Harmaline induces apoptosis and inhibits migration in A2780 ovarian cancer cells in vitro.

Ovarian cancer is one of the most prevalent malignancies in women. Harmaline is reported to have powerful anticancer properties. We aimed to investigate the apoptotic and antimetastatic properties of harmaline in A2780 ovarian cancer cells. Cell viability, apoptosis, migration, and invasion were investigated in cells treated with harmaline. Reactive oxygen species (ROS) production, mRNA expression of apoptosis-associated genes, MMP-2, and MMP-9 were measured. Harmaline attenuated the viability of A2780 ovarian cancer cells in a dose- and time-dependent way. Furthermore, compared to NIH/3T3 mouse normal cell line (IC50 = 417 µM), the malignant A2080 cells were more sensitive to harmaline (IC50 = 300 µM after 24 h). Harmaline increased the production of ROS, raised the mRNA expression of p53 and the Bax/Bcl2 ratio. Harmaline also increased the proportion of cells in the late apoptotic and necrotic phases. MMP-2 and MMP-9's mRNA expression, gelatinase activity, and migration of A2780 cells also decreased by harmaline. These findings suggest that harmaline may have the potential to be a therapeutic drug for ovarian cancer by triggering apoptosis and suppressing invasion and migration.

Effects of curcumin supplementation on insomnia and daytime sleepiness in young women with premenstrual syndrome and dysmenorrhea: A randomized clinical trial.

Objective: Premenstrual syndrome and primary dysmenorrhea are common gynecological complaints that are associated with psychological disorders. There is increasing evidence for the neuroprotective properties of curcumin, a polyphenolic natural product. This study aimed to assess the effects of curcumin on sleep complications in women with premenstrual syndrome and dysmenorrhea. Materials and Methods: This triple-masked, placebo-controlled clinical trial comprised 124 patients with both premenstrual syndrome and dysmenorrhea. Participants were randomly assigned to curcumin (n=57) or control (n=60) groups. Each participant received one capsule containing either 500 mg of curcumin plus piperine or placebo, daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Insomnia and sleepiness were assessed using standard questionnaires. Results: Scores for insomnia and daytime sleepiness were directly correlated with the Premenstrual Syndrome Screening Tool (PSST) score (p<0.05), but not with the visual analogue scale (VAS) score at baseline (p>0.05). There was a non-significant reduction in insomnia and sleepiness scores in both curcumin and placebo groups after the study intervention. Whilst, improvement rate of insomnia status, daytime sleepiness severity, short sleep duration and difficult sleep initiation was not statistically significant between the curcumin and placebo groups. Conclusion: Curcumin does not significantly affect sleep disorders in young women with premenstrual syndrome and dysmenorrhea.

Predicting the Cognitive Ability of Young Women Using a New Feature Selection Algorithm.

Cognitive abilities are the capabilities to perform mental processes that include executive function, comprehension, decision-making, work performance, and educational attainment. This study aimed to investigate the relationship between several biomarkers and individuals' cognitive ability using various machine learning methods. A total of 144 young women aged between 18 and 24 years old were recruited into the study. Cognitive performance was assessed using a standard questionnaire. A panel of biochemical, hematological, inflammatory, and oxidative stress biomarkers in serum and urine was measured for all participants. A novel combination of feature selection and feature scoring techniques within a hierarchical ensemble structure has been proposed to identify the most effective features in recognizing the importance of various biomarker signatures in cognitive abilities classification. Multiple feature selection methods were employed in conjunction with different classifiers to construct this model. In this manner, using three filter methods, the scores of each feature were considered. The combination of high-scoring features for each filter method was stored as the primary feature subset. A high-accuracy feature subset was selected by using a wrapper method. The collection of highly scored features from each filter method formed the primary feature subset. A wrapper method was also employed to select a feature subset with high accuracy. To ensure robustness and minimize random variations in the feature subset search process, a repeative tenfold cross-validation was conducted. The most frequently recurring features were determined. This iterative step facilitated the identification of an optimal feature subset, effectively reducing the dimensionality of features while maintaining accuracy. Among the 47 extracted factors, serum level of NOx (nitrite ± nitrate), alkaline phosphatase (ALP), and phosphate as well as blood platelet count (PLT) was entered into the model of cognitive abilities with the highest accuracy of approximately 70.9% using a decision tree classifier. Therefore, the serum levels of NOx, ALP, phosphate, and blood PLT count may be important markers of the cognitive abilities in apparently healthy young women. These factors my provide a simple procedure to identify mental abilities and earlier cognitive decline in healthy adults.

