Publications by authors named "Yuan Wu"

540 Publications

Distinguishing Rectal Cancer from Colon Cancer Based on the Support Vector Machine Method and RNA-sequencing Data.

Curr Med Sci 2021 Apr 20;41(2):368-374. Epub 2021 Apr 20.

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Several studies have indicated that rectal cancer is significantly different from colon cancer in terms of treatment, prognosis, and metastasis. Recently, the differential mRNA expression of colon cancer and rectal cancer has received a great deal of attention. The current study aimed to identify significant differences between colon cancer and rectal cancer based on RNA sequencing (RNA-seq) data via support vector machines (SVM). Here, 393 CRC samples from the The Cancer Genome Atlas (TCGA) database were investigated, including 298 patients with colon cancer and 95 with rectal cancer. Following the random forest (RF) analysis of the mRNA expression data, 96 genes such as HOXB13, PRAC, and BCLAF1 were identified and utilized to build the SVM classification model with the Leave-One-Out Cross-validation (LOOCV) algorithm. In the training (n=196) and the validation cohorts (n=197), the accuracy (82.1 % and 82.2 %, respectively) and the AUC (0.87 and 0.91, respectively) indicated that the established optimal SVM classification model distinguished colon cancer from rectal cancer reasonably. However, additional experiments are required to validate the predicted gene expression levels and functions.
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http://dx.doi.org/10.1007/s11596-021-2356-8DOI Listing
April 2021

Correlation of Seizure Increase and COVID-19 Outbreak in Adult Patients with Epilepsy: Findings and Suggestions from a Nationwide Multi-centre Survey in China.

Seizure 2021 Mar 31;88:102-108. Epub 2021 Mar 31.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China. Electronic address:

Objectives: To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis.

Methods: This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening.

Results: A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P < 0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P < 0.05) were independently related to seizure increase during the pandemic.

Conclusions: During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.
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http://dx.doi.org/10.1016/j.seizure.2021.03.029DOI Listing
March 2021

Menin-regulated Pbk controls high fat diet-induced compensatory beta cell proliferation.

EMBO Mol Med 2021 Apr 6:e13524. Epub 2021 Apr 6.

Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Pancreatic beta cells undergo compensatory proliferation in the early phase of type 2 diabetes. While pathways such as FoxM1 are involved in regulating compensatory beta cell proliferation, given the lack of therapeutics effectively targeting beta cell proliferation, other targetable pathways need to be identified. Herein, we show that Pbk, a serine/threonine protein kinase, is essential for high fat diet (HFD)-induced beta cell proliferation in vivo using a Pbk kinase deficiency knock-in mouse model. Mechanistically, JunD recruits menin and HDAC3 complex to the Pbk promoter to reduce histone H3 acetylation, leading to epigenetic repression of Pbk expression. Moreover, menin inhibitor (MI) disrupts the menin-JunD interaction and augments Pbk transcription. Importantly, MI administration increases beta cell proliferation, ameliorating hyperglycemia, and impaired glucose tolerance (IGT) in HFD-induced diabetic mice. Notably, Pbk is required for the MI-induced beta cell proliferation and improvement of IGT. Together, these results demonstrate the repressive role of the menin/JunD/Pbk axis in regulating HFD-induced compensatory beta cell proliferation and pharmacologically regulating this axis may serve as a novel strategy for type 2 diabetes therapy.
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http://dx.doi.org/10.15252/emmm.202013524DOI Listing
April 2021

Rapid electrochemical biosensor for sensitive profiling of exosomal microRNA based on multifunctional DNA tetrahedron assisted catalytic hairpin assembly.

Biosens Bioelectron 2021 Mar 29;183:113205. Epub 2021 Mar 29.

Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China; Huayin Medical Laboratory Center Co., Ltd., Guangzhou, 510515, PR China. Electronic address:

Profiling of exosomal microRNA (exo-miRNA) is very important for cancer diagnosis and treatment. However, rapid and sensitive determination the trace of exo-miRNA in clinical samples has not been developed. Herein, a robust electrochemical biosensor was proposed using multifunctional DNA tetrahedrons assisted catalytic hairpin assembly (MDTs-CHA) for exo-miRNA analysis. The MDTs-CHA, contained two multifunctional tetrahedrons (T1 and T2), leverage localized reaction and cascade amplification to enable rapid and ultrasensitive exo-miRNA analysis. Employing the MDTs-CHA, the electrochemical platform allowed quantitative measurement of exo-miRNA down to 7.2 aM in 30 min with good specificity. Furthermore, by profiling four tumor-associated exo-miRNAs (miR-1246, miR-221, miR-375, and miR-21) in a breast cancer cohort, this platform showed high efficiency (AUC: 0.989) and high sensitivity of 90.5% for breast tumors diagnoses, with 80% sensitivity for early diagnoses (stage I-IIa). Therefore, this platform has great potential in bioanalysis and clinical diagnostics.
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http://dx.doi.org/10.1016/j.bios.2021.113205DOI Listing
March 2021

Selection and Validation of Reference Genes for qRT-PCR Analysis in the Oil-Rich Tuber Crop Tiger Nut () Based on Transcriptome Data.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Innovation Academy for Seed Design, Chinese Academy of Sciences, Menglun, Mengla 666303, China.

Tiger nut (), a perennial C plant of the family, is an unconventional crop that is distinguished by its oil-rich tubers, which also possesses the advantages of strong resistance, wide adaptability, short life periods, and large biomass. To facilitate studies on gene expression in this species, we identified and validated a series of reference genes (RGs) based on transcriptome data, which can be employed as internal controls for qRT-PCR analysis in tiger nut. Fourteen putative candidate RGs were identified and evaluated across nine different tissues of two cultivars, and the RGs were analyzed using three different algorithms (geNorm, NormFinder, and BestKeeper). The stability rankings of the candidate RGs were merged into consensus lists with RankAggreg. For the below-ground storage organ of tiger nut, the optimal RGs were and in different developmental stages of tubers. and were the most stably expressed RGs among all tissues, while and exhibited the lowest expression stability. , and were compared to normalize the expression levels of the () and () genes across the same tissues. Our results showed that the RGs identified in this study, which exhibit more uniform expression patterns, may be utilized for the normalization of qRT-PCR results, promoting further research on gene expression in various tissues of tiger nut.
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http://dx.doi.org/10.3390/ijms22052569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961719PMC
March 2021

Tephrosia purpurea Represents a New Host of 16SrII-V Subgroup Phytoplasma Associated with Witches'-Broom Disease in China.

