Publications by authors named "Yang Yang"

6,937 Publications

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Rebalancing TGF-β/Smad7 signaling via Compound kushen injection in hepatic stellate cells protects against liver fibrosis and hepatocarcinogenesis.

Clin Transl Med 2021 Jul;11(7):e410

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Liver fibrosis and fibrosis-related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor-β (TGF-β) is a critical mediator of chronic liver fibrosis, targeting TGF-β isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF-β/Smad7 signaling.

Methods: A meta-analysis was performed to evaluate CKI intervention on viral hepatitis-induced fibrosis or cirrhosis in clinical randomized controlled trials (RCTs). Mice were given carbon tetrachloride (CCl ) injection or methionine-choline deficient (MCD) diet to induce liver fibrosis, followed by CKI treatment. We examined the expression of TGF-β/Smad signaling and typical fibrosis-related genes in hepatic stellate cells (HSCs) and fibrotic liver tissues by qRT-PCR, Western blotting, RNA-seq, immunofluorescence, and immunohistochemistry.

Results: Based on meta-analysis results, CKI improved the liver function and relieved liver fibrosis among patients. In our preclinical studies by using two mouse models, CKI treatment demonstrated promising antifibrotic effects and postponed hepatocarcinogenesis with improved liver function and histopathologic features. Mechanistically, we found that CKI inhibited HSCs activation by stabilizing the interaction of Smad7/TGF-βR1 to rebalance Smad2/Smad3 signaling, and subsequently decreased the extracellular matrix formation. Importantly, Smad7 depletion abolished the antifibrotic effect of CKI in vivo and in vitro. Moreover, matrine, oxymatrine, sophocarpine, and oxysophocarpine were identified as material basis responsible for the antifibrosis effect of CKI.

Conclusions: Our results unveil the approach of CKI in rebalancing TGF-β/Smad7 signaling in HSCs to protect against hepatic fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. Our study suggests that CKI can be a candidate for treatment of hepatic fibrosis and related oncogenesis.
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http://dx.doi.org/10.1002/ctm2.410DOI Listing
July 2021

Dimensionality reduction by UMAP reinforces sample heterogeneity analysis in bulk transcriptomic data.

Cell Rep 2021 Jul;36(4):109442

The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia; Shandong Artificial Intelligence Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China; Laboratory of Immunology for Environment and Health, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China. Electronic address:

Transcriptomic analysis plays a key role in biomedical research. Linear dimensionality reduction methods, especially principal-component analysis (PCA), are widely used in detecting sample-to-sample heterogeneity, while recently developed non-linear methods, such as t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), can efficiently cluster heterogeneous samples in single-cell RNA sequencing analysis. Yet, the application of t-SNE and UMAP in bulk transcriptomic analysis and comparison with conventional methods have not been achieved. We compare four major dimensionality reduction methods (PCA, multidimensional scaling [MDS], t-SNE, and UMAP) in analyzing 71 large bulk transcriptomic datasets. UMAP is superior to PCA and MDS but shows some advantages over t-SNE in differentiating batch effects, identifying pre-defined biological groups, and revealing in-depth clusters in two-dimensional space. Importantly, UMAP generates sample clusters uncovering biological features and clinical meaning. We recommend deploying UMAP in visualizing and analyzing sizable bulk transcriptomic datasets to reinforce sample heterogeneity analysis.
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http://dx.doi.org/10.1016/j.celrep.2021.109442DOI Listing
July 2021

TSH/miR-17-5p/ZNF367 axis is related to spontaneous abortion in patients with TSH above 2.5 mIU/L.

J Mol Endocrinol 2021 Jul 1. Epub 2021 Jul 1.

Z Shan, Endocrinology and Metabolism, Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, China.

Elevated thyroid stimulating hormone (TSH) is associated with an increased risk of spontaneous abortion (SA); however, the associated mechanism remains unclear. This study aimed to investigate the expression of microRNAs (miRNAs) and pathogenesis in the chorionic villi of TSH > 2.5 mIU/L-related SA patients. The chorionic villi were collected from pregnant women in the first trimester with TSH > 2.5 mIU/L with or without SA, as well as TSH < 2.5 mIU/L with or without SA to determine the level of miRNA expression. Differentially expressed miRNAs were confirmed by qRT-PCR in a total of 92 subjects. Cell counting kit-8 (CCK8), wound healing, transwell assays, and Western blotting were used to measure cellular biological functions and related protein in HTR-8/SVneo cells. The potential mechanisms were determined using a Luciferase reporter assay and rescue experiment. Compared with normal pregnant women, miR-17-5p was decreased and zinc finger protein 367 (ZNF367) was upregulated in the chorionic villi of TSH > 2.5 mIU/L-related SA patients. Using HTR-8/SVneo cells, we demonstrated that elevated TSH inhibited miR-17-5p expression, as well as trophoblast migration and invasion. The overexpression of miR-17-5p targeted and inhibited ZNF367 expression promoting the biological function of trophoblasts. Further studies confirmed that ZNF367 interference partially reversed the biological function of the miR-17-5p inhibitor on HTR-8/SVneo cells. Taken together, our results showed that miR-17-5p promoted biological function of trophoblasts by suppressing ZNF367.
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http://dx.doi.org/10.1530/JME-20-0335DOI Listing
July 2021

Alkoxy cyanoacrylate-based nanoparticles with stealth and brain-targeting properties.

J Drug Target 2021 Jul 28:1-33. Epub 2021 Jul 28.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping road, Beijing, 100850, China.

