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Overall Hsp70-Bag3 module represents a novel signaling node that responds to multiple stimuli and controls multiple physiological processes.

ZEB1 is a transcription factor that promotes metastatic and stem cell features, which has been associated with poor prognosis in cholangiocarcinoma (CCA), a desmoplastic cancer enriched in cancer-associated fibroblasts (CAF). Here, we aimed to define ZEB1 regulatory functions in malignant and stroma compartments of CCA.

Bioinformatic and immunohistochemical analyses were performed to determine correlations between ZEB1 and markers of progressiveness in human intrahepatic CCA (iCCA). Gain/loss of function models were generated in CCA cells, and liver myofibroblasts, as a model of CAF. Conditioned media (CM) was used to unravel tumor-stroma interplay. In vivo experiments were performed using xenograft CCA model. ZEB1 expression in tumor cells of human iCCA was associated with undifferentiated tumor and vascular invasion. In vitro, ZEB1 promoted epithelial-mesenchymal transition and stemness in tumor cells leading to cell migration and spheroid formation. In vivo, ZEB1-overexpressing CCA cells formed larger tumors with more abundant stroma. CCN2/CTGF expression was increased in tumor cells from ZEB1-overexpressing xenografts and correlated with ZEB1 expression in human tumors. In vitro, CM from ZEB1-overexpressing tumor cells or recombinant CTGF induced myofibroblast proliferation. ZEB1 was also expressed by CAF in human CCA and its expression correlated with CCN2 in myofibroblast and CCA stroma. In mice, co-transplantation of CCA cells with ZEB1-depleted myofibroblasts reduced CCA progressiveness compared to CCA cells/ZEB1-expressing myofibroblasts. Furthermore, ZEB1 controls the expression of paracrine signals (i.e. HGF and IL6) in tumor cells and myofibroblasts.

ZEB1 plays a key role in CCA progression by regulating tumor cell-CAF cross-talk, leading to tumor dedifferentiation and CAF activation.

ZEB1 plays a key role in CCA progression by regulating tumor cell-CAF cross-talk, leading to tumor dedifferentiation and CAF activation.IRE1 is an important central regulator of unfolded protein response (UPR) in the endoplasmic reticulum (ER) because of its ability to regulate cell fate as a function of stress sensing. When misfolded proteins accumulated in chondrocytes ER, IRE1 disintegrates with BIP/GRP78 and undergoes dimer/oligomerization and transautophosphorylation. These two processes are mediated through an enzyme activity of IRE1 to activate endoribonuclease and generates XBP1 by unconventional splicing of XBP1 messenger RNA. Thereby promoting the transcription of UPR target genes and apoptosis. this website The deficiency of inositol-requiring enzyme 1α (IRE1α) in chondrocytes downregulates prosurvival factors XBP1S and Bcl-2, which enhances the apoptosis of chondrocytes through increasing proapoptotic factors caspase-3, p-JNK, and CHOP. Meanwhile, the activation of IRE1α increases chondrocyte viability and reduces cell apoptosis. However, the understanding of IRE1 responses and cell death fate remains controversial. This review provides updated data about the role IRE1 plays in chondrocytes and new insights about the potential efficacy of IRE1 regulation in cartilage repair and osteoarthritis treatment.

To describe and compare onset and intensity of thoracic duct (TD) coloration in healthy dogs after intrahepatic injection of either indocyanine green (ICG) visualized by intraoperative near-infrared fluorescence lymphography (NIRFL) or direct thoracoscopic visualization of methylene blue dye (MB).

Prospective study.

Healthy adult Beagle dogs (n=5).

All dogs had biochemical panels and complete blood counts preoperatively. Computed tomography lymphography (CTL) was performed prior to a standard 3-port thoracoscopic approach. A mixture of MB and ICG was injected by ultrasound-guided percutaneous injection into right or left-sided hepatic lobes. Data collected included dose of contrast agent (MB vs. ICG), injection site, timing, and quality of operative TD identification. Potential hepatic injury was assessed by repeat laboratory evaluation and abdominal ultrasound 14 days postoperatively.

Preoperative CTL provided a diagnostic study in 5/5 dogs. After intrahepatic injection of combined dyes, NIRFL allowed visualization of TDs in 5/5 dogs, but MB did not result in visible TD coloration in any dog. Intrahepatic injection of ICG achieved successful NIRFL in a median time of 6minutes and persisted for the 20 minute observation period in all five dogs. All dogs recovered without complication and were subsequently adopted.

NIRFL of the TD can be achieved with intraoperative hepatic injection of ICG. Intrahepatic injection of MB did not result in visible TD coloration.

Hepatic intra-parenchymal injection is a reliable alternative portal into the TD system for intraoperative visualization of TD anatomy using ICG in dogs.

Hepatic intra-parenchymal injection is a reliable alternative portal into the TD system for intraoperative visualization of TD anatomy using ICG in dogs.Reliability of forensic evidences for presence of inorganic gunshot residue (iGSR) on a given surface strongly depends on the performance of scanning electron microscopy/energy dispersive X-ray spectrometry (SEM-EDS) method. This article presents the results from a study of the effect of SEM/EDS working parameters on the method performance and quality of iGSR data, as well as a development of a database of iGSR encountered in R Kosovo. The optimal working parameters of SEM/EDS were established by one-variable-at-a-time approach and the method was validated according to ASTM1588-10. The precision, trueness, and expanded uncertainty for PbBaSb particles were estimated and the method was assessed as a "fit for purpose" with a satisfactory performance (z-score less then 2). Expended uncertainty of quantification of GSR particles estimated by single laboratory and quality control approach was 6% (k = 2). The validated SEM/EDS method was applied for identification of characteristic iGSR particles in samples from shooting events in Kosovo. The method was demonstrated to be capable of providing a legal proof for iGSR existence on a specific surface. The quality of the results was not influenced by the origin of iGSR. Five hundred fifty-five samples from 144 cases occurred during the last 3 years were analyzed and 14% rate of positive results was found.