Baicalin induces apoptosis in SW620 human colorectal carcinoma cells in vitro and suppresses tumor growth in vivo

In the United States, colorectal cancer (CRC) is the second most frequent malignancy and the fourth most common cause of cancer death. Baicalin, a flavone derivative isolated and purified from the dry root of Scutellaria, was assessed for its antitumor effects in human SW620 CRC cells. Baicalin (200 μM) inhibited proliferation of SW620 cells. Baicalin (200 μM) increased activities of caspase-3, -8, and -9 in SW620 cells. Furthermore, flow cytometric analysis of baicalin-treated SW620 cells showed an increase in sub-G1 cells, and the dihydroethidium assay showed significant enhancement of intracellular peroxide production in baicalin-treated cells. Addition of N-acetylcysteine prevented most of the baicalin-induced apoptosis, which in turn mediated cytotoxicity in human SW620 cells. In vivo, baicalin (50 mg/kg/day, i.p.) treatment inhibited 55% of tumor growth in xenografted nude mice by 4 weeks, compared to that of the vehicle control (p < 0.05). Baicalin had no noteworthy influence on body weight. Thus, we suggest the development of baicalin as a potential leading antitumor agent in CRC.     

In vivo and in vitro investigations into the biosynthetic relatedness of the pseudopterosins

[formula: see text] Both in vivo and in vitro techniques have been developed to test putative intermediates in the biosynthetic pathway to the pseudopterosins, antiinflammatory compounds isolated from Pseudopterogorgia elisabethae. Furthermore, specific activity data we have obtained indicate that pseudopterosin A is a precursor to pseudopterosins B, C, and D. We conclude that in the biosynthesis xylose is attached to the diterpene skeleton to produce pseudopterosin A and is then aceylated to form pseudopterosins B-D.     

Naringenin protects HaCaT human keratinocytes against UVB-induced apoptosis and enhances the removal of cyclobutane pyrimidine dimers from the genome

Many naturally occurring agents are believed to protect against UV-induced skin damage. In this study, we have investigated the effects of naringenin (NG), a naturally occurring citrus flavonone, on the removal of UVB-induced cyclobutane pyrimidine dimers (CPD) from the genome and apoptosis in immortalized p53-mutant human keratinocyte HaCaT cells. The colony-forming assay shows that treatment with NG significantly increases long-term cell survival after UVB irradiation. NG treatment also protects the cells from UVB-induced apoptosis, as indicated by the absence of the 180 base pair DNA ladders and the appearance of sub-G1 peak using agarose gel electrophoresis and flow cytometric analysis, respectively. The UVB-induced poly (ADP-ribose) polymerase-1 (PARP-1) cleavage, caspase activation and Bax/Bcl2 ratio were modulated following NG treatment, indicating an antiapoptotic effect of NG in UVB-damaged cells that occurs at least in part via caspase cascade pathway. Moreover, treatment of UVB-irradiated HaCaT cells with NG enhances the removal of CPD from the genome, as observed by both direct quantitation of CPD in genomic DNA and immuno-localization of the damage within the nuclei. The study provides a molecular basis for the action of NG as a promising natural flavonoid in preventing skin aging and carcinogenesis.     

In vitro and in vivo metabolisms of K-48

Metabolic pathways of the oxime K-48 have been elucidated by means of in vitro and in vivo experiments. K-48 exposure to rat liver microsomal fraction resulted in the formation of a hydroxylated derivative, in addition to a small molecular fragment. The in vivo metabolism in rats was investigated after intramuscular administration of 50 μmol oxime. K-48 was present in the rat serum in unchanged form. Similarly, the analysis of rat cerebrospinal fluid indicated the sole occurrence of unchanged K-48. In contrast, unchanged K-48 was not found in the rat urine, where only the metabolite generated by epoxidation on the alkyl chain connecting the two pyridinium rings was present. The presence of unchanged K-48 in the serum and cerebrospinal fluid facilitates quantitative determination using HPLC separation and ultraviolet absorbance detection. Figure Suggested metabolic pathways of K-48     

In vitro and in vivo fluorescence monitoring of photosensitizers

The use of steady state fluorescence spectroscopy in the detection and monitoring of potential photochemotherapeutic agents is examined. Problems associated with both in vitro and in vivo fluorescence measurements are investigated, and typical data are presented. Recent results on the use of fluorescence in pharmacokinetic studies are discussed, and the relative merits of in vitro vs. in vivo methods are outlined.     

