Percentage Of Binding Research Articles

CLL Stereotyped Subset #4 Igs Acquire Binding to Viable B Lymphocyte Surfaces By Somatic Mutations, Isotype Class Switching, and with the Prerequisite of IG Self-Association

The selection and transformation of a normal B cell into the leukemic state in chronic lymphocytic leukemia (CLL) is mediated at least in part by the structure of the B cell receptor (BCR) immunoglobulin (IG) antigen binding site. A dramatic indication of the role played by BCR is demonstrated by those CLL cases expressing “stereotyped” BCR IGs, characterized by very similar VH CDR3 amino acid sequences often encoded by specific IGHV, IGHD, and IGHJ gene segments. CLL stereotyped subset #4 BCR IGs expressing IGHV4-34/IGHD5-18/IGHJ6 and IGKV2-30/IGKJ2 rearrangements are prime examples of this. Moreover, these clones are always IgG isotype class switched, and contain IGHV and IGLVκ somatic mutations. Moreover, some of these mutations are shared among patients, and are almost invariably similar physicochemically and located at specific positions in the antigen binding site. In the following study, we evaluated the effects of these unique, acquired structural changes on the (auto)antigenic specificities of subset #4, using 3 mAbs belonging to the subset.Gamma-irradiated Ramos B and Jurkat T cell line cells were incubated with subset #4 IGs under non-permeabilizing conditions, and binding to the B and T cell surfaces was detected by flow cytometry. Unlike most other CLL BCR IGs, the average binding percentage to apoptotic Ramos B cells of subset #4 mAbs was low. Conversely, each subset #4 IG bound live B cells well (CLL 183 - 44.8%; CLL 240 - 55.6%; CLL 342 - 52.0%). Moreover, all 3 IGs exhibited minimum binding to live and apoptotic Jurkat T cells. Next we exposed the subset #4 IGs to viable human B lymphocytes from tonsillectomy samples to confirm that binding was not limited to transformed B cells, and indeed the IGs bound well to CD19+ while minimally to CD3+ tonsil cells. When murine mAbs reactive with appropriate B-cell surface antigens were used to define subpopulations of normal B cells with which the subset #4 IGs interacted, we found that the subset #4 IGs and a non-subset #4 IGHV4-34-expressing CLL case (CLL 141) bound viable, naïve human B cells as expected from other studies. However, it became clear that the subset #4 IGs also interacted with viable memory B cells (CLL 183 - 28.1%; CLL 240 - 34.0%; CLL 342 - 42.7%; CLL 141 - 11.8%), a subpopulation that CLL 141 do not bind; the latter similar to IGHV4-34-expressing IGs in other disease states. Furthermore, although DNA and the “i” and “I” carbohydrate antigens are common targets of IGHV4-34 utilizing antibodies in systemic lupus erythematosus and cold agglutinin disease, respectively, the subset #4 Igs did not bind to either of these autoantigens when tested by ELISA or glycan binding arrays, respectively.Strikingly, subset #4 IG binding to viable Ramos B cells and memory B lymphocytes depended on an asparagine (N) to aspartic acid (D) mutation at position 66 of FR3 in the rearranged IGKV2-30 gene (N vs. D: 5.26% vs. 55.6%); this amino acid residue is shared by many other clones in this subset and comes about by somatic hypermutation (SHM). Interestingly and consistent with the previous finding, another focused mutation of this subset, glutamic acid (E) at position 28 of FR1 in the rearranged IGHV4-34 (G28E), was responsible for the loss of DNA binding and for the diminished I/i glycan binding.Finally, binding to viable Ramos B cells required the presence of the IgG isotype characteristic of this subset, since reactivity with Ramos B lymphocytes disappeared when the stereotyped antigen-binding site was linked to IgM (183, 240, 342 IgG vs. IgM: 44.8%, 55.6%, 51.2% vs. 24.5%, 1.85%, 7.02%, respectively). This requirement for IgG isotype binding to live Ramos B cells is likely due to the documented subset #4 self-association which requires the gamma isotype, since the change of a single amino acid at VH FR1 (E16HA), which disrupts self-association, eliminated binding to Ramos B lymphocytes.Together our findings indicate that distinct autoantigens mediate the positive and negative selection of the structural elements acquired by SHM and isotype class switching that are characteristic of this unique subset of stereotyped BCR IGs. Moreover, our data show that the reactivity of subset #4 IGs with viable B-cell surface requires the self-association of these IGs and, therefore, strongly suggests that viable B-cell surface binding is mediated by a non-conventional binding site created by self-associated surface membrane bound IGs. DisclosuresKolitz:Gilead, Novartis, and Seattle Genetics: Other: Travel Support; Boehringer Ingelheim, Cantex, Erytech, and Millennium: Research Funding; Gilead, Magellan, Novartis, Pharmacyclics, and Seattle Genetics: Consultancy; Gilead, Magellan, and Novartis: Honoraria; Celgene, Jazz: Equity Ownership. Stamatopoulos:Novartis SA: Research Funding; Abbvie: Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen Pharmaceuticals: Honoraria, Research Funding.

