Anaesthetics affect not only humans and animals but also plants. Plants exposed to certain anaesthetics lose their ability to respond adequately to various stimuli such as touch, injury or light. Available results indicate that anaesthetics modulate ion channel activities in plants, e.g. Ca2+ influx. The word anaesthesia means loss of sensation. Plants, as all living creatures, can also sense their environment and they are susceptible to anaesthesia. Although some anaesthetics are often known as drugs with well-defined target to their animal/human receptors, some other are promiscuous in their binding. Both have effects on plants. Application of general volatile anaesthetics (GVAs) inhibits plant responses to different stimuli but also induces strong cellular response. Of particular interest is the ability of GVAs inhibit long-distance electrical and Ca2+ signalling probably through inhibition of GLUTAMATE RECEPTOR-LIKE proteins (GLRs), the effect which is surprisingly very similar to inhibition of nerve impulse transmission in animals or human. However, GVAs act also as a stressor for plants and can induce their own Ca2+ signature, which strongly reprograms gene expression . Down-regulation of genes encoding enzymes of chlorophyll biosynthesis and pigment-protein complexes are responsible for inhibited de-etiolation and photomorphogenesis. Vesicle trafficking, germination, and circumnutation movement of climbing plants are also strongly inhibited. On the other hand, other cellular processes can be upregulated, for example, heat shock response and generation of reactive oxygen species (ROS). Upregulation of stress response by GVAs results in preconditioning/priming and can be helpful to withstand abiotic stresses in plants. Thus, anaesthetic drugs may become a useful tool for scientists studying plant responses to environmental stimuli.

Immunotherapy has revolutionized cancer treatment, but the limited availability of tumor-specific neoantigens still remains a challenge. The potential of alternative mRNA splicing-derived neoantigens as a source of new immunotherapy targets has gained significant attention. Tumors exhibit unique splicing changes and splicing factor mutations which are prevalent in various cancers and play a crucial role in neoantigen production. We present advances in splicing modulation approaches, including small-molecule drugs, decoy and splice-switching antisense oligonucleotides (SSOs), CRISPR, small interfering RNAs (siRNAs), and nonsense-mediated RNA decay (NMD) inhibition, that can be adapted to enhance antitumor immune responses. Finally, we explore the clinical implications of these approaches, highlighting their potential to transform cancer immunotherapy and broaden its efficacy.

Lysine acetylation is a major post-translational modification in histones and other proteins that is catalysed by the 'writer' lysine acetyltransferases (KATs) and mediates interactions with bromodomains (BrDs) and other 'reader' proteins. KATs and BrDs play key roles in regulating gene expression, cell growth, chromatin structure, and epigenetics and are often dysregulated in disease states, including cancer. There have been accelerating efforts to identify potent and selective small molecules that can target individual KATs and BrDs with the goal of developing new therapeutics, and some of these agents are in clinical trials. Here, we summarize the different families of KATs and BrDs, discuss their functions and structures, and highlight key advances in the design and development of chemical agents that show promise in blocking the action of these chromatin proteins for disease treatment.

Alzheimer's disease (AD), a prevalent neurodegenerative disorder, predominantly affects individuals over the age of 65 and poses significant challenges in terms of effective management and treatment. The disease's pathogenesis involves complex molecular pathways including misfolded proteins accumulation, neuroinflammation, and synaptic dysfunction. Recent insights have highlighted the role of microRNAs (miRNAs) as critical regulators within these pathways, where they influence gene expression and contribute to the pathophysiological landscape of AD. Notably, emerging research has demonstrated that polyphenols, including curcumin, might modulate miRNA activity, thus offering a novel approach to mitigate AD symptoms and progression. This review explores the potential mechanisms through which polyphenols regulate miRNA expression and activity, specifically focusing on autophagy enhancement and inflammation reduction in the context of AD. We provide a detailed examination of key studies linking miRNA dysregulation to AD pathogenesis and discuss how polyphenols might correct these aberrations. The findings presented here underscore the therapeutic potential of polyphenols in AD treatment via miRNA modulation, pointing to new directions in disease management strategies and highlighting the need for targeted research into miRNA-based interventions.

