Iranian Individuals Research Articles

Dietary acid load adopts the effect of ApoB ins/del genetic variant (rs11279109) on obesity trait, cardiovascular markers, lipid profile, and serum leptin level among patients with diabetes: a cross-sectional study

ApoB insertion/deletion (ins/del) genetic variant (rs11279109) is thought to be related to cardio-metabolic markers and obesity. This association has the potential to be modified by dietary patterns. Since the majority of studies concerned the role of dietary acid load (DAL) or ApoB in type 2 diabetes mellitus (T2DM) and its complications independently, and due to the insufficient data regarding the possible interactions between ApoB genetic variants and DAL on anthropometric and metabolic markers, we aimed to study the interaction between this genetic variant and dietary acid load (DAL) on cardio-metabolic markers, along with leptin among Iranian individuals with T2DM. 700 T2DM patients were randomly recruited. A validated semi-quantitative food frequency questionnaire was used for DAL calculation including potential renal acid load (PRAL) and net-endogenous acid production (NEAP). The polymerase chain reaction was used for genotyping the ApoB ins/del (rs11279109). The general linear model was applied to find the interactions in the crude and adjusted models. Patients with del/del genotype (rs11279109) with high PRAL intake have lower low-density lipoprotein cholesterol (LDL-C) (Pinteraction = 0.004), LDL/HDL ratio (Pinteraction = 0.02), total cholesterol (TC) (Pinteraction = 0.04), triglyceride (TG) (Pinteraction = 0.04), leptin (Pinteraction = 0.04) and interleukin-18 (IL-18) (Pinteraction = 0.04). Moreover, the interaction of gene and DAL in the PRAL method on TG concentration (P = 0.04), waist circumference (WC) (P = 0.04), and LDL/HDL ratio (P = 0.04) were significant. Eventually, a positive relationship was observed between the presence of the del/del genotype (rs11279109) and higher levels of TG, TC, LDL-C, IL-18, and LDL/HDL, in individuals with lower adherence to DAL, after adjusting for various covariates. Further studies are needed to investigate and confirm these findings.

Pharmacogenetic DPYD allele variant frequencies: A comprehensive analysis across an ancestrally diverse Iranian population.

Cancer treatment has improved over the past decades, but many cancer patients still experience adverse drug reactions (ADRs). Pharmacogenomics (PGx), known as personalized treatment, is a pillar of precision medicine that aims to optimize the efficacy and safety of medications by studying the germline variations. Germline variations in the DPYD lead to significant ADRs. The present cross-sectional study aims to evaluate the allele frequency of the DPYD gene variations in the Iranian population to provide insights into personalized treatment decisions in the Iranian population. The allele frequency of 51 pharmacogenetic variations in the clinically relevant DPYD was assessed in a representative sample set of 1142 unrelated Iranian individuals and subpopulations of different ethnic groups who were genotyped using the Infinium Global Screening Array-24 BeadChip. The genotyping assay revealed eight pharmacogenetic variants including DPYD rs1801265 (c.85T > C; DPYD*9A), rs2297595 (c.496A > G), rs1801158 (c.1601G > A; DPYD*4), rs1801159 (c.1627A > G; DPYD*5), rs1801160 (c.2194G > A; DPYD*6), rs17376848 (c.1896T > C), rs56038477 (c.1236G > A; HapB3), and rs75017182 (c.1129-5923C > G; HapB3) with minor allele frequency (MAF) ≥ 1%. The results of the study reveal significant genetic variations among Iranian population that could significantly influence clinical decision-making. These variants, with their potential to explain the substantial variability in drug response phenotypes among different populations, shed light on a crucial aspect of pharmacogenomics. These findings not only provide valuable insights but also inspire the design and implementation of future pharmacogenomic clinical trials, motivating further research in this crucial area.

