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Cells Aug 2023Although very common, the precise mechanisms that explain the symptomatology of neuroendocrine syncope (NES) remain poorly understood. This disease, which can be very... (Review)
Review
Although very common, the precise mechanisms that explain the symptomatology of neuroendocrine syncope (NES) remain poorly understood. This disease, which can be very incapacitating, manifests itself as a drop in blood pressure secondary to vasodilation and/or extreme slowing of heart rate. As studies continue, the involvement of the adenosinergic system is becoming increasingly evident. Adenosine, which is an ATP derivative, may be involved in a large number of cases. Adenosine acts on G protein-coupled receptors with seven transmembrane domains. A and A adenosine receptor dysfunction seem to be particularly implicated since the activation leads to severe bradycardia or vasodilation, respectively, two cardinal symptoms of NES. This mini-review aims to shed light on the links between dysfunction of the adenosinergic system and NHS. In particular, signal transduction pathways through the modulation of cAMP production and ion channels in relation to effects on the cardiovascular system are addressed. A better understanding of these mechanisms could guide the pharmacological development of new therapeutic approaches.
Topics: Animals; Syncope; Adenosine; Anura; Blood Pressure; Heart Rate
PubMed: 37626837
DOI: 10.3390/cells12162027 -
Cell Death & Disease Nov 2023Cervical cancer (CC) is a gynecological neoplasm with the highest incidence rate, primarily attributed to the persistent infection of high-risk Human papillomavirus... (Review)
Review
Cervical cancer (CC) is a gynecological neoplasm with the highest incidence rate, primarily attributed to the persistent infection of high-risk Human papillomavirus (HPV). Despite extensive research, the pathogenesis of CC remains unclear. N6-methyladenosine (m6A) methylation, the most prevalent form of epigenetic modification in RNA, is intricately linked to cell proliferation, metastasis, metabolism, and therapeutic resistance within the tumor microenvironment (TME) of CC. The involvement of the writer, reader, and eraser in m6A modification impacts the advancement of tumors through the regulation of RNA stability, nuclear export, translation efficiency, and RNA degradation. Here, we discuss the biogenesis of m6A, the atypical expressions of m6A regulators, the mechanisms of molecular interactions, and their functions in CC. Furthermore, we elucidate m6A modification of non-coding RNA. In the context of precision medicine, and with the advancements of genomics, proteomics, and high-throughput sequencing technologies, we summarize the application of m6A in the clinical diagnosis and treatment of CC. Additionally, new perspectives on detection methods, immune regulation, and nano-drug development are presented, which lay the foundation for further research of m6A and provide new ideas for the clinical treatment of CC.
Topics: Humans; Female; Uterine Cervical Neoplasms; Methylation; RNA; Adenosine; Cell Proliferation; Tumor Microenvironment
PubMed: 37951987
DOI: 10.1038/s41419-023-06265-2 -
Frontiers in Immunology 2023Little is known about the molecular profiling associated with the effect of cladribine in patients with multiple sclerosis (MS). Here, we aimed first to characterize the...
INTRODUCTION
Little is known about the molecular profiling associated with the effect of cladribine in patients with multiple sclerosis (MS). Here, we aimed first to characterize the transcriptomic and proteomic profiles induced by cladribine in blood cells, and second to identify potential treatment response biomarkers to cladribine in patients with MS.
METHODS
Gene, protein and microRNA (miRNA) expression profiles were determined by microarrays (genes, miRNAs) and mass spectrometry (proteins) in peripheral blood mononuclear cells (PBMCs) from MS patients after treatment with cladribine in its active and inactive forms. Two bioinformatics approaches to integrate the three obtained datasets were applied: (i) a multiomics discriminant analysis (DIABLO - Data Integration Analysis for Biomarker discovery using Latent variable approaches for Omics studies); and (ii) a multi-stage integration of features selected in differential expression analysis on each dataset and then merged. Selected molecules from the study were quantified by qPCR in PBMCs from MS patients receiving cladribine.
RESULTS
PBMCs treated with cladribine were characterized by a major downregulation of gene, protein, and miRNA expression compared with the untreated cells. An intermediate pattern between the cladribine-treated and untreated conditions was observed in PBMCs treated with cladribine in its inactive form. The differential expression analysis of each dataset led to the identification of four genes and their encoded proteins, and twenty-two miRNAs regulating their expression, that were associated with cladribine treatment. Two of these genes (PPIF and NHLRC2), and three miRNAs (miR-21-5p, miR-30b-5p, and miR-30e-5p) were validated in MS patients treated with cladribine.
DISCUSSION
By using a combination of omics data and bioinformatics approaches we were able to identify a multiomics molecular profile induced by cladribine in PBMCs. We also identified a number of biomarkers that were validated in PBMCs from patients with MS treated with cladribine that have the potential to become treatment response biomarkers to this drug.
Topics: Humans; Cladribine; Multiple Sclerosis; Leukocytes, Mononuclear; Proteomics; MicroRNAs; Biomarkers
PubMed: 37559720
DOI: 10.3389/fimmu.2023.1233546 -
Biomedicine & Pharmacotherapy =... Nov 2023Cancer therapy resistance (CTR) is the development of cancer resistance to multiple therapeutic strategies, which severely affects clinical response and leads to cancer... (Review)
Review
Cancer therapy resistance (CTR) is the development of cancer resistance to multiple therapeutic strategies, which severely affects clinical response and leads to cancer progression, recurrence, and metastasis. N6-methyladenosine (m6A) has been identified as the most common, abundant, and conserved internal transcriptional alterations of RNA modifications, regulating RNA splicing, translation, stabilization, degradation, and gene expression, and is involved in the development and progression of a variety of diseases, including cancer. Recent studies have shown that m6A modifications play a critical role in both cancer development and progression, especially in reversing CTR. Although m6A modifications have great potential in CTR, the specific molecular mechanisms are not fully elucidated. In this review, we summarize the potential molecular mechanisms of m6A modification in CTR. In addition, we update recent advances in natural products from Traditional Chinese Medicines (TCM) and small-molecule lead compounds targeting m6A modifications, and discuss the great potential and clinical implications of these inhibitors targeting m6A regulators and combinations with other therapies to improve clinical efficacy and overcome CTR.
Topics: Humans; Drug Resistance, Neoplasm; Neoplasms; Adenosine; Biological Products
PubMed: 37696088
DOI: 10.1016/j.biopha.2023.115477 -
International Journal of Molecular... Nov 2023The purinergic system has a dual role: the maintenance of energy balance and signaling within cells. Adenosine and adenosine triphosphate (ATP) are essential for... (Review)
Review
The purinergic system has a dual role: the maintenance of energy balance and signaling within cells. Adenosine and adenosine triphosphate (ATP) are essential for maintaining these functions. Sarcopenia is characterized by alterations in the control of energy and signaling in favor of catabolic pathways. This review details the association between the purinergic system and muscle and adipose tissue homeostasis, discussing recent findings in the involvement of purinergic receptors in muscle wasting and advances in the use of the purinergic system as a novel therapeutic target in the management of sarcopenia.
Topics: Humans; Sarcopenia; Adenosine Triphosphate; Adenosine; Receptors, Purinergic; Signal Transduction
PubMed: 38069224
DOI: 10.3390/ijms242316904 -
Natural Product Reports Sep 2023Covering: from 2000 up to the very early part of 2023-Adenosyl-L-methionine (SAM) is a naturally occurring trialkyl sulfonium molecule that is typically associated with... (Review)
Review
Covering: from 2000 up to the very early part of 2023-Adenosyl-L-methionine (SAM) is a naturally occurring trialkyl sulfonium molecule that is typically associated with biological methyltransfer reactions. However, SAM is also known to donate methylene, aminocarboxypropyl, adenosyl and amino moieties during natural product biosynthetic reactions. The reaction scope is further expanded as SAM itself can be modified prior to the group transfer such that a SAM-derived carboxymethyl or aminopropyl moiety can also be transferred. Moreover, the sulfonium cation in SAM has itself been found to be critical for several other enzymatic transformations. Thus, while many SAM-dependent enzymes are characterized by a methyltransferase fold, not all of them are necessarily methyltransferases. Furthermore, other SAM-dependent enzymes do not possess such a structural feature suggesting diversification along different evolutionary lineages. Despite the biological versatility of SAM, it nevertheless parallels the chemistry of sulfonium compounds used in organic synthesis. The question thus becomes how enzymes catalyze distinct transformations subtle differences in their active sites. This review summarizes recent advances in the discovery of novel SAM utilizing enzymes that rely on Lewis acid/base chemistry as opposed to radical mechanisms of catalysis. The examples are categorized based on the presence of a methyltransferase fold and the role played by SAM within the context of known sulfonium chemistry.
Topics: S-Adenosylmethionine; Methyltransferases; Catalysis
PubMed: 36891755
DOI: 10.1039/d2np00086e -
Frontiers in Immunology 2023
Topics: Humans; Adenosine; Immunotherapy; Neoplasms
PubMed: 37885877
DOI: 10.3389/fimmu.2023.1298487 -
Nutrients Dec 2023, also known as "zombie fungus", is a non-poisonous mushroom that parasitizes insects for growth and development by manipulating the host system in a way that makes the... (Review)
Review
, also known as "zombie fungus", is a non-poisonous mushroom that parasitizes insects for growth and development by manipulating the host system in a way that makes the victim behave like a "zombie". These species produce promising bioactive metabolites, like adenosine, β-glucans, cordycepin, and ergosterol. has been used in traditional medicine due to its immense health benefits, as it boosts stamina, appetite, immunity, longevity, libido, memory, and sleep. Neuronal loss is the typical feature of neurodegenerative diseases (NDs) (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS)) and neurotrauma. Both these conditions share common pathophysiological features, like oxidative stress, neuroinflammation, and glutamatergic excitotoxicity. bioactives (adenosine, N-(2-hydroxyethyl)-adenosine, ergosta-7, 9 (11), 22-trien-3β-ol, active peptides, and polysaccharides) exert potential antioxidant, anti-inflammatory, and anti-apoptotic activities and display beneficial effects in the management and/or treatment of neurodegenerative disorders in vitro and in vivo. Although a considerable list of compounds is available from , only a few have been evaluated for their neuroprotective potential and still lack information for clinical trials. In this review, the neuroprotective mechanisms and safety profile of extracts/bioactives have been discussed, which might be helpful in the identification of novel potential therapeutic entities in the future.
Topics: Neuroprotective Agents; Cordyceps; Agaricales; Neuroprotection; Adenosine
PubMed: 38201932
DOI: 10.3390/nu16010102 -
Journal of Orthopaedic Surgery and... Oct 2023N6-methyl adenosine (m6A) is the most common reversible mRNA modification in eukaryotes implicated in key roles in various biological processes. The purpose of our...
BACKGROUND
N6-methyl adenosine (m6A) is the most common reversible mRNA modification in eukaryotes implicated in key roles in various biological processes. The purpose of our analysis was to examine the association of ankylosing spondylitis (AS) with m6A methylation.
METHOD
We obtained 72 samples from the data set GSE73754, including 52 AS patients and 20 healthy people. We divided the samples into two groups: the experimental group and the control group, and then observed the differences of 26 m6A related genes in the two groups. We also analyzed the correlation between different m6A genes. We used a random forest tree model to screen seven m6A signature genes associated with AS to evaluate its prevalence. Next, the samples were classified according to the m6a content and differential genes. Immune analysis, gene ontology, and KEGG enrichment analyses were performed. Finally, we scored each sample with m6a and analyzed the relationship between different samples and inflammation-related factors.
RESULTS AND CONCLUSION
In conclusion, we screened out AS-related genes and the nomogram showed that they were negatively correlated with the incidence of AS. And we found that AS may have some relationship with immunity. Our analysis results could provide further insights into the treatment of AS.
Topics: Humans; Methylation; Spondylitis, Ankylosing; Inflammation; Adenosine; Gene Ontology
PubMed: 37805597
DOI: 10.1186/s13018-023-04254-x -
Science Advances Sep 2023-methyladenosine (mA) is the most abundant modification on messenger RNAs (mRNAs) and is catalyzed by methyltransferase-like protein 3 (Mettl3). To understand the role...
-methyladenosine (mA) is the most abundant modification on messenger RNAs (mRNAs) and is catalyzed by methyltransferase-like protein 3 (Mettl3). To understand the role of mA in a self-renewing somatic tissue, we deleted in epidermal progenitors in vivo. Mice lacking demonstrate marked features of dysfunctional development and self-renewal, including a loss of hair follicle morphogenesis and impaired cell adhesion and polarity associated with oral ulcerations. We show that Mettl3 promotes the mA-mediated degradation of mRNAs encoding critical histone modifying enzymes. Depletion of Mettl3 results in the loss of mA on these mRNAs and increases their expression and associated modifications, resulting in widespread gene expression abnormalities that mirror the gross phenotypic abnormalities. Collectively, these results have identified an additional layer of gene regulation within epithelial tissues, revealing an essential role for mA in the regulation of chromatin modifiers, and underscoring a critical role for Mettl3-catalyzed mA in proper epithelial development and self-renewal.
Topics: Animals; Mice; Histones; Methyltransferases; Adenosine; Cell Adhesion; RNA, Messenger; Catalysis
PubMed: 37656787
DOI: 10.1126/sciadv.adg5234