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Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentivi

Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy.

A paradigm shift has recently occurred in the field of cancer therapeutics. Traditional anticancer agents, such as chemotherapy, radiotherapy and small-molecule drugs targeting specific signalling pathways, have been joined by cellular immunotherapies based on T cell engineering. The rapid adoption of novel, patient-specific cellular therapies builds on scientific developments in tumour immunology, genetic engineering and cell manufacturing, best illustrated by the curative potential of chimeric antigen receptor (CAR) T cell therapy targeting CD19-expressing malignancies. However, the clinical

Cardiorespiratory fitness in long-term lymphoma survivors after high-dose chemotherapy with autologous stem cell transplantation.

BackgroundCardiorespiratory fitness as measured by peak oxygen consumption (VO2peak) is a strong predictor of longevity and may be compromised by anticancer therapy, inactivity, and smoking. We compared VO2peak among lymphoma survivors (LSs) with reference data from healthy sedentary subjects, after a 10.2-year (mean) follow-up post high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT). We further examined the association between VO2peak and treatment, physical activity, smoking, pulmonary, and cardiac function.MethodsLymphoma survivors treated with HDT-ASCT in Norway 198

Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.

This review underscores the dynamic role of the extracellular matrix (ECM) in regulating cellular behavior and maintaining tissue homeostasis, highlighting its pivotal involvement in aging, calcification, and cancer diseases. In healthy tissues, controlled ECM remodeling provides essential biochemical and mechanical cues, but dysregulation (driven by chronic inflammation, cellular senescence, and altered intercellular communication) leads to fibrosis, calcification, and the creation of a pro-tumorigenic microenvironment. Senescent cells contribute to these changes through senescence-associated

The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.

The cytokine network is the central regulatory system for intercellular communication within the immune system. Its proper function depends on the dynamic balance between pro-inflammatory and anti-inflammatory cytokines. Through complex positive and negative feedback loops, this balance precisely regulates the intensity and duration of immune responses, thereby playing a critical role in both physiological and pathological states. This review systematically summarizes the compositional features and classification framework of the cytokine network, as well as the mechanisms by which it maintain

Spectrum of sublytic astrocytopathy in neuromyelitis optica.

Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcript

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo

Совпадение в полном тексте источника
… Progenitor Cells | angiotensin-converting enzyme 2 (ACE2) | susceptible to virus docking | ( 38 ) SARS-CoV-infected cells | ACE2 | blocked the binding of viral spike (S) protein RBD to ACE2+ cells | ( 39 ) Bacterial | Staphylococcus aureus | bacterial pore-forming molecule, α-toxin | promote additional … Exosome-mediated transfer of ACE2 (Angiotensin-converting enzyme 2) from endothelial progenitor cells promotes survival and function of endothelial cell . …

NF-κB in biology and targeted therapy: new insights and translational implications.

NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other importa

YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?

YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet

The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.

The field of hematology has experienced a substantial evolution with the acknowledgment of epigenetic processes as essential factors in the development of hematological malignancies. This review article examines the influence of epigenetic alterations, namely DNA methylation and histone modifications, on the onset and advancement of conditions such as acute myeloid leukemia and myelodysplastic syndromes. We discuss how these epigenetic modifications lead to the deregulation of gene expression, eventually promoting leukemogenesis. The emergence of epigenetic therapies, such as DNA methyltransfe

Нейроинфламмация в нейродегенеративных заболеваниях: сосредоточение внимания на посредничестве лимфоцитов T.

Нейродегенеративные заболевания представляют собой группу заболеваний, характеризующихся постепенным ухудшением центральной нервной системы, что приводит к снижению когнитивных, моторных и эмоциональных способностей пациентов. Нейроинфламмация играет важную роль в развитии этих заболеваний. Вместе с тем исследования терапевтических подходов к целенаправленной борьбе с нейроинфламмацией носят ограниченный характер. Все шире признается роль лимфоцитов, которые являются важнейшими посредниками адаптивной иммунной реакции, в нейродегенеративных заболеваниях. В настоящем обзоре основное внимание уд

Двойная роль микроглии в множественном склерозе и его последствия для диагностики и ремонта.

