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Base excision repair (BER) corrects forms of oxidative, deamination, alkylation, and abasic single-base damage that appear to have minimal effects on the helix. Since its discovery in 1974, the field has grown in several facets: mechanisms, biology and physiology, understanding deficiencies and human disease, and using BER genes as potential inhibitory targets to develop therapeutics. Within its segregation of short nucleotide (SN-) and long patch (LP-), there are currently six known global mechanisms, with emerging work in transcription- and replication-associated BER. Knockouts (KOs) of BER genes in mouse models showed that single glycosylase knockout had minimal phenotypic impact, but the effects were clearly seen in double knockouts. However, KOs of downstream enzymes showed critical impact on the health and survival of mice. BER gene deficiency contributes to cancer, inflammation, aging, and neurodegenerative disorders. Medicinal targets are being developed for single or combinatorial therapies, but only PARP and APE1 have yet to reach the clinical stage.

Metabolic Dysfunction-Associated Steatotic Liver (MASL), previously named nonalcoholic fatty liver (NAFL), is a multifactorial disease in which metabolic, genetic, and environmental risk factors play a predominant role. Obesity and type 2 diabetes act as triggers of the inflammatory response, which contributes to the progression of MASL to Metabolic Dysfunction-Associated Steatohepatitis and the development of hepatocellular carcinoma. In the liver, several parenchymal, nonparenchymal, and immune cells maintain immunological homeostasis, and different regulatory pathways balance the activation of the innate and adaptative immune system. PD-1/PD-L1 signaling acts, in the maintenance of the balance between the immune responses and the tissue immune homeostasis, promoting self-tolerance through the modulation of activated T cells. Recently, PD-1 has received much attention for its roles in inducing an exhausted T cells phenotype, promoting the tumor escape from immune responses. Indeed, in MASLD, the excessive fat accumulation dysregulates the immune system, increasing cytotoxic lymphocytes and decreasing their cytolytic activity. In this context, T cells exacerbate liver damage and promote tumor progression. The aim of this review is to illustrate the main pathogenetic mechanisms by which the immune system promotes the progression of MASLD and the transition to HCC, as well as to discuss the possible therapeutic applications of PD-1/PD-L1 target therapy to activate T cells and reinvigorate immune surveillance against cancer. [ABSTRACT FROM AUTHOR]

Mitochondria are commonly perceived as "cellular power plants". Intriguingly, power conversion is not their only function. In the first part of this paper, we review the role of mitochondria in the evolution of eukaryotic organisms and in the regulation of the human body, specifically focusing on cancer and autism in relation to mitochondrial dysfunction. In the second part, we overview our previous works, revealing the physical principles of operation for proton-pumping complexes in the inner mitochondrial membrane. Our proposed simple models reveal the physical mechanisms of energy exchange. They can be further expanded to answer open questions about mitochondrial functions and the medical treatment of diseases associated with mitochondrial disorders. [ABSTRACT FROM AUTHOR]

This document is an editorial for a special issue of the International Journal of Molecular Sciences focused on current research on cancer biology and therapeutics. The editorial highlights the significance of cancer as a major health problem, with millions of deaths and patients expected in the future. The special issue presents various compounds and strategies that show promise in targeting and treating different types of cancer, including colon cancer, colorectal cancer, papillary thyroid carcinoma, liver cancer, Ewing sarcoma, cholangiocarcinoma, melanoma, and hepatocellular carcinoma. The studies discussed in the special issue explore the potential of these compounds to inhibit tumor growth, promote apoptosis, block cancer cell proliferation and migration, and target specific molecular mechanisms involved in cancer development. The editorial emphasizes the importance of these findings in improving cancer diagnosis and treatment and suggests that further research and development in these areas could lead to more effective therapies and better outcomes for cancer patients. [Extracted from the article]

Atherosclerotic cardiovascular disease (ASCVD) stands as the leading global cause of mortality. Addressing this vital and pervasive condition requires a multifaceted approach, in which antiplatelet intervention plays a pivotal role, together with antihypertensive, antidiabetic, and lipid-lowering therapies. Among the antiplatelet agents available currently, cilostazol, a phosphodiesterase-3 inhibitor, offers a spectrum of pharmacological effects. These encompass vasodilation, the impediment of platelet activation and aggregation, thrombosis inhibition, limb blood flow augmentation, lipid profile enhancement through triglyceride reduction and high-density lipoprotein cholesterol elevation, and the suppression of vascular smooth muscle cell proliferation. However, the role of cilostazol has not been clearly documented in many guidelines for ASCVD. We comprehensively reviewed the cardiovascular effects of cilostazol within randomized clinical trials that compared it to control or active agents and involved individuals with previous coronary artery disease or stroke, as well as those with no previous history of such conditions. Our approach demonstrated that the administration of cilostazol effectively reduced adverse cardiovascular events, although there was less evidence regarding its impact on myocardial infarction. Most studies have consistently reported its favorable effects in reducing intermittent claudication and enhancing ambulatory capacity in patients with peripheral arterial disease. Furthermore, cilostazol has shown promise in mitigating restenosis following coronary stent implantation in patients with acute coronary syndrome. While research from more diverse regions is still needed, our findings shed light on the broader implications of cilostazol in the context of atherosclerosis and vascular biology, particularly for individuals at high risk of ASCVD. [ABSTRACT FROM AUTHOR]

Gliomas are diffusely infiltrating brain tumors whose prognosis is strongly influenced by their extent of invasion into the surrounding brain tissue. While lower-grade gliomas present more circumscribed borders, high-grade gliomas are aggressive tumors with widespread brain infiltration and dissemination. Glioblastoma (GBM) is known for its high invasiveness and association with poor prognosis. Its low survival rate is due to the certainty of its recurrence, caused by microscopic brain infiltration which makes surgical eradication unattainable. New insights into GBM biology at the single-cell level have enabled the identification of mechanisms exploited by glioma cells for brain invasion. In this review, we explore the current understanding of several molecular pathways and mechanisms used by tumor cells to invade normal brain tissue. We address the intrinsic biological drivers of tumor cell invasion, by tackling how tumor cells interact with each other and with the tumor microenvironment (TME). We focus on the recently discovered neuronal niche in the TME, including local as well as distant neurons, contributing to glioma growth and invasion. We then address the mechanisms of invasion promoted by astrocytes and immune cells. Finally, we review the current literature on the therapeutic targeting of the molecular mechanisms of invasion. [ABSTRACT FROM AUTHOR]

