Potential Molecular Mechanisms of Alcohol Use Disorder with Non-Coding RNAs and Gut Microbiota for the Development of Superior Therapeutic Application.

Many investigations have evaluated the expression of noncoding RNAs (ncRNAs) as well as their related molecular functions and biological machineries in individuals with alcohol dependence. Alcohol dependence may be one of the most prevailing psychological disorders globally, and its pathogenesis is intricate and inadequately comprehended. There is substantial evidence indicating significant links between multiple genetic factors and the development of alcohol dependence. In particular, the critical roles of ncRNAs have been emphasized in the pathology of mental illnesses, probably including alcohol dependence. In the comprehension of the action of ncRNAs and their machineries of modification, furthermore, they have emerged as therapeutic targets for a variety of psychiatric illnesses, including alcohol dependence. It is worth mentioning that the dysregulated expression of ncRNAs has been regularly detected in individuals with alcohol dependence. An in-depth knowledge of the roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a more profound understanding of the practical roles of ncRNAs might make important contributions to the precise diagnosis and/or actual management of alcohol dependence. Here, in this review, we mostly focused on up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in individuals with alcohol dependence. Then, we present prospects for future research and therapeutic applications with a novel concept of the engram system.

Recent Progress of Chitosan Nanoparticles for the Development of Superior Delivery of Vaccines.

Chitosan seems to be an innovative biological material potentially utilized as a nanoparticle carrier for drug delivery, which could be low toxic, biocompatible, and easy to prepare. Chitosan nanoparticles have been employed in gene delivery. As a type of multifunctional adjuvant, chitosan nanoparticles could activate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway to induce cell protection and/or proliferation via the modulation of autophagy within dendritic cells. In general, adjuvants may improve the innate and/or adaptive immune responses to a vaccine antigen by facilitating the antigen presentation of antigen presenting cells such as dendritic cells. The choice of a suitable adjuvant has become vital for improved safety and/or expanded application of vaccines. Fortunately, chitosan nanoparticles could be designed to target the dendritic cells to be enhanced by its adjuvant effect and for stimulating robust immune responses. Therefore, chitosan nanoparticles may be a good immune stimulant with encouraging properties for the development of superior vaccine delivery. Indeed, vaccines could play a key role in human health. In this review, we summarize the concept and/or recent progress in the field of chitosan nanoparticles, providing a valuable resource for investigating the molecular mechanisms of chitosan for the development of a greater vaccine.

Inspiring Tactics with the Improvement of Mitophagy and Redox Balance for the Development of Innovative Treatment against Polycystic Kidney Disease.

Polycystic kidney disease (PKD) is the most common genetic form of chronic kidney disease (CKD), and it involves the development of multiple kidney cysts. Not enough medical breakthroughs have been made against PKD, a condition which features regional hypoxia and activation of the hypoxia-inducible factor (HIF) pathway. The following pathology of CKD can severely instigate kidney damage and/or renal failure. Significant evidence verifies an imperative role for mitophagy in normal kidney physiology and the pathology of CKD and/or PKD. Mitophagy serves as important component of mitochondrial quality control by removing impaired/dysfunctional mitochondria from the cell to warrant redox homeostasis and sustain cell viability. Interestingly, treatment with the peroxisome proliferator-activated receptor-α (PPAR-α) agonist could reduce the pathology of PDK and might improve the renal function of the disease via the modulation of mitophagy, as well as the condition of gut microbiome. Suitable modulation of mitophagy might be a favorable tactic for the prevention and/or treatment of kidney diseases such as PKD and CKD.

Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD.

Noncoding RNAs (ncRNAs), including circular RNAs (circRNAs) and N6-methyladenosine (m6A), have been shown to play a critical role in the development of various diseases including obesity and metabolic disorder-associated fatty liver disease (MAFLD). Obesity is a chronic disease caused by excessive fat accumulation in the body, which has recently become more prevalent and is the foremost risk factor for MAFLD. Causes of obesity may involve the interaction of genetic, behavioral, and social factors. m6A RNA methylation might add a novel inspiration for understanding the development of obesity and MAFLD with post-transcriptional regulation of gene expression. In particular, circRNAs, microRNAs (miRNAs), and m6A might be implicated in the progression of MAFLD. Interestingly, m6A modification can modulate the translation, degradation, and other functions of ncRNAs. miRNAs/circRNAs can also modulate m6A modifications by affecting writers, erasers, and readers. In turn, ncRNAs could modulate the expression of m6A regulators in different ways. However, there is limited evidence on how these ncRNAs and m6A interact to affect the promotion of liver diseases. It seems that m6A can occur in DNA, RNA, and proteins that may be associated with several biological properties. This study provides a mechanistic understanding of the association of m6A modification and ncRNAs with liver diseases, especially for MAFLD. Comprehension of the association between m6A modification and ncRNAs may contribute to the development of treatment tactics for MAFLD.

CircRNAs and RNA-Binding Proteins Involved in the Pathogenesis of Cancers or Central Nervous System Disorders.

Circular RNAs (circRNAs), a newly recognized group of noncoding RNA transcripts, have established widespread attention due to their regulatory role in cell signaling. They are covalently closed noncoding RNAs that form a loop, and are typically generated during the splicing of precursor RNAs. CircRNAs are key post-transcriptional and post-translational regulators of gene expression programs that might influence cellular response and/or function. In particular, circRNAs have been considered to function as sponges of specific miRNA, regulating cellular processes at the post-transcription stage. Accumulating evidence has shown that the aberrant expression of circRNAs could play a key role in the pathogenesis of several diseases. Notably, circRNAs, microRNAs, and several RNA-binding proteins, including the antiproliferative (APRO) family proteins, could be indispensable gene modulators, which might be strongly linked to the occurrence of diseases. In addition, circRNAs have attracted general interest for their stability, abundance in the brain, and their capability to cross the blood-brain barrier. Here, we present the current findings and theragnostic potentials of circRNAs in several diseases. With this, we aim to provide new insights to support the development of novel diagnostic and/or therapeutic strategies for these diseases.

Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy.

Mitophagy/autophagy plays a protective role in various forms of liver damage, by renovating cellular metabolism linking to sustain liver homeostasis. A characterized pathway for mitophagy is the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)/Parkin-dependent signaling pathway. In particular, PINK1-mediated mitophagy could play an indispensable role in improving the metabolic dysfunction-associated fatty liver disease (MAFLD) which could precede to steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. In addition, the PI3K/AKT/mTOR pathway might regulate the various characteristics of cellular homeostasis including energy metabolism, cell proliferation, and/or cell protection. Therefore, targeting mitophagy with the alteration of PI3K/AKT/mTOR or PINK1/Parkin-dependent signaling to eliminate impaired mitochondria might be an attractive strategy for the treatment of MAFLD. In particular, the efficacy of prebiotics for the treatment of MAFLD has been suggested to be useful via the modulation of the PI3K/AKT/mTOR/AMPK pathway. Additionally, several edible phytochemicals could activate mitophagy for the improvement of mitochondrial damages, which could also be a promising option to treat MAFLD with providing liver protection. Here, the potential therapeutics with several phytochemicals has been discussed for the treatment of MAFLD. Tactics with a viewpoint of prospective probiotics might contribute to the development of therapeutic interventions.

The Tryptophan and Kynurenine Pathway Involved in the Development of Immune-Related Diseases.

The tryptophan and kynurenine pathway is well-known to play an important role in nervous, endocrine, and immune systems, as well as in the development of inflammatory diseases. It has been documented that some kynurenine metabolites are considered to have anti-oxidative, anti-inflammatory, and/or neuroprotective properties. Importantly, many of these kynurenine metabolites may possess immune-regulatory properties that could alleviate the inflammation response. The abnormal activation of the tryptophan and kynurenine pathway might be involved in the pathophysiological process of various immune-related diseases, such as inflammatory bowel disease, cardiovascular disease, osteoporosis, and/or polycystic ovary syndrome. Interestingly, kynurenine metabolites may be involved in the brain memory system and/or intricate immunity via the modulation of glial function. In the further deliberation of this concept with engram, the roles of gut microbiota could lead to the development of remarkable treatments for the prevention of and/or the therapeutics for various intractable immune-related diseases.

UHRF1, a Regulator of Methylation, as a Diagnostic and Prognostic Marker for Lung Cancer.

We evaluated the value of UHRF1, a regulator of methylation, as a biomarker for lung cancer. UHRF1 is expressed at higher levels in both lung adenocarcinoma (AD) and squamous cell carcinoma (SQ); however, a meta-analysis showed that UHRF1 expression is correlated with worse survival in patients with AD but not in those with SQ. UHRF1 knockdown suppressed the growth of lung cancer cell lines through G1 cell cycle arrest in some cell lines. These results suggest that UHRF1 may server as a diagnostic marker for AD and SQ and as a prognostic marker for AD in lung cancer.