Plant Dis 2021 Mar 29. Epub 2021 Mar 29.

Coconut Research Institute of Chinese Academy of Tropical Agricultural Sciences, Wenchang, China;

Tephrosia purpurea is a medical plant with excellent insecticidal activity belonging to the family of Leguminosae distributed throughout southern of China (Pei et al., 2013). During January to February 2021, the plants showing abnormal symptoms including witches'-broom, internode shortening, leaf chlorosis and leaflet formation, as shown in Fig.1, were found in Ledong County of Hainan Province, a tropical island in China, with about 60 % incidence. The Tephrosia purpurea disease symptoms were suspected to be induced by phytoplasma, a phloem-limited prokaryotic pathogen which can not be cultured in vitro and which causes severe financial loss and ecological damage to the island. Total DNA from the symptomatic and asymptomatic samples of Tephrosia purpurea were extracted using 0.10 g fresh plant leaves and branches by CTAB method (Doyle and Doyle, 1990). 16S rRNA and secA gene sequence fragments of phytoplasma were detected through PCR amplification using primers R16mF2/R16mR1 (Gundersen and Lee, 1996) and secAfor1/secArev3 (Hodgetts et al., 2008). The two gene sequence fragments of phytoplasma were obtained from the DNA of six symptomatic plant samples whereas not from the DNA of six asymptomatic plant samples. These amplified products were sequenced and the data were deposited in GenBank. The two gene sequence fragments of the DNA obtained from the diseased plant samples were all identical, with a length of 1335 bp for the 16S rRNA (GenBank accession: MW616560) and 729 bp for the secA gene (MW603929). The secA gene fragment putatively encodes for 242 amino acids. The phytoplasma strain was named as Tephrosia purpurea witches'-broom (TpWB) phytoplasma, TpWB-hnld strain. 16S rRNA gene sequence fragment of TpWB-hnld was analyzed by online tool iPhyClassifier (Wei et al., 2007), indicating that the pathogen strain was a member of subgroup 16SrII-V and a 'Candidatus Phytoplasma aurantifolia'-related strain. Blast analysis based on the 16S rRNA gene sequence fragment of TpWB-hnld showed 100 % sequence identity with that of peanut witches'-broom group members (16SrII group), such as Cassava witches'-broom phytoplasma (KM280679) and Cleome sp. phytoplasma (KM280677); Blast analysis based on the secA gene sequence fragment of TpWB-hnld showed 100 % sequence identity with that of peanut witches'-broom group members (16SrII group), such as sesame phyllody phytoplasma (JN977044). Homology and phylogeny were analyzed using the software of DNAMAN 5.0 and MEGA 7.0, indicating that TpWB-hnld and other subgroup 16SrII-V phytoplasma strains, including Cassava witches'-broom phytoplasma, Cleome sp. phytoplasma, Crotalaria witches'-broom phytoplasma (EU650181) and Desmodium ovalifolium witches'-broom phytoplasma (GU113152), were clustered into one clade with 98 % bootstrap value based on the 16S rRNA gene sequence fragments; TpWB-hnld and sesame phyllody phytoplasma were clustered into one clade based on the secA gene sequence fragments. Multiple alignment based on the 16S rRNA gene sequence fragment showed that the TpWB-hnld phytoplasma strain showed 98 % sequence identity with TpWB phytoplasma strain (HG792252) belonging to 16SrII-M subgroup reported in India (Yadav et al., 2014). To our knowledge, this was the first time that 16SrII-V subgroup phytoplasma associated with Tephrosia purpurea witches'-broom disease was identified in China. Molecular analysis based on the 16S rRNA and secA gene sequence fragments indicated that TpWB-hnld phytoplasma was a member of subgroup 16SrII-V and a 'Candidatus Phytoplasma aurantifolia'-related strain.
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http://dx.doi.org/10.1094/PDIS-02-21-0357-PDNDOI Listing
March 2021

Expanding the Chemical Space of Succinate Dehydrogenase Inhibitors via the Carbon-Silicon Switch Strategy.

J Agric Food Chem 2021 Apr 28;69(13):3965-3971. Epub 2021 Mar 28.

Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health of Ministry of Science and Technology, Central China Normal University, Luoyu Road 152, Wuhan 430079, People's Republic of China.

The carbon-silicon switch strategy has become a key technique for structural optimization of drugs to widen the chemical space, increase drug activity against targeted proteins, and generate novel and patentable lead compounds. Flubeneteram, targeting succinate dehydrogenase (SDH), is a promising fungicide candidate recently developed in China. We describe the synthesis of novel SDH inhibitors with enhanced fungicidal activity to enlarge the chemical space of flubeneteram by employing the C-Si switch strategy. Several of the thus formed flubeneteram-silyl derivatives exhibited improved fungicidal activity against porcine SDH compared with the lead compound flubeneteram and the positive controls. Disease control experiments conducted in a greenhouse showed that trimethyl-silyl-substituted compound showed comparable and even higher fungicidal activities compared to benzovindiflupyr and flubeneteram, respectively, even with a low concentration of 0.19 mg/L for soybean rust control. Furthermore, compound encouragingly performed slightly better control than azoxystrobin and was less active than benzovindiflupyr at the concentration of 100 mg/L against soybean rust in field trials. The computational results showed that the silyl-substituted phenyl moiety in could form strong van der Waals (VDW) interactions with SDH. Our results indicate that the C-Si switch strategy is an effective method for the development of novel SDH inhibitors.
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http://dx.doi.org/10.1021/acs.jafc.0c07322DOI Listing
April 2021

The Association of Single-Nucleotide Polymorphism rs13181 in ERCC2 with Risk and Prognosis of Nasopharyngeal Carcinoma in an Endemic Chinese Population.

