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.

Can Berberine Serve as a New Therapy for Parkinson's Disease?

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurodegeneration and deposition of alpha-synuclein. Mechanisms associated with PD etiology include oxidative stress, apoptosis, autophagy, and abnormalities in neurotransmission, to name a few. Drugs used to treat PD have shown significant limitations in their efficacy. Therefore, recent focus has been placed on the potential of active plant ingredients as alternative, complementary, and efficient treatments. Berberine is an isoquinoline alkaloid that has shown promise as a pharmacological treatment in PD, given its ability to modulate several molecular pathway associated with the disease. Here, we review contemporary knowledge supporting the need to further characterize berberine as a potential treatment for PD.

An Update on the Effects of Probiotics on Gastrointestinal Cancers.

Because of their increasing prevalence, gastrointestinal (GI) cancers are regarded as an important global health challenge. Microorganisms residing in the human GI tract, termed gut microbiota, encompass a large number of living organisms. The role of the gut in the regulation of the gut-mediated immune responses, metabolism, absorption of micro- and macro-nutrients and essential vitamins, and short-chain fatty acid production, and resistance to pathogens has been extensively investigated. In the past few decades, it has been shown that microbiota imbalance is associated with the susceptibility to various chronic disorders, such as obesity, irritable bowel syndrome, inflammatory bowel disease, asthma, rheumatoid arthritis, psychiatric disorders, and various types of cancer. Emerging evidence has shown that oral administration of various strains of probiotics can protect against cancer development. Furthermore, clinical investigations suggest that probiotic administration in cancer patients decreases the incidence of postoperative inflammation. The present review addresses the efficacy and underlying mechanisms of action of probiotics against GI cancers. The safety of the most commercial probiotic strains has been confirmed, and therefore these strains can be used as adjuvant or neo-adjuvant treatments for cancer prevention and improving the efficacy of therapeutic strategies. Nevertheless, well-designed clinical studies are still needed for a better understanding of the properties and mechanisms of action of probiotic strains in mitigating GI cancer development.

Neuroprotective effects of probiotics bacteria on animal model of Parkinson's disease induced by 6-hydroxydopamine: A behavioral, biochemical, and histological study.

Parkinson's disease (PD) is an age-associated, progressive, and common neurodegenerative disorder. It is characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. The involvement of oxidative stress, inflammation, and dysbiosis in PD has been confirmed and probiotics also have the ability to regulate the mentioned mechanisms. Here, we assessed probiotics supplementation effects on experimental model of PD. Thirty Male Wistar rats were divided into three groups for a 14-day treatment. It was shown that a mixture of probiotics containing Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum could improve rotational behavior, cognitive function, lipid peroxidation, and neuronal damage in the group received probiotic supplementation compared to the other groups (P < 0001, P < .001, and P = .026, respectively). Taken together, these findings revealed that probiotics supplementation could be an appropriate complementary treatment for PD.

Therapeutic Potential of Berberine in the Treatment of Glioma: Insights into Its Regulatory Mechanisms.

Glioma is known as one of the most common primary intracranial tumors accounting for four-fifths of malignant brain tumors. There are several biological pathways that play a synergistic, pathophysiological role in glioma, including apoptosis, autophagy, oxidative stress, and cell cycle arrest. According to previous rese arches, the drugs used in the treatment of glioma have been associated with significant limitations. Therefore, improved and/or new therapeutic platforms are required. In this regard, multiple flavonoids and alkaloids have been extensively studied in the treatment of glioma. Berberine is a protoberberine alkaloid with wide range of pharmacological activities, applicable to various pathological conditions. Few studies have reported beneficial roles of berberine in glioma. Berberine exerts its pharmacological functions in glioma by controlling different molecular and cellular pathways. We reviewed the existing knowledge supporting the use of berberine in the treatment of glioma and its effects on molecular and cellular mechanisms.

Effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome (MetS) and related disorders. METHODS: Databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central library were searched until January 31th, 2019. RESULTS: 14 effect sizes from 12 studies were identified eligible to be included in current meta-analysis. Flaxseed supplementation resulted in a significant reduction in interleukin 6 (IL-6) (WMD: -0.22; 95% CI: -0.43, -0.01) and malondialdehyde (MDA) (WMD: -0.17; 95% CI: -0.31, -0.03) and a significant increase in total antioxidant capacity (TAC) levels (WMD: 137.25; 95% CI: 68.04, 206.47). Flaxseed oil supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSIONS: Overall, this meta-analysis demonstrated flaxseed oil supplementation decreased IL-6 and MDA levels, and increased TAC, but did not affect other biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. This suggests that flaxseed oil supplementation may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders.

