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.

Alternate-day modified fasting diet improves weight loss, subjective sleep quality and daytime dysfunction in women with obesity or overweight: a randomized, controlled trial.

Background: Both sleep time and quality can be associated with overweight or obesity. In obese people, visceral fat tissue develops, which results in an increment in the production of cytokines. The increased production of inflammatory cytokines can disturb the sleep/wake cycle. Therefore, weight loss by reducing fat tissue can improve sleep disorders. Intermittent fasting diets are popular and effective diets that can decrease body weight and improve anthropometric data and body composition. The present study aimed to evaluate the effect of Alternate-day Modified Fasting (ADMF) on sleep quality, body weight, and daytime sleepiness. Methods: Classification of 56 obese or overweight women, based on age and body mass index (BMI), was done using stratified randomization. Then individuals were assigned to the ADMF group (intervention) or Daily Calorie Restriction (CR) group (control) using the random numbers table for 8 weeks. We measured the Pittsburgh sleep quality Index (PSQI), weight, BMI, and the Epworth sleepiness scale (ESS) as primary outcomes and assessed subjective sleep quality (SSQ), sleep latency, sleep disturbances, habitual sleep efficiency, daytime dysfunction, and sleep duration as secondary outcomes at baseline and after the study. Results: Following an ADMF diet resulted in a greater decrease in weight (kg) [-5.23 (1.73) vs. -3.15 (0.88); P < 0.001] and BMI (kg/m2) [-2.05 (0.66) vs. -1.17 (0.34); P < 0.001] compared to CR. No significant differences were found in the changes of PSQI [-0.39 (1.43) vs. -0.45 (1.88); P = 0.73] and ESS [-0.22 (1.24) vs. -0.54 (1.67); P = 0.43] between two groups. Also, following the ADMF diet led to significant changes in SSQ [-0.69 (0.47) vs. -0.08 (0.40); P = <0.001], and daytime dysfunction [-0.65 (0.57) vs. 0.04 (0.75); P: 0.001] in compare with CR diet. Conclusion: These results suggested that an ADMF could be a beneficial diet for controlling body weight and BMI. The ADMF diet didn't affect PSQI and ESS in women with overweight or obesity but significantly improved SSQ and daytime dysfunction. Clinical Trial Registration: The Iranian Registry of Clinical Trials (IRCT20220522054958N3), https://www.irct.ir/trial/64510.

Effect of modified alternate day fasting diet on the severity of premenstrual syndrome and health-related quality of life in women with overweight or obesity: a trial study protocol.

INTRODUCTION: Premenstrual syndrome (PMS) includes a range of physical, behavioural and psychological symptoms and decreases women's health-related quality of life (HRQoL). It has been proposed that increased body mass index (BMI) is associated with menstrual problems and decreased HRQoL. The body fat amount plays a role in menstrual cycles by altering the oestrogen/progesterone ratio. Alternate day fasting as an unusual diet results in the improvement of anthropometric indices and reduction of body weight. This study aims to investigate the effect of a daily calorie restriction diet and a modified alternate day fasting diet on PMS and HRQoL. METHODS AND ANALYSIS: This 8-week open-label parallel randomised controlled trial examines the impact of a modified alternate-day fasting diet and daily caloric restriction on the severity of PMS and HRQoL in obese or overweight women. Using simple random sampling, women between the ages of 18 years and 50 years and 25 ≤ BMI ˂ 40 who meet the inclusion and exclusion criteria will be chosen from the Kashan University of Medical Sciences Centre. Patients will be randomised, based on BMI and age through stratified randomisation. Then by the random numbers table, they are allocated to fasting (intervention) or daily calorie restriction (control) groups. Outcomes are chosen for the trial: the difference in the severity of PMS, HRQoL, BMI, body fat mass, fat-free mass, waist-to-hip ratio, waist circumference, hip circumference, per cent body fat, skeletal muscle mass and visceral fat area from baseline to 8 weeks. ETHICS AND DISSEMINATION: The Kashan University of Medical Sciences Ethics Committee has approved the trial (IR.KAUMS.MEDNT.REC.1401.003) (17 April 2022). Results will be published in peer-reviewed academic journals and the participants will be informed via phone calls. TRIAL REGISTRATION NUMBER: IRCT20220522054958N1.

