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Continuing hyperglycemia causes and exacerbate oxidative stress. Betanin as the principal pigment of red beet root has antioxidant, anti-inflammatory, and anti-diabetic properties. The purpose of this study was to investigate the potency of betanin on antioxidant defense in STZ-induced diabetic rats' livers.STZ at a single dose of 60 mg/kg body weight was intraperitoneally injected and betanin (10, 20, and 40 mg/kg/day) was administered orally for 28 days. Malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC) levels, and the enzyme activity of superoxide dismutase (SOD), catalases and glutathione peroxidases (GPx) were evaluated in the liver. Furthermore, gene expression of Nrf2 and mentioned antioxidant enzymes were measured by Real-time PCR.Betanin (10 and 20 mg/kg) significantly reduced PC levels and increased antioxidant enzyme activity in diabetic rats compared to the control diabetic group (P 0.01). In comparison to the diabetic control group, all studied genes expression in diabetic rats were increased significantly with betanin at doses of 10 and 20 mg/kg (P 0.02). The increase in gene expression at 20 mg/kg of betanin was significantly stronger than others (P 0.015) except for the catalase (P = 0.201), that was almost the same. Moreover, treatment of diabetic rats with 20 mg/kg of betanin could significantly increase TAC levels (P 0.05) and decrease MDA levels (P 0.001) compared to diabetic control group.Betanin could increase the antioxidant capacity of liver tissue associated with the Nrf2-mediated pathway in a dose-dependent manner.

The aim of this paper is to propose a demountable shear wall (DSW) system for multistory precast concrete buildings. For this purpose, instead of a large wall panel, several slender walls are used by connecting to adjacent beams. To evaluate the efficiency of the DSW system, nonlinear cyclic and time history analyses are performed on eighteen 4-, 8- and 12-story models, including three conventional shear wall models and fifteen DSW models with various wall numbers. The results indicate that for DSW system, when using more walls with a smaller width, the structural deformation tends from flexural-type to almost shear-type. This result prevents the plastic strain from concentrating on the columns and walls of the first story and causes the damage to be uniformly distributed on the walls of all stories. The DSW models exhibit hysteretic behavior without significant strength degradation at high drift levels. Also, DSW models with more walls, while increasing the ductility factor (up to 30%) and creating a more uniform distribution of drifts, reveal less value of maximum floor acceleration (up to 48%) and story shear (up to 53%), compared to conventional shear wall models.

Background: Colorectal cancer is one of the most common gastrointestinal cancers worldwide with a high prevalence among middle-aged people. This study aimed to evaluate and compare changes in serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), as two important tumor markers, in the diagnosis of different stages of colorectal cancer. Materials and Methods: This basic research was conducted on hospitalized patients with colorectal cancer (n=67). At first, tissue samples and venous blood samples were collected from patients. Subsequently, CEA and CA19-9 tumor markers were measured by enzyme-linked fluorescence assay and cellular changes were investigated by hematoxylin and eosin staining. Results: In this study, 57.6% and 43.3% of the patients were male and female, of which 59.7% (40 patients) cases were over 61 years old. The most common sites of tissue involvement were found to be the rectum and sigmoid. In the acute phase of the disease, a decrease was observed in the number of red blood cells (P=0.0091) and the level of hemoglobin (P=0.141); however, the number of platelets remained unchanged (P=0.212). In addition, lymphocyte and neutrophil counts increased at first, while they decreased later. The findings showed that there was a significant relationship between these two tumor markers and disease levels. Conclusion: Our results indicated that although these tumor markers are not suitable factors for the diagnosis of this cancer in the early stages, they can be used as two important markers to diagnose the progression of the disease.

