Effects of crocin on inflammatory biomarkers and mental health status in patients with multiple sclerosis: A randomized, double-blinded clinical trial.

BACKGROUND: Multiple sclerosis (MS), as a demyelinating disease correlated with inflammation and oxidative stress, affects the central nervous system and causes a wide range of complications, including psychiatric disorders. Considering the anti-inflammatory and antioxidant properties associated with the bioactive components of saffron, such as crocin (trans-crocetin bis(ß-d-gentiobiosyl) ester), and their potential impact on ameliorating psychiatric symptoms, our study aimed to investigate the effect of crocin on biomarkers of inflammation, oxidative stress, and mental health, e.g., depression and anxiety in individuals with MS. METHOD: Patients with MS were randomized into two groups, taking either 15 mg crocin tablets twice a day (n = 25; 30 mg/day) or placebo tablets (n = 25) for 8 weeks. The valid and reliable Beck depression and anxiety scale questionnaire was recorded, and fasting blood samples were collected to measure biomarkers, including high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and nitric oxide (NO) at baseline and week 8 following the intervention. RESULTS: The data analysis using ANCOVA showed that supplementation with crocin for 8 weeks significantly lowered hs-CRP levels (p-value= 0.01). In addition, within-group comparisons showed crocin significantly decreased anxiety (p-value= 0.01). However, crocin did not affect serum MDA and NO after 8 weeks of intervention. CONCLUSION: Our findings suggest that crocin may keep promise in attenuating inflammation, evidenced by reducing hs-CRP in patients with MS. However, supplementation for 8 weeks may not be sufficient to improve mental health, and future clinical studies with higher sample sizes and various doses and durations are recommended.

Iranian specialists' approach to treatment escalation in multiple sclerosis patients with cognitive impairment.

Background: People with multiple sclerosis (MS) and their physicians recognize cognitive retention as an important desired outcome of disease-modifying therapies (DMTs). In this study, we attempted to gather the opinions of Iranian MS experts regarding the treatment approach toward clinical cases with different physical and cognitive conditions. Methods: Opinions of 20 MS specialists regarding the best approach to 6 case scenarios (with different clinical, cognitive, and imaging characteristics) were gathered via a form. Results: The estimated kappa of 0.16 [95% confidence interval (CI): 0.159-0.163; P < 0.001] suggested a poor degree of agreement on the treatment choice among the professionals. Conclusion: Although most specialists agreed with treatment escalation in cases with cognitive impairment, there was no general agreement. Furthermore, there was not enough clinical evidence in the literature to develop consensus guidelines on the matter.

Iranian specialists' approach to surgery in patients with multiple sclerosis.

Background: Data on perioperative risk stratification in patients with multiple sclerosis (MS) are limited. In this regard, the present study was conducted to investigate Iranian specialists' approach to surgical counseling for patients with MS (PwMS). Methods: 21 MS specialists were asked about 11 case scenarios with different MS disease statuses, disease-modifying therapies (DMTs), and urgency of the operation. The reasons for refusing surgery or factors that have to be considered before surgery were studied. Results: Overall, Fleiss Kappa was estimated to be 0.091 [95% confidence interval (CI): 0.090-0.093, P < 0.001] indicating a very poor level of agreement among responders. Conclusion: PwMS face surgery for various reasons. Risk assessment of surgery, the effect of various drugs such as anesthetics and DMT on patients, as well as many other aspects of MS are issues challenging the practitioners. Clarifying the various dimensions of these issues requires further research.

Prevalence of hallucinations in Parkinson's patients: meta-analysis of International studies.