Nanoparticles (NPs) with "stealth" properties have been designed to decrease the phagocytosis of such particles by mononuclear phagocytes and to protect them from enzymatic degradation, thus improving circulation time and bioavailability after intravenous administration. Brain-targeting modifications endow NPs with the capacity to cross the blood-brain barrier, facilitating chemotherapy for brain diseases such as glioma. In this study, newly designed alkoxy cyanoacrylate-based NPs with stealth and brain-targeting properties were synthesized and evaluated. The monomers for NP core polymerization were chemically modified to hydrophilic short alkoxy structure for stealth purposes and coated with polysorbate-80 for brain targeting. Two monomers [2-methoxyethyl cyanoacrylate and 2-(2-methoxyethyl)ethyl cyanoacrylate] were used to create NP and NP, respectively. Both NPs were successfully loaded with antisense oligonucleotide (ASON) of transforming growth factor beta 2. Compared to traditional n-butyl cyanoacrylate-based ASON-NP, ASON-NP was found to decrease phagocytosis by mononuclear macrophages (RAW264.7) and to increase cellular uptake by cancer cells. ASON-NP showed definite brain targeting and anti-cancer effects. This work provides a potential new strategy for preparing stealth NPs core, providing a new NP vehicle for clinical drug delivery that may be targeted to the brain and circulates in the blood for an extended period of time.
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http://dx.doi.org/10.1080/1061186X.2021.1961790DOI Listing
July 2021

Intentional Replantation of a Second Premolar with Internal Resorption and Root Fracture: A Case Report.

J Contemp Dent Pract 2021 May 1;22(5):562-567. Epub 2021 May 1.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China, e-mail:

Aim: This case aims to detail intentional replantation as a last resort to save an otherwise hopeless premolar with perforated internal resorption and root fracture.

Background: Internal root resorption, progressive destruction of intraradicular dentin, is a condition that sometimes renders a tooth non-restorable. In the rare cases reported where severe internal resorption leads to root fracture, extraction of the tooth seemed to be a common treatment of choice, and a few literatures had reported endodontic surgery as an alternative treatment option. To date, there had been no report of treating internal root resorption using intentional replantation.

Case Description: A 20-year-old male presented swelling at the buccal region of his left maxillary second premolar (#13). Clinical examination revealed a sinus tract and fractured dens evaginatus at the occlusal surface of the tooth. Radiographically, a large area of radiolucency was detected within the middle third of the root, where root fracture was present, leaving a triangular-shaped mature root apex. The condition was diagnosed as internal root resorption and root fracture. Endodontic surgery was excluded from treatment choices due to potential damage of periodontal bone. Instead, intentional replantation was performed, with the application of biomaterials including mineral trioxide aggregate (MTA) and platelet-rich fibrin (L-PRF). The tooth achieved satisfactory healing and remained asymptomatic after 2 years of follow-up.

Conclusion: The successful outcome of the case suggests that intentional replantation could preserve a fractured tooth caused by internal root resorption. Incorporated application of biomaterials, such as MTA and L-PRF, might as well improve the chances of saving this otherwise hopeless tooth.

Clinical Significance: Through careful planning and execution, intentional replantation is a viable alternative treatment option to preserve a fractured tooth caused by internal root resorption, while leaving periodontal bone architecture almost intact. How to cite this article: Yang Y, Zhang B, Huang C, Intentional Replantation of a Second Premolar with Internal Resorption and Root Fracture: A Case Report. J Contemp Dent Pract 2021;22(5):562-567.
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May 2021

Technical aspects of uniportal video-assisted thoracoscopic sleeve resections: Where are the limits?

JTCVS Tech 2020 Jun 4;2:160-164. Epub 2020 Mar 4.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1016/j.xjtc.2020.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298887PMC
June 2020

Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme.

Science 2021 Jul 27. Epub 2021 Jul 27.

Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.

Coronavirus 3'-5' exoribonuclease (ExoN), residing in the nonstructural protein (nsp) 10-nsp14 complex, boosts replication fidelity by proofreading RNA synthesis and is critical for the virus life cycle. ExoN also recognizes and excises nucleotide analog inhibitors incorporated into the nascent RNA, undermining the effectiveness of nucleotide analog-based antivirals. Here, we present cryo-electron microscopy structures of both wild-type and mutant SARS-CoV-2 nsp10-nsp14 in complex with an RNA substrate bearing a 3'-end mismatch at resolutions ranging from 2.5 Å to 3.9 Å. The structures reveal the molecular determinants of ExoN substrate specificity and give insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. Our findings provide guidance for rational design of improved anti-coronavirus therapies.
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http://dx.doi.org/10.1126/science.abi9310DOI Listing
July 2021

Evolution of nanomedicines for the treatment of autoimmune disease: from vehicles for drug delivery to inducers of bystander immunoregulation.

Adv Drug Deliv Rev 2021 Jul 24:113898. Epub 2021 Jul 24.

Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Alberta, T2N 4N1 Canada; Institut D'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, 08036, Spain. Electronic address:

Over the last two decades, the nanomedicine field has witnessed an explosive growth of research on the development of nanoparticle/microparticle (NP/MP)-based compounds for the treatment of autoimmune diseases. Studies have evaluated compounds generated with a broad range of materials with different shapes, sizes, surface chemistries and structures. A number of active pharmaceutical ingredients, including immunosuppressants, cytokines, nucleotides, peptides, proteins and immunomodulators of various types have been encapsulated into or incorporated onto the surface of these compounds, either individually or in combination, and delivered to animal models of autoimmune inflammation via different administration routes. These NP/MP-based compounds can be categorized into four different groups based on their intended mechanisms of action. Here, we review the engineering designs, the pharmacodynamic and therapeutic correlates and the disease specificity of nanomedicines belonging to each of these groups.
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http://dx.doi.org/10.1016/j.addr.2021.113898DOI Listing
July 2021

Recognizing binding sites of poorly characterized RNA-binding proteins on circular RNAs using attention Siamese network.

