Differential expression of CCN family members CYR611, CTGF and NOV in gastric cancer and their association with disease progression

CCN is an acronym for cysteine-rich protein 61 (CYR61), connective tissue growth factor (CTGF) and nephroblastoma overexpressed (NOV). Aberrations of certain CCN members including CYR61, CTGF, Wnt1-inducible signalling pathway protein (WISP)-1 and -3 have been reported in gastric cancer. The present study aimed to examine the clinical relevance of NOV along with CYR61 and CTGF in gastric cancer by analysing their transcript levels. CYR61, CTGF and NOV transcript expression in 324 gastric cancer samples with paired adjacent normal gastric tissues were determined using real-time quantitative PCR and the results were statistically analysed against patient clinicopathological data using SPSS software. NOV mRNA levels in gastric cancer tissues were significantly elevated when compared with levels in their paired adjacent non-cancerous tissues. Local advanced tumours with invasive expansion (T3 and T4) expressed higher levels of NOV (p=0.013) compared with the less invasive tumours (T1 and T2). CYR61 transcript levels were also significantly increased in gastric cancers compared with levels in the adjacent non cancerous tissues. Kaplan-Meier survival curves revealed that patients with CYR61-low transcript levels had longer overall survival (OS) (p=0.018) and disease-free survival (DFS) (p=0.015). NOV overexpression promoted the in vitro proliferation of AGS cells while the knockdown resulted in a reduced proliferation of HGC27 cells. A similar effect was observed for the invasion of these two gastric cancer cell lines. NOV expression was increased in gastric cancer which was associated with local invasion and distant metastases. Taken together, the expression of NOV and CYR61 was increased in gastric cancer. The elevated expression of CYR61 was associated with poorer survival. NOV promoted proliferation and invasion of gastric cancer cells. Further investigations may highlight their predictive and therapeutic potential in gastric cancer.Cancer Research Wales; Chinese Medical Research Scholarship of Cardiff UniversitySCI(E)[email protected]; [email protected]

Inhibition the ubiquitination of ENaC and Na,K-ATPase with erythropoietin promotes alveolar fluid clearance in sepsis-induced acute respiratory distress syndrome

Sepsis-induced acute respiratory distress syndrome (ARDS) causes significant fatalities worldwide and lacks pharmacological intervention. Alveolar fluid clearance (AFC) plays a pivotal role in the remission of ARDS and is markedly impaired in the pathogenesis of ARDS. Here, we demonstrated that erythropoietin could effectively ameliorate lung injury manifestations and lethality, restore lung function and promote AFC in a rat model of lipopolysaccharide (LPS)-induced ARDS. Moreover, it was proven that EPO-induced restoration of AFC occurs through triggering the total protein expression of ENaC and Na,K-ATPase channels, enhancing their protein abundance in the membrane, and suppressing their ubiquitination for degeneration. Mechanistically, the data indicated the possible involvement of EPOR/JAK2/STAT3/SGK1/Nedd4–2 signaling in this process, and the pharmacological inhibition of the pathway markedly eliminated the stimulating effects of EPO on ENaC and Na,K-ATPase, and subsequently reversed the augmentation of AFC by EPO. Consistently, in vitro studies of alveolar epithelial cells paralleled with that EPO upregulated the expression of ENaC and Na,K-ATPase, and patch-clamp studies further demonstrated that EPO substantially strengthened sodium ion currents. Collectively, EPO could effectively promote AFC by improving ENaC and Na,K-ATPase protein expression and abundance in the membrane, dependent on inhibition of ENaC and Na,K-ATPase ubiquitination, and resulting in diminishing LPS-associated lung injuries

Low-intensity anomaly involving ML≥4 events preceding strong earthquakes in Tibet

Seismic quiescence or enhanced phenomena are anomalous changes against the background of normal seismic activity. Preliminary studies have found that earthquakes with a magnitude of ML≥4 often occur at a low occurrence frequency before giant earthquakes in Tibet. This study analyzed the catalog of ML≥4 earthquakes from 2008 to 2022 and examined the anomalous occurrence of ML≥4 earthquakes preceding most ML≥6 earthquakes. When the monthly occurrence frequency of ML≥4 earthquakes was lower than 4 times over six consecutive months, the subsequent occurrence of ML≥6 earthquakes was highly likely as evidenced by observations. The anomalous characteristics of low-intensity activities were analyzed as a medium- and short-term forecasting index for large earthquakes in the Tibetan area

Regulatory Effect of Polysaccharides from Antrodia cinnamomea in Submerged Fermentation on Gut Microbiota in Mice with Antibiotic-Associated Diarrhea

In order to study the effect of polysaccharides produced by Antrodia cinnamomea in submerged fermentation on the intestinal flora of mice and, more broadly, to develop the potential and application value of A. cinnamomea in the field of functional food, we extracted and characterized intracellular polysaccharides (AIPS) and exopolysaccharides (AEPS) from the submerged cultured mycelia and broth of Antrodia cinnamomea. It was found that AIPS and AEPS were predominantly composed of glucose, galactose and mannose. Their average molecular masses were 3.52 × 106 and 4.16 × 105 Da, respectively. AEPS contained a pyran ring, while AIPS had (–C≡C–H) and (C–O) functional groups. Both AIPS and AEPS had strong digestive resistance as demonstrated by their resistance to α-amylase digestion and simulated gastric digestion. Intragastrically administered AIPS and AEPS significantly increased the relative abundance of some beneficial microorganisms (such as Lactobacillus) in the intestine of mice with lincomycin-caused diarrhea, and significantly reduced the relative abundance of some harmful microorganisms (such as Enterococcus, Staphylococcus, Parasutterella and Shigella) (P < 0.05), AEPS being more significantly better than AIPS. This study can provide a new idea and basis for the development of new multifunctional prebiotics

