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Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of sever

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… This is in part due to their lower expression of protein tyrosine phosphatase, receptor type C (aka CD45), leukocyte common antigen and the major histocompatibility complex (MHC) ( 13 , 14 ). …

Circadian clock and cancer.

Circadian rhythms play a critical role in regulating physiological and behavioral processes, such as the sleep-wake cycle, hormone secretion, and metabolism. These rhythms are controlled by endogenous biological clocks, which are synchronized with environmental cues, primarily the light-dark cycle. Notably, disruption or reprogramming of circadian rhythms is closely associated with cancer initiation, progression, and treatment response. At the molecular level, the dysregulation of core clock genes can disturb normal cellular rhythms, leading to aberrant cell proliferation, impaired DNA repair,

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… histocompatibility complex (MHC)/transporter associated with antigen processing (TAP)/beta-2 microglobulin (B2M)] display circadian expression and functional plasticity that are regulated by both clock and metabolic stress nodes (Myc, p53, HIF, AMPK-mTOR, and NAD⁺-SIRT1), thereby modulating immune escape … Major histocompatibility complex; mTOR. Mechanistic target of rapamycin; MYC. Myelocytomatosis oncogene; NAD. Nicotinamide adenine dinucleotide; NCOR. Nuclear receptor corepressor; NFIL3. Nuclear factor interleukin 3 regulated; NF-κB. Nuclear factor kappa B; NK. Natural killer; PD-1. …

Biological and clinical basis for molecular studies of interferons.

The cytokine family of interferons (IFNs) has multiple functions, including antiviral, anti-tumor, and immunomodulatory effects and regulation of cell differentiation. The multiple functions of the IFN system are thought to be an innate defense against microbes and foreign substances. The IFN system consists first of cells that produce IFNs in response to viral infection or other foreign stimuli and second of cells that establish the antiviral state in response to IFNs. This process of innate immunity involves multiple signaling mechanisms and activation of various host genes. Viruses have evo

Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications.

The peripheral nervous system undergoes sufficient stress when affected by diabetic conditions, chemotherapeutic drugs, and personal injury. Consequently, peripheral neuropathy arises as the most common complication, leading to debilitating symptoms that significantly alter the quality and way of life. The resulting chronic pain requires a treatment approach that does not simply mask the accompanying symptoms but provides the necessary external environment and neurotrophic factors that will effectively facilitate nerve regeneration. Under normal conditions, the peripheral nervous system self-r

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… Once organized within late-endosome development, the Golgi apparatus then supplies ILVs with major histocompatibility complex (MHC) class I and II molecules, growth factor receptors, and RNAs, encompassed by multivesicular bodies (MVBs) [ 233 , 236 ]. … histocompatibility complex | VPS | Vascular protein sorting-associated protein miRNA | MicroRNA | VTA1 | Vacuolar protein sorting-associated protein MITF | Melanocyte including transcription factor | WD | Wallerian degeneration MM | Multiple myeloma | WHO | World Health Organization MRI | Magnetic resonance …

Эволюция антиCD20 Лечения множественных склерозов: оптимизация характеристик и функций антител.

Истощение клеток B с помощью целевых агентов CD20 обычно используется для лечения множественных склерозов (MS), других аутоиммунных заболеваний и некоторых гематологов. Первоначальный очевидный успех с ритуксимабом в использовании MS и нейромиелитной оптики стимулировал развитие антиCD20 моноклональной антителной (mAb) терапии oprelizumab, atumumab и ublituximab, а также антиCD19 mAb inebilizumab. Хотя каждая из них является эффективной в плане целеопределения и истощения элементов В, структурные различия превращаются в различные механизмы действий, влияющие на поддержание истощения и безопасн

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… On B cells, CD20 is physically coupled to major histocompatibility complex (MHC) class II, CD40, the B-cell receptor (BCR), and the C-terminal-Src-kinase-binding protein. …

The Role of Fc-like Receptor 3 in the Pathophysiology of Rheumatoid Arthritis.

The pathogenesis of rheumatoid arthritis involves a complex interplay of genetic predisposition, environmental factors, and autoimmune mechanisms that lead to chronic inflammation of the synovial membrane. Fc-like receptor 3 (FcRL3) is a receptor encoded by the FCRL3 gene, located on the long arm of chromosome 1 at 1q23.1. Polymorphisms in the promoter region of FCRL3, rather than elsewhere in the gene, primarily affect the level of protein expression, which is of clinical significance. Understanding the structure of FcRL3, particularly in the context of genetic variants, is therefore importan

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… In the case of other genes (i.e., those not belonging to the major histocompatibility complex) whose variations influence the risk of developing RA, particular attention should be given to polymorphisms in the FCRL3 promoter region—specifically, single-nucleotide changes in this area. …

Latest advances in extracellular vesicles: from bench to bedside.