Pharmgenomics Pers Med 2021 17;14:359-367. Epub 2021 Mar 17.

Life Science Institute of Guangxi Medical University, Nanning, People's Republic of China.

Objective: We examined whether the single-nucleotide polymorphism (SNP) rs13181 in the gene encoding excision repair cross complementation group 2 (ERCC2) is associated with the risk and prognosis of nasopharyngeal carcinoma (NPC).

Methods: SNPs at rs13181 were genotyped in 439 NPC patients (NPC group) and 431 age- and gender-matched cancer-free controls (control group) from a region of China where NPC is endemic, and frequencies of GG, GT and TT genotypes were compared between the two groups in the case-control study. In a subset of 365 NPC cases, SNPs were examined for potential correlation with tumor-free survival time (TFS) and overall survival (OS).

Results: Relative to NPC risk with a TT genotype, NPC risk was similar with GT + GG genotypes (OR 1.052, 95% CI 0.656-1.688), after adjusting for gender, age, smoking history, and immunoglobin A against Epstein-Barr virus capsid antigen (EBV-VCA-IgA) status. Univariate analysis showed that the GG or GT genotype was associated with significantly worse TFS (p<0.001) and OS (p=0.010) than the TT genotype. Prognosis was significantly worse for men than for women (TFS, p=0.045; OS, p=0.031), for T3-T4 classification than for T1-T2 (TFS, p=0.009; OS, p=0.007), for N3 than for N0+N1+N2 (TFS, p<0.001; OS, p<0.001). Based on multivariate analysis, independent risk factors for poor TFS were GG or GT genotype (HR 2.629, 95% CI 1.625-4.254, p<0.001), T3-T4 classification (HR 2.146, 95% CI 1.244-3.701, p=0.006) and N3 (HR 2.527, 95% CI 1.574-4.059, p<0.001). GG or GT genotype (HR 2.217, 95% CI 1.283-3.832, p=0.004), gender (HR 1.989, 95% CI 1.046-3.785, p=0.036), T3-T4 (HR 2.431, 95% CI 1.306-4.526, p=0.005) and N3 (HR 2.693, 95% CI 1.637-4.432, p<0.001) were independent risk factors for poor OS.

Conclusion: The rs13181 SNP in ERCC2 does not appear to be associated with NPC risk, but it may serve as an independent prognostic factor for NPC recurrence and death.
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http://dx.doi.org/10.2147/PGPM.S296215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982703PMC
March 2021

Rare malignant spindle cell sarcoma of the left atrium diagnosed with TEE: A case report.

Medicine (Baltimore) 2021 Mar;100(10):e24033

Department of Ultrasound.

Introduction: One of the purposes of echocardiography is to determine the nature of a space-occupying lesion. The conventional transthoracic echocardiogram (TTE) is the preferred method for the diagnosis of cardiac space-occupying lesions as it can reveal the baseline information. For patients with poor conditions, however, TTE cannot clearly display the boundary, it has a limited role in determining the nature of the lesions.

Patient Concerns: A 47-year-old woman presented with intermittent fever for 7 days and chest distress/shortness of breath for 5 days.

Diagnosis: In our current case, we inferred the nature of space-occupying lesions in the left atrium more accurately using transesophageal echocardiography (TEE) than TTE, which may offer diagnostic evidence for surgical treatment.

Interventions: The patient underwent surgical resection of the left atrial tumor and reconstruction of the left atrial wall. However, the patient's posterior lobe of the mitral valve was infiltrated by tumor, which was difficult to completely remove.

Outcomes: Echocardiography was performed 3 months after surgery and the tumor recurred in the posterior lobe of the mitral valve. Although almost all tumors have been removed by surgery, the average survival time is often less than 1 year, as it is difficult to completely remove and easy to relapse with poor prognosis.

Conclusion: Transesophageal echocardiography (TEE) plays a relatively more important role in the determination and differential diagnosis of cardiac space-occupying lesions.
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http://dx.doi.org/10.1097/MD.0000000000024033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969263PMC
March 2021

Correlation of Lgr5 expression with clinicopathological features of colorectal cancer and its diagnostic and prognostic values.

J BUON 2021 Jan-Feb;26(1):87-92

Hepatobiliary and Pancreatic Surgery, the second affiliated Hospital of Kunming Medical University, Kunming 650000, P.R. China.

Purpose: To investigate the relationship between Leucine-rich repeat G-protein coupled receptor 5 (Lgr5) expression and clinicopathological features of colorectal cancer and its diagnostic and prognostic values.

Methods: The cancer and adjacent tissues of 98 patients with colorectal cancer undergoing resection in Jiangsu Cancer Hospital from 2011 to 2013 were enrolled. The intestinal mucosal tissue of 50 healthy subjects was enrolled as a control group. Western blot was used to detect the expression level of Lgr5 in colorectal cancer, Kaplan-Meier method to analyze the correlation of Lgr5 expression with the 5-year survival rate, Cox regression to analyze prognostic risk factors for the patients, and receiver operating characteristics (ROC) curve to analyze the diagnostic value of Lgr5 of the disease.

Results: The expression level of Lgr5 in the intestinal mucosal and adjacent tissues was significantly lower than that in the cancer tissue (p<0.05). The 5-year survival in the Lgr5 low expression group was higher than that in the Lgr5 high expression group (p=0.002). Lgr5 was an independent risk factor for the prognosis of colorectal cancer. The sensitivity, specificity and the area under the curve (AUC) of Lgr5 were 90.00%, 79.59% and 0.880, respectively (p<0.001).

Conclusion: Patients with a low 5-year survival rate have a high expression of Lgr5, which is closely related to the clinical staging, differentiation, depth of infiltration, lymph node metastasis, vascular invasion, liver metastasis and distant metastasis. Lgr5 is an independent prognostic risk factor for the patients and a better indicator for the diagnosis of colorectal cancer.
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March 2021

CAR T cells targeting CD13 controllably induce eradication of acute myeloid leukemia with a single domain antibody switch.

