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1.
J Chem Inf Model ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32364718

RESUMO

Hemolytic toxicity, as one of the key toxicity endpoints for small molecules, can cause lysis of the erythrocyte membrane and subsequent release of hemoglobin into blood plasma, leading to multiple acute and chronic adverse effects. Hence, it is necessary to assess the hemolytic toxicity of small molecules in an early stage of drug discovery and development process, and it is more significant to quantitatively predict the hemolytic toxicity of small molecules before costly and time-consuming experiments. Nevertheless, this endpoint has never been quantitatively predicted due to the lack of an appropriate dataset. In this work, we manually collected a quantitative hemolytic toxicity dataset containing 805 small molecules with experimental values of HD50 (50% hemolytic dose) from a variety of literature, built the first machine learning-based regression model to quantitatively predict the hemolytic toxicity of small molecules, and developed a pragmatic software for automatic prediction. Based on this model, we further implemented an automatic recursive fragmentation module to predict the hemolytic fragments with high fragment efficiency for the given compound(s), which may be of particular interest to experimental medicinal chemists. Therefore, we anticipate that this quantitative model may help medicinal chemists boost the development of promising lead compounds with low hemolytic toxicity or fuel the discovery of highly hemolytic chemical probes to delve into the in-depth mechanism of the hemolytic process.

2.
Nanoscale Horiz ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32322871

RESUMO

Numerous nanocarriers with pH-responsive properties have been designed and fabricated to reduce the adverse side effects of traditional chemotherapeutics, but these traditional nanocarriers are rarely reversible; this may cause "secondary" side effects on normal tissues, because the nanocarriers cannot be sealed again to prevent the leakage of incompletely released drugs after re-entering blood circulation. To overcome these limitations, we report herein the synthesis of a reversibly pH-responsive drug delivery system, which can achieve regulated drug release in a "release-stop-release" manner corresponding to changes in pH. Specifically, poly(tannic acid) as the "gatekeeper" was firstly deposited and polymerized on the surface of mesoporous silica nanoparticles (MSNs) via a modified mussel-inspired method similar to dopamine, and the formed polymer shell can be easily decorated with a targeting ligand HER2 antibody for the selective delivery of drugs to specific cells. The resulting nanocomposites exhibited good colloidal stability, good biocompatibility, high drug loading capacity and accurate HER2 antibody mediated targeting ability. Interestingly, a series of experiments fully demonstrated that the fabricated nanocomposites possessed intelligent reversible pH-responsive controlled release behavior through adjusting the density of the "gatekeeper" under different pH conditions, thereby achieving reversible switching from "on" to "off". Furthermore, in vitro and in vivo experiments verified that the fabricated targeting nanoparticles could efficiently inhibit tumor growth with minimal side effects. Meanwhile, these nanocarriers exhibited excellent reusability, in vitro cytotoxicity and minimal in vivo myocardial damage. Collectively, the reversible pH-operated nanovalve on the MSNs constructed here could serve as a nanoplatform to solve the problem of "secondary" side effects caused by residual drugs in irreversible "gatekeeper" systems.

3.
Animals (Basel) ; 10(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244599

RESUMO

This study investigated the influence of dietary supplementation with some antibiotic alternatives on growth performance, intestinal barrier, and immunity of lipopolysaccharide (LPS) challenged chicks. Wenshi females, aged 4 days, were allocated randomly into eight groups, each with six replicates of 20 birds (n = 120/treatment), which received a basal diet supplemented with 0 (control), 0 (LPS), 200 mg/kg aureomycin, 50 mg/kg mushroom polysaccharide, 100 mg/kg mushroom polysaccharide, 500 mg/kg nano-copper, 300 mg/kg copper loaded chitosan, and 500 mg/kg lysozyme for 21 days. On day 18 and 20, the control birds were injected with 0.5 mL saline solution, the other treatments were injected with 0.5 mL saline containing 500 µg LPS/kg body weight (BW). The results indicated that LPS treatment reduced the BW, average daily gain (ADG), and daily feed intake (ADFI) than the controls (p < 0.05), and the antibiotic and the tested alternatives could not retrieve the normal BW, ADG, and ADFI. The tested additives reduced several negative effects of LPS; they reduced diamine oxidase activity and inflammatory mediators in plasma, jejunal mucosa, spleen and thymus, increased content of immunoglobulin in plasma and jejunal mucosa, and decreased gene expression of inducible nitric oxide synthase and Cyclooxygenase 2 in jejunal mucosa.

