Concentrations of persistent organic pollutants in women’s serum in the European arctic Russia
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01.12.2021 |
Varakina Y.
Lahmanov D.
Aksenov A.
Trofimova A.
Korobitsyna R.
Belova N.
Sobolev N.
Kotsur D.
Sorokina T.
Grjibovski A.M.
Chashchin V.
Thomassen Y.
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Toxics |
10.3390/toxics9010006 |
0 |
Ссылка
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Persistent organic pollutants (POPs) are heterogeneous carbon-based compounds that can seriously affect human health. The aim of this study was to measure serum concentrations of POPs in women residing in the Euro-Arctic Region of Russia. A total of 204 women from seven rural settlements of the Nenets Autonomous Okrug (NAO) took part in the study. We measured serum concentrations of 11 polychlorinated biphenyls (PCBs) and 17 organochlorine pesticides (OCPs) across the study sites and among Nenets and non-Nenets residents. Measurement of POPs was performed using an Agilent 7890A gas chromatograph equipped with an Agilent 7000 series MS/MS triple quadrupole system. The concentrations of all POPs were low and similar to findings from other Arctic countries. However, significant geographic differences between the settlements were observed with exceptionally high concentrations of PCBs in Varnek located on Vaygach Island. Both ΣDDT (p = 0.011) and ΣPCB (p = 0.038) concentrations were significantly lower in Nenets. Our main findings suggest that the serum concentrations of the legacy POPs in women in the Euro-Arctic Region of Russia are low and similar to those in other Arctic countries. Significant variations between settlements, and between Nenets and non-Nenets residents, were found. Arctic biomonitoring research in Russia should include studies on the associations between nutrition and concentrations of POPs.
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CAR T cells in solid tumors: challenges and opportunities
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01.12.2021 |
Marofi F.
Motavalli R.
Safonov V.A.
Thangavelu L.
Yumashev A.V.
Alexander M.
Shomali N.
Chartrand M.S.
Pathak Y.
Jarahian M.
Izadi S.
Hassanzadeh A.
Shirafkan N.
Tahmasebi S.
Khiavi F.M.
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Stem Cell Research and Therapy |
10.1186/s13287-020-02128-1 |
0 |
Ссылка
© 2021, The Author(s). Background: CARs are simulated receptors containing an extracellular single-chain variable fragment (scFv), a transmembrane domain, as well as an intracellular region of immunoreceptor tyrosine-based activation motifs (ITAMs) in association with a co-stimulatory signal. Main body: Chimeric antigen receptor (CAR) T cells are genetically engineered T cells to express a receptor for the recognition of the particular surface marker that has given rise to advances in the treatment of blood disorders. The CAR T cells obtain supra-physiological properties and conduct as “living drugs” presenting both immediate and steady effects after expression in T cells surface. But, their efficacy in solid tumor treatment has not yet been supported. The pivotal challenges in the field of solid tumor CAR T cell therapy can be summarized in three major parts: recognition, trafficking, and surviving in the tumor. On the other hand, the immunosuppressive tumor microenvironment (TME) interferes with T cell activity in terms of differentiation and exhaustion, and as a result of the combined use of CARs and checkpoint blockade, as well as the suppression of other inhibitor factors in the microenvironment, very promising results were obtained from the reduction of T cell exhaustion. Conclusion: Nowadays, identifying and defeating the mechanisms associated with CAR T cell dysfunction is crucial to establish CAR T cells that can proliferate and lyse tumor cells severely. In this review, we discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.
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CAR T cells in solid tumors: challenges and opportunities
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01.12.2021 |
Marofi F.
Motavalli R.
Safonov V.A.
Thangavelu L.
Yumashev A.V.
Alexander M.
Shomali N.
Chartrand M.S.
Pathak Y.
Jarahian M.
Izadi S.
Hassanzadeh A.
Shirafkan N.
Tahmasebi S.
Khiavi F.M.