The ubiquitin-proteasome system (UPS) is an important type of protein post-translational modification that affects the quantity and quality of various proteins and influences cellular processes such as the cell cycle, transcription, oxidative stress, and autophagy. Nanomaterials (NMs), which exhibit excellent physicochemical properties, can directly interact with the UPS and act as molecular-targeted drugs to induce changes in biological processes. This review provides an overview of the influence of NMs on the UPS of misfolded proteins and key proteins, which are related to cancer, neurodegenerative diseases and oxidative stress. This review also summarizes the role of modification processes involved in ubiquitination the biological effects of NMs and the mechanism of such effects of NMs through regulation of the UPS. This review deepens our understanding of the influence of NMs on the protein degradation process and provides new potential therapeutic targets for disease.

Exposure to pollutants and chemicals during critical developmental periods in early life can impact health and disease risk across the life course. Research in environmental epigenetics has provided increasing evidence that prenatal exposures affect epigenetic markers, particularly DNA methylation. In this article, we discuss the role of DNA methylation in early life programming and review evidence linking the intrauterine environment to epigenetic modifications, with a focus on exposure to tobacco smoke, metals, and endocrine-disrupting chemicals. We also discuss challenges and novel approaches in environmental epigenetic research and explore the potential of epigenetic biomarkers in studies of pediatric populations as indicators of exposure and disease risk. Overall, we aim to highlight how advancements in environmental epigenetics may transform our understanding of early-life exposures and inform new approaches for supporting long-term health.

Air pollution is one of the leading causes of early deaths worldwide, with particulate matter (PM) as an emerging factor contributing to this trend. PM is classified based on its physical size, which ranges from PM10 (diameter ≤10 μm) to PM2.5 (≤2.5 μm) and PM0.5 (≤0.5 μm). Smaller-sized PM can move freely through the air and readily infiltrate deep into the lungs, intensifying existing health issues and exacerbating complications. Lung complications are the most common issues arising from PM exposure due to the primary site of deposition in the respiratory system. Conditions such as asthma, COPD, idiopathic pulmonary fibrosis, lung cancer and various lung infections are all susceptible to worsening due to PM exposure. PM can epigenetically modify specific target sites, further complicating its impact on these conditions. Understanding these epigenetic mechanisms holds promise for addressing these complications in cases of PM exposure. This involves studying the effect of PM on different gene expressions and regulation through epigenetic modifications, including DNA methylation, histone modifications and microRNAs. Targeting and manipulating these epigenetic modifications and their mechanisms could be promising strategies for future treatments of lung complications. This review mainly focuses on different epigenetic modifications due to PM2.5 exposure in the various lung complications mentioned above.

The progressive degeneration of dopaminergic neurons in the substantia nigra region of the brain leads to a deficiency of dopamine and, ultimately, the onset of Parkinson's disease (PD). Since there is currently no cure for PD, patients all around the world are dealing with symptomatic management. PD progression is influenced by multiple elements, such as environmental, biological, chemical, genetic, and epigenetic factors. Epigenetics is gaining increased attention due to its role in controlling the expression of genes that contribute to PD. Recent advancements in our understanding of the brain network and its related conditions have shown that alterations in gene expression may occur independently of genetic abnormalities. Therefore, a thorough investigation has been carried out to explore the significance of epigenetics in all degenerative disorders. Epigenetic modifications are essential for regulating cellular homeostasis. Therefore, a deeper understanding of these modifications might provide valuable insights into many diseases and potentially serve as targets for therapeutic interventions. This review article focuses on diverse epigenetic alterations linked to the progression of PD. These abnormalities are supported by numerous research on the control of gene expression and encompass all the epigenetic processes. The beginning of PD is intricately associated with aberrant DNA methylation mechanisms. DNA methyltransferases are the enzymes that create and preserve various DNA methylation patterns. Integrating epigenetic data with existing clinical methods for diagnosing PD may aid in discovering potential curative medicines and novel drug development approaches. This article solely addresses the importance of epigenetic modulators in PD, primarily the mechanisms of DNMTs, their roles in the development of PD, and their therapeutic approaches; it bypasses other PD therapies.

