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Ferroptosis is a regulated cell death process characterized by iron ion catalysis and reactive oxygen species, leading to lipid peroxidation. This mechanism plays a crucial role in age-related diseases, including cancer and cardiovascular and neurological disorders. To better mimic iron-induced cell death, predict the effects of various elements, and identify drugs capable of regulating ferroptosis, it is essential to develop precise models of this process. Such drugs can be tested on cellular models. Systems biology offers a powerful approach to studying biological processes through modeling, which involves accumulating and analyzing comprehensive research data. Once a model is created, it allows for examining the system's response to various stimuli. Our goal is to develop a modular framework for ferroptosis, enabling the prediction and screening of compounds with geroprotective and antiferroptotic effects. For modeling and analysis, we utilized BioUML (Biological Universal Modeling Language), which supports key standards in systems biology, modular and visual modeling, rapid simulation, parameter estimation, and a variety of numerical methods. This combination fulfills the requirements for modeling complex biological systems. The integrated modular model was validated on diverse datasets, including original experimental data. This framework encompasses essential molecular genetic processes such as the Fenton reaction, iron metabolism, lipid synthesis, and the antioxidant system. We identified structural relationships between molecular agents within each module and compared them to our proposed system for regulating the initiation and progression of ferroptosis. Our research highlights that no current models comprehensively cover all regulatory mechanisms of ferroptosis. By integrating data on ferroptosis modules into an integrated modular model, we can enhance our understanding of its mechanisms and assist in the discovery of new treatment targets for age-related diseases. A computational model of ferroptosis was developed based on a modular modeling approach and included 73 differential equations and 93 species.

This study aimed to construct genome-wide genetic and epigenetic networks (GWGENs) of atopic dermatitis (AD) and healthy controls through systems biology methods based on genome-wide microarray data. Subsequently, the core GWGENs of AD and healthy controls were extracted from their real GWGENs by the principal network projection (PNP) method for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. Then, we identified the abnormal signaling pathways by comparing the core signaling pathways of AD and healthy controls to investigate the pathogenesis of AD. Then, IL-1β, GATA3, Akt, and NF-κB were selected as biomarkers for their important roles in the abnormal regulation of downstream genes, leading to cellular dysfunctions in AD patients. Next, a deep neural network (DNN)-based drug-target interaction (DTI) model was pre-trained on DTI databases to predict molecular drugs that interact with these biomarkers. Finally, we screened the candidate molecular drugs based on drug toxicity, sensitivity, and regulatory ability as drug design specifications to select potential molecular drugs for these biomarkers to treat AD, including metformin, allantoin, and U-0126, which have shown potential for therapeutic treatment by regulating abnormal immune responses and restoring the pathogenic signaling pathways of AD.

Glioblastoma (GBM), a highly malignant tumour of the central nervous system, presents with a dire prognosis and low survival rates. The heterogeneous and recurrent nature of GBM renders current treatments relatively ineffective. In our study, we utilized an integrative systems biology approach to uncover the molecular mechanisms driving GBM progression and identify viable therapeutic drug targets for developing more effective GBM treatment strategies. Our integrative analysis revealed an elevated expression of CHST2 in GBM tumours, designating it as an unfavourable prognostic gene in GBM, as supported by data from two independent GBM cohorts. Further, we pinpointed WZ-4002 as a potential drug candidate to modulate CHST2 through computational drug repositioning. WZ-4002 directly targeted EGFR ( ERBB1 ) and ERBB2 , affecting their dimerization and influencing the activity of adjacent genes, including CHST2 . We validated our findings by treating U-138 MG cells with WZ-4002, observing a decrease in CHST2 protein levels and a reduction in cell viability. In summary, our research suggests that the WZ-4002 drug candidate may effectively modulate CHST2 and adjacent genes, offering a promising avenue for developing efficient treatment strategies for GBM patients.

Increasing evidence clearly shows that most functional molecules in the cell exert a dual role depending on the specific interactive context, biochemical pathway, or subcellular localization [...]., Competing Interests: The authors declare no conflicts of interest.

