Publications by authors named "Feifei Chen"

164 Publications

Rice Seed Purity Identification Technology Using Hyperspectral Image with LASSO Logistic Regression Model.

Sensors (Basel) 2021 Jun 26;21(13). Epub 2021 Jun 26.

School of Mathematics & Computer Science, Wuhan Polytechnic University, Wuhan 430023, China.

Hyperspectral technology is used to obtain spectral and spatial information of samples simultaneously and demonstrates significant potential for use in seed purity identification. However, it has certain limitations, such as high acquisition cost and massive redundant information. This study integrates the advantages of the sparse feature of the least absolute shrinkage and selection operator (LASSO) algorithm and the classification feature of the logistic regression model (LRM). We propose a hyperspectral rice seed purity identification method based on the LASSO logistic regression model (LLRM). The feasibility of using LLRM for the selection of feature wavelength bands and seed purity identification are discussed using four types of rice seeds as research objects. The results of 13 different adulteration cases revealed that the value of the regularisation parameter was different in each case. The recognition accuracy of LLRM and average recognition accuracy were 91.67-100% and 98.47%, respectively. Furthermore, the recognition accuracy of full-band LRM was 71.60-100%. However, the average recognition accuracy was merely 89.63%. These results indicate that LLRM can select the feature wavelength bands stably and improve the recognition accuracy of rice seeds, demonstrating the feasibility of developing a hyperspectral technology with LLRM for seed purity identification.
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http://dx.doi.org/10.3390/s21134384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271842PMC
June 2021

ANXA2 Facilitates Enterovirus 71 Infection by Interacting with 3D Polymerase and PI4KB to Assist the Assembly of Replication Organelles.

Virol Sin 2021 Jul 1. Epub 2021 Jul 1.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Similar to that of other enteroviruses, the replication of enterovirus 71 (EV71) occurs on rearranged membranous structures called replication organelles (ROs). Phosphatidylinositol 4-kinase III (PI4KB), which is required by enteroviruses for RO formation, yields phosphatidylinositol-4-phosphate (PI4P) on ROs. PI4P then binds and induces conformational changes in the RNA-dependent RNA polymerase (RdRp) to modulate RdRp activity. Here, we targeted 3D polymerase, the core enzyme of EV71 ROs, and found that the host factor Annexin A2 (ANXA2) can interact with 3D polymerase and promote the replication of EV71. Then, an experiment showed that the annexin domain of ANXA2, which possesses membrane-binding capacity, mediates the interaction of ANXA2 with EV71 3D polymerase. Further research showed that ANXA2 is localized on ROs and interacts with PI4KB. Overexpression of ANXA2 stimulated the formation of PI4P, and the level of PI4P was decreased in ANXA2-knockout cells. Furthermore, ANXA2, PI4KB, and 3D were shown to be localized to the viral RNA replication site, where they form a higher-order protein complex, and the presence of ANXA2 promoted the PI4KB-3D interaction. Altogether, our data provide new insight into the role of ANXA2 in facilitating formation of the EV71 RNA replication complex.
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http://dx.doi.org/10.1007/s12250-021-00417-4DOI Listing
July 2021

Effect of comprehensive nursing on the pain, anxiety and malnutrition of hepatitis B patients.

Am J Transl Res 2021 15;13(5):4656-4665. Epub 2021 May 15.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University Yuedong Hospital Meizhou 514700, Guangdong Provincial, China.

Objective: To explore the effect of comprehensive nursing on pain, anxiety and malnutrition of hepatitis B patients.

Methods: Totally 100 cases of hepatitis B patients received treatment in our hospital from July 2017 to July 2018 were divided into a study group (64 cases) and a control group (36 cases) for comprehensive nursing and routine nursing. The liver function, nutritional indexes, cognition of relevant nursing knowledge, VAS score, HAMD and HAMA scores, QOL score, total effective rate and incidence of adverse reactions were detected.

Results: Compared with the control group, the study group had lower liver function indexes and higher nutrition indexes, suggesting that the liver function of patients in the study group recovered better. Besides, the VAS score of the study group was lower, suggesting better pain relief in the study group. Moreover, the study group had higher scores of related nursing knowledge and lower scores of HAMD and HAMA, indicating that the nursing method in the study group was more effective in reducing depression and anxiety. Higher QOL score, higher total effective rate and lower incidence of adverse reactions of the study group revealed that the nursing mode adopted in this group was better for the recovery of patients.

Conclusion: Comprehensive nursing can effectively alleviate the pain of hepatitis B patients, relieve their anxiety and other negative emotions, and improve their malnutrition.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205827PMC
May 2021

A comparison of PMT-based and CCD-based sensors for electrochemiluminescence detection of sunset yellow in soft drinks.

Food Chem 2021 Nov 27;362:130219. Epub 2021 May 27.

College of Chemistry and Material Science, Huaibei Normal University, Huaibei 235000, China. Electronic address:

The use of artificial colorants in food is highly regulated due to their potential to harm human health. Thus, it is crucial to detect these substances effectively to ensure conformance with industrial standards. In this work, we prepared a photomultiplier tube (PMT)-based electrochemiluminescence (ECL) sensor and a charged coupled device (CCD)-based ECL sensor and compared their merits in the detection of sunset yellow (SY) dye. The sensors used C,N quantum dot-embedded g-CN nanosheets ([email protected]) as the ECL agent and KSO as the coreactant. SY was analyzed on the basis of amplification in the [email protected] ECL system. The PMT-based sensor realized ultrasensitive detection using a single electrode, especially at low concentrations of SY. A CCD-based sensor imaged the ECL phenomenon of an electrode array and provided the advantages of high throughput and time savings. Under optimized conditions, both sensors exhibited high specificity, reproducibility and stability; detection limits of 20 nM with PMT detection and 5 μM with CCD detection were determined for SY, with detection ranging over at least two decades. The practical feasibilities of these systems were confirmed by satisfactory detection of SY in real drink samples.
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http://dx.doi.org/10.1016/j.foodchem.2021.130219DOI Listing
November 2021

Design, synthesis, and antibacterial evaluation of vancomycin-LPS binding peptide conjugates.

Bioorg Med Chem Lett 2021 Aug 17;45:128122. Epub 2021 May 17.

CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Center for Biotherapeutics Discovery Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, PR China; School of Pharmaceutical Science and Technology, Hangzhou, Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, PR China. Electronic address:

Developing novel antibiotics is urgently needed with emergency of drug resistance. Vancomycin, the last resort for intractable Gram-positive bacterial infections, is ineffective against Gram-negative bacteria and vancomycin resistant bacteria. Herein, we report a series of novel vancomycin derivatives carrying LPS binding peptides, vancomycin-LPS binding peptide conjugates (VPCs). The LPS binding peptides were conjugated onto 4 sites of vancomycin via CuAAC or maleimide- sulfydryl addition, and the formed VPCs were screened against VISA/VRE and Gram-negative strains. VPCs exhibited enhanced activity against vancomycin resistant bacteria and obtained the activity against Gram-negative bacteria in vitro, providing a novel strategy for vancomycin modification and glycopeptide antibiotics synthesis.
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http://dx.doi.org/10.1016/j.bmcl.2021.128122DOI Listing
August 2021

Knockout of a highly GC-rich gene in Burkholderia pyrrocinia by recombineering with freeze-thawing transformation.

Mol Plant Pathol 2021 Jul 4;22(7):843-857. Epub 2021 May 4.

Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.

Genetic transformation is a valuable and essential method that provides powerful insights into the gene function of microorganisms and contributes to the construction of engineered bacteria. Here, we developed a novel genetic transformation system to easily knock out a highly GC-rich gene (74.71% GC) from Burkholderia pyrrocinia JK-SH007, a biocontrol strain of poplar canker disease. This system revealed a reliable selectable marker (trimethoprim resistance gene, Tmp) and a simplified, efficient transformation method (6,363.64 CFU/μg, pHKT2) that was developed via freeze-thawing. The knockout recombineering of B. pyrrocinia JK-SH007 was achieved through a suicide plasmid with a three-fragment mutagenesis construct. The three-fragment cassette for mutagenesis was generated by overlap extension and touchdown PCRs and composed of Tmp flanked by GC-rich upstream and downstream fragments from B. pyrrocinia JK-SH007. The mutant strain (ΔBpEG), which was verified by PCR, lost 93.3% of its ability to degrade carboxymethyl cellulose over 40 days. Overall, this system may contribute to future research on B. pyrrocinia traits.
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http://dx.doi.org/10.1111/mpp.13058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232026PMC
July 2021

Total and Semisyntheses of Polymyxin Analogues with 2-Thr or 10-Thr Modifications to Decipher the Structure-Activity Relationship and Improve the Antibacterial Activity.

J Med Chem 2021 05 28;64(9):5746-5765. Epub 2021 Apr 28.

CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China.

Herein, we report the total and semisyntheses of a series of polymyxin analogues with 2-Thr and 10-Thr modifications to reveal the structure-activity relationship (SAR), which has not been fully elucidated previously. We employed two total-synthetic strategies to facilitate the diversified replacements on 2-Thr or 10-Thr, respectively. Moreover, semisynthetic approaches were utilized to achieve selective esterification of 2-Thr or dual esterification of both 2- and 10-Thr. Based on the results of antibacterial assays, SAR analysis implicated that the replacement of 2-/10-Thr with amino acids carrying hydrophobic side chains can maintain the activity against but had varied effects on other tested Gram-negative bacteria. The aminoacetyl esterification on 2-/10-Thr achieved excellent antibacterial activity, and the compound exhibited 2-8-fold higher activity against different strains and lower toxicity toward the HK-2 cell line. This work explored the SAR of polymyxin 2-/10-Thr and provided a promising strategy for the development of novel polymyxin derivatives.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02217DOI Listing
May 2021

Effects of dacomitinib on the pharmacokinetics of poziotinib and .

Pharm Biol 2021 Dec;59(1):457-464

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Context: Dacomitinib and poziotinib, irreversible ErbB family blockers, are often used for treatment of non-small cell lung cancer (NSCLC) in the clinic.

Objective: This study investigates the effect of dacomitinib on the pharmacokinetics of poziotinib in rats.

Materials And Methods: Twelve Sprague-Dawley rats were randomly divided into two groups: the test group (20 mg/kg dacomitinib for 14 consecutive days) and the control group (equal amounts of vehicle). Each group was given an oral dose of 10 mg/kg poziotinib 30 min after administration of dacomitinib or vehicle at the end of the 14 day administration. The concentration of poziotinib in plasma was quantified by UPLC-MS/MS. Both effects of dacomitinib on poziotinib and the mechanism of the observed inhibition were studied in rat liver microsomes and human liver microsomes.

Results: When orally administered, dacomitinib increased the AUC, and decreased CL of poziotinib ( < 0.05). The IC values of M1 in RLM, HLM and CYP3A4 were 11.36, 30.49 and 19.57 µM, respectively. The IC values of M2 in RLM, HLM and CYP2D6 were 43.69, 0.34 and 0.11 µM, respectively, and dacomitinib inhibited poziotinib by a mixed way in CYP3A4 and CYP2D6. The results of the experiments were consistent with those of the experiments.

Conclusions: This research demonstrates that a drug-drug interaction between poziotinib and dacomitinib possibly exists when readministered with poziotinib; thus, clinicians should pay attention to the resulting changes in pharmacokinetic parameters and accordingly, adjust the dose of poziotinib in clinical settings.
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http://dx.doi.org/10.1080/13880209.2021.1914114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079061PMC
December 2021

Transition shock, preceptor support and nursing competency among newly graduated registered nurses: A cross-sectional study.

Nurse Educ Today 2021 Jul 7;102:104891. Epub 2021 Apr 7.

Nursing Department, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247 Beiyuan Street, Jinan City, Shandong Province 250033, PR China. Electronic address:

Background: Transition shock is highly prevalent among newly graduated registered nurses in their early career. Preceptors are widely used to support them in acquiring clinical nursing competencies and to promote their successful transition to practice. However, the mechanism by which transition shock and preceptor support are linked to nursing competency among newly graduated registered nurses remains unknown.

Objectives: The aim of the study was to examine the relationship between transition shock, preceptor support, and nursing competency in a sample of newly graduated registered nurses.

Design: A descriptive, cross-sectional design.

Settings: Six tertiary hospitals in the southeast of mainland China.

Participants: Newly graduated registered nurses undertaking their professional role in the first year.

