The Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges.

Hydrogen therapy has emerged as a possible approach for both preventing and treating cancer. Cancers are often associated with oxidative stress and chronic inflammation. Hydrogen, with its unique physiological functions and characteristics, exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties, making it an attractive candidate for cancer treatment. Through its ability to mitigate oxidative damage, modulate inflammatory responses, and sustain cellular viability, hydrogen demonstrates significant potential in preventing cancer recurrence and improving treatment outcomes. Preclinical studies have shown the efficacy of hydrogen therapy in several cancer types, highlighting its ability to enhance the effectiveness of conventional treatments while reducing associated side effects. Furthermore, hydrogen therapy has been found to be safe and well-tolerated in clinical settings. Nonetheless, additional investigations are necessary to improve a comprehensive understanding of the mechanisms underlying hydrogen's therapeutic potential and refine the administration and dosage protocols. However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies.

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.

Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

BACKGROUND: Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). OBJECTIVE: In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. RESULTS: Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. CONCLUSION: We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

Wortmannin Inhibits Cell Growth and Induces Apoptosis in Colorectal Cancer Cells by Suppressing the PI3K/AKT Pathway.

BACKGROUND: Colorectal cancer (CRC) remains a significant contributor to mortality, often exacerbated by metastasis and chemoresistance. Novel therapeutic strategies are imperative to enhance current treatments. The dysregulation of the PI3K/Akt signaling pathway is implicated in CRC progression. This study investigates the therapeutic potential of Wortmannin, combined with 5-fluorouracil (5-FU), to target the PI3K/Akt pathway in CRC. METHODS: Anti-migratory and antiproliferative effects were assessed through wound healing and MTT assays. Apoptosis and cell cycle alterations were evaluated using Annexin V/Propidium Iodide Apoptosis Assay. Wortmannin's impact on the oxidant/antioxidant equilibrium was examined via ROS, SOD, CAT, MDA, and T-SH levels. Downstream target genes of the PI3K/AKT pathway were analyzed at mRNA and protein levels using RTPCR and western blot, respectively. RESULTS: Wortmannin demonstrated a significant inhibitory effect on cell proliferation, modulating survivin, cyclinD1, PI3K, and p-Akt. The PI3K inhibitor attenuated migratory activity, inducing E-cadherin expression. Combined Wortmannin with 5-FU induced apoptosis, increasing cells in sub-G1 via elevated ROS levels. CONCLUSION: This study underscores Wortmannin's potential in inhibiting CRC cell growth and migration through PI3K/Akt pathway modulation. It also highlights its candidacy for further investigation as a promising therapeutic option in colorectal cancer treatment.

The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers.

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal-based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

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.

Dietary mineral intakes predict Coronavirus-disease 2019 (COVID-19) incidence and hospitalization in older adults.

BACKGROUND: The aim of this study was to determine the association between dietary mineral intake and Coronavirus-disease 2019 (COVID-19) infection and its associated hospitalization. METHODS: This cohort study utilized the MASHAD study population, which comprised individuals aged 35-65. Upon recruitment in 2007, dietary intake was documented using a validated 65-item food frequency questionnaire (FFQ). Data on COVID-19 PCR test results was collected from all relevant medical centers in Mashhad between February 2020 and June 2022. The regression model included dietary minerals and employed the backward variable selection method, along with advanced data analysis techniques. RESULTS: The final analysis involved 1957 participants, including 193 COVID-19-positive patients. The mean age was 49.71 and 50.28 years in the COVID-19-positive and negative groups, respectively (p = 0.12). Dietary intakes of magnesium, iron, and potassium were notably lower in COVID-19-positive patients (P < 0.05). Following adjustments for age and sex, dietary iron remained significantly associated with COVID-19 incidence (OR = 0.94, 95% CI: 0.90-0.98). Furthermore, a statistically significant relationship was observed between dietary zinc and hospitalization due to COVID-19 (OR = 0.69, 95% CI: 0.51-0.93). In dynamical system models, intakes of calcium, zinc, and iron below the cut-offs of 1138, 9.7, and 8.17 mg/day, respectively, were linked to an increased risk of COVID-19 incidence. CONCLUSION: Higher dietary iron and zinc intake are associated with decreased risk of COVID-19 infection and hospitalization, respectively.

Association between Genetic Variants Linked to Premature Ovarian Insufficiency and Inflammatory Markers: A Cross-Sectional Study.

