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Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study.

BACKGROUND AND OBJECTIVES: Cladribine tablets (CladT) represent an effective immune reconstitution therapy, administered in short treatment courses over two consecutive years. To better understand the amplitude of immune changes, we performed a comprehensive analysis during the 2-year study period for the entire MAGNIFY-MS population (N=270). In addition to lymphocyte kinetics, we studied intracellular cytokines serum proteins, and their associations with clinical outcomes. To put these changes into perspective, we analyzed transcriptional changes in T and B cells and associated biological pat

Последствия Anti-CD20 Терапия антитела на Иммунной Клеточной Динамике в релапсирующих и излучающих Множестве склерозов.

ВВЕДЕНИЕ: Эффективность anti-CD20 :: борьба с антителами в значительной степени способствовала углублению понимания нами проблемы патогенеза заболеваний и улучшению результатов лечения при повторном выбросе множественных склерозов (РРМС). Был проведен всеобъемлющий анализ периферийных иммунных клеток в сочетании с перспективной клинической характеристикой пациентов RRMS, проходящих лечение острелизумаба (OCR) или атумумаба (OFA), в целях более глубокого понимания иммунной реконституции после истощения клеток B. МЕТОДЫ: REBELLION-MS представляет собой продольный анализ пациентов RRMS, проходящи

CXCL13 как биомаркер: фон и полезность в многоразовом склерозе.

CXCL13 — хемокин, регулируемый в рамках CNS в множестве склерозов, нейроборлиозе Лайма и других подстрекательских болезнях, который все чаще используется в качестве биомаркера. Этот обзор служит основой для понимания его функций в иммунной системе и его связи с эктическими лимфоидными фолликулами. Кроме того, был рассмотрен вопрос о его полезности в случае множественного склероза и нейроборлиоза Лайма, а также потенциальные проблемы в его измерении. CXCL13 может быть исключительно полезным биомаркером для целого ряда подстрекательских заболеваний.

Extrahepatic Manifestations of Chronic HBV Infection and the Role of Antiviral Therapy.

The hepatitis B virus (HBV) infection leads to chronic hepatitis, cirrhosis, and hepatocarcinoma. However, about 20% of patients experience extrahepatic manifestations such as polyarteritis nodosa, non-rheumatoid arthritis, non-Hodgkin lymphoma, cryoglobulinemic vasculitis, and glomerulonephritis. These influence the patient's morbidity, quality of life and mortality. The treatment of an HBV infection is based on nucleotide analogues (NAs) which are safe and effective for the suppression of HBV-DNA in almost 100% of cases. A few studies have shown that NAs induce a viral response and an improv

Полиненасыщенные жирные добавки к кислоте в системе управления множественным склерозом: обзор анализа.

Полиинунасыщенные жирные кислоты (PUFA) уже давно исследованы в качестве потенциальной адъюнктурной терапии множественных склерозов из-за их иммуномодулятивных, антивоспалительных и нейрозащитных свойств. Вместе с тем имеющиеся данные по-прежнему являются разнородными и не были полностью картированы. Цель этого аналитического обзора заключалась в том, чтобы охарактеризовать данные о дополнении ПУФП, выявить тенденции в области исследований и пробелы в знаниях, а также придать контекстуальный характер результатам первичных исследований наряду с систематическими обзорами. Этот обзор был проведен

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… Current DMTs encompass several therapeutic classes with distinct mechanisms of action, including interferons, glatiramer acetate, teriflunomide, fumarates, sphingosine-1-phosphate receptor modulators such as fingolimod and siponimod, cladribine, monoclonal antibodies targeting immune cell trafficking …

Последние достижения в области мезенхимической стволовой клеточной терапии для множественных склерозов: клинические виды применения и проблемы.

Множественный склероз (MS), хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризуется воспалением, обезвоживанием и нейродегенерацией, что приводит к различным клиническим проявлениям, таким, как усталость, сенсорное расстройство и когнитивная дисфункция. Текущее фармакологическое лечение направлено прежде всего на иммунную модуляцию, но не позволяет остановить прогрессию заболеваний или полностью обратить на нет повреждения CNS. Лечение стволовыми клетками (MSC) является многообещающей альтернативой, используя иммуномудуляторы, нейрозащиту и регенеративные спосо

Ferroptosis and its emerging role in esophageal cancer.

The occurrence and development of tumors involve a series of life activities of cells, among which cell death has always been a crucial part in the research of tumor mechanisms and treatment methods. Ferroptosis is a non-apoptotic form of cell death, which is characterized by lipid peroxidation accumulation and further cell membrane rupture caused by excessive production of intracellular oxygen free radicals dependent on iron ions. Esophageal cancer is one of the common digestive tract tumors. Patients in the early stage are mainly treated with surgery, and the curative effect is awe-inspiring

Evaluating venetoclax and its potential in treatment-naïve acute myeloid leukemia.