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Stem Cell Research and Therapy |
10.1186/s13287-020-02128-1 |
0 |
Ссылка
© 2021, The Author(s). Background: CARs are simulated receptors containing an extracellular single-chain variable fragment (scFv), a transmembrane domain, as well as an intracellular region of immunoreceptor tyrosine-based activation motifs (ITAMs) in association with a co-stimulatory signal. Main body: Chimeric antigen receptor (CAR) T cells are genetically engineered T cells to express a receptor for the recognition of the particular surface marker that has given rise to advances in the treatment of blood disorders. The CAR T cells obtain supra-physiological properties and conduct as “living drugs” presenting both immediate and steady effects after expression in T cells surface. But, their efficacy in solid tumor treatment has not yet been supported. The pivotal challenges in the field of solid tumor CAR T cell therapy can be summarized in three major parts: recognition, trafficking, and surviving in the tumor. On the other hand, the immunosuppressive tumor microenvironment (TME) interferes with T cell activity in terms of differentiation and exhaustion, and as a result of the combined use of CARs and checkpoint blockade, as well as the suppression of other inhibitor factors in the microenvironment, very promising results were obtained from the reduction of T cell exhaustion. Conclusion: Nowadays, identifying and defeating the mechanisms associated with CAR T cell dysfunction is crucial to establish CAR T cells that can proliferate and lyse tumor cells severely. In this review, we discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.
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Tribbles homolog 2 (Trib2), a pseudo serine/threonine kinase in tumorigenesis and stem cell fate decisions
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01.12.2021 |
Fang Y.
Zekiy A.O.
Ghaedrahmati F.
Timoshin A.
Farzaneh M.
Anbiyaiee A.
Khoshnam S.E.
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Cell Communication and Signaling |
10.1186/s12964-021-00725-y |
0 |
Ссылка
The family of Tribbles proteins play many critical nonenzymatic roles and regulate a wide range of key signaling pathways. Tribbles homolog 2 (Trib2) is a pseudo serine/threonine kinase that functions as a scaffold or adaptor in various physiological and pathological processes. Trib2 can interact with E3 ubiquitin ligases and control protein stability of downstream effectors. This protein is induced by mitogens and enhances the propagation of several cancer cells, including myeloid leukemia, liver, lung, skin, bone, brain, and pancreatic. Thus, Trib2 can be a predictive and valuable biomarker for the diagnosis and treatment of cancer. Recent studies have illustrated that Trib2 plays a major role in cell fate determination of stem cells. Stem cells have the capacity to self-renew and differentiate into specific cell types. Stem cells are important sources for cell-based regenerative medicine and drug screening. Trib2 has been found to increase the self-renewal ability of embryonic stem cells, the reprogramming efficiency of somatic cells, and chondrogenesis. In this review, we will focus on the recent advances of Trib2 function in tumorigenesis and stem cell fate decisions. [MediaObject not available: see fulltext.]
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CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies
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01.12.2021 |
Marofi F.
Saleh M.M.
Rahman H.S.
Suksatan W.
Al-Gazally M.E.
Abdelbasset W.K.
Thangavelu L.
Yumashev A.V.
Hassanzadeh A.
Yazdanifar M.
Motavalli R.
Pathak Y.
Naimi A.
Baradaran B.
Nikoo M.
Khiavi F.M.
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Stem Cell Research and Therapy |
10.1186/s13287-021-02462-y |
0 |
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Adoptive cell therapy has received a great deal of interest in the treatment of advanced cancers that are resistant to traditional therapy. The tremendous success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of cancer, especially hematological cancers, has exposed CAR’s potential. However, the toxicity and significant limitations of CAR-T cell immunotherapy prompted research into other immune cells as potential candidates for CAR engineering. NK cells are a major component of the innate immune system, especially for tumor immunosurveillance. They have a higher propensity for immunotherapy in hematologic malignancies because they can detect and eliminate cancerous cells more effectively. In comparison to CAR-T cells, CAR-NK cells can be prepared from allogeneic donors and are safer with a lower chance of cytokine release syndrome and graft-versus-host disease, as well as being a more efficient antitumor activity with high efficiency for off-the-shelf production. Moreover, CAR-NK cells may be modified to target various antigens while also increasing their expansion and survival in vivo. Extensive preclinical research has shown that NK cells can be effectively engineered to express CARs with substantial cytotoxic activity against both hematological and solid tumors, establishing evidence for potential clinical trials of CAR-NK cells. In this review, we discuss recent advances in CAR-NK cell engineering in a variety of hematological malignancies, as well as the main challenges that influence the outcomes of CAR-NK cell-based tumor immunotherapies.
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Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients
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01.12.2021 |
Marofi F.
Rahman H.S.
Al-Obaidi Z.M.J.
Jalil A.T.
Abdelbasset W.K.
Suksatan W.
Dorofeev A.E.
Shomali N.
