Publications by authors named "Wei Duan"

411 Publications

Cancer Stem Cell-Targeted Gene Delivery Mediated by Aptamer-Decorated pH-Sensitive Nanoliposomes.

ACS Biomater Sci Eng 2021 Apr 19. Epub 2021 Apr 19.

Technical Research Centre, Indian Association for the Cultivation of Science, Kolkata 700032, India.

A new pH-responsive cationic co-liposomal formulation was prepared in this study using the twin version of the amphiphile palmitoyl homocysteine, TPHC; natural zwitterionic lipid, DOPE; and cholesterol-based twin cationic lipid, C5C, at specified molar ratios. This co-liposome was further decorated with a newly designed fluorescently tagged, cholesterol-tethered EpCAM-targeting RNA aptamer for targeted gene delivery. This aptamer-guided nanoliposomal formulation, C5C/DOPE/TPHC at 8:24:1 molar ratio, could efficiently transport the genes in response to low pH of cellular endosomes selectively to the EpCAM overexpressing cancer stem cells. This particular observation was extended using RNA against GFP to validate their transfection capabilities in response to EpCAM expression. Overall, the aptamer-guided nanoliposomal formulation was found to be an excellent transfectant for RNA gene delivery.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00110DOI Listing
April 2021

A co-delivery platform for synergistic promotion of angiogenesis based on biodegradable, therapeutic and self-reporting luminescent porous silicon microparticles.

Biomaterials 2021 May 26;272:120772. Epub 2021 Mar 26.

Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Insufficient angiogenesis happened in body defects such as ulceration, coronary heart disease, and chronic wounds constitutes a major challenge in tissue regeneration engineering. Owing to the poor bioactivity and maintenance of pro-angiogenic cells and factors during transplantation, new bioactive materials to tackle the barrier are highly desirable. Herein, we demonstrate a co-delivery platform for synergistic promotion of angiogenesis based on biodegradable, therapeutic, and self-reporting luminescent porous silicon (PSi) microparticles. The biodegradable and biocompatible PSi microparticles could quickly release therapeutic Si ions, which is bioactive to promote cell migration, tube formation, and angiogenic gene expression in vitro. To construct a highly efficient angiogenesis treatment platform, vascular endothelial growth factor (VEGF) was electrostatically adsorbed by PSi microparticles for effective drug loading and delivery. The dual therapeutic components (Si ions and VEGF) could release with the dissolution of Si skeleton, accompanying by the decay of photoluminescence (PL) intensity and blue shift of the maximum PL wavelength. Therefore, real-time drug release could be self-reported and assessed with the two-dimensional PL signal. The co-delivery of Si ions and VEGF displayed synergistic effect and highly efficient angiogenesis, which was evidenced by the enhancement of endothelial cell migration and tube formation in vitro with approximately 1.5-5 times higher than control. The blood vessel formation in vivo was also significantly improved as shown by the chick chorioallantoic membrane (CAM) model, in which the total length, size and junctions exhibited 2.1 ± 0.4, 4 ± 0.4, and 3.9 ± 0.3 times in comparison to control, respectively. The PSi and VEGF co-delivery system display great potential in tissue engineering as a biodegradable and self-reporting theranostic platform to promote angiogenesis.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120772DOI Listing
May 2021

Extent reflecting overall dietary amino acids composition adherence to the human requirement amino acids pattern is associated with the development of type 2 diabetes.

Aging (Albany NY) 2021 Mar 26;13(7):10141-10157. Epub 2021 Mar 26.

National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.

This study aimed to elucidate whether dietary amino acids (AAs) composition is associated with type 2 diabetes mellitus (T2DM) and to investigate how serum AAs profiles mediated this association. Two prospective cohorts of 1750 and 4024 adults were enrolled. Dietary AAs compositions index (AACI) was developed to reflect the overall quality of dietary AAs composition. Multivariate linear regression and logistic regression models were used to examine associations of AACI and T2DM. The AACI was associated with the incidence of T2DM with the relative risk and 95%CI from the bottom to the top tertiles being 1.00, 1.49 (0.88-2.51) and 2.27 (1.20-4.28), and 1.00, 1.58 (1.13-2.19) and 2.33 (1.56-3.47) in the two cohorts, respectively. The AACI was positively associated with serum valine, isoleucine, glutamic acid and phenylalanine, and it was negatively associated with serum glycine and histidine in both cohorts (<0.01). Valine, glutamic acid and histidine consistently and partially mediated the association between the AACI and T2DM in the two cohorts, with total mediation effects of 33.4% and 54.6%, respectively. Dietary AAs composition was associated with the incidence of T2DM, meanwhile, the relationship was mediated by some degree of serum AAs. Future dietary strategies should focus on the improvement of the overall quality of dietary AAs compositions.
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http://dx.doi.org/10.18632/aging.202777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064212PMC
March 2021

Tumor cell membrane-based peptide delivery system targeting the tumor microenvironment for cancer immunotherapy and diagnosis.

Acta Biomater 2021 Apr 2. Epub 2021 Apr 2.

