Advances in blood DNA methylation-based assay for colorectal cancer early detection: a systematic updated review.

Aim: 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. Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Epigenetics modification among vitrified oocytes and early embryos derived from them: a narrative review.

Vitrification has important application in assisted reproductive technology (ART) and this technique has been widely used in the cryopreservation of oocytes and embryos. However, due to susceptibility of epigenetic modifications to environmental changes induced by cryopreservation procedures, there are concerns about the potential epigenetic consequences of oocyte and embryo vitrification. This review comprehensively summarized the effect of cryopreservation-especially the vitrification method in ART-on oocytes and embryos. Various studies have reported changes in different aspects of genomic status which directly affect the quality of fertilized embryos.  The objective of this review is to assess existing literature on the epigenetic modifications that occur in vitrified oocytes and early embryos resulting from oocyte vitrification, including DNA modifications, RNA methylation, histone modification and microRNAs related to ART.

The Association of AMH Level with the Number and Quality of Oocytes in Women Undergoing IVF/ICSI: A Single-Center Study.

Background: The recognized role of Anti-Müllerian hormone (AMH) as a marker for women's biological age and ovarian reserve prompts debate on its efficacy in predicting oocyte quality during IVF/ICSI. Recent findings challenging this view compelled us to conduct this study to examine the correlation between AMH levels and quantity/quality of oocytes in IVF/ICSI procedures. Methods: The data were collected retrospectively from the medical records of 320 women between 25-42 years old. The included patients were divided into two groups: the high AMH group (>1.1 ng/ml) and the low AMH (=<1.1 ng/ml) group. The high AMH group comprised 213 patients, while the low AMH group consisted of 107 patients. Spearman's correlation coefficient and Multinomial logistic regression were computed to assess the relationships between different variables. Results: Significant positive correlations were detected between AMH level and the number of aspirated follicles (rho=0.741, p<0.001), retrieved oocytes (rho=0.659, p<0.001), M2 oocytes (rho=0.624, p<0.001), grade A embryos (rho=0.419, p<0.001), and grade AB embryos (rho=0.446, p<0.001. In contrast, AMH levels had negative associations with the number and duration of cycles (p<0.05). AMH emerged as a statistically significant independent predictor of the number of M2 oocytes. Conclusions: Serum AMH level could represent the quantity and quality of oocytes following IVF/ICSI treatments. Future studies should aim to delve deeper into the correlations between AMH levels and both the quality and quantity of embryos. Additionally, it would be beneficial to consider the influence of sperm factors, as well as assess pregnancy rates.

The relationship between preeclampsia risk and SENCR rs555172 gene polymorphism and expression.

Preeclampsia, the more severe manifestation of gestational hypertensive disorders, is a major cause of maternal and perinatal morbidity and mortality worldwide. Genetic polymorphisms in long non-coding RNAs (lncRNAs) are considered as potential genetic preeclampsia. This study aimed to explore the association between SENCR rs555172 SNP and PE risk in healthy pregnant women compared to women with preeclampsia. A total of 140 healthy pregnant women and 130 preeclampsia cases were included in the study. The rs555172 genotype was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of the SENCR gene was analyzed in 40 placenta tissue samples from both groups. Various statistical approaches were employed to assess the genotypic and allelic frequencies. The results showed no significant difference in the frequency of the rs555172 polymorphism between healthy pregnant women and those with preeclampsia in terms of the dominant (p=0.82), recessive (p=0.39), and over-dominant (p=0.42) models. Additionally, the analysis of SENCR relative expression revealed no significant difference between the two groups (p=0.48). In conclusion, the LncRNA SENCR rs555172(G/A) seems not associated with an increased risk of Preeclampsia in pregnant women.

Impact of Survivin rs9904341 and rs17878467 Polymorphisms On Risk of Preeclampsia in Iran.