BACKGROUND: Premature menopause (PM) is the cessation of ovarian function before age 40. PM women are more likely to have cardiovascular diseases (CVDs), diabetes, and mental disorders. This is the first study that assessed the association of single nucleotide polymorphisms (SNPs) with anti-heat shock protein 27 (Hsp27), High-sensitivity C-reactive protein (hs- CRP), and PM and serum pro-oxidant-antioxidant balance (PAB), as putative risk factors for CVDs. We aimed to explore the association of oxidative stress markers with eight different SNPs shown to be related to premature menopause. MATERIALS AND METHODS: In this cross-sectional research, we included 183 healthy women and 117 premature menopausal women. We determined baseline characteristics for all participants and measured serum hs-CRP, anti-HSP-27 antibody titer, and PAB levels using the established methods. Genotyping for eight SNPs was done using the tetra amplification refractory mutation system polymerase chain reaction (Tetra-ARMS PCR) and allele-specific oligonucleotide PCR (ASO-PCR) methods. RESULTS: We found a significant difference between mean serum PAB levels and the genetic variant of rs16991615 (P=0.03). ANCOVA showed a significant effect of the genotypes rs4806660 and rs10183486 on hs-CRP serum levels in the case and control groups, respectively (P=0.04 and P=0.007). ANCOVA also showed an association between rs244715 genotypes and anti-hsp27 serum levels in the case group (P=0.02). There was a significant effect of the genotypes of rs451417 on the serum hs-CRP level in the control group (P=0.03). CONCLUSION: There was a significant association of the genetic variants related to PM with oxidative stress and inflammatory markers (serum PAB, anti-hsp27 antibody, and hs-CRP). Accordingly, this seems to be an effective approach to predicting susceptible subjects for cardiovascular and mental disorders as well as various cancers.

Essential dataset features in a successful obesity registry: a systematic review.

BACKGROUND: The prevalence of obesity and the diversity of available treatments makes the development of a national obesity registry desirable. To do this, it is essential to design a minimal dataset to meet the needs of a registry. This review aims to identify the essential elements of a successful obesity registry. METHODS: We conducted a systematic literature review adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis recommendations. Google Scholar, Scopus and PubMed databases and Google sites were searched to identify articles containing obesity or overweight registries or datasets of obesity. We included English articles up to January 2023. RESULTS: A total of 82 articles were identified. Data collection of all registries was carried out via a web-based system. According to the included datasets, the important features were as follows: demographics, anthropometrics, medical history, lifestyle assessment, nutritional assessment, weight history, clinical information, medication history, family medical history, prenatal history, quality-of-life assessment and eating disorders. CONCLUSIONS: In this study, the essential features in the obesity registry dataset were demographics, anthropometrics, medical history, lifestyle assessment, nutritional assessment, weight history and clinical analysis items.

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.

The effects of powdered drinks enriched with curcumin and probiotics on lipid profile and atherogenic indices in patients with metabolic syndrome: A randomized, double-blinded, placebo-controlled clinical trial.

Cardiovascular disease is prevalent globally and is the most common complication of metabolic syndrome (MetS). Previous studies have suggested that curcumin and probiotics may improve the lipid profile, so we aimed to investigate the effects of the edible powder enriched with these substances on lipid profile level and atherogenic indices such as Atherogenic Coefficient (AC), Castelli Risk Index-I (CRI-I), Castelli Risk Index-II (CRI-II), and Atherogenic Index of Plasma (AIP). In the present parallel randomized double-blinded placebo-controlled clinical trial, 124 people with MetS with overweight or obesity were randomly allocated to 4 groups and were followed up for 8 weeks. The participants received a low-calorie diet and a daily sachet of enriched powder drink. The sachets contained either 109 CFU of probiotics or 1 g of curcumin, or probiotic + curcumin (pro + cur), or placebo, respectively. The fasting lipid profile and atherogenic indices were measured at the beginning and end of the study. One hundred and fourteen participants completed the study. At the end of the study, the within- and between-group comparisons showed no significant differences in lipid profile and atherogenic indices (p > .05). Based on the results of the current study, taking an oral powder containing 1 g curcumin and 109 CFU probiotics for 8 weeks had no effect on the lipid profile level and atherogenic indices; however, more studies are recommended.

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.

Interplay between LncRNA/miRNA and TGF-ß Signaling in the Tumorigenesis of Gynecological Cancer.

Gynecologic cancers are among the most common malignancies with aggressive features and poor prognosis. Tumorigenesis in gynecologic cancers is a complicated process that is influenced by multiple factors, including genetic mutations that activate various oncogenic signaling pathways, including the TGF-ß pathway. Aberrant activation of TGF-ß signaling is correlated with tumor recurrence and metastasis. It has been shown that non-coding RNAs (ncRNAs) have crucial effects on cancer cell proliferation, migration, and metastasis. Upregulation of various ncRNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs), has been reported in several tumors, like cervical, ovarian, and endometrial cancers, but their cellular mechanisms remain to be investigated. Thus, recognizing the role of ncRNAs in regulating the TGF-ß pathway may provide novel strategies for better treatment of cancer patients. The present study summarizes recent findings on the role of ncRNAs in regulating the TGF-ß signaling involved in tumor progression and metastasis in gynecologic cancers.

