Among all the cancers, colorectal cancer (CRC) has the third mortality rank in both genders. Cancer vaccines have shown promising results in boosting patients' immune systems to fight cancer. Using ...the IEDB database, we predicted mouse MHC‐I (H2‐Ld) binding epitopes from four tumor‐associated antigens (APC, KRAS, TP53, and PIK3CA) and designed a multi‐epitope vaccine. We expressed the candidate vaccine and encapsulated it into the cationic micelle with polyethyleneimine conjugated to oleic acid as its building blocks. We studied tumor inhibition effect, cytokine production, and lymphocyte proliferation in the mouse CRC model after vaccination. Our finding illustrated significant tumor growth inhibition in mouse models treated with the candidate nanovaccine. Besides the significant release of IFN‐γ and IL‐4 by immunized mouse spleen T‐lymphocytes, T‐cell proliferation assay results confirmed effective immune response after the vaccination. These results demonstrate the potential therapeutic effects of nanovaccines and could be a possible approach to CRC immunotherapy.
Blood and tissue levels of lncRNAs in periodontitis Sayad, Arezou; Ghafouri‐Fard, Soudeh; Shams, Bahareh ...
Journal of cellular physiology,
December 2020, 2020-12-00, 20201201, Letnik:
235, Številka:
12
Journal Article
Recenzirano
Periodontitis is a complex disorder that affects a large number of human beings from different ethnic groups. This condition has been associated with dysregulation of a number of genes, among them ...are long noncoding RNAs (lncRNAs). In the current study, we assessed the expression of four lncRNAs (BDNF‐AS, MIAT, MIR137HG, and PNKY) as well as BDNF in the peripheral blood and gingival tissues obtained from patients with periodontitis and healthy subjects. The expression of BDNF was significantly lower in blood samples of male patients with periodontitis compared with male controls (posterior β of RE = −4.754, p = .048). However, there was no significant difference in the expression of BDNF in tissue samples from the cases and controls. The expression of BDNF‐AS was significantly lower in the tissue samples of patients compared with control tissue samples (posterior β of RE = −2.151, p = .019). Such an expression difference was detected between male subgroups as well (posterior β of RE = −3.679, p = .009). However, expression of this lncRNA was not different in blood samples obtained from patients compared with healthy subjects. The expression of PNKY was significantly higher in tissue samples obtained from female patients compared with sex‐matched controls (posterior β of RE = 6.23, p = .037). Blood levels of this lncRNA were not different between cases and controls. There was no significant difference either in the tissue expression or in blood expression of MIR137HG or MIAT between cases and controls. The current study indicates the putative role of BDNF, BDNF‐AS, and PNKY in the pathophysiology of periodontitis and potentiates these genes as candidates for functional studies.
Tissue expression levels of BDNF and PNKY were correlated with age (p < .0001). Significant inverse correlations were detected between the tissue expression levels of PNKY and both BDNF‐AS and MIR137HG (r = −.73, p < .0001 and r = −.43, p < .0001, respectively). Significant pairwise correlations were found between blood levels of BDNF and both BDNF‐AS and PNKY, blood levels of MIR137HG, and MIAT as well as tissue levels of BDNF‐AS and MIR137HG.
Offshore platforms have a high potential for major accidents. This study aimed to model the occurrence of unsafe behaviors based on safety climate and organizational leadership style using the fuzzy ...logic approach. This study was conducted among five oil platforms located in the Persian Gulf. Multifactor leadership and standard occupational safety climate questionnaires measured organizational leadership style and safety climate, respectively. To determine unsafe behaviors, a checklist of unsafe acts was used. Data analysis was performed using one‐way ANOVA and Pearson correlation coefficients in R4.1.0. A fuzzy logarithmic model and MATLAB software were used for modeling. There was a significant inverse relationship between transformational and transactional leadership style and the occurrence of unsafe behaviors. Findings revealed a significant correlation between the dimensions of the safety of the workplace and the neglecting dangers and the occurrence of unsafe behaviors. The fuzzy logarithmic model results showed that mentioned parameters are important risk factors for predicting unsafe behaviors. Findings revealed that transformational and transactional leadership styles, the workplace's safety, and neglecting dangers in oil platforms are among essential factors in unsafe behaviors. Using fuzzy logarithmic models can also be an effective way to predict unsafe behaviors in different workplaces.
Non-small cell lung cancer (NSCLC) as the most frequent type of lung cancer is associated with extensive mortality. Researchers have studied the suitability of several molecules as biomarkers for ...early detection of this cancer. Long non-coding RNAs (lncRNAs) as the main regulators of gene expression have also been assessed in this regard.
