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From Nanoparticles to Cancer Nanomedicine: Old Problems with New Solutions.

Anticancer nanomedicines have been studied over 30 years, but fewer than 10 formulations have been approved for clinical therapy today. Despite abundant options of anticancer drugs, it remains challenging to have agents specifically target cancer cells while reducing collateral toxicity to healthy tissue. Nanocompartments that can be selective toward points deeply within malignant tissues are a promising concept, but the heterogeneity of tumor tissue, inefficiency of cargo loading and releasing, and low uniformity of manufacture required from preclinical to commercialization are major obstacle

Chimeric antigen receptor T-cell therapy in systemic lupus erythematosus: From B cell depletion to immune reprogramming.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which current immunosuppressive and biologic therapies often fail to achieve durable remission in refractory patients. The emergence of chimeric antigen receptor T-cell (CAR-T) therapy has introduced a fundamentally new therapeutic concept, shifting therapeutic strategies from transient immune suppression toward the possibility of durable immune reprogramming. Recent studies suggest that the benefit of CAR-T therapy extends beyond depletion of autoreactive B cells. By depleting disease-associated immune cell populations and

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… trap; Definition of remission in SLE Lupus low disease activity state NOD scid gamma (mouse model) Peripheral blood mononuclear cell SLE responder index 4 SLE responder index 6 Universal CD19-targeted CAR-T cells (CRISPR-edited allogeneic product) Universal chimeric antigen receptor T cell ( … During the early stages of SLE, apoptotic cells, neutrophil extracellular traps (NETs), and mitochondrial DNA released from platelets and erythrocytes serve as major sources of self-nucleic acids [ [6] , [7] , [8] ]. …

Nanovesicular Drug Delivery Systems for Overcoming Antibiotic Resistance.

Despite the early success of treating bacterial infections with antibiotics, resistance development has become a global problem. Treatment of organisms that have become resistant to common antibacterial agents is challenging and can cause severe and extended illness, longer hospital stays, and increased medical costs. Bacteria may develop antibiotic resistance by multiple biochemical pathways, including target-site gene mutations, decreased permeability, drug uptake or efflux mechanisms that remove the drug from the host cells, and alterations in metabolic pathways. Several strategies to overc

Иммунометаболизм в старении мозга и нейродегенерации: преодоление метаболических путей и иммунные ответные меры.

Сложный набор взаимодействий между иммунной системой и метаболизмом, известный как иммунометаболизм, стал критическим регулятором последствий заболеваний в центральной нервной системе. В ходе многочисленных исследований метаболические расстройства увязывались с ослабленной иммунной реакцией при старении мозга, нейродегенеративных расстройствах и травме мозга. В этом обзоре мы обсудим вопрос о том, как нарушения баланса иммунометаболизма мозга способствуют патофизиологии дисфункции мозга. В первой части обзора резюмируется вклад таких критических групп иммунной клетки, как микроглии, астроциты,

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… Abbreviations in figure: NET: neutrophil extracellular traps; NAD: nicotinamide adenine dinucleotide; TNFa: tumor necrosis factor-α; NF-κB: nuclear factor-κB; TLR4: toll-like receptor 4; STAT1: signal transducer and activator of transcription 1; TGFβ: transforming growth factor β. Figure 1. … Abbreviations in figure: NET: neutrophil extracellular traps; NAD: nicotinamide adenine dinucleotide; TNFa: tumor necrosis factor-α; NF-κB: nuclear factor-κB; TLR4: toll-like receptor 4; STAT1: signal transducer and activator of transcription 1; TGFβ: transforming growth factor β. …

Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.

Chimeric antigen receptor (CAR) T-cell therapy is a transformative immunotherapeutic approach, yet its application in solid tumors is hindered by the immunosuppressive tumor microenvironment (TME). The TME restricts T-cell trafficking, impairs effector functions, and promotes exhaustion through soluble factors, metabolic stress, and suppressive cell populations. Recent efforts to enhance CAR T-cell efficacy have focused on armoring strategies that 'reprogram' and 'boost' T-cell responses within the TME. These include engineered expression of dominant-negative receptors or cytokine-releasing co