Brief Bioinform 2021 Jul 23. Epub 2021 Jul 23.

Institute of Image Processing and Pattern Recognition, Shanghai Jiao Tong University, and Key Laboratory of System Control and Information Processing, Ministry of Education of China, Shanghai 200240, China.

Circular RNAs (circRNAs) interact with RNA-binding proteins (RBPs) to play crucial roles in gene regulation and disease development. Computational approaches have attracted much attention to quickly predict highly potential RBP binding sites on circRNAs using the sequence or structure statistical binding knowledge. Deep learning is one of the popular learning models in this area but usually requires a lot of labeled training data. It would perform unsatisfactorily for the less characterized RBPs with a limited number of known target circRNAs. How to improve the prediction performance for such small-size labeled characterized RBPs is a challenging task for deep learning-based models. In this study, we propose an RBP-specific method iDeepC for predicting RBP binding sites on circRNAs from sequences. It adopts a Siamese neural network consisting of a lightweight attention module and a metric module. We have found that Siamese neural network effectively enhances the network capability of capturing mutual information between circRNAs with pairwise metric learning. To further deal with the small-sample size problem, we have performed the pretraining using available labeled data from other RBPs and also demonstrate the efficacy of this transfer-learning pipeline. We comprehensively evaluated iDeepC on the benchmark datasets of RBP-binding circRNAs, and the results suggest iDeepC achieving promising results on the poorly characterized RBPs. The source code is available at https://github.com/hehew321/iDeepC.
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http://dx.doi.org/10.1093/bib/bbab279DOI Listing
July 2021

Efficacy and safety of anlotinib in patients with advanced malignancy: a single-center, single-arm, phase 2 trial.

Int J Clin Oncol 2021 Jul 23. Epub 2021 Jul 23.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Background: For advanced tumors that lack specific oncogenic alteration and are resistant to chemotherapy, anti-angiogenesis therapy or immunotherapy or a combination of the two are the most important treatments. Anlotinib is a newly developed oral small molecule receptor tyrosine kinases inhibitor with the potency of inhibiting tumor angiogenesis. This was an open-label, single-arm, phase 2 study to validate the efficacy and safety of anlotinib in patients with various cancer types.

Methods: Patients with advanced malignancy who have failed previous therapies or lack effective treatment choices received daily oral administration of 12 mg anlotinib on days 1-14 every 3 weeks until disease progression, intolerable toxicity or physician decision. The primary endpoint was objective response rate (ORR).

Results: A total of 93 eligible patients with 26 different cancer types were enrolled. The overall ORR was 21.5%. The median PFS was 5.7 months and median OS was 12.0 months. The most common treatment-related AE of all grades and of grade 3 was both hypertriglyceridemia at an incidence of 40.9% and 5.4%, respectively.

Conclusions: Anlotinib exhibits objective efficacy and safety in advanced malignancy and might be a possible treatment option for many types of cancer patients who have failed prior treatment and with no optimal therapy regimen.
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http://dx.doi.org/10.1007/s10147-021-01959-zDOI Listing
July 2021

Effects of post-washing on pretreated biomass and hydrolysis of the mixture of acetic acid and sodium hydroxide pretreated biomass and their mixed filtrate.

Bioresour Technol 2021 Jul 21;339:125605. Epub 2021 Jul 21.

Department of Biological and Agricultural Engineering, Kansas State University, Manhattan, KS 66506, USA. Electronic address:

Effects of post-washing [one-volume water (I-VW) or double-volume water (Ⅱ-VW)] on pretreated hemp and poplar biomass and enzymatic hydrolysis of the mixture of HOAc and NaOH pretreated biomass and their mixed filtrate were investigated. Compared to I-VW, Ⅱ-VW increased 3.76-6.80% of glucan content in NaOH pretreated biomass, diminished lignin recondensation, and heightened cellulose-related FTIR peak intensities, crystallinity index, and lignin removal. The pH of mixed filtrate was around 4.80, precipitating the NaOH soluble lignin partially. Although Ⅱ-VW showed lower lignin recoveries than I-VW, their FTIR characteristics were equivalent to the commercial alkali lignin. Enzymatic hydrolysis at solid loadings of 2.5-10% (w/v) demonstrated that I-VW and Ⅱ-VW had marginal variations in sugar concentration and conversion efficiency, indicating that I-VW is sufficient for post-washing pretreated biomass. Glucose concentration exhibited a quadratic correlation with solid loading and hemp biomass reached the maximum glucose (43.88 g/L) and total sugar (57.08 g/L) concentrations with I-VW.
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http://dx.doi.org/10.1016/j.biortech.2021.125605DOI Listing
July 2021

Interfacial Protection Engineering of Sodium Nanoparticles toward Dendrite-Free and Long-Life Sodium Metal Battery.

Small 2021 Jul 26:e2102400. Epub 2021 Jul 26.

School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, P. R. China.

The instability of interfacial solid-electrolyte interphase (SEI) layer of metallic sodium (Na) anode during cycles results in the rapid capacity decay of sodium metal batteries (SMBs). Herein, the concept of interfacial protection engineering of Na nanoparticles (Na-NPs) is proposed first to achieve stable, dendrite-free, and long-life SMB. Employing an ion-exchange strategy, conformal Sn-Na alloy-SEI on the interface of Na-NPs is constructed, forming [email protected] The stable alloy-based SEI layer possesses the following three advantages: 1) significantly enhancing the transport dynamics of Na ions and electrons; 2) enabling the well-distributed deposition of Na ions to avoid the growth of dendrites; and 3) protecting the [email protected] anode from the attack of electrolyte, thereby reducing the parasitic reaction and boosting the Coulombic efficiency of SMBs. Because of these virtues, the symmetric [email protected] cell shows an ultralow voltage hysteresis of 0.54 V at 10 mA cm after 600 h. Paired with the Na V (PO ) O F (NaVPF) cathode, the [email protected] full cell exhibits an initial discharge capacity of 89.2 mAh g at 1 C and a high capacity retention of 81.6% after 600 cycles.
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http://dx.doi.org/10.1002/smll.202102400DOI Listing
July 2021

Influence of Life Meaning on Subjective Well-Being of Older People: Serial Multiple Mediation of Exercise Identification and Amount of Exercise.

