The immunoregulatory property of mesenchymal stem cells in Crocin treatment by expression modulation of microRNA-155, microRNA-21, microRNA-23b, microRNA-126a, and their target inflammatory genes.

Mesenchymal stem cells (MSCs) have high priority in clinical applications for treatment of immune disorders because of their immunomodulatory function. A lot of researches have currently been undertaken to enhance the stemness capacities of the cells and pick an excellent type of MSCs for clinical approaches. This study aims to assess the immunomodulatory related MicroRNAs (miRNAs) expression as well as their target genes in both adipose derived stem cells (Ad-SCs) and dental pulp derived stem cell (DP-SCs) in the presence or lack of Crocin (saffron plant's bioactive compound). For this purpose, first MSCs were extracted from adipose and dental pulp tissues, and then their mesenchymal nature was confirmed using flow cytometry and differentiation tests. Following the cell treatment with an optimal-non-toxic dose of Crocin (Obtained by MTT test), the expression of 4 selected immunomodulatory-related micro-RNAs (Mir-126, -21, -23, and-155) and their target genes (PI3K/ Akt 1 and 2/ NFKB and RELA) were assessed by RT-PCR. Our findings revealed that miRNA-23 and miRNA-126 were up-regulated in both types of cells treated with Crocin, while in the other side, miRNA-21 and miRNA-155 were down-regulated in DP-SCs and were up-regulated in Ad-SCs under treatment. Moreover, the real-time PCR results indicated that Crocin could significantly down regulate the expression of PI3K/ Akt1/ Akt2/ NFKB/ RELA genes in DP-SCs and PI3K/Akt2 genes in Ad-SCs and up regulate the expression of Akt1/ NFKB/ RELA genes in recent cells. Based on the analysis of the obtained data, the immunoregulatory effects of Crocin were higher in DP-SCs than in Ad-SCs. In conclusion, Crocin could control essential signaling pathways related to the inflammation by regulating the expression of related- miRNAs genes that play a key function in the immune regulation pathways in MSCs. Our findings can give an understanding of the mechanisms by which Crocin enhances the immunomodulatory feature of MSCs. According to the research findings, DP-SCs are probably a better immunomodulator in Crocin treatment than Ad-SCs and it may be helpful for MSCs selection in clinical applications for modulation or treatment of autoimmune disorders.

Efficacy of Curcumin on Cognitive Function Scores in Women with Premenstrual Syndrome and Dysmenorrhea: A Triple-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome (PMS) and dysmenorrhea. METHODS: A randomized, triple-blind, placebo-controlled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days (7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups. RESULTS: Administration of curcumin was associated with a significant increase in memory score (P=0.002), inhibitory control and selective attention (P=0.020), and total cognitive ability task (P=0.024). In addition, significant increments were found in scores of memory (3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively; P=0.035), inhibitory control and selective attention (3.0±3.7 vs. 0.4±3.7; P=0.027) and total cognitive abilities (8.3±12.3 vs. 2.2±12.4; P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial. CONCLUSION: Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention. (Registration No. IRCT20191112045424N1, available at: https://www.irct.ir ).

Expression of immunomodulatory and tissue regenerative biomarkers in human dental pulp derived-mesenchymal stem cells treated with curcumin: an in vitro study.

BACKGROUND: Human Dental pulp derived-mesenchymal stem cells (hDP-MSCs) have the capability of selfrenewal, multipotency, as well as immunosuppressive properties. They are ideal candidates for regenerating damaged dental tissue and treating inflammation-related diseases. However, methods (such as genetic variation) to improve the immunomodulatory and regenerative efficiency of MSCs in different diseases still need to be developed. Curcumin (CUR) is known for its broad applications in regenerative medicine and the treatment of inflammatory disorders via its anti-inflammatory and anti-oxidant effects. This study was conducted to investigate the effect and underlying mechanisms of CUR on the immunomodulatory and regenerative function of hDP-MSCs and whether treating these cells with CUR can improve therapeutic efficacy. METHODS AND RESULTS: hDP-MSCs were isolated from dental pulp and then treated with CUR. Cell viability rate was observed in hDP-MSCs after treatment of CUR by MTT assay. Real-time quantitative (RT-PCR) was applied to estimate the expression of immunomodulatory and regenerative genes after treatment of CUR. The RT-PCR results showed that VEGF-A and STAT3 markers were up-regulated while HLA-G5 and VCAM-1 markers were down-regulated by CUR (20 µM) treatment in hDP-MSCs (P < 0.001). Besides, this research indicated that there were no significant changes in the expressions of RelA and DSPP after 48 h (P = 0.33, P = 1). CONCLUSION: Our findings demonstrate that CUR can enhance the immunomodulatory and regenerative effects of hDP-MSCs and improve their therapeutic efficacy. These findings can give an understanding of the mechanism for improving restorative and immunomodulatory activity in hDP-MSCs by curcumin.

