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Physiological changes during pregnancy make the individuals more susceptible to severe respiratory diseases. Hence, pregnant women with coronavirus disease 2019 (COVID-19) are likely at a higher risk. We investigated the effects of COVID-19 on T cell response and serum cytokine profile in pregnant patients. Peripheral blood mononuclear cells (PBMCs) of women with COVID-19 were collected during the first trimester of pregnancy, and the percentage of total lymphocytes, as well as CD4 + and CD8 + T cells, was assessed using flow cytometry. The expression of the programmed death-1 (PD-1) marker for exhausted T cells was evaluated. Additionally, the serum samples were provided to evaluate the levels of antiviral and proinflammatory cytokines, as well as laboratory serological tests. Pregnant women with COVID-19 presented lymphopenia with diminished CD4 + and CD8 + T cells. Besides, high expression levels of the PD-1 gene and protein were observed on PBMCs and T cells, respectively, when compared with normal pregnant individuals. Moreover, serum levels of TNF-α, IL-6, IL-1β, and IL-2 receptor were notably enhanced, while IFN-I α/β values were significantly decreased in the patients when compared with controls. Furthermore, hyperlipidemia, hyperglycemia, and hypertension were directly correlated with the disease although serum albumin and vitamin D3 levels adversely affected the viral infection. Our study showed extreme lymphopenia and poor T cell response while elevated values of serum inflammatory cytokines in infected pregnant women. Moreover, a hypertension background or metabolic changes, including hyperlipidemia, hyperglycemia, and vitamin D3 or albumin deficiency, might be promising prognostic factors in pregnant women with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study. Methods and results: Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002). Conclusions: Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy. [ABSTRACT FROM AUTHOR]

An electrochemical immunosensing platform was developed for the detection of receptor tyrosine kinase-orphan receptor-2 (ROR2) at a glassy carbon electrode (GCE) modified with the electrospun nanofiber containing polyvinylpyrrolidone (PVP), soy, and Au nanoparticles (AuNPs). The PVP/soy/AuNP nanofiber exhibited good electrochemical behavior due to synergistic effects between PVP, soy, and AuNPs. The PVP/soy in the modified film provided good mechanical strength, high porosity, flexible structures, and high specific surface area. On the other hand, the presence of AuNPs effectively improved conductivity, as well as the immobilization of anti-ROR2 on the modified GCE, leading to enhanced sensitivity. Various characterization approaches such as FE-SEM, FTIR, and EDS were used for investigating the morphological and structural features, and the elemental composition. The designed immunosensor performance was investigated using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). Under optimum conditions with a working potential range from −0.2 to 0.6 V (vs. SCE), sensitivity, linear range (LR), limit of detection (LOD), and correlation coefficient (R2) were acquired at 122.26 μA/cm2 dec, 0.01–1000 pg/mL, 3.39 fg/mL, and 0.9974, respectively. Furthermore, the determination of ROR2 in human plasma samples using the designed immunosensing platform was examined and exhibited satisfactory results including good selectivity against other proteins, reproducibility, and cyclic stability. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive brain disorder characterized by the ongoing decline of brain functions. Studies have revealed the detrimental effects of hyperphosphorylated tau (p-tau) protein fibrils in AD pathogenesis, highlighting the importance of this factor in the early-stage detection of AD conditions. We designed an electrochemical immunosensor for quantitative detection of the cis conformation of the p-tau protein (cis-p-tau) employing platinum nanoparticles (Pt NPs) supported on zeolitic imidazolate frameworks (ZIF) for modifying the glassy carbon electrode (GCE) surface. Under optimum conditions, the immunosensor selectively and sensitively detected cis-p-tau within the broad linear range of 1 fg mL−1 to 10 ng mL−1 and the low limit of detection (LOD) of 1 fg mL−1 with desired reproducibility and stability. Furthermore, the fabricated immunosensor's performance was examined for the cis-p-tau analysis in the serum of AD patients, indicating its accuracy and feasibility for real-sample analysis. Notably, this is the first application of Pt@ZIF-8 nanocomposite in fabricating a valid immunosensor for selective cis-p-tau detection, even in the presence of trans-p-tau. It is worth mentioning that the enzyme-linked immunosorbent assay (ELISA) reference technique is not able to evaluate pico- or femtomolar concentrations of cis-p-tau, making the fabricated immunosensor superior for early-stage measurement and screening of AD. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is a type of pregnancy-related disease that is not fully understood underlying mechanisms of it till now. Reported results from autophagy-related studies in PE show some controversial roles of this mechanism in PE development and progression. In this study, we aimed to evaluate the autophagy process in preeclampsia women. Materials and methods: Peripheral blood was taken from 50 preeclampsia women and 50 healthy pregnant women. After PBMC isolation, Total RNA and total protein were extracted from PBMCs to cDNA synthesis and real-time PCR and western blotting, respectively. Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes were evaluated using real-time PCR. Atg5, beclin1, LC3B, and FOXO1 expression at the protein level was evaluated by the western blot technique. Results: Real-time PCR results showed an increased expression of Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes in PE patients compared to the healthy pregnant women and also in LOPE patients in comparison with EOPE cases. Western blotting results revealed higher expression of Atg5, beclin1, LC3B, and FOXO1 proteins in PE women compared to healthy pregnant group and in LOPE patients in comparison with EOPE cases. Our findings revealed a positive correlation between proteinuria and protein levels of Atg5, beclin1, LC3B, and FOXO1 in LOPE patients. Conclusion: Our investigation showed an elevated activation of autophagy in PE women in comparison with healthy pregnant women which is in controversy with some other studies. More targeted and comprehensive studies regarding the relationship of autophagy in pre-eclamptic women are needed. [ABSTRACT FROM AUTHOR]