In this paper, the behavior of a natural rubber bearing system (NRBs) equipped with U-shaped dampers is investigated. The U-shaped dampers consist of shaped memory alloy (SMA), structural steel (SS), and combination of both SMA and SS. The combined Mooney-Rivlin and Prony models in ANSYS software is selected for modeling the rubber material. Two cyclic static and dynamic time-history analyses were selected to evaluate the behavior of NRBs equipped with dampers. The results show that the SMA dampers made of FeNiCuAlTaB with 13.5% super-elastic strain and low austenite finish temperature are the most appropriate candidates for use in high shear strain, steel-rubber bearings. The results showed that finite element analyses are able to accurately simulate the mechanical behavior of the damper. Having confirmed the validity of the analysis, the optimum thickness ratio of SMA to SS (tSMA/tSS) to maximize dissipated energy and minimize residual deformation for the dampers was found to be one. The results show that each damper typology has unique benefits; while the U-shaped SMA damper has super-elastic behavior and residual deformation reversibility, the SS dampers significantly increase the energy dissipation capacity. Lastly to illustrate how this could be instrumented on real-world infrastructure, several bridge models, with steel decks and concrete piers isolated by NRBs equipped with steel and SMA dampers, were evaluated.

Background Recent trials have revealed that sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are effective against hyperglycemia and also reduce micro- and macro-vascular complications in patients with type 2 diabetes mellitus (T2DM). Most of the beneficial cardiovascular effects have been investigated in patients with heart failure and coronary artery disease (CAD). Yet, few human studies have been conducted to investigate the molecular mechanisms underlying these clinically beneficial effects in patients with CAD. Accordingly, the EMPA-CARD trial was designed to focus on the molecular effects of empagliflozin in patients with T2DM and CAD. Methods In this multicenter, triple-blind randomized controlled trial, patients with documented known T2DM and CAD will be recruited. They will be randomized on a 1:1 ratio and assigned into two groups of empagliflozin 10 mg/daily and placebo. The primary endpoint is the effect of empagliflozin on changes of plasma interleukin 6 (IL-6) after 26 weeks of treatment. The secondary endpoints will consist of changes in other inflammatory biomarkers (Interleukin 1-beta and high-sensitive C-reactive protein), markers of oxidative stress, platelet function, and glycemic status. Discussion The EMPA-CARD trial mainly tests the hypothesis that SGLT2 inhibition by empagliflozin may improve inflammatory status measured as reduction in inflammatory biomarkers in patients with T2DM and CAD. The results will provide information about the underlying mechanisms of SGLT2 inhibition that mediate the beneficial effects of this medication on clinical outcomes. Trial registration Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

This article presents an experimental investigation of the mechanical and physical behaviors of Polymer Modified Concrete containing %2.5, 5%, 7.5% and %10 Unsaturated Polyester resin with %30, 37.5% and %45 styrene. Twelve mixtures were designed and compressive strength, splitting tensile strength, water absorption, stress-strain curve, modulus of elasticity, energy absorption capacity, failure crack mode and SEM analysis were examined. The results indicated, by replacing cement with Unsaturated Polyester, the compressive and tensile strengths and the water absorption decreased about %15 to %50, but the strain and the energy absorption were increased significantly up to %110 and %30 respectively. Also, adding the amount of styrene in resin led to increase both the compressive strength and energy absorption capacity up to 25%, but according to SEM images it led the formation of a thick polymeric region with compressed layers in ITZ, cause to decrease in tensile strength and water absorption down to 25%.