Methods: Convenience sampling was used to recruit 215 newly graduated registered nurses [184 female, 31 male] from six hospitals. Data on transition shock, preceptor support, and nursing competency were collected using questionnaires from November to December 2019.

Results: The nursing competency of critical thinking/research aptitude (mean = 2.68, SD = 0.63) was scored the lowest among participants. Transition shock (r = -0.21, p < .01) and perceptions of preceptor support (r = 0.56, p < .01) were statistically significantly correlated with nursing competency. Preceptor context, whether the assigned preceptor varied day by day, and the emotional challenges of transition shock were the main predictors of nursing competency (F = 36.86, p = .00), accounting for 34% of the variance in nursing competency.

Conclusions: Educational programs aimed at increasing critical thinking and research aptitude in the educational stage and the continuing educational stage can benefit newly graduated registered nurses. A well-organized transition program in hospitals including awareness and recognition of transition shock in newly graduated registered nurses is essential to enhance their competency in providing quality nursing. More support and assistance would be useful in promoting the preceptor's role in improving nursing competency of newly graduated registered nurses.
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http://dx.doi.org/10.1016/j.nedt.2021.104891DOI Listing
July 2021

Preoperative prediction of pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI.

Eur Radiol 2021 Apr 16. Epub 2021 Apr 16.

Department of Radiology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Guangzhou, Guangdong, 510630, People's Republic of China.

Purpose: To evaluate the value of gadobenate dimeglumine-enhanced MRI in predicting the pathologic grade of hepatocellular carcinoma (HCC).

Materials And Methods: Patients with pathologically proven HCC who underwent preoperative gadobenate dimeglumine-enhanced dynamic MRI were included. Two radiologists blinded to pathology results evaluated images in consensus. Lesions were evaluated quantitatively in terms of ratio of enhancement (RE), and qualitatively based on image features related to tumor aggressiveness. Logistic regression and ROC analyses were used to determine the value of these parameters to predict pathologic grade.

Results: In total, 221 patients (194 males, 27 females, aged 52.9 ± 11.7 years) with 49 poorly differentiated HCCs and 172 well/moderately differentiated HCCs were evaluated. Features significantly related to poorer pathologic grade at univariate analysis included lower RE in the early arterial phase (EAP) (p = 0.001), nonsmooth margins (p = 0.001), absence of capsule (p < 0.001), arterial peritumoral hyperenhancement (p < 0.001), higher AFP (p = 0.004), multiple tumors (p = 0.026), and larger tumor size (p = 0.028). At multivariate analysis, lower RE (EAP) (OR = 0.144, p = 0.002), absence of capsule (OR = 0.281, p = 0.004), and arterial peritumoral hyperenhancement (OR = 4.117, p < 0.001) were independent predictive factors for poorer pathologic grade. ROC analysis showed lower RE (EAP) was predictive of poorer pathologic grade (AUC = 0.667). AUC increased to 0.797 when combined with absence of capsule and presence of peritumoral hyperenhancement.

Conclusions: Lower RE (EAP), absence of capsule, and arterial peritumoral hyperenhancement were predictive biomarkers for poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI.

Key Points: • Gadobenate dimeglumine-enhanced dynamic MRI was a useful quantitative biomarker for preoperative prediction of pathologic grade in patients with HCC. • Lower RE in the early arterial phase, absence of capsule, and arterial peritumoral hyperenhancement were potential imaging indicators for preoperative prediction of poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced MRI. • A lower RE in the early arterial phase was effective at predicting poorer pathologic grade of HCCs but prediction is improved when combined with absence of capsule and presence of peritumoral hyperenhancement.
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http://dx.doi.org/10.1007/s00330-021-07891-0DOI Listing
April 2021

A facile method for vancomycin C-terminus functionalization and derivatization through hydrazide.

Bioorg Med Chem Lett 2021 Jun 9;42:128027. Epub 2021 Apr 9.

School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, PR China. Electronic address:

Over 60-year clinical use of vancomycin led to the emergence of vancomycin-resistant bacteria and threatened our health. To combat vancomycin-resistant strains, numerous vancomycin analogues were developed, such as Telavancin, Oritavancin and Dalbavancin. Extra structures embedded on C-terminus has been proved to be an effective strategy to promote antibacterial activity of vancomycin against vancomycin-resistant strains. Here, we reported a facile strategy, inspired by native chemical ligation, for vancomycin C-terminus functionalization and derivatization. The introduction of C-terminal hydrazide on vancomycin not only provided us an accessible method for C-terminus functionalization through carbonyl azide and thioester, also acted as an efficient site for vancomycin structure modifications. Based on hydrazide-vancomycin, we effectively conjugated cysteine and cysteine containing peptides onto vancomycin C-terminus, and two fluorescent FITC-vancomycin were prepared through Cys-Maleimide conjugation. Meanwhile, we introduced lipophilic structures onto vancomycin C-terminus via the hydrazide moiety. The obtained vancomycin derivatives were evaluated against both Gram-positive and negative bacteria strains.
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http://dx.doi.org/10.1016/j.bmcl.2021.128027DOI Listing
June 2021

A simple yet powerful test for assessing goodness-of-fit of high-dimensional linear models.

Stat Med 2021 06 31;40(13):3153-3166. Epub 2021 Mar 31.

Department of Statistics, George Washington University, Washington, District of Columbia, USA.

We evaluate the validity of a projection-based test checking linear models when the number of covariates tends to infinity, and analyze two gene expression datasets. We show that the test is still consistent and derive the asymptotic distributions under the null and alternative hypotheses. The asymptotic properties are almost the same as those when the number of covariates is fixed as long as p/n → 0 with additional mild assumptions. The test dramatically gains dimension reduction, and its numerical performance is remarkable.
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http://dx.doi.org/10.1002/sim.8968DOI Listing
June 2021

Dispatched nurses' experience of wearing full gear personal protective equipment to care for COVID-19 patients in China-A descriptive qualitative study.

J Clin Nurs 2021 Jul 24;30(13-14):2001-2014. Epub 2021 Mar 24.

Nursing Department, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan City, China.

Aims And Objectives: We explored dispatched nurses' experiences of wearing full gear personal protective equipment to care for patients with coronavirus disease-2019 (COVID-19) in Wuhan, China.

Background: Full gear personal protective equipment is the primary and foremost measure to prevent the contact and transmission of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2); however, working in full gear personal protective equipment may hinder nursing care activities and thus negatively affect patients' and nurses' health.

