Unraveling the genetic blueprint of doxorubicin-induced cardiotoxicity through systems genetics approaches.

Background: Anthracycline-induced cardiotoxicity (ACT) is a significant concern for cancer survivors, while genetic basis of ACT remains unclear. This study employs a murine genetic reference population (GRP) of BXD recombinant inbred strains, derived from DBA/2J (D2) and C57BL/6J (B6) crosses, to map quantitative trait loci (QTLs) linked to doxorubicin (DOX)-induced phenotypes through systems genetics approaches.

Methods: To model variability in ACT, 58 BXD strains and parental B6 and D2 mice (n ≥ 4 mice/sex/strain, 3-4-month-old) underwent an intraperitoneal injection of DOX (20 mg/kg).

Systems Genetics Reveals the Gene Regulatory Mechanisms of in the Development of Autism Spectrum Disorders.

Background: Autism spectrum disorder (ASD) involves complex interactions between genetic and environmental factors. Recent studies suggest that dysregulation of β-arrestin2 () in the central nervous system is linked to ASD. However, its specific mechanisms remain unknown.

Genetic mapping of electrocardiographic parameters in BXD strains reveals Chromosome 3 loci to be associated with cardiac repolarization abnormalities.

Risk factors for cardiac arrhythmias that can cause sudden death and heart failure include genetics, age, lifestyle, and other environmental factors. The study assessed electrocardiography (ECG) traits in BXD mice and explored associated quantitative trait loci (QTLs). Five-minute electrocardiograms were recorded in 44 BXD strains at 4-5 mo of age ( ≥ 5 mice/sex/strain).

Unraveling the Genetic Blueprint of Doxorubicin-Induced Cardiotoxicity Through Systems Genetics Approaches.

Background: Anthracycline-induced cardiotoxicity (ACT) is a significant concern for cancer survivors. The genetic basis of ACT remains unclear because of the impact of lifestyle and environmental factors in human studies. This study employs a murine genetic reference population (GRP) of BXD recombinant inbred strains, derived from DBA/2J (D2) and C57BL/6J (B6) crosses, to map quantitative trait loci (QTLs) linked to doxorubicin (DOX)-induced cardiotoxic phenotypes through systems genetics approaches.

Discovery of Novel Pain Regulators Through Integration of Cross-Species High-Throughput Data.

Aims: Chronic pain is an impeding condition that affects day-to-day life and poses a substantial economic burden, surpassing many other health conditions. This study employs a cross-species integrated approach to uncover novel pain mediators/regulators.

Methods: We used weighted gene coexpression network analysis to identify pain-enriched gene module.

Interplay of RNA mA Modification-Related Geneset in Pan-Cancer.

: N-methyladenosine (mA), is the most common modification found in mRNA and lncRNA in higher organisms and plays an important role in physiology and pathology. However, its role in pan-cancer has not been explored. : A total of 31 mA modification regulators, including 12 writers, 2 erasers, and 17 readers are identified in the current study.

Resveratrol enhances the antiliver cancer effect of cisplatin by targeting the cell membrane protein PLA2.

Background: In this study, we aimed to explore the mechanism by which resveratrol promotes cisplatin-induced death of HepG2 cells and to provide a potential strategy for resveratrol in the treatment of cancer.

Methods: HepG2 cells were exposed to a range of drug concentrations for 24 h: resveratrol (2.5 μg/mL [10.

Systems genetics identifies methionine as a high risk factor for Alzheimer's disease.

As a dietary strategy, methionine restriction has been reported to promote longevity and regulate metabolic disorders. However, the role and possible regulatory mechanisms underlying methionine in neurodegenerative diseases such as Alzheimer's disease (AD), remain unexplored. This study utilized the data from BXD recombinant inbred (RI) mice to establish a correlation between the AD phenotype in mice and methionine level.

Systems Genetics Analyses Reveals Key Genes Related to Behavioral Traits in the Striatum of CFW Mice.

The striatum plays a central role in directing many complex behaviors ranging from motor control to action choice and reward learning. In our study, we used 55 male CFW mice with rapid decay linkage disequilibrium to systematically mine the striatum-related behavioral functional genes by analyzing their striatal transcriptomes and 79 measured behavioral phenotypic data. By constructing a gene coexpression network, we clustered the genes into 13 modules, with most of them being positively correlated with motor traits.

Identification of hub genes and potential molecular mechanisms related to drug sensitivity in acute myeloid leukemia based on machine learning.

Acute myeloid leukemia (AML) is the most common form of leukemia among adults and is characterized by uncontrolled proliferation and clonal expansion of hematopoietic cells. There has been a significant improvement in the treatment of younger patients, however, prognosis in the elderly AML patients remains poor. We used computational methods and machine learning (ML) techniques to identify and explore the differential high-risk genes (DHRGs) in AML.

Systems genetics of influenza A virus-infected mice identifies TRIM21 as a critical regulator of pulmonary innate immune response.

Tripartite motif 21 (TRIM21) is a cytosolic Fc receptor that targets antibody-bound, internalized pathogens for destruction. Apart from this intrinsic defense role, TRIM21 is implicated in autoimmune diseases, inflammation, and autophagy. Whether TRIM21 participates in host interactions with influenza A virus (IAV), however, is unknown.

5-methylcytosine RNA modification regulators-based patterns and features of immune microenvironment in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous malignant disease of the blood cell. The current therapies for AML are unsatisfactory and the molecular mechanisms underlying AML are unclear. 5-methylcytosine (m5C) is an important posttranscriptional modification of mRNA, and is involved in the regulation of mRNA stability, translation, and other aspects of RNA metabolism.