Background: The DNA mismatch repair (MMR) system is one of the molecular pathways involved in colorectal cancer (CRC) carcinogenesis that consists of several genes, including MLH1 (MutL homolog 1), MSH6 (MutS homolog 6), MSH2 (MutS homolog 2), and MSH3 (MutS homolog 3). The protein encoded by PMS2 (post-meiotic segregation 2) is also essential for MMR. Here, we address the correlation between immunohistochemical and transcriptional expression of PMS2 with the tumor grade and clinical stage of non-hereditary/sporadic CRC disease. Methods: This study retrospectively analyzed 67 colorectal resections performed for 38 male and 29 female patients. Random biopsies were taken by a gastroenterologist from patients referring to three hospitals in the cities of Zanjan, Urmia and Qazvin (Iran) during 2017-2019. All specimens were examined and classified for localization of tumor, pathological stage and grade. The PMS2 protein expression was studied immunohistochemically and analysis of mRNA expression was performed in the same tissue sections. Results: Immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analysis showed a decrease in PMS2 expression compared with paracancerous tissue (P\textless 0.001), which correlated with tumor stage. In addition, reduced PMS2 expression was correlated with the tumor differentiation grade, underlining a connection between downregulation of PMS2 and progression of CRC. Comparing the PMS2 mRNA levels in different groups showed the following results: 0.92 ± 0.18 in patients with Stage I CRC tumor, 0.86 ± 0.38 in Stage â i, 0.50 ± 0.29 in Stage â ¢, and 0.47 ± 0.23 in Stage â £. Conclusion: These findings suggest that PMS2 may provide a potential reliable biomarker for CRC classification by combined immunohistochemical and mRNA analysis. © 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Signal transducer and activator of transcription 3 (STAT3) is a critical regulator for angiogenesis, cell cycle progression, apoptosis, and drug resistance. Resistance toward EGF receptor (EGFR) inhibitors is a significant clinical concern for metastatic colon cancer patients. The present study aimed to evaluate the blocking influences of STAT3 decoy oligodeoxynucleotides (ODNs) on the STAT3 survival signaling pathway in Erlotinib-resistant and non-resistant SW480 colon cancer cells. First, STAT3 decoy and scramble ODNs were designed according to STAT3 elements in the promoter region of the MYCT1 gene and tested for the interaction of STAT3 protein with designed ODNs via in silico molecular docking study. Then, the efficiency of transfection and subcellular localization of ODNs were assessed using flow cytometry and fluorescence microscopy, respectively. Cell viability, cell cycle and apoptosis tests, scratch and colony formation assays, and real-time PCR were also used to study the cancerous properties of cells. A considerable decrease in proliferation of colon cancer cells was observed with blockade of STAT3 signaling due to cell cycle arrest and induced apoptosis via down-regulation of cyclin D1 and Bcl-XL, respectively. Furthermore, upon transfecting STAT3 decoy ODNs, colony formation potential and migration activity in both SW480 colon cancer cell lines were decreased compared to control groups. From this study, it could be concluded that STAT3 is critical for cell growth inhibition and metastatic properties reduction of resistant SW480 colon cancer cells, therefore STAT3 decoy ODNs could be considered as potential therapeutics along with current remedies for treating drug-resistant colon cancer. This article is protected by copyright. All rights reserved.

Objective Irisin, mostly known as an exercise-induced fat browning myokine, has been recently detected in several cancer cells, and its potential for being utilized as a biomarker for early diagnosis of some cancers, such as Gastric cancer (GC), is the subject of speculation. The present study aims to compare serum irisin levels in GC patients and healthy controls and assess the interrelation between irisin and oxidative stress markers. Methods In this case-control study, 22 newly diagnosed GC patients and 29 healthy controls were recruited based on the inclusion criteria. Serum levels of irisin were quantified in duplicates by ELISA. Oxidative stress indices, including total antioxidant power in sera, thiol group, malondialdehyde, and superoxide dismutase concentrations, were also measured in both groups. An independent-sample t-test was used to compare the means between the two studied groups. Results Serum levels of irisin were significantly higher in the GC group compared with those of their healthy counterparts (p =0.032). No significant differences were observed between the two groups in terms of the serum total antioxidant power or the oxidative stress marker, including MDA, thiol groups, and SOD concentration in sera. Furthermore, there was no significant association between irisin, FRAP, the Thiol group, and the SOD activity. Conclusion According to the finding, the increased serum levels of irisin in GC patients can play a potential role in the early diagnosis of the GC patients; hence, this peptide can be employed as a new diagnostic indicator of GC. .

The behavior of natural rubber bearing incorporated with high toughness steel ring dampers (NRB-HTSRDs) is presented. These dampers are made of several steel rings, which are connected by weld in different configurations around the rubber bearing. The operational characteristics of this system including effective horizontal stiffness, secondary hardening, system stability, energy dissipation, equivalent viscous damping, and residual deformation were studied. The results showed that the energy dissipation in these dampers; is mainly revealed as yielding due to flexural deformation of the rings. All specimens of NRB-HTSRDs system; overally enhance the behavior and are considerably better than natural rubber bearing (NRB) or high damping rubber bearing (HDRB). The arrangement of HTSRD2, HTSRD4 and HTSRD6 have better behavior rather than HTSRD1, HTSRD3 and HTSRD5 due to modest initial stiffness at lower shear strains to control small lateral loads of the structure and undesirable effects on the flexibility of rubber bearing, and higher secondary hardening in larger shear strains that increases the energy dissipation and stability of the structure. Also, the specimens in which the rings have larger diameter and are only connected to the top and bottom plates, dissipate energy better than other specimens.

