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Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment.

Cancer progression and metastasis due to tumor immune evasion and drug resistance is strongly associated with immune suppressive cellular responses, particularly in the case of metastatic tumors. The myeloid cell component plays a key role within the tumor microenvironment (TME) and disrupts both adaptive and innate immune cell responses leading to loss of tumor control. Therefore, strategies to eliminate or modulate the myeloid cell compartment of the TME are increasingly attractive to non-specifically increase anti-tumoral immunity and enhance existing immunotherapies. This review covers cur

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… In addition to suppressing T cells, both PMN-MDSC and N2 TANs produce neutrophil extracellular traps (NETs). …

Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential.

Telomeres are the ends of linear chromosomes comprised of repetitive nucleotide sequences in humans. Telomeres preserve chromosomal stability and genomic integrity. Telomere length shortens with every cell division in somatic cells, eventually resulting in replicative senescence once telomere length becomes critically short. Telomere shortening can be overcome by telomerase enzyme activity that is undetectable in somatic cells, while being active in germline cells, stem cells, and immune cells. Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects t

Gene and Cell Therapy for Sarcomas: A Review.

Background: The heterogeneity of sarcomas and resulting distinct sub-type specific characteristics, their high recurrence rates, and tendency for distant metastasis, continue to present significant challenges to providing optimal treatments. Objective: To provide a comprehensive review of current literature and clinical trials in gene and cell therapies for sarcomas. Methods: A comprehensive literature search was conducted utilizing the following databases: PubMed, Medline, Google Scholar and clinicaltrials.gov. Search terms included "gene therapy", "cell therapy", "NK cell therapy, "CAR-T the

Myeloma Bone Disease: The Osteoblast in the Spotlight.

Lytic bone disease remains a life-altering complication of multiple myeloma, with up to 90% of sufferers experiencing skeletal events at some point in their cancer journey. This tumour-induced bone disease is driven by an upregulation of bone resorption (via increased osteoclast (OC) activity) and a downregulation of bone formation (via reduced osteoblast (OB) activity), leading to phenotypic osteolysis. Treatments are limited, and currently exclusively target OCs. Despite existing bone targeting therapies, patients successfully achieving remission from their cancer can still be left with chro

Tumor microenvironment signaling and therapeutics in cancer progression.

Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss t

Уточнение роли селинксора в множестве миеломы: стратегическое использование в изменяющемся ландшафте обработки.

Площадь лечения множественной миеломы (ММ) революционизировалась в прошлом two десятилетиями, приводящими к беспрецедентным глубоким и долговременным ответным мерам, продолжительному выживанию и улучшению качества жизни. Тем не менее ММ по-прежнему является неизлечимым заболеванием, и многие пациенты, особенно больные цитогенетическими заболеваниями высокого риска, почечными расстройствами или ранней резистентностью к лекарственным препаратам, по-прежнему сталкиваются с плохими последствиями. Селинксор, первый в классе, в устной форме биодоступный селективный ингибитор экспорта 1 (XPO1) продем

Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase

Nanohydroxyapatite (nHAp) Doped with Iron Oxide Nanoparticles (IO), miR-21 and miR-124 Under Magnetic Field Conditions Modulates Osteoblast Viability, Reduces Inflammation and Inhibits the Growth of Osteoclast - A Novel Concept for Osteoporosis Treatment: Part 1.

PURPOSE: Osteoporosis results in a severe decrease in the life quality of many people worldwide. The latest data shows that the number of osteoporotic fractures is becoming an increasing international health service problem. Therefore, a new kind of controllable treatment methods for osteoporotic fractures is extensively desired. For that reason, we have manufactured and evaluated nanohydroxyapatite (nHAp)-based composite co-doped with iron oxide (IO) nanoparticles. The biomaterial was used as a matrix for the controlled delivery of miR-21-5p and miR-124-3p, which have a proven impact on bone

Immune monitoring, immune phenotyping, and precision intervention in severe pneumonia: current evidence and translational challenges

Severe pneumonia remains a major cause of mortality in critically ill patients, with severe community-acquired pneumonia representing a clinically important and representative scenario. This review focuses primarily on severe community-acquired pneumonia as the clinical context, in which outcomes are determined by the interplay between pathogen burden and heterogeneity of host responses. Beyond pathogen-directed therapies, severe pneumonia is frequently characterized by dynamic and partially overlapping states of hyperinflammation, immune dysfunction, and subsequent immunosuppression. Differen

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… Zhang et al. ( 13 ) further observed a significant increase in neutrophil extracellular traps (NETs) in critically ill patients, which sustain inflammatory amplification through the formation of positive feedback loops. … IL-6, Interleukin 6; CXCL10, C-X-C motif chemokine ligand 10; NETs, neutrophil extracellular traps; mHLA-DR, monocyte human leukocyte antigen-DR. …

Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health burden, including both acute infections and persistent post-acute sequelae, also known as Long COVID (LC) in survivors. While clinical management has reduced case-fatality rates, a substantial proportion of patients develop LC, a heterogeneous syndrome with long-term symptoms. This complex continuum requires therapeutic strategies for both the acute and chronic phases. Plasma proteomics has emerged as a powerful tool in precision medicin

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Терапевтическое применение иммунобиологии в аутоиммунных и воспаленных заболеваниях.

