Publications by authors named "Ya Cao"

346 Publications

Recent advances in cell membrane camouflage-based biosensing application.

Biosens Bioelectron 2021 Dec 11;194:113623. Epub 2021 Sep 11.

Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, PR China; Center for Molecular Recognition and Biosensing, Shanghai Engineering Research Center of Organ Repair, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China. Electronic address:

Cell membrane, a semi-permeable membrane composed of phospholipid bilayers, is a natural barrier to prevent extracellular substances from freely entering the cell. Cell membrane with selective permeability and fluidity ensures the relative stability of the intracellular environment and enables various biochemical reactions to smoothly operate in an orderly manner. Inspired by the natural composition and transport process, various cell membranes and synthetic bionic films as the mimics of cell membranes have emerged as appealing camouflage materials for biosensing applications. The membranes are devoted to surface modification and substance delivery, and realize the detection or in situ analysis of multiple biomarkers, such as glucose, nucleic acids, virus, and circulating tumor cells. In this review, we summarize the recent advances in cell membrane camouflage-based biosensing applications, mainly focusing on the use of the membranes extracted from natural cells (e.g., blood cells and cancer cells) as well as biomimetic membranes. Materials and surfaces camouflaged with cell membranes are shown to have superior stability and biocompatibility as well as intrinsic properties of original cells, which greatly facilitate their use in biosensing. In specific, camouflage with blood cell membranes bestows low immunogenicity and prolonged blood circulation time, camouflage with cancer cell membranes provides homologous targeting ability, and camouflage with biomimetic membranes endows considerable plasticity for functionalization. Further research is expected to focus on the deeper understanding of cell-specific properties of membranes and the exploration of hybrid membranes, which might provide new development opportunities for cell membrane camouflage-based biosensing application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2021.113623DOI Listing
December 2021

Investigation on the Effects of MXene and β-Nucleating Agent on the Crystallization Behavior of Isotactic Polypropylene.

Polymers (Basel) 2021 Aug 31;13(17). Epub 2021 Aug 31.

State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, China.

The effects of MXene on the crystallization behavior of β-nucleated isotactic polypropylene (iPP) were comparatively studied. The commonly used MXene TiCT was prepared by selective etching and its structure and morphology were studied in detail. Then MXene and a rare earth β-nucleating agent (NA) WBG-II were nucleated with iPP to prepare samples with different polymorphic compositions. The crystallization, melting behavior, and morphologies of neat iPP, iPP/MXene, iPP/WBG-II, and iPP/MXene/WBG-II were comparatively studied. The crystallization behavior analysis reveals that a competitive relationship exists between MXene and WBG-II when they were compounded as α and β nucleating agents. In the system, the β-nucleation efficiency (NE) of WBG-II is higher than α-NE of MXene. The β-phase has relatively low thermal stability and would transform to α-phase when cooled below a critical temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym13172931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434311PMC
August 2021

In Situ Programmable DNA Circuit-Promoted Electrochemical Characterization of Stemlike Phenotype in Breast Cancer.

J Am Chem Soc 2021 Oct 8;143(39):16078-16086. Epub 2021 Sep 8.

Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China.

Breast cancer is one of the most common malignant diseases among women worldwide, and the existence of breast cancer stem cells is closely associated with poor outcomes. Herein, we report an electrochemical phenotyping method to characterize the stemlike phenotype in breast cancer, offering a low-cost but robust choice other than the highly expensive and experience-dependent flow cytometry. Specially, after immune-magnetic beads-assisted enrichment, an in situ programmable DNA circuit is designed using capture probes to bring in the toeholds for DNA assembly and effector probes to accelerate the removal of background signals. The electrochemical phenotyping method could sensitively determine breast cancer stem cells in a wide linear range and exhibit desirable accuracy and reliability. The method can not only monitor the phenotypic transition of breast cancer cells and the drug-reversed effect but also determinate stemlike phenotype in the mice bearing breast cancer xenograft tumor. Overall, the electrochemical phenotyping method may provide promising technical support for precise management of breast tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.1c06436DOI Listing
October 2021

Exploring Impacts of Hyper-Branched Polyester Surface Modification of Graphene Oxide on the Mechanical Performances of Acrylonitrile-Butadiene-Styrene.

Polymers (Basel) 2021 Aug 6;13(16). Epub 2021 Aug 6.

State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, China.

In this manuscript, the graphene oxide (GO) was modified by hyper-branched polyester (HBP). The effects of GO or modified GO (HBP-m-GO) on the mechanical performance and wearing properties were investigated. The results of X-ray photoelectron spectra (XPS), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM) revealed the successful grafting of HBP onto GO. The thermogravimetric analysis (TGA) indicated that the graft amount of HBP is calculated to be 9.6 wt%. The GO or HBP-m-GO was added into acrylonitrile-butadiene-styrene copolymer (ABS) to prepare the ABS/GO composites. The mechanical properties and wear performance of the composites were studied to comparatively study the impact of GO modification on the properties of the composites. The results revealed that the addition of GO has a significant effect on the mechanical properties of ABS, and when HBP-m-GO was added, the elastic modulus and tensile strength of ABS/HBP-m-GO increased evidently compared with ABS/GO. The tensile strength increased from 42.1 ± 0.6 MPa of pure ABS to 55.9 ± 0.9 MPa, up to 30%. Meanwhile, the elongation at break was significantly higher than ABS/GO to 20.1 ± 1.3%, slightly lower than that of pure ABS. For wear performance, the addition of raw GO decreased the friction coefficient, and when the HBP-m-GO was added, the friction coefficient of the ABS/HBP-m-GO dropped more evidently. Meanwhile, the weight loss during the wear test decreased evidently. The related mechanism was discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym13162614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399205PMC
August 2021

Effects of MXene on Nonisothermal Crystallization Kinetics of Isotactic Polypropylene.

