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1.
Food Chem ; 337: 127806, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32799167

RESUMO

Irradiation has been regarded as a perspective preservation technology to prolong the shelf life of goat meat. In order to evaluate the effect of irradiation on goat meat, the high-throughput proteomics was applied to observe the proteome profiles changes and off-flavor formation of irradiated goat meat. A total of 207 proteins with significant changes (fold change > 2 or < 0.5, P < 0.05, VIP > 1) was determined in five irradiation doses (0, 1, 2, 4 and 6 kGy). Among them, 26 proteins involving 7 functional enrichments terms were found to be related to off-flavor. Particularly, proteins involved in protein oxidation, cysteine and methionine metabolism lead to irradiation off-flavor formation. However, the irradiation off-flavor will gradually dissipate due to metabolic process during storage. This study was designed to provide a proteomic insight into irradiation off-flavor of goat meat and suggest an underlying connection between off-flavor formation and biological processes.

2.
CNS Neurosci Ther ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33085171

RESUMO

AIMS: Deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) is effective in temporal lobe epilepsy (TLE). Previous studies have shown that the basal ganglia are involved in seizure propagation in TLE, but the effects of ANT-DBS on the basal ganglia have not been clarified. METHODS: ANT-DBS was applied to monkeys with kainic acid-induced TLE using a robot-assisted system. Behavior was monitored continuously. Immunofluorescence analysis and Western blotting were used to estimate protein expression levels in the basal ganglia and the effects of ANT stimulation. RESULTS: The seizure frequency decreased after ANT-DBS. D1 and D2 receptor levels in the putamen and caudate were significantly higher in the ANT-DBS group than in the epilepsy (EP) model. Neuronal loss and apoptosis were less severe in the ANT-DBS group. Glutamate receptor 1 (GluR1) in the nucleus accumbens (NAc) shell and globus pallidus internus (GPi) increased in the EP group but decreased after ANT-DBS. γ-Aminobutyric acid receptor A (GABAA -R) decreased and glutamate decarboxylase 67 (GAD67) increased in the GPi of the EP group, whereas the reverse tendencies were observed after ANT-DBS. CONCLUSION: ANT-DBS exerts neuroprotective effects on the caudate and putamen, enhances D1 and D2 receptor expression, and downregulates GPi overactivation, which enhanced the antiepileptic function of the basal ganglia.

3.
J Cancer Res Ther ; 16(5): 1014-1019, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004742

RESUMO

Context: It is necessary to explore a minimally invasive, effective, and efficient treatment for those lung cancer patients who are poor candidates for surgery. Aim: This study aimed to investigate the application of microwave ablation (MWA) in the treatment of lung cancer. Settings and Design: A total of 43 patients with 44 pulmonary lesions were examined following identical procedures before being randomly divided into two groups. The experimental group consists of 17 patients with a total of 18 pulmonary lesions, while the control group consists of 26 patients with a total of 26 pulmonary lesions. Materials and Methods: The experimental group was treated using magnetic resonance imaging (MRI)-guided MWA while the control group was treated using computer tomography (CT)-guided MWA. A transverse relaxation time-turbo spin echo (T2-TSE) sequence was used for signal collection in the experimental group to determine puncture location and microwave needle position while T2-TSE, T1-turbo field echo, and diffusion-weighted MRI (DWI) sequences were used for timely efficacy evaluation. Whereas in the control group, CT axial scanning was performed to serve similar purposes. Statistical Analysis Used: A nonparametric Wilcoxon test, median (M [25%, 75%]). Results: All of the 44 lesions were successfully located on the first attempt. The mean time for scanning and locating lung lesions under MRI and CT guidance were 64.53 and 42.96 min, the mean times of positioning were 12 and 18 min, and the mean durations of MWA were 12.48 and 15.06 min, respectively. Conclusions: As a minimally invasive method for treating lung tumors, MRI-guided MWA requires fewer localization scans, a shorter MWA duration, no radiation, real-time observation of the curative effect, and it prevents overtreatment.