One of the definitions of chemical biology is that it is a scientific discipline spanning the fields of chemistry, biology, and physics; it primarily involves the application of chemical techniques, tools, analyses, and often compounds (also known as chemical probes), which are produced through synthetic chemistry, in order to study and manipulate biological systems [...].

Multiple alterations of cellular metabolism have been documented in experimental studies of autosomal dominant polycystic kidney disease (ADPKD) and are thought to contribute to its pathogenesis. To elucidate the molecular pathways and transcriptional regulators associated with the metabolic changes of renal cysts in ADPKD, we compared global gene expression data from human PKD1 renal cysts, minimally cystic tissues (MCT) from the same patients, and healthy human kidney cortical tissue samples. We found gene expression profiles of PKD1 renal cysts were consistent with the Warburg effect with gene pathway changes favoring increased cellular glucose uptake and lactate production, instead of pyruvate oxidation. Additionally, mitochondrial energy metabolism was globally depressed, associated with downregulation of gene pathways related to fatty acid oxidation (FAO), branched-chain amino acid (BCAA) degradation, the Krebs cycle, and oxidative phosphorylation (OXPHOS) in renal cysts. Activation of mTORC1 and its two target proto-oncogenes, HIF-1α and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3 , HK1/HK2 , ALDOA , ENO2 , PKM , LDHA/LDHB , MCT4 , PDHA1 , PDK1/3 , MPC1/2 , CPT2 , BCAT1 , NAMPT ); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1α, a transcriptional coactivator for transcription factors PPARα, ERRα, and ERRγ, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis. These data provide a comprehensive map of metabolic pathway reprogramming in ADPKD and highlight nodes of regulation that may serve as targets for therapeutic intervention.

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.

Combining new therapeutics with all- trans -retinoic acid (ATRA) could improve the efficiency of acute myeloid leukemia (AML) treatment. Modeling the process of ATRA-induced differentiation based on the transcriptomic profile of leukemic cells resulted in the identification of key targets that can be used to increase the therapeutic effect of ATRA. The genome-scale transcriptome analysis revealed the early molecular response to the ATRA treatment of HL-60 cells. In this study, we performed the transcriptomic profiling of HL-60, NB4, and K562 cells exposed to ATRA for 3-72 h. After treatment with ATRA for 3, 12, 24, and 72 h, we found 222, 391, 359, and 1032 differentially expressed genes (DEGs) in HL-60 cells, as well as 641, 1037, 1011, and 1499 DEGs in NB4 cells. We also found 538 and 119 DEGs in K562 cells treated with ATRA for 24 h and 72 h, respectively. Based on experimental transcriptomic data, we performed hierarchical modeling and determined cyclin-dependent kinase 6 (CDK6), tumor necrosis factor alpha (TNF-alpha), and transcriptional repressor CUX1 as the key regulators of the molecular response to the ATRA treatment in HL-60, NB4, and K562 cell lines, respectively. Mapping the data of TMT-based mass-spectrometric profiling on the modeling schemes, we determined CDK6 expression at the proteome level and its down-regulation at the transcriptome and proteome levels in cells treated with ATRA for 72 h. The combination of therapy with a CDK6 inhibitor (palbociclib) and ATRA (tretinoin) could be an alternative approach for the treatment of acute myeloid leukemia (AML).

The complex biology of the microbiome was elucidated once the genomics era began. The proteogenomic approach analyzes and integrates genetic makeup (genomics) and microbial communities' expressed proteins (proteomics). Therefore, researchers gained insights into gene expression, protein functions, and metabolic pathways, understanding microbial dynamics and behavior, interactions with host cells, and responses to environmental stimuli. In this context, our work aims to bring together data regarding the application of genomics, proteomics, and bioinformatics in microbiome research and to provide new perspectives for applying microbiota modulation in clinical practice with maximum efficiency. This review also synthesizes data from the literature, shedding light on the potential biomarkers and therapeutic targets for various diseases influenced by the microbiome.

Bone health is ensured by the coordinated action of two types of cells-the osteoblasts that build up bone structure and the osteoclasts that resorb the bone. The loss of balance in their action results in pathological conditions such as osteoporosis. Central to this study is a class of RNA-binding proteins (RBPs) that regulates the biogenesis of miRNAs. In turn, miRNAs represent a critical level of regulation of gene expression and thus control multiple cellular and biological processes. The impact of miRNAs on the pathobiology of various multifactorial diseases, including osteoporosis, has been demonstrated. However, the role of RBPs in bone remodeling is yet to be elucidated. The aim of this study is to dissect the transcriptional landscape of genes encoding the compendium of 180 RBPs in bone cells. We developed and applied a multi-modular integrative analysis algorithm. The core methodology is gene expression analysis using the GENEVESTIGATOR platform, which is a database and analysis tool for manually curated and publicly available transcriptomic data sets, and gene network reconstruction using the Ingenuity Pathway Analysis platform. In this work, comparative insights into gene expression patterns of RBPs in osteoblasts and osteoclasts were obtained, resulting in the identification of 24 differentially expressed genes. Furthermore, the regulation patterns upon different treatment conditions revealed 20 genes as being significantly up- or down-regulated. Next, novel gene-gene associations were dissected and gene networks were reconstructed. Additively, a set of osteoblast- and osteoclast-specific gene signatures were identified. The consolidation of data and information gained from each individual analytical module allowed nominating novel promising candidate genes encoding RBPs in osteoblasts and osteoclasts and will significantly enhance the understanding of potential regulatory mechanisms directing intracellular processes in the course of (patho)physiological bone turnover.

Control theory, a well-established discipline in engineering and mathematics, has found novel applications in systems biology. This interdisciplinary approach leverages the principles of feedback control and regulation to gain insights into the complex dynamics of cellular and molecular networks underlying chronic diseases, including neurodegeneration. By modeling and analyzing these intricate systems, control theory provides a framework to understand the pathophysiology and identify potential therapeutic targets. Therefore, this review examines the most widely used control methods in conjunction with genomic-scale metabolic models in the steady state of the multi-omics type. According to our research, this approach involves integrating experimental data, mathematical modeling, and computational analyses to simulate and control complex biological systems. In this review, we find that the most significant application of this methodology is associated with cancer, leaving a lack of knowledge in neurodegenerative models. However, this methodology, mainly associated with the Minimal Dominant Set (MDS), has provided a starting point for identifying therapeutic targets for drug development and personalized treatment strategies, paving the way for more effective therapies.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by enduring airflow limitation and chronic inflammation. Growing evidence highlights mitochondrial dysfunction as a critical factor in COPD development and progression. This review explores the cellular and molecular biology of mitochondria in COPD, focusing on structural and functional changes, including alterations in mitochondrial shape, behavior, and respiratory chain complexes. We discuss the impact on cellular signaling pathways, apoptosis, and cellular aging. Therapeutic strategies targeting mitochondrial dysfunction, such as antioxidants and mitochondrial biogenesis inducers, are examined for their potential to manage COPD. Additionally, we consider the role of mitochondrial biomarkers in diagnosis, evaluating disease progression, and monitoring treatment efficacy. Understanding the interplay between mitochondrial biology and COPD is crucial for developing targeted therapies to slow disease progression and improve patient outcomes. Despite advances, further research is needed to fully elucidate mitochondrial dysfunction mechanisms, discover new biomarkers, and develop targeted therapies, aiming for comprehensive disease management that preserves lung function and enhances the quality of life for COPD patients. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disease that affects millions of people worldwide. In 2014, psoriasis was recognized by the World Health Organization (WHO) as a serious non-communicable disease. In this study, a systems biology approach was used to investigate the underlying pathogenic mechanism of psoriasis and identify the potential drug targets for therapeutic treatment. The study involved the construction of a candidate genome-wide genetic and epigenetic network (GWGEN) through big data mining, followed by the identification of real GWGENs of psoriatic and non-psoriatic using system identification and system order detection methods. Core GWGENs were extracted from real GWGENs using the Principal Network Projection (PNP) method, and the corresponding core signaling pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Comparing core signaling pathways of psoriasis and non-psoriasis and their downstream cellular dysfunctions, STAT3, CEBPB, NF-κB, and FOXO1 are identified as significant biomarkers of pathogenic mechanism and considered as drug targets for the therapeutic treatment of psoriasis. Then, a deep neural network (DNN)-based drug-target interaction (DTI) model was trained by the DTI dataset to predict candidate molecular drugs. By considering adequate regulatory ability, toxicity, and sensitivity as drug design specifications, Naringin, Butein, and Betulinic acid were selected from the candidate molecular drugs and combined into potential multi-molecule drugs for the treatment of psoriasis.