4.
J Burn Care Res ; 41(3): 657-662, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32020201

RESUMO

In this study, we aimed to evaluate the therapeutic effects of autologous platelet-rich plasma (PRP) on deep partial-thickness burns in Bama pigs. Deep partial-thickness burn wounds were created on the back of Bama pigs. The reepithelialization time was compared between the PRP and control groups. The mean score of Ki67 (+) cells and α-SMA (+) vessels, the mean thickness of epidermis and dermis of the healing wounds were determined via H&E staining and immunohistochemical assay. The levels of the growth factors epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were examined by ELISA. Our data showed that the time to wound reepithelialization was shorter in the PRP group compared with the control group. The thickness of the epidermis was larger in the PRP group compared with the control group. On the 7th and 14th days after the treatment, the mean score of Ki67 (+) cells and α-SMA (+) vessels were higher in the PRP group compared with the control group. The PRP group showed higher levels of growth factors (EGF, bFGF, and VEGF) compared with the control group by ELISA. The results indicated that PRP could improve wound healing process of deep partial-thickness burns in Bama pigs. The PRP increased the thickness of epidermis of the healed wounds, cell proliferation, and angiogenesis. We demonstrated that applying PRP had a greater potential for the treatment of deep partial-thickness burns.

6.
Biotechnol Lett ; 42(5): 825-832, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31993846

RESUMO

OBJECTIVE: To effectively and conveniently detect pathogenic bacteria, this study aimed to develop label-free biosensors fabricated affinity peptides that can recognize targeted bacteria strains and enable precise quantitative detections. RESULTS: A 12-mer peptide with high binding affinity toward Escherichia coli O157:H7 was discovered by biopanning of phage-displayed peptide library. The peptide modified with glycine residues (G3) and one cysteine (C) residue at C-terminal, could self-assemble on gold electrodes, enabling electrochemical impedance spectroscopy (EIS) analysis for quantitative detection of E. coli O157:H7. This method showed a low detection limit of 20 CFU/mL and a liner range from 2 × 102 to 2 × 106 CFU/mL. CONCLUSION: It appears that, by designing and optimizing the structures of peptides, such a strategy can be greatly promising in developing quick, sensitive and quantitative biosensor of pathogens.

7.
ChemSusChem ; 13(7): 1793-1799, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-31994308

RESUMO

Owing to its large capacity and high average potential, the structure and reversible O-redox compensation mechanism of Na2 Mn3 O7 have recently been analyzed. However, capacity fade and low coulombic efficiency over multiple cycles have also been found to be a problem, which result from oxygen evolution at high charge voltages. Herein, a Na0.44 MnO2 ⋅Na2 Mn3 O7 heterojunction of primary nanosheets was prepared by a sol-gel-assisted high-temperature sintering method. In the nanodomain regions, the close contact of Na0.44 MnO2 not only supplies multidimensional channels to improve the rate performance of the composite, but also plays the role of pillars for enhancing the cycling stability and coulombic efficiency; this is accomplished by suppressing oxygen evolution, which is confirmed by high-resolution (HR)TEM, cyclic voltammetry, and charge/discharge curves. As the cathode of a Na-ion battery, at 200 mA g-1 after 100 cycles, the Na0.44 MnO2 ⋅Na2 Mn3 O7 heterojunction retains an 88 % capacity and the coulombic efficiency approaches 100 % during the cycles. At 1000 mA g-1 , the Na0.44 MnO2 ⋅Na2 Mn3 O7 heterojunction has a discharge capacity of 72 mAh g-1 . In addition, the average potential is as high as 2.7 V in the range 1.5-4.6 V. The above good performances indicate that heterojunctions are an effective strategy for addressing oxygen evolution by disturbing the long-range order distribution of manganese vacancies in the Mn-O layer.