A systematic review and meta-analysis: The effects of probiotic supplementation on metabolic profile in patients with neurological disorders.

BACKGROUND AND OBJECTIVE: The objective of meta-analysis of randomized controlled trials (RCTs) was to evaluate the effects of probiotic supplementation on metabolic status in patients with neurological disorders. METHODS: The following databases were search up to April 2019: Pubmed, Scopus, Google scholar, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95 % Confidence Intervals (95 % CI). RESULTS: Nine studies were included in this meta-analysis. The findings suggested that probiotic supplementation resulted in a significant reduction in C-reactive protein (CRP) [Weighted Mean Difference (WMD): -1.06; 95 % CI: -1.80, -0.32] and malondialdehyde (MDA) levels (WMD: -0.32; 95 % CI: -0.46, -0.18). Supplementation with probiotics also significantly reduced insulin (WMD: -3.02; 95 % CI: -3.88, -2.15) and homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.71; 95 % CI: -0.89, -0.52). Probiotics significantly reduced triglycerides (WMD: -18.38; 95 % CI: -25.50, -11.26) and VLDL-cholesterol (WMD: -3.16; 95 % CI: -4.53, -1.79), while they increased HDL-cholesterol levels (WMD: 1.52; 95 % CI: 0.29, 2.75). CONCLUSION: This meta-analysis demonstrated that taking probiotic by patients with neurological disorders had beneficial effects on CRP, MDA, insulin, HOMA-IR, triglycerides, VLDL-cholesterol and HDL-cholesterol levels, but did not affect other metabolic parameters.

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 effects of resveratrol intake on weight loss: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of resveratrol intake on weight loss. We searched the following databases until July 2018: MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Out of 831 reports, 36 RCTs were eligible for including to our meta-analysis. The pooled results, using random-effects model showed that resveratrol supplementation significantly decreased body weight (SMD = -0.17; 95% CI, -0.33, -0.01; P = 0.03; I2: 62.6), body mass index (BMI) (SMD = -0.20; 95% CI, -0.35, -0.05; P = 0.01; I2: 60.6), fat mass (SMD = -0.32; 95% CI, -0.62, -0.03; P = 0.03; I2: 77.9) and waist circumference (WC) (SMD = -0.42; 95% CI, -0.68, -0.16; P = 0.001; I2: 75.2), and significantly increased lean mass (SMD = 1.21; 95% CI, 0.75, 1.67; P < 0.001; I2: 87.6). We found no significant effect of resveratrol administration on leptin (SMD = -0.20; 95% CI, -0.68, 0.27; P = 0.40; I2: 85.3) and adiponectin levels (SMD = 0.08; 95% CI, -0.39, 0.55; P = 0.74; I2: 91.0). Resveratrol supplementation significantly decreased body weight in obese patients (SMD -0.43; 95% CI, -0.60, -0.26) compared with other diseases (SMD 0.02; 95% CI, -0.29, 0.33), and type 2 diabetes mellitus (SMD -0.17; 95% CI, -0.37, 0.02). Overall, the current meta-analysis demonstrated that resveratrol intake significantly reduced weight, BMI, WC and fat mass, and significantly increased lean mass, but did not affect leptin and adiponectin levels.

The effects of quercetin supplementation on lipid profiles and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

Aims: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to determine the effect of quercetin administration on lipid profiles and inflammatory markers among patients with metabolic syndrome (MetS) and related disorders.Methods: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until November 2018. Q-test and I2 statistics were applied to assess heterogeneity among included studies. Data were combined using fixed- or random-effects model and presented as standardized mean difference (SMD) with 95% confidence interval (CI).Results: Out of 591 citations, 16 RCTs were included in the meta-analysis. The pooled findings showed that quercetin consumption significantly decreased total-cholesterol (SMD = -0.98; 95% CI, -1.48, -0.49; p < 0.001; I2: 94.0), LDL-cholesterol (SMD = -0.88; 95% CI, -1.35, -0.41; p < 0.001; I2: 92.7) and C-reactive protein (CRP) levels (-0.64; 95% CI, -1.03, -0.25; p = 0.001; I2: 90.2). While, quercetin supplementation did not significantly affect triglycerides (TG) (SMD = -0.32; 95% CI, -0.68, 0.04; p = 0.08; I2: 84.8), HDL-cholesterol (SMD = 0.20; 95% CI, -0.20, 0.24; p = 0.84; I2: 70.6), interleukin 6 (IL-6) (SMD = -0.69; 95% CI, -1.69, 0.31; p = 0.17; I2: 94.5) and tumor necrosis factor-alpha (TNF-α) levels (SMD = -0.06; 95% CI, -0.25, 0.14; p = 0.58; I2: 35.6)Conclusions: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced total-cholesterol, LDL-cholesterol, and CRP levels, yet did not affect triglycerides, HDL-cholesterol, IL-6 and TNF-α among patients with MetS and related disorders.

