Epigenetic Modifications Research Articles

Integrated multi-omics reveals contrasting epigenetic patterns in leaf and root morphogenesis in Aegilops speltoides

Aegilops speltoides, the closest ancestor of the wheat B subgenome, has been well studied genomically. However, the epigenetic landscape of Ae. speltoides and the effects of epigenetics on its growth and development remain poorly understood. Here, we present a comprehensive multi-omics atlas of leaves and roots in Ae. speltoides, encompassing transcriptome, DNA methylation, histone modifications, and small RNA profiling. Divergent DNA methylation levels were detected between leaves and roots, and were associated with differences in accumulated 24-nt siRNAs. DNA methylation changes in promoters and gene bodies showed strong connections with altered expression between leaves and roots. Transcriptional regulatory networks (TRN) reconstructed between leaves and roots were driven by tissue-specific TF families. DNA methylation and histone modification act together as switches that shape root and leaf morphogenesis by modulating the binding of tissue-specific TFs to their target genes. The TRNs in leaves and roots reshaped during wheat polyploidization were associated with alterations in epigenetic modifications. Collectively, these results not only shed light on the critical contribution of epigenetic regulation in the morphogenesis of leaves and roots in Ae. speltoides but also provide new insights for future investigations into the complex interplay of genetic and epigenetic factors in the developmental biology of common wheat.

Genetic and immunological implications in fibromyalgia: A Literature Review

Fibromyalgia (FM), a musculoskeletal condition characterized by widespread pain and numerous associated symptoms, is a complex disorder with uncertain etiology and pathogenesis. Most of the patients suffering from this syndrome are undiagnosed due to a lack of standard diagnostic criteria. Recent studies have shown the involvement of immune dysfunction and various pro-inflammatory cytokines in FM. Since there is so much uncertainty regarding the pathogenesis of FM, treatment modalities are very limited and ineffective. This review aimed to analyze the immunological mechanisms behind FM, attempting to deepen the understanding of its pathogenesis. Additionally, the review elucidates FM's associations with autoimmune diseases, highlighting shared pathophysiological mechanisms and overlapping symptoms. We synthesized current literature available on Google Scholar, PubMed, Springer, and Web of Science, the review explored the intricate interactions between genetic predisposition, immune dysregulation, and environmental factors in FM pathogenesis. The inclusion criteria prioritized studies focusing on the immunological aspect of FM. In conclusion, immune dysfunction has a role to play in the pathogenesis of FM, and immunomodulatory therapies have proven to be beneficial in the treatment of FM. Genetic variants, epigenetic modifications, and gut microbiome alterations are potential triggers for immune system dysfunction, contributing to the manifestation and exaggeration of FM symptoms. This review provided a comprehensive resource for researchers and clinicians, a guide for future investigations and clinical management towards improved outcomes and enhanced quality of life for individuals with FM.

Degradation of IKZF1 prevents epigenetic progression of Tcell exhaustion in an antigen-specific assay.

In cancer, chronic antigen stimulation drives effector Tcells to exhaustion, limiting the efficacy of Tcell therapies. Recent studies have demonstrated that epigenetic rewiring governs the transition of Tcells from effector to exhausted states and makes a subset of exhausted Tcells non-responsive to PD1 checkpoint blockade. Here, we describe an antigen-specific assay for Tcell exhaustion that generates Tcells phenotypically and transcriptionally similar to those found in human tumors. We perform a screen of human epigenetic regulators, identifying IKZF1 as a driver of Tcell exhaustion. We determine that the IKZF1 degrader iberdomide prevents exhaustion by blocking chromatin remodeling at Tcell effector enhancers and preserving the binding of AP-1, NF-κB, and NFAT. Thus, our study uncovers a role for IKZF1 as a driver of Tcell exhaustion through epigenetic modulation, providing a rationale for the use of iberdomide in solid tumors to prevent Tcell exhaustion.

Kidney toxicology of a novel compound Lithium Bis(trifluoromethanesulfonyl)imide (LiTFSI, ie. HQ-115) used in energy applications: An epigenetic perspective

Exposure to emerging energy-based environmental contaminants such as lithium bis(trifluoromethanesulfonyl)imide (LiTFSI, trade name HQ-115), poses a significant threat to human health, yet its impact on kidney function and epigenetic regulation remains poorly understood. Here, we investigated the effects of LiTFSI exposure on kidney-related biochemical indicators, renal injuries, and epigenetic alterations in male CD-1 mice under both 14-day and 30-day exposure durations. Our study revealed that LiTFSI exposure led to changes in kidney-related markers, notably affecting serum bicarbonate levels, while relative kidney weight remained unaffected. Histological analysis revealed tubule dilation, inflammation, and loss of kidney structure in LiTFSI-exposed mice, alongside dysregulated expression of genes associated with inflammation, renal function, and uric acid metabolism. Epigenetic analysis further identified widespread DNA methylation changes in the two exposure regimes. Functional analysis revealed that differentially methylated regions are implicated in cell apoptosis and cancer-related pathways and are enriched with development-related transcription factor binding motifs, suggesting a potential mechanism of action underlying exposure induced kidney damage. These findings underscore the intricate interplay between environmental exposures, epigenetic modulation, and kidney health, emphasizing the need for additional research to unravel precise mechanisms and develop targeted interventions to mitigate the adverse effects of LiTFSI and exposure of similar clean energy compounds on human health.

The Metformin Immunoregulatory Actions in Tumor Suppression and Normal Tissues Protection.

The immune system is the key player in a wide range of responses in normal tissues and tumors to anticancer therapy. Inflammatory and fibrotic responses in normal tissues are the main limitations of chemotherapy, radiotherapy, and also some newer anticancer drugs such as immune checkpoint inhibitors (ICIs). Immune system responses within solid tumors including anti-tumor and tumor-promoting responses can suppress or help tumor growth. Thus, modulation of immune cells and their secretions such as cytokines, growth factors and epigenetic modulators, pro-apoptosis molecules, and some other molecules can be suggested to alleviate side effects in normal tissues and drug-resistance mechanisms in the tumor. Metformin as an anti-diabetes drug has shown intriguing properties such as anti-inflammation, anti-fibrosis, and anticancer effects. Some investigations have uncovered that metformin can ameliorate radiation/chemotherapy toxicity in normal cells and tissues through the modulation of several targets in cells and tissues. These effects of metformin may ameliorate severe inflammatory responses and fibrosis after exposure to ionizing radiation or following treatment with highly toxic chemotherapy drugs. Metformin can suppress the activity of immunosuppressive cells in the tumor through the phosphorylation of AMP-activated protein kinase (AMPK). In addition, metformin may stimulate antigen presentation and maturation of anticancer immune cells, which lead to the induction of anticancer immunity in the tumor. This review aims to explain the detailed mechanisms of normal tissue sparing and tumor suppression during cancer therapy using adjuvant metformin with an emphasis on immune system responses.

VascuFit: Aerobic exercise improves endothelial function independent of cardiovascular risk: A randomized-controlled trial.

Background and aimsEndothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50% of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs). MethodsSedentary adults with elevated CV risk between 40-60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n=30) or received standard exercise recommendations (n=14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses. ResultsbaFMD improved by 2.38% (CI:0.70-4.06, p=0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2% of dataset variability was higher in the NLPE-group compared to the control group (2.71±2.02 vs. 1.65±0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD. ConclusionsThe improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.

Artificial Intelligence Applications in Oral Cancer and Oral Dysplasia.

Oral squamous cell carcinoma (OSCC) is a highly unpredictable disease with devastating mortality rates that have not changed over the past decades, in the face of advancements in treatments and biomarkers, which have improved survival for other cancers. Delays in diagnosis are frequent, leading to more disfiguring treatments and poor outcomes for patients. The clinical challenge lies in identifying those patients at the highest risk of developing OSCC. Oral epithelial dysplasia (OED) is a precursor of OSCC with highly variable behavior across patients. There is no reliable clinical, pathological, histological, or molecular biomarker to determine individual risk in OED patients. Similarly, there are no robust biomarkers to predict treatment outcomes or mortality in OSCC patients. This review aims to highlight advancements in artificial intelligence (AI)-based methods to develop predictive biomarkers of OED transformation to OSCC or predictive biomarkers of OSCC mortality and treatment response. Biomarkers such as S100A7 demonstrate promising appraisal for the risk of malignant transformation of OED. Machine learning-enhanced multiplex immunohistochemistry workflows examine immune cell patterns and organization within the tumor immune microenvironment to generate outcome predictions in immunotherapy. Deep learning (DL) is an AI-based method using an extended neural network or related architecture with multiple "hidden" layers of simulated neurons to combine simple visual features into complex patterns. DL-based digital pathology is currently being developed to assess OED and OSCC outcomes. The integration of machine learning in epigenomics aims to examine the epigenetic modification of diseases and improve our ability to detect, classify, and predict outcomes associated with epigenetic marks. Collectively, these tools showcase promising advancements in discovery and technology, which may provide a potential solution to addressing the current limitations in predicting OED transformation and OSCC behavior, both of which are clinical challenges that must be addressed in order to improve OSCC survival.