Effect of curcumin on inflammatory biomarkers and iron profile in patients with premenstrual syndrome and dysmenorrhea: A randomized controlled trial.

Premenstrual syndrome (PMS) and primary dysmenorrhea are common gynecological problems and inflammation may have a role in their etiology. Curcumin is a polyphenolic natural product for which there is increasing evidence of anti-inflammatory and iron chelation effects. This study assessed the effects of curcumin on inflammatory biomarkers and iron profile in young women with PMS and dysmenorrhea. A sample of 76 patients was included in this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 38) and control groups (n = 38). Each participant received one capsule (500 mg of curcuminoid+ piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Serum iron, ferritin, total iron-binding capacity (TIBC) and high-sensitivity C-reactive protein (hsCRP), as well as white blood cell, lymphocyte, neutrophil, platelet counts, mean platelet volume (MPV) and red blood cell distribution width (RDW), were quantified. Neutrophil: lymphocyte ratio (NLR), platelet: lymphocyte ratio (PLR), and RDW: platelet ratio (RPR) were also calculated. Curcumin significantly decreased the median (interquartile range) serum levels of hsCRP [from 0.30 mg/L (0.0-1.10) to 0.20 mg/L (0.0-1.3); p = 0.041] compared with placebo, but did not show any difference for neutrophil, RDW, MPV, NLR, PLR and RPR values (p > 0.05). The treatment schedule was well-tolerated, and none of markers of iron metabolism statistically changed after the intervention in the curcumin group (p > 0.05). Curcumin supplementation may have positive effects on serum hsCRP, a marker of inflammation, with no any changes on iron homeostasis in healthy women with PMS and dysmenorrhea.

Association between adherence to a low carbohydrate dietary (LCD) pattern with breast milk characteristics and oxidative markers in infants' urine: a cross-sectional study.

BACKGROUND: Breast milk (BM) is a dynamic fluid that varies over time and between women. The variations in BM components are most likely associated with maternal diet quality. This study aimed to assess adherence to a low carbohydrate dietary (LCD) pattern with oxidative stress markers of BM characteristics and infants' urine. MATERIALS AND METHODS: In this cross-sectional study 350 breastfeeding mothers and their infants were recruited. BM samples were collected from mothers, and urine specimens were obtained from each infant. To evaluate LCD scores, subjects were divided into 10 deciles according to the percent of energy obtained from carbohydrates, proteins, and fats. Determination of total antioxidant activity was conducted using the ferric reducing antioxidant power (FRAP), 2, 2'-diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARs), and Ellman's assay. Biochemical assays of samples including calcium, total protein, and triglyceride level were also performed using commercial kits. RESULTS: Participants with the greatest LCD pattern adherence were placed into the last quartile (Q4), and those with the minimum LCD were in the first quartile (Q1). Individuals in the highest LCD quartile had significantly higher levels of milk FRAP, thiol, and protein, as well as infant urinary FRAP and lower milk MDA levels than those in the lowest quartile. Multivariate linear regression analyses indicated that higher score of the LCD pattern was associated with a higher level of milk thiol, protein, and lower level of milk MDA (p < 0.05). CONCLUSION: Our findings show that adherence to a LCD, as defined by a low level of carbohydrates in daily food intake, is linked with improved BM quality and markers of oxidative stress in infant urine.

The relationship between dietary patterns and insomnia in young women.