This document is an editorial from the International Journal of Molecular Sciences titled "Role of Phosphodiesterases in Biology and Pathology 2.0." It discusses the role of phosphodiesterases (PDEs) in the hydrolysis of cAMP and cGMP second messengers in cells. PDEs are involved in various physiological and pathological conditions, and their inhibitors have been used in the treatment of impotence and chronic pulmonary diseases. The special issue of the journal includes contributions that provide new insights into the role of PDEs in different conditions such as spinal cord injury, multiple sclerosis, skeletal muscle function, cardiac contractility, portal hypertension, liver cirrhosis, and cancer. The articles aim to encourage further research on PDE complexes and the development of new inhibitors for specific delivery and reduced side effects. [Extracted from the article]

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]

Androgenetic alopecia is a highly prevalent condition mainly affecting men. This complex trait is related to aging and genetics; however, multiple other factors, for example, lifestyle, are also involved. Despite its prevalence, the underlying biology of androgenetic alopecia remains elusive, and thus advances in its treatment have been hindered. Herein, we review the functional anatomy of hair follicles and the cell signaling events that play a role in follicle cycling. We also discuss the pathology of androgenetic alopecia and the known molecular mechanisms underlying this condition. Additionally, we describe studies comparing the transcriptional differences in hair follicles between balding and non-balding scalp regions. Given the genetic contribution, we also discuss the most significant risk variants found to be associated with androgenetic alopecia. A more comprehensive understanding of this pathology may be generated through using multi-omics approaches. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that regulates multiple processes, including gene transcription, protein synthesis, ribosome biogenesis, autophagy, cell metabolism, and cell growth [...].

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

The marine bacterium Streptomyces sp. HNS054 shows promise as a platform for producing natural products. Isolated from a marine sponge, HNS054 possesses several desirable traits for bioengineering: rapid growth, salt tolerance, and compatibility with genetic tools. Its genome contains 21 potential biosynthetic gene clusters, offering a rich source of natural products. We successfully engineered HNS054 to increase the production of aborycin and actinorhodin by 4.5-fold and 1.2-fold, respectively, compared to S. coelicolor M1346 counterparts. With its unique features and amenability to genetic manipulation, HNS054 emerges as a promising candidate for developing novel marine-derived drugs and other valuable compounds.

This document discusses the potential uses of bioactive compounds derived from agrifood byproducts in medicine and biology. Agrifood waste generates a significant amount of waste globally, and finding ways to reduce and repurpose this waste aligns with the circular economy and the European Union's green goals. Agrifood byproducts can be used in various sectors, such as agriculture, packaging, energy production, and cosmetics. These byproducts also contain valuable nutrients and bioactive compounds that have potential health benefits. The study of these substances can lead to the development of functional foods, formulations, and food supplements. The document emphasizes the need for further research in this field and acknowledges the contributions of the authors and reviewers. [Extracted from the article]

Epilepsy is a highly prevalent, severely debilitating neurological disorder characterized by seizures and neuronal hyperactivity due to an imbalanced neurotransmission. As genetic factors play a key role in epilepsy and its treatment, various genetic and genomic technologies continue to dissect the genetic causes of this disorder. However, the exact pathogenesis of epilepsy is not fully understood, necessitating further translational studies of this condition. Here, we applied a computational in silico approach to generate a comprehensive network of molecular pathways involved in epilepsy, based on known human candidate epilepsy genes and their established molecular interactors. Clustering the resulting network identified potential key interactors that may contribute to the development of epilepsy, and revealed functional molecular pathways associated with this disorder, including those related to neuronal hyperactivity, cytoskeletal and mitochondrial function, and metabolism. While traditional antiepileptic drugs often target single mechanisms associated with epilepsy, recent studies suggest targeting downstream pathways as an alternative efficient strategy. However, many potential downstream pathways have not yet been considered as promising targets for antiepileptic treatment. Our study calls for further research into the complexity of molecular mechanisms underlying epilepsy, aiming to develop more effective treatments targeting novel putative downstream pathways of this disorder.

