Knockdown of deoxythymidylate kinase suppresses progression and epithelial-mesenchymal-transition of lung adenocarcinoma via STAT3 signaling.

Current research has shown that inhibiting deoxythymidylate kinase (DTYMK) can significantly reduce development of lung cancer without liver kinase B1. However, its underlying regulatory mechanism is still unclear. We therefore aimed to investigate whether DTYMK inhibitors could suppress lung adenocarcinoma (LUAD) progression. In this study, human tissues, A549 cells, and xenograft tumors were used to explore the regulation and mechanism of DTYMK on LUAD cell proliferation and migration. Meanwhile, YMU1 (a DTYMK inhibitor) was applied to A549 cells and xenograft tumors to investigate its potential as a drug for LUAD. DTYMK was overexpressed in LUAD tissues and correlated with tumor stage. Knockdown of DTYMK suppressed cell viability, migration, and invasion. In addition, the activation of signal transducers and activators of transcription 3 (STAT3) was repressed upon DTYMK inhibition. YMU1 showed the same effect as DTYMK knockdown in vivo and in vitro. DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may have the potential to inhibit the development of LUAD.NEW & NOTEWORTHY DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may serve as a novel drug to suppress the development of LUAD.

Protein Tyrosine Phosphatase Receptor Type R (PTPRR) Reduces AChR Clustering by Dephosphorylating MuSK.

Neuromuscular junction (NMJ) formation and maintenance depend on the proper localization and concentration of various molecules at synaptic contact sites. Acetylcholine receptor (AChR) clustering on the postsynaptic membrane is a cardinal event in NMJ formation. Muscle-specific tyrosine kinase (MuSK), which functions depending on its phosphorylation, plays an essential role in AChR clustering. In the present study, we used plasmid-based biochemical screening and determined that protein tyrosine phosphatase receptor type R (PTPRR) is responsible for dephosphorylating MuSK on tyrosine residue 754. Furthermore, we showed that PTPRR significantly reduced MuSK-dependent AChR clustering in C2C12 myotubes. Collectively, these data illustrate a negative regulation function of PTPRR in AChR clustering.

Anti-inflammatory and anxiolytic activities of Euphorbia hirta extract in neonatal asthmatic rats.

The current study evaluated the anti-inflammatory and anxiolytic activities of Euphorbia hirta extract in neonatal asthmatic rats. Rats were assigned to the following groups: group I, sham (normal rats); group II, control (asthmatic rats); group III, E. hirta extract (100 µg/100 µl) and group IV, E. hirta extract (200 µg/100 µl). We performed a phytoscreening analysis of E. hirta extract. Inflammatory cell counts in the bronchoalveolar lavage fluid, levels of anti-inflammatory and antioxidant markers, apoptosis, and a histopathological analysis were carried out. An open field test determined anxiolytic activity, an elevated plus maze, a hole board test, and a cross test. The presence of 9,12,15-octadecatrien-1-ol, pentadecylic acid, ethyl linoleate, 1,2,3-trihydroxy benzene, gamma-tocopherol, 5-hydroxymethyl-2-furancarboxaldehyde, myristic acid, 7,10-octadecadienoic acid methyl ester, phytol, ethyl palmitate, and squalene in E. hirta extract was noted. Following treatment with E. hirta extract, total leukocytes, eosinophils, tumor necrosis factor-α (TNF-α), interleukin (IL-6), and lipid peroxidation were reduced, whereas antioxidant levels were increased. The mRNA expression levels of TNF-α, inducible nitric oxide synthase, IL-6, cyclooxygenase-2, caspase-3, p53, nerve growth factor precursor, and Bax were reduced, whereas that of Bcl-2 was increased. Apoptosis and caspase-3 protein expression were significantly reduced. Treatment of rats with E. hirta extract significantly reduced inflammation and eosinophil infiltration in the lungs. Taken together, these results led us to conclude that E. hirta extract has anti-inflammatory and anxiolytic effects on neonatal asthmatic rats with inflammation.