In the present study, we compared expression level of Fas-antisense 1 (FAS-AS1), Growth Arrest Specific 5 (GAS5), PVT1, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), taurine upregulated gene 1 (TUG1) and TNFα and hnRNPL related immunoregulatory LincRNA (THRIL) in 32 NSCLC samples and their corresponding adjacent non-cancerous tissues (ANCTs).
NEAT1 has been significantly over-expressed in NSCLC tissues obtained from male subjects compared with the corresponding ANCTs (Relative expression (REx) = 3.022, P = 0.019) but not in female subjects (P = 0.975). FAS-AS1 was significantly down-regulated in NSCLC tissues obtained from both males and females subjects compared with the corresponding ANCTs (REx = - 4.12 and - 3.14, P = 0.015 and 0.033 respectively). TUG1, GAS5, THRIL and HOTAIRM1 were significantly down-regulated in tumoral tissues obtained from male subjects compared with the corresponding ANCTs.
The observed dysregulation of these lncRNAs in NSCLC tissues compared with the corresponding ANCTs warrants future studies to confirm the results of the current study in larger sample sizes to elaborate their role as cancer biomarkers.
Contrast-induced nephropathy (CIN) remains to be a potentially serious complication of radiographic procedures and is the third leading cause of the acute kidney injury (AKI) among hospitalized ...patients. This clinical trial was performed to assess the preventive effect of oral nicorandil on CIN in high-risk patients undergoing cardiac catheterization.
In this prospective, randomized, controlled trial, 128 patients with at least two risk factors for CIN undergoing elective percutaneous coronary intervention (PCI) were randomly assigned to either the nicorandil group or the control group. Patients in the nicorandil group (n = 64) received 10 mg nicorandil, daily from 30 min before and up to 3 days after procedure and intravenous hydration for 2 h before and 6 h after the procedure, whereas patients in the control group (n = 64) just received intravenous hydration. Serum creatinine (SCr) was measured before contrast exposure and at 72 h. CIN was defined as an increase of 25% in SCr or > 0.5 mg/dL 72 h after contrast administration.
Contrast-induced nephropathy occurred in 14 out of 64 (21.9%) patients in the control group and in 3 out of 64 (4.7%) patients in the nicorandil group. There was a significant difference in the incidence of CIN between the two groups at 72 h after administering the radiocontrast agent (p = 0.008). Moreover, there were significant differences between the two groups in SCr and estimated glomerular filtration rate 72 h after radiocontrast administration (p < 0.05).
The findings revealed that oral nicorandil had substantial efficacy over hydration protocol for the development of CIN in high-risk patients undergoing cardiac catheterization.
Multiple sclerosis (MS) is a common disease of the central nervous system.This disease may be initiated by either vitamin deficiency or triggered by abnormality in CYP24A1 and vitamin D receptor.
In ...this case-control study, the expression of genes encoding vitamin D receptor (VDR) and CYP24A1 in relapsing-remitting MS (RR-MS) patients was compared with normal individuals in the Iranian population. RNA from whole blood of 50 RR-MS patients (HLA-DRB1*15-negative and responders to interferonbeta with a normal vitamin D level) and 50 normal controls was extracted. The levels of CYP24A1 and VDR expression were measured using real-time quantitative polymerase chain reaction.
The RR-MS group had a significantly more than 2 times higher expression level of VDR than the normal group (P=0.04). On the other hand, there was a 0.89 times decrease in the expression level of CYP24A1 in RR-MS patients which was not statistically significant. There was no linear correlation between the risk of expanded disability status scale of Kurtzke (EDSS) and the expression level of either CYP24A1 or VDR. In addition, the expression level of CYP24A1 or VDR was not correlated with the duration of the disease.
Up-regulation of VDR is likely to happen in RR-MS patients in the Iranian population. We did not observe a gene expression-phenotype correlation for CYP24A1 which may be due to limited statistical power as a result of the small sample size. Although the individuals taking part in this study had normal levels of vitamin D, the increase in VDR expression levels may perhaps be a response to a defect in vitamin D processing. Another possibility is that despite an increase in VDR expression level, factors such as micro-RNAs may result in their deactivation while an increase in VDR expression level can be seen as a compensatory response. Of course, further studies are required to identify the mechanism of action of vitamin D by analyzing genes involved in its signaling pathway, particularly VDR and CYP24A1.
Coronary artery disease (CAD) is among prominent causes of death throughout the world. Inflammatory processes participate in the pathogenesis of this disorder.