Key Laboratory of Nano-Bio Interface Research, Division of Nano biomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China. Electronic address:

The development of an effective delivery system for peptides targeting the tumor microenvironment has always been a hot topic of research in the field of cancer diagnosis and therapy. In this study, superparamagnetic iron oxide nanoparticles (SPIO NPs) were encapsulated with H460 lung cancer cell membranes (SPIO NP@M), and two peptides, namely PD-L1 inhibitory peptide (TPP1) and MMP2 substrate peptide (PLGLLG), were conjugated to the H460 membrane (SPIO NP@M-P). Homologous targeting, cytotoxicity, and pharmacokinetics of SPIO NP@M-P were evaluated. The TPP1 peptide was delivered and released to the tumor microenvironment through the homotypic effect of tumor cell membrane and specific digestion by the tumor-specific enzyme MMP2. The newly developed delivery system (SPIO NP@M-P) for the PD-L1 inhibitory peptide could effectively extend the half-life of the peptides (60 times longer than that for peptides alone) and could maintain the ability to reactivate T cells and inhibit the tumor growth both in vitro and in vivo. Furthermore, SPIO NPs in the system could be used as a tumor imaging agent and thus show the effect of peptide treatment. The SPIO NP@M might serve as a promising theranostic platform for therapeutic application of peptides in cancer therapy. STATEMENT OF SIGNIFICANCE: A multifunctional delivery system (SPIO NP@M) was constructed for effectively delivering therapeutic peptides into the tumor microenvironment for cancer diagnosis and therapy. In this paper, the TPP-1 peptide inhibiting the binding of PD-L1 and PD-1 was delivered and released into the tumor microenvironment by the homotypic targeting of H460 cell membrane and specific digestion by the MMP2 enzyme. SPIO NPs in this system were aggregated effectively at the tumor sites and were used for magnetic resonance imaging of tumors. The SPIO NP@M-P delivery system could effectively extend the half-life of the TPP-1 peptide (60 times longer than that of the free peptide) and could maintain the ability to re-activate T cells and inhibit tumor growth in vitro and in vivo. In conclusion, the SPIO NP@M system coated with lung cancer cell membrane and loaded with the PD-L1-blocking TPP-1 peptide could be a promising integrated platform for tumor diagnosis and treatment.
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http://dx.doi.org/10.1016/j.actbio.2021.03.056DOI Listing
April 2021

Synergistic and On-Demand Release of Ag-AMPs Loaded on Porous Silicon Nanocarriers for Antibacteria and Wound Healing.

ACS Appl Mater Interfaces 2021 Apr 31;13(14):16127-16141. Epub 2021 Mar 31.

Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.

Due to the abuse of antibiotics, antimicrobial resistance is rapidly emerging and becoming a major global risk for public health. Thus, there is an urgent need for reducing the use of antibiotics, finding novel treatment approaches, and developing controllable release systems. In this work, a dual synergistic antibacterial platform with on-demand release ability based on silver nanoparticles (AgNPs) and antimicrobial peptide (AMP) coloaded porous silicon (PSi) was developed. The combination of AgNPs and AMPs (Tet-213, KRWWKWWRRC) exhibited an excellent synergistic antibacterial effect. As a carrier, porous silicon can efficiently load AgNPs and AMP under mild conditions and give the platform an on-demand release ability and a synergistic release effect. The AgNPs and AMP coloaded porous silicon microparticles (AgNPs-AMP@PSiMPs) exhibited an acid pH and reactive oxygen species (ROS)-stimulated release of silver ions (Ag) and AMPs under bacterial infection conditions because of oxidation and desorption effects. Moreover, the release of the bactericide could be promoted by each other due to the interplay between AgNPs and Tet-213. antibacterial tests demonstrated that AgNPs-AMP@PSiMPs inherited the intrinsic properties and synergistic antibacterial efficiency of both bactericides. In addition, wound dressing loaded with AgNPs-AMP@PSiMPs showed outstanding bacteria-killing activity, accelerating wound-healing, and low biotoxicity in a-infected rat wound model. The present work demonstrated that PSiMPS might be an efficient platform for loading the antibiotic-free bactericide, which could synergistically and on-demand release to fight wound infection and promote wound healing.
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http://dx.doi.org/10.1021/acsami.1c02161DOI Listing
April 2021

The APEX1/miRNA-27a-5p axis plays key roles in progression, metastasis and targeted chemotherapy of gastric cancer.

Int J Pharm 2021 Apr 4;599:120446. Epub 2021 Mar 4.

National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China. Electronic address:

Gastric cancer (GC) presents a challenge for conventional therapeutics due to low targeting specificity and subsequent elicitation of multiple drug resistance (MDR). As an essential enzyme for DNA repair, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) exhibits multiple functions to affect cancer malignancy and is excessively expressed in GC. However, the roles APEX1 and its inhibitor miR-27a-5p play in modulating GC progression and MDR development remains unclear. Here, we verified APEX1 as a target of miR-27a-5p and subsequently established the APEX1-deleted SGC-7901 cell line by CRISPR/Cas9 editing. The roles of the APEX1/miR-27a-5p axis in GC progression, metastasis and doxorubicin (DOX) resistance were explored by the targeted chemotherapy facilitated by a GC-specific peptide (GP5) functionalized liposomal drug delivery formulation (GP5/Lipo/DOX/miR-27a-5p). The results showed that APEX1 deletion distinctly attenuated cell growth and metastatic properties in GC, and also sensitized GC cells to DOX. Notably, miR-27a-5p was validated as a suppressor of APEX1-dependent GC development and DOX resistance by a RAS/MEK/FOS and PTEN/AKT/SMAD2 pathway-dependent manner. The altered expression of epithelial-mesenchymal transition (EMT) signatures and signal pathway proteins in the APEX1-deleted cells implied that APEX1 potentially enhances DOX resistance of GC cells by altering the regulation of MAPK and AKT pathways, leading to compromised efficacy of chemotherapy or by initiating additional DNA damage response pathways. Taken together, these findings revealed that as a novel therapeutic target, APEX1/miR-27a-5p axis plays essential roles in modulating the GC development and MDR, and the GC targeted drug delivery formulation presents a strategic reference for the future designation of chemotherapeutics study.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120446DOI Listing
April 2021

Interaction between dietary branched-chain amino acids and genetic risk score on the risk of type 2 diabetes in Chinese.