AIM: There is mounting evidence that eating habits affect sleeping patterns and their quality. The goal of this study was to evaluate the associations between major dietary patterns, identified using principal component analysis (PCA) and insomnia in young women. METHODS: The study subjects comprised 159 healthy young women aged 18-25 years. Neuropsychological assessment was performed using standard instruments, including a cognitive ability questionnaire (CAQ), depression and anxiety stress scales (DASS-21), insomnia severity index (ISI), Epworth sleepiness scale (ESS), and quality of life questionnaire (QLQ). Dietary patterns were obtained from a 65-item validated food frequency questionnaire (FFQ) in this study, using PCA. RESULTS: Two major dietary patterns were identified that were termed: "Traditional" and "Western." The Western pattern was characterized by a high intake of snacks, nuts, dairy products, tea, fast foods, chicken, and vegetable oils. Subjects with moderate/severe insomnia were found to have lower scores for total cognitive ability task, nocturnal sleep hours, and physical and mental health, but higher scores for depression, anxiety, stress, and daytime sleepiness compared to those without insomnia (p < 0.05). After adjustment for potential confounders, high adherence to the Western dietary pattern was associated with higher odds of insomnia (OR = 5.9; 95% confidence intervals: 1.9-18.7; p = 0.003). CONCLUSION: Our findings indicated adherence to Western pattern may increase the odds of insomnia. Prospective research is required to determine the feasibility of targeting dietary patterns to decrease the odds of insomnia.

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 ).

Therapeutic effect of turmeric on radiodermatitis: A systematic review.

Radiodermatitis (RD) occurs in 95% of cancer patients undergoing radiation therapy. At present, there is no effective treatment for the management of this complication of radiotherapy. Turmeric (Curcuma longa) is a polyphenolic and biologically active natural compound with various pharmacological functions. The aim of this systematic review was to determine the efficacy of curcumin supplementation for reducing RD severity. This review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive literature search was conducted in Cochrane library, PubMed, Scopus, Web of Science, and MEDLINE databases. A total of seven studies comprising 473 cases and 552 controls were included in this review. Four studies demonstrated that curcumin supplementation had a beneficial effect on RD intensity. These data provide evidence for the potential clinical use of curcumin in supportive cancer care. Further large prospective and well-designed trials are warranted to exactly determine the "real effective extract, supplemental form and dose of curcumin" for RD prevention and treatment of patients receiving radiotherapy.

Harmaline exerts potentially anti-cancer effects on U-87 human malignant glioblastoma cells in vitro.

BACKGROUND: Harmaline is a ß-carboline alkaloid that can be extracted from the seeds of Peganum harmala. Harmaline has been shown to exhibit a potent cytotoxic effect against tumor cells. In this study, the anti-glioblastoma activity of harmaline was investigated in vitro. METHODS AND RESULTS: Cell viability, apoptosis, and cell cycle arrest were assessed in U-87 cells treated with harmaline at different doses. Reactive oxygen species (ROS) generation and the mRNA expression of apoptosis-associated genes were assessed. The anti-metastatic effect of harmaline on U-87 cells was evaluated by gelatin zymography assay where matrix metalloproteinase [MMP]-2/-9 enzymatic activity was measured, and the scratch assay was used to assess migratory responses. Flow cytometry demonstrated that harmaline could suppress the proliferation and induce sub-G1 cell cycle arrest and apoptotic cell death in glioblastoma cells. Harmaline treatment was also associated with an upregulation of the cell cycle-related genes, p21 and p53, and pro-apoptotic Bax, as well as the induction of ROS. The zymography assay indicated that the essential steps of metastasis were potently suppressed by harmaline through inhibiting the expression of MMP-2 and - 9. In addition, the migration of U-87 cells was significantly reduced after harmaline treatment. CONCLUSION: Our data suggest a basis for further research of harmaline which has potential cytotoxic activities in glioblastoma cells; inducing cell cycle arrest and apoptosis, repression of migration, possibly invasion, and metastasis.

A Mediterranean diet is associated with improved total antioxidant content of human breast milk and infant urine.