Chromatin Accessibility Plays an Important Epigenetic Role on Antibody Expression From CMV Promoter and DNA Elements Flanking the CHO TI Host Landing-Pad.

Targeted integration (TI) Chinese hamster ovary (CHO) platforms are commonly used for protein expression. However, the impact of epigenetic modifications on protein expression in TI cell lines remains elusive since almost all the epigenetic studies focus on random integration (RI) of the gene of interest and only within the promoter region. To address the impact of epigenetic modifications on TI CHO cells, we utilized a standard mAb-1 to identify and characterize TI clones with the same transgene copy numbers but different levels of transgene transcription and titer. Surprisingly, while CMV promoters were not methylated and histone acetylation/methylation was present, these epigenetic markers did not trend with mRNA transcription and protein expression in our TI model. Instead, ATAC-seq data analysis revealed that differences in chromatin accessibility within the TI site could be a major factor impacting these observed differences. However, neither chromatin accessibility nor histone acetylation/methylation profiles in early cultures were predictive of high-expressing clones early during the CLD process. Finally, modulation of the histone profiles (H3K27ac and H3K4me3) at the CMV promoters within the TI integration site using dCas9 fusion proteins was not effective in further increasing mAb titers which could have been likely due to interference of the dCas9 fusion proteins with transcription from the CMV promoters. Overall, our data suggests increasing chromatin accessibility at the TI site is the most effective way to increase mRNA transcription and hence, productivity in TI cell lines.

Harnessing Epigenetic Mechanisms to Overcome Immune Evasion in Cancer: The Current Strategies and Future Directions.

Combining epigenetic alterations with cancer immunotherapy offers a promising approach to improve therapeutic outcomes by targeting the complex biology of tumors. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) play a dual role in maintaining immune homeostasis and promoting cancer progression. Changes like hypomethylation in tumor cells can contribute to immune evasion and treatment resistance. Advances in epigenetic tools, particularly clustered regularly interspaced short palindromic repeat (CRISPR) and their associated protein (Cas9)-based epigenetic editing, allow for precise gene expression control, opening new avenues for research and therapy. The improved accuracy of CRISPR/dCas9 systems, when paired with appropriate delivery methods such as viral vectors or nanoparticles, has facilitated innovative combination therapies involving immune checkpoint inhibitors and epigenetic drugs. These combinations enhance the immune system's ability to recognize and destroy cancer cells. Despite these advancements, challenges like off-target effects, delivery issues, and resistance remain. Current research is focused on identifying new therapeutic targets, improving delivery systems, and using real-time feedback to refine treatment. Overall, combining immunotherapy with epigenetic modifications holds significant potential for personalized cancer treatment, paving the way for more effective and individualized therapeutic strategies that target both the immune system and the tumor microenvironment. Further development in this area is expected to revolutionize cancer therapy and improve patient outcomes.

FTO-mediated SMAD2 m6A modification protects cartilage against Osteoarthritis

N6-methyladenosine (m6A) modification is one of the most prevalent forms of epigenetic modification and plays an important role in the development of degenerative diseases such as osteoarthritis (OA). However, the evidence concerning the role of m6A modification in OA is insufficient. Here, m6A modification was increased in human OA cartilage and degenerated chondrocytes. Among all of the m6A enzymes, the expression of the demethylase fat mass and obesity-associated protein (FTO) decreased dramatically. Conditional knockout of FTO in chondrocytes accelerates OA progression. FTO transcription is regulated by runt-related transcription factor-1 (RUNX1). Reduced FTO elevates m6A modification at the adenosine N6 position in SMAD family member 2 (SMAD2) mRNA, whose stability is subsequently modulated by the recruited m6A reader protein YTH N6-methyladenosine RNA binding protein F2 (YTHDF2). Collectively, these findings reveal the function and mechanism of the m6A family member FTO in OA progression. Therefore, reducing m6A modification to increase SMAD2 stability by activating FTO might be a potential therapeutic strategy for OA treatment.

