Effect of wet-aging on meat quality and exudate metabolome changes in different beef muscles.

The aim of this study was to evaluate meat quality and changes in the meat exudate metabolome of different beef muscles (5 d postmortem, longissimus lumborum and psoas major muscles) during wet-aging (additional 3, 7, 14, 21, and 28 d of aging). Shear force of meat declined significantly (P < 0.001) with aging, meanwhile, increased myofibril fragmentation index, lipid and protein oxidation with aging were observed (P < 0.01). Psoas major (PM) showed significantly higher (P < 0.05) purge loss, centrifugal loss, and cooking loss, as well as higher tenderness and more severe lipid and protein oxidation (P < 0.01) than longissimus lumborum (LL) during aging. Principal component analysis of the metabolomic profiles revealed distinct clusters according to the period of aging and the type of muscle simultaneously. Overabundant amino acids, peptides, oxidized fatty acids, and hydroxy fatty acids were found in long-term aged meat exudates, and forty metabolites were significantly correlated with meat quality characteristics. Fifty-nine metabolites were significantly affected by muscle type. These results demonstrated the potential possibility of evaluating meat quality using meat exudate metabolomics.

Effects of different doses glimepiride intake on the pharmacokinetics of benzbromarone in rats.

Benzbromarone (BNR) is prescribed for the management of hyperuricemia, whereas glimepiride (GLM) for the treatment of Type 2 Diabetes Mellitus. Both drugs are certified to be mainly metabolized via cytochrome P450 (CYP) 2C9 in vivo and may have the potential drug-drug interactions. This study aims to investigate the possible influence of orally administered low- and high-dose glimepiride (GLM) on pharmacokinetic characteristics (PK) of benzbromarone (BNR) in rats. Fifteen rats were randomly assigned to group A, B and C (n=5) and administered 0.5% sodium carboxymethyl cellulose (CMC), 0.5mg/kg GLM (low-dose) and 1.0 mg/kg GLM (high-dose) once daily for 8 days, respectively, which were all followed with a single oral dose of BNR (9.0 mg/kg) on the day 8th. Blood samples were obtained from retro orbital plexus at the time points of 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12 and 24h and BNR in plasma was quantitated by HPLC-MS/MS assay. Resultantly a slight influence of GLM on PK of BNR could be found in rats. When compared with Group A, the half-life time (t1/2z) of BNR in Group B and C significantly decreased 52.39% and 73.49%, respectively, although other major PK parameters were negligibly changed by co-administration of GLM. On the whole, the combinational therapy of GLM at low or high dose would notably alter the elimination of BNR and the effect was dose-dependent.

Intra-articular injection PLGA blends sustained-release microspheres loaded with meloxicam: preparation, optimization, evaluation in vitro and in vivo.

Meloxicam (MLX) is a commonly used drug in the clinical treatment of osteoarthritis, but it is associated with gastrointestinal adverse reactions. Therefore, in this study, we developed a sustained-release microsphere formulation of MLX for topical administration of knee joint. The MLX-loaded PLGA microspheres (MLX-MS) were prepared by emulsion solvent evaporation method with optimization of formulation using orthogonal experimental design. Physicochemical characterization results show MLX-MS were spherical with a smooth surface, the particle size was about 100 µm, drug loading was 30%, and encapsulation efficiency was 76.8%. In addition, the in vivo pharmacokinetics, tissue distribution, and pharmacodynamics were evaluated in rats by intra-articular administration of MLX. The microspheres showed a typical long-term sustained release pattern with a low initial burst release. In contrast to oral administration, local injection of MLX-MS produced a much higher value of elimination half-life time(T1/2) and peak time (Tmax) in plasma, while the intestinal drug distribution was significantly decreased. MLX-MS could also cause a greater reduction in the body level of IL-6 and TNF-α, which was positively correlated with R2=0.981. A good linear relationship (R2 = 0.9945) between the in vitro and in vivo drug release from MLX-MS could be observed, bivariate correlation analysis. All the findings demonstrated that local administration of MLX-MS can prolong the action time of MLX and reduce side effects, thus would be a promising preparation for the treatment of arthritis.

Combination effect of azithromycin with TCM preparation Xiyanping injection against Klebsiella pneumoniae infection in rats.

