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Jentashapir Journal of Cellular and Molecular Biology - Volume:15 Issue: 1, Mar 2024

Jentashapir Journal of Cellular and Molecular Biology
Volume:15 Issue: 1, Mar 2024

  • تاریخ انتشار: 1403/01/06
  • تعداد عناوین: 5
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  • Sara Ehteshamipour, Sohameh Mohebbi, Esmaeil Rahimi, Narjes Khatoun Shabani Sadr, Bahram Mohamad Soltani, Mehrdad Behmanesh * Page 1
    Background

     Hypoxia-inducible factor 1α (HIF1α), a key transcription factor activated during low oxygen levels, influences cell cycle and metastasis. Hypoxia induces double-strand breaks (DSBs), a highly carcinogenic process.

    Objectives

     This study aimed to elucidate the impact of HIF1α down-regulation on the expression of XRCC4 and XRCC7, key components of the non-homologous end joining (NHEJ) pathway crucial for DSB repair.

    Methods

     HeLa and [human embryonic kidney (HEK)293] cells underwent culture, transfection with HIF1α small interfering ribonucleic acid (siRNA), and viability assessment after 48 hours. Subsequent examination included cell cycle alterations. Ribonucleic acid extraction, complementary deoxyribonucleic acid (cDNA) synthesis, and RT-qPCR were performed to compare the fold-change in HIF1α, XRCC4, and XRCC7 gene expression, followed by statistical analyses.

    Results

     Downregulating HIF1α using siRNA resulted in reduced viability and increased apoptosis in both HeLa and HEK293 cells 48 hours after transfection. The findings also indicated a significant decrease in XRCC4 expression; nevertheless, XRCC7 expression remained unchanged in both cell lines.

    Conclusions

     This study underscores that HIF1α potentially modulates the NHEJ pathway through XRCC4, presenting itself as a plausible target for cancer therapy.

    Keywords: Hypoxia, HIF1α, XRCC4, NHEJ, Apoptosis, siRNA
  • Behdad Amirgholami, Sara Masihi *, Reza Samie, Hamid Galehdari, GholamReza Shariati Page 2
    Background

     Noninvasive prenatal testing (NIPT) serves as a screening method to assess the risk of chromosomal abnormalities in the fetus, including trisomy 18, 21, and 13. The reliability and success of this test are influenced by the proportion of circulating cell-free DNA obtained from the feto-placental unit, known as the fetal fraction (FF).

    Objectives

     Our study aims to investigate the fetal and maternal factors affecting FF.

    Methods

     Our research involved 1 150 patients referred for NIPT due to various reasons such as maternal age over 35, high-risk screening tests in the first or second trimester, history of trisomy in previous pregnancies, or patient request. Patients completed a questionnaire providing variables including maternal and fetal age, body mass index (BMI), smoking status, multiple pregnancies, and medication use such as Heparin or enoxaparin. Noninvasive prenatal testing was conducted on blood samples using Ion proton technology by Premaitha of the UK. The results, including fetal sex, trisomy risk, fetal fraction, and abnormal sex chromosomes, were analyzed using IBM SPSS 27 to assess the relationship between FF percentage and other variables.

    Results

     The study included 1150 NIPT cases, with maternal ages ranging from 13 to 48 years, BMI from 15 to 70, and gestational age from 10 to 27 weeks. Among these, 96.4% were singleton pregnancies and 3.6% were twin pregnancies. Spontaneous pregnancies accounted for 88.9%, while 9.2% were IVF and 1.2% were IUI. Fetal sex distribution was 45.9% female and 54.1% male. FF ranged from 4% to 20.7%, with a mean FF of 11.07. No significant correlation was found between maternal age, fetal age, maternal BMI, trisomies, and FF.

    Conclusions

     We can see that maternal age has no significant correlation with the fetal fraction. Although fetal age increases, the fetal fraction does too, but this increase was not significant. Body mass index, the route of pregnancy, and the sex of the fetus had no effect on FF. Despite NIPS being safer and yielding better results, other factors can still influence the outcomes of NIPS. Therefore, this test remains a screening tool, and clinical counseling should be conducted both before and after the test.

    Keywords: Cell-Free DNA, Trisomy Screening, Fetal Fraction
  • Farideh Rezaei, Mohammad Shafiei *, Hamid Galehdari, Alireza Malayeri, Seyed Mehdi Kalantar Page 3
    Background

     Glioma, the predominant type of tumor in the central nervous system (CNS), is commonly treated with temozolomide chemotherapy, radiation therapy, and surgery. However, resistance to chemotherapy can sometimes lead to treatment failure and cancer recurrence. To improve treatment strategies for glioma, it is important to understand the tumor microenvironment (TME) and the molecular aspects that contribute to drug resistance.