Insulin-like growth factor-1 receptor (IGF-1R) is expressed in malignant and normal breast tissue, and its intermittent activation by multiple IGF-1 signaling pathways leads to neoplasm cell proliferation, impaired apoptosis, increased survival, and resistance to cytotoxic therapeutic agents. Therefore, simultaneous suppression of the receptor and its cognate ligand would be a powerful promising strategy inhibiting malignant phenotypes of breast cancer cells. In the present study, Methoxypoly(ethylene glycol) - Poly(caprolactone) was hybridized with Dimethyldioctadecylammonium bromide (DDAB) cationic lipid (mPEG-PCL-DDAB) nanoparticles (NPs) and used as a carrier for simultaneous delivery of lycopene and insulin-like growth factor 1 receptor-specific lycopene encapsulated-mPEG-PCL-DDAB nanoparticle/siRNA to MCF-7 breast cancer cells. Then, the antitumor effects of this construct were evaluated in vitro. The results demonstrated that the synthesized mPEG-PCL-DDAB nanoparticle had suitable physicochemical properties. The use of mPEG-PCL-DDAB nanoparticle-loaded anti-insulin-like growth factor 1 receptor-siRNA and lycopene dramatically induced the process of apoptosis and arrested cell cycle in the MCF-7 tumor cell lines. In general, the findings of this study demonstrated the potency of mPEG-PCL-DDAB nanoparticles for dual delivery of siRNA, and lycopene in breast cancer cell lines followed the induction of apoptosis.

The present paper is aimed to investigate the behavior of Natural Rubber Bearing incorporated with steel ring damper (NRB-SRD). These types of dampers are integrated of several steel rings which are considered with two configurations namely, continual steel ring damper and separate steel ring damper and are inserted between top and bottom plates. The performance characteristics of the system such as effective horizontal stiffness, energy dissipation, equivalent viscous damping and residual deformation are calculated and then compared with the results of high damping rubber bearings and also shape memory alloy (SMA)-lead core rubber bearing (SMA-LRB). The results show that the energy dissipation in steel rings are mainly based on plastic deformation due to flexural behavior of the rings. NRB-SRD shows better performance in energy dissipation comparing to SMA-LRB and HDRB. These additional dampers show higher stability and energy dissipation in low shear strains due to developing of link between structure and substructure having desirable initial stiffness under weak earthquakes and wind loads and also in higher shear strains due to creation of higher energy dissipation, stability and secondary stiffening.

This paper presents a stacking sequence optimization for maximizing the buckling load of rotationally restrained laminated composite rectangular plates with different boundary conditions resting on an elastic Pasternak foundation subjected to uniaxial and biaxial in-plane static loads. The Mindlin Plate Theory (MPT), which considers the first-order shear deformation effect, is used to extract the characteristic equations of the plates under in-plane loading, including plate-foundation interaction. The buckling problem of the laminated plates is analyzed by the Rayleigh–Ritz method. The aim of optimization is to maximize the buckling load and post-buckling load capacity by using the Genetic Algorithm (GA) method, and the design variable is the ply orientation. The results showed that the optimal orientation, θ, of the laminated square plate under biaxial in-plane loading with various conditions is 〖45〗^∘ approximately. The existence of a foundation, clamped boundary conditions, and high aspect ratio lead to increase the optimal orientation.