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]

Mycorrhizal symbiosis, the mutually beneficial association between plants and fungi, has gained significant attention in recent years due to its widespread significance in agricultural productivity. Specifically, arbuscular mycorrhizal fungi (AMF) provide a range of benefits to grain and oil crops, including improved nutrient uptake, growth, and resistance to (a)biotic stressors. Harnessing this symbiotic interaction using molecular and systems biology approaches presents promising opportunities for sustainable and economically-viable agricultural practices. Research in this area aims to identify and manipulate specific genes and pathways involved in the symbiotic interaction, leading to improved cereal and oilseed crop yields and nutrient acquisition. This review provides an overview of the research frontier on utilizing molecular and systems biology approaches for harnessing the symbiotic interaction in mycorrhizal symbiosis for grain and oil crop cultivation. Moreover, we address the mechanistic insights and molecular determinants underpinning this exchange. We conclude with an overview of current efforts to harness mycorrhizal diversity to improve cereal and oilseed health through systems biology. [ABSTRACT FROM AUTHOR]

This document is an editorial from the International Journal of Molecular Sciences titled "Application of Nanostructures in Biology and Medicine." It discusses the wide range of applications for nanomaterials in various fields, including energy, medicine, and industry. The document highlights the potential of nanoparticles and nanodevices in areas such as synthetic biology, drug delivery platforms, brain-computer interfaces, nanoelectronics, nanophotonics, and quantum communications technologies. The editorial also provides an overview of recent research in applied nanoscience, including materials science, chemistry, molecular and cell biology, and biotechnology. It features specific studies on the use of microparticles in pharmaceutics, metal-based nanoparticles in cancer therapy, nanoparticles in combating animal diseases, nanoparticles in wastewater treatment, chemical applications of mesoporous nanomaterials, and a new approach to assessing cell viability for implant development. [Extracted from the article]

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]

Traditional drug design requires a great amount of research time and developmental expense. Booming computational approaches, including computational biology, computer-aided drug design, and artificial intelligence, have the potential to expedite the efficiency of drug discovery by minimizing the time and financial cost. In recent years, computational approaches are being widely used to improve the efficacy and effectiveness of drug discovery and pipeline, leading to the approval of plenty of new drugs for marketing. The present review emphasizes on the applications of these indispensable computational approaches in aiding target identification, lead discovery, and lead optimization. Some challenges of using these approaches for drug design are also discussed. Moreover, we propose a methodology for integrating various computational techniques into new drug discovery and design.

Telomeres are part of chromatin structures containing repeated DNA sequences, which function as protective caps at the ends of chromosomes and prevent DNA degradation and recombination, thus ensuring the integrity of the genome. While telomere length (TL) can be genetically inherited, TL shortening has been associated with ageing and multiple xenobiotics and bioactive substances. TL has been characterised as a reliable biomarker for the predisposition to developing chronic pathologies and their progression. This narrative review aims to provide arguments in favour of including TL measurements in a complex prognostic and diagnostic panel of chronic pathologies and the importance of assessing the effect of different pharmacologically active molecules on the biology of telomeres. Medicines used in the management of cardiovascular diseases, diabetes, schizophrenia, hormone replacement therapy at menopause, danazol, melatonin, and probiotics have been studied for their positive protective effects against TL shortening. All these classes of drugs are analysed in the present review, with a particular focus on the molecular mechanisms involved. [ABSTRACT FROM AUTHOR]

