Effects of vitamin D supplementation on depression and some selected pro-inflammatory biomarkers: a double-blind randomized clinical trial.

BACKGROUND: Both augmented inflammatory reaction and low vitamin D status are associated with depression but the magnitude of their relationships is unclear. This study was, therefore, conducted to evaluate the effects of vitamin D supplementation on serum 25(OH)D concentration, depression severity and some pro-inflammatory biomarkers in patients with mild to moderate depression. METHODS: An 8-week double-blind randomized clinical trial (RCT) was performed on 56 (18-60 yrs) patients with mild to moderate depression, randomly assigned to intervention (50,000 IU cholecalciferol 2wks-1) and control (placebo) groups. Serum 25(OH)D, intact parathyroid hormone (iPTH), interlukin (IL)-1ß, IL-6, high-sensitivity C-reactive protein (hs-CRP) and depression severity (Beck Depression Inventory-II) (BDI-II)) were initially and finally assessed. RESULTS: At the end point, statistically significant changes were observed only in intervention group as compared with controls including increased 25(OH)D concentration (+ 40.83 ± 28.57 vs. + 5.14 ± 23.44 nmol L-1, P < 0.001) and decreased depression severity (-11.75 ± 6.40 vs. -3.61 ± 10.40, P = 0.003). No significant within- or between group differences were observed in serum IL-1ß, IL-6 and hs-CRP concentrations. CONCLUSION: Increased circulating 25(OH)D concentrations following 8-week vitamin D supplementation (50,000 IU 2wks-1) resulted in a significant decrease in BDI-II scores in patients with mild to moderate depression. However, this effect was independent of the serum concentrations of the studied inflammatory biomarkers. TRIAL REGISTRATION: The clinical trial registration code was obtained from the Iranian Registry of Clinical Trials (date of registration: 17/09/2018, registration number: IRCT20170926036425N1) and ClinicalTrials.gov (date of registration: 04/12/2018, registration number: NCT03766074).

The therapeutic effects of berberine plus sitagliptin in a rat model of fatty liver disease.

OBJECTIVES: Fatty liver disease (FLD) is a disorder related to accumulation of excess fat within the hepatocytes. In this study, the effects of Berberine, a natural compound, and Sitagliptin as a DPP-4 inhibitor, were observed in a rat model of FLD. MATERIALS AND METHODS: Forty male rats were divided into five groups (n=6) including the control group (normal food and water), high-fat group (high-fat diet (HF) for 6 weeks), Berberine group (HF with oral administration of Berberine at 150 mg/kg for 6 weeks), Sitagliptin group (HF with oral administration of Sitagliptin at 10 mg/kg for 6 weeks), and Berberine/ Sitagliptin group (HF diet within combination with oral administration of Berberine 75 mg/kg and Sitagliptin 5 mg/kg for 6 weeks). Animals were examined for weight gain, serum and hepatic biochemical parameters, tissue histology, expression of glucose transporter type 4 (GLUT4) mRNA, and protein expression of Adiponectin receptor2 (AdipoR2) and extracellular signal-regulated kinase (ERK) and phoERK. RESULTS: The results showed that ALT, AST, lipid profile, insulin, glucose, MDA, and TNF-α were significantly improved in high-fat rats treated with Berberine/ Sitagliptin compared with HF and Sitagliptin, and Berberine alone groups. SOD and adiponectin levels in Berberine/ Sitagliptin group were also significantly increased compared with the other groups. Immunoblot analysis showed that the expression of pho-ERK/ERK was significantly decreased and expression of AdipoR2 significantly increased in the Berberine/ Sitagliptin group compared with other groups. CONCLUSION: Co-administration of Berberine and Sitagliptin is an effective therapeutic regimen for conditions associated with hyperlipidemia.

The effects of nanocurcumin supplementation on inflammation in hemodialysis patients: A randomized controlled trial.

INTRODUCTION: Serum levels of several pro-inflammatory cytokines are higher in hemodialysis patients compared to healthy people. Curcumin has been shown to be able to decrease cytokines levels in nonuremic subjects. Our goal was to evaluate the effect of nanocurcumin administration on cytokines levels in hemodialysis patients. METHODS: The study was performed over a 3 months period on 54 hemodialysis patients who had been randomized to receive either nanocurcumin or placebo. Serum levels and gene expressions of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were evaluated using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). FINDINGS: Serum levels of IL-6 and TNF-α were similar in the two groups at baseline but were lower after 12 weeks of treatment with nanocurcumin compared to placebo (P = 0.024 for IL-6 and 0.02 for TNF). In the group given nanocurcumin, serum levels of both cytokines decreased substantially (P < 0.001 for each), whereas they were unchanged in the group given placebo. Gene expression for each cytokine in peripheral blood mononuclear cells (PBMCs) was reduced at 12 weeks vs. baseline in the group given nanocurcumin, and changes in gene expression correlated with changes in serum level for each of the two cytokines. DISCUSSION: The results indicate that nanocurcumin supplementation reduces both serum levels and gene expression of IL-6 and TNF-α in hemodialysis patients. The feasibility and potential clinical benefits of nanocurcumin treatment to reduce inflammation in hemodialysis patients warrant further study.

Improvement of NRF2 gene expression and antioxidant status in patients with type 2 diabetes mellitus after supplementation with omega-3 polyunsaturated fatty acids: A double-blind randomised placebo-controlled clinical trial.

BACKGROUND: Nrf2 is a transcription factor that induces the expression of several proteins with antioxidant properties such as sestrin2 (Sesn2) and is therefore considered as the major regulator of anti-oxidative defence system. OBJECTIVES: The aim of this research was to study the effect of supplementation with n-3 PUFAs on the antioxidant status and the gene expression of Nrf2 and Sestrin2 (Sesn2) in patients with type 2 diabetes mellitus (T2DM). PARTICIPANTS: Sixty patients with T2DM were enrolled in a placebo-controlled, double-blind, randomised clinical trial. INTERVENTION AND DESIGN: The participants were randomly allocated to two intervention groups receiving either n-3 PUFAs (2,700 mg/day) (n = 30) or placebo soft gels containing 900 mg of edible paraffin (n = 30). The main outcome measures were the expression of Sesn2 and Nrf2 genes which were assessed in peripheral blood mononuclear cells (PBMCs) after RNA extraction and cDNA synthesis by real-time PCR. Total antioxidant status in plasma samples was also measured based on the ferric reducing ability of plasma. RESULTS: NRF2 gene expression was significantly increased in n-3 PUFA-supplemented subjects, compared with the placebo group. Plasma total antioxidant status was also significantly augmented in n-3 PUFA-supplemented subjects. SESN2 gene expression was not significantly affected by n-3 PUFA supplementation although a slight up-regulation was observed. CONCLUSION: Supplementation with n-3 PUFAs enhanced NRF2 gene expression and improved overall antioxidant capacity and thus might be considered beneficial in the amelioration of oxidative stress and prevention of T2DM complications. TRIAL REGISTRATION: IRCT20150926024198N4.

The Effects of Nano-curcumin Supplementation on Serum Level of hs-CRP, Adhesion Molecules, and Lipid Profiles in Hemodialysis Patients, A Randomized Controlled Clinical Trial.

INTRODUCTION: Hemodialysis (HD) patients are considered as a high-risk population for cardiovascular disease, within which morbidity and mortality have been determined to be associated with dyslipidemia, pro-inflammatory cytokines, increased levels of C-reactive protein (CRP), and adhesion molecules (ICAM-1, VCAM-1). Different markers have been investigated to detect inflammation in hemodialysis patients, as well as the prognostic values of these markers. METHODS: The present study aimed to investigate the effect of nano-curcumin (120 mg) over 12 weeks on hs-CRP levels, adhesion molecules (ICAM-1, VCAM-1), and serum lipid profiles on hemodialysis patients in a randomized controlled clinical trial. RESULTS: The results revealed that the mean serum hs-CRP level in the nano-curcumin group exhibited a decrease by the end of the study, when compared to mean serum hs-CRP level in the placebo group. However, this between-group trend was not found to be statistically significant (P > .05). Nevertheless, a significant difference was determined between the values in the group receiving nano-curcumin, in comparison with the placebo group, at the end of the study (P < .001). Based on the attained results, mean serum levels of VCAM-1 in the nano-curcumin group were significantly reduced at the end of the study, compared with the placebo group (P < .001). Furthermore, the between-group changes comparison showed significant reductions in serum levels of ICAM- 1 in patients treated with nano-curcumin at the end of the study (P < .05). Additionally, though decreases in mean triglycerides, total cholesterol, LDL-C were noted, there were no statistically significant between-group differences (P > .05). Moreover, between-group changes comparison of HDL-C levels and fasting blood sugar did not show any significant changes. CONCLUSION: The current study indicates that nano-curcumin may show beneficial effects in lowering inflammation and hs-CRP levels, as well as adhesion molecules (ICAM-1, VCAM-1), in hemodialysis patients. However, the evidence is still insufficient.

