Activity

Lapatinib (LAP) is an anticancer drug generally used to treat breast and lung cancer. It exhibits hypersensitivity reactions in addition to dermatological adverse effects and photosensitivity. Moreover, LAP binds to serum proteins and is readily biotransformed in humans, giving rise to several metabolites, such as N- and O-dealkylated products (N-LAP and O-LAP, respectively). In this context, the aim of the present work is to obtain key information on drug@protein complexation, the first step involved in a number of hypersensitivity reactions, by a combination of fluorescence, femtosecond transient absorption spectroscopy and molecular dynamics (MD) simulations. Following this approach, the behavior of LAP and its metabolites has been investigated in the presence of serum proteins, such as albumins and α1-acid glycoproteins (SAs and AGs, respectively) from human and bovine origin. Fluorescence results pointed to a higher affinity of LAP and its metabolites to human proteins; the highest one was found for LAP@HSA. This is associated to the coplanar orientation adopted by the furan and quinazoline rings of LAP, which favors emission from long-lived (up to the ns time-scale) locally-excited (LE) states, disfavoring population of intramolecular charge transfer (ICT) states. Moreover, the highly constrained environment provided by subdomain IB of HSA resulted in a frozen conformation of the ligand, contributing to fluorescence enhancement. Computational studies were clearly in line with the experimental observations, providing valuable insight into the nature of the binding sites and the conformational arrangement of the ligands inside the protein cavities. Besides, a good correlation was found between the calculated binding energies for each ligand@protein complex and the relative affinities observed in competition experiments.Flavonoids such as naringenin, quercetin, and naringin are known to exhibit anticancer properties. In this study, we examined the effects of these flavonoids on cell viability and apoptotic pathways of cancer cells, either singly or in combination with the type 1 ribosome inactivating protein, Balsamin. Treatment with flavonoids (naringenin, quercetin, and naringin) plus Balsamin for 48 h reduced HepG2 and MCF-7 cell viability, increased the activation of caspase-3 and -8, and induced apoptosis through up-regulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes. Out of the three flavonoids tested, the Balsamin-Naringenin and Balsamin-Quercetin combinations appeared to be most effective compared to the Balsamin-Naringin combination. Balsamin combined with flavonoids also activated endoplasmic reticulum (ER)-stress-mediated apoptosis in breast cancer (MCF-7) cells, which was not activated by Balsamin treatment alone. These experimental results showed that Balsamin combined with flavonoids can reduce HepG2 and MCF-7 cells viability and induce apoptosis, which could be considered as a promising therapeutic approach to sensitize cells to Balsamin treatment, thereby improving its efficacy in breast or liver cancer therapy.Disturbance of epithelial barrier function causes chronic intestinal inflammation such as inflammatory bowel disease. CDDP solubility dmso Several studies have reported that Th2 cytokines such as interleukin (IL)-4 and IL-13 play an important role in the regulation of intestinal barrier function. However, the precise role of the IL-4 receptor α subunit (IL-4Rα) in intestinal inflammation remains unclear. Thus, we used an experimental colitis model to investigate the role of IL-4Rα in intestinal inflammation. IL-4Rα-deficient (IL-4Rα-/-) mice and their littermate wild-type (WT) mice were used. Experimental colitis was induced by administration of 3% dextran sulfate sodium (DSS) in the drinking water for seven days. Treatment with DSS caused body weight loss, an increase in the disease activity index and histological abnormalities in WT colitis mice, all of which were significantly attenuated in IL-4Rα-/- colitis mice. Neutrophil infiltration in the colonic mucosa was reduced in IL-4Rα-/- colitis mice compared with WT colitis mice. NADPH oxidase 1 expression and reactive oxygen species production were increased in the colons of IL-4Rα-/- mice. Furthermore, elevated intestinal permeability induced by DSS treatment was suppressed in IL-4Rα-/- colitis mice. These results demonstrate that IL-4Rα-/- mice exhibit reduced susceptibility to DSS-induced colitis. Our present findings suggest that IL-4Rα deficiency enhances intestinal mucosal barrier function through the upregulation of NADPH oxidase 1-dependent reactive oxygen species production, thereby suppressing the development of intestinal inflammation.Background Lung adenocarcinoma (LUAD) is the most common histologic type of non-small cell lung cancer (NSCLC; approximately 60%), and platinum-based chemotherapy is the cornerstone of the treatment for patients with LUAD. However, a considerable number of patients experience tumor recurrence after developing cisplatin (cis-diamminedichloroplatinum(II) or CDDP) resistance. Therefore, it is particularly important to screen primary CDDP-resistant LUAD patient populations, which can maximize the clinical benefits for these patients. Methods Data for 61 LUAD cell lines were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database to screen for mutations related to CDDP susceptibility, and we conducted whole-exome sequencing (WES) of tumors from 45 LUAD patients from Zhujiang Hospital of Southern Medical University. Subsequently, the clinical prognostic value of these mutations was verified by using The Cancer Genome Atlas (TCGA)-LUAD cohort and our cohort (n = 45). Results Based on drug sensitiv suggest that GREB1 mutations are potential biomarkers for screening of CDDP resistance among LUAD patients.Analysis of the most relevant studies on the pharmacological properties and molecular mechanisms of psoralidin, a bioactive compound from the seeds of Cullen corylifolium (L.) Medik. confirmed its complex therapeutic potential. In the last years, the interest of the scientific community regarding psoralidin increased, especially after the discovery of its benefits in estrogen-related diseases and as a chemopreventive agent. Growing preclinical pieces of evidence indicate that psoralidin has anticancer, antiosteoporotic, anti-inflammatory, anti-vitiligo, antibacterial, antiviral, and antidepressant-like effects. Here, we provide a comprehensive and critical review of psoralidin on its bioavailability, pharmacological activities with focus on molecular mechanisms and cell signaling pathways. In this review, we conducted literature research on the PubMed database using the following keywords “Psoralidin” or “therapeutic effects” or “biological activity” or “Cullen corylifolium” in order to identify relevant studies regarding PSO bioavailability and mechanisms of therapeutic effects in different diseases based on preclinical, experimental studies.