Effects of phytosomal curcumin treatment on modulation of immunomodulatory and pulp regeneration genes in dental pulp mesenchymal stem cells.

Dental pulp stem cells (DPSCs) are a new population of mesenchymal stem cells (MSCs) located in the oral cavity with potential capacities for tissue regeneration and immunomodulation. The purpose from this study was to determine effects of curcumin nanoparticle into phytosomal formulation (PC) on the relative expression of DSPP, VEGF-A, HLA-G5, VCAM1, RelA and STAT3 genes which are among the most important factors influencing processes of immunomodulatory and tissue regenerative by DPSCs. After isolation and culture of DPSCs, these cells were characterized according to predetermined criteria including flow cytometric analysis for detection of the most important cell surface markers and also evaluation of multilineage differentiation potential. Then, the MTT method was employed to check the cell viability in treatment with different concentrations of PC. Following DPSCs' treatment with an optimal-non-toxic dose of this nanoparticle, quantification of expression of target genes was performed using real-time PCR procedure. According to results of immunophenotyping analysis and cell differentiation experiments, the isolated cells were confirmed as MSCs as more than 99% of them expressed specific mesenchymal markers while only about 0.5% of them were positive for hematopoietic marker. The real-time PCR results indicated that PC significantly reduced the expression of RelA, STAT3, VCAM1 and HLA-G5 genes up to many times over while optimally enhanced the expression of DSPP and VEGF-A genes, although this enhance was statistically significant only for VEGF-A (all P < 0.001). The study suggests that PC affects the stemness capabilities of DPSCs and it may facilitate the development of MSCs-based therapeutics in regenerative dentistry.

An In Vitro Study of the Effects of Crocin on the Modulation of DSPP, VEGF-A, HLA-G5, STAT3 and CD200 Expression in Human Dental Pulp Stem Cells.

Dental pulp stem cells (DPSCs) have been recommended as promising candidate for cell-based therapeutic applications due to high potentials in tissue repair/regeneration and modulation of immune responses. The gene expression change strategy by natural plant enhancers is an available opportunity to improve the stemness properties of these cells. The objective of this research was the evaluation of Crocin effects (saffron plant's bioactive compound) on immunoregulation and tissue regeneration-related biomarkers expression in human DPSCs. Based on the results of cell viability assay, application of 400 µM and lower concentrations of Crocin had no toxic effects on DPSCs; however, the time-dependent cytotoxic effects were observed at higher concentrations. This study, probably for the first time, detected the surface expression of CD200 in DPSCs with a slight time-dependent upward trend and reported that treatment with Crocin could increase expression of this macromolecule up to many times over. Also, it revealed that this carotenoid significantly led to the time-dependent upregulation of dentin sialophosphoprotein, vascular endothelial growth factor A, human leukocyte antigen-G5, and signal transducer and activator of transcription-3 messenger ribonucleic acids (mRNAs); however, this significant upregulation for STAT3 occurred, followed by a remarkable reduction. The results of this study indicated that cell treatment with Crocin may be effective in improving the stemness capacities of DPSCs. Therefore, the study provided basis for more insights into the biological effects of Crocin on DPSCs that it may aid in the future improvement of mesenchymal stem cell-based therapies.

Immunomodulatory effects of phytosomal curcumin on related-micro RNAs, CD200 expression and inflammatory pathways in dental pulp stem cells.