Introduction It is suggested that air pollution exposure induces oxidative stress in the body and causes diseases. However, current evidence regarding the association of outdoor air pollution with some oxidative toxic stress (OTS) biomarkers in areas with different pollutant concentrations is equivocal. Objective The aim of study was to investigate the adverse effects of outdoor air pollution on human health, by evaluating potential oxidative and anti-oxidative biomarkers and p53 protein levels in subjects exposed to different outdoor air pollution from two polluted and less polluted cities of Iran. Material and methods In this cross-sectional study, a total of 203 healthy working men were selected from two cities. The activities of superoxide dismutase (SOD), catalase (CAT) and γ-glutamyltransferase (GGT) and the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS), were measured by the colorimetric method. The levels of p53 were measured by an ELISA method. Results The results showed a significant increase in the levels of p53 and MDA in the exposure group compared to the control group, while the activity of SOD and TAC was significantly decreased in the exposure group. No significant differences were found in activities of CAT and GGT, and levels of TOS between the two groups. Conclusions The findings obtained confirmed the implication of air pollution in the development of OTS, and suggested useful biomarkers to evaluate the air pollution-induced harmful effects on human health in the polluted areas.

Background: Recent trials have revealed that sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are effective against hyperglycemia and also reduce micro- and macro-vascular complications in patients with type 2 diabetes mellitus (T2DM). Most of the beneficial cardiovascular effects have been investigated in patients with heart failure and coronary artery disease (CAD). Yet, no human study has been conducted to investigate the mechanisms underlying these clinically beneficial effects in patients with CAD. Accordingly, the EMPA-CARD trial was designed to focus on the molecular effects of empagliflozin in patients with T2DM and CAD.Methods: In this multicenter, triple-blind randomized controlled trial, patients with documented known T2DM and CAD will be recruited. They will be randomized on a 1:1 ratio and assigned into two groups of empagliflozin 10 mg/daily and placebo. The primary endpoint is the effect of empagliflozin on changes of plasma interleukin 6 (IL-6) after 26 weeks of treatment. The secondary endpoints will consist of changes in other inflammatory biomarkers (Interleukin 1-beta and high-sensitive C-reactive protein), markers of oxidative stress, platelet function, and glycemic status. Discussion: The EMPA-CARD trial mainly tests the hypothesis that SGLT2 inhibition by empagliflozin may improve inflammatory status measured as reduction in inflammatory biomarkers in patients with T2DM and CAD. The results will provide information about the underlying mechanisms of SGLT2 inhibition that mediate the beneficial effects of this medication on clinical outcomes.Trial registration: Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective

To use siRNA molecule as a therapeutic agent in gene silencing, an efficient delivery system is necessary. Stability and clearance by reticuloendothelial of siRNA still remains the major challenges for clinical application. Herein, we could develop new lipid-polymer hybrid nanoparticles (LPHNP) as a siRNA carrier to silence insulin-like growth factor type I (IGF-1R) gene overexpression in MCF-7 human breast cancer cell line.Dimethyldioctadecylammonium bromide-methoxy poly(ethylene glycol)-poly (ε-caprolactone) (DDAB-mPEG-PCL) LPHNPs were synthesized using a single step nanoprecipitation method and characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM) microscope. Cytotoxicity of the nanoparticles was assessed in the MCF7 cell line using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Desired LPHNP-siRNA complex was determined using different Nitrogen:Phosphate ratio (N/P) ratios and gel retardation. To determine the encapsulation efficiency of siRNA (%) in LPHNP, its absorbance was measured. The effect of the siRNA-LPHNP complex on IGF-1R silencing was assessed by reverse transcription-polymerase chain reaction (RT-PCR) RESULTS: LPHNP was synthesized using a single-step sonication method with a size below 100 nM. The viability of cells treated with hybrid nanoparticles was significantly greater than the corresponding cationic lipid (P 0.01). As demonstrated by gel retardation assay, efficient siRNA binding to LPHNP occurred at N/P equal to 40 and siRNA encapsulation efficiency was found to be 95% ± 4 at this ratio. LPHNP-IGF-1R siRNA complex could be able to down-regulate the target more efficiently when it compared with the corresponded controls (P 0.001).In conclusion, our results suggest that DDAB cationic lipid and mPEG-PCL copolymer hybrid nanoparticle may be a good candidate for efficient siRNA delivery.

