurotoxicity (OXIPN) is the major dose-limiting and long-lasting side effect of oxaliplatin. N-3 PUFAs have neuroprotective property via their effects on voltage-gated ion channels and by reducing the production of proinflammatory cytokines that causes neuropathy. This study was a randomized double blind placebo controlled trial to find the possible advantages of n-3 PUFAs for preventing and reducing the severity of OXIPN in patients with colon cancer. METHODS: Eligible patients with colon cancer randomly allocated to take n-3 PUFAs pearls, 640 mg t.i.d during chemotherapy with oxaliplatin and one month after the cessation of the treatment or placebo. All patients were evaluated for incidence and severity of OXIPN based on "reduced Total Neuropathy Score" in which clinical and electrophysiological assessments were included. RESULTS: Seventeen patients (47 %) of the n-3 PUFA supplemented group (n = 36) did not develop PN while it was 11 %(4 patients) in the placebo group (n = 35). There was a significant difference in PN incidence (OR = 0.14, .95 % CI = (0.04 to 0.49), p = 0.002). The difference of OXIPN severity was significant between the two study groups (B = -1.61, 0.95 % CI = (-2.59 to -0.62), p = 0.001). CONCLUSIONS: N-3 PUFAs may have neuroprotective effect for reducing the incidence and severity of OXIPN. Finding an effective prophylactic or symptomatic therapy for OXIPN would significantly improve the patients' quality of life. TRIAL REGISTRATION: IRCT201112158397N2.

Prealbumin/CRP Based Prognostic Score, a New Tool for Predicting Metastasis in Patients with Inoperable Gastric Cancer.

Background. There is a considerable dissimilarity in the survival duration of the patients with gastric cancer. We aimed to assess the systemic inflammatory response (SIR) and nutritional status of these patients before the commencement of chemotherapy to find the appropriate prognostic factors and define a new score for predicting metastasis. Methods. SIR was assessed using Glasgow Prognostic Score (GPS). Then a score was defined as prealbumin/CRP based prognostic score (PCPS) to be compared with GPS for predicting metastasis and nutritional status. Results. 71 patients with gastric cancer were recruited in the study. 87% of patients had malnutrition. There was a statistical difference between those with metastatic (n = 43) and those with nonmetastatic (n = 28) gastric cancer according to levels of prealbumin and CRP; however they were not different regarding patient generated subjective global assessment (PG-SGA) and GPS. The best cut-off value for prealbumin was determined at 0.20 mg/dL and PCPS could predict metastasis with 76.5% sensitivity, 63.6% specificity, and 71.4% accuracy. Metastatic and nonmetastatic gastric cancer patients were different in terms of PCPS (P = 0.005). Conclusion. PCPS has been suggested for predicting metastasis in patients with gastric cancer. Future studies with larger sample size have been warranted.

Nutritional assessment of patients with acute leukemia during induction chemotherapy: association with hospital outcomes.

Cancer-related malnutrition causes morbidity and reduced survival. The aim of this study was to evaluate the nutritional and inflammatory status of patients with acute leukemia in association with duration of neutropenic fever (DNF) and length of hospital stay (LHS) during induction chemotherapy. Fifty-five patients with acute lymphoblastic leukemia (ALL) (n = 28) and acute myeloid leukemia (AML) (n = 27) completed the study. There were significant differences between the two groups according to LHS and DNF (p = 0.022 and p = 0.012, respectively): both had a longer period in patients with AML. The patients were statistically different according to body mass index (BMI), pre-albumin, high-sensitivity C-reactive protein (hs-CRP) and patient-generated subjective global assessment (PG-SGA) score (p = 0.049, p = 0.028, p < 0.001, p = 0.030). In patients with ALL, serum albumin and pre-albumin levels were associated with LHS and DNF, respectively. Moreover, PG-SGA score was associated with DNF. In patients with AML, BMI and second pre-albumin level < 10 mg/dL were associated with DNF. Pre-albumin was the common indicator for chemotherapy-related complications in patients with both ALL and AML. Early nutritional assessment can help to find patients with acute leukemia who need nutritional support, and it may contribute to better outcome and less toxicity.

Influence of chemotherapy on the lipid peroxidation and antioxidant status in patients with acute myeloid leukemia.

Chemotherapeutic agents used in patients with cancer cause to generate the enormous amounts of free radicals associated with cell injury. In this study we assess the effects of chemotherapy regimen on oxidant/antioxidant status in patients with acute myeloid leukemia (AML). 38 newly diagnosed patients with acute myeloid leukemia were recruited in this study. All patients received cytarabine and daunorubicin as chemotherapy regimen. Plasma levels of malondialdehyde (MDA), total antioxidant status (TAS), and the levels of erythrocyte activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined before chemotherapy and 14 days after chemotherapy with cytarabine and daunorubicin. Plasma MDA concentrations increased significantly (from 2.68 ± 0.89 nmol/L to 3.14 ± 1.29 nmol/L) during the 14 days post-chemotherapy period (P=0.04). Plasma TAS concentrations changed with chemotherapy from 1.09 ± 0.15 mmol/L to 1.02 ± 0.14 mmol/L with P=0.005. Erythrocyte SOD and GPX activity decreased overtime from 1157.24 ± 543.61 U/g Hb to 984.01 ± 419.09 U/g Hb (P=0.04) and 46.96 ± 13.70 U/g Hb to 41.40 ± 6.44 U/g Hb (P=0.02) respectively. We report here that there is an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant status. This suggests that chemotherapy causes these changes as a result of enormous production of reactive oxygen species in the patients with AML. Antioxidant supplementation must be approached with caution because of the probability of reduction the therapeutic efficacy of these cytotoxic drugs.

Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial.

BACKGROUND: Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. METHODS: This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". RESULTS: Twenty one patients (70%) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7%( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (-2.06 -0.02), p = 0.054). CONCLUSIONS: Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients' quality of life. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT01049295).