Pharmacokinetics, tissue distribution and plasma protein binding rate of palmatine following intragastric and intravenous administration in rats using liquid chromatography tandem mass spectrometry

Palmatine is a natural isoquinoline alkaloid widely found in traditional Chinese medicines. In this study, a simple, sensitive and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the quantification of palmatine in the plasma and tissue samples in rats. Sample preparation involved a simple protein precipitation extraction technique using acetonitrile as the precipitating solvent. Chromatographic separation was accomplished on an ACQUITY UPLC BEH C18 column with a mobile phase of acetonitrile-5 mM ammonium acetate solution (70:30, v/v) at a flow rate of 0.3 mL/min. Coptisine was selected as the internal standard. The protonated analytes were determined with MRM in the positive ion mode. The assay exhibited a linear dynamic range of 1.0−1000 ng/mL for palmatine in each biological matrix and the low limit of quantification was 1.0 ng/mL. Non-compartmental pharmacokinetic parameters indicated that there is a significant difference in the apparent distribution volume and half-life between intragastric and intravenous administration modes. Palmatine could be detected in different tissues and the content in liver and kidney is relatively high, suggesting that liver and kidney might be the targeting organs of palmatine. The plasma protein binding rate test showed that the percent binding of palmatine is medium, and was found to be higher in human than in rats.

Development and characterization of two novel 68 Ga-labelled neuropeptide Y short analogues with potential application in breast cancer imaging.

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8±0.4) for 68 Ga-L1 and (4.7±0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.

Quantum Chemical Studies on Structural, Spectroscopic, Thermochemistry, Photo-physical and Bioactivity Properties of m-Cresol Purple Dye

The m-Cresol purple molecule is analyzed using spectroscopy and quantum computational chemistry methods using the software program Gaussian 09. B3LYP 6-311G (d, p) level has been used to create stable conformation of molecular structure, vibrational frequencies, Mulliken atomic charges, and electronic absorption spectra. The active regions of the infrared intensities, polarizabilities, and first-order polarizabilities were determined. The visible ultrasonic absorption with DOS spectrum demonstrated the highest correlation both before and after UV exposure. Furthermore, ’Frontier’s molecular orbital analysis was determined, explaining the difference between HOMOs and LUMOs energies. Swiss ADME is used to measure physicochemical descriptors and the prediction of molecular dynamics, ADME (absorption, distribution, metabolism, excretion) coefficients, pharmaco-kinetics pH, log P, biological activity, and drug-like nature. Furthermore, the predictive model of BOILED-Egg, QSAR analysis, molecular lipophilicity, distribution of microorganisms, target binding percentages, and topology measurements are analyzed to help drug discovery.

