Cell Journal最新文献

Despite a lower estimated rate of cancer incidence in Iran compared to the global average, the trend is unfortunately increasing. This necessitates the implementation of early detection of cancer and targeted therapies to effectively treat various types of cancer. Therefore, the 5th "International Royan Cancer Conference: From Bench to Bedside" was held to focus on critical cancer-related aspects such as gene- and cell therapy, immunotherapy, oligonucleotides in cancer treatment, biosensors for detection, and drug delivery. The 2-day conference took place in February 2024 at the Royan Institute, Tehran. This collaborative effort brought together experts from both basic and clinical research fields. The primary objective of the conference was to address clinical challenges and harness the potential of basic sciences for early cancer diagnosis and treatment, with a robust emphasis on ethical considerations. The conference aimed to ensure optimal patient care while advancing scientific understanding in the field and facilitating effective research collaborations among researchers and enthusiasts dedicated to combating cancer.

In this article published in Cell J, Vol 26, No 1, 2024, on pages 81-90, the authors found that the affiliation of authors in address 1 and also the two corresponding authors had accidentally missed during the formatting of the paper. Therefore, we corrected them. The authors would like to apologize for any inconvenience.

Objective: Endometriosis, as a common inflammatory chronic disease is characterized by endometrial tissue growth outside the uterine cavity. It was reported that lipopolysaccharides (LPS) activate a transcription factor called LPSinduced tumor necrosis factor-alpha (LITAF) in macrophages, which induced transcription of cytokine genes such as tumor necrosis factor alpha (TNF-α). B-cell lymphoma 6 protein (BCL6) is a transcription factor which expression was increased in endometrial tissues of infertile women with endometriosis. In addition, it was shown that mRNA and protein of LITAF and BCL6 were inversely related in mature B lymphocytes and B-Cell lymphomas. Accordingly, we investigated gene expression of LITAF, BCL6 and ,TNF-α in eutopic and ectopic endometrial tissues of women with endometriosis compared to the controls.

Materials and methods: In this case-control study, 10 women with endometriosis (endometriosis group) and 10 women without endometriosis (control group) enrolled after diagnostic laparoscopy. Real-time polymerase chain reaction (PCR) technique was used to quantitatively analyze gene expression. One-Way ANOVA was used for data analysis.

Results: This study showed that LITAF gene expression was significantly higher in ectopic endometrial tissues compared to the control samples. Expression level of BCL6 gene was significantly increased in the ectopic tissues of women with endometriosis compared to the control and eutopic samples. Although TNF-ɑ gene expression was increased in the ectopic lesions compared to the eutopic and control endometrial samples, these differences were not significant.

Conclusion: The results suggested that over-expression of these inflammatory genes in ectopic endometrial lesions can be considered as a molecular scenario in pathophysiology of endometriosis by induction of inflammatory cascades and cellular proliferation.

Objective: Intraocular retinoblastoma (RB) is common in kids. Although the cause of this disease is a mutation in the RB1 gene, the formed cancerous mass in different patients is seen in non-invasive states, limited to the ocular cavity or in invasive states distributed to other parts of the body. Because this tumor's aggressiveness cannot be predicted early, these patients receive systemic chemotherapy with multiple drugs. Treating non-invasive and invasive tumors separately reduces chemical drug side effects. The aim of this study was to identify diagnostic biomarkers by separating miRNAs in blood serum from invasive and non-invasive RB patients.

Materials and methods: In this experimental study, selected three gene expression omnibus (GEO) datasets. Two were related to serum and tumor tissue miRNAs, and one was related to non-invasive and invasive RB gene expression. Examined RB gene-miRNA relationships. Then, we performed real-time polymerase chain reaction (PCR) on candidate miRNAs in the Y79 cell line and patient blood samples in non-invasive and invasive retinoblastoma.

