Volume 44, Issue 3

Objectives Prostate cancer (PCa) is one of the most common cancers in men with high mortality rate which is a major concern for men’s health. However, the molecular mechanisms remain poorly understood. miR-93 is an important oncogene which may have important function in prostate cancer.So, this study aimed to predict that encomir-93 mimic transfection on the expression of miR-93 and PSA and AR in prostate cancer LNcap cell line. Methods Lymph node carcinoma of the prostate (LNCaP) was cultured and then miR-93 mimics was designed, synthesized and the transfected to LNCaP. The expression level of prostate-specific antigen (PSA) and androgen receptor (AR) was determined via Real-time PCR after treated with 15 pmol of miR-93 mimics. Results miR-93 mimic transfection led to significant increase in PSA and AR expression in comparison with control group (p≤0.05). Conclusions The miR-93 and its target genes has important role in PCa progression via enhancement in PSA and AR expression. Further research on the function of the miR-93 and its target genes in tumorgenesis and progression PCa could be helpful for the treatment of prostate cancer.

Objectives Type 2 diabetic Mellitus (T2DM) is the most common systemic and endocrine disease in humans, and diabetic nephropathy is one of the most serious complications of this disorder. The polymorphisms in the apolipoprotein A5 (ApoA5) gene are strongly related to hypertriglyceridemia and are considered a predisposing factor for diabetic nephropathy. The current study proposed to examine the association of APOA5-S19W polymorphism with serum lipids levels in patients with type 2 diabetic nephropathy in Mazandaran province. Methods This case-control study was designed to determine the association of APOA5–S19W polymorphism with plasma lipid profile in 161 T2DM patients with nephropathy (DN+), without nephropathy (DN−), and in 58 healthy individuals. Lipid profile values were measured using Pars Azmoun commercial kits. S19W variant, one of the polymorphisms of the APOA5 gene, was determined by PCR–restriction fragment length polymorphism (PCR-RFLP) and Taq1 restriction enzyme. Results In comparison between the three groups, DN+ had a higher mean TG than DN− and the control group (p<0.001). The incidence of the G allele in DN+ was not significant compared to groups of DN−. Comparing the relationship between the mean of biochemical variables with CC and CG genotypes showed that the mean level of TG in people with CC genotype was increased compared to people with CG genotype in diabetic patients. However, this increase was not significant (p=0.19). Conclusions There was no association between SNP APOA5 S19W and serum lipids in diabetic patients with and without nephropathy.

Objectives We aimed to determine possible association between heterogeneity of Helicobacter pylori cytotoxin-associated gene pathogenicity island and gene expression profiles in patients with distinct histopathological changes. Methods Gastric biopsies were obtained from seventy five patients. Microbiological and pathological examinations were done and intactness of Helicobacter pylori cag PAI was determined by PCR using 11 pairs of primers flanking cagζ - cagA regions and cag PAI empty site. Alterations at mRNA levels of eight genes were investigated by real-time PCR and their association with cag PAI intactness and histopathological changes examined statistically. Results A larger proportion of cag PAI positive strains colonized patients with SAG (52.4%), followed by CG (33.3%), and IM (14.3%). Intact cag PAI was found in 87.5% of the strains obtained from patients with SAG, while significantly lower frequency was detected among those with CG (12.5%) and IM (0%). No significant difference was found among the studied histological groups and fold changes in gene expression of gastric biopsies of Helicobacter pylori infected patients with distinct cag PAI status. However, in each histological group, the strains with more complete gene cluster induced ( ErbB2 , CCNE1 , CTNNB1 , and MMP7 in SAG and IM groups) or reduced ( TP53 , in CG group) expression of the GC associated genes in relatively higher levels. APC , TP53 and E-cadherin were down-regulated in patients with SAG and IM compared with CG patients, irrespective to the status of cag PAI integrity. Conclusions Helicobacter pylori strains that carry more complete cag PAI segment could induce remarkably higher levels of mRNA changes of GC associated genes in all histopathological groups.

Objectives Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers. Methods Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait. Chemical analyzers were used to measure glycemic and lipid profiles, while ELISA was used to measure plasma levels of insulin and several inflammatory markers. Results Showed that the IL-6 and TREM1 were significantly higher in T2D compared to non-diabetic controls, and the uPAR level was borderline higher in T2D but significantly correlated with IL-6 levels. Unexpectedly, IL8 was significantly below normal in T2D and IL6/IL8 ratio was significantly higher in T2D patients. Unlike other tested markers, uPAR was in addition strongly correlated with insulin levels and HOMA-IR index. Conclusions Raised levels of IL6, TREMI, IL6/IL8 ratio, and the strong positive correlation of plasma levels of uPAR with IL-6, insulin, and HOMA-IR index, are reliable spectators of chronic inflammation in T2D patients. The reduced level of IL-8 in T2D was a peculiar observation that needs further explanation. Finally, the consequences and impact of the sustained rise of these inflammatory regulators in diabetic tissues need to be meticulously explored.

