The oxidative stress-associated long non-coding RNAs in pancreatic cancer.

PURPOSE: A lot of people are dying from pancreatic cancer (PC) annually. The early detection of this cancer is particularly challenging due to the fact that symptoms tend to appear in advanced stages. It has been suggested that oxidative stress may play a role in the development of PC. Several genes regulate this process, including long noncoding RNAs (lncRNAs). There is no comprehensive study on the expression pattern of lncRNAs related to oxidative stress in PC patients. In the present case-control study, we quantified levels of oxidative stress-associated lncRNAs in PC patients versus healthy controls. PATIENTS AND METHODS: In the present study, we investigated the expression levels of lincRNA-p21, LUCAT, RMST, FOXD3-AS1, and MT1DP lncRNAs in the peripheral blood mononuclear cells (PBMCs) of 53 â€‹PC patients and 50 healthy controls. The association between lncRNA expression and clinical and pathological characteristics was also evaluated. RESULTS: The expression of lincRNA-P21 and rhabdomyosarcoma 2-associated transcript (RMST) lncRNAs in PC patients has significantly decreased. Expression of lncRNA RMST was significantly higher in TNM stage III-IV patients in comparison to TNM stage I-II patients. In addition, a significant positive association was recognized between candidate lncRNA expression, and finally, the AUC values of the expression levels of lincRNA-p21 and RMST were 0.60 and 0.61, respectively. CONCLUSIONS: Altogether, our study suggests a possible role of lincRNA-p21 and RMST lncRNAs in the etiology of PC pathobiology, and their biomarker role may be understood in future studies.

Vitamin D changes expression of DNA repair genes in the patients with multiple sclerosis.

Oxidative stress (OS) plays an essential role in demyelination and tissue injury related to pathogenesis of multiple sclerosis (MS). On the other hand, vitamin D (VD) as an antioxidant reduces oxidative stress and has been used as adjuvant therapy in autoimmune diseases. Although VD supplementation is suggested as a protective and immunomodulation factor for MS patients, the molecular mechanisms remain unclear. Given that VD may modulate the immune system of MS patients through the DNA repair pathway, we aimed to evaluate the effects of VD supplementation in DNA repair genes expression including OGG1, MYH, MTH1, and ITPA. Transcript levels were measured using the RT-qPCR method in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) patients before and after two months of VD supplementation. Furthermore, in silico analysis and correlation gene expression analysis was performed to find the biological binding sites and the effect of NRF2 on the regulation of DNA repair genes. Our data revealed that in MS patients, 2-month VD treatment significantly altered the expression of MYH, OGG1, MTH1, and NRF2 genes. A significant correlation was observed between DNA repair genes and NRF2 expression, which was confirmed by the presence of antioxidant response element (ARE) binding sites in the promoter of OGG1, MYH, and MTH1 genes. This study demonstrated that the impact of VD on MS patients may be mediated through the improvement of DNA repair system efficiency. This finding brought some new evidence for the involvement of DNA repair genes in the physiopathology of MS patients.

An update on long intergenic noncoding RNA p21: a regulatory molecule with various significant functions in cancer.

Long intergenic noncoding RNA p21 was mapped on the human chromosome 6p21.2. Accordingly, it was firstly described by promoting the p53-dependent apoptosis in the mouse. Also, it is a new lncRNA playing some vital roles in the cell cycle, apoptosis, cell proliferation, tumorigenesis, invasion, metastasis, and angiogenesis. In this regard, it was shown that, lincRNA-p21 regulates these biological processes involved in carcinogenesis through various signaling pathways including Notch signaling, JAK2/STAT3, and AKT/mTOR pathways. Another mechanism by that lincRNA-p21 can affect these processes is a cross-talk with different miRNAs. In vitro and in vivo studies revealed dysregulation of lincRNA-p21 in various human cancers. In addition, emerging evidence demonstrated that, lincRNA-p21 can be considered as a potential prognostic and therapeutic biomarker in cancers. Also, lincRNA-p21 enhances the response to radiotherapy for colorectal cancer. However, the molecular mechanisms of lincRNA-p21 in carcinogenesis have not been fully elucidated so far. So, this review summarizes the function of lincRNA-p21, as a tumor suppressor factor in different biological processes implicated in cancers.