ACS Omega 2021 Aug 22;6(30):19973-19982. Epub 2021 Jul 22.

State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, No. 24 South Section 1, Yihuan Road, 610065 Chengdu, China.

MXenes, a family of two-dimensional transition-metal carbides/nitrides, have attracted great attention and shown promising application in polymer composites. In this study, a typical MXene TiCT was prepared by selective etching. The structure and morphology of TiCT were studied by X-ray diffraction (XRD), scanning electron microscopy, and transmission electron microscopy, and the results proved that TiCT was successively fabricated. Then, TiCT /isotactic polypropylene composites with different TiCT dosages were fabricated, and the nonisothermal crystallization kinetics and melting behavior of the composites were investigated. The results indicated that when a small amount of TiCT was added, the crystallization parameters including the crystallization peak temperature and the crystallization rate increased, suggesting that crystallization was promoted. When the weight percentage of TiCT exceeded 1%, the crystallization parameters showed a reverse trend, suggesting that crystallization was hindered. The activation energy of composites with 0, 0.25, 0.5, and 1 wt % TiCT were calculated to be -164.5, -196.5, -193.8, and -147.95 kJ/mol, respectively, revealing that the crystallization of composites is concentration-dependent. The impact of TiCT dosage on the crystalline structure of the composites was studied using XRD. The related mechanism was proposed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.1c02970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340379PMC
August 2021

A novel preoperative predictive model of 90-day mortality after liver resection for huge hepatocellular carcinoma.

Ann Transl Med 2021 May;9(9):774

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education; Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Hepatectomy for huge hepatocellular carcinoma (HCC) (diameter ≥10 cm) is characterized by high mortality. This study aimed to establish a preoperative model to evaluate the risk of postoperative 90-day mortality for huge HCC patients.

Methods: We retrospectively enrolled 1,127 consecutive patients and prospectively enrolled 93 patients with huge HCC who underwent hepatectomy (training cohort, n=798; validation cohort, n=329; prospective cohort, n=93) in our institute. Based on independent preoperative predictors of 90-day mortality, we established a logistic regression model and visualized the model by nomogram.

Results: The 90-day mortality rates were 9.6%, 9.2%, and 10.9% in the training, validation, and prospective cohort. The α-fetoprotein (AFP) level, the prealbumin levels, and the presence of portal vein tumor thrombosis (PVTT) were preoperative independent predictors of 90-day mortality. A logistic regression model, AFP-prealbumin-PVTT score (APP score), was subsequently established and showed good performance in predicting 90-day mortality (training cohort, AUC =0.87; validation cohort, AUC =0.91; prospective cohort, AUC =0.93). Using a cut-off of -1.96, the model could stratify patients into low risk (≤-1.96) and high risk (>-1.96) with different 90-day mortality rates (~30% ~2%). Furthermore, the predictive performance for 90-day mortality and overall survival was significantly superior to the Child-Pugh score, the model of end-stage liver disease (MELD) score, and the albumin-bilirubin (ALBI) score.

Conclusions: The APP score can precisely predict postoperative 90-day mortality as well as long-term survival for patients with huge HCC, assisting physician selection of suitable candidates for liver resection and improving the safety and efficacy of surgical treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-7842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246173PMC
May 2021

Identification of two immune subtypes in osteosarcoma based on immune gene sets.

Int Immunopharmacol 2021 Jul 30;96:107799. Epub 2021 May 30.

Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China. Electronic address:

Osteosarcoma (OS) is a highly aggressive cancer with poor prognosis, which mainly occurs in teenagers. Recent studies have shown that tumor-infiltrating immune cells play an important role in the progression of OS. In the present study, we identified two immune subtypes of OS (referred to as high and low immune cell infiltration subtypes, respectively) based on immune-related gene sets using TARGET and GEO cohort datasets. Elevated immune scores, increased stromal scores, decreased tumor purities, and higher infiltration of CD8 + T cells and M1 macrophages were observed for the high immune cell infiltration subtype. Moreover, the high immune cell infiltration subtype was characterized by high expression of immune checkpoint molecules. Gene set enrichment analysis showed that "B cell receptor signaling pathway" and "T cell receptor signaling pathway" gene sets were enriched in the high immune cell infiltration subtype. In addition, patients in the high immune cell infiltration subtype had better prognosis than patients in the low immune cell infiltration subtype. Furthermore, differentially expressed genes were screened according to the two OS subtypes and a risk model was generated by multivariate Cox regression analysis to predict the prognosis of OS patients. These results in this study showed that OS patients could be divided into two immune subtypes and offered a novel two-gene risk signature to predict the prognosis of patients with OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2021.107799DOI Listing
July 2021

Effects of Hyperbranched Polyester-Modified Carbon Nanotubes on the Crystallization Kinetics of Polylactic Acid.

ACS Omega 2021 Apr 6;6(15):10362-10370. Epub 2021 Apr 6.

State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, China.

