The Regulation Mechanisms and Clinical Application of MicroRNAs in Myocardial Infarction: A Review of the Recent 5 Years

Myocardial infarction (MI) is the most frequent end-point of cardiovascular pathology, leading to higher mortality worldwide. Due to the particularity of the heart tissue, patients who experience ischemic infarction of the heart, still suffered irreversible damage to the heart even if the vascular reflow by treatment, and severe ones can lead to heart failure or even death. In recent years, several studies have shown that microRNAs (miRNAs), playing a regulatory role in damaged hearts, bring light for patients to alleviate MI. In this review, we summarized the effect of miRNAs on MI with some mechanisms, such as apoptosis, autophagy, proliferation, inflammatory; the regulation of miRNAs on cardiac structural changes after MI, including angiogenesis, myocardial remodeling, fibrosis; the application of miRNAs in stem cell therapy and clinical diagnosis; other non-coding RNAs related to miRNAs in MI during the past 5 years.

Adipose Stem Cell-Based Treatments for Wound Healing

Wound healing is one of the most complex physiological regulation mechanisms of the human body. Stem cell technology has had a significant impact on regenerative medicine. Adipose stem cells (ASCs) have many advantages, including their ease of harvesting and high yield, rich content of cell components and cytokines, and strong practicability. They have rapidly become a favored tool in regenerative medicine. Here, we summarize the mechanism and clinical therapeutic potential of ASCs in wound repair.

Research Advances in Multi-Omics on the Traditional Chinese Herb Dendrobium officinale

Dendrobium officinale Kimura et Migo is an important epiphytic plant, belonging to the Orchidaceae family. There are various bioactive components in D. officinale plants, mainly including polysaccharides, alkaloids, and phenolic compounds. These compounds have been demonstrated to possess multiple functions, such as anti-oxidation, immune regulation, and anti-cancer. Due to serious shortages of wild resources, deterioration of cultivated germplasm and the unstable quality of D. officinale, the study has been focused on the biosynthetic pathway and regulation mechanisms of bioactive compounds. In recent years, with rapid developments in detection technologies and analysis tools, omics research including genomics, transcriptomics, proteomics and metabolomics have all been widely applied in various medicinal plants, including D. officinale. Many important advances have been achieved in D. officinale research, such as chromosome-level reference genome assembly and the identification of key genes involved in the biosynthesis of active components. In this review, we summarize the latest research advances in D. officinale based on multiple omics studies. At the same time, we discuss limitations of the current research. Finally, we put forward prospective topics in need of further study on D. officinale.

Myeloid Fbxw7 Prevents Pulmonary Fibrosis by Suppressing TGF-β Production

Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by an inexorable decline in lung function with limited treatment options. The abnormal expression of transforming growth factor-β (TGF-β) in profibrotic macrophages is linked to severe pulmonary fibrosis, but the regulation mechanisms of TGF-β expression are incompletely understood. We found that decreased expression of E3 ubiquitin ligase Fbxw7 in peripheral blood mononuclear cells (PBMCs) was significantly related to the severity of pulmonary fibrosis in IPF patients. Fbxw7 is identified to be a crucial suppressing factor for pulmonary fibrosis development and progression in a mouse model induced by intratracheal bleomycin treatment. Myeloid cell-specific Fbxw7 deletion increases pulmonary monocyte-macrophages accumulation in lung tissue, and eventually promotes bleomycin-induced collagen deposition and progressive pulmonary fibrosis. Notably, the expression of TGF-β in profibrotic macrophages was significantly upregulated in myeloid cell-specific Fbxw7 deletion mice after bleomycin treatment. C-Jun has long been regarded as a critical transcription factor of Tgfb1, we clarified that Fbxw7 inhibits the expression of TGF-β in profibrotic macrophages by interacting with c-Jun and mediating its K48-linked ubiquitination and degradation. These findings provide insight into the role of Fbxw7 in the regulation of macrophages during the pathogenesis of pulmonary fibrosis.

Two LysR family transcriptional regulators, McbH and McbN, activate the operons responsible for the midstream and downstream pathways of carbaryl degradation in Pseudomonas sp. strain XWY-1, respectively