Chartrand M.S.
Pathak Y.
Hassanzadeh A.
Baradaran B.
Ahmadi M.
Saeedi H.
Tahmasebi S.
Jarahian M.
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Stem Cell Research and Therapy |
10.1186/s13287-021-02420-8 |
0 |
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Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.
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Expression in escherichia coli and purification of folded rDer p 20, the arginine kinase from dermatophagoides pteronyssinus: A possible biomarker for allergic asthma
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01.01.2021 |
Sarzsinszky E.
Lupinek C.
Vrtala S.
Huang H.J.
Hofer G.
Keller W.
Chen K.W.
Panaitescu C.B.
Resch-Marat Y.
Zieglmayer P.
Zieglmayer R.
Lemell P.
Horak F.
Duchêne M.
Valenta R.
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Allergy, Asthma and Immunology Research |
10.4168/AAIR.2021.13.1.154 |
0 |
Ссылка
Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology. Arginine kinase (AK) was first identified as an allergen in the Indian-meal moth and subsequently shown to occur as allergen in various invertebrates and shellfish. The cDNA coding for AK from the house dust mite (HDM) species Dermatophagoides pteronyssinus, Der p 20, has been isolated, but no recombinant Der p 20 (rDer p 20) allergen has been produced and characterized so far. We report the expression of Der p 20 as recombinant protein in Escherichia coli. rDer p 20 was purified and shown to be a monomeric, folded protein by size exclusion chromatography and circular dichroism spectroscopy, respectively. Using AK-specific antibodies, Der p 20 was found to occur mainly in HDM bodies, but not in fecal particles. Thirty percent of clinically well-characterized HDM allergic patients (n = 98) whose immunoglobulin E (IgE) reactivity profiles had been determined with an extensive panel of purified HDM allergens (Der f 1, 2; Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 18, 21, 23 and 37) showed IgE reactivity to Der p 20. IgE reactivity to Der p 20 was more frequently associated with lung symptoms. AKs were detected in several invertebrates with specific antibodies and Der p 20 showed IgE cross-reactivity with AK from shrimp (Litopenaeus vannamei). Thus, Der p 20 is a cross-reactive HDM allergen and may serve as a diagnostic marker for HDM-induced lung symptoms such as asthma.
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Expression in escherichia coli and purification of folded rDer p 20, the arginine kinase from dermatophagoides pteronyssinus: A possible biomarker for allergic asthma
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01.01.2021 |
Sarzsinszky E.
Lupinek C.
Vrtala S.
Huang H.J.
Hofer G.
Keller W.
Chen K.W.
Panaitescu C.B.
Resch-Marat Y.
Zieglmayer P.
Zieglmayer R.
Lemell P.
Horak F.
Duchêne M.
Valenta R.
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Allergy, Asthma and Immunology Research |
10.4168/AAIR.2021.13.1.154 |
0 |
Ссылка
Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology. Arginine kinase (AK) was first identified as an allergen in the Indian-meal moth and subsequently shown to occur as allergen in various invertebrates and shellfish. The cDNA coding for AK from the house dust mite (HDM) species Dermatophagoides pteronyssinus, Der p 20, has been isolated, but no recombinant Der p 20 (rDer p 20) allergen has been produced and characterized so far. We report the expression of Der p 20 as recombinant protein in Escherichia coli. rDer p 20 was purified and shown to be a monomeric, folded protein by size exclusion chromatography and circular dichroism spectroscopy, respectively. Using AK-specific antibodies, Der p 20 was found to occur mainly in HDM bodies, but not in fecal particles. Thirty percent of clinically well-characterized HDM allergic patients (n = 98) whose immunoglobulin E (IgE) reactivity profiles had been determined with an extensive panel of purified HDM allergens (Der f 1, 2; Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 18, 21, 23 and 37) showed IgE reactivity to Der p 20. IgE reactivity to Der p 20 was more frequently associated with lung symptoms. AKs were detected in several invertebrates with specific antibodies and Der p 20 showed IgE cross-reactivity with AK from shrimp (Litopenaeus vannamei). Thus, Der p 20 is a cross-reactive HDM allergen and may serve as a diagnostic marker for HDM-induced lung symptoms such as asthma.
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Rodent and fly models in behavioral neuroscience: An evaluation of methodological advances, comparative research, and future perspectives
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01.01.2021 |
Moulin T.C.
Covill L.E.
Itskov P.M.