Poly-l-lactic acid (PLLA) is a prospective renewable and degradable material, but slow crystallization limits its processing and application. By dehydration condensation of hydroxyl-terminated hyperbranched resin (H202) and carboxylated carbon nanotubes (CNTs), a modified CNT, CNTs-H202, was obtained. Grafting was confirmed by Fourier transform infrared (FTIR) spectroscopy, and the grafting content was assessed by thermogravimetric analysis (TGA). Changes in surface atom content were explored by X-ray electron spectroscopy (XPS). Transmission electron microscopy (TEM) observed the increase of black dots on the surface of carbon nanotubes. PLLA/CNTs and PLLA/CNTs-H202 composites were prepared, and differential scanning calorimetry (DSC) was used to investigate the crystallization behavior of the composites. The results showed that during the cooling process, PLLA/CNTs-H202 had a larger crystalline full width at half-maximum (FWHM) compared with PLLA/CNTs and exhibited the ability to hinder chain segment movement during the subsequent reheating process. The crystallization activation energy was calculated by the Kissinger method, and it was found that the activation energy of the carbon tube increased slightly after grafting. Wide-angle X-ray diffraction (WAXD) once again proved the improvement of the crystallization ability. The results of polarized optical microscopy (PLOM) showed that the number of crystal nuclei increased and the crystal became smaller.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.1c00738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153785PMC
April 2021

Mechanistic Aspects Regarding the Ultraviolet Degradation of Polychlorinated Biphenyls in Different Media: Insights from Carbon and Chlorine Isotope Fractionation.

Environ Sci Technol 2021 06 18;55(11):7731-7740. Epub 2021 May 18.

State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China.

In this study, the carbon and chlorine isotope fractionation during ultraviolet-photolysis of polychlorinated biphenyls (PCBs, including PCB18, PCB77, PCB110, and PCB138) in n-hexane (Hex), methanol/water (MeOH/HO), and silica gel was first investigated to explore their mechanistic processes. We observed a significant variation in Λ (ε/ε) for the same PCBs in different photochemical systems, implying that PCB degradation processes in various photoreaction systems could differ. Although all substrates showed normal apparent carbon/chlorine kinetic isotope effects (C-/Cl-AKIE >1), the putative inverse C-AKIE of nondechlorinated pathways was suggested by C depletion of the average carbon isotope composition of PCB138 and corresponding dechlorinated products in MeOH/HO, which might originate from the magnetic isotope effect. Significant negative correlations were found between C-AKIE and relative disappearance quantum yields ("Φ") of ortho-dechlorinated substrates (PCB18, PCB110, and PCB138) in Hex and MeOH/HO. However, the C-AKIE and "Φ" of PCB77 (meta/para-dechlorinated congener) obviously deviated from the above correlations. Furthermore, significantly different product-related carbon isotope enrichment factors of PCB77 in Hex were found. These results demonstrated the existence of dechlorination position-specific and masking effects in carbon isotope fractionations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.1c00726DOI Listing
June 2021

TM2D1 contributes the epithelial-mesenchymal transition of hepatocellular carcinoma via modulating AKT/β-catenin axis.

Am J Cancer Res 2021 15;11(4):1557-1571. Epub 2021 Apr 15.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University Shanghai 200032, P. R. China.

Various epidemiology studies showed the correlation between Alzheimer's disease (AD) and low incidence of cancer. However, the etiology underlying etiology of AD-related carcinogenesis remains largely elusive. Our study focused on characterizing the role of TM2D1 (TM2 domain containing 1) in hepatocellular carcinoma. TM2D1 is also known as β-amyloid peptide binding protein and is critical to the pathogenesis of AD. We found that TM2D1 is increasingly expressed in HCC tumors relative to the peritumoral tissues of the matched tumors and high TM2D1 expression predicts unfavorable clinical outcomes. TM2D1 overexpression induced HCC cell proliferation, migration and invasion, which was related to the epithelial-mesenchymal transition (EMT) observed in these cells. Conversely, TM2D1 depletion led to opposite phenotype in HCC. Mechanistically, we found that TM2D1 promoted Akt and β-catenin hyper-activation, which corresponded with molecular marker change in EMT signaling pathway. Taken together, our results indicated that TM2D1 played an important role in the EMT process in HCC cells by activating AKT and β-catenin signaling and may become a promising therapeutic target in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085884PMC
April 2021

The complete mitochondrial genome of (Hemiptera: Pentatomidae) and phylogenetic analysis.

Mitochondrial DNA B Resour 2021 Apr 8;6(4):1326-1327. Epub 2021 Apr 8.

State Key Laboratory of Grassland Agro-Ecosystems, Lanzhou University, Lanzhou, China.

Here, we sequenced and annotated the complete mitochondrial genome (mitogenome) of (Hemiptera: Pentatomidae). This mitogenome was 15,118 bp long, comprising of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes ( and ) and a large non-coding control region. The mitogenome with an A + T content of 76.0%, presented a positive AT-skew (0.11) and a negative GC-skew (-0.13). Ten PCGs started with a typical ATN codon, two PCGs started with TTG (, ), whereas the remaining one used AAC (). All tRNAs had a typical secondary cloverleaf structure, except for which lacked the dihydrouridine arm. The Bayesian phylogenetic analysis based on mitogenomic data supported a sister relationship of and from the same tribe Nezarini and recovered a phylogeny of Pentatominae: (Menidini + (Strachiini + (Pentatomini + ((Cappaeini + Halyini) + (Eysarcorini + (Nezarini + Carpocori)))))).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2021.1909442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043517PMC
April 2021

A High-Accuracy Model Based on Plasma miRNAs Diagnoses Intrahepatic Cholangiocarcinoma: A Single Center with 1001 Samples.

Diagnostics (Basel) 2021 Mar 29;11(4). Epub 2021 Mar 29.

Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Objectives: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant cancer. More than 70% of patients are diagnosed at an advanced stage. The aim of this study was to evaluate the diagnostic value of plasma miR-21, miR-122, and CA19-9, hoping to establish a novel model to improve the accuracy for diagnosing iCCA.

Materials And Methods: Plasma miR-21 and miR-122 were detected in 359 iCCA patients and 642 controls (healthy, benign liver lesions, other malignant liver tumors). All 1001 samples were allocated to training cohort ( = 668) and validation cohort ( = 333) in a chronological order. A logistic regression model was applied to combine these markers. Area under the receiver operating characteristic curve (AUC) was used as an accuracy index to evaluate the diagnostic performance.