Acute Erythroid Leukemia (AEL) is a rare and aggressive subtype of Acute Myeloid Leukemia (AML). In 2022, the World Health Organization (WHO) defined AEL as a biopsy with ≥30% proerythroblasts and erythroid precursors that account for ≥80% of cellularity. The International Consensus Classification refers to this neoplasm as "AML with mutated TP53". Classification entails ≥20% blasts in blood or bone marrow biopsy and a somatic TP53 mutation (VAF > 10%). This type of leukemia is typically associated with biallelic TP53 mutations and a complex karyotype, specifically 5q and 7q deletions. Transgenic mouse models have implicated several molecules in the pathogenesis of AEL, including transcriptional master regulator GATA1 (involved in erythroid differentiation), master oncogenes, and CDX4. Recent studies have also characterized AEL by epigenetic regulator mutations and transcriptome subgroups. AEL patients have overall poor clinical outcomes, mostly related to their poor response to the standard therapies, which include hypomethylating agents and intensive chemotherapy. Allogeneic bone marrow transplantation (AlloBMT) is the only potentially curative approach but requires deep remission, which is very challenging for these patients. Age, AlloBMT, and a history of antecedent myeloid neoplasms further affect the outcomes of these patients. In this review, we will summarize the diagnostic criteria of AEL, review the current insights into the biology of AEL, and describe the treatment options and outcomes of patients with this disease. [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.

This review provides insights at the molecular level into the current and old methods for treating meniscal injuries. Meniscal injuries have been found to have a substantial impact on the progression of osteoarthritis. In line with the "save the meniscus" approach, meniscectomy is considered a last-resort treatment. Nevertheless, it is important to note that mechanical repair alone may not achieve the complete restoration of the meniscus. A deep understanding of the healing pathways could lead to future improvements in meniscal healing. The inclusion of cytokines and chemokines has the potential to facilitate the process of tear repair or impede the inflammatory catabolic cascade. MicroRNA (miRNA) could serve as a potential biomarker for meniscal degeneration, and RNA injections might promote collagen and growth factor production. The critical aspect of the healing process is angiogenesis within the inner zone of the meniscus. The use of collagen scaffolds and the implantation of autologous meniscus fragments have been successfully integrated into clinical settings. These findings are encouraging and underscore the need for well-designed clinical trials to explore the most effective factors that can enhance the process of meniscal repair.

DNA-targeted drugs constitute a specialized category of pharmaceuticals developed for cancer treatment, directly influencing various cellular processes involving DNA. These drugs aim to enhance treatment efficacy and minimize side effects by specifically targeting molecules or pathways crucial to cancer growth. Unlike conventional chemotherapeutic drugs, recent discoveries have yielded DNA-targeted agents with improved effectiveness, and a new generation is anticipated to be even more specific and potent. The sequencing of the human genome in 2001 marked a transformative milestone, contributing significantly to the advancement of targeted therapy and precision medicine. Anticipated progress in precision medicine is closely tied to the continuous development in the exploration of synthetic lethality, DNA repair, and expression regulatory mechanisms, including epigenetic modifications. The integration of technologies like circulating tumor DNA (ctDNA) analysis further enhances our ability to elucidate crucial regulatory factors, promising a more effective era of precision medicine. The combination of genomic knowledge and technological progress has led to a surge in clinical trials focusing on precision medicine. These trials utilize biomarkers for identifying genetic alterations, molecular profiling for potential therapeutic targets, and tailored cancer treatments addressing multiple genetic changes. The evolving landscape of genomics has prompted a paradigm shift from tumor-centric to individualized, genome-directed treatments based on biomarker analysis for each patient. The current treatment strategy involves identifying target genes or pathways, exploring drugs affecting these targets, and predicting adverse events. This review highlights strategies incorporating DNA-targeted drugs, such as PARP inhibitors, SLFN11, methylguanine methyltransferase (MGMT), and ATR kinase. [ABSTRACT FROM AUTHOR]

The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials.

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.

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.

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.

It is well established that cells, tissues, and organisms exposed to low doses of ionizing radiation can induce effects in non-irradiated neighbors (non-targeted effects or NTE), but the mechanisms remain unclear. This is especially true of the initial steps leading to the release of signaling molecules contained in exosomes. Voltage-gated ion channels, photon emissions, and calcium fluxes are all involved but the precise sequence of events is not yet known. We identified what may be a quantum entanglement type of effect and this prompted us to consider whether aspects of quantum biology such as tunneling and entanglement may underlie the initial events leading to NTE. We review the field where it may be relevant to ionizing radiation processes. These include NTE, low-dose hyper-radiosensitivity, hormesis, and the adaptive response. Finally, we present a possible quantum biological-based model for NTE.