This comprehensive review delves into the multifaceted roles of mesenchymal stem cells (MSCs) in leukemia, focusing on their interactions within the bone marrow microenvironment and their impact on leukemia pathogenesis, progression, and treatment resistance. MSCs, characterized by their ability to differentiate into various cell types and modulate the immune system, are integral to the BM niche, influencing hematopoietic stem cell maintenance and functionality. This review extensively explores the intricate relationship between MSCs and leukemic cells in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia. This review also addresses the potential clinical applications of MSCs in leukemia treatment. MSCs' role in hematopoietic stem cell transplantation, their antitumor effects, and strategies to disrupt chemo-resistance are discussed. Despite their therapeutic potential, the dual nature of MSCs in promoting and inhibiting tumor growth poses significant challenges. Further research is needed to understand MSCs' biological mechanisms in hematologic malignancies and develop targeted therapeutic strategies. This in-depth exploration of MSCs in leukemia provides crucial insights for advancing treatment modalities and improving patient outcomes in hematologic malignancies. [ABSTRACT FROM AUTHOR]

Two novel virulent phages of the genus Obolenskvirus infecting Acinetobacter baumannii, a significant nosocomial pathogen, have been isolated and studied. Phages Brutus and Scipio were able to infect A. baumannii strains belonging to the K116 and K82 capsular types, respectively. The biological properties and genomic organization of the phages were characterized. Comparative genomic, phylogenetic, and pangenomic analyses were performed to investigate the relationship of Brutus and Scipio to other bacterial viruses and to trace the possible origin and evolutionary history of these phages and other representatives of the genus Obolenskvirus. The investigation of enzymatic activity of the tailspike depolymerase encoded in the genome of phage Scipio, the first reported virus infecting A. baumannii of the K82 capsular type, was performed. The study of new representatives of the genus Obolenskvirus and mechanisms of action of depolymerases encoded in their genomes expands knowledge about the diversity of viruses within this taxonomic group and strategies of Obolenskvirus–host bacteria interaction. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are nanoparticles released from various cell types that have emerged as powerful new therapeutic option for a variety of diseases. EVs are involved in the transmission of biological signals between cells and in the regulation of a variety of biological processes, highlighting them as potential novel targets/platforms for therapeutics intervention and/or delivery. Therefore, it is necessary to investigate new aspects of EVs' biogenesis, biodistribution, metabolism, and excretion as well as safety/compatibility of both unmodified and engineered EVs upon administration in different pharmaceutical dosage forms and delivery systems. In this review, we summarize the current knowledge of essential physiological and pathological roles of EVs in different organs and organ systems. We provide an overview regarding application of EVs as therapeutic targets, therapeutics, and drug delivery platforms. We also explore various approaches implemented over the years to improve the dosage of specific EV products for different administration routes. [ABSTRACT FROM AUTHOR]

Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in endocrine and non-endocrine tissues, immune cells and the central nervous system (CNS). Post-release from secretory or immune cells, the first most appreciated role that SST exhibits is the antiproliferative effect in target tissue that served as a potential therapeutic intervention in various tumours of different origins. The SST-mediated in vivo and/or in vitro antiproliferative effect in the tumour is considered direct via activation of five different somatostatin receptor subtypes (SSTR1-5), which are well expressed in most tumours and often more than one receptor in a single cell. Second, the indirect effect is associated with the regulation of growth factors. SSTR subtypes are crucial in tumour diagnosis and prognosis. In this review, with the recent development of new SST analogues and receptor-specific agonists with emerging functional consequences of signaling pathways are promising therapeutic avenues in tumours of different origins that are discussed. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is a complex process that develops in chronic liver diseases. Even though the initiation and progression of fibrosis rely on the underlying etiology, mutual mechanisms can be recognized and targeted for therapeutic purposes. Irrespective of the primary cause of liver disease, persistent damage to parenchymal cells triggers the overproduction of reactive species, with the consequent disruption of redox balance. Reactive species are important mediators for the homeostasis of both hepatocytes and non-parenchymal liver cells. Indeed, other than acting as cytotoxic agents, reactive species are able to modulate specific signaling pathways that may be relevant to hepatic fibrogenesis. After a brief introduction to redox biology and the mechanisms of fibrogenesis, this review aims to summarize the current evidence of the involvement of redox-dependent pathways in liver fibrosis and focuses on possible therapeutic targets. [ABSTRACT FROM AUTHOR]

There is growing evidence that various ATP-binding cassette (ABC) transporters contribute to the growth and development of tumors, but relatively little is known about how the ABC transporter family behaves in hepatocellular carcinoma (HCC), one of the most common cancers worldwide. Cellular model studies have shown that ABCC6, which belongs to the ABC subfamily C (ABCC), plays a role in the cytoskeleton rearrangement and migration of HepG2 hepatocarcinoma cells, thus highlighting its role in cancer biology. Deep knowledge on the molecular mechanisms underlying the observed results could provide therapeutic insights into the tumors in which ABCC6 is modulated. In this study, differential expression levels of mRNA transcripts between ABCC6-silenced HepG2 and control groups were measured, and subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Real-Time PCR and Western blot analyses confirmed bioinformatics; functional studies support the molecular mechanisms underlying the observed effects. The results provide valuable information on the dysregulation of fundamental cellular processes, such as the focal adhesion pathway, which allowed us to obtain detailed information on the active role that the down-regulation of ABCC6 could play in the biology of liver tumors, as it is involved not only in cell migration but also in cell adhesion and invasion. [ABSTRACT FROM AUTHOR]

