Serum lipids and cognitive outcomes in multiple sclerosis; a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment is highly prevalent in multiple sclerosis (MS) with poorly understood underlying mechanisms. Lipids are considered to be associated with MS progression through the inflammatory and oxidative stress pathways, brain atrophy, cellular signaling, and tissue physiology. In addition, serum lipids are proposed as a modifiable factor affecting the neuropsychiatric condition; therefore, this study aims to assess the association between serum lipid levels and cognitive outcomes in MS. METHODS: This study was carried out following the PRISMA 2020 statement. A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase in March 2023, and the Joanna Briggs Institute (JBI)'s critical appraisal tools were utilized for risk of bias (RoB) assessments in the included studies. The quantitative synthesis was performed with the comprehensive meta-analysis (CMA3) software. RESULTS: Out of 508 screened records, 7 studies were eventually found to meet our inclusion criteria. In two studies, the course of MS in the sample of the study was only Relapsing-Remitting MS (RRMS), whereas the other five studies' sample was a combination of different phenotypes. Studies utilized different scales such as Minimal Assessment of Cognitive Function in MS (MACFIMS), Brief International Cognitive Assessment for MS (BICAMS), Montreal Cognitive Assessment (MoCA), Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for cognitive evaluations. Dealing with possible confounders such as age, disease duration and level of disability was the most common possible source of bias in the included studies. One study revealed an inverse relationship between serum levels of apolipoproteins (including ApoA-I, ApoB, and ApoB/ApoA-I) and Symbol Digit Modalities Test (SDMT) scores. Also, a correlation between 24S-hydroxycholesterol (24OHC) serum concentrations and SDMT score was reported in one study. The association between serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) and different aspects of cognitive function was reported in the studies; however, serum levels of high-density lipoprotein cholesterol (HDL) were not found to be associated. The quantitative synthesis revealed a significant correlation between TC and the MoCA scores (r =-0.238; 95 %CI: -0.366 to -0.100; p-value = 0.001); however, the correlation between TG levels and MoCA were not statistically significant (r:-0.070; 95 %CI: -0.209 to 0.072; p-value: 0.334). In addition, the mata-analyses were not associated with significant findings regarding the correlation between lipid profiles (including HDL, LDL, TG, and TC) and other cognitive assessment scales including SDMT, Brief Visuospatial Memory Test (BVMT), and California Verbal Learning Test (CVLT) (p-values>0.05). DISCUSSION: Available evidence suggested a link between TC and LDL with cognitive outcomes of MS patients which was not evident in our quantitative synthesis. The limited number of studies, high RoB, different cognitive assessment scales and reporting methods, and the cross-sectional design of the included studies, were the main limitations that alleviate the clinical significance of the findings of this study and suggested further investigations on this topic. FUNDING AND REGISTRATION: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71,909). This study is registered in the international prospective register of systematic reviews (PROSPERO ID: CRD42023441625).

The effect of Oenothera biennis (Evening primrose) oil on inflammatory diseases: a systematic review of clinical trials.

BACKGROUND: Evening primrose oil (EPO), extracted from the seeds of Oenothera biennis, has gained attention for its therapeutic effects in various inflammatory conditions. METHOD: We performed a systematic search in multiple databases and defined the inclusion criteria based on the following PICOs: P: Patients with a form of inflammatory condition, I: EPO, C: Placebo or other therapeutic interventions, O: changes in inflammatory markers or patients' symptoms; S: randomized controlled trials. The quality of the RCTs was evaluated using Cochrane's RoB tool. RESULTS: Several conditions were investigated in the literature. In rheumatoid arthritis, mixed results were observed, with some studies reporting significant improvements in symptoms while others found no significant impact. EPO showed some results in diabetes mellitus, atopic eczema, menopausal hot flashes, and mastalgia. However, it did not demonstrate effectiveness in chronic hand dermatitis, tardive dyskinesia, psoriatic arthritis, cystic fibrosis, hepatitis B, premenstrual syndrome, contact lens-associated dry eyes, acne vulgaris, breast cyst, pre-eclampsia, psoriasis, or primary Sjogren's syndrome. Some results were reported from multiple sclerosis after EPO consumption. Studies in healthy volunteers indicated no significant effect of EPO on epidermal atrophy, nevertheless, positive effects on the skin regarding hydration and barrier function were achieved. CONCLUSION: Some evidence regarding the potential benefits of EPO in inflammatory disorders were reported however caution is due to the limitations of the current survey. Overall, contemporary literature is highly heterogeneous and fails to provide strong recommendations regarding the efficacy of EPO on inflammatory disorders. Further high-quality studies are necessitated to draw more definite conclusions and establish O. biennis oil effectiveness as an assuring treatment option in alleviating inflammatory conditions.