Breast cancer is a prevalent and aggressive disease characterized by high metastasis, recurrence, and mortality rates. While cisplatin is an effective chemotherapy drug, its use is limited by its toxic effects on the body. Despite advancements in therapeutic strategies, the therapeutic response is often unsatisfactory due to drug resistance, leading to poor prognosis. Recent studies have shown that cisplatin interacts with long non-coding RNAs (lncRNAs) and accelerates the development of resistance in tumor cells to therapy. This interaction highlights the complex mechanisms involved in the response of cancer cells to chemotherapy. Several lncRNAs have been identified as key players in mediating cisplatin resistance in breast cancer. These lncRNAs include SNHG15, HULC, HCP5, MT1JP, LncMat2B, DLX6-ASL, Linc00665, CARMN, and Lnc-EinRP44-3:6. These lncRNAs have been shown to target microRNAs and mRNAs and modulate the expression of genes involved in cisplatin resistance, which is important in treating breast cancer.

Breast cancer's complexity and heterogeneity continue to present significant challenges in its treatment and management. Emerging research has underscored the pivotal role of microRNAs (miRNAs) in breast cancer pathogenesis, acting as crucial regulators of gene expression. This review delivers an in-depth analysis of miRNAs, highlighting their dual functions as both oncogenes and tumor suppressors, and detailing their impact on key biological processes, including cell proliferation, apoptosis, and metastasis. The mechanisms underlying miRNA action, particularly their interactions with target mRNAs and the factors influencing these dynamics, are thoroughly explored. Additionally, the review discusses the therapeutic prospects of miRNAs, with a focus on innovative delivery systems like nanoparticles that improve the stability and effectiveness of miRNA-based therapies. It also addresses the anticancer effects of natural compounds, such as genistein, hesperidin, quercetin, curcumin, resveratrol, epigallocatechin-3-gallate (EGCG), and glyceollins, which modulate miRNA expression and contribute to tumor growth inhibition. These advances seek to address the limitations of conventional therapies, paving the way for targeted interventions in breast cancer. By integrating current insights on miRNA biology, therapeutic strategies, and the potential of natural products to regulate miRNA expression, this review aims to shed light on miRNA- and natural product-based approaches as promising avenues for enhancing breast cancer treatment outcomes.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder, mainly comprising two subtypes: ulcerative colitis (UC) and Crohn's disease (CD). IBD, featured by recurrent symptoms and significant morbidity, poses a significant threat to global health and has an adverse impact on quality of life. Currently, there is no curative therapy for IBD, and the available medications are only for managing the disease condition, likely owing to the insufficient understanding of the underlying pathophysiology processes involved in IBD, and the lack of safe and effective medicines. Thus, novel targeted therapies for IBD are urgently needed for better efficacy with an improved adverse event profile. As the most extensively studied member of bromodomain and extra terminal domain (BET) family proteins, bromodomain-containing protein 4 (BRD4) is emerging as a promising epigenetic therapeutic target for IBD. Pharmacological inhibition of BRD4 with selective small molecule inhibitors shows potent anti-inflammatory effects in both in vitro and different IBD mouse models. Herein, we summarize current knowledge in understanding the role of BRD4 in the pathogenesis and development of IBD, and the clinical landscape of developing BET/BRD4 inhibitors and emerging BRD4-targeted degraders as promising therapeutical alternatives. Challenges and opportunities, as well as future directions in drug discovery by targeting BRD4 are also briefly discussed.

In degenerative joint disease like osteoarthritis (OA), bioactive compounds like resveratrol, epigallocatechin gallate, curcumin, and other polyphenols often target various signalling pathways, including NFκB, TGFβ, and Wnt/β-catenin by executing epigenetic-modifying activities. Epigenetic modulation can target genes of disease pathophysiology via histone modification, promoter DNA methylation, and non-coding RNA expression, some of which are directly involved in OA but have been less explored. OA patients often seek options that can improve the quality of their life in addition to existing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Although bioactive and natural compounds exhibit therapeutic potential against OA, several disadvantages loom, like insolubility and poor bioavailability. Nanoformulated bioactive compounds promise a better way to alleviate OA since they also control systemic events, including metabolic, immunological, and inflammatory responses, by modulating host gut microbiota that can regulate OA pathogenesis. Recent data suggest gut dysbiosis in OA. However, limited evidence is available on the role of bioactive compounds as epigenetic and gut modulators in ameliorating OA. Moreover, it is not known whether the effects of polyphenolic bioactive compounds on gut microbial response are mediated by epigenetic modulatory activities in OA. This narrative review highlights the nanotherapeutic strategies utilizing bioactive compounds, reporting their effects on chondrocyte growth, metabolism, and epigenetic modifications in osteoarthritis amelioration.

