Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, ...release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance. Therefore, exosomal miRNAs have a significant function in regulating cancer progression. Here, we briefly review recent findings regarding tumor-derived exosomes, including RNA sorting and delivering mechanism. We then describe the intercommunication occurring between different cells via exosomal miRNAs in tumor microenvironmnt, with impacts on tumor proliferation, vascularization, metastasis and other biological characteristics. Finally, we highlight the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and tumor resistance to therapeutics.
N6-methyladenosine (m6A) methylation, one of the most common RNA modifications, has been reported to execute important functions that affect normal life activities and diseases. Most studies have ...suggested that m6A modification can affect the complexity of cancer progression by regulating biological functions related to cancer. M6A modification of noncoding RNAs regulates the cleavage, transport, stability, and degradation of noncoding RNAs themselves. It also regulates cell proliferation and metastasis, stem cell differentiation, and homeostasis in cancer by affecting the biological function of cells. Interestingly, noncoding RNAs also play significant roles in regulating these m6A modifications. Additionally, it is becoming increasingly clear that m6A and noncoding RNAs potentially contribute to the clinical application of cancer treatment. In this review, we summarize the effect of the interactions between m6A modifications and noncoding RNAs on the biological functions involved in cancer progression. In particular, we discuss the role of m6A and noncoding RNAs as possible potential biomarkers and therapeutic targets in the treatment of cancers.
Multi-drug resistance (MDR) and hypervirulence (hv) were exhibited by different well-separated
lineages in the past, but their convergence clones-MDR-hypervirulent
(HvKPs)-both highly pathogenic and ...resistant to most available antibiotics, have increasingly been reported. In light of the clonal lineages and molecular characteristics of the studied MDR-HvKP strains found in the literature since 2014, this review discusses the epidemiology of MDR-HvKPs, in particular summarizing the three general aspects of plasmids-associated mechanisms underlying the formation of MDR-HvKPs clones: MDR-classic
(cKPs) acquiring hv plasmids, hvKPs obtaining MDR plasmids, and the acquisition of hybrid plasmids harboring virulence and resistance determinants. A deeper understanding of epidemiological characteristics and possible formation mechanisms of MDR-HvKPs is greatly needed for the proper surveillance and management of this potential threat.
Abstract
N
6
-methyladenosine (m
6
A), the most abundant modification in eukaryotic cells, regulates RNA transcription, processing, splicing, degradation, and translation. Circular RNA (circRNA) is a ...class of covalently closed RNA molecules characterized by universality, diversity, stability and conservatism of evolution. Accumulating evidence shows that both m
6
A modification and circRNAs participate in the pathogenesis of multiple diseases, such as cancers, neurological diseases, autoimmune diseases, and infertility. Recently, m
6
A modification has been identified for its enrichment and vital biological functions in regulating circRNAs. In this review, we summarize the role of m
6
A modification in the regulation and function of circRNAs. Moreover, we discuss the potential applications and possible future directions in the field.
Exosomes have emerged as critical mediators of intercellular communication, both locally and systemically, by regulating a diverse range of biological processes between cells. Circular RNA (circRNA) ...is a novel member of endogenous noncoding RNAs with widespread distribution and diverse cellular functions. Recently, circular RNAs have been identified for their enrichment and stability in exosomes. In this review, we outline the origin, biogenesis and function of exosomal circRNAs as well as their roles in various diseases. Although their precise roles and mechanisms of gene regulation remain largely elusive, exosomal circRNAs have potential applications as disease biomarkers and novel therapeutic targets.
The tumour microenvironment (TME) constitutes the area surrounding the tumour during its development and has been demonstrated to play roles in cancer-related diseases through crosstalk with tumour ...cells. Circular RNAs (circRNAs) are a subpopulation of endogenous noncoding RNAs (ncRNAs) that are ubiquitously expressed in eukaryotes and have multiple biological functions in the regulation of cancer onset and progression. An increasing number of studies have shown that circRNAs participate in the multifaceted biological regulation of the TME. However, details on the mechanisms involved have remained elusive until now. In this review, we analyse the effects of circRNAs on the TME from various perspectives, including immune surveillance, angiogenesis, hypoxia, matrix remodelling, exo-circRNAs and chemoradiation resistance. Currently, the enormous potential for circRNA use in targeted therapy and as noninvasive biomarkers have drawn our attention. We emphasize the prospect of targeting circRNAs as an essential strategy to regulate TME, overcome cancer resistance and improve therapeutic outcomes.