Effects of vitamin D supplementation on depression and some involved neurotransmitters.

BACKGROUND: Low vitamin D levels are associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis and depression but a causal relationship has not been established. This study aimed to evaluate the effects of vitamin D supplementation on depression severity, serum 25(OH)D, and some neurotransmitters in patients with mild to moderate depression. METHODS: An 8-week double-blind randomized clinical trial was conducted on 56 subjects with mild to moderate depression, aged 43.0 ± 1.15yrs. The patients were randomly allocated into two groups: intervention (50,000 IU cholecalciferol/2wks) and control (placebo). Biochemical parameters (serum 25(OH)D, iPTH, oxytocin and platelet serotonin), and depression severity (Beck Depression Inventory-II (BDI-II1)) were initially and finally assessed. RESULTS: Following intervention, significant changes were observed in the intervention group compared to the controls: 25(OH)D concentrations increased (+40.83±28.57 vs. +5.14±23.44 nmol/L, P<0.001) and BDI scores decreased (-11.75±6.40 vs. -3.61±10.40, P = 0.003). Oxytocin concentrations were significantly reduced in controls (-6.49±13.69 ng/mL, P = 0.01), but between -group differences were insignificant. Within- and between-group differences of platelet serotonin concentrations were not significant; however, the increment in controls was higher (+0.86±10.82 vs. +0.26±9.38 ng/mL, P = 0.83). LIMITATIONS: Study duration may not reflect the long-term effects of vitamin D on depression. It seems necessary to assess tryptophan-hydroxylasetypes1&2 in relation to vitamin D in serotonin pathways. CONCLUSIONS: Eight-week supplementation with 50,000 IU/2wks vitamin D, elevated 25(OH)D concentration of subjects with mild to moderate depression and significantly improved their depression severity. However, there was no evidence that the anti-depressive effect of vitamin D supplementation is mediated by the measured neurotransmitters.

Adjuvant therapy with γ-tocopherol-induce apoptosis in HT-29 colon cancer via cyclin-dependent cell cycle arrest mechanism.

Resistance to chemotherapy with 5-fluorouracil (5-FU) in patients with colorectal cancer (CRC) is the major obstacle to reach the maximum efficiency of CRC treatment. Combination therapy has emerged as a novel anticancer strategy. The present study evaluates the cotreatment of γ-tocopherol and 5-FU in enhancing the efficacy of chemotherapy against HT-29 colon cancer cells. Cytotoxic effect of this combination was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and a synergistic effect was evaluated by a combination index technique. Nuclear morphology was studied via 4',6-diamidino-2-phenylindole staining and flow cytometric assays were conducted to identify molecular mechanisms of apoptosis and cell cycle progression. We investigated the expression of Cyclin D1, Cyclin E, Bax, and Bcl-2 by a quantitative real-time polymerase chain reaction. The IC50 values for 5-FU and γ-tocopherol were 21.8 ± 2.5 and 14.4 ± 2.6 µM, respectively, and also this combination therapeutic increased the percentage of apoptotic cells from 35% ± 2% to 40% ± 4% (P < .05). Furthermore, incubation HT-29 colon cells with combined concentrations of two drugs caused significant accumulation of cells in the subGsubG1 phase. Our results presented the combination therapy with 5-FU and γ-tocopherol as a novel therapeutic approach, which can enhance the efficacy of chemotherapy.

Apoptotic efficacy and antiproliferative potential of silver nanoparticles synthesised from aqueous extract of sumac (Rhus coriaria L.).