BACKGROUND: Klebsiella pneumoniae is known as one of the most principal opportunistic human pathogens. Although antibiotics such as the first-line agent azithromycin (AZM) usually are efficient for the treatment of K. pneumonia-related infections, growing threat from antibiotic resistance has become a major challenge. Various preparations based on traditional Chinese medicine (TCM) clinical experience have been developed to help combat such a global public health threat, including Xiyanping injection (XYP) that is made from the natural product andrographolide with potent heat-clearing and toxin-resolving functions. PURPOSE: The present study aimed to demonstrate the therapeutic potential, as well as the action of mechanism of AZM in combination with XYP against K. pneumonia infection in rats. METHODS: Pneumonia model of K. pneumoniae infection in rats was established and subjected to various treatments. The lung histopathological lesions were evaluated. ELISA and Griess techniques were used to determine the level of crucial cytokines. The protein expressions of MAPKs and NF-κB pathways were analyzed by Western blotting. RESULTS: The combination in vivo could significantly inhibit the proliferation of K. pneumoniae in lung, improve the pathological changes of lung and reduce inflammatory factors in lung homogenate and bronchoalveolar lavage fluid, mainly by inactivating MAPKs and NF-κB signaling pathways. Combination therapy caused one-fold increase in apparent distribution volume of AZM in rats after multiple dosing, along with a significant increase of AZM level in lungs but obvious decrease in livers. CONCLUSION: The combination therapy of AZM and XYP showed increased antibacterial and anti-inflammatory properties, indicating that it might be used to treat K. pneumoniae infection.

Combination Therapy with TCM Preparation Kumu Injection and Azithromycin against Bacterial Infection and Inflammation: In Vitro and In Vivo.

Background: Azithromycin (AZM) is one of the most common broad-spectrum antibiotics. However, drug resistance is increasing and combination therapy has attracted great attention. AZM is usually combined with traditional Chinese medicine (TCM) preparations with heat-clearing and detoxifying effects, including Kumu injection (KM) made from Picrasma quassioides (D. Don) Benn. Purpose: The present study aimed to investigate synergistic antimicrobial and anti-inflammatory activities of KM plus AZM with the aim of understanding the mechanism of clinical efficacy of combination regimens. Methods: Seven common bacterial clinical isolates and LPS-induced RAW 264.7 cells were used for assay of in vitro potency. The minimum inhibitory concentration (MIC) was determined for each drug, followed by synergy testing through the checkerboard method and fractional inhibitory concentration index (FICI) for quantifying combined antibacterial effects. The rat model of Klebsiella pneumoniae-induced pneumonia was developed and subjected to various drug treatments, namely, AZM, KM, or AZM plus KM, intravenously administered at 75 mg/kg once a day for one week. The combination effects then were evaluated according to pharmacodynamics and pharmacokinetic assessments. Results: KM-AZM combination synergistically inhibits in vitro growth of all the test standard strains except Pseudomonas aeruginosa and also the drug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, Shigella dysenteriae, Klebsiella pneumoniae, and Escherichia coli. Despite an additive effect against NO, KM plus AZM at an equal dose could synergistically suppress overrelease of the inflammatory cytokines TNF-α and IL-6 by LPS-induced RAW 264.7 cells. The combination significantly inhibited the proliferation of K. pneumoniae in the rat lungs, mainly by inactivating MAPKs and NF-κB signaling pathways. KM-AZM combination caused a onefold increase in apparent distribution volume of AZM, along with a significant decrease of AZM level in the livers and heart for pharmacokinetics. Conclusion: KM-AZM combination displayed synergistic antibacterial and anti-inflammatory effects beneficial to the therapeutic potential against bacterial infection.

A New Insight into Toxicity of Colchicine Analogues by Molecular Docking Analysis Based on Intestinal Tight Junction Protein ZO-1.

