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The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC meta-GWAS (n = 3,418, n = 292,703) to conduct proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expressions were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections ( = 3.28e-5, 0.05/1,525). These proteins were involved in amino acids and organic acid synthesis pathways. Colocalization analysis further identified six proteins associated with TCs (VCAM1, LGMN, NPTX1, PLEKHA7, TNFAIP3, and BMP1). Tissue validation confirmed BMP1, LGMN, and PLEKHA7's differential expression between normal and TC tissues. We found limited evidence for linking circulating proteins and the risk of TCs. Our study highlighted the contribution of proteins, particularly those involved in amino acid metabolism, to TCs.
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http://dx.doi.org/10.1016/j.isci.2024.109961 | DOI Listing |
Zhong Nan Da Xue Xue Bao Yi Xue Ban
May 2025
Department of Information Network Center, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Objectives: Increasing detection of low-risk papillary thyroid carcinoma (PTC) is associated with overdiagnosis and overtreatment. N6-methyladenosine (mA)-mediated microRNA (miRNA) dysregulation plays a critical role in tumor metastasis and progression. However, the functional role of mA-miRNAs in PTC remains unclear.
View Article and Find Full Text PDFBrain Behav
September 2025
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Introduction: Inflammatory cytokine disturbance is a prominent outcome of immune dysregulation, extensively documented in bipolar disorder (BD). However, observational studies have exhibited inconsistent findings, and the causal relationships between inflammatory factors and BD remain unclear. Hence, this study aimed to uncover the causality between circulating inflammatory cytokines and BD.
View Article and Find Full Text PDFBrain
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Guangdong Provincial Key Laboratory of Non-human Primate Research, Guangdong-Hong Kong-Macau Institute of CNS Rege
Abnormal accumulation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Small interfering RNAs (siRNAs) targeting TDP-43 offer potential therapeutic strategies for these diseases. However, efficient and safe delivery of siRNAs to the central nervous system (CNS) remains a critical challenge.
View Article and Find Full Text PDFEur J Immunol
September 2025
CHU Nantes, Nantes Université, INSERM, Centre de Recherche Translationnelle En Transplantation et Immunologie (CR2TI), Nantes, France.
In the field of lung transplantation (LTx), the survival of lung transplant recipients (LTRs) is limited by events such as primary graft dysfunction (PGD), infections, and acute rejection (AR), which promote the development of chronic lung allograft dysfunction (CLAD). Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as key players in LTx because of their roles in immune regulation, inflammation, and antigen presentation. EVs carry immunologically active molecules such as MHC class I/II proteins, cytokines, and lung self-antigens (SAgs), suggesting their involvement in infections and both AR and CLAD.
View Article and Find Full Text PDFAnn Rheum Dis
September 2025
Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
Objectives: Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune condition needing targeted treatment approaches and improved understanding of molecular mechanisms driving clinical phenotypes. We utilised exploratory proteomics from a longitudinal North American cohort of patients with new-onset JDM to identify biological pathways at disease onset and follow-up, tissue-specific disease activity, and myositis-specific autoantibody (MSA) status.
Methods: We measured 3072 plasma proteins (Olink panel) in 56 patients with JDM within 12 weeks of starting treatment (from the Childhood Arthritis and Rheumatology Research Alliance Registry and 3 additional sites) and 8 paediatric controls.