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1.
J Adv Res ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38740260

RESUMEN

INTRODUCTION: The N-terminal domain of angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity. Its C-terminal fibrinogen-like (FBN) domain is a ligand of macrophage integrin αvß3. OBJECTIVES: ANGPTL3 might home to plaque where it directly regulates macrophage function via integrin αvß3 for atherosclerosis progression. METHODS: Ldlr-/- mice on a high-fat diet and ApoE-/- mice on a chow diet were received adeno-associated virus (AAV)-mediated Angptl3 gene transfer and followed up for 12 weeks. ApoE-/- mice were injected AAV containing FLAG-tagged Angptl3 cDNA for tracing. Atherosclerotic features were compared between Angptl3-/-ApoE-/- mice and ApoE-/- littermates. THP-1 cells were exposed to 0 or 50 µg/ml ANGPTL3 FBN domain for 24 h to evaluate Toll-like receptor (TLR)4 expression using western blot analysis and circulating cytokine and chemokine profiles by the MILLIPLEX MAP assay. Phospho-proteomic profile was established in ANGPTL3-treated macrophages. Integrin ß3 deficient THP-1 cells were obtained by sgRNAs targeting RGD sequence using Lentivirus-Cas9 system. RESULTS: Angptl3 overexpression increased atherosclerotic progression and CD68+ macrophages in plaque (p < 0.05 for all). By immunostaining, FLAG+ cells were identified in plaque of gene transferred ApoE-/- mice. Fluorescent immunostaining detected co-localisation of Angptl3 and CD68 in plaque macrophages. Phospho-proteomic analysis revealed that Angptl3 induced phosphorylation of proteins that were involved in the IL-17 signalling pathway in THP-1 cells. In vitro, ANGPTL3 treatment increased the production of interleukin (IL)-1ß and tumour necrosis factor-α in THP-1 cells (p < 0.05 for both). Exposure of ANGPTL3 to THP-1 cells induced Akt phosphorylation which was weakened in integrin ß3 deficient ones. ANGPTL3 elevated TLR4 expression via Akt phosphorylation. In response to lipopolysaccharide, nuclear factor-κB activity was 2.2-fold higher in THP-1 cells pre-treated with ANGPTL3 than in untreated cells (p < 0.05). CONCLUSIONS: Targeting ANGPTL3 could yield a dual benefit of lowering lipid levels in the blood and suppressing macrophage activation in plaque.

2.
Front Microbiol ; 14: 1171339, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37250032

RESUMEN

Background: The emergence of multi-drug resistant Staphylococcus aureus (S. aureus) has posed a challenging clinical problem for treating its infection. The development of novel or new antibacterial agents becomes one of the useful methods to solve this problem, and has received more attention over the past decade. Citral is reported to have antibacterial activity against S. aureus, but its mechanism is yet entirely clear. Methods: To reveal the antibacterial mechanism of citral against S. aureus, comparative transcriptomic analysis was carried out to analyze the gene expression differences between the citral-treated and untreated groups. The changes of protein, adenosine triphosphate (ATP) and reactive oxygen species (ROS) content in S. aureus caused by citral were also examined. Results: Six hundred and fifty-nine differentially expressed genes were obtained according to the comparative transcriptomic analysis, including 287 up-regulated genes and 372 down-regulated genes. The oxidoreductase activity and fatty acid degradation pathway were enriched in up-regulated genes, and ribosome and S. aureus infection pathway were enriched in down-regulated genes. Meanwhile, physiological trials revealed a decline in ATP and protein levels, but an increase in ROS content within the citral-treated group. Thus, it can be inferred that the antibacterial effects of citral against S. aureus were likely due to its ability to decrease ATP content by down-regulating ATP synthase genes (atpD and atpG), reduce protein content, induce cell membrane and cell wall damages, accumulate ROS, and down-regulate virulence factor genes to reduce pathogenicity. Conclusion: These findings revealed the antibacterial mechanism of citral was likely a type of multi-target mode that affected multiple molecular processes in S. aureus, which lays the groundwork for further exploitation of citral as a therapeutic candidate against S. aureus infections.

