JPH203 alleviates peritoneal fibrosis via inhibition of amino acid-mediated mTORC1 signaling.

Background And Aims: The mesothelial-mesenchymal transition (MMT) of mesothelial cells has been recognized as a critical process during progression of peritoneal fibrosis (PF). Despite its crucial role in amino acid transport and metabolism, the involvement of L-type amino acid transporter 1 (LAT1) and the potential therapeutic role of its inhibitor, JPH203, in fibrotic diseases remain unexplored. Considering the paucity of research on amino acid-mediated mTORC1 activation in PF, our study endeavors to elucidate the protective effects of JPH203 against PF and explore the involvement of amino acid-mediated mTORC1 signaling in this context.

The deubiquitinase USP5 promotes cholangiocarcinoma progression by stabilizing YBX1.

Aims: Ubiquitin specific peptidase 5 (USP5), a member of deubiquitinating enzymes, has garnered significant attention for its crucial role in cancer progression. This study aims to explore the role of USP5 and its potential molecular mechanisms in cholangiocarcinoma (CCA).

Main Methods: To explore the effect of USP5 on CCA, gain-of-function and loss-of-function assays were conducted in human CCA cell lines RBE and HCCC9810.

[Arterial partial pressure of oxygen and procalcitonin combined with ROX index predict the timing of tracheal intubation in patients with acute severe pancreatitis].

Objective: To investigate the efficacy of arterial partial pressure of oxygen (PaO), procalcitonin (PCT) combined with ROX index in predicting the timing of tracheal intubation in patients with acute severe pancreatitis (SAP).

Methods: A case-control study was conducted. A total of 148 patients with SAP admitted to Hunan Provincial People's Hospital from January 2019 to December 2022 were selected as the research objects.

Olmesartan alleviates SARS-CoV-2 envelope protein induced renal fibrosis by regulating HMGB1 release and autophagic degradation of TGF-β1.

Renal damage in severe coronavirus disease 2019 (COVID-19) is highly associated with mortality. Finding relevant therapeutic candidates that can alleviate it is crucial. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) have been shown to be harmless to COVID-19 patients, but it remains elusive whether ACEIs/ARBs have protective benefits to them.

Emerging role for branched-chain amino acids metabolism in fibrosis.

Fibrosis is a common pathological feature of organ diseases resulting from excessive production of extracellular matrix, which accounts for significant morbidity and mortality. However, there is currently no effective treatment targeting fibrogenesis. Recently, metabolic alterations are increasingly considered as essential factors underlying fibrogenesis, and especially research on metabolic regulation of amino acids is flourishing.

Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis.

Background And Aims: Renal fibrosis is the common outcome in all progressive forms of chronic kidney disease. Unfortunately, the pathogenesis of renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis. Ceria nanoparticles (CeNP-PEG) with strong ROS scavenging and anti-inflammatory activities have been applied for mitochondrial oxidative stress and inflammatory diseases.

A novel role of BK potassium channel activity in preventing the development of kidney fibrosis.

Kidney fibrosis is a common characteristic of chronic kidney disease and while the large conductance voltage and calcium-activated potassium channel (BK) is widely expressed in kidneys, its role in kidney fibrosis is unknown. To evaluate this, we found that BK protein expression was decreased in the fibrotic kidneys. Accompanying this was increased fibrotic marker protein expression of fibronectin, vimentin and α-smooth muscle actin and increased mRNA expressions of fibronectin, α-smooth muscle actin, collagen III and collagen I.

Activating BK channels ameliorates vascular smooth muscle calcification through Akt signaling.

Vascular calcification (VC) is characterized by pathological depositions of calcium and phosphate in the arteries and veins via an active cell-regulated process, in which vascular smooth muscle cells (VSMCs) transform into osteoblast/chondrocyte-like cells as in bone formation. VC is associated with significant morbidity and mortality in chronic kidney disease (CKD) and cardiovascular disease, but the underlying mechanisms remain unclear. In this study we investigated the role of large-conductance calcium-activated potassium (BK) channels in 3 experimental VC models.

The influx/efflux mechanisms of d-peptide ligand of nAChRs across the blood-brain barrier and its therapeutic value in treating glioma.

A d-peptide ligand of the nicotine acetylcholine receptors (nAChRs), termed CDX, enables drug delivery to the brain when incorporated into liposomes and has shown promise as a nanocarrier for treating brain diseases. However, few reports have described the mechanisms whereby CDX-modified liposomes traverse the blood-brain barrier (BBB). Here, we studied the molecular mechanisms enabling CDX (and its associated liposomes) to cross an in vitro BBB using a simulated cerebral endothelium monolayer formed by brain capillary endothelial cells (bEnd.

Structure and function of USP5: Insight into physiological and pathophysiological roles.

Deubiquitinase (DUB)-mediated cleavage of ubiquitin chains from substrate proteins plays a crucial role in various cellular processes, such as DNA repair and protein stabilization and localization. DUBs can be classified into five families based on their sequence and structural homology, and the majority belong to the ubiquitin-specific proteinase (USP) family. As one of the USPs, ubiquitin-specific proteinase 5 (USP5) is unique in that it can specifically recognize unanchored (not conjugated to target proteins) polyubiquitin and is essential for maintaining homeostasis of the monoubiquitin pool.

Mechanism of Regulation of Big-Conductance Ca-Activated K Channels by mTOR Complex 2 in Podocytes.

Podocytes, dynamic polarized cells wrapped around glomerular capillaries, are an essential component of the glomerular filtration barrier. BK channels consist of one of the slit diaphragm (SD) proteins in podocytes, interact with the actin cytoskeleton, and play vital roles in glomerular filtration. Mechanistic target of rapamycin (mTOR) complexes regulate expression of SD proteins, as well as cytoskeleton structure, in podocytes.

[Value of the diaphragm movement index tested by ultrosonography for ventilation weaning].

Objective: To evaluate the diaphragm movement index of mechanical ventilation weaning patients by ultrosonography, and to explore its value for weaning.

Methods: Forty patients undergoing invasive mechanical ventilation for at least 48 hours admitted to emergency intensive care unit (EICU) of Hunan Provincial People's Hospital from September 2017 to February 2018 were enrolled. Low level pressure support ventilation (PSV) was used for spontaneous breathing test (SBT), and bedside M-mode ultrasonography was used to assess the diaphragm movement index of the patient within 1 hour of SBT, including the excursion of the diaphragm, diaphragmatic-rapid shallow breathing index (D-RSBI).

Non-invasive detection of the early phase of kidney injury by photoacoustic/computed tomography imaging.

The early diagnosis of kidney diseases, which can remarkably impair the quality of life and are costly, has encountered great difficulties. Therefore, the development of methods for early diagnosis has great clinical significance. In this study, we used an emerging technique of photoacoustic (PA) imaging, which has relatively high spatial resolution and good imaging depth.

[Clinical effect of pulmonary rehabilitation therapy including respiratory exercise and vibration expectoration on patients with pulmonary infection after abdominal surgery].

Objective: To investigate the clinical effect of pulmonary rehabilitation therapy including respiratory exercise and vibration expectoration on patients with pulmonary infection after abdominal surgery.

Methods: A retrospective case control study was conducted. Seventy-six patients with pulmonary infection after abdominal surgery admitted to the First Affiliated Hospital of Hunan Normal University from September 2015 to September 2016 were enrolled.