BACKGROUND: The composition of breast milk (BM) is dynamic and can be influenced by maternal variables that include the diet and nutritional status. This study examined the association between maternal adherence to a Mediterranean diet (MedDiet) and total antioxidant content of BM and infant urine. METHODS: We collected 350 BM samples from mothers and urine samples from their infants. The dietary intakes of the mothers were recorded using a validated 65 items-food frequency questionnaire (FFQ). The total antioxidant status of the samples was assessed using the ferric reducing/antioxidant power (FRAP), the 1, 1-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARS), and thiol quantification assays. Milk protein, calcium, and triglyceride (TG) were also determined using standard biochemical kits. RESULTS: Subjects with the highest MedDiet scores were among the women in the highest tertile (T3) for consumption of dietary fiber, fruits, vegetables, nuts, legumes, and seeds, low-fat dairy, whole grains, and the lowest consumption of red meat, sweetened beverages, and sodium, compared to women in the first tertile (T1) with the lowest MedDiet scores. After adjustment for potential confounders, the individuals in the highest tertile for MedDiet score had a significantly higher level of milk DPPH, and infant urinary DPPH than the lowest tertile and had a significantly higher level of milk protein, FRAP and infant urinary FRAP compared to the T2 (P < 0.05). In addition, the mothers in the T3 for the MedDiet pattern had a significantly lower level of milk TG compared to those within the T1 (P < 0.05). CONCLUSION: Our findings show that a high maternal adherence to a MedDiet can affect BM composition and their infants' urine.

The association of maternal food quality score (FQS) with breast milk nutrient content and antioxidant content of infant urine: a cross-sectional study.

BACKGROUND: Breast milk (BM) is a complex fluid with a variable composition within women over time and between women in the population. The BM compositional differences are likely to be partly due to maternal dietary patterns. This study aimed to evaluate food quality score (FQS) in lactating mothers and its association with quality indicators of BM and antioxidant content of infant urine. METHODS: This cross-sectional study was undertaken in 350 lactating women aged 20 to 35 years. Data on dietary intake was collected using a validated food frequency questionnaire (FFQ) containing 65 food items. The FQS was calculated by integrating the scores obtained from healthy and unhealthy food groups. Subjects were categorized according to FQS adherence, with the greatest adherence being allocated to the third tertile and those with the lowest FQS in the first tertile. Antioxidant activity of the BM and infant urine samples was assessed using the Ferric reducing antioxidant power (FRAP), 2, 2'-diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARs), and Ellman's assay. The total content of BM protein, calcium, and triglyceride was measured using standard biochemical kits. RESULTS: BM from mothers from the third tertile of FQS contained significantly higher DPPH, thiol, calcium, and protein levels compared to BM from those in the lowest tertile (p˂0.05). Infant urinary DPPH and FRAP was also significantly higher in the highest tertile vs. the lowest tertile (p˂0.05). CONCLUSION: High maternal adherence to the FQS was associated with a high BM quality and antioxidant content of infant urine.

Maternal Adherence to a Dietary Approaches to Stop Hypertension (DASH) Dietary Pattern and the Relationship to Breast Milk Nutrient Content.

BACKGROUND: Maternal lifestyle factors, such as diet and nutritional status are likely to affect the composition of breast milk (BM). This study aimed to investigate the association between adherence to a Dietary Approaches to Stop Hypertension (DASH) dietary pattern (DP) and BM nutrient content. METHOD: A total of 700 milk samples were obtained from 350 lactating women. The dietary intakes of the women in the study were estimated using a validated food frequency questionnaire, which included 65 food items. The total antioxidant activity (TAC) of BM samples was evaluated using the Ferric reducing antioxidant power (FRAP), 2,2'-diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARS), and Ellman's assay. Also using commercially available kits, the total protein, calcium, and triglyceride contents in milk were determined. RESULTS: Individuals in the 3rd tertile of adherence to the DASH diet (highest adherence) consumed more dietary fiber, fruits, vegetables, nuts, legumes, and seeds, low-fat dairy, whole grain, less red and processed meat, sweetened beverages, and sodium than those in the first tertile (lowest adherence). Subjects in the 3rd tertile of DASH DP had higher values of milk DPPH and calcium compared to those in the first tertile (P < 0.05). Milk MDA and triglyceride were significantly lower in the 3rd tertile of DASH diet versus the first tertile (P < 0.05). CONCLUSION: Our study showed that high adherence to the DASH DP was associated with higher BM DPPH and calcium levels and lower amounts of BM MDA and triglyceride. The adherence to the healthy DPs such as the DASH can improve the quality of BM in lactating women.

The relationship between food quality score with inflammatory biomarkers, and antioxidant capacity in young women.

