Loss of PCAF in proximal tubular cells exacerbates renal fibrosis by promoting partial epithelial-to-mesenchymal transition.

Renal fibrosis is a consequence of chronic kidney disease, which is estimated to affect 10-14% of the global population. The molecular mechanisms in the pathogenesis of renal fibrosis are still unclear, and there is a lack of effective therapies. Here we identified decreased levels of p300/CBP-associated factor (PCAF) in kidney tissues with fibrosis and demonstrated that PCAF-specific knockout in proximal tubular cells accelerates renal fibrosis in both unilateral ureteral obstruction surgery and folic acid-induced models.

analysis highlights elevation of epithelial-to-mesenchymal transition characteristics in non-responding lupus nephritis patients.

ObjectiveLupus nephritis (LN) is a common complication in a significant proportion of systemic lupus erythematosus (SLE) patients. As a chronic autoimmune disease, LN leads to renal failure, substantially impacting patient quality of life and mortality rates. Current LN treatments primarily involve traditional immunosuppressants, such as azathioprine and mycophenolate mofetil (MMF).

Loss of p300 in proximal tubular cells reduces renal fibrosis and endothelial-mesenchymal transition.

Chronic kidney disease (CKD) has a high prevalence worldwide and is typically accompanied by severe fibrosis. However, the exact pathogenesis of renal fibrosis and effective treatments have yet to be identified. In this study, we found that expression of the histone-acetyltransferase p300 was increased in focal segmental glomerulosclerosis patients and several distinct mouse models of renal fibrosis.

Plumbagin ameliorates renal fibrosis by suppressing epithelial-mesenchymal transition.

Renal fibrosis is a common pathological feature of chronic kidney diseases (CKDs), driven by excessive extracellular matrix (ECM) accumulation. Despite its prevalence, therapeutic candidates specifically targeting fibrosis are limited, and the role of renal tubular epithelial cells in fibrosis pathogenesis remains unclear. In this study, we evaluated the anti-fibrotic effects of Plumbagin, a plant-derived natural compound, using a folic acid-induced renal fibrosis model that simulates proximal tubular injury-driven fibrosis.

Deubiquitinase inhibitor bAP-15 suppresses renal epithelial to mesenchymal transition via inhibition of p300 stability.

Renal fibrosis is an irreversible disease that is common in patients with chronic kidney disease. Elevated levels of the histone acetyltransferase p300 have been reported in various fibrotic diseases, including renal fibrosis, suggesting that p300 may be a promising therapeutic target. To investigate the specific deubiquitinase (DUB) involved in the regulation of p300 protein stability in renal epithelial cells, we tested 13 DUB inhibitors using a kidney tubular epithelial cell line.

JMJD4 promotes tumor progression via inhibition of the PDCD5-TP53 pathway.

Programmed cell death 5 (PDCD5) regulates cell death and suppresses tumor progression. Since the stability and nuclear translocation of PDCD5 are regulated by TP53-dependent cell death stimuli, knowledge of the regulatory mechanism of PDCD5 function is required to better understand the TP53-signaling pathway. We identified Jumonji domain-containing protein 4 (JMJD4) to be a PDCD5-interacting protein using liquid chromatography- mass spectrometry (LC-MS).

Generation of an induced pluripotent stem cell line from a patient with arrhythmogenic right ventricular cardiomyopathy harboring a TMEM43 splice-site variant.

Arrhythmogenic cardiomyopathy (ACM) is a cardiomyopathy that is predominantly inherited and characterized by cardiac arrhythmias and structural abnormalities. TMEM43 (transmembrane protein 43) is one of the well-known genetic culprits behind ACM. In this study, we successfully generated an induced pluripotent stem cell (iPSC) line, YCMi010-A, derived from a male patient diagnosed with ACM.

Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/β-catenin signal pathway.

Aims: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored.

Water Extract of Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes.

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death.

The deubiquitinase UCHL3 mediates p300-dependent chemokine signaling in alveolar type II cells to promote pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal, fibrotic, interstitial lung disease of unknown cause. Despite extensive studies, the underlying mechanisms of IPF development remain unknown. Here, we found that p300 was upregulated in multiple epithelial cells in lung samples from patients with IPF and mouse models of lung fibrosis.

Epigenetic regulator Cfp1 safeguards male meiotic progression by regulating meiotic gene expression.

Meiosis occurs specifically in germ cells to produce sperm and oocytes that are competent for sexual reproduction. Multiple factors are required for successful meiotic entry, progression, and termination. Among them, trimethylation of histone H3 on lysine 4 (H3K4me3), a mark of active transcription, has been implicated in spermatogenesis by forming double-strand breaks (DSBs).

Fermented L. Prevents Alcoholic Fatty Liver Disease in Mice by Regulating CYP2E1, SREBP-1c, and PPAR-.

We examined the efficacy of fermented L. (FT) on the development of alcoholic fatty liver in mice and investigated the underlying mechanism. The protective potential of FT against ethanol-induced fatty liver was determined using C57BL/6 male mice allocated into four groups (8 mice/group).

