Iridoid, phenylethanoid and flavonoid glycosides from .

As part of our continuing efforts to explore bioactive compounds from natural resources, a new iridoid glycoside, adoxosidic acid-6'-oleuroperic ester (), together with one known phenylethanoid glycoside () and two known flavonoid glycosides () were isolated from the fruit of . The structure of the new compound () was elucidated through 1D and 2D NMR spectroscopic data and HR-ESIMS. Interestingly, compound was a monoterpene ester of one iridoid glycoside.

Nanoparticle-delivered quercetin for cancer therapy.

Quercetin, a natural protective bioflavonoid, possesses diverse pharmacologic effects, such as antioxidant, anti-inflammatory, anti-proliferative, and anti-angiogenic activities. Recently, quercetin's effect in cancer prevention and treatment was recognized. However, the poor water solubility and low-bioavailability of quercetin limit its clinical use in cancer therapy.

Reductions in myeloid-derived suppressor cells and lung metastases using AZD4547 treatment of a metastatic murine breast tumor model.

Background: AZD4547, a small-molecule inhibitor targeting the tyrosine kinase of Fibroblast Growth Factor Receptors (FGFRs), is currently under phase II clinical study for human subjects having breast cancer, while the underlying mechanism remains elusive. The aim of this study is to explore the potential mechanism by which AZD4547 inhibits breast tumor lung metastases at the level of the tumor microenvironment.

Methods: First, through in vitro experiments, we investigated the efficacy of the FGFRs inhibitor AZD4547 on 4T1 tumor cells for their proliferation, apoptosis, migration, and invasion.

Prevention of postsurgical cauterization-induced peritoneal adhesions by biodegradable and thermosensitive micelles.

Postsurgical peritoneal adhesion is a major concern in clinical practice which causes significant morbidity and mortality. In this study, we investigated the efficacy of biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) micelles in preventing postsurgical cauterization-induced peritoneal adhesion. The biodegradable PEG-PCL-PEG copolymer could form nano-sized micelles in water, which instantly turned into a non-flowing gel at body temperature due to micellar aggregation.

Therapeutic target database update 2014: a resource for targeted therapeutics.

Here we describe an update of the Therapeutic Target Database (http://bidd.nus.edu.

In silico prediction of adverse drug reactions and toxicities based on structural, biological and clinical data.

Drug adverse effects (ADEs) and toxicities have been extensively studied from chemical structure, genetic, biological systems and clinical perspectives. The rapid accumulation of chemical, biological and clinical data are highly useful for characterizing and predicting ADEs, and have enabled increasing exploration of computational methods as low cost tools for predicting various ADEs and toxicities. This article reviews the strategies, current progresses, underlying difficulties and future prospects in using computational methods for predicting ADEs and toxicities.

Treating acute cystitis with biodegradable micelle-encapsulated quercetin.

Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles.

AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal peritoneal carcinomatosis model.

Background: Angiogenesis plays an important role in tumor growth and metastasis, therefore antiangiogenic therapy was widely investigated as a promising approach for cancer therapy. Recently, pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis. Adeno-associated virus (AAV) vectors have been intensively studied due to their wide tropisms, nonpathogenicity, and long-term transgene expression in vivo.

A novel vaccine delivery system: biodegradable nanoparticles in thermosensitive hydrogel.

In this work, a novel vaccine delivery system, biodegradable nanoparticles (NPs) in thermosensitive hydrogel, was investigated. Human basic fibroblast growth factor (bFGF)-loaded NPs (bFGF-NPs) were prepared, and then bFGF-NPs were incorporated into thermosensitive hydrogel to form bFGF-NPs in a hydrogel composite (bFGF-NPs/hydrogel). bFGF-NPs/hydrogel was an injectable sol at ambient temperature, but was converted into a non-flowing gel at body temperature.

Protective effects of IL-4 on Bacillus Calmette-Guerin and lipopolysaccharide induced immunological liver injury in mice.

