Modification In Disease Research Articles

DNA Methylation in Alzheimer's Disease.

To date, DNA methylation is the best characterized epigenetic modification in Alzheimer's disease. Involving the addition of a methyl group to the fifth carbon of the cytosine pyrimidine base, DNA methylation is generally thought to be associated with the silencing of gene expression. It has been hypothesized that epigenetics may mediate the interaction between genes and the environment in the manifestation of Alzheimer's disease, and therefore studies investigating DNA methylation could elucidate novel disease mechanisms. This chapter comprehensively reviews epigenomic studies, undertaken in human brain tissue and purified brain cell types, focusing on global methylation levels, candidate genes, epigenome wide approaches, and recent meta-analyses. We discuss key differentially methylated genes and pathways that have been highlighted to date, with a discussion on how new technologies and the integration of multiomic data may further advance the field.

Impaired glomerular filtration rate and associated factors among diabetic mellitus patients with hypertension in referral hospitals, Amhara Regional State, Ethiopia

Impaired glomerular filtration rate is common health problem in diabetic mellitus patients (DM) with hypertension (HTN). It is a major cause of morbidity, mortality, and poor quality of life. There is limited data on the prevalence and associated factors of impaired glomerular filtration among diabetic mellitus patients with hypertension in Ethiopia. Therefore, this study aimed to determine the prevalence of impaired glomerular filtration rate and associated factors among diabetic patients with hypertension in referral hospitals in Amhara Regional State, Ethiopia, 2020. An institution-based cross-sectional study was conducted in Amhara Regional referral hospitals from February 20 to April 30, 2020. Systemic sampling techniques were used to select diabetic mellitus patients with hypertension. Epi data version 3.0 was used to enter the coded data and then exported to STATA 14 for analysis. Glomerular filtration rate was estimated using the equations of collaboration with chronic kidney disease (CKD-EPI), diet modification in renal disease (MDRD-4), and creatinine clearance (CrCl). In bi-variable logistic regression, variables with a p-value of < 0.25 were included in multi-variable logistic regression. Using a 95% confidence interval, variables having a p-value ≤ 0.05 in multi-variable logistic regression were declared as statistically significant variables. In this study, a total of 326 study participants were involved, with a 100% response rate. The prevalence of an impaired glomerular filtration rate among diabetic patients with hypertension was 30.1% (95% CI 25.1%-35.1%), 36.6% (95% CI 30.1%-40.8%) and 45.4% (95% CI 39.9%-50.8%), using the equations CKD-EPI, MDRD-4, and CrCl, respectively. Being ≥ 55 years old (CKD-EPI AOR = 2.9, 95%: 1.5–5.5, MDRD-4 AOR = 2.1, 95% CI: 1.2–3.7, CrCl AOR = 5.9, 95% CI: 3.5–10.1), proteinuria (CKD-EPI AOR = 2.7, 95% CI: 1.4–5.3, MDRD-4 AOR = 1.9, 95% CI: 1.1–3.4, CrCl AOR = 1.7, 95% CI: 1.0-2.9), duration of the disease (≥ 5 years) (CKD-EPI AOR = 7.9, 95% CI: 4.2–13.0, MDRD-4 AOR = 7.4, 95% CI: 4.2–13.0, CrCl AOR = 1.9, 95% CI: 1.2–3.3), a glucose level of ≥ 150 mg/dl (CKD-EPI AOR = 2.3, 95% CI: 1.3–4.4, MDRD-4 AOR = 2.1, 95% CI: 1.2–3.8) were variables significantly associated with impaired glomerular filtration rate. The prevalence of impaired glomerular filtration rate among diabetic mellitus patients with hypertension was high. Independent predictors of impaired glomerular filtration rate were older age, duration of the disease, proteinuria, and higher blood glucose levels.