Background: Chronic renal failure is mainly connected with high and low parathyroid hormone (PTH) levels and immunological impairments. The present study aimed to evaluate T helper 17 (Th17) cells as a crucial modulator of the immune system and skeletal homeostasis in hemodialysis patients with impaired intact PTH (iPTH). Methods: In this research, blood samples were taken from ESRD patients with high (> 300 pg/mL), normal (150–300 pg/mL), and low (< 150 pg/mL) serum intact parathyroid hormone (iPTH(levels (n = 30 in each group). The frequency of Th17 (CD4+ IL17+) cells was evaluated by flow cytometry in each group. The expression levels of Th17 cell-related master transcription factors, cytokines in peripheral blood mononuclear cells (PBMC), and Th cells, and the level of the mentioned cytokines were determined in the supernatant of PBMCs. Results: The number of Th17 cells remarkably increased in subjects with high iPTH against low and normal iPTH. Also, RORɣt and STAT3 levels were significantly higher in high iPTH ESRD patients than in other groups in the expression of mRNA and protein levels. These findings are confirmed by evaluating the IL-17 and IL-23 in the supernatant of cultured PBMCs and isolated Th cells. Conclusion: Our findings indicated that increased serum PTH levels in hemodialysis cases may be involved in increasing the differentiation of CD4 + cells to Th17 cells in PBMC. [ABSTRACT FROM AUTHOR]

The disturbance of maternofetal immune tolerance is identified as one of the important issues in the pathology of preeclampsia (PE). PE exosomes are believed to possess significant roles in immune abnormalities. In this study, to assess the possible effects of PE exosomes in the pathophysiology of preeclampsia patients, exosomes were isolated from the serum of PE patients and incubated with peripheral blood mononuclear cells (PBMCs) of healthy pregnant women. Also, exosomes from healthy pregnant women were utilized as the control. Th17/Treg ratio in PE and healthy pregnant women and the effects of PE exosomes on expression level of Th17 and Treg transcription factors, as well as their related cytokines in PBMCs of healthy pregnant women, were evaluated. A significant decrease in Treg cell number and increase in Th17 cells and Th17/Treg ratio were observed in PE patients. Following PE-exosome intervention, a significant increase in mRNA expression level of RORγt, IL-17, IL-23, IL-1β, and IL-6, and significant decrease in IL-10 and TGFβ were evident. On the other hand, no significant difference in FoxP3 level was detected. Additionally, increased IL-6, IL-17, IL-23, and IL-1β levels and decreased IL-10 level in the supernatant of cultured PBMCs from healthy pregnant women following PE-exosome intervention were exhibited. However, TGF-β level did not change significantly. Based on our findings, PE exosomes are able to alter the activity of Th17 and Treg cells as well as their related gene expression and cytokine profiles. These findings support the probable role of PE exosomes in PE pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The Preeclampsia (PE) molecular mechanisms are not fully revealed and different biological processes are involved in the pathogenesis of PE. We aimed to evaluate adenosine and hypoxia-related signaling molecules in PE patients in the current study. Methods: Decidua tissue and peripheral blood samples were taken from 25 healthy pregnant and 25 PE women at delivery time. CD39, CD73, and Hypoxia-inducible factor-alpha (HIF-α) were evaluated in mRNA and protein level using real-time PCR and western blotting techniques, respectively. Also, miR-30a, miR-206, and miR-18a expression were evaluated by real-time PCR. At last, secretion levels of IGF and TGF-β in the taken serum of blood samples were measured by ELISA. Results: Our results revealed that Expression of CD39 is decreased in PE cases versus healthy controls at mRNA and protein levels (p = 0.0003 for both). CD73 and HIF-α showed an increased level of expression in PE patients at RNA and protein status (p = 0.0157 and p < 0.0001 for protein evaluation of CD73 and HIF-α, respectively). The miRNA-30a (p = 0.0037) and miR-206 (p = 0.0113) showed elevated expression in the decidua of the PE group. The concentration of secreted IGF-1 (p = 0.0002) and TGF-β (p = 0.0101) in serum samples of PE cases compared to the healthy group were decreased. Conclusion: In conclusion, our results showed that aberrant expression of molecules that are involved in ATP catabolism and the hypoxic conditions is observed in PE cases and involved in their hypertension and inflammation could be served as PE prognosis by more confirming in comprehensive future studies. miR-206 and miR-30a play a role by regulating CD39 and CD73 as molecules that are involved in ATP catabolism as well as regulating the production of IGF-1 in the process of hypertension, which is the main feature in patients with preeclampsia. On the other hand, decreased level of miR-18a lead to upregulation of HIF-1a, and the consequence condition of hypoxia increases hypertension and inflammation in these patients. [ABSTRACT FROM AUTHOR]

