Mesenchymal stromal cells (MSCs) are essential elements of the bone marrow (BM) microenvironment, which have been widely implicated in pathways that contribute to leukemia growth and resistance. Recent reports showed genotypic and phenotypic alterations in leukemia patient‐derived MSCs, indicating that MSCs might be educated/reprogrammed. However, the results have been inconclusive, possibly due to the heterogeneity of leukemia. Here, the authors report that acute myeloid leukemia (AML) induces MSCs towards an adipogenic differentiation propensity. RNAseq analysis reveal significant upregulation of gene expression enriched in the adipocyte differentiation process and reduction in osteoblast differentiation. The alteration is accompanied by a metabolic switch from glycolysis to a more oxidative phosphorylation‐dependent manner. Mechanistic studies identify that AML cell‐derived exosomes play a vital role during the AML cell‐mediated MSCs education/reprogramming process. Pre‐administration of mice BM microenvironment with AML‐derived exosomes greatly enhance leukemia engraftment in vivo. The quantitative proteomic analysis identified a list of exosomal protein components that are differently expressed in AML‐derived exosomes, which represent an opportunity for novel therapeutic strategies based on the targeting of exosome‐based AML cells‐MSCs communication. Collectively, the data show that AML‐educated MSCs tend to differentiate into adipocytes contributing to disease progression, which suggests complex interactions of leukemia with microenvironment components.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202105811

Acute Myeloid Leukemia Cells Educate Mesenchymal Stromal Cells toward an Adipogenic Differentiation Propensity with Leukemia Promotion Capabilities

Gastric cancer is one of the most common malignant tumours worldwide. Genetic and epigenetic alterations are key factors in gastric carcinogenesis and drug resistance to chemotherapy. Competing endogenous RNA (ceRNA) regulation models have defined circRNA/lncRNA as miRNA sponges that indirectly regulate miRNA downstream target genes. The ceRNA regulatory network is related to the malignant biological behaviour of gastric cancer. The circRNA/lncRNA-miRNA-mRNA axis may be a marker for the early diagnosis and prognosis of gastric cancer and a potential therapeutic target for gastric cancer. Exosomal ncRNAs play an important role in gastric cancer and are expected to be ideal biomarkers for the diagnosis, prognosis, and treatment of gastric cancer. This review summarizes the specific ceRNA regulatory network (circRNA/lncRNA-miRNA-mRNA) discovered in gastric cancer in recent years, which may provide new ideas or strategies for early clinical diagnosis, further development, and application. 

Research progress on the circRNA/lncRNA-miRNA-mRNA axis in gastric cancer.

Human diseases have been a critical threat from the beginning of human history. Knowing the origin, course of action and treatment of any disease state is essential. A microscopic approach to the molecular field is a more coherent and accurate way to explore the mechanism, progression, and therapy with the introduction and evolution of technology than a macroscopic approach. Non-coding RNAs (ncRNAs) play increasingly important roles in detecting, developing, and treating all abnormalities related to physiology, pathology, genetics, epigenetics, cancer, and developmental diseases. Noncoding RNAs are becoming increasingly crucial as powerful, multipurpose regulators of all biological processes. Parallel to this, a rising amount of scientific information has revealed links between abnormal noncoding RNA expression and human disorders. Numerous non-coding transcripts with unknown functions have been found in addition to advancements in RNA-sequencing methods. Non-coding linear RNAs come in a variety of forms, including circular RNAs with a continuous closed loop (circRNA), long non-coding RNAs (lncRNA), and microRNAs (miRNA). This comprises specific information on their biogenesis, mode of action, physiological function, and significance concerning disease (such as cancer or cardiovascular diseases and others). This study review focuses on non-coding RNA as specific biomarkers and novel therapeutic targets. 

/pdf/non-coding-rnas-in-human-health-and-disease-potential-h4w0c7n4.pdf

Non-coding RNAs in human health and disease: potential function as biomarkers and therapeutic targets

The atherosclerotic vascular disease is a cardiovascular continuum in which the main role is attributed to atherosclerosis, from its appearance to its associated complications. The increasing prevalence of cardiovascular risk factors, population ageing, and burden on both the economy and the healthcare system have led to the development of new diagnostic and therapeutic strategies in the field. The better understanding or discovery of new pathophysiological mechanisms and molecules modulating various signaling pathways involved in atherosclerosis have led to the development of potential new biomarkers, with key role in early, subclinical diagnosis. The evolution of technological processes in medicine has shifted the attention of researchers from the profiling of classical risk factors to the identification of new biomarkers such as midregional pro-adrenomedullin, midkine, stromelysin-2, pentraxin 3, inflammasomes, or endothelial cell-derived extracellular vesicles. These molecules are seen as future therapeutic targets associated with decreased morbidity and mortality through early diagnosis of atherosclerotic lesions and future research directions.

https://www.mdpi.com/1422-0067/23/9/4998/pdf?version=1651825665

Novel Biomarkers of Atherosclerotic Vascular Disease—Latest Insights in the Research Field

Aging-induced alternations of vasculature structures, phenotypes, and functions are key in the occurrence and development of vascular aging-related diseases. Multiple molecular and cellular events, such as oxidative stress, mitochondrial dysfunction, vascular inflammation, cellular senescence, and epigenetic alterations are highly associated with vascular aging physiopathology. Advances in nanoparticles and nanotechnology, which can realize sensitive diagnostic modalities, efficient medical treatment, and better prognosis as well as less adverse effects on non-target tissues, provide an amazing window in the field of vascular aging and related diseases. Throughout this review, we presented current knowledge on classification of nanoparticles and the relationship between vascular aging and related diseases. Importantly, we comprehensively summarized the potential of nanoparticles-based diagnostic and therapeutic techniques in vascular aging and related diseases, including cardiovascular diseases, cerebrovascular diseases, as well as chronic kidney diseases, and discussed the advantages and limitations of their clinical applications. 

/pdf/nanoparticles-in-the-diagnosis-and-treatment-of-vascular-12ufbn8q.pdf

Nanoparticles in the diagnosis and treatment of vascular aging and related diseases

Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are closely related to a variety of biological and functional aspects of human health. When the exosomal ncRNAs undergo tissue-specific changes due to diverse internal or external disorders, they can cause tissue dysfunction, aging, and diseases. In this review, we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases. In addition, we explore the current knowledge on the roles of exosomal miRNAs, lncRNAs, and circRNAs in human health and diseases, including cancers, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and infectious diseases, to determine their potential implication in biomarker identification and therapeutic exploration.

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases.

Atherosclerosis, a complex chronic inflammatory disease, involves multiple alterations of diverse cells, including endothelial cells (ECs), vascular smooth muscle cells (VSMCs), monocytes, macrophages, dendritic cells (DCs), platelets, and even mesenchymal stem cells (MSCs). Globally, it is a common cause of morbidity as well as mortality. It leads to myocardial infarctions, stroke and disabling peripheral artery disease. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that secreted by multiple cell types and play a central role in cell-to-cell communication by delivering various bioactive cargos, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Emerging evidence demonstrated that miRNAs and lncRNAs in EVs are tightly associated with the initiation and development of atherosclerosis. In this review, we will outline and compile the cumulative roles of miRNAs and lncRNAs encapsulated in EVs derived from diverse cells in the progression of atherosclerosis. We also discuss intercellular communications via EVs. In addition, we focused on clinical applications and evaluation of miRNAs and lncRNAs in EVs as potential diagnostic biomarkers and therapeutic targets for atherosclerosis.

/pdf/mechanisms-of-action-of-mirnas-and-lncrnas-in-extracellular-514plrf0zf.pdf

Mechanisms of Action of MiRNAs and LncRNAs in Extracellular Vesicle in Atherosclerosis

Vascular aging is a pivotal risk factor promoting vascular dysfunction, the development and progression of vascular aging-related diseases. The structure and function of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and macrophages are disrupted during the aging process, causing vascular cell senescence as well as vascular dysfunction. DNA methylation, an epigenetic mechanism, involves the alteration of gene transcription without changing the DNA sequence. It is a dynamically reversible process modulated by methyltransferases and demethyltransferases. Emerging evidence reveals that DNA methylation is implicated in the vascular aging process and plays a central role in regulating vascular aging-related diseases. In this review, we seek to clarify the mechanisms of DNA methylation in modulating ECs, VSMCs, fibroblasts, and macrophages functions and primarily focus on the connection between DNA methylation and vascular aging-related diseases. Therefore, we represent many vascular aging-related genes which are modulated by DNA methylation. Besides, we concentrate on the potential clinical application of DNA methylation to serve as a reliable diagnostic tool and DNA methylation-based therapeutic drugs for vascular aging-related diseases.

/pdf/roles-and-mechanisms-of-dna-methylation-in-vascular-aging-4eheesk8a1.pdf

Hui Xu

Papers

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases.

Mechanisms of Action of MiRNAs and LncRNAs in Extracellular Vesicle in Atherosclerosis

Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases.