Deregulated expressions of tumor-suppressive microRNAs (miRNAs) by epigenetic aberrations has a critical role in tumorigenesis. The aim of the present study was to investigate the epigenetic ...aberrations of miR205 and to understand how this modification may contribute to molecular events in glioblastoma multiform (GBM).
Quantitative RT-PCR and bisulfite genomic sequencing techniques were used to investigate gene expression and methylation levels of miR-205 in GBM tissues (n = 23), their matched adjacent normal tissues (n = 23) and glioblastoma U87MG cell line. Following treatment of cells with 5-aza-2'-deoxycitidine (5-aza-dC), DNA methylation and gene expression levels of miR-205 gene and protein expressions of its target mRNA were investigated.
Our study showed that gene expression level of miR-205 decreased in GBM tissues compared to controls (p < 0.01) and lower expression was significantly correlated with this miRNA promoter hypermethylation (r = -78; p < 0.01). Cell treatment with 5-aza-dC restored the hypermethylated promoter and gene expression of the miR205 and decreased target mRNA and proteins levels (p < 0.01).
In summary, our results offered that miR-205 is an epigenetically silenced tumor suppressive miRNA in GBM, suppresses enhanced target mRNA when induced by DNA demethylating agents.
•Serum levels of CTRP12 were found to be lower in CAD patients.•Serum levels of CTRP12 independently associated with risk of CAD.•CTRP12 negatively associated with BMI, HOMA-IR, TNF-α and IL-6 in CAD ...patients.•CTRP12 positively associated with adiponectin and HDL-C in CAD patients.
Coronary artery disease (CAD) is the leading cause of death worldwide. Atherosclerosis as the main underlying mechanism of CAD is associated with inflammation and adipose tissue dysfunction. C1q/TNF-related protein12 (CTRP12) is a newly discovered adipokine which is a paralog of adiponectin. CTRP12 has anti-inflammatory and insulin sensitizing effects. Circulating levels of this adipokine have been reported to be lower in patients with type 2 diabetes and women with polycystic ovarian syndrome. The present study was undertaken for the first time to evaluate serum levels of CTRP12 in CAD patients and its association with anthropometric and biochemical parameters.
Serum levels of CTRP12 were measured using ELISA kit in 188 CAD patients (angiography confirmed) and 70 controls. The serum levels of adiponectin, TNF-α and IL-6 were measured using ELISA kits.
Serum levels of CTRP12 were found to be lower in CAD patients (585.48 ± 201.67 pg/mL) than in the controls (814.86 ± 247.85 pg/mL; p < 0.001). CTRP12 also showed an independent association with the risk of CAD (OR CI = 0.998 0.996–0.999; p = 0.019). Moreover, it showed an inverse correlation with HOMA-IR (r = −0.298; p = 0.012) and TNF-α (r = −0.269; p = 0.023) and a positive correlation with adiponectin (r = 0.344; p = 0.003) in the controls. In CAD patients, CTRP12 was inversely correlated with BMI (r = −0.181, p = 0.013), HOMA-IR (r = -0.199; p = 0.006), TNF-α (r = -0.259; p < 0.001) and IL-6 (r = -320; p < 0.001) and a positive correlation with high density lipoprotein-cholesterol(r = 0.342; p < 0.001) and adiponectin (r = 0.398; p < 0.001).
The present study showed for the first time that serum levels of CTRP12 are independently associated with CAD and that CTRP12 is associated with several CAD risk factors. The results suggest a possible link between CTRP12 and pathogenic mechanisms of atherosclerosis, such as inflammation and high density lipoprotein-cholesterol metabolism; however, more study is required in this regard.
Aberrant DNA hypermethylation contributes to many cancers by silencing structurally normal tumor suppressive genes. MicroRNA-153 (miR-153) exerts a tumor suppressive function in glioblastoma ...multiforme (GBM) by silencing oncogenic targets. However, the mechanism underlying miR-153 regulation in glioma cells has not been studied.
The expression levels of miR-153 were determined by real-time PCR and genomic bisulfite modification technique was used to detect the DNA methylation status in the upstream region of miR-153 in GBM, their matched normal adjacent tissues, and the glioblastoma U87 cell line. Following treatment of cells with 5-aza-2'-deoxycitidine (5-aza-dC), the DNA methylation, gene expression and target proteins levels of miR-153 were determined.
This study confirmed that miR-153 is significantly downregulated and hypermethylated in GBM tissues compared to their matched normal adjacent tissues. Increased methylation level of miR-153 was significantly correlated with reduced miR-153 expression in GBM tissue specimens. Demethylation of cells by 5-aza-dC treatment led to reduction of miR-153 methylation level, re-expression of candidate microRNA, and downregulation of its target proteins levels.
Our data indicated that miR-153 acts as a tumor suppressor in GBM and is down-regulated by DNA methylation, suggesting that miR-153 may serve as a potential diagnostic or therapeutic target of GBM. (Clin. Lab. 2016;62:573-580. DOI: 10.7754/Clin.Lab.2015.150738)
Menopause, which occurs following a declined ovarian activity and reduced estrogen levels, can lead to long‐term changes in lipid and glycemic profiles and increases the risk of cardiovascular ...disease and osteoporosis. Cornelian cherry (Cornus mas) is rich in phytochemicals and antioxidants, which appears to be useful in reducing the postmenopausal complications. This interventional, double‐blinded, randomized clinical trial carried out on 84 menopaused women aged 45–60 years old. They were randomly divided into two groups. The treatment group received three capsules of 300 mg of Cornus mas extract (CME), and control group received three capsules of 300 mg of starch powder per day for 8 weeks. Then, BMI, waist circumference, glycemic indices, lipid profile, serum apoproteinase, apoprotein B100, fibrinogen, and leptin were measured. The dietary intakes were evaluated using 24‐hr dietary recall questionnaire. The consumption of CME in comparison with the control group resulted in a significant reduction in weight, body mass index, waist circumference, LDL to HDL ratio, total cholesterol to HDL ratio, and fibrinogen. There was also a significant increase in HDL and ApoA1 levels in the treatment group. Furthermore, there was a significant decrease in BMI, waist circumference, fasting insulin, and insulin resistance index after 8 weeks of using CME. Summing up the results, it can be concluded that CME can have possible effects on decreasing BMI, waist circumference, and improving some aspects of lipid profile and glycemic indices in postmenopausal women.
CTRP15 is a prologue of adiponectin which has shown to have favourable effects on glucose and lipid metabolism. Studies have reported lower levels of CTRP15 in T2DM and metabolic syndrome; however, ...its circulating levels have not been evaluated in CAD patients.
This case-control study was conducted on 190 angiographically confirmed coronary artery disease (CAD) patients and 70 controls. Serum levels of CTRP15, adiponectin, TNF-α, and IL-6 were measured using the ELISA technique.
CTRP15 was shown to occur in higher levels in CAD patients compared with controls. In CAD patients, CTRP15 showed a positive correlation with BMI, FBS, insulin, HOMA-IR, IL-6, and TNF-α and a negative correlation with HDL-C and adiponectin.
Elevated levels of CTRP15 in CAD patients and the relation of CTRP15 with pathogenic conditions such as insulin resistance, inflammation, and decreased adiponectin and HDL-C suggest a possible compensatory response to these conditions in CAD patients.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Theophylline synergistically enhanced apoptosis, reduced necrosis induced by berberine in MDA-MB-231 breast cancer cells.•Combination of theophylline and berberine ...reduced HMGB1 content/expression, MMP-9 expression and arrested the cells at G2/M phase.•In the cells treated with BBR + TH, Bax expression level and PARP cleavage were increased while Bcl2 expression was reduced.•Combination of exogenous cAMP represented similar effect on berberine toxicity compared to theophylline.