3.
Front Cell Infect Microbiol ; 13: 1126409, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36875515

RESUMEN

Mastitis is one of the most prevalent diseases of dairy cows. Currently, mastitis treatment in dairy cows is mainly based on antibiotics. However, the use of antibiotics causes adverse effects, including drug resistance, drug residues, host-microbiome destruction, and environmental pollution. The present study sought to investigate the potentiality of geraniol as an alternative to antibiotics for bovine mastitis treatment in dairy cows. Additionally, the effectiveness of treatment, improvement in inflammatory factors, the influence on microbiome, presence of drug residues, and drug resistance induction were compared and analyzed comprehensively.Geraniol showed an equivalent therapeutic rate as antibiotics in the mouse infection model and cows with mastitis. Moreover, geraniol significantly inhibited the pathogenic bacteria and restored the microbial community while increasing the abundance of probiotics in milk. Notably, geraniol did not destroy the gut microbial communities in cows and mice, whereas antibiotics significantly reduced the diversity and destroyed the gut microbial community structure. Additionally, no geraniol residue was detected in milk four days after treatment discontinuation, but, antibiotic residues were detected in milk at the 7th day after drug withdrawal. In vitro experiments revealed that geraniol did not induce drug resistance in the Escherichia coli strain ATCC25922 and Staphylococcus aureus strain ATCC25923 after 150 generations of culturing, while antibiotics induced resistance after 10 generations. These results suggest that geraniol has antibacterial and anti-inflammatory effects similar to antibiotics without affecting the host-microbial community structure or causing drug residues and resistance. Therefore, geraniol can be a potential substitute for antibiotics to treat mastitis or other infectious diseases and be widely used in the dairy industry.


Asunto(s)
Residuos de Medicamentos , Mastitis Bovina , Microbiota , Femenino , Animales , Bovinos , Ratones , Antibacterianos , Modelos Animales de Enfermedad , Escherichia coli
4.
J Ethnopharmacol ; 296: 115524, 2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-35811028

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum perforatum L. has a long history in many countries of being used as a herbal medicine. It is also widely used in Chinese herbal medicine for the treatment of infections. Hypericin, a main component extracted from Hypericum perforatum L., has attracted the attention of many researchers for its remarkable antiviral, antitumor and antidepressant effects. AIM OF THE STUDY: To find plant molecules that inhibit the alkaline nuclease (AN) of herpes simplex virus type 1 (HSV-1) and suppress viral replication. MATERIALS AND METHODS: Bioinformatics methods were used to determine which compounds from a variety of natural compounds in our laboratory interact with AN. By this means we predicted that hypericin may interact with AN and suppress HSV-1 replication. Experiments were then carried out to verify whether hypericin inhibits the bioactivity of AN. The Pichia pastoris expression system was used to obtain recombinant AN. The exonuclease and endonuclease activity of AN treated with hypericin were tested by electrophoresis. Immunohistochemical staining of the HSV-1 nucleocapsids was used to find out whether hypericin inhibits the intracellular function of AN. Real-time PCR and western blotting analysis were performed to test viral gene expression and viral protein synthesis. The extent of viral replication inhibited by hypericin was determined by a plaque assay and a time of addition assay. RESULTS: Recombinant AN was obtained by Pichia pastoris expression system. The exonuclease and endonuclease activity of recombinant AN were inhibited by hypericin in the electrophoresis assay. Hypericin showed no inhibitory effect on BeyoZonase™ Super Nuclease or DNase I. T5 Exonuclease activity was inhibited partially by10 µM hypericin, and was completely suppressed by 50 µM hypericin. Hind Ⅲ was inhibited by hypericin at concentrations greater than 100 µM, but EcoR I, BamH I, and Sal I were not inhibited by hypericin. HSV-1 nucleocapsids gathered in the nucleus when the viruses were treated with hypericin. Plaque formation was significantly reduced by hypericin (EC50 against HSV-1 F is 2.59 ± 0.08 µM and EC50 against HSV-1 SM44 is 2.94 ± 0.10 µM). UL12, ICP27, ICP8, gD, and UL53 gene expression (P < 0.01, 4.0 µM hypericin treated group vs control group) and ICP4 (P < 0.05, 6.0 µM hypericin treated group vs control group), ICP8 and gD (P < 0.05, 2.0 µM hypericin treated group vs control group) protein synthesis were inhibited by hypericin. In the time of addition assay, HSV-1 was suppressed by hypericin in the early stages of viral replication. Hypericin exhibits potent virucidal activity against HSV-1 and inhibits the adsorption and penetration of HSV-1. CONCLUSION: Hypericin inhibits the bioactivity of AN and suppresses HSV-1 replication. The data revealed a novel mechanism of the antiherpetic effect of hypericin.


