Obesity Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100585 - 100585
Published: Jan. 1, 2025
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)
Published: Oct. 2, 2023
The mammalian target of rapamycin (mTOR) is a protein kinase that controls cellular metabolism, catabolism, immune responses, autophagy, survival, proliferation, and migration, to maintain homeostasis. mTOR signaling cascade consists two distinct multi-subunit complexes named complex 1/2 (mTORC1/2). catalyzes the phosphorylation several critical proteins like AKT, C, insulin growth factor receptor (IGF-1R), 4E binding 1 (4E-BP1), ribosomal S6 (S6K), transcription EB (TFEB), sterol-responsive element-binding (SREBPs), Lipin-1, Unc-51-like autophagy-activating kinases. plays central role in regulating translation, lipid synthesis, nucleotide biogenesis lysosomes, nutrient sensing, signaling. emerging pieces evidence have revealed constitutive activation pathway due mutations/amplification/deletion either its (mTORC1 mTORC2) or upstream targets responsible for aging, neurological diseases, human malignancies. Here, we provide detailed structure mTOR, complexes, comprehensive regulators, as well downstream effectors cascades biomolecules, autophagy. Additionally, summarize potential long noncoding RNAs (lncRNAs) an important modulator Importantly, highlighted disorders, cancers, cancer stem cells, drug resistance. discuss developments therapeutic targeting with improved anticancer efficacy benefit patients clinics.
Language: Английский
Citations
312
Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16
Published: April 12, 2024
Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) certain stimuli such as trauma, infection, and neurodegenerative diseases. This is cellular immune response whereby glial cells are activated, inflammatory mediators liberated reactive oxygen nitrogen species synthesized. key process that helps protect brain from pathogens, but inappropriate, or protracted inflammation yields pathological states Parkinson’s disease, Alzheimer’s, Multiple Sclerosis, other disorders showcase various pathways neurodegeneration distributed in parts CNS. review reveals major neuroinflammatory signaling associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, stem cell therapy, genetic intervention, nanoparticles, aiming regulate neuroinflammation potentially impede decelerate advancement these conditions. A comprehensive understanding intricate connection between diseases pivotal for development future treatment strategies can alleviate burden imposed by devastating disorders.
Language: Английский
Citations
89
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: March 25, 2024
Abstract The innate immune pathway is receiving increasing attention in cancer therapy. This ubiquitous across various cell types, not only cells but also adaptive cells, tumor and stromal cells. Agonists targeting the have shown profound changes microenvironment (TME) improved prognosis preclinical studies. However, to date, clinical success of drugs remains limited. Interestingly, recent studies that activation can paradoxically promote progression. uncertainty surrounding therapeutic effectiveness targeted for a critical issue needs immediate investigation. In this review, we observe role demonstrates heterogeneity, linked development stage, status, specific types. We propose within TME, exhibits multidimensional diversity. diversity fundamentally rooted cellular heterogeneity manifested as variety signaling networks. pro-tumor effect essentially reflects suppression classical pathways potential alternative pathways. Refining our understanding tumor’s network employing appropriate strategies enhance ability harness anti-tumor ultimately bridge gap from application.
Language: Английский
Citations
51
Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)
Published: May 7, 2024
Abstract Background Tumor growth is closely linked to the activities of various cells in tumor microenvironment (TME), particularly immune cells. During progression, circulating monocytes and macrophages are recruited, altering TME accelerating growth. These adjust their functions response signals from stromal Tumor-associated (TAMs), similar M2 macrophages, key regulators TME. Methods We review origins, characteristics, TAMs within This analysis includes mechanisms through which facilitate evasion promote metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. Results instrumental mediating malignant behaviors. They release cytokines inhibit effector attract additional immunosuppressive primarily T cells, inducing exhaustion directly, influencing activity indirectly cellular interactions, or suppressing checkpoints. directly involved proliferation, angiogenesis, invasion, Summary Developing innovative tumor-targeted therapies immunotherapeutic currently a promising focus oncology. Given pivotal role evasion, several approaches have been devised them. include leveraging epigenetics, metabolic reprogramming, engineering repolarize TAMs, inhibiting recruitment activity, using as drug delivery vehicles. Although some these remain distant clinical application, believe future targeting will offer significant benefits cancer patients.