Berberine, is a plant alkaloid, proved to have anticancer effect on various cancers. Theophylline (TH), a natural product, is widely used in the treatment of respiratory difficulties. The present study designed to elucidate the effects of theophylline and berberine combination on breast cancer cells cytotoxicity, gene expression and cell cycle. MTT assay revealed that berberine inhibited MDA-MB-231 breast cancer cells viability in a time and dose dependent manner (IC50 of 100 μM) but theophylline had no considerably effect on the cells. Combined treatment of berberine and theophylline showed a synergistic anti-proliferation effect, IC50 of berberine reduced to 50 μM and the cells were arrested at G2/M phase. Combined treatment of Berberine and theophylline reduced extracellular level of HMGB1 and down regulated HMGB1 and MMP-9 mRNA expression. The results of flow cytometry using annexin/PI staining of the cells, HMGB1 release, and poly ADP ribose polymerase cleavage demonstrated that theophylline attenuated necrotic effect of berberine and increased the level of apoptotic cell death. Enhancement of Bax content detected by ELISA and upregulation of Bax mRNA expression, down-regulation of Bcl-2 expression and increase of anion superoxide production confirmed induction of apoptosis via intrinsic apoptotic pathway. Replacement of theophylline with exogenous cyclic AMP in combination treatment represented similar effect on berberine cytotoxicity. From the results it is concluded that synergistic anticancer effect of theophylline and berberine suggests that combination of these two drugs may be an effective therapeutic agent against breast cancer cell.
Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by neural inflammation and oxidative stress. In the current study, the protective effects of klotho and ...linagliptin treatment on human peripheral blood mononuclear cells (PBMCs) of AD patients and healthy controls (HCs) are assessed through measurement of inflammatory cytokines, signaling proteins, and miRNA expression. Sixteen diagnosed AD patients and sixteen HCs were enrolled in the study. Blood samples were obtained and PBMCs were isolated. PBMCs were treated with klotho at different concentrations (0.5, 1, and 2 nM) and linagliptin (50 μM). The concentration of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), epsilon isoform of protein kinase C (PKCε), phosphorylated cyclic AMP response element binding (pCREB), and Wnt1 were measured by ELISA. The expression of miR-29a and miR-195 was detected by real-time PCR. The results showed that klotho significantly reduced IL-1β, IL-6, and TNF-α levels in both groups of the experiment. Linagliptin also remarkably reduced TNF-α levels in the AD group. Moreover, klotho caused the downregulation of Wnt1 in the PBMCs of both groups and the upregulation of the pCREB in HCs. Meanwhile, klotho induced miR-29a expression in the PBMCs of HCs, while miR-29a expression was induced in the AD group by klotho and linagliptin. The current findings revealed that klotho alleviates inflammation in human PBMCs, probably through the suppression of inflammatory cytokines and the upregulation of miR-29a, and part of its beneficial effect is mediated through appropriate modulation of the Wnt1/pCREB signaling cascade. In addition, linagliptin exerts protective effects by reducing TNF-α and inducing miR-29a expression in PBMCs.
Atherosclerosis is a progressive inflammatory disease characterized by the accumulation of lipids in the arterial wall. Inflammation plays a key role in the pathogenesis of atherosclerosis and some ...previous studies have shown the role of adipokines during the inflammatory process of atherosclerosis. Therefore, the present study aimed to evaluate the impacts of adiponectin and CTRP15 on inflammatory cytokines secretions from THP1 and primary macrophages.
THP1 monocytes were differentiated to macrophages and primary monocytes were then isolated from patients with coronary artery disease and controls who were differentiated to macrophages. Macrophages were treated with LPS, LPS+adiponectin, and LPS+CTRP15.
