Cell Journal (Yakhteh)
Volume:24 Issue: 4, Apr 2022

Aberrant alterations in DNA methylation are known as one of the hallmarks of oncogenesis and play a vital role in the progression of acute myeloid leukemia (AML). SMG1 is a member of the Phosphoinositide 3-kinases family, acting as a tumor suppressor gene. The aim of this study was the evaluation of the expression level and methylation status of SMG1 in AML.

In this follow-up study on AML patients admitted to Shariati Hospital, Tehran, Iran, the methylation status of SMG1 [performed by methylation-specific polymerase chain reaction (PCR)] and its expression level (performed by qRT-PCR) were evaluated in three phases: newly diagnosed, under treatment and complete remission. The correlation of the methylation status of SMG1, its expression level, and clinical/paraclinical data was analyzed by SPSS ver.25.

This study on 18 patients and five control individuals showed that the CpG-islands of the SMG1 promoter in newly diagnosed cases is hypomethylated compared to the normal group (P=0.002) The fold change of SMG1 expression levels in new cases is 0.464 ± 0.468, while the fold change of SMG1 expression levels in under-treatment and in-remission patients is 0.973 ± 1.159 and 0.685 ± 0.885, respectively. In under-treatment patients, white blood cell (WBC) count decreases 114176.36 cell/μl with each unit of increase in fold change of SMG1 (P<0.0001), and Hb unit increases 2.062 g/dl with each unit of increase in fold change (P<0.0001) Also, in the remission phase, the Hb unit increases 1.395 g/dl with each unit increase in fold change (P=0.019).

The robust results of our study suggest that the methylation and expression of SMG1 have a high impact on the pathogenesis of AML. Also, the methylation and expression of SMG1 can play a prognostic role in AML.

Estrogen, a female hormone maintaining several critical functions in women's physiology, e.g., folliculogenesis and fertility, is predominantly produced by ovarian granulosa cells where aromatase enzyme converts androgen to estrogen. The principal enzyme responsible for this catalytic reaction is encoded by the CYP19A1 gene, with a long regulatory region. Abnormalities in this process cause metabolic disorders in women, one of the most common of which is polycystic ovary syndrome (PCOS). The main purpose of this research was to determine the effect of the promoters on aromatase expression in cells with normal and PCOS characteristics.

In this experimental study, four promoters of the CYP19A1 gene, including PII, I.3, I.4, and PII/ I .3 promoter fragments, were cloned upstream of the luciferase gene and transfected into normal and PCOS granulosa cells. Subsequently, the effect of follicle-stimulating hormone (FSH) on the activity of these regulatory regions was examined in the presence and absence of FSH. Western blotting was used to confirm aromatase expression in all groups. Data analysis was performed using ANOVA and paired sample t test, compared by post-hoc least significant difference (LSD) test.

Luciferase results confirmed the intense activity of PII promoter in the presence of FSH. Moreover, the study demonstrated reduced activity of PII promoter in normal granulosa cells, possibly due to the regulatory region of I.3 next to PII.

FSH stimulates transcription of aromatase enzyme by affecting PII promoter, a process regulated by the inhibitory role of the I.3 region in PII activity in granulosa cells. Given the distinct role of these promoters in normal and PCOS granulosa cells, the importance of nuclear factors residing in these regions can be discerned.

Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are two important enzymes involved in One-Carbon metabolism. These enzymes play important roles in modulating oxidative stress and inflammation in male factor infertility through participating in the synthesis of glutathione (GSH) antioxidants in the trans-sulfuration pathway. Besides, the direct release of hydrogen sulfide (H2S) has anti-inflammatory and antioxidant effects. Therefore, the expression of CBS and CSE genes at mRNA levels in infertile and varicocele men was evaluated and compared to the healthy counterparts to clarify their possible role in the pathology of male infertility.

In this case-control study, semen parameter assessment (concentration, morphology, and motility of sperms) was performed on 28 men with varicocele, 43 infertile men with abnormal sperm parameters, and 19 fertile men. RNA was extracted from sperm samples followed by cDNA synthesis and real-time polymerase chain reaction (PCR) using CBS, CSE, and GAPDH primers.