Иммунобиологика или биологическая экспертиза революционизировали терапевтическую парадигму аутоиммунных и подстрекательских заболеваний путем выборочного целеопределения и модуляции дисрегулированных иммунных путей. По сравнению с обычными широкоспектральными иммунопрепрессантами биологика обеспечивает более конкретный и основанный на механизмах рациональный подход, зачастую связанный с повышением эффективности и сокращением неблагоприятных явлений. В этом обзоре содержится всеобъемлющий обзор репертуара терапевтической биологики, механизмов их действий, важнейших клинических испытаний и клини

Acquired platelet disorders.

Platelets are essential to primary hemostasis, and defects in their number or function can lead to clinically significant bleeding or thrombosis. Acquired platelet disorders are far more common than the inherited forms and arise in a wide range of settings, including drug exposure, autoimmune, systemic, and critical illnesses. This review examines current understanding of the mechanisms driving acquired platelet dysfunction and outlines the diagnostic and therapeutic approaches that are shaping contemporary standards of care. Drug-related and immune-mediated platelet defects remain the most re

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… This is evident by increased expression of the surface P-selectin, formation of platelet–neutrophil complexes that promote neutrophil extracellular traps and amplify inflammation ( 17 , 18 ), and increased platelet aggregation with thrombin, when blood samples are taken beyond 20 min of alcohol ingestion … It also induces the release of neutrophil extracellular traps (NETs) and upregulates monocyte tissue factor expression, linking immune activation to thrombus formation. More elaboration on the interplay between inflammation and thrombosis is discussed by Iba and Levy ( 91 ). …

Next Generation Therapeutics for the Treatment of Myelofibrosis.

Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, bone marrow fibrosis, and a propensity towards transformation to acute leukemia. JAK inhibitors are the only approved therapy for myelofibrosis and have been successful in reducing spleen and symptom burden. However, they do not significantly impact disease progression and many patients are ineligible due to coexisting cytopenias. Patients who are refractory to JAK inhibition also have a dismal survival. Therefore, non-JAK inhibitor-based therapies are being explored in pre-clinical and clini

Developments in Point-of-Care Diagnostic Technology for Cancer Detection.

Cancer is the cause of death for one in seven individuals worldwide. It is widely acknowledged that screening and early diagnosis are of vital importance for improving the likelihood of recovery. However, given the costly, time-consuming, and invasive nature of the many methods currently in use, patients often do not take advantage of the services available to them. Consequently, many researchers are exploring the possibility of developing fast, reliable, and non-invasive diagnostic tools that can be used directly or by local physicians at the point-of-care. Herein, we look at the use of estab

Targeting fibrosis, mechanisms and cilinical trials.

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosi

Взаимодействие между нейтрофилами и элементами барьера крови и мозга в контексте множественного склероза и ишемического разрушения.

Барьер мозга крови (BBB) представляет собой полупроницаемую мембрану в физиологических условиях, но в патологии, такой, как множественный склероз (MS) и ишемический инсульт (IS), его проницаемость возрастает. В этом обзоре основное внимание уделяется нейтрофильам и их взаимодействию с клеточными компонентами ББД: эндотелиальными клетками (ЭК), перицитами (ПХ) и астроцитами (АК). В настоящее время нейтрофилы получают больше внимания, главным образом благодаря передовым методам исследований, которые показывают сложность их населения. Кроме того, нейтрофилы способны засекать внеклеточные везикли

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… In order to eliminate pathogens, neutrophils use phagocytosis, degranulate the contents of their granules, and produce neutrophil extracellular traps (NETs) [ 30 , 58 ]. Until recently, this function was considered the only goal of neutrophils. …

Identification of Common Differentially Expressed Genes and Potential Therapeutic Targets in Ulcerative Colitis and Rheumatoid Arthritis.

Ulcerative colitis (UC) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases (IMIDs) with similar symptoms and common genomics. However, the relationship between UC and RA has not been investigated thoroughly. Therefore, this study aimed to establish the differentially expressed genes (DEGs) and potential therapeutic targets in UC and RA. Three microarray datasets (GSE38713, GSE1919, and GSE12251) were selected from the Gene Expression Omnibus (GEO) database for analysis. We used R software to identify the DEGs and performed enrichment analyses. Search Tool for the Retrieval

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… Endocytosis of soluble immune complexes leads to their clearance by FcgammaRIIIB but induces neutrophil extracellular traps via FcgammaRIIA in vivo. Blood 120 4421–4431. 10.1182/blood-2011-12-401133 Chin C. H., Chen S. H., Wu H. H., Ho C. W., Ko M. T., Lin C. …

Interferon-Based Biopharmaceuticals: Overview on the Production, Purification, and Formulation.

The advent of biopharmaceuticals in modern medicine brought enormous benefits to the treatment of numerous human diseases and improved the well-being of many people worldwide. First introduced in the market in the early 1980s, the number of approved biopharmaceutical products has been steadily increasing, with therapeutic proteins, antibodies, and their derivatives accounting for most of the generated revenues. The success of pharmaceutical biotechnology is closely linked with remarkable developments in DNA recombinant technology, which has enabled the production of proteins with high specific

Cold atmospheric plasma sensitizes head and neck cancer to chemotherapy and immune checkpoint blockade therapy.

Head and neck cancer (HNC) is the seventh most prevalent cancer globally, often characterized by chemo-resistance and immunosuppression, which significantly hampers treatment efficacy. Cold atmospheric plasma (CAP) has recently emerged as a promising adjuvant oncotherapy with substantial potential and advantages. In this study, Piezobrush® PZ2, a handheld CAP unit based on the piezoelectric direct discharge technology, was used to generate and deliver non-thermal plasma. We aimed to investigate the effects of CAPPZ2 on various types of HNC cells and elucidate the underlying mechanisms. In addi