Genes Nutr 2021 Mar 4;16(1). Epub 2021 Mar 4.

National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150081, People's Republic of China.

Background And Objectives: Previous studies have found the important gene-diet interactions on type 2 diabetes (T2D) incident but have not followed branched-chain amino acids (BCAAs), even though they have shown heterogeneous effectiveness in diabetes-related factors. So in this study, we aim to investigate whether dietary BCAAs interact with the genetic predisposition in relation to T2D risk and fasting glucose in Chinese adults.

Methods: In a case-control study nested in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases, we obtained data for 434 incident T2D cases and 434 controls matched by age and sex. An unweighted genetic risk score (GRS) was calculated for 25 T2D-related single nucleotide polymorphisms by summation of the number of risk alleles for T2D. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and fasting glucose.

Results: Significant interactions were found between GRS and dietary BCAAs on T2D risk and fasting glucose (p for interaction = 0.001 and 0.004, respectively). Comparing with low GRS, the odds ratio of T2D in high GRS were 2.98 (95% CI 1.54-5.76) among those with the highest tertile of total BCAA intake but were non-significant among those with the lowest intake, corresponding to 0.39 (0.12) mmol/L versus - 0.07 (0.10) mmol/L fasting glucose elevation per tertile. Viewed differently, comparing extreme tertiles of dietary BCAAs, the odds ratio (95% CIs) of T2D risk were 0.46 (0.22-0.95), 2.22 (1.15-4.31), and 2.90 (1.54-5.47) (fasting glucose elevation per tertile: - 0.23 (0.10), 0.18 (0.10), and 0.26 (0.13) mmol/L) among participants with low, intermediate, and high genetic risk, respectively.

Conclusions: This study indicated that dietary BCAAs could amplify the genetic association with T2D risk and fasting glucose. Moreover, higher BCAA intake showed positive association with T2D when genetic predisposition was also high but changed to negative when genetic predisposition was low.
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http://dx.doi.org/10.1186/s12263-021-00684-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934387PMC
March 2021

Optimizing the CRISPR/Cas9 system for genome editing in grape by using grape promoters.

Hortic Res 2021 Mar 1;8(1):52. Epub 2021 Mar 1.

Beijing Key Laboratory of Grape Science and Enology, and CAS Key Laboratory of Plant Resources, Institute of Botany, The Innovative Academy of Seed Design, The Chinese Academy of Sciences, 100093, Beijing, People's Republic of China.

The efficacy of the CRISPR/Cas9 system in grapevine (Vitis vinifera L.) has been documented, but the optimization of this system, as well as CRISPR/Cas9-mediated multiplex genome editing, has not been explored in this species. Herein, we identified four VvU3 and VvU6 promoters and two ubiquitin (UBQ) promoters in grapevine and demonstrated that the use of the identified VvU3/U6 and UBQ2 promoters could significantly increase the editing efficiency in grape by improving the expression of sgRNA and Cas9, respectively. Furthermore, we conducted multiplex genome editing using the optimized CRISPR/Cas9 vector that contained the conventional multiple sgRNA expression cassettes or the polycistronic tRNA-sgRNA cassette (PTG) by targeting the sugar-related tonoplastic monosaccharide transporter (TMT) family members TMT1 and TMT2, and the overall editing efficiencies were higher than 10%. The simultaneous editing of TMT1 and TMT2 resulted in reduced sugar levels, which indicated the role of these two genes in sugar accumulation in grapes. Moreover, the activities of the VvU3, VvU6, and UBQ2 promoters in tobacco genome editing were demonstrated by editing the phytoene desaturase (PDS) gene in Nicotiana benthamiana leaves. Our study provides materials for the optimization of the CRISPR/Cas9 system. To our knowledge, our simultaneous editing of the grape TMT family genes TMT1 and TMT2 constitutes the first example of multiplex genome editing in grape. The multiplex editing systems described in this manuscript expand the toolbox of grape genome editing, which would facilitate basic research and molecular breeding in grapevine.
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http://dx.doi.org/10.1038/s41438-021-00489-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917103PMC
March 2021

[Application of double plasma molecular adsorption system in children with acute liver failure].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Feb;23(2):180-185

Intensive Care Unit, Hunan Children's Hospital, Changsha 410007, China.

Objective: To study the efficacy and safety of double plasma molecular absorption system (DPMAS) in the treatment of pediatric acute liver failure (PALF).

Methods: A prospective analysis was performed on the medical data of children with PALF who were hospitalized in the Intensive Care Unit (ICU), Hunan Children's Hospital, from March 2018 to June 2020. The children were randomly divided into two groups:plasma exchange group (PE group) and DPMAS group (=18 each). The two groups were compared in terms of clinical indices after treatment, laboratory markers before and after treatment, and adverse events after treatment.