Design: This descriptive qualitative inquiry followed the COREQ guidelines.

Methods: Individual semi-structured telephone interviews were conducted in a purposive sample of 15 frontline nurses who were dispatched to the outbreak epicentre from March to April 2020. Verbatim transcripts were content analysed.

Results: Four themes emerged from the data: inadequate preparedness for working with full gear personal protective equipment, full gear personal protective equipment stimulated stress responses, coping strategies and professional growth. Participants learned a great deal from problem-focussed and emotion-focussed strategies to tackle challenges related to the prolonged wearing of full gear personal protective equipment for quality nursing care and reduced risk of exposure. They became more vigilant to the adherence to evolving protocols and appropriate training concerning full gear personal protective equipment use.

Conclusions: Frontline nurses confronted various but diminishing challenges related to the use of full gear personal protective equipment when caring for patients with COVID-19 across the approximate 40-day period. Consistent use of coverall personal protective equipment to protect from SARS-CoV-2 in high exposure settings would be feasible if nurses were better prepared; therefore, scenario-based skill training concerning the prolonged use of full gear personal protective equipment should be offered regularly and intensively.

Relevance To Clinical Practice: This study informs future decisions concerning improved full gear personal protective equipment-related psychomotor training and promoting ways for nurses to cope with the stress that comes from working in highly contiguous environments.
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http://dx.doi.org/10.1111/jocn.15753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251170PMC
July 2021

Inhibition and Induction by Poziotinib of Different Rat Cytochrome P450 Enzymes and in an Cocktail Method.

Front Pharmacol 2020 5;11:593518. Epub 2021 Jan 5.

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Poziotinib is an orally active, irreversible, pan-HER tyrosine kinase inhibitor used to treat non-small cell lung cancer, breast cancer, and gastric cancer. Poziotinib is currently under clinical investigation, and understanding its drug-drug interactions is extremely important for its future development and clinical application. The cocktail method is most suitable for evaluating the activity of cytochrome P450 enzymes (CYPs). As poziotinib is partially metabolized by CYPs, cocktail probes are used to study the interaction between drugs metabolized by each CYP subtype. Midazolam, bupropion, dextromethorphan, tolbutamide, chlorzoxazone, phenacetin, and their metabolites were used to examine the effects of poziotinib on the activity of cyp1a2, 2b1, 2d1, 2c11, 2e1, and 3a1/2, respectively. The experiment was carried out by using rat liver microsomes (RLMs), whereas the experiment involved the comparison of the pharmacokinetic parameters of the probes after co-administration with poziotinib to rats to those of control rats treated with only probes. UPLC-MS/MS was used to detect the probes and their metabolites in rat plasma and rat liver microsomes. The results revealed that the half-maximal inhibitory concentration values of bupropion and tolbutamide in RLMs were 8.79 and 20.17 μM, respectively, indicating that poziotinib showed varying degrees of inhibition toward cyp2b1 and cyp2c11. Poziotinib was a competitive inhibitor of cyp2b1 and cyp2c11, with Ki values of 16.18 and 17.66 μM, respectively. No time- or concentration-dependence of inhibition by poziotinib was observed toward cyp2b1 and cyp2c11 in RLMs. Additionally, no obvious inhibitory effects were observed on the activity of cyp1a2, cyp2d1, cyp2e1, and cyp3a1/2. analysis revealed that bupropion, tolbutamide, phenacetin, and chlorzoxazone showed significantly different pharmacokinetic parameters after administration ( < 0.05); there was no significant difference in the pharmacokinetic parameters of dextromethorphan and midazolam. These results show that poziotinib inhibited cyp2b1 and cyp2c11, but induced cyp1a2 and cyp2e1 in rats. Thus, poziotinib inhibited cyp2b1 and cyp2c11 activity in rats, suggesting the possibility of interactions between poziotinib and these CYP substrates and the need for caution when combining them in clinical settings.
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http://dx.doi.org/10.3389/fphar.2020.593518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970697PMC
January 2021

The effects of autophagy in rat tracheal epithelial cells induced by silver nanoparticles.

Environ Sci Pollut Res Int 2021 Jun 29;28(22):27565-27576. Epub 2021 Jan 29.

School of Life and Environmental Sciences, Hangzhou Normal University, Yuhangtang Road 2318#, Hangzhou, 311121, Zhejiang Province, China.

The massive use of silver nanoparticles (AgNPs) is potentially harmful to exposed humans. Although previous studies have found that AgNPs can induce cell autophagy, few studies have focused on the toxic pathways and mechanisms of autophagy induced by AgNPs in rat respiratory epithelial (RTE) cells. In this study, RTE cells were exposed to two kinds of AgNPs in vitro to ascertain the influence of mTOR-autophagy pathway-associated protein expression, including Beclin1, LC3B, Atg5, and Atg7. After exposure to different sizes and concentrations of AgNPs for 12 h, the uptake of silver in RTE cells reached 0.45 μg/L to 1.11 μg/L, indicating that AgNPs can enter RTE cells, leading to toxic effects. Our study found that this toxic effect was related to autophagy caused by ROS accumulation that was mediated by the mTOR pathway. With increasing AgNP exposure concentrations, the expression of p-mTOR was significantly downregulated, and expression of the autophagy-related proteins Beclin1, LC3B, Atg5, and Atg7 was significantly increased in RTE cells in all exposed groups. At a concentration of 1000 μg/L, the expression of LC3BII/LC3BI in all exposed groups was 24.49 times and 12.71 times that of the control, and the expression of Atg7 in all exposed groups was 23.21 times and 13.21 times that of the control. The upregulation of autophagy-related proteins in the AgNP-10 nm exposure groups was greater than that of the AgNP-100 nm exposure group. In summary, the mTOR pathway mediates AgNP-induced autophagy in RTE cells, which leads to damage to the respiratory system barrier and human health risks. This study can facilitate the development of prevention and intervention policies against adverse consequences induced by AgNPs.
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http://dx.doi.org/10.1007/s11356-020-12259-wDOI Listing
June 2021

Endobronchial Ultrasound Elastography Combined With Computed Tomography in Differentiating Benign from Malignant Intrathoracic Lymph Nodes.

Surg Innov 2020 Dec 18:1553350620978027. Epub 2020 Dec 18.

Department of Respiratory Medicine, 385685Nanjing First Hospital, Affiliated to Nanjing Medical University, China.