One of the main characteristics of cancer cells is the alteration in lipid composition, which is associated with a significant monounsaturated fatty acids (MUFAs) enrichment. In addition to their structural functions in newly synthesized membranes in proliferating cancer cells, these fatty acids are involved in tumorigenic signaling. Increased expression and activity of stearoyl CoA desaturase (SCD1), i.e., an enzyme converting saturated fatty acids to Δ9-monounsaturated fatty acids, has been observed in various cancer cells. This increase in expression and activity has also been associated with cancer aggressiveness and poor patient outcome. Previous studies have also indicated the SCD1 involvement in increased cancer cells proliferation, growth, migration, epithelial to mesenchymal transition, metastasis, chemoresistance, and maintenance of cancer stem cells properties. Hence, SCD1 seems to be a player in malignancy development and may be considered a novel therapeutic target in cancers, including hepatocellular carcinoma (HCC). This review study aims to discuss the impact of SCD1 as a major component in lipid signaling in HCC. [ABSTRACT FROM AUTHOR]

Background: Recently, biosensors have become popular analytical tools for small analytes due to their high sensitivity and wide analytical range. In the present work, development of a novel biosensing method based on tungsten disulfide quantum dots (WS2 QDs)-Au for rapidly and selectively detecting c-Met protein is introduced. As a proof of concept, M13 bacteriophage-based biosensors were used for the electrochemical detection of c-Met protein as a colon cancer biomarker. Method: The M13 bacteriophage (virus), as the biorecognition element, was immobilized on glassy carbon electrodes which were modified by WS2 QDs-functionalized gold nanoparticles. The stepwise presence of the WS2 QDs, gold nanoparticles, and immobilized phage on glassy carbon electrodes were confirmed by scanning electron microscope (SEM) and square wave voltammetry (SWV) technique. Results: The designed biosensor was applied to measure the amount of c-Met protein in standard solutions, and consequently the desirable detection limit of 1 pg was obtained. Finally, as a proof of concept, the developed platform was used for the evaluation of c-Met protein in serum samples of colon cancer-suffering patients and the results were compared with the results of the common Elisa kit. Conclusions: As an interesting part of this study, some concentrations of the c-Met protein in colon cancer serum samples which could not be determined by Elisa, were easily analyzed by the developed bioassay system. The developed bioassay system has great potential to application in biomedical laboratories. [ABSTRACT FROM AUTHOR]

