An mTOR-Tfeb-Fabp7a Axis Ameliorates bag3 Cardiomyopathy via Decelerating Cardiac Aging.

While BAG3 has been identified as a causative gene for dilated cardiomyopathy, the major pathological events in BAG3-related cardiomyopathy that could be targeted for therapeutic benefit remain to be discovered. Here, we aim to uncover novel pathological events through genetic studies in a zebrafish bag3 cardiomyopathy model. Given the known cardioprotective effects of mtor inhibition and the fact that transcription factor EB (tfeb) encodes a direct downstream phosphorylation target of mTOR signaling, we generated a cardiomyocyte-specific transgenic line overexpressing tfeb (Tg[cmlc2:tfeb]).

Nothobranchius furzeri: a vertebrate model for studying cardiac aging and cellular senescence.

African turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate that can be bred in captivity, making it an ideal model organism for aging studies. However, whether the animal can be used for studying cardiac aging and whether cellular senescence contribute to this ageing process remain unclear. Here, we conducted a longitudinal study on the GRZ strain, aiming to identify phenotypic and functional markers for cardiac aging.

Analysis of biased allelic enhancer activity of schizophrenia-linked common variants.

Schizophrenia is a neuropsychiatric disorder with heritability estimates between 60% and 80%. Although genome-wide association studies have identified many genetic loci linked to the disorder, most of these are noncoding variants whose functional impacts are not well understood. To bridge this gap, we prioritized potential functional variants linked to schizophrenia by utilizing a human brain epigenomic roadmap.

Cardiomyocyte-specific activation of the sarcomere-localized Dnajb6b chaperone causes cardiomyopathy and heart failure through upregulated sarcoplasmic reticulum stress.

Aims: Despite abundant expression of DNAJB6 gene in the heart, its roles in cardiac diseases remain underexplored. We aimed to investigate the function of its zebrafish (Danio rerio) ortholog, the dnajb6b gene, in cardiomyopathy and heart failure.

Materials And Methods: Both loss-of-function mutation and gain-of-function transgenic approaches were employed in zebrafish.

Loss of lims1 causes aberrant cardiac remodeling and heart failure via activating gp130/Jak1/Stat3 pathway in zebrafish.

LIM zinc finger domain containing 1 (LIMS1), an evolutionally conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure.

The -Deficient Zebrafish: A Model for Renal Cystogenesis and an F0-Based Screen to Identify Genetic Modifiers of Kidney Cysts.

Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies. In this study, we investigated zebrafish mutants of , a newly identified ADPKD gene, and observed phenotypes similar to those seen in mammalian models, including kidney cysts and bone defects. Using efficient microhomology-mediated end joining (MMEJ)-based genome editing technology, we demonstrated that CRISPRants recapitulate mutant phenotypes while bypassing the early lethality of the mutants to allow for renal cyst analysis in adult fish.

An mTOR-Tfeb-Fabp7a signaling axis can be harnessed to ameliorate cardiomyopathy in adult zebrafish.

Dysregulated proteostasis in cardiomyocytes is an important pathological event in cardiomyopathy, which can be repaired by inhibiting mechanistic target of rapamycin (mTOR) for cardioprotective effects. Here, we aimed to uncover additional pathological events and therapeutic target genes via leveraging zebrafish genetics. We first assessed transcription factor EB ( ), a candidate gene that encodes a direct downstream phosphorylation target of mTOR signaling.

The Contribution of Mosaic Chromosomal Alterations to Schizophrenia.

Background: Mosaic chromosomal alterations are implicated in neuropsychiatric disorders, but the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages has not been fully established.

Methods: We analyzed blood-derived genotype arrays from 9715 patients with SCZ and 28,822 control participants of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mosaic chromosomal alterations. We focused on probable early developmental sCNVs through stringent filtering.

Lapatinib combined with doxorubicin causes dose-dependent cardiotoxicity partially through activating the p38MAPK signaling pathway in zebrafish embryos.

Because of its enhanced antitumor efficacy, lapatinib (LAP) is commonly used clinically in combination with the anthracycline drug doxorubicin (DOX) to treat metastatic breast cancer. While it is well recognized that this combination chemotherapy can lead to an increased risk of cardiotoxicity in adult women, its potential cardiotoxicity in the fetus during pregnancy remains understudied. Here, we aimed to examine the combination of LAP chemotherapy and DOX-induced cardiotoxicity in the fetus using a zebrafish embryonic system and investigate the underlying pathologic mechanisms.

FAdV-4-induced ferroptosis affects fat metabolism in LMH cells.

Ferroptosis is a form of controlled cell death that was first described relatively recently and that is dependent on the formation and accumulation of lipid free radicals through an iron-mediated mechanism. A growing body of evidence supports the close relationship between pathogenic infections and ferroptotic cell death, particularly for viral infections. Ferroptosis is also closely tied to the pathogenic development of hepatic steatosis and other forms of liver disease.

