Resveratrol Loaded Liposomes Disrupt Cancer Associated Fibroblast Communications within the Tumor Microenvironment to Inhibit Colorectal Cancer Aggressiveness

Colorectal cancer (CRC) is a cancer-associated fibroblast, CAF-rich tumor. CAF promotes cancer cell proliferation, metastasis, drug resistance via secretes soluble factors, and extracellular matrices which leads to dense stroma, a major barrier for drug delivery. Resveratrol (RES) is a polyphenolic compound, has several pharmacologic functions including anti-inflammation and anticancer effects. Considering tumor microenvironment of CRC, resveratrol-loaded liposome (L-RES) was synthesized and employed to inhibit CAF functions. The L-RES was synthesized by thin-film hydration method. The cytotoxicity of L-RES was evaluated using MTT assay. Effect of L-RES treated CAF on tumor spheroid growth was performed. Cell invasion was determined using spheroid invasion assay. The effect of L-RES on 5-fluorouracil (5-FU) sensitivity of CRC cells was determined in co-cultured tumor spheroids. Subtoxic dose of L-RES was selected to study possible inhibiting CAF functions. Decreased CAF markers, α-SMA and IL-6 levels, were observed in L-RES treated activated fibroblast. Interestingly, the activated fibroblast promoted invasive ability and drug resistance of CRC cells in co-culture condition of both 2D and 3D cultures and was attenuated by L-RES treatment in the activated fibroblast. Therefore, L-RES provides a promising drug delivery strategy for CRC treatment by disrupting the crosstalk between CRC cells and CAF

Inhibiting Metastasis and Improving Chemosensitivity via Chitosan-Coated Selenium Nanoparticles for Brain Cancer Therapy

Selenium nanoparticles (SeNPs) were synthesized to overcome the limitations of selenium, such as its narrow safe range and low water solubility. SeNPs reduce the toxicity and improve the bioavailability of selenium. Chitosan-coated SeNPs (Cs-SeNPs) were developed to further stabilize SeNPs and to test their effects against glioma cells. The effects of Cs-SeNPs on cell growth were evaluated in monolayer and 3D-tumor spheroid culture. Cell migration and cell invasion were determined using a trans-well assay. The effect of Cs-SeNPs on chemotherapeutic drug 5-fluorouracil (5-FU) sensitivity of glioma cells was determined in tumor spheroids. An in vitro blood–brain barrier (BBB) model was established to test the permeability of Cs-SeNPs. SeNPs and Cs-SeNPs can reduce the cell viability of glioma cells in a dose-dependent manner. Compared with SeNPs, Cs-SeNPs more strongly inhibited 3D-tumor spheroid growth. Cs-SeNPs exhibited stronger effects in inhibiting cell migration and cell invasion than SeNPs. Improved 5-FU sensitivity was observed in Cs-SeNP-treated cells. Cellular uptake in glioma cells indicated a higher uptake rate of coumarin-6-labeled Cs-SeNPs than SeNPs. The capability of coumarin-6 associated Cs-SeNPs to pass through the BBB was confirmed. Taken together, Cs-SeNPs provide exceptional performance and are a potential alternative therapeutic strategy for future glioma treatment

Natural infection of parvovirus in wild fishing cats (Prionailurus viverrinus) reveals extant viral localization in kidneys.

Carnivore protoparvovirus-1 (CPPV-1), a viral species containing feline panleukopenia virus (FPV) and canine parvovirus (CPV) variants, are widely spread among domestic and wild carnivores causing systemic fatal diseases. Wild fishing cats (Prionailurus viverrinus), a globally vulnerable species, have been found dead. Postmortem examination of the carcasses revealed lesions in intestine, spleen and kidney. CPPV-1 antigen identification in these tissues, using polymerase chain reaction (PCR) and immunohistochemistry (IHC), supported the infection by the virus. PCR- and IHC-positivity in kidney tissues revealed atypical localization of the virus while in situ hybridization (ISH) and transmission electron microscopy (TEM) with the pop-off technique confirmed the first description of viral localization in kidneys. Complete genome characterization and deduced amino acid analysis of the obtained CPPV-1 from the fishing cats revealed FPV as a causative agent. The detected FPV sequences showed amino acid mutations at I566M and M569R in the capsid protein. Phylogenetic and evolutionary analyses of complete coding genome sequences revealed that the fishing cat CPPV-1 genomes are genetically clustered to the FPV genomes isolated from domestic cats in Thailand. Since the 1970s, these genomes have also been shown to share a genetic evolution with Chinese FPV strains. This study is the first evidence of CPPV-1 infection in fishing cats and it is the first to show its localization in the kidneys. These findings support the multi-host range of this parvovirus and suggest fatal CPPV-1 infections may result in other vulnerable wild carnivores

Masculinization of Red Tilapia (<i>Oreochromis</i> spp.) Using 17α-Methyltestosterone-Loaded Alkyl Polyglucosides Integrated into Nanostructured Lipid Carriers

The aim of the present study was to optimize a masculinization platform for the production of all-male red tilapia fry by oral administration of 30 and 60 ppm of MT and alkyl polyglucoside nanostructured lipid carriers (APG-NLC) loaded with MT, respectively, for 14 and 21 days. The characterization, encapsulation efficiency and release kinetics of MT in lipid-based nanoparticles were assessed in vitro. The results showed that the MT-loaded nanoparticles were spherical, ranging from 80 to 125 nm in size, and had a negative charge with a narrow particle distribution. The APG-NLC loaded with MT provided higher physical stability and encapsulation efficacy than the NLC. The release rate constants of MT from MT-NLC and MT-APG-NLC were higher than those of free MT, which is insoluble in aqueous media. There was no significant difference in survival between the fish administered MT or the those fed orally with MT-APG-NLC fish. According to the logistic regression analysis, the sex reversal efficacy of MT-APG-NLC (30 ppm) and MT (60 ppm), resulted in significantly higher numbers of males after 21 days of treatment compared with the controls. The production cost of MT-APG-NLC (30 ppm) after 21 days of treatment was reduced by 32.9% compared with the conventional MT treatment group (60 ppm). In all the treatments, the length–weight relationship (LWR) showed negatively allomeric growth behavior (b n) of more than 1. Therefore, MT-APG-NLC (30 ppm) would seem to be a promising, cost-effective way to reduce the dose of MT used for the masculinization of farmed red tilapia