Immunological Testing Reveals Exposure to Malaria in the Hypoendemic Region of Iran.

Background. South eastern parts of Iran remain endemic for malaria infection. There is some concern that malaria infection may spread into Bushehr, which is located in the south western part bordering the Persian Gulf and at the periphery of the declared endemic region Hormozgan province due to frequency of visitors from eastern endemic areas and from neighboring malaria endemic countries. We investigated malaria prevalence in Bushehr. Methods and Results. Attempts were made to identify malaria active infection in blood smears and malaria specific antibody and antigens in serum samples. Traditional blood smears prepared from 1955 blood specimens yielded no definitive malaria positive case by microscopic technique. A total of 270 (13.8%) serum samples were positive for malaria antibodies. Using specific ELISA kits, presence of histidine rich proteins and lactate dehydrogenase antigens were investigated in serum samples. No histidine rich proteins specific for P. falciparum were detected amongst 270 antibody positive samples. However, six samples representing 0.3% of total population, were found to be positive for plasmodium pan specific lactate dehydrogenase antigens. This suggested the possibility of low level exposure to malaria in Bushehr community. Conclusions. Out of a total of 1955 samples tested, 270 (13.8%) were positive for malaria antibodies and six (0.3%) of these were positive for plasmodium-specific lactate dehydrogenase antigen suggesting a low level exposure to malaria in a hypoendemic region based on immunological testing. Since none of the 270 antibody samples were positive for histidine rich protein antigens, there is scope for further testing of blood samples by molecular methods such as polymerase chain reactions to confirm the plasmodium species and provide information valuable for future investigations. Our testing strategy for hypoemdemic malaria can be used as a template for investing malaria in 32 eliminating countries for testing ongoing transmission. This approach may be useful as a method in epidemiological studies.

Serum retinol levels are positively correlated with hemoglobin concentrations, independent of iron homeostasis: a population-based study.

Micronutrient interactions give rise to complex issues that have an impact on preventive strategies when multiple micronutrient deficiencies coexist. The aim of this population-based study was to determine the prevalence of vitamins A and E and iron deficiencies among women 15 to 49 years of age in the northern Persian Gulf region. We hypothesized that serum retinol levels may show correlations with hemoglobin (Hb) concentrations, independent of iron status. A total of 1242 nonpregnant women of reproductive age were selected via a multistage stratified random cluster sampling technique. Serum ferritin and soluble transferrin receptor levels were measured using enzyme immunoassay techniques. Serum retinol (vitamin A) and α-tocopherol (vitamin E) were determined for 727 women by high-performance liquid chromatography. The prevalence of anemia (Hb <12 g/dL), iron deficiency (serum ferritin <15 µg/L), and iron deficiency anemia was 8.7%, 25.4%, and 4.6%, respectively. Vitamin A (<0.7 µmol/L) and vitamin E (<11.6 µmol/L) deficiencies were found in 1.2% and 5.9% of the studied population, respectively. Multiple regression analysis revealed that serum retinol levels exhibit a significant association with Hb concentrations after controlling for serum ferritin levels, anemia associated with chronic disease, and risk factors for anemia. Therefore, most nonpregnant women of reproductive age in the northern Persian Gulf were found to have adequate serum vitamin A and E levels. However, the status of anemia and iron deficiency anemia could be considered a mild public health problem in this region. On the basis of multivariate analyses, we conclude that low serum retinol levels may contribute to anemia, independent of iron homeostasis.

Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women.

