Drug Des Dev Ther
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Charcot-Marie-Tooth (CMT) disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. ⋯ Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT.
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Burgeoning antibiotic resistance and unfavorable outcomes of inflammatory injury after Pseudomonas aeruginosa infection have necessitated the development of novel agents that not only target quorum sensing (QS) but also combat inflammatory injury with the least risk of resistance. This study aimed to assess the anti-QS and anti-inflammatory activities of baicalein, a traditional herbal medicine that is widely used in the People's Republic of China, against P. aeruginosa infection. We found that subminimum inhibitory concentrations of baicalein efficiently interfered with the QS-signaling pathway of P. aeruginosa via downregulation of the transcription of QS-regulated genes and the translation of QS-signaling molecules. ⋯ Baicalein reduced the P. aeruginosa-induced secretion of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNFα. In addition, baicalein suppressed P. aeruginosa-induced activation of the MAPK and NFκB signal-transduction pathways in cocultured macrophages; this may be the mechanism by which baicalein inhibits the production of proinflammatory cytokines. Therefore, our study demonstrates that baicalein represents a potential treatment for P. aeruginosa infection because it clearly exhibits both antibacterial and anti-inflammatory activities.
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To observe the effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome. ⋯ Xuanbai Chengqi decoction not only can improve the static lung compliance and dynamic compliance of patients with exogenous pulmonary distress syndrome but also can shorten the parenteral nutrition duration, as well as reducing the complication incidence rate and fatality rate.
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The quality of Chinese herbal medicine tablets suffers from batch-to-batch variability due to a lack of manufacturing process understanding. In this paper, the Panax notoginseng saponins (PNS) immediate release tablet was taken as the research subject. By defining the dissolution of five active pharmaceutical ingredients and the tablet tensile strength as critical quality attributes (CQAs), influences of both the manipulated process parameters introduced by an orthogonal experiment design and the intermediate granules' properties on the CQAs were fully investigated by different chemometric methods, such as the partial least squares, the orthogonal projection to latent structures, and the multiblock partial least squares (MBPLS). ⋯ From the calculated block importance in the projection indexes, the tableting unit was confirmed to be the critical process unit of the manufacturing line. The results demonstrated that the combinatorial use of different multivariate modeling methods could help in understanding the complex process relationships as a whole. The output of this study can then be used to define a control strategy to improve the quality of the PNS immediate release tablet.
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Prostate cancer is the most diagnosed noncutaneous cancer and ranks as the second leading cause of cancer-related deaths in American males. Metastasis is the primary cause of prostate cancer mortality. Survival rate is only 28% for metastatic patients, but is nearly 100% for patients with localized prostate cancers. ⋯ Additionally, the SPOCK1 knockdown decreased, whereas the SPOCK1 overexpression increased cell migration and invasion abilities in vitro. Injection of SPOCK1-depleted PC3 cells significantly decreased metastatic nodules in mouse lungs. These findings suggest that SPOCK1 is a critical mediator of tumor growth and metastasis in prostate cancer.