Leukemia 2021 Mar 12. Epub 2021 Mar 12.

Department of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

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http://dx.doi.org/10.1038/s41375-021-01208-2DOI Listing
March 2021

New ribotype from ST11 group revealed higher pathogenic ability than RT078.

Emerg Microbes Infect 2021 Dec;10(1):687-699

Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Yunnan Innovation Team of Standardization and Application Research in Tree Shrew, Kunming, China.

is the predominant antibiotic-associated enteropathogen associated with diarrhoea or pseudomembranous colitis in patients worldwide. Previously, we identified RT078 isolates (CD21062) from elderly patients in China, including two new ribotype strains (CD10010 and CD12038) belonging to the ST11 group, and their genomic features were also investigated. This study compared sporulation, spore germination, toxin expression, flagellar characteristics, and adhesion among these strains in vitro and analysed their pathogenic ability in vivo using animal models. The results showed sporulation and spore germination did not significantly differ among the three strains. CD10010 and CD12038 showed higher transcriptional levels of toxins until 48 h; thereafter, the transcriptional levels of toxins remained constant among RT078, CD10010, and CD12038. RT078 showed a loss of flagellum and its related genes, whereas CD12038 showed the highest motility in vitro. Both CD10010 and CD12038 initially showed phase OFF, and the flagellar switch reversed to phase ON after 48 h in swim agar. Flagellar proteins and toxins were both upregulated when phase OFF changed to phase ON status, enhancing their pathogenic ability. CD12038 showed the highest adhesion to Hep-2 cells. Histopathology and inflammation scores demonstrated that CD12038 caused the most severe tissue damage and infection in vivo. The new ribotype strains, particularly CD12038, exhibit higher pathogenic ability than the typical RT078 strain, both in vitro and in vivo. Therefore, more attention should be paid to this new strain in epidemiological research; further studies are warranted.
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http://dx.doi.org/10.1080/22221751.2021.1900748DOI Listing
December 2021

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Regenerative Potential and Challenges.

Biology (Basel) 2021 Feb 25;10(3). Epub 2021 Feb 25.

Faculty of Pharmacy, AIMST University, Kedah 08100, Malaysia.

Evidence suggests that stem cells exert regenerative potential via the release of extracellular vesicles. Mesenchymal stem cell extracellular vesicles (MSCEVs) offer therapeutic benefits for various pathophysiological ailments by restoring tissues. Facts suggest that MSCEV action can be potentiated by modifying the mesenchymal stem cells culturing methodology and bioengineering EVs. Limited clinical trials of MSCEVs have questioned their superiority, culturing quality, production scale-up and isolation, and administration format. Translation of preclinically successful MSCEVs into a clinical platform requires paying attention to several critical matters, such as the production technique, quantification/characterization, pharmacokinetics/targeting/transfer to the target site, and the safety profile. Keeping these issues as a priority, the present review was designed to highlight the challenges in translating preclinical MSCEV research into clinical platforms and provide evidence for the regenerative potential of MSCEVs in various conditions of the liver, kidney, heart, nervous system, bone, muscle, cartilage, and other organs/tissues.
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http://dx.doi.org/10.3390/biology10030172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996168PMC
February 2021

Engineering extracellular vesicles with platelet membranes fusion enhanced targeted therapeutic angiogenesis in a mouse model of myocardial ischemia reperfusion.

Theranostics 2021 6;11(8):3916-3931. Epub 2021 Feb 6.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai 200032, China.

Therapeutic angiogenesis is one promising strategy for the treatment of ischemic heart disease, which is the leading cause of death globally. In recent years, extracellular vesicles (EVs) have quickly gained much attention as a cell-free approach to stimulate angiogenesis. However, clinical applications of EVs are limited by their insufficient targeting capability. Herein, we introduce a method to enhance therapeutic angiogenesis based on platelet membrane-engineered EVs.

Methods: Platelet-mimetic EVs (P-EVs) were fabricated by fusing the membranes of EVs with platelet membranes by extrusion. A mouse model of myocardial ischemia reperfusion (MI/R) was established and injected with PBS, EVs, and P-EVs to evaluate their targeting ability and therapeutic angiogenesis efficacy.

Results: P-EVs inherited the adhesive proteins and natural targeting ability to injured vasculature of platelets and retained the pro-angiogenic potential of EVs. In the MI/R model, P-EVs preferentially accumulated in the injured endothelium of the ischemic hearts and enhanced the angiogenesis potency of EVs.

Conclusions: This engineering strategy to modify pre-isolated EVs with platelet membranes by membrane fusion bestows EVs with the targeting ability of platelets and offers an exciting opportunity to design other targeted EVs fused with cell membranes from different sources for therapeutic angiogenesis.
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http://dx.doi.org/10.7150/thno.52496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914364PMC
February 2021

mutations are associated with favorable outcomes to immune checkpoint inhibitors across multiple cancer types.

J Immunother Cancer 2021 Mar;9(3)

Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, USA

Background: Low-density lipoprotein receptor-related protein 1b (encoded by ) is a putative tumor suppressor, and preliminary evidence suggests mutated cancers may have improved outcomes with immune checkpoint inhibitors (ICI).

Methods: We conducted a multicenter, retrospective pan-cancer analysis of patients with alterations treated with ICI at Duke University, Johns Hopkins University (JHU) and University of Michigan (UM). The primary objective was to assess the association between overall response rate (ORR) to ICI and pathogenic or likely pathogenic (P/LP) alterations compared with variants of unknown significance (VUS). Secondary outcomes were the associations with progression-free survival (PFS) and overall survival (OS) by status.

Results: We identified 101 patients (44 Duke, 35 JHU, 22 UM) with alterations who were treated with ICI. The most common tumor types by alteration (P/LP vs VUS%) were lung (36% vs 49%), prostate (9% vs 7%), sarcoma (5% vs 7%), melanoma (9% vs 0%) and breast cancer (3% vs 7%). The ORR for patients with P/LP versus VUS alterations was 54% and 13%, respectively (OR 7.5, 95% CI 2.9 to 22.3, p=0.0009). P/LP alterations were associated with longer PFS (HR 0.42, 95% CI 0.26 to 0.68, p=0.0003) and OS (HR 0.62, 95% CI 0.39 to 1.01, p=0.053). These results remained consistent when excluding patients harboring microsatellite instability (MSI) and controlling for tumor mutational burden (TMB).

Conclusions: This multicenter study shows significantly better outcomes with ICI therapy in patients harboring P/LP versus VUS alterations, independently of TMB/MSI status. Further mechanistic and prospective validation studies are warranted.
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http://dx.doi.org/10.1136/jitc-2020-001792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929846PMC
March 2021

A Novel Insight Into Fecal Occult Blood Test for the Management of Gastric Cancer: Complication, Survival, and Chemotherapy Benefit After R0 Resection.

Front Oncol 2020 11;10:526746. Epub 2021 Feb 11.

Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Background: Previous studies have shown that the all-cause mortality and non-colorectal cancer mortality of patients with fecal occult blood test (FOBT) positivity are significantly increased, implying that FOBT results may have more prognostic value.

Methods: Retrospective analysis was performed for gastric cancer (GC) patients who underwent R0 gastrectomy from July 2007 to July 2014 at our hospital. Propensity score matching (PSM) was used to reduce confounding bias and a computerized technique for the nearest available score matching without replacement was applied. The cumulative survival rate was calculated using the Kaplan-Meier method and a log-rank test. Cox proportional hazards regression and logistic regression was used to determine the independent prognostic factors associated with survival and postoperative complications, respectively. The expression level of tumor-associated macrophages (TAMs) and proinflammatory cytokines (TNF-α, IL-6) were evaluated by immunohistochemical (IHC).

Results: A total of 3,003 patients were included and 246 patients (8.2%) were in preoperative FOBT positive status. There was no significant difference in demographic data between preoperative FOBT positive and negative group after a 1:4 PSM. The overall postoperative complications, major complications, and anastomotic leakage were significantly higher in the preoperative FOBT-positive group than in the preoperative FOBT-negative group. Moreover, preoperative FOBT-positivity was an independent risk factor for 5-year overall survival (OS) (HR: 1.32, p = 0.005). For stage II/III patients, the postoperative adjuvant chemotherapy (PAC) benefit was found in preoperative FOBT-negative group (5-year OS: 49.9 . 36.8%, p = 0.001), whereas the PAC benefit was lost in preoperative FOBT-positive groups (5-year OS: 40.8 . 37.7% p = 0.896). Finally, IHC found that preoperative FOBT-positivity in patients was significantly associated with higher TAMs infiltration and higher expression of IL-6 and TNF-α in tumor tissues than in the preoperative FOBT-negative group.

Conclusion: As a simple and low-cost method, preoperative FOBT results can predict both complications and survival after R0 gastrectomy for GC. More importantly, stage II/III GC patients with FOBT-positive seem not benefit from PAC alone. Further exploration is warranted.
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http://dx.doi.org/10.3389/fonc.2020.526746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905191PMC
February 2021

Waltheria indica is a New Host of Phytoplasma Belongs to 16SrI-B Subgroup Associated with Virescence Symptoms in China.

Plant Dis 2021 Feb 25. Epub 2021 Feb 25.

Coconut Research Institute, Plant Protection, Wenqing Avenue, NO.496, Coconut Research Institute, Wenchang City, Hainan Province, China, 571339;

Waltheria indica L. is a kind of medicinal plants belonging to the family of Sterculiaceae distributed in China, which extracts with many active compounds used for treatment of rheumatism and sore pains (Hua et al., 2019). During September to November 2020, the plants showing abnormal symptoms including floral virescence, leaf chlorosis and leaflet, as shown in Fig.1, were found in Dingan county of Hainan province, China, with about 70% incidence. The disease symptoms which were suspected to be infected by the phytoplasma, a phloem-limited cell-wall-less prokaryotic pathogen could not be cultured in vitro, severely impacted Waltheria indica growth resulting in financial loss and ecological damage in the location. For identification of the causal pathogen, the total DNA of symptom or symptomless Waltheria indica samples were extracted using 0.10 g fresh plant tissues using CTAB method. PCR reactions were performed using primers R16mF2/R16mR1 (Lee et al., 1993) and AYgroelF/AYgroelR (Mitrović et al., 2011) specific for phytoplasma 16S rRNA and groEL gene fragments. The target productions of the two gene fragments of phytoplasma were detected in the DNA from four symptomatic plant samples whereas not in the DNA from the symptomless plant samples. The PCR productions were sequenced and the data were deposited in GenBank. The two gene fragments of the DNA extracted from the symptom plant samples were all identical, with the length of 1340 bp 16S rRNA (GenBank accession: MW353909) and 1312 bp groEL (MW353709) gene sequence fragments, putatively encoding 437 (groEL) amino acids sequence. The phytoplasma strain was named as Waltheria indica virescence (WiV) phytoplasma, WiV-hnda strain. A Blast search based on the 16S rRNA gene fragment of WiV-hnda phytoplasma strain revealed the highest level of sequence identities (99.85%) with that of 16SrI aster yellows group members (16SrI-B subgroup), such as Onion yellows phytoplasma strain OY-M (AP006628) from Japan (Oshima et al., 2004); Periwinkle virescence phytoplasma strain PeV-hnhk (KP662136), Chinaberry witches'-broom phytoplasma strain CWB-hnsy1 (KP662119) and CWB-hnsy2 (KP662120), all the strains from Hainan island of China (Yu et al., 2017). A Blast search based on the groEL gene sequence fragment of WiV-hnda indicated 99.92% sequence identity with that of 16SrI aster yellows group members (16SrI-B subgroup) such as Onion yellows phytoplasma strain OY-M (AP006628). Homology and phylogenetic analysis by DNAMAN 5.0 and MEGA 7.0 software indicated that the phytoplasma strains of WiV-hnda, OY-M, PeV-hnhk, CWB-hnsy1 and CWB-hnsy2 were clustered into one clade based on the 16S rRNA gene fragments. WiV-hnda, OY-M and Aster yellow witches'-broom (AYWB) (CP000061) phytoplasma strains were clustered into one clade based on the groEL gene fragments. To our knowledge, this was the first time that Waltheria indica virescence disease induced by 16SrI-B subgroup phytoplasma strain was reported in China. Genetic analysis showed that WiV-hnda was closely related to the phytoplasma strains causing Onion yellows in Japan, Periwinkle virescence and Chinaberry witches'-broom disease in China.
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http://dx.doi.org/10.1094/PDIS-12-20-2762-PDNDOI Listing
February 2021

