Autoimmune disorders and thyroid diseases (TDs) frequently coexist, yet their causal relationships and underlying mechanisms remain poorly characterized.
We conducted bidirectional two-sample Mendelian randomization (MR) analyses integrating univariable, multivariable, and Bayesian-weighted approaches. Genome-wide association data from 10.3 million individuals (FinnGen, UK Biobank, and public repositories) were analyzed to assess causal effects between 12 autoimmune diseases and 6 TDs. Genetic instruments were rigorously selected (p < 5 × 10–8, F > 10, LD clumping r2 < 0.001), with multivariable MR adjusting for BMI, smoking, and alcohol consumption.
Autoimmune diseases demonstrated significant causal effects on hyperthyroidism (OR = 2.12, 95% CI 1.95–2.31), hypothyroidism (OR = 1.61, 1.58–1.64), and Hashimoto’s thyroiditis (OR = 1.50, 1.32–1.58). Reverse MR revealed reciprocal risks, with hyperthyroidism increasing autoimmune disease susceptibility (OR = 1.12, 1.11–1.12). Graves’ disease exhibited the strongest bidirectional associations (hyperthyroidism OR = 2.46, 2.37–2.56; reverse OR = 1.91, 1.86–1.96). Type 1 diabetes and rheumatoid arthritis showed moderate bidirectional effects (OR range: 1.12–1.95), while systemic lupus erythematosus increased papillary thyroid cancer risk (OR = 1.18, 1.08–1.28). Ankylosing spondylitis reduced hypothyroidism risk (OR = 0.97, 0.96–0.98). Multivariable MR confirmed persistence effects after covariate adjustment (OR range 1.11–4.11, all p < 0.01).
This MR study establishes bidirectional causality between autoimmune diseases and TDs, with disease-specific effect magnitudes. The findings advocate for:
| 1. | Enhanced thyroid surveillance in autoimmune patients (particularly Graves’ disease/systemic lupus erythematosus); |
| 2. | Reciprocal autoimmune screening in thyroid disorder cohorts; |
| 3. | Mechanistic investigations into shared pathways (e.g., human leukocyte antigen-mediated immunity). |
These results provide an evidence base for developing targeted prevention strategies and dual-diagnosis clinical protocols.
MicroRNAs are endogenous molecules that play a significant regulatory role in numerous physiological processes in plants and animals. The pivotal role of miRNAs is gene silencing by binding to a mature transcript’s 3′ UTR region which could be promising biomarkers for various diseases. Lemon balm (Melissa officinalis) possesses innumerable ethnomedicinal significance. Abundant studies have well-documented the cross-kingdom post-transcriptional regulatory potential of plant-derived small noncoding microRNAs. Under the aegis of a plant genomics approach, substantial advances in the first-ever in-silico microRNA analysis of Melissa officinalis were implemented. The present work aims to identify and uncover the role of Melissa officinalis plant miRNAs in Neurodegenerative disorders. The current study records the transcriptome-wide identification of 29 novel conserved miRNAs using sequence similarity search and mfold web server respectively, with a total of 99 potential human gene targets and top 10 prospective hub nodes as ESR1, CASP8, SPTBN1, RPL27A, IRF8, PRKCB, QKI, IGF2BP1, TTLL12 and NUP153 which were identified using psRNATarget and Cytoscape; targeted by miRNA families such as miR4995, miR397b, miR397-5p, miR397b-5p, miR396g-3p, miR2914, and miR397. Moreover, targeted genes were annotated by Funrich software, and a disease association study was conducted in the KEGG mapper database. The identified class of small RNAs were found to be associated with neurodegenerative disease, and various carcinomas. Consequently, identified top 4 hub genes CASP8, SPTBN1, PRKCB, and TTLL12 show their crucial involvement in the Neurodegenerative disorder pathways such as Alzheimer’s, Parkinson’s, Huntington’s, Spinocerebellar ataxia, and Axonal diseases. The findings can further contribute to understanding miRNA function and their regulatory mechanism in humans, leading to further implementation of other research objectives.
Aberrant DNA methylation is prevalent in acute lymphoblastic leukemia (ALL), particularly in adult cases, where abnormally high methylation levels correlate significantly with patient age and survival outcomes. Indeed, older patients are more frequently classified into high-risk subgroups due to gene dysfunction driven by aberrant methylation, highlighting its prognostic value. Thus, DNA methylation serves as a valuable prognostic marker for adult patients and supports the therapeutic use of hypomethylating agents (HMAs). In this review, we summarize the latest insights into DNA methylation and its regulation in the context of adult B-ALL and outline the potential clinical application of HMAs for adult patients.
Histone post-translational modifications (HPTMs) are essential for chromatin structure, transcriptional regulation, and DNA repair. Lysine succinylation (Ksuc), a recently identified HPTM, involves the addition of succinyl groups to lysine residues, altering their chemical environment and impacting histone-DNA interactions. This review provides a detailed account of histone lysine succinylation, focusing on its research history, specific modification sites, and regulatory mechanisms. Succinylation primarily occurs at the globular domain and C-terminal regions of histones, with key sites such as H3K79 and H3K122 extensively being studied. Succinyl-CoA serves as the donor molecule for this modification, with enzymatic pathways involving KAT2A, HAT1, and p300, as well as non-enzymatic pathways influenced by metabolic intermediates. Desuccinylation is regulated by enzymes such as sirtuin family and HDAC family members. Histone lysine succinylation enhances chromatin accessibility, promotes gene transcription, and facilitates DNA damage repair. Additionally, this modification is implicated in the progression of diseases such as cancer and hepatitis B virus (HBV) infection, highlighting its potential as a therapeutic target. By exploring the interplay between histone succinylation and cellular metabolism, this review underscores the significance of this novel modification in epigenetic regulation and disease development.
Lead Contact: Jinke Gu.
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