Asunto(s)
Herpesvirus Humano 1 , Animales , Antracenos , Antivirales/química , Antivirales/farmacología , Chlorocebus aethiops , Endonucleasas , Exonucleasas/metabolismo , Exonucleasas/farmacología , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/metabolismo , Perileno/análogos & derivados , Saccharomycetales , Células Vero , Replicación Viral
5.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(3): 462-470, 2022 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-35788515

RESUMEN

Percutaneous pulmonary puncture guided by computed tomography (CT) is one of the most effective tools for obtaining lung tissue and diagnosing lung cancer. Path planning is an important procedure to avoid puncture complications and reduce patient pain and puncture mortality. In this work, a path planning method for lung puncture is proposed based on multi-level constraints. A digital model of the chest is firstly established using patient's CT image. A Fibonacci lattice sampling is secondly conducted on an ideal sphere centered on the tumor lesion in order to obtain a set of candidate paths. Finally, by considering clinical puncture guidelines, an optimal path can be obtained by a proposed multi-level constraint strategy, which is combined with oriented bounding box tree (OBBTree) algorithm and Pareto optimization algorithm. Results of simulation experiments demonstrated the effectiveness of the proposed method, which has good performance for avoiding physical and physiological barriers. Hence, the method could be used as an aid for physicians to select the puncture path.


Asunto(s)
Neoplasias Pulmonares , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Punciones , Tórax , Tomografía Computarizada por Rayos X
6.
Front Plant Sci ; 13: 904178, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35720564

RESUMEN

As an important economic and medicinal crop, Amomum tsao-ko is rich in volatile oils and widely used in food additives, essential oils, and traditional Chinese medicine. However, the lack of the genome remains a limiting factor for understanding its medicinal properties at the molecular level. Here, based on 288.72 Gb of PacBio long reads and 105.45 Gb of Illumina paired-end short reads, we assembled a draft genome for A. tsao-ko (2.70 Gb in size, contig N50 of 2.45 Mb). Approximately 90.07% of the predicted genes were annotated in public databases. Based on comparative genomic analysis, genes involved in secondary metabolite biosynthesis, flavonoid metabolism, and terpenoid biosynthesis showed significant expansion. Notably, the DXS, GGPPS, and CYP450 genes, which participate in rate-limiting steps for terpenoid backbone biosynthesis and modification, may form the genetic basis for essential oil formation in A. tsao-ko. The assembled A. tsao-ko draft genome provides a valuable genetic resource for understanding the unique features of this plant and for further evolutionary and agronomic studies of Zingiberaceae species.

7.
Infect Drug Resist ; 15: 3161-3171, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35747334

RESUMEN

Purpose: To compare antimicrobial resistance, virulence, clinical characteristics, and risk factors between carbapenem-resistant K. pneumoniae (CRKP) and carbapenem-susceptible K. pneumoniae (CSKP) isolates from patients with bloodstream infections (BSIs) in China. Patients and Methods: The clinical data of 103 patients with K. pneumoniae BSI from 10 hospitals were retrospectively analyzed. The minimum inhibitory concentrations of 15 antibiotics against the bacteria were determined. A Galleria mellonella infection model was used to evaluate virulence of the isolates. Kaplan-Meier curves were calculated to evaluate the 28-day and in-hospital survival rates of the isolates. The risk factors for CRKP and CSKP infection and respective mortality rate were evaluated by univariate analysis, and independent risk factors were evaluated using the multivariate logistic regression model. Results: Our results indicated that CRKP isolates were more resistant to most tested antibiotics than CSKP isolates. The G. mellonella infection model was used to demonstrate that CRKP isolates were more virulent than CSKP isolates. We found that in-hospital deaths occurred in 39.3% (22/56) of patients with CRKP BSIs and were significantly higher than those in patients with CSKP infections (19.1%, 9/47). Patients infected with CRKP isolates had poorer outcomes than those infected with the CSKP strains. For in-hospital mortality of CRKP BSIs, the independent risk factors included carbapenem-resistant Enterobacterales bacteremia and length of hospitalization after the onset of BSI. Conclusion: Our findings confirm that CRKP isolates are more drug-resistant than CSKP isolates and are associated with poorer outcomes. To prevent CRKP infection, strict infection control strategies and active surveillance should be implemented in hospitals.