Language: Английский
Citations
44
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: April 29, 2024
Abstract Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs been trend this area. Recently, dual blockade durvalumab plus tremelimumab has also emerged an effective for advanced However, majority HCC patients obtain benefits. Understanding immunological rationale exploring novel ways to improve efficacy immunotherapy drawn much attention. review, we summarize latest area, ongoing clinical trials immune-based therapies, well strategies chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, bispecific antibodies.
Language: Английский
Citations
39
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: March 8, 2024
Abstract Circular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs controlling macrophage function remains elusive. Exosomes serve as cargo for and a crucial mediators facilitating communication between cells tumor microenvironment. In this study, we found that circATP8A1, previously unreported circular RNA, is highly expressed both tissues exosomes derived from plasma. Increased circATP8A1 was associated with advanced TNM stage worse prognosis patients cancer. We showed knockdown significantly inhibited proliferation invasion vitro vivo. Functionally, exosome induced M2 polarization macrophages through STAT6 pathway instead STAT3 pathway. Mechanistically, shown to activate competitive binding miR-1-3p, confirmed by Fluorescence Situ Hybridization (FISH), RNA immunoprecipitation, pulldown, Luciferase reporter assays. The reversal circATP8A1-induced activation observed upon blocking miR-1-3p. Macrophages treated overexpressing were able promote migration, while reversed these effects summary, exosome-derived induce via circATP8A1/miR-1-3p/STAT6 axis, progression. Our results highlight potential prognostic biomarker therapeutic target
Language: Английский
Citations
34
Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)
Published: May 29, 2024
Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.
Language: Английский
Citations
29
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)
Published: Jan. 25, 2024
Abstract Fatty acid metabolism, particularly fatty synthesis, is a very important cellular physiological process in which nutrients are used for energy storage and biofilm synthesis. As key enzyme the synthase (FASN) receiving increasing attention. Although previous studies on FASN have mainly focused various malignancies, many recently reported that regulates survival, differentiation, function of immune cells, subsequently participates occurrence development immune-related diseases. However, few to date systematically summarized molecular mechanisms cell biology related In this review, we discuss regulatory effect progress research implications Understanding diseases can offer insights into novel treatment strategies clinical
Language: Английский
Citations
24
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)
Published: April 1, 2024
Abstract Macrophages, as pivotal cells within the tumour microenvironment, significantly influence impact of and reactions to treatments for solid tumours. The rapid evolution bioengineering technology has revealed vast potential engineered macrophages in immunotherapy, disease diagnosis, tissue engineering. Given this landscape, goal harnessing innovating a novel strategy immunotherapy cannot be overstated. diverse strategies realm cancer encompassing macrophage drug delivery systems, chimeric antigen receptor therapy, synergistic treatment approaches involving bacterial outer membrane vesicles macrophages, are meticulously examined review. These methodologies designed enhance therapeutic efficacy against tumours, particularly those that drug-resistant metastatic. Collectively, these immunotherapies poised supplement refine current paradigms, thus heralding new frontier fight malignant
Language: Английский
Citations
21
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: Jan. 21, 2024
The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by stiffness solid tumors often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors corresponding mechanotransducers the cytoplasm, modulating phenotype of TAMs. Currently, tuning TAM polarization through stimulation has received increasing attention, whereas its effect on fate rarely been summarized. A better understanding relationship between will contribute to development new strategies for cancer therapy. In this review, we first introduced overall stiffness, analyzed changes mediated tumor progression, finally summarized effects targeting prognosis provide insight into field.
Language: Английский
Citations
20