Comparison of the effect of modified intermittent fasting and daily calorie restriction on sleep quality, anthropometric data, and body composition in women with obesity or overweight: study protocol of a randomized controlled trial.

BACKGROUND: Sleep disturbances are common in nearly one-third of adults. Both low quality of sleep and sleep time could be related to increased obesity. An increase in visceral adipose tissue can result in the secretion of inflammatory cytokines. Inflammatory cytokines can lead to a disturbance of the sleep-wake rhythm. Therefore, weight loss may improve sleep quality and duration. Intermittent fasting diet as a popular diet reduces body weight and improves anthropometric indices. This study is performed to further investigate the effect of a modified intermittent fasting diet on sleep quality and anthropometric indices. METHODS: This is an open-label randomized controlled trial to evaluate the effect of daily calorie restriction (control) and modified intermittent fasting (intervention) on sleep quality, anthropometric data, and body composition in women with obesity or overweight for 8 weeks. Fifty-six participants will be classified using stratified randomization based on body mass index (BMI) and age. Then, participants will be assigned to one of the two groups of intervention or control using the random numbers table. The sleep quality, daytime sleepiness, and insomnia will be evaluated by using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Insomnia Severity Index respectively. The primary outcomes chosen for the study were as follows: the difference in sleep quality, daytime sleepiness, insomnia, BMI, fat-free mass (FFM), body fat mass, waist circumference, and waist-to-hip ratio from baseline to 8 weeks. Secondary outcomes chosen for the study were as follows: the difference in hip circumference, the visceral fat area, percent body fat, soft lean mass, skeletal muscle mass, extracellular water ratio, and total body water from baseline to 8 weeks. DISCUSSION: This study will investigate the effect of intermittent fasting intervention compared with daily calorie restriction on sleep quality and anthropometric indices. The information gained will enhance our understanding of fasting interventions, which can be used to improve clinical dietary recommendations. The findings will help to disclose as yet the unknown relationship between diet and sleep quality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20220522054958N3. Registered on 8 July 2022. https://www.irct.ir/trial/64510 .

Omega-3 fatty acids: Current insights into mechanisms of action in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is one of the autoimmune diseases characterized by the lack of self-tolerance and the formation of immune complexes and nuclear autoantigens resulting in inflammation in multiple organs. Nowadays, the major aim of SLE therapy is the control of disease activity. However, the biological heterogeneity between patients and the absence of safe and specific targeted treatments complicate the lupus management. Therefore, the potential prophylactic effects of natural therapy considering the potential side effects of classical pharmacology, also the role of diet therapy in decreasing co-morbidities and improving quality of life in SLE patients could be a promising approach to SLE disease. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are one of the agents that are considered for their preventive and therapeutic properties in disease activity of SLE and the related complications. The intake of omega-3 PUFAs likely has a direct relationship with improvements in inflammatory, cardiovascular, depressive, and neuromotor symptoms of the patients. The current review summarizes clinical and preclinical studies with comprehensive insights into the mechanisms of action of omega-3 fatty acids (omega-3 FAs) in Systemic Lupus Erythematosus to provide an update on the negative and positive aspects of the intake of omega-3 FAs in SLE patients.

Schizophrenia, Curcumin and Minimizing Side Effects of Antipsychotic Drugs: Possible Mechanisms.

Schizophrenia is a mental disorder characterized by episodes of psychosis; major symptoms include hallucinations, delusions, and disorganized thinking. More recent theories focus on particular disorders of interneurons, dysfunctions in the immune system, abnormalities in the formation of myelin, and augmented oxidative stress that lead to alterations in brain structure. Decreased dopaminergic activity and increased phospholipid metabolism in the prefrontal cortex might be involved in schizophrenia. Antipsychotic drugs used to treat schizophrenia have many side effects. Alternative therapy such as curcumin (CUR) can reduce the severity of symptoms without significant side effects. CUR has important therapeutic properties such as antioxidant, anti-mutagenic, anti-inflammatory, and antimicrobial functions and protection of the nervous system. Also, the ability of CUR to pass the blood-brain barrier raises new hopes for neuroprotection. CUR can improve and prevent further probable neurological and behavioral disorders in patients with schizophrenia. It decreases the side effects of neuroleptics and retains lipid homeostasis. CUR increases the level of brain-derived neurotrophic factor and improves hyperkinetic movement disorders. CUR may act as an added counteraction mechanism to retain cell integrity and defense against free radical injury. Thus it appears to have therapeutic potential for improvement of schizophrenia. In this study, we review several properties of CUR and its ability to improve schizophrenia and minimize the side effects of antipsychotic drugs, and we explore the underlying mechanisms by which CUR affects schizophrenia and its symptoms.