In the present article, we developed a highly sensitive label-free electrochemical immunosensor based on NiFe-layered double hydroxides (LDH)/reduced graphene oxide (rGO)/gold nanoparticles modified glassy carbon electrode for the determination of receptor tyrosine kinase-like orphan receptor (ROR)-1. In this electrochemical immunoassay platform, NiFe-LDH/rGO was used due to great electron mobility, high specific surface area and flexible structures, while Au nanoparticles were prepared and coated on the modified electrodes to improve the detection sensitivity and ROR1 antibody immobilizing (ROR1Ab). The modification procedure was approved by using cyclic voltammetry and differential pulse voltammetry based on the response of peak current to the step by step modifications. Under optimum conditions, the experimental results showed that the immunosensor revealed a sensitive response to ROR1 in the range of 0.01–1 pg mL−1, and with a lower limit of quantification of 10 attogram/mL (10 ag mL−1). Furthermore, the designed immunosensor was applied for the analysis of ROR1 in several serum samples of chronic lymphocytic leukemia suffering patients with acceptable results, and it also exhibited good selectivity, reproducibility and stability. [ABSTRACT FROM AUTHOR]

Migraine is one of the most common recurrent types of headache and is the seventh cause of disability. This neurological disorder is characterized by having pain in head and other various symptoms such as nausea, emesis, photophobia, phonophobia, and sometimes visual sensory disorders. Magnesium (Mg) is a necessary ion for human body and has a crucial role in health and life maintenance. One of the main roles of Mg is to conserve neurons electric potential. Therefore, magnesium deficiency can cause neurological complications. Migraine is usually related to low amounts of Mg in serum and cerebrospinal fluid (CSF). Deficits in magnesium have significant role in the pathogenesis of migraine. Mg has been extensively used in migraine prophylaxis and treatment. This review summarizes the role of Mg in migraine pathogenesis and the potential utilizations of Mg in the prevention and treatment of migraine with the emphasis on transdermal magnesium delivery. [ABSTRACT FROM AUTHOR]

Male reproductive organ plays an important role in sperm production, maintenance and entry to the female reproductive tract, as well as generation and secretion of male sex hormones responsible for the health of male reproductive system. The purpose of this paper is to discuss the experimental and clinical evidence on the utilization of tissue engineering techniques in treating male infertility. Tissue engineering (TE) and regenerative medicine have developed new approaches to treat patients with reproductive disorders such as iatrogenic injuries, congenital abnormalities, and trauma. In some cases, including congenital defects and undescended testis or hypogonadism, the sperm samples are not retrieved. This makes TE a possible future strategy for restoration of male fertility. Here, we have summarized the recent advances in experimental and clinical application of cell-, tissue-, and organ-based regenerative medicine in male reproductive disorders. [ABSTRACT FROM AUTHOR]

This review (with 118 refs.) discusses the progress made in electroanalytical methods based on the use of organic and inorganic nanomaterials for the determination of bacteria, specifically of E. coli, Salmonella, Staphylococcus, Mycobacterium, Listeria and Klebsiella species. We also discuss advantages and limitations of electrochemical methods. Strategies based on the use of aptamers, DNA and antibodies are covered. Following an introduction into electrochemical biosensing, a first large section covers methods for pathogen detection using metal nanoparticles, with subsections on silver nanoparticles, gold nanoparticles, magnetic nanoparticles and carbon-based nanomaterials. A second large section covers methods based on the use of organic nanocomposites, graphene and its derivatives. Other nanoparticles are treated in a final section. Several tables are presented that give an overview on the wealth of methods and materials. A concluding section summarizes the current status, addresses challenges, and gives an outlook on potential future trends. [ABSTRACT FROM AUTHOR]

This review (with 77 refs.) describes the progress that has been made in biosensors for the detection of autoimmune diseases, mainly via detection of autoantibodies. In addition, specific proteins, cytokines and ions have also been introduced as promising diagnostic biomarkers. Following an introduction into the various kinds of autoimmune diseases, we first discuss the state of the art in respective electrochemical biosensors and nanobiosensors (with subsections on amperometric, impedimetric, voltammetric and photoelectrochemical methods). The next large chapter covers optical methods (with subsections on electrochemiluminescence, fluorescence and surface plasmon resonance). We then make a critical comparison between commercially available kits used for detection of autoimmune diseases with the established biosensors. Several Tables are also presented that give an overview on the wealth of methods and nanomaterials. Finally, in the conclusion part, we summarize the current status, addresse present issues, and give an outlook on potential future opportunities. [ABSTRACT FROM AUTHOR]

The architecture of a wireless video sensor network node has an impact on the performance of a wireless sensor network. Due to nature of WVSN applications, the node should be capable of potentially performing image processing algorithms while simultaneously has high networking capabilities. Providing an optimum architecture in which both parameters are addressed is the main challenge in WVSN. This paper reviews suggested architectures for the node and based on that three base architectures are proposed and implemented. The performance of the nodes is then evaluated at node and network level and the results are included in the paper. Based on the results, an optimized architecture is introduced. This architecture separates the node to a network and an application part. This brings the flexibility of implementing the optimized solution for each part, without considering the other. The network part is implemented using a microcontroller. It is capable of adopting operating systems that are widely used in Wireless Sensor Networks. On the other hand, the application part is implemented using FPGA, that provides a power-optimized and stand-alone solution for the node with high computation capabilities. [ABSTRACT FROM AUTHOR]