Preeclampsia (PE) is a hypertensive disorder that affects pregnancy, mother, and fetus. Early diagnosis of PE remains a challenge. This study aimed to investigate the association between survivin two (rs9904341 and rs17878467) SNPs and PE risk in healthy pregnant women compared to women with preeclampsia. A sample of 166 healthy pregnant women and 160 cases with preeclampsia was included and genotyped for rs9904341 with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and rs17878467 with amplification-refractory mutation system (ARMS) PCR. The genotypic and allelic assessments were performed using various statistical approaches. The frequency of rs9904341 and rs17878467 polymorphisms was not significantly different between PE and healthy pregnant women. rs9904341: codominant (p = 0.5), dominant (p = 0.24), recessive (p = 0.61), over-dominant model (p = 0.38), and log additive (p = 0.25). rs17878467: codominant (p = 0.41), dominant (p = 0.23), recessive (p = 0.4), over-dominant model (p = 0.42), and log additive (p = 0.24). The frequency of survivin rs9904341 CG and CC genotypes was higher in severe PE women compared to controls and this polymorphism was associated with PE severity only in the dominant model (OR = 1.84, CI 1.04-3.26, P = 0.034). There was a significant association between survivin rs9904341 polymorphism and PE severity. No relationship was found between survivin rs9904341 and rs17878467 polymorphisms and PE onset. The allelic and genotypic frequencies of survivin rs9904341 and rs17878467 polymorphisms are not significantly different between the preeclampsia and control groups in all genetic models. Haplotype analysis showed lower frequency G rs9904341 T rs17878467 haplotype in PE woman and this haplotype was associated with lower risk of PE (OR = 0.54, CI 0.33-0.91, P = 0.02).

Quality of Life in Breast Cancer Patients: A Systematic Review of the Qualitative Studies.

OBJECTIVE: Quality of life (QoL) in breast cancer patients is still an important topic. Despite numerous quantitative scales, qualitative studies can help to in-depth understand the QoL of breast cancer patients. The purpose of this systematic review was to integrate qualitative studies on the QoL of women with breast cancer. METHODS: A literature search was performed in electronic databases including PubMed, Scopus, and Web of Science from January 1, 2010 until June 28, 2022 to find out qualitative studies assessing breast cancer patient's QoL. Two authors independently evaluated methodological quality according to the consolidated criteria for reporting qualitative research (COREQ) checklist. Data were extracted and reported by themes for cancer-free women and patients with metastatic cancer separately. RESULTS: In all, 1565 citations were retrieved. After removing 1387 duplicate and irrelevant papers, the full texts of 27 articles were reviewed and finally, 9 were eligible for evaluation. In quality checking of the citations, all articles gained the required quality score. After examining and merging similar topics, nine major themes were extracted. Physical, spiritual, and psychological aspects of QoL were the common issues in cancer-free women (before and after the COVID-19 pandemic) and patients with metastatic cancer. Perception of cancer and social life were the other main concerns in cancer-free women, whereas, in metastatic patients' overall survival and planning for the future and their children's life was the focus of interest. Women with metastatic disease showed more vulnerability in coping compared to cancer-free women. CONCLUSION: This review provides an opportunity to have a closer look into the several domains of QoL in women with breast cancer. In-depth information provided by this review might help to develop interventions for patients and their families to support women to cope much better with their life challenges.

Maternal and Fetal Factors Affecting Cell-Free Fetal DNA (cffDNA) Fraction: A Systematic Review.

Background: 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. Methods: 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. Results: 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, hemoglobin-related 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 ß-hCG, PAPP-A, living in high altitude, and twin pregnancy. Conclusion: 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 post-NIPS counseling should be conducted as part of standard clinical practice.

Emerging Role of Tumor-Educated Platelets as a New Liquid Biopsy Tool for Colorectal Cancer.

Colorectal cancer (CRC) is a major cause of cancer-associated death universally. Currently, the diagnosis, prognosis, and treatment monitoring of CRC mostly depends on endoscopy integrated with tissue biopsy. Recently, liquid biopsy has gained more and more attention in the area of molecular detection and monitoring of tumors due to ease of sampling, and its safe, non-invasive, and dynamic nature. Platelets, despite their role in hemostasis and thrombosis, are known to have an active, bifacial relationship with cancers. Platelets are the second most common type of cell in the blood and are one of the wealthy liquid biopsy biosources. These cells have the potential to absorb nucleic acids and proteins and modify their transcriptome with regard to external signals, which are termed tumor-educated platelets (TEPs). Liquid biopsies depend on TEPs' biomarkers which can be used to screen and also detect cancer in terms of prognosis, personalized treatment, monitoring, and prediction of recurrence. The value of TEPs as an origin of tumor biomarkers is relatively new, but platelets are commonly isolated using formidable and rapid techniques in clinical practice. Numerous preclinical researches have emphasized the potential of platelets as a new liquid biopsy biosource for detecting several types of tumors. This review discusses the potential use of platelets as a liquid biopsy for CRC.