Background Delivery of siRNA has been one of the major challenges to application of siRNA therapeutics. Polymer/lipid hybrid nanoparticles (HNPs) combine the advantages of both polymeric and liposomal carriers with remarkable properties for efficient siRNA encapsulation and delivery. Objective Herein, PLA-PEG-PLA/lipid hybrid nanoparticles were fabricated and utilized for siRNA encapsulation. Transfection efficiency of complex HNPs/siRNA was investigated in MCF7 breast cancer cells. Methods PLA-PEG-PLA copolymer was synthesized by ring opening polymerization and its hybridization with cationic lipid was performed using sonication method. Quality controls and HNP cytotoxicity were determined using DLS, AFM, SEM, and MTT assay, respectively. Cellular uptake of HNP/siRNA complex was investigated by flow cytometry and fluorescence microscope. Silencing activity of HNPs/siRNA complexes was analyzed using semi-quantitative RT-PCR. Results Fabricated HNPs exhibited improved biocompatibility compared to the cognate lipid nanoparticles and showed high siRNA encapsulation efficiency (80% ± 5). HNPs were capable of transferring of IGF-1R-siRNA into MCF7 cells, which resulted in expression down regulation of IGF-1R gene (70% ± 3). Conclusion The excellent cyto-compatibility, high cellular uptake, and remarkable gene silencing ability made HNPs promising carriers for efficient siRNA delivery.

Graphene oxide (GO) and gold/graphene oxide (Au/GO) nanocomposites were fabricated through a facile chemical route and their application as excellent nanocarriers for curcumin delivery were also demonstrated. The structure and physical properties of GO and Au/GO nanocomposite were investigated by transmission electron microscope, X-ray diffraction, Fourier-transform infrared spectroscopy and UV–visible spectrophotometry. Curcumin was chosen as a model drug to be loaded onto the GO via π–π stacking and hydrophobic interaction. The cytotoxicity of GO, Au/GO, and curcumin-loaded Au/GO nanocomposite (Au/GO/Cur) was investigated on the MCF7 breast cancer cell line, and HEK293 (human embryonic kidney 293) cells. The toxicity of the nanocomposites were also tested against brine shrimp (Artemia salina) larva, and human red blood cells (RBC) membrane disruption. The Au/GO/Cur system indicated cancer cell-specific properties with no noticeable toxicity on normal healthy cells after 48 and 72 h incubation with different concentrations in comparison to GO. In addition, the Au/GO/Cur nanocomposite did not show a strong lethal effect on brine shrimp larva (50% lethal concentration or LC50 = 657.35 µg/mL). The effect of the nanocomposite on the integrity of RBC membranes was negligible and confirmed its hemocompatibility and biocompatibility. Thus, the prepared nanocomposite system offers a novel formulation that combines the unique properties of a biodegradable material for biomedical applications.

Given the high rate of cancer mortality in the world, trying to find appropriate therapeutic strategies is a very crucial issue. Since insulin-like growth factor −1(IGF-1) and its receptor (IGF-1R) play a significant role in tumor formation and progression, targeting them can have a vital effect on cancer treatment. Lycopene is a natural antioxidant that exerts its anti-tumor effect by regulating IGF-I signaling and cell cycle arrest, making it a suitable therapeutic agent for reducing tumor induction. However, the utilization of lycopene is limited due to its high lipophilicity and very low solubility in biological body fluids. To overcome this problem, polymer lipid hybrid nanocarriers that have a core-shell structure have received much attention in recent years. In this study, to produce lipid-hybrid nanoparticles (NPs), methoxypolyethylene glycol-polycaprolactone (mPEG-PCL) copolymers were applied for lycopene loading due to biocompatibility, biodegradability, non-toxic nature, small size, amphiphilic properties, and stability of these NPs in the circulatory system. Furthermore, the use of the cationic lipid of Dimethyldioctadecylammonium bromide (DDAB) increased the cellular uptake of nanocarriers. This study proposed mPEG-PCL-DDAB as a potent nanocarrier for drug delivery to MCF-7 breast cancer cell lines, in vitro, and their applicability for the IGF-1R silencing, as a promising anti-cancer therapeutic approach, for the first time.

