Targeting Stat3 with conditional knockout or PROTAC technology alleviates renal injury by Limiting pyroptosis.

Background: Acute kidney injury (AKI) is a critical clinical syndrome with high morbidity, mortality, and no effective treatment in clinical practice. The role of the Signal Transducer and Activator of Transcription 3 (Stat3) in AKI remains controversial, and its complex regulatory mechanisms must be further explored.

Methods: We generated renal tubular epithelial cells Stat3 conditional knockout (cKO) mice and used them in cecal ligation and puncture (CLP) and ischaemia-reperfusion (I/R) induced AKI models.

exacerbates acute renal inflammation by enhancing N4-acetylcytidine modification of the CCL2/CXCL1 axis.

Inflammation plays an essential role in eliminating microbial pathogens and repairing tissues, while sustained inflammation accelerates kidney damage and disease progression. Therefore, understanding the mechanisms of the inflammatory response is vital for developing therapies for inflammatory kidney diseases like acute kidney injury (AKI), which currently lacks effective treatment. Here, we identified N-acetyltransferase 10 () as an important regulator for acute inflammation.

Nursing management of intracranial hypertension in adults with severe brain injury in a neurosurgery intensive care unit: a best practice implementation project.

Introduction: The nursing management of intracranial hypertension in adult patients with severe brain injury is crucial for maintaining the stability of intracranial pressure, which ultimately improves patient outcomes.

Objectives: This project aimed to implement evidence-based practices for the nursing management of intracranial hypertension in adult patients with severe brain injury.

Methods: This evidence implementation project was conducted in a neurosurgery intensive care unit in a large tertiary hospital in Guangzhou, China.

Hierarchical supramolecules composed of starch-based nanocluster aggregates with light-responsive mechanical strain for remotely rapid and precise actuation.

Hierarchical supramolecular systems, characterized by nanoscale sensitivity and macroscopic tangible changes, offer promising perspectives for the design of remotely controllable, rapid, and precise actuation materials, serving as a potential substitution for non-intelligent and complex actuation switches. Herein, we reported on the disassembly of orderly and rigid starch helical covalent structures, and their subsequent reassembly into a hierarchical supramolecular gel composed of nanocluster aggregates, integrating supramolecular interactions of three different scales. The incorporation of photo-sensitive FeTA, a complex of trivalent iron ions and tannic acid, significantly enhances the photo-responsive strain capacity of the hierarchical supramolecular gel.

Coriaceumins A-D, the First Nitrogen-Containing Crenulide Diterpenoids from the Brown Alga Collected in the East China Sea.

A phytochemical investigation of an East China Sea collection of the brown alga has led to the isolation of four novel nitrogen-containing crenulide diterpenoids, named coriaceumins A-D (-), two rare nitrogenous xenicane diterpenoids, dictyolactams C () and D (), and one known crenulide diterpenoid, hydroxycrenulide (). The structures of the new compounds were elucidated by detailed spectroscopic data analyses, including HRESIMS and 1D/2D NMR. The absolute configurations were determined by a comparison of the experimental ECD spectra with the spectra computed by DFT-based quantum chemical calculations.

Compound-42 alleviates acute kidney injury by targeting RIPK3-mediated necroptosis.

Background And Purpose: Necroptosis plays an essential role in acute kidney injury and is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like pseudokinase (MLKL). A novel RIPK3 inhibitor, compound 42 (Cpd-42) alleviates the systemic inflammatory response. The current study was designed to investigate whether Cpd-42 exhibits protective effects on acute kidney injury and reveal the underlying mechanisms.

RIPK3 inhibitor-AZD5423 alleviates acute kidney injury by inhibiting necroptosis and inflammation.

Acute kidney injury (AKI) is a clinical syndrome that is defined as a sudden decline in renal function and characterized by inflammation and programmed cell death of renal tubular epithelial cells. Necroptosis is a form of regulated cell death that requires activation of receptor interacting protein kinase 3 (RIPK3) and its phosphorylation of the substrate MLKL. RIPK3 plays an important role in acute kidney injury, and hence developing its inhibitors is considered as one of the promising strategies aimed at prevention and treatment of AKI.

Cpd-0225 attenuates renal fibrosis via inhibiting ALK5.

Chronic kidney disease (CKD) is an increasing public health concern, characterized by a reduced glomerular filtration rate and increased urinary albumin excretion. Renal fibrosis is an important pathological condition in patients with CKD. In this study, we evaluated the anti-fibrotic effect of Cpd-0225, a novel transforming growth factor-β (TGF-β) type I receptor (also known as ALK5) inhibitor, in vitro and in vivo, by comparing its effect with that of SB431542, a classic ALK5 inhibitor, which has not entered the clinical trial stage owing to multiple side effects.

miR-301a-3p promotes hepatic stellate cells activation and liver fibrogenesis via regulating PTEN/PDGFR-β.

Hepatic fibrosis is an essential pathology of multiple chronicliverdiseases. The aim of this study was to investigate the role of miR-301a-3p in hepatic fibrosis. We found that miR-301a-3p was upregulated in hepatic fibrosis patients and in culture-activated human hepatic stellate cells (HSCs).

Targeted inhibition of TGF-β type I receptor by AZ12601011 protects against kidney fibrosis.

Renal fibrosis, a common feature of chronic kidney disease, causes the progressive loss of renal function, in which TGF-β plays a critical role. In this study, we found that expression levels of TGF-β and its receptor 1 (TGF-βR1) were both significantly increased in obstructive fibrosis kidneys. AZ12601011 is a small molecular inhibitor of TGF-βR1; however, its therapeutic potential for renal fibrosis remains unclear.

Inhibition of attenuates renal injury and inflammation by alleviating m6A modifications via IGF2BP2-dependent mechanisms.

The role of -methyladenosine (m6A) modifications in renal diseases is largely unknown. Here, we characterized the role of -adenosine-methyltransferase-like 3 (METTL3), whose expression is elevated in renal tubules in different acute kidney injury (AKI) models as well as in human biopsies and cultured tubular epithelial cells (TECs). silencing alleviated renal inflammation and programmed cell death in TECs in response to stimulation by tumor necrosis factor-α (TNF-α), cisplatin, and lipopolysaccharide (LPS), whereas overexpression had the opposite effects.

Toll-like receptor 9 is correlated to disease activity in Chinese systemic lupus erythematosus population.

Background: Toll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models. Its pathogenic role in human SLE, however, was poorly elucidated. This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE.