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Neutrophil extracellular traps drive peritoneal inflammation and tissue remodeling in pediatric peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) sustains children with chronic kidney disease stage 5 (CKD5) but promotes peritoneal membrane remodeling. Neutrophil extracellular traps (NETs) orchestrate antimicrobial defense and sterile inflammation; their involvement in PD-induced transformation is unknown. METHODS: Forty-five children were enrolled in the International Pediatric Peritoneal Biobank. Peritoneal biopsies taken at PD initiation and after ≥ 12 months of low-glucose-degradation-product PD were compared with surgical biopsies from non-uremic peers. Histomorphometry quantified microvessel de

How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health.

Recent studies support the influence of paternal lifestyle and diet before conception on the health of the offspring via epigenetic inheritance through sperm DNA methylation, histone modification, and small non-coding RNA (sncRNA) expression and regulation. Smoking may induce DNA hypermethylation in genes related to anti-oxidation and insulin resistance. Paternal diet and obesity are associated with greater risks of metabolic dysfunction in offspring via epigenetic alterations in the sperm. Metabolic changes, such as high blood glucose levels and increased body weight, are commonly observed in

The emerging role of epigenetic regulation in pain sensitization associated with headache disorders.

BACKGROUND: Headache disorders, including migraine, tension-type headache, and cluster headache, are among the most prevalent and disabling neurological conditions. Although genetic factors contribute to their pathogenesis, they fail to fully account for their clinical heterogeneity, episodic nature, and varied treatment responses. This review synthesizes current evidence on the role of epigenetic mechanisms—including DNA methylation, histone modifications, non-coding RNAs, and RNA modifications—in the pathophysiology of headache disorders. PRINCIPAL FINDINGS: Evidence from both human studies

Изменения лакта и лактилации в неврологических расстройствах.

Значительное внимание стало уделяться изучению изменений в лактилации различных целевых органов как в области здравоохранения, так и в области болезней. Многие жизненно важные процессы и начало болезней связаны не только с избытком белков, но и в первую очередь регулируются различными посттрансляционными изменениями белков. Лактат, который раньше считался лишь побочным продуктом анаэробного метаболизма, превратился в важнейшую энергетическую субстрату и сигнализирующую молекулу, связанную как с физиологическими, так и патологическими процессами в нервной системе. Кроме того, в недавних исследо

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… This study revealed that lactate can act as a substrate for the PTMs of histones. Specifically, PTMs of histones are covalent modifications that occur after protein translation. … Brg1: Brahma-related gene 1; DNA: deoxyribonucleic acid; GCN5: general control nonderepressible 5; GLUTs: glucose transporters; HBO1: histone acetyltransferase binding to ORC1; HDAC1: histone deacetylase 1; HDAC2: histone deacetylase 2; HDAC3: histone deacetylase 3; HDAC8: histone deacetylase 8; KAT: …

The outcome of tissue cryopreservation on the cellular, molecular and epigenetic characteristics of endometrial tissue and stromal cells.

RESEARCH QUESTION: What impact does the cryopreservation of endometrial tissue have on cell characteristics and molecular and epigenetic profile changes in endometrial tissue and stromal cells? DESIGN: Cellular properties, such as proliferation efficiency, surface marker expression and the differentiation potency of endometrial stromal cells (ESC) isolated from fresh (Native) and cryopreserved (Cryo) tissue were compared. Moreover, changes in the expression of genes associated with pluripotency, endometrial function and epigenetic regulation and microRNA (miRNA, miR) were assessed, as were le

Propionate-producing engineered probiotics ameliorated murine ulcerative colitis by restoring anti-inflammatory macrophage via the GPR43/HDAC1/IL-10 axis.

