Curriecahill4991

ells from injury of TNF-α and IL-6, and alleviated both ER stress and apoptosis proteins in vitro. CONCLUSION CQCQD may alleviate SAP-related AKI by inhibiting ER stress-related apoptosis. OBJECTIVE To assess geniposide's effects in New Zealand rabbits with high-fat diet induced atherosclerosis and to explore the underpinning mechanisms. MATERIALS AND METHODS Aorta histological changes were evaluated by intravenous ultrasound (IVUS) and H&E staining. Lipid accumulation in the aortic was quantified by Oil Red O staining. Then, RNA sequencing (RNA-seq) was carried out for detecting differentially expressed genes in rabbit high-fat diet induced atherosclerosis. The levels of the cytokines CRP, IL-1β and IL-10 were determined by ELISA. Protein levels of iNOS and Arg-1 were assessed by Western blot and immunohistochemical staining. The mRNA expression levels of NR4A1, CD14, FOS, IL1A, iNOS and Arg-1 were detected by quantitative real-time PCR (qPCR). RESULTS Geniposide markedly reduced the degree of atherosclerotic lesions in aorta tissues. RNA-seq and qPCR demonstrated that NR4A1, CD14, FOS and IL1A mRNA amounts were overtly increased in New Zealand rabbits with high-fat diet induced atherosclerosis. Moreover, geniposide reduced iNOS (M1 phenotype) mRNA and protein amounts as well as IL-1β secretion, which were enhanced in New Zealand rabbits with high-fat diet induced atherosclerosis. Besides, Arg-1 (M2 phenotype) mRNA and protein amounts were significantly increased after geniposide treatment, as well as IL-10 secretion. CONCLUSION These findings suggest that geniposide could inhibit the progression of and stabilize atherosclerotic plaques in rabbits by suppressing M1 macrophage polarization and promoting M2 polarization through the FOS/MAPK signaling pathway. Skeletal system is a highly dynamic system going through continuous resorption and reconstruction to maintain homeostasis, which is influenced by numerous factors. Once the balance is disrupted, various kinds of bone diseases may occur such as osteoporosis. It has been well known that ATP (adenosine triphosphate), an important signaling molecule, is important in maintaining the dynamic balance of bone matrix. ATP mainly functions through P2X receptors, a kind of ATP receptors expressed by various kinds of bone cells to regulate the whole network of skeleton system. Among P2X receptors, P2X7 plays a crucial role in bone since P2X7 is widely expressed by bone cells and the mutation of P2X7 receptor is associated with kinds of bone diseases. It's acknowledged that P2X7 acts as a potential therapeutic target for clinical treatment of bone-related diseases but further investigations are needed for the practical application. However, since P2X7 has a complicated effect in many aspects, the exact role of P2X7 in skeleton system is ambiguous. This review discusses the function of P2X7 in bone and other cells and their general effect on skeleton system, especially focusing on the possible clinical application for bone diseases. PURPOSE Urokinase receptor (uPAR) promotes extracellular matrix proteolysis, regulates adhesion and cell migration, transduces intracellular signals through interactions with the lateral partners. Quisinostat The expression of uPAR and urokinase (uPA) is significantly upregulated in peripheral nerves after injury, however, little is known about uPAR function in nerve regeneration or the molecular mechanisms involved. The purpose of this study is to investigate the role of uPAR in nerve regeneration after traumatic injury of n. Peroneus communis in uPA-/-, uPAR-/- or control mice (WT) and in neuritogenesis in an in vitro Neuro 2A cell model. RESULTS Electrophysiological analysis indicates that nerve recovery is significantly impaired in uPAR-/- mice, but not in uPA-/- mice. These data correlate with the reduced amount of NF200-positive axons in regenerating nerves from uPAR-/- mice compared to uPA-/- or control mice. There is an increase in uPAR expression and remarkable colocalization of uPAR with α5 and β1 integrin in uPA-/- mice in recovering nerves, pointing to a potential link between uPAR and its lateral partner α5β1-integrin. Using an in vitro model of neuritogenesis and α325 blocking peptide, which abrogates uPAR-α5β1 interaction in Neuro 2A cells but has no effect on their function, we have further confirmed the significance of uPAR-α5β1 interaction. CONCLUSION Taken together, we report evidence pointing to an important role of uPAR, rather than uPA, in peripheral nerve recovery and neuritogenesis. BACKGROUND We previously observed that amphiregulin (Areg), a ligand of epithelial growth factor receptor (EGFR), was highly expressed in lipopolysaccharide (LPS)-induced acute lung injury (ALI) lung tissues mainly by the classically activated (M1) alveolar macrophages (AMs). Areg also plays a protective role in LPS-induced injury in lung tissues and alveolar epithelial cells (AECs). However, whether Areg is co-expressed with tumor necrosis factor (TNF)-α in ALI lung tissues, and can directly inhibit TNF-α-induced AEC injury remains unclear. METHODS We first detected the kinetic expressions of Areg and TNF-α in LPS-stimulated lung tissues and M1 AMs and then identified the role of exogenous recombinant Areg (rmAreg) in the injured lung tissues. The effect of Areg on TNF-α-induced apoptosis in MLE-12 cells, a kind of AECs, was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The activation of the EGFR-AKT pathway and caspase-3, -8, and -9 were detected by Western blotting. The EGFR knockdown by small interfering RNA was used to assess the role of EGFR in Areg functions. RESULTS Areg production occurred in close parallel with TNF-α expression in M1 AMs and ALI lung tissues, and rmAreg attenuated LPS-induced ALI in mice. TNF-α stimulation induced significant apoptosis in MLE-12 cells, but this apoptosis was inhibited under rmAreg treatment. Moreover, rmAreg enhanced the activation of EGFR and AKT, and reduced the expressions of cleaved caspase-3, -8, and -9 in ALI lung tissues and TNF-α-challenged MLE-12 cells. However, the EGFR knockdown significantly inhibited the Areg-induced improvement in apoptosis, enhancement of EGFR and AKT activation, and reduction of cleaved caspase-3, -8, and -9 expressions. CONCLUSIONS Areg and TNF-α were synchronously produced by ALI lung tissues and M1 AMs, and Areg directly inhibited the TNF-induced apoptosis and transduction of caspase death signals in AECs via the EGFR pathway.