majid zaki-dizaji

Colorectal cancer (CRC) is a common malignancy with high mortality. Despite advancements in understanding its molecular causes and improved drug therapies, patient survival rates remain low. The main reasons for the high mortality rate are cancer metastasis and the emergence of drug-resistant cancer cell populations. While genetic changes are recognized as the main driver of CRC occurrence and progression, recent studies suggest that epigenetic regulation is a crucial marker in cancer, influencing the interplay between genetics and the environment. Research has shown the significant regulatory roles of non-coding RNAs (ncRNAs) in CRC development. This review explores epigenetically regulated ncRNAs and their functions, aiming to understand key regulatory mechanisms that impact CRC development. Additionally, it discusses the potential use of these ncRNAs in CRC diagnosis, prognosis, and targeted treatments.

Hyperglycemia in pregnancy is believed to be associated with negative pregnancy outcomes. However, establishing a causal connection between diabetes mellitus (DM) and adverse pregnancy results is challenging due to the limitations inherent in traditional observational studies.

Our study used a two-sample Mendelian randomization (MR) technique to examine the possible influence of pregestational diabetes mellitus (PGDM) on adverse pregnancy outcomes. Summary-level data were obtained from genome-wide association studies (GWAS) of European ancestry and FinnGen biobank. The primary analysis employed the random-effects multiplicative inverse variance weighted (IVW) technique to appraise causal relationships between PGDM and adverse outcomes. Heterogeneity and pleiotropy were assessed using Cochran’s Q statistic, Rucker’s Q statistic, and the I² statistic. Sensitivity analyses were conducted using MR-Egger and weighted median methods. Additionally, outlier detection techniques, including MR-PRESSO and RadialMR, were applied.

The results from the IVW method indicated no significant causal association between PGDM and stillbirth (SB) (OR (SE)=0.99 (0.001); P value=0.992), miscarriage (MIS) (OR (SE)=0.97 (0.016); P value=0.125), and preterm birth (PTB) (OR (SE)=1.072 (0.028); P value=0.014). Pleiotropy and heterogeneity tests revealed no evidence of pleiotropy for SB, MIS, and PTB (MR–Egger intercept P value=0.296, 0.525, and 0.532, respectively), with no observed heterogeneity for SB, MIS, and PTB (Q- P values of IVW were 0.929, 0.999, and 0.069, and MR–Egger were 0.931, 0.999, and 0.065, respectively).

Our findings indicate that there is no direct causal link between PGDM and the likelihood of MIS, SB, and PTB.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide. Early detection is crucial for improving survival rates. Liquid biopsies, specifically analyzing circulating tumor-educated platelets (TEPs), have emerged as a promising tool for early CRC detection and monitoring treatment efficacy. This study investigated the expression levels of two specific circRNAs, hsa_circ_0004771 and hsa_circ_0019120, in the platelets of patients with CRC, advanced polyps, and healthy controls.

Blood samples were obtained from 25 individuals with CRC, 25 individuals with advanced polyps, and 25 healthy controls. Platelet-derived total RNA was extracted, and expression analysis was conducted using reverse transcription quantitative PCR (RT-qPCR). Differential expression and receiver operating characteristic (ROC) curve analysis were performed using GraphPad Prism.

Both circRNAs were found to be upregulated in platelets from individuals with advanced polyps and CRC compared to healthy individuals. However, the upregulation was statistically significant only for hsa_circ_0004771 in CRC patients (p-value = 0.0036) and for hsa_circ_0019120 in both advanced polyp (p-value = 0.0175) and CRC patients (p-value = 0.0356). The combined analysis of both circRNAs achieved an area under the curve (AUC) of 0.8348 (95% CI: 0.7131 to 0.9565) with a sensitivity of 84% and specificity of 80% (p-value = 0.0002).

This study showed that hsa_circ_0004771 and hsa_circ_0019120 dysregulated in both CRC and polyps and have potential as a novel diagnostic biomarker of CRC.