Comparative analysis of laparoscopic nissen fundoplication and rossetti modification in gastroesophageal reflux disease: A focus on life quality enhancement

ObjectiveThis study aims to investigate the focus of surgical treatment of gastroesophageal reflux disease (GERD) on enhancing life quality beyond symptom relief. The comparison involves laparoscopic Nissen fundoplication and Rossetti modification techniques. MethodsPatients intolerant to or experiencing relapse after medical therapy underwent either standard Nissen procedure (Group 1, n=61) or Rossetti modification (Group 2, n=42). A disease-specific quality of life questionnaire for GERD was utilized for evaluating life quality preoperatively and 2 years postoperatively. Symptom scores and patient satisfaction were also assessed. ResultsPreoperatively, groups were similar in symptom duration, hiatal hernia presence, and DeMeester scores (p=0.127, p=0.427, and 0.584, respectively). Both groups exhibited a statistically significant increase in life quality postoperatively (p<0.001), with no significant intergroup difference. Symptoms decreased after both surgeries, except for dysphagia and bloating. Bloating significantly increased in both groups after surgery (p=0.018 and p=0.017, respectively), and dysphagia increased significantly only in Group 2 (p=0.007). The surgery refusal rate was significantly higher in Group 2 for similar preoperative symptoms (p=0.040). ConclusionDespite increased life quality scores, the combination of increased dysphagia and bloating in patients undergoing Rossetti modification resulted in a decreased satisfaction rate.

Sodium arsenite induces hepatic stellate cells activation by m6A modification of TGF-β1 during liver fibrosis

The compound known as Sodium arsenite (NaAsO2), which is a prevalent type of inorganic arsenic found in the environment, has been strongly associated with liver fibrosis (LF), a key characteristic of nonalcoholic fatty liver disease (NAFLD), which has been demonstrated in our previous study. Our previous research has shown that exposure to NaAsO2 triggers the activation of hepatic stellate cells (HSCs), a crucial event in the development of LF. However, the molecular mechanism is still unknown. N6-methyladenosine (m6A) modification is the most crucial post-transcriptional modification in liver disease. Nevertheless, the precise function of m6A alteration in triggering HSCs and initiating LF caused by NaAsO2 remains unknown. Here, we found that NaAsO2 induced LF and HSCs activation through TGF-β/Smad signaling, which could be reversed by TGF-β1 knockdown. Furthermore, NaAsO2 treatment enhanced the m6A modification level both in vivo and in vitro. Significantly, NaAsO2 promoted the specific interaction of METTL14 and IGF2BP2 with TGF-β1 and enhanced the TGF-β1 mRNA stability. Notably, NaAsO2-induced TGF-β/Smad pathway and HSC-t6 cells activation might be avoided by limiting METTL14/IGF2BP2-mediated m6A modification. Our findings showed that the NaAsO2-induced activation of HSCs and LF is made possible by the METTL14/IGF2BP2-mediated m6A methylation of TGF-β1, which may open up new therapeutic options for LF brought on by environmental hazards.

Women's reproductive risk score and healthy lifestyle modification in cardiovascular disease: Findings from the UK Biobank

Background and aimsReproductive risk factors are associated with increased risk of cardiovascular disease (CVD) in women. However, the combined effects of the composite reproductive risk factors on CVD are unknown. This study was performed to construct a reproductive risk score (RRS) to measure reproductive status, examine the association between RRS and CVD, and explore the modification effect of healthy lifestyle on the association in women in the UK Biobank cohort. MethodsThe RRS was constructed in 74,141 female participants with data about the items derived for the RRS in the UK Biobank. The RRS was derived from 17 baseline variables, all of which indicated women's reproductive health status. We defined four categories of RRS status: low-risk group (score 0–1); low-intermediate group (score 2–3); high-intermediate group (score 4–5); and high-risk group (score 6–13). We also constructed a healthy lifestyle score (HLS) with five related factors, and categorized into unhealthy lifestyle group (score: 0–1), intermediate lifestyle group (score: 2–3) and healthy lifestyle group (score: 4–5). ResultsEach point increase in the RRS was associated with a 22 % higher risk of CVD (adjusted hazard ratio (aHR): 1.22; 95 % confidence interval (CI): 1.16 to 1.28), 23 % higher risk of IHD (1.23; 1.17 to 1.31) and 19 % higher risk of stroke (1.19; 1.07 to 1.32). The percentage population-attribution risks (PAR%) were 16 % (95 % CI: 8 to 24) for CVD, 15 % (95 % CI: 6 to 24) for IHD and 18 % (95 % CI: 1 to 33) for stroke. A healthy lifestyle significantly attenuated RRS associations with the incidence of CVD and IHD. The attributable proportions due to additive interaction (p < 0.001) between RRS and HLS were 0.14 (95 % CI: 0.07 to 0.22) for CVD and 0.15 (95 % CI: 0.09 to 0.23) for IHD, respectively. ConclusionsHigh RRS was associated with increased risks of CVD, IHD and stroke in female participants in the UK Biobank. The early-stage identification of women with reproductive risk using synthesised indicators and appropriate healthy lifestyle interventions could be useful for the prevention of early CVD and the extension of healthy active life expectancy.

440 Patient Education on Lifestyle Modification and Nutrition Management in Chronic Kidney Disease (CKD) using Artificial Intelligence in reference to NKF KDOQI guidelines

440 Patient Education on Lifestyle Modification and Nutrition Management in Chronic Kidney Disease (CKD) using Artificial Intelligence in reference to NKF KDOQI guidelines

Impact and Assessment of Climate Change on Agricultural Production in India: A Geographical Perspective

Climate change is an imminent global challenge that poses significant threats to our planet’s ecosystems, human societies, and overall well-being. Climate change refers to long-term shifts in temperature and weather patterns (UN) 2023 has shown all too clearly that climate change is here, and human activities have been the main driver of climate change. At the core of climate change is Global Warming which has triggered the melting of glaciers, sea level rise, weather fluctuation, erratic rainfall, and an increase in temperature patterns over the next century is predicted. The main objectives of this research paper is to examine the various causes of climate change in India and what is the impact of climate change on agricultural production in different parts of the country. The entire study is based on secondary sources of data. The result of the study shows that agricultural sector, which is already having difficulties as a result of the growing need for food, is being negatively impacted by climate change. In India, agriculture is very important because it is the foundation of the country's economy and provides a living for most of the population. 17.4% of India's GDP, or its gross domestic product, is derived from agriculture (Economic Survey, 2015–16). Drought, heat waves, storms, flooding, delayed monsoons, and variations in seasonal temperatures are some of the elements that negatively affect agricultural operations, such as planting, tending, and harvesting crops like Zaid, Rabi, and Kharif. These factors affect India's agricultural productivity as well as livestock farming. The study also reveals that Climate change has resulted in altered cropping patterns and decreased output of crops such as sugarcane, ground nuts, and paddy in states like Gujarat, Maharashtra, Orissa, West Bengal, Uttar Pradesh, and Bihar. Some Indian states, including Bihar, Maharashtra, and Kerala, have demonstrated climate variability by experiencing drought-like conditions in certain areas and flood-prone areas in others. Also, it results in the failure of crops, which drives farmers in some states to take their own lives due to crippling debt. On top of that, there is a risk to food security, a change in the quality of nutrition, a modification in pest and disease, but—above all—it is making life harder for the people having poor socio-economic status.

Pharmacotherapy for Disease Modification in Early Parkinson's Disease: How Early Should We Be?