BACKGROUND: Parkinson's disease (PD) is one of the common causes of disability in the elderly. This study aims to estimate the prevalence of hallucinations in Parkinson's patients in the world. METHODS: A systematic review of PubMed/Medline, ISI Web of Knowledge, and Google Scholar was conducted from 2017 to 2022. This study investigated the prevalence of hallucinations in Parkinson's patients. Point prevalence was analyzed with a 95% confidence interval. The variances of each study were calculated using the binomial distribution formula The researcher used Cochrane Q-test with a significance level of less than 0.1 to check the heterogeneity between studies and the change index assigned to heterogeneity I2. Due to the heterogeneity between the studies, the random effects model was used to combine the results of the studies. All statistical analyses were performed by STATA version 14 software using meta-analysis commands. RESULTS: Reports indicated that the prevalence of hallucinations in Parkinson's patients in 32 studies was 28% (0.22-0.34 = 95%CI). The highest prevalence was 34% and 95% CI = 0.07- 0.61 in developing countries and 27% with CI = 0.33-0.21 in developed countries. Reports showed the prevalence in men was 30% (CI = 0.22-0.38) and in women 23% (95% CI = 0.14-0.31). CONCLUSIONS: Considering the relatively high prevalence of hallucinations in these patients, checking up for the presence of hallucinations on every visit of Parkinson's patients is recommended, and providing appropriate treatment for that is necessary.

The effects of spirulina intake on clinical and metabolic parameters in Alzheimer's disease: A randomized, double-blind, controlled trial.

The current study aimed to determine the effects of spirulina intake on cognitive function and metabolic status among patients with Alzheimer's disease (AD). This randomized, double-blind, controlled clinical trial was done among 60 subjects with AD. Patients were randomly assigned to receive either 500 mg/day spirulina or a placebo (each n = 30) twice a day for 12 weeks. Mini-mental state examination score (MMSE) was recorded in all patients before and after intervention. Blood samples were obtained at baseline and after 12 weeks' intervention to determine metabolic markers. Compared with placebo, spirulina intake resulted in a significant improvement in MMSE score (spirulina group: +0.30 ± 0.99 vs. Placebo group: -0.38 ± 1.06, respectively, p = 0.01). In addition, spirulina intake decreased high-sensitivity C-reactive protein (hs-CRP) (spirulina group: -0.17 ± 0.29 vs. Placebo group: +0.05 ± 0.27 mg/L, p = 0.006), fasting glucose (spirulina group: -4.56 ± 7.93 vs. Placebo group: +0.80 ± 2.95 mg/dL, p = 0.002), insulin (spirulina group: -0.37 ± 0.62 vs. Placebo group: +0.12 ± 0.40 µIU/mL, p = 0.001) and insulin resistance (spirulina group: -0.08 ± 0.13 vs. Placebo group: 0.03 ± 0.08, p = 0.001), and increased insulin sensitivity (spirulina group: +0.003 ± 0.005 vs. Placebo group: -0.001 ± 0.003, p = 0.003) compared with the placebo. Overall, our study showed that spirulina intake for 12 weeks in patients with AD improved cognitive function, glucose homeostasis parameters, and hs-CRP levels.

Correlation of Serum Levels of Interleukine-16, CCL27, Tumor Necrosis Factor-related Apoptosis-inducing Ligand, and B-cell Activating Factor with Multiple Sclerosis Severity.

The pathogenic roles of Interleukine-16 (IL-16), CCL27, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and B-cell activating factor (BAFF) has been shown in some autoimmune and inflammatory diseases. We aimed to correlate the circulatory changes of such factors with the severity of disease in patients with multiple sclerosis (MS). This case-control study was conducted on 84 MS patients and 83 healthy controls. We measured the serum levels of IL-16, CCL27, TRAIL, and BAFF in all participants by enzyme-linked immune sorbent assay. Using the expanded disability status scale (EDSS), we evaluated the severity of MS. Finally, we assessed the correlation between serum levels of such factors with the severity of MS. We found increased serum levels of CCL27, IL-16, and BAFF in patients with MS compared to those in healthy subjects. However, no difference was found in serum levels of TRAIL between the patients and controls. In addition, a significant positive correlation between serum levels of CCL27, IL-16, TRAIL, and BAFF with disease severity according to EDSS score was determined. We showed higher serum levels of CCL27, BAFF, TRAIL, and IL-16 in MS patients with more severe disabilities than mild forms. Such finding may represent their contribution to the pathogenesis of MS. Blocking such molecules may yield new treatments for MS.

Development of clinical-guideline-based mobile application and its effect on head CT scan utilization in neurology and neurosurgery departments.