8.
Angew Chem Int Ed Engl ; 59(9): 3491-3494, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-31901005

RESUMO

We have developed a highly efficient and practical approach for palladium-catalyzed trifluoroacetate-promoted N-quinolylcarboxamide-directed glycosylation of inert ß-C(sp3 )-H bonds of N-phthaloyl α-amino acids with glycals under mild conditions. For the first time, C(sp3 )-H activation for glycosylation was achieved to build C-alkyl glycosides. This method facilitates the synthesis of various ß-substituted C-alkyl glycoamino acids and offers a tool for glycopeptide synthesis.

9.
Chem Commun (Camb) ; 56(11): 1633-1636, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31939462

RESUMO

We utilized solution-phase biopanning to obtain a de novo peptide (LA12) that specifically bound to the core region of the human amylin monomer. LA12 stabilized the random coil conformation of amylin to suppress aggregation in a dose-dependent manner with the highest suppression effect of 78% and reduced the cytotoxicity of amylin.


Assuntos
Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Peptídeos/farmacologia , Multimerização Proteica/efeitos dos fármacos , Animais , Bioprospecção/métodos , Linhagem Celular Tumoral , Humanos , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptídeos/toxicidade , Ligação Proteica , Estabilidade Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína/efeitos dos fármacos , Ratos
10.
J Agric Food Chem ; 68(5): 1373-1381, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927950

RESUMO

Most of the microorganisms can form biofilms, which makes biofilms an abundant bioresource to be exploited. Due to the limitations of the application of current immobilization methods for biofilms, we developed an immobilization method called the biofilm polysaccharide display (BPD) strategy while maintaining the native biofilm structure and catalytic microenvironment of Clostridium acetobutylicum B3. Lipase Lip181 showed significant improvements in stability after chemical immobilization. For example, immobilized Lip181 retained 74.23% of its original activity after incubation for 14 days, while free Lip181 was totally deactivated. In addition, immobilized Lip181 maintained high residual activity (pH 5.0-11.0), which showed improved resistance to pH changes. Notably, this method did not decrease but slightly increased the relative activity of Lip181 from 6.39 to 6.78 U/mg. Immobilized Lip181 was used to prepare cinnamyl acetate, and it showed a maximum yield of 85.09%. Overall, this biofilm immobilization method may promote the development of biocatalytic and biofilm materials.


Assuntos
Materiais Biocompatíveis/química , Biofilmes , Clostridium acetobutylicum/química , Lipase/metabolismo , Polissacarídeos/química , Biocatálise , Clostridium acetobutylicum/fisiologia , Estabilidade Enzimática , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Lipase/química , Polissacarídeos/metabolismo
11.
Cell Tissue Res ; 379(1): 181-193, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768712

RESUMO

Diabetes mellitus (DM) often causes delayed wound healing in patients, which can lead to limb loss, disability, and even death. Many conventional therapeutic strategies have been proposed, but there is still no effective therapy for DM wounds. This study aimed to explore the effects of CD271 and phosphorylated tyrosine kinase receptor A (pTrkA) on the migration and proliferation abilities of epidermal stem cells (eSCs) and on the activation of DM wound healing. We investigated the interventional effects of CD271-overexpressing eSC (CD271 eSC) treatment and pTrkA inhibition (through k252a treatment) on delayed wound healing using mice with streptozotocin-induced DM. The migration and proliferation abilities of control eSCs, CD271 eSCs, and k252a-treated CD271 eSCs were observed under high-glucose conditions. Decreases in CD271 and increases in pTrkA were observed in DM mouse skin compared with control mouse skin; in addition, the rate of wound closure in DM mice was promoted by CD271 eSC treatment but delayed by pTrkA inhibition. Furthermore, the CD271 eSC migration and proliferation were greater than of control eSCs. Compared with that of CD271 eSCs, the number of CD271+k252a eSCs decreased significantly under high-glucose conditions. In parallel, the expression levels of the pERK, pAkt, and pJNK pathways increased in CD271 eSCs and decreased in CD271+k252a eSCs under high glucose. Our findings demonstrate that CD271 and pTrkA affect DM wound closure by promoting the eSC migration and proliferation. This mechanism involving the pERK, pAkt, and pJNK pathways might be a new therapeutic target for the treatment of delayed wound re-epithelialization in DM.

