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Liquid–liquid phase separation (LLPS), an emerging biophysical phenomenon, can sequester molecules to implement physiological and pathological functions. LLPS implements the assembly of numerous membraneless chambers, including stress granules and P‐bodies, containing RNA and protein. RNA–RNA and RNA–protein interactions play a critical role in LLPS. Scaffolding proteins, through multivalent interactions and external factors, support protein–RNA interaction networks to form condensates involved in a variety of diseases, particularly neurodegenerative diseases and cancer. Modulating LLPS phenomenon in multiple pathogenic proteins for the treatment of neurodegenerative diseases and cancer could present a promising direction, though recent advances in this area are limited. Here, we summarize in detail the complexity of LLPS in constructing signaling pathways and highlight the role of LLPS in neurodegenerative diseases and cancers. We also explore RNA modifications on LLPS to alter diseases progression because these modifications can influence LLPS of certain proteins or the formation of stress granules, and discuss the possibility of proper manipulation of LLPS process to restore cellular homeostasis or develop therapeutic drugs for the eradication of diseases. This review attempts to discuss potential therapeutic opportunities by elaborating on the connection between LLPS, RNA modification, and their roles in diseases. [ABSTRACT FROM AUTHOR]

Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of RNA modification regulators operating through various pathways, play pivotal roles in driving the progression of haematological malignancies. Among RNA modifications, N6‐methyladenosine (m6A) RNA modification, the most abundant internal mRNA modification, stands out as the most extensively studied modification. This prominence underscores the crucial role of the layer of epitranscriptomic regulation in controlling haematopoietic cell fate and therefore the development of haematological malignancies. Additionally, other RNA modifications (non‐m6A RNA modifications) have gained increasing attention for their essential roles in haematological malignancies. Although the roles of the m6A modification machinery in haematopoietic malignancies have been well reviewed thus far, such reviews are lacking for non‐m6A RNA modifications. In this review, we mainly focus on the roles and implications of non‐m6A RNA modifications, including N4‐acetylcytidine, pseudouridylation, 5‐methylcytosine, adenosine to inosine editing, 2′‐O‐methylation, N1‐methyladenosine and N7‐methylguanosine in haematopoietic malignancies. We summarise the regulatory enzymes and cellular functions of non‐m6A RNA modifications, followed by the discussions of the recent studies on the biological roles and underlying mechanisms of non‐m6A RNA modifications in haematological malignancies. We also highlight the potential of therapeutically targeting dysregulated non‐m6A modifiers in blood cancer. [ABSTRACT FROM AUTHOR]

Background: Hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, predisposing them to life‐threatening diseases. Varied responses to management strategies suggest the possibility of multiple subtypes. Hypothesis/Objective: To identify and characterize HTG subtypes in Miniature Schnauzers through cluster analysis of lipoprotein profiles. We hypothesize that multiple phenotypes of primary HTG exist in this breed. Animals: Twenty Miniature Schnauzers with normal serum triglyceride concentration (NTG), 25 with primary HTG, and 5 with secondary HTG. Methods: Cross‐sectional study using archived samples. Lipoprotein profiles, generated using continuous lipoprotein density profiling, were clustered with hierarchical cluster analysis. Clinical data (age, sex, body condition score, and dietary fat content) was compared between clusters. Results: Six clusters were identified. Dogs with primary HTG were dispersed among 4 clusters. One cluster showed the highest intensities for triglyceride‐rich lipoprotein (TRL) and low‐density lipoprotein (LDL) fractions and also included 4 dogs with secondary HTG. Two clusters had moderately high TRL fraction intensities and low‐to‐intermediate LDL intensities. The fourth cluster had high LDL but variable TRL fraction intensities with equal numbers of NTG and mild HTG dogs. The final 2 clusters comprised only NTG dogs with low TRL intensities and low‐to‐intermediate LDL intensities. The clusters did not appear to be driven by differences in the clinical data. Conclusions and Clinical Importance: The results of this study support a spectrum of lipoprotein phenotypes within Miniature Schnauzers that cannot be predicted by triglyceride concentration alone. Lipoprotein profiling might be useful to determine if subtypes have different origins, clinical consequences, and response to treatment. [ABSTRACT FROM AUTHOR]

Interferon-stimulated gene 20 kDa protein (ISG20) is a relatively understudied antiviral protein capable of inhibiting a broad spectrum of viruses. ISG20 exhibits strong RNase properties, and it belongs to the large family of DEDD exonucleases, present in both prokaryotes and eukaryotes. ISG20 was initially characterized as having strong RNase activity in vitro, suggesting that its inhibitory effects are mediated via direct degradation of viral RNAs. This mechanism of action has since been further elucidated and additional antiviral activities of ISG20 highlighted, including direct degradation of deaminated viral DNA and translational inhibition of viral RNA and nonself RNAs. This review focuses on the current understanding of the main molecular mechanisms of viral inhibition by ISG20 and discusses the latest developments on the features that govern specificity or resistance to its action. [ABSTRACT FROM AUTHOR]

There is growing evidence that epigenetic dysregulation plays a role in neurodevelopmental disorders. In humans, folate is one of the main donors of the methyl group required for the synthesis of S‐adenosylmethionine, which in turn is needed for DNA and histone methylation as key neurodevelopment processes. Folate deficiency during pregnancy has been correlated with neural tube defects and with a higher incidence of neurocognitive and/or neurobehavioral deficits. A similar outcome may be exerted by gene polymorphisms in folate or folate‐related pathways. This has been documented by numerous case/control association studies performed on neurodevelopmental disorders such as autism spectrum disorder and attention deficit hyperactivity disorder. In this regard, the folate cycle represents a "perfect model" of how genetics influences epigenetics. Gene variants in folate and folate‐related pathways can be considered risk factors for neurodevelopmental disorders and should therefore be assessed by genetic testing in pregnant women. High‐risk women should be considered for folate supplementation during pregnancy. Here, we review all published case/control association studies on gene polymorphisms in folate and folate‐related pathways performed on neurodevelopmental disorders, provide an overview of neurodevelopment and DNA methylation changes occurring at this time, and describe the biological basis of neurodevelopmental disorders and recent evidence of their epigenetic dysregulation. [ABSTRACT FROM AUTHOR]