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a glycoprotein present in the prostate, that is overexpressed in prostate cancer (PCa). Recently, PSMA-directed radiopharmaceuticals have been developed, allowing the pinpointing of tumors with the Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging techniques. The aim of the present work was to standardize and validate an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11, as well as to produce a radiopharmaceutical for PET imaging of PCa malignancies. [68Ga]Ga-PSMA-11 was evaluated to determine the radiochemical purity (RCP), stability in saline solution and serum, lipophilicity, affinity to serum proteins, binding and internalization to lymph node carcinoma of the prostate (LNCaP) cells, and ex vivo biodistribution in mice. The radiopharmaceutical was produced with an RCP of 99.06 ± 0.10%, which was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). The product was stable in saline solution for up to 4 h (RCP > 98%) and in serum for up to 1 h (RCP > 95%). The lipophilicity was determined as −3.80 ± 0.15, while the serum protein binding (SPB) was <17%. The percentages of binding to LNCaP cells were 4.07 ± 0.51% (30 min) and 4.56 ± 0.46% (60 min), while 19.22 ± 2.73% (30 min) and 16.85 ± 1.34% (60 min) of bound material was internalized. High accumulation of [68Ga]Ga-PSMA-11 was observed in the kidneys, spleen, and tumor, with a tumor-to-contralateral-muscle ratio of >8.5 and a tumor-to-blood ratio of >3.5. In conclusion, an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11 was standardized and the product was evaluated, thus verifying its characteristics for PET imaging of PCa tumors in a clinical environment.

Optimization of process conditions for the removal of zinc and lead by ultrafiltration using biopolymer

Water pollution by the discharge of industrial effluents containing heavy metal contaminants has become a worldwide environmental problem. The major pollutants present in industrial effluents are Cu(II), Ni(II), Zn(II), Pb(II), and Cr(VI). To protect the environment from the harmful effects of these heavy metals, we need a proficient technology. The size-enhanced ultrafiltration (SEUF) is a competent technique for the removal and recovery of heavy metal contaminants from the effluent. This paper deals with the removal of Zn(II) and Pb(II) by size-enhanced ultrafiltration with biopolymer carboxymethyl chitosan (CMCh). The design of experiments was performed by response surface methodology (RSM). The significance of the process parameters and the predicted model equations have been validated through analysis of variance (ANOVA). The effects of process conditions such as pH of feed solution, loading rate, and concentration of metal ions on percentage retention and binding capacity of CMCh have been investigated. The optimized process parameters have been compared with the experimental findings. The results depict the success of the process in the removal and recovery of Zn(II) and Pb(II) by SEUF using carboxymethyl chitosan. The characteristics of CMCh complexation with metal ions have been analyzed through SEM and EDAX and FTIR.

Synthesis and characterization of tetracycline-imprinted membranes: A detailed positron annihilation lifetime spectroscopy investigation.

Molecularly imprinted thin membranes for selective removal of tetracycline from real water samples were prepared using the radiation-induced polymerization method. The chemical and physical characterization of the membranes was conducted by FTIR, XPS, AFM and SEM analyses. The effect of the template on the size and the size distribution of the pores in the membrane structure was investigated by positron annihilation lifetime spectroscopy (PALS) experiments. The presence of the template molecule causes the formation of larger cavities, which have a strong correlation to the molecular size of the template molecule. The density of the free volume holes in the imprinted network shows a significant increase due to the presence of the template molecule. The binding performances of the membranes were tested against various factors such as pH, time and initial concentration of template molecules. The specific selectivity of the membranes was investigated by cross-reactivity experiments. The binding capacity of the imprinted membranes was obtained at 14.5μmol g-1 , with the highest imprinting factor (2.84) for tetracycline. The imprinting factor was obtained at 1.44, 1.25 and 1.57 for oxytetracycline hydrochloride, doxycycline hyclate and chlortetracycline, respectively. The binding capability of the imprinted membranes in real water samples was promising for the application of the membranes as a filter material for removal of tetracycline with high binding capacity. Tetracycline binding percentage of the membranes was determined at 92.4, 81.1., 75.0 and 68.7 for ultra-pure water, tap water and natural water samples collected from different sources, respectively.

