Publications by authors named "Chen Li"

6,942 Publications

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Scutellarin ameliorates colitis-associated colorectal cancer by suppressing Wnt/β-catenin signaling cascade.

Eur J Pharmacol 2021 Jun 9:174253. Epub 2021 Jun 9.

State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address:

Dysregulated Wnt/β-catenin signaling pathway plays a critical role in the pathogenesis of colorectal cancer (CRC). Scutellarin, a flavonoid compound in Scutellaria barbata, has been reported to suppress CRC, with the action mechanism elusive. In this study, Scutellarin was found to inhibit the carcinogenesis of colitis-associated cancer (CAC) in mice caused by azoxymethane/dextran sulfate sodium, with alleviation of pathologic symptoms. Besides, Scutellarin attenuated mouse serum concentrations of TNF-α and IL-6, heightened Bax expression and diminished B-cell lymphoma-2 (Bcl-2) level in CAC tissues of mice, through down-regulating Wnt/β-catenin signaling cascade. In CRC HT-29 cells, Scutellarin retarded the proliferation and migration, induced apoptosis, with boosted Bax expression and decreased Bcl-2 level, which may be attributed to its repression of Wnt/β-catenin signals in HT-29 cells. Our findings demonstrate that Scutellarin may ameliorate colitis-associated colorectal cancer by weakening Wnt/β-catenin signaling cascade.
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http://dx.doi.org/10.1016/j.ejphar.2021.174253DOI Listing
June 2021

Senolytics improve bone forming potential of bone marrow mesenchymal stem cells from aged mice.

NPJ Regen Med 2021 Jun 11;6(1):34. Epub 2021 Jun 11.

UConn Center on Aging, Farmington, CT, USA.

The osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) declines dramatically with aging. By using a calvarial defect model, we showed that a senolytic cocktail (dasatinib+quercetin; D + Q) improved osteogenic capacity of aged BMSC both in vitro and in vivo. The study presented a model to assess strategies to improve bone-forming potential on aged BMSCs. D + Q might hold promise for improving BMSC function in aged populations.
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http://dx.doi.org/10.1038/s41536-021-00145-zDOI Listing
June 2021

Viperin_sv1 promotes RIG-I expression and suppresses SVCV replication through its radical SAM domain.

Dev Comp Immunol 2021 Jun 8:104166. Epub 2021 Jun 8.

College of Fisheries, Huazhong Agricultural University, Wuhan 430070, Hubei, China; Hubei Engineering Technology Research Center for Aquatic Animal Diseases Control and Prevention, Wuhan 430070, Hubei, China. Electronic address:

SVCV infection is known to activate the host's innate immune responses, including the production of interferon (IFN) and interferon-stimulated genes (ISGs). Viperin_sv1 is a novel splice variant of viperin, which is induced during SVCV infection and proves to positively regulate the IFN activation and production. However, the underlying mechanism remains unsolved. In this study, the P protein of SVCV was identified to be the key to induce the mRNA modification and production of viperin_sv1 during the virus infection. Besides, Viperin_sv1 was able to trigger the RLR signaling cascades to activate type-1 interferon response. Additional analysis revealed that viperin_sv1 promoted the stability and function of RIG-I, which result in the production of IFN and ISGs. Moreover, the central SAM domain of viperin_sv1 was demonstrated to be essential for regulating RIG-I protein expression and inducing IFN production. Furthermore, this study also showed that SVCV replication could be inhibited by the viperin_sv1 SAM domain. In conclusion, our study demonstrates that viperin_sv1 reduces the replication of SVCV by promoting the RIG-I protein expression. Our findings identified the antiviral function played by the SAM domain of viperin_sv1 and suggested an antiviral mechanism that is conserved among different species.
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http://dx.doi.org/10.1016/j.dci.2021.104166DOI Listing
June 2021

Optical Coherence Tomography Angiography Compared with Multimodal Imaging for Diagnosing Neovascular Central Serous Chorioretinopathy.

Am J Ophthalmol 2021 Jun 8. Epub 2021 Jun 8.

Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong; 2010 Retina & Macula Centre, Hong Kong.

Purpose: To assess the diagnostic accuracy of optical coherence tomography angiography (OCTA) compared with multimodal imaging for CNV in CSC eyes and to determine the features that predicted CNV.

Design: Prospective cross-sectional study.

Methods: Consecutive CSC patients were recruited from retina clinic. The reference standard for CNV was determined by interpretation of multimodal imaging with OCTA, structural OCT line scan, fluorescein angiography (FA), indocyanine green angiography (ICGA), ultra-widefield fundus photography and fundus autofluorescence (FAF). Two independent masked graders examined OCTA without FA and ICGA to diagnose CNV. Univariate and multivariate analyses were performed to evaluate factors associated with CNV.

Results: CNV was detected in 69 eyes in 64 out of 277 CSC patients according to reference standard. The two masked graders who examined OCTA had sensitivity of 81.2% (95% Confidence Interval [CI], 71.9%-90.4%) and 78.3% (95% CI, 68.5%-88.0%), specificity of 97.3% (95% CI, 95.9%-98.8%) and 96.2% (95% CI, 94.5%-98.0%), positive predictive values of 82.4% (95% CI, 73.3%-91.4%) and 76.1% (95% CI, 66.1%-86.0%), and negative predictive values of 97.1% (95% CI, 95.6%-98.7%) and 96.7% (95% CI, 95.0%-98.3%). Their mean AUC was 0.88 with good agreement (Kappa coefficient 0.80 [95% CI, 0.72-0.89]). Flat irregular pigment epithelial detachment on structural OCT, neovascular network on OCTA and ill-defined late leakage on FA significantly correlated with CNV in CSC from multiple regression (P < 0.001, P < 0.001 and P = 0.005, respectively).

Conclusions: There is discordance between OCTA and multimodal imaging in diagnosing CNV in CSC. This study demonstrated the caveats in OCTA interpretation, such as small extrafoveal lesions and retinal pigment epithelial alterations. Comprehensive interpretation of OCTA with dye angiography and structural OCT is recommended.
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http://dx.doi.org/10.1016/j.ajo.2021.05.029DOI Listing
June 2021

Neutrophil-lymphocyte ratio as a prognostic factor for minute clear cell renal cell carcinoma diagnosed using multi-slice spiral CT.

Medicine (Baltimore) 2021 Jun;100(23):e26292

Department of Radiology, Urumqi Friendship Hospital, No. 558 Shengli Road, Tianshan District, 830049 Urumqi, P.R. China.

Abstract: Minute clear cell renal cell carcinoma (MccRCC) has a diameter of <1.5 cm and can be diagnosed using multi-slice spiral CT (MSCT). Recently, the role of the neutrophil-lymphocyte ratio (NLR) in the development of MccRCC has attracted attention. This study aimed to further explore the relationship between the NLR and MccRCC.This was a prospective study of 100 patients who were diagnosed with MccRCC using MSCT at Urumqi Friendship Hospital, China. The study investigated a series of pretreatment factors, including NLR and patients' general clinical data. Statistical methods employed included Pearson's chi-square test, Spearman-rho correlation test, Cox regression analysis, and receiver operator characteristic curve analysis.Based on Pearson's χ2, Spearman-rho test, and univariate/multivariate Cox regression analysis, the overall survival of patients with MccRCC was shown to be significantly related to NLR (P < .001). NLR (hazard ratio = 50.676, 95%CI, 17.543-146.390, P < .001) is a significant independent risk-factor for MccRCC. A receiver operator characteristic curve was plotted to examine specificity and sensitivity between NLR and MccRCC (area under curve = 0.958, P < .001).The level of the NLR plays a crucial role in the survival of patients with MccRCC, as diagnosed with MSCT. The higher the NLR, the worse the prognosis for patients with MccRCC.
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http://dx.doi.org/10.1097/MD.0000000000026292DOI Listing
June 2021

ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron.

Acta Pharmacol Sin 2021 Jun 10. Epub 2021 Jun 10.

Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China.

Ferroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and HO via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica, which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and HO. Furthermore, brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine (500 μM) or improved by ferric ammonium citrate (500 μM). Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1 (50 μM) or liproxstatin-1 (30 μM) rescued brucine-induced glioma cell death. Moreover, knockdown of ATF3 prevented brucine-induced accumulation of iron and HO and glioma cell death. We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced HO accumulation via upregulating NOX4 and SOD1 to generate HO on one hand, and downregulating catalase and xCT to prevent HO degradation on the other hand. HO then contributed to brucine-triggered iron increase and transferrin receptor upregulation, as well as lipid peroxidation. This was further verified by treating glioma cells with exogenous HO alone. Moreover, HO reversely exacerbated brucine-induced ER stress. Taken together, ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing HO and iron.
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http://dx.doi.org/10.1038/s41401-021-00700-wDOI Listing
June 2021

Preparation and evaluation of chiral open-tubular columns supported with zeolite silica nanoparticles and single/dual chiral selectors using capillary electrochromatography with amperometric detection.

J Chromatogr A 2021 May 28;1651:462298. Epub 2021 May 28.

School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China. Electronic address:

In this work, novel stationary phase coatings by zeolite SiONPs coupled with β-cyclodextrin (β-CD) or β-CD/L-phenylalanine were developed for chiral open-tubular capillary electrochromatography (OT-CEC). The OT columns were prepared taking advantage of the strong adhesion of polydopamine in one-step method. Scanning electron micrography and electroosmotic flow were used to characterize the prepared single/dual-selector OT columns. Chiral separation of four chiral analytes (catechin/epicatechin, ephedrine/pseudoephedrine, ritodrine and salbutamol) was carried out in order to evaluate the performance of the prepared columns in OT-CEC with amperometric detection system. In terms of migration time, peak area, resolution, and selectivity factor of catechin/epicatechin and salbutamol, the run-to-run, day-to-day, and column-to-column repeatability were within 8.9%. Under the optimum conditions, the developed methods were applied for the analyses of Chinese herbal medicine Catechu herbs and salbutamol aerosol samples.
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http://dx.doi.org/10.1016/j.chroma.2021.462298DOI Listing
May 2021

Integrating Facial and Intraoral Scans for Digital Esthetic and Occlusal Design: A Technical Report.

J Prosthodont 2021 Jun 9. Epub 2021 Jun 9.

Professor, Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, PR China.

The provisional prosthesis is a prerequisite for prosthodontic rehabilitation. The purpose of this technique was to register facial and intraoral scans predicably. A 3D virtual patient was created through facial scans, intraoral scans, digital face-bow transfer, and digital cross-articulation technique. This virtual patient allowed predictable positioning of intraoral scans to a virtual articulator by using digital face-bow transfer. The resulted virtual patient facilitated the design of definitive prostheses following a facially generated treatment planning principle. In addition, virtual articulator was used to improve occlusal design on the definitive prostheses and reduce the need for intraoral adjustment. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jopr.13397DOI Listing
June 2021

Chemical Composition, Antimicrobial and Insecticidal Activities of Essential Oils of Discarded Perfume Lemon and Leaves ( (L.) Burm. F.) as Possible Sources of Functional Botanical Agents.