12.
Sci Total Environ ; 705: 135868, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31818567

RESUMO

Global urban growth leads to a great increase in the impervious surface area (ISA) such as roads, plazas, airports, and parking lots, and consequently reshapes hydrological regimes in urban basins. Beijing, the capital of China, has experienced rapid urban growth since the 1980s. However, the spatial-temporal variability of the ISA and its impact on flooding risk are unclear. This study monitored urban growth (i.e., the evolution of the ISA) in Beijing for the period of 1980-2015 based on Landsat data, and identified the response of surface runoff yield using a land-surface hydrological model. The modeling at a relatively high spatial resolution (~6 km) was driven with retrieved long-term ISA dynamics, Global LAnd Surface Satellite (GLASS) product, and climate forcings. The results show that the impervious surface fraction (ISF) in Beijing increased from 8.73% (1448.16 km2) in 1980 to 22.22% (3685.92 km2) in 2015. With a demarcation at around the year 2000, the ISA growth presents a new pattern with a northeast-southwest direction from the Core Functional Zone (Core-Zone). Due to the ISA expansion, the simulated runoff coefficient in 2010 is approximately doubled compared to that of 1980. We identified an ISF threshold of approximately 6%, beyond which every 1% increase in the ISF may increase the surface runoff by approximately 5.51 mm/year, and thereby poses a high potential flooding risk even under a moderate rainfall event. In four typical historical storms, the sensitivity coefficients of surface runoff to precipitation and ISF were 0.97 and 0.63, respectively, indicating impervious surfaces dramatically enhanced the potential flooding risk. Our findings have implications for urban planning and the construction of sponge city in Beijing.

13.
Poult Sci ; 98(12): 6826-6836, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504946

RESUMO

This study investigated the effects of the dietary threonine (Thr) levels on the performance, offspring traits, embryo amino acid transportation, and protein deposition in breeder hens of yellow-feathered chickens. In total, 720 breeder hens of Lingnan yellow-feathered chickens were randomly assigned to 1 of 6 dietary treatments, with 6 replicates per treatment (20 birds per replicate). The breeder hens were fed either basal diet (Thr = 0.38%) or basal diet supplemented with 0.12, 0.24, 0.36, 0.48, or 0.60% Thr from 197 to 266 D. There was a positive response in terms of the laying rate after adding different levels of Thr to the diet, but no significant effects on the average daily gain, average daily egg weight, feed conversion ratio, average broken eggs, and unqualified egg rate (P > 0.05). However, the eggshell strength and eggshell percentage decreased in a linear manner as the dietary Thr concentration increased (P = 0.05). Dietary supplementation with Thr had significant effects on the expression of mucin 2 (MUC2) in the uterus and zonula occludens protein 1 (ZO-1) in the duodenum of breeders (P < 0.05). In chick embryos at embryonic age 18 D, significant upregulation of poultry target of rapamycin (pTOR) occurred in the liver and breast muscle, as well as threonine dehydrogenase (TDH) in the thigh, and aminopeptidase (ANPEP) (P < 0.05) in the duodenum and ileum due to dietary Thr supplementation, but there were no effects on MUC2 expression in the duodenum and ileum (P > 0.05). The livability of the progeny broilers tended to increase with the dietary Thr concentration (quadratic, P = 0.08). Thus, dietary supplementation with Thr had positive effects on the laying production by breeder hens and offspring performance, and it also regulated the expression levels of genes related to amino acid transportation and protein deposition. The optimal dietary Thr concentration that maximized the laying rate in yellow-feathered chicken breeders aged 197 to 266 D was 0.68% according to quadratic regression analysis.

14.
J Bacteriol ; 201(23)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31501283

RESUMO

Functional genetic analysis of Chlamydia has been a challenge due to the historical genetic intractability of Chlamydia, although recent advances in chlamydial genetic manipulation have begun to remove these barriers. Here, we report the development of the Himar C9 transposon system for Chlamydia muridarum, a mouse-adapted Chlamydia species that is widely used in Chlamydia infection models. We demonstrate the generation and characterization of an initial library of 33 chloramphenicol (Cam)-resistant, green fluorescent protein (GFP)-expressing C. muridarum transposon mutants. The majority of the mutants contained single transposon insertions spread throughout the C. muridarum chromosome. In all, the library contained 31 transposon insertions in coding open reading frames (ORFs) and 7 insertions in intergenic regions. Whole-genome sequencing analysis of 17 mutant clones confirmed the chromosomal locations of the insertions. Four mutants with transposon insertions in glgB, pmpI, pmpA, and pmpD were investigated further for in vitro and in vivo phenotypes, including growth, inclusion morphology, and attachment to host cells. The glgB mutant was shown to be incapable of complete glycogen biosynthesis and accumulation in the lumen of mutant inclusions. Of the 3 pmp mutants, pmpI was shown to have the most pronounced growth attenuation defect. This initial library demonstrates the utility and efficacy of stable, isogenic transposon mutants for C. muridarum The generation of a complete library of C. muridarum mutants will ultimately enable comprehensive identification of the functional genetic requirements for Chlamydia infection in vivo IMPORTANCE Historical issues with genetic manipulation of Chlamydia have prevented rigorous functional genetic characterization of the ∼1,000 genes in chlamydial genomes. Here, we report the development of a transposon mutagenesis system for C. muridarum, a mouse-adapted Chlamydia species that is widely used for in vivo investigations of chlamydial pathogenesis. This advance builds on the pioneering development of this system for C. trachomatis We demonstrate the generation of an initial library of 33 mutants containing stable single or double transposon insertions. Using these mutant clones, we characterized in vitro phenotypes associated with genetic disruptions in glycogen biosynthesis and three polymorphic outer membrane proteins.

15.
J Bacteriol ; 201(23)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31501285

RESUMO

Lateral gene transfer (LGT) among Chlamydia trachomatis strains is common, in both isolates generated in the laboratory and those examined directly from patients. In contrast, there are very few examples of recent acquisition of DNA by any Chlamydia spp. from any other species. Interspecies LGT in this system was analyzed using crosses of tetracycline (Tc)-resistant C. trachomatis L2/434 and chloramphenicol (Cam)-resistant C. muridarum VR-123. Parental C. muridarum strains were created using a plasmid-based Himar transposition system, which led to integration of the Camr marker randomly across the chromosome. Fragments encompassing 79% of the C. muridarum chromosome were introduced into a C. trachomatis background, with the total coverage contained on 142 independent recombinant clones. Genome sequence analysis of progeny strains identified candidate recombination hot spots, a property not consistent with in vitro C. trachomatis × C. trachomatis (intraspecies) crosses. In both interspecies and intraspecies crosses, there were examples of duplications, mosaic recombination endpoints, and recombined sequences that were not linked to the selection marker. Quantitative analysis of the distribution and constitution of inserted sequences indicated that there are different constraints on interspecies LGT than on intraspecies crosses. These constraints may help explain why there is so little evidence of interspecies genetic exchange in this system, which is in contrast to very widespread intraspecies exchange in C. trachomatis IMPORTANCE Genome sequence analysis has demonstrated that there is widespread lateral gene transfer among strains within the species C. trachomatis and with other closely related Chlamydia species in laboratory experiments. This is in contrast to the complete absence of foreign DNA in the genomes of sequenced clinical C. trachomatis strains. There is no understanding of any mechanisms of genetic transfer in this important group of pathogens. In this report, we demonstrate that interspecies genetic exchange can occur but that the nature of the fragments exchanged is different than those observed in intraspecies crosses. We also generated a large hybrid strain library that can be exploited to examine important aspects of chlamydial disease.