Slowing or halting progression continues to be a major unmet medical need in Parkinson's disease (PD). Numerous trials over the past decades have tested a broad range of interventions without ultimate success. There are many potential reasons for this failure and much debate has focused on the need to test 'disease-modifying' candidate drugs in the earliest stages of disease. While generally accepted as a rational approach, it is also associated with significant challenges around the selection of trial populations as well as trial outcomes and durations. From a health care perspective, intervening even earlier and before at-risk subjects have gone on to develop overt clinical disease is at the heart of preventive medicine. Recent attempts to develop a framework for a biological definition of PD are aiming to enable 'preclinical' and subtype-specific diagnostic approaches. The present review addresses past efforts towards disease-modification, including drug targets and reasons for failure, as well as novel targets that are currently being explored in disease-modification trials in early established PD. The new biological definitions of PD may offer new opportunities to intervene even earlier. We critically discuss the potential and challenges around planning 'disease-prevention' trials in subjects with biologically defined 'preclinical' or prodromal PD.

Research Progress of mRNA Modification in Chronic Liver Disease

Chemical markers that modified DNA and its protein scaffold had emerged as a crucial area of epigenetic research. As the research advanced, regulatory mechanisms similar to those discovered in DNA were identified in messenger RNA (mRNA) and other RNA types. The liver, the largest organ in the body, primarily responsible for metabolic functions, uniquely depended on mRNA modifications for its physiological functions and pathological states. In recent years, critical breakthroughs were made in the realm of methylation modifications, particularly in N6-methyladenosine (m6A), N5-methylcytosine, and N1-methyladenosine. This paper primarily focused on the role of m6A modifications in chronic liver diseases such as viral hepatitis, non-alcoholic fatty liver disease, and hepatocellular carcinoma, while also discussing the clinical implications of mRNA modifications.

How should we be using biomarkers in trials of disease modification in Parkinson's disease?

The recent validation of the α-synuclein seed amplification assay as a biomarker with high sensitivity and specificity for the diagnosis of Parkinson's disease has formed the backbone for a proposed staging system for incorporation in Parkinson's disease clinical studies and trials. The routine use of this biomarker should greatly aid in the accuracy of diagnosis during recruitment of Parkinson's disease patients into trials (as distinct from patients with non-Parkinson's disease parkinsonism or non-Parkinson's disease tremors). There remain, however, further challenges in the pursuit of biomarkers for clinical trials of disease modifying agents in Parkinson's disease, namely: optimizing the distinction between different α-synucleinopathies; the selection of subgroups most likely to benefit from a candidate disease modifying agent; a sensitive means of confirming target engagement; and the early prediction of longer-term clinical benefit. For example, levels of CSF proteins such as the lysosomal enzyme β-glucocerebrosidase may assist in prognostication or allow enrichment of appropriate patients into disease modifying trials of agents with this enzyme as the target; the presence of coexisting Alzheimer's disease-like pathology (detectable through CSF levels of amyloid-β42 and tau) can predict subsequent cognitive decline; imaging techniques such as free-water or neuromelanin MRI may objectively track decline in Parkinson's disease even in its later stages. The exploitation of additional biomarkers to the α-synuclein seed amplification assay will, therefore, greatly add to our ability to plan trials and assess the disease modifying properties of interventions. The choice of which biomarker(s) to use in the context of disease modifying clinical trials will depend on the intervention, the stage (at risk, premotor, motor, complex) of the population recruited and the aims of the trial. The progress already made lends hope that panels of fluid biomarkers in tandem with structural or functional imaging may provide sensitive and objective methods of confirming that an intervention is modifying a key pathophysiological process of Parkinson's disease. However, correlation with clinical progression does not necessarily equate to causation, and the ongoing validation of quantitative biomarkers will depend on insightful clinical-genetic-pathophysiological comparisons incorporating longitudinal biomarker changes from those at genetic risk with evidence of onset of the pathophysiology and those at each stage of manifest clinical Parkinson's disease.

Adipose METTL14-Elicited N6 -Methyladenosine Promotes Obesity, Insulin Resistance, and NAFLD Through Suppressing β Adrenergic Signaling and Lipolysis.

