Microbiome as a biomarker and therapeutic target in pancreatic cancer.

Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.

Association of high-sensitivity C-reactive protein and hematologic-inflammatory indices with risk of cardiovascular diseases: a population-based study with partial least squares structural equation modeling approach.

Partial least squares structural equation modeling is a simple approach that may be used to determine the factors associated with diseases. In the current study, we aimed to explore the most associated high-sensitivity C-reactive protein (hs-CRP) as well as hematologic-inflammatory indices for the risk of cardiovascular disease (CVD). A total of 7362 healthy (non-CVD) participants aged 35-65 years old from baseline investigation were evaluated in the Phase 2 follow-up. Of these, 1022 individuals were found to have CVDs in the second phase (10-year follow-up) of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. We used partial least squares structural equation modeling to develop a prediction model for association of CVD risk factors and hs-CRP as well as hematologic-inflammatory indices in the study population. According to the study, age had the most significant impact on the presence of CVD. Increasing in age by one unit raises the risk of CVD by 0.166. Also, serum hs-CRP was found to have the second-highest impact on CVD; increasing in age by one unit raises the risk of CVD by 0.042. The study also discovered a strong and significant correlation between red cell distribution width (RDW) and CVD. Moreover, the study found that several factors such as hemoglobin (HGB), neutrophil (NEUT), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and platelet-to-lymphocyte ratio (PLR) have indirect effects on CVD that are mediated by hs-CRP while controlling for age, sex and social-economic factors. Generally, the results showed that age, hs-CRP, and RDW were the most important risk factors on CVD.

The protective effect of parthenolide in an in vitro model of Parkinson's disease through its regulation of nuclear factor-kappa B and oxidative stress.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, and is due to the degeneration of dopaminergic neurons. It is multifactorial, caused by genetic and environmental factors and currently has no definitive cure. We have investigated the protective effects of parthenolide (PTN), a compound with known anti-inflammatory and antioxidant properties, in an in vitro model of PD, that is induced by 6-OHDA, and that causes neurotoxicity in SH-SY5Y human neuroblastoma cells. METHODS AND RESULTS: SH-SY5Y cells were pretreated with PTN to assess its protective effects in 6-OHDA-induced cellular damage. Cell viability was measured using Alamar blue. Apoptosis was evaluated using an Annexin V-FITC/PI kit. Reactive oxygen species (ROS) levels were quantified, and expression levels of apoptotic markers (Bax, Bcl-2, p53) and NF-κB were analyzed via Western blotting and Quantitative real-time- (qRT-) PCR. We found that 6-OHDA reduced cell viability, that was inhibited significantly by pre-treatment with PTN (p < 0.05). Flow cytometry revealed that PTN reduced apoptosis induced by 6-OHDA. PTN also reduced the ROS levels raised by 6-OHDA (p < 0.05). Moreover, PTN decreased the expression of Bax, p53, NF-κB, and p-NF-κB that were increased by treatment with 6-OHDA. CONCLUSION: These findings indicate the potential beneficial effects of PTN in an in vitro model of PD via mitigating oxidative stress and inflammation, suggested PTN as a promising agent to be used for PD therapy, warranting further investigation in preclinical and clinical studies.

The associations of oxidative stress and inflammatory markers with obesity in Iranian population: MASHAD cohort study.

BACKGROUND: Low-grade inflammation and stress oxidative condition play a role in the pathogenesis of obesity, and the serum levels of these markers, such as pro-oxidant-antioxidant balance (PAB), high-sensitivity C-reactive protein (hs-CRP), and uric acid may indicate obesity progression. In this study, we aimed to investigate the relationship between obesity with PAB, hs-CRP, and uric acid in the Iranian population. METHODS: This study was derived from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. A total of 7985 subjects aged 35 to 65 years were divided into three groups according to body mass index (BMI) as: normal, overweight and obese groups. Anthropometric indices and biochemical parameters such as PAB, superoxide dismutase type 1 (SOD1), hs-CRP, and uric acid were measured in all the participants. We evaluated the association of obesity with inflammatory factors by using multivariate regression analysis. Also, those participants with hypertension, an endocrine disorder, history of cardiovascular diseases and diabetes mellitus were excluded from the study. RESULTS: There was a positive significant correlation between BMI and serum PAB, hs-CRP and uric acid (p < 0.001). While no statistically significant relation was observed between BMI and SOD1 (p = 0.85). Multivariate regression analysis showed that the risk of overweight and obesity increased 1.02 and 1.03-fold according to increase 10 units of PAB raise in comparison to reference group (normal weight) [(odds ratio (OR): 1.02, 95% CI (1.01-1.03)] and [OR: 1.03, 95% CI (1.01-1.04)], respectively). In addition, hs-CRP serum concentration was significantly associated with a high risk of obesity [(OR: 1.02; 95% CI (1.01-1.03)]. While the high levels of serum uric acid were associated with increased odds of overweight and obesity risk [OR: 1.4; CI (1.39-1.58) and OR: 1.76; CI (1.63-1.89), respectively]. CONCLUSIONS: Generally, we showed a significant association between BMI and serum PAB, hs-CRP values and uric acid levels, suggesting the role of these factors as risk stratification factors for obesity.

