Результаты поиска

Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.

CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated proteins) has undergone marked advancements since its discovery as an adaptive immune system in bacteria and archaea, emerged as a potent gene-editing tool after the successful engineering of its synthetic guide RNA (sgRNA) toward the targeting of specific DNA sequences with high accuracy. Besides its DNA editing ability, further-developed Cas variants can also edit the epigenome, rendering the CRISPR-Cas system a versatile tool for genome and epigenome manipulation and a pioneering force in precision medic

Совпадение в полном тексте источника
… Additionally, strategies such as beta-2-microglobulin (B2M) knockout can further reduce alloreactivity by eliminating major histocompatibility complex (MHC) class I expression. …

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

Совпадение в полном тексте источника
… ROS also enhance cross‐presentation via lysosomal ROS/calcium and mitochondrial mtROS‐dependent major histocompatibility complex I (MHC I) antigen processing. … ROS levels also play a role in the major histocompatibility complex I (MHC I)‐mediated presentation of processed antigens to CD8+ T cells; during this process, mitochondria regulate the cross‐presentation capabilities of plasmacytoid DCs (pDCs) in a ROS‐dependent manner. …

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

Совпадение в полном тексте источника
… ICP47 is an inhibitor of transporter associated with antigen presentation (TAP), a protein responsible for transferring the antigen-major histocompatibility complex (MHC) type I complex to the plasma membrane, leading to impaired antigen presentation in HSV-infected cells [ 50 , 51 ]. …

CAR-T cell therapy: Where are we now, and where are we heading?

Chimeric antigen receptor (CAR)-T-cell therapies have exhibited remarkable efficacy in the treatment of hematologic malignancies, with 9 CAR-T-cell products currently available. Furthermore, CAR-T cells have shown promising potential for expanding their therapeutic applications to diverse areas, including solid tumors, myocardial fibrosis, and autoimmune and infectious diseases. Despite these advancements, significant challenges pertaining to treatment-related toxic reactions and relapses persist. Consequently, current research efforts are focused on addressing these issues to enhance the safe

Совпадение в полном тексте источника
… INTRODUCTION Chimeric antigen receptor (CAR)-T-cell therapy is an adoptive cell therapy that bypasses major histocompatibility complex-dependent immune tolerance and tumor escape; it targets a broad array of antigens (proteins, carbohydrates, and glycolipids), 1 and has higher durability than conventional …

Bispecific antibodies in multiple myeloma treatment: A journey in progress.

The incorporation of novel agents and monoclonal antibody-based therapies into the treatment of multiple myeloma (MM) has significantly improved long-term patient survival. However, the disease is still largely incurable, with high-risk patients suffering shorter survival times, partly due to weakened immune systems. Bispecific molecules, including bispecific antibodies (BisAbs) and bispecific T-cell engagers (BiTEs), encourage immune cells to lyse MM cells by simultaneously binding antigens on MM cells and immune effector cells, bringing those cells into close proximity. BisAbs that target B-

Совпадение в полном тексте источника
… The immunomodulatory effect of these agents is independent of antigen presentation on the major histocompatibility complex (MHC) class I, can occur in the absence of co-stimulation, and bypass the normal dependence on antigen-presenting cells or cytokines ( 28 , 29 ), making them suitable for use in …

Bispecific antibody targets and therapies in multiple myeloma.

Recently, several bispecific antibodies (BsAbs) have been approved for the treatment of relapsed multiple myeloma (MM) after early phase trials in heavily pre-treated patients demonstrated high response rates and impressive progression-free survival with monotherapy. These BsAbs provide crucial treatment options for relapsed patients and challenging decisions for clinicians. Evidence on the optimal patient population, treatment sequence, and duration of these therapeutics is unknown and subject to active investigation. While rates of cytokine release syndrome and neurotoxicity appear to be low

Совпадение в полном тексте источника
… LAVA-051: CD1d is a class I major histocompatibility complex-like molecule that can be expressed by various myeloid, lymphoid, and plasma cell disorders. In MM, CD1d is highly expressed in the early stages of the disease; however, CD1d expression is lost with disease progression. …

Chimeric Antigen Receptor T-Cell Therapy in Metastatic Castrate-Resistant Prostate Cancer.