The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies.

Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD.

Glycemic control and associated factors among type 2 diabetes mellitus patients: a cross-sectional study of Azar cohort population.

BACKGROUND: Despite the growing prevalence of diabetes and its complications, there is a dearth of data regarding factors associated with glycemic control. Therefore, in this cross-sectional study, we aimed to identify factors influencing glycemic control in patients with type 2 diabetes mellitus (T2DM) in the Iranian population. METHODS: This cross-sectional study was conducted among the Azar cohort population and the glycemic control status of patients with T2DM was investigated. Possible risk factors including age, sex, marital status, educational level, smoking status, sleep duration, family history of diabetes and hypertension, socioeconomic status, physical activity level, and co-existence of other chronic diseases and their relationship with glycemic control status were also assessed. Multivariate logistic regression analysis was used to identify determinants of glycemic control. RESULTS: Among 1,710 T2DM patients (60.2% female), the overall prevalence of poor glycemic control was 56.8%. In the unadjusted logistic regression analysis model, a low wealth score index significantly increased the risk of poor glycemic control (OR: 1.49;1.10-2.02). Variables significantly associated with poor glycemic control even after adjusting for confounding factors were first-degree family history of diabetes (OR: 1.34; 1.08-1.65), and sleep duration (OR: 1.29 ;1.02-1.62 for 6.6-8 h/d; OR:1.42;1.10-1.88 for > 8 h/d). Interestingly, we found that the co-existence of ≥ 3 chronic diseases with diabetes decreased the risk of poor glycemic control. CONCLUSIONS: In the current study, most of the patients with T2DM had uncontrolled glycemic control. Due to the individual and social costs of diabetes complications, it is necessary to suggest tailored and effective interventions for controlling blood glucose levels in people with diabetes.

Shining a Light on Selenium: a Meta-analysis of Supplementation in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system. Selenium is a trace element with significant antioxidant activity. This study aimed to seek evidence concerning selenium supplementation in MS. A systematic search was performed on PubMed, Web of Science, Scopus, and Embase databases to identify the studies assessing the consumption rate, efficacy, and safety of selenium and selenium-containing supplementations in MS patients. The meta-analysis was performed using the Comprehensive Meta-Analysis and the risk of bias was evaluated using the Joanna Briggs Institute's critical appraisal tools. A total of 9 studies were included, which consisted of six studies regarding the rate of selenium supplement consumption in MS patients, with a total sample size of 2381 patients. Based on the quantitative synthesis, 14.3% (95% CI, 12.8-16.0%; I2, 3.58%) of MS patients had current selenium supplements usage, and 11.3% (95% CI, 7.6-16.6%; I2, 81.40%) of patients had used selenium supplements previously. Although there is no evidence regarding supplementation with selenium alone, three RCT studies reported the safety of selenium-containing supplementation use in MS with improved inflammation and oxidative stress conditions. The findings of this study show that over 10% of patients with MS used selenium supplements, with no clinical significance supporting the benefits. There is a lack of evidence regarding the safety and efficacy of selenium supplements in MS patients. Due to the limited number of included studies and the lack of comprehensive and specific studies regarding selenium supplements in MS, the results must be interpreted with caution, and future clinical trials are required.

Obesity from a sign of being rich to a disease of the new age: A historical review.

