Current Drug Metabolism - Volume 21, Issue 8, 2020

Glioblastoma multiforme (GBM), as the most lethal brain tumor, continues to be incurable. Considering the high mortality rate of GBM, it is crucial to develop new treatment approaches. Conventional therapies, including maximal surgical resection, radiation therapy, and chemotherapy (typically temozolomide), have not led to significant changes in the survival rates of GBM patients. However, emerging modalities, such as the use of tyrosine kinase inhibitors, mTOR inhibitors, NF-ΚB modulators, nitrosoureas, and immunotherapeutic agents have shown promising in improving GBM outcomes. In this context, we reviewed the current status of GBM treatment, the efficacy of existing standard therapies in improving disease outcomes, and future therapeutic directions.

Background: Breast cancer is a heterogeneous disease typically prevalent among women and is the second-largest cause of death worldwide. Early diagnosis is the key to minimize the cancer-induced complication, however, the conventional diagnostic strategies have been sluggish, complex, and, to some extent, non-specific. Therapeutic tools are not so convenient and side effects of current therapies offer the development of novel theranostic tool to combat this deadly disease. Objective: This article aims to summarize the advances in the diagnosis and treatment of breast cancer with gold nanoparticles (GNP or AuNP). Methods: A systematic search was conducted in the three popular electronic online databases including PubMed, Google Scholar, and Web of Science, regarding GNP as breast cancer theranostics. Results: Published literature demonstrated that GNPs tuned with photosensitive moieties, nanomaterials, drugs, peptides, nucleotide, peptides, antibodies, aptamer, and other biomolecules improve the conventional diagnostic and therapeutic strategies of breast cancer management with minimum cytotoxic effect. GNP derived diagnosis system assures reproducibility, reliability, and accuracy cost-effectively. Additionally, surface-modified GNP displayed theranostic potential even in the metastatic stage of breast cancer. Conclusion: Divergent strategies have shown the theranostic potential of surface tuned GNPs against breast cancer even in the metastatic stage with minimum cytotoxic effects both in vitro and in vivo.

Background: Tumor-targeted delivery by nanoparticles is a great achievement towards the use of highly effective drug at very low doses. The conventional development of tumor-targeted delivery by nanoparticles is based on enhanced permeability and retention (EPR) effect and endocytosis based on receptor-mediated are very demanding due to the biological and natural complications of tumors as well as the restrictions on the design of the accurate nanoparticle delivery systems. Methods: Different tumor environment stimuli are responsible for triggered multistage drug delivery systems (MSDDS) for tumor therapy and imaging. Physicochemical properties, such as size, hydrophobicity and potential transform by MSDDS because of the physiological blood circulation different, intracellular tumor environment. This system accomplishes tumor penetration, cellular uptake improved, discharge of drugs on accurate time, and endosomal discharge. Results: Maximum drug delivery by MSDDS mechanism to target therapeutic cells and also tumor tissues and sub cellular organism. Poorly soluble compounds and bioavailability issues have been faced by pharmaceutical industries, which are resolved by nanoparticle formulation. Conclusion: In our review, we illustrate different types of triggered moods and stimuli of the tumor environment, which help in smart multistage drug delivery systems by nanoparticles, basically a multi-stimuli sensitive delivery system, and elaborate their function, effects, and diagnosis.

Background: Deoxynivalenol contamination is increasing worldwide, presenting great challenges to food security and causing great economic losses in the livestock industry. Objective: This study was conducted to determine the protective effect of baicalin zinc as a dietary supplement on pigs fed with a deoxynivalenol contaminated diet. Methods: A total of 40 weaned pigs (21 d of age; 6.13 ± 0.42 kg average BW) were randomly assigned (10 pigs/group) to 4 dietary treatments: basal diet (Con group), basal diet + 4 mg/kg DON (DON group), basal diet + 5 g/kg BZN (BZN group), and basal diet + 5 g/kg BZN + 4 mg/kg DON (DBZN group) for a 14-d period. Seven randomly-selected pigs from each treatment were killed for blood and tissue sampling. Results: The results showed that piglets challenged with DON exhibited significantly reduced levels of ADG, ADFI, and F/G (p < 0.05). BZN supplemented diets significantly suppressed the protein expression of p-Nrf2, p-NF-kB, and HO-1 in the jejunum of DON challenged piglets (p < 0.05). In liver, DON markedly increased the mRNA expression of P70S6K and HSP70 in piglets fed the basal diet, but significantly reduced that of HO-1, NQO-1, NF-kB, AMPKα2 and HSP70 in piglets fed the BZN supplemented diet (p < 0.05). Dietary supplementation with BZN markedly increased the T-AOC level of serum in weaned piglets (p < 0.05). In jejunum, dietary supplementation with BZN activated the mRNA expression of ZIP4 in piglets (p < 0.05), BZN supplementation significantly suppressed the activity of sucrose and increased the protein concentration in chyme (p < 0.05). Conclusion: BZN can play a protective role by reducing oxidative stress and enhancing nutrient absorption in pigs fed DON-contaminated diets.

Background: The red-crowned crane (Grus japonensis) is one of the most vulnerable bird species in the world. Mycotoxins are toxic secondary metabolites produced by fungi and considered naturally unavoidable contaminants in animal feed. Our recent survey indicated that the mycotoxins had the potential to contaminate redcrowned crane’s regular diets in China. Objective: This experiment was conducted to investigate the protective effects of mycotoxin binder montmorillonite (Mont) on growth performance, serum biochemistry and oxidative stress parameters of the red-crowned crane. Methods: 16 red-crowned cranes were divided into four groups and fed one of the following diets; a selected diet, regular diet, or the selected diet or regular diet with 0.5% montmorillonite added to the diets. The cranes' parameters of performance, hematology, serum biochemistry and serum oxidative stress were measured. Results: Consuming regular diets decreased the average daily feed intake (ADFI), levels of haemoglobin (Hb), platelet count (PLT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), but increased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK) and lactate dehydrogenase (LDH). The supplementation of 0.5% Mont provided protection for the red-crowned crane in terms of feed intake, serum biochemistry and oxidative stress. Moreover, Mont supplementation had no adverse effect on the health of red-crowned crane. Conclusions: Taken together, these findings suggested that the addition of dietary Mont is effective in improving the health of red-crowned crane.

Background: Flavonoid compounds are one kind of active ingredients isolated from a traditional Chinese herb Zizyphi spinosae semen (ZSS). Studies have shown that ZSS flavonoids have significant antioxidant effects. Methods: In this study, the Caco-2 cell monolayer model was constructed to investigate the intestinal absorption characteristics and mechanism of Isovitexin (IV), Swertisin (ST), Isovitexin-2''-O-β-D-glucopyranoside (IVG), Spinosin (S), 6'''-p-coumaroylspinosin (6-CS) and 6'''-feruloylspinosin (6-FS). Results: The results of the bidirectional transport assay showed that the six flavonoids have good intestinal absorption in a near-neutral and 37°C environment, and the absorbability in descending order was 6-FS>6- CS>IVG>S>IV>ST. The results of carrier inhibition experiments and transport kinetics indicated that the absorption mechanism of six flavonoids was energy-dependent monocarboxylate transporter (MCT)-mediated active transport. In particular, the para-cellular pathway also participated in the transport of IV, ST, IVG and S. Furthermore, the efflux process of six flavonoids was mediated by P-glycoprotein (P-gp) and multidrug resistance protein (MRP), which may result in a decrease of bioavailability. Conclusion: Our findings provide significant information for revealing the relationship between the intestinal absorption mechanism of flavonoids and its structure as well as laying a basis for the research of flavonoid preparations.