Результаты поиска

Cellular Therapy for Systemic Autoimmune Diseases: New Opportunities for Future Research and Interdisciplinary Collaboration.

Systemic autoimmune diseases (sAIDs) affect 1 in 10 people and represent a leading cause of death in women under the age of 65 years. Despite the emergence of targeted-biologic therapies, mortality rates for sAIDs have not improved. Emerging cellular therapies represent a promising therapeutic strategy for patients living with sAIDs given their potential to induce sustained remission and limit long-term exposure to glucocorticoids. Encouraging outcomes from a case series of patients with systemic lupus erythematosus, idiopathic inflammatory myopathy, and systemic sclerosis (SSc) have ignited c

Совпадение в полном тексте источника
… In a mouse sclerodermatous‐like cGVHD model, chimeras receiving an allograft containing STAT3‐ablated donor CD4 + T cells did not develop classic clinical or pathologic alloimmune tissue injury manifestations, 64 emphasizing the critical role of alloreactivity in cGVHD pathogenesis. …

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

Совпадение в полном тексте источника
… Next, chimeras were removed from the data using RDP gold v9 as the reference database; the remaining sequences were clustered into OTUs. Taxonomic assignments were performed by applying the SINTAX algorithm against GTDB (r202) ( Parks et al., 2018 ). …

Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.

BackgroundRearrangements of the histone-lysine-N-methyltransferase (KMT2A), previously referred to as mixed-lineage leukemia (MLL), are among the most common chromosomal abnormalities in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), involving numerous different fusion partners. KMT2A-rearranged (KMT2A-r) leukemia is characterized by a rapid onset, aggressive progression, and significantly worse prognosis compared to non-KMT2A-r leukemias. Even with contemporary chemotherapeutic treatments and hematopoietic stem cell transplantations (HSCT), patients with KM

Совпадение в полном тексте источника
… Proteasome Inhibition Proteolysis‐targeting chimera (PROTAC) degraders have been investigated as a possible therapeutic alternative to inhibit canonical and non‐canonical oncogenic activity [ 60 ]. …

Ubiquitylomics: An Emerging Approach for Profiling Protein Ubiquitylation in Skeletal Muscle.

Skeletal muscle is a highly adaptable tissue, finely tuned by various physiological and pathological factors. Whilst the pivotal role of skeletal muscle in overall health is widely acknowledged, unravelling the underlying molecular mechanisms poses ongoing challenges. Protein ubiquitylation, a crucial post-translational modification, is involved in regulating most biological processes. This widespread impact is achieved through a diverse set of enzymes capable of generating structurally and functionally distinct ubiquitin modifications on proteins. The complexity of protein ubiquitylation has

Совпадение в полном тексте источника
… Small molecules such as proteolysis targeting chimera (PROTAC) and molecular glues have been developed to redirect E3 ligases for the degradation of non‐native substrates (known as neo‐substrates) associated with disease [ 62 ]. …

Multiple myeloma: the (r)evolution of current therapy and a glance into future.

Over the past 20 years, the regulatory approval of several novel agents to treat multiple myeloma (MM) has prolonged median patient survival from 3 to 8-10 years. Increased understanding of MM biology has translated to advances in diagnosis, prognosis, and response assessment, as well as informed the development of targeted and immune agents. Here we provide an overview of the recent progress in MM, and highlight research areas of greatest promise to further improve patient outcome in the future.

Совпадение в полном тексте источника
… Specifically, degronimids, also known as proteolysis-targeting chimeras (PROTAC), are designed by conjugating the small-molecule binder of the target protein to an E3 ubiquitin ligase binding scaffold, such as the analogs of thalidomide which bind CRBN. 51 This approach will allow for the therapeutic …

Molecular Approaches To Target GPCRs in Cancer Therapy

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… The use of membrane disrupting peptides linked to GPCR peptide agonists has been proposed in alternative to toxin-ligand chimeras. …

Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.

Hyperactivation of the RAS-RAF-MEK-ERK cascade - a mitogen-activated protein kinase pathway - has a well-known association with oncogenesis of leading tumor entities, including non-small cell lung cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, and malignant melanoma. Increasing evidence shows that genetic alterations leading to RAS-RAF-MEK-ERK pathway hyperactivation mediate contact- and soluble-dependent crosstalk between tumor, tumor microenvironment (TME) and the immune system resulting in immune escape mechanisms and establishment of a tumor-sustaining environment. Consequ

Совпадение в полном тексте источника
… Furthermore, KRAS-directed therapeutic approaches based on novel mechanisms such as vaccines, adoptive T cell therapy, proteolysis-targeting chimeras (PROTACs), and CRISPR/Cas9 technology are emerging and are being currently investigated ( 33 ). … Furthermore, pharmacological, proteasome-mediated selective degradation of RAF1 by means of proteolysis-targeting chimeras (PROTAC) could lead to another strategy in specifically targeting RAF1 ( 134 ). …

Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.