Sperm concentration and motility in infertile and varicocele groups were significantly lower (P=0.001), while spermatoza normal morphology was higher than fertile group (P=0.05). The expression levels of both CBS and CSE genes in infertile (P=0.04 and P=0.037 respectively) and varicocele (P=0.01 and P=0.046 respectively) groups were significantly lower than fertile group. Additionally, CBS gene expression indicated a positive correlation with expression of CSE gene (r=0.296, P=0.025) and sperm parameters.

In light of our findings, there is a valid rationale to consider the primary role of CBS and CSE enzymes impairment in male factor infertility which specifically may point to a deficit in the release of essential antioxidants including the H2S as a molecular basis of infertility and warrants further investigation.

COVID-19 is an infectious disease that has become pandemic with a high mortality rate. This study aims to provide new insight into the relations between SARS-CoV-2 and the Endocrine system.

In this cross-sectional study, we have hospitalized 60 patients with a positive SARA-CoV-2 PCR test. The information of complete blood count and endocrine hormones was obtained when the patients were admitted to the hospital or for a maximum of 4 days onset the hospitalization.

Of 60 patients with COVID-19, forty-four (73.33%) had at least one abnormality mean item >×3. In total, 26 (43.33%), 21 (35%), 18 (30%), 13 (21.67%), 31 (51.67%), 12 (20%), 30 (50%), 25 (41.67%) patients having estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, testosterone, cortisol and thyroid stimulating hormone (TSH) abnormal test results, respectively. There was no change in creatinine levels. FSH has shown drastic changes in both sexes’ intensity (F: 769, P<0.0001). Although TSH had many abnormalities in women, analysis has shown no significant P value (P=0.4558). Furthermore, prolactin and testosterone mean level in men and the estradiol mean level in women have shown no significant P value (P=0.2077, P=0.1446, P=0.1351, respectively).

Results suggest that COVID-19 affects directly or non-directly glands and related hormones.

Colonic anastomosis is associated with serious complications leading to significant morbidity and mortality. Fibroblasts have recently been introduced as a practical alternative to stem cells because of their differentiation capacity, anti-inflammatory, and regenerative properties. The aim of this study was to evaluate the effects of intramural injection of fibroblasts on the healing of colonic anastomosis in rats.

Inbred mature male Wistar rats were used in this experimental study (n=36). Fibroblasts were isolated from the axillary skin of a donor rat. In the sham group, manipulation on descending colon was done during laparotomy. A 5 mm segment of the colon was resected, and end-to-end anastomosis was performed. In the control group, 0.5 ml of phosphate buffer saline (PBS) was injected into the colonic wall and in the treatment group, 1×106 fibroblasts were transplanted. Following euthanasia on day 7, intra-abdominal adhesion, leakage and peritonitis were evaluated by necropsy. Mechanical properties were assessed using bursting pressure and tensile tests. Inflammation, angiogenesis, and collagen deposition were examined histopathologically.

The mean scores for adhesion and leakage were decreased in the treatment group versus control samples. Lower infiltration of inflammatory cells was observed in the treatment group (P=0.03). Angiogenesis and collagen deposition scores were significantly increased in the fibroblast transplanted group (P=0.03). Tensile mechanical properties of the colon were significantly increased in the treatment group compared to the control sample (P=0.01). There was no significant difference between the control and treatment groups in terms of bursting pressure (P=0.10). Positive weight changes were found in sham and treatment groups, but the control rats lost weight after 7 days.

The results suggested that allotransplantation of dermal fibroblasts could improve the necroscopic, histopathological, and biomechanical indices of colonic anastomosis repair in rats.

Salivary gland tumors (SGTs) show some aggressive and peculiar clinicopathological behaviors that might be related to the components of the tumor microenvironment, especially mesenchymal stem cells (MSCs)-associated proteins. However, the role of MSCs-related proteins in SGTs tumorigenesis is poorly understood. This study aimed to isolate and characterize MSCs from malignant and benign tumor tissues and to identify differentially expressed proteins between these two types of MSCs.