BACKGROUND: There is little evidence regarding the adoption and intention of using mobile apps by health care professionals (HCP) and the effectiveness of using mobile apps among physicians is still unclear. To address this challenge, the current study seeks two objectives: developing and implementing a head CT scan appropriateness criteria mobile app (HAC app), and investigating the effect of HAC app on CT scan order. METHODS: A one arm intervention quasi experimental study with before/after analysis was conducted in neurology & neurosurgery (N&N) departments at the academic hospital. We recruited all residents' encounters to N&N departments with head CT scan to examine the effect of HAC app on residents' CT scan utilization. The main outcome measure was CT scan order per patient for seven months at three points, before the intervention, during the intervention, after cessation of the intervention -post-intervention follow-up. Data for CT scan utilization were collected by reviewing medical records and then analyzed using descriptive statistics, Kruskal-Wallis, and Mann-Whitney tests. A focus group discussion with residents was performed to review and digest residents' experiences during interaction with the HAC app. RESULTS: Sixteen residents participated in this study; a total of 415 N&N encounters with CT scan order, pre-intervention 127 (30.6%), intervention phase 187 (45.1%), and 101 (24.3%) in the post-intervention follow-up phase were included in this study. Although total CT scan utilization was statistically significant during three-time points of the study (P = 0.027), no significant differences were found for CT utilization after cessation of the intervention (P = 1). CONCLUSION: The effect of mobile devices on residents' CT scan ordering behavior remains open to debate since the changes were not long-lasting. Further studies based on real interactive experiences with mobile devices is advisable before it can be recommended for widespread use by HCP.

Probiotics and the Treatment of Parkinson's Disease: An Update.

Parkinson's disease (PD) is a progressive neurological disorder characterized by motor and non-motor features. Although some progress has been made in conventional PD treatments, these breakthroughs have yet to show high efficacy in treating this neurodegenerative disease. Probiotics are live microorganisms that confer health benefits on the host when administered in adequate amounts. Probiotics have putative anticancer, antioxidative, anti-inflammatory, and neuroprotective effects. Multiple lines of evidence show that probiotics control and improve several motor and non-motor symptoms in patients and experimental animal models of PD. Probiotic supplementation mediates these pharmacological effects by targeting a variety of cellular and molecular processes, i.e., oxidative stress, inflammatory and anti-inflammatory pathways, as well as apoptosis. Herein, we summarize the effects of probiotics on motor and non-motor symptoms as well as various cellular and molecular pathways in PD.

Neurofilament light chain as a biomarker for diagnosis of multiple sclerosis.

The treatments for multiple sclerosis (MS) have improved over the past 25 years, but now the main question for physicians is deciding who should receive treatment, for how long, and when to switch to other options. These decisions are typically based on treatment tolerance and a reasonable expectation of long-term efficacy. A significant unmet need is the lack of accurate laboratory measurements for diagnosis, and monitoring of treatment response, including deterioration and disease progression. There are few validated biomarkers for MS, and in practice, physicians employ two biomarkers discovered fifty years ago for MS diagnosis, often in combination with MRI scans. These biomarkers are intrathecal IgG and oligoclonal bands in the CSF (cerebrospinal fluid). Neurofilament light chain (NfL) is a relatively new biomarker for MS diagnosis and follow up. Neurofilaments are neuron-specific cytoskeleton proteins that can be measured in various body compartments. NfL is a new biomarker for MS that can be measured in serum samples, but this still needs further study to specify the laboratory cut-off values in clinical practice. In the present review we discuss the evidence for NfL as a reliable biomarker for the early detection and management of MS. Moreover, we highlight the correlation between MRI and NfL, and ask whether they can be combined.

Prevalence of Suicidal Ideation in Multiple Sclerosis Patients: Meta-Analysis of International Studies.

The aim of this study is to estimate the worldwide prevalence of suicidal ideation in multiple sclerosis patients. Two researchers selected words such as "epidemiology" or "prevalence" or "incidence" and "suicidal ideation in multiple sclerosis" and searched them as relevant keywords in international databases such as PubMed, Web of Science CINAHL, Embase, Psyc INFO, and Scopus. A point prevalence with 95% confidence interval was estimated. The variances of each study were calculated using the binomial distribution formula. Heterogeneity among the studies was tested by a Q-Cochran test with a significance level less than 0.1. Index of changes attributed to heterogeneity (I2) was assessed. From among the 170 total articles found from 2011 to February 2019, we pooled and analyzed the data of eight final eligible studies, based on the inclusion criteria. The prevalence of suicidal ideation in multiple sclerosis patients was estimated as 13% (CI 95% = 0.09-0.17). A subgroup analysis was conducted based on the type of countries; it revealed that prevalence is higher in developed countries (15%; CI 95% = 0.1-0.2). Pooled worldwide prevalence of suicidal ideation in the MS population was calculated at 13% by random effect. It is recommended that training, counseling, and psychological support be used to help these patients.