Degenerative skeletal diseases, including osteoporosis, osteoarthritis, and intervertebral disc degeneration, are prevalent age-related conditions characterized by progressive tissue degeneration and functional decline. Histone modifications are covalent modifications of histone residues, catalyzed by specific enzymes, that modulate chromatin architecture and transcriptional activity. Accumulating evidence highlights the critical involvement of histone modifications in orchestrating disease-associated transcriptional programs. In osteoporosis, histone modifications regulate osteoblast and oste

Совпадение в полном тексте источника
… Innovations in drug delivery systems The development of innovative delivery approaches, including prodrugs, nanoparticle-based delivery systems, and proteolysis targeting chimeras (PROTACs), has garnered significant attention [ 302 ]. …

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for th

Leveraging Dietary Interventions to Benefit Patients with Hematologic Malignancies and Clonal Hematopoiesis.

Diet is a modifiable factor that influences multiple pathways relevant to hematologic malignancy, including systemic inflammation, immune cell activity, gut microbiota composition, and cancer cell metabolism. Translation of preclinical findings into clinical practice for hematologic malignancies remains nascent, although momentum is building to evaluate dietary interventions as a component of supportive and disease-modifying care. This review examines the mechanistic rationale for dietary interventions across the spectrum of clonal hematologic disorders and synthesizes current clinical evidenc

Совпадение в полном тексте источника
… These findings, derived in a partial bone marrow chimera model in mice, will require validation in human cohorts before clinical inference is appropriate, but they provide a mechanistic rationale for evaluating dietary interventions in human CHIP carriers at elevated cardiovascular risk. 2.2. …

The Application of Aptamer and Research Progress in Liver Disease.

Aptamers, as a kind of small-molecule nucleic acid, have attracted much attention since their discovery. Compared with biological reagents such as antibodies, aptamers have the advantages of small molecular weight, low immunogenicity, low cost, and easy modification. At present, aptamers are mainly used in disease biomarker discovery, disease diagnosis, treatment, and targeted drug delivery vectors. In the process of screening and optimizing aptamers, it is found that there are still many problems need to be solved such as the design of the library, optimization of screening conditions, the tr

Совпадение в полном тексте источника
… Existing RNA, DNA aptamers, and siRNAs are covalently or non-covalently combined to form chimeras, and modified, such as polyethylene glycol (PEG), to prolong degradation time and improve their bioavailability in vivo [ 77 ], while its side effects are significantly lower than those of chemotherapy and …

Internalized Functional DNA Aptamers as Alternative Cancer Therapies.

Despite major advances, cancer remains one of the largest burdens of disease worldwide. One reason behind this is that killing tumor cells without affecting healthy surrounding tissue remains a largely elusive prospect, despite the widespread availability of cytotoxic chemotherapeutic agents. To meet these modern healthcare requirements, it is essential to develop precision therapeutics that minimise off-target side-effects for various cancer types. To this end, highly specific molecular targeting agents against cancer are of great interest. These agents may work by targeting intracellular sig

Совпадение в полном тексте источника
… Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat. Biotechnol. 27 (9), 839–849. 10.1038/nbt.1560 Deng B., Lin Y., Wang C., Li F., Wang Z., Zhang H., et al. (2014). Aptamer binding assays for proteins: the thrombin example–a review. Anal. …

Does the B7-H3 Immune Checkpoint Have High Potential as a Therapeutic Target?

B7-H3 (CD276), a member of the B7 family of proteins, is known to play a key role in the progression of a number of cancers. This protein is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. Various investigations, including a number of clinical trials, have reported high levels of expression of this protein in cancerous tissues compared to their healthy counterparts. This difference in expression attracted various research efforts to establish whether such a difference can be linked to the therapeutic potential of this molecule. It is worth noting t

Совпадение в полном тексте источника
… N-deglycosylation targeting chimera (DGlyTAC): A strategy for immune checkpoint proteins inactivation by specifically removing N-glycan. Signal Transduct. Target. Ther. 2025;10:139. doi: 10.1038/s41392-025-02219-6. 47. Lee H.-H., Wang Y.-N., Xia W., Chen C.-H., Rau K.-M., Ye L., Wei Y., Chou C. …

Ферроптоз в множестве миеломы: молекулярные механизмы и терапевтические возможности.

Множественная миелома (ММ) — гематологическая порча, вызванная распространением клональных плазменных клеток, и остается в значительной степени неизлечимой из-за рецидива заболеваний и приобретенной лекарственной устойчивости. Ферроптоз, основанная на железной зависимости форма регулируемой клеточной смертности, характеризующейся чрезмерным липидным пероксидацией, стала потенциальной терапевтической целью в раке и все чаще причастна к биологии MM. В отличие от апоптоза и других классических путей смерти клеток, ферроптоз тесно связан с дисрегулируемым метаболизмом железа, окислительным стрессо

Совпадение в полном тексте источника
… Early studies have also explored GPX4-targeting proteolysis-targeting chimeras (PROTACs), which promote GPX4 degradation rather than merely inhibiting its enzymatic activity ( 76 ). …

Stem cell revolution: bridging the gap between research and clinical application.