Does an alternate-day modified fasting diet improve premenstrual syndrome symptoms and health-related quality of life in obese or overweight women with premenstrual syndrome? A randomized, controlled trial.

Background: Premenstrual syndrome disorder (PMS) is a condition that affects health-related quality of life (HRQoL) and encompasses a variety of symptoms, including psychological, physical, and behavioral symptoms. Some evidence suggests that an increase in body mass index (BMI) can reduce both HRQoL and menstrual quality. This is because the body fat tissue can affect menstrual cycles by changing the estrogen/progesterone ratio. This study investigated the impact of two diets alternate-day modified fasting (ADMF) and daily calorie restriction (DCR) - on PMS syndrome and HRQoL. Methods: The study was a randomized controlled, open-label trial that lasted for 8 weeks and involved 60 obese/overweight women. Participants were recruited from the Health Service Centers of Kashan University of Medical Sciences using simple random sampling. The study compared the impact of the ADMF and DCR diets on HRQoL and PMS symptoms. Patients were classified based on their BMI and age and then allocated to either the intervention (ADMF) or control (DCR) group using a random numbers table. The study measured HRQoL, PMS severity, weight, BMI, body fat mass, waist circumference, fat-free mass, and skeletal muscle mass before and after the study. The study had an almost 18% dropout rate. Results: Significant improvements were observed in mood lability (p = 0.044) and expressed anger (p < 0.001) in relation to PMS symptoms. However, no significant differences were detected in the changes of other COPE subscales. The ADMF diet had a significant impact on the 12-item Short-Form Health Survey (SF-12) total score (p < 0.001) and physical function subscales (p = 0.006) as well as mental health (p < 0.001) when compared to the control diet. This implies that the ADMF diet increased both SF-12 total score and its subscales. The intervention led to improvements in HRQoL, physical function, and mental health. Additionally, significant improvements in BMI and weight were observed between the two groups pre- and post-study (p < 0.001). Anthropometric data, including body fat mass and waist circumference, showed a significant improvement (p < 0.001 and p = 0.029, respectively) before and after the study. However, there were no significant changes in fat-free mass (p = 0.936) and skeletal muscle mass (p = 0.841) between the two groups. Conclusion: The study suggested that ADMF can improve HRQoL, mood lability, and expressed anger. It also showed that ADMF can reduce waist circumference, weight, and body fat mass in obese/overweight women. Clinical trial registration: The Iranian Registry of Clinical Trials (IRCT20220522054958N1).

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.

Food security, mental health, and socioeconomic status: A cross-sectional study among medical college students in central part of Iran, Kashan.

BACKGROUND AND AIMS: Food security is a complex and multidimensional issue that has been recognized as a serious public health problem all over the world for the past two decades. The present study was designed and conducted to determine the prevalence of food insecurity among college students at the Kashan University of Medical Sciences and some related factors including socioeconomic and mental health determinants. METHODS: The present study is a cross-sectional study conducted on 358 students who were currently studying at the Kashan University of Medical Sciences. The students who were pregnant or had a special diet to follow were excluded. Samples were selected by the systematic method. Food security was measured using United States Department of Agriculture. Food Frequency Questionnaire, 21-items Depression Anxiety Stress Scales, and Socioeconomic Questionnaire were used to investigate the nutrients intake, depression/anxiety status, and socioeconomic factors, respectively. Chi-square, independent t-test, and logistic regression were used to analyze the data. RESULTS: Based on the findings of the present study, 16.8% of students experienced different levels of food insecurity, and 83.2% of participants were categorized as food secure. Gender, financial assistance, health insurance, depression, and students' occupation are associated with food insecurity (P < .05). Additionally, the results of the logistic regression analysis showed that depression (OR 1.04; 95% CI 1.01-1.07), and students' jobs (OR 0.43; 95% CI 0.23-0.80) have the greatest impact on students' food insecurity. CONCLUSION: The findings of the present study show that economic factors and gender have a significant impact on students' food security. Moreover, the association of food insecurity with mental disorders such as depression was demonstrated in the current study. However, we could not detect any significant association between daily energy intake and macronutrients which indicates the requirement for more detailed studies.