Objective: Mice injected with Bacillus Calmette-Guérin (BCG) were challenged with lipopolysaccharide (LPS) to induce inflammatory liver injury. This study was performed to explore the protective effects of interleukin (IL)-4 against liver injury induced by BCG and LPS in mice.

Materials And Methods: Mice injected with BCG (125 mg/kg) were challenged with LPS (10 μg/kg) to induce the model of inflammatory liver injury.

Enhanced antitumor efficacy by blocking activation of the phosphatidylinositol 3-kinase/Akt pathway during anti-angiogenesis therapy.

Anti-angiogenesis has been a promising strategy for cancer therapy. However, many signal pathways are activated during anti-angiogenic treatment to counteract the therapeutic efficacy. Among these pathways, evidence has directly pointed to the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway, whose activation resulted in tolerance to the absence of nutrients and oxygen when tumor angiogenesis has been inhibited.

Effect of training data size and noise level on support vector machines virtual screening of genotoxic compounds from large compound libraries.

Various in vitro and in-silico methods have been used for drug genotoxicity tests, which show limited genotoxicity (GT+) and non-genotoxicity (GT-) identification rates. New methods and combinatorial approaches have been explored for enhanced collective identification capability. The rates of in-silco methods may be further improved by significantly diversified training data enriched by the large number of recently reported GT+ and GT- compounds, but a major concern is the increased noise levels arising from high false-positive rates of in vitro data.

Preparation of N-trimethyl chitosan-protein nanoparticles intended for vaccine delivery.

In this paper, various N-trimethyl chitosan (TMC) of different molecular-weights (approximately 100 KD, approximately 200 KD, and approximately 400 KD, respectively) with the approximately degree of quartenization (DQ) of 40% were successfully synthesized. In vitro cytotoxicity of TMC solution showed the dependence of TMC concentration from 20 microg/ml to 500 microg/ml on the relative cell activity. Molecular weight of TMC did not greatly affect the cytotoxicity of TMC against HEK293 and L929 cells.

A novel drug and gene co-delivery system based on Poly(epsilon-caprolactone)-Poly(ethylene glycol)-Poly(epsilon-caprolactone) grafted polyethyleneimine micelle.

In this paper, we prepared a novel cationic self-assembled micelle from poly(epsilon-caprolactone)-poly(ethyl glycol)-poly(epsilon-caprolactone) grafted polyethyleneimine (PCEC-g-PEI). The PCEC-g-PEI micelles, formed by self-assembly method, had mean particle size of ca. 82 nm and zeta potential of +22.

Preparation and characterization of a porous scaffold based on poly(D,L-lactide) and N-hydroxyapatite by phase separation.

In this study, a series of porous scaffolds were prepared from poly(D,L-lactide) (PLA) and nanohydroxyapatite (HA) using the phase separation method. HA/PLA composite membranes and PLA membranes with a microporous structure (pore size around 10-20 μm) were observed by scanning electron microscopy and these micropores were well distributed throughout the PLA membranes. The surface morphology of HA/PLA composite membranes was significantly improved compared to pure PLA membrane.

Development of PLGA nanoparticles simultaneously loaded with vincristine and verapamil for treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared.

Antitumor and anti-angiogenesis immunity induced by CR-SEREX-identified Xenopus RHAMM.

Immunization with xenogeneic antigens is an attractive approach to induce cross-reactive humoral and cellular immunity to inhibit tumor growth or angiogenesis. To identify novel xenogenic targets for immunotherapy, we have developed a modified serological expression cloning (SEREX) strategy, termed Cross-reactive SEREX (CR-SEREX). Among 78 positive clones identified by CR-SEREX, Xenopus receptor for hyaluronic-acid-mediated motility (xRHAMM) was most frequently identified (18 times), indicating the strongest immunogenic potential for xenogenic immunotherapy.

