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The expression of the stimulator of interferon genes (STING) in liver tissues is associated with the progression of human nonalcoholic fatty liver disease. Specifically, STING-expressing macrophages, in particular, monocyte-derived macrophages, are positively correlated with the degree of liver inflammation and/or fibrosis progression, which appeared to be mediated by the activation of the STING-TBK1 signaling pathway in macrophage.
In this paper, the authors found that conditional ablation of Shp2 in mouse K14-positive corneal epithelium (Shp2K14ce-cko) impairs corneal innervation and results in corneal epithelial thinning, which resembles neurotrophic keratopathy. Furthermore, the data indicate that Shp2 signaling plays a pivotal role in corneal epithelial homeostasis.
Transient receptor ion channels have emerged as critical channels/receptors in numerous physiological and pathological conditions. In this paper the authors discuss our current understanding of the role of macrophage transient receptor potential channel subfamily V member 4 (TRPV4) in various inflammatory conditions.
The authors investigated the potential mechanisms of interleukin-33 (IL-33) in the pathogenesis of ulcerative colitis. IL-33 was found to sustain mucosal inflammation by down-regulation of protective ABCG5/8 during recovery from colitis. These results may help to increase understanding regarding the IL-33-mediated pathogenesis of ulcerative colitis and potentially contribute to creation of a novel therapeutic strategy.
Digital image analysis (DIA) of multiplex fluorescence-based immunohistochemistry and visual chromogenic evaluation of CDX2, SOX2, SOX9, E-cadherin, and β-catenin in colorectal cancer are comparable, recognizing prognostic value of CDX2 and negative correlation with SOX2. Membrane staining is best evaluated visually, while DIA enables single-cell coexpression analysis and improves visualization and detection of clinicopathological and biological associations.
High expression of the transcription factor ETS2 plays important role in a mouse model of renal fibrosis and in TGF-β1-treated human tubular epithelial cells (HK2). ETS2 promotes TGF-β1-induces epithelial-to-mesenchymal transition (EMT) phenotypic inversion and the expression of EMT markers in HK2 cells by enhancing transcription of JUNB. These findings suggest that ETS2 could be a novel target for the prevention the progression of renal fibrosis.
The authors designed an adapter multiplex PCR amplicon with multiple domain melting curves to rapidly detect and genotype at least 20 ALK fusion variants in one tube with HRM. In addition, they introduced feature extraction of the second derivative curve to assist visual analysis to automatically discriminate ALK fusion variants.
The expression of HIP/PAP and its mouse counterpart, Reg3B, is markedly unregulated in fibrotic livers. Ectopic HIP/PAP potently protects from CCl4- and BDL-induced liver fibrosis in mice. This study shows that downregulation of TGF-βRII expression is one of the important underlying mechanisms for HIP/PAP in suppression of hepatic fibrosis.
The authors examined the capability of propagation-based phase-contrast tomography (PB-PCT) with single-distance phase retrieval for longitudinal in vivo monitoring of bone changes using monochromatic synchrotron light. The application of PB-PCT to the measurement of bone defect healing in mice demonstrated its potential for tracking volumetric and mineral-density changes in newly formed bone.
Polydatin (PD) protects against LPS-induced vascular leakage in multiple organs and this effect is dependent on SIRT3 activation. PD enhances SIRT3-mediated deacetylation of SOD2 and CypD, thus suppressing mitochondrial dysfunction and subsequent endothelial barrier dysfunction. In addition, RAGE is involved in LPS-regulated SIRT3 signaling.
The authors reveal that TRPV4, a thermosensitive ion channel, is constitutively active in the brain. They found that local brain temperature is increased at epileptogenic foci, and that hyperthermia lead TRPV4 over-activation and hyper-neuronal activities. Notably, brain cooling treatment drastically suppresses epileptic discharges dependent on the inactivation of TRPV4.
The two Na+ and water pore-forming claudins, claudin-2 and claudin-15, are reciprocally regulated during human development. This study shows that expression of these claudins is altered in celiac disease, graft-versus-host disease, and common variable immunodeficiency, but that the specific claudin affected differed between children and adults, suggesting distinct contributions to diarrheal pathophysiology.
Most of the cancer-associated genes mutated only in high-grade gastrointestinal stromal tumors (GISTs) are mainly involved in cell cycle control. High-grade GISTs had more MYC copy number gains than matched low-grade tumors. The authors show that alterations in cell cycle regulation-associated genes, may promote primary progression from low-grade GISTs to high-grade tumors by regulating tumor cell proliferation.
The authors provide an in-depth explanation of how HO-1 activation, through PI3K/Akt pathway, protects the lung from oxidative injury in the setting of sepsis by regulating mitochondrial quality control. This study presents a rationale for developing HO-1 therapy to prevent sepsis-related lung injury.
While the transcription factor TBX3 is widely studied in tumorigenesis, the functionality of the two isoforms (TBX3iso1 and TBX3iso2) which differ in their DNA-binding domain is not well understood. By utilizing a nude mouse xenograft model, the authors identified differential tumorigenic potential between TBX3 isoforms, with TBX3iso1 (but not TBX3iso2) promoting invasive carcinoma in vivo through induction of angiogenesis. This process is moderated by downstream mediators osteopontin (OPN) and hyaluronan synthase 2 (HAS2).
The endocannabinoid (EC) system has been implicated in the pathogenesis nonalcoholic fatty liver diseases (NAFLD). Here the authors demonstrate that endocannabinoid receptor 1 (CB1) receptor knockout in vivo and pharmacologic antagonization of CB1 in cell culture decreases expression of lipid droplet binding protein perilipin 2, which might be an essential step in lipid breakdown. Thus, pharmacologic modulation of the CB1-perilipin 2 axis might represent a novel therapeutic approach for the treatment of steatosis.
Bone marrow aspirate (BMA) differential cell counts (DCCs) are critical for classification of hematologic disorders. Manual DCCs are still considered the gold standard as a reliable automated method is yet to be developed. Digital pathology and machine learning represent a highly promising technology for this purpose. The authors report their experience developing machine learning algorithms to detect and classify BMA cells. Promising early results signify an important initial step in the effort to devise a reliable, objective method to automate DCCs.
This study suggests a potential mechanism wherein microRNA-21-5p (miR-21-5p) inhibition downregulates autophagy, migration ability, and LC3B expression via PTEN/AKT signaling in electron beam (EB)-irradiated keloid fibroblasts, effectively preventing local invasion and recurrence. Therefore, miR-21-5p could be a new therapeutic target, to replace EB irradiation, and control keloid relapse.