Results: Plasma miR-21 and miR-122 were significantly higher in iCCA patients than those in controls. Higher plasma miR-21 level was significantly correlated with larger tumor size ( = 0.030). A three-marker model was constructed by using miR-21, miR-122 and CA19-9, which showed an AUC of 0.853 (95% CI: 0.824-0.879; sensitivity: 73.0%, specificity: 87.4%) to differentiate iCCA from controls. These results were subsequently confirmed in the validation cohort with an AUC of 0.866 (0.825-0.901). The results were similar for diagnosing early (stages 0-I) iCCA patients (AUC: 0.848) and CA19-9 iCCA patients (AUC: 0.795).

Conclusions: We established a novel three-marker model with a high accuracy based on a large number of participants to differentiate iCCA from controls. This model showed a great clinical value especially for the diagnosis of early iCCA and CA19-9 iCCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11040610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066692PMC
March 2021

RIP3 mediates TCN-induced necroptosis through activating mitochondrial metabolism and ROS production in chemotherapy-resistant cancers.

Am J Cancer Res 2021 1;11(3):729-745. Epub 2021 Mar 1.

Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South University Changsha 410078, Hunan, PR China.

Resisting cell death is one of the hallmarks of cancer. Necroptosis is a form of non-caspase dependent necrotic cell death mediated by receptor-interacting protein kinase-1/3 (RIP1/3), which represents another mode of programmed cell death besides apoptosis. RIP3 also acts as an energy metabolism regulator associated with switching cell death from apoptosis to necroptosis. Trichothecin (TCN) is a sesquiterpenoid originating from endophytic fungi and shows potent anti-tumor bioactivity. Our current findings reveal that RIP3 mediates TCN-induced necroptosis through up-regulating and to promote mitochondria energy metabolism and ROS production. RIP3 might be involved in sensitizing tumor cells to chemotherapy induced by TCN. Therefore, activating RIP3 to initiate necroptosis contributes to the bioactivity of TCN. Moreover, TCN could be exploited for therapeutic gain through up-regulating RIP3 to sensitize cancer chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994173PMC
March 2021

[Progress on relationship between IL-23/IL-17 axis and inflammatory bowel disease].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Mar;37(3):271-277

Department of Immunology, School of Basic Medicine, Xi'an Medical University, Xi'an 710021, China.

Chronic inflammatory damage of intestinal mucosa is an important characteristic of inflammatory bowel disease (IBD). Studies have shown that the interleukin 23 (IL-23)/IL-17 axis is involved in intestinal mucosal inflammatory injury and plays a crucial role in the development and prognosis of IBD. IL-23 is one of the upstream molecules of IL-17, which can promote Th17 cell activation, proliferation and the secretion of inflammatory cytokines. Moreover, IL-23 is involved in the inflammatory response process of various immune cells such as neutrophils, macrophages, regulatory T cells (Tregs), the group 3 innate lymphocytes (ILC3) during IBD. Previous studies demonstrated that IL-23 and IL-17 increased in IBD, which lead to an imbalance between Tregs and auto-reactive T cells to exacerbate the inflammatory pathological damage of the intestinal mucosa. Notably, although IL-23/IL-17 is potential therapeutic target for inflammation-related diseases and anti-IL-23 strategies has proven to be effective in treating IBD, the strategy of blocking IL-17 to treat IBD has failed. Therefore, a deep understanding of the relationship between IL-17/IL-23 axis and IBD is necessary for the study of IBD treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2021

Gene Expression Profile and Prognostic Value of m6A RNA Methylation Regulators in Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2021 12;8:85-101. Epub 2021 Mar 12.

Department of Pathology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, People's Republic of China.

Background: N6-methyladenosine (m6A) RNA methylation is the most prevalent modification of mammalian RNA, and it is associated with tumorigenesis and cancer progression. Its regulation is mediated via m6A-related regulators, including "erasers," "readers," and "writers". The present study evaluated the expression profile, risk signature and prognostic value of 13 m6A regulators in hepatocellular carcinoma (HCC) using different datasets, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and clinical samples.

Methods: We used 374 HCC samples derived from the TCGA database, 569 HCC samples from 2 GEO datasets, and clinical tumour and nontumour tissues derived from 60 patients with HCC who underwent surgery in Xinqiao Hospital Chongqing to assess the gene expression profiles and prognostic values of m6A-related regulators in HCC.

Results: Eight of 13 core m6A-related regulators were overexpressed in all databases, including TCGA, GSE, clinical tumour and nontumour tissues of HCC. Two clusters (Cluster 1 and Cluster 2) were identified via consensus clustering. Cluster 2 was associated with poorer prognosis, higher tumour grade, higher AFP levels, and worse outcome compared to Cluster 1, which indicates that these m6A-related regulators are highly correlated with HCC malignancy. We performed survival analyses using the Log rank tests and a Cox regression model. Gene enrichment analysis was used to detect the related KEGG and GO pathways. We derived a prognostic risk signature using five selected m6A-related regulators.

Conclusion: Our work suggested that m6A-related regulators might be key participants in the tumour progression of HCC and potential biomarkers with prognostic value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JHC.S296438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966299PMC
March 2021

Relation of Decreased Functional Connectivity Between Left Thalamus and Left Inferior Frontal Gyrus to Emotion Changes Following Acute Sleep Deprivation.

Front Neurol 2021 26;12:642411. Epub 2021 Feb 26.

Department of Neurology, Secondary Medical Center, National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, Beijing, China.

