Probiotics for the Management of Oral Mucositis: An Interpretive Review of Current Evidence.

Mucositis is one of the major side effects of anti-cancer therapies. Mucositis may lead to other abnormalities such as depression, infection, and pain, especially in young patients. Although there is no specific treatment for mucositis, several pharmacological and non-pharmacological options are available to prevent its complications. Probiotics have been recently considered as a preferable protocol to lessen the complications of chemotherapy, including mucositis. Probiotics could affect mucositis by anti-inflammatory and anti-bacterial mechanisms as well as augmenting the overall immune system function. These effects may be mediated through anti microbiota activities, regulating cytokine productions, phagocytosis, stimulating IgA releasement, protection of the epithelial shield, and regulation of immune responses. We have reviewed available literature pertaining to the effects of probiotics on oral mucositis in animal and human studies. While animal studies have reported protective effects of probiotics on oral mucositis, the evidence from human studies is not convincing.

Soy Isoflavones and Bone Health: Focus on the RANKL/RANK/OPG Pathway.

Bone remodels via resorption and formation, two phenomena that continuously occur in bone turnover. The RANKL/RANK/OPG pathway is one of the several mechanisms that affect bone turnover. The RANKL/OPG ratio has a substantial role in bone resorption. An imbalance between formation and resorption is related to an increased RANKL/OPG balance. OPG, a member of this system, can bind to RANKL and suppress RANK-RANKL interaction, and subsequently, inhibit further osteoclastogenesis. The serum levels of RANKL and OPG in the bone microenvironment are vital for osteoclasts formation. The RANK/RANKL/OPG system plays a role in the pathogenesis of bone disorders. This system can be considered a new treatment target for bone disorders. Soy isoflavones affect the RANK/RANKL/OPG system through numerous mechanisms. Soy isoflavones decrease RANKL levels and increase OPG levels. Therefore, isoflavones improve bone metabolism and decrease bone resorption. Soy isoflavones decrease serum markers of bone resorption and improve bone metabolism. However, while the available data are promising, the results of several studies reported no change in RANKL and OPG levels with isoflavones supplementation. In this regard, current evidence is insufficient for conclusive approval of the efficacy of isoflavones on RANKL/RANK/OPG and further research, including animal and human studies, are needed to confirm the effect of soy isoflavones on the RANKL/RANK/OPG pathway. This study was a review of available evidence to determine the role of isoflavones in bone hemostasis and the RANK/RANKL/OPG pathway. The identification of the effects of isoflavones on the RANKL/RANK/OPG pathway directs future studies and leads to the development of effective treatment strategies for bone disorders.

Quercetin as an anticancer agent: Focus on esophageal cancer.

Esophageal cancer (EC) is regarded as the sixth highest contributor to all cancer-related mortality, worldwide. In spite of advances in the treatment of EC, currently used methods remain ineffective. Quercetin, as a dietary antioxidant, is a plant flavonol from the flavonoid group of polyphenols, and can be found in numerous vegetables, fruits, and herbs. Quercetin can affect the processes of cancer-related diseases via cell proliferation inhibitory effects, potential apoptosis effects, and antioxidant properties. Of the various types of cancer, the use of quercetin has now become prominent in the treatment of EC. In this review, we discuss how quercetin may be an important supplement for the prevention, treatment, and management of EC, owing to its natural origin, and low-cost relative to synthetic cancer drugs. However, most findings cited in the current study are based on in vitro and in vivo studies, and thus, further human-based research is necessitated. PRACTICAL APPLICATIONS: In spite of advances in the treatment of esophageal cancer, currently used methods remain ineffective, therefore, an alternative or complementary therapy is required. Quercetin, as a dietary antioxidant, can affect the processes of cancer-related diseases via cell proliferation inhibitory effects, potential proapoptotic functions, and antioxidant properties. Quercetin may be an important supplement for the prevention, treatment, and management of EC, owing to its natural origin. The low cost of quercetin as supplement or dietary intake, relative to synthetic cancer drugs, is an advantage of the compound which should be considered.

RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling.

Bones as an alive organ consist of about 70% mineral and 30% organic component. About 200 million people are suffering from osteopenia and osteoporosis around the world. There are multiple ways of protecting bone from endogenous and exogenous risk factors. Planned physical activity is another useful way for protecting bone health. It has been investigated that arranged exercise would effectively regulate bone metabolism. Until now, a number of systems have discovered how exercise could help bone health. Previous studies reported different mechanisms of the effect of exercise on bone health by modulation of bone remodeling. However, the regulation of RANKL/RANK/OPG pathway in exercise and physical performance as one of the most important remodeling systems is not considered comprehensive in previous evidence. Therefore, the aim of this review is to clarify exercise influence on bone modeling and remodeling, with a concentration on its role in regulating RANKL/RANK/OPG pathway.