MicroRNAs (miRNAs) are molecules that influence messenger RNA (mRNA) expression levels by binding to the 3' untranslated region (3' UTR) of target genes. Host miRNAs can influence flavivirus replication, either by inducing changes in the host transcriptome or by directly binding to viral genomes. The 3' UTR of the flavivirus genome is a conserved region crucial for viral replication. Cells might exploit this well-preserved region by generating miRNAs that interact with it, ultimately impacting viral replication. Despite significant efforts to identify miRNAs capable of arresting viral replication, the potential of all these miRNAs to interact with the flavivirus 3' UTR is still poorly characterised. In this context, bioinformatic tools have been proposed as a fundamental part of accelerating the discovery of interactions between miRNAs and the 3' UTR of viral genomes. In this study, we performed a computational analysis to reveal potential miRNAs from human and mosquito species that bind to the 3' UTR of flaviviruses. In humans, miR-6842 and miR-661 were found, while in mosquitoes, miR-9-C, miR-2945-5p, miR-11924, miR-282-5p, and miR-79 were identified. These findings open new avenues for studying these miRNAs as antivirals against flavivirus infections.

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]

Muscle wasting can be caused by nutrition deficiency and inefficient metabolism of amino acids, including Branched Chain Amino Acids (BCAAs). Branched Chain Amino Acids are a major contributor to the metabolic needs of healthy muscle and account for over a tenth of lean muscle mass. Branched chain alpha-ketoacid dehydrogenase (BCKD) is the rate limiting enzyme of BCAA metabolism. Inhibition of BCKD is achieved through a reversible phosphorylation event by Branched Chain a-ketoacid dehydrogenase kinase (BCKDK). Our study set out to determine the importance of BCKDK in the maintenance of skeletal muscle. We used the Gene Expression Omnibus Database to understand the role of BCKDK in skeletal muscle pathogenesis, including aging, muscular disease, and interrupted muscle metabolism. We found BCKDK expression levels were consistently decreased in pathologic conditions. These results were most consistent when exploring muscular disease followed by aging. Based on our findings, we hypothesize that decreased BCKDK expression alters BCAA catabolism and impacts loss of normal muscle integrity and function. Further research could offer valuable insights into potential therapeutic strategies for addressing muscle-related disorders. [ABSTRACT FROM AUTHOR]

The SLC22 family of OATs, OCTs, and OCTNs is emerging as a central hub of endogenous physiology. Despite often being referred to as "drug" transporters, they facilitate the movement of metabolites and key signaling molecules. An in-depth reanalysis supports a reassignment of these proteins into eight functional subgroups, with four new subgroups arising from the previously defined OAT subclade: OATS1 (SLC22A6, SLC22A8, and SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, and Slc22a22), and OATS4 (SLC22A9, SLC22A10, SLC22A24, and SLC22A25). We propose merging the OCTN (SLC22A4, SLC22A5, and Slc22a21) and OCT-related (SLC22A15 and SLC22A16) subclades into the OCTN/OCTN-related subgroup. Using data from GWAS, in vivo models, and in vitro assays, we developed an SLC22 transporter-metabolite network and similar subgroup networks, which suggest how multiple SLC22 transporters with mono-, oligo-, and multi-specific substrate specificity interact to regulate metabolites. Subgroup associations include: OATS1 with signaling molecules, uremic toxins, and odorants, OATS2 with cyclic nucleotides, OATS3 with uric acid, OATS4 with conjugated sex hormones, particularly etiocholanolone glucuronide, OCT with neurotransmitters, and OCTN/OCTN-related with ergothioneine and carnitine derivatives. Our data suggest that the SLC22 family can work among itself, as well as with other ADME genes, to optimize levels of numerous metabolites and signaling molecules, involved in organ crosstalk and inter-organismal communication, as proposed by the remote sensing and signaling theory.

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.