Organoids refer to 3D cultures established to recapitulate histology, pathology, architecture, and genetic traits of various organs and tissues in the body, thereby replacing 2D cell cultures, xenograft, and animal models. Organoids form a 3D in vitro mimic of original tissues like the liver and are derived from embryonic or adult tissue stem cells. Liver and bile duct tumor organoids, also called, tumoroids capture genetic diversity, cellular, and pathophysiological properties of original tumors.
View Article and Find Full Text PDFInterrupted ER homeostasis contributes to the etiology of obesity cardiomyopathy although it remains elusive how ER stress evokes cardiac anomalies in obesity. Our study evaluated the impact of ER stress inhibition on cardiac anomalies in obesity. Lean and ob/ob obese mice received chemical ER chaperone tauroursodeoxycholic acid (TUDCA, 50 mg/kg/d, p.
View Article and Find Full Text PDFAims: Heart failure with preserved ejection fraction (HFpEF) is a devastating health issue although limited knowledge is available for its pathogenesis and therapeutics. Given the perceived involvement of mitochondrial dysfunction in HFpEF, this study was designed to examine the role of mitochondrial dynamics in the etiology of HFpEF.
Method And Results: Adult mice were placed on a high fat diet plus l-NAME in drinking water ('two-hit' challenge to mimic obesity and hypertension) for 15 consecutive weeks.
A comprehensive view of the role of NLRP3/caspase-1/GSDMD-mediated pyroptosis in pressure overload cardiac hypertrophy is presented in this study. Furthermore, mitigation of NLRP3 deficiency-induced pyroptosis confers cardioprotection against pressure overload through activation of TAK1, whereas this salutary effect is abolished by inhibition of TAK1 activity, highlighting a previously unrecognized reciprocally regulatory role of NLRP3-TAK1 governing inflammation-induced cell death and hypertrophic growth. Translationally, this study advocates strategies based on inflammation-induced cell death might be exploited therapeutically in other inflammatory and mechanical overload disorders, such as myocardial infarction and mitral regurgitation.
View Article and Find Full Text PDFClinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity.
View Article and Find Full Text PDFMitochondrial aldehyde dehydrogenase (ALDH2) offers proven cardiovascular benefit, although its impact on diabetes remains elusive. This study examined the effects of ALDH2 overexpression and knockout on diabetic cardiomyopathy and the mechanism involved with a focus on mitochondrial integrity. Mice challenged with streptozotocin (STZ, 200 mg/kg, via intraperitoneal injection) exhibited pathological alterations, including reduced respiratory exchange ratio, dampened fractional shortening and ejection fraction, increased left ventricular end-systolic and diastolic diameters, cardiac remodeling, cardiomyocyte contractile anomalies, intracellular Ca2+ defects, myocardial ultrastructural injury, oxidative stress, apoptosis, and mitochondrial damage, which were overtly attenuated or accentuated by ALDH2 overexpression or knockout, respectively.
View Article and Find Full Text PDFHeart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks.
View Article and Find Full Text PDFBackground: Doxorubicin (DOX) is among the most widely employed antitumor agents, although its clinical applications have been largely hindered by severe cardiotoxicity. Earlier studies described an essential role of mitochondrial injury in the pathogenesis of DOX cardiomyopathy. PHB2 (Prohibitin 2) is perceived as an essential regulator for mitochondrial dynamics and oxidative phosphorylation (OXPHOS) although its involvement in DOX cardiomyopathy remains elusive.
View Article and Find Full Text PDFIntroduction: Liver fibrosis is a life-threatening pathological anomaly which usually evolves into advanced liver cirrhosis and hepatocellular carcinoma although limited therapeutic option is readily available. FUN14 domain containing 1 (FUNDC1) is a mitophagy receptor with little information in liver fibrosis.
Objective: This study was designed to examine the role for FUNDC1 in carbon tetrachloride (CCl4)-induced liver injury.
Biochim Biophys Acta Gen Subj
February 2023
Background: Uncorrected obesity facilitates premature aging and cardiovascular anomalies. This study examined the interaction between obesity and aging on cardiac remodeling and contractile function.
Methods: Cardiac echocardiographic geometry, function, morphology, intracellular Ca handling, oxidative stress (DHE fluorescence), STAT3 and stress signaling were evaluated in young (3-mo) and old (12- and 18-mo) lean and leptin deficient ob/ob obese mice.
Trastuzumab (TZM) is commonly used for target therapy in breast cancer patients with high HER2 although the cardiotoxicity restricts its clinical usage. DNA damage and ferroptosis are implicated in anti-tumor drug cardiotoxicity. Given the emerging use of SGLT2 inhibitors in clinical cardiology, this study evaluated the impact of SGLT2 inhibitor Empagliflozin on TZM-induced cardiotoxicity, and mechanism involved with a focus on DNA damage and ferroptosis.
View Article and Find Full Text PDFThe study aimed to investigate the influences of aldehyde dehydrogenase 2 (ALDH2) on cardiomyocyte apoptosis in heart failure (HF) rats through regulating the PTEN induced putative kinase 1 (PINK1)-Parkin signaling pathway-mediated mitophagy. The rat model of HF was established, and the rats were randomly divided into model group (HF model, n=20) and ALDH2 group (intervention with ALDH2, n=20), with a normal group (n=20) set. After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats.
View Article and Find Full Text PDFType 2 diabetes mellitus (T2DM or T2D) is a devastating metabolic abnormality featured by insulin resistance, hyperglycemia, and hyperlipidemia. T2D provokes unique metabolic changes and compromises cardiovascular geometry and function. Meanwhile, T2D increases the overall risk for heart failure (HF) and acts independent of classical risk factors including coronary artery disease, hypertension, and valvular heart diseases.
View Article and Find Full Text PDFPurpose: To uncover the biological role of LINC00355 in regulating the proliferative and apoptotic potentials in hepatocellular carcinoma (HCC), and the underlying mechanism.
Methods: LINC00355 levels in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After knockdown of LINC00355 or miR-217-5p in Hub7 and Hep3B cells, proliferative and apoptotic potentials were assessed by cell counting kit-8 (CCK-8), colony formation assay and flow cytometry.
Acute myocardial infarction (MI), caused by acute coronary artery obstruction, is a common cardiovascular event leading to mortality. Nuclear dot protein 52 (NDP52) is an essential selective autophagy adaptor, although its function in MI is still obscure. This study was designed to examine the function of NDP52 in MI and the associated mechanisms.
View Article and Find Full Text PDFBerberine has been verified to protect cardiac function in patients with heart failure (HF). However, the mechanism(s) involved in berberine-mediated cardioprotective effects has not been clearly elucidated. The aim of this study was to further investigate the mechanism(s) involved in the beneficial effects of berberine on transverse aortic contraction (TAC)-induced chronic HF.
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