Front Chem 2021 24;9:679116. Epub 2021 May 24.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.

Two essential oils were isolated from discarded perfume lemon and leaves ( (L.) Burm. F.) by hydro-distillation with good yield (0.044% for perfume lemon and 0.338% for leaves). Their biological activities were evaluated against five selected bacterial strains and (, Diptera: Culicidae). Chemical composition indicated that both essential oils were rich in essential phytochemicals including hydrocarbons, monoterpenes and sesquiterpene. These constituents revealed some variability among the oils displaying interesting chemotypes ()-(+)-limonene (12.29-49.63%), citronellal (5.37-78.70%) and citronellol (2.98-7.18%). The biological assessments proved that the two essential oils had similar effect against bacterial (inhibition zones diameter ranging from 7.27 ± 0.06 to 10.37 ± 0.15 mm; MICs and MBCs ranging from 1.6 to 6.4 mg/mL); against larvae (LC ranging from 384.81 to 395.09 ppm) and adult mosquito (LD ranging from 133.059 to 218.962 μg/cm); the activity of the two chemotypes (()-(+)-limonene and citronellal): larvae (LC ranging from 267.08 to 295.28 ppm), which were all presented in dose-dependent manners. Through this work, we have showcased that recycling and reusing of agriculture by-products, such as discarded perfume lemon and leaves can produce eco-friendly alternatives in bacterial disinfectants and mosquito control product.
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http://dx.doi.org/10.3389/fchem.2021.679116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184092PMC
May 2021

Comparative Study on Supercapacitive and Oxygen Evolution Reaction Applications of Hollow Nanostructured Cobalt Sulfides.

Nanotechnology 2021 Jun 9. Epub 2021 Jun 9.

Key Laboratory for Magnetism and Magnetic Materials - Ministry of Education, Lanzhou University, Tianshui South Road, Chengguan District, Lanzhou City, Gansu Province, Lanzhou, Gansu, 730000, CHINA.

Due to the diversity of sulfur valence in cobalt-based sulfides, it is difficult to control the crystal phase and composition of the products during synthesis. Herein, a one-pot hydrothermal method is reported to self-assemble the cobalt sulfides (CoS2, Co9S8 and Co3S4) with hollow nanostructures. The whole preparation process is simple and mild, avoiding high temperature calcination. The performances of the three kinds of cobalt sulfide in superior supercapacitors and electrocatalytic oxygen evolution performance applications follow the order of CoS2 > Co9S8 > Co3S4. Further analysis demonstrates that the performance difference in these cobalt sulfides may be attributed to three factors: the presence of S22-, the coordination environment of Co and the presence of continuous network of Co-Co bonds. The distinctive electrochemical performance of CoS2 and Co9S8 may help us to better understand the excellent electrochemical activity of metal polysulfides and metal sulfides after doping or alloying. Therefore, this work may provide a reference in understanding and designing the electrode materials for highly efficient applications in the fields of energy storage and conversion.
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http://dx.doi.org/10.1088/1361-6528/ac09aaDOI Listing
June 2021

Multidisciplinary treatment of primary intracranial yolk sac tumor: A case report and literature review.

Medicine (Baltimore) 2021 May;100(19):e25778

Department of Radiation Oncology, Hebei General Hospital, Shijiazhuang.

Rationale: Intracranial yolk sac tumors (YSTs) are rare malignancies with limited treatment options and a dismal prognosis. They are usually managed with surgical resection and chemoradiotherapy.

Patient Concerns: Here, we report a patient with primary YST in the pineal region who achieved long term survival. Despite undergoing treatment, he experienced several recurrences over a 15-year period.

Diagnosis: Brain magnetic resonance imaging (MRI) demonstrated the presence of space-occupying lesions in the pineal region and the medial tail of the left lateral ventricle. The tumors were excised, and the histological diagnosis suggested an intracranial YST.

Interventions: The patient achieved long term survival after combined modality therapy including surgery, stereotactic radiosurgery (SRS)/intensity modulated radiation therapy (IMRT), chemotherapy, and targeted therapy.

Outcomes: The disease remained stable. However, the patient gave up treatment and passed away in October 2020, with a total survival of about 15 years.

Lessons: To the best of our knowledge, this patient with intracranial YST had received a longer survival compared with other published reports. We summarize previously published reports of intracranial YST and discuss the importance of multidisciplinary treatment. SRS may have a role, as a focal boost to residual tumor after resection or in case of recurrence after conventional radiotherapy, in the multimodality management of intracranial YSTs.
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http://dx.doi.org/10.1097/MD.0000000000025778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133229PMC
May 2021

The roles of PKC-δ and PKC-ε in myocardial ischemia/reperfusion injury.

Pharmacol Res 2021 Jun 5:105716. Epub 2021 Jun 5.

National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address:

Ischemia and reperfusion (I/R) cause a reduction in arterial blood supply to tissues, followed by the restoration of perfusion and consequent reoxygenation. The reestablishment of blood flow triggers further damage to ischemic tissue through reactive oxygen species (ROS) accumulation, interference with cellular ion homeostasis, opening of mitochondrial permeability transition pores (mPTPs) and promotion of cell death (apoptosis or necrosis). PKC-δ and PKC-ε, belonging to a family of serine/threonine kinases, have been demonstrated to play important roles during I/R injury in cardiovascular diseases. However, the cardioprotective mechanisms of PKC-δ and PKC-ε in I/R injury have not been elaborated until now. This article discusses the roles of PKC-δ and PKC-ε during myocardial I/R in redox regulation (redox signaling and oxidative stress), cell death (apoptosis and necrosis), Ca overload, and mitochondrial dysfunction.
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http://dx.doi.org/10.1016/j.phrs.2021.105716DOI Listing
June 2021

Potential biomarkers for inherited thrombocytopenia 2 identified by plasma proteomics.

Platelets 2021 Jun 8:1-8. Epub 2021 Jun 8.

Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Army Medical University, Chongqing, China.

Inherited thrombocytopenia 2 (THC2) is difficult to diagnose due to the lack of specific clinical characteristics and diagnostic methods. To identify potential plasma protein biomarkers for THC2, we collected the plasma samples from a THC2 family (9 THC2 and 15 non-THC2 members), enriched the medium and low abundant proteins using Proteominer and analyzed the protein profiles using the liquid chromatography-mass spectrometry in data independent acquisition mode. Initially, we detected 784 proteins in the plasma samples of this family and identified 27 up-regulated and 36 down-regulated in the THC2 group compared to the non-THC2 group (|log ratio| >1 and -value <0.05). To improve the predictive power, top eight dysregulated proteins (B7Z2B4, LTF, HP, ERN1, IGHV1-8, A0A0X9V9C4, VH6DJ, and D3JV41) were selected by an area under the curve-based random forest process to construct a clinical model. Multivariate analysis with random forest and support vector machine showed that the prediction model provided high discrimination ability for THC2 diagnosis (AUC: 1.000 and 0.967, respectively). The potential plasma protein biomarkers will be tested in more THC2 patients and other thrombocytopenia patients to further validate their specificity and sensitivity.
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http://dx.doi.org/10.1080/09537104.2021.1937594DOI Listing
June 2021

A Novel Virus of Associated with Sexual Precocity in .

mSystems 2021 Jun 8:e0000321. Epub 2021 Jun 8.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Laboratory for Marine Fisheries Science and Food Production Processes, Pilot National Laboratory for Marine Science and Technology (Qingdao), Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture and Rural Affairs, Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Qingdao, China.

Since 2010, sexual precocity, a typical sign of the iron prawn syndrome (IPS), resulting in the reduced size of farmed giant freshwater prawns , has caused substantial production losses. However, the cause of IPS was not clear. We ran tests for eight major shrimp pathogens, but none were detected from IPS-affected prawns. We performed the histopathological examination of tissues and identified an eosinophilic inclusion in the perinuclear cytoplasm of cells in various tissues associated with nervous and endocrinal functions in the compound eyes. A subsequent bioassay with viral extracts of IPS-affected samples reproduced the gross signs of IPS. Metatranscriptomic sequencing identified a novel virus of in all IPS-affected prawns, which was not found in samples without IPS. This virus contains a positive-sense, single-stranded RNA genome of 12,630 nucleotides (nt). Phylogenetic analysis of the conserved RdRp and NS3 domains showed that it may belong to a new genus between Jingmenvirus and . Under transmission electron microscopy (TEM), putative virus particles showed as spherical with a diameter of 40 to 60 nm. hybridization found hybridization signals consistent with the histopathology in the compound eyes from IPS-affected . We provisionally name this virus infectious precocity virus (IPV) and propose the binominal Latin name gen. nov., sp. nov. We developed a nested reverse transcription-PCR diagnostic assay and confirmed that all IPS-affected prawns tested IPV positive but normal prawns tested negative. Collectively, our study revealed a novel virus of associated with sexual precocity in . The iron prawn syndrome (IPS), also described as sexual precocity, results in the reduced size of farmed prawns at harvest and significant economic losses. IPS has been frequently reported in populations of farmed since 2010, but the cause was heretofore unknown. Here, we reported a novel virus identified from prawns with IPS using infection experiments, metatranscriptomic sequencing, and transmission electron microscopy and provisionally named it infectious precocity virus (IPV). Phylogenetic analysis showed that IPV represents a new genus, proposed as gen. nov., in the family . This study provides novel insight that a viral infection may cause pathological change and sexual maturation and subsequently affect crustacean growth. Therefore, we call for quarantine inspection of IPV in transboundary trade of live and enhanced surveillance of IPV in aquaculture in the region and globally.
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http://dx.doi.org/10.1128/mSystems.00003-21DOI Listing
June 2021

circ-PTTG1IP/miR-671-5p/TLR4 axis regulates proliferation, migration, invasion and inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis.

Gen Physiol Biophys 2021 May;40(3):207-219

Integrated Chinese and Western Medicine, General Hospital of Central Theater Command, Wuhan, Hubei, China.

