The novel GSDMD inhibitor GI-Y2 exerts antipyroptotic effects to reduce atherosclerosis.

Introduction: Gasdermin D (GSDMD) and the pyroptosis it mediates are importantly involved in cardiovascular diseases (CVDs). Identifying and developing new inhibitors of GSDMD could be a promising strategy for treating pyroptosis-mediated diseases, such as atherosclerosis.

Objectives: We aimed to develop new inhibitor of GSDMD in atherosclerosis, as well as clarify the mechanisms underlying this inhibiting effect.

MYSM1 Mediates Cardiac Parthanatos and Hypertrophy by Deubiquitinating PARP1.

Background: Cardiac hypertrophy constitutes the primary pathological basis for heart failure and exerts a considerable influence on morbidity and mortality. Deubiquitinating enzymes are crucial regulators of protein degradation and play a pivotal role in cardiac pathophysiology. This study aimed to clarify the involvement of a deubiquitinating enzyme, MYSM1 (Myb-like, SWIRM, and MPN domains 1), in cardiac hypertrophy and to explore the underlying mechanism.

Deubiquitinase MYSM1 drives myocardial ischemia/reperfusion injury by stabilizing STAT1 in cardiomyocytes.

Myocardial ischemia/reperfusion (I/R) injury leads to irreversible cardiomyocyte death and aggravates myocardial infarction. Deubiquitinating enzymes (DUBs) are essential for maintaining substrate protein stability and functionality, playing significant roles in cardiac pathophysiology. In this study, we aimed to clarify the regulatory role of a DUB, Myb-like, SWIRM, and MPN domains 1 protein (MYSM1), in myocardial I/R injury and explore the molecular mechanism behind.

JOSD2 inhibits angiotensin II-induced vascular remodeling by deubiquitinating and stabilizing SMAD7.

Increased level of angiotensin II (Ang II) plays a central role in the development of hypertensive vascular remodeling. In this study, we identified the deubiquitinating enzyme Josephin domain-containing protein 2 (JOSD2) as a protective factor and investigated its molecular mechanism in Ang II-induced vascular remodeling. First, we found that JOSD2 was upregulated in aortic smooth muscle cells, but not in endothelial cells of Ang II-challenged mouse vascular tissues.

Deubiquitinase MYSM1 promotes doxorubicin-induced cardiotoxicity by mediating TRIM21-ferroptosis axis in cardiomyocytes.

Anthracycline antitumor drug doxorubicin (DOX) induces severe cardiotoxicity. Deubiquitinating enzymes (DUBs) are crucial for protein stability and function and play a significant role in cardiac pathophysiology. By comparing RNA sequencing datasets and conducting functional screening, we determined that Myb-like, SWIRM, and MPN domains 1 (MYSM1) is a key regulator of DOX-induced cardiotoxicity.

GSDMD Mediates Ang II-Induced Hypertensive Nephropathy by Regulating the GATA2/AQP4 Signaling Pathway.

Aim: Hypertensive nephropathy is a common complication of hypertension. However, no effective measures are currently available to prevent the progression of renal insufficiency. Gasdermin D (GSDMD) is a crucial mediator of pyroptosis that induces an excessive inflammatory response.

Cardiomyocyte-derived USP28 negatively regulates antioxidant response and promotes cardiac hypertrophy via deubiquitinating TRIM21.

Cardiac hypertrophy is an important pathological basis for heart failure. Most physiological activities of cardiomyocytes are regulated by proteins and their post-translational modification. Deubiquitinating enzymes (DUBs) are involved in protein stability maintenance and closely related to myocardial hypertrophy.

Deubiquitinase JOSD2 improves calcium handling and attenuates cardiac hypertrophy and dysfunction by stabilizing SERCA2a in cardiomyocytes.

Cardiac hypertrophy leads to myocardial dysfunction and represents a serious threat to global public health security. Deubiquitinating enzymes (DUBs) mainly maintain the stability of substrate proteins and are essential to cardiac pathophysiology. Here, we explored the role and regulating mechanism of a DUB, Josephin domain-containing protein 2 (JOSD2), in cardiac hypertrophy.

Schisandrin B alleviates angiotensin II-induced cardiac inflammatory remodeling by inhibiting the recruitment of MyD88 to TLRs in mouse cardiomyocytes.

Cardiac tissue remodeling is characterized by altered heart tissue architecture and dysfunction, leading to heart failure. Sustained activation of the renin-angiotensin-aldosterone system (RAAS) greatly promotes the development of myocardial remodeling. Angiotensin II (Ang II), which is the major component of RAAS, can directly lead to cardiac remodeling by inducing an inflammatory response.

Local adjuncts to minimally invasive endoscopic interventions for benign laryngotracheal stenosis: a meta-analysis.

Background: Benign laryngotracheal stenosis is widely managed with minimally invasive endoscopic interventions, such as laser incision or excision scar, and dilation. However, various endoscopic treatments are significantly associated with a high recurrence rate. Local auxiliary measures, including inhalation of steroids, injection of steroids, and local topical application of mitomycin C, have been studied in order to increase the success rate.

Macrophage-Derived GSDMD Plays an Essential Role in Atherosclerosis and Cross Talk Between Macrophages via the Mitochondria-STING-IRF3/NF-κB Axis.

Background: Macrophages play a crucial role in atherosclerotic plaque formation, and the death of macrophages is a vital factor in determining the fate of atherosclerosis. GSDMD (gasdermin D)-mediated pyroptosis is a programmed cell death, characterized by membrane pore formation and inflammatory factor release.

Methods: and mice, bone marrow transplantation, and AAV (adeno-associated virus serotype 9)-F4/80-shGSDMD (shRNA-GSDMD) were used to examine the effect of macrophage-derived GSDMD on atherosclerosis.

Deubiquitinase OTUD6a drives cardiac inflammation and hypertrophy by deubiquitination of STING.

Background: Cardiac hypertrophy is a crucial pathological characteristic of hypertensive heart disease and subsequent heart failure. Deubiquitinating enzymes (DUBs) have been found to be involved in the regulation of myocardial hypertrophy. OTU Domain-Containing Protein 6a (OTUD6a) is a recently identified DUB.

OTUD6A in tubular epithelial cells mediates angiotensin II-induced kidney injury by targeting STAT3.

Kidney fibrosis is a prominent pathological feature of hypertensive kidney diseases (HKD). Recent studies have highlighted the role of ubiquitinating/deubiquitinating protein modification in kidney pathophysiology. Ovarian tumor domain-containing protein 6 A (OTUD6A) is a deubiquitinating enzyme involved in tumor progression.

Inflammatory endotypes of adenoidal hypertrophy based on a cluster analysis of biomarkers.

Objective: To identify adenoid inflammatory endotypes based on inflammatory markers, match endotypes to phenotypes, and predict endotypes.

Methods: This cross-sectional study included 72 children with adenoid hypertrophy. Thirteen inflammatory markers and total immunoglobulin E (TIgE) in adenoid tissue were analyzed using Luminex and enzyme-linked immunosorbent assay (ELISA) for performing cluster analysis.

Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD.

Background: Doxorubicin (Dox), which is an anticancer drug, has significant cardiac toxicity and side effects. Pyroptosis occurs during Dox-induced cardiotoxicity (DIC), and drug inhibition of this process is one therapeutic approach for treating DIC. Previous studies have indicated that emodin can reduce pyroptosis.

Novel GSDMD inhibitor GI-Y1 protects heart against pyroptosis and ischemia/reperfusion injury by blocking pyroptotic pore formation.

Activation of gasdermin D (GSDMD) and its concomitant cardiomyocyte pyroptosis are critically involved in multiple cardiac pathological conditions. Pharmacological inhibition or gene knockout of GSDMD could protect cardiomyocyte from pyroptosis and dysfunction. Thus, seeking and developing highly potent GSDMD inhibitors probably provide an attractive strategy for treating diseases targeting GSDMD.

CENPN suppresses autophagy and increases paclitaxel resistance in nasopharyngeal carcinoma cells by inhibiting the CREB-VAMP8 signaling axis.

Chemotherapeutic resistance is one of the most common reasons for poor prognosis of patients with nasopharyngeal carcinoma (NPC). We found that CENPN can promote the growth, proliferation and apoptosis resistance of NPC cells, but its relationship with chemotherapeutic resistance in NPC is unclear. Here we verified that the CENPN expression level in NPC patients was positively correlated with the degree of paclitaxel (PTX) resistance and a poor prognosis through analysis of clinical cases.

Gasdermin D affects aortic vascular smooth muscle cell pyroptosis and Ang II-induced vascular remodeling.

Vascular smooth muscle cells (VSMCs) are primarily responsible for vasoconstriction and the regulation of blood pressure1. Pyroptosis, a particular form of regulated cell death, is involved in multiple vascular injuries, including hypertensive vascular dysfunction. This pyroptotic cell death is mediated by the pore-forming protein of Gasdermin D (GSDMD).

USP25 Ameliorates Pathological Cardiac Hypertrophy by Stabilizing SERCA2a in Cardiomyocytes.

Background: Pathological cardiac hypertrophy can lead to heart failure and is one of the leading causes of death globally. Understanding the molecular mechanism of pathological cardiac hypertrophy will contribute to the treatment of heart failure. DUBs (deubiquitinating enzymes) are essential to cardiac pathophysiology by precisely controlling protein function, localization, and degradation.

The efficiency of endoscopic versus open surgical interventions in adult benign laryngotracheal stenosis: a meta-analysis.

Background: The optimal treatments for adult benign laryngotracheal stenosis presently remains controversial. The majority of the disadvantages of endoscopic interventions with high recurrence rate and open surgical therapy accompanied by sophisticated techniques, complication and mortality, highlights the dilemma of option for treatments.

Purpose: To compare endoscopic treatments with open surgical interventions in adult patients with benign laryngotracheal stenosis, analyze their clinical outcomes, recurrence, complication and mortality.

Establishment of prognostic nomogram for T1N0M0 glottic squamous cell carcinoma: an SEER database analysis.

Objectives: The study aimed to construct prognostic models for OS and CSS in patients with T1N0M0 glottic SCC. In addition, we used PSM to re-assess the effect of surgery alone and radiation alone.

Methods: The Surveillance, Epidemiology, and End Results database was searched for patients with confirmed T1N0M0 glottic SCC.

Schisandrin B protects against LPS-induced inflammatory lung injury by targeting MyD88.

Background: Acute lung injury (ALI) is a challenging clinical syndrome that manifests as an acute inflammatory response. Schisandrin B (Sch B), a bioactive lignan from Schisandra genus plants, has been shown to suppress inflammatory responses and oxidative stress. However, the underlying molecular mechanisms have remained elusive.

Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88-Dependent Inflammation.

Diabetes manifests as chronic inflammation and leads to the development diabetic cardiomyopathy (DCM). Targeting key proteins in inflammatory signaling may provide new therapy for DCM. In this study, the authors explore the pharmacological effects and mechanisms of Schisandrin B (Sch B), a natural compound with anti-inflammatory activity against DCM.