Currently, nanotechnology and nanoparticles (NPs) are recognised due to their extensive applications in medicine and the treatment of certain diseases, including cancer. Silver NPs (AgNPs) synthesised by environmentally friendly method exhibit a high medical potential. This study was conducted to determine the cytotoxic and apoptotic effects of AgNPs synthesised from sumac (Anacardiaceae family) fruit aqueous extract (AgSu/NPs) on human breast cancer cells (MCF-7). The anti-proliferative effect of AgSu/NPs was determined by MTT assay. The apoptotic properties of AgSu/NPs were assessed by morphological analysis and acridine orange/propidium iodide (AO/PI) and DAPI staining. The mechanism of apoptosis induction in treated cells was investigated using molecular analysis. Overall results of morphological examination and cytotoxic assay revealed that AgSu/NPs exert a concentration-dependent inhibitory effect on the viability of MCF-7 cells (IC50 of ∼10 µmol/48 h). AO/PI staining confirmed the occurrence of apoptosis in cells treated with AgSu/NPs. In addition, molecular analysis demonstrated that the apoptosis in MCF-7 cells exposed to AgSu/NPs was induced via up-regulation of Bax and down-regulation of Bcl-2. These findings suggested the potential use of AgSu/NP as cytotoxic and pro-apoptotic efficacy and its possible application in modern medicine for treating certain disorders, such as cancer.

Thymoquinone recovers learning function in a rat model of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease is a neurodegenerative disorder characterized by accumulation of amyloid beta in the hippocampus. In recent decades, herbal medicine has been widely used to treat many neurodegenerative disorders,as in comparison to conventional drugs, herbal remedies exert minimal side effects. Here, the effects of thymoquinone, as the main active component of Nigella sativa, on passive avoidance memory in rat model of Alzheimer's disease, were evaluated. MATERIALS AND METHODS: Hippocampal injection of amyloid beta (Aß) was used to induce Alzheimer's disease in male Wistar rats, followed by intra peritoneal administrations of 5 and 10 mg/kg thymoquinone on a daily basis for 4 weeks. Animals were subjected to fear learning behavior in passive avoidance test and histopathological analysis of the hippocampus was done. Shuttle box test was used to evaluate the condition studying memory. Thioflavin-S and Hematoxylin and Eosine staining were done to confirm Aß plaque formation and to evaluate the effect of thymoquinone on the pyramidal cells in the hippocampal CA1 region. RESULTS: Amyloid beta caused cognitive dysfunction reflected by increasing initial and step-through latency along with plaque formation and degeneration of pyramidal cells in the hippocampus. Thymoquinone administration ameliorated this effect by significant reductions in plaque formation in CA1 region of the hippocampus and increased latency time. It also increased the number of surviving neurons in the hippocampus. CONCLUSION: It seems that thymoquinone improved learning function in a rat model of Alzheimer's disease. Thus, thymoquinone could be possibly used as an anti-neurodegenerative agent for protecting hippocampal neurons against neurotoxic effects of Aß in patients with Alzheimer's disease.

Fluorescence bio-barcode DNA assay based on gold and magnetic nanoparticles for detection of Exotoxin A gene sequence.

Bio-barcode DNA based on gold nanoparticle (bDNA-GNPs) as a new generation of biosensor based detection tools, holds promise for biological science studies. They are of enormous importance in the emergence of rapid and sensitive procedures for detecting toxins of microorganisms. Exotoxin A (ETA) is the most toxic virulence factor of Pseudomonas aeruginosa. ETA has ADP-ribosylation activity and decisively affects the protein synthesis of the host cells. In the present study, we developed a fluorescence bio-barcode technology to trace P. aeruginosa ETA. The GNPs were coated with the first target-specific DNA probe 1 (1pDNA) and bio-barcode DNA, which acted as a signal reporter. The magnetic nanoparticles (MNPs) were coated with the second target-specific DNA probe 2 (2pDNA) that was able to recognize the other end of the target DNA. After binding the nanoparticles with the target DNA, the following sandwich structure was formed: MNP 2pDNA/tDNA/1pDNA-GNP-bDNA. After isolating the sandwiches by a magnetic field, the DNAs of the probes which have been hybridized to their complementary DNA, GNPs and MNPs, via the hydrogen, electrostatic and covalently bonds, were released from the sandwiches after dissolving in dithiothreitol solution (DTT 0.8M). This bio-barcode DNA with known DNA sequence was then detected by fluorescence spectrophotometry. The findings showed that the new method has the advantages of fast, high sensitivity (the detection limit was 1.2ng/ml), good selectivity, and wide linear range of 5-200ng/ml. The regression analysis also showed that there was a good linear relationship (∆F=0.57 [target DNA]+21.31, R2=0.9984) between the fluorescent intensity and the target DNA concentration in the samples.