Circular RNAs (circRNAs) are related to rheumatoid arthritis (RA) development. However, the function and mechanism of circRNA pituitary tumor-transforming 1 interacting protein (circ- PTTG1IP) in RA are unknown. The expression of circ-PTTG1IP in synovial tissues of RA patients and fibroblast-like synoviocytes from RA patients (RA-FLSs) were detected by RT-qPCR. The results uncovered that circ-PTTG1IP was overexpressed in RA patients and RA-FLSs, and circ-PTTG1IP knockdown suppressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs. Besides, we found that circ-PTTG1IP could directly bind to miR-671-5p, and toll-like receptor 4 (TLR4) was a target of miR-671-5p, which was confirmed by dual-luciferase reporter assay. miR-671-5p inhibitor attenuated the effects of circ-PTTG1IP knockdown on RA-FLSs, while the effects of miR-671-5p mimic on RA-FLSs were partly reversed by TLR4 overexpression. Furthermore, circ-PTTG1IP could upregulate TLR4 expression by miR-671-5p. Thus, circ-PTTG1IP knockdown repressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs by regulating the miR-671-5p/TLR4 axis.
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http://dx.doi.org/10.4149/gpb_2021014DOI Listing
May 2021

Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection.

Cell Mol Immunol 2021 Jun 7. Epub 2021 Jun 7.

Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1038/s41423-021-00708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182358PMC
June 2021

Recent progress in targeted delivery vectors based on biomimetic nanoparticles.

Signal Transduct Target Ther 2021 Jun 7;6(1):225. Epub 2021 Jun 7.

Department of Pharmacy, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Over the past decades, great interest has been given to biomimetic nanoparticles (BNPs) since the rise of targeted drug delivery systems and biomimetic nanotechnology. Biological vectors including cell membranes, extracellular vesicles (EVs), and viruses are considered promising candidates for targeted delivery owing to their biocompatibility and biodegradability. BNPs, the integration of biological vectors and functional agents, are anticipated to load cargos or camouflage synthetic nanoparticles to achieve targeted delivery. Despite their excellent intrinsic properties, natural vectors are deliberately modified to endow multiple functions such as good permeability, improved loading capability, and high specificity. Through structural modification and transformation of the vectors, they are pervasively utilized as more effective vehicles that can deliver contrast agents, chemotherapy drugs, nucleic acids, and genes to target sites for refractory disease therapy. This review summarizes recent advances in targeted delivery vectors based on cell membranes, EVs, and viruses, highlighting the potential applications of BNPs in the fields of biomedical imaging and therapy industry, as well as discussing the possibility of clinical translation and exploitation trend of these BNPs.
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http://dx.doi.org/10.1038/s41392-021-00631-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182741PMC
June 2021

Rspo3 regulates the abnormal differentiation of small intestinal epithelial cells in diabetic state.

Stem Cell Res Ther 2021 Jun 7;12(1):330. Epub 2021 Jun 7.

Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao University, 16 Jiang Su Road, Qingdao, Shandong, 262000, P.R. China.

Background: The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism.

Methods: Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7+/+Lepr/JNju (DM) mice, and the expression of R-Spondin 3 (Rspo3) was detected by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. The role of Rspo3 in the abnormal differentiation of IECs during DM was confirmed by knockdown experiments. Through miRNA expression profiling, bioinformatics analysis, and RT-qPCR, we further analyzed the differentiation-related miRNAs in the IECs from mice with DM.

Results: Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression.

Conclusions: Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM.
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http://dx.doi.org/10.1186/s13287-021-02385-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186182PMC
June 2021

Histidine Triad Nucleotide Binding Protein 1 Attenuates Cardiac Hypertrophy via Suppressing Homeobox A5 Expression.

Circulation 2021 Jun 8. Epub 2021 Jun 8.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China.

Cardiac hypertrophy is an important pre-pathology of heart failure, which will ultimately lead to heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. The aim of this study is to elucidate the effects and mechanisms of histidine triad nucleotide binding protein 1 (HINT1) in cardiac hypertrophy and heart failure. HINT1 was down-regulated in human hypertrophic heart samples compared with non-hypertrophic samples by mass spectrometry analysis. knockout mice were challenged with TAC (transverse aortic constriction) surgery. Cardiac specific overexpression of HINT1 mice by intravenous injection of adeno-associated viral (AAV9) encoding Hint1 under the cardiac troponin T (cTnT) promoter were subjected to TAC. Unbiased transcriptional analyses were used to identify the downstream targets of HINT1. AAV9 bearing shRNA against () was administrated to investigate whether the effects of on cardiac hypertrophy were HOXA5 dependent. RNA-Seq analysis was performed to recapitulate possible changes in transcriptome profile. Co-immunoprecipitation assays and cellular fractionation analyses were conducted to examine the mechanism by which HINT1 regulates the expression of HOXA5. The reduction of HINT1 expression was observed in the hearts from hypertrophic patients and pressure overloaded-induced hypertrophic mice, respectively. In deficient mice, cardiac hypertrophy was deteriorated after TAC. Conversely, cardiac specific overexpression of HINT1 alleviated cardiac hypertrophy and dysfunction. Unbiased profiler PCR-array showed Homeobox A5 (HOXA5) is one target for HINT1, and the cardioprotective role of HINT1 was abolished by HOXA5 knockdown . Hoxa5 was identified to affect hypertrophy through TGF-β signal pathway. Mechanically, HINT1 inhibited PKCβ1 membrane translocation and phosphorylation via direct interaction, attenuating MEK/ERK/YY1 signal pathway, down-regulating HOXA5 expression and eventually attenuating cardiac hypertrophy. HINT1 protects against cardiac hypertrophy through suppressing HOXA5 expression. These findings indicate that HINT1 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051094DOI Listing
June 2021

A retrospective pilot study of preoperative mobilization program for older adults with hip fracture.

Geriatr Nurs 2021 Jun 4;42(4):908-914. Epub 2021 Jun 4.

