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Epigenetic Mechanism and Therapeutic Implications of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia attacking 1. 5-2.0% of general population worldwide. It has a significant impact on morbidity and mortality globally and its prevalence increases exponentially with age. Therapies like catheter ablation or conventional antiarrhythmic drugs have not provided effective solution to the recurrence for AF over the past decades. Over 100 genetic loci have been discovered to be associated with AF by Genome-wide association studies (GWAS) but none has led to a therapy. Recently potential involvement of epigenetics (DNA methylation, histone modific

Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease.

Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as ev

Сексуальный и клинический профиль испаноязычных лиц с проблемным участием в сексуальной деятельности в Интернете: сравнение между субклиническими и клиническими группами.

С учетом быстрого роста цифровых технологий и последствий этой клинической картины все большую озабоченность вызывает проблематическое участие в онлайновой сексуальной деятельности (ОСА). Однако по-прежнему отсутствует консенсус в отношении нозологических и диагностических критериев этого формирующегося состояния. Хотя в ряде исследований были изучены характеристики и прогнозы проблемной КССА, лишь немногие из них опирались на клинические пробы или всеобъемлющие диагностические инструменты, охватывающие все существующие диагностические предложения. В рамках этого исследовательского исследовани

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… Nevertheless, a major methodological limitation of this initial classification was that it was derived from the authors’ clinical experience and observations, without the support of any analytical approach for group identification (e.g., cluster or latent class analysis). … In particular, clustering techniques such as latent class analysis could be particularly useful for advancing classification systems through a data-driven approach. Another limitation of this study relates to the statistical approach used. …

Histone modifications across cancers: mechanisms, therapy and clinical translation.

Cancer continues to be a major cause of death across the globe, and epigenetic dysregulation, including histone modifications, has been recognized as a major hallmark of cancer development, heterogeneity, and drug resistance. This review seeks to offer an overview of histone modifications in cancer, including the more studied histone modifications such as acetylation and methylation, as well as the less explored histone modifications such as phosphorylation, ubiquitination, and glycosylation. It also examines the role of histone modifications in the dysregulation of the three categories of enz

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of

Megakaryocyte Contribution to Bone Marrow Fibrosis: many Arrows in the Quiver.

In Primary Myelofibrosis (PMF), megakaryocyte dysplasia/hyperplasia determines the release of inflammatory cytokines that, in turn, stimulate stromal cells and induce bone marrow fibrosis. The pathogenic mechanism and the cells responsible for progression to bone marrow fibrosis in PMF are not completely understood. This review article aims to provide an overview of the crucial role of megakaryocytes in myelofibrosis by discussing the role and the altered secretion of megakaryocyte-derived soluble factors, enzymes and extracellular matrices that are known to induce bone marrow fibrosis.

KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, m

Polycythemia Vera: Barriers to and Strategies for Optimal Management.

Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality of life and severe complications. Despite the increasingly in-depth knowledge of this condition, it necessitates a multifaceted management approach to mitigate symptoms and prevent thrombotic and hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection and hydroxycarbamide associated with antiplatelet therapy have a central role and are now accompanied by other drugs, such as interferon and Janus kinase inhibitors. On

The multiple roles of interferon regulatory factor family in health and disease.

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of v

Биология и болезни крыс

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Interleukin-6: obstacles to targeting a complex cytokine in critical illness.

Circulating concentrations of the pleiotropic cytokine interleukin-6 (IL-6) are known to be increased in pro-inflammatory critical care syndromes, such as sepsis and acute respiratory distress syndrome. Elevations in serum IL-6 concentrations in patients with severe COVID-19 have led to renewed interest in the cytokine as a therapeutic target. However, although the pro-inflammatory properties of IL-6 are widely known, the cytokine also has a series of important physiological and anti-inflammatory functions. An adequate understanding of the complex processes by which IL-6 signalling occurs is c

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… Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2:611–620. doi: 10.1016/S2213-2600(14)70097-9. 93. Wiedemann HP, Wheeler AP, Bernard GR, et al. … Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study. Intensive Care Med. 2018;44:1859–1869. doi: 10.1007/s00134-018-5378-3. 98. Del Valle DM, Kim-Schulze S, Huang HH, et al. …

Транскриптомное профилирование после разрушения клеток В свидетельствует о том, что в множестве склерозов происходят изменения в центральных и периферийных иммунных клетках.