Background and Objective: Obesity has historically been seen as a sign of wealth and social privilege, as can be inferred from studying the ancient works. We aimed to report the causes, diagnostic approaches, and treatment among the authentic books of traditional Iranian medicine. Methods: We searched the original versions of historical books and used a narrative approach to report the history of obesity. Results: Obesity was often seen as an indicator of complete health. Obesity in healthy women was a requirement for beauty, based on descriptions of women from the Zoroaster period and from antiquity to the late Qajar period. This point of view existed during various ages. However, after the constitutional period, the view of obesity changed into that of an illness, due to modern ideas and offshore role models, especially during the Pahlavi era. This change led to serious attempts to treat obesity. Obesity is a critical problem that needs immediate attention to prevent substantial health consequences. Different medical paradigms have presented their criteria and foundations throughout history. The emphasis of Iranian alternative medicine was on prevention and the maintenance of health, with the next step being treatment. Prevention, treatment, consuming medicinal plants, and recovery have often been written about in the traditional books of medicine. Conclusions: Throughout the traditional Iranian medical texts, physicians have made recommendations about maintaining an appropriate body weight. The best treatment was prevention and a healthy lifestyle. The treatments for controlling and restricting obesity included paying attention to nourishment, mobility, and even the habitat.

Berberine-induced glucagon-like peptide-1 and its mechanism for controlling type 2 diabetes mellitus: a comprehensive pathway review.

Introduction: A growing number of studies have thus far showed the association between type 2 diabetes mellitus (DM) and the intestinal microbiome homoeostasis. As reported, the gut microflora can be significantly different in patients with type 2 DM (T2DM) compared to those in healthy individuals.Methods: The authors collected the relevant articles published until 2022 and these are carefully selected from three scientific databases based on keywords.Discussion: This review highlights research on the anti-diabetic properties of berberine (BBR)-induced glucagon-like peptide-1 (GLP-1), as a glucose-lowering factor and a balance regulator in the microbial flora of the intestines, which plays an important role in adjusting the signalling pathways affecting insulin secretion.Results: Considering the anti-diabetic characteristics of the BBR-induced GLP-1, BBR makes a promising complementary treatment for reducing the clinical symptoms of DM by reducing the hyperglycaemia. Berberin might be a safe and effective drug for T2DM with little or no adverse effects.HighlightsBerberine induces GLP-1 insulin secretion by PLC2 pathway in the intestinalBerberine-induced GLP-1 decreases mitochondrial stress and relocates cytochrome c out of the mitochondria.Berberine induces GLP-1 secretion in the intestine by altering the bacterial profile, thus could possibly lighten diabetes symptomsBerberine-induced SCFA production, SCFA causes GLP-1 secretion from the intestinal L-Cell.Preventing mitochondrial damage, reducing adipose tissue fat, and reducing oxidative stress are thus among the results of BBR-induced GLP-1.The lower costs of BBR, and its limited side effects and higher availability, make it a promising supplementary medicine for DM.

Lipid Profile as a Predictive Marker for Organ Dysfunction after Thoracoabdominal Surgery: A Cross-sectional Study.

Background: Plasma total cholesterol is considered a negative acute phase reactant. In various pathological conditions, such as trauma, sepsis, burns, and liver dysfunction, as well as post-surgery, serum cholesterol level decreases. This study aimed to investigate the role of lipid profiles in determining the probability of organ dysfunction after surgery. Methods: This cross-sectional study included patients who underwent thoracoabdominal surgery and were admitted to the intensive care unit of Imam Reza Hospital in Tabriz, Iran, between October 2016 and September 2018. During the first two days of admission, blood samples were taken, and serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and albumin were measured. The relation between the changes in these laboratory markers and six organ functions including cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic, length of stay in the hospital and intensive care unit, mechanical ventilation duration, and vasopressor use were investigated. The independent t test was used to compare continuous variables. The association between different variables and organ dysfunction and mortality was evaluated by using logistic regression. Results: The serum TC increased the risk of mortality (OR=1.09, 95%CI=1.06-1.11, P<0.001), renal dysfunction (OR=1.09, 95%CI=1.06-1.12; P<0.001), liver dysfunction (OR=1.07, 95%CI=1.03-1.10; P<0.001), respiratory dysfunction (OR=1.08, 95%CI=1.05-1.13; P<0.001). Moreover, LDL, HDL, and TG were found to be inversely related to mortality, organ dysfunction, length of stay in the hospital and intensive care unit, mechanical ventilation duration, and vasopressor use. Conclusion: TC could be considered a risk factor for mortality, organ dysfunction, and clinical outcomes. On the other hand, LDL, HDL, and TG played a protective role in the patients' mortality, organ dysfunction, and clinical outcomes.

