分类: 药物科学 >> 生物化学 提交时间: 2024-06-14
摘要: Hyperlipidemia (HLP) is a prevalent systemic metabolic disorder characterized by disrupted lipid metabolism. Statin drugs have long been the primary choice for managing lipid levels, but intolerance issues have prompted the search for alternative treatments. Matrine, a compound derived from the traditional Chinese medicine Kushen, exhibits anti-inflammatory and lipid-lowering properties. Nevertheless, the mechanism by which matrine modulates lipid metabolism remains poorly understood. Here, we investigated the molecular mechanisms underlying matrine’s regulation of lipid metabolism. Employing quantitative proteomics, we discovered that matrine increases the expression of LDL receptor (LDLR) in HepG2 and A549 cells, with subsequent experiments validating its role in enhancing LDL uptake. Notably, in hyperlipidemic hamsters, matrine effectively lowered lipid levels without affecting body weight, which highlights LDLR as a critical target for matrine’s impact on hyperlipidemia. Moreover, matrine’s potential inhibitory effects on tumor cell LDL uptake hint at broader applications in cancer research. Additionally, Thermal Proteome Profiling (TPP) analysis identified lipid metabolism-related proteins that may interact with matrine. Together, our study reveals matrine’s capacity to upregulate LDLR expression and highlights its potential in treating hyperlipidemia. These findings offer insights into matrine’s mechanism of action and open new avenues for drug research and lipid metabolism regulation.
分类: 药物科学 >> 生物化学 提交时间: 2024-06-14
摘要: Gemcitabine (GEM) is a potent chemotherapeutic agent widely employed in the treatment of various cancers, notably pancreatic cancer. Despite its clinical success, challenges related to GEM resistance and toxicity persist. Therefore, there is a pressing need for a deeper understanding of its intracellular mechanisms and potential targets. In this study, we utilized quantitative proteomics and thermal proteome profiling (TPP) to elucidate the effects of GEM. Our proteomic analysis revealed that GEM primarily affected DNA synthesis, leading to the upregulation of cell cycle and DNA replication proteins. Additionally, enrichment analysis highlighted the activation of the p53 pathway, shedding light on GEM-induced apoptosis mechanisms. Notably, we observed the upregulation S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator, in response to GEM treatment. Combining SKP2 inhibition with GEM showed synergistic effects in both cellular and animal models, suggesting SKP2 as a potential target for enhancing GEM sensitivity and overcoming chemoresistance. Furthermore, through TPP, we explored potential binding targets of GEM, which implies GEM’s broad anticancer effects. Together, these findings provide valuable insights into GEM’s molecular mechanisms and offer potential targets for improving treatment efficacy. This research holds the promise of advancing personalized treatment strategies and opening avenues for novel combination therapies to enhance outcomes in pancreatic cancer.
分类: 药物科学 >> 药物化学 提交时间: 2024-02-07
摘要: A new cembranolide, namely, sinupendunculide A (1), along with eight known related compounds (29), was isolated from the South China Sea Soft coral Sinularia pendunculata. The structure of sinupendunculide A (1) was established by extensive spectroscopic analysis and X-ray diffraction experiments. In a bioassay, anti-colorectal cancer (CRC) activity was performed, and the results showed that several compounds exhibited cytotoxicity against RKO cells, and a preliminary structure-activity relationship was analysed. Meanwhile, the most effective compound 7 was proven to increase reactive oxygen species levels, which promoted cell apoptosis and inhibited cell proliferation.
分类: 光学 >> 量子光学 提交时间: 2023-02-19
摘要: Quantum transducers that can convert quantum signals from the microwave to the optical domain are a crucial optical interface for quantum information technology. Coherent microwave-to-optics conversions have been realized with various physical platforms, but all of them are limited to low efficiencies of less than 50\%, the threshold of the no-cloning quantum regime. Here we report a coherent microwave-to-optics transduction using Rydberg atoms and off-resonant scattering technique with an efficiency of $82\pm 2\%$ and a bandwidth of about 1 MHz. The high conversion efficiency is maintained for microwave photons range from thousands to about 50, suggesting that our transduction is readily applicable to the single-photon level. Without requiring cavities or aggressive cooling to quantum ground states, our results would push atomic transducers closer to practical applications in quantum technologies.
分类: 天文学 >> 天文学 提交时间: 2023-02-19
摘要: We summarize recent progress in the development, application, and understanding of effective field theories and highlight promising directions for future research. This Report is prepared as the TF02 "Effective Field Theory" topical group summary for the Theory Frontier as part of the Snowmass 2021 process.