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Since the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and γH2AX foci links to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+;Trp53flox/flox;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3μm micropores. To search for pancreatic cancer cell-of-origin, analysis of single-cell datasets revealed that the ECM ..read more

Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RORγt in sepsis patients. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA sequencing (scRNA-seq) analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA ..read more

The impact of the functions of serine—a non-essential amino acid—on the pathogenesis of inflammatory bowel diseases (IBD) is unclear. Using human patient samples and mouse models of colitis, Bai and Saha et al (Am J Pathol, AJPA-D-23-00501) studied this impact. Serine synthesis selectively increases in the epithelial cells of colons from both patients with IBD and mouse models of colitis. Inhibiting serine synthesis impaired epithelial cell proliferation in vivo. Dietary removal of serine also sensitized mice to acute chemically-induced colitis but improved inflammation in chronic colitis mode ..read more

Hepatocyte nuclear factor 4 alpha (HNF4α) is a nuclear factor essential for liver function that regulates the expression of cMyc and plays an important role in proliferation and differentiation during liver regeneration. This study investigated the role of HNF4α-cMyc interaction in regulating liver injury and regeneration using the choline-deficient and ethionine-supplemented (CDE) diet model. WT, hepatocyte-specific HNF4α-KO, cMyc-KO, and HNF4α-cMyc double knockout (DKO) mice were fed a CDE diet for one week to induce subacute liver injury ..read more

Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network (GRAPE-Net), leveraging hematoxylin and eosin (H&E) stained whole slide images (WSIs) to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues ..read more

Two major constituents of exfoliation material (XFM), fibrillin- 1 and lysyl oxidase-like 1 (encoded by FBN1 and LOXL1) are implicated in exfoliation glaucoma (XFG), yet their individual contributions to ocular phenotype are minor. To test the hypothesis that a combination of FBN1 mutation and LOXL1 deficiency exacerbates ocular phenotypes, pan-LOX inhibitor, β-aminopropionitrile (BAPN) was used to treat adult wild-type (wt) and Fbn1C1041G/+ mice for 8 weeks and their eyes were examined. Although intraocular pressure was not changed and XFM not detected in the eyes, BAPN treatment worsened opt ..read more

Acute lung injury (ALI) is a devastating clinical disease caused by different factors, with high morbidity and mortality. It has been shown that lung injury and inflammation caused by lipopolysaccharide (LPS) can be modulated by NLRP3 inflammasome activation, yet its exact function within the airway epithelium is still unknown. Meanwhile, glucose transporter protein 1 (GLUT1) has been shown to contribute to a number of inflammatory illnesses, including ALI. The present study was aimed to assess GLUT1's function in NLRP3 inflammasome activation of airway epithelium in LPS-induced acute lung inj ..read more

Interactions between endothelial cells (EC) and mural pericytes (PC) are critical to maintaining the stability and function of the microvascular wall. Abnormal interactions between these two cell types are a hallmark of progressive fibrotic diseases, such as systemic sclerosis (SSc, scleroderma). However, the role that PCs play in signaling microvascular dysfunction remains underexplored. It is hypothesized that integrin-matrix interactions contribute to PC migration from the vascular wall and conversion into interstitial myofibroblasts ..read more