Результаты поиска

Multiomics Analysis Reveals Molecular Changes during Early Progression of Precancerous Lesions to Lung Adenocarcinoma in Never-Smokers.

Lung cancer is the most common cause of cancer mortality globally, and the prevalence of lung adenocarcinoma, the most common lung cancer su … s suggest possible approaches for early disease interception. Significance: Integrative analysis of multiomics data revealed coordination between immune and nonimmune cells during early progression of precancerous lesions to lung adenocarcinomas and shed light on the molecular characteristics of clinically defined subtypes.

Multiomics approach reveals the comprehensive interactions between nutrition and children's gut microbiota, and microbial and host metabolomes.

The gut microbiome can modulate nutrient metabolism to produce many metabolites interacting with the host. However, the intricate interactions among dietary intake, the gut microbiome and metabolites, and host metabolites need to be further explored although some studies have been devoted to it. Here, in a cross-sectional studies, 88 children aged 2-12 years were enrolled from northwestern China. The dietary intake data were collected via a designed food frequency questionnaire to calculate plant-based diet indices (PDIs). Stool and plasma samples were collected for metagenomic and broad-targe

Понимание роли потенциальных биомаркеров в ослаблении множественной склерозовой прогрессии с помощью мультиомики и сетевого подхода.

Множественный склероз (MS) — сложное неврологическое расстройство, отмеченное нейроинфламмацией и обезвоживанием. Понимание молекулярной основы имеет жизненно важное значение для разработки эффективных методов лечения. Целью этого исследования является разъяснение молекулярной динамики НР с использованием мультиомики и сетевого подхода. МЕТОДЫ: Мы закупали дифференциально выраженные гены у пациентов с MS и здоровый контроль, используя набор данных mRNA из общедоступной базы данных. ДЭГ были подвергнуты воздействию нетрайтно взвешенных генных сетей совместного выражения (РГКН) для идентификации

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is a complex neurological disorder marked by neuroinflammation and demyelination. Understanding its molecular basis is vital for developing effective treatments. This study aims to elucidate the molecular progression of MS using multiomics and network-based approach. METHODS: We procured differentially expressed genes in …

Exploring the mechanism of Xingpi Capsule in diarrhea predominant-irritable bowel syndrome treatment based on multiomics technology.

BACKGROUND: Xingpi Capsule (XP), a commercially available over-the-counter herbal medicine in China, plays a prominent role in treating diarrhea-predominant irritable bowel syndrome (IBS-D). Nevertheless, the potential mechanisms remain unclear. PURPOSE: This study aimed to investigate XP efficacy in IBS-D and elucidate the underlying molecular mechanisms. METHODS: A rat IBS-D model was established by senna decoction gavage combined with restraint stress and swimming exhaustion. The changes in rat body weight and stool were recorded daily. Colon pathological changes and the number of colonic

Multiomics implicate gut microbiota in low cypermethrin (CP) exposure induced multiorgan toxicological effects in pubertal male rats.

Cypermethrin (CP), widely used as a broad-spectrum pesticide, has raised concerns over its frequent presence in the environment and potential health risks. The present study focused on incorporating the gut-organ axis theory to reinterpret the toxicological effects and mechanisms following CP exposure at environmentally relevant concentrations (0.1 mg/kg/d and 0.5 mg/kg/d) in pubertal male rats. The results showed alterations in histopathological and organosomatic indices in the liver, brain, and epididymis. Through multiomics network analysis, it was found that Lachnospiraceae and Ruminococca…

Multiomic Single-Cell Sequencing Identifies BCR::ABL1 as an Acquired Resistance Mechanism in FLT3+ AML.

BCR::ABL1 acquisition is an emerging but poorly characterized resistance mechanism in FLT3-mutated AML. Using multiomic single-cell DNA sequencing, we characterized clonal evolution in a patient with FLT3-ITD AML who acquired BCR::ABL1 with FLT3 inhibitor resistance. Phylogenetic reconstruction confirmed BCR::ABL1 as a branch event co-occurring with FLT3-ITD and restricted to specific blast populations, supporting BCR::ABL1 acquisition as a resistance mechanism.