Magnetic Fe0/iron oxide-coated diatomite as a highly efficient adsorbent for recovering phosphorus from water

A mild hydrothermal method to functionalize diatomite with Fe0/iron oxide nanoparticles (Fe0/FeOx-DE) was attempted and its performance as a new magnetic adsorbent to recover phosphorus from water was investigated in batch studies. The method effectively improved the dispersion of nanoparticles, and the adsorption capacity increased from 3.51 mg P/g for raw diatomite to 37.0 mg P/g for Fe0/FeOx-DE. Transmission electron microscope (TEM) and X-ray diffraction (XRD) showed that Fe0/FeOx nanoparticles had been successfully loaded onto the diatomite. Solution pH largely affected phosphorus recovery efficiency, it had a better effect around pH 7–9. Data of adsorption experiments were fitted well to Langmuir isotherm model and pseudo-second-order kinetic model, and the process was spontaneous and endothermic at thermodynamic study. After Fe0/FeOx-DE was regenerated three times by NaOH solution, the phosphorus binding percentage remained at 66.8%. Fe0/FeOx-DE also displayed an excellent selectivity for P in examination of coexisting anions except SO42-. The adsorption mechanism was interpreted by electrostatic attraction, chemical precipitation and ligand exchange. This study on immobilising Fe0/iron oxide particles onto diatomite opens a new avenue for the practical application of iron-loaded compounds and the phosphate-loaded composites can be used as a fertilizer or soil amendment directly to achieve phosphorus recovery.

Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses.

BackgroundFirst‐generation cephalosporins have good activity against gram‐positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses.ObjectiveTo optimise the dosages of the two first‐generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts.Study designExperimental study with single administration.MethodsDrug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six horses were measured using LC‐MS/MS. Data were modelled using a nonlinear mixed effect modelling followed by Monte Carlo simulations. Minimum inhibitory concentrations (MICs) against Streptococcus zooepidemicus and Staphylococcus aureus isolated from horses were determined by the microbroth dilution method.ResultsThe percentages of CET and CEZ binding to serum proteins were 19.9% ± 8.4% and 15.2% ± 8.5% respectively. For both CET and CEZ, the MIC90 against S. zooepidemicus was 0.12 mg/L and against S. aureus was 0.5 mg/L. For CET, to achieve a probability of target attainment (PTA) of 90% for a PK/PD target of a free serum plasma concentration exceeding the MIC90 for 40% of the dosing interval, an empirical CET dosage regimen of 22 mg/kg bwt q8h and 22 mg/kg bwt q4h i.v. administration were required for S. zooepidemicus and S. aureus respectively. For CEZ, the corresponding dosage regimens were 10 mg/kg bwt q12h and 10 mg/kg bwt q8h.Main limitationsSmall sample size only in healthy horses.ConclusionsFor CET, more frequent administration than that currently recommended (22 mg/kg bwt q6–12h) is required to empirically control S. aureus infection in horses. For CEZ, less frequent administration compared to the dosage regimen currently proposed (10–22 mg/kg bwt q6h) could control S. zooepidemicus and S. aureus infections in horses.

The In Vitro Adsorption Ability of Lactobacillus acidophilus NCFM to Benzo(a)pyrene in PM2.5.