Adiponectin and CTRP15 have reduced IL-6 and TNF-α secretions from LPS-induced THP1 macrophages, and the CTRP15 indicated a more potent anti-inflammatory property compared to adiponectin. In addition, adiponectin reduced cytokines’ expressions and secretions in primary macrophages of both patient and control groups. However, CTRP15 has only reduced cytokines’ expressions and secretions in controls and it was not able to ameliorate inflammation in macrophages of CAD patients.
The results of the present study indicate anti-inflammatory impact of adiponectin and CTRP15, while this property was stronger for CTRP15. In addition, it seems likely that anti-inflammatory CTRP15′s impact on macrophages in the CAD patients was weaker than macrophages from the controls.
Keywords CTRP; Adipokie; Inflammation; Cytokine; Macrophage Atherosclerosis is a progressive inflammatory disease characterized by the accumulation of lipids in the arterial wall. Inflammation plays ...a key role in the pathogenesis of atherosclerosis and some previous studies have shown the role of adipokines during the inflammatory process of atherosclerosis. Therefore, the present study aimed to evaluate the impacts of adiponectin and CTRP15 on inflammatory cytokines secretions from THP1 and primary macrophages. Methods THP1 monocytes were differentiated to macrophages and primary monocytes were then isolated from patients with coronary artery disease and controls who were differentiated to macrophages. Macrophages were treated with LPS, LPS+adiponectin, and LPS+CTRP15. Results Adiponectin and CTRP15 have reduced IL-6 and TNF-alpha secretions from LPS-induced THP1 macrophages, and the CTRP15 indicated a more potent anti-inflammatory property compared to adiponectin. In addition, adiponectin reduced cytokines' expressions and secretions in primary macrophages of both patient and control groups. However, CTRP15 has only reduced cytokines' expressions and secretions in controls and it was not able to ameliorate inflammation in macrophages of CAD patients. Conclusion The results of the present study indicate anti-inflammatory impact of adiponectin and CTRP15, while this property was stronger for CTRP15. In addition, it seems likely that anti-inflammatory CTRP15's impact on macrophages in the CAD patients was weaker than macrophages from the controls. Author Affiliation: (a) Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran (b) Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran (c) Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran (d) Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran * Corresponding author. Article History: Received 18 October 2020; Revised 26 January 2021; Accepted 4 February 2021 Byline: Reza Ahmadi (a), Reza Fadaei (b), Abolfazl Shokoohi Nahrkhalaji (c), Ghodratollah Panahi (d), Soudabeh Fallah Fallah.s@iums.ac.ir (c,*)
Growing evidence suggests that adipokines may be therapeutic targets for cardiometabolic diseases such as type 2 diabetes mellitus (T2DM). C1q TNF Related Protein 3 (CTRP3) is a newly discovered ...adipokine which shares properties with adiponectin. The literature about the association between circulating levels of CTRP3 and T2DM has been conflicting. The present study reassessed the data on circulating CTRP3 levels in T2DM patients compared to controls through a systematic review and meta-analysis.
A literature search was performed in Medline, Embase, Scopus, and Web of science to identify studies that measured circulating CTRP3 levels in T2DM patients and controls.
The search identified 124 studies of which 59 were screened for title and abstract and 13 were subsequently screened at the full text stage and 12 studies included into the meta-analysis. Subgroup analyses, depending on the presence of T2DM complications, matching for BMI, age, and cut off value of fasting blood sugar and HOMA-IR, were performed.
The results show that circulating CTRP3 levels are negatively associated with T2DM status (SMD: −0.837; 95% CI: (−1.656 to −0.017); p = 0.045). No publication bias was identified using the Begg’s rank correlation and Egger’s linear regression tests (P = 1 and P = 0.44, respectively). Meta-regression demonstrated significant association between CRTP3 levels with BMI (slope: 0.11; 95% CI: 0.04–0.19; p = 0.001) and sex (slope: −0.07; 95% CI: −0.12 to −0.01; p = 0.008).
The present systematic review and meta-analysis evidences a negative association between circulating level of CTRP3 and T2DM status. BMI and sex may modify this association.