Results: Compared with the PE group, the DPMAS group had a significantly lower number of times of artificial liver support therapy and a significantly shorter duration of ICU stay ( < 0.05), while there was no significant difference in the 12-week survival rate between the two groups ( > 0.05). There was no significant difference in laboratory markers between the two groups before treatment ( > 0.05). After treatment, both groups had reductions in the levels of total bilirubin, interleukin-6, and tumor necrosis factor-α, and the DPMAS group had significantly greater reductions than the PE group ( < 0.05). Both groups had a significant reduction in alanine aminotransferase ( < 0.05), while there was no significant difference between the two groups ( > 0.05). The PE group had a significant increase in albumin, while the DPMAS group had a significant reduction in albumin ( < 0.05). The PE group had a significant reduction in prothrombin time, while the DPMAS group had a significant increase in prothrombin time ( < 0.05). There was no significant difference between the two groups in the rebound rate of total bilirubin and the overall incidence rate of adverse events after treatment ( > 0.05).

Conclusions: DPMAS is safe and effective in the treatment of PALF and can thus be used as an alternative to artificial liver support therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921536PMC
February 2021

An Open-label, Multicenter, Single-arm, Phase II Study of Fluzoparib in Patients with Germline Mutation and Platinum-sensitive Recurrent Ovarian Cancer.

Clin Cancer Res 2021 May 8;27(9):2452-2458. Epub 2021 Feb 8.

Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.

Purpose: Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline -mutated recurrent ovarian cancer.

Patients And Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1.

Results: A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5-18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6-78.2] and 70.8% (95% CI, 61.5-79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3-13.9) and 10.3 months (95% CI, 9.2-12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2-96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred.

Conclusions: Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline -mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3546DOI Listing
May 2021

Flavan-3-ols in Vitis seeds: Their extraction and analysis by HPLC-ESI-MS/MS.

Food Res Int 2021 Jan 30;139:109911. Epub 2020 Nov 30.

Beijing Key Laboratory of Grape Science and Enology and Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, PR China. Electronic address:

An orthogonal L4 × 2 test design was applied to select the optimum conditions for extracting flavan-3-ols in grape seeds. Highest yield of flavan-3-ols was achieved with 80% methanol, a ratio [1:30 (g/mL)] of sample-to-solvent, sonication for 20 min, and extraction at 25 °C for 12 h in darkness. The optimized analytical method for HPLC separation was a multistep gradient elution using 1% formic acid (A) and acetonitrile containing 1% formic acid (B), at a flow rate of 0.6 mL/min in 36 min. Moreover, fourteen flavan-3-ols were separated and identified using HPLC-ESI-MS/MS, including four monomers ((+)-catechin, (-)-epicatechin, epigallocatechin gallate and epicatechin gallate) and ten oligomers (three dimers, four trimers, two tetramers and one pentamer). The optimized method was used to determine flavan-3-ols content and compositions among ten representative cultivars. The new wine grape - Beihong, had higher flavan-3-ols content and polymerization than classic wine grapes - Cabernet Sauvignon, Merlot, Semillon and Riesling.
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http://dx.doi.org/10.1016/j.foodres.2020.109911DOI Listing
January 2021

Refined tooth and pulp segmentation using U-Net in CBCT image.

Dentomaxillofac Radiol 2021 Jan 15:20200251. Epub 2021 Jan 15.

College of Electronics and Information Engineering, Tongji University, Shanghai 201804, China.

Objectives: The aim of this study was extracting any single tooth from a CBCT scan and performing tooth and pulp cavity segmentation to visualize and to have knowledge of internal anatomy relationships before undertaking endodontic therapy.

Methods: We propose a two-phase deep learning solution for accurate tooth and pulp cavity segmentation. First, the single tooth bounding box is extracted automatically for both single-rooted tooth (ST) and multirooted tooth (MT). It is achieved by using the Region Proposal Network (RPN) with Feature Pyramid Network (FPN) method from the perspective of panorama. Second, U-Net model is iteratively performed for refined tooth and pulp segmentation against two types of tooth ST and MT, respectively. In light of rough data and annotation problems for dental pulp, we design a loss function with a smoothness penalty in the network. Furthermore, the multi-view data enhancement is proposed to solve the small data challenge and morphology structural problems.

Results: The experimental results show that the proposed method can obtain an average dice 95.7% for ST, 96.2% for MT and 88.6% for pulp of ST, 87.6% for pulp of MT.

Conclusions: This study proposed a two-phase deep learning solution for fast and accurately extracting any single tooth from a CBCT scan and performing accurate tooth and pulp cavity segmentation. The 3D reconstruction results can completely show the morphology of teeth and pulps, it also provides valuable data for further research and clinical practice.
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http://dx.doi.org/10.1259/dmfr.20200251DOI Listing
January 2021

Age-related cognitive decline is associated with microbiota-gut-brain axis disorders and neuroinflammation in mice.

Behav Brain Res 2021 Mar 7;402:113125. Epub 2021 Jan 7.

Departmen Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China. Electronic address:

Age-related cognitive decline is associated with chronic low grade neuroinflammation that may result from a complex interplay among many factors, such as bidirectional communication between the central nervous system (CNS) and gut microbiota. The present study used 2-month-old (young group) and 15-month-old (aged group) male C57BL/6 mice to explore the potential association between age-related cognitive decline and the microbiota-gut-brain axis disorder. We observed that aged mice exhibited significant deficits in learning and memory, neuronal and synaptic function compared with young mice. Aged mice also exhibited significant dysbiosis of the gut microbiota. Disruptions of the intestinal barrier and blood-brain barrier were also observed, including increases in intestinal, low-grade systemic and cerebral inflammation. Furthermore, plasma and brain levels of lipopolysaccharide (LPS) were significantly higher in aged mice compared with young mice, with increasing expression of Toll-like receptor 4 (TLR4) and myeloid differential protein-88 (MyD88) and the nuclear translocation of nuclear factor κB (NF-κB) in intestinal and brain tissues. These findings showed that microbiota-gut-brain axis dysfunction that occurs through LPS-induced activation of the TLR4/NF-κB signaling pathway is implicated in age-related neuroinflammation and cognitive decline.
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http://dx.doi.org/10.1016/j.bbr.2021.113125DOI Listing
March 2021

Autobiographical and episodic memory deficits in schizophrenia: A narrative review and proposed agenda for research.