Venetoclax (ABT-199), a BH3-mimetic and selective BCL-2 inhibitor, was recently approved by the US Food and Drug Administration (FDA) for the treatment of acute myeloid leukemia (AML) in adult patients aged 75 years or older, or otherwise unable to tolerate intensive induction chemotherapy, in combination with either hypomethylating agents or low-dose cytarabine. In this review article, we discuss venetoclax's mechanism of action, in relation to both the BCL-2 protein family in general and BH3-mimetic activity in particular. We then outline the pharmacological advances that preceded and facili

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

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therap

Virtual Screening of FDA-Approved Compounds: Exploring New Alternatives for HIV Treatment.

Human immunodeficiency virus (HIV) infection remains a significant public health challenge, particularly because of the emergence of drug-resistant strains against the drugs currently used in highly active antiretroviral therapy (HAART). The ongoing search for new molecules with therapeutic potential remains crucial. In this study, a virtual screening approach was employed to identify novel candidates with therapeutic potential for HIV. High-throughput screening (HTS) data were used to train and validate quantitative structure-activity relationship (QSAR) models, which were subsequently applie

Hypophosphatemic rickets: diagnosis and treatment.

Hypophosphatemicrickets (HR) represents a heterogeneous group of disorders characterized by renal phosphate wasting, impaired bone mineralization, and skeletal deformities. This narrative review provides an overview of phosphate homeostasis and the molecular mechanisms underlying HR, focusing on the role of Fibroblast Growth Factor 23 (FGF23) in regulating renal phosphate use and vitamin D metabolism. The clinical, biochemical, and genetic features of both FGF23-dependent and -independent forms of HR are discussed, including X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic

Эпигенетические достижения в педиатрическом многоразовом склерозе: ДНК-метилирование примечательно участие Эпштейна-Барра заражённых вирусом и принимающих иммунных сетей.

СПРАВОЧНАЯ ИНФОРМАЦИЯ И ЦЕЛИ: Педиатрический множественный склероз (PedMS) предоставляет уникальную возможность для изучения патогенеза MS с учетом короткого интервала между воздействием на окружающую среду и возникновением заболеваний. Цель этого исследования состояла в том, чтобы выявить различные метилированные регионы (ДМР), которые способствуют взаимодействию между экологическими факторами и геномными факторами на ранних этапах заболевания. В этом многоцентровом исследовании мы проанализировали периферическую ДНК крови. 175 Итальянские предметы122 Пациенты педиатрии, 53 - здоровый контрол

Alcohol Consumption and Autoimmune Diseases.

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system's regulatory mechanisms to avoid attacking the body's tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immun

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy.

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy reg

NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances.

The transcription factor nuclear factor-κB (NF-κB) plays a complicated role in multiple tumors. Mounting evidence demonstrates that NF-κB activation supports tumorigenesis and development by enhancing cell proliferation, invasion, and metastasis, preventing cell death, facilitating angiogenesis, regulating tumor immune microenvironment and metabolism, and inducing therapeutic resistance. Notably, NF-κB functions as a double-edged sword exerting positive or negative influences on cancers. In this review, we summarize and discuss recent research on the regulation of NF-κB in cancer cell deaths,

Immunomodulatory effects of exercise in cancer prevention and adjuvant therapy: a narrative review.

Successful application of cancer immunotherapy has rekindled hope in cancer patients. However, a number of patients are unresponsive to immunotherapy and related treatments. This unresponsiveness in cancer patients toward different treatment regimens can be mainly attributed to severe immune dysfunction in such patients. Several reports indicate that physical exercise can significantly lead to improved cancer patient outcomes. Since exercise gets immense response from the immune system, it can be utilized to improve immune function. Leukocytes with enhanced functions are substantially mobilize

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics.

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly a

Hallmarks of ribosomopathies.

Ribosomopathies are diseases caused by defects in ribosomal constituents or in factors with a role in ribosome assembly. Intriguingly, congenital ribosomopathies display a paradoxical transition from early symptoms due to cellular hypo-proliferation to an elevated cancer risk later in life. Another association between ribosome defects and cancer came into view after the recent discovery of somatic mutations in ribosomal proteins and rDNA copy number changes in a variety of tumor types, giving rise to somatic ribosomopathies. Despite these clear connections between ribosome defects and cancer,

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2.

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen s