International Journal of Molecular Sciences

BackgroundPlacenta accreta spectrum (PAS) is characterized by abnormal trophoblastic invasion into the uterine myometrium and is a cause of postpartum hemorrhage and maternal death. Protease-activated receptor-1 (PAR-1) promotes various cellular actions, including invasion. Here, we analyzed the expression of PAR-1, platelet antigen, and fibrin in PAS. MethodsWe analyzed 49 PAS cases (placenta accreta vera [accreta vera], 31 cases; placenta increta [increta], 8 cases; placenta percreta [percret...

BackgroundMultiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system affecting 2.8 million people worldwide. Both genetic and environmental factors contribute to MS risk, with Epstein-Barr virus (EBV) infection being an important environmental factor. To better clarify the role of EBV in MS, we examined its impact on gene expression, chromatin accessibility, and transcription factor binding in primary B cells and EBV-transformed B cells derived from patient...

Background and ObjectiveFOLR3 serves as an important member of the folate metabolic pathway and plays a crucial role in various malignant tumors. However, the expression pattern, diagnostic value, and regulatory mechanism of FOLR3 in endometrial cancer (EC) remain unclear. This study aimed to explore the expression characteristics, clinical significance, and related molecular regulatory networks of FOLR3 in EC through bioinformatics analysis. MethodsTCGA datasets served as training sets, while ...

BackgroundUterine atony ([~]70%), lacerations ([~]20%) and placenta-related problems ([~]10%) are assumed main reasons for postpartum hemorrhage genesis. Coagulation components predictive for postpartum blood loss can be identified prepartum and before traditionally assumed main reasons are observed. ObjectivesTo better understand postpartum hemorrhage genesis, we prospectively researched prepartum clinical information, presence of assumed main reasons and peripartum coagulation changes in part...

BackgroundPost-viral diseases, including post-COVID-19 syndrome (PCS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), cause substantial long-term morbidity. Persistent cardiovascular (CV) risk after acute infection highlights the need for accessible tools to quantify microvascular health. MethodsAll Eyes on PCS is a prospective, observational study investigating the retinal microcirculation using retinal vessel analysis (RVA). We compared RVA parameters in 102 PCS patients with...

Autoimmune demyelinating central nervous system (CNS) disorders encompass a wide array of clinical entities ranging from the organ specific Multiple Sclerosis (MS) to systemic autoimmune diseases (SADs) such as Systemic Lupus Erythematosus (SLE) and Sjogrens syndrome (SS). Despite international research efforts, distinction of these entities at clinical, imaging and laboratory level remains challenging, with almost 20% of patients being misdiag-nosed with MS, out of which more than 50% carry the...

Leber hereditary optic neuropathy (LHON) is primarily caused by pathogenic mitochondrial DNA (mtDNA) variants, most commonly the m.11778G>A variant in the MT-ND4 gene. The presence of this variant alone is insufficient to trigger disease symptoms, of which vision loss is the hallmark. Given the incomplete penetrance and inter-population variability in modifying factors, this study aimed to investigate two previously proposed genetic risk factors for LHON in the Polish population. Using quantitat...

BackgroundImmune function alters with age, and is often accompanied by chronic, low-grade inflammation (inflammageing). In individuals with frailty, inflammageing is increased, reducing immune function and increasing susceptibility to serious outcomes from infection. In this study we investigated the changes that take place in human neutrophils during healthy ageing and ageing with frailty (FR) using RNAseq and functional assays. We also compared neutrophil phenotype in frailty with rheumatoid a...

Epstein-Barr virus (EBV) is strongly implicated as an essential environmental trigger of multiple sclerosis (MS), yet the host genetic mechanisms governing EBV activity and how infection triggers the disease are not known. We developed a pipeline to quantify EBV DNA from whole-genome sequencing data and applied it to population-scale cohorts. Using this pipeline, we performed a cross-ancestry genome-wide association study (GWAS) of EBV DNA positivity in 617,186 individuals and identified 39 inde...

Cervical intraepithelial neoplasia grade 2 (CIN2) lesions show variable outcomes, and accurate prediction of regression remains a major clinical challenge. We developed an interpretable machine learning pipeline that integrates quantitative histological, clinical, and human papillomavirus (HPV) -genotyping data to predict lesion regression within one and two years. Using panoptic segmentation of routine hematoxylin and eosin (H&E) -stained biopsies, we extracted human-interpretable morphological...