Melatonin supplementation and the effects on clinical and metabolic status in Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was performed to evaluate the impact of melatonin supplementation on clinical and metabolic profiles in people with Parkinson's disease (PD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted among 60 patients with PD. Participants were randomly divided into two groups to intake either 10 mg melatonin (two melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day, 1 h before bedtime for 12 weeks. RESULTS: Melatonin supplementation significantly reduced the Unified Parkinson's Disease Rating Scale (UPDRS) part I score (ß -2.33; 95% CI, -3.57, -1.09; P < 0.001), Pittsburgh Sleep Quality Index (PSQI) (ß -1.82; 95% CI, -3.36, -0.27; P = 0.02), Beck Depression Inventory (BDI) (ß -3.32; 95% CI, -5.23, -1.41; P = 0.001) and Beck Anxiety Inventory (BAI) (ß -2.22; 95% CI, -3.84, -0.60; P = 0.008) compared with the placebo treatment. Compared with the placebo, melatonin supplementation resulted in a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (ß -0.94 mg/L; 95% CI, -1.55, -0.32; P = 0.003) and a significant elevation in plasma total antioxidant capacity (TAC) (ß 108.09 mmol/L; 95% CI, 78.21, 137.97; P < 0.001) and total glutathione (GSH) levels (ß 77.08 µmol/L; 95% CI, 44.29, 109.86; P < 0.001). Additionally, consuming melatonin significantly decreased serum insulin levels (ß -1.79 µIU/mL; 95% CI, -3.12, -0.46; P = 0.009), homeostasis model of assessment-insulin resistance (HOMA-IR) (ß -0.47; 95% CI, -0.80, -0.13; P = 0.007), total- (ß -13.16 mg/dL; 95% CI, -25.14, -1.17; P = 0.03) and LDL- (ß -10.44 mg/dL; 95% CI, -20.55, -0.34; P = 0.04) compared with the placebo. CONCLUSIONS: Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles.

The correlation of helios and neuropilin-1 frequencies with parkinson disease severity.

OBJECTIVES: Parkinson disease (PD), a neurodegenerative disease, has also some immunologic basis in which several regulatory factors, like Helios and Neuropilin-1 (NRP-1) may show some roles in its pathogenesis. We aimed to evaluate the circulatory frequency of T regulatory cells (Tregs) expressing Helios and NRP-1 in PD. PATIENTS AND METHODS: In this case-control study, 83 patients with PD and 83 healthy controls were enrolled. The diagnosis of PD was accomplished in accordance with clinical diagnostic criteria of the UK Parkinson Disease Society Brain Bank. The modified Hoehn and Yahr (H and Y) were used to measure the severity of PD. Flow cytometry was used to evaluate the circulatory frequency of CD4+CD25+Foxp3+Tregs expressing and Helios and NRP-1 in all participants. Also, correlation of H and Y with such frequencies was evaluated. RESULTS: Our findings showed that frequency of CD4+CD25+Foxp3+Tregs expressing NRP-1 (P = 0.04) and Helios (P = 0.01) in patients with PD was significantly higher than those in healthy subjects. The frequency of Tregs expressing Helios and NRP-1 showed a negative correlation with H and Y criteria and disease duration. Multiple linear regression analysis indicated that the severity of PD is the only effective factor on the frequency of CD4+CD25+Foxp3+NRP-1+Tregs (P = 0.012) and CD4+CD25+FoxP3+ Helios + Tregs (P = 0.038). CONCLUSION: Our study showed that the increased frequency of Tregs expressing Helios and NRP-1 is associated with the severity of PD.

Melatonin and Parkinson Disease: Current Status and Future Perspectives for Molecular Mechanisms.