8.
Eur J Clin Microbiol Infect Dis ; 41(1): 79-86, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34562152

RESUMEN

This study is to analyze the dynamic changes of inflammation and oxidative stress in mice infected with MRSA and to provide experimental basis for clinically formulating reasonable treatment plans. We established a model of MRSA infection in mice, detected the fluctuations in the concentration of proinflammatory cytokines and oxidative stress factors with time, and combined with the results of microscopic examination of tissue sections to explain the infection in vivo caused by MRSA. The results showed that on the 1st, 3rd, and 7th day of MRSA infection, the number of leukocytes and eosinophils decreased at first and then increased, monocytes increased continuously, and neutrophils and basophils decreased. At the same time, the levels of proinflammatory cytokines IL-1ß, IL-6, and TNF-α increased. The concentration of glutathione peroxide decreased, and the oxidative metabolites increased. Tissue sections also showed that inflammation and oxidative stress occurred in mice. It is obvious that MRSA infection can lead to significant inflammation and oxidative stress. Therefore, while treating MRSA infection, attention should be paid to the levels of inflammation and oxidative stress in different periods to achieve better treatment effects.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina/fisiología , Estrés Oxidativo , Infecciones Estafilocócicas/inmunología , Animales , Femenino , Glutatión/inmunología , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Masculino , Staphylococcus aureus Resistente a Meticilina/genética , Ratones , Ratones Endogámicos ICR , Infecciones Estafilocócicas/genética , Infecciones Estafilocócicas/microbiología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
9.
Infect Drug Resist ; 14: 2991-3000, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34385822

RESUMEN

INTRODUCTION: Antibiotics wee widely used as feed additives in animal husbandry. With the increase of drug resistance of bacteria, there is an urgent need to find alternatives to antibiotics. Clinically, methicillin-resistant Staphylococcus aureus (MRSA) infections account for about 25% to 50% of Staphylococcus aureus infections worldwide. Similarly, it is also one of the pathogens that cause serious animal infections. METHODS: We established a mouse model of systemic infection of MRSA to study the preventive effect of geraniol on MRSA and the immunomodulatory effect of geraniol. The mice in the experiment were injected with geraniol by intramuscular injection and were fed intraperitoneally with minimum lethal dose of MRSA. Then, the survival rate, inflammatory cytokines, oxidative stress factors in serum were measured. These values were used to estimate the bacterial load in different organs and to assess histopathological changes in the lungs, liver and kidneys. RESULTS: The above-mentioned two ways of using geraniol could prevent MRSA infection in vivo in mice and showed a significant dose-response relationship. In other words, geraniol significantly decreased the concentrations of inflammatory cytokines and oxidative stress factors in MRSA-infected mice. At the same time, the level of glutathione peroxidase also increased in a dose-proportional relationship. In the group of mice treated with geraniol, their superoxide dismutase levels were significantly higher than those in the vancomycin. After treatment with geraniol, the burden of MRSA decreased. No obvious histopathological abnormalities were found in the liver and kidney of MRSA-infected mice. In addition, geraniol improved the inflammatory changes in the lungs. CONCLUSION: The results indicated that geraniol was a natural substance that could be used as an anti-inflammatory, antioxidant and antibacterial substance to protect mice from MRSA systemic infection. Generally, the research shows that as a natural medicine, geraniol has broad potential in the development and application of antibiotic substitutes.