4.
Inorg Chem ; 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32862642

RESUMO

Metal-organic frameworks (MOFs) with cuprous-halide-aggregates have shown superiority as organic LED (OLED) and semiconductor materials, while engineering MOF flexibility by involving the expansion of cuprous aggregates remains a great challenge. In this particular work, a dissolution-recrystallization structural transformation (DRST) with the dramatic growth of CuI-I aggregates, from 2D NJNU-100 to 3D NJNU-101 has been successfully realized. The unsaturated coordination nodes (2-positional nitrogen atoms) in NJNU-100 have been demonstrated to be the driven force for DRST to NJNU-101 via the formation of coordination bonds. The structural transformation process was irreversible and observed with optical microscopy and powder XRD. The expansion of CuI-I aggregates was also computational simulated accompanying with the rotation of the neutral tripodal TTTMB ligand (1,3,5-tris(1,2,4-triazol-1-ylmethyl)-2,4,6-trimethylbenzene) and the reduction of CuII to CuI. Moreover, the intermediate product NJNU-102 was captured by adding the planar molecular anthrancene to shut down the reaction, where only partial 2-positional nitrogen atoms coordinated to the aggregates and the anthrancene was oxidized to anthraquinone. NJNU-102 has further confirmed that DRST involved the breakage and recombination of coordination bonds and the electron transfer. NJNU-100 and NJNU-101 could be applied as semiconductor and OLED materials. This work has provided insights for crystal engineering, especially for the construction of the CuIxXy aggregates, and illustrated that DRST could be controlled with a rational design (as the unsaturated coordination modes).

5.
Artigo em Inglês | MEDLINE | ID: mdl-32959645

RESUMO

Cancer chemotherapy is challenged by multidrug resistance (MDR) mainly attribute to overexpressed transmembrane efflux pump P-glycoprotein (P-gp) in cancer cells. Improving drug delivery efficacy while co-delivering P-gp inhibitors to suppress drug efflux is an often-used nano-strategy for combating MDR, which is however challenged by cascaded bio-barriers en route to cancer cells and P-gp inhibitors' adverse effects. To effectively breach the cascaded bio-barriers while avoiding P-gp inhibitors' adverse effects, a stealthy, sequentially-responsive doxorubicin (DOX) delivery nanosystem (RCMSNs) is fabricated, composed of extracellular-tumor-acidity responsive polymer shell (PEG-b-PLLDA), pH/redox-dual responsive mesoporous silica nanoparticles-based carriers (MSNs-SS-Py), and cationic ß-cyclodextrin-PEI (CD-PEI) gatekeepers. PEG-b-PLLDA corona makes RCMSNs stealthy with prolonged blood-circulation time. Once reaching tumors, extracellular acidity degrades PEG-b-PLLDA, reversing nanosystem's surface charges to be positive, which drastically improves RCMSNs' tumor accumulation, penetration, and cellular internalization. Within cancer cells, CD-PEI gatekeepers detach to allow DOX unloading in response to intracellular acidity and glutathione, and functionally act as a P-gp inhibitor dampening P-gp's efflux activity by impairing ATP production. Thus, the resultant high-efficacy drug delivery along with reduced P-gp function cooperatively reverse MDR in vitro. Importantly, in preclinical tumor models, DOX@RCMSNs potently suppress MDR tumor growth without eliciting systemic toxicity, demonstrating their potential of clinical translation.

6.
J Am Heart Assoc ; 9(18): e016518, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32893710

RESUMO

Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4-week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4-week washout period. The primary outcome was difference in oxidized low-density lipoprotein cholesterol (LDL-C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short-chain and branched-chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL-C (-2.73 U/L), total cholesterol (-5.03 mg/dL), LDL-C (-3.87 mg/dL), and body weight (-0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, including l-carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL-C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae. Conclusions The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL-C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL-C observed with the VD. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02942628.

7.
Cancer Med ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32931665

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide and tends to be detected at an advanced stage. More effective biomarkers for HCC screening and prognosis assessment are needed and the mechanisms of HCC require further exploration. The role of MAOA in HCC has not been intensively investigated. METHODS: In-house tissue microarrays, genechips, and RNAsequencing datasets were integrated to explore the expression status and the clinical value of MAOA in HCC. Immunohistochemical staining was utilized to determine MAOA protein expression. Intersection genes of MAOA related co-expressed genes and differentially expressed genes were obtained to perform functional enrichment analyses. In vivo experiment was conducted to study the impact of traditional Chinese medicine nitidine chloride (NC) on MAOA in HCC. RESULTS: MAOA was downregulated and possessed an excellent discriminatory capability in HCC patients. Decreased MAOA correlated with poor prognosis in HCC patients. Downregulated MAOA protein was relevant to an advanced TNM stage in HCC patients. Co-expressed genes that positively related to MAOA were clustered in chemical carcinogenesis, where CYP2E1 was identified as the hub gene. In vivo experiment showed that nitidine chloride significantly upregulated MAOA in a nude mouse HCC model. CONCLUSIONS: A decreased MAOA level is not only correlated with aggressive behaviors in males but also serves as a promising biomarker for the diagnosis and prognosis of HCC patients. Moreover, MAOA may play a role in AFB1 toxic transformation through its synergistic action with co-expressed genes, especially CYP3A4. MAOA also serves as a potential therapy target of NC in HCC patients.

