Development of Enzyme Linked Immunosorbent Assay for humoral immuneresponse and infection monitoring of anthrax

ΔΕΝ ΔΙΑΤΙΘΕΤΑΙ ΠΕΡΙΛΗΨΗImmune assays were taken into consideration to diagnose and quantify metabolites such as antigen and antibody. Enzyme-Linked Immunosorbent Assays (ELISAs), which are used to detect antigens and antibodies, generated several periods of infectious and vaccination conditions. There is an extensive range of commercial infectious disease ELISA kits useful for the detection of human and animal IgG, IgA, IgM antibodies and microorganism antigens. Anthrax is one of the serious infectious diseases caused by rod-shaped, gram-positive bacteria known as Bacillus anthracis. Subunit or attenuated vaccines applied against anthrax disease increase the antibody against the Protective Antigen (PA) which has a critical role as a toxin of B. anthracis. Herein, the ELISA was developed using PA domain 4 and anthrax Lethal Factor to detect IgG antibody in serum. Besides, the level of anti-LF antibodies were determined as a complementary test to measure variance in antibody titers associated with vaccination or infection that leads to detection of anthrax in livestock. The results show that we developed high-quality ELISA kit that can be used to test immunogenicity of vaccines and infections in mice. We tried to develop the Anti- PA4 ELISA kit and conduct the validation studies to evaluate the fluctuation level of the antibody in the anthrax vaccine and distinction between disease and vaccination in mice

CD73 regulates zoledronate-induced lymphocyte infiltration in triple-negative breast cancer tumors and lung metastases

IntroductionBisphosphonates (BPs) are bone-protecting osteoclast inhibitors, typically used in the treatment of osteoporosis and skeletal complications of malignancies. When given in the adjuvant setting, these drugs may also prevent relapses and prolong overall survival in early breast cancer (EBC), specifically among postmenopausal patients. Because of these findings, adjuvant nitrogen-containing BPs (N-BPs), such as zoledronate (ZOL), are now the standard of care for high-risk EBC patients, but there are no benefit-associated biomarkers, and the efficacy remains low. BPs have been demonstrated to possess anti-tumor activities, but the mechanisms by which they provide the beneficial effects in EBC are not known. MethodsWe used stably transfected 4T1 breast cancer cells together with suppression of CD73 (sh-CD73) or control cells (sh-NT). We compared ZOL effects on tumor growth and infiltrating lymphocytes (TILs) into tumors and lung metastases using two mouse models. B cell depletion was performed using anti-CD20 antibody.ResultsSh-CD73 4T1 cells were significantly more sensitive to the growth inhibitory effects of n-BPs in vitro. However, while ZOL-induced growth inhibition was similar between the tumor groups in vivo, ZOL enhanced B and T lymphocyte infiltration into the orthotopic tumors with down-regulated CD73. A similar trend was detected in lung metastases. ZOL-induced tumor growth inhibition was found to be augmented with B cell depletion in sh-NT tumors, but not in sh-CD73 tumors. As an internal control, ZOL effects on bone were similar in mice bearing both tumor groups.DiscussionTaken together, these results indicate that ZOL modifies TILs in breast cancer, both in primary tumors and metastases. Our results further demonstrate that B cells may counteract the growth inhibitory effects of ZOL. However, all ZOL-induced TIL effects may be influenced by immunomodulatory characteristics of the tumor

ПЕТРОХИМИЧЕСКИЕ И СТРУКТУРНЫЕ ХАРАКТЕРИСТИКИ МЕДНО-ПОРФИРОВОГО ОРУДЕНЕНИЯ В РУДОПРОЯВЛЕНИИ АСТАНЕ СРЕДНЕЙ ЧАСТИ МАГМАТИЧЕСКОЙ ДУГИ УРУМИЕ-ДОХТАР (ИРАН)