Results: Fourteen high-expression and 7 low-expression miRNAs resulted. MiR-181, miR-135a, miR-20a, miR-373, and miR-191 were common genes with differential genes between invasive and non-invasive retinoblastoma. Only MiR-181 was upregulated in the Y79 RB cell line. Other candidate miRNAs expressed less. Invasive retinoblastomas increased serum miR-20a and miR-191.

Conclusion: Integrated and regular bioinformatics analyses found important miRNAs in patients' and miR-20a, miR- 191, and miR-135a can distinguish non-invasive and invasive retinoblastoma, suggesting further research.

Objective: This study aimed to investigate the relationship between follicular fluid Bisphenol A (BPA) concentrations with alterations in the expressions of NOTCH1-3, CASPASE 3/7, HLA-G, and ICAM-1 genes and the number of retrieved mature oocytes (MII oocyte) in the cumulus cells of infertile poor ovarian response stimulates women.

Materials and methods: In this prospective cohort study, 80 infertile unexpected poor ovarian response (POR) subjects were selected on the basis of subgroup 1a of the POSEIDON classification. They were divided into two groups: group 1 consisted of 40 women, each with a higher number of metaphase II (MII) oocytes (G1, 3-4 oocytes retrieved), while group 2 comprised of 40 women, each with a lower number of MII oocytes (G2, ≤2 oocytes retrieved). The expressions of the studied genes were evaluated by quantitative-real time polymerase chain reaction (PCR). The concentration of BPA in follicular fluid was measured with HPLC.

Results: The expression levels of NOTCH1-3, HLA-G, and ICAM-1 genes were significantly lower in G2 than G1 (P<0.05). Meanwhile, CASPASE 3/7 expression levels were higher in unexpected POR patients in G2 compared to G1 (P<0.05). There was a significant direct correlation between the levels of NOTCH1-3, HLA-G and ICAM-1 gene expressions and there was also a significant inverse correlation (P<0.05) between the levels of CASPASE 3/7, with the number of MII oocytes and embryo development between the two groups. The concentration of BPA in the follicular fluids of G2 was higher compared to G1 (P<0.05).

Conclusion: A higher concentration of BPA was associated with a lower number of mature oocytes and oocyte quality in these patients. Also, alterations of NOTCH1-3, CASPASE 3/7, HLA-G, and ICAM-1 transcript levels in unexpected POR women were associated with BPA concentration.

Objective: The relationship between oxidative stress (OS), insulin resistance (IR), and polycystic ovary syndrome (PCOS) is an important medical issue in human reproduction. Some of the oxidative phosphorylation (OXPHOS) genes have been previously studied in granulosa and muscle cells of PCOS patients. Cumulus cells (CCs) remain close to the oocyte even after ovulation. This research has been designed to compare the expression of OXPHOS genes in CCs of PCOS, with or without insulin resistance.

Materials and methods: In this experimental study, patients were included in PCOS insulin-resistant, PCOS insulinsensitive (IS), and control (fertile women with male infertility history) groups. The expression of NCF2, TXNIP, UCP2, NDUFB6, ATP5H, COX7C, NDUFA3, SDHA, and SDHB was studied by real-time polymerase chain reaction (PCR), and normalization was performed considering HPRT1 and CYC1 as reference genes. One-way ANOVA and Tukey test were used for data analysis.

Results: The results showed that the expression of NCF2, TXNIP, UCP2, and ATP5H was significantly higher in the IR group than IS and control groups (P<0.01). NDUFB6 showed the highest expression in the IS group, which was significantly different from other groups (P<0.01). The other genes of interest, except COX7C, were observed with the most transcriptional levels in the IS group, although there was no significant difference for those genes.

Conclusion: Altered expression of genes involved in mitochondrial function compared to the control group in CCs of both IR and IS categories of the PCOS patients suggests that alteration in OXPHOS genes can contribute to the pathophysiology of PCOS.

Objective: Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur after administration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule with anti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model of OHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictor proteins and ovarian histological changes in an experimental OHSS rat model.