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 Therapeutic Potential of Quercetin in Parkinson's Disease: Insights into its Molecular and Cellular Regulation.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc). PD is a multifactorial disorder, with several different factors being suggested to play a synergistic pathophysiological role, including oxidative stress, autophagy, underlying pro-inflammatory events and neurotransmitters abnormalities. Overall, PD can be viewed as the product of a complex interaction of environmental factors acting on a given genetic background. The importance of this subject has gained more attention to discover novel therapies to prevent as well as treat PD. According to previous research, drugs used to treat PD have indicated significant limitations. Therefore, the role of flavonoids has been extensively studied in PD treatment. Quercetin, a plant flavonol from the flavonoid group, has been considered as a supplemental therapy for PD. Quercetin has pharmacological functions in PD by controlling different molecular pathways. Although few studies intended to evaluate the basis for the use of quercetin in the context of PD have been conducted so far, at present, there is very little evidence available addressing the underlying mechanisms of action. Various principal aspects of these treatment procedures remain unknown. Here, currently existing knowledge supporting the use of quercetin for the clinical management of PD has been reviewed.

Joint Application of Magnetic Resonance Imaging and Biochemical Biomarkers in Diagnosis of Multiple Sclerosis.

Multiple Sclerosis (MS), an autoimmune disorder associated with spinal cord and brain, chiefly affects the white matter. Regarding the complexity as well as heterogenic etiology of this disease, the treatment of MS has been a challenging issue up to now. Researchers are working to develop new therapeutic strategies and drugs as complementary therapies. MS diagnosis significantly depends on the findings of Magnetic Resonance Imaging (MRI) examination. In this imaging technique, gadolinium is used as a contrast agent to reveal active plaques intending to destroy the bloodbrain barrier. It also detects plaques that are not correlated with the neurological symptoms. It has been attempted to determine biomarkers related to different dimensions of MS in various organizational hierarchy levels of the human anatomy (i.e., cells, proteins, RNA, and DNA). These biomarkers are appropriate diagnostic tools for MS diagnosis. In this review, we summarized the application of MRI and biochemical biomarkers to monitor MS patients. Moreover, we highlighted the joint application of MRI and biomarkers for the diagnosis of MS subjects.

The effects of vitamin D supplementation on expanded disability status scale in people with multiple sclerosis: A critical, systematic review and metaanalysis of randomized controlled trials.

In this meta-analysis of randomized controlled trials (RCTs), the effects of vitamin D supplementation on the scores for the expanded disability status scale (EDSS) in people with multiple sclerosis (MS) are assessed. The following databases were search up to January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95% Confidence Intervals (95% CI). Six studies were included in this meta-analysis. The findings demonstrated that supplementation with vitamin D alone and vitamin D plus calcium did not affect the EDSS score (WMD -0.11 (-0.33, 0.11); P = 0.32). In addition, subgroup analysis showed that vitamin D supplementation alone, when compared to the use of a placebo, and vitamin D plus calcium supplementation compared with the control did not affect EDSS (WMD -0.13 (-0.30, 0.11); P = 0.29) and (WMD -0.08 (-0.57, 0.41); P = 0.29), respectively. Overall, this meta-analysis indicated that taking vitamin D in people with MS had no significant effect on EDSS.