Within the Urumieh-Dokhtar Magmatic Arc in the central part of Iran, the formation of which is associated with the Neotethys closure, there are many porphyry copper deposits and ore occurrences. One of them is the Astaneh porphyry copper ore deposit, located in the central part of the Saveh-Ardestan ore region southeast of Ardestan city. The purpose of this study is to investigate the petrochemical characteristics of rocks and to determine the relationship between the distribution of porphyry copper mineralization and tectonic position of faults within the study area. To achieve the goal, there were used the structural and geological data obtained in the fieldwork, as well as the results of mineralogical and geochemical analyses. The obtained results show that rocks of different composition of the Astaneh ore deposit (andesite, andesite-basalt, basalt, trachybasalt) were formed in the suprasubduction zone, and probably in the environment prior to the collision of the of continental plates. Paragenetic relationships and mineralogical analysis show that the evolution of mineralization of the Astaneh ore deposit can be divided into three stages: pre-ore, hypogene and supergene mineralization. Geochemical research based on the study of the content of the major chemical elements in the rocks of the region shows that igneous rocks belong to calc-alkaline basalts and geodynamically can be attributed to the products of magmatism of the ensial island arc. The results concluded that the main stages of the formation of a porphyry copper ore deposit in the study area attain maximum spatio-temporal similarity with the tectonomagmatic phases of the development of the Neotethys Ocean. In addition, the Southern Ardestan fault, running through the study area and intersecting the basement structures, forms wide permeable zones favorable for the formation of porphyry copper deposits therein.В пределах магматической дуги Уромие-Дохтар в центральной части Ирана, образование которой связано с закрытием Неотетиса, расположено множество медно-порфировых месторождений и рудопроявлений. Одно из них – медно-порфировое рудопроявление Астане, которое находится в центральной части рудного района Саве-Ардестан, расположенного юго-западнее г. Ардестан. Целью данного исследования является изучение петрохимических характеристик горных пород и определение взаимосвязи между распределением меднопорфирового оруденения и положением тектонических разломов в пределах изучаемой территории. Для достижения цели были использованы структурно-геологические и минералого-геохимические данные, полученные как в ходе проведения полевых работ, так и по результатам лабораторных исследований. Результаты исследования доказывают, что разнообразные по составу горные породы рудопроявления Астане (андезит, андезибазальт, базальт, трахибазальт) сформировались в надсубдукционной зоне и, вероятно, в обстановке, предшествовавшей столкновению континентальных плит. Парагенетические связи и минералогический анализ показали, что эволюция минерализации рудопроявления Астане может быть разделена на три этапа: дорудный, рудный и гипергенный. Геохимические исследования, основанные на изучении содержания главных химических элементов в породах района, определяют, что магматические породы относятся к известково-щелочным базальтам и со стороны геодинамической обстановки могут быть отнесены к продуктам магматизма континентальной островной дуги энсиалического типа. В результате изучения был сделан вывод о том, что основные этапы формирования медно-порфирового рудопроявления на исследуемой территории демонстрируют максимальное временное и пространственное сходство с тектономагматическими фазами развития океана Неотетис. Кроме того, разлом Южный Ардестан, проходящий через изучаемую территорию и секущий структуры фундамента, образует широкие проницаемые зоны, благоприятные для формирования медно-порфировых рудопроявлений

CD73 regulates zoledronate-induced lymphocyte infiltration in triple-negative breast cancer tumors and lung metastases

Introduction: Bisphosphonates (BPs) are bone-protecting osteoclast inhibitors, typically used in the treatment of osteoporosis and skeletal complications of malignancies. When given in the adjuvant setting, these drugs may also prevent relapses and prolong overall survival in early breast cancer (EBC), specifically among postmenopausal patients. Because of these findings, adjuvant nitrogen-containing BPs (N-BPs), such as zoledronate (ZOL), are now the standard of care for high-risk EBC patients, but there are no benefit-associated biomarkers, and the efficacy remains low. BPs have been demonstrated to possess anti-tumor activities, but the mechanisms by which they provide the beneficial effects in EBC are not known. Methods: We used stably transfected 4T1 breast cancer cells together with suppression of CD73 (sh-CD73) or control cells (sh-NT). We compared ZOL effects on tumor growth and infiltrating lymphocytes (TILs) into tumors and lung metastases using two mouse models. B cell depletion was performed using anti-CD20 antibody. Results: Sh-CD73 4T1 cells were significantly more sensitive to the growth inhibitory effects of n-BPs in vitro. However, while ZOL-induced growth inhibition was similar between the tumor groups in vivo, ZOL enhanced B and T lymphocyte infiltration into the orthotopic tumors with down-regulated CD73. A similar trend was detected in lung metastases. ZOL-induced tumor growth inhibition was found to be augmented with B cell depletion in sh-NT tumors, but not in sh-CD73 tumors. As an internal control, ZOL effects on bone were similar in mice bearing both tumor groups. Discussion: Taken together, these results indicate that ZOL modifies TILs in breast cancer, both in primary tumors and metastases. Our results further demonstrate that B cells may counteract the growth inhibitory effects of ZOL. However, all ZOL-induced TIL effects may be influenced by immunomodulatory characteristics of the tumor.Peer reviewe

