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Молекулярная динамическая симуляция диких и мутантных протеиновых субъектов бета-белка типа 8 (PSMB8): Последствия для восстановления воспаления в экспериментальном аутоиммунном энцефаломиэлите патогенез.

Множественный склероз (MS) — аутоиммунное и хроническое заболевание мозга и спинного мозга. В НР наблюдается подстрекательский прогресс, характеризующийся своими отличительными подстрекательскими знаками. Гистологические и клинические характеристики MS разделяются экспериментальным аутоиммунным энцефаломелитом (EAE). Генетические и экологические факторы способствуют развитию НР. В болезни EAE-MS уровень протеазонного компонента бета-типа 8 (PSMB8), закодированного геном PSMB8, увеличивается и регулирует подстрекательскую реакцию в этой болезни. У людей синдром Накахо-Нишимура вызван мутации в

Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immu

Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.

Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serv

7-day longitudinal proteomics of critically ill patients: a pilot study.

An adult's health, indicated by measurable parameters, is stable over time. With the exception of circadian rhythms, variability in these parameters typically does not exceed 20%. In this pilot study, we looked into the stability of proteome in intensive care unit (ICU) patients. This was a single-center, prospective, observational pilot study of blood plasma from adult ICU patients with statistically heterogeneous patterns of clinically observed parameters. Eight week-long batches from seven patients (one patient participated twice) were analyzed by means of bottom-up proteomics. The data wer

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… In order to find these associations, we performed canonical correlation analysis (CCA 30 , . In Figure S4, CA matrices for all data (Fig. S4a), for the positive trend (by CRP) group (Fig. S4b), and for the negative trend group (Fig. S4c) are given. …

The Fifth International Meeting of ISEV, ISEV2016, Rotterdam, The Netherlands, 4 - 7 May, 2016.

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The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance.

Esophageal cancer (EC) is the seventh most common cancer worldwide and the sixth leading cause of death, according to Globocan 2018. Despite efforts made for therapeutic advances, EC remains highly lethal, portending a five-year overall survival of just 15-20%. Hence, the discovery of new molecular targets that might improve therapeutic efficacy is urgently needed. Due to high proliferative rates and also the limited oxygen and nutrient diffusion in tumors, the development of hypoxic regions and consequent activation of hypoxia-inducible factors (HIFs) are a common characteristic of solid tumo

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BackgroundThis study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets.MethodsTotal RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside.

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of num

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… Li et al. used principal component analysis for feature reduction and sparse canonical correlation analysis to infer edge weights for gene pairs. A network-based pathway-extending approach using DNA methylation and gene expression data identified altered pathways [ 77 ]. …

Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes in the blood. These cells migrate to and proliferate in the bone marrow and lymphoid tissues. Despite the development of new therapies for CLL, drug resistance and disease relapse still occur; novel treatment approaches are therefore still needed. Inhibition of the angiogenesis involved in the progression of CLL might be a relevant therapeutic strategy. The literature data indicate that vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase-9 are pro-angiogen

Identification of potential biomarkers and therapeutic targets for osteoarthritis associated with arginine and proline metabolism based on transcriptome sequencing and bioinformatics.

Background and objectivesOsteoarthritis (OA) is a chronic degenerative joint disease. Approximately 300 million people worldwide suffer from OA, which shows a high incidence in middle-aged and elderly populations, with a prevalence of 50% among individuals aged over 60 years. Its core clinical symptoms consist of joint pain, swelling, and dysfunction. Studies have shown that arginine and proline metabolism play an important role in the pathogenesis and progression of OA, but the specific mechanism is still unclear. This study aimed to identify biomarkers and drug therapeutic targets for OA ass

BATF2 является регулятором интерферона β, сигнализирующего в астроцитах во время нейроинфламмации.

