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In this study, oxidative stress was investigated as the possible mechanism of action of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in primary brain tumors (PBT). The levels of seven OCP residues and enzymatic antioxidant biomarkers including erythrocyte acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and paraoxonase-1 (PON-1) along with non-enzymatic oxidative biomarkers including malondialdehyde (MDA), protein carbonyl (PC), total antioxidant capacity (TAC), and nitric oxide (NO) were measured in blood samples of 73 patients with PBT and 104 healthy controls. A significant association was found between farming activities and PBT (55% of patients were engaged in farming activities while 45% had no farming experience). The mean levels of β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 4,4 DDT, MDA, PC, NO, SOD, CAT, and GPx were significantly higher in PBT patients, whereas the levels of TAC, PON-1, and AChE were significantly lower in these patients. Regression analysis showed that PBT was correlated with β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, and 4,4 DDT. Based on these results, it can be concluded that OCPs and OPPs may play a role in PBT development through the formation of reactive oxygen species (ROS) and promoting oxidative stress.

Background. Asthma is known as a disease that causes breathing problems in children and adults and is also associated with chronic inflammation and oxidative stress of the airways. Nasturtium officinale (NO) possesses a wide range of pharmacological properties, particularly anti-inflammation and antioxidant potentials. Thus, this study for the first time was aimed to investigate anti-inflammatory and antioxidative activities of NO extract (NOE) in an ovalbumin-induced rat model of asthma. Materials and Methods. Forty-four male Wistar rats were sensitized with ovalbumin (OVA) to induce asthma symptoms. The animals were allocated into five groups: control (C), asthmatic (A), A + NOE (500 mg/kg), NOE (500 mg/kg), and A + dexamethasone (DX, 2.5 mg/kg). After 7 days, blood and tissue samples were taken from the rats. Then, the level of inflammatory markers, oxidative stress parameters, and antioxidant enzymes activity were measured. Results. The obtained results showed that OVA-sensitive rats significantly increased the levels of pro-inflammatory cytokines IL-1B, TGF-β, and SMA-α compared to the control group ( p < 0.05 ), while treatment with NOE remarkably reduced the SMA-α gene expression compared to the asthma group ( p < 0.05 ). Furthermore, it decreased the expression of IL-1B and TNF-α genes, although it was not statistically significant. The level of glutathione peroxidase (GPX) significantly reduced in A group compared to the C group ( p < 0.05 ), whereas NOE administration significantly increased this marker ( p < 0.05 ). Moreover, NOE attenuated inflammation and alveolar injury in the lungs of OVA-sensitive rat compared to the nontreated A group. Conclusions. Overall, our findings demonstrated that NOE somewhat is able to reduce airway inflammation by reducing inflammatory and increasing GPX activity. Indeed, further experiments investigating the impact of different extract doses are needed to confirm the antioxidant and anti-inflammatory effects of NOE.

miRNA-148b belongs to the family miR-148/-152, with significant differences in nonseed sequences, which can target diverse mRNA molecules. Reportedly, it may undergo deregulation in lung and ovarian cancers and downregulation in gastric, pancreatic and colon cancers. However, there is a need for further studies to better characterize its mechanism of action and in different types of cancer. In this review, we focus on the aberrant expression of miR-148b in different cancer types and highlight its main target genes and signaling pathways, as well as its pathophysiologic role and relevance to tumorigenesis in several types of cancer.Lay abstract miRNA-148b, or miR-148b, is a tumor suppressor that can regulate invasion-, apoptosis- and proliferation-related oncogenes. miR-148b prognostic and diagnostic potential has been the center of focus recent investigations and extensive studies have been performed on miR-148b regulation in carcinogenesis. Here, we review the role of miR-148b in various cancers and its potential therapeutic application as a target or biomarker.