The global cancer burden remains high; thus, a better understanding of the molecular mechanisms driving carcinogenesis is needed to improve current prevention and treatment options. We previously detected the ZNF643/ZFP69B gene upregulated in multiple tumors, and we speculated it may play a role in tumor biology. To test this hypothesis, we employed TCGA-centered databases to correlate ZNF643 status with various clinicopathological parameters. We also performed RNA-seq analysis and in vitro studies assessing cancer cell phenotypes, and we searched for ZNF643-bound genomic loci. Our data indicated higher levels of ZNF643 in most analyzed tumors compared to normal samples, possibly due to copy number variations. ZNF643 mRNA correlated with diverse molecular and immune subtypes and clinicopathological features (tumor stage, grade, patient survival). RNA-seq analysis revealed that ZNF643 silencing triggers the deregulation of the genes implicated in various cancer-related processes, such as growth, adhesion, and immune system. Moreover, we observed that ZNF643 positively influences cell cycle, migration, and invasion. Finally, our ChIP-seq analysis indicated that the genes associated with ZNF643 binding are linked to adhesion and immune signaling. In conclusion, our data confirm the oncogenic properties of ZNF643 and pinpoint its impact on cell adhesion and immune processes. [ABSTRACT FROM AUTHOR]

The International Journal of Molecular Sciences has published a special issue titled "Carnivorous Plant Biology: From Gene to Traps." The issue includes six contributions, including five original articles and one review, covering various aspects of carnivorous plant biology such as phytochemistry, physiology, cytology, and ecology. The articles explore topics such as secondary metabolites in the Sarraceniaceae family, the interaction between an aquatic carnivorous plant and a crustacean, the trapping system of the Byblis genus, the photosynthetic efficiencies of sundew species, and the morphology of Pinguicula species. These studies provide new insights into the biology of carnivorous plants and their ecological interactions. [Extracted from the article]

Fibrous dysplasia (FD) is a rare, non-hereditary skeletal disorder characterized by its chronic course of non-neoplastic fibrous tissue buildup in place of healthy bone. A myriad of factors have been associated with its onset and progression. Perturbation of cell–cell signaling networks and response outputs leading to disrupted building blocks, incoherent multi-level organization, and loss of rigid structural motifs in mineralized tissues are factors that have been identified to participate in FD induction. In more recent years, novel insights into the unique biology of FD are transforming our understandings of its pathology, natural discourse of the disease, and treatment prospects. Herein, we built upon existing knowledge with recent findings to review clinical, etiologic, and histological features of FD and discussed known and potential mechanisms underlying FD manifestations. Subsequently, we ended on a note of optimism by highlighting emerging therapeutic approaches aimed at either halting or ameliorating disease progression. [ABSTRACT FROM AUTHOR]

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most challenging malignancies to treat, with a complex interplay of molecular pathways contributing to its aggressive nature. Galectin-1 (Gal-1), a member of the galectin family, has emerged as a pivotal player in the PDAC microenvironment, influencing various aspects from tumor growth and angiogenesis to immune modulation. This review provides a comprehensive overview of the multifaceted role of Galectin-1 in PDAC. We delve into its contributions to tumor stroma remodeling, angiogenesis, metabolic reprogramming, and potential implications for therapeutic interventions. The challenges associated with targeting Gal-1 are discussed, given its pleiotropic functions and complexities in different cellular conditions. Additionally, the promising prospects of Gal-1 inhibition, including the utilization of nanotechnology and theranostics, are highlighted. By integrating recent findings and shedding light on the intricacies of Gal-1's involvement in PDAC, this review aims to provide insights that could guide future research and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Tendon aging is associated with an increasing prevalence of tendon injuries and/or chronic tendon diseases, such as tendinopathy, which affects approximately 25% of the adult population. Aged tendons are often characterized by a reduction in the number and functionality of tendon stem/progenitor cells (TSPCs), fragmented or disorganized collagen bundles, and an increased deposition of glycosaminoglycans (GAGs), leading to pain, inflammation, and impaired mobility. Although the exact pathology is unknown, overuse and microtrauma from aging are thought to be major causative factors. Due to the hypovascular and hypocellular nature of the tendon microenvironment, healing of aged tendons and related injuries is difficult using current pain/inflammation and surgical management techniques. Therefore, there is a need for novel therapies, specifically cellular therapy such as cell rejuvenation, due to the decreased regenerative capacity during aging. To augment the therapeutic strategies for treating tendon-aging-associated diseases and injuries, a comprehensive understanding of tendon aging pathology is needed. This review summarizes age-related tendon changes, including cell behaviors, extracellular matrix (ECM) composition, biomechanical properties and healing capacity. Additionally, the impact of conventional treatments (diet, exercise, and surgery) is discussed, and recent advanced strategies (cell rejuvenation) are highlighted to address aged tendon healing. This review underscores the molecular and cellular linkages between aged tendon biomechanical properties and the healing response, and provides an overview of current and novel strategies for treating aged tendons. Understanding the underlying rationale for future basic and translational studies of tendon aging is crucial to the development of advanced therapeutics for tendon regeneration. [ABSTRACT FROM AUTHOR]

The chorioallantoic membrane (CAM) can be used as a valuable research tool to examine tumors. The CAM can be used to investigate processes such as migration, invasion, and angiogenesis and to assess novel antitumor drugs. The CAM can be used to establish tumors in a straightforward, rapid, and cost-effective manner via xenotransplantation of cells or tumor tissues with reproducible results; furthermore, the use of the CAM adheres to the three "R" principle, i.e., replace, reduce, and refine. To achieve successful tumor establishment and survival, several technical aspects should be taken into consideration. The complexity and heterogeneity of diseases including neuroblastoma and cancers in general and their impact on human health highlight the importance of preclinical models that help us describe tumor-specific biological processes. These models will not only help in understanding tumor biology, but also allow clinicians to explore therapeutic alternatives that will improve current treatment strategies. In this review, we summarize the technical characteristics as well as the main findings regarding the use of this model to study neuroblastoma for angiogenesis, metastasis, drug sensitivity, and drug resistance. [ABSTRACT FROM AUTHOR]

Aging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. Although not usually considered a pathogenic event, photoaging affects cutaneous biology, increasing the risk of skin carcinogenesis. At the cellular level, aging is typified by the rise of senescence cells a condition characterized by reduced or absent capacity to proliferate and aberrant hyper-secretory activity. Senescence has a double-edged sword in cancer biology given that senescence prevents the uncontrolled proliferation of damaged cells and favors their clearance by paracrine secretion. Nevertheless, the cumulative insults and the poor clearance of injured cells in the elderly increase cancer incidence. However, there are not conclusive data proving that aged skin represents a permissive milieu for tumor onset. On the other hand, tumor cells are capable of activating resident fibroblasts onto a pro-tumorigenic phenotype resembling those of senescent fibroblasts suggesting that aged fibroblasts might facilitate cancer progression. This review discusses changes that occur during aging that can prime neoplasm or increase the aggressiveness of melanoma and non-melanoma skin cancer. [ABSTRACT FROM AUTHOR]

Pitaya (Hylocereus spp.) is a member of the cactus family that is native to Central and South America but is now cultivated throughout the sub-tropical and tropical regions of the world. It is of great importance due to its nutritional, ornamental, coloring, medicinal, industrial, and high consumption values. In order to effectively utilize and develop the available genetic resources, it is necessary to appreciate and understand studies pertaining to the usage, origin, nutrition, diversity, evaluation, characterization, conservation, taxonomy, and systematics of the genus Hylocereus. Additionally, to gain a basic understanding of the biology of the plant, this review has also discussed how biotechnological tools, such as cell and tissue culture, micropropagation (i.e., somatic embryogenesis, organogenesis, somaclonal variation, mutagenesis, androgenesis, gynogenesis, and altered ploidy), virus-induced gene silencing, and molecular marker technology, have been used to enhance pitaya germplasm. [ABSTRACT FROM AUTHOR]

Chemical exposure can profoundly affect our health, some being voluntary (food and drugs) and some involuntary (environmental contaminants) [...].

HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, supporting a re-consideration of immunohistochemical negative scores of 0, 1+ and the 2+/in situ hybridization (ISH) negative phenotype. In the present review, we outline the criteria needed to exactly distinguish HER2-low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody–drug conjugates (ADCs) in treating these groups of tumors. In particular, trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC, has been recently approved by the US Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06 trial, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally, we hope that new guidelines may help to codify HER2-low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) hold unique biological characteristics that directly involve them in hematogenous dissemination. Studying CTCs systematically is technically challenging due to their extreme rarity and heterogeneity and the lack of specific markers to specify metastasis-initiating CTCs. With cutting-edge technology, single-cell RNA sequencing (scRNA-seq) provides insights into the biology of metastatic processes driven by CTCs. Transcriptomics analysis of single CTCs can decipher tumor heterogeneity and phenotypic plasticity for exploring promising novel therapeutic targets. The integrated approach provides a perspective on the mechanisms underlying tumor development and interrogates CTCs interactions with other blood cell types, particularly those of the immune system. This review aims to comprehensively describe the current study on CTC transcriptomic analysis through scRNA-seq technology. We emphasize the workflow for scRNA-seq analysis of CTCs, including enrichment, single cell isolation, and bioinformatic tools applied for this purpose. Furthermore, we elucidated the translational knowledge from the transcriptomic profile of individual CTCs and the biology of cancer metastasis for developing effective therapeutics through targeting key pathways in CTCs. [ABSTRACT FROM AUTHOR]

Biodiversity within the animal kingdom is associated with extensive molecular diversity. The expansion of genomic, transcriptomic and proteomic data sets for invertebrate groups and species with unique biological traits necessitates reliable in silico tools for the accurate identification and annotation of molecules and molecular groups. However, conventional tools are inadequate for lesser-known organismal groups, such as eukaryotic pathogens (parasites), so that improved approaches are urgently needed. Here, we established a combined sequence- and structure-based workflow system to harness well-curated publicly available data sets and resources to identify, classify and annotate proteases and protease inhibitors of a highly pathogenic parasitic roundworm (nematode) of global relevance, called Haemonchus contortus (barber's pole worm). This workflow performed markedly better than conventional, sequence-based classification and annotation alone and allowed the first genome-wide characterisation of protease and protease inhibitor genes and gene products in this worm. In total, we identified 790 genes encoding 860 proteases and protease inhibitors representing 83 gene families. The proteins inferred included 280 metallo-, 145 cysteine, 142 serine, 121 aspartic and 81 "mixed" proteases as well as 91 protease inhibitors, all of which had marked physicochemical diversity and inferred involvements in >400 biological processes or pathways. A detailed investigation revealed a remarkable expansion of some protease or inhibitor gene families, which are likely linked to parasitism (e.g., host–parasite interactions, immunomodulation and blood-feeding) and exhibit stage- or sex-specific transcription profiles. This investigation provides a solid foundation for detailed explorations of the structures and functions of proteases and protease inhibitors of H. contortus and related nematodes, and it could assist in the discovery of new drug or vaccine targets against infections or diseases. [ABSTRACT FROM AUTHOR]

Mechanical unloading during microgravity causes skeletal muscle atrophy and impairs mitochondrial energetics. The elevated production of reactive oxygen species (ROS) by mitochondria and Nox2, coupled with impairment of stress protection (e.g., SIRT1, antioxidant enzymes), contribute to atrophy. We tested the hypothesis that the SIRT1 activator, SRT2104 would rescue unloading-induced mitochondrial dysfunction. Mitochondrial function in rat gastrocnemius and soleus muscles were evaluated under three conditions (10 days): ambulatory control (CON), hindlimb unloaded (HU), and hindlimb-unloaded-treated with SRT2104 (SIRT). Oxidative phosphorylation, electron transfer capacities, H2O2 production, and oxidative and antioxidant enzymes were quantified using high-resolution respirometry and colorimetry. In the gastrocnemius, (1) integrative (per mg tissue) proton LEAK was lesser in SIRT than in HU or CON; (2) intrinsic (relative to citrate synthase) maximal noncoupled electron transfer capacity (ECI+II) was lesser, while complex I-supported oxidative phosphorylation to ECI+II was greater in HU than CON; (3) the contribution of LEAK to ECI+II was greatest, but cytochrome c oxidase activity was lowest in HU. In both muscles, H2O2 production and concentration was greatest in SIRT, as was gastrocnemius superoxide dismutase activity. In the soleus, H2O2 concentration was greater in HU compared to CON. These results indicate that SRT2104 preserves mitochondrial function in unloaded skeletal muscle, suggesting its potential to support healthy muscle cells in microgravity by promoting necessary energy production in mitochondria. [ABSTRACT FROM AUTHOR]