A rising star involved in tumour immunity: Lactylation.

In recent years, continuous exploration worldwide has revealed that some metabolites produced during cellular and tissue metabolism can act as signalling molecules to exert different effects on the human body. These metabolites may act as cofactors for proteases or as post-translational modifications linked to proteins. Lactate, a traditional metabolite, is found at high levels in the tumour microenvironment (TME). Many studies have shown that lactate influences tumorigenesis and development via different mechanisms, not only through the metabolic reprogramming of tumours but also through its significant impact on tumour immunity. Previously, tumour cells were reported to use glucose and glutamine to fuel lactate metabolism; however, lactate serves not only as an energy source for tumour cells but also as a precursor substance needed for the post-translational modification of proteins. Recent studies identified a novel form of epigenetic modification, lactate-mediated histone lysine lactylation (Kla) and demonstrated that histone lactylation directly stimulates chromatin after gene transcription; consequently, lactylation has become a popular research topic in recent years. This article focuses on the research progress and application prospects of lactylation in the context of tumour immunity.

Comprehensive analysis of bulk, single-cell RNA sequencing, and spatial transcriptomics revealed IER3 for predicting malignant progression and immunotherapy efficacy in glioma

BackgroundAs part of stress-triggered molecules, immediate early response 3 (IER3) dysregulation has been reported to sustain pro-oncogenic pathways and precede malignant transformation. However, the role of IER3 in glioma pathology is ill-defined.MethodsImmunohistochemistry (IHC) assay and publicly available glioma datasets were used to calculate the IER3 expression level in glioma. Wound healing, invasion and cell counting kit-8 (CCK8) assays were applied to measure the cell viability and capacities of migration and invasion of glioma cells in vitro. The immunofluorescence (IF) assay was used to assess the expression associations of IER3 with CCL2 and TGFBI. Cox regression analysis and Kaplan-Meier (K-M) curve were introduced to compute the prognosis-predicting value of IER3. Variations in copy number (CNVs), single nucleotide (SNVs), and methylation profiles were analyzed to illustrate the epigenetic modifications of IER3. Gliomas were divided into two subgroups using the restricted cubic spline (RCS) method.Results IER3was overexpressed and hypomethylated in gliomas and significantly associated with the dismal prognosis of glioma samples. Samples in the high IER3 subgroup were characterized by increased infiltration of tumor-associated monocytes/macrophages (TAMMs), as well as the elevated sensitivity to Dabrafenib, an inhibitor of BRAF. In addition, this subgroup demonstrated a low mutation rate of IDH, high gain rates of BRAF, ELTD1, and PDGFA. Gliomas with relatively low IER3 expression demonstrated a less invasive subtype and were featured by favorable prognosis, increased response to immunotherapy, and adjuvant chemotherapy plus radiotherapy. The IF assay revealed that IER3 was co-localized and co-expressed with TGFBI. The glioma cells with small interfering RNA (siRNA)-silenced IER3 displayed lower migration, invasion, proliferation, and cell viability than the control group.ConclusionsIn this study, we identified IER3 upregulation as an essential biomarker that could assist in adjuvant therapy and prognosis prediction for gliomas.

KDM1A/LSD1 inhibition enhances chemotherapy response in ovarian cancer.