Loss of MIG-6 results in endometrial progesterone resistance via ERBB2.

Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis.

Beneficial Effects of a Combination of L. and Against Beta-Amyloid Peptide-Induced Neurodegeneration in Mice.

Both (CL) and Tanaka (CJ) have been used to treat various diseases due to their anti-inflammatory and antioxidative stress activities. In this study, we investigated the ameliorative effect of the combination of CL extract and CJ extract (CCC) against beta-amyloid (A) peptide-induced neurological damage. CCC prevented neurocytotoxicity .

Generation of a human induced pluripotent stem cell line YCMi004-A from a patient with dilated cardiomyopathy carrying a protein-truncating mutation of the Titin gene and its differentiation towards cardiomyocytes.

Dilated cardiomyopathy (DCM) is a heart muscle disease that causes heart failure and is the leading cause for heart transplantation. It is a heart muscle disease resulted from a variety of genetics, toxic, metabolic, and infectious causes. One of the most prevalent genetic causes of DCM is a protein-truncating variant in the Titin gene (TTNtv).

Establishment of a novel human iPSC line (YCMi003-A) from a patient with dilated cardiomyopathy carrying genetic variant LMNA p.Asp364His.

Cardiac laminopathy caused by mutations in the LMNA gene are common and highly penetrant with a poor prognosis. We have generated a novel human induced pluripotent stem cell(iPSC) lines YCMi003-A from a patient with dilated cardiomyopathy associated with genetic variant LMNA c.1090G > C; p.

Water Extract of Prevents Inflammatory Skin Diseases In Vitro Models.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by immune hypersensitivity reaction. The cause of AD is unclear, but its symptoms have a negative effect on quality of life; various treatment methods to alleviate these symptoms are underway. In the present study, we aimed to evaluate in vitro antioxidant and anti-inflammatory effects of water extract (RCW) on AD.

Club cell-specific role of programmed cell death 5 in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) causes progressive fibrosis and worsening pulmonary function. Prognosis is poor and no effective therapies exist. We show that programmed cell death 5 (PDCD5) expression is increased in the lungs of patients with IPF and in mouse models of lung fibrosis.

Aucuparin Suppresses Bleomycin-Induced Pulmonary Fibrosis Via Anti-Inflammatory Activity.

Idiopathic pulmonary fibrosis (IPF) is a lung disease that results in scarring of the lungs for an unknown reason. Although many studies have been conducted on IPF, precise mechanisms and treatments have not yet been identified. In this study, we found that aucuparin, a natural product isolated from , inhibited pulmonary fibrosis in a bleomycin (BLM)-induced lung fibrosis mouse model.

Field-based rational design of p300 histone acetyltransferase inhibitor and systematic evaluation as an anti-fibrotic agent.

(E)-3-(3-(4-((3-Carbamoylbenzyl)oxy)-3-iodo-5-methoxyphenyl) acryloyl)benzamide (A6) was found to be a potent p300 inhibitor (IC50 = 870 nM) showing a similar binding mode to that of acetyl-CoA, a p300 substrate, and effective anti-fibrotic activity in both TGF-β1-stimulated lung fibroblast cells and bleomycin-induced in vivo lung fibrosis mice.

Plumbagin Suppresses Pulmonary Fibrosis via Inhibition of p300 Histone Acetyltransferase Activity.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis similar to that of malignancy. The causes of IPF are not clearly known, and there is no effective therapy to date. In this study, the natural compound plumbagin, which was isolated from root extract, was screened for p300 inhibitory activity.

Effects of Water Extract on Alcoholic and Nonalcoholic Fatty Liver Impairment.

The aim of this study was to investigate the potential protective effects of the hot water extract of (EJW) on EtOH- or free fatty acid (FFA)-induced fatty liver injury . HepG2/2E1 cells were exposed to EtOH and HepG2 cells were exposed to a mixture of FFAs (oleic acid:palmitic acid, 2:1) to stimulate oxidative stress and to induce lipid accumulation, respectively. Antioxidant activity was significantly increased and lipid accumulation was inhibited in cells pretreated with EJW compared to those in cells exposed to EtOH or FFA only.

Branch Water Extract Increases the Immunostimulatory Activity of RAW264.7 Macrophages and Primary Mouse Splenocytes.

Polyacetylenes in the bark of trees have been reported to promote immune cell proliferation and to strengthen the innate immune system. The immunomodulatory potential of branch water extract (DBW) was evaluated by determining its effect on cell viability and the expression of cytokines and immune effector molecules in mouse RAW264.7 macrophages and splenocytes.

Water Extract of L. Ameliorates Non-Alcoholic Fatty Liver Disease.

Our aim was to investigate whether hot water extract (CLW) of L. could prevent non-alcoholic fatty liver disease (NAFLD). HepG2 cells were treated with free fatty acid (FFA) mixture (oleic acid: palmitic acid, 2:1) for 24 h to stimulate in vitro fatty liver.