Association between cannabis use and risk of diabetes mellitus type 2: A systematic review and meta-analysis.

BACKGROUND: Cannabis consumption exerts multiple effects on metabolism via various pathways, including glucose regulation and insulin secretion. Studies concerning the association between cannabis use and diabetes mellitus type 2 are discrepant. OBJECTIVE: This study was conducted to evaluate the association between cannabis use and type 2 diabetes mellitus (T2DM). SEARCH METHODS: We searched PubMed, Scopus, Embase, Proquest, Web of Science, and Cochrane Library with no time, language or study types restriction until July 1, 2022, using various forms of "cannabis" and "diabetes mellitus" search terms. SELECTION CRITERIA: Randomized control trials, cohort, and case-control studies investigating the relationship between cannabis consumption and diabetes mellitus type 2 were included. DATA COLLECTION AND ANALYSIS: The Newcastle-Ottawa scale was used to assess the quality of studies. We pooled odds ratio (OR) with 95% confidence interval (CI) using the random-effects model, generic inverse variance method, DerSimonian and Laird approach. MAIN RESULTS: A meta-analysis of seven studies, containing 11 surveys and 4 cohorts, revealed that the odds of developing T2DM in individuals exposed to cannabis was 0.48 times (95% CI: 0.39 to 0.59) lower than in those without cannabis exposure. CONCLUSIONS: A protective effect of cannabis consumption on the odds of diabetes mellitus type 2 development has been suggested. Yet given the considerable interstudy heterogeneity, the upward trend of cannabis consumption and cannabis legalization is recommended to conduct studies with higher levels of evidence.

Clinical efficacy and safety of melatonin supplementation in multiple sclerosis: a systematic review.

BACKGROUND: Melatonin is a neurohormone secreted predominantly by the pineal gland that is demonstrated to be associated with the pathogenesis of multiple sclerosis (MS). This research desires to evaluate the tolerability and beneficial effects of exogenous melatonin supplementations in patients with MS. METHODS: This study was executed following the PRISMA 2020 statement. Both observational and interventional studies which reported the clinical effectiveness and/or safety of melatonin supplementation in patients with MS were included in this systematic review. Ovid, PubMed, Scopus, Embase, and Web of Science databases were searched and the risk of bias in included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools based on study design. RESULTS: Out of 1304 results of database searches, finally, 14 articles, including 7 randomized controlled trials (RCTs), 6 case-control studies, and one quasi-experimental study, were included based on the full-text review. Included phenotypes of MS were mostly relapsing-remitting MS (RRMS) (in 11 studies); it was secondary progressive MS (SPMS) in only one study, and two other studies had a mixture of the different phenotypes. The course of treatment with melatonin supplementation was between 2 weeks and 12 months. There were no substantial safety issues. Although melatonin was associated with enhanced oxidative stress and inflammation status, concerning the clinical benefits, limited studies suggested improvements in sleep conditions, cognitive outcomes, and fatigue in MS. DISCUSSION: There are insufficient data to support the regular melatonin prescription in MS. Limitations such as the small number of included studies, the diversity of the dosage, route, and duration of melatonin administration, and the diversity of assessment tests lead to unconvincing findings in this study. There is a need for future studies to achieve a comprehensive judgment on this subject.

A comprehensive insight into the molecular and cellular mechanisms of action of resveratrol on complications of sepsis a systematic review.

Sepsis and septic shock are still one of the most important medical challenges. Sepsis is an extreme and uncontrolled response of the innate immune system to invading pathogenesis. Resveratrol (3,5,4'-trihydroxytrans-stilbene), is a phenolic and non-flavonoid compound naturally produced by some plants and fruits. The object of the current study is to systematically review the impacts of resveratrol and its mechanisms of function in the management of sepsis and its related complications. The guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements were applied to perform the study (PROSPERO: CRD42021289357). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords. Study criteria were met by 72 out of 1415 articles screened. The results of this systematic review depict that resveratrol can reduces the complications of sepsis by affecting inflammatory pathways, oxidative stress, and modulating immune responses. Future human randomized clinical trials are necessary due to the promising therapeutic effects of resveratrol on sepsis complications and the lack of clinical trials in this regard.

Is early age at menarche associated with multimorbidity? Findings from the Azar Cohort study.

AIMS: This study aimed to assess the association of age at menarche (AAM) with multimorbidity and chronic diseases. METHODS: We used data regarding the reproductive history of 8,294 female participants of the Azar Cohort Study. A questionnaire assessed the participants' demographic information, reproductive history, personal behaviors, smoking status, socioeconomic status, activity status, and wealth score index. RESULTS: Among 8,286 women included in the analysis, the AAM was < 12 years (early) in 648 (7.8%), 12-14 years (normal) in 4,911 (59.3%), and > 14 years (late) in 2,727 (32.9%) individuals. Early menarche was associated with a high risk of diabetes, obesity, and high WHR. On the other hand, late menarche was associated with higher rates of hypertension, stroke, and diabetes but a lower risk of MM, rheumatoid disease, obesity, abdominal obesity, and WHtR. CONCLUSION: Changes in AAM have significant health implications. Factors predisposing individuals to early menarche and its consequences should be considered in chronic disease prevention strategies for adolescents and young adults.

The association of parity number with multimorbidity and polypharmacy among Iranian women in the Azarcohort: a cross-sectional study.

OBJECTIVE: We aimed to study the association of parity number with multimorbidity (MM) and polypharmacy among women in the Azar cohort population. PATIENTS & METHODS: This cross-sectional investigation was based on data from the Azar Cohort Study. Information regarding demographics, personal habits, physical activity level, medical and reproductive history, and anthropometric measurements of 8,290 females (35-70 years) were evaluated. Ordinal logistic and logistic regression analyses were conducted to assess for associations of parity number with multimorbidity (MM), polypharmacy, chronic disease, and abdominal obesity. RESULTS: More educated participants and people in the fifth quintile of the Wealth Score Index were less likely to have a higher parity number. With increasing parity numbers, the prevalence of MM, polypharmacy, hypertension, cardiovascular disease, fatty liver disease, stroke, rheumatoid diseases, chronic obstructive pulmonary disease, and cancers tended to rise. Moreover, we found that increasing parity numbers (especially when ≥ 5) enhanced the odds of abdominal obesity, waist-to-hip ratio ≥ 0.85, and waist-to-height ratio ≥ 0.5; these significant associations were more obvious in parity numbers ≥ 9 and WHtR ≥ 0.5. CONCLUSION: The parity number is associated with MM and polypharmacy in Iranian women enrolled in the Azar Cohort Study. Further studies exploring the pathways (biological, social, and environmental) underlying these relationships will provide clues for preventing morbidity and premature mortality among susceptible andhighly parous women.

Association between leukocyte telomere length and COVID-19 severity.

Background: Inter-individual variations in the clinical manifestations of SARS-CoV-2 infection are among the challenging features of COVID-19. The known role of telomeres in cell proliferation and immune competency highlights their possible function in infectious diseases. Variability in telomere length is an invaluable parameter in the heterogeneity of the clinical presentation of diseases. Result: In this study, our aim was to investigate the possible association between leukocyte telomere length (LTL) and COVID-19 severity. LTL was measured in 100 patients with moderate and severe forms of COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong inverse correlation between relative LTL and COVID-19 severity. Conclusions: These findings suggest that LTL can be a useful parameter for predicting disease severity in patients, as individuals with short telomeres may have a higher risk of developing severe COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1186/s43042-023-00415-z.