On a worldwide scale, the outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to extensive damage to the health system as well as the global economy. Hitherto, there has been no approved drug or vaccine for this disease. Therefore, the use of general antiviral drugs is at the first line of treatment, though complicated with limited effectiveness and systemic side effects. Given the pathophysiology of the disease, researchers have proposed various strategies not only to find a more specific therapeutic way but also to reduce the side effects. One strategy to accomplish these goals is to use CRISPR/Cas13 system. Recently, a group of scientists has used the CRISPR/Cas13 system, which is highly effective in eliminating the genome of RNA viruses. Due to the RNA nature of the coronavirus genome, it seems that this system can be effective against the disease. The main challenge regarding the application of this system is to deliver it to the target cells efficiently. To solve this challenge, it seems that using virosomes with protein S on their membrane surface can be helpful. Studies have shown that protein S interacts with its specific receptor in target cells named Angiotensin-Converting Enzyme 2 (ACE2). Here, we propose if CRISPR/Cas13 gene constructs reach the infected cells efficiently using a virosomal delivery system, the virus genome will be cleaved and inactivated. Considering the pathophysiology of the disease, an important step to implement this hypothesis is to embed protein S on the membrane surface of virosomes to facilitate the delivery of gene constructs to the target cells.

Background: Organochlorine pesticide (OCP) exposure and epigenetic modifications have been well-documented in brain cancer incidence; however, their associations remain ambiguous. In this paper, we examined the effect of seven OCPs on the methylation status of two tumor suppressor genes (RRP22 and P16) and four histone marks (H4K16ac, H3K9ac, H4K20me3, and H3k4me2) in 73 patients with a primary brain tumor (PBT).Methods and results: The results of methylation-specific PCR (MSP) revealed the hypermethylation of P22 and P16 promoter regions in PBT patients. Moreover, western blot analysis demonstrated significantly low levels of H3K9ac, H4K20me3, and H3K4me2 in PBT patients in comparison with the controls. In addition, our study provides supportive evidence that OCP exposure at both high and low levels significantly affected RRP22 and P16 methylation and was related to an increased risk of glioma and PBT, respectively. We found no associations between histone modifications and exposure to OCPs in PBT incidence. Conclusion: The results of this study indicated that RRP22 and P16 promoter hypermethylation, as well as H4K20 and H3K4 demethylation and H3K9 deacetylation, are significantly associated with PBT risk. Moreover, our study demonstrated that OCP exposure is related to the increased risk of PBT incidence, mainly among individuals with RRP22 and P16 promoter region methylation.

Pesticides are potentially hazardous chemicals that can cause injury to human health and the environment. The purpose of this study was to evaluate organophosphate pesticides (OPPs) and organochlorine pesticides (OCPs) exposure in farmworkers' children aged 6 to 11 years in Jiroft city in southeastern Iran. One hundred twenty farmworkers' children as case and 53 non-farmworkers' children aged 6 to 11 years as control were selected and the serum levels of OCPs were measured by using gas chromatography in all participants. In addition, erythrocyte acetylcholinesterase (AChE) and arylesterase activity of paraoxonase-1 (PON-1) were measured to evaluate OPPs effects. Catalase (CAT), superoxide dismutase3 (SOD3), glutathione peroxidase (GPx3) activities, and the levels of serum malondialdehyde (MDA), total antioxidant capacity (TAC), nitric oxide (NO), and protein carbonyl (PC) were measured to investigate OCPs and OPPs effects on oxidative stress (OS). The serum levels of beta-HCH, 4,4 DDE, and 4,4 DDT in the case group were significantly higher than the control group. In addition, in the case group, AChE, PON-1, CAT, SOD3, and GPx3 activities and the levels TAC were significantly lower, while MDA, PC, and NO levels were significantly higher than the control group. OCPs as illegal pesticides are present in southeast Iran and children are exposed to OCPs and OPPs in the studied area. In addition, higher serum levels of pesticides may be a major contributor in OS development, as a cause of many diseases.

Chemical pesticides or insecticides with complex structures are highly abundant in the biosphere and have inevitable side effects on farmland, natural resources, and human health. Deltamethrin is the most popular and widely used pesticide that disrupts the cellular calcium channels. In the present study, isolated strains of bacteria were examined to determine the ones that were capable of degrading deltamethrin. Different species of bacteria were evaluated in terms of the capability to degrade deltamethrin. It is important to note that Streptomyces rimosus was able to degrade up to 200 mg/L deltamethrin concentration and could be grown in mineral salt medium agar containing deltamethrin to be used as a source of carbon and energy. The results demonstrated that there is a diversity of deltamethrin-degrading bacteria in agricultural soil ecosystems. The application of these bacteria, especially S. rimosus, might be used as a bioremediation technique to decrease pesticide contamination of the ecosystem.