Retraction notice to "Effluent containing Rubrivivax gelatinosus promoting the yield, digestion system, disease resistance, mTOR and NF-kB signaling pathway, intestinal microbiota and aquaculture water quality of crucian carp" [Fish & Shellfish Immunology 94 (2019) 166-174].

Fish Shellfish Immunol 2021 Apr 15;111:229. Epub 2021 Feb 15.

School of Environment and Resources, Dalian Minzu University, Dalian, 116600, China; School of Resources and Environment, Northeast Agricultural University, Harbin, 150030, China.

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http://dx.doi.org/10.1016/j.fsi.2021.02.008DOI Listing
April 2021

Retraction notice to "Regulation of the disease resistance and mTOR and NF-kB signaling pathway of Tilapia mossambica by Rhodopseudomonas capsulatus wastewater treatment" [Fish & Shellfish Immunol. 94 (2019) 697-704].

Fish Shellfish Immunol 2021 Apr 15;111:230. Epub 2021 Feb 15.

School of Environment and Resources, Dalian Minzu University, Dalian, 116600, China; School of Resources and Environment, Northeast Agricultural University, Harbin, 150030, China.

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http://dx.doi.org/10.1016/j.fsi.2021.02.009DOI Listing
April 2021

Polymorphisms in the DC-SIGN gene and their association with the severity of hand, foot, and mouth disease caused by enterovirus 71.

Arch Virol 2021 Apr 15;166(4):1133-1140. Epub 2021 Feb 15.

Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.

Severe hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection is associated with high mortality and disability. DC-SIGN, a receptor for EV71, is widely distributed in dendritic cells and may influence the severity of HFMD caused by EV71 infection. This observational study attempts to explore whether single-nucleotide polymorphisms (SNPs) in DC-SIGN are related to the severity of EV71-associated HFMD. Based on linkage disequilibrium and functional predictions, two DC-SIGN SNPs were selected and tested to explore their potential association with the severity of HFMD caused by EV71 infection. Two hundred sixteen Han Chinese children with HFMD caused by EV71 were enrolled to obtain clinical data, including the severity of HFMD, serum DC-SIGN levels, and DC-SIGN SNPs. We found a significant association between the rs7248637 polymorphism (A vs. G: OR = 0.644, 95% CI = 0.515-0.806) and the severity of HFMD caused by EV71 infection, as well as the rs4804800 polymorphism (A vs. G: OR = 1.539, 95% CI =1.229-1.928). These two DC-SIGN SNPs may have an effect on the severity of HFMD caused by EV71 infection.
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http://dx.doi.org/10.1007/s00705-021-04991-6DOI Listing
April 2021

Dedifferentiated chondrsarcoma: a clinicopathologic analysis of 25 cases.

BMC Musculoskelet Disord 2021 Feb 15;22(1):189. Epub 2021 Feb 15.

Department of Radiology, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China.

Background: To investigate the clinical, imaging and pathological features of dedifferentiated chondrosarcoma for better diagnosis.

Methods: Patients who had been confirmed to have dedifferentiated chondrosarcoma were enrolled in this study and analyzed in the clinical, imaging and pathological data.

Results: Twenty-five patients had pathologically confirmed dedifferentiated chondrosarcoma including 15 males and 10 females with an age range of 24-74 (median 58, interquartile range 49-65). Ten patients had the tumor at the femur, four at the ilium, two at the humerus, two at the tibia, two at cotyle, and one at each of the following locations: scapula, sacrum, rib, pubic branch, and calcaneus. Twenty-one patients had local pain and a soft tissue mass while the other four patients had only local pain without a soft tissue mass. Four patients had pathological fractures. Imaging showed extensive bone destruction with calcification inside the lesion and possible pathological fractures. On gross observation of the specimen, the chondrosarcoma components were usually located inside the bone, and the dedifferentiated sarcoma components were mainly located outside the bone. Microscopy showed the dedifferentiated tumor had two components: well-differentiated chondrosarcoma and poorly differentiated non-chondral sarcoma including malignant fibrous histiocytoma in eleven cases, osteosarcoma in ten cases, fibrosarcoma in two, liomyosarcoma in one, and lipoblastoma in the remaining one.. Followed up from 3 moths to 60 months (mean 15.6), eight patients died with a survival time of 10-23 months (mean 16), and the other 17 patients survived with the survival duration from three to 60 months (15).

Conclusion: Dedifferentiated chondrosarcoma is a fatal disease with multiple components, and most of the cases have dual morphological and imaging features of chondrosarcoma and non-chondrosarcoma. The imaging presentations are primarily of common central chondrosarcoma, combined with cortical destruction, soft tissue mass, and pathological fractures.
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http://dx.doi.org/10.1186/s12891-021-04053-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885579PMC
February 2021

-3 Polyunsaturated Fatty Acids Facilitate the Repair of Peripheral Nerve Defects with Chemically Extracted Acellular Allograft in Rats.

Biomed Res Int 2021 26;2021:2504276. Epub 2021 Jan 26.

Second Affiliated Hospital of Nan Hua University, No. 35 Jiefang Road, Zhengxiang District, Hengyang City, Hunan Province 421001, China.

Acellular allograft (ACA) improves the repair and reconstruction of long peripheral nerve defects. -3 Polyunsaturated fatty acids (PUFAs) carry a neuroprotective potential, and their effects on ACA bridging were elucidated. Thirty rats with long gap sciatic nerve defects (15 mm long) were randomly divided into three groups ( = 10): ACA, ACA + PUFAs, and autograft (AU). Limb condition, wet weight of tibialis anterior muscle (TAM), nerve electrophysiology, S-100, horseradish peroxidase (HRP), and percentage of splenic CD4+ and CD8 + T-lymphocytes were evaluated for 12 weeks after the operation. Rats in the AU and ACA + PUFA groups showed superior condition in affected limbs compared to the ACA group. At 12 wk after surgery, the wet weight of TAM in the ACA + PUFA group was higher than that in the ACA group (0.4519 ± 0.1185 vs. 0.3049 ± 0.1272; < 0.01) but lower than that in the AU group (0.4519 ± 0.1185, 0.5628 ± 0.0092; < 0.05). In all the three groups, sole irritation elicited withdrawal reflex, and S-100 staining was detected in plantar skin. Moreover, horseradish peroxidase staining was overt in both the ventral horn and dorsal root ganglion of the spinal cord. Nerve conduction velocity (m/s), amplitude of action potential (mV), or somatosensory evoked potentials in ACA + PUFAs (28.81 ± 1.04, 2.20 ± 0.27, 6.98 ± 0.29) were significantly different from that in the AU (35.71 ± 1.28, 1.81 ± 0.19, 8.15 ± 0.52; < 0.05) and ACA (20.03 ± 1.94, 2.95 ± 0.36, 5.22 ± 0.53; < 0.01) groups. The percentages of splenic CD4+ and CD8+ cells were similar among the three groups. Omega-3 PUFAs improve the bridging effect of ACA on long gap peripheral nerve defects by promoting neuroprotection without arousing an immune response.
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http://dx.doi.org/10.1155/2021/2504276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857881PMC
January 2021

Facile route to bulk ultrafine-grain steels for high strength and ductility.

Nature 2021 02 10;590(7845):262-267. Epub 2021 Feb 10.

Department of Materials Science and Engineering, The University of Sheffield, Sheffield, UK.

Steels with sub-micrometre grain sizes usually possess high toughness and strength, which makes them promising for lightweighting technologies and energy-saving strategies. So far, the industrial fabrication of ultrafine-grained (UFG) alloys, which generally relies on the manipulation of diffusional phase transformation, has been limited to steels with austenite-to-ferrite transformation. Moreover, the limited work hardening and uniform elongation of these UFG steels hinder their widespread application. Here we report the facile mass production of UFG structures in a typical Fe-22Mn-0.6C twinning-induced plasticity steel by minor Cu alloying and manipulation of the recrystallization process through the intragranular nanoprecipitation (within 30 seconds) of a coherent disordered Cu-rich phase. The rapid and copious nanoprecipitation not only prevents the growth of the freshly recrystallized sub-micrometre grains but also enhances the thermal stability of the obtained UFG structure through the Zener pinning mechanism. Moreover, owing to their full coherency and disordered nature, the precipitates exhibit weak interactions with dislocations under loading. This approach enables the preparation of a fully recrystallized UFG structure with a grain size of 800 ± 400 nanometres without the introduction of detrimental lattice defects such as brittle particles and segregated boundaries. Compared with the steel to which no Cu was added, the yield strength of the UFG structure was doubled to around 710 megapascals, with a uniform ductility of 45 per cent and a tensile strength of around 2,000 megapascals. This grain-refinement concept should be extendable to other alloy systems, and the manufacturing processes can be readily applied to existing industrial production lines.
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http://dx.doi.org/10.1038/s41586-021-03246-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888382PMC
February 2021

Using solenoid as multipurpose tool for measuring beam parameters.

Rev Sci Instrum 2021 Jan;92(1):013301

Department of Physics and Astronomy, Stony Brook University, Stony Brook, New York 11794, USA.

Solenoids are frequently used for focusing low-energy beams. In this paper, we show how they can serve as multipurpose diagnostics tools to measure various beam parameters, including energy, emittance, the second moments of the transverse distribution, and the beam position and angle with respect to the solenoid's axis. The energy measurement is based on rotation of the plane of the transverse motion, as opposed to generating dispersion with a dipole. Measurement of the beam trajectory with respect to the solenoid axis is done by analyzing the beam orbit downstream of the solenoid while varying its current. The second moments are calculated by analyzing the beam image on a profile monitor while accounting for the beam rotation caused by the solenoid. We describe in detail the corresponding procedures and the experimental results of these measurements.
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http://dx.doi.org/10.1063/5.0015618DOI Listing
January 2021

Comprehensive Review of Methodology to Detect Reactive Oxygen Species (ROS) in Mammalian Species and Establish Its Relationship with Antioxidants and Cancer.

Antioxidants (Basel) 2021 Jan 18;10(1). Epub 2021 Jan 18.

Faculty of Pharmacy, AIMST University, Kedah 08100, Malaysia.

Evidence suggests that reactive oxygen species (ROS) mediate tissue homeostasis, cellular signaling, differentiation, and survival. ROS and antioxidants exert both beneficial and harmful effects on cancer. ROS at different concentrations exhibit different functions. This creates necessity to understand the relation between ROS, antioxidants, and cancer, and methods for detection of ROS. This review highlights various sources and types of ROS, their tumorigenic and tumor prevention effects; types of antioxidants, their tumorigenic and tumor prevention effects; and abnormal ROS detoxification in cancer; and methods to measure ROS. We conclude that improving genetic screening methods and bringing higher clarity in determination of enzymatic pathways and scale-up in cancer models profiling, using omics technology, would support in-depth understanding of antioxidant pathways and ROS complexities. Although numerous methods for ROS detection are developing very rapidly, yet further modifications are required to minimize the limitations associated with currently available methods.
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http://dx.doi.org/10.3390/antiox10010128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831054PMC
January 2021

Stacking Fault Driven Phase Transformation in CrCoNi Medium Entropy Alloy.

Nano Lett 2021 Feb 19;21(3):1419-1426. Epub 2021 Jan 19.

Department of Physics, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.

Phase transformation is an effective means to increase the ductility of a material. However, even for a commonly observed face-centered-cubic to hexagonal-close-packed (-to-) phase transformation, the underlying mechanisms are far from being settled. In fact, different transformation pathways have been proposed, especially with regard to nucleation of the phase at the nanoscale. In CrCoNi, a so-called medium-entropy alloy, an -to- phase transformation has long been anticipated. Here, we report an loading study with neutron diffraction, which revealed a bulk -to- phase transformation in CrCoNi at 15 K under tensile loading. By correlating deformation characteristics of the phase with the development of the phase, it is shown that the nucleation of the phase was triggered by intrinsic stacking faults. The confirmation of a bulk phase transformation adds to the myriads of deformation mechanisms available in CrCoNi, which together underpin the unusually large ductility at low temperatures.
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http://dx.doi.org/10.1021/acs.nanolett.0c04244DOI Listing
February 2021

Research advances for exosomal miRNAs detection in biosensing: From the massive study to the individual study.

Biosens Bioelectron 2021 Apr 31;177:112962. Epub 2020 Dec 31.

School of Basic Medicine, Guangdong Medical University, Dongguan, 523808, PR China; School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, PR China. Electronic address:

Exosomal miRNAs (exo-miRNAs) derived from cancer cell play a vital role in cancer development and can be considered as a potential biomarker for cancer diagnostic. However, the shortage of sensitive preparatory and analytical technologies limits their clinical applications. Thus, sensitive and reliable sensing of exo-miRNAs is essential in medical diagnostics. Mounting number of biosensor strategies are thus actively being proposed to deal with these challenges, including nanoparticle, isothermal amplification, and microfluidic chips. Moreover, some delivery strategies have been found for individual exo-miRNAs detection, such as membrane fusion, nano-sized probe and membrane denatured. Therefore, we summarize and discuss the recent progress of emerging biosensor assays for sensing exo-miRNAs. In addition, challenges and outlook for exo-miRNAs detection are considered.
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http://dx.doi.org/10.1016/j.bios.2020.112962DOI Listing
April 2021

Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation.

Cell Death Dis 2021 Jan 12;12(1):78. Epub 2021 Jan 12.

Department of Cardiology, Zhongshan Hospital, Fudan University; Shanghai Institute of Cardiovascular Diseases; National Clinical Research Center for Interventional Medicine, Shanghai, China.

Coronary microembolization (CME), a common reason for periprocedural myocardial infarction (PMI), bears very important prognostic implications. However, the molecular mechanisms related to CME remain largely elusive. Statins have been shown to prevent PMI, but the underlying mechanism has not been identified. Here, we examine whether the NLRP3 inflammasome contributes to CME-induced cardiac injury and investigate the effects of statin therapy on CME. In vivo study, mice with CME were treated with 40 mg/kg/d rosuvastatin (RVS) orally or a selective NLRP3 inflammasome inhibitor MCC950 intraperitoneally (20 mg/kg/d). Mice treated with MCC950 and RVS showed improved cardiac contractile function and morphological changes, diminished fibrosis and microinfarct size, and reduced serum lactate dehydrogenase (LDH) level. Mechanistically, RVS decreased the expression of NLRP3, caspase-1, interleukin-1β, and Gasdermin D N-terminal domains. Proteomics analysis revealed that RVS restored the energy metabolism and oxidative phosphorylation in CME. Furthermore, reduced reactive oxygen species (ROS) level and alleviated mitochondrial damage were observed in RVS-treated mice. In vitro study, RVS inhibited the activation of NLRP3 inflammasome induced by tumor necrosis factor α plus hypoxia in H9c2 cells. Meanwhile, the pyroptosis was also suppressed by RVS, indicated by the increased cell viability, decreased LDH and propidium iodide uptake in H9c2 cells. RVS also reduced the level of mitochondrial ROS generation in vitro. Our results indicate the NLRP3 inflammasome-dependent cardiac pyroptosis plays an important role in CME-induced cardiac injury and its inhibitor exerts cardioprotective effect following CME. We also uncover the anti-pyroptosis role of RVS in CME, which is associated with regulating mitochondrial ROS.
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http://dx.doi.org/10.1038/s41419-021-03389-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804109PMC
January 2021

LncRNA DHRS4-AS1 Inhibits the Stemness of NSCLC Cells by Sponging miR-224-3p and Upregulating TP53 and TET1.

Front Cell Dev Biol 2020 23;8:585251. Epub 2020 Dec 23.

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. This study aimed to examine the roles of DHRS4-AS1/miR-224-3p signaling in the cancer cell stemness of NSCLC. Real-time PCR showed that DHRS4-AS1 was downregulated in cancerous tissues, and bioinformatics analysis revealed that high DHRS4-AS1 expression indicated a good prognosis for NSCLC patients. Sphere and colony formation assays showed that DHRS4-AS1 overexpression significantly suppressed NSCLC cell colony formation and stem cell-like properties. DHRS4-AS1 also abrogated the expression of OCT4, SOX2, CD34, and CD133, markedly inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors, N-cadherin, ZEB1, and Vimentin, and increased E-cadherin expression in spheres. Furthermore, luciferase reporter assays and real-time PCR analysis demonstrated that DHRS4-AS1 and miR-224-3p were antagonistically repressed in NSCLC cells. RNA immunoprecipitation (RIP) analysis revealed that DHRS4-AS1 interacted with miR-224-3p. DHRS4-AS1 partially reversed the miR-224-3p-decreased TP53 and TET1, resulting in the inhibition of tumor growth . Finally, TP53 and TET1 were antagonistically regulated by DHRS4-AS1 and miR-224-3p in NSCLC cells. In conclusion, TP53- and TET1-associated DHRS4-AS1/miR-224-3p axis is an essential mechanism by which NSCLC modulates cancer cell stemness.
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http://dx.doi.org/10.3389/fcell.2020.585251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786137PMC
December 2020