Department of Orthopedics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China.

Objective: To investigate the feasible effect of a preoperative mobilization program for older hip fracture patients who waited more than two days before surgery.

Methods: A total of 38 patients with hip fracture were analyzed in this retrospective descriptive pilot study. The modified Barthel index (MBI) was used to measure functional outcome. Visual analogue scale (VAS) was used to evaluate the changes of pain degree during preoperative mobilization. The perioperative complications were recorded.

Results: After the preoperative mobilization program was implemented, the MBI score was improved immediately and further improved after surgery until 3 months after discharge. On the premise of analgesia, no patient experienced severe pain during preoperative mobilization. Perioperative complications occurred in 2 (5.3%) patients.

Conclusion: For older patients with hip fracture, the preoperative mobilization program may be a feasible method, which may have a positive effect on promoting functional recovery and preventing perioperative complications.
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http://dx.doi.org/10.1016/j.gerinurse.2021.04.022DOI Listing
June 2021

Pan-cancer Network Disorders Revealed by Overall and Local Signaling Entropy.

J Mol Cell Biol 2021 Jun 7. Epub 2021 Jun 7.

CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Tumor development is a process involving loss of the differentiation phenotype and acquisition of stem-like characteristics, which is driven by intracellular rewiring of signaling network. The measurement of network reprogramming and disorder would be challenging due to the complexity and heterogeneity of tumors. Here, we proposed signaling entropy to assess the degree of tumor network disorder. We calculated signaling entropy for 33 tumor types in The Cancer Genome Atlas database based on transcriptomic and proteomic data. The signaling entropy of tumors was significantly higher than that of normal samples and was highly correlated with cell stemness, cancer type, tumor grade, and metastasis. We further demonstrated the sensitivity and accuracy of using local signaling entropy in prognosis prediction and drug response evaluation. Overall, signaling entropy could reveal cancer network disorders related to tumor malignant potency, clinical prognosis, and drug response.
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http://dx.doi.org/10.1093/jmcb/mjab031DOI Listing
June 2021

Hole doping and chemical pressure effects on the strong coupling superconductor PdTe.

Phys Chem Chem Phys 2021 Jun 7. Epub 2021 Jun 7.

Graduate School of Science and Technology, Okayama University, Okayama 700-8530, Japan. and Research Institute for Interdisciplinary Science, Okayama University, Okayama 700-8530, Japan.

Chemical doping of known superconductors is a probate strategy to test and enhance our understanding of which parameters control the critical temperature Tc and the critical magnetic fields. The transition metal chalcogenide PdTe is considered a conventional type II superconductor but its resilience to magnetic Fe doping is noteworthy. Isoelectronic Ni doping has been performed, but the effects of doping charges into PdTe have been so far unexplored. We follow two strategies to introduce holes into PdTe and to exert chemical pressure on it: by pnictogen doping on the chalcogen site PdTe1-xSbx and by systematically introducing a Pd deficiency in Pd1-yTe. We find that the superconducting Tc is very sensitive to both kinds of doping. We employ density functional theory to rationalize the observations. We conclude that in PdTe, the effects of charge doping take the lead but we can also identify a structural parameter that correlates with Tc.
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http://dx.doi.org/10.1039/d1cp01071aDOI Listing
June 2021

Exact Analytical Solution of the Ground-State Hydrogenic Problem with Soft Coulomb Potential.

Authors:
Chen Li

J Phys Chem A 2021 Jun 7. Epub 2021 Jun 7.

Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

We provide the exact analytical solution of the ground-state hydrogenic problem with soft Coulomb potential in 1-, 2- and 3-D. We show that the wave function is an analytical function of the inverse of the soft Coulomb potential and identify a power term, an exponentially decaying term and a mildly varying modulator function on the exponential. In approaching the bare Coulomb limit, only the exponentially decaying term survives in 2D and 3D and converges to the well-known result. This is in contrast with the 1D case, where the wave function shrinks to a delta function with a total energy of minus infinity. The asymptotic behavior of the energy in such limit has been analyzed. Moreover, by analyzing the solution in different dimensions, we find that the total energy increases with dimension and scales linearly rather than quadratically with the nuclear charge in the large limit.
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http://dx.doi.org/10.1021/acs.jpca.1c00698DOI Listing
June 2021

Associations Between Single-Child Status and Metabolic Syndrome in Children and Adolescents in China.

Front Pediatr 2021 20;9:661164. Epub 2021 May 20.

Menzies Health Institute Queensland, Griffith University, Brisbane, QLD, Australia.