10.
BMC Complement Med Ther ; 20(1): 318, 2020 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-33076882

RESUMEN

BACKGROUND: Multidrug-resistant pathogens are resistant to many antibiotics and associated with serious infections. Amomum tsaoko Crevost et Lemaire, Sanguisorba officinalis, Terminalia chebula Retz and Salvia miltiorrhiza Bge, are all used in Traditional Chinese Medicine (TCM) against multidrug-resistant pathogens, and the purpose of this study was to evaluate the antibacterial and anti-virulence activity of extracts derived from them. METHODS: The antibacterial activity of ethanol and aqueous extracts from these four plants was examined against several multi-drug resistant bacterial strains, and their anti-virulence potential (including quorum quenching activity, biofilm inhibition, and blocking production of virulence factor δ-toxin) was assessed against different S. aureus strains. The chemical composition of the most effective extract was determined by LC-FTMS. RESULTS: Only extracts from S. officinalis and A. tsaoko were shown to exhibit limited growth inhibition activity at a dose of 256 µg·mL-1. The S. officinalis ethanol extract, the ethanol and aqueous extract of A. tsaoko, and the aqueous extract of S. miltiorrhiza all demonstrated quorum quenching activity, but didn't significantly inhibit bacterial growth. The ethanol extract of S. officinalis inhibited bacterial toxin production and biofilm formation at low concentrations. Chemical composition analysis of the most effective extract of S. officinalis showed that it mainly contained saponins. CONCLUSIONS: The most active extract tested in this study was the ethanol root extract of S. officinalis. It inhibited δ-toxin production and biofilm formation at low concentrations and saponins may be its key active components. While the four plants showed no direct antibacterial effects, their anti-virulence properties may be key to fighting bacterial infections.


Asunto(s)
Antibacterianos/farmacología , Antivirales/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Viral Múltiple/efectos de los fármacos , Medicina Tradicional China , Extractos Vegetales/farmacología , Antibacterianos/química , Antivirales/química , Estructura Molecular , Extractos Vegetales/química
11.
Medicine (Baltimore) ; 99(22): e19801, 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32481362

RESUMEN

INTRODUCTION: Chorea is considered a special complication of diabetes mellitus. Here we report a case of chorea associated with non-ketotic hyperglycemia (NKH). PATIENT CONCERNS: The patient was a 79-year-old Asian woman. She had a history of type 2 diabetes mellitus more than 30 years, but with a poor control of blood sugar. She complained of acute onset of right limb involuntary activities, and being admitted to neurology department. DIAGNOSIS: The patient was then diagnosed with NKH chorea. INTERVENTIONS: Intravenous infusion of insulin was given to reduce blood glucose. Haloperidol was used to control motor symptoms. OUTCOMES: Her symptoms improved quickly after treatment. In the past year, the patient's blood sugar was well controlled and her chorea did not recur. LESSONS: If there are sudden abnormal movements in patients, in addition to thinking of chorea, hepatolenticular degeneration and other diseases, we should also pay attention to blood sugar, especially in diabetic patients with poor blood sugar control and negative ketone, we should consider the possibility of NKK chorea. CONCLUSIONS: NKH chorea is a special complication of diabetes.


Asunto(s)
Corea/etiología , Diabetes Mellitus Tipo 2/complicaciones , Hiperglucemia/complicaciones , Anciano , Femenino , Humanos
12.
J Toxicol Sci ; 44(4): 299-307, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30944282

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) leads to serious infections, but it is not known whether it changes the expression of kidney drug metabolizing enzymes during infection. The mice were infected with different doses of MRSA and the oxidative stress and inflammation levels in the kidney were examined. The mRNA expression and activity of cytochrome P450 enzyme was analysed. Mice infected with high levels of MRSA showed a decrease in renal antioxidant capability and an elevated level of oxidative metabolites, which was accompanied by the release of inflammatory cytokines. The levels of interleukin 1ß, tumour necrosis factor alpha, and macrophage inflammatory protein-1α were significantly increased along with the levels of nitric oxide and malondialdehyde. On day 7, mRNA expression of Cyp1a2, 2d22, and 3a11 were decreased by the high level of MRSA, but the low level of MRSA increased their expressions. Cyp2e1 mRNA expression was increased by MRSA in the kidney of mice. High dose of MRSA infection increased the oxidative stress and inflammatory response in mouse kidney, leading to the decrease in the expression of renal drug-metabolizing enzymes and no recovery within 7 days.