Epigenetic dysregulation has long been recognized as a significant contributor to tumorigenesis and tumor maintenance, impacting all recognized cancer hallmarks. Although some epigenetic drugs have received regulatory approval for certain hematological malignancies, their efficacy in treating solid tumors has so far been largely disappointing. However, recent advancements in developing new compounds and a deeper understanding of cancer biology have led to success in specific solid tumor subtypes through precision medicine approaches. Moreover, epigenetic drugs may play a crucial role in synergizing with other anticancer treatments, enhancing the sensitivity of cancer cells to various anticancer therapies, including chemotherapy, radiation therapy, hormone therapy, targeted therapy, and immunotherapy. In this review, we critically evaluate the evolution of epigenetic drugs, tracing their development from initial use as monotherapies to their current application in combination therapies. We explore the preclinical rationale, completed clinical studies, and ongoing clinical trials. Finally, we discuss trial design strategies and drug scheduling to optimize the development of possible combination therapies.

Heavy metals like arsenic, mercury, cadmium, and lead are harmful pollutants that can change how our genes are regulated without altering the DNA sequence, specifically through a process called DNA methylation (DNAm) at 5-methylcytosine, an epigenetic mark that we will focus on in this review. These changes in DNAm are most sensitive during pregnancy, a critical time for development when these modifications can affect how traits are expressed. Historically, most research on these environmental effects has focused on adults, but now there is more emphasis on studying the impacts during early development and childhood. The placenta acts as a protective barrier between the mother and the baby, and by examining it, scientists can identify changes in key genes that might affect long-term health. This review looks at how exposure to heavy metals during pregnancy can cause changes in the gene regulation by DNAm in newborns, as seen in their umbilical cord blood. These changes reflect the baby's genetic state during pregnancy and can be influenced by the mother's environment and genetics, as well as the baby's own genetics.

Inflammation is an essential step for the etiology of multiple diseases. Clinically, due to the limitations of current drugs for the treatment of inflammatory diseases, such as serious side effects and expensive costs, it is urgent to explore novel mechanisms and medicines. Natural products have received extensive attention recently because of their multi-component and multi-target characteristics. Epigenetic modifications are crucial pathophysiological targets for developing innovative therapies for pharmacological interventions. Investigations examining how natural products improving inflammation through epigenetic modifications are emerging. This review state that natural products relieve inflammation via regulating the gene transcription levels through chromosome structure regulated by histone acetylation levels and the addition or deletion of methyl groups on DNA duplex. They could also exert anti-inflammatory effects by modulating the proteins in typical inflammatory signaling pathways by ubiquitin-related degradation and the effect of glycolysis derived free glycosyls. Studies on epigenetic modifications have the potential to facilitate the development of natural products as therapeutic agents. Future research directed at better understanding of how natural products modulate inflammatory processes through less studied epigenetic modifications including neddylation, SUMOylation, palmitoylation and lactylation, may provide new implications. Meanwhile, higher quality preclinical studies and more powerful clinical evidence are still needed to firmly establish the clinical efficacy of the natural products. Trial Registration: ClinicalTrials.gov Identifier: NCT01764204; ClinicalTrials.gov Identifier: NCT05845931; ClinicalTrials.gov Identifier: NCT04657926; ClinicalTrials.gov Identifier: NCT02330276.

B cells are crucial component of humoral immunity, and their role in the tumor immune microenvironment (TME) has garnered significant attention in recent years. These cells hold great potential and application prospects in the field of tumor immunotherapy. Research has demonstrated that the TME can remodel various B cell functions, including proliferation, differentiation, antigen presentation, and antibody production, thereby invalidating the anti-tumor effects of B cells. Concurrently, numerous immune checkpoints (ICs) on the surface of B cells are upregulated. Aberrant B-cell IC signals not only impair the function of B cells themselves, but also modulate the tumor-killing effects of other immune cells, ultimately fostering an immunosuppressive TME and facilitating tumor immune escape. Blocking ICs on B cells is beneficial for reversing the immunosuppressive TME and restoring anti-tumor immune responses. In this paper, the intricate connection between B-cell ICs and the TME is delved into, emphasizing the critical role of targeting B-cell ICs in anti-tumor immunity, which may provide valuable insights for the future development of tumor immunotherapy based on B cells.

