Curcuminoid-Piperine Combination Improves Radical Scavenging Activity in Women with Premenstrual Syndrome and Dysmenorrhea: A Post-hoc Analysis of a Randomized Clinical Study.

Oxidative stress maybe involved in the patho-etiology of menstrual-associated complications. Curcuminoids, are polyphenolic natural compounds that have potentially important functional activities. This triple-blind, randomized, placebo-controlled trial was performed to investigate the effects of a curcuminoids on oxidative stress and antioxidant capacity in girls with premenstrual syndrome (PMS) and dysmenorrhea. Eighty young girls with both PMS and dysmenorrhea were randomly given either curcuminoids (500 mg+5 mg piperine) or a placebo daily, for a period from 7 days pre- until 3 days post- initiation of menstrual bleeding for 3 successive menstrual cycles. The total antioxidant capacity and free radical scavenging activity of serum and urine were quantified via ferric reducing/antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) methods, respectively. There were no significant differences between the placebo and curcumin groups, with respect to the age, dietary intake and biochemical/anthropometric indices (p>0.05). The curcumin treatment significantly increased the free-radical scavenging activity of serum compared to the treatment with placebo (p=0.031). Although, no significant changes were found in serum and urinary levels of FRAP, DPPH and MDA between the groups (p>0.05). Curcumin treatment did increase free-radical scavenging activity and antioxidant potential in girls with PMS and dysmenorrhea. Investigations with higher doses and duration of curcumin are required to verify our findings.

Medicinal Chemistry of Antisense Oligonucleotides for Therapeutic Use in SARS-CoV-2: Design Strategies and Challenges for Targeted Delivery.

BACKGROUND: The evolution of novel Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) strains with greater degrees of infectivity, resistance to vaccine-induced acquired immunity, and more severe morbidity have contributed to the recent spread of COVID-19. In light of this, novel therapeutic alternatives with improved effectiveness and fewer side effects have become a necessity. Despite many new or repurposed antiviral agents recommended for Coronavirus disease (COVID-19) therapy, this objective remains unfulfilled. Under these circumstances, the scientific community holds the significant responsibility to develop classes of novel therapeutic modalities to combat SARS-CoV-2 with the least harmful side effects. OBJECTIVE: Antisense Oligonucleotides (ASOs) are short single-stranded oligonucleotides that allow the specific targeting of RNA, leading to its degradation. They may also prevent cellular factors or machinery from binding to the target RNA. It is possible to improve the pharmacokinetics and pharmacodynamics of ASOs by chemical modification or bioconjugation, which may provide conditions for customization of a particular clinical target. This study aimed to outline the potential use of ASOs in the treatment of COVID-19 disease, along with the use of antisense stabilization and transfer methods, as well as future challenges and limitations. METHODS: We have reviewed the structure and properties of ASOs containing nucleobase, sugar, or backbone modifications, and provided an overview of the therapeutic potential, delivery challenges, and strategies of ASOs in the treatment of COVID-19. RESULTS: The first-line therapy for COVID-19-infected individuals, as well as the development of oligonucleotide-based drugs, warrants further investigation. Chemical changes in the oligonucleotide structure can affect the biological processes. These chemical alterations may lead to enhanced potency, while changing the pharmacokinetics and pharmacodynamics. CONCLUSION: ASOs can be designed to target both coding and non-coding regions of the viral genome to disrupt or completely degrade the genomic RNA and thereby eliminate SARS-CoV-2. They may be very effective in areas, where vaccine distribution is challenging, and they may be helpful for future coronavirus pandemics.

The impacts of dipeptidyl- peptidase 4 (DPP-4) inhibitors on common female malignancies: A systematic review.