Protectin conjugates in tissue regeneration 1 alleviates sepsis-induced acute lung injury by inhibiting ferroptosis

Background: Acute lung injury (ALI) is a common and serious complication of sepsis with high mortality. Ferroptosis, categorized as programmed cell death, contributes to the development of lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is an endogenous lipid mediator that exerts protective effects against multiorgan injury. However, the role of PCTR1 in the ferroptosis of sepsis-related ALI remains unknown. Methods: A pulmonary epithelial cell line and a mouse model of ALI stimulated with lipopolysaccharide (LPS) were established in vitro and in vivo. Ferroptosis biomarkers, including ferrous (Fe2+), glutathione (GSH), malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE), were assessed by relevant assay kits. Glutathione peroxidase 4 (GPX4) and prostaglandin-endoperoxide synthase 2 (PTGS2) protein levels were determined by western blotting. Lipid peroxides were examined by fluorescence microscopy and flow cytometry. Cell viability was determined by a CCK-8 assay kit. The ultrastructure of mitochondria was observed with transmission electron microscopy. Morphology and inflammatory cytokine levels predicted the severity of lung injury. Afterward, related inhibitors were used to explore the potential mechanism by which PCTR1 regulates ferroptosis. Results: PCTR1 treatment protected mice from LPS-induced lung injury, which was consistent with the effect of the ferroptosis inhibitor ferrostatin-1. PCTR1 treatment decreased Fe2+, PTGS2 and lipid reactive oxygen species (ROS) contents, increased GSH and GPX4 levels and ameliorated mitochondrial ultrastructural injury. Administration of LPS or the ferroptosis agonist RSL3 resulted in reduced cell viability, which was rescued by PCTR1. Mechanistically, inhibition of the PCTR1 receptor lipoxin A4 (ALX), protein kinase A (PKA) and transcription factor cAMP-response element binding protein (CREB) partly decreased PCTR1 upregulated GPX4 expression and a CREB inhibitor blocked the effects ofPCTR1 on ferroptosis inhibition and lung protection. Conclusion: This study suggests that PCTR1 suppresses LPS-induced ferroptosis via the ALX/PKA/CREB signaling pathway, which may offer promising therapeutic prospects in sepsis-related ALI

Continual Segment: Towards a Single, Unified and Accessible Continual Segmentation Model of 143 Whole-body Organs in CT Scans

Deep learning empowers the mainstream medical image segmentation methods. Nevertheless current deep segmentation approaches are not capable of efficiently and effectively adapting and updating the trained models when new incremental segmentation classes (along with new training datasets or not) are required to be added. In real clinical environment, it can be preferred that segmentation models could be dynamically extended to segment new organs/tumors without the (re-)access to previous training datasets due to obstacles of patient privacy and data storage. This process can be viewed as a continual semantic segmentation (CSS) problem, being understudied for multi-organ segmentation. In this work, we propose a new architectural CSS learning framework to learn a single deep segmentation model for segmenting a total of 143 whole-body organs. Using the encoder/decoder network structure, we demonstrate that a continually-trained then frozen encoder coupled with incrementally-added decoders can extract and preserve sufficiently representative image features for new classes to be subsequently and validly segmented. To maintain a single network model complexity, we trim each decoder progressively using neural architecture search and teacher-student based knowledge distillation. To incorporate with both healthy and pathological organs appearing in different datasets, a novel anomaly-aware and confidence learning module is proposed to merge the overlapped organ predictions, originated from different decoders. Trained and validated on 3D CT scans of 2500+ patients from four datasets, our single network can segment total 143 whole-body organs with very high accuracy, closely reaching the upper bound performance level by training four separate segmentation models (i.e., one model per dataset/task)

Polyimide/mesoporous silica nanocomposites: Characterization of mechanical and thermal properties and tribochemistry in dry sliding condition

Mesoporous silica (MPS) with tunable mesopore channels can be used to reinforce polymers and has great potential in tribological applications, which is rarely investigated by research community. In this study, comprehensive properties of polyimide (PI)/MPS nanocomposites were investigated. The results demonstrated a slightly decreased tensile strength but increased modulus, microhardness and thermal stability of the PI/MPS nanocomposites. In particular, tribological properties of PI/MPS nanocomposites as functions of MPS content, applied load and sliding speed were systematically investigated. The incorporation of 1.5 wt.% MPS increased the anti-wear resistance of PI by more than 14-fold while the coefficient of friction decreased by 27%. This was highly associated with the formation of high-quality transfer film on the bearing steel counterpart surface.Relevant tribochemistry was thoroughly revealed by X-ray photoelectron spectroscopy (XPS) analysis on the transfer film and Raman analysis on the worn surfaces. This study confirmed the high efficiency of using MPS to reinforce PI polymer for tribological applications and elaborated tribochemistry to further understand the tribochemical process in polymer-metal rubbing systems