In vitro and in vivo metabolism studies of dimethazine

The use of anabolic steroids is prohibited in sports. Effective control is done by monitoring their metabolites in urine samples collected from athletes. Ethical objections however restrict the use of designer steroids in human administration studies. To overcome these problems alternative in vitro and in vivo models were developed to identify metabolites and to assure a fast response by anti‐doping laboratories to evolutions on the steroid market. In this study human liver microsomes and an uPA^+/+‐SCID chimeric mouse model were used to elucidate the metabolism of a steroid product called ‘Xtreme DMZ’. This product contains the designer steroid dimethazine (DMZ), which consists of two methasterone molecules linked by an azine group. In the performed stability study, degradation from dimethazine to methasterone was observed. By a combination of LC‐High Resolution Mass Spectrometry (HRMS) and GC‐MS(/MS) analysis methasterone and six other dimethazine metabolites (M1–M6), which are all methasterone metabolites, could be detected besides the parent compound in both models. The phase II metabolism of dimethazine was also investigated in the mouse urine samples. Only metabolites M1 and M2 were exclusively detected in the glucuro‐conjugated fraction; all other compounds were also found in the free fraction. For effective control of DMZ misuse in doping control samples, screening for methasterone and methasterone metabolites should be sufficient. Copyright © 2016 John Wiley & Sons, Ltd.     

In vitro and in vivo imaging with quantum dots

Quantum dots (QDs), also named semiconductor nanocrystals, have initiated a new realm of bioscience by combining nanomaterials with biology, which will profoundly influence future biological and biomedical research. In this review, we describe the extraordinary optical properties of QDs and developments in methods for their synthesis. We focus on fluorescent imaging with QDs both in vitro and in vivo, and the cytotoxicity of QDs and potential barriers to their use in practical biomedical applications. Finally, we provide insights into improvements aimed at decreasing the cytotoxicity of QDs and the future outlook of QD applications in biomedical fields.

Hydroxypyridinone complexes with aluminium. In vitro/vivo studies and perspectives

Hydroxypyridinones are a class of dioxo ligands under active development, as efficient Al (and Fe) chelators for potential medical uses. A wide range of those compounds has been designed aimed at improving their physico-chemical and pharmacokinetic properties. In this paper, we make a review on the literature results related to the design, chemistry, metal binding interaction, lipo-hydrophilic character and some biological assays of bidentate and hexadentate hydroxypyridinones. Among the different types of hydroxypyridinones, the 3-hydroxy-4-pyridinones deserved special attention because they are good orally active aluminium-chelators, and they seem to be the main candidates for replacement of desferrioxamine. The interaction of the bidentate hydroxypyridinones with Al as well as the in vivo studies have been more systematically reported than those of the hexadentate derivatives. The development of the hexadentate hydroxypyridinones is quite recent but, at physiological conditions, they have higher affinity for these M³⁺ ions than the bidentate derivatives. Despite only studies on hexadentate hydroxypyridinone-iron interactions are known and described herein, special attention was deserved to these results because of the in vivo/vitro similarity between the physico-chemical properties of these ions. The high Al affinity and favourable lipo-hydrophilic balance of the hydroxypyridinones suggest that their use as Al scavengers should be highly considered in future prospects.     

In vivo and in vitro production of alkaloids by Haplophyllum patavinum

A protocol for shoot induction from callus of Haplophyllum patavinum was established. Two known furoquinoline (skimmianine and haplopine), and three quinolone (edulinine, ribalinine and isoplatydesmine) alkaloids were isolated for the first time from plant material, callus and shoot cultures of this species. The structures of these compounds have been characterised on the basis of spectroscopic evidence.     

Surface modification of titanium by anodic oxidation in phosphoric acid at low potentials. Part 2. In vitro and in vivo study

Electrochemical studies in SBF solution were performed, in order to determine the best corrosion resistance condition, comparing as‐received titanium, covered with its native surface oxide, and titanium anodized in phosphoric acid. The results indicate that the anodic films obtained at a constant potential of 30 V have higher barrier effect, and the protective layer remains effective against the aggressive anions present in SBF after 30 days of immersion. Due to the promising corrosion performance in simulated biological media coupled with the biocompatible surface characteristics, anodic films on titanium obtained at 30 V were implanted on Wistar Rats to compare the osseointegration results of this modified surface with that corresponding to as‐received titanium. It was found that, after 8 weeks of implantation, although the amount of bone surrounding the implant did not differ across the two different surface implants conditions, bone formation at the implant interface was found to be more homogeneous in anodized titanium. Copyright © 2013 John Wiley & Sons, Ltd.     

In vivo and in vitro medical diagnoses of toxic cadmium in rats

Rat exposed to toxic cadmium chronically and acutely are diagnosed byin vivo promt gamma-ray activation andin vitro neutron activation using nuclear reactor neutron beam. Linear correlation of bothin vivo andin vitro methods is established, damage level of 1.7 mg/g Cd in kidneys and 0.16 mg/g Cd in liver are confirmed by biochemical diagnosis. Features ofin vivo andin vitro nuclear medical diagnoses of cadmium contamination, serving as the basis for future research and correletion to human beings, are discussed.     