Harm avoidance and incompleteness core motivations in obsessive-compulsive disorder: validation of the Farsi version of the Obsessive-Compulsive Trait Core Dimensions Questionnaire (F-OC-TCDQ) in Iran

BackgroundAttention to the heterogeneous manifestations of obsessive-compulsive symptoms observed in clinical and nonclinical populations has motivated researchers to use tools to identify homogeneous subgroups of obsessive-compulsive disorder (OCD) patients. The Obsessive-Compulsive Trait Core Dimensions Questionnaire (OC-TCDQ) is used to evaluate two motivational dimensions of OCD (harm avoidance (HA) and incompleteness (INC)), which has been developed in recent years based on the core dimensions model, and to classify homogeneous subgroups. This study aimed to validate the Farsi version of the OC-TCDQ in Iran.MethodsThe psychometric properties of the OC-TCDQ were tested in two clinical samples (209 patients with OCD) and nonclinical samples (209 participants without OCD). Confirmatory factor analysis (CFA) was conducted to test the two-factor structure. The measurement invariance between the clinical and nonclinical groups was evaluated. Reliability was tested using Cronbach’s alpha, split-half, and retesting (two-week intervals). Convergent and divergent validity were analysed with Pearson’s correlation and the incremental validity of this scale in predicting Yale-Brown Obsession Scale (Y-BOCS) and Beck Anxiety Inventory (BAI) scores using hierarchical regression analysis. The discriminant validity of the two clinical and nonclinical groups was investigated with a t-test.ResultsSimilar to the original version, the CFA showed a good fit for the two-factor structure. The invariance of measurement between samples, good internal consistency and retest reliability, and convergent and divergent validity of this scale were confirmed. The results of hierarchical regression analysis indicated the increasing validity of this scale in predicting the Y-BOCS and BAI compared to the OBQ-44 (p < 0.05), and comparing the scores of two groups with and without OCD indicated its discriminant validity (p < 0.01).ConclusionThese findings show that the Farsi-OC-TCDQ is a valid tool for evaluating the motivational dimensions of harm avoidance and incompleteness in Iranian individuals with and without OCD, and it allows us to compare the scores across groups.

Predictors of Attitudes toward Aging in Middle-Aged Individuals: A Cross-Sectional Study

Objective: Attitudes toward aging (ATA) are among the most important determinants of well-being in old age. However, little research has examined factors contributing to their formation in middle-aged individuals. This study aimed to investigate predictors of attitudes toward aging among Iranian middle-aged individuals in 2022. Method: This study recruited 330 people with a mean age of 56.5 ± 5.6 using multistage cluster sampling. Data were collected using a three-part questionnaire, including demographic factors, an attitude toward aging questionnaire (AAQ), and a multidimensional scale of perceived social support (MSPSS). The obtained data were analyzed using SPSS (v.22) statistical software to conduct t-tests, ANOVA, Pearson correlation, and linear regression. Results: According to bivariate analysis, perceived social support (PSS), age, level of education, and perceived income adequacy (PIA) had a significant relation with the total ATA score (P &lt; 0.05). According to regression analysis, family support (β = 0.288, P &lt; 0.001), friend support (β = 0.188, P &lt; 0.001), significant others support (β = 0.130, P = 0.04), age (β = 0.118, P = 0.002), and PIA (β = 0.290, P &lt; 0.001) were the predictor factors of ATA and explained 41% of the variance. PSS and PIA were the predictors of all dimensions of ATA. Conclusion: The results highlight the role of potentially modifiable factors, such as PSS, PIA, and level of education, in shaping ATA. This requires interventions and policies that effectively promote social and financial support in middle-aged individuals.

Understanding Family Reactions to Transgender Children in Iranian Culture: A Qualitative Study.

The family plays a crucial role in shaping children's identity and understanding of gender-based roles. This study aims to explore the experiences of Iranian transgender individuals with their families' reactions to their transgender identity disclosure. In 2018, nurse researchers conducted this qualitative study on 11 transgender individuals in Iran using a phenomenological approach, targeted and snowball sampling, and Colaizzi's seven-step method for data analysis. Rigor was ensured by adhering to Lincoln and Guba's standards. The study found varied reactions to transgender children among Iranian families, including abuse to avoid stigma. The study revealed two main themes, maladaptive and adaptive reactions, and identified six categories: denial of reality, mourning, coercion, deprivation, support out of necessity, and compromise of family reactions. Education and support systems may help address the cultural challenges that face families with transgender children. The findings offer insights for enhancing public awareness of the transgender community in conservative cultures.