Despite newer advances in cancer treatment, chemotherapy is still one of the most widely used treatment strategies in this field. However, this treatment strategy faces major challenges. Doxorubicin (Dox) is an effective chemotherapeutic agent used to treat various cancers. However, several studies have shown that the use of Dox in therapeutic concentrations is associated with serious side effects, such as cardiac toxicity. The use of natural products in combination with chemotherapeutic agents to reduce side effects is a novel approach, and several studies have shown promising results. In this regard, we examined the effect of Crocin on doxorubicin-induced cardiotoxicity in rat and H9c2 cell line. The in vitro model on H9C2 cells and the in vivo models on rats were treated with doxorubicin. Cell viability, DNA damage, and apoptosis were measured in H9C2 cell line in the presence and absence of Crocin. Oxidative stress and various inflammatory parameters, as well as cardiac function tests, also were assessed in doxorubicin-induced cardiotoxicity animal model in the presence and absence of Crocin. Our results showed that Crocin can significantly decrease apoptosis in H9C2 cell line through a reduction in ROS production and DNA damages. Moreover, evaluation of the effect of Crocin on doxorubicin-induced cardiotoxicity animal model showed that Crocin also can significantly reduce oxidative stress and inflammatory parameters in the serum of the animals. Assessment of cardiac function revealed that Crocin has a significant protective effect against doxorubicin-induced cardiotoxicity in the animal model. Our data indicate that Crocin significantly attenuated doxorubicin-induced cardiotoxicity. Hence, Crocin could be potentially used as an adjuvant treatment in combination with Dox to reduce cardiotoxicity.

Many questions on the SARS-CoV-2 pathogenesis remain to answer. The SARS-CoV-2 genome encodes some accessory proteins that are essential for infection. Notably, accessory proteins of SARS-CoV-2 play significant roles in affecting immune escape and viral pathogenesis. Therefore SARS-CoV-2 accessory proteins could be considered putative drug targets. IFN-I and IFN-III responses are the primary mechanisms of innate antiviral immunity in infection clearance. Previous research has shown that SARS-CoV-2 suppresses IFN-β by infecting host cells via ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, and ORF9b. Furthermore, ORF3a, ORF7a, and ORF7b have a role in blocking IFNα signaling, and ORF8 represses IFNβ signaling. The ORF3a, ORF7a, and ORF7b disrupt the STAT1/2 phosphorylation. ORF3a, ORF6, ORF7a, and ORF7b could prevent the ISRE promoter activity. The main SARS-CoV-2 accessory proteins involved in immune evasion are discussed here for comprehensive learning on viral entry, replication, and transmission in vaccines and antiviral development.

Multiple sclerosis (MS) is a specific type of chronic immune-mediated disease in which the immune responses are almost run against the central nervous system (CNS). Despite intensive research, a known treatment for MS disease yet to be introduced. Thus, the development of novel and safe medications needs to be considered for the disease management. Application of mesenchymal stem cells (MSCs) as an emerging approach was recruited forthe treatment of MS. MSCs have several sources and they can be derived from the umbilical cord, adipose tissue, and bone marrow. Chemokines are low molecular weight proteins that their functional activities are achieved by binding to the cell surface G protein-coupled receptors (GPCRs). Chemokine and chemokine receptors are of the most important and effective molecules in MSC trafficking within the different tissues in hemostatic and non-hemostatic circumstances. Chemokine/chemokine receptor axes play a pivotal role in the recruitment and oriented trafficking of immune cells both towards and within the CNS and it appears that chemokine/chemokine receptor signaling may be the most important leading mechanisms in the pathogenesis of MS. In this article, we hypothesized that the chemokine/chemokine receptor axes network have crucial and efficacious impacts on behavior of the MSCs, nonetheless, the exact responsibility of these axes on the targeted tropism of MSCs to the CNS of MS patients yet remained to be fully elucidated. Therefore, we reviewed the ability of MSCs to migrate and home into the CNS of MS patients via expression of various chemokine receptors in response to chemokines expressed by cells of CNS tissue, to provide a great source of knowledge.