White adipose tissue (WAT) lipolysis releases free fatty acids as a key energy substance to support metabolism in fasting, cold exposure, and exercise. Atgl, in concert with Cgi-58, catalyzes the first lipolytic reaction. The sympathetic nervous system (SNS) stimulates lipolysis via neurotransmitter norepinephrine that activates adipocyte β adrenergic receptors (Adrb1-3). In obesity, adipose Adrb signaling and lipolysis are impaired, contributing to pathogenic WAT expansion; however, the underling mechanism remains poorly understood. Recent studies highlight importance of N6 -methyladenosine (m6A)-based RNA modification in health and disease. METTL14 heterodimerizes with METTL3 to form an RNA methyltransferase complex that installs m6A in transcripts. Here, this work shows that adipose Mettl3 and Mettl14 are influenced by fasting, refeeding, and insulin, and are upregulated in high fat diet (HFD) induced obesity. Adipose Adrb2, Adrb3, Atgl, and Cgi-58 transcript m6A contents are elevated in obesity. Mettl14 ablation decreases these transcripts' m6A contents and increases their translations and protein levels in adipocytes, thereby increasing Adrb signaling and lipolysis. Mice with adipocyte-specific deletion of Mettl14 are resistant to HFD-induced obesity, insulin resistance, glucose intolerance, and nonalcoholic fatty liver disease (NAFLD). These results unravel a METTL14/m6A/translation pathway governing Adrb signaling and lipolysis. METTL14/m6A-based epitranscriptomic reprogramming impairs adipose Adrb signaling and lipolysis, promoting obesity, NAFLD, and metabolic disease.

Epigenetic modification in diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefore, novel therapeutic methods, targets and biomarkers are urgently needed to meet clinical requirements. In recent years, increasing attention has been given to the role of epigenetic modification in the pathogenesis of DKD. Epigenetic variation mainly includes DNA methylation, histone modification and changes in the noncoding RNA expression profile, which are deeply involved in DKD-related inflammation, oxidative stress, hemodynamics, and the activation of abnormal signaling pathways. Since DKD is reversible at certain disease stages, it is valuable to identify abnormal epigenetic modifications as early diagnosis and treatment targets to prevent the progression of end-stage renal disease (ESRD). Because the current understanding of the epigenetic mechanism of DKD is not comprehensive, the purpose of this review is to summarize the role of epigenetic modification in the occurrence and development of DKD and evaluate the value of epigenetic therapies in DKD.

Epigenetic modification in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic, epigenetic, and environmental factors. Recent advance in genomics and epigenetics have revealed epigenetic mechanisms in PD. These epigenetic modifications include DNA methylation, post-translational histone modifications, chromatin remodeling, and RNA-based mechanisms, which regulate cellular functions in almost all cells. Epigenetic alterations are involved in multiple aspects of neuronal development and neurodegeneration in PD. In this review, we discuss current understanding of the epigenetic mechanisms that regulate gene expression and neural degeneration and then highlight emerging epigenetic targets and diagnostic and therapeutic biomarkers for treating or preventing PD.

Role of Nutrition in Gastroesophageal Reflux, Irritable Bowel Syndrome, Celiac Disease, and Inflammatory Bowel Disease.