Probiotics and bone disorders: the role of RANKL/RANK/OPG pathway.

The skeleton is the framework and in charge of body configuration preservation. As a living tissue, bones are constantly being formed and absorbed. Osteoblasts and osteoclasts are the main bone cells and balance between their activities indicates bone health. Several mechanisms influence the bone turnover and RANKL/RANK/OPG pathway is one of them. This system, whose components are part of the tumor necrosis factor (TNF) superfamily, exists in many organs and could play a role in bone modeling and remodeling. RANKL/RANK pathway controls osteoclasts activity and formation. In addition, they are identified as key factors on bone turnover in different pathological situations. At the same time, OPG (RANKL's decoy receptor) plays role as a bone-protective factor by binding to RANKL and prevention of extra resorption. The lack of balance between RANKL and OPG could result in excessive bone resorption. Probiotics, the beneficial microorganisms for human health, entail bones in their advantages. Recent studies suggest that probiotics could reduce inflammatory factors (for example TNF-α and IL-1ß) and increase bone OPG expression. In addition, probiotics have shown to maintain bones in various ways. Although current evidence is not enough for definitive approval of probiotics' efficacy on RANKL/RANK/OPG, its positive responses from conducted studies are significant. Understanding of the probiotics' effects on RANKL/RANK/OPG pathway will help focus future studies, and assist in developing efficient treatment strategies.

A comparison between the effects of flaxseed oil and fish oil supplementation on cardiovascular health in type 2 diabetic patients with coronary heart disease: A randomized, double-blinded, placebo-controlled trial.

This study compared the effects of flaxseed and fish oil supplementation on cardiovascular risk parameters in diabetic patients with coronary heart disease. Participants were randomly allocated into three intervention groups to receive either 1,000 mg of omega-3 fatty acids from fish oil or 1,000 mg of omega-3 fatty acids from flaxseed oil or placebo (n = 30 each group) twice a day for 12 weeks. A significant reduction in insulin levels (.04) was observed following flaxseed oil and fish oil supplementation compared with the placebo. In addition, a significant reduction in high-sensitivity C-reactive protein (.02) was seen after flaxseed oil supplementation compared with the placebo and a significant increase in total nitrite (.001) was seen after flaxseed oil and fish oil intake compared with placebo. Additionally, a significant increase in total antioxidant capacity (p < .001) after consuming flaxseed oil and fish oil compared with placebo and glutathione levels (.001) after consuming fish oil compared with flaxseed oil and placebo was observed. Overall, our study revealed the beneficial effects of flaxseed oil and fish oil supplementation on few metabolic profiles. This study suggests that the effect of flaxseed oil in reducing insulin and increasing total nitrite and total antioxidant capacity is similar to fish oil.

Retraction Note to: Effect of N-acetyl cysteine (NAC) supplementation on positive and negative syndrome scale in schizophrenia: a systematic review and meta-analysis of randomised controlled trials.

The authors have retracted this article [1] because there are fundamental errors in the data presented that undermine the conclusions drawn. All authors agree with this retraction. The authors are re-analysing their data and intend to submit a new manuscript for peer review in due course.

Effect of N-acetyl cysteine (NAC) supplementation on positive and negative syndrome scale in schizophrenia: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To conduct a systematic review and meta-analysis of published randomised controlled trials on the efficacy of NAC supplementation on positive and negative syndrome scale in schizophrenia. METHODS: A meta-analysis was conducted, and studies were identified by a search of electronic databases from inception to May 2018. Combined and stratified analyses were used. RESULTS: Seven trials were identified, and data from n = 447 participants were included. Pooled analysis showed improvement of positive and negative syndrome scale following NAC treatment compared with placebo, for total (SMB = - 0.96) [95% CI - 1.69, - 0.24; P = 0.009], general (SMB = - 1.04) [95% CI - 1.80, - 0.27; P = 0.008] and negative (SMB = - 0.73) [95% CI - 1.29, - 0.17; P = 0.01] scores, respectively. Significant heterogeneity was found, and subgroup analysis showed significant reductions in studies with a treatment duration of ≤ 24 weeks, with a considerable effect size on total, general, and negative scores (Total SMD = - 0.83; General SMD = - 0.67; Negative SMD = - 1.09) following NAC. CONCLUSIONS: NAC improved all aspects of positive and negative syndrome scale in schizophrenic populations and may be more efficacious with treatment durations up to 24 weeks.

The effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.