Since the outbreak of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the control of virus spread has remained challenging given the pitfalls of the current diagnostic tests. Nevertheless, RNA amplification techniques have been the gold standard among other diagnostic methods for monitoring clinical samples for the presence of the virus. In the current paper, we review the shortcomings and strengths of RT-PCR (real-time polymerase chain reaction) techniques for diagnosis of coronavirus disease (COVID)-19. We address the repercussions of false-negative and false-positive rates encountered in the test, summarize approaches to improve the overall sensitivity of this method. We discuss the barriers to the widespread use of the RT-PCR test, and some technical advances, such as RT-LAMP (reverse-transcriptase-loop mediated isothermal amplification). We also address how other molecular techniques, such as immunodiagnostic tests can be used to avoid incorrect interpretation of RT-PCR tests.

Cyclic nucleotide phosphodiesterase (PDE) enzymes are a large superfamily of enzymes that catalyze the conversion reaction of cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) to AMP and GMP, respectively. In some cancer cells, PDE-5 has been shown to be overexpressed in multiple human carcinomas. It seems that the inhibition of PDE-5 may has anticancer effects. Cisplatin is one of the prevalent chemo-agents to treat solid tumors. However, its clinical usefulness is hindered by dose-limiting toxicities, especially on the kidneys (nephrotoxicity) and ears (ototoxicity). In this study, the antitumor activity of the sildenafil as a PDE-5 inhibitor alone and in combination with cisplatin on human mammary adenocarcinomas and MCF-7 and MDA-MB-468 was assessed.Sildenafil as PDE type 5 (PDE5) inhibitor is the drugs that we combined with the cisplatin (chemotherapeutic agent), in vitro. Human mammary adenocarcinomas and MCF-7 and MDA-MB-468 cell lines were cultured in standard conditions. At time point, following 24 h and 48 h incubation, the cell lines were treated by cisplatin in the presence/absence of sildenafil. Cell viability, apoptosis, and reactive oxygen species (ROS) were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, real-time polymerase chain reaction, and Western blot; and fluorimetric methods, respectively. Statistical analysis was performed using SPSS software SPSS (SPSS Inc., Chicago, IL, USA).In MCF-7 cell line, following 24 h incubation, combinations of sildenafil with cisplatin (P0.001) showed decreased cell viability when compared to sildenafil and cisplatin alone. Moreover in MDA-MB-468 cell line, following 24 h incubation, data did not show any significant changes on cell viability when treated with cisplatin, in the presence or absence of sildenafil. However, following 48 h incubation, combinations of cisplatin with sildenafil (P0.001) were showed decreased cell viability when compared to cisplatin and sildenafil alone in both MCF-7 and MDA-MB-468 cell lines. Concerning the ROS production and apoptosis, data showed that both processes increase significantly in the presence of the sildenafil in comparison absent it.Our data showed that the combination of sildenafil with cisplatin can improve cell toxicity and anticancer effect of cisplatin. And also sildenafil as a PDE-5 inhibitor could be used as additive treatment in combination with cisplatin to make a reduction in cisplatin dosage and its side effects.

Skeletal muscle injuries are one of the most common problems in the worldwide which impose a substantial financial burden to the health care system. Accordingly, it widely accepted that muscle regeneration is a promising approach that can be used to treat muscle injury patients. However, the underlying mechanisms of muscle regeneration have yet to be elucidated. The muscle structure and muscle-related gene expression are highly conserved between human and zebrafish. Therefore, the zebrafish can be considered as an ideal animal model in muscle regeneration studies. In this study, Tol2 transposase was applied to produce Tg(mylpfa: cfp-nfsB) zebrafish model that express a fusion protein composed of cyan fluorescent protein (CFP) and nitrorudactase (NTR) under control of mylpfa promoter. The results showed that MTZ (Metronidazole) treatment of Tg(mylpfa:cfp-nfsB) zebrafish larvae can lead to muscle injury by selective ablation of muscle cells. And also, results confirmed the muscle regeneration ability of the transgenic larvae after withdrawal of Mtz for three days. Overall, The results of this study suggest that the Tg(mylpfa:cfp-nfsB) zebrafish model can be used in muscle regeneration study in order to elucidate the mechanisms of this process.

Leukemia is known as a progressive malignant disease, which destroys the blood-forming organs and results in adverse effects on the proliferation and development of leukocytes and their precursors in the blood and bone marrow. There are four main classes of leukemia including acute leukemia, chronic leukemia, myelogenous leukemia, and lymphocytic leukemia. Given that a variety of internal and external factors could be associated with the initiation and progression of different types of leukemia. One of the important factors is epigenetic regulators such as microRNAs (miRNAs) and long noncoding RNAs (ncRNA). MiRNAs are short ncRNAs which act as tumor suppressor (i.e., miR-15, miR-16, let-7, and miR-127) or oncogene (i.e., miR-155, miR-17-92, miR-21, miR-125b, miR-93, miR-143-p3, miR-196b, and miR-223) in leukemia. It has been shown that deregulation of these molecules are associated with the initiation and progression of leukemia. Hence, miRNAs could be used as potential therapeutic candidates in the treatment of patients with leukemia. Moreover, increasing evidence revealed that miRNAs could be used as diagnostic and prognostic biomarkers in monitoring patients in early stages of disease or after received chemotherapy regimen. It seems that identification and development of new miRNAs could pave to the way to the development new therapeutic platforms for patients with leukemia. Here, we summarized various miRNAs as tumor suppressor and oncogene which could be introduced as therapeutic targets in treatment of leukemia.

Coronary artery disease (CAD) is the world's largest cause of death. The association of CAD with inflammation is well established. Recently, it has been confirmed that the C1q/TNF-related protein 12 (CTRP12) has a great anti-inflammatory effect. However, few data are available regarding the serum CTRP12 concentration levels in CAD patients.The study was performed to evaluate the correlation between the serum levels of CTRP12 and the CAD severity regarding to the number of affected vessels.About 200 suspected CAD patients and 50 healthy ones as a control, were evaluated based on case-control study. According to the results of angiography, patients were divided into CAD+ (n = 150) with any major coronary artery stenosis ≥50% and CAD- (n = 50) with50% stenosis of the arteries. The CAD+patients were categorized into one- (1VD), two- (2VD) and three-vessel disease (3VD) based on the number of stenotic vessels. In the current study, different parameters such as CTRP12, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were evaluated, and also lipid profiles, hs-CRP and demographic factors were investigated as well.Data revealed that CTRP12 and TAC levels in CAD + group were significantly lower than control subjects (P 0.05). CTRP12 levels were found to be significantly lower in the 3VD compared with 1VD and 2VD subgroups (p 0.01 and p 0.05, respectively).Our results confirmed that serum CTRP12 level is inversely associated with CAD severity. Therefore, it may be used as a prediction marker for CAD.

Introduction: Tumor growth depends on intrinsic properties of malignant tumor and tumor microenvironment. Cytokines are secreted substances of the tumor microenvironment which are widely produced by tumor and immune cells. The aim of this research was to evaluate concentrations of interleukin 4 (IL-4), interleukin 7 (IL-17) and interferon gamma (IFN-γ) in the breast cancer microenvironment. Methods: One hundred sixteen women between 18-73 years of age (61.15 ± 24.39) were enrolled in this study. Based on pathologic diagnostic assessment, patients were divided into 2 categories: those affected with benign breast tumor, and the subjects suffering from malignant breast tumors. Biopsy specimens were collected. Following homogenization, IFN-γ, IL-17, and IL-4 concentrations were determined in tumor tissues, adjacent tissues of the tumor, and blood serum samples of these 2 groups of patients by enzyme-linked immunosorbent assay (ELISA) method. Results: Concentrations of IFN-γ, IL-17, and IL-4 were measured in tumor tissue samples, adjacent tissues of the tumor, and blood serum samples in both groups. Malignant breast tumor samples had significantly higher concentrations of IL-4 and IL-17 compared with benign breast tumor samples. And also the concentration of IFN-γ in adjacent tissues of the tumor and in blood serums in patients with malignant breast tumors was significantly higher than that in the benign breast tumor samples. However, there was no significant difference between the concentration of IFN-γ in neoplastic breast tumor tissues and that in the benign breast tumor tissues (P > 0. 05). Conclusion: Our data indicated that IL-17 and IL-4 cytokines but not IFN-γ had higher concentrations in the subjects with malignant tumor compared with those with benign tumor. The present findings indicated that the concentrations of IL-4 and IL-17 in tumor tissues may be associated with the severity of breast malignancy.

Aims Recent studies suggest that direct exposure of cells to fractionated radiotherapy might induce radioresistance. However, the effects of fractionated radiotherapy on the non-irradiated bystander cells remain unclear. We hypothesized that fractionated radiotherapy could enhance radioresistance and proliferation of bystander cells. Main methods Human tumor cell lines, including A549 and HT29 were irradiated (2 Gy per day). The irradiated cells (either A549 or HT29) were co-cultured with non-irradiated cells of the same line using transwell co-culture system. Tumor cell proliferation, radioresistance and apoptosis were measured using MTT assay, clonogenic survival assay and Annexin-V in bystander cells, respectively. In addition, activation of Chk1 (Ser 317), Chk2 (Thr 68) and Akt (Ser473) were measured via western blot. Key findings Irradiated HT29 cells induced conventional bystander effects detected as modulation of clonogenic survival parameters (decreased area under curve, D10 and ED50 and increased α) and proliferation in recipient neighbors. While, irradiated A549 cells significantly enhanced the radioresistance and proliferation of bystander cells. These changes were accompanied with enhanced activation of Chk1, Chk2 and Akt in non-irradiated bystander A549 cells. Moreover, both bystander effects (damaging and protective) were mediated through secreted factors. Significance These findings suggest that fractionated radiotherapy could promote proliferation and radioresistance of bystander cells probably through survival and proliferation pathways.

Fluctuation of nucleic acid expression and ultrasensitive and specific detection of these variations in expression is a crucial subject in molecular medicine and clinical theranostics. A novel DNAzyme-coupled branched hybridization chain reaction (b-HCR) assay is reported for efficient signal-amplified detection of miRNA in this study. This assay was composed of a translator (T) hybridized with miR-21 to initiate the first HCR by hairpin 1 (H1) and hairpin 2 (H2). The primary HCR provided a backbone chain for numerous branches budding through hairpin 3 (H3) and hairpin 4 (H4) assembles. In the presence of hemin, the G-rich domains embedded in H1 and H4 produce an active G-quadruplex DNAzyme upon exposure to a target that could catalyze the oxidation of colorless substrate to colored product. The present approach has the potential to be used for quantitative detection of miR-21 with a sensitivity and a dynamic range of 1 pM and 1 pM to 1 nM, respectively.

Background: Diabetes is a major worldwide health problem. It is widely accepted that the beta cell mass decreases in type I diabetes (T1D). Accordingly, beta cell regeneration is a promising approach to increase the beta cell mass in T1D patients. However, the underlying mechanisms of beta cell regeneration have yet to be elucidated. One promising avenue is to create a relevant animal model to explore the underlying molecular and cellular mechanisms of beta cell regeneration. The zebrafish can be considered a model in beta cell regeneration studies because the pancreas structure and gene expression pattern are highly conserved between human and zebrafish. Materials and Methods: In this study, the Tol2 transposase was exploited to generate a Tg(Ins:egfp-nfsB) zebrafish model that expressed a fusion protein composed of enhanced green fluorescent protein (EGFP) and nitroreductase (NTR) under control of the Ins promoter. Results: Metronidazole (MTZ) treatment of Tg(ins:egfp-nfsB) zebrafish larvae led to selective ablation of beta cells. Proof-of-concept evidence for beta cell regeneration in the transgenic larvae was observed two days after withdrawal of MTZ. Conclusion: This study suggests that the Tg(ins:egfp-nfsB) zebrafish can be used as a disease model to study beta cell regeneration and elucidate underlying mechanisms during the regeneration process. [GMJ.2019;8:e1056]

Gene therapy is known as one of the most advanced approaches for therapeutic prospects ranging from tackling genetic diseases to combating cancer. In this approach, different viral and nonviral vector systems such as retrovirus, lentivirus, plasmid and transposon have been designed and employed. These vector systems are designed to target different therapeutic genes in various tissues and cells such as tumor cells. Therefore, detection of the vectors containing therapeutic genes and monitoring of response to the treatment are the main issues that are commonly faced by researchers. Imaging techniques have been critical in guiding physicians in the more accurate and precise diagnosis and monitoring of cancer patients in different phases of malignancies. Imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are non-invasive and powerful tools for monitoring of the distribution of transgene expression over time and assessing patients who have received therapeutic genes. Here, we discuss most recent advances in cancer gene therapy and molecular approaches as well as imaging techniques that are utilized to detect cancer gene therapeutics and to monitor the patients' response to these therapies worldwide, particularly in Iranian Academic Medical Centers and Hospitals.Cancer Gene Therapy advance online publication, 18 November 2016; doi:10.1038/cgt.2016.62.