There remains a paucity of data on the efficacy of nutritional interventions in luminal gastrointestinal disorders. This review appraises the evidence supporting dietary modification in gastroesophageal reflux disease (GERD), irritable bowel syndrome, Celiac disease, and inflammatory bowel disease. Alhough the use of elimination diets; high fat/low carb; low fermentable oligosaccharides, disaccharides, monosaccharides and polyols; and lactose-free diets in GERD have been studied, the evidence supporting their efficacy remains weak and mixed. Patients with GERD should avoid eating within 3 hours of lying recumbent. Studied dietary interventions for disorders of gut-brain interaction include low fermentable oligosaccharides, disaccharides, monosaccharides and polyols and gluten-restricted and lactose-free diets. While all can be effective in carefully, individually selected patients, the evidence for each intervention remains low. In patients with inflammatory bowel disease, enteral nutrition is established in pediatric populations as useful in reducing inflammation and partial enteral nutrition has a growing evidence base for use in adults and children. Specific carbohydrate diets and the Crohn's disease exclusion diet show promising evidence but require further study to validate their efficacy prior to recommendation. Overall, the evidence supporting nutritional therapy across luminal gastrointestinal disorders is mixed and often weak, with few well-designed randomized controlled trials (RCTs) demonstrating consistent efficacy of interventions. RCTs, particularly cross-over RCTs, show potential to compare dietary interventions.

RNA Epigenetics in Chronic Lung Diseases.

Chronic lung diseases are highly prevalent worldwide and cause significant mortality. Lung cancer is the end stage of many chronic lung diseases. RNA epigenetics can dynamically modulate gene expression and decide cell fate. Recently, studies have confirmed that RNA epigenetics plays a crucial role in the developing of chronic lung diseases. Further exploration of the underlying mechanisms of RNA epigenetics in chronic lung diseases, including lung cancer, may lead to a better understanding of the diseases and promote the development of new biomarkers and therapeutic strategies. This article reviews basic information on RNA modifications, including N6 methylation of adenosine (m6A), N1 methylation of adenosine (m1A), N7-methylguanosine (m7G), 5-methylcytosine (m5C), 2'O-methylation (2'-O-Me or Nm), pseudouridine (5-ribosyl uracil or Ψ), and adenosine to inosine RNA editing (A-to-I editing). We then show how they relate to different types of lung disease. This paper hopes to summarize the mechanisms of RNA modification in chronic lung disease and finds a new way to develop early diagnosis and treatment of chronic lung disease.

M6A RNA methylation in brain injury and neurodegenerative disease

N6-methyladenosine (m6A), the most prevalent post-transcriptional RNA modification throughout the eukaryotic transcriptome, participates in diverse biophysiological processes including cell fates, embryonic development and stress responses. Accumulating evidence suggests that m6A modification in neural development and differentiation are highly regulated processes. As RNA m6A is crucial to protein translation and various bioprocesses, its modification dysregulation may also be associated with brain injury. This review highlights the biological significance of m6A modification in neurodegenerative disease and brain injury, including cerebrovascular disorders, is highlighted. Emphasis is placed on recent findings that elucidate the relevant molecular functional mechanism of m6A modification after brain injury and neurodegenerative disease. Finally, a neurobiological basis for further investigation of potential treatments is described.

Combining Isoprenoid Probes with Antibody Markers for Mass Cytometric Analysis of Prenylation in Single Cells.

Protein prenylation is an essential post-translational modification that plays a key role in facilitating protein localization. Aberrations in protein prenylation have been indicated in multiple disease pathologies including progeria, some forms of cancer, and Alzheimer's disease. While there are single-cell methods to study prenylation, these methods cannot simultaneously assess prenylation and other cellular changes in the complex cell environment. Here, we report a novel method to monitor, at the single-cell level, prenylation and expression of autophagy markers. An isoprenoid analogue containing a terminal alkyne, substrate of prenylation enzymes, was metabolically incorporated into cells in culture. Treatment with a terbium reporter containing an azide functional group, followed by copper-catalyzed azide-alkyne cycloaddition, covalently attached terbium ions to prenylated proteins within cells. In addition, simultaneous treatment with a holmium-containing analogue of the reporter, without an azide functional group, was used to correct for non-specific retention at the single-cell level. This procedure was compatible with other mass cytometric sample preparation steps that use metal-tagged antibodies. We demonstrate that this method reports changes in levels of prenylation in competitive and inhibitor assays, while tracking autophagy molecular markers with metal-tagged antibodies. The method reported here makes it possible to track prenylation along with other molecular pathways in single cells of complex systems, which is essential to elucidate the role of this post-translational modification in disease, cell response to pharmacological treatments, and aging.