Association of T-wave electrocardiogram changes and type 2 diabetes: a cross-sectional sub-analysis of the MASHAD cohort population using the Minnesota coding system.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) has become a major health concern with an increasing prevalence and is now one of the leading attributable causes of death globally. T2DM and cardiovascular disease are strongly associated and T2DM is an important independent risk factor for ischemic heart disease. T-wave abnormalities (TWA) on electrocardiogram (ECG) can indicate several pathologies including ischemia. In this study, we aimed to investigate the association between T2DM and T-wave changes using the Minnesota coding system. METHODS: A cross-sectional study was conducted on the MASHAD cohort study population. All participants of the cohort population were enrolled in the study. 12-lead ECG and Minnesota coding system (codes 5-1 to 5-4) were utilized for T-wave observation and interpretation. Regression models were used for the final evaluation with a level of significance being considered at p < 0.05. RESULTS: A total of 9035 participants aged 35-65 years old were included in the study, of whom 1273 were diabetic. The prevalence of code 5-2, 5-3, major and minor TWA were significantly higher in diabetics (p < 0.05). However, following adjustment for age, gender, and hypertension, the presence of TWAs was not significantly associated with T2DM (p > 0.05). Hypertension, age, and body mass index were significantly associated with T2DM (p < 0.05). CONCLUSIONS: Although some T-wave abnormalities were more frequent in diabetics, they were not statistically associated with the presence of T2DM in our study.

Triglyceride glucose index and triglyceride HDL ratio as predictors of coronary artery stenosis in diabetic and non-diabetic patients.

BACKGROUND AND AIM: The current study investigated the association between triglyceride-glucose index (TyG) and triglyceride/HDL-C indices and coronary atherosclerosis extent in diabetic and non-diabetic patients. METHODS AND RESULTS: In this case-control study, 1538 individuals were classified into two groups: diabetic and non-diabetic subjects. Each group was further grouped as follows: (1) angiography+ (2) angiography-and (3) subjects without a history of cardiovascular diseases. The TyG and TG/HDL-C indices were compared between the subgroups of the diabetic (n = 407) and non-diabetic (n = 1131) groups. In both diabetic and non-diabetic patients, there was no significant association in TG/HDL-C; and diabetic subjects, angiography+ and angiography-groups had significantly higher TyG (p < 0.05). A high TyG index was associated with a higher risk of angiography+ (OR: 1.883 (1.410-2.514)). CONCLUSIONS: The TyG index, but not the TG/HDL-C, was an independent marker for predicting the severity of coronary stenosis in non-diabetic patients.

Anxiety, a significant risk factor for coronary artery disease: what is the best index.

BACKGROUND: Coronary artery disease (CAD) is known as the leading cause of disability and death globally. Anxiety disorders are also recognized as common types of mental disorders that substantially impact global health. Iran ranks among the countries with a high incidence of CAD and anxiety disorders. Therefore, the present study aims to determine the potential association and epidemiological aspects of anxiety and CAD within the population of Mashhad, the second most popoulos city in Iran. METHODS: The present study is based on extracted data from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study which is a 10-year prospective cohort study intended to assess the effects of various CAD risk factors among Mashhad city residents. Anxiety scores were assessed at the baseline using Beck Anxiety Inventory and individuals were classified based on the BAI 4-factor structure model which included autonomic, cognitive, panic, and neuromotor components. Accordingly, the association between baseline anxiety scores and the BAI four-factor model with the risk of CAD events was analyzed using SPSS software version 21. RESULTS: Based on the results, 60.4% of the sample were female, and 5.6% were classified as having severe forms of anxiety. Moreover, severe anxiety was more prevalent in females. Results showed a 1.7% risk of CAD (p-value < 0.001) over 10 years with one unit increase in anxiety score. Based on the 4-factor model structure, we found that only panic disorder could significantly increase the risk of CAD by 1.1% over the 10-year follow-up (p-value < 0.001). CONCLUSION: Anxiety symptoms, particularly panic disorder, are independently and significantly associated with an increased overall risk of developing CAD over a 10-year period. Therefore, further studies are warranted to investigate the mechanisms through which anxiety may cause CAD, as well as possible interventions to mitigate these processes.