Inflammatory bowel disease (IBD) is a chronic and unspecific inflammatory disorder of the gastrointestinal tract, and current treatment options often fail to maintain long-term remission. Studies have shown that propionate level is reduced in fecal samples from patients with IBD. Propionate can ameliorate IBD through intestinal epithelial cells and immune regulation, but its effects on the inflammatory microenvironment and macrophage differentiation have not been widely studied. To address this, we constructed an engineered propionate-producing probiotic (EcNP3) to achieve sustained restoratio

Epigenetic changes driven by environmental pollutants in lung carcinogenesis: a comprehensive review.

Lung cancer remains the leading cause of cancer-related mortality globally, with environmental pollutants identified as significant risk factors, especially for nonsmokers. The intersection of these pollutants with epigenetic mechanisms has emerged as a critical area of interest for understanding the etiology and progression of lung cancer. Epigenetic changes, including DNA methylation, histone modifications, and non-coding RNAs, can induce alterations in gene expression without affecting the DNA sequence and are influenced by environmental factors, contributing to the transformation of normal

The methyltransferase MLL4 promotes nonalcoholic steatohepatitis by enhancing NF-κB signaling.

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem worldwide, ranging from non-alcoholic fatty liver (NAFL) to the more severe metabolic non-alcoholic steatohepatitis (NASH). Although many studies have elucidated the pathogenesis of NAFLD, the epigenetic regulatory mechanism from NAFL to NASH remains incompletely understood. The histone H3 lysine 4 methyltransferase, MLL4 (also called KMT2D), is a critical epigenetic transcriptional coactivator that mediates overnutrition-induced steatosis in mice, but its potential role in the progression of NASH remains largely unknown. He

Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis.

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05%

Neutrophil extracellular traps are associated with airways inflammation and increased severity of lung disease in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterised by inflammatory lung disease and large numbers of airways neutrophils. In health, neutrophils undergo apoptosis and removal from the airway. Since CF neutrophils are known to engage in apoptosis less efficiently, we wanted to assess whether alternative forms of neutrophil clearance such as NETosis were prominent in the CF airway. METHODS: Sputum and blood were collected from 45 CF and 15 healthy control (HC) participants. Neutrophil morphology and biochemical properties were assessed in CF and HC sputum. Neutrophil extracellular traps (NETs) w

Real-Time, High-Throughput Microscopic Quantification of Human Neutrophil Extracellular Trap Release and Assessing the Pharmacology of Antagonists.

Neutrophils play an important role in innate immune defense by using several strategies, including the release of neutrophil extracellular traps (NETs) in a process referred to as NETosis. However, in the past two decades, it has become clear that the accumulation of NETs in tissues contributes to the pathophysiology of multiple inflammatory and autoimmune diseases. Therefore, interest in the development of NETosis antagonists has risen. Variable and non-standardized methods to detect and analyze NETosis were developed concomitantly, each with its own advantages and limitations. Here, we descr

Epigenetic-related transcriptional reprogramming elucidated by identification and validation of a novel reference gene combination for RT-qPCR studies in porcine oocytes of contrasting quality.

BACKGROUND: Reliable RT-qPCR results are dependent on appropriate normalisation. Oocyte maturation studies can be challenging in this respect, as the stage of development can distinctively affect reference gene transcript abundance. The aim of this study was to validate the use of reference genes in oocyte in vitro maturation RT-qPCR studies, and thereafter, examine the abundance of transcripts supporting histone modification during oocyte and early embryo development in oocytes of contrasting quality. METHODS AND RESULTS: Total RNA from oocytes from prepubertal gilts and sows was extracted e

С-терминальный связывающий белок 2 - новый дезинфицирующий опухоль, направленный на MYC-IRF4 ось в множестве миеломы.

Клетки с множественной миеломой (MM) подвержены зависимости от MYC, а их непосредственные цели по трансактивации IRF4 направлены на распространение и выживание. MYC и IRF4 по-прежнему считаются "ненаркоманными", поскольку большинство мелких ингибиторов молекулярного происхождения страдают от низкой производительности, неоптимальных фармакокинетических свойств и нежелательных нецелевых эффектов. Косвенное подавление MYC/IRF4 проявляется в качестве терапевтической уязвимости MM. Здесь мы обнаружили неоцененную опухоль, впечатляющую роль связующего белка С-терминала 2 (CTBP2) в MM путем сильного

Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes … uggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.