Diet has the potential to decrease oxidative stress and inflammation and this may be beneficial in several diseases. This study investigated the association between food quality score (FQS) with antioxidant and inflammatory properties in 171 apparently healthy young women. This cross-sectional study was conducted using a validated food frequency questionnaire to determine the dietary intake of participants. FQS was calculated by summing all the scores obtained from healthy and unhealthy food groups. The total antioxidant capacity and free radical scavenging activity of serum and urine were quantified using the ferric reducing/antioxidant power (FRAP) and α, α-diphenyl-ß-picrylhydrazyl (DPPH) methods, respectively. Malondialdehyde (MDA) was measured using the formation of thiobarbituric acid reactive substances (TBARS). White blood cell (WBC) and neutrophil counts, mean platelet volume (MPV) and red blood cell distribution width (RDW), were measured. Neutrophil: lymphocyte ratio (NLR), platelet: lymphocyte ratio (PLR), and RDW: platelet ratio (RPR) were also calculated. A high food quality (rich in fruit and vegetables, nuts, whole grain, and low intake of sweetened beverage, potato chips and fried food from outside the home) was related to lower hematological inflammatory biomarkers including WBC count, RDW, NLR, and PLR. Multivariable-adjusted odds ratios (95% CIs) demonstrated that higher FQS group (third tertile vs. first tertile) was associated with a significant lower levels of urinary FRAP (ORadj  = 0.82; 95%CI: 0.70 to 0.97), and DPPH. High food quality was associated with reduced of markers of inflammation and oxidative stress in Iranian young girl.

Evaluation of Serum Cortisol Levels and Response to Cosyntropin Test in Methadone-treated Opium Addicts.

Background: Opium has been used for thousands of years for medical and analgesic purposes, and its misuse has also increased in recent years. Methadone, a synthetic opioid, has been used as an analgesic and to help patients quit opium addiction. However, some evidence suggests that long-term use of opioids can affect the hypothalamic-pituitary-adrenal axis. Objectives: We aimed to evaluate the serum cortisol level and response to the cosyntropin stimulation test in opium addicts on methadone treatment. Methods: The study was conducted in November 2019 at Imam Reza Hospital Rehab Center, Birjand, Iran. Thirty-eight methadone-treated opium addicts participated in the study. A blood sample was initially obtained, then 250 µg intramuscular cosyntropin was injected. After 30 and 60 minutes, two other blood samples were obtained. The data were analyzed using SPSS. Results: There was a significant difference between serum cortisol levels and the normal value in methadone users (9.46 ± 5.42 vs. 14 µg/dL) (P < 0.001). The mean response to the cosyntropin stimulation test in methadone users was 9.34 ± 8.11 µg/dL. Also, 55% of the participants had adrenal insufficiency. Conclusions: Serum cortisol levels significantly differed from normal values in methadone-treated patients. Therefore, we recommend measuring serum cortisol levels in methadone-treated patients before major medical procedures to consider the stress doses of corticosteroids.

Association between adherence to the dietary approaches to stop hypertension (DASH) diet and maternal and infant sleep disorders.

BACKGROUND: Maternal diet is known to be important to both mother and infant health. The purpose of this study was to evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern (DP) and sleep problems in mothers and their infants. METHODS: The study included 350 breastfeeding mothers with an average age of 29.5 ± 5.9 years. Psychological functions were performed using standard questionnaires, including a Quality-of-Life Questionnaire (QLQ), Edinburgh Postnatal Depression Scale (EPDS), Spielberger Anxiety Questionnaire (SAQ), Pittsburg Sleep Quality Index (PSQI), and Infant Sleep Questionnaire (ISQ). Also, a standardized food frequency questionnaire (FFQ) was used to identify adherence to the DASH DP. RESULTS: Subjects in the highest tertile of DASH DP had significantly lower scores of mother's sleep latency (0.70 ± 1.18 vs. 1.24 ± 1.3; P value = 0.031), sleep disorders (4.3 ± 1.6 vs. 5.3 ± 2.4; P value= 0.032) and higher mother sleep efficiency compared to those in the lowest tertile (97.5 ± 89 vs. 54.8 ± 90; P value= 0.011). Also, infants of mothers with higher adherence to a DASH DP had lower sleep disorders compared with subjects with low adherence (4.9 ± 3.8 vs. 5.7 ± 3.2; P value= 0.017). After controlling for the mother's education, economic status, age, body mass index (BMI), and energy intake, adherence to the DASH pattern was associated with shorter sleep latency (ß = 0.60; 95%CI: 0.49-0.82), fewer sleep disorders score in mothers (ß = 0.92; 95%CI: 0.85-0.99) and their infants (ß = 0.90; 95%CI: 0.84-0.96) as well as high mother's sleep efficiency (ß = 1.2; 95%CI: 1.1-1.31). CONCLUSIONS: According to our findings, adherence to DASH DP is associated with a lower score for sleep disorders in mothers and their infants.