The association between lifelines diet score (LLDS) with depression and quality of life in Iranian adolescent girls.

BACKGROUND: It has been proposed that a greater degree of adherence to a healthy dietary pattern is associated with a lower risk of depression and a poor quality of life (QoL). The Lifelines diet score (LLDS) is a new, evidence-base scoring system to define the quality of diet. We designed a cross-sectional study to investigate the association between LLDS with depression and QoL in Iranian adolescent girls. METHODS: A total of 733 female adolescents were recruited from Mashhad and Sabzevar cities, Iran. Depression and QoL were assessed utilizing the Beck Depression Inventory (BDI) and SF-12v2 questionnaires, respectively. The LLDS was defined by dividing intakes of 12 food groups with negative or positive health effects into quintiles ranging 12 to 60 points. To explore the association between LLDS with QoL and depression, logistic regression was used in crude and adjusted models. RESULTS: The prevalence of depression and poor QoL was 24% and 49%, respectively. After adjusting for confounding factors, adolescent girls in the highest quartile of LLDS compared with the participants in the lowest quartile had a 42% lower probability of reporting depressive symptoms (OR: 0.58; 95% CI: 0.35-0.97, P = 0.03). In addition, the participants in the highest quartile of LLDS had lower odds of poor QoL compared with the subjects in the lowest quartile (OR: 0.65; 95% CI: 0.42-0.92, P = 0.04). CONCLUSIONS: There is an inverse relationship between LLDS with risk of depression and poor QoL. Prospective and interventional investigations are needed to reach a clear vision.

The association between hyperuricemia and insulin resistance surrogates, dietary- and lifestyle insulin resistance indices in an Iranian population: MASHAD cohort study.

BACKGROUND: Previous studies have reported insulin resistance (IR) to be associated with hyperuricemia. In this study, we aimed to assess the possible associations between the empirical dietary index for IR (EDIR), the empirical lifestyle index for IR (ELIR), and non-insulin-based surrogates (triglyceride-glucose (TyG) index, triglyceride-to-high-density-lipoprotein-cholesterol (TG/HDL-C) ratio, metabolic score for insulin resistance (METS-IR) and TyG with body mass index (TyG-BMI)) and hyperuricemia in an Iranian population. METHODS: In this cross-sectional study, 6457 participants aged 35-65 years were recruited as part of the MASHAD cohort study. EDIR and ELIR were calculated using dietary intakes, body mass index, and physical activity information. Insulin resistance surrogates including TyG, TyG-BMI, TG/HDL-C, and METS-IR were calculated for all participants. Hyperuricemia was defined as serum uric acid ≥ 7 mg/dl in men or ≥ 6 mg/dl in women. Multivariable logistic regression models were applied to determine the association between indexes of IR and hyperuricemia. RESULTS: The mean ELIR and IR surrogates (TyG, TyG-BMI, TG/ HDL, and METS-IR) were significantly higher in subjects with hyperuricemia compared to non-hyperuricemic subjects (p < 0.001). After adjusting for confounding variables, the association between hyperuricemia and EDIR was not significant, but ELIR had a significant association in all models (p < 0.001). All four IR surrogates (TyG, TyG-BMI, TG/ HDL, and METS-IR) showed a significant association with hyperuricemia (p < 0.001). CONCLUSION: There was a significant association between indexes of insulin resistance: TyG, TyG-BMI, TG/HDL-c, METS-IR, and ELIR with hyperuricemia, in a population sample from northeastern Iran.

Micronutrients intake and genetic variants associated with premature ovarian insufficiency; MASHAD cohort study.