Prognostic values of modified NUTRIC score to assess outcomes in critically ill patients admitted to the intensive care units: prospective observational study.

PURPOSE: Modified Nutrition Risk in the Critically Ill (NUTRIC) score (mNUTRIC score) have been validated as screening tool for quantifying risk of adverse outcome critically ill patients admitted to the intensive care units (ICUs). The aim of this study was to evaluate the prognostic value of mNUTRIC score to assess outcomes in this population. MATERIALS AND METHODS: This prospective, observational study was conducted on adult patients admitted to the general ICUs of two university affiliated hospital in northwest of Iran. The association between the mNUTRIC score and outcomes was assessed using the univariate and multivariate binary logistic regression. The performance of mNUTRIC score to predict outcomes was assessed using the receiver operating characteristic (ROC)-curve. RESULTS: In total 445 ICU patients were enrolled. Based on mNUTRIC score, 62 (13.9%) and 383 (86.1%) individuals were identified at high and low nutritional risk, respectively. The area under the curve (AUC) for predicting ICU mortality, using vasopressor, duration of vasopressor, and mechanical ventilation (MV) duration were (AUC: 0.973, 95% CI: 0.954-0.986, P < 0.001), (AUC: 0.807, 95% CI: 0.767-0.843, P < 0.001), (AUC: 0.726, 95% CI: 0.680-0.769, P < 0.001) and (AUC: 0.710, 95% CI: 0.666-0.752, P < 0.001), respectively. CONCLUSIONS: An excellent and good predictive performance of the mNUTRIC score was found regarding ICU mortality and using vasopressor, respectively. However, this predictive was fair for MV and vasopressor duration and poor for ICU and hospital length of stay.

Taurine in Septic Critically Ill Patients: Plasma versus Blood.

Purpose: Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body's antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. Methods: In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. Results: Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (P<0.001). There was not a significant correlation between the blood and plasma taurine levels in control and septic patients. In addition, there was not any correlation between the severity of the disease, organ failure, mortality, and plasma as well as the blood concentration of taurine. Conclusion: In septic patients, taurine concentration in plasma and blood are low and high, respectively. These concentrations are not linked to each other and not associated with the patients' outcome, and the disease severity, and organ failure.

Metformin: new applications for an old drug.

Metformin is a biguanide, evolved as one of the most widely used medicines. The applications of this component include but are not limited to reducing blood glucose, weight loss, and polycystic ovary syndrome. Studies about other probable indications have emerged, indicating that this agent can also be utilized for other purposes. In this review, applications of metformin are noticed based on the current evidence. Metformin commonly is used as an off-label drug in non-alcoholic fatty liver disease (NAFLD), but it worsens inflammation and should not be used for this purpose, according to the latest research. Metformin decreased the risk of death in patients with liver cirrhosis. It is an effective agent in the prevention and improvement of survival in patients suffering hepatocellular carcinoma. There is evidence of the beneficial effects of metformin in colorectal cancer, early-stage prostate cancer, breast cancer, urothelial cancer, blood cancer, melanoma, and bone cancer, suggesting metformin as a potent anti-tumor agent. Metformin shows neuroprotective effects and provides a potential therapeutic benefit for mild cognitive impairment and Alzheimer's disease (AD). It also has been shown to improve mental function and reduce the incidence of dementia. Another condition that metformin has been shown to slow the progression of is Duchenne muscular dystrophy. Regarding infectious diseases, tuberculosis (TB) and coronavirus disease (COVID-19) are among the conditions suggested to be affected by metformin. The beneficial effects of metformin in cardiovascular diseases were also reported in the literature. Concerning renal function, studies showed that daily oral administration of metformin could ameliorate kidney fibrosis and normalize kidney structure and function. This study reviewed the clinical and preclinical evidence about the possible benefits of metformin based on recent studies. Numerous questions like whether these probable indications of metformin can be observed in non-diabetics, need to be described by future basic experiments and clinical studies.

An umbrella review of systematic reviews with meta-analysis on the role of vitamins in Parkinson's disease.