The objective of this work was to explore the ability of lactic acid bacteria strains to bind benzo(a)pyrene (B(a)P) existing in PM2.5. In this study, we examined the ability of Lactobacillus acidophilus NCFM to bind B(a)P in the simulated PM2.5 environment. Among the tested 5 strains, Lactobacillus acidophilus NCFM exhibited the best capacity to bind B(a)P, and its B(a)P binding percentage was 60.00%. Simulations of organic and inorganic systems which represent PM2.5 indicated that B(a)P could be absorbed by strain L. acidophilus NCFM. For the inorganic system of pH 5, L. acidophilus NCFM bound 92.74% B(a)P with a cell concentration of 1 × 1010 cfu/mL at 37°C for 8 hr. Regarding the organic system with pH 6, 73.00% B(a)P was bound by strain L. acidophilus NCFM after this bacterium was incubated at 37°C for 10 min. A quick B(a)P binding by this probiotic bacterium took place in the organic system. The removal of B(a)P from PM2.5 was significantly related to incubation time, cultivation temperature, pH, and cell concentration. Thus, our finding shows that long-term consumption of L. acidophilus NCFM is beneficial for the reduction of B(a)P towards the population who are exposed to PM2.5, although the ability of this bacterium to adsorb B(a)P is partly affected by the differences in the origin of PM2.5.

Platelet hyaluronidase 2 enrichment in acute coronary syndromes: a conceivable role in monocyte-platelet aggregate formation

Acute Coronary Syndromes (ACS) with plaque erosion display dysregulated hyaluronan metabolism, with increased hyaluronidase-2 (HYAL2) expression. However, the expression and the role of this enzyme on platelets has never been explored. We evaluated the platelet’s HYAL2 (pltHYAL2) levels on I) stable angina (SA) and II) ACS patients, furtherly sub-grouped in Intact-Fibrous-Cap (IFC) and Ruptured-Fibrous-Cap (RFC), according to Optical Coherence Tomography. We assessed the HYAL2 role through an in vitro model setting of co-cultured monocytes and platelets, before and after treatment with low-molecular-weight hyaluronic acid (HA) as pro-inflammatory stimulus and with or without HYAL2-antibody to inhibit HYAL2 activity. ACS patients exhibit higher pltHYAL2 levels comparing to SA, with the higher expression for IFC group. The addition of HYAL2-antibody significantly reduced the percentage of monocyte-platelet binding, suggesting that pltHYAL2 enrichment at the site of the culprit lesion is a key mediator in the systemic thrombo-inflammatory status of ACS presenting with plaque erosion.

Aflatoxin B1 and Sterigmatocystin Binding Potential of Non-Lactobacillus LAB Strains.

Research on the ability of lactic acid bacteria (LAB) to bind aflatoxin B1 (AFB1) has mostly been focusing on lactobacilli and bifidobacteria. In this study, the AFB1 binding capacities of 20 Enterococcus strains belonging to E. casseliflavus, E. faecalis, E. faecium, E. hirae, E. lactis, and E. mundtii, 24 Pediococcus strains belonging to species P. acidilactici, P. lolii, P. pentosaceus, and P. stilesii, one strain of Lactococcus formosensis and L. garviae, and 3 strains of Weissella soli were investigated in MRS broth at 37 °C at 0.2 µg/mL mycotoxin concentration. According to our results, among non-lactobacilli LAB, the genera with the best AFB1 binding abilities were genus Pediococcus, with a maximum binding percentage of 7.6% by P. acidilactici OR83, followed by genus Lactococcus. For AFB1 bio-detoxification purposes, beside lactobacilli, pediococci can also be chosen, but it is important to select a strain with better binding properties than the average value of its genus. Five Pediococcus strains have been selected to compare their sterigmatocystin (ST) binding abilities to AFB1 binding, and a 2–3-fold difference was obtained similar to previous findings for lactobacilli. The best strain was P. acidilactici OR83 with 18% ST binding capacity. This is the first report on ST binding capabilities of non-Lactobacillus LAB strains.