Human dental pulp stem cells (hDPSCs) have significant potential of immunomodulatory for therapeutic and regenerative biomedical applications compared to other mesenchymal stem cells (MSCs). Nowadays, alteration of gene expression is an important way to improve the performance of MSCs in the clinic. MicroRNAs (miRs) and CD200 are known to modulate the immune system in MSCs. Curcumin is famous for its anti-inflammatory impacts. Phytosomal curcumin (PC) is a nanoparticle synthesized from curcumin that removes the drawbacks of curcumin. The purpose of this research was to assess the effects of PC on the expression of the CD200 and four key miRNAs in immune system. PC (30 µM) treatment of hDPSCs could ameliorate their immunoregulatory property, presented by reduced expressions of miR-21, miR-155 and miR-126, as well as enhanced expressions of miR-23 and CD200. The PC was also able to reduce PI3K\AKT1\NF-κB expressions that were target genes for these miRs and involved in inflammatory pathways. Moreover, PC was more effective than curcumin in improving the immune modulation of hDPSCs. Evidence in this study suggested that PC mediates immunoregulatory activities in hDPSC via miRs and CD200 to regulate PI3K\AKT1\NF-κB signalling pathways, which may provide a theoretical basis for PC in the treatment of many diseases. SIGNIFICANCE OF THE STUDY: Autoimmune diseases or tooth caries are partly attributed to global health problems and their common drug treatments have several side effects. The goal of this study is dentin regeneration and autoimmune diseases treatment via stem cell-based approaches with phytosomal curcumin (PC), for the first time. Because dental pulp stem cells have unique advantages (including higher immunomodulatory capacity) over other mesenchymal stem cells, we considered them the best option for treating these diseases. Using PC, we try to increase the immunomodulatory properties of these cells.

The association between adherence to a dietary approaches to stop hypertension (DASH) diet and neuro-psychological function in young women.

BACKGROUND: The adherence to a Dietary Approaches to Stop Hypertension (DASH) diet may have a bidirectional relationship with mental wellbeing. We aimed to evaluate the association between compliance with a DASH diet and neuro-psychological function in young women. METHODS: In this cross-sectional study, a total of 181 girls aged between 18 and 25 years were recruited. The dietary intakes of study participants were evaluated using a valid and reliable food frequency questionnaire (FFQ) containing 65 food items. Neuropsychological function of participants was evaluated using standard questionnaires. RESULTS: As may be expected, individuals in the highest tertile (T3) of adherence to DASH diet (highest adherence) were found to consume more folate, fruits, vegetables, low fat dairy, nuts, legume, and seed, less sweetened beverage and sodium, compared to the participants in the lowest tertile (T1, lowest adherence). There was a significant negative correlation between cognitive function and consumption of red and processed meat (r = - 0.168; p < 0.05); quality of life score with dietary sodium (r = - 0.151; p < 0.01) and depression score with dietary vegetables (r = - 0.174; p < 0.05). In multivariate multinomial logistic regression analyses adjusted for age, BMI and energy intake, adherence to a DASH-style diet was associated with a lower stress score (OR = 0.70; 95%CI: 0.34-1.47, P = 0.067; T3 vs. T1) and difficulty with sleep initiation (OR = 0.46; 95%CI: 0.21-1.00, P = 0.017; T3 vs. T1). CONCLUSION: Adherence to a DASH diet may be associated with reduced stress and difficulty with initiating sleep.

A study of the association of cognitive abilities and emotional function with allergic disorders in young women.

BACKGROUND: Allergic disorders may have a bidirectional causal relationship with mental disorders. In this cross-sectional study, we aimed to assess the associations between cognitive abilities and emotional function tests and quality of life with the presence of allergic disease in young women. METHODS: A diagnosis of allergic disorders, comprising allergic rhinitis (AR), asthma and atopic dermatitis (AD), was confirmed by a specialist in allergy. The presence and severity of depression, anxiety, stress, insomnia and sleepiness were evaluated using validated questionnaires. Cognitive abilities and quality of life were assessed using standard instruments. RESULTS: Among 181 female young participants, the prevalence of AR, asthma and AD were 26.5%, 2.8%, and 14.9% respectively. The AR group had higher scores than the non-AR group for depression, anxiety, insomnia, and lower scores for physical and mental health-related quality of life. Moreover, the AD cases had higher scores on the depression and stress scale compared to those without it (p < 0.05). Asthmatic patients also had significantly higher insomnia severity and lower physical health-related quality of life than non-asthmatic. CONCLUSION: There was a high prevalence of psychological/psychiatric disorders that included: anxiety, and sleep problems among allergic women, and a reduced quality of life that may be associated with it.

Impact of a Nordic diet on psychological function in young students.

BACKGROUND: There has been a rapid increase in the prevalence of psychiatric and psychological disease, and this has attracted interest in identifying modifiable lifestyle factors that may affect an individual's mood. Diet is one potential lifestyle factor that may affect psychological function. AIM: This study aimed to investigate the relationship between adherence to the health-promoting Nordic diet (ND) with neuropsychological function in young women. METHODS: The study comprised 181 female students aged between 18 and 25 years. Psychological function was evaluated using a series of standardized questionnaires, including the Cognitive Ability Questionnaire, Depression Anxiety Stress Scale, Insomnia Severity Index, Epworth Sleep Scale and Quality of Life Questionnaire. A validated food frequency questionnaire, which included 65 types of foods, was used to evaluate the amount of different foods consumed. RESULTS: Evaluation of the dietary composition of the participants showed that the rate of adherence to the ND was positively associated with total energy, carbohydrates, protein, fibre, iron, magnesium, potassium, zinc, folate, phosphorus, vitamin C, thiamine, riboflavin, niacin, vitamins B6 and B12, carotene, whole grain, legumes, cabbage/vegetables, vegetables and fruit (p<0.05). Linear regression showed cabbage/vegetable consumption was inversely related to scores of stress (ß=-0.04; p=0.038) and anxiety (ß=-0.02; p=0.049) and directly associated with the quality-of-life score (0.02; p=0.036). CONCLUSIONS: Adherence to a ND with a high intake of cabbage/vegetables was inversely associated with stress and anxiety scores and directly associated with health-related quality of life.

A study of the association between cognitive abilities and dietary intake in young women.

BACKGROUND: Cognitive abilities comprise activities that relate to receiving and responding to information from the environment, internal processing, making complex decisions, and then responding to this in the context of behavior. AIM: The current study investigated the association between dietary intake and seven aspects of cognitive abilities among healthy young women. METHODS: The study was carried out among 182 women aged 18-25 years. A valid and reliable food frequency questionnaire containing 65 food items was used to estimate dietary intake. Neuropsychological function and cognitive abilities of participants were determined using standard questionnaires. RESULTS: Significant differences were found in depression, anxiety, stress, physical, and mental health-related quality of life as well as daytime sleepiness for the participants in different quartiles of cognitive abilities score (p<0.05). Participants in the fourth quartile of cognitive abilities score consumed significantly higher energy, carbohydrate, protein, calcium, iron, zinc, vitamin A, thiamin, and riboflavin compared to those in the lowest quartile (p<0.05). There were strong correlations between total cognitive abilities score and dietary sodium, calcium, phosphorus, and thiamin (p<0.05). Using stepwise multiple linear regression analysis, iron and thiamin were statistically significant factors for the prediction of cognitive abilities. CONCLUSIONS: These findings demonstrate that neurocognitive function is related to dietary macro and micronutrients including energy, carbohydrate, protein, calcium, iron, zinc, vitamin A, thiamin, and riboflavin on cognitive performance among young women without memory deficit.

Neuropsychological function is related to irritable bowel syndrome in women with premenstrual syndrome and dysmenorrhea.

BACKGROUND: There is increasing evidence demonstrating the co-occurrence of primary dysmenorrhea (PD), premenstrual syndrome (PMS), and irritable bowel syndrome (IBS) in women. This study aimed to investigate whether women who have symptoms of IBS in addition to PD and PMS also report more severe or frequent menstruation-associated symptoms and psychological complications compared to women with PD and PMS alone. METHODS: The study group included 182 female University students aged 18-25 years. IBS was diagnosed using the Rome III criteria. The severity of PMS and PD was determined using a 10-point visual analog scale and PSST (Premenstrual Syndrome Screening Tool), respectively. Neuropsychological functions including cognitive function, depression score, anxiety score, stress, insomnia, daytime sleepiness, quality of life and personality were assessed using standard questionnaires. RESULTS: Of the 182 young females, 31 (17.0%) had IBS. Average days of bleeding during the menstrual cycle and mean pain severity on the PSST scale were significantly greater in the group with IBS compared to the non-IBS group (p < 0.01). The non-IBS individuals scored more favorably than the women with IBS with respect to severity of depression, insomnia, daytime sleepiness (p < 0.05). The PSST scores were significantly correlated with scores for depression (r = 0.29; p < 0.001), anxiety (r = 0.28; p < 0.001), stress (r = 0.32; p < 0.001), insomnia (r = 0.34; p < 0.001) and daytime sleepiness (r = 0.31; p < 0.001); while, they were negatively correlated with cognitive abilities (r = - 0.20; p = 0.006) and quality of life (r = - 0.42; p < 0.001). Linear regression analysis showed that the PSST scores were possibly significant factors in determining the scores for depression, anxiety, stress, quality of life, insomnia and daytime sleepiness (p < 0.05). CONCLUSION: IBS is related to psychological comorbidities, in particular depression, sleep problems and menstrual-associated disorders. IBS may exacerbate the features of PMS which should be taken into account in the management of PMS.