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.

The hypotensive effect of salt substitutes in stage 2 hypertension: a systematic review and meta-analysis.

BACKGROUND: Hypertension (HTN) is a ubiquitous risk factor for numerous non-communicable diseases, including cardiovascular disease and stroke. There are currently no wholly effective pharmacological therapies for subjects with HTN. However, salt substitutes have emerged as a potential therapy for the treatment of HTN. The aim of the present study was to assess the effect of salt substitutes on reducing systolic blood pressure (SBP) and diastolic BP (DBP), following a meta-analysis of randomized controlled trials. METHODS: Studies were found via systematic searches of the Pubmed/Medline, Scopus, Ovid, Google Scholar and Cochrane library. Ten studies, comprised of 11 trials and 1119 participants, were included in the meta-analysis. RESULTS: Pooled weighted mean differences showed significant reductions of SBP (WMD - 8.87 mmHg; 95% CI - 11.19, - 6.55, p < 0.001) and DBP (WMD - 4.04 mmHg; 95% CI - 5.70, - 2.39) with no statistically significant heterogeneity between the 11 included comparisons of SBPs and DBPs. The stratified analysis of trials based on the mean age of participants showed a significant reduction in the mean difference of SBP in both adults (< 65 years old) and elderly (≥65 years old). However, the DBP-lowering effect of salt substitutes was only observed in adult patients (WMD - 4.22 mmHg; 95% CI - 7.85, - 0.58), but not in the elderly subjects. CONCLUSIONS: These findings suggest that salt-substitution strategies could be used for lowering SBP and DBP in patients with stage 2 HTN; providing a nutritional platform for the treatment, amelioration, and prevention of HTN.

The effect of psyllium supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/AIMS: Global incidence of hypertension is estimated to be, in excess of, one billion people, and given the efficacy of soluble dietary fibers, in particular, Psyllium, to positively impact blood pressure in patients with hypertension, it is of clinical importance that consensus on its supplementation be established. Therefore, the aim of the study was systematically review and meta-analyze the effect of psyllium supplementation on blood pressure of hypertensive patients in randomized controlled trials. METHODS: We searched six universal databases including; Pubmed/Medline, Ovid, Cochrane Library, Google Scholar, Embase, and Scopus until November 2018. Both combined and stratified analyzes were conducted. A fixed-effects or random- effects model was used to assess the mean effect sizes. RESULTS: An eventual 11 trials with 592 participants were considered as eligible for inclusion in the present meta-analysis. The meta-analysis revealed a significant reduction of 2.04 mmHg in systolic blood pressure (weighted mean difference, -2.04; 95% confidence interval, -2.82 to -1.63; p < 0.001). Whilst meta-regression highlighted that the hypotensive effect of psyllium was stronger in subjects with higher baseline blood pressure. CONCLUSION: Given the overarching benefits and lack of reported side effects, particularly for hypertensive patients, health care providers and clinicians should consider the use of psyllium supplementation for the treatment or abatement of hypertension, or hypertensive symptoms.

Effect of Lactobacillusplantarum containing probiotics on blood pressure: A systematic review and meta-analysis.