Parkinson disease (PD) is a chronic and neurodegenerative disease with motor and nonmotor symptoms. Multiple pathways are involved in the pathophysiology of PD, including apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and changes in the neurotransmitters. Preclinical and clinical studies have shown that melatonin supplementation is an appropriate therapy for PD. Administration of melatonin leads to inhibition of some pathways related to apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and dopamine loss in PD. In addition, melatonin improves some nonmotor symptom in patients with PD. Limited studies, however, have evaluated the role of melatonin on molecular mechanisms and clinical symptoms in PD. This review summarizes what is known regarding the impact of melatonin on PD in preclinical and clinical studies.

The investigation of relevancy between PIAS1 and PIAS2 gene expression and disease severity of multiple sclerosis.

Introduction: PIAS1 and PIAS2 (protein inhibitor of activated STAT 1,2) play key roles in the pathogenesis of autoimmune and inflammatory diseases. This study aims to evaluate the gene expression of these factors in multiple sclerosis (MS) patients compared to healthy individuals and correlate them with the severity of MS. Materials and methods: Sixty participants, including 30 patients with MS and 30 healthy controls were studied. The expression of PIAS1 and PIAS2 genes in peripheral blood samples of all participants was measured by real-time PCR. The severity of MS was evaluated using the Expanded Disability Status Scale (EDSS). Finally, we evaluated the correlation between the expression of PIAS1 and PIAS2 genes with disease severity. Results: The expression of PIAS1 gene was increased in patients with MS compared to healthy subjects (P value<.001). Also, there was a significant correlation between the expression of PIAS1 and PIAS2 genes with disease severity according to EDSS. Conclusion: Our study suggests the expression of PIAS1 and PIAS2 genes as a prognostic and diagnostic marker in MS disease.

Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer's disease: A randomized, double-blind, controlled trial.

BACKGROUND AND AIMS: Combined probiotic and selenium supplementation may improve Alzheimer's disease (AD) by correcting metabolic abnormalities, and attenuating inflammation and oxidative stress. This study aimed to determine the effects of probiotic and selenium co-supplementation on cognitive function and metabolic status among patients with AD. METHODS: This randomized, double-blind, controlled clinical trial was conducted among 79 patients with AD. Patients were randomly assigned to receive either selenium (200 µg/day) plus probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum (2 × 109 CFU/day each) (n = 27), selenium (200 µg/day) (n = 26) or placebo (n = 26) for 12 weeks. RESULTS: Selenium supplementation, compared with the placebo, significantly reduced serum high sensitivity C-reactive protein (hs-CRP) (P < 0.001), insulin (P = 0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (P = 0.002), LDL-cholesterol (P = 0.04) and total-/HDL-cholesterol ratio (P = 0.004), and significantly increased total glutathione (GSH) (P = 0.001) and the quantitative insulin sensitivity check index (QUICKI) (P = 0.01). Compared with only selenium and placebo, probiotic and selenium co-supplementation resulted in a significant increase in mini-mental state examination score (+1.5 ± 1.3 vs. +0.5 ± 1.2 and -0.2 ± 1.1, respectively, P < 0.001). Probiotic plus selenium intake resulted in a significant reduction in hs-CRP (-1.6 ± 1.4 vs. -0.8 ± 1.0 and +0.1 ± 0.5 mg/L, respectively, P < 0.001), and a significant increase in total antioxidant capacity (+89.4 ± 129.6 vs. +20.0 ± 62.5 and -0.7 ± 27.2 mmol/L, respectively, P = 0.001) and GSH (+122.8 ± 136.5 vs. +102.2 ± 135.2 and +1.5 ± 53.2 µmol/L, respectively, P = 0.001) compared with only selenium and placebo. In addition, subjects who received probiotic plus selenium supplements had significantly lower insulin levels (-2.1 ± 2.5 vs. -1.0 ± 1.3 and +0.7 ± 2.0 µIU/mL, respectively, P < 0.001), HOMA-IR (-0.5 ± 0.6 vs. -0.2 ± 0.3 and +0.1 ± 0.4, respectively, P < 0.001), and higher QUICKI (+0.01 ± 0.01 vs. +0.005 ± 0.007 and -0.002 ± 0.01, respectively, P < 0.006) compared with only selenium and placebo. Additionally, probiotic and selenium co-supplementation resulted in a significant reduction in serum triglycerides (-17.9 ± 26.1 vs. -3.5 ± 33.9 and +0.3 ± 9.3 mg/dL, respectively, P = 0.02), VLDL- (-3.6 ± 5.2 vs. -0.7 ± 6.8 and +0.05 ± 1.8 mg/dL, respectively, P = 0.02), LDL- (-8.8 ± 17.8 vs. -8.1 ± 19.2 and +2.7 ± 19.0 mg/dL, respectively, P = 0.04) and total-/HDL-cholesterol (-0.3 ± 0.7 vs. -0.4 ± 0.9 and +0.3 ± 0.6, respectively, P = 0.005) compared with only selenium and placebo. CONCLUSIONS: Overall, we found that probiotic and selenium co-supplementation for 12 weeks to patients with AD improved cognitive function and some metabolic profiles. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT20170612034497N5).

Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: The investigation was done to assess the impacts of probiotic supplementation on movement and metabolic parameters in individuals with Parkinson's disease (PD). METHODS: The study is randomized, double-blind, placebo-controlled clinical trial, which was done in sixty people with PD. Individuals were randomly divided into two groups in order to take either 8 × 109 CFU/day probiotic or placebo (n = 30 each group) that lasted 12 weeks. The Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was recorded at pre- and post-intervention. RESULTS: Compared with the placebo, consuming probiotic decreased MDS-UPDRS (-4.8 ± 12.5 vs. +3.8 ± 13.0, P = 0.01). Probiotic supplementation also reduced high-sensitivity C-reactive protein (-1.6 ± 2.5 vs. +0.1 ± 0.3 mg/L, P < 0.001) and malondialdehyde (-0.2 ± 0.3 vs. +0.1 ± 0.3 µmol/L, P = 0.006), and enhanced glutathione levels (+40.1 ± 81.5 vs. -12.1 ± 41.7 µmol/L, P = 0.03) in comparison with the placebo. Additionally, probiotic consumption resulted in a statistically significant reduction in insulin levels (-2.1 ± 3.4 vs. +1.5 ± 5.1 µIU/mL, P = 0.002) and insulin resistance (-0.5 ± 0.9 vs. +0.4 ± 1.2, P = 0.002), and a statistically significant rise in insulin sensitivity (+0.01 ± 0.02 vs. -0.006 ± 0.02, P = 0.01) in comparison with the placebo. Probiotic intake had no any significant impact on other metabolic profiles. CONCLUSIONS: Our study evidenced that 12 weeks of probiotic consumption by individuals with PD had useful impacts on MDS-UPDRS and few metabolic profiles. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017082434497N4.

The Effects of Curcumin on Glycemic Control and Lipid Profiles Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Metaanalysis of Randomized Controlled Trials.

BACKGROUND: This systematic review and meta-analysis of randomized controlled trials (RCTs), were performed to determine the effects of curcumin intake on glycemic control and lipid profiles among patients with metabolic syndrome (MetS) and related disorders. METHODS: We searched the following databases up until January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and evaluated for quality of the studies in accordance with the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (MDs) with 95% confidence intervals (95% CI). RESULTS: Twenty-six trials with 1890 participants were included in the current meta-analysis. The findings demonstrated the significant association between curcumin intake and reduced fasting glucose levels (SMD -0.78; 95% CI, -1.20, -0.37; P<0.001), homeostasis model of assessment-estimated insulin resistance (SMD -0.91; 95% CI, -1.52, -0.31; P=0.003) and HbA1c (SMD -0.92; 95% CI, -1.37, -0.47; P<0.001). In addition, curcumin supplementation was significantly associated with triglyceride (SMD -1.21; 95 % CI, -1.78, -0.65; P<0.001) and total cholesterol reduction (SMD -0.73; 95 % CI, -1.32, -0.13; P= 0.01). However, curcumin intake significantly increased insulin levels (SMD 0.92; 95% CI, 0.06, 1.78; P=0.036). We found no significant effect of curcumin supplementation on LDL- (SMD -0.52; 95% CI, -1.14, 0.11; P=0.10) and HDL-cholesterol levels (SMD 0.28; 95% CI, -0.22, 0.77; P=0.27). CONCLUSION: Overall, curcumin consumption was associated with a significant reduction in fasting glucose, HOMA-IR, HbA1c, triglycerides and total cholesterol levels among patients with MetS and related disorders, but did not affect LDL- and HDL-cholesterol levels.

