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Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma.

Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First-in-class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre-clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second-generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Rece

Клиническое воздействие Fingolimod-Associated Lymphopendia в многоразовом склерозе: исследование реального мирового культа.

Предыстория и цели: финолимод, a sphingosine-1-phosphate Рецепторный модулятор представляет собой эффективную, корректирующую заболевания терапию для восстановления форм множественного склероза (MS). Хотя лимфакопания является общепризнанным фармакологическим эффектом, ее клиническое значение остается неопределенным. В этом исследовании была дана оценка частотности и серьезности связанной с фенолимодом лимфопенсии, продольных гематологических изменений и их связи с клиническими результатами в реальной когорте MS. Материалы и методы: Это ретроспективное исследование 143 взрослые с РС, которые н

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… Previous studies have reported several potential predictors of severe fingolimod-associated lymphopenia, including lower baseline lymphocyte count, lower BMI and previous interferon-beta exposure [ 16 ]. …

Clinical features and prognosis analysis of patients with follicular lymphoma: a real-world study in China.

Follicular lymphoma (FL) is a common indolent B-cell lymphoma with heterogeneous clinical behavior. Prognostic data from Chinese real-world populations remain Limited. We retrospectively analyzed 118 patients with newly diagnosed FL treated at our center from January 2022 to December 2024. Clinical features, laboratory indicators, immune markers, and treatment responses were evaluated. Survival outcomes were analyzed using Kaplan-Meier and Cox regression methods. The follow-up ended on January 31, 2025, with a median follow-up duration of 11.2 months (range, 1.1-36.0 months). The 2-year overal

Воздействие витамина D на герпесвирусные инфекции.

Помимо своей классической роли в регулировании метаболизма кальция и фосфата, витамин D также оказывает значительное влияние на модуляцию иммунитета. Витамин D регулирует иммунную реакцию, переходя от воспламенительного состояния к более толерогенному one путем увеличения выброса антивоспалительных цитокинов при одновременном ослаблении регулирования проинфламаторных цитокинов. Таким образом, низкий уровень витамина D связан с повышенным риском возникновения аутоиммунных заболеваний, таких, как множественный склероз и тип 1 диабет. Кроме того, этот прохормон также способствует высвобождению хо

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer.

Ovarian cancer (OV) is highly heterogeneous tumor with a very poor prognosis. Studies increasingly show that T cell exhaustion is prognostically relevant in OV. The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis. The single RNA-sequencing (scRNA-seq) data of five OV patients were analyzed, and six major cell clusters were identified after threshold screening. Further clustering of T cell-associated clusters revealed four subtypes. Pathways related to oxidative phosphorylation, G2M checkpoint, JAK-STAT and MAPK signalin

Cytopenia after CAR-T Cell Therapy-A Brief Review of a Complex Problem.

Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has emerged as an efficacious and life extending treatment modality with high response rates and durable remissions in patients with relapsed and refractory non-Hodgkin lymphoma (NHL), follicular lymphoma, and B-cell acute lymphoblastic leukemia (B-ALL) as well as in other diseases. Prolonged or recurrent cytopenias after CAR-T therapy have increasingly been reported at varying rates, and the pathogenesis of this complication is not yet well-understood but is likely contributed to by multiple factors. Current studies reported are primarily

Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils.

Background Myeloid dysfunction is an emerging hallmark of microenvironment changes occurring in multiple myeloma (MM). Our previous work showed that FcγRI/CD64 overexpression in neutrophils of newly diagnosed MM patients is associated to inferior outcomes, reduced oxidative bursts and phagocytosis, with an increased risk of bacterial infections. Pomalidomide is a novel immune-modulatory drug approved for relapsed/refractory patients (RRMM), with drug-related neutropenia as major limitation to treatment. Patients and methods Herein, we describe a prospective analysis of 51 consecutive RRMM pati

Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated substantial efficacy against various hematological malignancies. The remarkable success of CAR-T cell therapy in targeting B-cell malignancies has generated significant interest in its potential application for treating autoimmune diseases (ADs). By engineering T cells to express CARs that specifically recognize B-cell antigens, researchers aim to selectively eliminate or modulate the dysregulated autoimmune responses underlying disease pathology. Early clinical trials targeting the B-cell marker CD19 have shown promising results,

Whole genome sequencing in adults with clinical hallmarks of hypophosphatasia negative for ALPL variants.

BackgroundHypophosphatasia (HPP) is a rare disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (ALP), encoded by the ALPL gene. The primary objective was to explore novel ALPL variants by whole genome sequencing (WGS) in patients with HPP who previously tested negative by standard methods for ALPL variants. The secondary objective was to search for genes beyond ALPL that may reduce ALP activity or contribute to HPP symptoms.Methods and resultsWGS was performed in 16 patients clinically diagnosed with HPP who had ALP activity below the normal range and tested negativ

Повсеместность коморбидной мигрени в множестве склерозов: сосуществуют ли множественный склероз и мигрень?