Front Public Health 2021 8;9:515484. Epub 2021 Jul 8.

School of Psychology, Beijing Sport University, Beijing, China.

This study aimed to explore the relationship between life meaning and subjective well-being among older people and the mediating role of subjective exercise identification and objective amount of exercise. A total of 352 older respondents completed four questionnaires: the Chinese life meaning scale, the University of Newfoundland Happiness Scale, the physical activity habits questionnaire, and the exercise identification questionnaire designed for this study. Gender differences existed in the respondents' perception of life meaning, and men had a better perception of life meaning ( = 2.28, = 0.63, < 0.05). There were age differences in the subjective well-being of older people ( = 5.69, η = 0.03, < 0.01); the subjective well-being of older individuals steadily declines with rising age. Life meaning not only directly affected the subjective well-being of the respondents but also indirectly influenced their subjective well-being through the following three pathways: life meaning → exercise identification → subjective well-being (mediating effect of 22%); life meaning → amount of exercise → subjective well-being (mediating effect of 22%); and life meaning → exercise identification → amount of exercise → subjective well-being (serial multiple mediation effect of 27%). The more positive the life meaning perception of older people is, the higher their experience of subjective well-being. For older people to sense the meaning of life, we recommend that they realize the importance of physical activities and take the initiative to engage in physical activities to obtain higher subjective well-being.
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http://dx.doi.org/10.3389/fpubh.2021.515484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295607PMC
July 2021

Multiple Extramedullary-Bone Related and/or Extramedullary Extraosseous Are Independent Poor Prognostic Factors in Patients With Newly Diagnosed Multiple Myeloma.

Front Oncol 2021 7;11:668099. Epub 2021 Jul 7.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Extramedullary (EM) lesions are common in multiple myeloma (MM) and are often related to the poor prognosis of MM but are scarcely understood.

Methods: In this retrospective study, the baseline characteristics of 357 newly diagnosed patients with extramedullary multiple myeloma (EMM) and their impact on the prognosis were analyzed. All patients received first-line treatment with bortezomib-based regimen.

Results: The overall incidence rate of EM was 22.4%, and the detection rate of PET/CT was significantly higher than other imaging methods (P = 0.015). The cohorts consisted of 10 cases of extramedullary extraosseous (EME) and 70 cases of extramedullary-bone related (EMB), including 53 cases with single site involvement (one case with EME) and 27 cases with multiple sites (>1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, >245u/L) and are inclined to early-stage revised international staging system (R-ISS). Compared to patients without EM, those with EMM had worse progression-free survival (PFS) (P = 0.014) and overall survival (OS) (P = 0.032). In addition, patients without EM and those with a single site of EMB had similar PFS and OS, while patients with multiple sites of EMB or EME and multiple sites of EMB with EME had poor PFS and OS. Multivariate analysis confirmed that multiple sites of EMB and/or EME were independent prognostic predictors affecting PFS and OS in newly diagnosed MM patients.

Conclusions: This study suggested that among patients treated with bortezomib-based regimens, multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients, while a single site of EMB does not affect the survival of newly diagnosed MM patients. Thus, these findings could be used as a reference for the study of EMM patients in the new drug era, but prospective clinical studies are needed to provide evidence-based data for the diagnosis and treatment of EMM.
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http://dx.doi.org/10.3389/fonc.2021.668099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295340PMC
July 2021

Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling.

Exp Ther Med 2021 Sep 1;22(3):946. Epub 2021 Jul 1.

The Fourth Department of Oncology, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264001, P.R. China.

Salinomycin is a polyether antiprotozoal antibiotic that is widely used as an animal food additive. Some antifungal, antiparasitic, antiviral and anti-inflammatory activities have been reported for salinomycin. Recently, the anti-cancer effect of salinomycin has been demonstrated in breast cancer; however, the underlying mechanism remains unknown. The present study aimed to investigate the functional roles of salinomycin in the progression of prostate cancer cells using the DU145 and PC-3 cell lines. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the expression of oxidative stress and endoplasmic reticulum stress-related molecules, and flow cytometry was performed to detect the apoptosis rate of DU145 and PC-3 cells after salinomycin treatment. The results demonstrated that salinomycin inhibited the viability and induced the apoptosis of PC-3 and DU145 cells in a dose-dependent manner. Furthermore, salinomycin increased the production of reactive oxygen species (ROS) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and the lipid peroxidation. In addition, salinomycin induced the activation of unfolded protein response and endoplasmic reticulum stress in DU145 and PC-3 cells, as indicated by the elevated expression of binding immunoglobulin protein, activating transcription factor 4, phosphorylated eukaryotic initiation factor 2α, phosphorylated protein kinase RNA-like endoplasmic reticulum kinase and C/EBP homologous protein. In addition, salinomycin significantly downregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, NAD(P)H quinone dehydrogenase 1 and glutamate-cysteine ligase catalytic subunit and decreased the activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase in PC-3 and DU145 cells. Furthermore, the Nrf2 activator, tert-butylhydroquinone, significantly reversed the therapeutic effects of salinomycin by stimulating the Nrf2 pathway and increasing the activity of antioxidant enzymes. Taken together, these findings demonstrated that salinomycin may trigger apoptosis by inducing oxidative and ER stress in prostate cancer cells via suppressing Nrf2 signaling.
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http://dx.doi.org/10.3892/etm.2021.10378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281384PMC
September 2021

High Prevalence of Extended-Spectrum Beta-Lactamases in Strains Collected From Strictly Defined Community-Acquired Urinary Tract Infections in Adults in China: A Multicenter Prospective Clinical Microbiological and Molecular Study.