Previous studies have recommended that probiotics may have blood pressure (BP)-lowering effects. However, they examined all probiotic strains (multi/single probiotics) simultaneously. In respect to strain specificity properties of probiotic, the aim of the present study was to systematically investigate the role of Lactobacillus plantarum as an anti-hypertensive agent by performing a meta-analysis of randomized controlled trials. PubMed, Scopus, Cochrane Library and Google Scholar were used from inception until October 2018 to identify eligible trials. We used random-effects model as the preferable method to assess the combined treatment effect. We further conducted sensitivity analysis and stratified analysis. Seven studies with 653 participants were included in the meta-analysis. The pooled weighted mean difference (WMD) with the random effects model showed a significant effects of Lactobacillus plantarum supplementation on improvement of SBP with no statistically significant heterogeneity (WMD: -1.58 mmHg, 95 % CI: -3.05 to 0.11) (heterogeneity P = 0.14; I² = 36 %). The overall effect in the DBP showed significant pooled estimates (WMD: -0.92 mmHg, 95 % CI: -1.49 to -0.35) with a complete homogeneity between the studies (heterogeneity P = 0.46; I² = 0 %). The findings of the present meta-analysis study support the use of Lactobacillus plantarum supplementation for lowering systolic and diastolic blood pressure. The clinical significance of blood pressure-lowering effect of Lactobacillus Plantarum supplementation is not considerable; however, given the overarching benefits evident and concurrent lack of specific side effects, further trials are warranted to clarify the effects of Lactobacillus Plantarum probiotics particularly for hypertensive patients.

Cocoa Consumption and Blood Pressure in Middle-Aged and Elderly Subjects: a Meta-Analysis.

PURPOSE OF REVIEW: The effect of cocoa consumption on blood pressure (BP) has been investigated in previous studies; however, to date, no meta-analysis has been conducted specific to middle-aged and elderly subjects. Thus, the aim of the present study was to evaluate the effect of cocoa consumption on indices of blood pressure, in middle-aged and elderly subjects. RECENT FINDINGS: Pubmed/Medline™, Cochrane Library™, Google Scholar™, and Scopus™ were searched until March 2019. The quantitative Jadad scale was used as the systematic assessment of bias in the included trials. We used a random effects model to estimate the pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs). We further conducted sensitivity analysis and stratified analysis by baseline blood pressure, follow-up duration, and mean age. Thirteen studies with 758 total participants were included in the present meta-analysis. A significant reduction in SBP by 2.77 (95% CI - 5.28, - 0.27, P = 0.03, I2 = 89%) and DBP by 1.47 mm/Hg (- 95% CI - 2.40, - 0.55, P = 0.001, I2 = 45%) were observed after cocoa consumption. Stratified analyses showed BP-lowering effects of cocoa consumption in longer-term duration and hypertensive subgroups. Our meta-analysis showed a significant inverse association between cocoa consumption and SBP/DBP. However, the analysis could not conclude any beneficial effect of cocoa consumption on blood pressure in normotensive/elevated blood pressure subjects. Therefore, further studies are warranted to affirm the efficacy of cocoa consumption for the improvement of blood pressure in elderly subjects.

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.

N-3 fatty acids as preventive and therapeutic agents in attenuating PCOS complications.

To our knowledge, in spite of several trials exploring the beneficial effect of n-3 polyunsaturated fatty acids (PUFA) on polycystic ovary syndrome (PCOS), no comprehensive evidence has investigated the effects of n-3 PUFA consumption on PCOS complications. Therefore, our aim was to conduct a review to investigate the possible effect and related mechanisms. A comprehensive systematic search was conducted in Embase, MEDLINE/PubMed, Google Scholar, and SCOPUS, to identify studies investigating n-3 fatty acids as a preventative or therapeutic agent for the attenuation of PCOS complications. Subsequently, the impact of omega-3 on PCOS, omega-3 and inflammation, omega-3 and insulin resistance, omega-3 and adipokines, omega-3 and lipid metabolism, omega-3 and endothelial function and omega-3 and hormonal factors were discussed. There are multiple mechanisms by which n-3 PUFAs may exert their beneficial effects on PCOS, including anti-obesity, glycemic and hormonal hemostasis, anti-inflammatory, regulation of adipokine production and enhancement of endothelial function. N-3 PUFAs are a promising agent in relieving complications associated with PCOS. Although most of the studies in patients with PCOS reported an improvement in most complications after administration of omega-3 supplements, there is a distinct dearth of studies investigating the dietary intake of these types of fatty acids. Moreover, favorable effects regarding the improvement of dyslipidemia, regulation of adipokines, regulation of hormonal factors and enhancement of endothelial function are limited. Therefore, more trials are warranted to investigate palatable mechanisms for clarifying the metabolic and hormonal effects of these agents in PCOS.