8.
J Cell Mol Med ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32975374

RESUMO

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has rapidly spread worldwide, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics of COVID-19 patients remains limited. Herein, we collected blood samples from 18 healthy donors (HDs) and 38 COVID-19 patients to analyse changes in the adaptive immune cell populations and their phenotypes. We observed that the lymphocyte percentage moderately decreased, CD4 and CD8 T cell percentage among lymphocytes were similar, and B cell percentage was increased in COVID-19 patients in comparison to that in HDs. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 infection increased the percentage of T follicular helper- and germinal centre B-like cells in the blood. The parameters in COVID-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells are activated naturally and are functional during SARS-CoV-2 infection. These data provide evidence that the adaptive immunity in most patients could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.

9.
J Cell Mol Med ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32918374

RESUMO

It is growingly concerned about methamphetamine (MA)-induced lung toxicity. IMP1 is identified as a key molecule for cell life processes, but the role of IMP1 in MA-induced senescence remains unclear. The purpose of this study was to investigate whether chronic exposure to MA can cause autophagy and senescence of the lungs, whether there are interactions between Mammalian target of rapamycin (mTOR) and IMP1 and whether IMP1 is involved in pulmonary senescence promoted by mTOR-autophagy. The rats were randomly divided into control group and MA group, following by H&E staining, immunohistochemistry staining and Western blot. The alveolar epithelial cells were proceeded by ß-galactosidase staining, cell cycle detection, transfection and co-immunoprecipitation. Long-term exposure to MA led to the thickening of alveolar septum and more compact lungs. MA promoted the conversion of LC3-I to LC3-II and inhibited the activation of mTOR to induce autophagy. Bioinformatics and co-immunoprecipitation results presented the interactions between IMP1 and mTOR. MA induced cell senescence by decreasing IMP1, up-regulating p21 and p53, arresting cell cycle and increasing SA-ß-gal. Overexpression of IMP1 reduced p21 and SA-ß-gal to inhibit the senescence of alveolar epithelial cells. These results demonstrated that mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

10.
J Cell Mol Med ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: covidwho-798142

RESUMO

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has rapidly spread worldwide, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics of COVID-19 patients remains limited. Herein, we collected blood samples from 18 healthy donors (HDs) and 38 COVID-19 patients to analyse changes in the adaptive immune cell populations and their phenotypes. We observed that the lymphocyte percentage moderately decreased, CD4 and CD8 T cell percentage among lymphocytes were similar, and B cell percentage was increased in COVID-19 patients in comparison to that in HDs. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 infection increased the percentage of T follicular helper- and germinal centre B-like cells in the blood. The parameters in COVID-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells are activated naturally and are functional during SARS-CoV-2 infection. These data provide evidence that the adaptive immunity in most patients could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.

11.
J Cell Mol Med ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: covidwho-796054

RESUMO

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has rapidly spread worldwide, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics of COVID-19 patients remains limited. Herein, we collected blood samples from 18 healthy donors (HDs) and 38 COVID-19 patients to analyse changes in the adaptive immune cell populations and their phenotypes. We observed that the lymphocyte percentage moderately decreased, CD4 and CD8 T cell percentage among lymphocytes were similar, and B cell percentage was increased in COVID-19 patients in comparison to that in HDs. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 infection increased the percentage of T follicular helper- and germinal centre B-like cells in the blood. The parameters in COVID-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells are activated naturally and are functional during SARS-CoV-2 infection. These data provide evidence that the adaptive immunity in most patients could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.

12.
J Cell Mol Med ; 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: covidwho-735930

RESUMO

A novel pneumonia-associated respiratory syndrome named coronavirus disease-2019 (COVID-19), which was caused by SARS-CoV-2,broke out in Wuhan, China, in the end of 2019. Unfortunately, there is no specific antiviral agent or vaccine available to treat SARS-CoV-2 infections. The information regarding the immunological characteristics in COVID-19 patients remains limited. Here, we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes on γδ T cell population. In comparison with HD, the γδ T cell percentage decreased, while the activation marker CD25 expression increased in response to SARS-CoV-2 infection. Interestingly, the CD4 expression was upregulated in γδ T cells reflecting the occurrence of a specific effector cell population, which may serve as a biomarker for the assessment of SARS-CoV-2 infection.