16.
Colloids Surf B Biointerfaces ; 184: 110433, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31522024

RESUMO

Surface fabrication is an effective method for functional materials development. This work investigated the use of cellulose-binding domain (CBD) fused detergent lipase for fabrication of easy-cleaning surfaces. As a result, the CBD conjugated Lipase-A (LipA-CBD) demonstrated a multi-layer self-assemble on cotton fabric surface and enhanced hydrophobicity as detected by both scanning electron microscope and water contact angle measurement. Compared to the normal cotton surfaces, such self-assembly bioactive surfaces afforded effective easy-cleaning functionality against both water and lipids based stains with the most significant stain removing ratio as examined through the simulated laundering test. Additionally, this surface assembled LipA-CBD presented good thermal stability with 15 days of half-life detected for 70°C and over 60 days for room temperature. Although there is a gradual decrease in sun irradiation stability and laundering durability, the functionality could be quickly recovered by re-applying the LipA-CBD as the self-assembly coating in the rinsing process. These results presented a green, simple and timesaving method to develop new easy-cleaning cotton fabrics via interfacial self-assembly of biomacromolecules.

17.
J Pharmacol Exp Ther ; 371(1): 208-218, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31375639

RESUMO

Blockade of interleukin (IL)-23 or IL-17 with biologics is clinically validated as a treatment of psoriasis. However, the clinical impact of targeting other nodes within the IL-23/IL-17 pathway, especially with small molecules, is less defined. We report on a novel small molecule inverse agonist of retinoid acid-related orphan receptor (ROR) γt and its efficacy in preclinical models of psoriasis and arthritis. 1-(2,4-Dichloro-3-((1,4-dimethyl-6-(trifluoromethyl)-1H-indol-2-yl)methyl)benzoyl)piperidine-4-carboxylic acid (A-9758) was optimized from material identified from a high-throughput screening campaign. A-9758 is selective for RORγt and exhibits robust potency against IL-17A release both in vitro and in vivo. In vivo, we also show that IL-23 is sufficient to drive the accumulation of RORγt+ cells, and inhibition of RORγt significantly attenuates IL-23-driven psoriasiform dermatitis. Therapeutic treatment with A-9758 (i.e., delivered during active disease) was also effective in blocking skin and joint inflammation. Finally, A-9758 exhibited efficacy in an ex vivo human whole blood assay, suggesting small molecule inverse agonists of RORγt could be efficacious in human IL-17-related diseases. SIGNIFICANCE STATEMENT: Using a novel small molecule inverse agonist, and preclinical assays, we show that RORγt is a viable target for the inhibition of RORγt/Th17-driven diseases such as psoriasis. Preclinical models of psoriasis show that inhibition of RORγt blocks both the accumulation and effector function of IL-17-producing T cells.

18.
Poult Sci ; 98(11): 5714-5723, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376347

RESUMO

This study evaluated the effect of the dietary replacement of 1% lard (CT) with 1% perilla oil (PO), 0.9% perilla oil + 0.1% anise oil (PA), or 0.9% perilla oil + 0.1% ginger oil (PG) on indices of lipid metabolism, antioxidant capacity, meat quality, and fatty acid profiles from Yellow-feathered chickens at day 63. Compared with the CT chickens, those given perilla oil had decreased (P < 0.05) plasma lipid levels including triglycerides (TG), total cholesterol (TCH), and low-density lipoprotein cholesterol (LDL-C). Hepatic TG, TCH levels, and fatty acid synthase activity were also decreased (P < 0.05) in chickens fed diets containing perilla oil. Abdominal fat percentage was significantly decreased in birds fed the PG compared to CT diets. Birds fed the PA or PG diets had increased (P < 0.05) hepatic total SOD, glutathione peroxidase, and glutathione-S-transferase than in chickens given PO alone. In addition, the content of reduced glutathione (GSH) in breast muscle was lower (P < 0.05) in birds fed PO compared with those given PG, and the reverse was true for content of malondialdehyde. Compared with the CT diet, the PO diet decreased breast muscle shear values and increased yellowness (b*) of breast muscle (P < 0.05). Birds fed the PA or PG diets had meat with better overall acceptability than those fed the CT diet. Chickens fed perilla oil diets exhibited higher contents of α-linolenic acid (C18:3n-3), DHA (22:6n-3), polyunsaturated fatty acids, and n-3 fatty acids, together with a lower content of myristic acid (C14:0), palmitic acid (C16:0), stearic acid (C18:0), total saturated fatty acids, and n-6/n-3 ratio compared to controls (P < 0.05). These findings indicate that perilla oil has the potential to decrease lipid-related indices and improve fatty acid profiles of breast meat in chickens without adverse effect on antioxidant status or meat quality; this was even better when perilla oil was given together with anise oil or ginger oil.