Recurrent or repeated implantation failure (RIF) is a significant challenge that hampers the success rate of assisted reproductive technology (ART) in achieving pregnancy. The underlying mechanisms of RIF remain unclear. Recent studies have identified distinct expression patterns of circular RNAs (circRNAs) in the endometrial tissues of individuals with RIF. The objective of this research is to evaluate the expression of six candidate circRNAs in the plasma of RIF patients.

The study included a total of sixty participants, comprising 30 RIF patients and 30 age-matched controls. Specific primers were designed for six circRNAs (hsa_circ_0001713, hsa_circ_0004121, hsa_circ_0030162, hsa_circ_0034642, hsa_circ_0034762, and hsa_circ_0092337), and expression analysis was carried out by RT-qPCR. Blood samples were collected from individuals during the implantation window, and cell-free RNA was extracted from plasma. Statistical analysis was performed using Graphpad Prism software.

Control and RIF groups had mean ages of 34.68 ± 6.2 and 36.80 ± 3.8 years, respectively. Plasma from RIF patients showed significant downregulation of hsa_circ_0030162 (p=0.02) and upregulation of hsa_circ_0004121 (p=0.003) compared to controls. Bioinformatic analysis predicted hsa-miR-125a-3p and hsa-miR-125a-5p as potential targets of hsa_circ_0030162 and hsa_circ_0004121, respectively.

This study demonstrates the differential plasma expression of hsa_circ_0030162 and hsa_circ_0004121 in RIF patients, consistent their expression in endometrial tissue. These circRNAs may contribute to RIF pathogenesis. Further research is needed to validate these findings and explore their clinical utility.

COVID-19 infection during pregnancy could be associated with placental histopathological changes such as vascular diseases and malperfusion. There are studies showing that mRNA vaccines are not associated with significant placental pathological changes. Our objective was to evaluate the placental histopathology in pregnant women who received Sinopharm, an inactivated virus vaccine, during pregnancy.

The study included placental samples collected from mothers who gave birth of living singletons through elective cesarean sections performed between March 2022 and May 2022 at Imam Khomeini Hospital Complex. The study included women who had no history of positive reverse transcription polymerase chain reaction (RT-PCR) testing for COVID-19 during pregnancy, and had received at least one dose of COVID-19 vaccine during their pregnancy. Humoral levels of anti-SARS-CoV-2 spike IgG were measured in both the mothers and neonates.

The study included 20 mother-neonate pairs. The mean maternal age was 34±3.6 years, and all mothers received Sinopharm vaccine as their first and second doses. The last vaccine dose was administered during pregnancy, with 3 mothers receiving it in the first trimester, 9 in the second trimester, and 8 in the third trimester. The histopathological findings in the placental samples included decidual vasculopathy, subchorionic thrombosis, and chronic histiocytic intervillositis. All mothers and neonates, except one pair, were positive for anti-spike antibody.

Multiple abnormal histopathological findings were reported in placenta of vaccinated mothers. However, similar to previous studies, these placental findings are considered mild lesions and have been observed in both vaccinated and unvaccinated mothers.

A systematic review was conducted to summarize the methylated circulating tumor DNA (ctDNA) markers reported over the last decade for early detection of colorectal cancer (CRC) and to identify the main technical challenges that are impeding their clinical implementation.

CRC is a major cause of cancer deaths worldwide, but early detection is key for successful treatment. Non-invasive methods such as methylated ctDNA testing show promise for improving detection and monitoring of CRC.

A comprehensive search was performed using Web of Science, PubMed, and Scopus up to December 30, 2023, limited to articles published in the last 10 years (after 2012), while including advanced adenoma/stage 0 or stage I/II samples in biomarker validation.