13.
J Cell Mol Med ; 24(19): 11603-11606, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32864865

RESUMO

A novel pneumonia-associated respiratory syndrome named coronavirus disease-2019 (COVID-19), which was caused by SARS-CoV-2,broke out in Wuhan, China, in the end of 2019. Unfortunately, there is no specific antiviral agent or vaccine available to treat SARS-CoV-2 infections. The information regarding the immunological characteristics in COVID-19 patients remains limited. Here, we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes on γδ T cell population. In comparison with HD, the γδ T cell percentage decreased, while the activation marker CD25 expression increased in response to SARS-CoV-2 infection. Interestingly, the CD4 expression was upregulated in γδ T cells reflecting the occurrence of a specific effector cell population, which may serve as a biomarker for the assessment of SARS-CoV-2 infection.

14.
Exp Lung Res ; 46(8): 308-319, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32748703

RESUMO

AIM OF THE STUDY: The mechanism by which primary shock wave causes lung injury is unclear. The aim of this study is to find the changes of protein that can be helpful in understanding blast-induced lung injury. MATERIAL AND METHODS: A quantitative analysis of their global proteome was conducted in lung from mice with blast injury using LC-MS/MS. Protein annotation, unsupervised hierarchical clustering, functional classification, functional enrichment and cluster, and protein-protein interaction analyses were performed. Furthermore, western blotting was used to validate the changed protein levels. RESULTS: A total of 6498 proteins were identified, of which 5520 proteins were quantified. The fold-change cutoff was set at 1.2; 132 proteins were upregulated, and 104 proteins were downregulated. The bioinformatics analysis indicated that the differentially expressed proteins were involved in the cholesterol metabolism, asthma, nonalcoholic fatty liver disease. Remarkably, the processes related to the change of oxidative phosphorylation including the NADH dehydrogenase, Cytochrome C reductase, Cytochrome C oxidase and F-type ATPase were significantly upregulated, which were further verified by western blotting. CONCLUSION: These results confirmed that the oxidative phosphorylation is critical to blast-induced lung injury. LC/MS-based profiling presented candidate target/pathways that could be explored for future therapeutic development.

15.
Fish Physiol Biochem ; 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32749664

RESUMO

An emerging concept is that the hypothalamic nutrient sensor can regulate peripheral energy metabolism via a brain-liver circuit. Valine is an essential branched-chain amino acid (BCAA) that drives intracellular signaling cascades by the activation of target of rapamycin complex 1 (TORC1) which is critical to protein metabolism in mammals. However, in teleost fish, it remains scarce in this area especially about how the intraventricular (ICV) injection of valine can mediate the protein metabolism in peripheral organs. This study would tentatively explore the effects of ICV injection of valine on protein metabolism in peripheral organs through evaluating the postprandial ammonia-N excretion rate in Chinese perch. The control group was injected with 5-µL PBS, and the Val group was injected with 20-µg L valine dissolved into 5-µL PBS. The ammonia-N excretion rate of Val group was lower than control group at 4-, 12-, and 24-h postinjection, while the concertation of plasma glucose was increased sharply at 0.5-, 4-, 12-, and 24-h postinjection. We further checked both mRNA level and the enzyme activity of glutamate dehydrogenase (GDH) in the liver and adenosine monophosphate deaminase (AMPD) in muscle, and we found that they were obviously decreased in Val group at 4-, 12-, and 24-h postinjection. The phosphorylation level of ribosomal protein S6, a downstream target protein of TORC1, was markedly enhanced in the liver of Val group at 4-, 12-, and 24-h postinjection. Collectively, these results illustrated that ICV injection of valine can attenuate protein degradation in peripheral organs by depressing the GDH and AMPD enzyme activity; on the other hand, the injected valine can trigger the activation of TORC1 in the liver via a brain-liver circuit and then interdict proteolysis.

16.
Food Funct ; 11(8): 7104-7114, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32744543

RESUMO

A water-soluble neutral homopolysaccharide (PLP-1) was obtained from the roots of Pueraria lobata by DEAE cellulose and Sephadex G-200 gel chromatography purification. The average molecular weight of PLP-1 was 16.2 kDa. Monosaccharide composition analysis showed that PLP-1 was composed of glucose as a glucan. The structure of PLP-1 was characterized on the basis of extensive physical and chemical analysis, which indicated that the backbone of PLP-1 was mainly composed of →3)-α-d-Glcp(1→ and →4)-ß-d-Glcp(1→ with a molar ratio of 7.0 : 1.0. Moreover, the hypoglycemic activity of PLP-1 was investigated by palmitic acid and high glucose induced insulin resistant HepG2 cells. The results elucidated that PLP-1 could decrease the glucose concentration by up-regulating the expression of PI3K and AKT, and down-regulating the expression of FoxO1, PCK2, and G6Pase in insulin resistant cells. Therefore, PLP-1 could serve as a dietary supplement to ameliorate insulin resistance for diabetic patients.