Objectives MicroRNA expression disruptions play an important function in the expansion of gastric cancer. Previous investigation has indicated that miR-372-5p doing as an oncogene in several malignancies. CDX1 and CDX2, as target genes of miR-372-5p, play the role of tumor suppressors and oncogenes in gastric cancer cells, respectively. The current investigation explored the effects of miR-372-5p regulation on CDX2 and CDX1 in AGS cell lines and studied their molecular mechanism. Methods hsa-miR-372-5p miRCURY LNA miRNA Inhibitors and Mimic were transfected into AGS cell line. The cell viability and cell cycle calculation were defined by MTT assay and flow cytometry, respectively. The Expression levels of miR-372-5p, CDX1, CDX2 and transfection efficiency were measured using Real-time PCR. Statistical investigation p values <0.05 were considered to be meaningful. Results miR-372-5p particularly was upregulated in control cells and also after transfection by mimic. While its expression was reduced by the inhibitor. Upregulation of miR-372-5p remarkably increased cell growth and led to accumulation in the G2/M phase, although the inhibitor decreased cell growth and accumulation in the S phase. Accordingly, upregulation of miR-372-5p increased CDX2 and decreased CDX1 expression. By inhibition of miR-372-5p, expression of CDX2 was decreased and expression of CDX1 was increased. Conclusions Up and down-regulation of miR-372-5P has a potential effect on the expression levels of its target genes, CDX1 and CDX22. Accordingly, the downregulation of miR-372-5p may be assumed as a possible therapeutic target in treating gastric cancer.

Objectives Saliva is one of the most promising body fluids in the research of new biomarker for various diseases diagnosis. However, serial sampling in this condition is very dangerous and pose iatrogenic anemia with blood loss. This study was done to evaluate the cost-effectiveness of point-of-care salivary tests and identify the validity of salivary markers. Methods Rats were randomly assigned to four experimental groups: (1) control (2) IR-3 h (3) IR-6 h (4) IR-24 h. Both renal pedicles were occluded for 55 min and then were declamped to allow reperfusion for 3, 6 and 24 h in IR groups. After reperfusion, all rats received pilocarpine 1 mg/kg to collect saliva. Plasma samples were also collected. Renal parameters including Cr, uric acid, and urea, malondialdehyde (MDA) levels, Bax/Bcl2 ratio, nitrite/nitrate ratio, corticosterone levels and oxidant/antioxidant ratio were measured in both plasma and salivary samples. Results There were significant increased level of renal function parameters, MDA levels, Bax/Bcl2 ratio, nitrite/nitrate ratio and corticosterone in both saliva and plasma. The comparison of above parameters in both saliva and plasma showed significant correlation. Conclusions This study demonstrated that concentrations of indices specifically renal functional parameters increase in saliva in the IR-induced kidney injury in male rats and result indicate the potential of saliva as a tool to monitoring AKI. Measurement of salivary parameters may can become reliable diagnostic tests for patients with AKI.

Objectives To determine whether inhibition of kinase signaling will suppress resistin-induced liver cancer progression. Resistin is located in monocytes and macrophages of adipose tissue. This adipocytokine is an important link between obesity, inflammation, insulin resistance, and cancer risk. Pathways that resistin is known to be involved include but are not limited to mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinases (ERK). The ERK pathway promotes cellular proliferation, migration, survival of cancer cells, and tumor progression. The Akt pathway is known to be up-regulated in many cancers including liver cancer. Methods Using an in vitro model, HepG2 and SNU-449 liver cancer cells were exposed to resistin ± ERK, Akt, or both inhibitors. The following physiological parameters were assessed: cellular proliferation, ROS, lipogenesis, invasion, MMP, and lactate dehydrogenase activity. Results The inhibition of kinase signaling suppressed resistin-induced invasion and lactate dehydrogenase in both cell lines. In addition, in SNU-449 cells, resistin increased proliferation, ROS, and MMP-9 activity. Inhibition of PI3K and ERK decreased phosphorylated Akt and ERK, and pyruvate dehydrogenase. Conclusions In this study, we describe the effect of Akt and ERK inhibitors to determine if inhibition suppresses resistin-induced liver cancer progression. Resistin promotes cellular proliferation, ROS, MMP, invasion and LDH activity in SNU-449 liver cancer cells which is differentially mediated by Akt and ERK signaling pathways.