Clin Psychol Rev 2021 02 11;83:101956. Epub 2020 Dec 11.

University Hospital of Strasbourg - Department of Psychiatry, University of Strasbourg, INSERM U1114, FMTS, France. Electronic address:

Schizophrenia is associated with memory disorders that affect patients in their daily life. Patients complain about difficulty to remember knowledge that has been recently learnt together with its context (episodic memory, EM) but also more complex events that have been personally experienced (autobiographical memory, AM). While deficits at both encoding and retrieval have been shown to account for EM disorders in schizophrenia, the cognitive mechanisms involved in AM disorders are more difficult to approach. This is partly explained by the conceptual difference between EM and AM. Some methodological limitations inherent to the AM research also reduce the possibility to investigate the early processing of complex and dynamic real-life events at encoding; rather the retrieval processes engaged have therefore been the focus of the bulk of extant research. The aim of this review is to summarize the main findings related to EM and AM research in patients with schizophrenia, to discuss the putative mechanisms that may account for patients' AM impairment, based in particular on the literature about EM, and to provide an agenda for future research aiming to further elucidate the role of encoding deficits in AM in patients.
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http://dx.doi.org/10.1016/j.cpr.2020.101956DOI Listing
February 2021

Kikuchi's disease with hemophagocytic lymphohistiocytosis: A case report and literature review.

Medicine (Baltimore) 2020 Dec;99(51):e23500

Department of Pediatric Emergency Center, Hunan Children's Hospital, Changsha, Hunan,China.

Introduction: Kikuchi's disease (KD) is a rare form of necrotizing lymphadenitis that rarely occurs in association with hemophagocytic lymphohistiocytosis (HLH) in children.

Patient Concerns: We report the case of a 4-year-5-month-old boy who suffered from fever, cervical lymphadenopathy, pancytopenia, hypertriglyceridemia, splenomegaly, low NK cell activity.

Diagnoses: A diagnosis of KD with HLH was made based on the results of biopsy of cervical lymph node and HLH-2004 trial guidelines.

Interventions: The patient was treated with corticosteroids, cyclosporine, etoposide, continuous hemodiafiltration (HDF), and plasma exchange (PE).

Outcomes: He showed a complete response to therapy, and his condition gradually improved. He was discharged on day 45 after admission due to his good recovery status.

Conclusion: HLH can be associated with KD, especially in childhood, and may have an aggressive clinical course. Continuous HDF and PE and chemotherapy should be reserved for those patients who fail to respond to IVIG and corticosteroids.
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http://dx.doi.org/10.1097/MD.0000000000023500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748204PMC
December 2020

An aptamer-based drug delivery agent (CD133-apt-Dox) selectively and effectively kills liver cancer stem-like cells.

Cancer Lett 2021 Mar 19;501:124-132. Epub 2020 Dec 19.

Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia. Electronic address:

Liver cancer has no effective therapies, hence a poor survival. Cancer stem-like cells not only contribute to cancer initiation and progression, but also to drug resistance, cancer metastasis, and eventually treatment failure. Hence, any approaches that can effectively kill cancer stem-like cells hold a great potential for cancer treatment. CD133 is a robust marker for liver cancer stem-like cells. We developed a specific aptamer against CD133 (CD133-apt), and then loaded this aptamer with an anticancer drug doxorubicin (CD133-apt-Dox). The efficacy of CD133-apt-Dox in targeting liver cancer stem-like cells and its overall effect in treating liver cancer were investigated using multiple in vitro and in vivo studies including in patients-derived liver cancer organoids. We have observed that CD133-apt could preferably delivered doxorubicin to CD133-expressing cells with efficient drug accumulation and retention. CD133-apt-Dox impaired the self-renewal capacity of liver cancer stem-like cells and attenuated their stem-ness phenotypes in vitro or in vivo. CD133-apt-Dox significantly inhibited the growth of liver cancer cells and patients-derived organoids and reduced the growth of xenograft tumours in nude mice inhibited the growth of DEN-induced liver cancer in immunocompetent mice. Hence, aptamer-mediated targeting of CD133 is a highly promising approach for liver cancer therapy.
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http://dx.doi.org/10.1016/j.canlet.2020.12.022DOI Listing
March 2021

Streptococcus gordonii infectious endocarditis presenting as a neurocysticercosis mimic - A rare manifestation.

J Infect Public Health 2021 Jan 17;14(1):39-41. Epub 2020 Dec 17.

Department of Neurology, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University (Third Military Medical University), Chongqing 400037, China. Electronic address:

Infective endocarditis (IE) usually presents with nonspecific signs and symptoms, which delay diagnosis and proper treatment. Here, we describe a patient with initial clinical and radiological features compatible with neurocysticercosis who was later found to have IE. Furthermore, the patient course was complicated by multiple neurological complications (brain abscess, meningitis, infected intracranial aneurysm, subarachnoid hemorrhage and hemorrhage), and patient ultimately deceased. To our knowledge, an IE case mimicking neurocysticercosis and progressing with prominent and complicated neurological manifestations has not been previously reported. We therefore describe the challenges of neurocysticercosis diagnosis based on serum ELISA and radiological findings. For patient diagnosed as neurocysticercosis, clinical follow-up is recommended and presence of systemic symptoms should be red flags for another underlying disease.
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http://dx.doi.org/10.1016/j.jiph.2020.11.013DOI Listing
January 2021

Porous FeO Nanorods on Hierarchical Porous Biomass Carbon as Advanced Anode for High-Energy-Density Asymmetric Supercapacitors.