Stem cells are characterized by their capacity for self-renewal and their potential for multi-directional differentiation, enabling them to develop into various functional tissues and organs under specific conditions. Their applications hold considerable promise, and the market for stem cell products is progressively expanding. Internationally, several stem cell products have received approval for market release; however, in China, the field remains largely undeveloped, presenting substantial opportunities for growth. Recent years have witnessed significant advancements in stem cell research,

Совпадение в полном тексте источника
… Embryonic chimeras with human pluripotent stem cells. Methods Mol Biol. 2019;2005:125–51. 104. Gong Z, Shu Z, Zhou Y, Chen Y, Zhu H. KLF2 regulates stemness of human mesenchymal stem cells by targeting FGFR3. Biotech Histochem. 2023;98:447–55. 105. …

Стратегии защиты от нейропии в множестве склерозов: обновление статуса и формирующиеся парадигмы.

ВВЕДЕНИЕ: MS представляет собой континуум заболеваний, в котором с момента начала и с течением времени происходит злокачественное воспаление и нейродегенерация. Недавний прогресс в недостатке патобиологии MS создает новые перспективы для новых терапевтических стратегий нейрозащиты. ОБЛАСТЬ ПРИМЕНЕНИЯ: Авторы кратко рассматривают механизмы, лежащие в основе воспаления и нейродегенерации в MS, и обсуждают нынешние и формирующиеся стратегии поощрения нейрозащиты в MS. Данные были получены в значительной степени на основе обширного обзора опубликованной литературы, имеющейся на PubMed (до 5 марта

Совпадение в полном тексте источника
… PROTAC (proteolysis-targeting chimera) is a molecule that acts by mediated targeted protein degradation [ 176 ]. Its use in neurology is limited by its low CNS penetration and by the fact that BSN is not accessible in its presynaptic state. …

Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy.

Lymphocyte collection by apheresis for CAR-T production usually does not include blood mobilized using granulocyte colony stimulating factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinics, makes it necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent works

Совпадение в полном тексте источника
… With the increased use of unrelated donors for hematopoietic cell transplantation, there is renewed interest in the use of large volumes of frozen mobilized apheresis products that could represent a source for DLI as a complementary treatment to prevent or treat the appearance of mixed chimeras. …

Targeting the E2F1/Rb/HDAC1 axis with the small molecule HR488B effectively inhibits colorectal cancer growth.

Colorectal cancer (CRC), the third most common cancer worldwide, remains highly lethal as the disease only becomes symptomatic at an advanced stage. Growing evidence suggests that histone deacetylases (HDACs), a group of epigenetic enzymes overexpressed in precancerous lesions of CRC, may represent promising molecular targets for CRC treatment. Histone deacetylase inhibitors (HDACis) have gradually become powerful anti-cancer agents targeting epigenetic modulation and have been widely used in the clinical treatment of hematologic malignancies, while only few studies on the benefit of HDACis in

Совпадение в полном тексте источника
… The binding interaction of the protein-ligands complex has been observed by using UCSF Chimera 1.16 and BIOVIA Discovery Studio Visualizer v21.1.0.20298 (BIOVIA). The lowest energy conformation was selected for molecular dynamics (MD) simulation analysis. …

Recent Progress in CDK4/6 Inhibitors and PROTACs.

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based

Совпадение в полном тексте источника
… Bridged Proteolysis Targeting Chimera (PROTAC) Enables Degradation of Undruggable Targets J. Am. Chem. Soc. 2022 144 22622 22632 10.1021/jacs.2c09255 36448571 PMC9772293 109. Li Z. Ma S. Zhang L. Zhang S. Ma Z. Du L. Li M. Targeted Protein Degradation Induced by HEMTACs Based on HSP90 J. Med. …

Engineering Next-Generation CAR-T Cells for Better Toxicity Management.

Immunoadoptive therapy with genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) has revolutionized the treatment of patients with hematologic cancers. Although clinical outcomes in B-cell malignancies are impressive, researchers are seeking to enhance the activity, persistence, and also safety of CAR-T cell therapy-notably with a view to mitigating potentially serious or even life-threatening adverse events like on-target/off-tumor toxicity and (in particular) cytokine release syndrome. A variety of safety strategies have been developed by replacing or adding variou

Совпадение в полном тексте источника
… This chimera contained the T-cell receptor (TCR)’s constant domains and the antibody’s variable domain, thus combining the latter’s high specificity and affinity with the T lymphocytes’ functional capacities (i.e., homing, tissue penetration, and cytotoxicity). …