The thalamus is a key node for sleep-wake pathway gate switching during acute sleep deprivation (ASD), and studies have shown that it plays a certain role in emotion changes. However, there are no studies on the association between the thalamus and emotion changes in ASD. In this study, we used resting-state functional magnetic resonance imaging (R-fMRI) to explore whether changes in the functional connections between the thalamus and other brain regions are related to emotion changes and further explored the function of the thalamus under total ASD conditions. Thirty healthy, right-handed adult men underwent emotional assessment according to the Profile of Mood States Scale and R-fMRI scans before and after ASD. The correlations between changes in functional connectivity between the thalamus and other brain regions and emotion changes were then studied. Positive emotions and psychomotor performance were reduced, and negative emotions were increased following ASD. The functional connections between the left thalamus and left middle temporal gyrus, left inferior frontal gyrus, right thalamus, right inferior temporal gyrus, left middle temporal pole gyrus, right calcarine, left cuneus, left rectus and left medial superior frontal gyrus were significantly altered. Decreased functional connectivity between left thalamus and left inferior frontal gyrus related to emotion changes following ASD. This study finds that functional changes in the thalamus are associated with emotion changes during ASD, suggesting that the left thalamus probably plays an essential role in emotion changes under ASD conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.642411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952868PMC
February 2021

Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication.

NPJ Precis Oncol 2021 Mar 2;5(1):14. Epub 2021 Mar 2.

Key Laboratory of Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.

p18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the protein stability of p18. In this paper, we identified CYLD as a deubiquitinase of p18, which binds to and removes the K48-linked polyubiquitylation chains conjugated onto p18, thus stabilizing the p18 protein. Loss of CYLD causes the degradation of p18 and induces the G1/S transition. Epstein-Barr virus (EBV), is the human oncovirus etiologically linked to nasopharyngeal carcinoma (NPC). Here we found that EBV drives a replication passive environment by deregulating the CYLD-p18 axis. Functionally, CYLD inhibits cell proliferation and tumorigenesis through p18 in vivo. Restoring CYLD prevents EBV induced viral replication and tumor growth. Collectively, our results identify CYLD directly stabilizes p18 to regulate the cellular G1/S transition. The reconstitution of CYLD-p18 axis could be a promising approach for EBV-positive cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41698-021-00153-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925679PMC
March 2021

Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF-kB signaling pathways synergistically.

Clin Transl Med 2021 02;11(2):e335

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Objective: Differentiation-inducing therapy for tumors is a strategy that aims to induce the differentiation and maturation of cancer stem cells (CSCs). The differentiation-inducing capacity of arsenic trioxide (ATO) in hepatocellular carcinoma (HCC) and the underlying mechanism were previously unknown.

Methods: In the present study, we explored the ATO-induced differentiation of CSCs in HCC by detecting the expression of CSC-related markers and tumorigenicity variation in vivo and in vitro. We developed a combined chemotherapeutic approach to HCC by characterizing the effects of combinatorial treatment with 5-fluorouracil (5-FU)/cisplatin and ATO in vitro and in patient-derived xenograft models. Changes in gene expression patterns were investigated by gene microarray analysis.

Results: ATO effectively induced differentiation of CSCs by downregulation of CSC-related genes and suppression of tumorigenicity capability. Combinatorial treatment with ATO and 5-FU/cisplatin significantly enhanced therapeutic effects in HCC cells compared with the treatment with 5-FU/cisplatin alone. Synergistic inhibition of the LIF/JAK1/STAT3 and NF-kB signaling pathways by ATO and 5-FU/cisplatin is a potential molecular mechanism underlying the differentiation effect.

Conclusions: ATO induced the differentiation of HCC CSCs and potentiated the cytotoxic effects of 5-FU/cisplatin through synergistic inhibition of the LIF/JAK1/STAT3 and NF-kB signaling pathways. These results offer new insights for the clinical treatment of HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ctm2.335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901720PMC
February 2021

()-Epigallocatechin-3-Gallate Inhibits EBV Lytic Replication via Targeting LMP1-Mediated MAPK Signal Axes.

Oncol Res 2021 Sep 17;28(7):763-778. Epub 2021 Feb 17.

Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South UniversityChangshaP.R. China.

EpsteinBarr virus (EBV)-encoded latent membrane protein 1 (LMP1) plays an important oncogenic role in the viral latent infection. Recently, increasing evidence indicates that the high expression of LMP1 during EBV lytic cycle is related to the viral lytic replication. However, the mechanism by which LMP1 regulates EBV lytic replication remains unclear. ()-Epigallocatechin-3-gallate (EGCG) prevents carcinogenesis by directly targeting numerous membrane proteins and effectively inhibits EBV lytic cascade. Here, we demonstrated that LMP1 promotes EBV lytic replication through the downstream signal molecules MAPKs, including ERKs, p38, and JNKs. LMP1 induces the phosphorylation of p53 through MAPKs to enhance the ability of wild-type p53 (wt-p53) to activate expression of BZLF1 gene, while the JNKs/c-Jun signal axis appears to be involved in EBV lytic replication induced by LMP1 in p53 mutant manner. We provided the first evidence that EGCG directly targets the viral membrane LMP1 ( =0.36 M, =1) using fluorescence quenching, isothermal titration calorimetry (ITC) assay, and CNBR-activated Sepharose 4B pull-down affinity chromatography. Furthermore, we revealed that EGCG inhibits EBV lytic replication via suppressing LMP1 and thus blocking the downstream MAPKs/wt-p53 signal axis in AGS-EBV cells and JNKs/c-Jun signal axis in p53 mutant B95.8 cells. Our study, for the first time, reports the binding and inhibitory efficacy of EGCG to the LMP1, which is a key oncoprotein encoded by EBV. These findings suggest the novel function of LMP1 in the regulation of EBV lytic cycle and reveal the new role of EGCG in EBV-associated malignancies through suppressing viral reactivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3727/096504021X16135618512563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420900PMC
September 2021

Subarachnoid hemorrhage caused by spontaneous intracranial hypotension: two rare cases report.