Множественный склероз (MS) является хроническим воспалительным заболеванием, вызывающим многофукаловое демиэлирование и повреждение аксона в центральной нервной системе. Последние исследования свидетельствуют о том, что среди пациентов, страдающих НР, наблюдается более высокий уровень заболеваемости мигренью, чем среди населения в целом. В ходе этого перекрестного исследования, проведенного в одном центре, была проведена оценка распространенности мигрени среди пациентов, проходящих курс лечения с целью изменения болезней (ДМТ). МЕТОДЫ: Всего 205 Включены пациенты с сенсорным синдромом. Все уча

Group-Based Trajectory Modeling of Platelet in Patients with Aplastic Anemia: A Study Based on the MIMIC Database.

BackgroundPlatelets are the main components supporting coagulation and hemostasis. Nevertheless, no sufficient research has been done on how variations in platelet counts during hospital stays affect aplastic anemia (AA) patients' prognoses.ObjectiveThis study proposes to evaluate the association between alterations in platelet levels and illness risk in patients with AA using group-based trajectory modeling (GBTM).MethodsGBTM was used to group AA patients based on changes in platelet levels. Cox regression models were used to evaluate the relationship between platelet levels and patients' 30-

Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to hi

Цереброспинный грипп и биомаркеры крови для нейроаксональных повреждений при многоразовом склерозе

После появления новых данных о том, что нейродегенеративные процессы в множестве склероза (MS) присутствуют на ранних стадиях, был проявлен активный научный интерес к биомаркерам нейро-аксональных повреждений в жидкостях организма пациентов, страдающих с склерозом. Недавно проведенные исследования позволили ввести новые потенциальные биомаркеры, но в то же время прояснили патогенетическое и клиническое значение хорошо известных. В настоящем документе рассматриваются имеющиеся данные о биомаркерах нейроаксональных повреждений в крови и цереброспинных жидкостях и освещается их связь с клинически

Coronary atherosclerosis and chemotherapy: From bench to bedside.

Cardiovascular disease, particularly coronary artery disease, is the leading cause of death in humans worldwide. Coronary heart disease caused by chemotherapy affects the prognosis and survival of patients with tumors. The most effective chemotherapeutic drugs for cancer include proteasome inhibitors, tyrosine kinase inhibitors, immune checkpoint inhibitors, 5-fluorouracil, and anthracyclines. Animal models and clinical trials have consistently shown that chemotherapy is closely associated with coronary events and can cause serious adverse cardiovascular events. Adverse cardiovascular events a

Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tum

Restoring the Immunity in the Tumor Microenvironment: Insights into Immunogenic Cell Death in Onco-Therapies.

Immunogenic cell death (ICD) elicited by cancer therapy reshapes the tumor immune microenvironment. A long-term adaptative immune response can be initiated by modulating cell death by therapeutic approaches. Here, the major hallmarks of ICD, endoplasmic reticulum (ER) stress, and damage-associated molecular patterns (DAMPs) are correlated with ICD inducers used in clinical practice to enhance antitumoral activity by suppressing tumor immune evasion. Approaches to monitoring the ICD triggered by antitumoral therapeutics in the tumor microenvironment (TME) and novel perspective in this immune sy

Applied information retrieval and multidisciplinary research: new mechanistic hypotheses in complex regional pain syndrome.

BackgroundCollaborative efforts of physicians and basic scientists are often necessary in the investigation of complex disorders. Difficulties can arise, however, when large amounts of information need to reviewed. Advanced information retrieval can be beneficial in combining and reviewing data obtained from the various scientific fields. In this paper, a team of investigators with varying backgrounds has applied advanced information retrieval methods, in the form of text mining and entity relationship tools, to review the current literature, with the intention to generate new insights into th

Current State of Human Gene Therapy: Approved Products and Vectors.

In the realm of gene therapy, a pivotal moment arrived with Paul Berg's groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause-the genetic level. Presently, the gene therapy landscape stands adorned with 22 approved in vivo and ex vivo products, including IMLYGIC, LUXTURNA, Zolgensma, Spinraza, Patisiran, and many more. In this comprehensive exploration, we delve into a rich ass

Эпштейн-Барр Вирус: больше чем просто инфекция.

Хотя вирус Эпштейн-Барр обычно ассоциируется с доброкачественным инфекционным мононуклеозом, он в настоящее время признается в качестве одного из основных движителей сложных иммунопатологических расстройств. Замыкаясь между литическими репликациями и стратегическими программами запоздалости, EBV перепрограммирует биологию B-клеток, чтобы избежать иммунного наблюдения и нарушить гомеостаз. Центральным элементом этого патогенеза является вирусный протеин EBNA1, который приводит к автоматическому иммунитету с помощью молекулярной имитации с принимающими антигенами, включая GlialCAM в множестве ск

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