In recent years, tumor immunotherapy has made significant progress. However, tumor immunotherapy, particularly immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors), benefits only a tiny ...proportion of patients in solid cancers. The tumor microenvironment (TME) acts a significant role in tumor immunotherapy. Studies reported that tumor-associated macrophages (TAMs), as one of the main components of TME, seriously affected the therapeutic effect of PD-1/PD-L1 inhibitors. In this review, we analyzed TAMs from epigenetic and single-cell perspectives and introduced the role and mechanisms of TAMs in anti-programmed death protein 1(anti-PD-1) therapy. In addition, we summarized combination regimens that enhance the efficacy of tumor PD-1/PD-L1 inhibitors and elaborated on the role of the TAMs in different solid cancers. Eventually, the clinical value of TAMs by influencing the therapeutic effect of tumor PD-1/PD-L1 inhibitors was discussed. These above are beneficial to elucidate poor therapeutic effect of PD-1/PD-L1 inhibitors in solid tumors from the point of view of TAMs and explore the strategies to improve its objective remission rate of solid cancers.
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•Aging in soil lead the surface of PS-MP being wrapped by soil particles.•The wrapping effects of soil particles induced the formation of protective layer.•Protective layer increased ...the particle size of PS-MP and decreased its ingestion.•The aging of PS-MP in the soil decreased its toxicity to earthworms.
The recent discovery of microplastics contaminants in most ecosystems has raised major health issues, yet knowledge on their impact on soil organisms is limited, especially their toxicity evolution with aging. Herein, the toxicity of polystyrene microplastic (PS-MP) to earthworm (Eisenia fetida) along with aging was investigated. Results showed that the 28 d-LC50 (50% lethal concentration) of PS-MP was 25.67 g kg−1, whereas that increased to 96.47 g kg−1 after PS-MP initially aged in soil for 28 days, indicating the toxicity of PS-MP decreased with aging. Laser scanning confocal microscope and scanning electron microscope (SEM) found that the toxicity of PS-MP to earthworm may be due to the ingestion of PS-MP by earthworms and the physical damage (e.g., epidermis abrasion and setae loss) of PS-MP to earthworms. Similarly, the levels of reactive oxygen species, antioxidant enzyme activities and malondialdehyde content increased with PS-MP concentrations from 0.1 to 1.5 g kg−1, but decreased with aging from 7 to 28 days. The integrated biomarker response index also confirmed that the toxicity of PS-MP decreased with aging. SEM found that PS-MP were progressively covered by soil particles during soil aging, inducing the formation of protective layer and increasing the particle size of PS-MP, which prevented direct contact with earthworms and decreased the ingestion of PS-MP, in turn decreased PS-MP toxicity. Overall, our study provides valuable insights for elucidating the effect of aging on the toxicity of microplastics.
A pre-metastatic niche is a microenvironment prepared for the colonization of circulating tumor cells in specific organs. Exosomes are extracellular vesicles with a variety of biological functions. ...Exosomes play an irreplaceable role in the development of pre-metastatic niches, and mainly function as communication medium. In this review, we analyzed the effects of exosomes on pre-metastatic niches from various perspectives, including inflammation, immune response, angiogenesis, organotropism, matrix remodeling and biomarker expression. In particular, exosomes express programmed death ligand 1 (PD-L1) and cause the immune escape of tumor cells. The immunomodulatory effects of exosomes and their potential in liquid diagnosis have drawn our attention. The potential value of exosomes and pre-metastatic niches will be realized in the field of immunity therapy.
Generalized pustular psoriasis (GPP) is a rare and severe auto-inflammatory skin disease that is characterized by recurrent, acute onset, and generalized pustular eruptions on erythematous, inflamed ...skin. GPP is traditionally classified as a variant of psoriasis vulgaris, even though recent clinical, histological and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, variants of IL36RN, CARD14, AP1S3 and MPO genes have been identified as causative or contributing to genetic defects in a proportion of patients affected by GPP. These disease-related genes are involved in common inflammatory pathways, in particular in the IL-l/IL-36-chemokines-neutrophil pathogenic axis. At present, no standard therapeutic guidelines have been established for GPP management, and there is a profound need for novel efficacious treatments of GPP. Among them, biological agents antagonizing the IL-36 pathway are promising therapeutics. The aim of the present review is to provide the most recent updates on the genetics, genotype-phenotype correlation and pathological basis of GPP, as well as on biologic treatments available for GPP and relative clinical courses.
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