Asunto(s)
Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Expresión Génica , Riñón/enzimología , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas/enzimología , Infecciones Estafilocócicas/genética , Animales , Citocinas/metabolismo , Inflamación , Mediadores de Inflamación/metabolismo , Riñón/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones Endogámicos , Óxido Nítrico/metabolismo , Estrés Oxidativo , ARN Mensajero/genética , ARN Mensajero/metabolismo
13.
J Sci Food Agric ; 99(9): 4423-4429, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30891759

RESUMEN

BACKGROUND: Citral is an active component of many plant extracts, and it is a safe additive used in food and cosmetics. A previous study showed that citral has a good antibacterial effect against methicillin-resistant Staphylococcus aureus (MRSA) in vitro, but its in vivo anti-infective activity has not been studied. Anti-MRSA activity and the preliminary mechanism of citral against MRSA were investigated in MRSA-infected KM mice. The ED50 was calculated using Karber's method. Groups were selected for inflammatory and oxidative stress level tests, and lung and liver tissues were counterstained with HE for detection of pathological changes. Cytokines and oxidative factors were evaluated using the ELISA method (one-way ANOVA computed using SPSS 19.0.). RESULTS: With the increase in the concentration of citral, the survival rate of MRSA-infected mice increased accordingly. The ED50 values of citral for intramuscular injection and intragastric administration were 0.09 and 0.26 g kg-1 respectively. Citral significantly reduced cytokines (IL-1ß, IL-6, TNF-α) and oxidative factors (malondialdehyde and hydroxyl radicals) of MRSA-infected mice, whereas it increased gluthtione and superoxide dismutase levels. Citral can reduce the lung inflammatory infiltrates infected by MRSA. CONCLUSIONS: Citral exerted a dose-dependent anti-MRSA effect and ameliorated MRSA-induced abnormal changes in inflammation and oxidative stress. This indicates that citral has the potential for development as a new anti-MRSA drug. © 2019 Society of Chemical Industry.


Asunto(s)
Antibacterianos/administración & dosificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Monoterpenos/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Monoterpenos Acíclicos , Animales , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Ratones , Estrés Oxidativo/efectos de los fármacos , Infecciones Estafilocócicas/genética , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
14.
Pharm Biol ; 56(1): 337-343, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29969356

RESUMEN

CONTEXT: Citral is used as a potential natural treatment for various infectious diseases. OBJECTIVE: To examine the effect of citral on the mRNA expression and activities of cytochrome P450 (CYP450) enzymes and establish the relationship between citral-induced liver injury and oxidative stress. MATERIALS AND METHODS: ICR mice were randomly divided into citral (20, 200, and 2000 mg/kglow), Tween-80, and control groups (0.9% saline), 10 mice in each group. The citral-treated groups were intragastrically administered citral for 3 d, control groups treated with 0.5% Tween-80 and 0.9% saline in the same way. Liver injury and CYP450 enzymes were analyzed by analyzing the histopathological changes and the changes of related enzymes. RESULTS: Citral treatment (2000 mg/kg) for 3 d increased serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels, as well as glutathione, gydroxyl radicals, malonaldehyde and total superoxide dismutase contents, but decreased the content of total antioxidant capacity. In doses of 20 and 200 mg/kg groups mice, the contents of NO were decreased significantly and other changes were similar to the 2000 mg/kg group mice, but the liver damage was most severe in the 2000 mg/kg group. Citral induced the mRNA expression and activities of CYP450 1A2, 2D22, and 2E1 in the liver of mice at doses of 20 and 200 mg/kg. There were no changes in testing indexes in Tween-80 treated group mice. Due to its toxic effects, the CYP induction effect of citral negatively correlated with its dose. Although the mRNA expression of CYP450 3A11 was induced by citral, its activity was not affected by low and moderate doses of citral. CYP450 3A11 activity was significantly decreased by high-dose citral. CONCLUSIONS: Citral is hepatotoxic and induced oxidative stress in higher dose, which has a negative effect on CYP450 enzymes. These data suggest caution needs to be taken in order to avoid citral-drug interactions in human beings.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Monoterpenos/metabolismo , Monoterpenos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Monoterpenos Acíclicos , Animales , Antioxidantes/metabolismo , Antioxidantes/toxicidad , Interacciones Farmacológicas/fisiología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/fisiología
15.
Infect Drug Resist ; 11: 229-238, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29491713