Front Chem 2020 26;8:611852. Epub 2020 Nov 26.

Department of Electronic Engineering, College of Internet-of-Things (IoT), Jiangnan University, Wuxi, China.

In this study, a novel negative electrode material was prepared by aligning α-FeO nanorods on a hierarchical porous carbon (HPC) skeleton. The skeleton was derived from wheat flour by a facile hydrothermal route to enhance conductivity, improve surface properties, and achieve substantially good electrochemical performances. The α-FeO/HPC electrode exhibits enhanced specific capacitance of 706 F g, which is twice higher than that of α-FeO. The advanced α-FeO/HPC//PANI/HPC asymmetrical supercapacitor was built with an expanded voltage of 2.0 V in 1 M LiSO, possessing a specific capacitance of 212 F g at 1 A g and a maximum energy density of 117 Wh kg at 1.0 kW kg, along with an excellent stability of 5.8% decay in capacitance after 5,000 cycles. This study affords a simple process to develop asymmetric supercapacitors, which exhibit high electrochemical performances and are applicable in next-generation energy storage devices, based on α-FeO hybrid materials.
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http://dx.doi.org/10.3389/fchem.2020.611852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726331PMC
November 2020

Dual-Cross-Linked Network Hydrogels with Multiresponsive, Self-Healing, and Shear Strengthening Properties.

Biomacromolecules 2021 02 15;22(2):800-810. Epub 2020 Dec 15.

Department of Chemical and Materials Engineering, University of Alberta, 116 Street and 85th Avenue, Edmonton, Alberta T6G 2G6, Canada.

Dual-cross-linked network (DCN) hydrogels with multiresponsive and self-healing properties are attracting intensive interests due to their enhanced mechanical strength for a wide range of applications. Herein, we developed a DCN hydrogel that combines a dynamic imine and a benzoxaboronic ester with a neutral p value (∼7.2) as dual linkages and contains biocompatible zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) [poly(MPC)] as the backbone. Oscillatory rheology result indicated shear strengthening mechanical properties compared to the single-cross-linked network (SCN) hydrogels, which use either imine bond or benzoxaboronic ester as the linkage alone. Due to the coexistence of stimuli-responsive imine and benzoxaboronic ester, the DCN hydrogels show sensitive multiple responsiveness to pH, sugar, and hydrogen peroxide. The dynamic nature of the dual linkages endows the DCN hydrogels with excellent self-healing ability after fracture. More importantly, the excellent biocompatibility and performance in three-dimensional (3D) cell encapsulation were established by a cytotoxicity Live/Dead assay, indicating DCN hydrogel's great potential as a cell culture scaffold. The biocompatible poly(MPC)-based backbone and the rapid formation of the cross-linking network make the DCN hydrogels promising candidates for future biomedical applications.
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http://dx.doi.org/10.1021/acs.biomac.0c01548DOI Listing
February 2021

Influenza Vaccination and Non-Pharmaceutical Measure Effectiveness for Preventing Influenza Outbreaks in Schools: A Surveillance-Based Evaluation in Beijing.

Vaccines (Basel) 2020 Dec 1;8(4). Epub 2020 Dec 1.

Department of National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Although schools are known to play a major role in the spread of influenza virus, few studies have evaluated the effectiveness of vaccination and non-pharmaceutical measures for preventing influenza outbreaks in schools. We investigated all febrile illness outbreaks in primary and secondary schools in Beijing reported between August 2018 and July 2019. We obtained epidemiological information on febrile illness outbreaks and oral pharyngeal swabs from students in the outbreaks to test for influenza virus. We surveyed schools that did not report febrile illness outbreaks. We developed multi-level models to identify and evaluate factors associated with serious influenza outbreaks and explored the association of vaccine coverage and outbreaks using multi-stage regression models. We identified a total of 748 febrile illness outbreaks involving 8176 students in Beijing; 462 outbreaks were caused by influenza virus. Adjusted regression modeling showed that large class size (odds ratio (OR) = 2.38) and the number of days from identification of the first case to initiation of an intervention (OR = 1.17) were statistically significant and positively associated with serious outbreaks, and that high vaccination coverage (relative risk (RR) = 0.50) was statistically significant and negatively associated with outbreaks. Multi-stage regression modeling showed that RR decreased fastest when vaccination coverage was 45% to 51%. We conclude that high influenza vaccination coverage can prevent influenza outbreaks in schools and that rapid identification of febrile children and early initiation of non-pharmaceutical measures can reduce outbreak size.
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http://dx.doi.org/10.3390/vaccines8040714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712374PMC
December 2020

Impaired Coupling of the Brain's Default Network During Sleep Deprivation: A Resting-State EEG Study.

Nat Sci Sleep 2020 10;12:937-947. Epub 2020 Nov 10.

Sleep and NeuroImaging Center, Faculty of Psychology, Southwest University, Chongqing 400715, People's Republic of China.

Introduction: Sleep deprivation (SD) has a negative influence on mood and emotion processing, and previous studies have elucidated the impaired coupling within the default network (DN) after SD. However, the dynamic characteristic with high temporal precision was rarely investigated in the DN after SD.