The emergence of precision biology has been driven by the development of advanced technologies and techniques in high-resolution biological research systems. Enhancer-mediated transcriptional regulation, a complex network of gene expression and regulation in eukaryotes, has attracted significant attention as a promising avenue for investigating the underlying mechanisms of biological processes and diseases. To address biological problems with precision, large amounts of data, functional information, and research on the mechanisms of action of biological molecules is required to address biological problems with precision. Enhancers, including typical enhancers and super enhancers, play a crucial role in gene expression and regulation within this network. The identification and targeting of disease-associated enhancers hold the potential to advance precision medicine. In this review, we present the concepts, progress, importance, and challenges in precision biology, transcription regulation, and enhancers. Furthermore, we propose a model of transcriptional regulation for multi-enhancers and provide examples of their mechanisms in mammalian cells, thereby enhancing our understanding of how enhancers achieve precise regulation of gene expression in life processes. Precision biology holds promise in providing new tools and platforms for discovering insights into gene expression and disease occurrence, ultimately benefiting individuals and society as a whole. [ABSTRACT FROM AUTHOR]

The mammalian formin family comprises fifteen multi-domain proteins that regulate actin dynamics and microtubules in vitro and in cells. Evolutionarily conserved formin homology (FH) 1 and 2 domains allow formins to locally modulate the cell cytoskeleton. Formins are involved in several developmental and homeostatic processes, as well as human diseases. However, functional redundancy has long hampered studies of individual formins with genetic loss-of-function approaches and prevents the rapid inhibition of formin activities in cells. The discovery of small molecule inhibitor of formin homology 2 domains (SMIFH2) in 2009 was a disruptive change that provided a powerful chemical tool to explore formins' functions across biological scales. Here, I critically discuss the characterization of SMIFH2 as a pan-formin inhibitor, as well as growing evidence of unexpected off-target effects. By collating the literature and information hidden in public repositories, outstanding controversies and fundamental open questions about the substrates and mechanism of action of SMIFH2 emerge. Whenever possible, I propose explanations for these discrepancies and roadmaps to address the paramount open questions. Furthermore, I suggest that SMIFH2 be reclassified as a multi-target inhibitor for its appealing activities on proteins involved in pathological formin-dependent processes. Notwithstanding all drawbacks and limitations, SMIFH2 will continue to prove useful in studying formins in health and disease in the years to come. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is the most aggressive and frequent primary malignant tumor of the central nervous system and is associated with poor overall survival even after treatment. To better understand tumor biochemical alterations and broaden the potential targets of GB, this study aimed to evaluate differential plasma biomarkers between GB patients and healthy individuals using metabolomics analysis. Plasma samples from both groups were analyzed via untargeted metabolomics using direct injection with an electrospray ionization source and an LTQ mass spectrometer. GB biomarkers were selected via Partial Least Squares Discriminant and Fold-Change analyses and were identified using tandem mass spectrometry with in silico fragmentation, consultation of metabolomics databases, and a literature search. Seven GB biomarkers were identified, some of which were unprecedented biomarkers for GB, including arginylproline (m/z 294), 5-hydroxymethyluracil (m/z 143), and N-acylphosphatidylethanolamine (m/z 982). Notably, four other metabolites were identified. The roles of all seven metabolites in epigenetic modulation, energy metabolism, protein catabolism or folding processes, and signaling pathways that activate cell proliferation and invasion were elucidated. Overall, the findings of this study highlight new molecular targets to guide future investigations on GB. These molecular targets can also be further evaluated to derive their potential as biomedical analytical tools for peripheral blood samples. [ABSTRACT FROM AUTHOR]

The efficacy of current immunotherapies remains limited in many solid epithelial malignancies. Recent investigations into the biology of butyrophilin (BTN) and butyrophilin-like (BTNL) molecules, however, suggest these molecules are potent immunosuppressors of antigen-specific protective T cell activity in tumor beds. BTN and BTNL molecules also associate with each other dynamically on cellular surfaces in specific contexts, which modulates their biology. At least in the case of BTN3A1, this dynamism drives the immunosuppression of αβ T cells or the activation of Vγ9Vδ2 T cells. Clearly, there is much to learn regarding the biology of BTN and BTNL molecules in the context of cancer, where they may represent intriguing immunotherapeutic targets that could potentially synergize with the current class of immune modulators in cancer. Here, we discuss our current understanding of BTN and BTNL biology, with a particular focus on BTN3A1, and potential therapeutic implications for cancer. [ABSTRACT FROM AUTHOR]

Migraine and sarcoidosis are two distinct medical conditions that may have some common biological and clinical pathways. Sarcoidosis is a chronic granulomatous disease characterized by the formation of granulomas in various organs, including the lungs, skin, cardiovascular system, lymph nodes, and brain. Migraine is a common comorbidity in sarcoidosis patients and a common neurological disorder characterized by recurrent headaches that can be accompanied by other symptoms, such as nausea, vomiting, and sensitivity to light and sound. There have been several reports of individuals with neurosarcoidosis experiencing migraines, though the exact relationship between the two disorders is not well understood. Both conditions have been associated with inflammation and the activation of the immune system. In sarcoidosis, the formation of granulomas is thought to be an immune response to the presence of an unknown antigen. Similarly, the pain and other symptoms associated with migraines are thought to be caused by inflammation in the brain and the surrounding blood vessels. There is also evidence to suggest an interplay of environmental and genetic factors playing a role in both conditions, but evidence is inconsistent with the hypothesis of shared genetic susceptibility. This review aims to illustrate common clinical and biological pathways between migraine and sarcoidosis, including inflammation and dysregulation of the immune system, with a focus on the cumulative burden of concurrent disorders and therapeutic implications. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the first worldwide most frequent cancer in both sexes and the most commonly diagnosed in females. Although BC mortality has been thoroughly declining over the past decades, there are still considerable differences between women diagnosed with early BC and when metastatic BC is diagnosed. BC treatment choice is widely dependent on precise histological and molecular characterization. However, recurrence or distant metastasis still occurs even with the most recent efficient therapies. Thus, a better understanding of the different factors underlying tumor escape is mainly mandatory. Among the leading candidates is the continuous interplay between tumor cells and their microenvironment, where extracellular vesicles play a significant role. Among extracellular vesicles, smaller ones, also called exosomes, can carry biomolecules, such as lipids, proteins, and nucleic acids, and generate signal transmission through an intercellular transfer of their content. This mechanism allows tumor cells to recruit and modify the adjacent and systemic microenvironment to support further invasion and dissemination. By reciprocity, stromal cells can also use exosomes to profoundly modify tumor cell behavior. This review intends to cover the most recent literature on the role of extracellular vesicle production in normal and cancerous breast tissues. Specific attention is paid to the use of extracellular vesicles for early BC diagnosis, follow-up, and prognosis because exosomes are actually under the spotlight of researchers as a high-potential source of liquid biopsies. Extracellular vesicles in BC treatment as new targets for therapy or efficient nanovectors to drive drug delivery are also summarized. [ABSTRACT FROM AUTHOR]

In multicellular organisms, interactions between cells and intercellular communications form the very basis of the organism's survival, the functioning of its systems, the maintenance of homeostasis and adequate response to the environment. The accumulated experimental data point to the particular importance of intercellular communications in determining the fate of cells, as well as their differentiation and plasticity. For a long time, it was believed that the properties and behavior of cells were primarily governed by the interactions of secreted or membrane-bound ligands with corresponding receptors, as well as direct intercellular adhesion contacts. In this review, we describe various types of other, non-classical intercellular interactions and communications that have recently come into the limelight—in particular, the broad repertoire of extracellular vesicles and membrane protrusions. These communications are mediated by large macromolecular structural and functional ensembles, and we explore here the mechanisms underlying their formation and present current data that reveal their roles in multiple biological processes. The effects mediated by these new types of intercellular communications in normal and pathological states, as well as therapeutic applications, are also discussed. The in-depth study of novel intercellular interaction mechanisms is required for the establishment of effective approaches for the control and modification of cell properties both for basic research and the development of radically new therapeutic strategies. [ABSTRACT FROM AUTHOR]

There is a large unmet medical need to develop disease-modifying treatment options for individuals with age-related degenerative diseases of the central nervous system. The sigma-2 receptor (S2R), encoded by TMEM97, is expressed in brain and retinal cells, and regulates cell functions via its co-receptor progesterone receptor membrane component 1 (PGRMC1), and through other protein–protein interactions. Studies describing functions of S2R involve the manipulation of expression or pharmacological modulation using exogenous small-molecule ligands. These studies demonstrate that S2R modulates key pathways involved in age-related diseases including autophagy, trafficking, oxidative stress, and amyloid-β and α-synuclein toxicity. Furthermore, S2R modulation can ameliorate functional deficits in cell-based and animal models of disease. This review summarizes the current evidence-based understanding of S2R biology and function, and its potential as a therapeutic target for age-related degenerative diseases of the central nervous system, including Alzheimer's disease, α-synucleinopathies, and dry age-related macular degeneration. [ABSTRACT FROM AUTHOR]

The skin is the outermost protective barrier of the human body. Its role is to protect against different physical, chemical, biological and environmental stressors. The vast majority of studies have focused on investigating the effects of single environmental stressors on skin homeostasis and the induction of several skin disorders, such as cancer or ageing. On the other hand, much fewer studies have explored the consequences of the co-exposure of skin cells to two or more stressors simultaneously, which is much more realistic. In the present study, we investigated, using mass-spectrometry-based proteomic analysis, the dysregulated biological functions in skin explants after their co-exposure to ultraviolet radiation (UV) and benzo[a]pyrene (BaP). We observed that several biological processes were dysregulated, among which autophagy appeared to be significantly downregulated. Furthermore, immunohistochemistry analysis was carried out to validate the downregulation of the autophagy process further. Altogether, the output of this study provides an insight into the biological responses of skin to combined exposure to UV + BaP and highlights autophagy as a potential target that might be considered in the future as a novel candidate for pharmacological intervention under such stress conditions. [ABSTRACT FROM AUTHOR]

Cancer of unknown primary (CUP) encloses a group of heterogeneous tumours, the primary sites for which cannot be identified at the time of diagnosis, despite extensive investigations. CUP has always posed major challenges both in its diagnosis and management, leading to the hypothesis that it is rather a distinct entity with specific genetic and phenotypic aberrations, considering the regression or dormancy of the primary tumour; the development of early, uncommon systemic metastases; and the resistance to therapy. Patients with CUP account for 1–3% of all human malignancies and can be categorised into two prognostic subsets according to their clinicopathologic characteristics at presentation. The diagnosis of CUP mainly depends on the standard evaluation comprising a thorough medical history; complete physical examination; histopathologic morphology and algorithmic immunohistochemistry assessment; and CT scan of the chest, abdomen, and pelvis. However, physicians and patients do not fare well with these criteria and often perform additional time-consuming evaluations to identify the primary tumour site to guide treatment decisions. The development of molecularly guided diagnostic strategies has emerged to complement traditional procedures but has been disappointing thus far. In this review, we present the latest data on CUP regarding the biology, molecular profiling, classification, diagnostic workup, and treatment. [ABSTRACT FROM AUTHOR]

Defensins have long been considered as merely antimicrobial peptides. Throughout the years, more immune-related functions have been discovered for both the α-defensin and β-defensin subfamily. This review provides insights into the role of defensins in tumor immunity. Since defensins are present and differentially expressed in certain cancer types, researchers started to unravel their role in the tumor microenvironment. The human neutrophil peptides have been demonstrated to be directly oncolytic by permealizing the cell membrane. Further, defensins can inflict DNA damage and induce apoptosis of tumor cells. In the tumor microenvironment, defensins can act as chemoattractants for subsets of immune cells, such as T cells, immature dendritic cells, monocytes and mast cells. Additionally, by activating the targeted leukocytes, defensins generate pro-inflammatory signals. Moreover, immuno-adjuvant effects have been reported in a variety of models. Therefore, the action of defensins reaches beyond their direct antimicrobial effect, i.e., the lysis of microbes invading the mucosal surfaces. By causing an increase in pro-inflammatory signaling events, cell lysis (generating antigens) and attraction and activation of antigen presenting cells, defensins could have a relevant role in activating the adaptive immune system and generating anti-tumor immunity, and could thus contribute to the success of immune therapy. [ABSTRACT FROM AUTHOR]

I sincerely thank the authors for their contributions to this Special Issue and believe that these notions would help to further our understanding of molecular and cellular mechanisms of bone and cartilage biology, as well as contribute to the development of therapeutic strategies for bone and cartilage diseases. Recent technical and conceptual advances in molecular and cellular biology have dramatically advanced bone and cartilage biology. This Special Issue aims to provide novel notions for skeletal development, and bone and cartilage diseases. This progress has also improved our understanding of the molecular pathogenesis of bone and cartilage diseases, including osteoporosis, osteoarthritis, and rheumatoid arthritis. [Extracted from the article]

Despite continuing progress in medical and surgical procedures, staphylococci remain the major Gram-positive bacterial pathogens that cause a wide spectrum of diseases, especially in patients requiring the utilization of indwelling catheters and prosthetic devices implanted temporarily or for prolonged periods of time. Within the genus, if Staphylococcus aureus and S. epidermidis are prevalent species responsible for infections, several coagulase-negative species which are normal components of our microflora also constitute opportunistic pathogens that are able to infect patients. In such a clinical context, staphylococci producing biofilms show an increased resistance to antimicrobials and host immune defenses. Although the biochemical composition of the biofilm matrix has been extensively studied, the regulation of biofilm formation and the factors contributing to its stability and release are currently still being discovered. This review presents and discusses the composition and some regulation elements of biofilm development and describes its clinical importance. Finally, we summarize the numerous and various recent studies that address attempts to destroy an already-formed biofilm within the clinical context as a potential therapeutic strategy to avoid the removal of infected implant material, a critical event for patient convenience and health care costs. [ABSTRACT FROM AUTHOR]

This article discusses the biology and toxicity of gametes, embryos, and cancer cells in reproductive systems. It highlights the importance of germ cells in maintaining reproductive function and the factors that can cause DNA damage and abnormal metabolism in these cells. The article also explores the genetic and epigenetic changes that can lead to aging and the impact of somatic cell aging on germ cell development. Additionally, it discusses the genotoxicity of nanoparticles and the patterns of chromosomal abnormalities based on age. The article concludes by emphasizing the ongoing research on various factors affecting the reproductive system and the interest in understanding the effects of environmental factors and aging on reproductive cell health. [Extracted from the article]

Although it may not seem like it, chemical biology has existed for a long time from today's perspective. Today, it is no longer possible to trace who first used the term/phrase "chemical biology", but it is clear that the concepts of chemical biology go back a long way [[4]]. Using a chemical biology platform, scientists use international research infrastructure (e.g., Instruct-ERIC [[34]]) to make cutting-edge technologies and methods used in structural biology available to each other, with the aim of driving and supporting innovation in the biomedical sciences. Thus, chemical biology has become an important interdisciplinary field that is rooted in/seeks to link bioorganic, medicinal, and supramolecular chemistry with genetics, biochemistry, molecular biology, metabolic engineering, and pharmacology, using all known available analytical/bioanalytical methods or tools [[7]]. [Extracted from the article]

Prostate cancer (PCa) is today the second most common cancer in the world, with almost 400,000 deaths annually. Multiple factors are involved in the etiology of PCa, such as older age, genetic mutations, ethnicity, diet, or inflammation. Modern treatment of PCa involves radical surgical treatment or radiation therapy in the stages when the tumor is limited to the prostate. When metastases develop, the standard procedure is androgen deprivation therapy, which aims to reduce the level of circulating testosterone, which is achieved by surgical or medical castration. However, when the level of testosterone decreases to the castration level, the tumor cells adapt to the new conditions through different mechanisms, which enable their unhindered growth and survival, despite the therapy. New knowledge about the biology of the so-called of castration-resistant PCa and the way it adapts to therapy will enable the development of new drugs, whose goal is to prolong the survival of patients with this stage of the disease, which will be discussed in this review. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) has been introduced and applied to a wide spectrum of acute and chronic ligament and tendon pathologic conditions. Although the biological effect of PRP has been studied thoroughly in both animal and human studies, there is no consensus so far on the exact mechanism of its action as well as the optimal timing and dosage of its application. Therefore, we conducted a systematic review aiming to evaluate the molecular effect of the administration of PRP in tendoligamentous injuries and degenerative diseases. The literature search revealed 36 in vitro and in vivo studies examining the healing and remodeling response of animal and human ligament or tendon tissues to PRP. Platelet-rich plasma added in the culture media was highly associated with increased cell proliferation, migration, viability and total collagen production of both ligament- and tendon-derived cells in in vitro studies, which was further confirmed by the upregulation of collagen gene expression. In vivo studies correlated the PRP with higher fibroblastic anabolic activity, including increased cellularity, collagen production and vascularity of ligament tissue. Similarly, greater metabolic response of tenocytes along with the acceleration of the healing process in the setting of a tendon tear were noticed after PRP application, particularly between the third and fourth week after treatment. However, some studies demonstrated that PRP had no or even negative effect on tendon and ligament regeneration. This controversy is mainly related to the variable processes and methodologies of preparation of PRP, necessitating standardized protocols for both investigation and ap-plication. [ABSTRACT FROM AUTHOR]

The selection of plant genotypes with improved productivity and tolerance to environmental constraints has always been a major concern in plant breeding. Classical approaches based on the generation of variability and selection of better phenotypes from large variant collections have improved their efficacy and processivity due to the implementation of molecular biology techniques, particularly genomics, Next Generation Sequencing and other omics such as proteomics and metabolomics. In this regard, the identification of interesting variants before they develop the phenotype trait of interest with molecular markers has advanced the breeding process of new varieties. Moreover, the correlation of phenotype or biochemical traits with gene expression or protein abundance has boosted the identification of potential new regulators of the traits of interest, using a relatively low number of variants. These important breakthrough technologies, built on top of classical approaches, will be improved in the future by including the spatial variable, allowing the identification of gene(s) involved in key processes at the tissue and cell levels. [ABSTRACT FROM AUTHOR]

Two-Spotted Spider Mites (TSSMs, Tetranychus urticae Koch 1836 (Acari: Tetranychidae)) is one of the most important pests in many crop plants, and their feeding activity is based on sucking leaf cell contents. The purpose of this study was to evaluate the interaction between TSSMs and their host Lima bean (Phaseolus lunatus) by analyzing the metabolomics of leaf pigments and the transcriptomics of TSSM guanine production. We also used epifluorescence, confocal laser scanning, and transmission electron microscopies to study the morphology and structure of TSSMs and their excreta. Finally, we evaluated the potential photosynthetic ability of TSSMs and the activity and content of Ribulose-1,5-bisphosphate Carboxylase/Oxigenase (RubisCO). We found that TSSMs express several genes involved in guanine production, including Guanosine Monophosphate Synthetase (GMPS) and decoyinine (DCY), a potential inhibitor of GMPS, was found to reduce TSSMs proliferation in infested Lima bean leaves. Despite the presence of intact chloroplasts and chlorophyll in TSSMs, we demonstrate that TSSMs do not retain any photosynthetic activity. Our results show for the first time the transcriptomics of guanine production in TSSMs and provide new insight into the catabolic activity of TSSMs on leaf chlorophyll and carotenoids. Finally, we preliminary demonstrate that DCY has an acaricidal potential against TSSMs. [ABSTRACT FROM AUTHOR]

This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2–3 conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas. Central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively. CDKN2A/B deletions are also frequent in conventional CS, as well as COL2A1 mutations. Dedifferentiated CS develops when low-grade conventional CS transforms into a high-grade sarcoma and most frequently exhibits features of osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma. Their molecular characteristics are similar to conventional CS. Mesenchymal CS is a totally different pathological entity exhibiting recurrent translocations. Their clinical presentation and management are different too. The standard treatment of CSs is wide en-bloc resection. CS are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in an attempt to achieve local control in unresectable tumors. Chemotherapy is possibly effective in mesenchymal chondrosarcoma and is of uncertain value in dedifferentiated chondrosarcoma. Due to resistance to standard anticancer agents, the prognosis is poor in patients with metastatic or unresectable chondrosarcomas. Recently, the refined characterization of the molecular profile, as well as the development of new treatments, allow new therapeutic options for these rare tumors. The efficiency of IDH1 inhibitors in other malignancies suggests that these inhibitors will be part of IDH1/2 mutated conventional CS management soon. Other treatment approaches, such as PIK3-AKT-mTOR inhibitors, cell cycle inhibitors, and epigenetic or immune modulators based on improving our understanding of CS molecular biology, are emerging. [ABSTRACT FROM AUTHOR]

Several studies have indicated that a neutrophil extracellular trap (NET) formation, apart from its role in host defense, can contribute to or drive pathogenesis in a wide range of inflammatory and thrombotic disorders. Therefore, NETs may serve as a therapeutic target or/and a diagnostic tool. Here, we compare the most commonly used techniques for the assessment of NET formation. Furthermore, we review recent data from the literature on the application of basic laboratory tools for detecting NET release and discuss the challenges and the advantages of these strategies in NET evaluation. Taken together, we provide some important insights into the qualitative and quantitative molecular analysis of NETs in translational medicine today. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) has been recognized as a gasotransmitter in the mainstream of plant research since the beginning of the 21st century. It is produced in plant tissue and the environment. It influences plant physiology during every ontogenetic stage from seed germination to plant senescence. In this review, we demonstrate the increased interest in NO as a regulatory molecule in combination with other signalling molecules and phytohormones in the information network of plant cells. This work is a summary of the current knowledge on NO action in seeds, starting from seed pretreatment techniques applied to increase seed quality. We describe mode of action of NO in the regulation of seed dormancy, germination, and aging. During each stage of seed physiology, NO appears to act as a key agent with a predominantly beneficial effect. [ABSTRACT FROM AUTHOR]

Network biology has garnered tremendous attention in understanding complex systems of cancer, because the mechanisms underlying cancer involve the perturbations in the specific function of molecular networks, rather than a disorder of a single gene. In this article, we review the various computational tactics for gene regulatory network analysis, focused especially on personalized anti-cancer therapy. This paper covers three major topics: (1) cell line's (or patient's) cancer characteristics specific gene regulatory network estimation, which enables us to reveal molecular interplays under varying conditions of cancer characteristics of cell lines (or patient); (2) computational approaches to interpret the multitudinous and massive networks; (3) network-based application to uncover molecular mechanisms of cancer and related marker identification. We expect that this review will help readers understand personalized computational network biology that plays a significant role in precision cancer medicine. [ABSTRACT FROM AUTHOR]

Adolescents and young adults (AYA) with rhabdomyosarcoma (RMS) form a subgroup of patients whose optimal clinical management and best possible access to care remain a challenge and whose survival rates lag behind that of children diagnosed with histologically similar tumors. A better understanding of tumor biology that differentiates children (PEDS-) from AYA-RMS could provide critical information and drive new initiatives to improve their final outcome. We investigated the functional role of miRNAs implicated in AYA-RMS development, as they have the potential to lead to discovery of new targets pathways for a more tailored treatment in these age groups of young RMS patients. MiR-223 and miR-486 were observed de-regulated in nine RMS tissues compared to their normal counterparts, yet only miR-223 replacement impaired proliferation and aggressiveness of AYA-RMS cell lines, while inducing apoptosis and determining cell cycle arrest. Interestingly, IGF1R resulted in the direct target of miR-223 in AYA-RMS cells, as demonstrated by IGF1R silencing. Our results highlight an exclusive functional role of miR-223 in AYA-RMS development and aggressiveness. [ABSTRACT FROM AUTHOR]

Double-stranded RNA-binding proteins (dsRBPs) are major players in the regulation of gene expression patterns. Among them, Nuclear Factor 90 (NF90) has a plethora of well-known functions in viral infection, transcription, and translation as well as RNA stability and degradation. In addition, NF90 has been identified as a regulator of microRNA (miRNA) maturation by competing with Microprocessor for the binding of pri-miRNAs in the nucleus. NF90 was recently shown to control the biogenesis of a subset of human miRNAs, which ultimately influences, not only the abundance, but also the expression of the host gene and the fate of the mRNA target repertoire. Moreover, recent evidence suggests that NF90 is also involved in RNA-Induced Silencing Complex (RISC)-mediated silencing by binding to target mRNAs and controlling their translation and degradation. Here, we review the many, and growing, functions of NF90 in RNA biology, with a focus on the miRNA pathway and RISC-mediated gene silencing. [ABSTRACT FROM AUTHOR]