Множественный склероз (MS) представляет собой сложное, генетически смешанное аутоиммунное заболевание CNS, в котором истощение клеток с антиCD20 средоточием B является весьма эффективным средством лечения ранних заболеваний. Хотя в предыдущих исследованиях изучалось воздействие истощения клеток B на отдельные поднаборы иммунных клеток с использованием методов, основанных на потоках цитометрии, терапевтическое воздействие на иммунный ландшафт пациента неизвестно. В этом исследовании мы изучали вопрос о том, как методы лечения, разрушающие клетки B, модифицируют иммунный ландшафт с использование

Inflammatory Manifestations, Therapeutic Interventions, and Cancer Risk in Psoriasis: Current Epidemiological and Mechanistic Evidence.

Psoriasis is a chronic, autoimmune skin disease driven by persistent inflammation and immune dysfunction that severely impairs quality of life and is associated with serious comorbidities, including psoriatic arthritis, cardiovascular diseases (CVDs), and depression. Emerging epidemiological evidence suggests an association between psoriasis and an increased risk of certain malignancies, such as breast cancer (BC) and non-Hodgkin's lymphoma (NHL), although the strength and consistency of these associations vary across study designs, and the underlying thrombo-inflammatory mechanisms remain inc

Keyword Index for Volume 104

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Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer.

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of t

Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL).

A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTO

Application of GPRC5D Targeting Therapy in Relapsed Refractory Multiple Myeloma.

BackgroundAs a rapidly developing therapeutic method, targeted therapy plays an important role in the treatment of multiple myeloma. In recent years, mature B cell antigen-targeting therapy has brought new hope for patients with refractory/relapsed disease. While an increasing number of patients with relapse are exposed to this type of drug, changing the therapeutic target may be an effective strategy for patients with relapse/refractory multiple myeloma.ObjectivesThe expression of G protein-coupled receptor, class C Group 5 member D (GPRC5D), on the surface of myeloma tumor cells makes it a p

Природные клетки убийцы в множестве склерозов: враги или друзья?

Множественный склероз (MS) — иммунное расстройство, связанное с центральной нервной системой (CNS), в которой происходит демиэлизация. Считается, что инициирование и прогрессирование MS в значительной степени зависят от CD4+T лимфоцитов, однако новые данные подчеркивают участие врожденной иммунной системы в реакции на болезни MS. В целом некоторые виды иммунных клеток играют определенную роль, при этом существенно важное значение имеют клетки естественного убийцы (НК). В ходе аутоиммунной болезни, как, например, MS, различные подвиды клеток естественного убийцы функционируют по-разному. У люде

Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.

The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabe

Нетипичные неблагоприятные явления в реальном мире в исследовании долгосрочной иммуномодуляции в связи с множественным склерозом и расстройством спектра нейромилита.

КОЛИЧЕСТВО: Иммунотерапии являются неотъемлемой частью борьбы с множественным склерозом (МС) и связанными с ним демиелиническими заболеваниями, однако негативные реакции на наркотики существенно сказываются на терпимости методов лечения, позволяющих регулировать заболевания (ДМТ). ЦЕЛИ: Цель настоящего исследования заключается в оценке характеристик безопасности ДМТ в рамках реальной группы населения, затронутой МЗ и связанными с ними заболеваниями, и в выявлении нетипичных неблагоприятных явлений (АЭ) и явлений исключительной тяжести. МЕТОДЫ: Был проведен ретроспективный анализ 3850 больные с