Multiomic single nuclei profiling the mouse hippocampus reveals that ACSS2 confers neuronal resilience to tauopathy.

INTRODUCTION: Epigenomic dysregulation contributes to Alzheimer's disease (AD) and related tauopathies. Acetyl-CoA synthetase 2 (ACSS2), a nuclear-localized metabolic enzyme in neurons, supports histone acetylation and learning-related gene expression. We examined how ACSS2 loss affects molecular and behavioral phenotypes in a mouse model of tauopathy. METHODS: We induced tauopathy in ACSS2 knockout and control mice via injection of pathological human tau. We assessed transcriptomic, epigenomic, and behavioral changes, and tested long-term acetate supplementation as a rescue strategy. RESULT

Multiomic analysis identifies glutaminolysis-dependent metabolic enhancement of immune memory utilised for vaccine development.

Vaccines work by inducing an immunological memory response to protect against infection or disease. More effective vaccines are required to improve protection of high-risk groups such as the elderly. Here we screen transcriptional signatures of T cell memory against repurposable drug signatures, identifying a subclass of lysine deacetylase inhibitors (KDACi) capable of promoting a memory precursor phenotype in primary T cells. Leveraging combined acetylomic, metabolomic, transcriptomic and epigenomic analyses, we identify enhanced glutaminolysis as the mechanism responsible for the KDACi effec

Multiomic profiling of responses to clinical and novel bisphosphonates reveals extraskeletal effects on ageing related signatures.

Bisphosphonates (BPs) have been used effectively to treat excessive bone loss for over 50 years. Recent clinical evidence suggests extra-skeletal benefits but how this occurs remains unknown. Here we use a panel of human, murine and cellular assessments to chart BP-induced ageing-related changes both systemically and at local organ sites. In vivo spatial transcriptomics in aged mice treated with zoledronate showed a shift in cellular composition towards that of young animals specifically in heart, liver and intestine, with upregulation of genes governing detoxification, mitochondrial stability

Decoding age-stratified clinical and molecular heterogeneity in male breast cancer through multiomic profiling.

OBJECTIVE: Age-associated molecular heterogeneity is well described in female breast cancer but remains insufficiently characterized in male breast cancer (MBC). We profiled age-stratified clinical and molecular differences between younger (≤55 years) male breast cancer (YMBC) and older (>55 years) male breast cancer (OMBC). METHODS: We retrospectively analyzed 347 patients with MBC diagnosed at Fudan University Shanghai Cancer Center by integrating clinicopathological data, RNA sequencing, and whole-exome sequencing (WES). Survival, differential expression, and mutational signature analyses

A multiomic investigation of human milk-derived extracellular vesicles in perinatal HIV and antiretroviral therapy exposure.

BACKGROUND: Human milk (HM) is beneficial for early infant development, and breastfeeding is recommended globally for women with HIV (WHIV) on antiretroviral therapy (ART). HM has a high extracellular vesicle (EV) content, and distinct HM fractions may be enriched for unique small metabolites, lipids, oxylipins, and microRNAs, which may differ by HIV/ART exposure. Our objective was to characterize the metabolomic and miRNA differences between milk fractions and in relation to HIV/ART. METHODS: HM was collected at 6 weeks postpartum from WHIV receiving ART and HIV-seronegative women in South A

Multiomic analyses on the contribution of transposable elements to the cis-regulatory landscape of different types of immune cells.

BACKGROUND: Transposable elements (TEs) are mobile DNA elements abundant in eukaryote genomes. While recognized as key contributors to cis-regulatory elements (CREs), their association with the cell-specific regulatory landscape of various immune cells remain largely unclear. This study aims at depicting the association of TEs with the CREs in diverse types of human immune cells in peripheral blood, with special focus on monocytes which are crucial for innate immunity. RESULTS: Using single-cell multiomic data of human peripheral blood mononuclear cells (PBMCs), we annotated the cell-specific

Comprehensive Multiomic Analysis Reveals Metabolic Reprogramming Underlying Human Fontan-Associated Liver Disease.