Int J Neurosci 2021 Feb 8:1-5. Epub 2021 Feb 8.

Department of Neurology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.

Background: Spontaneous intracranial hypotension (SIH) combined with subarachnoid hemorrhage (SAH) has rarely been reported. Herein, we report two patients with SIH who suffered from diffuse non-aneurysmal SAH and expanded the symptom spectrum of SIH.

Case Presentation: (1) A 55-year-old male was diagnosed with SIH based on orthostatic headache and diffuse pachymeningeal enhancement on brain MRI. One more month later, his headache was exacerbated, and brain CT showed diffuse SAH. Lumber puncture showed bloody cerebrospinal fluid (CSF) with a low CSF pressure of 20 mmHO after a 30 mL intrathecal injection of saline. The patient was treated with a lumbar epidural blood patch and recovered. (2) A 41-year-old male presented with orthostatic headache and nuchal pain. The brain CT scan confirmed the diagnosis of SAH. Brain MRI revealed diffuse dural thickening and bilateral frontoparietal subdural fluid collection. Lumber puncture showed bloody CSF with low CSF pressure. Then, an epidural blood patch was performed with satisfactory results.

Conclusion: Dilation and rupture of intracranial venous structures might play significant roles in SIH combined with SAH. We should be alert to SIH patients who develop a new persistent severe headache without relief after lying down or a suddenly changed state of consciousness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00207454.2021.1881094DOI Listing
February 2021

The complete mitochondrial genome of (Hemiptera: Lygaeidae).

Mitochondrial DNA B Resour 2020 Oct 5;5(3):3483-3484. Epub 2020 Oct 5.

State Key Laboratory of Grassland Agro-Ecosystems, Lanzhou University, Lanzhou, People's Republic of China.

Here, we sequenced and annotated the complete mitochondrial genome (mitogenome) of (Hemiptera: Lygaeidae). This mitogenome was 14575 bp long, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA unit genes (), and a putative control region. All genes were arranged in the same order as that of most true bugs. Eleven PCGs started with a typical ATN, and the remaining two PCGs started with TTA () and TTG (). The mitogenome with an A + T content of 76.42% showed a positive AT-skew (0.15) and a negative GC-skew (-0.15). With the exception of that lacked the dihydrouridine arm, all tRNAs had a typical cloverleaf secondary structure. Phylogenetic analysis based on the concatenated nucleotide sequences of the 13 PCGs showed that clustered with other three Lygaeidae species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2020.1827062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783115PMC
October 2020

Targeting the signaling in Epstein-Barr virus-associated diseases: mechanism, regulation, and clinical study.

Signal Transduct Target Ther 2021 Jan 12;6(1):15. Epub 2021 Jan 12.

The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.

Epstein-Barr virus-associated diseases are important global health concerns. As a group I carcinogen, EBV accounts for 1.5% of human malignances, including both epithelial- and lymphatic-originated tumors. Moreover, EBV plays an etiological and pathogenic role in a number of non-neoplastic diseases, and is even involved in multiple autoimmune diseases (SADs). In this review, we summarize and discuss some recent exciting discoveries in EBV research area, which including DNA methylation alterations, metabolic reprogramming, the changes of mitochondria and ubiquitin-proteasome system (UPS), oxidative stress and EBV lytic reactivation, variations in non-coding RNA (ncRNA), radiochemotherapy and immunotherapy. Understanding and learning from this advancement will further confirm the far-reaching and future value of therapeutic strategies in EBV-associated diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-020-00376-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801793PMC
January 2021

Overexpression of chemokine receptor lymphotactin receptor 1 has prognostic value in clear cell renal cell carcinoma.

Mol Genet Genomic Med 2021 01 30;9(1):e1551. Epub 2020 Dec 30.

Department of Pathology, Xinqiao Hospital, Third Military Medical University (Army Medical University, Chongqing, P. R. China.

Background: Clear cell renal cell carcinoma (ccRCC) is an aggressive subtype of renal cell carcinoma. X-C motif chemokine receptor 1 (XCR1) exerts important roles in tumor progression; however, its role in ccRCC is unclear.

Methods: We utilized publicly available data from The Cancer Genome Atlas (TCGA) to assess the role of XCR1 in ccRCC and validated the results in 36 samples from patients with ccRCC who underwent curative resection in Xinqiao Hospital Chongqing. XCR1 overexpression was identified in ccRCC, which was confirmed by qRT-PCR assay and immunohistochemical staining of ccRCC samples.

Results: For the TCGA and clinical data, Kaplan-Meier survival analysis revealed that higher XCR1 expression in ccRCC was related to longer overall survival. Cox regression analysis suggested that XCR1 is an independent risk factor for ccRCC. GSEA analysis suggested that XCR1 is associated with the JAK/STAT signaling pathway. XCR1 knockdown by small interfering RNA (siRNA) significantly increased ccRCC cell proliferation and migration, and decreased cell apoptosis.

Conclusion: We found higher XCR1 expression in ccRCC compared with that in normal tissues is related to longer overall survival in patients with ccRCC. XCR1 knockdown significantly increased RCC cells proliferation and migration, and decreased apoptosis. XCR1 might be used as a prognostic biomarker in ccRCC in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963425PMC
January 2021

Identification of dual therapeutic targets assisted by in situ automatous DNA assembly for combined therapy in breast cancer.

Biosens Bioelectron 2021 Mar 17;176:112913. Epub 2020 Dec 17.

Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China. Electronic address:

Breast cancer is the most common malignant disease among women worldwide. Nowadays, combined therapy against several therapeutic targets is becoming a promising treatment to enhance the survival rate of the patients with some lethal subtypes, and also proposes high demand on the discrimination of the co-existing targets in breast cancer. In this work, we designed in situ automatous DNA assembly reaction and applied it for the simultaneous identification of dual therapeutic targets using electrochemical techniques. Taking triple-negative breast cancer cell MDA-MB-231 as a model, chained strand displacement reactions were initiated after the capture probes recognized the surface biomarkers, epidermal growth factor receptor and intercellular adhesion molecule-1, respectively. Then, an increased electrochemical signaling was created to reveal the co-expression of the two targets using quantum dots as electrochemical labeling. Electrochemical results demonstrated high sensitivity and specificity of our method toward the identification of the coexisted therapeutic targets even in the serum samples, which also allowed to monitor the enhanced efficiency of combined therapy. Therefore, our method suggested a potential use in the accurate identification of therapeutic targets in breast cancer that might provide more information to facilitate the combined therapy in clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2020.112913DOI Listing
March 2021

Assessment of true vertical root fracture line in endodontically treated teeth using a new subtraction software - A Micro-CT and CBCT study.

Aust Endod J 2021 Aug 14;47(2):290-297. Epub 2020 Dec 14.

Department of Dentomaxillofacial Radiology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

This study aimed to find true facture lines in endodontically treated teeth on CBCT images using digital subtraction and to evaluate the influence of width of facture lines in the diagnosis. Thirty-two endodontically treated teeth with vertical root fractures (VRFs) from 30 patients were included in this study. The CBCT images of the patients and the micro-CT images of extracted teeth were imported into our digital subtraction software to distinguish the true facture lines from the streak artefacts. Of them, 23(71.87%) teeth did not present true fracture lines on the CBCT images (CBCT negative), and 9 (28.13%) teeth presented true fracture lines on the CBCT images (CBCT positive). The width of the facture lines was significantly different between these two groups (P < 0.05). To summarise, for in vivo endodontically treated teeth with subtle VRFs, many true fractures lines could not be demonstrated on CBCT images and wider fractures could be better distinguished.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aej.12476DOI Listing
August 2021

ANTs and cancer: Emerging pathogenesis, mechanisms, and perspectives.

Biochim Biophys Acta Rev Cancer 2021 01 11;1875(1):188485. Epub 2020 Dec 11.

Key Laboratory of Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South University, Changsha 410078, China; Cancer Research Institute and School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha 410078, China; Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha 410078, China; Molecular Imaging Research Center of Central South University, Changsha 410008, Hunan, China; Research Center for Technologies of Nucleic Acid-Based Diagnostics and Therapeutics Hunan Province, Changsha 410078, China; National Joint Engineering Research Center for Genetic Diagnostics of Infectious Diseases and Cancer, Changsha 410078, China. Electronic address:

Adenine nucleotide translocases (ANTs) are a class of transporters located in the inner mitochondrial membrane that not only couple processes of cellular productivity and energy expenditure, but are also involved in the composition of the mitochondrial membrane permeability transition pore (mPTP). The function of ANTs has been found to be most closely related to their own conformational changes. Notably, as multifunctional proteins, ANTs play a key role in oncogenesis, which provides building blocks for tumor anabolism, control oxidative phosphorylation and glycolysis homeostasis, and govern cell death. Thus, ANTs constitute promising targets for the development of novel anticancer agents. Here, we review the recent findings regarding ANTs and their important mechanisms in cancer, with a focus on the therapeutic potential of targeting ANTs for cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbcan.2020.188485DOI Listing
January 2021

Circulating tumor cell detection and single-cell analysis using an integrated workflow based on ChimeraX -i120 Platform: A prospective study.

Mol Oncol 2021 Sep 25;15(9):2345-2362. Epub 2020 Dec 25.

Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single-cell molecular analysis is required. We developed the ChimeraX -i120 platform to facilitate negative enrichment, immunofluorescent labeling, and machine learning-based identification of CTCs. Analytical performances were evaluated, and a total of 477 participants were enrolled to validate the clinical feasibility of ChimeraX -i120 CTC detection. We analyzed copy number alteration profiles of isolated single cells. The ChimeraX -i120 platform had high sensitivity, accuracy, and reproducibility for CTC detection. In clinical samples, an average value of > 60% CTC-positive rate was found for five cancer types (i.e., liver, biliary duct, breast, colorectal, and lung), while CTCs were rarely identified in blood from healthy donors. In hepatocellular carcinoma patients treated with curative resection, CTC status was significantly associated with tumor characteristics, prognosis, and treatment response (all P < 0.05). Single-cell sequencing analysis revealed that heterogeneous genomic alteration patterns resided in different cells, patients, and cancers. Our results suggest that the use of this ChimeraX -i120 platform and the integrated workflow has validity as a tool for CTC detection and downstream genomic profiling in the clinical setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1878-0261.12876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410565PMC
September 2021

Global immune characterization of HBV/HCV-related hepatocellular carcinoma identifies macrophage and T-cell subsets associated with disease progression.

Cell Discov 2020 Dec 8;6(1):90. Epub 2020 Dec 8.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China.