Стратегия FACS-Proteomics, направленная на экстраклелектальную эмоциональную характеристику однофенотипов в биологических жидкостях: изучение роли лейкоцитных ЭМ в множественном склерозе.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Изоляция и протеомика внеклеточной везиклетки (ЭМ) от жидкостей организма сопряжены с трудностями из-за их большой неоднородности. Недавно мы продемонстрировали, что срабатывание ячеек (FACS) с флюоресцентной активацией эффективно изолирует весь ЭМ-диапазон непосредственно от нетронутых жидкостей тела, что позволяет провести всеобъемлющий протеомикальный анализ ЭМ. Здесь мы впервые описали однофенотипный ЭВ, сортируя лейкоцитные ЭВ (Leuko EVs) из периферической крови и слез здоровых добровольцев.Используя оптимизированный и запатентованный протокол пятна всего ЭМ-отсека,

Рецепт 1 в диабете и его хронические осложнения: механизмы сигнализации и новые терапевтические достижения.

Диабет моллюсков (DM) — системное метаболическое расстройство, характеризующееся хронической гипергликемией, которая может оказывать воздействие на почки, сетчатку, периферийные нервы и сердечно-сосудистую систему, что в конечном счете приводит к многочисленным хроническим осложнениям. 1 (PAR1) — G-белковый рецептор, приводимый в действие через каноническое декольте, например тромбинированный декольте и неканоническое декольте, например, декольте с помощью активированного белка C или матрицы Metalloproteinase-1. Эти режимы активации инициируют различные каналы подачи сигналов вниз по течению,

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,

Selinexor: Targeting a novel pathway in multiple myeloma.

Selinexor is an orally bioavailable selective inhibitor of nuclear export compound that inhibits exportin-1 (XPO1), a novel therapeutic target that is overexpressed in multiple myeloma (MM) and is responsible for the transport of ∼220 nuclear proteins to the cytoplasm, including tumour suppressor proteins. Inhibition of this process has demonstrated substantial antimyeloma activity in preclinical studies, both alone and in combination with established MM therapeutics. Based on a clinical trial programme encompassing multiple combination regimens, selinexor-based therapy has been approved for t

Secukinumab in the Treatment of Plaque Psoriasis in Patients with Malignancy.

Although available data are conflicting, psoriasis seems to be associated with an increased baseline risk of malignancy. In addition, some antipsoriatic systemic treatments have been associated with risk of malignancy. There is not enough data on the association of interleukin (IL)-17 and IL-23 inhibitors with malignancy rate, but there have been no cases reported so far. Secukinumab is a recombinant human monoclonal immunoglobulin G1/κ antibody that selectively targets IL-17A; it was demonstrated to be effective and safe for the treatment of moderate to severe psoriasis that may be appropriat

MicroRNAs in Aseptic Loosening of Prosthesis: Pathophysiology and Potential Therapeutic Approaches.

OBJECTIVES: Aseptic loosening (AL) is one of the leading causes of total joint arthroplasty (TJA) revision. Discovering the roles of microRNAs (miRNA/miR) in ontogenesis and osteolysis has attracted more attention to diagnosing and treating bone disorders. This review aimed to summarize miRNA biogenesis and describe the involvement of miRNAs in AL of implants. METHODS: A detailed search was carried out on scientific search engines, including Google Scholar, Web of Science, and PubMed, to find appropriate papers related to subjects. The search process was performed using the following keywords

A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer.

Cancer is the second leading cause of death in the United States and is a major public health concern worldwide. Basic, clinical and epidemiological research is leading to improved cancer detection, prevention, and outcomes. Recent technological advances have allowed unbiased and comprehensive screening of genome-wide gene expression. Small non-coding RNAs (sncRNAs) have been shown to play an important role in biological processes and could serve as a diagnostic, prognostic and therapeutic biomarker for specific diseases. Recent findings have begun to reveal and enhance our understanding of th

Renal Involvement in Mixed Cryoglobulinemic Vasculitis: Current Perspectives.