Front Microbiol 2021 7;12:663033. Epub 2021 Jul 7.

Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: The objective of the study was to investigate the antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) positive rates of from community-acquired urinary tract infections (CA-UTIs) in Chinese hospitals.

Materials And Methods: A total of 809 isolates from CA-UTIs in 10 hospitals (5 tertiary and 5 secondary hospitals) from different regions in China were collected during the period 2016-2017 according to the strict inclusion criteria. Antimicrobial susceptibility testing was carried out by standard broth microdilution method. Isolates were categorized as ESBL-positive, ESBL-negative, and ESBL-uncertain groups according to the CLSI recommended phenotypic screening method. ESBL and AmpC genes were amplified and sequenced on ESBL-positive and ESBL-uncertain isolates.

Results: The antimicrobial agents with susceptibility rates of greater than 95% included imipenem (99.9%), colistin (99.6%), ertapenem (98.9%), amikacin (98.3%), cefmetazole (97.9%), nitrofurantoin (96%), and fosfomycin (95.4%). However, susceptibilities to cephalosporins (varying from 58.6% to 74.9%) and levofloxacin (48.8%) were relatively low. In the phenotypic detection of ESBLs, ESBL-positive isolates made up 38.07% of strains isolated from CA-UTIs, while 2.97% were ESBL-uncertain. Antimicrobial susceptibilities of imipenem, cefmetazole, colistin, ertapenem, amikacin, and nitrofurantoin against ESBL-producing strains were greater than 90%. The percentage of ESBL-producing strains was higher in male (53.6%) than in female patients (35.2%) ( < ). CTX-M-14 (31.8%) was the major CTX-M variant in the ESBL-producing , followed by CTX-M-55 (23.4%), CTX-M-15 (17.5%), and CTX-M-27 (13.3%). The prevalence of carbapenem-resistant among CA-UTI isolates was 0.25% (2/809).

Conclusion: Our study indicated high prevalence of ESBL in strains from strictly defined community-acquired urinary tract infections in adults in China. Imipenem, colistin, ertapenem, amikacin, and nitrofurantoin were the most active antimicrobials against ESBL-positive isolates. is the predominant gene in ESBL-producing and ESBL-uncertain strains. Our study indicated that the use of cephalosporins and fluoroquinolone needs to be restricted for empirical treatment of CA-UTIs in China.
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http://dx.doi.org/10.3389/fmicb.2021.663033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292957PMC
July 2021

Histogram models based on intravoxel incoherent motion diffusion-weighted imaging to predict nodal staging of rectal cancer.

Eur J Radiol 2021 Jul 20;142:109869. Epub 2021 Jul 20.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. No.17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. Electronic address:

Purpose: To develop a model based on histogram parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for predicting the nodal staging of rectal cancer (RC).

Material And Methods: A total of 95 RC patients who underwent direct surgical resection were enrolled in this prospective study. The nodal staging on conventional magnetic resonance imaging (MRI) was evaluated according to the short axis diameter and morphological characteristics. Histogram parameters were extracted from apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) maps. Multivariate binary logistic regression analysis was conducted to establish models for predicting nodal staging among all patients and those underestimated on conventional MRI.

Results: The combined model based on multiple maps demonstrated superior diagnostic performance to single map models, with an area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy of 0.959, 94.3%, 88.3%, and 90.5%, respectively. The AUC of the combined model was significantly higher than that of the conventional nodal staging (P < 0.001). Additionally, 85.0% of the underestimated patients had suspicious lymph nodes with 5-8 mm short-axis diameter. The histogram model for these subgroups of patients showed good diagnostic efficacy with an AUC, sensitivity, specificity, and accuracy of 0.890, 100%, 75%, and 80.5%.

Conclusion: The histogram model based on IVIM-DWI could improve the diagnostic performance of nodal staging of RC. In addition, histogram parameters of IVIM-DWI may help to reduce the uncertainty of nodal staging in underestimated patients on conventional MRI.
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http://dx.doi.org/10.1016/j.ejrad.2021.109869DOI Listing
July 2021

Ethyl pyruvate: A newly discovered compound against ischemia-reperfusion injury in multiple organs.

Pharmacol Res 2021 Jul 21:105757. Epub 2021 Jul 21.

Department of Paediatrics, Shenmu Hospital, School of Life Sciences and Medicine, Northwest University, Guangming Road, Shenmu, China. Electronic address:

Ischemia-reperfusion injury (IRI) is a process whereby an initial ischemia injury and subsequent recovery of blood flow, which leads to the propagation of an innate immune response and the changes of structural and functional of multiple organs. Therefore, IRI is considered to be a great challenge in clinical treatment such as organ transplantation or coronary angioplasty. In recent years, ethyl pyruvate (EP), a derivative of pyruvate, has received great attention because of its stability and low toxicity. Previous studies have proved that EP has various pharmacological activities, including anti-inflammation, anti-oxidative stress, anti-apoptosis, and anti-fibrosis. Compelling evidence has indicated EP plays a beneficial role in a variety of acute injury models, such as brain IRI, myocardial IRI, renal IRI, and hepatic IRI. Moreover, EP can not only effectively inhibit multiple IRI-induced pathological processes, but also improve the structural and functional lesion of tissues and organs. In this study, we review the recent progress in the research on EP and discuss their implications for a better understanding of multiple organ IRI, and the prospects of targeting the EP for therapeutic intervention.
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http://dx.doi.org/10.1016/j.phrs.2021.105757DOI Listing
July 2021

Single-cell alternative polyadenylation analysis delineates GABAergic neuron types.

BMC Biol 2021 Jul 23;19(1):144. Epub 2021 Jul 23.

Department of Biological Sciences, Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, 75080, USA.

Background: Alternative polyadenylation (APA) is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in biological processes, such as cell proliferation and differentiation. Single-cell RNA-seq technologies are widely used in gene expression heterogeneity studies; however, systematic studies of APA at the single-cell level are still lacking.

Results: Here, we described a novel computational framework, SAPAS, that utilizes 3'-tag-based scRNA-seq data to identify novel poly(A) sites and quantify APA at the single-cell level. Applying SAPAS to the scRNA-seq data of phenotype characterized GABAergic interneurons, we identified cell type-specific APA events for different GABAergic neuron types. Genes with cell type-specific APA events are enriched for synaptic architecture and communications. In further, we observed a strong enrichment of heritability for several psychiatric disorders and brain traits in altered 3' UTRs and coding sequences of cell type-specific APA events. Finally, by exploring the modalities of APA, we discovered that the bimodal APA pattern of Pak3 could classify chandelier cells into different subpopulations that are from different laminar positions.

Conclusions: We established a method to characterize APA at the single-cell level. When applied to a scRNA-seq dataset of GABAergic interneurons, the single-cell APA analysis not only identified cell type-specific APA events but also revealed that the modality of APA could classify cell subpopulations. Thus, SAPAS will expand our understanding of cellular heterogeneity.
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http://dx.doi.org/10.1186/s12915-021-01076-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299648PMC
July 2021

Efficient Source Camera Identification with Diversity-Enhanced Patch Selection and Deep Residual Prediction.

Sensors (Basel) 2021 Jul 9;21(14). Epub 2021 Jul 9.

Department of Biomedical Engineering, Imperial College London, London SW7 2AZ, UK.

Source camera identification has long been a hot topic in the field of image forensics. Besides conventional feature engineering algorithms developed based on studying the traces left upon shooting, several deep-learning-based methods have also emerged recently. However, identification performance is susceptible to image content and is far from satisfactory for small image patches in real demanding applications. In this paper, an efficient patch-level source camera identification method is proposed based on a convolutional neural network. First, in order to obtain improved robustness with reduced training cost, representative patches are selected according to multiple criteria for enhanced diversity in training data. Second, a fine-grained multiscale deep residual prediction module is proposed to reduce the impact of scene content. Finally, a modified VGG network is proposed for source camera identification at brand, model, and instance levels. A more critical patch-level evaluation protocol is also proposed for fair performance comparison. Abundant experimental results show that the proposed method achieves better results as compared with the state-of-the-art algorithms.
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http://dx.doi.org/10.3390/s21144701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309546PMC
July 2021

TSC1/2 mutations-a unique type of mutation suitable for liver transplantation of Hepatocellular carcinoma.

J Gastrointest Oncol 2021 Jun;12(3):1074-1085

Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: This study aimed to investigate the relationship between the prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation and mammalian target of rapamycin (mTOR) pathway-related genes-.

Methods: We retrospectively analyzed the clinical data of 46 patients who underwent liver transplantation for HCC and performed next generation sequencing to analyze the relationship between the efficacy of sirolimus after liver transplantation for HCC and mutations in mTOR pathway-related genes, especially tuberous sclerosis complex (TSC) mutations.

Results: The average age of 46 patients with liver transplantation for HCC was 51±21 years. After surgery, 35 patients received an anti-rejection/anti-tumor regimen that included sirolimus, and 11 patients did not receive sirolimus. There was no significant difference in survival rate between the two groups (P=0.761). The gene sequencing results showed mTOR-related pathway mutations in 10 patients, of whom five (10.9%) had TSC1/2 mutations. Of the 35 patients using sirolimus, those with mTOR-related mutations had significantly better survival rates than patients without mTOR-related mutations (P=0.016).

Conclusions: According to genetic sequencing results, a personalized treatment plan for specific genetic mutations should be selected in patients undergoing liver transplantation for HCC. Patients with mTOR-related gene mutations, especially TSC mutations, can gain significant benefits from the use of mTOR inhibitors such as sirolimus.
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http://dx.doi.org/10.21037/jgo-20-378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261316PMC
June 2021

Inhalable nanocatchers for SARS-CoV-2 inhibition.

Proc Natl Acad Sci U S A 2021 07 2;118(29). Epub 2021 Jul 2.

Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China;

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.
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http://dx.doi.org/10.1073/pnas.2102957118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307760PMC
July 2021

Ferroptosis-Strengthened Metabolic and Inflammatory Regulation of Tumor-Associated Macrophages Provokes Potent Tumoricidal Activities.

Nano Lett 2021 Jul 22. Epub 2021 Jul 22.

School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, People's Republic of China.

Modulation of tumor-associated macrophages (TAMs) holds promise for cancer treatment, mainly relying on M1 signaling activation and pro-inflammatory promotion. Nevertheless, the antitumor activity is often limited by the anti-inflammatory factors in the tumor microenvironment. Moreover, the metabolic function of TAMs is also critical to tumor progression. However, there are a few strategies that can simultaneously regulate both inflammatory and metabolic functions to achieve safe and potent antitumor activation of TAMs. Herein, we demonstrate that an iron-based metal organic framework nanoparticle and a ferroptosis-inducing agent synergistically induce mitochondrial alternation in TAMs, resulting in a radical metabolic switch from mitochondrial oxidative phosphorylation to glycolysis, which is resistant to anti-inflammatory stimuli challenge. The ferroptosis stress strengthened by the nanoformulation also drives multiple pro-inflammatory signaling pathways, enabling macrophage activation with potent tumoricidal activities. The ferroptosis-strengthened macrophage regulation strategy present in this study paves the way for TAM-centered antitumoral treatment to overcome the limitations of conventional methods.
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http://dx.doi.org/10.1021/acs.nanolett.1c01401DOI Listing
July 2021

Therapeutic Effects of Ba-Duan-Jin versus Pregabalin for Fibromyalgia Treatment: Protocol for a Randomized Controlled Trial.