Sphingosine-1-phosphate (S1P) can regulate several physiological and pathological processes. S1P signaling via its cell surface receptor S1PR1 has been shown to enhance tumorigenesis and stimulate growth, expansion, angiogenesis, metastasis, and survival of cancer cells. S1PR1-mediated tumorigenesis is supported and amplified by activation of downstream effectors including STAT3, interleukin-6, and NF-κB networks. S1PR1 signaling can also trigger various other signaling pathways involved in carcinogenesis including activation of PI3K/AKT, MAPK/ERK1/2, Rac, and PKC/Ca, as well as suppression of cyclic adenosine monophosphate (cAMP). It also induces immunological tolerance in the tumor microenvironment, while the immunosuppressive function of S1PR1 can also lead to the generation of pre-metastatic niches. Some tumor cells upregulate S1PR1 signaling pathways, which leads to drug resistant cancer cells, mainly through activation of STAT3. This signaling pathway is also implicated in some inflammatory conditions leading to the instigation of inflammation-driven cancers. Furthermore, it can also increase survival via induction of anti-apoptotic pathways, for instance, in breast cancer cells. Therefore, S1PR1 and its signaling pathways can be considered as potential anti-tumor therapeutic targets, alone or in combination therapies. Given the oncogenic nature of S1PR1 and its distribution in a variety of cancer cell types along with its targeting advantages over other molecules of this family, S1PR1 should be considered a favorable target in therapeutic approaches to cancer. This review describes the role of S1PR1 in cancer development and progression, specifically addressing breast cancer, glioma, and hematopoietic malignancies. We also discuss the potential use of S1P signaling modulators as therapeutic targets in cancer therapy. [ABSTRACT FROM AUTHOR]

Exclusive benefits gained by using the image and video sensors in Wireless Sensor Networks (WSNs), make the Wireless Video Sensor Networks (WVSNs), design and development of their structures, a trending topic. The main challenges of WSNs which are more critical in WVSNs are throughput and end-to-end delay. The radio transceivers recently used in WSN motes can work on different channels with very low switching time. Therefore, many multichannel protocols are proposed to improve the efficiency and throughput and decrease the packet drop rate of the network. Proposed algorithms rarely provide a particular solution to the end-to-end problem. Such delays are necessary parameters in real-time applications. In this paper a real-time multichannel protocol called RTMCH is suggested to address the end-to-end delay of a stream in WVSN. A flow-based channel assignment strategy is used for this purpose. Orthogonal channels are assigned to each flows based on many-to-one data-flow to minimize the contention and collision between different flows. Transmission power is a parameter that can be controlled to achieve desired link quality and to control link delay. Channel assignment problem aligns to a constrained optimization problem to make the specified end-to-end delay of each flow. A channel assignment and real-time packet forwarding scheme are then presented. Simulation results based on realistic channel and radio model shows that the RTMCH can efficiently use multiple channels and transmission power to meet specified end-to-end delay. The results also show better performance for RTMCH over a recent real-time protocol and basic multichannel schemes. [ABSTRACT FROM AUTHOR]