Previously, a LysR family transcriptional regulator McbG that activates the mcbBCDEF gene cluster involved in the upstream pathway (from carbaryl to salicylate) of carbaryl degradation in Pseudomonas sp. strain XWY-1 has been identified by us ( Appl. Environ. Microbiol. 2021, 87(9): e02970-20.). In this study, we identified McbH and McbN, which activate mcbIJKLM cluster (responsible for the midstream pathway, from salicylate to gentisate) and mcbOPQ cluster (responsible for the downstream pathway, from gentisate to pyruvate and fumarate), respectively. They both belong to the LysR family of transcriptional regulators. Gene disruption and complementation study reveal that McbH is essential for transcription of the mcbIJKLM cluster in response to salicylate and McbN is indispensable for the transcription of the mcbOPQ cluster in response to gentisate. The results of electrophoretic mobility shift assay (EMSA) and DNase I footprinting showed that McbH binds to the 52-bp motif in the mcbIJKLM promoter area and McbN binds to the 58-bp motif in the mcbOPQ promoter area. The key sequence of McbH binding to mcbIJKLM promoter is a 13-bp motif that conforms to the typical characteristics of LysR family. However, the 12-bp motif that is different from the typical characteristics of the LysR family regulator binding site sequence is identified as the key sequence for McbN to bind to the mcbOPQ promoter. This study reveals the regulatory mechanism for the midstream and downstream pathway of carbaryl degradation in strain XWY-1 and further enriches the members of the LysR transcription regulator family. IMPORTANCE: The enzyme-encoding genes involved in the complete degradation pathway of carbaryl in Pseudomonas sp. strain XWY-1 include mcbABCDEF , mcbIJKLM and mcbOPQ . Previous studies demonstrated that the mcbA gene responsible for hydrolysis of carbaryl to 1-naphthol is constitutively expressed and the transcription of mcbBCDEF was regulated by McbG. However, the transcription regulation mechanisms of mcbIJKLM and mcbOPQ have not been investigated yet. In this study, we identified two LysR-type transcriptional regulators, McbH and McbN, which activate the mcbIJKLM cluster responsible for the degradation of salicylate to gentisate and mcbOPQ cluster responsible for the degradation of gentisate to pyruvate and fumarate, respectively. The 13-bp motif is critical for McbH to bind to the promoter of mcbIJKLM , and 12-bp motif different from the typical characteristics of the LTTR binding sequence affects the binding of McbN to promoter. These findings help to expand the understanding of the regulatory mechanism of microbial degradation of carbaryl.

Explore synergistic and competitive miRNA regulation mechanisms in the miRNA-mRNA regulatory network from the information decomposition perspective

Since multiple microRNAs can target 3' untranslated regions of the same mRNA transcript, it is likely that these endogenous microRNAs may form synergistic alliances, or compete for the same mRNA harbouring overlapping binding site matches. Synergistic and competitive microRNA regulation is an intriguing yet poorly elucidated mechanism. We here introduce a computational method based on the multivariate information measurement to quantify such implicit interaction effects between microRNAs. Our informatics method of integrating sequence and expression data is designed to establish the functional correlation between microRNAs. To demonstrate our method, we exploited TargetScan and The Cancer Genome Atlas data. As a result, we indeed observed that the microRNA pair with neighbouring binding site(s) on the mRNA is likely to trigger synergistic events, while the microRNA pair with overlapping binding site(s) on the mRNA is likely to cause competitive events, provided that the pair of microRNAs has a high functional similarity and the corresponding triplet presents a positive/negative 'synergy-redundancy' score.

NAPRT Expression Regulation Mechanisms: Novel Functions Predicted by a Bioinformatics Approach

The nicotinate phosphoribosyltransferase (NAPRT) gene has gained relevance in the research of cancer therapeutic strategies due to its main role as a NAD biosynthetic enzyme. NAD metabolism is an attractive target for the development of anti-cancer therapies, given the high energy requirements of proliferating cancer cells and NAD-dependent signaling. A few studies have shown that NAPRT expression varies in different cancer types, making it imperative to assess NAPRT expression and functionality status prior to the application of therapeutic strategies targeting NAD. In addition, the recent finding of NAPRT extracellular form (eNAPRT) suggested the involvement of NAPRT in inflammation and signaling. However, the mechanisms regulating NAPRT gene expression have never been thoroughly addressed. In this study, we searched for NAPRT gene expression regulatory mechanisms in transcription factors (TFs), RNA binding proteins (RBPs) and microRNA (miRNAs) databases. We identified several potential regulators of NAPRT transcription activation, downregulation and alternative splicing and performed GO and expression analyses. The results of the functional analysis of TFs, RBPs and miRNAs suggest new, unexpected functions for the NAPRT gene in cell differentiation, development and neuronal biology.

Targeting Epigenetics and Non-coding RNAs in Myocardial Infarction: From Mechanisms to Therapeutics

Myocardial infarction (MI) is a complicated pathology triggered by numerous environmental and genetic factors. Understanding the effect of epigenetic regulation mechanisms on the cardiovascular disease would advance the field and promote prophylactic methods targeting epigenetic mechanisms. Genetic screening guides individualised MI therapies and surveillance. The present review reported the latest development on the epigenetic regulation of MI in terms of DNA methylation, histone modifications, and microRNA-dependent MI mechanisms and the novel therapies based on epigenetics.

Endophytic Fungi: From Symbiosis to Secondary Metabolite Communications or Vice Versa?

Endophytic fungi (EF) are a group of fascinating host-associated fungal communities that colonize the intercellular or intracellular spaces of host tissues, providing beneficial effects to their hosts while gaining advantages. In recent decades, accumulated research on endophytic fungi has revealed their biodiversity, wide-ranging ecological distribution, and multidimensional interactions with host plants and other microbiomes in the symbiotic continuum. In this review, we highlight the role of secondary metabolites (SMs) as effectors in these multidimensional interactions, and the biosynthesis of SMs in symbiosis via complex gene expression regulation mechanisms in the symbiotic continuum and via the mimicry or alteration of phytochemical production in host plants. Alternative biological applications of SMs in modern medicine, agriculture, and industry and their major classes are also discussed. This review recapitulates an introduction to the research background, progress, and prospects of endophytic biology, and discusses problems and substantive challenges that need further study.