. This study was to combine endobronchial ultrasound elastography (UE) with computed tomography (CT) to identify benign and malignant thoracic lymph nodes (LNs) more objectively and accurately. A total of 42 patients with intrathoracic lymphadenopathy required for endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) examination were enrolled. All patients were examined by enhanced chest CT, B-mode ultrasound, and endobronchial ultrasound (EBUS)-guided elastography before EBUS-TBNA. Each lymph node was assessed by describing the characteristics of CT image (short diameter, texture, shape, boundary, and mean CT value), B-mode ultrasound (short diameter, echo characteristic, shape, and boundary), and elastography (image type, grading score, strain rate, and blue area ratio). The pathological results were used as the gold standard. The characteristics were compared alone and in combination between benign and malignant LNs. . The blue area ratio of elastography combined with CT had better diagnostic value in differentiating benign and malignant LNs than elastography alone, with the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) being 92%, 96%, 80%, 94%, and 86% vs 81%, 77%, 93%, 97%, and 56%, respectively. Elastography combined with B-mode ultrasound and CT characteristics showed the highest diagnostic value. Accuracy, sensitivity, specificity, PPV, and NPV were all 100%. . Endobronchial UE combined with CT and B-mode ultrasound imaging shows a greater diagnostic value in differentiating benign and malignant intrathoracic LNs than either imaging alone.
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http://dx.doi.org/10.1177/1553350620978027DOI Listing
December 2020

Radiographic anatomy and clinical significance of percutaneous endoscopic transforaminal oblique fixation from posterior corner in lumbar spine.

Ann Transl Med 2020 Nov;8(21):1391

Department of Spine Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Endoscopic transforaminal decompression and interbody fusion (ETDIF) has been widely discussed due to its advantages of less trauma, less bleeding, quick recovery, high safety, and relatively fewer complications, as well as adverse factors such as incomplete decompression, steep learning curve, low fusion rate, and high radiation risk. Furthermore, this technique requires the use of supplemental posterior pedicle-screw. Decompression, interbody fusion and percutaneous pedicle screw implantation are not completed in a single channel. Percutaneous endoscopic transforaminal oblique fixation from posterior corner in lumbar spine (PETOFPC) overcomes the above limitations. The purpose of this study is to confirm the anatomical feasibility for PETOFPC in the posterolateral transforaminal approach and to provide anatomic data for the design of new integrated fixable and fused interbody cage.

Methods: Sixty volunteers (22 men and 38 women) who underwent lumbar CT scans were collected and sent to the GEAW4.4 workstation. As a cohort study, the distances and angles of each path in the sagittal and axial planes were measured and analyzed statistically.

Results: The lengths of each path are not less than 40mm, and the longest can be up to 46mm. The paths in full-length group are about 5mm longer than that in medium group. PE (from point P to target E) path was the optimal path. The angles of each path were significantly different (P≤0.001), namely, a1 > a2 > a3, b1 > b2 > b3, and c1 < c2 < c3.

Conclusions: This study confirms anatomic feasibility for PETOFPC and provides anatomic data for the design of new integrated fixable and fused interbody cage. PETOFPC may be a very promising technology and have great clinical significance.
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http://dx.doi.org/10.21037/atm-20-2046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723534PMC
November 2020

In Vitro and In Vivo Rat Model Assessments of the Effects of Vonoprazan on the Pharmacokinetics of Venlafaxine.

Drug Des Devel Ther 2020 10;14:4815-4824. Epub 2020 Nov 10.

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, Zhejiang 323000, People's Republic of China.

Purpose: The purpose of the present study was to investigate the effects of vonoprazan on the pharmacokinetics of venlafaxine in vitro and in vivo.

Methods: The mechanism underlying the inhibitory effect of vonoprazan on venlafaxine was investigated using rat liver microsomes. In vitro, the inhibition was evaluated by determining the production of O-desmethylvenlafaxine. Eighteen male Sprague-Dawley rats were randomly divided into three groups: control group, vonoprazan (5 mg/kg) group, and vonoprazan (20 mg/kg) group. A single dose of 20 mg/kg venlafaxine was administrated to rats orally without or with vonoprazan. Plasma was prepared from blood samples collected via the tail vein at different time points and concentrations of venlafaxine and its metabolite, O-desmethylvenlafaxine, were determined by ultra-performance liquid chromatography-tandem mass spectrometry.

Results: We observed that vonoprazan could significantly decrease the amount of O-desmethylvenlafaxine (IC = 5.544 μM). Vonoprazan inhibited the metabolism of venlafaxine by a mixed inhibition, combining competitive and non-competitive inhibitory mechanisms. Compared with that in the control group (without vonoprazan), the pharmacokinetic parameters of venlafaxine and its metabolite, O-desmethylvenlafaxine, were significantly increased in both 5 and 20 mg/kg vonoprazan groups, with an increase in MR.

Conclusion: Vonoprazan significantly alters the pharmacokinetics of venlafaxine in vitro and in vivo. Further investigations should be conducted to check these effects in humans. Therapeutic drug monitoring of venlafaxine in individuals undergoing venlafaxine maintenance therapy is recommended when vonoprazan is used concomitantly.
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http://dx.doi.org/10.2147/DDDT.S276704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667002PMC
November 2020

The Utility of Novel Urinary Biomarkers in Mice for Drug Development Studies.

Int J Toxicol 2021 Jan-Feb;40(1):15-25. Epub 2020 Nov 9.

241854Janssen Research & Development, LLC, San Diego, CA, USA.

Novel urinary protein biomarkers have recently been identified and qualified in rats for the early detection of renal injury in drug development studies. However, there are few reports on the utility of these renal biomarkers in mice, another important and widely used preclinical animal species for drug development studies. The purpose of this study was to assess the value of these recently qualified biomarkers for the early detection of drug-induced kidney injury (DIKI) in different strains of mice using multiple assay panels. To this end, we evaluated biomarker response to kidney injury induced by several nephrotoxic agents including amphotericin B, compound X, and compound Y. Several of the biomarkers were shown to be sensitive to DIKI in mice. When measured, urinary albumin and neutrophil gelatinase-associated lipocalin were highly sensitive to renal tubular injury, regardless of the assay platforms, mouse strain, and nephrotoxic agents. Depending on the type of renal tubular injury, kidney injury molecule-1 was also highly sensitive, regardless of the assay platforms and mouse strain. Osteopontin and cystatin C were modestly to highly sensitive to renal tubular injury, but the assay type and/or the mouse strain should be considered before using these biomarkers. Calbindin D28 was highly sensitive to injury to the distal nephron in mice. To our knowledge, this is the first report that demonstrates the utility of novel urinary biomarkers evaluated across multiple assay platforms and nephrotoxicants in different mice strains with DIKI. These results will help drug developers make informed decisions when selecting urinary biomarkers for monitoring DIKI in mice for toxicology studies.
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http://dx.doi.org/10.1177/1091581820970498DOI Listing
November 2020

Mutation-induced remodeling of the BfmRS two-component system in clinical isolates.