We studied the immune responses to heat shock protein (Hsp)-27 and pro-oxidant–antioxidant balance (PAB) values in patients with valvular heart disease, but free of angiographically evident coronary artery disease (CAD). Patients who were candidates for valvuloplasty surgery and 30 healthy matched controls were recruited. The anti-Hsp-27 antibody titers were 0.35 ± 0.04 absorbency units (AU) in the valvuloplasty group, being significantly higher than for the controls (0.11 ± 0.02 AU; P < .05). The PAB values were significantly higher in cases (134.67 ± 13.69 Hamidi-Koliakos(HK) unit) when compared with controls (49.78 ± 6.75 HK unit; P < .05). In cases, the ejection fraction was inversely correlated with anti-Hsp-27 antibody ( P < .05) but was not significantly related to PAB values ( P > .05). Based on the echocardiographic findings, the patients had no evident heart failure, but the high levels of anti-Hsp-27 and PAB values in patients with valvular heart disease may indicate that these variables can be used as markers of heart failure. However, a longitudinal study is required to confirm this hypothesis.

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = –0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.

OBJECTIVES We have assessed the relationship between indices of adiposity and antibody titers to Hsp-27 in healthy subjects. DESIGN Two-hundred and fifty subjects were studied, including 50 normal-weight subjects (body-mass-index (BMI) 25 kg/m(2)), 100 overweight subjects (BMI 25 to 30 kg/m(2)) (n=100) and 100 obese subjects (BMI ≥ 30 kg/m(2)). RESULTS Anti-Hsp27-antibody levels in obese subjects were [0.34 (0.20-0.39) absorbency unit], being significantly higher than overweight and normal-weight groups (P

OBJECTIVE To investigate the association between serum antibody titers to Hsp27 (anti-Hsp27) and pro-oxidant-antioxidant balance (PAB) in patients with angiographically-defined coronary artery disease (CAD) with or without the metabolic syndrome (MS). DESIGN Subjects (n=243) were classified into MS+ (n=161) and MS- (n=82) subgroups, based on the AHA/NHBLI criteria. RESULTS Serum anti-Hsp27 titers were found to be significantly higher in the MS+ vs. MS- group. However, no significant difference was observed in serum PAB values. When assessed for individual components of MS, increased serum anti-Hsp27 was found to be higher in subgroups with elevated triglycerides, elevated blood pressure and reduced high-density lipoprotein cholesterol (HDL-C). Subgroups of patients with elevated triglycerides had higher PAB values. HDL-C was the only significant predictor of anti-Hsp27 in the population as a whole. CONCLUSION The evidence from this investigation indicates the presence of elevated anti-Hsp27 in patients with concurrent CAD and MS compared to those with CAD alone.

We assessed the changes in serum antiheat shock protein (HSP)-27 antibody and high-sensitivity C-reactive protein (hsCRP) levels, following the placement of a drug-eluting stent (DES) or bare-metal stent (BMS) in patients with stable coronary artery disease. Either a BMS or DES was implanted in 137 patients (82 BMS; 55 DES). Anti-HSP27 and hsCRP levels were measured 24 hours before and 24 hours after stenting. Median hsCRP serum levels increased significantly to 60.78 (10.13-84.87) and 77.80 (50.00-84.84) mg/L for BMS and DES groups (P = .006 and P = .000, respectively); this increase did not differ significantly between the 2 groups. Median anti-HSP27 antibody levels decreased to 0.26 (0.17-0.49) and 0.21 (0.16-0.29) absorbency units in BMS and DES groups (P = .045 and P = < 0.001, respectively). The changes in anti-HSP27 antibody titers were significant between the 2 groups (P = .015). Bare-metal stent and DES differ in stimulation of immune rather than inflammatory responses. Less stent restenosis after DES compared with BMS implantation could, in part, be attributed to differences in immune responses.

It has been suggested that antioxidized low-density lipoprotein (anti-oxLDL) antibodies play a role in the pathogenesis of atherosclerosis. The aim of this study was to measure serum ox-LDL IgG levels in 31 patients with angiographically defined coronary artery disease (CAD) (≥50% stenosis in at least one major coronary artery; CAD+group) and compare these levels with those of 32 subjects with −group) and 24 healthy age- and sex-matched controls using ELISA. We did not find any significant difference between CAD+, CAD−, and control groups in regard to oxLDL IgG levels (P=0.83). Serum oxLDL IgG levels did not differ between 1VD (one vessel disease), 2VD (2 vessels disease), and 3VD (3 vessels disease) subgroups of CAD+patients (P=0.20). Serum anti-oxLDL titers were only significantly correlated with LDL-C in the CAD+group (P<0.05) and waist and hip circumference (P<0.05andP<0.01, resp.) in the CAD−group. In stepwise regression analysis, none of the conventional cardiovascular risk factors was associated with serum ox-LDL IgG levels. The present results suggest that serum levels of ox-LDL IgG are neither associated with the presence and severity of CAD nor with the conventional cardiovascular risk factors.

We have measured the pro-oxidant-antioxidant-balance (PAB) levels in patients with defined coronary artery disease (CAD) and compared them with concentrations in healthy subjects.Based on angiography results, 400 patients with stable CAD were divided into CAD- and CAD+, this being further subcategorized into groups with single-, double- and triple-vessel disease (VD).The mean PAB values in the healthy subjects, was significantly lower than for other groups (P0.001). In CAD- patients, PAB levels were 123.2 ± 43.9, which was not statistically different compared to groups with SVD, 2VD and 3VD (P0.05). In the CAD+ group, PAB values in 1VD, 2VD and 3VD were not significantly different among patients with SVD, 2VD and 3VD (P0.05).In conclusion, we found higher levels of oxidative stress in CAD+ patients compared to healthy subjects. The oxidation level was not related to measures of the extent of CAD such as number of stenosed vessels.

Antibody titers to several heat shock proteins (anti-Hsps) have been reported to be associated with the severity and progression of cardiovascular disease. However, there are little data regarding anti-Hsp27 titers in patients with coronary artery disease (CAD). A total of 400 patients with suspected CAD were recruited. Based on the results of coronary angiography, these patients were classified into CAD(+) (n = 300) and CAD(-) (n = 100) groups defined as patients with ≥50% and50% stenosis of any major coronary artery, respectively. Eighty-three healthy subjects were also recruited as the control group. Serum anti-Hsp27 IgG titers were measured using an in-house enzyme-linked immunosorbent assay. CAD(+) patients had significantly higher anti-Hsp27 titers compared with both CAD(-) and control groups. Anti-Hsp27 titers were also higher in the CAD(-) group compared with the control group. With regard to the number of affected vessels in the CAD(+) group, patients with three-vessel disease had higher anti-Hsp27 titers compared with both two-vessel disease (2VD) and one-vessel disease (1VD) subgroups. However, there was no significant difference between 1VD and 2VD subgroups. In multiple linear regression analysis, the number of narrowed vessels and smoking were significant independent determinants of serum anti-Hsp27 titers. The present findings indicate that serum anti-Hsp27 titers may be associated with the presence and severity of coronary artery disease.

In this study we aimed to assess the changes in pro-oxidant-antioxidant balance (PAB) after the placement of either a drug-eluting-stent (DES) or bare-metal-stent (BMS) in patients with stable coronary artery disease.Percutaneous coronary interventions (PCI) with either BMS or DES were undertaken for 152 patients (82 in the BMS and 70 in the DES groups respectively). PAB values were measured 24h before and after PCI.Baseline PAB values were 80.68 (64.98-99.37) and 98.86 (64.70-140.62) for BMS and DES group, respectively, which were not significantly different between the 2 groups (P0.05). Following PCI, median PAB values decreased to 72.10 (61.40-96.13) and 81.40 (54.15-121.90) in BMS and DES groups, respectively. The reduction was significant in both BMS and DES groups (P0.05). The changes in PAB values were -2.81 (-12.76 to 2.31) for BMS and -2.82 (-29.88 to 8.93) for DES group, which were not significantly different between the 2 groups (P0.05).We found that the reported difference in clinical outcomes following DES or BMS implantation cannot be attributed to differences in early changes in oxidative stress induction as assessed by changes in PAB values.