To evaluate the associations between single-child status and metabolic syndrome (MS) and to identify the highest risk group of MS among single children. Differences in participants' characteristics by sex were examined by Student's -test for continuous variables and Pearson's chi-squared test for categorical variables. Multivariate logistic regression analysis was performed to estimate the odds ratios () and 95% confidence intervals () for MS and its components according to the single-child status. Radar maps were used to compare the composition of different components in MS. In total, 11,784 (5,880 boys) children and adolescents were included in this study, with a mean age of (11.3 ± 3.1) years. MS was observed in 7.1% of participants, with a higher prevalence in boys (8.2%) than girls (5.9%) ( < 0.05). The prevalence of MS, elevated blood pressure and abdominal obesity in single children were higher than that in children with siblings, particularly in boys ( < 0.001). Elevated risk of abdominal obesity was observed in single children [boys (1.56, 95% CI: 1.31, 1.85), girls (1.40, 95% CI: 1.19, 1.63)], however, increased ORs of elevated blood pressure and metabolic syndrome were observed in single-child boys only (1.19, 95% CI: 1.01, 1.40 and 1.76, 95% CI: 1.34, 2.31, respectively). Results showed that a statistically significant association between single child status and MS was mainly observed in urban boys (2.04, 95% CI: 1.33, 3.12) and rural boys (1.50, 95% CI: 1.05, 2.15), but not in girls. Among all the combinations of MS, two combinations were significantly associated with the single-child status, including the combination of elevated blood pressure, abdominal and low HDL-C (1.45, 1.04, 2.04) and the combination of elevated blood pressure, abdominal obesity, low HDL-C and hypertriglyceridemia (2.04, 1.40, 3.06) ( < 0.05). The present study found that single children and adolescents had a higher risk of MS, elevated blood pressure and abdominal obesity. The associations were stronger in urban boys. Further attention should be directed to the prevention and control strategies targeting the high-risk population of MS.
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http://dx.doi.org/10.3389/fped.2021.661164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173115PMC
May 2021

CircHACE1 functions as a competitive endogenous RNA to curb differentiated thyroid cancer progression by upregulating Tfcp2L1 through adsorbing miR-346.

Endocr J 2021 Jun 4. Epub 2021 Jun 4.

Department of Endocrinology, Taizhou People's Hospital, Taizhou City, Jiangsu Province, China.

Circular RNAs (circRNAs) are correlated with the occurrence and progression of differentiated thyroid cancer (THCA). However, the regulatory mechanism of circRNAs in differentiated THCA is unclear. In the present study, we analyzed the circRNA microarray dataset (GSE93522) of thyroid tumors and discovered that circRNA HACE1 (circHACE1) was downregulated in differentiated THCA. We detected circHACE1 expression by quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function experiments were performed to analyze the biological function of circHACE1 in differentiated THCA cells in vitro. The regulatory mechanism of circHACE1 in differentiated THCA was explored through bioinformatics analysis, dual-luciferase reporter, RIP (RNA immunoprecipitation), and/or RNA pull-down assays. The biological function of circHACE1 in THCA was confirmed by xenograft assay. We verified that circHACE1 was downregulated in differentiated THCA. Also, differentiated THCA patients with low circHACE1 expression were associated with TNM grade, lymphoid node metastasis, tumor size, and poor prognosis. CircHACE1 overexpression decreased xenograft tumor growth in vivo and induced cell cycle arrest, apoptosis, impeded proliferation, migration, and invasion in differentiated THCA cells in vitro. CircHACE1 could function as a microRNA (miR)-346 sponge and regulated Tfcp2L1 (transcription factor CP2 like 1) expression. MiR-346 overexpression offset circHACE1 elevation-mediated effects on malignant behaviors of differentiated THCA cells. Furthermore, Tfcp2L1 silencing counteracted the suppressive impact of miR-346 inhibitor on the malignancy of differentiated THCA cells. In conclusion, circHACE1 adsorbed miR-346 and elevated Tfcp2L1 expression, thus curbing cell malignancy in differentiated THCA, manifesting that circHACE1 might be a target for differentiated THCA treatment.
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http://dx.doi.org/10.1507/endocrj.EJ20-0806DOI Listing
June 2021

Feasibility of pharmacometabolomics to identify potential predictors of paclitaxel pharmacokinetic variability.

Cancer Chemother Pharmacol 2021 Jun 5. Epub 2021 Jun 5.

Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.

Purpose: Paclitaxel is a commonly used chemotherapy drug with substantial variability in pharmacokinetics (PK) that affects treatment efficacy and toxicity. Pharmacometabolomic signatures that explain PK variability could be used to individualize dosing to improve therapeutic outcomes. The objective of this study was to identify pretreatment metabolites or metabolomic signatures that explain variability in paclitaxel PK.

Methods: This analysis was conducted using data previously collected on a prospective observational study of 48 patients with breast cancer receiving weekly 80 mg/m paclitaxel infusions. Paclitaxel plasma concentrations were measured during the first infusion to estimate paclitaxel time above threshold (T) and maximum concentration (C). Metabolites measured in pretreatment whole blood by nuclear magnetic resonance spectrometry were analyzed for an association with T and C using Pearson correlation followed by stepwise linear regression.

Results: Pretreatment creatinine, glucose, and lysine concentrations were positively correlated with T, while pretreatment betaine was negatively correlated and lactate was positively correlated with C (all uncorrected p < 0.05). After stepwise elimination, creatinine was associated with T, while betaine and lactate were associated with C (all p < 0.05).

Conclusion: This study identified pretreatment metabolites that may be associated with paclitaxel PK variability demonstrating feasibility of a pharmacometabolomics approach for understanding paclitaxel PK. However, identification of more robust pharmacometabolomic predictors will be required for broad and routine application for the clinical dosing of paclitaxel.
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http://dx.doi.org/10.1007/s00280-021-04300-7DOI Listing
June 2021

Insights into influences of sucrose amendment on nitrification and denitrification in sewage sludge composting.

Chemosphere 2021 Aug 15;276:130245. Epub 2021 Mar 15.

Institute of Microbiology, Heilongjiang Academy of Sciences, 150010, Harbin, China.