Effects of curcumin-piperine supplementation on systemic immunity in young women with premenstrual syndrome and dysmenorrhea: A randomized clinical trial.

INTRODUCTION: Premenstrual syndrome (PMS) and primary dysmenorrhea (PD) are common gynecological complications and there is evidence that inflammation may be an important factor in their etiology. There is a relationship between PMS and PD with susceptibility to allergic disorders. We aimed to assess the effect of curcumin co-administered with piperine on serum IL-10, IL-12 and IgE levels in patients with PD and PMS. MATERIALS AND METHODS: A sample of 80 patients were recruited to this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 40) and control groups (n = 40). Each participant received one capsule (500 mg of curcuminoid plus piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. RESULTS: Serum IgE, IL-10 and IL-12 levels were quantified by using an ELISA kit. No significant differences were found between the two groups at baseline, including: age, BMI, and dietary intakes (P > 0.05). Curcumin + piperine treatment was associated with a significant reduction in the mean serum levels of IgE [from 223.6 ± 258.7 IU/mL to 161.3 ± 240.7; P = 0.001]; but there were no significant changes in the placebo group (P = 0.12). Serum concentrations of IL-10 and IL-12 before and after the trial period did not differ significantly between the two groups (P > 0.05). CONCLUSION: Curcumin plus piperine might be have positive effect on serum IgE levels with no significant changes on serum IL-10 and IL-12 in healthy young women with PMS and PD. Studies with higher doses and longer durations of treatment with curcumin are required to confirm these findings.

Thymol has anticancer effects in U-87 human malignant glioblastoma cells.

BACKGROUND: Thymol (2-isopropyl-5-methylphenol) is a colorless crystalline derivative of cymene, that possesses pleotropic pharmacological properties, including analgesic, antibacterial, antispasmodic, and anti-inflammatory activities. Thymol has also been recognized for its beneficial effect as an anti-tumor agent, but the precise mechanism for this has not been fully elucidated. We aimed to identifying whether thymol exerts anti-cancer activity in human U-87 malignant glioblastoma (GB) cells (U-87). METHODS AND RESULTS: Cell viability and apoptosis was evaluated in U-87 cells treated with thymol at different concentrations. Reactive oxygen species (ROS) production, mRNA expressions of apoptosis-related genes and cell cycle characteristics were assessed. The cytotoxic activity of the co-exposure of thymol and temozolomide (TMZ) was also evaluated. The half-maximal inhibitory concentration (IC50) of thymol in the U-87 cells was 230 µM assessed at 24 h after exposure. Thymol did not exhibit any cytotoxic effects on normal L929 cells at this concentration. Thymol treatment increased the expression of Bax and p53, and also increased apoptotic cell death, and excessive generation of ROS. Moreover, the cytotoxic activity of thymol on the U-87 cells may be related to the arrest of the cell cycle at the G0/G1 interface. Combination therapy showed that the cytotoxic effects of thymol synergized with TMZ, and combined treatment had more cytotoxic potential compared to either of the agents alone. CONCLUSIONS: Our data indicate the potential cytotoxic activities of thymol on U-87 cells. Further studies are required to evaluate the spectrum of the antitumor activity of thymol on GB cells.

The association of maternal dietary quality and the antioxidant-proxidant balance of human milk.