CD4+CD25+ regulatory T (Treg) cells and Th17 cells play important roles in peripheral immunity. Immune responses are main elements in the pathogenesis of ischemic stroke (IS). The contribution of Th17 cells in IS patients has not been proved, and whether the balance of Treg/Th17 cells is changed in IS patients remains unidentified. In the present study, we studied Th17 and Treg cell frequency, cytokine secretion, expression of transcription factors, and microRNAs related to Th17 and Treg cells differentiation, which is compared between IS patients and control group. Thirty patients with IS and 30 individuals as control group were enrolled in this study. The frequency of Th17 and Treg lymphocytes, the expression of transcription factors and microRNAs related to these cells, and the serum levels of associated cytokines were assessed by flow cytometry, real-time PCR, and ELISA, respectively. A significant reduction in proportion of peripheral Treg cell frequency and the levels of TGF-β and FOXP3 expression were observed in patients with IS compared with controls, while the proportions of Th17 were increased dramatically, and these effects were along with increases in the levels of IL-17A and RORγt expression in IS patients. The levels of mir-326 and mir-106b-25 expression were increased in patients with IS. These studies suggest that the increase in proportion of Th17 cells and decrease in Treg cells might contribute to the pathogenesis of IS. Manipulating the balance between Tregs and Th17 cells might be helpful for the treatment of IS. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor I receptor (IGF-IR) is expressed on breast cancer cells and involves in metastasis, survival, and proliferation. Currently, application of IGF-IR-targeting monoclonal antibodies (mAbs), alone or in combination with other drugs, is a promising strategy for breast cancer therapy. Single-chain fragment variable (scFv) antibodies have been introduced as appropriate tools for tumor-targeting purposes because of their advantages over whole antibodies. In the present study, we employed a naïve phage library and isolated scFvs against a specific epitope from extracellular domain of IGF-IR by panning process. The selected scFvs were further characterized using polyclonal and monoclonal phage ELISA, soluble monoclonal ELISA, and colony PCR and sequencing. Antiproliferative and apoptotic effects of selected scFv antibodies on breast cancer cell lines were also evaluated by MTT and Annexin V/PI assays. The results of ELISA indicated specific reactions of the isolated scFvs against the IGF-IR peptide, and analyses of PCR product and sequencing confirmed the presence of full length V and Vκ inserts. Treatment of MCF7 and SKBR3 cells with anti-IGF-IR scFv led to a significant growth inhibition. The results also showed that scFv treatment significantly augmented trastuzumab growth inhibitory effects on SKBR3 cells. The percentage of the apoptotic MCF7 and SKBR3 cells after 24-h treatment with scFv was 39 and 30.70 %, respectively. Twenty-four-hour treatment with scFv in combination with trastuzumab resulted in 44.75 % apoptosis of SKBR3 cells. Taken together, our results demonstrate that the targeting of IGF-IR by scFv can be an effective strategy in the treatment of breast cancer and provide further evidence for effectiveness of dual targeting of HER2 and IGF-IR in breast cancer therapy. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer and the second leading cause of cancer-related deaths among women worldwide. Although patients are often diagnosed in the early and curable stages, the treatment of metastatic breast cancer remains a major clinical challenge. The combination of chemotherapy with new targeting agents, such as bevacizumab, is helpful in improving patient survival; however, novel treatment strategies are required to improve clinical outcomes. The insulin-like growth factor-I receptor (IGF-IR) is a tyrosine kinase cell surface receptor which is involved in the regulation of cell growth and metabolism. Previous studies have shown that activation of the IGF-IR signaling pathway promotes proliferation, survival, and metastasis of breast cancer cells. Additionally, overexpression of IGF-IR is associated with breast cancer cell resistance to anticancer therapies. Recently, IGF-IR has been introduced as a marker of stemness in breast cancer cells and there is also accumulating evidence that IGF-IR contributes to the establishment and maintenance of breast cancer epithelial-mesenchymal transition (EMT). Therefore, pharmacological or molecular targeting of IGF-IR could be a promising strategy, in the treatment of patients with breast cancer, particularly in order to circumvent the therapeutic resistance and targeting breast cancer stem/progenitors. Currently, many strategies have been developed for targeting IGF-IR, some have entered clinical trials and some are in preclinical stages for breast cancer therapy. In this review, we will first discuss on the biology of IGF-IR in an attempt to find the role of this receptor in breast cancer and then discuss about therapeutic strategies to target this receptor. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is a heterogeneous neurological disorder with multifactorial etiologies characterized by demyelination, axonal degeneration, and oligodendroglial death. It is believed that both genetics and environmental risk factors such as infection are involved in disease etiology. Accumulating evidence indicates that alteration in purinergic system signaling is involved in immunity and inflammation. Adenosine, a key purine nucleoside, has been shown to be produced during metabolic stress, including ischemia, inflammatory condition, and tissue injury. Methods: Extracellular adenosine directly affects various physiological and pathological processes of MS by stimulating G protein-coupled adenosine receptors A1, A2A, A2B, and A3 on the surface of immune cells. It has been suggested that promotion of adenosinergic system may be an important factor in MS pathophysiology and considered as promising therapeutic target for this disease. Conclusion: In this review, we will discuss about the immunopathologic effects of adenosine on MS and its animal model, experimental autoimmune encephalomyelitis. [ABSTRACT FROM AUTHOR]