Besides other benefits, curcumin is getting more recognized for its antioxidant and anti-inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin-containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta-analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL-6) (SMD -2.08; 95% CI [-3.90, -0.25]; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (SMD -0.65; 95% CI [-1.20, -0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD -3.14; 95% CI [-4.76, -1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor-alpha (SMD -1.62; 95% CI [-3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [-1.06, 1.74], p = 0.63). Overall, this meta-analysis suggests that taking curcumin-containing supplements may exert anti-inflammatory and antioxidant properties through a significant reduction in IL-6, hs-CRP, and MDA levels.

The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to evaluate the effect of the co-administration of vitamin D and omega-3 fatty acid on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome (PCOS). METHODS: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 60 subjects, aged 18-40 years old with PCOS. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 2000 mg/day omega-3 fatty acid from fish oil (n = 30) or placebo (n = 30) for 12 weeks. Gene expression analysis of inflammatory cytokines was conducted on peripheral blood mononuclear cells (PBMCs) of PCOS women using RT-PCR method. RESULTS: Vitamin D and omega -3 fatty acid co-supplementation significantly decreased serum total testosterone levels (-0.2 ±â€¯0.5 vs. + 0.1 ±â€¯0.4 ng/mL, P = 0.02) compared with the placebo. In addition, vitamin D and omega-3 fatty acid co-supplementation resulted in a significant improvement in beck depression inventory (-1.4 ±â€¯1.6 vs. -0.5 ±â€¯0.6, P = 0.01), general health questionnaire scores (-4.5 ±â€¯4.3 vs. -1.9 ±â€¯2.3, P = 0.005) and depression anxiety and stress scale scores (-5.0 ±â€¯5.1 vs. -2.3 ±â€¯3.5, P = 0.01) compared with the placebo. Additionally, vitamin D and omega-3 fatty acid co-administration significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (-1.2 ±â€¯1.9 vs. + 0.1 ±â€¯0.7 mg/L, P = 0.001) and malondialdehyde (MDA) levels (-0.4 ±â€¯0.4 vs. + 0.2 ±â€¯0.6 µmol/L, P < 0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (+ 114.6 ±â€¯122.2 vs. -2.4 ±â€¯168.2 mmol/L, P = 0.003) compared with the placebo. Results of RT-PCR demonstrated that vitamin D and omega-3 fatty acid co-supplementation significantly downregulated gene expression of interleukin-1 (IL-1) (P = 0.03), and upregulated vascular endothelial growth factor (VEGF) (P = 0.004) in PBMCs of subjects with PCOS, when compared with placebo. CONCLUSIONS: Overall, the co-administration of vitamin D and omega-3 fatty acid for 12 weeks had beneficial effects on mental health parameters, serum total testosterone, hs-CRP, plasma TAC and MDA levels, and gene expression of IL-1 and VEGF among women with PCOS.

The effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to evaluate the effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome (PCOS). METHODS: Forty PCOS women were allocated into two groups and treated with 1000mg omega-3 fatty acids plus 400 IU vitamin E supplements (n = 20) or placebo (n = 20) per day for 12 weeks. Parameters of mental health were recorded at baseline and after the 12-week intervention. Gene expression related to insulin and inflammation were measured in blood samples of PCOS women. RESULTS: After the 12-week intervention, compared with the placebo, omega-3 and vitamin E co-supplementation led to significant improvements in beck depression inventory total score (- 2.2 ± 2.0 vs. - 0.2 ± 1.3, P = 0.001), general health questionnaire scores (- 5.5 ± 4.6 vs. - 1.0 ± 2.3, P < 0.001) and depression anxiety and stress scale scores (- 7.2 ± 5.2 vs. - 1.3 ± 1.3, P < 0.001). Compared with the placebo, omega-3 and vitamin E co-supplementation could up-regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) expression (P = 0.04) in peripheral blood mononuclear cells (PBMC) of PCOS women. In addition, compared with the placebo, omega-3 and vitamin E co-supplementation down-regulated interleukin-8 (IL-8) (P = 0.003) and tumor necrosis factor alpha (TNF-α) expression (P = 0.001) in PBMC of PCOS women. There were no significant difference between-group changes in glucose transporter 1 (GLUT-1), IL-6 and transforming growth factor beta (TGF-ß) in PBMC of PCOS women. CONCLUSION: Omega-3 and vitamin E co-supplementation was effective in improving parameters of mental health, and gene expression of PPAR-γ, IL-8 and TNF-α of women with PCOS.

Effects of a Multispecies Probiotic Supplement on Bone Health in Osteopenic Postmenopausal Women: A Randomized, Double-blind, Controlled Trial.

OBJECTIVE: The development of alternative approaches to prevent and/or treat osteoporosis, as a chronic progressive bone disease, is being considered currently. Among dietary supplements, probiotics may have favorable effects on bone metabolism. Therefore, the aim of this study was to evaluate the effects of a multispecies probiotic supplementation on bone biomarkers and bone density in osteopenic postmenopausal women. METHODS: This randomized double-blind placebo-controlled clinical trial was performed on 50 patients with osteopenia aged 50-72 years. Participants were randomly assigned to take either a multispecies probiotic supplement (GeriLact; n = 25) or placebo (n = 25) for 6 months. GeriLact contains 7 probiotic bacteria species. Participants received 500 mg Ca plus 200 IU vitamin D daily. Bone mineral density (BMD) of lumbar spine and total hip and blood biomarkers including bone-specific alkaline phosphatase (BALP), osteocalcin (OC), collagen type 1 cross-linked C-telopeptide (CTX), deoxypyridinoline (DPD), parathyroid hormone (PTH), 25-OH vitamin D, and serum pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß) were assessed at baseline and at the end of the study. RESULTS: The multispecies probiotic significantly decreased BALP (p = 0.03) and CTX (p = 0.04) levels in comparison with the control group but had no effect on BMD of the spine and total hip. Moreover, there was a statistically significant decrease in serum PTH (p = 0.01) and TNF-α (p = 0.02) in the intervention group compared to the placebo group. CONCLUSIONS: These results may suggest the favorable effects of the multispecies probiotic supplementation for 6 months on bone health in postmenopausal women due to slowing down the rate of bone turnover.

Effects of a Multispecies Probiotic Mixture on Glycemic Control and Inflammatory Status in Women with Gestational Diabetes: A Randomized Controlled Clinical Trial.

Objective. This trial aims to examine the effects of a Probiotic Mixture (VSL#3) on glycemic status and inflammatory markers, in women with GDM. Materials and Methods. Over a period of 8 weeks, 82 women with gestational diabetes were randomly assigned to either an intervention group (n = 41) which were given VSL#3 capsule or to a control group which were given placebo capsule (n = 41). Fasting plasma glucose, homeostatic model assessment of insulin resistance, glycosylated hemoglobin, high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6, Interferon gamma, and interleukin-10 were measured before and after the intervention. Results. After 8 wk of supplementation FPG, HbA1c, HOMA-IR, and insulin levels remained unchanged in the probiotic and placebo groups. The comparison between the two groups showed no significant differences with FPG and HbA1c, but there were significant differences in insulin levels and HOMA-IR (16.6 ± 5.9; 3.7 ± 1.5, resp.). Unlike the levels of IFN-g (19.21 ± 16.6), there was a significant decrease in levels of IL-6 (3.81 ± 0.7), TNF-α (3.10 ± 1.1), and hs-CRP (4927.4 ± 924.6). No significant increase was observed in IL-10 (3.11 ± 5.7) in the intervention group as compared with the control group. Conclusions. In women with GDM, supplementation with probiotics (VSL#3) may help to modulate some inflammatory markers and may have benefits on glycemic control.

Evaluation of protein concentration and limiting amino acids including lysine and met + cys in prestarter diet on performance of broilers.

Four experiments were conducted, in two stages, to evaluate protein and limiting amino acids' (lysine and methionine + cystine) levels in pre-starter diets on broilers' performance. In each experiment of Stage 1, 640 new-born male Ross 308 cockerels were randomly allocated to eight dietary treatments with a 2 × 4 factorial arrangement. In experiment 1-1, two levels of crude protein (CP: 21% and 23.2%) and four levels of Lys (1.2, 1.3, 1.4, and 1.5%) and in experiment 1-2, two levels of CP (21 and 23.2%) and four levels of Met + Cys (0.85, 0.90, 0.95, and 1.00%) were used. In Stage 2, the optimum levels of Lys and Met + Cys obtained from Stage 1 (1.3 and 1.5% Lys, 0.90 and 1.00% Met + Cys in experiment 1-1 and 1-2, resp.) with two levels of CP (21 and 23.2%) were used in two separate simultaneous experiments with a 2 × 2 factorial arrangement for male and female birds. The levels of CP significantly influenced BWG and FCR in experiment 1-1. Dietary levels of Lys affect BWG (experiment 1-1) and FI (experiments 1-1 and 2-1) significantly. In experiments 1-2 and 2-2, the different levels of Met + Cys did not affect BWG, FI, and FCR of male or female broilers. The results of these experiments indicated that the optimal level of dietary protein and Lys were 23.2% and 1.5%, respectively. Diets with 1% Met + Cys caused optimal performance.