Molecular Aspects of Medicine最新文献

Protein folding represents a vital process for any living organism. While significant insights have been gained from studying single-domain proteins, our current knowledge on the folding mechanisms of multidomain proteins remains relatively limited, primarily due to their inherent complexity. The principal aim of this review lies in summarizing the emerging view pertaining multi-domain folding, emphasizing their modular nature, which minimizes misfolding and facilitates evolutionary innovation. We discuss the energetic interplay between domains, highlighting particularly the cases where domain interactions lead to transient misfolded intermediates. These interactions can result in diverse effects, including cooperative folding and domain-specific perturbations, which are particularly relevant to the pathogenesis of neurodegenerative diseases like polyglutamine disorders. The review underscores the critical need to understand multidomain folding, to better comprehend and potentially mitigate the molecular underpinnings of protein misfolding diseases.

This review provides a comprehensive overview of the evolving landscape of cancer vaccines, highlighting their potential to revolutionize tumor prevention. Building on the success of vaccines against virus-related cancers, such as HPV- and HBV-associated cervical and liver cancers, the current challenge is to extend these achievements to the prevention of non-viral tumors and the treatment of preneoplastic or early neoplastic lesions. This review analyzes the critical aspects of preventive anti-cancer vaccination, focusing on the choice of target antigens, the development of effective vaccine platforms and technologies, and the use of various model systems for preclinical testing, from laboratory rodents to companion animals.

Microplastics (MPs) are known as substantial environmental and health threats because of their pervasive existence and potential function in human diseases. This study is the first research in which a comprehensive analysis of various impacts of MPs on cancer cells is performed through pharmacological and in silico approaches. Moreover, our results demonstrate that MPs have both promotive and suppressive impacts on cancer cells, changing some of the important features of these kinds of cells including cellular viability, migration, metastasis, and apoptosis. Furthermore, the present study displayed that AP-2 complex subunit mu-1 (AP2M1), Asialoglycoprotein receptor 2 (ASGR2), Bax inhibitor-1 (BI-1), and Ferritin Heavy Chain, and pivotal role in the progression of cancers mediated by MPs. Moreover, our in-silico analysis identified Goserelin, Paclitaxel, Raloxifene, Exemestane, Epirubicin, Trametinib, Vemurafenib, Pactitaxel, and Sorafenib as potential anticancer agents for curing MPS-based cancer. Besides, our results demonstrated that MPs can exacerbate the development of tumor cells by affecting some important mechanisms including oxidative stress, immune suppression, and adjusting of critical signaling pathways. Interestingly, some sorts of MPs also displayed suppressive effects on cancer cells in some particular contexts, highlighting their complicated biological roles in different biological interactions. Ultimately the present survey tries to demonstrate the crucial roles of MPs in cancer cells and the different mechanisms that occur in the mentioned cells in order to emphasize performing more studies about clarifying the roles of MPs in carcinogenesis.

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC and other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 and SETD2, which play key roles in signaling pathway transduction, chromatin remodeling and DNA repair. The PI3K/AKT/mTOR signaling pathway is particularly important in the pathogenesis of RCC. Mutations in genes such as PIK3CA, MTOR and PTEN are closely associated with metabolic abnormalities and tumor cell proliferation. Clinically, mTOR inhibitors and VEGF-targeted drugs have shown significant efficacy in personalized therapy. Abnormal regulation of metabolic reprogramming, especially glycolysis and glutamine metabolic pathways, provides tumor cells with continuous energy supply and survival advantages, and GLS1 inhibitors have shown promising results in preclinical studies. This paper also explores the potential of immune checkpoint inhibitors in combination with other targeted drugs, as well as the promising application of nanotechnology in drug delivery and targeted therapy. In addition, unique molecular mechanisms are revealed and individualized therapeutic strategies are explored for specific subtypes such as TFE3, TFEB rearrangement type and SDHB mutant type. The review summarizes the common gene mutations in RCC and their molecular mechanisms, emphasizes their important roles in tumor diagnosis, treatment and prognosis, and looks forward to the application prospects of multi-pathway targeted therapy, metabolic targeted therapy, immunotherapy and nanotechnology in RCC treatment, providing theoretical support and clinical guidance for individualized treatment and new drug development.