Introduction: Acute respiratory infection (ARI) is one of the main causes of morbidity and mortality all around the world. The aim of this study was to determine the frequency, mortality and association with clinical entities of influenza virus type A, influenza virus type B, respiratory syncytial virus (RSV), coronavirus, and adenoviruses in patients with ARI. Materials and Methods: During September 2014 till May 2015, 143 respiratory inpatients samples for viral testing collected from central Hospital in Northwest of Iran. A real-time reverse transcription-PCR (RT-PCR) assay was done to allow in one test the detection of influenza A and B viruses. Also, RSV and adenovirus were identified by Immunochromatography test. Results: Twenty-four (46%) cases were positive for influenza A, which 11 (46%) of them were subtype H1N1 and 13 (54%) cases were subtype H3N2. Also, 21 (40%) cases were positive for influenza B, 5 (10%) cases were positive for RSV, and 2 (4%) cases were positive for adenovirus. One of the patients was positive for both influenza A and adenovirus. Two of the patients were positive for both influenza A and RSV. None of the patients were positive for coronavirus. Conclusions: Our findings show the importance of influenza virus type A, influenza virus type B, RSV, and adenoviruses associated with ARI in hospitalized patient and the different epidemiological patterns of the viruses in Tabriz, Iran. [ABSTRACT FROM AUTHOR]

The immunosuppressive factors in tumor microenvironment enhance tumor growth and suppress anti-tumor immune responses. Adenosine is an important immunosuppressive factor which can be secreted by both tumor and immune cells trough action of two cell surface ecto-nucleotidase molecules CD39 and CD73. Blocking the adenosine generating molecules has emerged as an effective immunotherapeutic approach for treatment of cancer. In this study, CD73-siRNA encapsulated into chitosan-lactate (ChLa) nanoparticles (NPs) was employed to suppress the expression of CD73 molecule on 4T1 breast tumor cells, in vitro. ChLa NPs were generated through ionic gelation of ChLa by tripolyphosphate (TPP). Small interfering RNA (SiRNA)-loaded NPs had about 100 nm size with a polydispersive index below 0.3 and a zeta potential about 13. Our results showed that ChLa NPs with Ch 50 kDa exhibit the best physicochemical features with the high siRNA encapsulation capacity. Synthesized NPs were able to fully bind with siRNA, protect them against serum and heparin degradation, and promote the transfection process. While the NPs exhibited low toxicity during 72 h cell culture, the transfection of Ch-plasmid expressing green fluorescent protein (pEGFP) NPs was efficient in 4T1 cells with a transfection rate of 53.6 % as detected by flow cytometry. In addition, CD73-siRNA-loaded ChLa NPs could efficiently suppress the expression of CD73 as assayed by real-time polymerase chain reaction and flow cytometry. As a conclusion, CD73-siRNA-loaded ChLa NPs may be considered as a promising therapeutic tool for cancer therapy; however, further in vivo investigations are necessary. [ABSTRACT FROM AUTHOR]

The tumor microenvironment is a complex and heterogeneous milieu in which multiple interactions occur between tumor and host cells. Immunosuppressive cells which are present in this microenvironment, such as regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs), play an important role in tumor progression, via down-regulation of antitumor responses. MDSCs represent a heterogeneous group of cells originated from the myeloid lineage that are in the immature state. These cells markedly accumulate under pathologic conditions, such as cancer, infection, and inflammation, and use various mechanisms to inhibit both adaptive and innate immune responses. These immunosuppressive mechanisms include deprivation of T cells from essential amino acids, induction of oxidative stress, interference with viability and trafficking of T cells, induction of immunosuppressive cells, and finally polarizing immunity toward a tumor-promoting type 2 phenotype. In addition to suppression of antitumor immune responses, MDSCs can also enhance the tumor metastasis and angiogenesis. Previous studies have shown that increased frequency of MDSCs is related to the tumor progression. Moreover, various drugs that directly target these cells or reverse their suppressive activity can improve antitumor immune responses as well as increase the efficacy of immunotherapeutic intervention. In this review, we will first discuss on the immunobiology of MDSCs in an attempt to find the role of these cells in tumor progression and then discuss about therapeutic approaches to target these cells. [ABSTRACT FROM AUTHOR]