Ovarian cancer (OCa) is the deadliest of all gynecological cancers. The standard treatment for OCa is platinum-based chemotherapy, such as carboplatin or cisplatin in combination with paclitaxel. Most patients are initially responsive to these treatments; however, nearly 90% will develop recurrence and inevitably succumb to chemotherapy-resistant disease. Recent studies have revealed that the epigenetic modifier lysine-specific histone demethylase 1A (KDM1A/LSD1) is highly overexpressed in OCa. However, the role of KDM1A in chemoresistance and whether its inhibition enhances chemotherapy response in OCa remains uncertain. Analysis of TCGA datasets revealed that KDM1A expression is high in patients who poorly respond to chemotherapy. Western blot analysis show that treatment with chemotherapy drugs cisplatin, carboplatin, and paclitaxel increased KDM1A expression in OCa cells. KDM1A knockdown (KD) or treatment with KDM1A inhibitors NCD38 and SP2509 sensitized established and patient-derived OCa cells to chemotherapy drugs in reducing cell viability and clonogenic survival and inducing apoptosis. Moreover, knockdown of KDM1A sensitized carboplatin-resistant A2780-CP70 cells to carboplatin treatment and paclitaxel-resistant SKOV3-TR cells to paclitaxel. RNA-seq analysis revealed that a combination of KDM1A-KD and cisplatin treatment resulted in the downregulation of genes related to epithelial-mesenchymal transition (EMT). Interestingly, cisplatin treatment increased a subset of NF-κB pathway genes, and KDM1A-KD or KDM1A inhibition reversed this effect. Importantly, KDM1A-KD, in combination with cisplatin, significantly reduced tumor growth compared to a single treatment in an orthotopic intrabursal OCa xenograft model. Collectively, these findings suggest that combination of KDM1A inhibitors with chemotherapy could be a promising therapeutic approach for the treatment of OCa.

Generation and Characterization of Induced Pluripotent Stem Cells Carrying An ASXL1 Mutation.

Additional sex combs-like 1 (ASXL1) is an epigenetic modulator frequently mutated in myeloid malignancies, generally associated with poorprognosis. Current models for ASXL1-mutated diseases are mainly based on the complete deletion of Asxl1 or overexpression of C-terminal truncations in mice models. However, these models cannot fully recapitulate the pathogenesis of myeloid malignancies. Patient-derived induced pluripotent stem cells (iPSCs) provide valuable disease models that allow us to understand disease-related molecular pathways and develop novel targeted therapies. Here, we generated iPSCs from a patient with myeloproliferative neoplasm carrying a heterozygous ASXL1 mutation. The iPSCs we generated exhibited the morphology of pluripotent cells, highly expressed pluripotent markers, excellent differentiation potency in vivo, and normal karyotype. Subsequently, iPSCs with or without ASXL1 mutation were induced to differentiate into hematopoietic stem/progenitor cells, and we found that ASXL1 mutation led to myeloid-biased output and impaired erythroid differentiation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that terms related to embryonic development, myeloid differentiation, and immune- and neural-related processes were most enriched in the differentially expressed genes. Western blot demonstrated that the global level of H2AK119ub was significantly decreased when mutant ASXL1 was present. Chromatin Immunoprecipitation Sequencing showed that most genes associated with stem cell maintenance were upregulated, whereas occupancies of H2AK119ub around these genes were significantly decreased. Thus, the iPSC model carrying ASXL1 mutation could serve as a potential tool to study the pathogenesis of myeloid malignancies and to screen targeted therapy for patients.

Promising and challenging phytochemicals targeting LC3 mediated autophagy signaling in cancer therapy.