Rheumatol Ther 2021 Jul 22. Epub 2021 Jul 22.

Department of Rheumatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Introduction: Fibromyalgia is characterized by multi-focal pain and is associated with fatigue, unrefreshing sleep and psychological impairment. Pregabalin is one of the most frequently used agents in fibromyalgia treatment. However, it has failed to demonstrate benefit over placebo for reducing fatigue and psychological impairment, and may cause adverse effects (e.g. somnolence, dizziness). "Ba-Duan-Jin" (BDJ) is a common form of "Qigong" exercise for health promotion in China. Growing evidence suggests that BDJ may achieve satisfactory control of fibromyalgia-related symptoms in Chinese patients. Therefore, we wish to ascertain if BDJ could overcome the disadvantages of pregabalin.

Methods: A single-blind randomized controlled trial has been designed which will recruit 104 patients with fibromyalgia (age 18-70 years) with a visual analog scale (VAS) pain score of ≥ 40 mm These patients will be randomly assigned to one of two groups: (1) BDJ group (to undertake guided BDJ exercise and take a placebo capsule) or (2) pregabalin group (to take a pregabalin capsule and receive wellness education and guided muscle-relaxation exercises). The primary endpoint will be changes in the VAS score for pain. The secondary endpoints will be changes in the score for the Revised Fibromyalgia Impact Questionnaire, Multidimensional Fatigue Inventory-20, Pittsburgh Sleep Quality Index, Beck II Depression Inventory, Perceived Stress Scale and Short Form-36 Health Survey Questionnaire. These parameters will be assessed at 0, 4, 8, 12 and 24 weeks of follow-up.

Planned Outcomes: Our results are expected to provide more clinical evidence for the beneficial effects of BDJ in treating fibromyalgia.

Trial Registration: NCT03797560.
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http://dx.doi.org/10.1007/s40744-021-00341-9DOI Listing
July 2021

Comparative Transcriptome Analyses of the Developmental Stages of .

Front Vet Sci 2021 5;8:677045. Epub 2021 Jul 5.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Science, Lanzhou, China.

Cerebral coenurosis, caused by the larvae of (, is a fatal central nervous system disease in sheep and other herbivores and occasionally humans. Comparative transcriptomic profiles of the developmental stages of the parasite remain unknown. In this study, RNA sequencing was used to determine the transcriptome profiles of different stages of the life cycle of , including Oncosphere, (Pro with Cyst), and Adult (Adu), as well as scolex-neck proglottids (Snp), immature-mature proglottids (Imp), and gravid proglottids (Grp) of the adult stage. A total of 42.6 Gb (average 6.1 Gb) Illumina pair-end reads with a 125-bp read length were generated for seven samples. The total number of differentially expressed genes (DEGs) in the various life stages ranged from 2,577 to 3,879; however, for the tissues of the adult worm, the range was from 1,229 to 1,939. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs mainly participated in cellular and metabolic processes, binding and catalytic activity, genetic information processing, and environmental information processing. In addition, a large number of genes related to development and parasite-host interaction were identified. Quantitative reverse transcription-polymerase chain reaction confirmed that the levels of 28 selected DEGs were consistent with those determined using RNA sequencing. The present study provides insights into the mechanisms of the development and parasitic life of .
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http://dx.doi.org/10.3389/fvets.2021.677045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287169PMC
July 2021

Author Correction: Adductor canal block versus femoral nerve block for total knee arthroplasty: a meta-analysis of randomized controlled trials.

Sci Rep 2021 Jul 21;11(1):15230. Epub 2021 Jul 21.

Department of Orthopedics, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, 610041, People's Republic of China.

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http://dx.doi.org/10.1038/s41598-021-94766-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295281PMC
July 2021

The brain basis of handwriting deficits in Chinese children with developmental dyslexia.

Dev Sci 2021 Jul 20. Epub 2021 Jul 20.

Center for Brain Disorders and Cognitive Sciences, Shenzhen University, Shenzhen, 518060, China.

Abundant behavioral studies have demonstrated high comorbidity of reading and handwriting difficulties in developmental dyslexia (DD), a neurological condition characterized by unexpectedly low reading ability despite adequate nonverbal intelligence and typical schooling. The neural correlates of handwriting deficits remain largely unknown, however, as well as the extent that handwriting deficits share common neural bases with reading deficits in DD. The present work used functional magnetic resonance imaging (fMRI) to examine brain activity during handwriting and reading tasks in Chinese dyslexic children (n = 18) and age-matched controls (n = 23). Compared to controls, dyslexic children exhibited reduced activation during handwriting tasks in brain regions supporting sensory-motor processing (including supplementary motor area and postcentral gyrus) and visual-orthography processing (including bilateral precuneus and right cuneus). Among these regions, the left supplementary motor area and the right precuneus also showed a trend of reduced activation during reading tasks in dyslexics. Moreover, increased activation was found in the left inferior frontal gyrus and anterior cingulate cortex in dyslexics, which may reflect more efforts of executive control to compensate for the impairments of motor and visual-orthographic processing. Finally, dyslexic children exhibited aberrant functional connectivity among brain areas for cognitive control and sensory-motor processes during handwriting tasks. Together, these findings suggest that handwriting deficits in DD are associated with functional abnormalities of multiple brain regions implicated in motor execution, visual-orthographic processing and cognitive control, providing important implications for the diagnosis and treatment of dyslexia. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/desc.13161DOI Listing
July 2021

Inhibition of Orthotopic Genital Cancer Induced by Subcutaneous Administration of Human Papillomavirus Peptide Vaccine with CpG Oligodeoxynucleotides as an Adjuvant in Mice.