Sucrose amendment could promote ammonia assimilation and reduce nitrogen loss in sewage sludge (SS) composting, but the effects of sucrose amendment on nitrification and denitrification are still unknown that were firstly researched in present paper. Result showed that sucrose amendment reduced 33.0% of NO emission by changing the physicochemical indexes, nitrogen forms, related bacteria and functional genes. In the sucrose treatment, the higher nitrifying bacteria community, amoA and nxrA genes abundance were, the lower hao, narG、nirS、nirK and norB genes abundance were. Based on the correlation analysis, the number of nitrifying bacteria was significantly positively correlated with NO and nxrA abundance, indicating that sucrose amendment promoted the growth of nitrifying bacteria, the contents of NO and the activity of nitrite oxidation. Moreover, contents of NO were positively correlated with NO emission, narG, nirS and norB abundance, indicating that denitrification was the main path of NO generated.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130245DOI Listing
August 2021

Early prediction of anastomotic leakage after laparoscopic rectal surgery using creactive protein.

Authors:
Dongai Jin Li Chen

Medicine (Baltimore) 2021 Jun;100(22):e26196

Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Abstract: At present, anterior resection of the rectum or transabdominal rectal resection is the most common surgical technique for rectal cancer. Laparoscopic techniques are popular, and the efficacy and safety of laparoscopic rectal surgery have been confirmed. However, postoperative anastomotic leakage is a common, severe complication that leads to high mortality. Thus, early diagnosis of anastomotic leakage is important for reducing clinical consequences.The aim of this study was to determine whether C-reactive protein (CRP) is a good predictor of anastomotic leakage in laparoscopic transabdominal rectal resection.Our retrospective study involved a series of 196 rectal cancer patients who underwent laparoscopic transabdominal rectal resection without ileostomy between May 2013 and April 2015 at the Sir Run Run Shaw Hospital, Zhejiang University College of Medicine. The following patient data were collected: demographic data, manifestations of the complication, CRP levels and neutrophil percentage during the first 7 postoperative days.Anastomotic leakage was detected in 11 patients (5.6%). Each group showed significant differences (P < .05) in CRP levels on postoperative days 3 to 7; compared with other groups, the anastomotic leakage group showed significant differences in CRP levels (P < .05) on postoperative day 6. When patients were divided into groups with or without anastomotic leakage, CRP was a reliable predictor on postoperative days 4 to 7 (P < .05, area under the curve > 0.800). The best combination was CRP on postoperative day 6 (area under the curve = 0.932) with a cut-off of 76.6 mg/L, resulting in a sensitivity of 83.3%, a specificity of 94.6% and a negative predictive value of 99%.CRP is a reliable predictor of anastomotic leakage after laparoscopic transabdominal rectal resection surgery. High CRP levels on postoperative days 4 to 7 indicate the need for a more careful patient evaluation.
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http://dx.doi.org/10.1097/MD.0000000000026196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183725PMC
June 2021

Quercetin and non-alcoholic fatty liver disease: A review based on experimental data and bioinformatic analysis.

Food Chem Toxicol 2021 Jun 2;154:112314. Epub 2021 Jun 2.

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Wuhan, 430030, China; Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address:

Quercetin, a polyphenol widely present in the plant kingdom, has received great interest due to pleiotropic effects. As evidenced by animal and cellular studies, quercetin exerts hepatoprotection against non-alcoholic fatty liver disease (NAFLD), particularly in hepatic steatosis and hepatitis. Mechanically, various hypotheses of such protective effects have been actively proposed, including improving fatty acid metabolism, anti-inflammation, anti-oxidant, modulating gut microbiota and bile acid, etc. Here, the role of quercetin in NAFLD was summarized. With a particular focus on molecular mechanism, we comprehensively discussed the pathways of quercetin on NAFLD based on the analysis from Gene Expression Omnibus (GEO) database and experimental evidence.
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http://dx.doi.org/10.1016/j.fct.2021.112314DOI Listing
June 2021

Cost-effectiveness analysis of a community-based colorectal cancer-screening program in Shanghai, China.

J Dig Dis 2021 Jun 4. Epub 2021 Jun 4.

Diversion of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Aim: This study investigated the cost-effectiveness of a community-based colorectal cancer-screening program (C-CRCSP) in Shanghai, China, with a comparison of urban, suburban, and rural areas.

Methods: A Markov model was constructed to evaluate the cost-effectiveness of a 25-year-long annual C-CRCSP with 100,000 samples. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER) referring to either life-years gained, or quality-adjusted life-years (QALYs) gained. The threshold was gross domestic product per capita. Univariate and multivariate sensitivity analyses were performed to investigate the influence of compliance, prevalence, technological performance, price, and an annual cost discount rate (3.5%) on ICERs. A probabilistic sensitivity analysis evaluated the probability of cost-effectiveness of C-CRCSP at different maximum acceptable ceiling ratios.

Results: Compared with no screening, the C-CRCSP could result in total gains of 7840 QALYs and 2210 life-years, at a total cost of CNY 58.54 million; that is, the ICERs were CNY 7460/QALY and CNY 26,650/life-year. Stratifying by residency, the highest cumulative gains in QALYs and life-years were estimated for the rural population, followed by the suburban and urban. The cost for the urban population was 3- and 6-fold that of the suburban and rural populations. The ICERS for QALYs ranged from 2180 (rural) to 16,840 (urban).

Conclusion: The cost-effectiveness of a C-CRCSP in Shanghai was most favorable for the rural population, while the urban population would realize lesser benefit in terms of QALYs. ICERs could be enhanced by measures that increase compliance. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1751-2980.13027DOI Listing
June 2021