A chromatographic approach to development of 5-aminosalicylate/folic acid fixed-dose combinations for treatment of Crohn\u2019s disease and ulcerative colitis

Medication adherence is an important factor in inflammatory bowel disease therapy, which includes regular supplementation of malabsorbed vitamins. Absorption of folic acid is limited due to the damaging of the gastrointestinal tract, which can increase the chances to develop megaloblastic anaemia and colorectal cancer. In this work, 5-aminosalicylates (mesalazine, balsalazide, sulfasalazine and olsalazine) and folic acid were characterized regarding their pharmacokinetic related properties (hydrophobicity, phospholipid and plasma protein binding) using the biomimetic chromatographic approach. Despite the high binding percentage of 5-aminosalicylates for human serum albumin (> 61.44%), results have shown that folic acid binding to human serum albumin protein is far greater (69.40%) compared to α1-acid-glycoprotein (3.45%). Frontal analysis and zonal elution studies were conducted to provide an insight into the binding of folic acid to human serum albumin and potential competition with 5-aminosalicylates. The analytical method for the simultaneous determination of assay in proposed fixed-dose combinations was developed and validated according to ICH Q2 (R1) and FDA method validation guidelines. Separation of all compounds was achieved within 16 min with satisfactory resolution (Rs > 3.67) using the XBridge Phenyl column (150 × 4.6 mm, 3.5 µm). High linearity (r > 0.9997) and precision (RSD < 2.29%) was obtained, whilst all recoveries were within the regulatory defined range by British (100.0 ± 5.0%) and United States Pharmacopeia (100.0 ± 10.0%).

Peptide Ligands Specifically Targeting HER2 Receptor and the Role Played by a Synthetic Model System of the Receptor Extracellular Domain: Hypothesized Future Perspectives.

A short (Fab)trastuzumab-derived peptide specific for HER2 receptor was identified. Its affinity for the model system HER2-DIVMP was found in a nanomolar range. The structural determinants responsible for the interaction between this ligand (A9) and HER2-DIVMP were investigated by both computational and NMR analysis. Next, the possibility of using A9 as HER2- specific probe for the nuclear medicine imaging was evaluated by conjugating A9 with the DTPA chelator and radiolabeling it with 111In. The developed probe retained a nanomolar affinity to HER2-overexpressing cancer cells, however, some unspecific binding also occurred. The peptide internalization into cells by receptor-mediated endocytosis was also studied. Future perspectives are aimed at using A9 as a probe for molecular imaging diagnostics as well as active targeting of anticancer drugs. Lead structure optimization is needed to minimize the percentage of A9 unspecific binding and to increase the binding affinity to the receptor.

Tight sorption of arsenic, cadmium, mercury, and lead by edible activated carbon and acid-processed montmorillonite clay.

Heavy metal exposure in humans and animals commonly occurs through the consumption of metal-contaminated drinking water and food. Although many studies have focused on the remediation of metals by purification of water using sorbents, limited therapeutic sorbent strategies have been developed to minimize human and animal exposures to contaminated water and food. To address this need, a medical grade activated carbon (MAC) and an acid processed montmorillonite clay (APM) were characterized for their ability to bind heavy metals and mixtures. Results of screening and adsorption/desorption isotherms showed that binding plots for arsenic, cadmium, and mercury sorption on surfaces of MAC (and lead on APM) fit the Langmuir model. The highest binding percentage, capacity, and affinity were shown in a simulated stomach model, and the lowest percentage desorption (< 18%) was shown in a simulated intestine model. The safety and protective ability of MAC and APM were confirmed in a living organism (Hydra vulgaris) where 0.1% MAC significantly protected the hydra against As, Cd, Hg, and a mixture of metals by 30-70%. In other studies, APM showed significant reduction (75%) of Pd toxicity, compared with MAC and heat-collapsed APM, suggesting that the interlayer of APM was important for Pb sorption. This is the first report showing that edible sorbents can bind mixtures of heavy metals in a simulated gastrointestinal tract and prevent their toxicity in a living organism. Graphical abstract.