After identifying 694 articles, removing duplicates and screening titles, abstracts, and full texts, a total of 62 articles were found to meet the inclusion criteria. Among the single biomarkers, MYO1-G, SEPT9, SDC2, and JAM3 revealed the highest sensitivity for polyps and stage I/II CRC. For multi-biomarkers with suitable sensitivity, combinations of SFRP1, SFRP2, SDC2, PRIMA1, or ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, VIM or ZFHX4, ZNF334, ELOVL2, UNC5C, LOC146880, SFMBT2, GFRA1 were identified for polyps and stage I/II CRC.

Enhancing sensitivity and specificity of molecular screening methods is crucial for improving CRC detection. Identifying a select few valuable biomarkers is key to reducing costs, despite challenges posed by low ctDNA levels in plasma, particularly in early-stage cancers.

Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in maternal plasma. However, despite increased sensitivity, it has a number of limitations that may complicate of its results interpretation. Therefore, elucidating factors affecting fetal fraction, as a critical limitation, guides its clinical application.

In this report, systematic search was carried out through PubMed, Web of Science, and Scopus databases until February 11, 2022 by using keywords consist of "noninvasive prenatal screening", "NIPT", "noninvasive prenatal", "cell free DNA" and "fetal fraction". The articles were screened for eligibility criteria before data extraction.

A total of 39 eligible studies, most published between 2010 and 2020, were included. Based on the results of studies, a negative correlation between maternal age and BMI/body weight with fetal fraction was found. Furthermore, LDL, cholesterol, triglyceride level, metformin, heparin and enoxaparin therapy, hemoglobinrelated hemoglobinopathies, and physical activity showed to have negative associations. Interestingly, it seems the ethnicity of patients from South and East Asia has a correlation with fetal fraction compared to Caucasians. Positive correlation was observed between gestational age, free β-hCG, PAPP-A, living in high altitude, and twin pregnancy.

Considering each factor, there was significant inconsistency and controversy regarding their impact on outcomes. Indeed, multiple factors can influence the accuracy of NIPS results, and it is worth noting that the impact of these factors may vary depending on the individual’s ethnic background. Therefore, it is important to recognize that NIPS remains a screening test, and comprehensive pre- and postNIPS counseling should be conducted as part of standard clinical practice.

The emergence and fast spread of coronavirus disease 2019 (COVID-19) threatens the world as a new public health crisis. Little is known about its effects during pregnancy. This study aimed to investigate the clinical manifestations of COVID-19 on maternal and neonatal outcomes.

In this systematic review, PubMed, Scopus, Web of Science, and Google Scholar databases were searched focusing on pregnancy and perinatal outcomes of COVID-19.

The initial search yielded 1236 articles, from which finally 21 unique studies, involving 151 pregnant women and 17 neonates, met the criteria. Mean ± SD age of included mothers and mean ± SD gestational age at admission were 30.6 ± 6.2 years and 30.8 ± 8.9 weeks, respectively. The common symptoms were fever, cough, fatigue, dyspnea and myalgia. The mortality rates of pregnant women and neonates were 28 out of 151 (18.5%) and 4 out of 17 (23.5%), respectively. Most of the neonates were preterm at the time of delivery. Three neonates had positive RT-PCR test on the first day after birth and three others on day two. On the average, neonate’s PCR became positive on day 4 for the first time.

Early diagnosis of COVID-19 is crucial due to the possibility of the prenatal complications. Strict prevention strategies may reduce the risk of mother to infant transmission.