In this experimental study, MSC-like cells derived from benign (pleomorphic adenoma, n=5) and malignant (mucoepidermoid carcinoma, n=5) tumor tissues were verified by fluorochrome antibodies and flow cytometric analysis. Differentially expressed proteins were identified using two-dimensional polyacrylamide gel electrophoresis (2DE) and Mass spectrometry.

Results showed that isolated cells strongly expressed characteristic MSCs markers such as CD44, CD73, CD90, CD105, and CD166, but they did not express or weakly expressed CD14, CD34, CD45 markers. Furthermore, the expression of CD24 and CD133 was absent or near absent in both isolated cells. Results also discovered overexpression of Annexin A4 (Anxa4), elongation factor 1-delta (EF1-D), FK506 binding protein 9 (FKBP9), cytosolic platelet-activating factor acetylhydrolase type IB subunit beta (PAFAH1B), type II transglutaminase (TG2), and s-formylglutathione hydrolase (FGH) in MSCs isolated from the malignant tissues. Additionally, heat shock protein 70 (Hsp70), as well as keratin, type II cytoskeletal 7 (CK-7), were found to be overexpressed in MSCs derived from the benign ones.

Malignant and benign SGTs probably exhibit a distinct pattern of tissue proteins that are most likely related to the metabolic pathway. However, further studies in a large number of patients are required to determine the applicability of identified proteins as new targets for cancer therapy.

Tumor drug resistance is a vital obstacle to chemotherapy in lung cancer. Methionine adenosyltransferase 2A has been considered as a potential target for lung cancer treatment because targeting it can disrupt the tumorigenicity of lung tumor-initiating cells. In this study, we primarily observed the role of methionine metabolism in cisplatin-resistant lung cancer cells and the functional mechanism of MAT2A related to cisplatin resistance.

In this experimental study, we assessed the half maximal inhibitory concentration (IC50) of cisplatin in different cell lines and cell viability via Cell Counting Kit-8. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of relative proteins and genes. Crystal violet staining was used to investigate cell proliferation. Additionally, we explored the transcriptional changes in lung cancer cells via RNA-seq.

We found H460/DDP and PC-9 cells were more resistant to cisplatin than H460, and MAT2A was overexpressed in cisplatin-resistant cells. Interestingly, methionine deficiency enhanced the inhibitory effect of cisplatin on cell activity and the pro-apoptotic effect. Targeting MAT2A not only restrained cell viability and proliferation, but also contributed to sensitivity of H460/DDP to cisplatin. Furthermore, 4283 up-regulated and 5841 down-regulated genes were detected in H460/DDP compared with H460, and 71 signal pathways were significantly enriched. After treating H460/DDP cells with PF9366, 326 genes were up-regulated, 1093 genes were down-regulated, and 13 signaling pathways were significantly enriched. In TNF signaling pathway, CAS7 and CAS8 were decreased in H460/DDP cells, which increased by PF9366 treatment. Finally, the global histone methylation (H3K4me3, H3K9me2, H3K27me3, H3K36me3) was reduced under methionine deficiency conditions, while H3K9me2 and H3K36me3 were decreased specially via PF9366.

Methionine deficiency or MAT2A inhibition may modulate genes expression associated with apoptosis, DNA repair and TNF signaling pathways by regulating histone methylation, thus promoting the sensitivity of lung cancer cells to cisplatin.

HASPIN acts in chromosome segregation via histone phosphorylation. Recently, HASPIN inhibitors have been shown to suppress growth of various cancer cells. Pancreatic cancer has no symptom in the early stages and may progress before detection. So, the 5-year survival rate is low. Here, we reported that administration of the HASPIN inhibitor, CHR-6494, to mice bearing pancreatic BxPC-3-Luc cancer cells significantly suppressed growth of BxPC-3-Luc cells. CHR-6494 might be a useful agent for treating pancreatic cancer.