Phytochemicals possess a wide range of anti-tumor properties, including the modulation of autophagy and regulation of programmed cell death. Autophagy is a critical process in cellular homeostasis and its dysregulation is associated with several pathological conditions, such as cancer, neurodegenerative diseases, and diabetes. In cancer, autophagy plays a dual role by either promoting tumor growth or suppressing it, depending on the cellular context. During autophagy, autophagosomes engulf cytoplasmic components such as proteins and organelles. LC3-II (microtubule-associated protein 1 light chain 3-II) is an established marker of autophagosome formation, making it central to autophagy monitoring in mammals. To explore the regulatory role of phytochemicals in LC3-mediated autophagy and their potential therapeutic impact on cancer. The review emphasizes the involvement of autophagy in tumor promotion and suppression, particularly focusing on autophagy-related signaling pathways like oxidative stress through the NRF2 pathway, and its implications for genomic stability in cancer development. The review focuses on a comprehensive analysis of bioactive compounds including Curcumin, Celastrol, Resveratrol, Kaempferol, Naringenin, Carvacrol, Farnesol, and Piperine. Literature on these compounds was examined to assess their influence on autophagy, LC3 expression, and tumor-related signaling pathways. A systematic literature search was conducted across databases including PubMed, Scopus, and Web of Science from inception to 2023. Studies were selected from prominent databases, focusing on their roles in cancer diagnosis and therapeutic interventions, particularly in relation to LC3-mediated mechanisms. Phytochemicals have been shown to modulate autophagy through the regulation of LC3-II levels and autophagic flux in cancer cells. The interaction between autophagy and other cellular pathways such as oxidative stress, inflammation, and epigenetic modulation highlights the complex role of autophagy in tumor biology. For instance, Curcumin and Resveratrol have been reported to either induce or inhibit autophagy depending on cancer type, influencing tumor progression and therapeutic responses. Targeting autophagy through LC3 modulation presents a promising strategy for cancer therapy. The dual role of autophagy in tumor suppression and promotion, however, necessitates careful consideration of the context in which autophagy is induced or inhibited. Future research should aim to delineate these context-specific roles and explore how phytochemicals can be optimized for therapeutic efficacy. Novel therapeutic strategies should focus on the use of bioactive compounds to fine-tune autophagy, thereby maximizing tumor suppression and inducing programmed cell death in cancer cells.

291P Novel insights into the expression and the epigenetic modulation of LKB1, a potential diagnostic and therapeutic player in Duchenne muscular dystrophy

291P Novel insights into the expression and the epigenetic modulation of LKB1, a potential diagnostic and therapeutic player in Duchenne muscular dystrophy

The m6A and immune regulatory gene signature predicts the prognosis and correlates with immune infiltration of head and neck squamous cell carcinoma

Recent investigations have underscored the epigenetic modulation of the immune response; however, the interplay between RNA N6-methyladenosine (m6A) modification and immunomodulation in head and neck squamous cell carcinoma (HNSC) remains relatively unexplored. To bridge this knowledge gap, we undertook an extensive examination of the potential contributions of m6A modification and immunomodulation in HNSC. We amalgamated and deduplicated 27 m6A -related genes (m6AGs) and 1342 immune regulation-related genes (IMRGs), resulting in a comprehensive dataset encompassing 1358 genes. This dataset was scrutinized for m6A modification and immunomodulatory patterns within HNSC specimens. Employing Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) technique, we developed a prognostic risk model for m6A regulator-mediated methylation modification and immunomodulation-related differentially expressed genes (m6A&IMRDEGs). Our differential expression analysis delineated 29 m6A&IMRDEGs, and Weighted Gene Co-expression Network Analysis (WGCNA) elucidated two module genes (IL11 and MMP13) subjected to correlation analysis. The prognostic prediction models revealed that the clinical predictive efficacy peaked for 1-year forecasts, followed sequentially by 3-year and 5-year predictions. The risk scores derived from the model adeptly categorized HNSC patients into high- and low-risk cohorts, with the high-risk group exhibiting a more unfavorable prognosis. Protein-Protein Interaction (PPI) analysis identified 7 hub genes implicated in m6A and immune regulation, namely BPIFB1, BPIFB2, GP2, MUC5B, MUC7, PIP, and SCGB3A1. Furthermore, we noted marked disparities in the expression profiles of 18 immune cell types between the high- and low-risk groups. Our results substantiate that the clustering subpopulations and risk models associated with m6A and immune regulatory genes portend a poor prognosis in HNSC. The risk score emerges as a potent prognostic biomarker and predictive metric for HNSC patients. A thorough assessment of m6A and immune regulatory genes in HNSC will augment our comprehension of the tumor immune microenvironment and facilitate the advancement of HNSC therapeutics.

The Role of Protein Post-Translational Modifications in Fruit Ripening

Fruit ripening represents a multifaceted biological process intricately controlled by an array of plant hormones, transcription factors, and epigenetic modifications. These regulatory mechanisms are crucial in determining fruit quality and post-harvest shelf life. Recent advancements in proteomics have shifted the focus toward understanding protein post-translational modifications (PTMs), which play a crucial role in modulating protein function. PTMs enhance protein activity and stability by altering their properties after biosynthesis, thereby adding an additional layer of regulation to the ripening process. This paper provides a comprehensive review of the roles of PTMs, including ubiquitination, phosphorylation, redox modifications, and glycosylation in regulating fruit ripening. Emphasis is placed on the intricate interplay between these PTMs and key regulator factors such as plant hormones, transcriptional mechanisms, and epigenetic modifications. By exploring these interactions, this review seeks to enhance our understanding of the complex regulatory network underlying fruit ripening and to offer novel perspectives on strategies for fruit preservation.

