The complete genome of 2,6-dichlorobenzamide (BAM) degrader Aminobacter sp. MSH1 suggests a polyploid chromosome, phylogenetic reassignment, and functions of plasmids

Aminobacter sp. MSH1 (CIP 110285) can use the pesticide dichlobenil and its recalcitrant transformation product, 2,6-dichlorobenzamide (BAM), as sole source of carbon, nitrogen, and energy. The concentration of BAM in groundwater often exceeds the threshold limit for drinking water, requiring additional treatment in drinking water treatment plants or closure of the affected abstraction wells. Biological treatment with MSH1 is considered a potential sustainable alternative to remediate BAM-contamination in drinking water production. We present the complete genome of MSH1, which was determined independently in two institutes at Aarhus University and KU Leuven. Divergences were observed between the two genomes, i.e. one of them lacked four plasmids compared to the other. Besides the circular chromosome and the two previously described plasmids involved in BAM catabolism, pBAM1 and pBAM2, the genome of MSH1 contained two megaplasmids and three smaller plasmids. The MSH1 substrain from KU Leuven showed a reduced genome lacking a megaplasmid and three smaller plasmids and was designated substrain MK1, whereas the Aarhus variant with all plasmids was designated substrain DK1. A plasmid stability experiment indicate that substrain DK1 may have a polyploid chromosome when growing in R2B medium with more chromosomes than plasmids per cell. Finally, strain MSH1 is reassigned as Aminobacter niigataensis MSH1.

Recent Progress of Oridonin and Its Derivatives for the Treatment of Acute Myelogenous Leukemia

First stage human clinical trial (CTR20150246) for HAO472, the L-alanine-(14-oridonin) ester trifluoroacetate, was conducted by a Chinese company, Hengrui Medicine Co. Ltd, to develop a new treatment for acute myelogenous leukemia. Two patents, WO2015180549A1 and CN201410047904.X, covered the development of the I-type crystal, stability experiment, conversion rate research, bioavailability experiment, safety assessment, and solubility study. HAO472 hewed out new avenues to explore the therapeutic properties of oridonin derivatives and develop promising treatment of cancer originated from naturally derived drug candidates. Herein, we sought to overview recent progress of the synthetic, physiological, and pharmacological investigations of oridonin and its derivatives, aiming to disclose the therapeutic potentials and broaden the platform for the discovery of new anticancer drugs.

Structural characteristics and physicochemical properties of fresh-water fish gelatins with different molecular weights and their potential application to food capsule film fabrication

This work is aimed to investigate the effects of molecular weights on physicochemical properties of fish gelatins and their potential application to food capsule film fabrication. Firstly, high/medium/low component fish gelatins (HCG/MCG/LCG) were obtained by ultrafiltration. Physicochemical property assay results showed that high molecular weight content of gelatin contributed to the increase in gelling strength, viscosity, melting point, and denaturation temperature due to extensive inter–intra molecular interactions. Meanwhile, parameters (temperature, weight ratio, and drying time) had been comprehensively investigated to determine the effects of three molecular weights of gelatins on capsule film manufacture. MCG-derived capsule film was found to achieve good balance among tensile strength, elongation at break, and dissolution rate constant. Furthermore, 90-day acceleration storage stability experiment suggested that MCG showed an appropriate ɛ-amino acid residue content and crosslink density. This work provides a comprehensive insight into the effect of molecular weights on physicochemical properties of fish gelatins and their application in food capsule film manufacture.

Solubility and stability of melatonin in propylene glycol, glycofurol, and dimethyl sulfoxide

Introduction: Local administration of melatonin might prove useful in future clinical studies. Melatonin possesses poor solubility and stability in aqueous solutions. The aim of this study was to investigate the solubility and stability of melatonin when dissolved in glycofurol, propylene glycol, and dimethyl sulfoxide (DMSO). Methods: Two experiments were performed: solubility and stability. In the solubility experiment, we dissolved melatonin in 20% propylene glycol and 20% glycofurol solutions, respectively. For the stability experiment, we prepared three different formulations: melatonin and glycofurol (20% w/w, 10 mg/g); melatonin, glycofurol, and DMSO (20%, 40% w/w, 10 mg/g); and melatonin and DMSO (50% w/w, 1 mg/g). All three solutions were stored at 25°C for 45 days. Concentrations of melatonin in all solutions were measured through high-performance liquid chromatography. Results: Melatonin demonstrated poor solubility in propylene glycol (3.6–3.8 mg/g) and better solubility in glycofurol (10.5–11.1 mg/g). All three formulations of the stability experiment showed no degradation of melatonin over 45 days. Discussion: Glycofurol and DMSO provide better solubility and stability than aqueous solutions. The formulations used in this experiment have adequate stability to be used in clinical trials.