In the current case-control study, we ...compared expression levels of three inflammation-associated genes namely Antisense noncoding RNA in the INK4 locus (ANRIL), NKILA and IL-1B between CAD patients and matched healthy subjects.
ANRIL, IL-1B and NKILA were significantly down-regulated in CAD patients compared with controls (p values of <.0001, .023 and <.0001, respectively). When evaluating study participants based on their gender, the differences in expression levels of ANRIL and NKILA were significant in both male and female patients compared with the matched controls. However, IL-1B was only down-regulated in female patients compared with female controls.
Taken together, our study revealed dysregulation of inflammation-associated genes in the peripheral blood of CAD patients and supported the previously suggested role of inflammation in the pathogenesis of CAD.
Bipolar disorder (BD) is a multifactorial condition. Several signaling pathways affect development of this disorder. With the purpose of exploring the role of vitamin D receptor (VDR) signaling in ...this disorder, we measured expression of selected mRNA coding genes and long non-coding RNAs (lncRNAs) in this pathway in patients versus normal subjects.
We measured expression of VDR-associated lncRNAs and mRNAs (SNHG6, MALAT1, Linc00511, Linc00346, VDR and CYP27B1) in the peripheral blood of BD patients vs. healthy individuals.
Expression of SNHG6 was significantly higher in cases vs. controls (Posterior beta = 1.29, P value < 0.0001. Subgroup analysis by sex revealed significant results in both subgroups (P value < 0.0001 and P value = 0.023 for males and females, respectively). Expression of CYP27B1 was up-regulated in cases vs. controls (Posterior beta = 0.415, P < 0.0001). Such pattern was also detected among males (P < 0.0001), but not females (P = 0.419). Similarly, MALAT1 and Linc00346 were up-regulated in total cases vs. controls (Posterior beta = 0.694, P < 0.0001 and Posterior beta = 0.4, P = 0.012, respectively) and in male cases compared with male controls (Posterior beta = 0.712, P < 0.0001 and Posterior beta = 0.41, P value = 0.038, respectively). Expression of VDR was up-regulated in total cases compared with controls (Posterior beta = 0.683, P value = 0.001). Finally, expression of Linc00511 was not different between groups. MALAT1, SNHG6, CYP27B1, VDR and Linc00346 had AUC values of 0.95, 0.94, 0.91, 0.85 and 0.83 in differentiation of male patients from controls, respectively.
The current study suggests VDR-associated genes as possible markers for BD.
Objectives
Dysregulation of peripheral immune responses has been detected in schizophrenic patients. Cytokines as the main regulators of immunological processes are also involved in brain ...development, which supports their putative role in the pathogenesis of schizophrenia.
Methods
In the present study, we compared transcript levels of interleukin (IL)‐1, IL‐2, IL‐6, chemokine (C‐X‐C) ligand 8 (CXCL8), transforming growth factor‐β (TGF‐β) and tumor necrosis factor‐α (TNF‐α) in the blood of 50 schizophrenic patients and 50 healthy participants.
Results
IL‐6 transcript levels were significantly higher in male participants compared with female participants (P = 0.005). TGF‐β transcript levels were significantly higher in patients compared with healthy participants (P = 0.001). In addition, there was a significant difference in its expression between cases and controls based on the sex of the participants. TNF‐α transcript levels were higher in male schizophrenic patients (P = 0.007) and in female patients aged <50 years compared with the age‐ and sex‐matched healthy participants (P = 0.048). Transcript levels of other cytokines were not significantly different between cases and controls, which might be due to the effects of antipsychotic treatment in patients.
Conclusion
The present study provides further evidence for abnormal transcript levels of cytokines in schizophrenic patients, as well as distinct regulation of cytokine expression in women and men.
We showed dysregulation of expression of certain cytokines in schizophrenic patients in a sex‐specific manner, which might be due to the sex‐specific nature of schizophrenia or clozapine treatment. Future studies are required to explore the exact mechanisms of such findings. We state the small sample size and lack of expression assay at the protein level as limitations of our study.
Long chain omega-3 fatty acids (omega-3 FAs) supplements have been shown to exert beneficial effects in patients with epilepsy through elevation of seizure thresholds and dampening of inflammatory ...responses. In this triple blind randomized, placebo-controlled parallel group trial of omega-3 FA supplementation, 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) as well as placebo capsules were administered twice a day in 50 patients with refractory seizure during a 16-week period respectively. Seizure frequency and duration were reduced after completion of the treatment in the supplement group. The supplementation resulted in a significant decrease in TNF-α and IL-6 concentrations. Further studies are needed to compare different omega-3 FA compositions and determine the most effective dose and treatment duration as well as the long term benefits of this supplementation.
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