Night eating habits, sleep quality, and depression, are they associated with vitamin D status?

INTRODUCTION: In addition to the well-established roles of vitamin D on bone health, it also appears to be an effective factor on mental health and circadian behaviors, that include eating and sleeping habits. OBJECTIVE: This study aimed to assess the association between vitamin D status with night eating habits, sleep quality and depression in female college students. MATERIALS AND METHODS: This cross-sectional study studied healthy female students from Shiraz University of Medical Sciences, Iran. Demographic and anthropometric information as well as data on sleep quality and depression were recorded and serum levels of 25-hydroxyvitamin D were measured. A 3-day food record questionnaire was completed to assess night eating habits. Data analyses were undertaken using Chi-square, Mann-Whitney U test and logistic regression. A P-value of <0.05 was considered significant. RESULTS: The study participants comprised of 272 female students with median (Inter Quartile Range) age of 22 (21-24) years. The majority of the participants (82.3 %) were classified as night eaters, who had higher rates of poor sleep quality compared to non-night eaters (P < 0.05). With 1 ng/ml increase in serum levels of 25-hydroxyvitamin D, the odds of being a night eater fell by 3 % (OR = 0.97; 95%CI = 0.95, 0.99), and the odds of having depression or poor sleep quality decreased by 5 % (OR = 0.95; 95%CI = 0.93, 0.97) and 6 % (OR = 0.94; 95%CI = 0.91, 0.97), respectively. CONCLUSION: There was an inverse association between serum 25-hydroxyvitamin D level with night eating habits, depression and poor sleep quality. This association needs be confirmed using cohort and interventional studies.

The Potential Therapeutic Applications of CRISPR/Cas9 in the Treatment of Gastrointestinal Cancers.

Gastrointestinal (GI) cancer is one the most prevalent types of cancer. Despite current chemotherapy's success, patients with GI cancer continue to have a dismal outcome. The onset and progression of cancer are caused by alterations and the abnormal expression of several families of genes, like tumor-suppressor genes, oncogenes, and chemotherapy-resistant genes. The final purpose of tumor therapy is to inhibit cellular development by modifying mutations and editing the irregular expression of genes It has been reported that CDH1, TP53, KRAS, ARID1A, PTEN, and HLA-B are the commonly mutated genes in GI cancer. Gene editing has become one potential approach for cases with advanced or recurrent CRC, who are nonresponsive to conventional treatments and a variety of driver mutations along with progression cause GI progression. CRISPR/Cas9 technique is a reliable tool to edit the genome and understand the functions of mutations driving GI cancer development. CRISPR/Cas9 can be applied to genome therapy for GI cancers, particularly with reference to molecular-targeted medicines and suppressors. Moreover, it can be used as a therapeutic approach by knocking in/out multiple genes. The use of CRISPR/ Cas9 gene editing method for GI cancer therapy has therefore resulted in some improvements. There are several research works on the role of CRISPR/Cas9 in cancer treatment that are summarized in the following separate sections. Here, the use of CRISPR/Cas9-based genome editing in GI and the use of CRISPR/Cas9 is discussed in terms of Targeting Chemotherapy Resistance-related Genes like; KRAS, TP53, PTEN, and ARID1A.

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.

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.

Genetic Determinants of Response to Statins in Cardiovascular Diseases.

Despite extensive efforts to identify patients with cardiovascular disease (CVD) who could most benefit from the treatment approach, patients vary in their benefit from therapy and propensity for adverse drug events. Genetic variability in individual responses to drugs (pharmacogenetics) is considered an essential determinant in responding to a drug. Thus, understanding these pharmacogenomic relationships has led to a substantial focus on mechanisms of disease and drug response. In turn, understanding the genomic and molecular bases of variables that might be involved in drug response is the main step in personalized medicine. There is a growing body of data evaluating drug-gene interactions in recent years, some of which have led to FDA recommendations and detection of markers to predict drug responses (e.g., genetic variant in VKORC1 and CYP2C9 genes for prediction of drug response in warfarin treatment). Also, statins are widely prescribed drugs for the prevention of CVD. Atorvastatin, fluvastatin, rosuvastatin, simvastatin, and lovastatin are the most common statins used to manage dyslipidemia. This review provides an overview of the current knowledge on the pharmacogenetics of statins, which are being used to treat cardiovascular diseases.

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.

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.