Valproic Acid Treatment after Traumatic Brain Injury in Mice Alleviates Neuronal Death and Inflammation in Association with Increased Plasma Lysophosphatidylcholines.

The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has neuroprotective and anti-inflammatory effects in experimental traumatic brain injury (TBI), which have been partially attributed to the epigenetic disinhibition of the transcription repressor RE1-Silencing Transcription Factor/Neuron-Restrictive Silencer Factor (REST/NRSF). Additionally, VPA changes post-traumatic brain injury (TBI) brain metabolism to create a neuroprotective environment. To address the interconnection of neuroprotection, metabolism, inflammation and REST/NRSF after TBI, we subjected C57BL/6N mice to experiment

High Homocysteine-Thiolactone Leads to Reduced MENIN Protein Expression and an Impaired DNA Damage Response: Implications for Neural Tube Defects.

DNA damage is associated with hyperhomocysteinemia (HHcy) and neural tube defects (NTDs). Additionally, HHcy is a risk factor for NTDs. Therefore, this study examined whether DNA damage is involved in HHcy-induced NTDs and investigated the underlying pathological mechanisms involved. Embryonic day 9 (E9) mouse neuroectoderm cells (NE4C) and homocysteine-thiolactone (HTL, active metabolite of Hcy)-induced NTD chicken embryos were studied by Western blotting, immunofluorescence. RNA interference or gene overexpression techniques were employed to investigate the impact of Menin expression changes

Glucose Deprivation Promotes Pseudohypoxia and Dedifferentiation in Lung Adenocarcinoma.

UNLABELLED: Increased utilization of glucose is a hallmark of cancer. Sodium-glucose transporter 2 (SGLT2) is a critical player in glucose uptake in early-stage and well-differentiated lung adenocarcinoma (LUAD). SGLT2 inhibitors, which are FDA approved for diabetes, heart failure, and kidney disease, have been shown to significantly delay LUAD development and prolong survival in murine models and in retrospective studies in diabetic patients, suggesting that they may be repurposed for lung cancer. Despite the antitumor effects of SGLT2 inhibition, tumors eventually escape treatment. Here, we

Characterization of a novel HDAC2 pathogenetic variant: a missing puzzle piece for chromatinopathies.

Histone deacetylases (HDACs) are enzymes pivotal for histone modification (i.e. acetylation marks removal), chromatin accessibility and gene expression regulation. Class I HDACs (including HDAC1, 2, 3, 8) are ubiquitously expressed and they often participate in multi-molecular protein complexes. To date, three neurodevelopmental disorders caused by mutations in genes encoding for HDACs (HDAC4, HDAC6 and HDAC8) and thus belonging to the group of chromatinopathies, have been described. We performed whole exome sequencing (WES) for a patient (#249) clinically diagnosed with the chromatinopathy Ru

Maternal Substance Use and Early-Life Adversity: Inducing Drug Dependence in Offspring, Interactions, Mechanisms, and Treatments.

The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol use. Mothering is limited by maternal addiction because of the separation. Maternal separation (MS) leads to the development of behavioural and neuropsychiatric issues in the future. Despite the importance of this issue, empirical investigations of the influences of maternal substance use and separation on substance use problems in offspring are limited, and studies that consider both effects are rare. This study aims to review a few studies on the mechanisms, treatments,

De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder.

Histone deacetylase 3 (HDAC3) is a crucial epigenetic modulator essential for various developmental and physiological functions. Although its dysfunction is increasingly recognized in abnormal phenotypes, to our knowledge, there have been no established reports of human diseases directly linked to HDAC3 dysfunction. Using trio exome sequencing and extensive phenotypic analysis, we correlated heterozygous de novo variants in HDAC3 with a neurodevelopmental disorder having variable clinical presentations, frequently associated with intellectual disability, developmental delay, epilepsy, and musc