QTL analysis to identify genes involved in the trade-off between silk protein synthesis and larva-pupa transition in silkworms

BackgroundInsect-based food and feed are increasingly attracting attention. As a domesticated insect, the silkworm (Bombyx mori) has a highly nutritious pupa that can be easily raised in large quantities through large-scale farming, making it a highly promising source of food. The ratio of pupa to cocoon (RPC) refers to the proportion of the weight of the cocoon that is attributed to pupae, and is of significant value for edible utilization, as a higher RPC means a higher ratio of conversion of mulberry leaves to pupa. In silkworm production, there is a trade-off between RPC and cocoon shell ratiao(CSR), which refers the ratio of silk protein to the entire cocoon, during metamorphosis process. Understanding the genetic basis of this balance is crucial for breeding edible strains with a high RPC and further advancing its use as feed.ResultsUsing QTL-seq, we identified a quantitative trait locus (QTL) for the balance between RPC and CSR that is located on chromosome 11 and covers a 9,773,115-bp region. This locus is an artificial selection hot spot that contains ten non-overlapping genomic regions under selection that were involved in the domestication and genetic breeding processes. These regions include 17 genes, nine of which are highly expressed in the silk gland, which is a vital component in the trade-off between RPC and CSR. These genes are annotate with function related with epigenetic modifications and the regulation of DNA replication et al. We identified one and two single nucleotide polymorphisms (SNPs) in the exons of teh KWMTBOMO06541 and KWMTBOMO06485 genes that result in amino acid changes in the protein domains. These SNPs have been strongly selected for during the domestication process. The KWMTBOMO06485 gene encodes the Bombyx mori (Bm) tRNA methyltransferase (BmDnmt2) and its knockout results in a significant change in the trade-off between CSR and RPC in both sexes.ConclusionsTaken together, our results contribute to a better understanding of the genetic basis of RPC and CSR. The identified QTL and genes that affect RPC can be used for marker-assisted and genomic selection of silkworm strains with a high RPC. This will further enhance the production efficiency of silkworms and of closely-related insects for edible and feed purposes.

MicroRNA expression signature in gastrointestinal stromal tumour & their molecular & histological features.

Background & objectives In gastrointestinal stromal tumour (GIST), not only genetic abnormalities are responsible for adverse clinical events, but epigenetic modifications also play a crucial role. MicroRNA (miRNA) dysregulation plays a significant role in carcinogenesis as miRNAs serve as natural silencer for their targets. Our study aimed to explore the miRNAs expression and its association with molecular and histopathological characteristics of GIST. Methods Fifty GIST samples, including 45 formalin fixed paraffin embedded (FFPE) and fresh tissues were included. Peripheral non-tumour tissues were used as controls. All the cases were confirmed using immunohistochemistry. RNA was extracted using miRNA-specific kit, and the expression was performed using RT-qPCR. The data were evaluated using AriaMx software version 1.5 (Agilent, US). MiRNAs expression was analyzed by using the relative quantification method (ΔΔCT). Results miR-221, miR-222, miR-494 and miR-34a showed significant down-regulation in tumours relative to non-tumour tissues. The expression levels of these miRNAs were significantly down-regulated in c-KIT (proto-oncogene encoding the tyrosine kinase transmembrane receptor)-positive tumours compared to c-KIT-negative. Further analysis revealed that reduced expression was associated with spindle subtypes and gastric localization. However, there was no significant correlation with other histological features. Additionally, miR-221/222, and miR-494 were down-regulated in most of the KIT exon 11 mutant subtypes, while miRNA-34a was associated with platelet derived growth factor receptor alpha (PDGFRA) mutations. Interpretation & conclusions The present study showed that the down-regulation of these miRNAs may help better molecular classification and characterization of GISTs. Our results offer new insight into the association between miRNAs and histological features, enabling a more thorough understanding of GISTs at the molecular level.