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1.
Biochem Pharmacol ; 222: 116098, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431231

RESUMO

Cancer remains a formidable challenge, continually revealing its intricate nature and demanding novel treatment approaches. Within this intricate landscape, the tumor microenvironment and its dynamic components have gained prominence, particularly macrophages that can adopt diverse polarization states, exerting a profound influence on cancer progression. Recent revelations have spotlighted lactic acid as a pivotal player in this complex interplay. This review systematically explores lactic acid's multifaceted role in macrophage polarization, focusing on its implications in carcinogenesis. We commence by cultivating a comprehensive understanding of the tumor microenvironment and the pivotal roles played by macrophages. The dynamic landscape of macrophage polarization, typified by M1 and M2 phenotypes, is dissected to reveal its substantial impact on tumor progression. Lactic acid, a metabolic byproduct, emerges as a key protagonist, and we meticulously unravel the mechanisms underpinning its generation within cancer cells, shedding light on its intimate association with glycolysis and its transformative effects on the tumor microenvironment. Furthermore, we decipher the intricate molecular framework that underlies lactic acid's pivotal role in facilitating macrophage polarization. Our review underscores lactic acid's dual role in carcinogenesis, orchestrating tumor growth and immune modulation within the tumor microenvironment, thereby profoundly influencing the balance between pro-tumor and anti-tumor immune responses. This duality highlights the therapeutic potential of selectively manipulating lactic acid metabolism for cancer treatment. Exploring strategies to inhibit lactic acid production by tumor cells, novel approaches to impede lactic acid transport in the tumor microenvironment, and the burgeoning field of immunotherapeutic cancer therapies utilizing lactic acid-induced macrophage polarization form the core of our investigation.


Assuntos
Ácido Láctico , Macrófagos , Humanos , Ácido Láctico/metabolismo , Macrófagos/metabolismo , Carcinogênese/metabolismo , Microambiente Tumoral
2.
Vaccines (Basel) ; 11(3)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36992270

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40-100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell-cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA.

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