In vitro and in vivo capacity of yeast-based products to bind to aflatoxins B1 and M1 in media and foodstuffs: A systematic review and meta-analysis

The aflatoxins are hepatotoxic and carcinogenic metabolites produced by Aspergillus species during growth on crop products. In this regard, a systematic review to collect the quantitative data regarding the in vitro capacity of yeasts-based products to bind to aflatoxin B1 (AFB1) and/or aflatoxin M1 (AFM1) was performed. After screening, 31 articles which met the inclusion criteria was included and then the pooled decontamination of aflatoxins in the defined subgroups (the type of foods, pH, contact time, temperature, yeast species, and aflatoxin type) was calculated by the random effect model (REM). The overall binding capacity (BC) of aflatoxins by yeast was 52.05% (95%CI: 49.01–55.10), while the lowest and highest aflatoxins’ BC were associated with Yeast Extract Peptone (2.79%) and ruminal fluid + artificial saliva (96.21%), respectively. Regarding the contact time, temperature, pH and type of aflatoxins subgroups, the binding percentages varied from 50.83% (>300 min) to 52.66% (1–300 min), 50.71% (0–40 °C) to 88.39% (>40 °C), 43.03% (pH: 3.1–6) to 44.56% (pH: 1–3) and 59.35% (pH > 6), and 48.47% (AFB1) to 69.03% AFM1, respectively. The lowest and highest aflatoxins’ BC was related to C. fabianii (18.45%) and Z. rouxii (86.40%), respectively. The results of this study showed that variables such as temperature, yeast, pH and aflatoxin type can be considered as the effective factors in aflatoxin decontamination.

Characterization of Bioactive Ligands with Antioxidant Properties of Kiwifruit and Persimmon Cultivars Using In Vitro and in Silico Studies

The current study attempted to understand the interaction profiles of phytoconstituents in new and traditionally used fruit cultivars with human serum albumin (HSA) in the context of predicting the biological role under in vivo conditions. Therefore, polyphenols, flavonoids, flavanols, tannins, vitamin C, secondary metabolites and their antioxidant capacities of organic kiwifruit Actinidia (A.) eriantha cv. Bidan (AEB) and A. arguta cv. Cheongsan (AAC), as new cultivars grown in Korea, and widely consumed A. deliciosa cv. Hayward (ADH) and Diospyros kaki Thunb. cv. Fuyu (DKF) were determined and compared. All investigated fruits showed relatively high antioxidant capacities. To complement the bioactivity of these fruits, the binding properties between extracted polyphenols and HSA were determined by 3D-fluorescence spectroscopy and docking studies. The most bioactive was AEB with the highest percentage of binding, following by AAC, ADH and DKF. Our study for the first time unveils the differential binding properties of kiwifruit and persimmon phytoconstituents with HSA. Although cultivars possess virtually the same phytoconstituents, presence of one unique compound significantly alters the binding properties of HSA. The results of fluorescence quenching and molecular docking showed that these fruits possess multiple properties, which have a great potential to be used in industry with emphasis on the formulation of functional foods and medicinal applications.

Determining the Drug-Like Properties of Ailanthone, a Novel Chinese Medicine Monomer with Anti-CRPC Activity.

Approximately 40% of compounds with therapeutic potential cannot be successfully developed into drugs owing to their poor pharmaceutical properties, emphasising the need to profile their drug-like properties as early as possible during preclinical development. This study aimed to evaluate the drug-like properties of ailanthone, a novel Chinese medicine monomer that was shown to have activity against castration-resistant prostate cancer tumour growth and metastasis in our previous study. The drug-like properties detected in the present study included effects on permeability, liver microsome stability, plasma protein binding rate, plasma stability, and human ether-à-go-go-related gene inhibition. Additionally, the following results were obtained: the efflux ratio of ailanthone was > 32 during permeability detection; the half-life and intrinsic clearance (Clint) in mouse, rat, and human liver microsomes were > 145 min and < 9.6 µL/min/mg protein, respectively. The Clint(liver) of ailanthone was < 38.0, < 17.3, and < 8.6 mL/min/kg body weight in mice, rats, and humans, respectively. The plasma protein binding percentage of ailanthone was 16.6 ± 4.2% in human plasma, with 62.5% remaining at 120 min after incubation. The IC50 value of ailanthone for the human ether-à-go-go-related gene channels was > 30 µM. Collectively, these results and those from our previous study indicate that the pharmacokinetic properties of ailanthone are suitable for the potential development of this compound as an oral or intravenous drug for the treatment of castration-resistant prostate cancer.