INTRODUCTION: This umbrella review aimed to systematically review the available literature and assess the association of dietary intake or serum levels of different vitamins and the risk of PD, to help find out more efficient treatments for PD patients by replenishing the deficiency of vitamins. METHODS: Pubmed/Medline, Scopus, Google Scholar and hand searching bibliographies of retrieved articles in duplicate, were used to detect all relevant meta-analyses investigating the relationship between vitamins and PD. After study selection, data were extracted from previously published meta-analyses and pooled by Review Manager version 5.4 and CMA software version 2.2.064 to achieve effect sizes. Level of statistical significance was set at P ≤ 0.05. RESULTS: 14 meta-analyses were included in the meta-review. Serum vitamin D and B12 levels were significantly lower in PD (SMD = -0.67 and SMD = -0.40 respectively). Homocysteine (Hcy) levels were significantly higher in PD patients (SMD = 1.26). Also the odds ratio for highest vs. lowest vitamin E intake was 0.73 which was significant. However, there was no significant difference between vitamin A, C and B6 intake or serum levels in PD vs. control groups. CONCLUSION: Serum vitamin D and B12 levels were significantly lower in PD in comparison to healthy individuals, while Hcy level was significantly higher in PD patients. Also higher vitamin E intake was associated with significantly lower risk of development of PD in comparison to lower vitamin E intake. However, there was no significant difference between risk of PD and higher vitamin A, C and B6 intake or serum levels of folate.

Saffron as a promising therapy for diabetes and Alzheimer's disease: mechanistic insights.

The prevalence of both Alzheimer's disease (AD) and diabetes mellitus is increasing with the societies' aging and has become an essential social concern worldwide. Accumulation of amyloid plaques and neurofibrillary tangles (NFTs) of tau proteins in the brain are hallmarks of AD. Diabetes is an underlying risk factor for AD. Insulin resistance has been proposed to be involved in amyloid-beta (Aß) aggregation in the brain. It seems that diabetic conditions can result in AD pathology by setting off a cascade of processes, including inflammation, mitochondrial dysfunction, and ROS and advanced glycation end products (AGEs) synthesis. Due to the several side effects of chemical drugs and their high cost, using herbal medicine has recently attracted attention for the treatment of diabetes and AD. Saffron and its active ingredients have been used for its anti-inflammatory, anti-oxidant, anti-diabetic, and anti-AD properties. Therefore, in the present review paper, we take account of the clinical, in vivo and in vitro evidence regarding the anti-diabetic and anti-AD effects of saffron and discuss the preventive or postponing properties of saffron or its components on AD development via its anti-diabetic effects.

Effects of Probiotics Supplementation on CRP, IL-6, and Length of ICU Stay in Traumatic Brain Injuries and Multiple Trauma Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Method: This meta-analysis aims to evaluate the effectiveness of probiotics in reducing inflammatory biomarkers and the length of intensive care unit (ICU) stays. PubMed-Medline, SCOPUS, Embase, and Google Scholar databases up to July 2021 were searched. The meta-analysis was carried out using random-effect analysis. To determine the sources of heterogeneity, subgroup analyses were performed. In case of the presence of publication bias, trim and fill analysis was carried out. The Cochrane Collaboration tool was used for checking the quality assessment. We hypothesized that probiotics would improve inflammatory markers (CRP and IL-6) and the length of ICU stay in traumatic brain injury and multiple trauma patients. Results: The present meta-analysis, which includes a total of seven studies, showed that there were no significant effects of probiotics supplementation on interleukin (IL)-6 (Hedges's g = -2.46 pg/ml; 95% CI: -12.16, 7.25; P=0.39), C-reactive protein (CRP) (Hedges's g = -1.10 mg/L; 95% CI: -2.27, 0.06; P=0.06), and the length of staying in ICU. The overall number of RCTs included in the analysis and the total sample size were insufficient to make firm conclusions. Conclusion: As a result, more carefully designed RCTs are needed to investigate the effect of probiotics on inflammatory biomarkers and the length of ICU stay in traumatic brain injuries and multiple trauma patients in greater detail.