Life sciences
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Many μ-opioid receptor (MOR)-associated proteins can regulate the MOR signaling pathway. Using a bacterial two-hybrid screen, we found that the C-terminal of the MOR associated with heat shock protein 90 isoform β (Hsp90β). Here, we explored the effect of Hsp90β on MOR signaling transduction and function. ⋯ Hsp90β is a positive co-regulator of the MOR via the activation of a G-protein-dependent and β-arrestin-dependent pathway. Hsp90β has the potential to improve the pharmacologic profile of existing opiates. It is conceivable that in future clinical treatments, the Hsp90β inhibitor, 17-AAG, could decrease the tolerance and dependence in cancer patients induced by opioids.
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Rehmanniae Radix (RR) and Cornus officinalis (CO) are a typical herbal pair used to treat diabetic nephropathy (DN) in clinical practice. DN can be effectively treated by catalpol (Cat) and loganin (Log), the main active components of RR and CO respectively, through combating apoptosis, oxidative stress and inflammation. Herein, a spontaneous DN and podocyte injury model induced by advanced glycation end products (AGEs), i.e. KK-Ay mice, was used to explore the cooperative effects of Log and Cat on DN and the mechanism targeting the AGEs-RAGE (receptor for AGE) pathway. ⋯ Log and Cat cooperatively resisted the apoptosis of podocytes upon DN by targeting AGEs-RAGE and its downstream pathways p38 MAPK and Nox4.
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In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics. ⋯ The present study provided a comprehensive targeting of the first resolved COVID+19 structure of Mpro and found a suitable save drugs for repurposing against the viral Mpro. Ribavirin, telbivudine, vitamin B12 and nicotinamide can be combined and used for COVID treatment. This initiative relocates already marketed and approved safe drugs for potential use in COVID-treatment.
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Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by unbalanced proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Prohibitin 1 (PHB1) is known for its significant anti-proliferative activity. However, the role of PHB1 in PASMCs and PAH have not been elucidated. ⋯ PHB1 contributes to pulmonary vascular remodeling by accelerating proliferation of PASMCs which involves AKT phosphorylation.
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This study was aimed to synthesize novel caffeic acid derivatives and evaluate their potential applications for the treatment of oxidative stress associated disease. ⋯ Caffeic acid sulfonamide derivatives were synthesized with simple reactions under mild conditions. They might protect cells from H2O2-induced oxidative injury via Nrf2 pathway.