Colchicine (COL) is a well-known plant alkaloid long used for medical purposes due to the selective anti-inflammatory effect on acute gouty arthritis. It is also a kind of mitosis toxin with strong inhibitory effects of cell division and is therefore being applied to the treatment of various cancers. However, this product shows a variety of adverse effects that are significantly correlated with the dosage and have attracted much attention. For the first time, the present work obtained a new insight into the gastrointestinal toxicity of colchicine analogues by molecular docking analysis, which was based on the 3D structure of intestinal tight junction protein ZO-1 and the ligand library containing dozens of small-molecule compounds with the basic skeleton of COL and its metabolites. The binding energy and mode of protein-ligand interaction were investigated to better understand the structure-toxicity relationships of COL analogues and the mechanism of action as well. Cluster analysis clearly demonstrated the strong correlation between the binding energy and toxicity of ligand molecules. The interaction mode further revealed that the hydrogen bonding (via the C-7 amide or C-9 carbonyl group) and hydrophobic effect (at ring A or C) were both responsible for ZO-1-related gastrointestinal toxicity of COL analogues, while metabolic transformation via phase I and/or phase II reaction would significantly attenuate the gastrointestinal toxicity of colchicine, indicating an effective detoxication pathway through metabolism.

Research progress in strategies to improve the efficacy and safety of doxorubicin for cancer chemotherapy.

INTRODUCTION: DOX exerts strong anticancer activity and is commonly used to treat different cancers, including bone sarcomas, soft tissues, bladder, ovary, stomach, thyroid, breast, acute lymphoblastic leukemia, Hodgkin lymphoma, lung cancer, and myeloblastic leukemia. However, the cumulative doses of DOX above 550mg/m2 cause irreversible cardiotoxicity and other severe adverse effects. In this context, concerning DOX, several patents have been published in the last two decades. This activity highlights various aspects of DOX, such as registered patent analysis, pharmacological action, toxicityminimization, formulation development such as those approved by FDA, under clinical trials, and newly developed nano-delivery systems. AREAS COVERED: This review analyzes the different aspects of DOX-based chemotherapeutics and the development of drug delivery systems in theliterature published from 2000 to early 2020. EXPERT OPINION: DOX-based chemotherapy is still few steps away from being "perfect and safe" therapy. Certain severe systemic side effects are associated with DOX therapy. It is expected that, in the near future, DOX therapy can be much effective by selecting an ideal nanocarrier system, DOX conjugates, proper structural modifications, DOX-immunotherapy, and combination therapy. The advanced formulationsof DOX from the registered patents and recent research articles need clinical trials to bring safe treatment for cancer patients.

Enhanced phosphorus flux from overlying water to sediment in a bioelectrochemical system.

This report proposed a novel technique for the regulation of phosphorus flux based on a bioelectrochemical system. In the simulated water system, a simple in situ sediment microbial fuel cell (SMFC) was constructed. SMFC voltage was increased with time until it was 0.23V. The redox potential of the sediment was increased from -220mV to -178mV during the process. Phosphorus concentration in the water system was decreased from 0.1mg/L to 0.01mg/L, compared with 0.09mg/L in the control. The installation of a SMFC produced an external current and internal circuit, which promoted the transfer of phosphate in overlying water to the sediment, enhanced the microbial oxidation of Fe(2+), and increased the formation of stable phosphorus in sediment. In conclusion, phosphorus flux from the overlying water to sediment was enhanced by SMFC, which has the potential to be used for eutrophication control of water bodies.

[The research on the relationship between the polymorphism of T105A locus in MC1R gene and coat color in dogs].

In order to detect the polymorphism of T105A in MC1R gene in dogs and to analyze the relationship between the genetic polymorphisms and phenotypes of dog coat color, the blood samples of 111 cross-breed dogs were taken and their genomic DNAs were extracted. The phenotypes of dog coat color were recorded. The T105A locus of MC1R gene in the canine was detected through the technology of PCR-RFLP. Furthermore, the polymorphic fragments at T105A were sequenced. The relationships between the polymorphism of T105A and coat color trait were analyzed by the statistical methods of bivarate correlation analysis. By the method of PCR-RFLP, the T105A polymorphism was found with two alleles A and B and three genotypes AA, AB and BB. The frequencies of two alleles were 72.97% and 27.03%, respectively. The heterozygosity of T105A locus was 0.39. The frequencies of three genotypes were 55.86%, 34.23% and 9.91%, respectively. According to the results of sequencing, one base change from G to A at the position 105 was found at T105A locus and it altered amino acid at the position 105 from alanine to threonine. According to the statistical analysis, no significant association between the polymorphism of MC1R gene and the coat color was found and the result may be due to the differences of genetic background. Further research on MC1R gene should be done in pure breed dogs.