18.
Medicine (Baltimore) ; 99(30): e21331, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791730

RESUMO

The aim of this study was to elucidate the possible association between migration inhibitory factor (MIF)-173G/C gene polymorphisms and transcript and plasma levels of MIF in spinal tuberculosis (TB) patients. Clinical data were collected from 254 spinal TB patients and 262 healthy controls participating in the study. The genotype of the MIF-173G/C gene was amplified by polymerase chain reaction and genotyped by DNA sequencing technology. The level of mRNA expression was determined by real-time polymerase chain reaction and MIF plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. The frequency of the C allele and GC+CC genotype in MIF-173G/C was over-represented in spinal TB patients. The mean MIF mRNA level in spinal TB patients and patients with the GG and GC+CC genotype were significantly lower than controls; however, our study also indicated that the MIF concentration in spinal TB patients and patients with the GG and GC+CC genotypes were significantly higher than controls. Spinal TB patients with the GG genotype had higher MIF plasma levels than patients with the GC+CC genotype. The C-reactive protein level and erythrocyte sedimentation rate was correlated with the MIF plasma level. In summary, the association between the MIF-173G/C genetic polymorphism, reduced transcript and increased plasma levels of MIF in spinal TB patients, and MIF may play an important role in the occurrence, development, and damage of spinal TB in the northern Province population of China.


Assuntos
Fatores Inibidores da Migração de Macrófagos/sangue , Polimorfismo Genético/genética , RNA Mensageiro/genética , Tuberculose da Coluna Vertebral/genética , Adulto , Alelos , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA/métodos
19.
J Ethnopharmacol ; 264: 113212, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32768643

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion (CIR) injury is one of the main diseases leading to death and disability. Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Panax ginseng, has neuroprotective effects on anti-CIR injury. However, the underlying molecular mechanism of its therapeutic effects is not clear. AIM OF THE STUDY: To systematically study and explore the mechanism of Acanthopanax senticosus (Rupr. & Maxim.) Harms extract (ASE) in the treatment of CIR injury based on metabolomics and transcriptomics. MATERIALS AND METHODS: The pharmacological basis of ASE in the treatment of CIR was evaluated, and samples were used in plasma metabolomics and brain tissue transcriptomics to reveal potential biomarkers. Finally, according to online database, we analyzed biomarkers identified by the two technologies, explained reasons for the therapeutic effect of ASE, and identify therapeutic targets. RESULTS: A total of 53 differential metabolites (DMs) were identified in plasma and 3138 differentially expressed genes (DEGs) were identified in brain tissue from three groups of rats, including sham, ischemia-reperfusion (I/R), and ASE groups. Enrichment analysis showed that Nme6, Tk1, and Pold1 that are involved in the production of deoxycytidine and thymine were significantly up-regulated and Dck was significantly down-regulated by the intervention with ASE. These findings indicated that ASE participates in the pyrimidine metabolism by significantly regulating the balance between dCTP and dTTP. In addition, ASE repaired and promoted the lipid metabolism in rats, which might be due to the significant expression of Dgkz, Chat, and Gpcpd1. CONCLUSIONS: The findings of this study suggest that ASE regulates the significant changes in gene expression in metabolites pyrimidine, and lipid metabolism in CIR rats and plays an active role in the treatment of CIR injury through multiple targets and pathways.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32766212

RESUMO

This paper investigates the conformational stability of porcine pancreatic lipase (PPL) in three non-aqueous organic solvents, including dimethyl sulfoxide (DMSO), propylene glycol (PRG), and ethanol (EtOH) through molecular dynamic (MD) simulation. The root mean square deviations (RMSDs), radius of gyration (Rg), solution accessible surface area (SASA), radial distribution function (RDF), hydrogen bond (H-bond), Ramachandran plot analysis, secondary structure, and enzyme substrate affinity of the PPL in the various organic solvents were comparatively investigated. The results showed that the backbone and active pocket RMSD, and hydrophilic ASA of PPL in three solvents increase with the increase in the solvent LogP, while the Rg, hydrophobic ASA, and H-bond between the solvent and PPL decrease. Among the three organic solvents, DMSO acts as a better solvent, in which the PPL can be loose and extended, and retains its native backbone in DMSO compared to PRG and EtOH. Moreover, Ramachandran plot analysis indicated that the PPL structure quality in DMSO was higher than that in PRG and EtOH. Also, the molecular docking results showed that PPL in DMSO exhibited the highest enzyme-substrate affinity.

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