Diverse immune cells in the tumor microenvironment form a complex ecosystem, but our knowledge of their heterogeneity and dynamics within hepatocellular carcinoma (HCC) still remains limited. To assess the plasticity and phenotypes of immune cells within HBV/HCV-related HCC microenvironment at single-cell level, we performed single-cell RNA sequencing on 41,698 immune cells from seven pairs of HBV/HCV-related HCC tumors and non-tumor liver tissues. We combined bio-informatic analyses, flow cytometry, and multiplex immunohistochemistry to assess the heterogeneity of different immune cell subsets in functional characteristics, transcriptional regulation, phenotypic switching, and interactions. We identified 29 immune cell subsets of myeloid cells, NK cells, and lymphocytes with unique transcriptomic profiles in HCC. A highly complex immunological network was shaped by diverse immune cell subsets that can transit among different states and mutually interact. Notably, we identified a subset of M2 macrophage with high expression of CCL18 and transcription factor CREM that was enriched in advanced HCC patients, and potentially participated in tumor progression. We also detected a new subset of activated CD8 T cells highly expressing XCL1 that correlated with better patient survival rates. Meanwhile, distinct transcriptomic signatures, cytotoxic phenotypes, and evolution trajectory of effector CD8 T cells from early-stage to advanced HCC were also identified. Our study provides insight into the immune microenvironment in HBV/HCV-related HCC and highlights novel macrophage and T-cell subsets that could be further exploited in future immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41421-020-00214-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721904PMC
December 2020

Detection of circulating tumour cells enables early recurrence prediction in hepatocellular carcinoma patients undergoing liver transplantation.

Liver Int 2021 03 29;41(3):562-573. Epub 2020 Nov 29.

Department of Liver Surgery & Transplantation, Liver Cancer Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.

Background & Aims: Liver transplantation (LTx) is one of the most effective treatments for hepatocellular carcinoma (HCC); however, tumour recurrence after LTx often leads to poor outcomes. This study investigated the value of circulating tumour cells (CTCs) as a predictor of recurrence following LTx in patients with HCC.

Methods: This analysis included 193 patients with HCC who underwent LTx at our institute and accepted pre- and post-operative CTC detection; 38 were selected for serial CTC monitoring. The predictive value of CTCs for tumour recurrence in patients with HCC following LTx was evaluated. Single-cell whole genome sequencing was used to characterize CTCs.

Results: Overall, the CTC burden decreased after LTx (P < .05). Post-operative CTC count ≥ 1 per 5 mL peripheral blood was identified as a potential biomarker for predicting tumour recurrence after LTx, especially in patients with no detectable CTCs prior to LTx and negative tumour serological biomarkers. The predictive value of post-operative CTC count ≥ 1 per 5 mL blood was retained in patients who did not meet the Milan criteria, University of California San Francisco (UCSF) criteria, or Fudan criteria (all P < .05). Furthermore, post-operative serial CTC detection may be useful in post-surgical surveillance for HCC recurrence.

Conclusions: CTCs may be a useful biomarker to evaluate recurrence risk following LTx in patients with HCC. Evaluation based on CTC detection may enhance the post-transplant management of HCC, and improve the therapeutic efficacy of LTx.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14734DOI Listing
March 2021

Targeting Epstein-Barr virus oncoprotein LMP1-mediated high oxidative stress suppresses EBV lytic reactivation and sensitizes tumors to radiation therapy.

Theranostics 2020 25;10(26):11921-11937. Epub 2020 Oct 25.

Key Laboratory of Cancer Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, China.

Generating oxidative stress is a critical mechanism by which host cells defend against infection by pathogenic microorganisms. Radiation resistance is a critical problem in radiotherapy against cancer. Epstein-Barr virus (EBV) is a cancer-causing virus and its reactivation plays an important role in the development of EBV-related tumors. This study aimed to explore the inner relationship and regulatory mechanism among oxidative stress, EBV reactivation, and radioresistance and to identify new molecular subtyping models and treatment strategies to improve the therapeutic effects of radiotherapy. ROS, NADP/NADPH, and GSSG/GSH were detected to evaluate the oxidative stress of cells. 8-OHdG is a reliable oxidative stress marker to evaluate the oxidative stress in patients. Its concentration in serum was detected using an ELISA method and in biopsies was detected using IHC. qPCR array was performed to evaluate the expression of essential oxidative stress genes. qPCR, Western blot, and IHC were used to measure the level of EBV reactivation and . A Rta-IgG ELISA kit and EBV DNA detection kit were used to analyze the reactivation of EBV in serum from NPC patients. NPC tumor tissue microarrays was used to investigate the prognostic role of oxidative stress and EBV reactivation. Radiation resistance was evaluated by a colony formation assay. Xenografts were treated with NAC, radiation, or a combination of NAC and radiation. EBV DNA load of tumor tissue was evaluated using an EBV DNA detection kit. Oxidative stress, EBV reactivation, and the apoptosis rate in tumor tissues were detected by using 8-OHdG, EAD, and TUNEL assays, respectively. We found that EBV can induce high oxidative stress, which promotes its reactivation and thus leads to radioresistance. Basically, EBV caused NPC cells to undergo a process of 'Redox Resetting' to acquire a new redox status with higher levels of ROS accumulation and stronger antioxidant systems by increasing the expression of the ROS-producing enzyme, NOX2, and the cellular master antioxidant regulator, Nrf2. Also, EBV encoded driving protein LMP1 promotes EBV reactivation through production of ROS. Furthermore, high oxidative stress and EBV reactivation were positively associated with poor overall survival of patients following radiation therapy and were significant related to NPC patients' recurrence and clinical stage. By decreasing oxidative stress using an FDA approved antioxidant drug, NAC, sensitivity of tumors to radiation was increased. Additionally, 8-OHdG and EBV DNA could be dual prognostic markers for NPC patients. Oxidative stress mediates EBV reactivation and leads to radioresistance. Targeting oxidative stress can provide therapeutic benefits to cancer patients with radiation resistance. Clinically, we, for the first time, generated a molecular subtyping model for NPC relying on 8-OHdG and EBV DNA level. These dual markers could identify patients who are at a high risk of poor outcomes but who might benefit from the sequential therapy of reactive oxygen blockade followed by radiation therapy, which provides novel perspectives for the precise treatment of NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.46006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667690PMC
June 2021
-->