Exploring the Interaction between Major Dietary Patterns and Overweight/Obesity Status in Relation to the Chance of Anxiety among Iranian Population: A YaHS-TAMYZ study

Background: Anxiety is one of the most prevalent mental illnesses globally. While there are long-established, separate, and bidirectional connections between nutrition, excess body weight, and anxiety, it is still unclear how these variables interact and affect anxiety state. The aim of the current investigation was to determine whether there was a significant interaction between major dietary patterns (DPs) and overweight/obesity status in relation to the chance of anxiety among Iranian individuals in Yazd, Iran. Methods: This cross-sectional study was conducted on baseline data of a large Iranian cohort study (Yazd Health Study: YaHS-TAMYZ). Dietary intakes were collected via a validated food frequency questionnaire. Major DPs were identified by principal component analysis (PCA). Then, body weight was assessed via an accurate body analyzer. Anxiety score was also evaluated using the validated scale-21 (DASS-21) questionnaire. Finally, the interaction between DPs and overweight/obesity in relation to the odds of anxiety was assessed using a multivariable adjusted binary logistic regression. Results: In total, 5781 participants were included in the present investigation. Individuals with the highest adherence to "high animal protein" DP and with overweight/obesity state had significantly lower odds of anxiety compared to those with the lowest imitation and normal body weight (P for interaction: 0.03). Conclusion: Findings of the current study revealed that the “high animal protein” DP may be inversely linked to the lower chance of anxiety in participants with overweight/obesity. Yet, further long-term prospective investigations are required to confirm the results.

Can herbal teas be used as complementary therapies for kidney disorders? Results from a cross-sectional study

IntroductionChronic kidney disease (CKD) has limited treatment options and is becoming more and more common. Since apparent evidence in the literature shows that herbs may be reno-protective, we discussed different kinds of herbal tea in relation to CKD and related disorders. MethodsThis cross-sectional study was conducted in health care centres located in a region in central Iran by enroling subjects aged 18 years and older. A self-reported questionnaire was used to evaluate the frequency and type of herbal tea drinks by participants. Anthropometric characteristics were measured and blood samples were obtained using a standard procedure. The Kidney Disease Outcome Quality Initiative (K/DOQI) guideline was the reference for diagnosis of CKD. Through multiple logistic models, the association between herbal tea drinking with CKD and related disorders was examined. ResultsOverall, 3 322 subjects were examined in this study. Three types of herbal tea were consumed by the study participants including green tea, chamomile-thyme tea, and borage tea. No statistically significant consistent associations between kidney disorders, including CKD, haematuria, albuminuria, and kidney stone and consumption of these herbal preparations were identified. ConclusionOverall, this study failed to suggest any consistent association between renal function and three categories of herbal tea in adult Iranian individuals.

Eating Disorder Psychopathology and Insomnia in Iranian Individuals: A Network Analysis

Eating Disorder Psychopathology and Insomnia in Iranian Individuals: A Network Analysis

The human SMAD9 (GCC) repeat links to natural selection and late-onset neurocognitive disorders.

Whereas (GCC)-repeats are overrepresented in genic regions, and mutation hotspots, they are largely unexplored with regard to their link with natural selection. Across numerous primate species and tissues, SMAD9 (SMAD Family Member 9) reaches highest level of expression in the human brain. This gene contains a (GCC)-repeat in the interval between + 1 and + 60 of the transcription start site, which is in the high-ranking (GCC)-repeats with respect to length. Here we sequenced this (GCC)-repeat in 396 Iranian individuals, consisting of late-onset neurocognitive disorder (NCD) (N = 181) and controls (N = 215). We detected two predominantly abundant alleles of 7 and 9 repeats, forming 96.2% of the allele pool. The (GCC)7/(GCC)9 ratio was in the reverse order in the NCD group versus controls (p = 0.005), resulting from excess of (GCC)7 in the NCD group (p = 0.003) and (GCC)9 in the controls (p = 0.01). Five genotypes, predominantly consisting of (GCC)7 and lacking (GCC)9 were detected in the NCD group only (p = 0.008). The patients harboring those genotypes received the diagnoses of Alzheimer's disease (AD) and vascular dementia (VD). Five genotypes consisting of (GCC)9 and lacking (GCC)7 were detected in the control group only (p = 0.002). The group-specific genotypes formed approximately 4% of the genotype pool in the human samples studied. We propose natural selection and a novel locus for late-onset AD and VD at the SMAD9 (GCC)-repeat in humans.

Translation and Evaluation of Psychometric Properties of the Persian 8-Item Internalized Transphobia (IT) Scale in Iranian Transgenders.