Tumor cells use several mechanisms such as soluble immune modulators or suppressive immune cells to evade from anti-tumor responses. Immunomodulatory cytokines, such as transforming growth factor-β, interleukin (IL)-10, and IL-35, soluble factors, such as adenosine, immunosuppressive cells, such as regulatory T cells, NKT cells and myeloid-derived suppressor cells (MDSCs), are the main orchestra leaders involved in immune suppression in cancer by which tumor cells can freely expand without immune cell-mediated interference. Among them, MDSCs have attracted much attention as they represent a heterogenous population derived from myeloid progenitors that are expanded in tumor condition and can also shift toward other myeloid cells, such as macrophages and dendritic cells, after tumor clearing. MDSCs exert their immunosuppressive effects through various immune and non-immune mechanisms which make them as potent tumor-promoting cells. Although, there are several studies regarding the immunobiology of MDSCs in different solid tumors, little is known about the precise characteristics of these cells in hematological malignancies, particularly B cell malignancies. In this review, we tried to clarify the precise role of MDSCs in B cell-derived malignancies. [ABSTRACT FROM AUTHOR]

The selective and efficient drug delivery to tumor cells can remarkably improve different cancer therapeutic approaches. There are several nanoparticles (NPs) which can act as a potent drug carrier for cancer therapy. However, the specific drug delivery to cancer cells is an important issue which should be considered before designing new NPs for in vivo application. It has been shown that cancer cells over-express folate receptor (FR) in order to improve their growth. As normal cells express a significantly lower levels of FR compared to tumor cells, it seems that folate molecules can be used as potent targeting moieties in different nanocarrier-based therapeutic approaches. Moreover, there is evidence which implies folate-conjugated NPs can selectively deliver anti-tumor drugs into cancer cells both in vitro and in vivo. In this review, we will discuss about the efficiency of different folate-conjugated NPs in cancer therapy. [ABSTRACT FROM AUTHOR]

Identification of regulatory T cells (Tregs) has led to breaking the dichotomy of the Th1/Th2 axis in the immunopathology of several diseases such as autoimmune diseases and cancer. Despite the presence of extensive information about immunobiology of Tregs in pathogenesis of autoimmune diseases, little is known about the frequency and function of these cells in hematologic malignancies, particularly chronic lymphocytic leukemia (CLL). Recent data have demonstrated increased frequency and intact functional capacity of CD4 Tregs in CLL patients. However, the precise role of these cells in the immunopathology of CLL is not well known. While targeting Tregs in cancer diseases seems to be an interesting immunotherapeutic approach, such therapeutic interventions in CLL might be deleterious due to suppression of the tumor-specific adaptive and innate immune responses. Thus, the precise biological and regulatory functions of all Tregs subsets should be carefully investigated before planning any immunotherapeutic interventions based on targeting of Tregs. In this communication, we review the recent data published on immunobiology of Tregs in CLL and discuss about the possibility of targeting Tregs in CLL. [ABSTRACT FROM AUTHOR]

Little is known regarding the precise role of different subsets of natural killer T (NKT) cells in the immunopathogenesis of cancer diseases, particularly hematopoietic malignancies. Although it is well known that NKT cells counteract tumor immunity, conflicting reports on the role of NKT cells in hematopoietic malignancies support more investigations to clarify the interactions between NKT cells and the tumor. Among the hematopoietic malignancies, B cell malignancies derive from different stages of B cell maturation in which T cells play a pivotal role. There is evidence which implies the protective role of some subsets of NKT cells in solid cancers as well as B cell malignancies. In this review, we will discuss recent advances about the immunobiology of NKT cells and their precise role in the immunopathogenesis and treatment of different B cell malignancies. [ABSTRACT FROM AUTHOR]

The aim of the present study is to evaluate the effects of quercetin, a dietary flavonoid, on human prostate adenocarcinoma PC-3 cells. Lactate dehydrogenase (LDH) release, microculture tetrazolium test (MTT assay) and real-time PCR array were employed to evaluate the effects of quercetin on cell cytotoxicity, cell proliferation and expression of various genes in PC-3 cell line. Quercetin inhibited cell proliferation and modulated the expression of genes involved in DNA repair, matrix degradation and tumor invasion, angiogenesis, apoptosis, cell cycle, metabolism and glycolysis. No cytotoxicity of quercetin on PC-3 cells was observed. Taken together, as shown by the issues of the current study, the manifold inhibitory effects of quercetin on PC-3 cells may introduce quercetin as an efficacious anticancer agent in order to be used in the future nutritional transcriptomic investigations and multi-target therapy to overcome the therapeutic impediments against prostate cancer. [ABSTRACT FROM AUTHOR]

In the original article the terms RORγt and GF-β were misspelled throughout the text. They should read RORγt and TGF-β instead. We apologize for the inconvenience. The original article has been corrected. [ABSTRACT FROM AUTHOR]