    Objectives

     The present study aimed to investigate the effects of sialic acid on drug resistance development in temozolomide-treated cells by analyzing the expression patterns of ABCB1 and ABCC1 genes, known for their role in drug resistance mechanisms.

    Methods

     This study examined the effects of temozolomide, sialic acid, and the combination of both on cell viability and apoptosis. IC50 and EC50 values were used to measure treatment effectiveness, and the expression of ABCB1 and ABCC1 genes was assessed by real-time PCR in different treatment groups.

    Results

     Temozolomide and sialic acid both had effects on cell viability, morphology, and the expression of ABCB1 and ABCC1 genes. These alterations may be associated with the development of drug resistance in cancer cells, providing insight into the underlying mechanisms.

    Conclusions

     The study suggests that sialic acid promotes cancer progression and reduces the effectiveness of anticancer drugs. Therefore, targeting sialic acid or its production and using combination drugs could be a promising strategy to counter its negative impact on treatment outcomes.

    Keywords: Glioma, Temozolomide, Sialic Acid, Drug Resistance, ABC Transporters
  • Ghazal Davodi-Boroujerdi, Ayda Khayyat Naghadehi, Farzaneh Nazari-Serenjeh, Sakineh Alijanpour, Zahra Ghasemzadeh *, Ali Rastqar Page 4

    Alzheimer's disease (AD) stands as the most prevalent neurodegenerative disorder, marked by neuronal loss, synaptic dysfunction, atrophy in various brain regions, cognitive decline, dementia, the production of β-amyloid (Aβ) peptide, and the presence of neurofibrillary tangles. Melatonin, also known as N-acetyl 5-methoxy tryptamine, is a hormone regulated by circadian rhythms and plays a crucial role in certain neurodegenerative conditions, including AD. In individuals with AD, alterations have been observed in the pineal gland hormone melatonin (MLT), the activity of enzymes associated with MLT synthesis, and the density of MT1 receptors in the suprachiasmatic nucleus (SCN) of the hypothalamus. The growing body of literature indicates a rising interest in utilizing MLT for AD intervention. Melatonin has shown several potential benefits in AD, such as mitigating mitochondrial dysfunction, reducing Aβ toxicity, scavenging free radicals, and even ameliorating circadian dysregulation, which includes addressing issues like sundowning and sleep disturbances. Recent studies suggest that MLT might serve as a potential biomarker for assessing the severity and progression of AD. This paper aimed to provide an overview of recent research on three key aspects: (1) MLT physiology, (2) the role of MLT in the learning and memory processes, and (3) an exploration of studies investigating the role of MLT in AD.

    Keywords: Alzheimer's Disease, Pineal Gland, Melatonin
  • Hojjat Hosseini, Ata A Ghadiri, Abdolah Mousavi Salehi, Saber Rokhafrooz, Mahin Najafian, Mehri Ghafourian * Page 5
    Background

     Preeclampsia (PE) is a pregnancy-related syndrome characterized by hypertension and proteinuria, affecting approximately 6-8% of pregnancies and contributing to about 40% of premature births.

    Objectives

     This study aimed to explore the polymorphisms -634C/G and +936C/T in the VEGF gene and their association with serum VEGF levels in pregnant women with PE.

    Methods

     In this case-control study, peripheral blood samples were collected from 135 women with PE and 135 normal pregnant women as the control group. DNA extraction was performed using the phenol-chloroform method. The VEGF gene polymorphisms were detected using the PCR-RFLP method using specific primers. Additionally, serum VEGF concentrations were measured using the ELISA method.

    Results

     Maternal age, gestational week, maternal hemoglobin, and BMI were significantly correlated with the likelihood of developing PE, whereas the season of occurrence was not found to be a significant factor. No significant difference was observed in the -634C/G and +936C/T polymorphisms of the VEGF gene between the two groups. Moreover, serum VEGF levels in PE patients were significantly higher than in the control group (P < 0.001).

    Conclusions

     Although serum VEGF concentrations were significantly elevated in women with PE, the -634C/G and +936C/T polymorphisms of the VEGF gene do not appear to be associated with the onset of PE. Further research is necessary to fully elucidate the risk factors of PE syndrome.

    Keywords: Preeclampsia, Single Nucleotide Polymorphisms, VEGF