Objectives Metabolic syndrome (MetS) may cause premature development of some diseases. PON1 genes may be involved in the pathogenesis of MetS. The aim of study was to evaluate the association between Q192R and L55M gene polymorphisms and its enzyme activity with the MetS components in subjects with and without MetS. Methods Polymerase Chain Reaction and Restriction Fragment Length Polymorphism analysis were performed to determine polymorphisms of the paraoxonase1 gene in subjects with and without metabolic syndrome. Biochemical parameters were measured by spectrophotometer. Results The MM, LM, and LL genotype frequencies of the PON1 L55M polymorphism were 10.5, 43.4, and 46.1%, and 22.4, 46.6, and 31% and; the QQ, QR, and RR genotype frequencies of the PON1 Q192R polymorphism were 55.4, 38.6 and 6%; and 56.5, 34.8 and 8.7% in subjects with and without MetS, respectively. The L and M allele frequencies were 68 and 53%; and 32 and 47% for PON1 L55M in subjects with and without MetS, respectively. The Q and R allele frequencies for PON1 Q192R were 74 and 26% in both groups. There were significant differences in HDL-cholesterol level and PON1 activity in the genotypes QQ, QR, and RR of the PON1 Q192R polymorphism in subjects with MetS. Conclusions The PON1 Q192R genotypes had only effected on PON1 activity and HDL-cholesterol level in subjects with MetS. Different genotypes of the PON1 Q192R seem to be important candidates to make the subjects susceptible to MetS in the Fars ethnic group.

Objectives Metabolic syndrome (MS) is a collection of metabolic disorders including hyperglycemia, hypertension and dyslipidemia. The outcome of metabolic syndrome depends on structural changes in heart like increased left atrial size or increased left ventricular mass. This study was done to determine the echocardiography abnormalities in metabolic syndrome. Methods After obtaining informed consent, 75 subjects with metabolic syndrome and 75 controls were included in the study. 2D echo/M mode examination was performed for all. Aortic root, left atrial size, left atrial volume, septal wall thickness during systole (SWs) and diastole (SWd), posterior wall thickness during systole (PWs) and diastole (PWd), left ventricle dimension during systole (LVDs) and diastole (LVDd), and ejection fraction were measured. The values were compared between the groups. Results After adjustment for age, sex, smoking, alcohol and BMI; left ventricular diameter in systole and diastole was significantly more than controls (p<0.001); HR of 1.29 (95% CI 1.13–1.46), 1.29 (95% CI 1.15–1.45) respectively. Left ventricular mass and left atrial volume were increased significantly in subjects with metabolic syndrome (p<0.001); HR were 1.06 (95% CI 1.03–1.08), 1.13 (95% CI 1.06–1.19) respectively. Ejection fraction was low normal in subjects with metabolic syndrome compared to controls (p<0.05); HR 0.90 (95% CI 0.83–0.98). Conclusions Cardiac abnormalities were common in subjects with metabolic syndrome, predominantly affecting the left ventricular mass, diameter and left atrial volume. Early life style modifications are essential to prevent these complications.

Objectives The present study sought to examine the relationship of betatrophin with certain key enzymes, namely lactate dehydrogenase-5 (LDH5), citrate synthase (CS), and acetyl-CoA carboxylase-1 (ACC1), in insulin-resistant mice. Methods Eight-week-old male C57BL6/J mice were used in this study (experimental group n=10 and control group n=10). S961 was administered using an osmotic pump to induce insulin resistance in the mice. The betatrophin, LDH5, CS, and ACC1 expression levels were determined from the livers of the mice using the real-time polymerase chain reaction (RT-PCR) method. Moreover, biochemical parameters such as the serum betatrophin, fasting glucose, insulin, triglyceride, total cholesterol, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels were analyzed. Results The betatrophin expression and serum betatrophin (p=0.000), fasting glucose, insulin, triglyceride (p≤0.001), and total cholesterol (p=0.013) levels were increased in the experimental group. In addition, the CS gene expression level was statistically significantly decreased in the experimental group (p=0.01). Although strong correlation was found between the expression and serum betatrophin and triglyceride levels, no correlation was found between the betatrophin gene expression and the LDH5, ACC1, and CS gene expression levels. Conclusions The betatrophin level appears to play an important role in the regulation of triglyceride metabolism, while insulin resistance increases both the betatrophin gene expression and serum levels and decreases the CS expression level. The findings suggest that betatrophin may not regulate carbohydrate metabolism through CS and LDH5 or lipid metabolism directly through the ACC1 enzyme.