Prostate cancer is the most commonly diagnosed solid-organ cancer amongst males worldwide. Metastatic castrate-resistant prostate cancer (mCRPC) is a rapidly fatal end-sequelae of prostate cancer. Therapeutic options for men with mCRPC are limited and are not curative in nature. The recent development of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the treatment of treatment-resistant haematological malignancies, and several studies are underway investigating the utility of this technology in the treatment of solid tumours. In this review, we evaluate the current treatme

Совпадение в полном тексте источника
… The key strength of CAR-T cell therapy is that specific tumour antigens can be targeted to direct an immunological response, independent of antigen-presenting cells (APCs), as well as the major histocompatibility complex system (MHC) [ 55 ]. …

How to Treat Melanoma? The Current Status of Innovative Nanotechnological Strategies and the Role of Minimally Invasive Approaches like PTT and PDT.

Melanoma is the most aggressive type of skin cancer, the incidence and mortality of which are increasing worldwide. Its extensive degree of heterogeneity has limited its response to existing therapies. For many years the therapeutic strategies were limited to surgery, radiotherapy, and chemotherapy. Fortunately, advances in knowledge have allowed the development of new therapeutic strategies. Despite the undoubted progress, alternative therapies are still under research. In this context, nanotechnology is also positioned as a strong and promising tool to develop nanosystems that act as drug ca

Совпадение в полном тексте источника
… In parallel, another important factor was the increase in the expression of the major histocompatibility complex Class I, typically downregulated in cancer cells, as well as costimulatory molecules. Lastly, a syngeneic murine melanoma model was established through inoculation of SM1 cells. …

Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer.

For nearly three decades, chimeric antigen receptors (CARs) have captivated the interest of researchers seeking to find novel immunotherapies to treat cancer. CARs were first designed to work with T cells, and the first CAR T cell therapy was approved to treat B cell lymphoma in 2017. Recent advancements in CAR technology have led to the development of modified CARs, including multi-specific CARs and logic gated CARs. Other immune cell types, including natural killer (NK) cells and macrophages, have also been engineered to express CARs to treat cancer. Additionally, CAR technology has been ada

Совпадение в полном тексте источника
… To become fully activated, T cells must receive primary stimulation through the interaction of the T cell receptor (TCR) and specific antigen peptide presented on the major histocompatibility complex (MHC). …

Emerging therapeutics in the management of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) pandemic has placed a tremendous burden on healthcare systems globally. Therapeutics for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical trials. Currently, there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19. A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 pandemic. We

Совпадение в полном тексте источника
… MultiStem cells lack major histocompatibility complex (MHC) II, which means that they do not create a proliferative response when cultured alongside allogeneic T-cells and ultimately that they reduce T cell proliferation when the T cells are stimulated with irradiated, allogeneic stimulator cells[ 80 …

Tyrosine Kinase Inhibitors, Antibody-Drug Conjugates, and Bispecific Antibodies in Oncogene-Driven Non-Small-Cell Lung Cancer: Evolving Roles in Treatment Sequencing and Resistance Management.

The treatment landscape of oncogene-driven non-small-cell lung cancer (NSCLC) has evolved substantially with the development of targeted therapies directed against actionable molecular alterations. Tyrosine kinase inhibitors (TKIs) remain the cornerstone of treatment for many driver-defined subsets; however, acquired resistance, central nervous system progression, and tumor heterogeneity continue to limit long-term disease control. This review examines the mechanistic foundations, clinical evidence, resistance patterns, and emerging therapeutic roles of TKIs, antibody-drug conjugates (ADCs), a

Совпадение в полном тексте источника
… Loss of major histocompatibility complex class I expression impairs TCR co-stimulatory signaling required for optimal T-cell–mediated killing [ 135 ]. …

Машинное обучение для уточнения интерпретации изображений магнитного резонанса в управлении множественным склерозом: обзор повествования.