Methods: Here, the resting-state EEG after nocturnal sleep (NS) and SD was collected from 31 participants. The cortical electrical activities of the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC) were reconstructed applying the eLORETA, and the functional connectivity (FC) of PCC-aMPFC was calculated using the power envelope connectivity (PEC).

Results: Compared with NS, the power spectrums of the PCC and the FC of PCC-aMPFC were significantly reduced in the α band after SD. Interestingly, the impaired PCC-aMPFC integration was positively correlated with the decreased positive affect, implying that the DN plays a critical role in the subjective mood state. Our moderation analysis further revealed that the intensity of the DN posterior-anterior interaction moderated sleep loss and positive affect.

Discussion: Overall, the results reveal the strong relationship between the uncoupling of DN and the feeling down of mood. Our research may contribute towards a better understanding of the mood and cognition processing after sleep loss.
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http://dx.doi.org/10.2147/NSS.S277655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667510PMC
November 2020

Exosomes and breast cancer drug resistance.

Cell Death Dis 2020 11 17;11(11):987. Epub 2020 Nov 17.

St George and Sutherland Clinical School, Faculty of Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia.

Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention. The functional proteins or non-coding RNAs contained in exosomes secreted from tumor and stromal cells mediate drug resistance by regulating drug efflux and metabolism, pro-survival signaling, epithelial-mesenchymal transition, stem-like property, and tumor microenvironmental remodeling. In this review, we summarize the underlying associations between exosomes and drug resistance of BC and discuss the unique biogenesis of exosomes, the change of exosome cargo, and the pattern of release by BC cells in response to drug treatment. Moreover, we propose exosome as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistance of BC.
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http://dx.doi.org/10.1038/s41419-020-03189-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673022PMC
November 2020

Reproducibility of power spectrum, functional connectivity and network construction in resting-state EEG.

J Neurosci Methods 2021 01 24;348:108985. Epub 2020 Oct 24.

Sleep and NeuroImaging Center, Faculty of Psychology, Southwest University, Chongqing, 400715, China; Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, Chongqing, 400715, China; National Demonstration Center for Experimental Psychology Education (Southwest University), Chongqing, 400715, China. Electronic address:

Background: Characteristics from resting-state electroencephalography (rsEEG) provides relevant information about individual differences in cognitive tasks and personality traits. Due to its increasing application, it is crucial to know the reproducibility of several analysis measures of rsEEG.

New Method: A new brain network construction method was proposed based on simplified forward model (SFM). In addition, we aimed to carry out an extensive examination of the reproducibility of the power spectrum and functional connectivity at both the sensor-level and the source-level. We systematically proposed multiple new pipelines by integration source imaging, time-course extraction and network reconstruction.

Results/comparison With Existing Method(s): Our results revealed that the reproducibility of eyes-closed was slightly higher than that of eyes-open, and the relative power was more repeatable than the absolute power, especially in high-frequency bands. The reproducibility of the sensor-level was higher than that of the source-level, both for power and connectivity. Remarkably, connectivity measures could be separated into two classes according to their reproducibility. Notably, the reproducibility of power envelope correlation (PEC) was generally the highest among those connectivity measures which are insensitive to volume conduction effect. For the whole-brain network construction, single dipole modeling was better than the dimensionality reduction methods, such as mean or principal component analysis (PCA) of multiple dipoles of a region.

Conclusions: In conclusion, our results described the reproducibility of rsEEG power spectrum, connectivity measures, and network constructions, which could be considered in assessing inter-individual differences in brain-behavior relationships, as well as automatic biometric applications.
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http://dx.doi.org/10.1016/j.jneumeth.2020.108985DOI Listing
January 2021

Screening and identification of a specific peptide binding to breast cancer cells from a phage-displayed peptide library.

Biotechnol Lett 2021 Jan 3;43(1):153-164. Epub 2020 Nov 3.

Laboratory of Tumor Molecular and Cellular Biology, College of Life Sciences, Shaanxi Normal University, 620 West Chang'an Avenue, Xi'an, 710119, Shaanxi, China.

Objectives: Breast cancer is a popular fatal malignant tumor for women with high of rates incidence and mortality. Development of the new approaches for breast cancer targeted diagnosis and chemotherapy is emergently needed by the current clinical practice, the important first step is finding a breast cancer specifically binding molecule or fragment as early clinical indicators.

Results: By a phage-displayed peptide library, a 12-mer peptide, CSB1 was screened out using MCF-7 cells as the target. The consequently results under immunofluorescence and laser scanning confocal microscope (LSCM) indicated that CSB1 bound MCF-7 cells and breast cancer tissues specifically and sensitively with high affinity. Bioinformatics analysis suggested that the peptide CSB1 targets the 5-Lipoxygenase-Activating Protein (FLAP), which has been implicated in breast cancer progression and prognosis.

Conclusions: The peptide, CSB1 is of the potential as a candidate to be used for developing the new approaches of molecular imaging detection and targeting chemotherapy of breast cancer in the future.
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http://dx.doi.org/10.1007/s10529-020-03044-3DOI Listing
January 2021

Phthalide derivative CD21 alleviates cerebral ischemia-induced neuroinflammation: Involvement of microglial M2 polarization via AMPK activation.

Eur J Pharmacol 2020 Nov 11;886:173552. Epub 2020 Sep 11.

Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China. Electronic address:

Microglia can be activated to become the classic phenotype (M1) or alternative phenotype (M2), which play an important role in regulating neuroinflammatory response and tissue repair after ischemic stroke. CD21, a novel phthalide derivative, is a potential neuroprotectant against ischemic brain injury. The present study further investigated the effects of CD21 on post-ischemic microglial polarization and the underlying mechanisms. Transient middle cerebral artery occlusion (tMCAO) was used as a mouse model of ischemic stroke, while BV2 cells stimulated with conditioned medium collected from oxygen-glucose deprivation-treated HT22 cells were used in in vitro ischemic studies. The current results showed that CD21 dose-dependently and significantly improved neurological outcomes in tMCAO mice. Biochemical analyses revealed that CD21 decreased the expression of M1 phenotype markers (CD86, interleukin-1β and inducible nitric oxide synthase) and increased the expression of M2 phenotype markers (CD206, interleukin-10 and YM1/2) in both ischemic brain tissues and BV2 cells. Meanwhile, CD21 decreased the production of proinflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α), promoted the release of the antiinflammatory cytokine (interleukin-10), and enhanced the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) in ischemic brain tissue and BV2 cells. Furthermore, the AMPK inhibitor (compound C) reversed these effects of CD21 in BV2 cells. These findings indicate that CD21 alleviates post-ischemic neuroinflammation through induction of microglial M2 polarization that is at least in part medicated by AMPK activation, suggesting that CD21 may be a promising candidate for protecting against ischemic brain injury.
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http://dx.doi.org/10.1016/j.ejphar.2020.173552DOI Listing
November 2020

Role of presymptomatic transmission of COVID-19: evidence from Beijing, China.

J Epidemiol Community Health 2021 01 27;75(1):84-87. Epub 2020 Aug 27.

University of New South Wales, Sydney, Australia.

Background: The presymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented in limited clusters, and it is predicted through modelling. However, there is a lack of evidence from observations with a large sample size.

Methods: We used data from meticulous contact tracing of people exposed to cases of SARS-CoV-2 to estimate the proportion of cases that result from the presymptomatic transmission of the virus in Beijing during January 2020 and February 2020.

Results: The results showed that presymptomatic transmission occurred in at least 15% of 100 secondary COVID-19 cases. The earliest presymptomatic contact event occurred 5 days prior to the index case's onset of symptoms, and this occurred in two clusters.

Conclusions: The finding suggested that the contact tracing period should be earlier and highlighted the importance of preventing transmission opportunities well before the onset of symptoms.
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http://dx.doi.org/10.1136/jech-2020-214635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788477PMC
January 2021

SDN-Based Survivability Analysis for V2I Communications.

Sensors (Basel) 2020 Aug 19;20(17). Epub 2020 Aug 19.

School of Information Science and Technology, Nantong University, Nantong 226019, China.

In vehicle-to-infrastructure (V2I) communications, various failures in the dynamic movement pose serious link interruptions. To study the continuous service quality for the V2I network when this issue happens, this paper proposes a survivability analysis and establishes the communication architecture for software-defined network (SDN)-based V2I communications. With the controllable advantages of SDN centralized management, the multi-path transmission control protocol is used to seamlessly switch the transmission information between the V2I links of each vehicle node. Specifically, according to the analysis of specific fault types for V2I links, the definitions of SDN-based V2I survivability is provided to establish the corresponding survivability mode. To further verify the survivability model, a full-state search is adopted by means of probability model checker PRISM. In addition, multi-directional probability and expected reward evaluation analyses are carried out from the point of view of time. The simulation results show that, with the failure of multiple V2I links, the network quality of service (QoS) correspondingly declines, but the network still survives, due to the multi-path transmission control protocol (MPTCP) action. Moreover, with a high fault repair rate, the service performance and survivability of the network is improved rapidly.
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http://dx.doi.org/10.3390/s20174678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506569PMC
August 2020

The critical size of gold nanoparticles for overcoming P-gp mediated multidrug resistance.

Nanoscale 2020 Aug 17;12(31):16451-16461. Epub 2020 Jun 17.

School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.

Multidrug resistance (MDR) remains a huge obstacle during cancer treatment. One of the most studied MDR mechanisms is P-glycoprotein (P-gp) mediated drug efflux. Based on the three-dimensional structural characteristics of P-gp, gold nanoparticles (AuNPs) with average sizes of 4.1 nm and 5.4 nm were designed for the construction of nanodrug delivery systems (NanoDDSs), with the anticancer molecules 2-(9-anthracenylmethylene)-hydrazinecarbothioamide (ANS) and 6-mercaptopurine (6-MP) modified on the AuNP surfaces through the thiol group. In vitro cytotoxicity results suggested that the larger sized AuNPs can effectively decrease the drug resistance index of MCF-7/ADR cells to ∼2. Verapamil and P-gp antibody competitive experiments, combined with the cellular uptake of AuNPs, indicated that larger NanoDDSs were more conducive to intracellular drug accumulation and thus had improved anticancer activities, due to a size mismatch between the nanoparticles and the active site of P-gp, and, therefore, reduced drug efflux was seen. Measurements of ATPase activity and intracellular ATP levels indicated that the larger nanoparticles do not bind well to P-gp, thus avoiding effective recognition by P-gp. This was further evidenced by the observation that 4.1 nm and 5.4 nm NanoDDS-treated MCF-7/ADR cells showed remarkable differences in energy-related metabolic pathways. Therefore, the critical size of AuNPs for overcoming MDR was identified to be between 4.1 nm and 5.4 nm. This provides a more accurate description of the composite dimension requirements for NanoDDSs that are designed to overcome MDR.
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http://dx.doi.org/10.1039/d0nr03226cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430045PMC
August 2020