Sci Signal 2020 11 3;13(656). Epub 2020 Nov 3.

College of Life Science, Northwest University, Xi'an 710127, China.

Genetic mutations are a primary driving force behind the adaptive evolution of bacterial pathogens. Multiple clinical isolates of , an important human pathogen, have naturally evolved one or more missense mutations in , which encodes the sensor histidine kinase of the BfmRS two-component system (TCS). A mutant BfmS protein containing both the L181P and E376Q substitutions increased the phosphorylation and thus the transcriptional regulatory activity of its cognate downstream response regulator, BfmR. This reduced acute virulence and enhanced biofilm formation, both of which are phenotypic changes associated with a chronic infection state. The increased phosphorylation of BfmR was due, at least in part, to the cross-phosphorylation of BfmR by GtrS, a noncognate sensor kinase. Other spontaneous missense mutations in , such as A42E/G347D, T242R, and R393H, also caused a similar remodeling of the BfmRS TCS in This study highlights the plasticity of TCSs mediated by spontaneous mutations and suggests that mutation-induced activation of BfmRS may contribute to host adaptation by during chronic infections.
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http://dx.doi.org/10.1126/scisignal.aaz1529DOI Listing
November 2020

Lymphomatoid papulosis subtype C: A case report and literature review.

Dermatol Ther 2021 01 3;34(1):e14452. Epub 2020 Nov 3.

Department of Dermatology, Clinical Medical College, Yangzhou University, Yangzhou, China.

Lymphomatoid papulosis (LyP) is a rare CD30 lymphoproliferative primary skin disease with a benign clinical course and malignant histopathology. LyP is classified into seven subtypes based on histopathology: subtypes A through F and LyP with 6p25.3 chromosome rearrangement. We present here, a case report of a 51-year-old man, afflicted with multiple papules and nodules on his left arm for over 3 months and diagnosed with LyP subtype C. The patient refused treatment, and his lesions faded with no visible rash on the left arm 14 months after diagnosis.
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http://dx.doi.org/10.1111/dth.14452DOI Listing
January 2021

Inhibitory Effect of Imperatorin on the Pharmacokinetics of Diazepam In Vitro and In Vivo.

Front Pharmacol 2020 16;11:01079. Epub 2020 Sep 16.

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Background: Diazepam is a benzodiazepine drug used to treat anxiety, insomnia, and muscle spasms. Imperatorin is a phytochemical isolated from medicinal plants and is widely used in herbal medicine. The aim of this study was to investigate the interactions between imperatorin and diazepam and and to provide evidence-based guidance for the safe clinical use of the drug.

Methods: In vitro inhibition of imperatorin was assessed by incubating rat liver microsomes with diazepam to determine IC values and the type of inhibition. For assessment, six rats were pretreated with 50 mg/kg imperatorin for two weeks, six were administered saline, and a single dose of 10 mg/kg diazepam was administered orally to both groups 30 min after the administration of imperatorin.

Results: Imperatorin inhibited the metabolism of diazepam the competitive mechanism of CYP450. The IC values of imperatorin to nordazepam and temazepam were 1.54 μM and 1.80 μM, respectively. The inhibitory constant values for temazepam and nordazepam were 1.24 μM and 1.29 μM, respectively. Long-term administration of imperatorin significantly increased the AUC, AUC, and Cmax of diazepam, while Vz/F and CLz/F were decreased significantly ( < 0.05). In turn, the AUC, AUC, and Cmax of nordazepam and temazepam decreased significantly, and Vz/F and CLz/F increased significantly ( < 0.05).

Conclusions: This study demonstrates that imperatorin inhibits the metabolism of diazepam both and . These results indicated that more attention should be paid when taking diazepam together with food or herbs containing IMP, although further investigation is still needed.
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http://dx.doi.org/10.3389/fphar.2020.01079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525091PMC
September 2020

Inhibitory Effect of Imperatorin on the Pharmacokinetics of Diazepam In Vitro and In Vivo.

Front Pharmacol 2020 16;11:01079. Epub 2020 Sep 16.

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Background: Diazepam is a benzodiazepine drug used to treat anxiety, insomnia, and muscle spasms. Imperatorin is a phytochemical isolated from medicinal plants and is widely used in herbal medicine. The aim of this study was to investigate the interactions between imperatorin and diazepam and and to provide evidence-based guidance for the safe clinical use of the drug.

Methods: In vitro inhibition of imperatorin was assessed by incubating rat liver microsomes with diazepam to determine IC values and the type of inhibition. For assessment, six rats were pretreated with 50 mg/kg imperatorin for two weeks, six were administered saline, and a single dose of 10 mg/kg diazepam was administered orally to both groups 30 min after the administration of imperatorin.

Results: Imperatorin inhibited the metabolism of diazepam the competitive mechanism of CYP450. The IC values of imperatorin to nordazepam and temazepam were 1.54 μM and 1.80 μM, respectively. The inhibitory constant values for temazepam and nordazepam were 1.24 μM and 1.29 μM, respectively. Long-term administration of imperatorin significantly increased the AUC, AUC, and Cmax of diazepam, while Vz/F and CLz/F were decreased significantly ( < 0.05). In turn, the AUC, AUC, and Cmax of nordazepam and temazepam decreased significantly, and Vz/F and CLz/F increased significantly ( < 0.05).

Conclusions: This study demonstrates that imperatorin inhibits the metabolism of diazepam both and . These results indicated that more attention should be paid when taking diazepam together with food or herbs containing IMP, although further investigation is still needed.
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http://dx.doi.org/10.3389/fphar.2020.01079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525091PMC
September 2020

Diagnostic values of Xpert MTB/RIF, T-SPOT.TB and adenosine deaminase for HIV-negative tuberculous pericarditis in a high burden setting: a prospective observational study.

