Tripterygium wilfordii Hook F. (TwHF) is a traditional Chinese herb and has a broad spectrum of biological functions including immunosuppression and anti-inflammatory effects. When used in combination with other standard of care medications, such as glucocorticoids and calcineurin inhibitors like cyclosporine A, for treating glomerular diseases, TwHF demonstrates a remarkable dose-sparing effect, the molecular mechanism for which remains largely unknown. In an in vitro model of podocytopathy elicited by a diabetic milieu, triptolide, the major active component of TwHF, at low doses, potentiated the beneficial effect of cyclosporine A, and protected podocytes against diabetic milieu-elicited injury, mitigated cytoskeleton derangement, and preserved podocyte filtration barrier function, entailing a synergistic cytoskeleton-preserving and podocyte protective effect of triptolide and cyclosporine A. Mechanistically, inhibitory phosphorylation of GSK3β, a key molecule recently implicated as a convergence point of podocytopathic pathways, is likely required for the synergistic effect of triptolide and cyclosporine A on podocyte protection, because the synergistic effect was largely blunted in cells expressing the constitutively active GSK3β. Ergo, a synergistic podocyte cytoskeleton-stabilizing mechanism seems to underlie the cyclosporine A-sparing effect of triptolide in glomerulopathies. Combined triptolide and cyclosporine A therapy at reduced doses may be an invaluable regimen for treating diabetic nephropathy. AJTR Copyright © 2020.Previous studies have reported that p27 deletion stimulates the proliferation of bone marrow mesenchymal stem cells (BM-MSCs) and their differentiation into osteoblasts, it also increases bone marrow hematopoietic progenitor cells (HPCs). However, it is unknown whether the enhanced hematopoiesis induced by p27 deficiency was associated with releasing hematopoietic stem cell (HSC) and HPC supporting factors by BM-MSCs. To answer this question, we cultured the BM-MSCs from wild-type (WT) or p27 knockout (KO) mice, analyzed their proliferation, apoptosis and osteogenesis and harvested their conditioned medium (CM); We also cultured the bone marrow cells (BMCs) with normal medium or CM from WT or KO BM-MSCs and analyzed changes of HSCs and HPCs and colony forming cells (CFCs). Our results showed that the proliferation and osteogenic differentiation of BM-MSCs were increased significantly and their apoptosis was reduced significantly in p27 deficient mice. Simultaneously, we demonstrated that the CM from p27 deficiciency stimulates HSC/HPC expansion by increasing secretion of IL22 by BM-MSCs and activating IL22-Stat3 signaling in HSCs and HPCs.  https://www.selleckchem.com/products/2-nbdg.html  AJTR Copyright © 2020.BACKGROUND Cancer metastasis is the major reason for cancer-related deaths, but the mechanism of cancer metastasis still unclear. Adrenomedullin (ADM), a peptide hormone, functions as a local paracrine and autocrine mediator with multiple biological activities, such as angiogenesis, cell proliferation, and anti-inflammation. However, the expression and potential function of ADM in triple-negative breast cancer (TNBC) remain unclear. METHODS Real-time polymerase chain reaction and western blotting were performed to examine the expression of ADM in TNBC tissues and cell lines. A total of 458 TNBC tissue samples and adjacent nontumor tissue samples were detected by immunochemistry to determine the correlation between ADM expression and clinicopathological characteristics. We determined the role and mechanistic pathways of ADM in tumor metastasis in cell lines. RESULTS Our data showed that ADM expression was noticeably decreased in TNBC samples and cell lines. Low expression levels correlate with an increased risk of recurrence and metastasis. Furthermore, low ADM expression was associated with poor prognosis and was an independent marker for TNBC. In vitro, ADM may decrease cancer cell invasion, which is likely the result of its effect on the cancer cell epithelial-mesenchymal transition. CONCLUSIONS Our findings suggest that ADM is a valuable biomarker for TNBC prognosis and an anti-metastasis candidate therapeutic target in triple-negative breast cancer. AJTR Copyright © 2020.Accumulating evidence indicates that competing endogenous RNA networks play a critical role in cirrhosis progression. However, their biological role and regulatory mechanisms in liver sinusoidal endothelial cells (LSECs) have not been explored. Here, we exposed LSECs to starvation and lipopolysaccharide (LPS) treatment and assessed changes in TUG1 and miR-142-3p expression, autophagy, and endothelial-mesenchymal transition (EndMT). We confirmed the effects of targeted binding between miR-142-3p and TUG1 or ATG5 by luciferase activity and radio-immunoprecipitation assay. Using an in vivo rat model of cirrhosis, we evaluated autophagy and EndMT in LSECs by immunofluorescence co-localization and immunohistochemical staining. The diagnostic efficiency of miR-142-3p and LPS were determined by receiver-operating characteristic curve analysis. We found that LSECs survived starvation by activating autophagy. LPS treatment enhanced autophagy and promoted EndMT of LSECs by upregulating TUG1. Our rat model of cirrhosis confirmed that serum LPS level, autophagy, and EndMT were increased in LSECs. TUG1 was highly expressed in LSECs, and TUG1 knockdown suppressed ATG5-mediated autophagy and EndMT of LSECs. TUG1 regulated ATG5 via shared miR-142-3p response elements. miR-142-3p was expressed at low levels in LSECs and negatively regulated autophagy and EndMT by reducing ATG5 expression. Our results suggest that TUG1 promotes LPS-induced autophagy and EndMT of LSECs by functioning as an endogenous sponge for miR-142-3p and promoting the expression of ATG5. LPS and miR-142-3p are potential diagnostic and therapeutic targets in cirrhosis. AJTR Copyright © 2020.An increased fracture risk is often observed in cancer patients undergoing radiotherapy (RT), particularly at sites within the field of radiation. Therefore, the development of appropriate therapeutic options to prevent RT-induced bone loss is urgently needed. A soluble form of the BMP receptor type 1A fusion protein (mBMPR1A-mFc) serves as an antagonist to endogenous BMPR1A. Previous studies have shown that mBMPR1A-mFc treatment increases bone mass in both ovary-intact and ovariectomized via promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. The present study was designed to investigate whether mBMPR1A-mFc administration prevents radiation-induced bone deterioration in mice. We constructed an animal model of radiation-induced osteoporosis by exposure to a 2-Gy dose of X-rays. Micro-CT, histomorphometric, bone-turnover, and mechanical analyses showed that mBMPR1A-mFc administration prevented trabecular microarchitecture deterioration after RT because of a marked increase in bone formation and a decrease in bone resorption.