Correlation of serum levels and gene expression of tumor necrosis factor-α-induced protein-8 like-2 with Parkinson disease severity.

Different immune-mediated mechanisms involved in the pathogenesis of Parkinson disease (PD) as a neurodegenerative and inflammatory disease. According to our knowledge, there is no report evaluating Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2), a cytokine maintaining immune homeostasis, in PD. We analyzed the correlation of the serum levels and circulatory gene expression of TIPE2 with severity of PD. In this case-control study, 43 patients with PD and 40 healthy subjects were enrolled. The diagnosis of PD was performed byclinical diagnostic criteria of the UK Parkinson's Disease Society Brain Bank. The severity of PD was evaluated by modified Hoehn and Yahr (H and Y) scale. Serum levels and gene expression of TIPE2 were assessed by Elisa and real time PCR, respectively. The mean serum levels and gene expression of TIPE2 in patients with PD did not have significant difference compared to healthy subjects. Linear multiple regression analysis showed that increased serum levels of TIPE2 are positively related to age and severity of PD (P ≤ 0.0001). In addition, the gene expression of TIPE2 was found to be associated with age (P < 0.0001). Our study showed that the serum levels of TIPE2 and its gene expression might be important prognostic biomarkers of PD.

High-dose ω-3 Fatty Acid Plus Vitamin D3 Supplementation Affects Clinical Symptoms and Metabolic Status of Patients with Multiple Sclerosis: A Randomized Controlled Clinical Trial.

Background: Combined omega-3 fatty acid and vitamin D supplementation may improve multiple sclerosis (MS) by correcting metabolic abnormalities and attenuating oxidative stress and inflammation. Objective: This study aimed to determine the effects of ω-3 fatty acid and vitamin D cosupplementation on the disability score and metabolic status of patients with MS. Methods: This was a randomized, placebo-controlled clinical trial with Expanded Disability Status Scale (EDSS) score and inflammation as primary outcomes and oxidative stress biomarkers and metabolic profile as secondary outcomes. Patients, aged 18-55 y, were matched for disease EDSS scores, gender, medications, BMI, and age (n = 53) and randomly received a combined 2 × 1000 mg/d ω-3 fatty acid and 50,000 IU/biweekly cholecalciferol supplement or placebo for 12 wk. The placebos were matched in colour, shape, size, packaging, smell, and taste with supplements. Fasting blood samples were collected at baseline and end of intervention to measure different outcomes. Multiple linear regression models were used to assess treatment effects on outcomes adjusting for confounding variables. Results: Patients taking ω-3 fatty acid plus vitamin D supplements showed a significant improvement in EDSS (ß -0.18; 95% CI: -0.33, -0.04; P = 0.01), compared with placebo. Serum high-sensitivity C-reactive protein (ß -1.70 mg/L; 95% CI: -2.49, -0.90 mg/L; P < 0.001), plasma total antioxidant capacity (ß +55.4 mmol/L; 95% CI: 9.2, 101.6 mmol/L; P = 0.02), total glutathione (ß +51.14 µmol/L; 95% CI: 14.42, 87.87 µmol/L; P = 0.007), and malondialdehyde concentrations (ß -0.86 µmol/L; 95% CI: -1.10, -0.63 µmol/L; P < 0.001) were significantly improved in the supplemented group compared with the placebo group. In addition, ω-3 fatty acid and vitamin D cosupplementation resulted in a significant reduction in serum insulin, insulin resistance, and total/HDL-cholesterol, and a significant increase in insulin sensitivity and serum HDL-cholesterol concentrations. Conclusion: Overall, taking ω-3 fatty acid and vitamin D supplements for 12 wk by patients with MS had beneficial effects on EDSS and metabolic status. This trial was registered at the Iranian website (www.irct.ir) for registration of clinical trials as IRCT2017090133941N20.