Множественный склероз (MS) — аутоиммунное заболевание мозга и спинного мозга с как воспалительными, так и нейродегенеративными свойствами. Несмотря на то, что достижения в области методов визуализации, в частности магнитно-резонансной съемки (MRI), улучшили процесс диагностики, его причины неизвестны, лекарство по-прежнему остается неизлечимым, а фактологическая база для управления лечением отсутствует. Для понимания MS стали использоваться такие методы расчета, как машинное обучение (ML). Опубликованные вычислительные исследования на основе MS MRI можно разбить на пять категорий: автоматизиро

Совпадение в полном тексте источника
… Several types of inflammatory cells are likely to be involved in the pathogenesis of MS, including CD4 + T-lymphocytes, which recognize antigen peptide fragments bound to major histocompatibility complex class II proteins. …

RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.

In the last decades, colorectal cancer (CRC) has emerged as a global problem, representing approximately 10% of all malignant tumors and the second leading cause of cancer-related death. Colitis-associated cancer (CAC) arises from chronic unresolved inflammation and is typically characterised by poor prognosis. Among key cellular regulators, the small GTPase RHOA controls cytoskeleton dynamics in various cell types and, thereby, key biological processes. Although it has been linked to various diseases, the role of RHOA in cancer remains controversial. RHOA has been proposed as a biomarker in c

Совпадение в полном тексте источника
… Similarly, mechanical forces generated within normal epithelial cells have been linked to the recognition and removal of transformed cells via immunological ligand-receptor interactions, such as leukocyte immunoglobulin-like receptor B3 (LILRB3) on normal cells detecting major histocompatibility complex …

Integumentary System

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

Совпадение в полном тексте источника
… Langerhans cells express CD1, class II major histocompatibility complex (MHC) antigens, CD45, vimentin, and S-100. The long dendritic processes of Langerhans cells traverse the intercellular space to the granular cell layer, where they function in immunosurveillance as antigen-presenting cells. …

COVID-19 Therapeutic Options Under Investigation.

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexame

Совпадение в полном тексте источника
… This process interferes with the antigen processing, dimerization of the major histocompatibility complex (MHC) class II, antigen presentation, and the stimulation of CD4+ T cells. …

Immunotherapies for Aging and Age-Related Diseases: Advances, Pitfalls, and Prospects.

Aging is characterized by a gradual decline in the functionality of all the organs and tissues, leading to various diseases. As the global population ages, the urgency to develop effective anti-aging strategies becomes increasingly critical due to the growing severity of associated health problems. Immunotherapy offers novel and promising approaches to combat aging by utilizing approaches including vaccines, antibodies, and cytokines to target specific aging-related molecules and pathways. In this review, we summarize the recent advancements of immunotherapies to eliminate senescence cells and

Совпадение в полном тексте источника
… DR4-AL179, the vaccine loaded with the immunodominant type II collagen COL2 peptide (259–273) that binds to major histocompatibility complex II (MHC), exhibited robust effectiveness in suppressing arthritis progression in mouse model of RA [ 123 ]. …

Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

Targeting the proteasome in cancer therapy: development and future opportunities in natural products.

BACKGROUND: The ubiquitin-proteasome pathway is a critical therapeutic target in malignancies, particularly multiple myeloma. The development of proteasome inhibitors (PIs) has marked a milestone in multiple myeloma therapy and now constitutes the backbone of frontline treatment regimens. However, primary and acquired resistance remain a major challenge, underscoring the need to identify new PIs as well as agents that can resensitize resistant cells. METHOD: This review provides an overview of the current clinical applications of PIs and offers a comprehensive summary of natural products that

Molecular mechanisms of the preventable causes of cancer in the United States.

Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer deaths in the United States alone. The public health burden associated with these numbers has motivated enormous research efforts into understanding the root causes of cancer. These efforts have led to the recognition that between 40% and 45% of cancers are associated with preventable risk factors and, importantly, have identified specific molecular mechanisms by which these exposures modify human physiology to induce or promote cancer. The increasingly refined knowledge of these mechanisms, which we summarize here,

Cellular senescence-from solid organs to vascularized composite allotransplants.

Vascularized composite allotransplantation (VCA) has emerged as a novel therapy approach to restore form and function in patients with severe tissue defects of the face, hand, and abdominal wall, among other anatomical regions. The composite allografts comprise different tissues such as skin, muscle, or bone. Clinical data demonstrate promising mid- and long-term outcomes following VCA surgery, but our understanding of the cellular interactions and molecular pathways in VCA surgery is oftentimes deduced from solid organ transplantation (SOT). In SOT, the concept of cellular senescence has grow