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1.
Pestic Biochem Physiol ; 202: 105945, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38879302

ABSTRACT

With the widespread utilization of the sanitizing product benzethonium chloride (BEC) throughout the coronavirus pandemic, concerns have emerged regarding its potential hazards. Nevertheless, the long-term and multigenerational toxic effects of BEC on aquatic organisms remains unexplored. This study investigates acute and chronic toxicity, oxidative stress, mitochondrial membrane potential, ATP concentrations, and gene expression using Daphnia carinata as the model organism. Meanwhile, hierarchical clustering analysis was utilized to investigate phenotypic effects among different treatment groups. The integrated biomarker response index version 2 (IBRv2) was employed to estimate the deviation in toxic effects over two generations. These results indicated that D. carinata in the second generation exhibited higher survival rate and lower levels of oxidative stress than the first generation. However, the higher sublethal effects were found in the second generation as follows, the weakened growth performance, mitochondrial membrane potential depolarization, reduced ATP concentrations, and down-regulated gene expression. The mitochondrial toxicity induced by BEC may account for the distinct toxic effects exhibited in two generations. The findings here can assist with the evaluation of potential risk for BEC on aquatic organisms, and provide new insight into the cross-generational toxicity mechanisms of pollutants in aquatic ecosystems.


Subject(s)
Daphnia , Membrane Potential, Mitochondrial , Oxidative Stress , Animals , Daphnia/drug effects , Daphnia/genetics , Membrane Potential, Mitochondrial/drug effects , Oxidative Stress/drug effects , Adenosine Triphosphate/metabolism , Water Pollutants, Chemical/toxicity
2.
Article in English | MEDLINE | ID: mdl-38551431

ABSTRACT

Objective: The objective of this study was to evaluate the effects of comfort care on perioperative outcomes and postoperative recovery of breast cancer patients. Evaluating comfort care is important in the context of breast cancer surgery because it can potentially alleviate pain, improve patient comfort, enhance postoperative recovery, and reduce complications, ultimately leading to better patient outcomes. Methods: Between March 2020 and December 2021, 78 patients undergoing breast cancer surgery at our hospital were randomly assigned to receive either routine nursing (routine group) or comfort care (experimental group). The comfort care intervention included various components such as health education, preoperative care, intraoperative care, postoperative care, pain care, and psychological care. The routine group received standard nursing care following medical advice. Results: The patient characteristics between the two groups were comparable. Comfort care resulted in significantly higher visual analog scale (VAS) scores, indicating reduced pain, and better improvement in functional recovery of the upper limb compared to routine nursing. Comfort care was also associated with better postoperative recovery, as evidenced by lower self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores. The experimental group had a significantly lower incidence of complications compared to the routine group. Additionally, the experimental group reported better 24-hour comfort and higher nursing satisfaction. Conclusion: In conclusion, comfort care effectively reduces postoperative pain, promotes postoperative recovery, improves patient emotions, lowers the incidence of complications, and enhances comfort and care satisfaction in breast cancer patients undergoing radical surgery. These findings highlight the importance of incorporating comfort care interventions in the perioperative management of breast cancer patients. Further research and implementation of comfort care strategies may have implications for improving clinical practice and patient outcomes in the future.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(5): 1492-1495, 2023.
Article in Chinese | MEDLINE | ID: mdl-37846706

ABSTRACT

OBJECTIVE: To investigate the identification and molecular biological mechanism of a case of B(A)04 allele. METHODS: The ABO blood groups of the proband and his nine family members were analyzed serologically and DNA sequencing was used to accurately determine the genotypes of these ten specimens. The cartoon models of local active center of enzymes of the GTA,GTB and the GTB mutant were constructed to explore the possible molecular mechanism leading to abnormal enzyme-catalyzed A antigen synthesis. RESULTS: The serological results suggested that the ABO blood groups of the proband, his elder brother and his maternal grandmother were AweakB or B(A); the ABO blood group of his mother was type AB, his uncle and elder aunt were type B, and his father was type O. ABO blood group gene sequencing results showed that 6 out of 10 members of the family carried the B(A)04 allele. Molecular structure models suggested that the spatial distance of critical amino acid residues in the catalytic center of the GTB mutant enzyme was greater than that of GTB, which might cause the enzyme to abnormally catalyze the synthesis of A antigen. CONCLUSION: The characteristics of serological reactions of B(A) blood subgroup are complicated, and its identification needs to be combined with molecular biology and pedigree investigation. It is speculated that the B(A) phenotype may be associated with a larger volume of the catalytic center in the GTB mutant.

4.
Cell Commun Signal ; 21(1): 212, 2023 08 18.
Article in English | MEDLINE | ID: mdl-37596634

ABSTRACT

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract. The absorption of SCFAs is mediated by substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled monocarboxylate transporter 1, which promote cellular metabolism. An increasing number of studies have implicated metabolites produced by microorganisms as crucial executors of diet-based microbial influence on the host. SCFAs are important fuels for intestinal epithelial cells (IECs) and represent a major carbon flux from the diet, that is decomposed by the gut microbiota. SCFAs play a vital role in multiple molecular biological processes, such as promoting the secretion of glucagon-like peptide-1 by IECs to inhibit the elevation of blood glucose, increasing the expression of G protein-coupled receptors such as GPR41 and GPR43, and inhibiting histone deacetylases, which participate in the regulation of the proliferation, differentiation, and function of IECs. SCFAs affect intestinal motility, barrier function, and host metabolism. Furthermore, SCFAs play important regulatory roles in local, intermediate, and peripheral metabolisms. Acetate, propionate, and butyrate are the major SCFAs, they are involved in the regulation of immunity, apoptosis, inflammation, and lipid metabolism. Herein, we review the diverse functional roles of this major class of bacterial metabolites and reflect on their ability to affect intestine, metabolic, and other diseases. Video Abstract.


Subject(s)
Butyrates , Fatty Acids, Volatile , Propionates , Gastrointestinal Tract , Apoptosis
5.
Huan Jing Ke Xue ; 44(7): 3788-3796, 2023 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-37438278

ABSTRACT

To prevent disease spreading during the COVID-19 epidemic, Shenzhen adopted lockdown measures in March of 2022. This provided an opportunity to study the response of changes in anthropogenic volatile organic compounds (AVOCs) in Shenzhen to emission reduction and to evaluate the effectiveness of current emission reduction measures. This study analyzed the variety of AVOCs before, during, and after the epidemic lockdown based on the online observation data of pollutants at Lianhua Station in Shenzhen from March 7, 2022 to March 27, 2022. Additionally, the sensitivity of ozone formation and the assessment of the reduction effect of precursors was conducted by an observation based model(OBM). The results showed that:affected by regional influences and the interference of meteorological conditions, the average value of AVOCs in Shenzhen urban areas did not drop significantly during the lockdown period compared to that before the lockdown. However, the peak of AVOCs at the morning peak time under the influence of "sea and land wind" during the epidemic lockdown period dropped by 46% on average compared with that during the non-lockdown period, and the aromatic hydrocarbon component dropped the most by 59%. Additionally, under the influence of continuous easterly wind, or during the accumulation and increase of AVOCs affected by regional transmission, aromatic components also decreased by an average of 25% and 21%, respectively. During the lockdown period of the epidemic in Shenzhen, the O3 formation in urban areas was still AVOCs-limited. Increasing the emission reduction ratio of AVOCs was the most effective measure to reduce O3 in the short term. In order to ensure the effectiveness of emission reduction, it was recommended that the coordinated emission reduction ratio of AVOCs and NOx should be greater than 1:2. It was only possible to enter the downward channel of O3 if the deep emission reduction was more than 60%. This study revealed that the emission reduction of AVOCs during the morning traffic peak during the epidemic lockdown period was conducive to inhibiting the formation of O3, whereas the control of NOx would promote it. Strengthening the control of local aromatic hydrocarbon components during the regional impact process could also significantly reduce O3 production. At this stage, Shenzhen should strengthen the management and control of industrial solvents, especially to reduce the aromatic hydrocarbon components in the solvent source that have a greater impact on the generation of O3. Further, Shenzhen should continue to promote the reform of the energy structure of motor vehicles to reduce the emission of VOCs in fuel combustion.


Subject(s)
COVID-19 , Environmental Pollutants , Ozone , Volatile Organic Compounds , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Industry
6.
Open Med (Wars) ; 17(1): 2098-2108, 2022.
Article in English | MEDLINE | ID: mdl-36578556

ABSTRACT

Melanoma is a rare, fatal type of skin tumor. Although EPH receptor A3 (EphA3) is deregulated in melanoma, its detailed role remained uncharacterized. Using real time quantitative PCR analysis and western blotting, EphA3 was identified to be upregulated in melanoma tissues and cells, while miR-3666 showed an opposite expression trend. Cell counting kit-8, scratch wound, and in vivo assays proved that EphA3 silence inhibited the melanoma cell proliferation and migration and retarded tumor growth in vivo. Furthermore, western blotting results displayed that EphA3 silence resulted in a low expression of p38-MAPK and p-ERK1/2. Mechanically, miR-3666 was proved to target EphA3 3'UTR by the luciferase reporter assay. Furthermore, miR-3666 mimic compromised the driven melanoma cell proliferation and migration by EphA3 overexpression. In addition, induction of ERK1/2 and p38 MAPK pathways offset the positive effect of EphA3 overexpression on melanoma cells. In conclusion, miR-3666 downregulated EphA3 expression and retarded melanoma malignancy via inactivating ERK1/2 and p38 MAPK pathways. Hence, miR-3666/EphA3 axis may represent a druggable target against melanoma progression.

8.
J Biomed Opt ; 27(2)2022 02.
Article in English | MEDLINE | ID: mdl-35137573

ABSTRACT

SIGNIFICANCE: Full-field optical angiography is critical for vascular disease research and clinical diagnosis. Existing methods struggle to improve the temporal and spatial resolutions simultaneously. AIM: Spatiotemporal absorption fluctuation imaging (ST-AFI) is proposed to achieve dynamic blood flow imaging with high spatial and temporal resolutions. APPROACH: ST-AFI is a dynamic optical angiography based on a low-coherence imaging system and U-Net. The system was used to acquire a series of dynamic red blood cell (RBC) signals and static background tissue signals, and U-Net is used to predict optical absorption properties and spatiotemporal fluctuation information. U-Net was generally used in two-dimensional blood flow segmentation as an image processing algorithm for biomedical imaging. In the proposed approach, the network simultaneously analyzes the spatial absorption coefficient differences and the temporal dynamic absorption fluctuation. RESULTS: The spatial resolution of ST-AFI is up to 4.33 µm, and the temporal resolution is up to 0.032 s. In vivo experiments on 2.5-day-old chicken embryos were conducted. The results demonstrate that intermittent RBCs flow in capillaries can be resolved, and the blood vessels without blood flow can be suppressed. CONCLUSIONS: Using ST-AFI to achieve convolutional neural network (CNN)-based dynamic angiography is a novel approach that may be useful for several clinical applications. Owing to their strong feature extraction ability, CNNs exhibit the potential to be expanded to other blood flow imaging methods for the prediction of the spatiotemporal optical properties with improved temporal and spatial resolutions.


Subject(s)
Image Processing, Computer-Assisted , Neural Networks, Computer , Algorithms , Angiography , Animals , Capillaries , Chick Embryo , Image Processing, Computer-Assisted/methods
9.
Curr Med Sci ; 41(6): 1158-1164, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34971441

ABSTRACT

OBJECTIVE: To explore a new artificial intelligence (AI)-aided method to assist the clinical diagnosis of tibial plateau fractures (TPFs) and further measure its validity and feasibility. METHODS: A total of 542 X-rays of TPFs were collected as a reference database. An AI algorithm (RetinaNet) was trained to analyze and detect TPF on the X-rays. The ability of the AI algorithm was determined by indexes such as detection accuracy and time taken for analysis. The algorithm performance was also compared with orthopedic physicians. RESULTS: The AI algorithm showed a detection accuracy of 0.91 for the identification of TPF, which was similar to the performance of orthopedic physicians (0.92±0.03). The average time spent for analysis of the AI was 0.56 s, which was 16 times faster than human performance (8.44±3.26 s). CONCLUSION: The AI algorithm is a valid and efficient method for the clinical diagnosis of TPF. It can be a useful assistant for orthopedic physicians, which largely promotes clinical workflow and further guarantees the health and security of patients.


Subject(s)
Algorithms , Artificial Intelligence/statistics & numerical data , Orthopedics , Physicians , Tibial Fractures/diagnosis , Adult , Feasibility Studies , Female , Humans , Male , X-Rays
10.
Anal Chem ; 93(48): 16059-16067, 2021 12 07.
Article in English | MEDLINE | ID: mdl-34793122

ABSTRACT

Exosomes are a promising noninvasive tumor biomarker for cancer diagnosis and classification. However, efficient capture and precise analysis of exosomes in complex biological samples remain challenging. Here, sensitive profiling of exosomes with an integrated separation-detection strategy of 37 min is performed based on boronic acid-directed coupling immunoaffinity. The modification of g-C3N4 nanosheets with boronic acid (BCNNS) contributes to antibody binding under physiological conditions, which is accompanied by fluorescence enhancement. When exosomes are captured by an antibody equipped with BCNNS, a decrease in fluorescence can be induced; moreover, using the dispersion property of BCNNS, the exosomes can be separated by a simple centrifugation step. The protocol shows a favorable sensitivity with a detection limit of 2484 particles/mL. By changing only the fused antibody, exosome phenotype information profiling can be achieved, and exosomes derived from four different cell lines (HeLa, HepG2, MCF-7, and MCF-10A) can be successfully distinguished. More significantly, the positive prediction accuracy results reach 100% for serum samples from different individuals and have the advantage of multiple parameters; thus, the method has great potential in noninvasive diagnosis and point-of-care testing.


Subject(s)
Exosomes , Biomarkers, Tumor , Boronic Acids , HeLa Cells , Humans
12.
Huan Jing Ke Xue ; 42(9): 4191-4201, 2021 Sep 08.
Article in Chinese | MEDLINE | ID: mdl-34414717

ABSTRACT

As an important precursor of ozone, volatile organic compounds (VOCs) have attracted much attention. This study analyzed the temporal variation and composition of atmospheric VOCs in the coastal background of the Pearl River Delta, using real-time online monitoring data of VOCs obtained at the Yangmeikeng Ecological Environment Monitoring Station from August 2019 to July 2020. The major sources of VOCs were identified using a receptor model based on the PMF (positive matrix factorization) and HYSPLIT (hybrid single particle Lagrangian integrated trajectory) models. The results showed that the annual mean concentration of anthropogenic VOCs in the coastal background area of the Pearl River Delta was 9.30×10-9(volume fraction). There was obvious seasonal variation of VOCs in this area, with higher values in autumn and winter and lower values in summer. The coastal background area of the Pearl River Delta exhibited a different diurnal variation pattern to that of cities and other backgrounds. While the peak of VOCs concentration mainly occurred in the morning, from 10:00 to 11:00, concentration remained at a low level during the early morning and after 15:00. Ethylene, propylene, toluene, isopentane, isoprene, m/p-xylene, n-butane, and acetylene were the key species that affected the chemical composition of VOCs. The air masses affecting the coastal background area of the Pearl River Delta were mainly short-distance air masses from elsewhere in the province (25%), ocean air masses (27%), coastal air masses (31%), and inland air masses outside the province (17%). Among them, the average concentration of VOCs was lowest under the influence of ocean air masses, which is mainly affected by the mixed source of ship emissions and aging VOCs, gasoline volatilization, and vehicle emissions. In comparison, the concentration level of VOCs increased by 70.1% to 148.8% under the influence of other air masses. The transmission effects of industrial sources, LNG and LPG volatiles, and petrochemical sources were more prominent. Generally, the atmosphere of coastal background areas was severely affected by anthropogenic pollution, especially by air pollution masses transported from the land, while the impact of pollution by ships near shore and tourist traffic cannot be ignored.


Subject(s)
Air Pollutants , Volatile Organic Compounds , Air Pollutants/analysis , Environmental Monitoring , Rivers , Vehicle Emissions/analysis , Volatile Organic Compounds/analysis
13.
ACS Appl Mater Interfaces ; 13(20): 23384-23395, 2021 May 26.
Article in English | MEDLINE | ID: mdl-33982571

ABSTRACT

Construction of multifunctional nonviral gene vectors to execute defined tasks holds great potential for the precise and effective treatment of gene-associated diseases. Herein, we have developed four large π-conjugation triphenylamine derivatives bearing two polar [12]aneN3 heads and a lipophilic tail for applications in gene delivery, one/two-photon-triggered near-infrared (NIR) fluorescence bioimaging, and combined photodynamic therapy (PDT) and gene therapy of cancer. These compounds possess typical NIR aggregation-induced emission characteristics, mega Stokes shifts, strong two-photon excitation fluorescence, and excellent DNA condensation abilities. Among them, vector 4 with a tail of n-hexadecane realized a transfection efficiency as high as 6.7 times that of the commercial transfection agent Lipofectamine 2000 in HEK293T cell lines. Using vector 4 as an example, transfection process tracking and ex vivo/in vivo tumoral imaging and retention with high resolution, high brightness, deep tissue penetration, and good biosafety were demonstrated. In addition, efficient singlet oxygen (1O2) generation by the DNA complex formed by vector 4 (4/DNA) resulted in effective PDT. Combined with anticancer gene therapy, collaborative cancer treatment with a dramatically enhanced cancer cell-killing effect was achieved. The development of this "three birds, one stone" approach suggests a new and promising strategy for better cancer treatment and real-time tracking of gene delivery.


Subject(s)
Antineoplastic Agents , Fluorescent Dyes , Genetic Vectors , Theranostic Nanomedicine/methods , Animals , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Carriers/metabolism , Female , Fluorescent Dyes/chemistry , Fluorescent Dyes/metabolism , Genetic Therapy , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Photochemotherapy , Spectroscopy, Near-Infrared
14.
J Stroke Cerebrovasc Dis ; 29(8): 104867, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32689632

ABSTRACT

OBJECTIVE: To establish a model for predicting the outcome according to the clinical and computed tomography(CT) image data of patients with intracerebral hemorrhage(ICH). METHODS: The clinical and CT image data of the patients with ICH in Qinghai Provincial People's Hospital and Xuzhou Central Hospital were collected. The risk factors related to the poor outcome of the patients were determined by univariate and multivariate logistic regression analysis. To determine the effect of factors related to poor outcome, the nomogram model was made by software of R 3.5.2 and the support vector machine operation was completed by software of SPSS Modelor. RESULTS: A total of 8265 patients were collected and 1186 patients met the criteria of the study. Age, hospitalization days, blend sign, intraventricular extension, subarachnoid hemorrhage, midline shift, diabetes and baseline hematoma volume were independent predictors of poor outcome. Among these factors, baseline hematoma volume๥20ml (odds ratio:13.706, 95% confidence interval:9.070-20.709, p < 0.001) was the most significant factor for poor outcome, followed by the volume among 10ml-20ml (odds ratio:11.834, 95% confidence interval:7.909-17.707, p < 0.001). It was concluded that the highest percentage of weight in outcome was baseline hematoma volume (25.0%), followed by intraventricular hemorrhage (23.0%). CONCLUSION: This predictive model might accurately predict the outcome of patients with ICH. It might have a wide range of application prospects in clinical.


Subject(s)
Cerebral Hemorrhage/diagnostic imaging , Decision Support Techniques , Nomograms , Support Vector Machine , Tomography, X-Ray Computed , Cerebral Hemorrhage/physiopathology , Cerebral Hemorrhage/therapy , China , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors
15.
Mater Sci Eng C Mater Biol Appl ; 110: 110688, 2020 May.
Article in English | MEDLINE | ID: mdl-32204117

ABSTRACT

HYPOTHESIS: Osseointegration can be enhanced by introducing bioactive polyelectrolyte-multilayer films on implant surfaces. To guarantee films to function successfully in use, keeping structural integrity during implanting is necessary, which requires films with strong adhesion and cohesion to resist the mechanical damage. Catechol is considered as the origin of amazing adhesion of mussels. We hypothesize that catechol functionalization of polyelectrolytes enables film construction on implants in a non-aggressive way, and helps films resist mechanical damages during implanting. EXPERIMENTS: With lipopolysaccharide-amine nanopolymersomes (NPs), catechol-functionalized hyaluronic acid and NPs (cHA, cNPs) as a polycation, polyanion and primer, respectively, catechol-functionalized polyelectrolyte-multilayer films (cPEMs) were constructed on substrates via Layer-by-layer self-assembly. Effects of catechol functionalization on construction, surface properties, assembly mechanisms, structural integrity, mechanical properties and cytotoxicity of cPEMs were studied. FINDINGS: Self-adhesive cPEMs can be constructed on substrates, which grow exponentially and are driven by coordination, covalent bonding, electrostatic interactions, hydrogen bonding, etc. cPEMs with suitable catechol concentrations can resist mechanical damage to keep structural integrity in simulated clinical implantation, show stronger adhesion and cohesion than non-catechol-functionalized films in nanoscratch and nanoindentation tests, and are non-cytotoxic to MSCs. With excellent drug-loading and cytosolic-delivery capacity of NPs, cPEM is promising in improving osseointegration of implants.


Subject(s)
Adhesives/chemistry , Titanium/chemistry , Animals , Catechols/chemistry , Cells, Cultured , Dental Implants , Hyaluronic Acid/chemistry , Nanoparticles/chemistry , Osseointegration/drug effects , Polyelectrolytes/chemistry , Polymers/chemistry , Prostheses and Implants , Rats , Rats, Sprague-Dawley , Surface Properties/drug effects
16.
EBioMedicine ; 53: 102693, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32114385

ABSTRACT

BACKGROUND: Treatment of Crohn's disease (CD) remains to be a challenge due to limited insights for its pathogenesis. We aimed to determine the role of O-Linked ß-N-acetylglucosamine (O-GlcNAc) in the development of CD and evaluate therapeutic effects of O-GlcNAc inhibitors on CD. METHODS: O-GlcNAc in intestinal epithelial tissues of CD, adherent-invasive Escherichia coli (AIEC) LF82-infected cells and mice was determined by immunoblot and immunohistochemistry. AIEC LF82 and dextran sulfate sodium were administrated into C57BL/6 mice for estabolishing inflammatory bowel disease model and for therapeutic study. FINDINGS: O-GlcNAc was increased in intestinal epithelial tissues of CD patients and AIEC LF82-infected mice. Infection of AIEC LF82 up-regulated the level of UDP-GlcNAc and increased O-GlcNAc in human colon epithelial HCT116 and HT-29 cells. We identified that IKKß and NF-κB were O-Glycosylated in AIEC LF82-treated cells. Mutations of IKKß (S733A) and p65 (T352A) abrogated the O-GlcNAc in IKKß and NF-κB and inhibited AIEC LF82-induced activation of NF-κB. Application of 6-diazO-5-oxO-L-norleucine, an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAc, inactivated NF-κB in AIEC LF82-infected cells, enhanced the formation of autophagy, promoted the removal of cell-associated AIEC LF82, alleviated intestinal epithelial inflammation, and improved the survival of the colitis mice. INTERPRETATION: Intestinal inflammation in CD is associated with increased O-GlcNAc modification, which is required for NF-κB activation and suppression of autophagy. Targeting O-GlcNAc could be an effective therapy for inflammatory bowel disease. FUNDING: National Natural Science Foundation of China (Nos. 81573087 and 81772924) and International Cooperation Foundation of Jilin Province (20190701006GH).


Subject(s)
Acetylglucosamine/metabolism , Crohn Disease/metabolism , NF-kappa B/metabolism , Protein Processing, Post-Translational , Acetylation , Animals , Autophagy , Female , HCT116 Cells , HT29 Cells , Humans , Intestinal Mucosa/metabolism , Male , Mice , Mice, Inbred C57BL
17.
Chem Biol Drug Des ; 92(2): 1458-1467, 2018 08.
Article in English | MEDLINE | ID: mdl-29671947

ABSTRACT

The antibiotic resistance (ARE) subfamily of ABC (ATP-binding cassette) proteins confers resistance to a variety of clinically important ribosome-targeting antibiotics and plays an important role in infections caused by pathogenic bacteria. However, inhibitors of ARE proteins have rarely been reported. Here, OptrA, a new member of the ARE proteins, was used to study inhibitors of these types of proteins. We first confirmed that destroying the catalytic activity of OptrA could restore the sensitivity of host cells to antibiotics. Then, fragment-based screening, a drug screening method, was used to screen for inhibitors of OptrA. The competitive saturation transfer difference experiments, docking, and molecular dynamics were used to determine the binding sites and mode of interactions between OptrA and fragment screening hits. In this study, we first find a novel and specific inhibitor of OptrA (CP1), which suppressed the ATPase activity of OptrA in vitro by 30%. A hydrogen bond formed between the 8-position phenylcyclic cyano group in CP1 and the amino acid residue Lys-271 allows CP1 to form a stable complex with OptrA protein. These findings provide a theoretical basis for the further optimization of the inhibitor structure to obtain inhibitors with higher efficiencies.