Williams M.J.
Schiöth H.B.
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Neuroscience and Biobehavioral Reviews |
10.1016/j.neubiorev.2020.11.014 |
0 |
Ссылка
© 2020 The Authors The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.
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Rodent and fly models in behavioral neuroscience: An evaluation of methodological advances, comparative research, and future perspectives
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01.01.2021 |
Moulin T.C.
Covill L.E.
Itskov P.M.
Williams M.J.
Schiöth H.B.
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Neuroscience and Biobehavioral Reviews |
10.1016/j.neubiorev.2020.11.014 |
0 |
Ссылка
© 2020 The Authors The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.
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Quantitation of Molecular Pathway Activation Using RNA Sequencing Data
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01.01.2020 |
Borisov N.
Sorokin M.
Garazha A.
Buzdin A.
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Methods in Molecular Biology |
10.1007/978-1-0716-0138-9_15 |
1 |
Ссылка
© Springer Science+Business Media, LLC, part of Springer Nature 2020. Intracellular molecular pathways (IMPs) control all major events in the living cell. IMPs are considered hotspots in biomedical sciences and thousands of IMPs have been discovered for humans and model organisms. Knowledge of IMPs activation is essential for understanding biological functions and differences between the biological objects at the molecular level. Here we describe the Oncobox system for accurate quantitative scoring activities of up to several thousand molecular pathways based on high throughput molecular data. Although initially designed for gene expression and mainly RNA sequencing data, Oncobox is now also applicable for quantitative proteomics, microRNA and transcription factor binding sites mapping data. The Oncobox system includes modules of gene expression data harmonization, aggregation and comparison and a recursive algorithm for automatic annotation of molecular pathways. The universal rationale of Oncobox enables scoring of signaling, metabolic, cytoskeleton, immunity, DNA repair, and other pathways in a multitude of biological objects. The Oncobox system can be helpful to all those working in the fields of genetics, biochemistry, interactomics, and big data analytics in molecular biomedicine.
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Highly diversified shrew hepatitis B viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses
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20.08.2019 |
Rasche A.
Lehmann F.
König A.
Goldmann N.
Corman V.
Moreira-Soto A.
Geipel A.
van Riel D.
Vakulenko Y.
Sander A.
Niekamp H.
Kepper R.
Schlegel M.
Akoua-Koffi C.
Souza B.
Sahr F.
Olayemi A.
Schulze V.
Petraityte-Burneikiene R.
Kazaks A.
Lowjaga K.
Geyer J.
Kuiken T.
Drosten C.
Lukashev A.
Fichet-Calvet E.
Ulrich R.
Glebe D.
Drexler J.
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Proceedings of the National Academy of Sciences of the United States of America |
10.1073/pnas.1908072116 |
0 |
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© 2019 National Academy of Sciences. All rights reserved. Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs to elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic and host range. The phylogenetically divergent shrew HBVs comprise separate species termed crowned shrew HBV (CSHBV) and musk shrew HBV (MSHBV), each containing distinct genotypes. Recombination events across host orders, evolutionary reconstructions, and antigenic divergence of shrew HBVs corroborated ancient origins of mammalian HBVs dating back about 80 million years. Resurrected CSHBV replicated in human hepatoma cells, but human- and tupaia-derived primary hepatocytes were resistant to hepatitis D viruses pseudotyped with CSHBV surface proteins. Functional characterization of the shrew sodium taurocholate cotransporting polypeptide (Ntcp), CSHBV/MSHBV surface peptide binding patterns, and infection experiments revealed lack of Ntcp-mediated entry of shrew HBV. Contrastingly, HBV entry was enabled by the shrew Ntcp. Shrew HBVs universally showed mutations in their genomic preCore domains impeding hepatitis B e antigen (HBeAg) production and resembling those observed in HBeAg-negative human HBV. Deep sequencing and in situ hybridization suggest that HBeAg-negative shrew HBVs cause intense hepatotropic monoinfections and low within-host genomic heterogeneity. Geographical clustering and low MSHBV/CSHBV-specific seroprevalence suggest focal transmission and high virulence of shrew HBVs. HBeAg negativity is thus an ancient HBV infection pattern, whereas Ntcp usage for entry is not evolutionarily conserved. Shrew infection models relying on CSHBV/MSHBV revertants and human HBV will allow comparative assessments of HBeAg-mediated HBV pathogenesis, entry, and species barriers.