Extracellular vesicles (EVs) are small membraned vesicles and approximately 50-150 nm in diameter. Almost all of the type of cells releases the EVs and circulates in the body fluids. EVs contain multiple functional components, such as mRNAs, microRNAs (miRNAs), DNAs, and proteins, which can be transferred to the recipient cells, resulting in phenotypic changes. Recently, EV research has focused on their potential as a drug delivery vehicle and in targeted therapy against specific molecules. Moreover, some surface proteins are specific to particular diseases, and therefore, EVs also have promis

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… Several classically used exosome markers, like major histocompatibility complex (MHC), flotillin, and Hsp70 proteins, are similarly present in all EVs, and they also identified proteins specifically enriched in small EVs, and defined a set of five protein categories displaying different relative abundance …

Математическое моделирование нейроинфламмации в нейродегенеративных заболеваниях.

Связанные с возрастом нейродегенеративные заболевания, такие, как амиотропический боковой склероз (ALS), болезнь Альцгеймера (AD) и болезнь Паркинсона (PD), вызывают все большую озабоченность в сфере общественного здравоохранения. В то время как патология этих заболеваний является сложной, хроническое центральное воспаление, или нейроинфламмация, обычно наблюдается по многим нейродегенеративным заболеваниям. Несмотря на огромные ресурсы и перспективные доклинические тесты, эффективных методов лечения заболеваний не существует. Такая неудача объясняется плохим биологическим пониманием этой реак

Преодоление препятствий: развитие клеточной терапии в области аутоиммунной борьбы с заболеваниями.

Аутоиммунные заболевания возникают в результате дисрегламента в иммунной системе, что приводит к агрессивному нападению на ткани самого организма. Патогенез этих условий является многофакторным, охватывающим сложные взаимосвязи между генетическими предрасположениями, экологическими детерминантами и гормональными колебаниями. Диапазон аутоиммунных заболеваний является широким и оказывает воздействие на множество систем органов, при этом можно привести такие примечательные примеры, как ревматуидный артрит (RA), системный волчан (SLE), множественный склероз (MS), псориаз и витилиго. Несмотря на з

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… These receptors can redirect lymphocytes to recognize and exert their effects under specific conditions, offering non-major histocompatibility complex (MHC)-restricted recognition of cell surface components. …

Advances of DNA Damage Repair-Related Drugs and Combination With Immunotherapy in Tumor Treatment.

Cancer therapy has been an important and popular area in cancer research. With medical technology developing, the appearance of various targeted drugs and immunotherapy offer more choices to cancer treatment. With the increase in drug use, people have found more and more cases in which tumors are resistant to DNA damage repair (DDR)-based drugs. Recently, the concept of combination therapy has been brought up in cancer research. It takes advantages of combining two or more therapies with different mechanisms, aiming to benefit from the synergistic effects and finally rescue patients irresponsi

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… In addition, exposure in ionizing radiation upregulates major histocompatibility complex 1 (MHC-1) expression in cancer cells so that the TAA presenting of CD8+ lymphocytes is enhanced. …

A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy.

Clinical trials of cancer immunotherapy (IO) were historically based on a drug development paradigm built for chemotherapies. The remarkable clinical activity of programmed cell death protein 1/programmed death ligand 1 blockade, chimeric antigen receptor-T cells, and T cell engagers yielded new insights into how the mechanistic underpinnings of IO are reflected in the clinic. These insights and the sheer number of novel immunotherapies currently in the pipeline have made it clear that our strategies and tools for IO drug development must adapt. Recent innovations like engineered T cells and t

Methamphetamine induces transcriptional changes in cultured HIV-infected mature monocytes that may contribute to HIV neuropathogenesis.

HIV-associated neurocognitive impairment (HIV-NCI) persists in 15-40% of people with HIV (PWH) despite effective antiretroviral therapy. HIV-NCI significantly impacts quality of life, and there is currently no effective treatment for it. The development of HIV-NCI is complex and is mediated, in part, by the entry of HIV-infected mature monocytes into the central nervous system (CNS). Once in the CNS, these cells release inflammatory mediators that lead to neuroinflammation, and subsequent neuronal damage. Infected monocytes may infect other CNS cells as well as differentiate into macrophages,

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… We found that molecules such as Major Histocompatibility Complex (MHC) class II molecules including HLA-DMA , HLA-DMB , HLA-DPA1 , HLA-DQB1 , HLA-DRA , and HLA-DRB , and toll like receptor transcripts, TLR5 , TLR7 , and TLR8 , were downregulated by meth ( Figures 3B, C ), which is consistent with predicted …

Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers.

Though early-stage colorectal cancer has a high 5 year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical

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… CAA, cancer-associated antigen; CAR, chimeric antigen receptor; MHCI, major histocompatibility complex class I; TCR, T cell receptor. Created in BioRender. 2.2.3. Natural Killer Cell Therapy Natural killer (NK) cells are an essential component of the anti-tumor response. …

Потенциальная роль TNFRSF12A в установлении связи между глиобластомой и болезнью Альцгеймера через общие пути подавления опухолей.