Glycoproteomics

Protein glycosylation involves the co-translational or post-translational addition of glycans to proteins and is a crucial protein modification in health and disease. The aim of glycoproteomics is to understand how glycosylation shapes biological processes by understanding peptide sequences, glycan structures and sites of modification in a system-wide context. Over the past two decades, mass spectrometry (MS) has emerged as the primary technique for studying glycoproteins, with intact glycopeptide analysis — the study of glycopeptides decorated with their native glycan structures — now a preferred approach across the community. In this Primer, we discuss glycoproteomic methods for studying glycosylation classes, including best practices and critical considerations. We summarize how glycoproteomics is used to understand glycosylation at a systems level, with a specific focus on N-linked and O-linked glycosylation (both mucin-type and O-GlcNAcylation). We cover topics that include sample selection; techniques for protein isolation, proteolytic digestion, glycopeptide enrichment and MS fragmentation; bioinformatic platforms and applications of glycoproteomics. Finally, we give a perspective on where the field is heading. Overall, this Primer outlines the current technologies, persistent challenges and recent advances in the exciting field of glycoproteomics.

Methyltransferase-like 3 leads to lung injury by up-regulation of interleukin 24 through N6-methyladenosine-dependent mRNA stability and translation efficiency in mice exposed to fine particulate matter 2.5

Fine particulate matter 2.5 (PM2.5) exposure leads to the progress of pulmonary disease. It has been reported that N6-methyladenosine (m6A) modification was involved in various biological processes and diseases. However, the critical role of m6A modification in pulmonary disease during PM2.5 exposure remains elusive. Here, we revealed that lung inflammation and mucus production caused by PM2.5 were associated with m6A modification. Both in vivo and in vitro assays demonstrated that PM2.5 exposure elevated the total level of m6A modification as well as the methyltransferase like 3 (METTL3) expression. Integration analysis of m6A RNA immunoprecipitation-seq (meRIP-seq) and RNA-seq discovered that METTL3 up-regulated the expression level and the m6A modification of Interleukin 24 (IL24). Importantly, we explored that the stability of IL24 mRNA was enhanced due to the increased m6A modification. Moreover, the data from qRT-PCR showed that PM2.5 also increased YTH N6-Methyladenosine RNA Binding Protein 1 (YTHDF1) expression, and the up-regulated YTHDF1 augmented IL24 mRNA translation efficiency. Down-regulation of Mettl3 reduced Il24 expression and ameliorated the pulmonary inflammation and mucus secretion in mice exposed to PM2.5. Taken together, our finding provided a comprehensive insight for revealing the significant role of m6A regulators in the lung injury via METTL3/YTHDF1-coupled epitranscriptomal regulation of IL24.

Emerging role of protein modification in inflammatory bowel disease.

The onset of inflammatory bowel disease (IBD) involves many factors, including environmental parameters, microorganisms, and the immune system. Although research on IBD continues to expand, the specific pathogenesis mechanism is still unclear. Protein modification refers to chemical modification after protein biosynthesis, also known as post-translational modification (PTM), which causes changes in the properties and functions of proteins. Since proteins can be modified in different ways, such as acetylation, methylation, and phosphorylation, the functions of proteins in different modified states will also be different. Transitions between different states of protein or changes in modification sites can regulate protein properties and functions. Such modifications like neddylation, sumoylation, glycosylation, and acetylation can activate or inhibit various signaling pathways (e.g., nuclear factor-‍κB (NF-‍κB), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT)) by changing the intestinal flora, regulating immune cells, modulating the release of cytokines such as interleukin-1β (IL-‍‍1β), tumor necrosis factor-α (TNF‍-‍α), and interferon-‍γ (IFN-‍γ), and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier. In this review, we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.