The inhibition of DPP-4 is an important therapy for controlling hyperglycemia in patients with type 2 diabetes (T2DM). However, the role of DPP-4 in cancer is not yet clear, with some studies suggesting that it may either promote or suppress tumors. This makes it crucial to have personalized treatment for diabetic women with cancer to effectively manage their diabetes whilst and preventing cancer mortality. To address this issue, we conducted an integrative in-silico analysis and systematic review of the literature to comprehensively examine the relationship between DPP-4 expression and the effects of its inhibitors on prevalent female malignancies. We specifically chose studies that examined the effects of DPP-4 expression and DPP-4 inhibition on prevalent cancers in women, such as breast cancer (BC), ovarian cancer (OV), cervical cancer (CC), and endometrial cancer (EC). These studies comprised those conducted both in vivo and in vitro. The review of the literature indicated that DPP-4 inhibition may worsen aggressive traits such as metastasis, EMT, and chemotherapy resistance in BC cells. However, cohort studies on diabetic and BC patients did not confirm these findings. In vitro studies indicate that on OV, DPP-4 upregulation has been shown to prevent metastasis, while cervical cancer (CC) appears to be influenced by DPP-4 expression in terms of cell migration. sitagliptin, a pharmaceutical inhibitor of DPP-4, had a significant impact on reducing adhesion in CC cells in vitro. Overexpression of DPP-4 increased cell migration and proliferation in CC and EC cells, and hence the application of sitagliptin is expected to prevent this effect. On the other hand, the result of in-silico data confirmed that a significant correlation exists between DPP-4 expression and immune cell infiltration in breast, ovarian, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) as well as downregulated in these cancers compared to their normal tissue samples. Furthermore, a significant (p < 0.05) effect on OS of BC and CESC patients has been reported due to the elevation of DPP-4 methylation on a specific CPG Island. These findings could aid in creating specialized treatments for diabetic women with specific malignancies, but caution should be exercised when considering the patient's medical history and cancer type.

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.

Association of major and minor ECG abnormalities with traditional cardiovascular risk factors in the general population: a large scale study.

Cardiovascular disease (CVD) can be determined and quantified using the electrocardiogram (ECG) analysis. Identification of the risk factors associated with ECG abnormalities may advise prevention approaches to decrease CVD burden. In this study we aimed to investigate the association between CVD risk factors and minor and major ECG abnormalities in a general Iranian adult population. This study was conducted in 2010 and covered a population of 9035 males and females aged 35 to 65 years recruiting from the phase I of Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. The participants were drawn by a stratified cluster random sampling technique. The Bivariate and multinomial logistic regression analysis were conducted considering gender stratification to explore the association of ECG abnormalities with traditional cardiovascular risk factors. There was a significant association between minor and major ECG abnormalities and hypertension (HTN), type 2 diabetes (T2DM), smoking, and physical activity (p < 0.005). There was a significant trend, in both genders, for increasing major abnormalities as the number of CVD risk factors increased. But, only in women, the minor abnormalities increase in frequency as the number of CVD risk factors increased. The results of multinomial logistic regression showed that men with HTN [ARRR = 1.25, 95% CI 0.99, 1.57] and T2DM [ARRR = 1.31, 95% CI 0.99, 1.74] had the highest likelihood to have major abnormalities, although these are not statistically significant. For women, those with HTN had the highest likelihood to have major [ARRR = 1.36, 95% CI 1.13, 1.63] and minor [ARRR = 1.35, 95% CI 1.15, 1.58] abnormalities. Also, women aged > 60 years were more likely to have major [ARRR = 2.01, 95% CI 1.49, 2.74] and minor [ARRR = 1.59, 95% CI 1.20, 2.10] abnormalities compared to women aged < 45 years. Age and HTN were significantly associated with major and minor ECG abnormalities in women, and, on the other hand, HTN and T2DM were associated with major abnormalities in men. Taken together, these findings suggest that healthcare providers should advise preventive approaches to the asymptomatic adults with both major and minor electrocardiographic abnormalities that may predict cardiovascular risk.

Syndecans and diabetic complications: A narrative review.

Syndecan (SDC) is a member of the heparan sulfate proteoglycan (HSPG) family. It appears to play a role in the aetiology of diabetic complications, with decreased levels of SDCs being reported in the kidney, retina, and cardiac muscle in models of diabetes mellitus (DM). The reduced levels of SDCs may play an important role in the development of albuminuria in DM. Some studies have provided the evidence supporting the mechanisms underlying the role of SDCs in DM. However, SDCs and the molecular mechanisms involved are complex and need to be further elucidated. This review focuses on the underlying molecular mechanisms of SDCs that are involved in the development and progression of the complications of DM, which may help in developing new strategies to prevent and treat these complications.