Objectives In this study, metabolic syndrome-affected rats were studied to examine how intermittent and continuous swimming training influenced adipokines and pro-inflammatory cytokines. Methods Forty-eight male Wistar rats were randomized in this experimental study into four groups (n=8), including normal control (NC), metabolic syndrome (MS), continuous swimming training with metabolic syndrome (CT-MS: load 0–3% body mass, 5 d/wk, for 8 weeks), and intermittent swimming training with metabolic syndrome (IT-MS: load 5–16% body mass, 5 d/wk, for 8 weeks). The serum levels of metrnl, adipolin, irisin, leptin, TNF-α, and IL-6 were measured using the ELISA test. Results The IT-MS and NC groups exhibited significantly lower leptin concentrations than the CT-MS group (p=0.001). The irisin, meteorin, and adipolin serum levels increased significantly in CT-MS and IT relative to the NC and CT-MS groups (p=0.001), with the changes being more pronounced in the IT group (p=0.05). TNF-α and IL-6 were inclined in the CT-MS group compared with the other three groups (p=0.001), while IL-6 was increased in the IT group (p=0.024). Conclusions Intermittent swimming is more effective than continuous swimming training in improving adipokines in rats with metabolic syndrome.

Objectives A rehabilitation program for patients with COVID-19 may be required to improve related side effects. This study aimed to investigate the effect of a four-week home workout on body composition and serum levels of IL-6 and cortisol in men recovering from COVID-19. Methods The present study is quasi-experimental. To this end, 45 healthy individuals in Tehran were purposefully divided into three groups: those who recovered after COVID-19 (n=30), including two groups of exercise and non-exercise, and individuals who did not have COVID-19 (control) (15=n). The four-week training program included three days of training per week with Traband resistance stretches, weight body training, and cardio exercises. The smirnov-Kolmogorov test was employed for data normality. A one-way analysis of variance test will be used to compare both the mean of variables in groups and the mean of variables before and after the exercise, correlated t-test was employed at a significance level of 0.05. Results The results showed that serum levels of interleukin 6 and cortisol were significantly reduced in the recovered training group (p=0.001) and the non-trained recovery group (p=0.001) and a significant difference was observed between the groups (p=0.001). Furthermore, only in the recovered training group, did the fat percentage (p=0.001) and muscle mass (p=0.001) respectively decreased and increased. Conclusions Four-week home training improves body composition by reducing body fat percentage and increasing muscle mass. In addition, lowering interleukin-6 and cortisol leads to reduced inflammation, faster recovery, and increased immunity.

DNA methylation is the most important epigenetic element that activates the inhibition of gene transcription and is included in the pathogenesis of all types of malignancies. Remarkably, the effectors of DNA methylation are DNMTs (DNA methyltransferases) that catalyze de novo or keep methylation of hemimethylated DNA after the DNA replication process. DNA methylation structures in cancer are altered, with three procedures by which DNA methylation helps cancer development which are including direct mutagenesis, hypomethylation of the cancer genome, and also focal hypermethylation of the promoters of TSGs (tumor suppressor genes). Conspicuously, DNA methylation, nucleosome remodeling, RNA-mediated targeting, and histone modification balance modulate many biological activities that are essential and indispensable to the genesis of cancer and also can impact many epigenetic changes including DNA methylation and histone modifications as well as adjusting of non-coding miRNAs expression in prevention and treatment of many cancers. Epigenetics points to heritable modifications in gene expression that do not comprise alterations in the DNA sequence. The nucleosome is the basic unit of chromatin, consisting of 147 base pairs (bp) of DNA bound around a histone octamer comprised of one H3/H4 tetramer and two H2A/H2B dimers. DNA methylation is preferentially distributed over nucleosome regions and is less increased over flanking nucleosome-depleted DNA, implying a connection between nucleosome positioning and DNA methylation. In carcinogenesis, aberrations in the epigenome may also include in the progression of drug resistance. In this report, we report the rudimentary notes behind these epigenetic signaling pathways and emphasize the proofs recommending that their misregulation can conclude in cancer. These findings in conjunction with the promising preclinical and clinical consequences observed with epigenetic drugs against chromatin regulators, confirm the important role of epigenetics in cancer therapy.