Гены, подавляющие опухоль, являются критическими регуляторами клеточного гомеостаза и широко изучаются в области онкологической биологии. Однако их роль в нейродегенеративных заболеваниях, особенно в болезни Альцгеймера, остается слабой. Недавние данные об обратной связи между раком и АД указывают на существование общих молекулярных механизмов. Мы провели комплексный анализ для выявления ТГС, которые могут участвовать как в AD, так и в глиобластоме (GBM), с использованием менделийской случайности, транскриптомного профилирования (булка и одноклеточная RNA-seq), вывода в отношении связи между к

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… Midkine (MK), macrophage migration inhibitory factor (MIF), chemokine (C–C motif) ligand (CCL), granulin precursor (GRN), major histocompatibility complex class I (MHC-I), and oncostatin M (OSM) exhibited a significant rise in their information flow only in GBM (Fig. 3 j, k). …

Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer.

The G protein-coupled receptor Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations o

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… Moreover, inhibition of Smo in BCC cells has been linked to increased levels of the major histocompatibility complex (MHC) Class I molecules [ 75 ], surface recognition elements that attract cytotoxic T-cells to tumours. …

Ремонт тканей в центральной нервной системе: эпигенетическое программирование регуляторных Т клеток.

Регулирующие Т клетки хорошо известны своей иммуномодуляционной ролью, но также их регенеративная функция все чаще признается в различных типах тканей, включая скелетные мышцы, легкие и центральную нервную систему (ЦНС). В CNS Tregs, как было показано, поощряют дифференциацию олигодендроцитов в прекурсорных клетках, и их взаимодействие с микроглией поддерживает стимулирующую регенеративную микроокружную среду в мозгу. Подавляющая функция Tregs в значительной степени зависит от эпигенетической сигнатуры, в частности метилации ДНК, определенной сети связанных с Treg генов, включая FOXP3, CTLA4,

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… Reciprocally, microglial major histocompatibility complex II (MHC II) expression is required to sustain local Treg numbers and function, collectively supporting tissue preservation and motor recovery ( 15 , 35 ). …

Direct immunoactivation by chemotherapeutic drugs in cancer treatment.

The immune system plays a crucial role in recognizing and eliminating pathogenic substances and malignant cells in the body. For cancer treatment, immunotherapy is becoming the standard treatment for many types of cancer and is often combined with chemotherapy. Although chemotherapeutic agents are often reported to have adverse effects, including immunosuppression, they can also play a positive role in immunotherapy by directly stimulating the immune system. This has been demonstrated in preclinical and clinical studies in the past decades. Chemotherapeutics can activate immune cells through d

Advances in nanomaterial-mediated CRISPR/Cas delivery: from lipid nanoparticles to vesicle-derived systems.

Gene and genome editing therapies are increasingly connected with nanomaterials, which protect and transport fragile nucleic acids and CRISPR/Cas systems through biological barriers safely and accurately. This review discusses how different nanocarriers, including lipid-based, polymeric, inorganic, and vesicle-derived systems, can improve delivery efficiency, cell targeting, endosomal escape, and intracellular movement for gene and genome editing. It summarizes findings from early clinical and preclinical studies, comparing several carrier types such as ionizable lipid nanoparticles, polymeric

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… This occurs through enhanced presentation of antigen fragments via major histocompatibility complexes (MHCs), the expression of juxtacrine co-stimulatory receptors, and the release of pro-inflammatory cytokines. … The figure also includes essential labels such as IFN-γ (interferon-γ), IL (interleukin), MHC (major histocompatibility complex), TCR (T-cell receptor), and TNF (tumor necrosis factor). Reprinted from Stater et al. (2021) with permission of Elsevier. Diagram illustrating immune response pathways. …

CAR-T Cell Therapy in Ovarian Cancer: Where Are We Now?

The success of chimeric antigen receptor T-cell (CAR-T) therapies in the treatment of hematologic malignancies has led to the investigation of their potential in the treatment of solid tumors, including ovarian cancer. While the immunosuppressive microenvironment of ovarian cancer has been a barrier in their implementation, several early phase clinical trials are currently evaluating CAR-T cell therapies targeting mesothelin, folate receptor a, HER2, MUC16, and B7H3. Ongoing challenges include cytokine-associated and "on-target, off-tumor" toxicities, while most common adverse events include c

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… This leads to an immune response that is independent of the major histocompatibility complex (HLA)-antigen, avoiding certain tumor escape mechanisms such as MHC-1 downregulation [ 7 , 8 ]. Once activated, T cells release cytokines such as interferon- γ, perforin, and granzyme to induce cell lysis. …

Взгляды на амбулаторное лечение би-специальных T-Cell-Worker терапий для нескольких миелом.

В последние несколько лет была разработана новая перспективная терапия под названием < < Участок Т-клеток > > (TCE), которая в настоящее время доступна во многих странах для пациентов с повторной или рефрактной множественной миеломой. Лица, занимающиеся деятельностью Т-клеток, связаны с устойчивыми показателями эффективности и беспрогрессивными льготами по выживанию у пациентов с хорошо обработанной миеломой. Однако такие осложнения, как синдром высвобождения цитокина (CRS), синдром нейротоксичности, связанный с иммунным эффектом клеток (ICANS), и инфекционные заболевания затрудняю

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… This activation is independent of the major histocompatibility complex (MHC) and from antigen-presenting cells [ 5 , 6 ]. …