Erlotinib is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor, but the development of erlotinib resistance during chemotherapy can lead to treatment failure. To shed light on the erlotinib-resistant pathway, this study investigated the effect of combination therapy using curcumin- and erlotinib-loaded nanoparticles on the expression of alphav beta3 integrin and pyruvate dehydrogenase kinase 4 (PDK4) in an erlotinib-resistant SW480 colon cancer cell line. An erlotinib-resistant SW480 colon cancer cell line was produced by long-term exposure to erlotinib. Curcumin-loaded Methoxy poly ethylene glycol Poly caprolactone (cur/mPEG-PCL) and erlotinib-loaded mPEG-PCL (erl/mPEG-PCL) micelles were provided using a single step nanoprecipitation method and used as combination therapy of resistant SW480 cancer cells. After that, gene expression levels of PDK4, alphav, and beta3 mRNA were determined by the semiquantitative reverse transcription-polymerase chain reaction. Protein levels of whole alphav beta3 integrin were evaluated using the enzyme-linked immunosorbent assay method. In SW480 cell line, the IC50 of nonresistant and resistant cells was 87.6 +/- 1.2 nM and 19.1 +/- 0.14 muM, for erlotinib and it was about 21.8 and 30 muM for curcumin, respectively. Although PDK4 expression was not significantly different in resistant and nonresistant cells, its expression was up regulated (1.4 fold) in resistant cells by a combination therapy of cur/mPEG-PCL at a dose of 3 muM and erl/mPEG-PCL at a dose of 5 muM. beta3 mRNA and the protein level of whole alphav beta3 integrin was significantly higher in resistant SW480 cells as compared with those in nonresistant cells. In terms of treatment, a combination of 6-muM cur/mPEG-PCL and 5-muM erl/mPEG-PCL down regulated beta3 gene expression 6.6-fold in resistant cells as compared with nonresistant cells. At the protein level, a combination of 3-muM-cur/mPEG-PCL and 10-muM erl/mPEG-PCL reduced alphav beta3 protein in resistant cells. The results indicated that combination therapy using cur/mPEG-PCL and erl/mPEG-PCL could decrease alphav beta3 integrin expression and increase PDK4 gene expression in resistant colon cancer cells, which may have effects on drug resistance signaling pathways.

The DNA mismatch repair (MMR) system is one of the molecular pathways involved in colorectal cancer (CRC) carcinogenesis that consists of several genes, includingThis study retrospectively analyzed 67 colorectal resections performed for 38 male and 29 female patients. Random biopsies were taken by a gastroenterologist from patients referring to three hospitals in the cities of Zanjan, Urmia and Qazvin (Iran) during 2017-2019. All specimens were examined and classified for localization of tumor, pathological stage and grade. The PMS2 protein expression was studied immunohistochemically and analysis of mRNA expression was performed in the same tissue sections.Immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analysis showed a decrease in PMS2 expression compared with paracancerous tissue (These findings suggest that

C-reactive protein (CRP) is considered to be an inflammatory marker in type 2 diabetes (T2D) and it is produced by liver cells. The evidence has suggested that resveratrol has anti-inflammatory effect. This study aimed to evaluate the effect of resveratrol supplementation on CRP level in patients with T2D using a systematic review and meta-analysis of randomized controlled trials.Electronic databases were completely searched using Medline, ISI Web of Science, EMBASE and Cochrane Library and Scopus until October 2019. Meta-analysis was performed using random-effects model and inverse variance method. Heterogeneity and publication bias were evaluated in selected studies. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity. Meta-regression was performed to assess the effect of potential confounders on the estimated effect sizes.Six trials comprising a total of 491 subjects were included in this meta-analysis. The results showed significant reduction in the level of CRP [SMD (-0.34 mg/l) (95 % CI, -0.52, to -0.16) p0.05] in participants with T2D following supplementation with resveratrol. No significant publication bias was observed in the meta-analysis. Subgroup and sensitivity analyses indicated that the pooled effects of resveratrol supplementation on CRP level in T2D patients were affected by resveratrol dose and duration of resveratrol. Random-effects meta-regression did not indicate any significant association of CRP level with potential confounders including resveratrol dose, duration of treatment, age and gender of type 2 diabetic patients.We found a significant reduction in CRP level in patients with type 2 diabetes, who received resveratrol supplementation.