BACKGROUND AND AIM: premature ovarian insufficiency (POI) is defined as the menopause before 40 years of age, and its prevalence is reported to be two-fold higher in Iranian women than the average for woman globally. POI is associated with several cardio/cerebrovascular complications as well as an increased overall mortality. Genetic factors, and serum levels of minerals and vitamin D, have been reported to be related to the prevalence of POI. We have investigated the association between some POI -related genotypes with the serum levels of some important micronutrients. METHODS: One hundred and seventeen women with POI and 183 controls without any renal, hepatic, and thyroid abnormalities were recruited as part of the MASHAD study. Demographic and anthropometric features were recorded and blood samples were collected and processed. DNA was extracted from the buffy coat of blood samples from all participants and 8 POI-related single nucleotide polymorphisms (SNPs) were determined using ASO-PCR or Tetra ARMS-PCR. Serum minerals and vitamin D concentrations were measured using routine methods. RESULTS: In women with POI, serum copper, phosphate, and calcium were significantly different for those with rs244715, rs16991615, and rs4806660 genotypes, respectively. In our control population, significant differences were also found in serum copper concentrations between different genotypes of rs4806660, rs7246479, rs1046089, and rs2303369. After adjusting for all confounding factors, the women with POI carrying TC genotype (rs4806660) had a lower risk to have serum copper levels < 80 (µg/dL) than those carrying a TT genotype. Furthermore, women with POI carrying GG genotype (rs244715) had a 6-fold higher risk to have serum copper levels > 155 than those carrying AA genotype. CONCLUSION: The C and G alleles of the rs4806660 and rs244715 polymorphisms respectively are independently associated with serum copper in women with POI. Further studies are necessary to investigate the association of serum copper and other micronutrients in women and other POI -related polymorphisms.

Predicting the 10-year incidence of dyslipidemia based on novel anthropometric indices, using data mining.

BACKGROUND: The aim was to establish a 10-year dyslipidemia incidence model, investigating novel anthropometric indices using exploratory regression and data mining. METHODS: This data mining study was conducted on people who were diagnosed with dyslipidemia in phase 2 (n = 1097) of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study, who were compared with healthy people in this phase (n = 679). The association of dyslipidemia with several novel anthropometric indices including Conicity Index (C-Index), Body Roundness Index (BRI), Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), Abdominal Volume Index (AVI), Weight-Adjusted-Waist Index (WWI), A Body Shape Index (ABSI), Body Mass Index (BMI), Body Adiposity Index (BAI) and Body Surface Area (BSA) was evaluated. Logistic Regression (LR) and Decision Tree (DT) analysis were utilized to evaluate the association. The accuracy, sensitivity, and specificity of DT were assessed through the performance of a Receiver Operating Characteristic (ROC) curve using R software. RESULTS: A total of 1776 subjects without dyslipidemia during phase 1 were followed up in phase 2 and enrolled into the current study. The AUC of models A and B were 0.69 and 0.63 among subjects with dyslipidemia, respectively. VAI has been identified as a significant predictor of dyslipidemias (OR: 2.81, (95% CI: 2.07, 3.81)) in all models. Moreover, the DT showed that VAI followed by BMI and LAP were the most critical variables in predicting dyslipidemia incidence. CONCLUSIONS: Based on the results, model A had an acceptable performance for predicting 10 years of dyslipidemia incidence. Furthermore, the VAI, BMI, and LAP were the principal anthropometric factors for predicting dyslipidemia incidence by LR and DT models.

Factors associated with prolonged QTc interval in Iranian population: MASHAD cohort study.

AIM: QTc interval prolongation is a growing global issue which can cause torsades de pointes, a potentially fatal arrhythmia. We aimed to identify risk factors for prolonged QT interval in men and women. METHODS: The Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study collected electrocardiogram interval data. QT was corrected for heart rate using the Bazett's formula. Ordinal logistic regression with crude (univariable) and adjusted (multivariate) association analyses in the form of odds ratio and corresponding 95% confidence interval (CI) were used to identify the factors associated with QTc prolongation. RESULTS: A total of 8878 individuals including 5318 females and 3560 males, aged 35 to 65 years, were included in this cross-sectional study. Participants with QTc prolongation were more likely to be older and have hypercholesterolemia, hypertension (HTN), and Type 2 diabetes mellitus (T2DM), but to have lower levels of physical activity (P < 0.05). Age (OR = 1.68, 95%CI = 1.18-2.39), hypercholesterolemia (OR = 1.77, 95%CI = 1.24-2.51), HTN (OR = 1.36, 95%CI = 1.06-1.73), T2DM (OR = 1.59, 95%CI = 1.19-2.13), severe anxiety (OR = 1.80, 95%CI = 1.05-3.11) and mild depression (OR = 1.38, 95%CI = 1.01-1.88) were independent risk factors for prolonged QTc interval in men. For women, only HTN (OR = 1.29, 95%CI = 1.02-1.63) and T2DM (OR = 1.50, 95%CI = 1.14-1.97) were independent risk factors. CONCLUSIONS: Older age, Hypercholesterolemia, HTN, T2DM, severe anxiety and mild depression in men, and HTN and T2DM in women were associated with high risk of prolonged QTc interval. Healthcare practitioners should be aware of the risk factors of QTc interval prolongation and should exercise caution in the management of certain patients.

Age-specific reference intervals for routine biochemical parameters in healthy neonates, infants, and young children in Iran.

Age and sex need to be considered in the establishment of reference intervals (RIs), especially in early life when there are dynamic physiological changes. Since data for important biomarkers in healthy neonates and infants are limited, particularly in Iranian populations, we have determined age-specific RIs for 7 laboratory biochemical parameters. This cross-sectional study comprised a total of 344 paediatric participants (males: 158, females: 186) between the ages of 3 days and 30 months (mean age: 12.91 ± 7.15 months). Serum levels of creatinine, urea, uric acid, calcium, phosphate, vitamin D and high-sensitivity C-reactive protein (hs-CRP) were measured using an Alpha classic-AT plus auto-analyser. We determined age-specific RIs using CLSI Ep28-A3 and C28-A3 guidelines. No sex partitioning was required for any of the biomarkers. Age partitioning was required for kidney function tests and phosphate. The serum concentration of urea and creatinine increased with age, while phosphate and uric acid decreased with age. Age partitioning was not required for serum calcium, vitamin D, and hs-CRP, which remained relatively constant throughout the age range. Age-specific RIs for 7 routine biochemical markers were determined to address critical gaps in RIs in early life to help improve clinical interpretation of blood test results in young children, including neonates. Established age partitions demonstrate the biochemical changes that take place during child growth and development. These novel data will ultimately better disease management in the Iranian paediatric population and can be of value to clinical and hospital laboratories with similar populations.

The nexus of natural killer cells and melanoma tumor microenvironment: crosstalk, chemotherapeutic potential, and innovative NK cell-based therapeutic strategies.

The metastasis of melanoma cells to regional lymph nodes and distant sites is an important contributor to cancer-related morbidity and mortality among patients with melanoma. This intricate process entails dynamic interactions involving tumor cells, cellular constituents, and non-cellular elements within the microenvironment. Moreover, both microenvironmental and systemic factors regulate the metastatic progression. Central to immunosurveillance for tumor cells are natural killer (NK) cells, prominent effectors of the innate immune system with potent antitumor and antimetastatic capabilities. Recognizing their pivotal role, contemporary immunotherapeutic strategies are actively integrating NK cells to combat metastatic tumors. Thus, a meticulous exploration of the interplay between metastatic melanoma and NK cells along the metastatic cascade is important. Given the critical involvement of NK cells within the melanoma tumor microenvironment, this comprehensive review illuminates the intricate relationship between components of the melanoma tumor microenvironment and NK cells, delineating their multifaceted roles. By shedding light on these critical aspects, this review advocates for a deeper understanding of NK cell dynamics within the melanoma context, driving forward transformative strategies to combat this cancer.

The circadian clock as a potential biomarker and therapeutic target in pancreatic cancer.

Pancreatic cancer (PC) has a very high mortality rate globally. Despite ongoing efforts, its prognosis has not improved significantly over the last two decades. Thus, further approaches for optimizing treatment are required. Various biological processes oscillate in a circadian rhythm and are regulated by an endogenous clock. The machinery controlling the circadian cycle is tightly coupled with the cell cycle and can interact with tumor suppressor genes/oncogenes; and can therefore potentially influence cancer progression. Understanding the detailed interactions may lead to the discovery of prognostic and diagnostic biomarkers and new potential targets for treatment. Here, we explain how the circadian system relates to the cell cycle, cancer, and tumor suppressor genes/oncogenes. Furthermore, we propose that circadian clock genes may be potential biomarkers for some cancers and review the current advances in the treatment of PC by targeting the circadian clock. Despite efforts to diagnose pancreatic cancer early, it still remains a cancer with poor prognosis and high mortality rates. While studies have shown the role of molecular clock disruption in tumor initiation, development, and therapy resistance, the role of circadian genes in pancreatic cancer pathogenesis is not yet fully understood and further studies are required to better understand the potential of circadian genes as biomarkers and therapeutic targets.

Association between biochemical and hematologic factors with COVID-19 using data mining methods.