Use of data-mining to support real-world cost analyses: An example using HER2-positive breast cancer in Iran

INTRODUCTION: Patient registries play an important role in obtaining real-world evidence of the cost-effectiveness of treatments. However, their implementation is costly and sometimes infeasible in many middle-income countries (MICs). We explored the combination of data-mining and a large claims database to estimate the direct healthcare costs of HER2-positive breast cancer (BC) treatment in Iran and the fraction of total costs from trastuzumab use.METHOD: We performed a retrospective analysis of claims data from the Iran Social Security Organization, a health insurer which covers approximately 50%(~40 million) of the Iranian population, in the period of 21/03/2011-20/03/2014. A data-mining algorithm using R software and validated using patient dossiers in the Cancer Research Center identified 1295 patients and divided them into the three main HER2-positive breast cancer stages (early, loco-regional and advanced). A payer perspective was used to calculate the absolute and relative direc

Low‐temperature growth of high resistivity GaAs by photoassisted metalorganic chemical vapor deposition

We report the photoassisted low‐temperature (LT) metalorganic chemical vapor deposition (MOCVD) of high resistivity GaAs. The undoped as‐grown GaAs exhibits a resistivity of ∼106 Ω cm, which is the highest reported for undoped material grown in the MOCVD environment. Photoassisted growth of doped and undoped device quality GaAs has been achieved at a substrate temperature of 400 °C in a modified atmospheric pressure MOCVD reactor. By using silane as a dopant gas, the LT photoassisted doped films have high levels of doping and electron mobilities comparable to those achieved by MOCVD for growth temperatures, Tg≳600 °C

Vascular adhesion protein-1 is actively involved in the development of inflammatory lesions in rat models of multiple sclerosis

Background: Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial cell molecule and primary amine oxidase that mediates leukocyte entry to sites of inflammation. However, there is limited knowledge of the inflammation-related expression of VAP-1 in the central nervous system (CNS). Therefore, we investigated the expression of VAP-1 within the CNS vasculature in two focal rat models of experimental autoimmune encephalomyelitis (EAE) mimicking multiple sclerosis (MS).Methods: EAE was induced either with Bacillus Calmette-Guerin, resulting in a delayed-type hypersensitivity-like pathogenesis (fDTH-EAE), or with myelin oligodendrocyte glycoprotein (fMOG-EAE). A subgroup of fMOG-EAE rats were treated daily with a selective VAP-1 inhibitor (LJP1586; 5 mg/kg). On 3 and 14 days after lesion activation, rat brains were assessed using magnetic resonance imaging (MRI), and ex vivo autoradiography was conducted to evaluate the binding of Gallium-68-labelled VAP-1 ligand. Histology and immunohistochemistry (OX-42, VAP-1, intercellular adhesion protein-1 [ICAM-1], P-selectin) supported the ex vivo autoradiography.Results: EAE lesions showed MRI-detectable signal changes and binding of the VAP-1-targeting radiotracer in both rat models. Some of the VAP-1 positive vessels showed morphological features typical for high endothelial-like venules at sites of inflammation. Inhibition of VAP-1 activity with small molecule inhibitor, LJP1586, decreased lymphocyte density in the acute inflammatory phase of fMOG-EAE lesions (day 3, P = 0.026 vs. untreated), but not in the remission phase (day 14, P = 0.70 vs. untreated), and had no effect on the amount of OX-42-positive cells in either phase. LJP1586 treatment reduced VAP-1 and ICAM-1 expression in the acute inflammatory phase, whereas P-selectin remained not detectable at all studied stages of the disease.Conclusions: Our results revealed that VAP-1 is expressed and functionally active in vasculature within the induced focal EAE lesions during the acute phase of inflammation and remains expressed after the acute inflammation has subsided. The study indicates that VAP-1 is actively involved in the development of inflammatory CNS lesions. During this process, the endothelial cell lesion-related vasculature seem to undergo a structural transformation from regular flat-walled endothelium to HEV-like endothelium