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Mucositis and Infection in Hematology Patients.

Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care. Nevertheless, important and debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever and bloodstream infections. Exploring potential interacting mechanisms and directed therapies to counteract mucosal barrier injury is of the utmost importance if we are to continue to improve care for this increasingly growing patient population. In this perspective, I highlight recent advanc

Adult-Onset Hyperammonemia: Case Report and Review of Literature.

INTRODUCTION: Hyperammonemia is a life-threatening condition most associated with liver disease, though non-cirrhotic causes are increasingly recognized. CASE PRESENTATION: We report an 18-year-old female presenting with 1 week of progressive confusion, abdominal pain, and nausea. Initial evaluation showed normal routine laboratories but markedly elevated ammonia and respiratory alkalosis. She rapidly deteriorated, requiring intubation and intensive care. Ammonia peaked at 795 µg/dL and improved rapidly after urgent venous hemofiltration and medical therapy, with full neurological recovery by

Нейтрофилы, НЕТ и множественный склероз: мини-обзор.

Множественный склероз (MS), хроническое аутоиммунное и дегенеративное заболевание, характеризующееся активацией различных провокационных клеток, приводит к обезвоживанию и нейрональным травмам. Нейтрофилы, которые часто недооцениваются в MS, получают все большее внимание за свои важные функции у пациентов MS и экспериментальную аутоиммунную энцефаломиелитную модель (EAE). Нейтрофилы играют многообразную роль в посредничестве патогенеза аутоиммунных заболеваний, и многочисленные исследования свидетельствуют о том, что нейтрофилы могут играть решающую роль благодаря образованию нейтрофильной вне

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… Exposure to diverse stimuli ultimately results in the breakdown of the neutrophil cytoskeleton, chromatin decondensation, and histone citrullination. … These inhibitors have validated the critical enzymatic role of both human and mouse PAD4 in histone citrullination and NET formation ( 87 ). …

Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement.

Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two establis

Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may trigger severe pneumonia in coronavirus disease of 2019 (COVID-19) patients through release of damage-associated molecular patterns (DAMPs) and recruitment of neutrophils in the lungs. Activated neutrophils induce inflammation and severe alveolar injury by releasing neutrophil extracellular traps (NETs). The backbones of many DAMPs and NETs are made of extracellular, cell-free DNA decorated with highly toxic compounds such as elastase, myeloperoxidase and citrullinated histones. Dornase alfa is a FDA-approved recombin

Декодирование связи между микроорганизмами и автоиммунизацией: многоаспектный обзор данных по конкретным патогенам, которые вызывают аутоиммунные заболевания.

Происхождение и прогрессирование аутоиммунных заболеваний (АИД) являются результатом совокупного воздействия генетической восприимчивости, дефектов иммунной реакции и экологических факторов. Среди них микроорганизмы, являющиеся ключевыми экологическими факторами, широко гипотезуют для того, чтобы сыграть свою роль в инициировании АИД, однако точная причинно-следственная связь еще не доказана. Цель этого обзора заключается в глубоком изучении ключевой роли конкретных микробных инфекций в инициировании АИД путем интеграции данных, полученных с помощью three - измерения: эпидемиологические исслед

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… Studies have found that citrullinated peptides derived from EBNA-1 and EBNA-2 proteins share homologous sequences with human citrullinated peptides, which may explain the early appearance of ACPA several years before clinical RA onset [ 36 ]. … Clinical and experimental research findings P.gingivalis can express peptidylarginine deiminase (PAD), a key enzyme for protein citrullination in the body. Bacterial PAD may generate new autoantigens by citrullinating host proteins (such as human α-enolase), thereby disrupting immune tolerance. …

Neutrophil extracellular traps in homeostasis and disease.

Neutrophil extracellular traps (NETs), crucial in immune defense mechanisms, are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins. Our comprehension of NETs in pathogen clearance, immune regulation and disease pathogenesis, has grown significantly in recent years. NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation. Evidence suggests that excessive accumulation of NETs can result in vessel occlusion, tissue damage, and prolonged inflammatory responses, thereby contributing to the

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… by peptidyl arginine deiminases (PAD) is named histone citrullination, and it is noteworthy that citrullinated histones have been recognized as one of the major sources of autoantibodies in certain autoimmune diseases, such as rheumatoid arthritis (RA). 118 , 119 In addition, histones also have immunophysiological … histones, which may further fuel the autoimmune response in RA. 389 , 397 ACPAs have been reported to recognize autoantigens presented on NETs, especially the citrullinated histones. 398 – 400 Additionally, NETs have been implicated in disrupting the cartilage structure and facilitating its citrullination …

Биомаркеры по исследованиям в области клинической медицины: исследование литературы в базе данных PubMed и критическая оценка.