Assuntos
Galinhas/metabolismo , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Carne/análise , Ácido alfa-Linoleico/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Masculino , Valor Nutritivo , Óleos Vegetais/administração & dosagem , Óleos Vegetais/metabolismo , Distribuição Aleatória , Ácido alfa-Linoleico/administração & dosagem
19.
Int J Biol Macromol ; 140: 1037-1046, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31449862

RESUMO

Azo dyes are the most widely applied chemical dyes that have also raised great concerns for environmental contamination and human health issues. There has been a growing interest in discovering bioremediation methods to degrade azo dyes for environmental and economic purposes. Azoreductases are key enzymes evolved in nature capable of degrading azo dyes. The current work reports the identification, expression, and properties of a novel azoreductase (AzoRed2) from Streptomyces sp. S27 which shows an excellent stability against pH change and organic solvents. To overcome the requirements of coenzyme while degrading azo dyes, we introduced a coenzyme regeneration enzyme, Bacillus subtilis glucose 1-dehydrogenase (BsGDH), to construct a recycling system in living cells. The whole-cell biocatalyst containing AzoRed2 and BsGDH was used to degrade a representative azo dye methyl red. The degradation rate of methyl red was up to 99% in 120 min with high substrate concentration (250 µM) and no external coenzyme added. The degradation rate was still 98% in the third batch trial. To sum up, a novel azoreductase with good properties was found, which was applied to construct whole-cell biocatalyst. Both the enzymes and whole-cell biocatalysts are good candidates for the industrial wastewater treatment and environmental restoration.

20.
Eur J Med Chem ; 180: 398-416, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31325786

RESUMO

In this work, aiming at finding a novel, potent, and selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor with good pharmacokinetic profiles for the treatment of diabetes, we focus on modifying the sugar moiety of SGLT2 inhibitors, which dominates the binding with glucose binding site of hSGLT, via removing the C-6 hydroxy group to adjust the physicochemical properties and target-recognition manners of SGLT2 inhibitors. In addition, tofogliflozin containing a special O-spiroketal C-arylglucoside scaffold, displayed good efficacy and bioavailability both in animals and in humans. Therefore, a series of 6-deoxy O-spiroketal C-arylglucosides as novel SGLT2 inhibitors were designed, synthesized, and evaluated in this work. The structure-activity relationship (SAR) research on this novel series and a comprehensive in vitro and in vivo biological evaluation afforded compound 39 with high in vitro hSGLT2 inhibitory activity (IC50 = 4.5 nM), good pharmacokinetic profiles, and more remarkable efficacy in C57BL/6J mice and Sprague-Dawley rats than marketed drug tofogliflozin.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Desenho de Fármacos , Inibidores do Transportador 2 de Sódio-Glicose/síntese química , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Animais , Compostos Benzidrílicos/síntese química , Compostos Benzidrílicos/química , Compostos Benzidrílicos/farmacologia , Relação Dose-Resposta a Droga , Glucosídeos/síntese química , Glucosídeos/química , Glucosídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Inibidores do Transportador 2 de Sódio-Glicose/química , Compostos de Espiro/síntese química , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Relação Estrutura-Atividade
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