Lanthanum-based metal organic framework (La-MOF) use of 3,4-dihydroxycinnamic acid as drug delivery system linkers in human breast cancer therapy.

Metal organic frameworks (MOFs) have received a lot of attention in the research community due to their unique physical properties, which make them ideal materials for targeted drug delivery systems. In this paper, we describe the synthesis of a non-toxic La-based MOF with 3,4-dihydroxycinnamic acid (3,4-DHCA) as a linker. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), nitrogen adsorption-desorption measurements, and X-ray powder diffraction (XRD) have all been used to characterize it thoroughly. The La-based MOF showed good biocompatibility with the human breast cancer cell line MDA-MB-468. The ability of 3,4-DHCA to treat MDA-MB-468 cells was confirmed by 40.35% cell viability with La-based MOF. Based on the findings, La-based MOF can be recommended as a promising candidate for anticancer delivery.

Atypical presentation of cardiomyopathy in a case of maternal mortality that was demonstrated as hypovolemic shock.

Periconceptional and prenatal care should be continued even during COVID-19 pandemics. Indeed, prevention and intervention programs for managing heart failure with aggressive resuscitation and invasive monitoring help to provide the best outcomes in cardiomyopathies. PPH may be associated with cardiac diseases and the resuscitation measures need modification to prevent maternal mortality.

Maternal and Neonatal Complications, Outcomes and Possibility of Vertical Transmission in Iranian Women with COVID-19.

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

Polymorphism of the DNA repair gene XDP increases the risk of systemic lupus erythematosus but not multiple sclerosis in the Iranian population.

BACKGROUND: Xeroderma pigmentosum group D ( XPD ) is an essential component of the nucleotide excision repair (NER) pathway, which can play a major role in DNA repair processes. A deficiency in this pathway was suggested as a causative factor of autoimmune diseases. Therefore, the current study aimed to investigate the relationship between XPD Lys751Gln polymorphism (rs13181) as one of the most common XDP polymorphisms and the risk of two important auto-immune diseases,namely systemic lupus erythematosus (SLE) and multiple sclerosis (MS) in the Iranian population. METHODS: 165 SLE patients and 165 age- and gender-matched healthy controls, and 150 MS patients and 150 age- and gender-matched healthy controls were genotyped for XPD rs13181 A/C polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The results of the present study have indicated that both C allele frequency ( P = 0.012; odds ratio: 1.5; 95% confidence interval: 1.1-2.07) and CC genotype ( P = 0.007; odds ratio: 2.46; 95% confidence interval: 1.2-4.7) in SLE patient were significantly higher than those in control group. Furthermore, there were no significant differences between MS patients and normal subjects concerning the genotype and the allele frequencies. CONCLUSION: Our findings suggested that XPD rs13181 A/C polymorphism may be a crucial risk factor for the development of SLE but not MS in Iranian patients.

MiR-4485-3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia.

Asthenozoospermia (AZS), which characterised by reduced forward sperm motility, is a common cause of male infertility. Recently, mitochondrial dysfunction reported in AZS men came to attention for finding the molecular aetiology of AZS. Mitochondria-related microRNAs (miRNAs) are the most important regulators of mitochondrial function through post-transcriptionally modulation of gene expression. Therefore, this study aims to evaluate the expression of four recently reported mitochondrial-related miRNAs (miR-4485-3p/4484/4461 and 4463) in the sperm sample of asthenozoospermic men. RNA was extracted from spermatozoa of 74 volunteers (39 patients with idiopathic AZS and 35 controls with normal fertility), and relative gene expression analysis was performed by quantitative PCR. We used SNORD48 as a normaliser gene, and quantification was calculated by 2-ΔΔCt method. The expression of miR-4484 and miR-4461 was not detected in the spermatozoa of cases and controls. However, miR-4485-3p (p = .006) was significantly downregulated in the AZS men compared with the controls, but the miR-4463 expression was not significantly different between the two groups (p = .5). Bioinformatic analysis identified three target genes for miR-4485-3p (DNAH1, KIT and PARK7) that are related to male infertility. In conclusion, the downregulation of miR-4485-3p was associated with idiopathic AZS, which could be a molecular link between mitochondrial dysfunction and AZS.