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Recombinant allergens for immunotherapy: State of the art
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01.08.2019 |
Zhernov Y.
Curin M.
Khaitov M.
Karaulov A.
Valenta R.
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Current Opinion in Allergy and Clinical Immunology |
10.1097/ACI.0000000000000536 |
1 |
Ссылка
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Purpose of review More than 30 years ago, the first molecular structures of allergens were elucidated and defined recombinant allergens became available. We review the state of the art regarding molecular AIT with the goal to understand why progress in this field has been slow, although there is huge potential for treatment and allergen-specific prevention. Recent findings On the basis of allergen structures, several AIT strategies have been developed and were advanced into clinical evaluation. In clinical AIT trials, promising results were obtained with recombinant and synthetic allergen derivatives inducing allergen-specific IgG antibodies, which interfered with allergen recognition by IgE whereas clinical efficacy could not yet be demonstrated for approaches targeting only allergen-specific T-cell responses. Available data suggest that molecular AIT strategies have many advantages over allergen extract-based AIT. Summary Clinical studies indicate that recombinant allergen-based AIT vaccines, which are superior to existing allergen extract-based AIT can be developed for respiratory, food and venom allergy. Allergen-specific preventive strategies based on recombinant allergen-based vaccine approaches and induction of T-cell tolerance are on the horizon and hold promise that allergy can be prevented. However, progress is limited by lack of resources needed for clinical studies, which are necessary for the development of these innovative strategies.
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Identification of surface epitopes associated with protection against highly immune-evasive VlsE-expressing Lyme disease spirochetes
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01.08.2018 |
Batool M.
Caoili S.
Dangott L.
Gerasimov E.
Ionov Y.
Piontkivska H.
Zelikovsky A.
Waghela S.
Rogovskyy A.
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Infection and Immunity |
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3 |
Ссылка
© 2018 American Society for Microbiology. The tick-borne pathogen Borrelia burgdorferi is responsible for approximately 300,000 Lyme disease (LD) cases per year in the United States. Recent increases in the number of LD cases, in addition to the spread of the tick vector and a lack of a vaccine, highlight an urgent need for designing and developing an efficacious LD vaccine. Identification of protective epitopes that could be used to develop a second-generation (subunit) vaccine is therefore imperative. Despite the antigenicity of several lipoproteins and integral outer membrane proteins (OMPs) on the B. burgdorferi surface, the spirochetes successfully evade antibodies primarily due to the VlsE-mediated antigenic variation. VlsE is thought to sterically block antibody access to protective epitopes of B. burgdorferi. However, it is highly unlikely that VlsE shields the entire surface epitome. Thus, identification of subdominant epitope targets that induce protection when they are made dominant is necessary to generate an efficacious vaccine. Toward the identification, we repeatedly immunized immunocompetent mice with live-attenuated VlsE-deleted B. burgdorferi and then challenged the animals with the VlsE-expressing (host-adapted) wild type. Passive immunization and Western blotting data suggested that the protection of 50% of repeatedly immunized animals against the highly immune-evasive B. burgdorferi was antibody mediated. Comparison of serum antibody repertoires identified in protected and nonprotected animals permitted the identification of several putative epitopes significantly associated with the protection. Most linear putative epitopes were conserved between the main pathogenic Borrelia genospecies and found within known subdominant regions of OMPs. Currently, we are performing immunization studies to test whether the identified protection-associated epitopes are protective for mice.
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Experimental evaluation of the protective efficacy of tick-borne encephalitis (TBE) vaccines based on European and Far-Eastern TBEV strains in mice and in vitro
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16.07.2018 |
Chernokhaeva L.
Rogova Y.
Kozlovskaya L.
Romanova L.
Osolodkin D.
Vorovitch M.
Karganova G.
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Frontiers in Microbiology |
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0 |
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© 2018 Chernokhaeva, Rogova, Kozlovskaya, Romanova, Osolodkin, Vorovitch and Karganova. Tick-borne encephalitis (TBE), caused by the TBE virus (TBEV), is a serious public health threat in northern Eurasia. Three subtypes of TBEV are distinguished. Inactivated vaccines are available for TBE prophylaxis, and their efficacy to prevent the disease has been demonstrated by years of implication. Nevertheless, rare TBE cases among the vaccinated have been registered. The present study aimed to evaluate the protective efficacy of 4 TBEV vaccines against naturally circulating TBEV variants. For the first time, the protection was evaluated against an extended number of phylogenetically distinct TBEV strains isolated in different years in different territories. The protective effect did not strongly depend on the infectious dose of the challenge virus or the scheme of vaccination. All vaccines induced neutralizing antibodies in protective titers against the TBEV strains used, although the vaccines varied in the spectra of induced antibodies and protective efficacy. The protective efficacy of the vaccines depended on the individual properties of the vaccine strain and the challenge virus, rather than on the subtypes. The neutralization efficiency appeared to be dependent not only on the presence of antibodies to particular epitopes and the amino acid composition of the virion surface but also on the intrinsic properties of the challenge virus E protein structure.