Sci Rep 2020 10 1;10(1):16325. Epub 2020 Oct 1.

Department of Medical Records, Henan Chest Hospital, Zhengzhou, Henan Province, People's Republic of China.

The diagnosis of tuberculous pericarditis (TBP) remains challenging. This prospective study evaluated the diagnostic value of Xpert MTB/RIF (Xpert) and T-SPOT.TB and adenosine deaminase (ADA) for TBP in a high burden setting. A total of 123 HIV-negative patients with suspected TBP were enrolled at a tertiary referral hospital in China. Pericardial fluids were collected and subjected to the three rapid tests, and the results were compared with the final confirmed diagnosis. Of 105 patients in the final analysis, 39 (37.1%) were microbiologically, histopathologically or clinically diagnosed with TBP. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) for Xpert were 66.7%, 98.5%, 96.3%, 83.3%, 44.0, 0.338, and 130.0, respectively, compared to 92.3%, 87.9%, 81.8%, 95.1%, 7.6, 0.088, and 87.0, respectively, for T-SPOT.TB, and 82.1%, 92.4%, 86.5%, 89.7%, 10.8, 0.194, and 55.8, respectively, for ADA (≥ 40 U/L). ROC curve analysis revealed a cut-off point of 48.5 spot-forming cells per million pericardial effusion mononuclear cells for T-SPOT.TB, which had a DOR value of 183.8, while a cut-off point of 41.5 U/L for ADA had a DOR value of 70.9. Xpert (Step 1: rule-in) followed by T-SPOT.TB [cut-off point] (Step 2: rule-out) showed the highest DOR value of 252.0, with only 5.7% (6/105) of patients misdiagnosed. The two-step algorithm consisting of Xpert and T-SPOT.TB could offer rapid and accurate diagnosis of TBP.
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http://dx.doi.org/10.1038/s41598-020-73220-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530650PMC
October 2020

More serious autophagy can be induced by ZnO nanoparticles than single-walled carbon nanotubes in rat tracheal epithelial cells.

Environ Toxicol 2021 Feb 20;36(2):238-248. Epub 2020 Sep 20.

School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang Province, China.

Metal oxide nanoparticles and carbon nanoparticles, as common nanoparticles (NPs), can cause autophagy in certain cells, which will lead to biohealth risk issues. This study determined the difference in autophagy induced by zinc oxide nanoparticles (ZnO NPs) and single-walled carbon nanotubes (SWCNTs) in respiratory epithelial cells. ICP-OES results showed that NPs uptake as well as the intercellular contents of particles affected cytotoxicity in a dose-dependent manner. ZnO NPs-30 nm had a distinct green dot structure representing autophagy, the SWCNTs exposure group had a few green light spots at a concentration of 10 μg/L. The ROS content of the ZnO NP-30 nm exposure group had the greatest increase at a concentration of 1000 μg/L, which was 2.5 times higher than that of the control, the SWCNTs exposure group showed a 2.2-fold increase. A slight downregulation of p-mTOR was detected, and the ZnO NPs-30 nm treatment group had the significant downregulation rate. The gene and protein expression levels of Beclin-1 and LC3B were upregulated as the exposure concentration increased. The protein expression of Beclin-1 and LC3B in the 1000 μg/L ZnO NPs-30 nm exposure group were 5.21 times and 4.12 times that of the control, respectively. The mRNA expression of Beclin-1 and LC3B in the 1000 μg/L ZnO NPs-30 nm exposure group were 5.04 times and 3.61 times that of the control, respectively. At any concentration, the effect of ZnO NPs-30 nm was greater than that of the SWCNTs. Interaction and crosstalk analysis showed that exposure to ZnO NPs-30 nm caused autophagy through the aggregation of undegraded autophagosomes, whereas SWCNTs exposure induced diminished intercellular oxidative stress to inhibit autophagy. Therefore, this study demonstrated that the effects of autophagy induced by ZnO NPs-30 nm and SWCNTs were different. The health risks of ZnO-30 nm NPs are higher than those of SWCNTs.
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http://dx.doi.org/10.1002/tox.23029DOI Listing
February 2021

Stimuli-responsive functional materials for soft robotics.

J Mater Chem B 2020 Sep 9. Epub 2020 Sep 9.

Robotics Institute, School of Mechanical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. and State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai 200240, China.

Functional materials have spurred the advancement of soft robotics with the potential to perform safe interactions and adaptative functions in unstructured environments. The responses of functional materials under external stimuli lend themselves to programmable actuation and sensing, opening up new possibilities of robot design with built-in mechanical intelligence and unlocking new applications. Here, we review the development of stimuli-responsive functional materials particularly used for soft robotic systems. This review covers five representative types of soft stimuli-responsive functional materials, namely (i) dielectric elastomers, (ii) hydrogels, (iii) shape memory polymers, (iv) liquid crystal elastomers, and (v) magnetic materials, with focuses on their inherent material properties, working mechanisms, and design strategies for actuation and sensing. We also highlight the state-of-the-art applications of soft stimuli-responsive functional materials in locomotion robots, grippers and sensors. Finally, we summarize the current challenges and map out future trends for engineering next-generation functional materials for soft robotics.
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http://dx.doi.org/10.1039/d0tb01585gDOI Listing
September 2020

Effects of avitinib on the pharmacokinetics of osimertinib in vitro and in vivo in rats.

Thorac Cancer 2020 10 19;11(10):2775-2781. Epub 2020 Aug 19.

VIP Ward, Suzhou Dushuhu Public Hospital, Dushuhu Public Hospital Affiliated to Soochow University, The First Affiliated Hospital of Soochow University, Dushuhu Branch, Suzhou, Jiangsu, China.

Background: Avitinib is one type of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study was to investigate the effect of avitinib on the pharmacokinetics of osimertinib, one FDA approved third-generation TIKI, both in vitro and in vivo.