Астроцитический интерферон (IFN) (IFN) (информация) связан с уменьшением нейроинфламмации; однако эффекторы вниз по течению, ответственные за регулирование этой защиты, неизвестны. Здесь мы идентифицируем удельный коэффициент транскрипции IFN, основной коэффициент транскрипции лейцина АТФ-подобный АТФ2, который играет ключевую роль в модулировании последствий ITFN, сигнализирующих в астроцитах. Последовательность иммунопреобразования Хроматина показала, что НИМФ2 связывает и предотвращает перевыражение регулятивных факторов IFN (IRF)1 и IRF1, таких как caspase-1. Мы также показываем, что мыши

Use of Intravenous Iodinated Contrast Media in Patients With Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Intravenous iodinated contrast media are commonly used with CT to evaluate disease and to determine treatment response. The risk of acute kidney injury (AKI) developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated. This is due primarily to historic lack of control groups sufficient to separate contrast-induced AKI (CI-AKI; ie, AKI caused by contrast media administration) from contrast-associated AKI (CA-AKI; ie, AKI coincident to contrast media administration). Although the true risk of CI-AKI remains uncertain for pati

WT1 gene: a potential therapeutic target for multiple cancer treatment strategies.

The Wilms' Tumor 1 (WT1) gene has attracted significant attention in oncological research owing to its involvement in the pathogenesis of a variety of malignancies. Initially identified in association with Wilms' tumor, a pediatric renal carcinoma, WT1 is now recognized for its broader implications in the etiology of multiple cancers, including leukemia, ovarian cancer, and lung cancer. This review offers a comprehensive analysis of the historical development of WT1 research, explores its mechanisms in cancer progression, and assesses its potential as a therapeutic target, with an emphasis on

Selected Abstracts from the 12th Annual Meeting of the Clinical Immunology Society: 2021 Virtual Annual Meeting: Immune Deficiency and Dysregulation North American Conference.

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Targeting nuclear import and export in hematological malignancies.

The transport of proteins across the nuclear membrane is a highly regulated process, essential for the cell function. This transport is actively mediated by members of the karyopherin family, termed importins, or exportins, depending on the direction of transport. These proteins play an active part in tumorigenesis, through aberrant localization of their cargoes, which include oncogenes, tumor-suppressor genes and mediators of key signal transduction pathways. Overexpression of importins and exportins is reported in many malignancies, with implications in cell growth and viability, differentia

Genetically Modified T-Cell-Based Adoptive Immunotherapy in Hematological Malignancies.

A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs) play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (

Mucosal-Associated Invariant T Cells in Health and Disease.

Mucosal-associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate-like T lymphocytes that are restricted by major histocompatibility complex Class I-related (MR1) molecules. They can be activated either in a T-cell receptor-MR1- or cytokine-dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individual

Advances in the assessment of minimal residual disease in mantle cell lymphoma.

The clinical impact of minimal residual disease detection at early time points or during follow-ups has been shown to accurately predict relapses among patients with lymphomas, mainly in follicular and diffuse large B cell lymphoma. The field of minimal residual disease testing in mantle cell lymphoma is still evolving but has great impact in determining the prognosis. Flow cytometry and polymerase chain reaction-based testing are most commonly used methods in practice; however, these methods are not sensitive enough to detect the dynamic changes that underline lymphoma progression. Newer meth

Больше, чем сумка его частей: разорванная периферия мультиплексных сетей мозга в множестве склероза.

У людей с множественным склерозом (PwMS) были выявлены нарушения в работе сетей мозга, измеряемые с помощью структурных (MRI), диффузионных (dMRI) или функциональных (fMRI) MRI, что свидетельствует об актуальности регионов в ядре коннектома, но дает неоднозначные результаты в зависимости от изученной области подключения. Используя многослойный сетевой подход, мы интегрировали эти three Условия для отображения обогащенного представления организации мозга с ядром и исследования его изменений в PwMS. В этом ретроспективном поперечном исследовании мы выбрали PwMS и здоровый контроль с полными муль

Epoetin beta for the treatment of chemotherapy-induced anemia: an update.

Epoetin beta belongs to the class of erythropoiesis-stimulating agents (ESAs) that are currently available to treat anemic patients receiving chemotherapy. Chemotherapy-induced anemia affects a high percentage of cancer patients and, due to its negative effects on disease outcome and the patient's quality of life, should be treated when first diagnosed. Initial trials with ESAs have shown efficacy in improving quality of life and reducing the need for blood transfusions in patients with chemotherapy-induced anemia. However, recent meta-analyses have provided conflicting data on the impact of E