Internalized transphobia (IT) is influenced by societal norms and expectations, and it can have significant negative effects on the well-being and mental health of transgender individuals. The aim of this study was to translate and evaluate the psychometric properties of the Persian 8-item IT scale among Iranian transgender individuals in order to enhance the quality and quantity of research in this field. This cross-sectional and methodological study utilized convenience sampling to recruit 119 transgender individuals in Mashhad, the second most populous city in Iran, in 2021. The Persian translation of the IT scale was developed using the backward-forward translation method. Subsequently, various types of validity and reliability were assessed, including content validity using the content validity index (CVI) and content validity ratio (CVR), face validity based on the impact score, construct validity through confirmatory factor analysis (CFA), internal consistency measured by Cronbach's alpha, and test-retest stability analyzed using the intraclass correlation coefficient (ICC). The CVR ranged from 0.600 to 1, the CVI ranged from 0.800 to 1, and the impact score exceeded 1.5, indicating the appropriate content and face validity of the 8-item IT scale. The construct validity analysis revealed that the questionnaire is one-dimensional. The internal consistency, as measured by Cronbach's alpha, was 0.917, and the ICC for test-retest stability was 0.871. The Persian version of the IT scale demonstrated high and acceptable psychometric properties. The brevity of this scale facilitates its dissemination and utilization in clinical settings.

Angiotensin-converting enzyme I/D gene polymorphism and risk of type 2 diabetes mellitus in Iranian individuals

This study aimed to examine the relationship between type 2 diabetes mellitus (T2DM) and renin-angiotensin system gene polymorphisms in the Iranian population. Additionally, we performed a straightforward meta-analysis of the present articles to better understand this role. A total of 100 Iranian individuals, 50 patients with T2DM, and 50 age-matched healthy individuals were included in this study. DNA was extracted using the salting-out approach, polymerase chain reaction was used to amplify the angiotensin-converting enzyme (ACE) gene, electrophoresis techniques were used, and genotyping was performed. We also searched PubMed, Web of Science, Scopus, and Google Scholar databases for papers published in 2023. We found a significantly higher frequency of I/D genotype in the patient group than in the control group, and the risk of T2DM was 10 times higher in individuals with the I/D genotype (OR, 10 [95% CI, 3.7 to 27]; p < 0.0001) and also 2.85 time higher in individuals with the D allele OR, 2.85 [95% CI, 1.55 to 5.24]; p < 0.001). The ACE polymorphism alleles D and I/D genotypes may increase the risk of developing T2DM in an Iranian population.

Health susceptibility perceptions among Iranian, Afghan and Tajik minorities in three Nordic countries

PurposeThis research paper aims to delve into the perceptions of health susceptibility among Iranian, Afghan and Tajik individuals hailing from asylum-seeking or refused asylum-seeking backgrounds currently residing in Finland, Norway and Sweden.Design/methodology/approachSemi-structured interviews were conducted between May and October 2022 involving a sample size of 27 participants. An adapted framework based on the health belief model along with previous studies served as a guide for formulating interview questions.FindingsNotably influenced by cultural background, religious beliefs, psychological states and past traumatic experiences during migration journeys – before arrival in these countries till settling down – subjects’ perception of health concerns emerged significantly shaped. Additionally impacting perspectives were social standing, occupational status, personal/family medical history, lifestyle choices and dietary preferences nurtured over time, leading to varying degrees of influence upon individuals’ interpretation about their own wellness or illness.Practical implicationsInsights garnered throughout the authors’ analysis hold paramount significance when it comes to developing targeted strategies catering culturally sensitive health-care provisions, alongside framing policies better aligned with primary care services tailored explicitly around singular demands posed by these specific communities dwelling within respective territories.Originality/valueThis investigation represents one among few pioneering initiatives assessing perceptions regarding both physical and mental well-being within minority groups under examination across Nordic nations, unveiling complexities arising through intersecting factors like individual attributes mingling intricately with socio-cultural environments, thereby forming unique viewpoints towards health-care belief systems prevalent among such population segments.

A Hypermutable Region in the DISP2 Gene Links to Natural Selection and Late-Onset Neurocognitive Disorders in Humans.