The bone and fat interface is implicated in the pathogenesis of postmenopausal osteoporosis. The association between circulating omentin-1 levels and bone mineral density (BMD) in postmenopausal women has never been assessed. A total of 382 healthy postmenopausal women were randomly selected. Omentin-1, visfatin, adiponectin, the receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin, high sensitivity C-reactive protein, degradation products of C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific enzyme-linked immunosorbent assay methods. BMD was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy X-ray absorptiometry. In multivariable-adjusted linear regression, serum omentin-1 levels were inversely correlated with BMD at the lumbar spine (ß=-0.11, p=0.020). In multiple regression analyses, serum visfatin and adiponectin levels were not significantly correlated with BMD at different skeletal sites after controlling for age, body mass index, and bone-related markers. However, the highest quartile of adiponectin compared to the lowest quartile, after adjusting for potential confounders, revealed an inverse association with BMD in the lumbar spine (ß=-0.19, p=0.010). In conclusion, circulating omentin-1 levels had an inverse correlation with BMD at the lumbar spine in Iranian postmenopausal women. To further understand the role of omentin-1 in bone and mineral metabolism, large-scale longitudinal studies focusing on BMD and osteoporotic fractures are warranted.

Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data.

BACKGROUND: Epidemiological studies on genital human papilloma viruses infection (HPVs) in general population are crucial for the implementation of health policy guidelines for developing the strategies to prevent the primary and secondary cervical cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study is to compare the prevalence rate of genital HPV infection among reproductive women with our previous clinic-based data, which showed a prevalence rate of 5% in women in southern Iran. RESULTS: Using general primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%, 95% CI 0.23-1.55%) tested positive for HPV DNA. Overall, seven different HPV genotypes were detected: six types (16, 18, 31, 33, 51 and 56) were carcinogenic, or "high risk genotypes" and one genotype (HPV-66) was "probably carcinogenic." CONCLUSIONS: In a population-based study, the prevalence of HPV infection among southern Iranian women was lower than that observed worldwide. However, our gynaecological clinic-based study on the prevalence of HPV infection showed results comparable with other studies in the Middle East and Persian Gulf countries. Since gynaecological clinic-based data may generally overestimate HPV prevalence, estimates of prevalence according to clinic-based data should be adjusted downward by the population-based survey estimates.

Reduced serum osteocalcin concentrations are associated with type 2 diabetes mellitus and the metabolic syndrome components in postmenopausal women: the crosstalk between bone and energy metabolism.

Although it has been shown that osteocalcin functions as a hormone in the regulation of glucose metabolism and fat mass, no population-based study to date has addressed serum osteocalcin levels in relation to energy metabolism concurrent with bone metabolism in postmenopausal women. In a population-based study, cardiovascular risk factors, high-sensitivity C-reactive protein (hs-CRP), osteoprotegerin, receptor activator of nuclear factor-κB ligand, osteocalcin, CrossLaps, alkaline phosphatase, and bone mineral density (BMD) at the lumbar spine (L2-L4) and the proximal femur were measured in 382 Iranian postmenopausal women. In multiple logistic regression analysis, lower osteocalcin and CrossLaps levels were associated with a higher odds ratio (OR) of having type 2 diabetes mellitus when adjustments were made for age, hs-CRP, cardiovascular risk factors, BMD, and markers of bone metabolism [OR 5.17, CI (2.66-10.04), p < 0.0001 and OR 2.51, CI (1.37-4.61), p = 0.003, respectively]. However, lower alkaline phosphatase levels were associated with a lower OR of having type 2 diabetes mellitus [OR 0.28, CI (0.15-0.52), p < 0.0001] in regression analysis. No significant difference was found between serum osteocalcin levels of those with and without metabolic syndrome. Among the metabolic syndrome components, low osteocalcin levels had significant associations with elevated blood glucose [OR 1.89, CI (1.16-3.07), p = 0.010] and elevated waist circumference [OR 2.53, CI (1.13-5.67), p = 0.024] in multivariate analyses. In conclusion, serum osteocalcin was independently associated with glucose intolerance and abdominal obesity as the components of metabolic syndrome and type 2 diabetes mellitus in postmenopausal women. Since CrossLaps and alkaline phosphatase levels were independently associated with the presence of type 2 diabetes mellitus, the unique contribution of osteocalcin in glucose metabolism could not be concluded.