Exploring the Regulation and Function of in the Development of Early-Onset Dilated Cardiomyopathy and Congestive Heart Failure Using Systems Genetics Approach.

Background: Cardiomyopathies, diseases affecting the myocardium, are common causes of congestive heart failure (CHF) and sudden cardiac death. Recently, biallelic variants in ribosomal protein L3-like (RPL3L) have been reported to be associated with severe neonatal dilated cardiomyopathy (DCM) and CHF. This study employs a systems genetics approach to gain understanding of the regulatory mechanisms underlying the role of in DCM.

Comparative Root Transcriptome Profiling and Gene Regulatory Network Analysis between Eastern and Western Carrot ( L.) Cultivars Reveals Candidate Genes for Vascular Tissue Patterning.

Carrot ( L.) is a highly consumed vegetable rich in carotenoids, known for their potent antioxidant, anti-inflammatory, and immune-protecting properties. While genetic and molecular studies have largely focused on wild and Western carrot cultivars (cvs), little is known about the evolutionary interactions between closely related Eastern and Western cvs.

Exploring Early-Stage Retinal Neurodegeneration in Murine Pigmentary Glaucoma: Insights From Gene Networks and miRNA Regulation Analyses.

Purpose: Glaucoma is a group of heterogeneous optic neuropathies characterized by the progressive degeneration of retinal ganglion cells. However, the underlying mechanisms have not been understood completely. We aimed to elucidate the genetic network associated with the development of pigmentary glaucoma with DBA/2J (D2) mouse model of glaucoma and corresponding genetic control D2-Gpnmb (D2G) mice carrying the wild type (WT) Gpnmb allele.

Expression Levels of the Gene in the Heart Are Highly Associated with Cardiac and Glucose Metabolism-Related Phenotypes and Functional Pathways.

Background: Troponin-I interacting kinase encoded by the gene is expressed in nuclei and Z-discs of cardiomyocytes. Mutations in were identified in patients with cardiac conduction diseases, arrhythmias, and cardiomyopathy.

Methods: We performed cardiac gene expression, whole genome sequencing (WGS), and cardiac function analysis in 40 strains of BXD recombinant inbred mice derived from C57BL/6J (B6) and DBA/2J (D2) strains.

A new gene-scoring method for uncovering novel glaucoma-related genes using non-negative matrix factorization based on RNA-seq data.

Early diagnosis and treatment of glaucoma are challenging. The discovery of glaucoma biomarkers based on gene expression data could potentially provide new insights for early diagnosis, monitoring, and treatment options of glaucoma. Non-negative Matrix Factorization (NMF) has been widely used in numerous transcriptome data analyses in order to identify subtypes and biomarkers of different diseases; however, its application in glaucoma biomarker discovery has not been previously reported.

Differential Expression of MicroRNAs and Predicted Drug Target in Amyotrophic Lateral Sclerosis.

ALS (Amyotrophic Lateral Sclerosis) is a rare type of neurodegenerative disease. It shows progressive degradation of motor neurons in the brain and spinal cord. At present, there is no treatment available that can completely cure ALS.

Identification of Potential Biomarkers for Group I Pulmonary Hypertension Based on Machine Learning and Bioinformatics Analysis.

A number of processes and pathways have been reported in the development of Group I pulmonary hypertension (Group I PAH); however, novel biomarkers need to be identified for a better diagnosis and management. We employed a robust rank aggregation (RRA) algorithm to shortlist the key differentially expressed genes (DEGs) between Group I PAH patients and controls. An optimal diagnostic model was obtained by comparing seven machine learning algorithms and was verified in an independent dataset.

Weighted gene co-expression network analysis identifies key hub genes and pathways in acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. However, there is a gap in understanding the molecular basis of the disease, partly because key genes associated with AML have not been extensively explored. In the current study, we aimed to identify genes that have strong association with AML based on a cross-species integrative approach.

Transcriptomic analysis of the Non-Obstructive Azoospermia (NOA) to address gene expression regulation in human testis.

There is a need to understand the molecular basis of testes under Non-Obstructive Azoospermia (NOA), a state of failed spermatogenesis. There has been a lack of attention to the transcriptome at the level of alternatively spliced mRNAs (iso-mRNAs) and the mechanism of gene expression regulation. Hence, we aimed to establish a reliable iso-mRNA profile of NOA-testes, and explore molecular mechanisms - especially those related to gene expression regulation.

Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and functional analyses using BXD family mice.

Background: Copper (Cu) is essential for the functioning of various enzymes involved in important cellular and physiological processes. Although critical for normal cardiac function, excessive accumulation, or deficiency of Cu in the myocardium is detrimental to the heart. Fluctuations in cardiac Cu content have been shown to cause cardiac pathologies and imbalance in systemic Cu metabolism.

EWI2 and its relatives in Tetraspanin-enriched membrane domains regulate malignancy.

Experimental studies on immunoglobulin superfamily (IgSF) member EWI2 reveal that it suppresses a variety of solid malignant tumors including brain, lung, skin, and prostate cancers in animal models and inhibits tumor cell movement and growth in vitro. While EWI2 appears to support myeloid leukemia in mouse models and maintain leukemia stem cells. Bioinformatics analyses suggest that EWI2 gene expression is downregulated in glioblastoma but upregulated in melanoma, pancreatic cancer, and liver cancer.

Echocardiography phenotyping in murine genetic reference population of BXD strains reveals significant QTLs associated with cardiac function and morphology.

The genetic reference population of recombinant inbred BXD mice has been derived from crosses between C57BL/6J and DBA/2J strains. The DBA/2J parent exhibits cardiomyopathy phenotypes, whereas C57BL/6J has normal heart. BXD mice are sequenced for studying genetic interactions in cardiomyopathies.