Methods: The in vitro metabolic stability and inhibitory effect of avitinib on osimertinib were assessed with rat liver microsomes (RLM) to determine its IC values. For the in vivo study, 18 Sprague-Dawley rats were randomly divided into three groups: the avitinib multiple dose group (30 mg/kg avitinib once daily for seven days), the avitinib single dose group (PEG200 once daily for six days and a dose of 30 mg/kg avitinib in PEG200 on day 7) and the control group (equal amounts of PEG200 once daily for seven days). Next, all rats were given osimertinib at a dosage of 10 mg/kg. UPLC/MS-MS was used for the determination of the concentration of osimertinib in plasma.

Results: In vitro analysis revealed that the IC value of osimertinib in rat liver microsomes was 27.6 μM. When rats were pretreated with avitinib, the values of AUC and MRT of the osimertinib were increased, and its C and T were significantly extended, whereas the values of CLz/F were significantly decreased (P < 0.05).

Conclusions: Both in vitro and in vivo results demonstrated that a drug-drug interaction between avitinib and osimertinib occurred and more attention should be paid when avitinib and osimertinib are synchronously administered in clinic.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Osimertinib is the only market available third-generation EGFR-TKI and it has been reported that some drugs could have drug-drug interactions with it.

What This Study Adds: For the first time, we systematically investigated the effect of avitinib, one newly developed third-generation EGFR-TKI, on the pharmacokinetics of osimertinib both in vitro and in vivo using a rat model.
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http://dx.doi.org/10.1111/1759-7714.13587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529555PMC
October 2020

Accumulation and depuration of dissolved hexavalent chromium and effects on the antioxidant response in bighead carp (Aristichthys nobilis).

Environ Toxicol Pharmacol 2020 Nov 6;80:103465. Epub 2020 Aug 6.

Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, College of Fisheries, Huazhong Agricultural University, Shizishan Street 1, 430070, Wuhan, PR China. Electronic address:

The present study investigated the accumulation and depuration effects of hexavalent chromium (Cr) in ten tissues (gills, intestines, liver, kidney, blood, heart, bladder, spleen, skin and muscle) of the bighead carp (Aristichthys nobilis). Fish were exposed to graded levels of waterborne Cr (0.01, 0.1, 1 and 5 mg/L) for 4, 7 and 14 days, and subsequently transferred to Cr-free water for 14 days. After 14-day exposure, a dose-dependent increase of Cr has been observed in most tissues. While after 14-day depuration, Cr contents were significantly decreased in various tissues except in kidney and spleen where Cr contents significantly increased at the group of 5 mg/L. Considering that Cr highly accumulated in gills, intestines, liver and kidney, the oxidative damage of Cr on the four tissues were further investigated and found that the antioxidant response to Cr were organ-specific. The results in this study indicated that a 14-day period is effective for accumulation and depuration of Cr in bighead carp and there was no health risk of fish muscle consumption. Additionally, the delayed efflux of Cr in the fish kidney and spleen indicates that high importance should be attached to them when evaluating the toxic effects and risk assessments of Cr.
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http://dx.doi.org/10.1016/j.etap.2020.103465DOI Listing
November 2020

Evaluation of acacetin inhibition potential against cytochrome P450 in vitro and in vivo.

Chem Biol Interact 2020 Sep 30;329:109147. Epub 2020 Jul 30.

Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. Electronic address:

Acacetin is a natural flavonoid that is widely distributed in plants and possesses numerous pharmacological activities. The aim of the present study was to investigate the effects of acacetin on the activities of the cytochrome P450 family members CYP1A2, CYP2B1, CYP2C11, CYP2D1, CYP2E1, and CYP3A2 in rat liver microsomes in vitro and rats in vivo to evaluate potential herb-drug interactions by using a cocktail approach. Phenacetin, bupropion, tolbutamide, dextromethorphan, chlorzoxazone, and midazolam were chosen as the probe substrates. An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous detection of the probe substrates and their metabolites. In vitro, the mode of acacetin inhibition of CYP2B1, CYP2C11, and CYP2E1 was competitive, while mixed inhibition was observed for CYP1A2 and CYP3A2. The Ki values in this study were less than 8.32 μM. In vivo, the mixed probe substrates were administered by gavage after daily intraperitoneal injection with 50 mg/kg acacetin or saline for 2 weeks. The main pharmacokinetic parameters, area under the plasma concentration-time curve (AUC), plasma clearance (CL), and maximum plasma concentration (C) of the probe substrates were significantly different in the experimental group than in the control group. Overall, the in vitro and in vivo results indicated that acacetin would be at high risk to cause toxicity and drug interactions via cytochrome P450 inhibition.
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http://dx.doi.org/10.1016/j.cbi.2020.109147DOI Listing
September 2020

Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats.

Pharm Biol 2020 Dec;58(1):630-635

Division of Cardiology, Internal Medicine Department, Beijing Hospital, Beijing, P.R. China.

Context: Rivaroxaban and ticagrelor are two common drugs for the treatment of atrial fibrillation and acute coronary syndrome. However, the drug-drug interaction between them is still unknown.

Objective: To investigate the effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats both and .

Materials And Methods: A sensitive and reliable UPLC-MS/MS method was developed for the determination of rivaroxaban in rat plasma. Ten Sprague-Dawley rats were randomly divided into ticagrelor pre-treated group (10 mg/kg/day for 14 days) and control group. The pharmacokinetics of orally administered rivaroxaban (10 mg/kg, single dose) with or without ticagrelor pre-treatment was investigated with developed UPLC-MS/MS method. Additionally, Sprague-Dawley rat liver microsomes were also used to investigate the drug-drug interaction between these two drugs .

Results: The (221.34 ± 53.33 691.18 ± 238.31 ng/mL) and the AUC (1060.97 ± 291.21 3483.03 ± 753.83 μg·h/L) of rivaroxaban increased significantly ( < 0.05) with ticagrelor pre-treatment. The MRT of rivaroxaban increased from 4.41 ± 0.79 to 5.97 ± 1.11 h, while the intrinsic clearance decreased from 9.93 ± 2.55 to 2.89 ± 0.63 L/h/kg (both  < 0.05) after pre-treated with ticagrelor. Enzyme kinetic study indicated that ticagrelor decreased rivaroxaban metabolic clearance with the IC value of 14.04 μmol/L.

Conclusions: Our and results demonstrated that there is a drug-drug interaction between ticagrelor and rivaroxaban in rats. Further studies need to be carried out to verify whether similar interactions truly apply in humans and whether these interactions have clinical significance.
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http://dx.doi.org/10.1080/13880209.2020.1785510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470163PMC
December 2020
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