BACKGROUND: The Fontan operation is the current standard of care for single-ventricle congenital heart disease. Almost all patients with Fontan operation develop liver fibrosis at a young age, known as Fontan-associated liver disease (FALD). The pathogenesis and mechanisms underlying FALD remain little understood, and there are no effective therapies. We aimed to present a comprehensive multiomic analysis of human FALD, revealing the fundamental biology and pathogenesis of FALD. METHODS AND RESULTS: We recently generated a single-cell transcriptomic and epigenomic atlas of human FALD using si

Multiomic analysis uncovers a continuous spectrum of differentiation and Wnt-MDK-driven immune evasion in hepatoblastoma.

BACKGROUND & AIMS: Hepatoblastoma is the most common pediatric cancer of the liver, with the majority of cases displaying activating mutations in the Wnt/β-catenin pathway. Understanding the complex milieu of the tumor microenvironment has resulted in promising new therapies for adult cancers, but similar approaches in pediatric cancers are still lacking. We aimed to provide a comprehensive analysis of the tumor microenvironment of hepatoblastoma, unveiling its spatial architecture and key signaling mechanisms. METHODS: Single-cell/-nucleus RNA-sequencing (RNA-seq) (n = 15), spatial transcrip

A multiomic framework for predicting laryngo-esophageal dysfunction following induction chemotherapy in hypopharyngeal-laryngeal carcinoma.

BACKGROUND: Pre-treatment predictors of laryngeal preservation (LP) and survival in advanced laryngeal-hypopharyngeal squamous-cell carcinoma (LHSCC) represent an unmet clinical need. MATERIALS AND METHODS: A multicentric, international, retrospective series of LHSCC patients undergoing induction chemotherapy (IC) within an LP protocol was analyzed. The primary objective was to develop a predictive model by exploiting multiomics data (clinical, genomics, radiomics). Endpoints were laryngo-esophageal dysfunction (LED), response to IC, overall survival (OS), and progression-free survival (PFS).…

Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients.

Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds previously uncharacterized populations of absorptive and secretory epithelial

Multiomic Selection of Cancer-Testis Antigens as Precision Immuno-oncologic Targets in Head and Neck Cancer.

IMPORTANCE: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignant neoplasm with an increasing need for precision therapeutics. Cancer-testis antigens (CTAs) represent promising targets given their aberrant tumor expression and otherwise localized expression to immune-privileged tissues with no (testis-restricted) or minimal (testis-selective) expression in other human body sites. Despite their potential, limited studies rigorously evaluate CTAs as therapeutic targets in HNSCC. OBJECTIVE: To orthogonally validate and present specific CTAs as potential precision immuno-oncolo

Multiomic Immune Profiling of Pediatric Transplant Recipients Identifies Cell States Associated with Vaccine Response.

KEY POINTS: Pediatric transplant recipients have oligoclonal expansion of CD8 + T cells and polyclonal expansion of CD4 + T cells versus healthy children. Analysis of vaccine responses revealed patients with intact T cell immunity but impaired humoral immunity. A subset of pediatric transplant recipients exhibit an atypical B cell population previously associated with excessive immune activation. BACKGROUND: Immunosuppressive therapy after solid organ transplantation inhibits protective immunity to pathogens and vaccines. However, the specific cell states associated with failure to generate r

Leveraging single cell multiomic analyses to identify factors that drive human chondrocyte cell fate.

UNLABELLED: Cartilage plays a crucial role in skeletal development and function, and abnormal development contributes to genetic and age-related skeletal disease. To better understand how human cartilage develops in vivo , we jointly profiled the transcriptome and open chromatin regions in individual nuclei recovered from distal femurs at 2 fetal timepoints. We used these multiomic data to identify transcription factors expressed in distinct chondrocyte subtypes, link accessible regulatory elements with gene expression, and predict transcription factor-based regulatory networks that are import

An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients.

To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved. Within this cohort, the highest diagnostic yield was obtained for patients from Asia (57.5%, mainly from