Aristolochic acid is an established human carcinogen. Previous reports have demonstrated a link between aristolochic acid exposure and liver cancer prevalence in Asia. The C3a/C3AR axis plays an essential role in regulating cancer cell migration and invasion. Here, we focused on the relationship between AA I-induced migration, invasion and epithelial-mesenchymal transition in HCC cells, as well as the possible role of the C3a/C3AR axis in these effects. HCC cells were exposed to different concentrations of AA I for 24 h. Cell migration and invasion abilities were evaluated with wound healing assays and Transwell invasion assays. The protein and mRNA expression levels were detected by western blot, immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR) assays. Furthermore, the level of complement component C3a in the cell supernatant was determined by enzyme-linked immunosorbent assay. C3aRA, a C3a receptor antagonist, was used to block the C3a-C3aR axis. The results showed that aristolochic acid I promoted HCC cell invasion and migration. AAI exposure also induced EMT in HCC cells through E-cadherin downregulation and Snail, N-cadherin, and vimentin upregulation. AAI exposure increased the levels of secreted C3a and the expression of C3aR protein and mRNA in HCC cells. We further found that AA I-induced C3a/C3AR activation was involved in these effects. AA I-induced epithelial-to-mesenchymal transition (EMT), cell migration, and invasion were decreased by C3aR inhibition. Overall, our results suggest that AA I induces HCC cell migration and invasion through the EMT process, which is regulated by C3a/C3aR axis activation.

Cereus hildmannianus (K.) Schum. (syn. C. peruvianus) is a native medicinal plant in the Neotropical region. C. hildmannianus cladodes extracts are used in folk medicine for weight loss, reducing cholesterol, low-density lipoprotein (LDL) levels, as diuretic and cardiotonic, and to treat various diseases, including pulmonary disorders, rheumatism, and in topical treatment for wounds and lithiasis. Fruits and flowers of C. hildmmanianus have high nutritional value.

In this review, previous reports on C. hildmannianus (syn. C. peruvianus) concerning its botanical description, geographical distribution, ethnomedicinal use, phytochemistry, in vitro and in vivo pharmacological properties, food benefits and plant biotechnology were summarized.

Scientific search engines, including ScienceDirect, Capes Journals Portal, Google Scholar, PubMed, Scielo, and Scifinder, were consulted to gather data on C. hildmannianus. The present review is an up-to-date and comprehensive analysis of phytochemical compounds, ethnomes from various morphological parts of the plant of C. hildmannianus were highlighted in this review, which provides information for future studies, commercial exploration and reveals that this plant has a huge potential for pharmaceutical and nutraceutical applications.

Geissoschizine methyl ether (GM), an indole alkaloid from Uncaria hook, is an active ingredient in the traditional Japanese Kampo medicine yokukansan, which is used to treat neurosis, insomnia, irritability, and night crying in children.

Recent our pharmacokinetic studies suggested that there may be gender differences in the plasma concentrations of GM in rats, but not in humans. However, the details of this difference remain unverified. The purpose of this study was to clarify the reasons for the gender differences in rats.

GM plasma pharmacokinetics was compared in male and female rats orally administered yokukansan (4 g/kg). To confirm the involvement of cytochrome P450 (CYP) in GM liver metabolism, GM was incubated with male and female rat liver S9 fraction in the absence or presence of 1-aminobenzotriazole (a nonspecific CYP inhibitor). CYP isoforms involved in GM metabolism were estimated using recombinant rat CYP isoforms and anti-rat CYP antibodies.

The maximum GM plasma concentrations were sidependent metabolism of GM.

These results suggest that the cause of gender differences in plasma GM pharmacokinetics in rats is most likely because of male-dependent CYP2C11 and CYP3A2, and provide also useful information to further evaluate the pharmacological and toxicological effects in future. This study is the first to demonstrate that the gender differences in plasma GM pharmacokinetics in rats are caused by the gender-dependent metabolism of GM.Mammalian cells have become the predominant expression system for the production of biopharmaceuticals due to their capabilities in posttranslational modifications. In recent years, the efficacy of these production processes has increased significantly through technical improvements. However, the state of the art in the development of producer cell lines includes many manual steps and is as such very time and cost consuming. Torin 1 mw In this study we developed a process combination of Raman micro-spectroscopy, laser-induced forward transfer (LIFT) and surface-enhanced Raman spectroscopy (SERS) as an automated machine system for the identification, separation and characterization of single cell-clones for biopharmaceutical production. Raman spectra showed clear differences between individual antibody-producing and non-producing chinese hamster ovary (CHO) cells after their stable transfection with a plasmid coding for an immunoglobulin G (IgG) antibody. Spectra of producing CHO cells exhibited Raman signals characteristic for human IgG. Individual producing CHO cells were successfully separated and transferred into a multiwell plate via LIFT. Besides, changes in concentration of human IgG in solution were detected via SERS. SERS spectra showed the same peak patterns but differed in their peak intensity. Overall, our results show that identification of individual antibody-producing CHO cells via Raman micro-spectroscopy, cell separation via LIFT and determination of changes in concentrations of overexpressed protein via SERS are suitable and versatile tools for assembling a fully automated system for biopharmaceuticals manufacturing.Nitric oxide (NO)-dependent signaling and cytotoxic effects are mediated in part via protein S-nitrosylation. The magnitude and duration of S-nitrosylation are governed by the two main thiol reducing systems, the glutathione (GSH) and thioredoxin (Trx) antioxidant systems. In recent years, approaches have been developed to harness the cytotoxic potential of NO/nitrosylation to inhibit tumor cell growth. However, progress in this area has been hindered by insufficient understanding of the balance and interplay between cellular nitrosylation, other oxidative processes and the GSH/Trx systems. In addition, the mechanistic relationship between thiol redox imbalance and cancer cell death is not fully understood. Herein, we explored the redox and cellular effects induced by the S-nitrosylating agent, S-nitrosocysteine (CysNO), in GSH-sufficient and -deficient human tumor cells. We used l-buthionine-sulfoximine (BSO) to induce GSH deficiency, and employed redox, biochemical and cellular assays to interrogate molecular mechanisms.