In this work, a simple label-free electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA) was developed. At first, the GC electrode was coated with partially reduced graphene oxide (rGO) to form a platform to bind the antibody. After activating the carboxyl groups of rGO through the EDC/NHS linker, the electrode surface was covered with the antibody. Then, the electrochemical behavior of the antibody-modified electrode and the parameters of the interactions of antibody-antigen immune complexes were investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). This immune-complex layer was found to attenuate the electrochemical current which can be used as a good signal to determine the antigen concentration. The proposed immunosensor exhibited a good amperometric response to CEA within a concentration range of 0.1–5 ng mL−1 with a detection limit of 0.05 ng ml−1. Furthermore, the developed method was evaluated for the detection of CEA in the real sample (human blood serum), and the results were comparable with the reference values obtained by the standard enzyme-linked immunosorbent assay (ELISA). Our findings suggest the present immunosensor as a good candidate for application in clinical screening.

BACKGROUND Osteoporosis is a systemic bone disease which leads to a reduction in bone mass. Many studies have shown that up to 80% of bone mineral density (BMD) variations are attributed to genetic factors. Arachidonate 12-lipoxygenase enzyme, encoded by the ALOX12 gene, produces lipid peroxides as reactive oxygen species (ROS), leading to oxidative stress and the development of osteoporosis. Selenium (Se) is incorporated into selenoproteins, which may reduce the risk of osteoporosis. OBJECTIVES We aimed to investigate the association of 2 ALOX12 single nucleotide polymorphisms (SNPs) and serum Se level with lumbar spine and femoral neck BMD among elderly individuals living in Amirkola, Iran. MATERIAL AND METHODS The study consisted of 180 individuals aged ≥60 years (90 healthy and 90 osteoporotic patients). We examined the effect of 2 ALOX12 SNPs (rs2292350 and rs9897850), using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) on both BMD regions measured by dual energy X-ray absorptiometry (DXA). Serum Se level was measured using an atomic absorption spectrophotometer PGG990 AAS (PG Instruments Ltd., Luterworth, USA). RESULTS The rs2292350 SNP showed a significant association with femoral neck BMD (p = 0.04). Moreover, in terms of serum Se level, a significant difference was found between the patient group (57.58 ±25.54 μg/L) and the control group (81.09 ±25.58 μg/L) (p < 0.001). In addition, individuals with higher serum Se levels also had higher BMD of the lumbar spine (r2 = 0.392; p < 0.001) and the femoral neck (r2 = 0.478; p < 0.001). CONCLUSIONS The results suggested that genetic variation in ALOX12 might influence BMD variations in our recruited participants. As for the patients with lower serum Se levels, it was observed that serum Se deficiency was accompanied by some ALOX12 variation, contributing to the development of osteoporosis.

PURPOSE Serum and intracellular instability limits the therapeutic applications of short interfering RNA (siRNA) as a radiopharmaceutical. Chemical modifications like phosphorothioate (PS) substitution and 2'-O-methoxy (2'-O-Me) modifications could eliminate such limitations. In this study, the effects of PS and 2'-O-Me modifications at the backbone of siRNA on serum stability and RNA interference activity were investigated. MATERIALS AND METHODS Fully PS and 2'-O-Me-modified type 1 insulin-like growth factor receptor (IGF-1R) siRNA was radiolabeled with lutetium-177 ((177)Lu) through p-SCN-Bn-DTPA as a chelator. After purification with Vivaspin and PD-10 columns, the radiolabs were examined for stability in serum by instant thin-layer chromatography and polyacrylamide gel electrophoresis. The level of IGF-1R in response to the modified and labeled IGF-1R siRNA was examined using RT-PCR and ELISA assay in colon cancer cells. The effects of such siRNA on the prevention of proliferation of colon cancer cells and its apoptosis were investigated using MTT assay and Annexin-V/propidium iodide double staining, respectively. Cellular accumulation quantities of the labeled and modified IGF-1R siRNA were determined using a γ-counter by taking advantage of (177)Lu as a γ-emitter. RESULTS Both the modified (177)Lu-siRNA complex and the modified nonlabeled siRNA showed significant stability in serum. The levels of IGF-1R mRNA and protein significantly decreased with both the labeled and nonlabeled IGF-1R siRNAs, but no such reduction in IGF-1R was observed with luciferase siRNA (P