In vitro and in vivo evaluation of β-cyclodextrin-based nanosponges of telmisartan

Telmisartan (TEL) is a BCS Class II drug having dissolution rate limited bioavailability. The aim of work was to enhance the solubility of TEL so that bioavailability problems are solved. β-Cyclodextrin (β-CD) based nanosponges (NSs) were formed by cross-linking β-CD with carbonate bonds, which were porous as well as nanosized. Drug was incorporated by solvent evaporation method. The effect of ternary component alkalizer (NaHCO₃) on solubility of TEL was studied. In order to find out the solubilization efficiency of NS, phase solubility study was carried out. Saturation solubility and in vitro dissolution study of β-CD complex of TEL was compared with plain TEL and NS complexes of TEL. The NS and NS complexes of TEL were characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, nuclear magnetic resonance and scanning electron microscope. It was found that solubility of TEL was increased by 8.53-fold in distilled water; 3.35-fold in 0.1 N HCl and 4.66-fold in phosphate buffer pH 6.8 by incorporating NaHCO₃ in drug–NS complex than TEL. It was found that the NaHCO₃ in NS based complex synergistically enhanced dissolution of TEL by modulating microenvironmental pH and by changing amorphization of the drug. The highest solubility and in vitro drug release was observed in inclusion complex prepared from NS and NaHCO₃. An increase of 54.4 % in AUC was seen in case the ternary NS complex whereas β-CD ternary complex exhibited an increase of 79.65 %.     

In vitro and short-term in vivo characteristics of a Kel-F thin film modified glucose sensor.

A new outer layer composition, consisting of polytetrafluoroethylene (PTFE), Kel-F oil, and Nafion, is suggested to minimize the detrimental effect of dissolved oxygen and to extend the linear response range of a glucose oxidase(GOx)-based sensor using nonconducting polymer. The morphology of Kel-F/PTFE/Kel-F/Nafion polymeric laminate was followed during fabrication by SEM. When Kel-F film was formed on the PTFE outer layer, the linear response was extended to 21 mM, at a sensitivity of 2.8 +/- 0.8 nA/mM mm2. We demonstrate that a sensor without Kel-F/PTFE/Kel-F/Nafion outer layer is relatively oxygen dependent, whereas by comparison a sensor with Kel-F/PTFE/Kel-F/Nafion outer layer is oxygen independent. The current of such a glucose sensor implanted in the subcutaneous tissue stabilized within 60 min, and the lag between blood glucose changes and sensor output was within 1 min. The in vivo characteristics of the glucose sensor described show great promise for one-point in vivo calibration.     

In vitro chemoenzymatic and in vivo biocatalytic syntheses of new beauvericin analogues

New beauvericins have been synthesized using the nonribosomal peptide synthetase BbBEAS from the entomopathogenic fungus Beauveria bassiana. Chemical diversity was generated by in vitro chemoenzymatic and in vivo whole cell biocatalytic syntheses using either a B. bassiana mutant or an E. coli strain expressing the bbBeas gene.     

In vitro and in vivo degradation of an injectable bone repair composite

In vitro and in vivo degradation behaviors of an injectable bone regeneration composite (IBRC) which comprised of nano-hydroxyapatite/collagen (nHAC) particles in alginate hydrogel carrier were investigated. In vitro degradation quantitative testing indicated that the alginate had a faster degradation rate in simulated body fluid (SBF) than in deionized water at 37 °C. Similarly, IBRC also had a higher degradation rate in SBF than in deionized water at 37 °C, which was evaluated by alginate molecular weight measurement, mechanical properties test and degradation kinetics evaluation. But molecular weight of alginate degraded slower in IBRC than that in aqueous solution. In vitro results showed that degradation medium SBF had influence on degradation of alginate molecules. In the in vivo degradation study, surprisingly, there was no obvious decreasing of molecular weight of alginate from 0 to 8 weeks. IBRC degraded mostly after 24 weeks implantation and was replaced by connective tissue. No fibrous capsule and acute inflammatory reaction were found during the observed 24 weeks after IBRC implantation. There is only a mild short-term inflammatory response in rat dorsum muscle. These results indicated that IBRC had a controllable degradability and biocompatibility. Therefore, IBRC may be a promising degradable material for bone repair and bone tissue engineering.     

In vivo anti-inflammatory and in vitro antioxidant activities of Moroccan medicinal plants

Five ethanol extracts of wild plants from the Casablanca region (Morocco) used in local traditional medicine for the treatment of inflammatory diseases were evaluated for their in vivo topical anti-inflammatory activity (inhibition of carrageenan-induced ear edema in mice) and in vitro antioxidant and antiradical properties (inhibition of linoleic acid oxidation, DPPH radical scavenging). All the extracts showed an anti-inflammatory effect: 300 microg/cm2 provoked edema reductions ranging from 22 to 28%. All the extracts also exerted radical scavenging and/or antioxidant properties, the most active plant being Mentha pulegium L. (Lamiaceae), which contained the highest amount of phenolics (339 mg/g), and flavonoids (16.7 mg/g).