Genetic aspects of idiopathic asthenozoospermia as a cause of male infertility.

Infertility is a worldwide problem affecting about 15% of couples trying to conceive. Asthenozoospermia (AZS) is one of the major causes of male infertility, diagnosed by reduced sperm motility, and has no effective therapeutic treatment. To date, a few genes have been found to be associated with AZS in humans and mice, but in most of cases its molecular aetiology remains unknown. Genetic causes of AZS may include chromosomal abnormalities, specific mutations of nuclear and mitochondrial genes. However recently, epigenetic factors, altered microRNAs expression signature, and proteomics have shed light on the pathophysiological basis of AZS. This review article summarises the reported genetic causes of AZS.

Expression Analysis of the CRISP2, CATSPER1, PATE1 and SEMG1 in the Sperm of Men with Idiopathic Asthenozoospermia.

BACKGROUND: 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. METHODS: 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 method. Mann-Whitney test was used to compare the expression levels between the case and control groups with significance level of p<0.05. RESULTS: 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. CONCLUSION: 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.

MicroRNA profiling in spermatozoa of men with unexplained asthenozoospermia.

Asthenozoospermia (AZS) which is characterised by decreased sperm motility is one of the main causes of male infertility. Recent studies demonstrated altered microRNAs (miRNAs) in total semen, seminal plasma and spermatozoa of asthenozoospermic men. In line with these studies, it was aimed to evaluate the miRNA expression profile in spermatozoa of unexplained asthenozoospermic men. Thirty-nine cases with idiopathic AZS and 35 fertile and healthy men as control were included. After total RNA extraction from spermatozoa, high-throughput sequencing technology was employed to display miRNA profiles in spermatozoa samples pooled from AZS cases and healthy controls. Relative quantification by real-time PCR was performed to validate RNA-seq results. SNORD48 was used as normaliser gene, and fold change was calculated by 2-ΔΔCt method. Profiling results showed that 18 altered miRNAs in AZS men in comparison to controls. Subsequently, seven miRNAs were selected to validate by RT-PCR that showed MiR-888-3p significantly overexpressed in AZS cases (p = 0.014) in comparison with controls. It seems upregulation of miR-888-3p was associated with idiopathic AZS. This finding paves the way to the future investigation on the actual molecular role of miR-888-3p in aetiology of AZS.

Virulence Genes Profile of Multidrug Resistant Pseudomonas aeruginosa Isolated from Iranian Children with UTIs.

Virulent and resistant strains Pseudomonas aeruginosa (P. aeruginosa) is one of the most important cause of UTIs in pediatrics. The present study was carried to investigate the frequency of virulence factors in the multi-drug resistant strains of P. aeruginosa isolated from pediatrics hospitalized due to the UTIs. One-hundred and forty three urine samples were collected from pediatric patients suffered from UTIs. Samples were cultured and those that were P. aeruginosa positive were analyzed for the presence of putative virulence genes. Seventy one out of 143 samples (49.65%) were positive for P. aeruginosa. Monthly, sex and age-dependent prevalence were seen for P. aeruginosa. Bacterial strains had the highest levels of resistance against ampicillin (95.77%), gentamicin (92.95%) and ciprofloxacin (81.69%). Of 71 P. aeruginosa isolates, 12 strains were resistant to more than 9 antibiotics (16.90%). The most commonly detected virulence factors in the cases of urethral infections were exoU and plcH while those of pyelonephritis and cystitis were were exoS and lasB. Our findings should raise awareness about antibiotic resistance in hospitalized pediatrics with UTIs in Iran. Clinicians should exercise caution in prescribing antibiotics, especially in cases of UTIs. Such information can help in identifying these virulence genes as useful diagnostic markers for clinical P. aeruginosa strains isolated from UTIs.