Микроглия играет ключевую роль в развитии, иммунной слежке и восстановлении центральной нервной системы. Эти клетки играют многогранную роль в множестве склероза (MS), при этом есть основания полагать, что микроглия может способствовать как активному воспалению, так и воспалению. Например, было продемонстрировано, что микроглия может поддерживать разработку олигодендроцитов и фигоцитоза миелиновых обломков, способствуя тем самым надлежащему восстановлению. Однако чрезмерная активация микроглии в повреждениях MS усугубляет нейроинфламму, высвобождая подстрекательские цитокины и облегчая активац

Oral Mucositis Induced By Anticancer Therapies.

Oral mucositis induced by conventional cytotoxic cancer therapies is a common and significant clinical problem in oncology. Mucositis symptoms, which include severe pain, may lead to dose reductions and unplanned interruptions of chemotherapy and/or radiotherapy, and often affect patients' quality of life. In addition, ulcerative mucositis represents a risk factor for local or systemic infectious complications that may be life-threatening in immunosuppressed patients. The development of biologically based targeted cancer therapies, which aim to block the growth, spread, and survival of tumors

Amino acid metabolism in primary bone sarcomas.

Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, bu

Integrin Signaling Shaping BTK-Inhibitor Resistance.

Integrins are adhesion molecules that function as anchors in retaining tumor cells in supportive tissues and facilitating metastasis. Beta1 integrins are known to contribute to cell adhesion-mediated drug resistance in cancer. Very late antigen-4 (VLA-4), a CD49d/CD29 heterodimer, is a beta1 integrin implicated in therapy resistance in both solid tumors and haematological malignancies such as chronic lymphocytic leukemia (CLL). A complex inside-out signaling mechanism activates VLA-4, which might include several therapeutic targets for CLL. Treatment regimens for this disease have recently shi

Innovative Approaches in Bone Tissue Engineering: Strategies for Cancer Treatment and Recovery.

Cancer has rapidly emerged as a leading global cause of premature mortality, with significant economic implications projected to reach USD 25.2 trillion from 2020 to 2050. Among the various types of cancer, primary bone cancers, though uncommon, are projected to see nearly 4000 new cases diagnosed in the United States in 2024. The complexity of treating bone cancer arises from its rarity, diversity, and the challenges associated with surgical interventions, metastatic spread, and post-operative complications. Advancements in bone tissue engineering (BTE) have introduced innovative therapeutic

Contemporary Perspectives on Chronic Renal Disorders.

The prevalence of renal diseases and its associated burden on healthcare have tremendously risen in the past few years. From simple markers assessing kidney function, current renal research delves into understanding the diseases at the cellular and molecular levels and not just at treating, but at improving quality of life, arresting progression and providing personalized diagnostics and therapy. This narrative review highlights the improvements in diagnostic applications of kidney disease and briefly discusses a few notable biomarkers emphasizing the high throughput omics technologies, as wel

Нейтрофилы, НЕТ и множественный склероз: мини-обзор.

Множественный склероз (MS), хроническое аутоиммунное и дегенеративное заболевание, характеризующееся активацией различных провокационных клеток, приводит к обезвоживанию и нейрональным травмам. Нейтрофилы, которые часто недооцениваются в MS, получают все большее внимание за свои важные функции у пациентов MS и экспериментальную аутоиммунную энцефаломиелитную модель (EAE). Нейтрофилы играют многообразную роль в посредничестве патогенеза аутоиммунных заболеваний, и многочисленные исследования свидетельствуют о том, что нейтрофилы могут играть решающую роль благодаря образованию нейтрофильной вне

The functional imperative in high-grade glioma.

Precision oncology has emerged as a promising strategy for treating high-grade gliomas, yet its clinical impact has been disappointing, with over 300 clinical trials on targeted therapies failing to yield substantial improvements in patient outcomes. Current approaches primarily focus on static, marker-driven tumor features, which capture only a small portion of the complex biology that governs therapeutic responses. Functional precision oncology (FPO) offers a complementary approach, enhancing treatment selection in a personalized manner by dynamically testing patient-derived tumor cells agai