Children with cyanotic Congenital Heart Disease (CHD) are at higher risk for delay in their growth and development due to more energy consumption during their activities. In addition, they are more prone to respiratory infection and hospitalization. Due to the nature of disease, these patients suffer from a chronic hypoxia and its impact on growth and development is not well investigated. This study was designed to find out which physical growth and neurodevelopmental parameters of these patients are affected by chronic hypoxia in comparison with acyanotic disease. 81 children with CHD (34 cyanotic and 47 acyanotic), aged between 6 months to 3 years from Children’s Medical Center affiliated to Tehran University of Medical Sciences in Tehran were recruited from January 2013 to January 2014. Growth parameters including weight, height, and head circumference were checked and then these indices were categorized into three groups of Failure To Thrive (FTT). Functional development was assessed by using modified Denver Developmental Screening Test (DDST II). In acyanotic group, Ventricular Septal Defect (VSD) and in the cyanotic group, tetralogy of fallot (TOF) were the most prevalent disorders. Growth indices were low in 52% of patients (70% of cyanotic and 38.2% acyanotic), and also weight and height parameters were significantly lower in the cyanotic group (p= 0.009 and p= 0.05). 62% of cyanotic patients and 17% of acyanotic patients had delay at least in one of their neurological development indices (Gross motor, fine motor, speech or psychosocial behavior). This study also demonstrates an association between neurodevelopment delay and FTT in cyanotic patients, but not in acyanotic ones. Results in this study suggest that children with cyanotic CHD are more prone to delay in their development besides their growth possibly due to the nature of their disease. Therefore, chronic hypoxia can be a risk factor influencing neurodevelopment of the patients and appropriate intervention is required to gain better outcome.

The purpose of this study was to analyze the expression level of CRISP2, CATSPER1, PATE1 and SEMG1 genes in the sperm of men with asthenozoospermia (AZS). AZS is a cause of infertility in men in which the motility of the sperm is reduced. So far, a few genes have been associated with AZS; however, in most of the cases, its molecular etiology is unclear. A total of 35 subjects with idiopathic AZS and 35 fertile and healthy men as control were included. In study after total RNA extraction and cDNA synthesis, relative quantification was performed. B2M was used as the normalizer gene and fold change was calculated by 2−ΔΔCt</sup>method. Mann-Whitney test was used to compare the expression levels between the case and control groups with significance level of p<0.05. Our results showed that CRISP2 (p=0.03) and SEMG1 (p=0.03) were significantly down- and up-regulated in AZS men respectively compared to the controls. But CATSPER1 and PATE1 did not show significant changes. Down-regulation of CRISP2 and up-regulation of SEMG1 were associated with AZS, which could be suggested as the potential candidate genes for the development of a diagnostic marker or potentially for more studies for treatment of AZS.

BackgroundAtaxia telangiectasia (A-T) is a common genetically inherited cause of early childhood-onset ataxia. The infrequency of this disease, vast phenotype variation, disorders with features similar to those of A-T, and lack of definite laboratory test, make diagnosis difficult. In addition, there is no rapid reliable laboratory method for identifying A-T heterozygotes, who susceptible to ionizing radiation (IR), atherosclerosis, diabetes, and cancers. We used SMC1pSer966 (pSMC1) in-cell colorimetric ELISA to diagnosis and screen in A-T families.
With informed consent, 2cc peripheral blood was collected from the 15 A-T patients, their parents, and 24 healthy controls with no family history of malignancy, diabetes, and atherosclerosis. Extracted peripheral blood mononuclear cells (PBMCs) were cultured in poly-L-Lysine treated 96-well plate with density of 70,000 cells per well. SMC1 phosphorylation was evaluated with cell-based ELISA kit 1 hour after 5 Gy IR and the pSMC1data normalized with Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
SMC1 phosphorylation was significantly low in A-T`s PBMC (mean standard deviation [SD]: 0.075 0.034) in comparison to carriers (mean SD: 0.190 0.060) and healthy controls (mean SD: 0.312 .081), but unluckily could only discriminate A-T patients (Area Under the Curve -receiver operating characteristic [AUC-ROC]: 1.00, 1.00-1.00). This method in spite of rapidness and simplicity showed poor imprecision (22.49% coefficient of variation [CV] for intraday imprecision).
It seems pSMC1 assessment by in-cell ELISA can be used for detection of A-T patients, but it may not sensitive enough for identification of carriers. This ELISA test is very simple, rapid, and requires less than 2cc blood. Thus it may be proposed for the early differential diagnosis of A-T as an alternative method.