IN VITRO ANTI-INFLAMMATORY ACTIVITY TEST OF TINOCRISPOSIDE AND FREEZE-DRIED AQUEOUS EXTRACT OF TINOSPORA CRISPA STEMS ON HUMAN RED BLOOD CELL BY INCREASING MEMBRANE STABILITY EXPERIMENT

Objective: This study was aimed to evaluate the anti-inflammatory effect of isolated tinocrisposide and freeze-dried aqueous extract of Tinospora crispa stems on human red blood cell (HRBC) by increasing membrane stability in vitro models. Methods: Anti-inflammatory effect of tinocrisposide and FDAETCS was evaluated by in vitro HRBC membrane stabilization method. The study was separated into two steps which were a hemolytic and a membrane stabilization experiment. The hemoglobin that was released throughout the damaged erythrocytes membrane was then quantified at the wavelength of (λ) 560 nm. Results: The hemoglobin in the HBRC supernatant that treated with tinocrisposide at concentration of 100, 200, 400, 600, 800, and 1000 μg/ml showed an absorbance at λ 560 nm of 0.060, 0.061, 0.071, 0.072, 0.075, and 0.0793, respectively, and the calculated hemolysis percentage was 0.032, 0.097, 1.203, 1.236, 1.641, and 2.079%, respectively. We found a linear correlation between concentration and hemolytic activity of tinocrisposide, with regression equation, y=0.0023x−0.1312 (r=0.929). Meanwhile, the HBRC supernatant that treated with FDAETCS at concentration of 100, 200, 400, 600, and 800 μg/ml showed an absorbance at λ 560 nm of 0.063, 0.064, 0.066, 0.067, and 0.077, respectively, and revealed the hemolytic percentage of 0.347, 0.473, 0.693, 0.992, and 1.896%, respectively. It also gave a linear correlation between FDAETCS concentration and hemolytic activity percentage, with regression equation, y=0.002x+0.0222 (r=0.895). Moreover, in HRBC membrane stability experiment, tinocrisposide concentration of 100, 200, 400, 800, and 1000 μg/ml gave absorbance at λ 560 nm of 0.818, 0.808, 0.798, 0.789, 0.773, and 0.761, respectively, and calculated HRBC membrane stabilization activity as much as 5.437, 6.533, 7.707, 8.748, 10.597, and 12.100%, respectively. Meanwhile, the positive control ibuprofen 25 μg/ml only exerted the membrane stability of 5.620%. It was found a linear correlation between tinocrisposide concentration and membrane stability percentage, with the regression equation, y=0.0072x+4.8312 (r=0.9932). Treated FDAETCS in the concentration of 100, 200, 400, and 800 μg/ml gave the absorbance at λ 560 nm of 0.802, 794, 0.777, 0.791, and 0.792, with stability membrane percentage of 7.283, 8.208, 10.944, 8.555, and 8.401%, respectively. It can be seen that the FDAETCS concentrations and its hemolytic percentage showed a parabolic relationship, which gave a maximum at a concentration of the extract of 400 mg/ml with membrane stabilizing of 10.944%. Conclusion: It can be concluded that tinocrisposide and FDAETCS have an anti-inflammatory activity by increase the membrane stability of lysosome cell that has equal physiological properties with erythrocytes membrane cell and it has no hemolytic activity.

Design Method for Proportion of Cement-Foamed Asphalt Cold Recycled Mixture

Through foaming experiment of Zhongtai AH-70 asphalt, the best foaming temperature water consumption and influence factors of foamed asphalt’s foaming features are determined; By designing the proportion of foamed asphalt cold in-place recycled mixture combined with the water stability experiment, for this mixture the best foamed asphalt addition is 3%, and proportion of the mixture is RAP: fine aggregate: cement=75:23:2. Using SEM technology, the mechanism of increasing on the intensity of foamed asphalt mixture resulted by the addition of cement was analysed. This research provides reference for cement admixture’s formulation in the designing of foamed asphalt cold in-place recycled mixture.

Performance on Water Stability of Cement-Foamed Asphalt Cold Recycled Mixture

Through designing the mixture proportion of foamed asphalt cold in-place recycled mixture combined with the water stability experiment, it shows that the addition of cement can obviously improve foamed asphalt mixture’s water stability and the best cement admixture is between 1% ~ 2%; Using digital imaging microscope and SEM technology, the mechanism of increasing on the intensity of foamed asphalt mixture resulted by adding cement was analyzed. It revealed that the cement hydration products contained in the foamed asphalt mixture hydrolyzed into space mesh structure and wrapped up the aggregate particle, this is the main reason that the cement can enhance the mixture’s intensity as well as the water stability. This research provides reference for cement admixture’s formulation in the designing of foamed asphalt cold in-place recycled mixture.

Training a Drug to Do New Tricks: Insights on Stability of Meropenem Administered as a Continuous Infusion

Background: The antibiotic armamentarium used to combat multi-drug resistant organisms (MDROs) include carbapenems. Continuous infusion (CI) dosing is frequently employed to maximize beta-lactam efficacy; however, use of meropenem CI has been limited due to concerns with product instability. Objective: The primary objective of this study was to quantify meropenem serum concentrations to reflect drug stability when administered as CI over 8- or 12-h exchanges. In addition, a stability experiment was performed to further establish meropenem integrity over 12 h. The secondary objectives were to assess the ability of meropenem to achieve target pharmacokinetic/pharmacodynamic (PK/PD) exposures relative to the minimum inhibitory concentration (MIC) of the pathogen, and to determine clinical cure. Methods: This was a retrospective, observational study on use of CI meropenem (infused either over 8- or 12- h) at a 1% concentration. The stability experiment was conducted on 1% meropenem at room temperature. Results: In 22 patients, a median meropenem daily dose of 6 g/day (range 2-6 g/day) resulted in a median serum concentration of 17.8 mg/L (interquartile range, 9.3-27.8 mg/L). In 95% of cases, meropenem delivered as CI resulted in free drug concentrations at or above the MIC of the pathogen for the entire dosing interval. Clinical cure was achieved in 80% of patients included in this review. The stability experiment revealed negligible drug degradation at the end of the 12-h dosing interval. Conclusions: The data from this study provides compelling evidence for the use of meropenem as CI utilizing either a 12- or 8-h exchange process.