BACKGROUND: Human milk composition varies over time within an individual mother as well as between lactating mothers due to several factors including maternal health, diet, and nutritional status. Therefore, improving nutrition status during gestation and breastfeeding is crucial for improving the health of both mothers and infants. Diet can enhance the oxidant-antioxidant balance of human milk. This study aimed to investigate the association between human milk oxidant-antioxidant balance with dietary patterns of lactating mothers identified by using principal component analysis. METHOD: This cross-sectional study included 350 breastfeeding women between the ages of 20 to 35 years. The dietary intakes of the women in the study were estimated using a validated food frequency questionnaire, which included 65 food items. The oxidant-antioxidant balance of milk samples was assessed using the ferric reducing antioxidant power (FRAP), 2, 2'-diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARs), and Ellman's assay. The milk concentration of total protein, calcium, and triglyceride was also measured using commercial kits. RESULT: Two predominant dietary patterns were recognized that we defined as a healthy and unhealthy pattern. There were higher levels of DPPH and thiol in the milk from mothers in the third tertile (highest adherence) of a healthy dietary pattern compared to the first tertile (lowest adherence; p < 0.05). Milk calcium and thiol were significantly lower in the third tertile of mothers with an unhealthy dietary pattern versus the first tertile (P < 0.05). In multivariate multinomial logistic regression analyses adjusted for mother's age, body mass index (BMI), energy intake, and infant's sex, adherence to a healthy dietary pattern was associated with higher levels of milk DPPH (OR = 1.32, 95% confidence interval (CI): 1.01, 1.80) and milk thiol (OR = 1.21, 95% CI: 1.10, 1.50). On the other adherence to the unhealthy dietary pattern was correlated with low levels of milk thiol (OR = 1.29; 95%CI: 1.09, 1.59) and milk calcium (OR = 1.28; 95%CI: 1.11, 1.55). CONCLUSION: Our findings demonstrated that adherence to a healthy dietary pattern, identified by higher consumption of green vegetables, other vegetables, and fruits is associated with a higher milk oxidant-antioxidant status in breastfeeding mothers.

Review on the Therapeutic Potential of Curcumin and its Derivatives on Glioma Biology.

Gliomas are common and aggressive brain tumors that carry a poor prognosis. The current multimodal therapeutic option for glioma includes surgery subsequently temozolomide chemotherapy and/or radiation; but gliomas are often associated with multidrug resistance, intensive adverse events, and tumor relapse. Thus, novel interventions that can enhance successful chemo-prevention and overcome therapeutic resistance are urgently needed. Phytochemicals have several biological properties with multi-target sites and relatively limited degrees of toxicity. Curcumin is a natural polyphenolic compound with several anti-tumor effects which potentially inhibit tumor growth, development, proliferation, invasion, dissemination, and angiogenesis in different human malignancies. Experimental model studies have demonstrated that curcumin attenuates glioma cell viability by G2/M cell cycle arrest, apoptosis, induction of autophagy, gene expression alteration, and disruption of multi-molecular pathways. Moreover, curcumin has been reported to re-sensitize cancer to chemotherapeutics as well as augment the effect of radiotherapy on glioma cells. In this review, we have provided an update on the in vitro and in vivo effects of curcumin-based therapy on gliomas. We have also discussed the use of curcumin in combination therapies, its effectiveness on drug-resistant cells, and new formulations of curcumin in the treatment of gliomas.

Molecular Targets of Curcumin and Its Therapeutic Potential for Ovarian Cancer.

Ovarian cancer is the fifth most common gynecological cancer in women globally. Conventional chemotherapy is the first therapeutic approach in the treatment of ovarian cancer, but its success is limited by severe side effects, transient response, and the high prevalence of relapse. Curcumin is a natural product found in the rhizome extract of Curcuma longa and has been extensively used over the last decades for its unique biological and medicinal properties, which include: having antioxidant, analgesic, anti-inflammation, and anti-tumor activities. Curcumin exerts its anticancer properties against ovarian cancer via multiple mechanisms: interfering with cellular interactions necessary for metastasis and recurrence of OC cells, increasing pro-apoptotic proteins as well as inducing or suppressing generation of different molecules such as cytokines, transcription factors, enzymes, protein kinases, and growth factors. Moreover, curcumin down-regulates various signaling pathways such as PI3K/Akt, Wnt/ß-catenin, JAK/STAT3, and MEK/ERK1/2 axes, which at least in part have a role in inhibiting further tumor proliferation, growth, and angiogenesis. In this review, we overview the potential of incorporating curcumin into the treatment of ovarian cancer. In particular, we summarize the preclinical evidence supporting its use in combination with current chemotherapeutic regimens as well as new analogues and formulations under investigation.