The Effects of Resveratrol Supplementation on Endothelial Function and Blood Pressures Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: There are current trials investigating the effect of resveratrol supplementation on endothelial function and blood pressures among patients with metabolic syndrome (MetS); however, the findings are controversial. AIM: This systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to summarize the effects of resveratrol supplementation on endothelial activation and blood pressures among patients with MetS and related disorders. METHODS: We searched systematically online databases including: PubMed-Medline, Embase, ISI Web of Science and Cochrane Central Register of Controlled Trials until October, 2018. Two independent authors extracted data and assessed the quality of included articles. Data were pooled using the fixed- or random-effects model and considered as standardized mean difference (SMD) with 95% confidence intervals (95% CI). RESULTS: Out of 831 electronic citations, 28 RCTs (with 33 findings reported) were included in the meta-analyses. The findings showed that resveratrol intervention significantly increased flow-mediated dilatation (FMD) levels (SMD 1.77; 95% CI 0.25, 3.29; P = 0.02; I2: 96.5). However, resveratrol supplements did not affect systolic blood pressure (SBP) (SMD - 0.27; 95% CI - 0.57, 0.03; P = 0.07; I2: 88.9) and diastolic blood pressure (DBP) (SMD - 0.21; 95% CI - 0.52, 0.11; P = 0.19; I2: 89.8). CONCLUSIONS: Resveratrol supplementation significantly increased FMD among patients with MetS and related disorders, but did not affect SBP and DBP. Additional prospective studies are needed to investigate the effect of resveratrol supplementation on endothelial function and blood pressures, using higher-dose of resveratrol with longer durations.

The effects of acupuncture and electroacupuncture on Parkinson's disease: Current status and future perspectives for molecular mechanisms.

Among the progressive neurodegenerative disorders, Parkinson's disease (PD) is the second most common. Different factors have critical role in pathophysiology of PD such as apoptosis pathways, inflammatory cytokines, oxidative stress, and neurotransmitters and its receptors abnormalities. Acupuncture and electroacupuncture were considered as nondrug therapies for PD. Although numerous studies has been conducted for assessing the mechanism underlying electroacupuncture and acupuncture, various principal aspects of these treatment procedures remain not well-known. There have also been few investigations on the molecular mechanism of acupuncture and electroacupuncture therapy effects in PD. This review evaluates the effects of electroacupuncture and acupuncture on the molecular mechanism in PD.

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).

Melatonin, a calpain inhibitor in the central nervous system: Current status and future perspectives.

Dysregulation of neuronal Ca2+ and oxidative stress plays an important role in the activation of cysteine proteases including calpains and caspases that contribute to neuronal death. In neurodegenerative diseases, traumatic brain injury, stroke, and neuropathic pain calpain activities are markedly increased. Melatonin is a beneficial supplement in the treatment of central nervous system (CNS) disorders. Melatonin is a potent antioxidant and works as a free-radical scavenger to regulate a large number of molecular pathways, including oxidative stress, inflammation, apoptosis, and cell death under different pathological conditions. However, limited studies have evaluated the inhibitory effect of melatonin on calpains. This review summarizes the current knowledge related to the effects of melatonin on calpains in some of the common CNS disorders.

Melatonin and pancreatic cancer: Current knowledge and future perspectives.

Pancreatic cancer has a high mortality rate due to the absence of early symptoms and subsequent late diagnosis; additionally, pancreatic cancer has a high resistance to radio- and chemotherapy. Multiple inflammatory pathways are involved in the pathophysiology of pancreatic cancer. Melatonin an indoleamine produced in the pineal gland mediated and receptor-independent action is the pancreas and other where has both receptors. Melatonin is a potent antioxidant and tissue protector against inflammation and oxidative stress. In vivo and in vitro studies have shown that melatonin supplementation is an appropriate therapeutic approach for pancreatic cancer. Melatonin may be an effective apoptosis inducer in cancer cells through regulation of a large number of molecular pathways including oxidative stress, heat shock proteins, and vascular endothelial growth factor. Limited clinical studies, however, have evaluated the role of melatonin in pancreatic cancer. This review summarizes what is known regarding the effects of melatonin on pancreatic cancer and the mechanisms involved.

The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was conducted to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in subjects with Parkinson's disease (PD). PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed in 40 subjects with PD. Participants were randomly allocated into two groups to take either 1000 mg/day of omega-3 fatty acids from flaxseed oil plus 400 IU/day of vitamin E supplements or placebo (n = 20 each group) for 12 weeks. Gene expression related to inflammation, insulin and lipid were quantified in peripheral blood mononuclear cells (PBMC) of PD patients with RT-PCR method. RESULTS: After the 12-week intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.002) in PBMC of subjects with PD. In addition, omega-3 fatty acids and vitamin E co-supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03), and downregulated oxidized low-density lipoprotein receptor (LDLR) (P = 0.002) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on gene expression of interleukin-1 (IL-1) and IL-8 in PBMC of patients with PD. CONCLUSIONS: Overall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PD patients significantly improved gene expression of TNF-α, PPAR-γ and LDLR, but did not affect IL-1 and IL-8.