جستجوی مقالات مرتبط با کلیدواژه « telomere length » در نشریات گروه « پزشکی »

Sulfur mustard (SM), a chemical weapon used in the Iraq-Iran war from 1983-1988, has multiple chronic complications. This study aimed to evaluate one of the long-act effects of SM, i.e. the senescence according to the severity of injury in veterans via the estimation of biological health score (BHS) and relative telomere length (TL) of immune cells. 

SM-chemical veterans were categorized into three groups according to the percentage of chemical injury (5-20%, 25-45%, and 50-70%). Healthy volunteers also participated as a control group. Eighteen biomarkers from different physiological systems (inflammatory/immune, endocrine, cardiovascular, and metabolic), and organs (liver and kidney) were used to estimate BHS. The TL of immune cells was also measured for each participant by monochrome multiplex real-time PCR. 

There were significant correlations between age-adjusted TL (negative), BHS, and BHS/TL ratio (positive) and the percentage of injury. The TL was significantly decreased in all veterans with different injuries compared to healthy participants while it did not change in veterans with the injury percentages of 25-45% and 50-70%. The BHS in three groups of veterans was significantly higher than in healthy individuals. The BHS/TL ratio was significantly changed between all groups and increased with the progress of injury. 

The BHS and TL may not individually be accurate indices for the determination of senescence and biological aging while the ratio of these two parameters improves this defect and could be a more reliable index indicating biological aging in chemical veterans with different percentages of injury.

A predominant challenge in the discovery approach to curative leukemia is investigating the effect of mesenchymal stem cells (MSCs) on leukemic cells. We aimed to investigate the role of MSCs in targeting telomerase enzyme and consequently telomere length of leukemic cells. For this purpose, the KG1 cell as leukemia cell line was co-cultured with MSCs in the trans-well system. After seven days of co-culture, KG1 cells were collected, and telomerase activity, telomere length, and hTERT gene expression were analyzed by PCR-ELISA TRAP assay and real-time PCR, respectively. Also, the potentially involved ERK pathway was analyzed at gene and protein levels by real time PCR and flow cytometry, respectively. It was found that MSCs caused a significant decrease in telomerase activity, telomere length, and hTERT gene expression. The following results showed that MSCs resulted in a significant decrease in the ERK expression levels. It can be concluded that the co-culture of MSCs with KG1 cells be involved in the telomerase targeting via ERK signaling pathways. This study concluded that the co-culture of MSCs with AML leukemic cells could secrete a significant amount of cytokines that cause to inhibit the proliferation of AML cell lines via ERK signaling pathway. The recognition of cytokines as well as growth factors involved in the anti-proliferative effect of MSCs requires further investigation. This effect as a therapeutic strategy could be considered in the basic experimental studies.

Mesenchymal stem cells (MSCs) as undifferentiated cells are specially considered in cell-based cancer therapy due to unique features such as multi-potency, pluripotency, and self-renewal. A multitude of cytokines secreted from MSCs are known to give such multifunctional attributes, but details of their role are yet to be unknown. In the present study, MSCs were cultured, characterized and co-cultured with Molt-4 cells as acute lymphoblastic leukemia cell line in a trans-well plate. Then, cultured Molt-4 alone and Molt-4 co-cultured with MSCs (10:1) were collected on day 7 and subjected to real time-PCR and Western blotting for gene and protein expression assessment, respectively. Ki-67/caspase-3 as well as telomere length were investigated by flow cytometry and real time-PCR, respectively. The results showed that MSCs caused significant decrease in telomere length as well as hTERT gene expression of Molt-4 cells. Also, gene and protein expression of BAD and P53 were significantly increased. Furthermore, the flow cytometry analysis indicated the decrease and increase of the Ki-67 and caspaspase-3 expression, respectively. It was concluded that MSCs co-cultured with Molt-4 cells could be involved in the promotion of Molt-4 cell apoptosis via caspase-3, BAD, and P53 expression. In addition, the decrease of telomere length is another effect of MSCs on Molt-4 leukemic cells.

The effect of mesenchymal stem cells (MSCs) on the immortality features of malignant cells, such as hematologic cancerous cells, are controversial, and the associated mechanisms are yet to be well understood. The aim of the present study was to investigate the in vitro effect of bone marrow-derived MSCs (BMSCs) on the chronic myeloid leukemia cell line K562 through telomere length measurements, telomerase activity assessments, and hTERT gene expression. The possible signaling pathways involved in this process, including Wnt-5a/β-catenin and P53, were also evaluated.

Two cell populations (BMSCs and K562 cell line) were co-cultured on transwell plates for 7 days. Next, K562 cells were collected and subjected to quantitative real-time PCR, PCR-ELISA TRAP assay, and the ELISA sandwich technique for telomere length, hTERT gene expression, telomerase activity assay, and cytokine measurement, respectively. Also, the involvement of the mentioned signaling pathways in this process was reported by real-time PCR and Western blotting through gene and protein expression, respectively.

The results showed that BMSCs caused significant decreases in telomere length, telomerase activity, and the mRNA level of hTERT as a regulator of telomerase activity. The significant presence of interleukin (IL)-6, IL-8, and transforming growth factor beta (TGF-β) was obvious in the co-cultured media. Also, BMSCs significantly decreased and increased the gene and protein expression of β-catenin and P53, respectively.

It was concluded that the mentioned effects of IL-6, IL-8, and TGF-β cytokines secreted from MSCs on K562 cells as therapeutic agents were applied by Wnt-5a/β-catenin and P53 pathways.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not completely reversible by administration of inhaled bronchodilators. Many studies propose that telomere length shortening might have occurred in COPD patients. We aimed to determine the telomere length in COPD patients and compare the results of non-smoking and smoking control subjects.

In our case-control study, 84 clinically stable COPD patients were recruited on admission to Masih Daneshvari Hospital. Eighty-five healthy controls were also selected including 45 non-smokers and 40 smokers admitted for diseases other than COPD. Spirometry was done for all subjects. Telomere length was measured by quantitative real time PCR as described by Cawthon. The telomere repeat copy number (T) to single-gene copy number(S) ratio was calculated using the comparative Ct method.

The mean ±SD of age was 64.33±10.04 years in patients and 65.06 ±10.02 years in controls (P=0.693). The mean ±SD of FEV1 was 1.62±0.75 L in patients, 2.84±0.54 L in smoker controls and 2.83±0.56 L in non-smoker controls; significant differences were detected in this regard between cases and controls (P<0.001). T/S ratio was significantly lower in COPD patients (0.61±0.08) than in the control subjects (0.69±0.09) (P<0.001). However, telomere length was shorter in the patients than in controls in each age group (P<0.001). Additionally, there were no statistically significant differences in telomere length between the smoker and non-smoker control subjects. Regarding the correlation between BMI and telomere length, there were no significant differences among the patients and control groups.

In conclusion, we found that telomere length in COPD patients was shorter than that in smoker and non-smoker controls, irrespective of age, sex, spirometric variables, BMI and history of cigarette smoking.