BACKGROUND AND AIM: Coronavirus disease (COVID-19) is an infectious disease that can spread very rapidly with important public health impacts. The prediction of the important factors related to the patient's infectious diseases is helpful to health care workers. The aim of this research was to select the critical feature of the relationship between demographic, biochemical, and hematological characteristics, in patients with and without COVID-19 infection. METHOD: A total of 13,170 participants in the age range of 35-65 years were recruited. Decision Tree (DT), Logistic Regression (LR), and Bootstrap Forest (BF) techniques were fitted into data. Three models were considered in this study, in model I, the biochemical features, in model II, the hematological features, and in model II, both biochemical and homological features were studied. RESULTS: In Model I, the BF, DT, and LR algorithms identified creatine phosphokinase (CPK), blood urea nitrogen (BUN), fasting blood glucose (FBG), total bilirubin, body mass index (BMI), sex, and age, as important predictors for COVID-19. In Model II, our BF, DT, and LR algorithms identified BMI, sex, mean platelet volume (MPV), and age as important predictors. In Model III, our BF, DT, and LR algorithms identified CPK, BMI, MPV, BUN, FBG, sex, creatinine (Cr), age, and total bilirubin as important predictors. CONCLUSION: The proposed BF, DT, and LR models appear to be able to predict and classify infected and non-infected people based on CPK, BUN, BMI, MPV, FBG, Sex, Cr, and Age which had a high association with COVID-19.

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.

Association of dietary and blood inflammatory indicators with depression, anxiety, and stress in adults with vitamin D deficiency.

BACKGROUND: There is growing evidence that vitamin D may be related to mental health. The aim of the current study was to investigate the association of dietary and blood inflammatory factors with mental health disorders in subjects with vitamin D deficiency, shedding further light on the complex interplay of these conditions. METHOD: In this cross-sectional study, 306 subjects completed the validated Depression, Anxiety, and Stress Scale questionnaire to evaluate their depression, anxiety, and stress scores. Dietary inflammatory index (DII) and healthy eating index (HEI) were calculated using a validated 65-item food frequency questionnaire. Blood samples were taken and vitamin D, cytokine, and hs-CRP levels were measured using enzyme-linked immunosorbent assay kits. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) were calculated using standard laboratory methods. RESULTS: The subjects were divided into two groups based on their vitamin D levels: a vitamin D < 20 µg/dl group (N = 257) and a vitamin D ≥ 20  µg/dl group (N = 49). Between group analysis revealed that only DII (p = 0.015), platelet (p = 0.04), and hs-CRP (p = 0.015) were significantly different. In adults with vitamin D levels below 20 µg/dl, NLR and DII were significantly higher in subjects with anxiety (p < 0.05), and this relationship remained significant only for NLR after adjusting for age and sex. Additionally, PLR and HEI were significantly different in depressed compared to non-depressed subjects, and this association remained significant only for HEI after adjusting for age and sex. CONCLUSION: In subjects with vitamin D deficiency, increased levels of PLR, NLR, and DII were associated with depression and anxiety, while HEI was negatively associated with depression. These associations were not found in subjects with vitamin D levels ≥20 µg/dl.

Dietary acid load, depression, and anxiety: results of a population-based study.

BACKGROUND: Dietary acid load seems to be associated with psychological disorders through several mechanisms, and may barricade their treatment and recovery. The aim of current study was to evaluate the relationship between dietary acid load, using potential renal acid load (PRAL) and dietary acid load (DAL) scores, with the severity of depression and anxiety among Iranian adults. METHODS: A total of 6531 participants aged 35-65 years were recruited in this cross-sectional study. A validated food frequency questionnaire (FFQ) was used to assess dietary intakes of participants. DAL was estimated using PRAL and DAL scores. Depression and anxiety were screened using Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). RESULTS: In the fully adjusted model, women with the highest DAL or PRAL had higher odds of more severe depression compared to those in the lowest category (OR = 1.20; 95% CI = 1.03-1.42 and OR = 1.20; 95% CI = 1.03-1.39, respectively). No significant association was observed between DAL and PRAL and depression severity in men and in the population as a whole. Regarding the association between PRAL and anxiety severity, there was no significant association when separated by sex. However, in the fully adjusted model for the whole population, participants in the highest tertile of PRAL had 13% greater odds of more severe anxiety than the lowest tertile (OR: 1.13, 95% CI: 1.01-1.13). No significant association was observed between DAL and anxiety severity in women, men or in the whole population. CONCLUSION: Women, but not men, with higher dietary acid load had significantly higher odds of having more severe depression. A significant positive association was also observed between dietary acid load and anxiety in the whole population.

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.