Биомаркер, короткая форма "биологического маркера", появилась в научной литературе в 1940-х годах. С тех пор было предложено множество различных определений, однако общеприменимое объяснение термина " биомаркер " в науке является чрезвычайно сложным. Слово "биомаркер" встречается в 1.3 million статьи в научной базе данных PubMed , которая в настоящее время включает более 39 million Ссылки на биомедицинскую литературу. Биомаркеры тесно связаны со здоровьем и болезнями человека. В настоящей статье делается попытка подойти к многогранному термину "биомаркет" и оценить его с клинической

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… The highest rankings were observed for citrullination (17.7%) and DNA methylation (17.9%). 4. … Interestingly, arginine has a low fraction value, yet its PTM by N G -methylation (to ADMA and SDMA) and N G -citrullination (to citrulline) resulted in much higher values ( Table 8 ). …

Therapeutic Potential of Antibody-Drug Conjugate-Based Therapy in Head and Neck Cancer: A Systematic Review.

BackgroundAntibody-drug conjugates (ADCs) are designed to deliver potent cytotoxic agents into tumor tissues. During the last two decades, a plethora of ADCs have been successfully developed and used for several indications, including hematologic and solid tumors. In this work, we systematically reviewed the progress in ADC development for the treatment of HNC.MethodsThis review was registered in PROSPERO database. A comprehensive search was conducted following PRISMA guidelines and using PubMed, Scopus and Web of Science database.ResultsIn total, 19 studies were included. Due to the significa

Intestinal/Multivisceral Transplantation

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Терапия сотовой связи для руматоидного артрита.

Химерическая антигенная рецепторная (CAR) клеточная терапия Т произвела революцию в лечении лейкемии, лимфомы и множественных миеломы, реанимировав на поверхности этих клеток антигены CD19 и BCMA. В последнее время появляется все больше свидетельств того, что эти клеточные методы лечения могут также быть направлены против аутоиммунных заболеваний, включая системный волчаньий эритематос, системный склероз, расстройство спектрального спектра нейромиелита, миастения гравис, идиопатический воспалительный миосит, множественный склероз и ревматоидный артрит. На сегодняшний день ten Пациенты с ревмат

Exploring neutrophil extracellular traps: mechanisms of immune regulation and future therapeutic potential.

Neutrophil extracellular traps (NETs) are complex, web-like structures consisting of DNA intertwined with antimicrobial proteins, which neutrophils release upon immune activation. These structures play a crucial role in pathogen elimination, particularly in infectious diseases. However, their involvement in various pathological conditions is multifaceted and context-dependent, while NETs contribute to host defense against infections, they can also exacerbate sterile inflammation, autoimmune disorders, and tumor progression. This review provides a comprehensive analysis of the molecular mechani

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… Concurrently, peptidylarginine deiminase 4 (PAD4) catalyzes the citrullination of nuclear histones, thereby promoting additional chromatin relaxation. … Histone citrullination Thrombomodulin and zinc chelators inhibit citrullinated histone H3, thereby attenuating immunothrombosis in sepsis and pancreatic cancer. …

Аутоиммунные реакции на белки, связанные с миелином, в качестве диагностических и прогнозирующих биомаркеров релапсирующего многократного склероза: ассоциации с герпесвирусом-6 и вирусом Эпштейн-Барр.

патогенез релапсирующего многократного склероза (RRMS) связан с аутоиммунными атаками миелиновых белков и возобновлением вируса Эпштейн-Барр (EBV) и человеческого герпесвируса 6 (HV-6). Однако связь между вирусными реактивными и аутоиммунными биомаркерами остается неясной. ЦЕЛИ: Изучение ответов иммуноглобулина (Ig)G/IgA/IgM на белки, связанные с миелином, совместно с EBV и HHV-6 репликационные маркеры в RRMS.Мы наняли 55 пациентов с RRMS и 63 здоровыми средствами контроля и провели оценку ответов IgG/IgA/IgM по семи компонентам, связанным с миелином, а также по EBV с применением ядерного анти

Unraveling the mechanisms of bone diseases: targeting dendritic cells in osteoimmunology for internal homeostasis balance.

Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types, which need to precisely mediated for effective healing post-damage. The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system. Despite the significant advancements in understanding osteoimmunology, the precise role of dendritic cells (DCs) in this field remains under investigation. As key antigen-presenting cells, DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis. Recent researches have fur

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… peptide autoantibodies—rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (CCP). 74 Studies have found that there are amounts of IL-17, as well as activated CD4 + T cells and DCs in the synovial fluid of RA. 75 , 76 Following the citrullination of amino acid residues, matrix … Citrullination controls dendritic cell transdifferentiation into osteoclasts. J. Immunol. 202 , 3143–3150 (2019). 78. Zhou, L., Li, L., Wang, Y., Gao, Q. & Geng, Y. Q. …

Chimeric antigen receptor T cell therapy for the treatment of systemic rheumatic diseases: a comprehensive review of recent literature.

Systemic rheumatoid diseases (SRDs) are autoimmune and inflammatory disorders that affect multiple organ systems, impacting patients' quality of life, and survival rates. Standard treatment requires continuous drug therapy and immunosuppression. Chimeric antigen receptor (CAR) T cell therapy has the potential to target and eliminate pathologically activated immune cells and re-establish tolerance in organs affected by dysregulated immunity, making them a promising treatment option for autoimmune diseases. In autoimmune diseases, CAR T cells have the advantage of being able to kill B cells effe

Recurrent headache as the main symptom of acquired cerebral toxoplasmosis in nonhuman immunodeficiency virus-infected subjects with no lymphadenopathy: the parasite may be responsible for the neurogenic inflammation postulated as a cause of different types of headaches.

Headache and/or migraine, a common problem in pediatrics and internal medicine, affect about 5% to 10% children and adolescents, and nearly 30% of middle-aged women. Headache is also one of the most common clinical manifestations of acquired Toxoplasma gondii infection of the central nervous system (CNS) in immunosuppressed subjects. We present 11 apparently nonhuman immunodeficiency virus-infected children aged 7 to 17 years (8 girls, 3 boys) and 1 adult woman with recurrent severe headaches in whom latent chronic CNS T. gondii infection not manifested by enlarged peripheral lymph nodes typic

Peripheral neuropathy associated with monomethyl auristatin E-based antibody-drug conjugates.

Since the successful approval of gemtuzumab ozogamicin, antibody-drug conjugates (ADCs) have emerged as a pivotal category of targeted therapies for cancer. Among these ADCs, the use of monomethyl auristatin E (MMAE) as a payload is prevalent in the development of ADC drugs, which has significantly improved overall therapeutic efficacy against various malignancies. However, increasing clinical observations have raised concerns regarding the potential nervous system toxicity associated with MMAE-based ADCs. Specifically, a higher incidence of peripheral neuropathy has been reported in ADCs inco

Paraneoplastic scleroderma: a patient with a history of breast cancer presenting with sclerodactyly and Raynaud's phenomenon.

A woman in her 70s with a past history of breast cancer in remission presented with several months of dyspnoea, skin tightness and Raynaud's phenomenon. Physical examination was significant for hypertension, hypoxaemia, sclerodactyly, diffuse crackles on auscultation and mild respiratory distress. Work-up revealed elevated serum creatinine, elevated right ventricular systolic pressure on echocardiography and nuclear bone scan findings of osseous metastatic disease. Captopril was initiated with concern for scleroderma renal crisis. The scleroderma panel was positive for RNA polymerase 11 and 15

Вакцины для аутоиммунных заболеваний: остановка трюков, восстановление сбалансированности системного обзора с качественным синтезом.

ЦЕЛЬ: критически проанализировать научные данные о вакцинах, предназначенных для профилактики аутоиммунных заболеваний, включая two - основные стратегии:1) вакцины, направленные против патогенов, связанных с спровоцирующим заболеванием, включая вирус Эпштейн-Барр (ЭБВ), энтеровирус и пиогены Стрептокококка; и2) подходы к толерогенной вакцине, ориентированные на иммунную реакцию в целях восстановления терпимости к самоантигенам. МЕТОДЫ: Мы провели тщательный систематический обзор клинических испытаний, наблюдений, метаанализа и доклинических данных. Широкий поиск был проведен в биомедицинских б

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

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… Citrullination Arginine (R) → Citrulline (Cit), e.g., H3R2Cit, H4R3Cit Writer: Peptidylarginine deiminases (PADs, e.g., PAD4); Eraser: No clear specific eraser identified yet; Reader: To be further studied Regulates chromatin structure and immune response; PAD4-mediated histone citrullination promotes … Citrullination is a special post-translational modification, where the amino acid arginine, which is one of the most common residues found on histone tails, is converted into citrulline. …