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New Missense Mutation His2026Arg in the Factor VIII Gene Was Revealed in Two Female Patients with Clinical Manifestation of Hemophilia A
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01.06.2018 |
Surin V.
Salomashkina V.
Pshenichnikova O.
Perina F.
Bobrova O.
Ershov V.
Budanova D.
Gadaev I.
Konyashina N.
Zozulya N.
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Russian Journal of Genetics |
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0 |
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© 2018, Pleiades Publishing, Inc. Hemophilia A is a recessive X-linked hereditary disease, so its manifestation in women is extremely rare and can be a result of an asymmetric X-chromosome inactivation or, even more rarely, of a presence of mutations in both FVIII gene alleles. We conducted a mutation screening of the FVIII gene in two female patients with clinical hemophilia A manifestation in this study. One patient had a hereditary disease; the second one was diagnosed with acquired hemophilia A as an adult. Both patients carried the same missense mutation His2026Arg. The patient with the hereditary form of the disease also had previously known microinsertion c.4379_4380 insA (p.Asn1460Lys-fs*1). We found no additional aberrations by sequencing of all functionally significant parts of the factor VIII gene of the patient with acquired hemophilia but showed clear asymmetric inactivation of X-chromosomes. Therefore, one of the possible explanations for the emergence of the hemophilic syndrome in this case can be the delayed manifestation of the FVIII gene germline mutation owing to the enhancement of hematopoiesis clonality with age.
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Human endometrial stem cells: High-yield isolation and characterization
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01.03.2018 |
Kovina M.
Krasheninnikov M.
Dyuzheva T.
Danilevsky M.
Klabukov I.
Balyasin M.
Chivilgina O.
Lyundup A.
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Cytotherapy |
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© 2018 International Society for Cellular Therapy Background: Menstrual blood is only recently and still poorly studied, but it is an abundant and noninvasive source of highly proliferative mesenchymal stromal cells (MSCs). However, no appropriate isolation method has been reported due to its high viscosity and high content of clots and desquamated epithelium. Methods: We studied three different isolation approaches and their combinations: ammonium-containing lysing buffer, distilled water and gradient-density centrifugation. We tested the proliferative capacity, morphology, surface markers and pluripotency of the resulting cells. Results: Our isolation method yields up to four million nucleated cells per milliliter of initial blood, of which about 0.2–0.3% are colony-forming cells expressing standard mesenchymal markers CD90, CD105 and CD73, but not expressing CD45, CD34, CD117, CD133 or HLA-G. The cells have high proliferative potential (doubling in 26 h) and the ability to differentiate into adipocytes and osteocytes. Early endometrial MSCs (eMSCs) express epithelial marker cytokeratin 7 (CK7). CK7 is easily induced in later passages in a prohepatic environment. We show for the first time that a satisfactory and stable yield of eMSCs is observed throughout the whole menstrual period (5 consecutive days) of a healthy woman. Discussion: The new cost/yield adequate method allows isolation from menstrual blood a relatively homogenous pool of highly proliferative MSCs, which seem to be the best candidates for internal organ therapy due to their proepithelial background (early expression of CK7 and its easy induction in later passages) and for mass cryobanking due to their high yield and availability.
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M cells are the important post in the initiation of immune response in intestine
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01.01.2018 |
Bykov A.
Karaulov A.
Tsomartova D.
Kartashkina N.
Goriachkina V.
Kuznetsov S.
Stonogina D.
Chereshneva Y.