Cryoglobulinemia is a rare disorder characterized by the presence of abnormal proteins (cryoglobulins) in the blood that precipitate at low temperatures. It presents with a wide clinical spectrum, from mild symptoms to severe, life-threatening disease. In mixed cryoglobulinemia (MC), vascular damage results from immune complexes-typically monoclonal IgM with rheumatoid factor activity and polyclonal IgG (Type II), or polyclonal/oligoclonal IgM and IgG (Type III). These complexes can obstruct small blood vessels, leading to ischemia and leukocytoclastic vasculitis. Renal involvement occurs in a

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… In recent years, interest in neutrophil extracellular traps (NETs) has also focused on immune-mediated GN. NETs, released by activated neutrophils, containing granules, chromatin, histones, and autoantigens that can perpetuate inflammation. … traps (NETs), monoclonal gammopathy of renal significance (MGRS), rituximab (RTX). …

Диет модернизирует терапевтическое воздействие диметилфумарата, поддерживаемого иммунометаболическим нейтрофильным рецептором HCAR2.

Монометилфумарат (ММФ) и его пронаркодиметилфумарат (ДМП) в настоящее время являются наиболее широко используемыми агентами для лечения множественных склерозов (МС). Однако не все пациенты получают помощь от ДМФ. Мы предположили, что переменная реакция пациентов может быть связана с их питанием. В поддержку этой гипотезы мыши, подвергшиеся экспериментальному аутоиммунальному энцефаломиэлиту (EAE), являющемуся моделью MS, не пользовались лечением DMF при питании богатой лауричной кислотой диетой. В противоположность этому, мыши на нормальном питании чау (NC) и даже мыши на рационе с высоким сод

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… Indeed, diet had a marked effect on the transcriptional profile of neutrophils, and MMF inhibited neutrophil adhesion to endothelial cells and the formation of neutrophil extracellular traps (NETs) if mice were on HFb diet but less so on LA diet. … In the left panels, representative images from the HFbD group are shown. ( B ) MMF treatment significantly reduced the phorbol 12-myristate 13-acetate (PMA)-triggered release of neutrophil extracellular traps (NETs, arrows) when mice were fed HFbD but not NCD or LAD. …

The roles of inflammasomes in cancer.

Inflammation is a key characteristic of all stages of tumor development, including tumor initiation, progression, malignant transformation, invasion, and metastasis. Inflammasomes are an important component of the inflammatory response and an indispensable part of the innate immune system. Inflammasomes regulate the nature of infiltrating immune cells by signaling the secretion of different cytokines and chemokines, thus regulating the anti-tumor immunity of the body. Inflammasome expression patterns vary across different tumor types and stages, playing different roles during tumor progression

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Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis.

Although progress has been made in the treatment of cancer, particularly for the four major types of cancers affecting the lungs, colon, breast and prostate, resistance to cancer treatment often emerges upon inhibition of major signaling pathways, which leads to the activation of additional pathways as a last-resort survival mechanism by the cancer cells. This signaling plasticity provides cancer cells with a level of operational freedom, reducing treatment efficacy. Plasticity is a characteristic of cancer cells that are not only able to switch signaling pathways but also from one cellular st

Organic Nanoparticles in Progressing Cardiovascular Disease Treatment and Diagnosis.

Cardiovascular diseases (CVDs), the world's most prominent cause of mortality, continue to be challenging conditions for patients, physicians, and researchers alike. CVDs comprise a wide range of illnesses affecting the heart, blood vessels, and the blood that flows through and between them. Advances in nanomedicine, a discipline focused on improving patient outcomes through revolutionary treatments, imaging agents, and ex vivo diagnostics, have created enthusiasm for overcoming limitations in CVDs' therapeutic and diagnostic landscapes. Nanomedicine can be involved in clinical purposes for CV

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy.

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening co

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… Moreover, some studies have explored the function of neutrophil extracellular traps (NETs). … Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020;136:1169–1179. doi: 10.1182/blood.2020007008. 135. Barnes, B. J. et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J. Exp. …

Review: progression and heterogeneity of multiple sources of mesenchymal stromal cells for the treatment of rheumatoid arthritis.

Rheumatoid arthritis is often a neglected autoimmune disease characterized by inflammation and destruction of the joints leading to pain, swelling and restricted movement, particularly affecting specific population groups and severely reducing the quality of life of patients. Certain risk factors (smoking, diet, infections) contribute to the increased prevalence of the disease in patients, with targeted interventions to alleviate symptoms. Due to the complexity of current medications and the lack of a systematic approach to decision-making, Mesenchymal stromal cells therapy has become increasi