Development of glycyrrhetinic acid-modified stealth cationic liposomes for gene delivery.

The glycyrrhetinic acid-modified stealth cationic liposomes (GA-PEG-CLs) loaded with pDNA (GA-PEG-CLPs) were developed and found to transfect human hepatocellular carcinoma cell line HepG2 with high efficiency. GA-PEG-CLs were comprised of DOTAP, cholesterol (Chol) and glycyrrhetinic acid-polyethyleneglycol-cholesterol conjugate (GA-PEG-Chol). Agarose gel electrophoresis revealed that 5% GA-PEG-CLs constituted by DOTAP/Chol/GA-PEG-Chol at molar ratio of 50:45:5 could completely entrap pDNA at a lower liposomes/pDNA weight ratios of 4:1 (N/P ratio: 1.

Gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal delivery of interleukin-4 using ultradeformable cationic liposome.

Background: Topical transdermal gene delivery to the skin shows great potential for painless, non-invasive administration of vaccines and therapeutic agents. Interleukin (IL)-4 strategies have shown a good antipsoriatic effect in clinic trials. To date, no information has been acquired on the effectiveness of gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal penetration of murine IL-4 (mIL-4) using ultradeformable cationic liposome (UCL).

Efficient inhibition of lung cancer in murine model by plasmid-encoding VEGF short hairpin RNA in combination with low-dose DDP.

Background: VEGF is a well-validated target for antiangiogenic intervention in cancer. To date, RNAi technology has been proven to be a promising approach for targeted therapy. DDP is frequently used as a first-line drug in chemotherapy for lung cancer but usually causes severe toxicity.

Chitosan-alginate sponge: preparation and application in curcumin delivery for dermal wound healing in rat.

A biodegradable sponge, composed of chitosan (CS) and sodium alginate (SA), was successfully obtained in this work. The sponge was ethereal and pliable. The chemical structure and morphology of the sponges was characterized by FTIR and SEM.

Reversion of multidrug resistance by co-encapsulation of vincristine and verapamil in PLGA nanoparticles.

Multidrug resistant (MDR) cancer may be treated using combinations of encapsulated cytotoxic drugs and chemosensitizers. To optimize the effectiveness of this combinational approach, poly(d,l-lactide-co-glycolide acid) (PLGA) nanoparticles formulations capable of delivering a cytotoxic drug, vincristine, a chemosensitizer, verapamil, or their combination were prepared via combining O/W emulsion solvent evaporation and salting-out method. Moreover, this work evaluated a number of approaches for the administration of chemosensitizer-cytotoxic drug combinations in a systematic fashion.

Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel: part 1--Synthesis, characterization, and acute toxicity evaluation.

In this work, biodegradable PCL-PEG-PCL (PCEC) triblock copolymers were successfully synthesized at one-step. Aqueous solution of PCEC copolymer displayed thermosensitive sol-gel-sol transition behavior, which is flowing sol at low temperature and turns into non-flowing gel at body temperature. The cytotoxicity of PCEC copolymer was evaluated by cell viability assay using HEK293 and WISH cells.

Acute toxicity evaluation of biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PEG-PCL-PEG hydrogel.

In this work, a biodegradable poly(ethylene glycol)-poly(epsilon-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) triblock copolymer was successfully synthesized. The aqueous solution of such PECE copolymer displayed special sol-gel-sol transition as temperature increase, which is a flowing sol at low-temperature and turns into a nonflowing gel at body temperature. The cytotoxicity of PECE copolymer was evaluated by cell viability assay using HEK 293 cells.

Suppression of lung cancer in murine model: treated by combination of recombinant human endostsatin adenovirus with low-dose cisplatin.

Background: The sustained growth of tumors necessitates neovascularization. As one of the potent endogenous vascular inhibitors, endostatin has been widely used in antiangiogenesis therapy for tumor. Cisplatin is normally administered in chemotherapy for lung cancer but accompanied with serious side effects.