Materials and methods: In this experimental study, 30 adult female rats (two months old) were randomly divided into six groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by 30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days), iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone (P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes.

Results: Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atretic follicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of the VEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantly attenuated all molecular and histological alterations observed in the OHSS animals.

Conclusion: Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patients by reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings are similar to CAB and can be a new avenue for future research on BET.

Objective: Celiac disease is a common chronic inflammatory condition of the small intestine caused by permanent intolerance to gluten/gliadin. It has been demonstrated that oxidative stress is one of the mechanisms that is involved in gliadin toxicity, and there is a correlation between oxidative damage with this disease. Similarly, increased oxidative stress was repeatedly reported in infertile men which led to low-quality of sperm function. Therefore, we aimed to assess sperm parameters and chromatin status in men with Celiac disease.

Materials and methods: In this case-control study, semen samples were collected from 11 fertile men without Celiac and 10 men with diagnostic Celiac disease. Basic semen analyses were performed according to the World Health Organization (WHO) 2010 protocol. The percentage of sperm with persistence histones, protamine deficiency, DNA fragmentation, malondialdehyde (MDA), and intracellular reactive oxygen species (ROS) were assessed using aniline blue, chromomycin A3, sperm chromatin structure assay, thiobarbituric acid reactive substances (TBARS) assay, and diacetyldichlorofluorescein staining, respectively.

Results: Unlike the sperm parameters, which did not show significant differences between men with Celiac disease and fertile individuals, sperm chromatin maturation (persistence histones and protamine deficiency) and sperm DNA damage in men with Celiac disease were significantly higher compared to fertile individuals (P<0.05). In addition, the percentage of sperm viability in these individuals was significantly lower than that in the fertile individuals (P<0.05). We did not observe any significant differences in sperm lipid peroxidation and intracellular ROS levels between the two study groups (P>0.05).

Conclusion: Celiac disease affects sperm chromatin maturation and DNA fragmentation, emphasizing its impact on reproductive health.

In this article published in Cell J, Vol 18, No 2, Jul-Sep (Summer) 2016, on pages 179-188, the authors found that Figure 2A was the same as the one that has already been published and it was confusing. The following figure's legend is corrected in reference 9. The authors would like to apologies for any inconvenience caused.

Objective: Multiple sclerosis (MS) has a multi-factorial etiology involving genetic factors. Fingolimod (Gilenya ®, FTY720) modulates the G-protein-coupled sphingosine 1-phosphate (S1P) receptors, S1PR1, 2, 3, 4 and 5. Variation in the human S1PR1 coding sequence results in heterogeneity in the function of the receptor. Interleukin-17, producing CD4+ T cells, tends to be increased after treatment with Fingolimod. The aim of the study was to investigate singlenucleotide polymorphisms (SNPs) in the S1PR1 gene or interleukin-17 (IL-17) levels in a small group of Iranian relapsing-remitting MS patients treated with Fingolimod.

Materials and methods: In this case-control study, the genomic DNA of 94 MS patients treated with Fingolimod was extracted and Sanger sequencing was performed on polymerase chain reaction (PCR) products to detect variants in the S1PR1 gene. Quantification of IL-17 from the serum of the patients was performed using a commercially available enzyme-linked immunosorbent assay (ELISA).

Results: Among 94 relapsing-remitting MS patients treated with Fingolimod, 69 (73.4%) were responders and 25 (26.6%) were non-responders. There were four novel and five common SNPs in the S1PR1 gene and no significant association between SNP genotype and drug response was detected. In a subset of 34 patients, there was no significant difference in IL-17 serum concentrations before or after treatment and no association with S1PR1 polymorphisms was determined.

Conclusion: This study is the first in Iran to investigate association between SNPs of the S1PR1 gene or IL-17 levels with fingolimod response in a small group of Iranian relapsing remitting MS patients. There was no association with S1PR1 gene SNPs or IL-17 levels before or after treatment.