RESUMEN

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a very damaging and widespread pathogen, which is associated with many diseases and causes serious infections. MRSA infection can modulate the effects of drugs, which may occur through an influence on cytochrome P450 (CYP450), the drug-metabolizing enzyme in the liver. In this study, we evaluated the underlying mechanism of drug failure or poisoning in MRSA infection. MATERIALS AND METHODS: Mice were infected with three different doses of MRSA and the changes in CYP450 expression, cytokines, and oxidative stress markers were evaluated. RESULTS: The administration of an attack dose of MRSA caused serious symptoms of infection and resulted in a 40% mortality rate in the mice. MRSA induced strong inflammation and oxidative stress in the mice, predominantly caused by significant increases in interleukin (IL)-1ß, IL-4, IL-6, macrophage inflammatory protein, glutathione S-transferase (GST), and malondialdehyde, and decreases in oxygen radical absorbance capacity and glutathione levels in the liver. The expression of IL-2, tumor necrosis factor-α, and GST was briefly suppressed, but increased on days 3 and 7. The increased inflammation and oxidative stress further induced a significant decrease in the mRNA levels and activities of CYP450 1A2, 2D22, 2E1, and 3A1 in MRSA-infected mice within the first day of infection. CONCLUSION: These results show that MRSA infection leads to inflammation and oxidative stress, and reduces the expression levels and activities of drug metabolism enzymes, which decreased drug metabolism in patients infected with MRSA. Therefore, to avoid a drug overdose, the plasma concentration of patients with MRSA infection should be continuously monitored.

16.
Mitochondrial DNA B Resour ; 2(1): 327-328, 2017 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-33473816

RESUMEN

In this study, we sequenced the complete mitochondrial genome of Thermophis shangrila by using the next-generation sequencing technique. The total length of the mitogenome was 17,407 bp, which was composed of 13 protein coding genes, two rRNA genes (12s and 16s rRNA), 22 tRNA genes, and two control regions (CRI and CRII). The base composition was 32.6% for A, 23.9% for T, 30.0% for C, and 13.5% for G. We added a fragment about 150 bp in length at control region I, which Peng et al. failed to obtain using Sanger dideoxy sequencing.

17.
Mitochondrial DNA B Resour ; 2(2): 391-392, 2017 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-33473837

RESUMEN

The complete mitochondrial genome of Thermophis baileyi was sequenced using the next-generation sequencing (NGS) in the present study. The total length of the mitogenome was 17,355 bp, which was composed of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes (12s and 16s rRNA), and 2 control regions (CR I and CR II). The base composition was 32.4% for A, 23.8% for T, 30.2% for C, and 13.6% for G. Coding genes of each protein in the mtDNA had the same start and stop codons among three Thermophis species.

18.
Molecules ; 21(11)2016 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-27809255

RESUMEN

PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as purification and quantification. Site-specific modification by mPEG-succinimidyl carbonate (mPEG-SC) is a widely used method for N-terminal conjugation. In this study, we used it for site-directed modification on two ribosome-inactivating proteins (RIPs), alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30), from Momordica charantia L. According to the optimization of previous modification conditions, we compared Macro-Cap SP with SP-Sepharose FF chromatography for separating the final mPEGylated RIPs. Two kinds of methods both can obtain homogenous mPEGylated RIPs which were identified by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), and matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) analysis. We also used iodine staining method to detect the amount of unmodified PEG. Furthermore, the inhibition activity of both mPEGylated and non-PEGylated RIPs against human lung adenocarcinoma epithelial A549 cells was detected. All of the results suggested that the mPEGylated α-MMC/MAP30 might be potentially developed as new anti-tumor drugs.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos , Neoplasias Pulmonares/tratamiento farmacológico , Momordica charantia/química , Polietilenglicoles/química , Proteínas Inactivadoras de Ribosomas Tipo 2 , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Inactivadoras de Ribosomas Tipo 2/química , Proteínas Inactivadoras de Ribosomas Tipo 2/farmacología
19.
Int J Mol Sci ; 17(6)2016 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-27338374