(CCG) short tandem repeats (STRs) are predominantly enriched in genic regions, mutation hotspots for C to T truncating substitutions, and involved in various neurological and neurodevelopmental disorders. However, intact blocks of this class of STRs are widely overlooked with respect to their link with natural selection. The human neuron-specific gene, DISP2 (dispatched RND transporter family member 2), contains a (CCG) repeat in its 5' untranslated region. Here, we sequenced this STR in a sample of 448 Iranian individuals, consisting of late-onset neurocognitive disorder (NCD) (N = 203) and controls (N = 245). We found that the region spanning the (CCG) repeat was highly mutated, resulting in several flanking (CCG) residues. However, an 8-repeat of the (CCG) repeat was predominantly abundant (frequency = 0.92) across the two groups. While the overall distribution of genotypes was not different between the two groups (p > 0.05), we detected four genotypes in the NCD group only (2% of the NCD genotypes, Mid-p = 0.02), consisting of extreme short alleles, 5- and 6-repeats, that were not detected in the control group. The patients harboring those genotypes received the diagnoses of probable Alzheimer's disease and vascular dementia. We also found six genotypes in the control group only (2.5% of the control genotypes, Mid-p = 0.01) that consisted of the 8-repeat and extreme long alleles, 9- and 10-repeats, of which the 10-repeat was not detected in the NCD group. The (CCG) repeat specifically expanded in primates. In conclusion, we report an indication of natural selection at a novel hypermutable region in the human genome and divergent alleles and genotypes in late-onset NhCDs and controls. These findings reinforce the hypothesis that a collection of rare alleles and genotypes in a number of genes may unambiguously contribute to the cognition impairment component of late-onset NCDs.

Evaluation of elevated serum apelin-13 and D-dimer concentrations in individuals diagnosed with pulmonary embolism

BackgroundGiven the limited specificity of D-dimer, there is a perceived need to discover a more precise marker for diagnosing individuals who are suspected of having pulmonary embolism (PE). In this study, by evaluating the increase in the serum level of Apelin-13 and D-dimer, we found valuable findings about Apelin-13, which can be suggested as an auxiliary and non-invasive diagnostic biomarker in individuals with suspected PE, based on the obtained results.MethodsIn this case-control study, 52 Iranian individuals were included, all of whom were suspected to have PE. These individuals were then divided into two groups based on the results of CT angiography, which is considered the gold standard imaging method for diagnosing PE. The two groups were patients with PE and patients without PE. Finally, the levels of certain markers in the serum were compared between the two groups.ResultsThe mean serum D-dimer levels in patients with PE were significantly elevated (p < 0.001) in comparison to those without PE (1102.47 to 456.2 ng/ml). Furthermore, the mean level of Apelin-13 was significantly higher in patients with PE (49.8 to 73.11 ng/L) (p < 0.001). The cutoff point of Apelin-13 has been calculated at 58.50 ng/ml, with 90.9% sensitivity and 90% specificity. The D-dimer cutoff point was 500 ng/ml, with 95.5% sensitivity and 43.3% specificity.ConclusionsBased on the results of this study, the serum level of Apelin-13 can be used as a novel diagnostic and screening biomarker in patients with pulmonary thromboembolism.

Toll-like receptor 9 (TLR9) genetic variants rs187084 and rs352140 confer protection from Behcet’s disease among Iranians

BackgroundBehcet’s disease (BD) is a multisystem and multifactorial autoimmune disease characterized by relapsing episodes of oral aphthae, genital ulcers, and ocular and skin lesions. Toll-like receptor 9 (TLR9) has pro-inflammatory roles and its genetic variants might be involved in the pathogenesis of inflammatory diseases. MethodsTwo hundred five BD patients and 207 age and sex-matched healthy controls were evaluated for TLR9 single nucleotide polymorphisms − 1486 T/C (rs187084) and + 2848:G/A (rs352140) using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR).ResultsHealthy individuals had a significantly higher frequency of rs187084 AG and AG + GG genotypes than BD patients (p = 0.02 and p = 0.018; respectively). Of interest, healthy males had a significantly higher frequency of rs187084 AG + GG genotype and G allele than male BD patients (p = 0.035 and p = 0.045; respectively). However, rs187084 AG genotype and G allele frequencies were significantly higher in male patients with genital aphthous (p = 0.01 and p = 0.046; respectively). Furthermore, a significantly higher frequency of rs352140 CT and TT + CT genotypes was detected in healthy individuals than in BD patients (p = 0.01, and p = 0.032; respectively). Such results were also seen in healthy females than female patients (p = 0.001, and p = 0.004; respectively). Haplotype analysis revealed a significantly higher frequency of A-C and G-C haplotypes among patients and healthy subjects, respectively (p = 0.002 and p = 0.000; respectively).ConclusionOur data suggested that rs187084 AG and AG + GG genotypes and rs352140 CT and TT + CT genotypes protect Iranian individuals from BD but rs187084 AG genotype and G allele predispose male BD individuals to genital aphthous. However, additional studies are required to verify these results.