Cancer Manag Res 2021 12;13:5559-5572. Epub 2021 Jul 12.

Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning, People's Republic of China.

Purpose: Persistent high-risk human papillomavirus (HPV) infection is the most common cause of cervical cancer and its precursor lesions. Although prophylactic HPV vaccines have been applied in the general population for the prevention of HPV infections, no licensed therapeutic HPV vaccine is currently available to treat preexisting HPV infections or HPV-associated diseases, including cervical cancer.

Materials And Methods: The most common murine cervical cancer model used for the evaluation of the efficacy of a therapeutic HPV vaccine in preclinical studies is the ectopic model, which is established by the subcutaneous inoculation of tumor cells, such as TC-1 cells, into the flank of an animal. We have previously demonstrated the efficacy of a therapeutic HPV peptide vaccine adjuvanted with unmethylated cytosine-phosphate-guanosine oligodeoxynucleotide in the clearance of ectopic subcutaneous tumors in C57BL/6 mice after vaccination. In the current study, we established orthotopic genital tumors by injecting TC-1 cells into the vaginal submucosa close to the cervix and assessed whether the subcutaneous administration of the therapeutic vaccine could inhibit the growth of genital tumors. Additionally, we evaluated the effect of the vaccination on the tumor microenvironment.

Results: The results showed that the vaccination induced an increase in infiltrating CD4+ and CD8+ T cells, a decrease in myeloid-derived suppressor cells and cancer-associated fibroblasts, as well as the differential expression of a panel of cytokines, chemokines, and matrix metalloproteinases within the tumor microenvironment.

Conclusion: The administration of the vaccine resulted in the inhibition of established implanted orthotopic genital tumors by inducing strong antitumor immune responses and reversed tolerogenic local immunosuppression in a mouse model of orthotopic genital cancer.
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http://dx.doi.org/10.2147/CMAR.S309226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285235PMC
July 2021

Cell membrane covered polydopamine nanoparticles with two-photon absorption for precise photothermal therapy of cancer.

J Colloid Interface Sci 2021 Jul 6;604:596-603. Epub 2021 Jul 6.

CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. Electronic address:

Hypothesis: In view of the photothermal effect of polydopamine (PDA) nanoparticles and their internal D-π-D structures during assembly, the two-photon excited properties of PDA were studied toward the biomedical application. Further, the PDA molecules were coordinated with Mn and the assembled nanoparticles were covered by cancer cell membranes, the complex system could be used directly for the treatment of cancer with photothermal and chemodynamic therapy.

Experiments: The two-photon excited PDA-Mn nanoparticles were used for the photothermal therapy combined with chemodynamic therapy. The complexes were coated with cancer cell membranes in order to enhance the tumor homologous efficiency. Multi-modal bioimaging and anti-tumor detections were carried out both in vitro and in vivo.

Findings: PDA nanoparticles were demonstrated to have both good two-photon excited fluorescence and photothermal efficiency. The assembled nanoparticles modified with Mn and cancer cell membranes have an obvious targeting and synergetic anti-cancer efficiency. The system creates a simple way for a precise operation with multi-modal imaging function.
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http://dx.doi.org/10.1016/j.jcis.2021.07.004DOI Listing
July 2021

Melamine impairs working memory and reduces prefrontal activity associated with inhibition of AMPA receptor GluR2/3 subunit expression.

Toxicol Lett 2021 Jul 16. Epub 2021 Jul 16.

Behavioural Neuroscience Lab, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China; Department of Pediatric, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China; Department of Neurology, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China. Electronic address:

Recent studies have reported that melamine can accumulate in several regions of the brain including the medial prefrontal cortex (mPFC). Although melamine accumulation in the hippocampus has been verified to induce cognitive impairments, whether it can cause mPFC-dependent working memory deficits is still unknown. After chronic treatment with melamine (150 (Mel(150)) or 300 (Mel(300)) mg/kg), rats were tested during both delay nonmatching-to-sample spatial and odor discrimination tasks. Levels of AMPA receptor subunits in the mPFC were detected using western blotting. To further explore the mechanism at the cellular level, prefrontal activity was recorded during the odor discrimination. The working memory of Mel(150) rats was found to be significantly impaired in a 3-minute delay odor discrimination task (control: n = 6, Mel(150): n = 6; P < 0.05). Compared with the control group (n = 6), rats in the 300 mg/kg Mel(300)-treated group (n = 8) displayed working memory deficits in 60-second delay Y-maze task (P < 0.05), 1-minute and 3-minute delay odor discrimination tasks (both P < 0.05). The levels of AMPA receptor mGluR2/3 subunit were significantly decreased in rats of the Mel(150) (n = 7) and Mel(300) (n = 7) groups (both P < 0.05). Exposure to 150 (n = 7) or 300 mg/kg (n = 7) melamine resulted in significant inhibition of the regular-spiking neuron activity during the delay period of the memory test (both P < 0.05). Intraperitoneal (n = 7) and intra-mPFC (n = 6) infusions of GluR2/3 agonists, effectively enhanced the neural correlate (both P < 0.05) while rescuing cognitive deficits in Mel(300)-treated rats (both P < 0.05). Collectively, these findings suggested that melamine could induce prefrontal dysfunction and cause cognitive impairments.
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http://dx.doi.org/10.1016/j.toxlet.2021.07.009DOI Listing
July 2021
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