Personalized Approaches to Cardiovascular Disease: Insights into FDA-Approved Interventions and Clinical Pharmacogenetics.

Cardiovascular diseases place a considerable burden on global health systems, contributing to high rates of morbidity and mortality. Current approaches to detecting and treating Cardiovascular Diseases (CVD) often focus on symptomatic management and are initiated after the disease has progressed. Personalized medicine, which tailors medical interventions to individual characteristics, has emerged as a promising strategy for improving cardiovascular health outcomes. This article provides an overview of personalized medicine in the context of CVD, with a specific emphasis on FDA-approved interventions. It explores the potential benefits, challenges, and future directions of personalized medicine in cardiovascular disorders. By reviewing the advancements in this field, this article underscores the importance of early detection, intervention, and innovative treatment options in reducing the impact of CVD on individuals and society.

The associations between plant-based dietary indices with depression and quality of life and insomnia among Iranian adolescent girls in 2015.

Although previous research has explored the link between plant-based diets and mental health outcomes, there has been limited study on the quality levels of plant foods in this context. This study was conducted on 733 adolescent girls from cities in northeastern Iran. The validated Iranian version of the Insomnia Severity Index, SF-12v2 questionnaire and Persian version of the Beck Depression Inventory used to assess insomnia and poor quality of life (QoL) and depression, respectively. Dietary intakes assessed using a valid and reliable food frequency questionnaire. The association of scores of plant based dietary index (PDI) and poor QoL, depression and insomnia explored by binary logistic regression. The unadjusted model showed subjects in the highest quartile of healthy PDI had lower chances of insomnia than those in the lowest quartile (OR: 0.50; 95% CI 0.27-0.91, P = 0.024). The association persisted across various adjusted models. Subjects in the highest quartile of unhealthy PDI (uPDI) had higher chances of depression than those in the lowest quartile (OR: 1.83; 95% CI 1.09-3.08, P = 0.022). The significance of the association was maintained after adjusting for other confounders. A healthy plant-based dietary index is associated with a lower odds of insomnia. An unhealthy plant-based dietary index was associated to an increased chance of depression. Findings need to be confirmed by future studies.

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.

The therapeutic impact of programmed death - 1 in the treatment of colorectal cancer.

Colorectal cancer (CRC) is the most common type of newly diagnosed cancer. Metastatic spread and multifactorial chemoresistance have limited the benefits of current therapies. Hence, it is imperative to identify new therapeutic agents to increase treatment efficacy. One of CRC's most promising immunotherapeutic targets is programmed death-1 (PD-1), a cell surface receptor that regulates immune responses. In this paper, we provide an overview of the therapeutic impact of PD-1 in the treatment of CRC. Cancer cells can exploit the PD-1 pathway by upregulating its programmed death-ligand 1 (PD-L1) ligand to evade immune surveillance. The binding of PD-L1 to PD-1 inhibits T cell function, leading to tumor immune escape. PD-1 inhibitors, such as pembrolizumab and nivolumab, block the PD-1/PD-L1 interaction. Clinical trials evaluating PD-1 inhibitors in advanced CRC have shown promising results. In patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors characterized by high mutation rates and increased immunogenicity, PD-1 blockade has demonstrated remarkable efficacy. As a result, pembrolizumab and nivolumab have received accelerated approval by regulatory authorities for the treatment of MSI-H/dMMR metastatic CRC. Additionally, combination approaches, such as combining PD-1 inhibitors with other immunotherapies or targeted agents, are being explored. Despite the success of PD-1 inhibitors in CRC, challenges still exist. Immune-related adverse events can occur and require close monitoring. In conclusion, PD-1 inhibitors have demonstrated significant therapeutic impact, particularly in patients with MSI-H/dMMR tumors.

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.

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 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.

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.

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.

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.

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.

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.