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Russian Journal of Infection and Immunity |
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© Saint Petersburg Pasteur Institute. All rights reserved. Microfold cells (M cells) are specialized intestinal epithelial cells that initiate mucosal immune responses. These unique phagocytic epithelial cells are specialized for the transfer of a broad range of particulate antigens and microorganisms across the follicle-associated epithelium (FAE) into the gut-associated lymphoid tissue (GALT) by a process termed transcytosis. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. Active sampling of intestinal antigen initiates regulated immune responses that ensure intestinal homeostasis. The delivery of luminal substances across the intestinal epithelium to the immune system is a critical event in immune surveillance resulting in tolerance to dietary antigens and immunity to pathogens (e.g., bacteria, viruses, and parasites) and their toxins. Several specialized mechanisms transport luminal antigen across the gut epithelium. Discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery oral vaccine to M cells. Recent studies demonstrated that M cells utilize several receptors to recognize and transport specific luminal antigens. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity. How this process is regulated is largely unknown. This review aims to show a new understanding of the factors that influence the development and function of M cells; to show the molecules expressed on M cells which appear to be used as immunosurveillance receptors to sample pathogenic microorganisms in the gut; to note how certain pathogens appear to exploit M cells to inject the host; and, finally, how this knowledge is used to specifically "target" antigens to M cells to attempt to improve the efficacy of mucosal vaccines. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells.
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Some molecular mechanisms of bacteria parasitization in host cell cytosol
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01.01.2018 |
Boychenko M.
Kravtsova E.
Volchkova E.
Belaya O.
Kolaeva N.
Kanshina N.
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Infektsionnye Bolezni |
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© 2018 Dynasty Publishing House. All rights reserved. Replication of Francisella and Shigella in cytosole of host cell is correlated with their ability to escape from phagosome (containing bacteria vacuole) and to modulate innate immunity of host. Francisella T6CC and some undeterminated products of pathogenicity island's genes take part in such processes. Shigella T3CC and autotransporter protein IscA provide this processes together with spreading bacteria intra colonic epithelium.
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Role of mycoplasma infection in acute bronchial asthma in children
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01.01.2018 |
Gorina L.
Krylova N.
Goncharova S.
Rakovskaya I.
Barkhatova O.
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Infektsionnye Bolezni |
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© 2018, Dynasty Publishing House. All rights reserved. The objective. To specify the duration of persistence of antigens and DNA of Mycoplasma pneumoniae (M. pneumoniae) and Mycoplasma hominis (M. hominis) cells in the free state and as part of circulating immune complexes in blood of children suffering from bronchial asthma. Patients and methods. In the University Children’s Clinical Hospital of the Sechenov University, 161 children aged 1 to 14 years were observed. Group 1 (treatment group) included 126 children with bronchial asthma. 55 children (43.7%) had a mild course of disease, 52 children – moderate (42.1%) and 19 children (15.1%) – severe. All children were in the exacerbation period. Group 2 (control) consisted of 35 children with ARVI. The mean age of children in group 1 – 5.4 ± 1.8 years (79 boys (62.7%) and 47 girls (37.3%)); in group 2 – 5.7 ± 1.9 years (20 boys (57.1%) and 15 girls (42.9%). Diagnostic methods used: cultivation of mycoplasmas, preparation of immune serums, aggregate-haemagglutination assays (AHAA), polymerase chain reaction (PCR), direct immunofluorescence (DIF), methods of detection of circulating immune complexes (CIC). Results. AHAA examination of 126 serum samples of children from group 1 with BA, M. pneumoniae and M. hominis antigens in the free state were found in 73 and 50% of cases, respectively. In children of group 2 AHAA detected M. pneumoniae and M. hominis significantly more rarely: M. pneumoniae was found in 3 (8.6%) children (p = 95.3), M. hominis – in 2 (5.7%) children (p = 97.1). Further examination of serum samples of children with BA found M. pneumoniae and M. hominis cell DNA in 7.14 and 16.6% of cases, respectively. The work has shown that M. pneumoniae antigens are found in the composition of CIC in 55.5% of cases, M. hominis antigens – in 46.8% of cases, DNA – in 26.98 and 46.8%, respectively. For treatment of mycoplasma infection, children with BA received three azitromicin courses in the dose 10 mg/kg for 3 days with a 4-day interval. Conclusion. These data are indicative of long-term persistence of mycoplasma cell antigens and DNA in the free state and in CIC in blood of children with BA. Mycoplasmas can be regarded as one of the factors of inducing BA exacerbations in children. Tests for mycoplasma infection are indicated in patients with BA. Addition of macrolides to standard BA therapy in children with mycoplasma infection, as a rule, yields positive results.
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