RESUMEN

Staphylococcus epidermidis, especially methicillin-resistant strains, may be the source of surgical site infections and may be a reservoir of staphylococcal cassette chromosome mec (SCCmec) for S. aureus. The aim of this study was to investigate the prevalence of methicillin-resistant S. epidermidis (MRSE) on the abdominal skin of females before laparotomy and determine the molecular characteristics and antimicrobial susceptibility patterns of these isolates. MRSE was found in 54 of 157 isolates based on mecA gene detection, and there was no difference in icaA gene carriage rate between MRSE and methicillin-susceptible S. epidermidis (MSSE) isolates. Antimicrobial susceptibility profiles were determined by broth microdilution antimicrobial susceptibility testing according to the latest CLSI manuals. All MRSE isolates had unfavorable antimicrobial susceptibility patterns. Twenty-three MRSE strains (42.6%) were multi-drug resistant. SCCmec typing and pulsed field gel electrophoresis (PFGE) typing was performed. Thirty-nine (72.2%) had a single SCCmec type, whereas 1.9% had two types. Fourteen strains (25.9%) were non-typeable (NT). The most frequent MRSE genotype was SCCmec type IVa. High diversity with PFGE patterns was obtained for MRSE, and there were no isolates exhibiting identical pulsotype. The results confirm that methicillin-resistant strains are frequently present among S. epidermidis on the abdominal skin of females before laparotomy. Moreover, resistance profiles seem to have no association with the SCCmec types or PFGE types for most common antibiotics.


Asunto(s)
Proteínas Bacterianas/genética , Resistencia a la Meticilina , Piel/microbiología , Staphylococcus epidermidis/efectos de los fármacos , Abdomen/microbiología , Abdomen/cirugía , Adulto , Proteínas Bacterianas/metabolismo , Femenino , Humanos , Laparotomía , Persona de Mediana Edad , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/aislamiento & purificación
20.
J Tradit Chin Med ; 36(6): 799-804, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-29949841

RESUMEN

OBJECTIVE: To evaluate the anti-infectious efficacy of essential oil extracted from Caoguo (Fructus Tsaoko). METHODS: Minimum inhibitory concentrations (MICs) against clinical isolates of three extracts and the essential oil from Caoguo (Fructus Tsaoko) were determined by the agar dilution method. The antiinfectious efficacy of the essential oil was evaluated using a mouse peritonitis model which was infected with Staphylococcus aureus or Escherichia coli. The chemical components of the essential oil were identified. RESULTS: The results showed that the essential oil exhibited strong antibacterial activity in vitro, with MICs ranging from 22.49 to 1438.91 µg/mL. The results of in vivo anti-infectious efficacy showed that the Caoguo (Fructus Tsaoko) essential oil can protect the mice from Staphylococcus aureus or Escherichia coli infection. The compositions of the essential oil and relative component percentages were examined. A total of 32 compounds, were identified. The major compounds of essential oil were 1, 8-cineole (25.92%) and geraniol (13.69%). CONCLUSION: Our findings suggest that Caogu (Fructus Tsaoko) essential oil has broad-spectrum antibacterial properties. It warrants further investigation as an antibacterial agent targeting some bacterium with multi-drug resistance.


Asunto(s)
Amomum/química , Antibacterianos/administración & dosificación , Aceites Volátiles/administración & dosificación , Aceites de Plantas/administración & dosificación , Animales , Antibacterianos/análisis , Antibacterianos/aislamiento & purificación , Escherichia coli/efectos de los fármacos , Femenino , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/análisis , Aceites Volátiles/aislamiento & purificación , Aceites de Plantas/análisis , Aceites de Plantas/aislamiento & purificación , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología
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