Biofilm formation is a common mechanism by which bacteria undergo phenotypic changes to adapt to environmental stressors. The formation of biofilms has a detrimental impact in clinical settings by contributing to chronic infections and promoting antibiotic resistance. Delving into the molecular mechanisms, the quorum sensing (QS) system involves the release of chemical signals for bacterial cell-to-cell communication, which activates and regulates the expression of various genes and virulence factors, including those related to biofilm formation. Accordingly, the QS system becomes a potential target for combating biofilm-associated concerns. Natural products derived from plants have a long history of treating infectious diseases in humans due to their antimicrobial properties, making them valuable resources for screening anti-biofilm agents. This review aims to discover the mechanisms by which phytochemical agents inhibit QS, potentially offering promising new therapies for treating biofilm-associated infections. By targeting the QS system, these phytochemical agents can prevent bacterial aggregation and biofilm formation while also diminishing other bacterial virulence factors. Additionally, it is important to focus on the advancement of techniques and experiments to investigate their molecular mechanisms. A thorough understanding of these mechanisms may encourage further studies to evaluate the safety and efficacy of phytochemical agents used alone or in combination with other strategies.

KDM4A-F enzymes are a subfamily of histone demethylases containing the Jumonji C domain (JmjC) using Fe(II) and 2-oxoglutarate for their catalytic function. Overexpression or deregulation of KDM4 enzymes is associated with various cancers, altering chromatin structure and causing transcriptional dysfunction. As KDM4 enzymes have been associated with malignancy, they may represent novel targets for developing innovative therapeutic tools to treat different solid and blood tumors. KDM4A is the isozyme most frequently associated with aggressive phenotypes of these tumors. To this aim, industrial and academic medicinal chemistry efforts have identified different KDM4 inhibitors. Industrial and academic efforts in medicinal chemistry have identified numerous KDM4 inhibitors, primarily pan-KDM4 inhibitors, though they often lack selectivity against other Jumonji family members. The pharmacophoric features of the inhibitors frequently include a chelating group capable of coordinating the catalytic iron within the active site of the KDM4 enzyme. Nonetheless, non-chelating compounds have also demonstrated promising inhibitory activity, suggesting potential flexibility in the drug design. Several natural products, containing monovalent or bivalent chelators, have been identified as KDM4 inhibitors, albeit with a micromolar inhibition potency. This highlights the potential for leveraging them as templates for the design and synthesis of new derivatives, exploiting nature's chemical diversity to pursue more potent and selective KDM4 inhibitors.

Epigenetic modifiers (miRNAs, histone methyltransferases (HMTs)/demethylases, and DNA methyltransferases/demethylases) are associated with cancer proliferation, metastasis, angiogenesis, and drug resistance. Among these modifiers, HMTs are frequently overexpressed in various cancers, and recent studies have increasingly identified these proteins as potential therapeutic targets. In this review, we discuss members of the SET and MYND domain-containing protein (SMYD) family that are topics of extensive research on the histone methylation and nonhistone methylation of cancer-related genes. Various members of the SMYD family play significant roles in cancer proliferation, metastasis, and drug resistance by regulating cancer-specific histone methylation and nonhistone methylation. Thus, the development of specific inhibitors that target SMYD family members may lead to the development of cancer treatments, and combination therapy with various anticancer therapeutic agents may increase treatment efficacy.

Due to the absence of screening protocols, high-grade serous ovarian cancer (HGSOC) patients are frequently diagnosed at an advanced stage, which significantly reduces the survival rate. Moreover, relapse occurs in approximately 70% of HGSOC patients after primary treatment. Predicting resistance to primary chemotherapy remains a challenge. In the research setting, transcriptomic analyses have emerged as powerful tools for predicting which HGSOC patients are likely to benefit from primary treatment. The aim of this review was to investigate the literature demonstrating the potential of transcriptomic signatures as biomarkers for assessing the risk of resistance to platinum-based chemotherapy.