Design and synthesis of highly selective Janus kinase 3 covalent inhibitors for the treatment of rheumatoid arthritis.

Selective inhibition of Janus kinase 3 (JAK3) is a promising strategy for the treatment of autoimmune diseases. Based on the discovery of a hydrophobic pocket unutilized between the lead compound RB1 and the JAK3 protein, a series of covalent JAK3 inhibitors were prepared by introducing various aromatic fragments to RB1. Among them, J1b (JAK3 IC = 7.

Uncovering the Pharmacological Mechanism of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Against Lung Cancer Based on Network Pharmacology and Experimental Evaluation.

2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1,4-Dione (DMDD) was purified from the roots of Previous research demonstrated that DMDD is a small molecular compound with significant therapeutic potential for tumors. However, the potential targets and pharmacological mechanism of DMDD to treat lung cancer has not been reported. We employed network pharmacology and experimental evaluation to reveal the pharmacological mechanism of DMDD against lung cancer.

SIRPB1 promotes prostate cancer cell proliferation via Akt activation.

Background: Signal regulatory protein β1 (SIRPB1) is a signal regulatory protein member of the immunoglobulin superfamily and is capable of modulating receptor tyrosine kinase-coupled signaling. Copy number variations at the SIRPB1 locus were previously reported to associate with prostate cancer aggressiveness in patients, however, the role of SIRPB1 in prostate carcinogenesis is unknown.

Methods: Fluorescence in situ hybridization and laser-capture microdissection coupled with quantitative polymerase chain reaction was utilized to determine SIRPB1 gene amplification and messenger RNA expression in prostate cancer specimens.

Macrofluidic recirculating model of skeletal metastasis.

While microfluidic systems model aspects of metastasis, they are limited to artificially created tissues of limited complexity. We set out to develop an in vitro model of tumor cell migration from a primary tumor to a distant site that allows use of tissue. Accordingly, we created a macrofluidic model using culture plate wells connected with type I collagen-coated large bore tubing and has recirculating media.

Prostate cancer promotes a vicious cycle of bone metastasis progression through inducing osteocytes to secrete GDF15 that stimulates prostate cancer growth and invasion.

Bone is the most frequent site of prostate cancer (PCa) metastasis; however, little is known about the role of the most common cell in bone, the osteocyte (OCy), in cancer biology. In this study we explored the crosstalk between PCa cells and OCys to determine if it contributes to PCa progression. PCa cells induced OCys to promote PCa proliferation, migration and invasion.

Down-regulation of E-cadherin enhances prostate cancer chemoresistance via Notch signaling.

Background: The chemoresistance of prostate cancer (PCa) is invariably associated with the aggressiveness and metastasis of this disease. New emerging evidence indicates that the epithelial-to-mesenchymal transition (EMT) may play pivotal roles in the development of chemoresistance and metastasis. As a hallmark of EMT, E-cadherin is suggested to be a key marker in the development of chemoresistance.

[Enhancement of GA3 and EDTA on Lolium perenne to remediate Pb contaminated soil and its detoxification mechanism].

A pot experiment was conducted to study the effects of plant growth regulator GA3 and metal chelate EDTA on enhancing the remediation of Pb contaminated soil, and the detoxification mechanism of Lolium perenne grown on Pb contaminated soil at 250 and 500 mg · kg(-1). The results showed that cell wall deposition and vacuolar compartmentalization played important roles in the detoxification of Pb in L. perenne shoot.