Effects of type II collagen hydrolysates on osteoarthritis through NF-ĸB, Wnt/β-catenin and MAPK pathways

Osteoarthritis (OA), a degenerative disease, has attracted extensive attention all over the world. In the study, medial meniscus resection (MMx) and anterior to medial collateral ligament (ACL) operation rat model...

The Fission Yeast Cell Integrity Pathway: A Functional Hub for Cell Survival upon Stress and Beyond

The survival of eukaryotic organisms during environmental changes is largely dependent on the adaptive responses elicited by signal transduction cascades, including those regulated by the Mitogen-Activated Protein Kinase (MAPK) pathways. The Cell Integrity Pathway (CIP), one of the three MAPK pathways found in the simple eukaryote fission of yeast Schizosaccharomyces pombe, shows strong homology with mammalian Extracellular signal-Regulated Kinases (ERKs). Remarkably, studies over the last few decades have gradually positioned the CIP as a multi-faceted pathway that impacts multiple functional aspects of the fission yeast life cycle during unperturbed growth and in response to stress. They include the control of mRNA-stability through RNA binding proteins, regulation of calcium homeostasis, and modulation of cell wall integrity and cytokinesis. Moreover, distinct evidence has disclosed the existence of sophisticated interplay between the CIP and other environmentally regulated pathways, including Stress-Activated MAP Kinase signaling (SAPK) and the Target of Rapamycin (TOR). In this review we present a current overview of the organization and underlying regulatory mechanisms of the CIP in S. pombe, describe its most prominent functions, and discuss possible targets of and roles for this pathway. The evolutionary conservation of CIP signaling in the dimorphic fission yeast S. japonicus will also be addressed.

Qihuzha Granule Alleviated Cyclophosphamide-induced Immune Deficiency in Mice via IL-6 Related Signaling Pathways

BackgroundQihuzha granule (QHZG) is a Chinese patent medicine, composed of 11 kinds of edible medicinal plants, which is used to treat dyspepsia and anorexia in children caused by spleen and stomach deficiency syndrome. However, its role and mechanism in immunosuppression induced by cyclophosphamide remained unclear. The purpose of this study is to investigate the effect of QHZG on immunosuppression induced by cyclophosphamide in mice and its possible mechanism.MethodsThe immunosuppression injury model was induced by intraperitoneal injection of cyclophosphamide (100 mg/kg); the mRNA level of cytokines (IL-2/4/6, IFN-γ) and critical targets of signaling pathways related to immune regulation (JNK, ERK, P38, JAK2, SRC and STAT3) were tested by QPCR; related protein levels were detected by western blotting; hematoxylin-eosin (HE) staining was employed to observe the histological alterations; macrophages and neutrophils in the mouse spleen were examined by immunofluorescence analysis. ResultsQHZG significantly increased the spleen index and thymus index of mice with immunodeficiency induced by cyclophosphamide and up-regulated the mRNA expression of cytokines (IL-2/4/6, IFN-γ) and critical targets of signaling pathways related to immune regulation (JNK, ERK, P38, JAK2, SRC and STAT3), which were decreased by cyclophosphamide treatment. The results of immunofluorescence staining and histological analysis showed that QHZG could also protect mice from immunosuppressive injury caused by cyclophosphamide via keeping structural integrity of spleen, and partially restoring the production levels of macrophages and monocytes in the spleen. Further studies indicated that QHZG could significantly counter the decline of phosphorylated protein levels of JAK2/SRC-STAT3 axes (P-JAK2, P-SRC and P-STAT3), and MAPK pathways (P-JNK, P-ERK and P-P38) induced by cyclophosphamide, suggesting that the protective effects of QHZG on immunosuppressive injury triggered by cyclophosphamide were involved in JAK2/SRC-STAT3 axes, and MAPK pathways. Meanwhile, we also found that QHZG could partially restore the vital phosphorylated proteins of PI3K/Akt/mTOR signaling pathway (P-Akt, P-mTOR), which were reduced by cyclophosphamide. The data implied that PI3K signaling pathway was also responsible for the protection of QHZG against the immunosuppression induced by cyclophosphamide in mice. ConclusionsOur study demonstrated that QHZG protected mice from cyclophosphamide-triggered immunosuppressive injury via IL-6 and its downstream signaling pathways including PI3K/Akt/mTOR signal pathway and JAK2-SRC/MAPK/STAT3 axes. These results suggested that QHZG might serve as a new drug for the treatment of the immunosuppression caused by cyclophosphamide therapy.