A novel homozygote nonsense variant of MSH4 leads to primary ovarian insufficiency and non-obstructive azoospermia.

Both non-obstructive azoospermia (NOA) and primary ovarian insufficiency (POI) are pathological conditions characterized by premature and frequently complete gametogenesis failure. Considering that the conserved meiosis I steps are the same between oogenesis and spermatogenesis, inherited defects in meiosis I may result in common causes for both POI and NOA. The present research is a retrospective investigation on an Iranian family with four siblings of both genders who were affected by primary gonadal failure. Proband, an individual with NOA, was subjected to clinical examination, hormonal assessment, and genetic consultation. After reviewing the medical history of other infertile members of the family, patients with NOA went through genetic investigations including karyotyping and assessment of Y chromosome microdeletions, followed by Whole exome sequencing (WES) on the proband. After analyzing WES data, the candidate variant was validated using Sanger sequencing and traced in the family. WES analysis of the proband uncovered a novel homozygote nonsense variant, namely c.118C>T in MSH4. This variant resulted in the occurrence of a premature stop codon in residue 40 of MSH4. Notably, the variant was absent in all public exome databases and in the exome data of 400 fertile Iranian individuals. Additionally, the variant was found to co-segregate with infertility in the family. It was also observed that all affected members had homozygous mutations, while their parents were heterozygous and the fertile sister had no mutant allele, corresponding to autosomal recessive inheritance. In addition, we conducted a review of variants reported so far in MSH4, as well as available clinical features related to these variants. The results show that the testicular sperm retrieval and ovarian stimulation cycles have not been successful yet. Overall, the results of this study indicate that the identification of pathogenic variants in this gene will be beneficial in selecting proper therapeutic strategies. Also, the findings of this study demonstrate that clinicians should obtain the history of other family members of the opposite sex when diagnosing for POI and/or NOA.

Human Immunodeficiency Virus-1 Drug Resistance Mutations in Iranian Treatment-experienced Individuals.

Human immunodeficiency virus-1 infection still remains a global health threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence of drug-resistance mutations and treatment failure in HIV-infected patients persist. In this study, we investigated the development of drug resistance in HIV-1-infected individuals receiving antiretroviral therapy for 6-10 years. In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1 viral load and drug-resistance mutations were assessed using molecular techniques. The demographic and epidemiological characteristics of the participants were also analyzed: Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between viral load and CD4 count, as well as epidemiological factors, such as vertical transmission, history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10 (83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment were infected with CRF35_AD. Our study provides important insights into the characteristics and development of drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran. The findings underline the need for regular viral load monitoring, individualized treatment selection, and targeted interventions to optimize treatment outcomes and prevent the further spread of drug-resistant strains.

Evaluation of MMP-9, IL-6, TNF-α levels and peripheral blood mononuclear cells genes expression of MMP-9 and TIMP-1 in Iranian patients with coronary artery disease.

Coronary artery disease (CAD) is the main cause of death and is characterized by atherosclerosis in coronary arteries. Inflammation plays a crucial role in the progression and development of atherosclerosis. The present study consisted of 132 Iranian individuals who underwent coronary angiography, 65 patients with CAD, and 67 controls. The matrix metalloproteinase-9 (MMP-9), TNF-α, IL-6, and vitamin D serum levels were measured by the ELISA technique. The gene expression of MMP-9 and tissue inhibitors of metalloproteinase (TIMP-1) was estimated by real-time PCR assay. A considerable increase in levels and PBMC gene expression of MMP-9 and serum levels of IL-6 and TNF-α were found in CAD patients compared with controls. A significant decrease was detected in vitamin D levels of CAD patients in comparison with controls. A considerable direct correlation was found between MMP-9 levels and MMP-9 and TIMP1 gene expression in CAD patients. MMP-9 levels positively correlated with LDL-C in CAD patients. The correlation between TIMP1 gene expression and IL-6 levels was also negatively significant. There were positive correlations between MMP-9 levels with IL-6 and TNF-α serum levels in CAD patients. This study showed that the interaction between MMPs, TIMP1, and cytokines could play a role in the pathogenesis of atherosclerosis. The present study suggested that high levels of TNF-α and IL-6 and vitamin D deficiency in our studied patients could disturb the MMP-9/TIMP-1 balance and lipid metabolism, leading to plaque formation/ rupture in predisposed CAD patients.

Evaluation of a new fusion antigen, cd loop and HAP2-GCS1 domain (cd-HAP) of Plasmodium falciparum Generative Cell Specific 1 antigen formulated with various adjuvants, as a transmission blocking vaccine

BackgroundMalaria is a major global health challenge, and for the elimination and eradication of this disease, transmission-blocking vaccines (TBVs) are a priority. Plasmodium falciparum Generative Cell Specific 1 (PfGCS1), a promising TBV candidate, is essential for gamete fertilization. The HAP2-GCS1 domain of this antigen as well as its cd loop could induce antibodies that partially inhibit transmission of P. falciparum.MethodsIn the current study, a new synthetic fusion antigen containing cd loop and HAP2-GCS1 domain (cd-HAP) of PfGCS1 was evaluated as a transmission blocking vaccine candidate. Initially, the profile of naturally acquired IgG antibodies to the cd-HAP antigen was analysed in Iranian individuals infected with P. falciparum, to confirm that this new fusion protein has the appropriate structure containing common epitopes with the native form of PfGCS1. Then, the immunogenicity of cd-HAP was evaluated in BALB/c mice, using different adjuvant systems such as CpG, MPL, QS-21, and a combination of them (CMQ). Furthermore, the blocking efficacy of polyclonal antibodies induced against these formulations was also assessed by oocyst intensity and infection prevalence in the Standard Membrane Feeding Assay (SMFA).ResultsThe naturally acquired antibodies (dominantly IgG1 and IgG3 subclasses) induced in P. falciparum-infected individuals could recognize the cd-HAP antigen which implies that the new fusion protein has a proper conformation that mimics the native structure of PfGCS1. Concerning the immunogenicity of cd-HAP antigen, the highest IgG levels and titers, by a Th1-type immune profile, and elevated antibody avidity were induced in mice immunized with the cd-HAP antigen formulated with a combination of adjuvants (P < 0.0001). Additionally, cytokine profiling of the immunized mice displayed that a high level of IFN-γ response, a Th1-type immune response, was produced by splenocytes from immunized mice that received cd-HAP antigen in combination with CMQ adjuvants (P < 0.0001). This formulation of cd-HAP antigen with CMQ adjuvants could reduce oocyst intensity and infection prevalence by 82%, evidenced by the SMFA and hold significant implications for future malaria vaccine development.ConclusionAltogether, the results showed that cd-HAP antigen formulated with a combination of the adjuvants (CMQ), could be a promising formulation to develop a PfGCS1-based transmission-blocking vaccine.

A GCC repeat in RAB26 undergoes natural selection in human and harbors divergent genotypes in late-onset Alzheimer’s disease

Although mainly located in genic regions and being mutation hotspots, intact blocks of CG-rich trinucleotide short tandem repeats (STRs) are largely overlooked with respect to their link with natural selection. The human RAB26 (member RAS oncogene family) directs synaptic and secretory vesicles into preautophagosomal structures, inhibition of which specifically disrupts axonal transport of degradative organelles and leads to an axonal dystrophy, resembling Alzheimer's disease (AD). Human RAB26 contains a GCC repeat in the top 1st percent in respect of length. Here we sequenced this STR in 441 Iranian individuals, consisting of late-onset neurocognitive disorder (NCD) (N = 216) and controls (N = 225). In both groups, the 12-repeat allele and the 12/12 genotype were predominantly abundant. We found excess of homozygosity for non-12 alleles in the NCD group (Mid-P exact = 0.027). Furthermore, divergent genotypes were detected that were specific to the NCD group (2.8% of genotypes) (Mid-P exact = 0.006) or controls (3.1% of genotypes) (Mid-P exact = 0.004). The patients harboring divergent genotypes received the diagnosis of AD. Based on the predominant abundance of the 12-repeat and 12/12 genotype in both groups, excess of non-12 homozygosity in the NCD group, and divergent genotypes across the NCD and control groups, we propose natural selection at this locus and link with late-onset AD. Our findings strengthen the hypothesis that a collection of rare genotypes unambiguously contribute to the pathogenesis of late-onset NCDs, such as AD.