Subject(s)
ATP-Binding Cassette Transporters/antagonists & inhibitors , Anti-Bacterial Agents/chemistry , Bacterial Proteins/antagonists & inhibitors , ATP-Binding Cassette Transporters/metabolism , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/metabolism , Bacterial Proteins/metabolism , Binding Sites , Catalytic Domain , Cyanides/chemistry , Cyanides/metabolism , Drug Resistance, Multiple, Bacterial/drug effects , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Structure, Tertiary
18.
Oncol Lett ; 15(2): 2153-2160, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29434919

ABSTRACT

Serine/threonine kinase 33 (STK33) is a novel protein that has been the focus of an increasing number of studies in recent years; however, the role of STK33 in tumorigenesis remains controversial. Previous studies have demonstrated that STK33 is overexpressed in several human cancers and exerts a pro-tumorigenic effect through the promotion of cell proliferation. However, the role of STK33 in colorectal cancer (CRC), which is one of the most aggressive human malignancies, remains unclear. The aim of the current study was to investigate the methylation status of STK33 in CRC and to determine its clinical significance. The results demonstrated that STK33 was hypermethylated in CRC cell lines and promoted the proliferation of CRC cells. In addition, the methylation status and expression of STK33 in 94 pairs of cancer and noncancerous tissues obtained from patients with CRC was investigated. STK33 methylation was significantly increased in cancer tissues when compared with adjacent noncancerous tissues (P<0.001). STK33 methylation was associated with lymph node metastasis (P<0.05), tumor invasion (P<0.05), distant metastases (P<0.01) and tumor stage (P<0.01). Reduced STK33 mRNA and protein expression in CRC was associated with STK33 hypermethylation (P<0.001). In addition, patients with hypermethylated STK33 exhibited shorter overall survival rates when compared with those with unmethylated STK33 (P<0.01). In conclusion, the results of the current study suggest that STK33 hypermethylation may be a promising novel biomarker for the diagnosis, prognosis and suitable treatment of CRC.

19.
Front Microbiol ; 8: 2263, 2017.
Article in English | MEDLINE | ID: mdl-29187848

ABSTRACT

The ability to form biofilms on surfaces makes Staphylococcus aureus the main pathogenic factor in implanted medical device infections. The aim of this study was to discover a biofilm inhibitor distinct from the antibiotics used to prevent infections resulting from S. aureus biofilms. Here, we describe kaempferol, a small molecule with anti-biofilm activity that specifically inhibited the formation of S. aureus biofilms. Crystal violet (CV) staining and fluorescence microscopy clearly showed that 64 µg/ml kaempferol inhibited biofilm formation by 80%. Meanwhile, the minimum inhibitory concentration (MIC) and growth curve results indicated that kaempferol had no antibacterial activity against the tested bacterial strain. Kaempferol inhibited the primary attachment phase of biofilm formation, as determined by a fibrinogen-binding assay. Moreover, a fluorescence resonance energy transfer (FRET) assay and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses revealed that kaempferol reduced the activity of S. aureus sortaseA (SrtA) and the expression of adhesion-related genes. Based on these results, kaempferol provides a starting point for the development of novel anti-biofilm drugs, which may decrease the risk of bacterial drug resistance, to prevent S. aureus biofilm-related infections.

20.
Appl Microbiol Biotechnol ; 101(17): 6671-6681, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28710559

ABSTRACT

Staphylococcus aureus (S. aureus) biofilms are clinically serious and play a critical role in the persistence of chronic infections due to their ability to resist antibiotics. The inhibition of biofilm formation is viewed as a new strategy for the prevention of S. aureus infections. Here, we demonstrated that minimum inhibitory concentrations (MICs) of aloe-emodin exhibited no bactericidal activity against S. aureus but affected S. aureus biofilm development in a dose-dependent manner. Further studies indicated that aloe-emodin specifically inhibits the initial adhesion and proliferation stages of S. aureus biofilm development. Scanning electron microscopy (SEM) indicated that the S. aureus ATCC29213 biofilm extracellular matrix is mainly composed of protein. Laser scanning confocal microscope assays revealed that aloe-emodin treatment primarily inhibited extracellular protein production. Moreover, the Congo red assay showed that aloe-emodin also reduced the accumulation of polysaccharide intercellular adhesin (PIA) on the cell surface. These findings will provide new insights into the mode of action of aloe-emodin in the treatment of infections by S. aureus biofilms.


Subject(s)
Anthraquinones/pharmacology , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Biofilms/growth & development , Staphylococcus aureus/drug effects , Bacterial Adhesion/drug effects , Bacterial Proteins/metabolism , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Polysaccharides, Bacterial/antagonists & inhibitors , Staphylococcus aureus/physiology , Staphylococcus aureus/ultrastructure
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