Hereditary ataxias are complicated neurological disorders with enormous genetic heterogeneity as well as the diverse genetic mechanism. Among different genetic mechanism, tandem nucleotide repeat expansion (TNRex) are the most common cause for genetic ataxias followed by single nucleotide variations in over 200 genes. The detection and the diagnosis of tandem nucleotide repeats in clinics and laboratories has been at large common in comparison with SNVs owing to the large number of the mutations...

IntroductionBreast Cancer (BC) remains a significant clinical challenge, and despite well-established screening strategies, new biomarkers could improve BC detection, treatment and management. Urine represents a headily accessible liquid biopsy for diagnosis and extracellular vesicle (EV) transfer of oncogenic proteins, RNAs, and metabolites that promote tumor growth, invasion, metastasis, and immune evasion. AimsTo compare the whole urine and urinary EV metabolomes and identify BC specific met...

Microtia is a common congenital craniofacial malformation characterized by the partial or complete absence of the external ear structure. Despite its relatively high incidence, the pathogenesis of microtia remain poorly understood. In this study, we analyzed both single-cell and bulk RNA sequencing data from microtia cases and identified a population of COL1+HES1+ mesenchymal stem cell in perichondrium with significantly higher expression of the CRABP2 gene, a gene that encodes a nuclear transpo...

ObjectiveTo determine alterations in circulating Tau and phosphorylated Tau (pTau) profiles in pediatric and adult patients with spinal muscular atrophy (SMA). MethodsCirculating total Tau, pTau-181, pTau-217, pTau-262, and pTau-396 concentrations were measured across three cohorts: 1) adults including healthy controls, SMA patients, and ALS patients; 2) pediatric SMA patients and age-matched controls; and 3) pediatric SMA patients treated with onasemnogene abeparvovec. ResultsDistinct alterat...

The use of semaglutide (SE), a glucagon-like peptide-1 receptor agonist (GLP-1RA) with glucose-lowering and weight-loss effects, has risen rapidly, particularly among women of reproductive age. While preclinical studies suggest benefits for ovarian function via the hypothalamic-pituitary-ovarian axis, its impact on the endometrial-embryo interface remains unclear. Here, we show that GLP-1R is dynamically expressed in fertile human endometrium, restricted to epithelial cells and markedly upregula...

Inflammatory resolution is essential for tissue health, yet its dynamics remain difficult to study in humans. Menstruation is a recurrent, non-pathological inflammatory process that provides a natural window into inflammation and repair. We developed and validated a standardized menstrual sampling and RNA-seq workflow, analyzing more than 1,000 samples from over 300 individuals. We show that menstrual transcriptomes are dominated by two major biological confounders: heterogeneous tissue composit...

Gout is driven by an interleukin-1{beta}-mediated intense innate immune reaction to monosodium urate (MSU) crystals (MSUc). In cell culture models of inflammatory gout there is a synergistic effect of phagocytosis of MSUc and TLR2 and TLR4 activation by agonists such as free fatty acid and lipopolysaccharide (LPS) in NLRP3-inflammasome activation and IL-1{beta} secretion. A substantial number of gout patients do not report a dietary trigger, and observational studies associate airborne particula...

Stromal tumor-infiltrating lymphocytes (sTILs) are promising biomarkers for predicting therapeutic outcomes in triple-negative breast cancer (TNBC), with higher sTIL levels correlating with improved chemotherapy response and survival outcomes. Currently, sTILs are manually evaluated by pathologists, which is prone to inter-reader variability. In this study, we have developed an AI-driven TIL segmentation pipeline to process entire diagnostic hematoxylin-and-eosin-stained whole slide images for r...

ObjectiveProstate cancer (PCa) constitutes a considerable public health concern worldwide, primarily attributable to its elevated mortality rates. Changes in exosome are shown to significantly influence tumor development. This study aimed to investigate the prognostic value of exosome-related genes (ERGs) in PCa. MethodsPCa single-cell RNA sequencing (scRNA-seq) and transcriptome datasets were obtained from public databases, with ERGs extracted from existing literature. Candidate genes were ide...

Cancer heterogeneity is traditionally attributed to multiple parallel signaling pathways. This belief is challenged here by proposing the ER/PR axis as the dominant pathway underlying the full spectrum of breast cancer. Absolutely quantitated ER, PR, Her2 and Ki67 protein levels were accumulated over 8 years from 1652 specimens collected non-selectively and measured with Quantitative Dot Blot (QDB) method over time. Cox analysis showed ER and Ki67 as independent adverse prognostic factors while ...