Genome-wide investigation and expression profiling of gene family in rapeseed under salinity and ABA stress.

The () () gene family is a little-known gene family characterized by a conserved LOR domain in the proteins. Limited research in showed that family members played important roles in () defense. Nevertheless, there is a paucity of research investigating the role of the gene family towards their responses to abiotic stresses and hormone treatments.

Using Zebrafish Animal Model to Study the Genetic Underpinning and Mechanism of Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly right ventricular involvement. ACM is one of the major conditions associated with an increased risk of sudden cardiac death, most notably in young individuals and athletes. ACM has strong genetic determinants, and genetic variants in more than 25 genes have been identified to be associated with ACM, accounting for approximately 60% of ACM cases.

Cinnamaldehyde causes developmental neurotoxicity in zebrafish the oxidative stress pathway that is rescued by astaxanthin.

Toxicology studies provide a reliable dose range for the use of compounds. Zebrafish show unique advantages in toxicology research. Cinnamaldehyde (Cin) is one of the main active compounds isolated from trees and other species of the genus .

TMT-based quantitative proteomics analysis reveals the role of Notch signaling in FAdV-4-infected LMH cell.

Fowl adenovirus serotype 4 (FAdV-4) is recognized as a pathogen that causes hydropericardium syndrome. Irrespective of the pathway used by the virus to invade the chicken, the pathological characteristics of the disease include degeneration and necrosis of hepatocytes, formation of intranuclear inclusions, as well as inflammatory cell infiltration. Liver dysfunction constitutes one of the critical factors leading to death.

Genetic Susceptibility and Mechanisms Underlying the Pathogenesis of Anthracycline-Associated Cardiotoxicity.

Anthracyclines are chemotherapeutic agents widely used to treat a variety of cancers, and these drugs have revolutionized our management of cancer patients. The dose-dependent cardiotoxicity of anthracyclines, however, remains one of the leading causes of chemotherapy treatment-associated mortality in cancer survivors. Patient threshold doses leading to anthracycline-induced cardiotoxicity (AIC) are highly variable among affected patients.

A Primer Genetic Toolkit for Exploring Mitochondrial Biology and Disease Using Zebrafish.

Mitochondria are a dynamic eukaryotic innovation that play diverse roles in biology and disease. The mitochondrial genome is remarkably conserved in all vertebrates, encoding the same 37-gene set and overall genomic structure, ranging from 16,596 base pairs (bp) in the teleost zebrafish () to 16,569 bp in humans. Mitochondrial disorders are amongst the most prevalent inherited diseases, affecting roughly 1 in every 5000 individuals.

FAdV-4 induce autophagy via the endoplasmic reticulum stress-related unfolded protein response.

Hydropericardium syndrome caused by the fowl adenovirus serotype 4 (FAdV-4) is prevalent disease in China with a high mortality rate. Many studies have demonstrated some viral infections to induce stress in the endoplasmic reticulum (ER). When the ER stress exceeds or persists, it activates autophagy, eventually triggering the onset of diseases.

Application of an F0-based genetic assay in adult zebrafish to identify modifier genes of an inherited cardiomyopathy.

Modifier genes contribute significantly to our understanding of pathophysiology in human diseases; however, effective approaches to identify modifier genes are still lacking. Here, we aim to develop a rapid F0-based genetic assay in adult zebrafish using the bag3 gene knockout (bag3e2/e2) cardiomyopathy model as a paradigm. First, by utilizing a classic genetic breeding approach, we identified dnajb6b as a deleterious modifier gene for bag3 cardiomyopathy.

An Knock-in Zebrafish Experimental Model Used in Evaluation of the Amantadine Drug Safety During Early Cardiogenesis.

Background: Drug exposure during gestation or in prematurely born children represents a significant risk to congenital heart disease (CHD). Amantadine is an antiviral agent also effective in the treatment of Parkinson's disease. However, while its potential side effects associated with tetralogy of fallot (ToF) and birth defects were implicated, its underlying etiologic mechanisms of action remain unknown.

Inhibition of mTOR or MAPK ameliorates vmhcl/myh7 cardiomyopathy in zebrafish.

Myosin heavy chain 7 (MYH7) is a major causative gene for hypertrophic cardiomyopathy, but the affected signaling pathways and therapeutics remain elusive. In this research, we identified ventricle myosin heavy chain like (vmhcl) as a zebrafish homolog of human MYH7, and we generated vmhcl frameshift mutants. We noted vmhcl-based embryonic cardiac dysfunction (VEC) in the vmhcl homozygous mutants and vmhcl-based adult cardiomyopathy (VAC) phenotypes in the vmhcl heterozygous mutants.