Antioxidant and Glucose Lowering Effects of Hydroethanolic Extract of Baillonella toxisperma Pulp

Hyperglycemia and oxidative stress play an important role in the pathogenesis of diabetes. Their management is a key point in the prevention and treatment of this disease which is a potential cause of mortality in the world. We evaluated the antioxidant and glucose lowering effects of hydroethanolic extract of Baillonella toxisperma pulp. The total polyphenol and flavonoid contents were determined and the antioxidant activity was evaluated by 3 mechanisms: scavenging by DPPH•, ABTS• and NO• radicals; reducing property by MoO42+ and Fe3+ reduction; metal chelation by Cu2+ and Fe2+. Glucose adsorption capacity was evaluated followed by the capacity to promote insulino-sensitivity through glucose uptake by yeast and muscle cell assays. The hydroethanolic extract of B. toxisperma pulp possessed high total polyphenols and flavonoids; 459.55 µg Equivalent Gallic Acid/mg and 252.15 µg of Equivalent Catechin /mg respectively. This showed their ability to scavenge DPPH•, ABTS• and NO• radicals with SC50 of 3.49, 3.24 and 4.28 mg/ml respectively. The extract also reduced MoO42+ and Fe3+ and chelated Cu2+ through inhibiting their capacity to induce hemolysis with the IC50 of 3.49 mg/ml. The extract showed a high glucose binding capacity with a glucose binding percentage rise of 60 %. It increased yeast cell absorption of glucose with the increasing percentage varying from 42.97 to 56.62 %. In the muscle cells, after 30 min of administration of the extract, we also noted an increased glucose absorption with the percentage glucose reducing to 22 %. We demonstrated that hydroethanolic extract of B. toxisperma pulp possess antiradical, reducing, metal chelating, glucose binding and insulino-sensitivity promoting properties. These mechanisms imply that B. toxisperma pulp is both a good antioxidant and an antihyperglycemiant, thus a potential agent in the management of diabetes and its complications.

Pharmacokinetic profiles of amoxicillin trihydrate in freshwater crocodiles (Crocodylus siamensis) after intramuscular administration at two doses.

The aim of the present study was to elucidate the pharmacokinetic profiles of amoxicillin trihydrate (AMX) in Siamese freshwater crocodiles (Crocodylus siamensis). Crocodiles were administered a single intramuscular injection of AMX, at a dose of either 5 or 10mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 120hr. The plasma concentrations of AMX were measured using a validated liquid chromatography tandem-mass spectrometry method. AMX plasma concentrations were quantifiable for up to 72hr (5mg/kg b.w.) and 96hr (10mg/kg b.w.). The elimination half-life (t1/2λ z ) of AMX following dosing at 5mg/kg b.w. (8.72±0.61hr) was almost identical to that following administration at 10mg/kg b.w (8.98±1.13hr). The maximum concentration and area under the curve from zero to the last values of AMX increased in a dose-dependent fashion. The average binding percentage of AMX to plasma protein was 21.24%. Based on the pharmacokinetic data, susceptibility break point, and the surrogate PK-PD index (T>MIC, 0.25 μg/ml), intramuscular administration of AMX at dose of 5mg/kg b.w. every 4days might be appropriate for the treatment of susceptible bacterial infections in freshwater crocodiles.