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Andrographolide * A potential fix for chikungunya nausea and also viral joint disease.
ile toxin. Clinicians should not neglect glutamate dehydrogenase-positive patients, even when they are Clostridioides difficile toxin-negative, and consider them as having poor prognostic potential. Geriatr Gerontol Int 2020; 20 1138-1144.Ligustilide is one of the most abundant bioactive ingredients in Rhizoma Chuanxiong that has been widely prescribed for medicinal purposes in China. To better understand the disposition and action of ligustilide, it is necessary to investigate the metabolic profiles. The in vitro metabolism was elucidated through incubating ligustilide with human and rat hepatocytes at 37°C. The incubation samples were collected at predefined time points to determine the metabolic stability. Upon metabolite identification and profiling, the incubation samples were analyzed by ultra-high-performance liquid chromatography combined with diode array detector and high-resolution mass spectrometry. The structures of the metabolites were characterized based on their mass spectrometry spectra, tandem mass spectrometry spectra, and fragmentation patterns. Ligustilide showed fast metabolism with high intrinsic clearance both in rat and human hepatocyte incubations. The half-lives of ligustilide in rat and human hepatocyte incubations were 8.0 and 15.0 min, respectively. Most of the parent (>90%) was biotransformed into the metabolites. Among these metabolites, M1 (senkyunolide I) was the major metabolite both in rat and human hepatocytes with the percentage of 42 and 70%, respectively. The metabolic pathways of ligustilide included epoxidation, epoxide hydrolysis, aromatization, hydroxylation, and glutathionylation. This work provided an overview of the metabolic profiles of ligustilide, which would be helpful for us to understand the action of this compound.Transient signaling orchestrates complex spatiotemporal behaviour in living organisms via (bio)chemical reaction networks (CRNs). Compartmentalization of signal processing is an important aspect for controlling such networks. However, artificial CRNs mostly focus on homogeneous solutions to program autonomous self-assembling systems, which limits their accessible behaviour and tuneability. Here, we introduce layered compartments housing antagonistic pH-modulating enzymes and demonstrate that transient pH signals in a supernatant solution can be programmed based on spatial delays. This overcomes limitations of activity mismatches of antagonistic enzymes in solution and allows to flexibly program acidic and alkaline pH lifecycles beyond the possibilities of homogeneous solutions. Lag time, lifetime, and the pH minima and maxima can be precisely programmed by adjusting spatial and kinetic conditions. We integrate these spatially controlled pH flips with switchable peptides, furnishing time-programmed self-assemblies and hydrogel material system.Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β (TGF-β) superfamily, is a prognostic biomarker of cervical cancer. In addition, GDF15 has been reported to enhance the migration of colorectal cancer cells and liver cancer stem-like cells. However, the mechanism by which GDF15 promotes cervical cancer cell migration is not completely understood. Here, we report that GDF15 expression is enhanced in cervical cancer tissues, as well as in cultured cervical cancer cells. ShGDF15 transfection markedly inhibited expression of Vimentin, N-cadherin and Snail1, and resulted in up-regulation of E-cadherin expression in HT-3 and HeLa cells. Moreover, knockdown of GDF15 suppressed wound healing rate and reduced the number of invasive cells. Furthermore, knockdown of GDF15 significantly suppressed the expression of phosphorylated Smad2 and Smad3. The addition of TGF-β1 partially abolished the inhibitory effects of GDF15 knockdown on the migration and invasion of cervical cancer cells. In summary, we report here that GDF15 knockdown inhibits migration and invasion of cervical cancer cells in vitro through the TGF-β/Smad2/3/Snail1 pathway.Acute lung injury (ALI) involves series of inflammatory pathologies and cause high morbidity. Salviplenoid A (SA) was a new sesquiterpenoid from the traditional inflammatory herb Salvia plebeia. In our previous study, SA exhibited antiinflammatory activity in RAW264.7 cells. However, the extensive effects of SA in human cells and in vivo and the active mechanisms are unclear. Thus, in this study, we sought to access its effects in vitro and in vivo and to investigate its mechanisms. SA was proved to inhibit the induction of proinflammatory cytokines in human cell types, including pulmonary epithelial cells and endothetial cells. It also depressed monocyte adhesion. Moreover, SA potently attenuated the acute lung inflammation in the LPS-induced mouse model shown by down-regulation of proinflammatory mediators, inhibition of polymorphonuclear neutrophil infiltration, and alleviation of related symptoms like alveolar congestion and mucus secretion. Further evaluation confirmed that SA regulated NF-κB pathway by inhibiting the IκB-α phosphorylation. And it markedly mediated Nrf2/HO-1 pathway by activating the Nrf2/HO-1 expression and promoting Nrf2 nuclear translocation. Therefore, SA could attenuate acute lung inflammation via suppressing NF-κB and activating Nrf2, which provide a theoretical basis for the potential application of SA in clinic.The peach fruit moth (PFM), Carposina sasakii Matsumura, is a major phytophagous orchard pest widely distributed across Northeast Asia. APIIIa4 Here, we report the chromosome-level genome for the PFM, representing the first genome for the family Carposinidae, from the lepidopteran superfamily Copromorphoidea. The genome was assembled into 404.83 Mb sequences using PacBio long-read and Illumina short-read sequences, including 275 contigs, with a contig N50 length of 2.62 Mb. All contigs were assembled into 31 linkage groups assisted by the Hi-C technique, including 30 autosomes and a Z chromosome. BUSCO analysis showed that 98.3% of genes were complete and 0.4% of genes were fragmented, while 1.3% of genes were missing in the assembled genome. In total, 21,697 protein-coding genes were predicted, of which 84.80% were functionally annotated. Because of the importance of diapause triggered by photoperiod in PFM, five circadian genes in the PFM as well as in the other related species were annotated, and potential genes related to diapause and photoperiodic reaction were also identified from transcriptome sequencing.
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