Publications by authors named "Shasha Zhou"

39 Publications

Isolation and characterization of porcine monoclonal antibodies revealed two distinct serotype-independent epitopes on VP2 of foot-and-mouth disease virus.

J Gen Virol 2021 Jul;102(7)

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou 730046, PR China.

Pigs are susceptible to foot-and-mouth disease virus (FMDV), and the humoral immune response plays an essential role in protection against FMDV infection. However, little information is available about FMDV-specific mAbs derived from single B cells of pigs. This study aimed to determine the antigenic features of FMDV that are recognized by antibodies from pigs. Therefore, a panel of pig-derived mAbs against FMDV were developed using fluorescence-based single B cell antibody technology. Western blotting revealed that three of the antibodies (1C6, P2-7E and P2-8G) recognized conserved antigen epitopes on capsid protein VP2, and exhibited broad reactivity against both FMDV serotypes A and O. An alanine-substitution scanning assay and sequence conservation analysis elucidated that these porcine mAbs recognized two conserved epitopes on VP2: a linear epitope (KKTEETTLL) in the N terminus and a conformational epitope involving residues K63, H65, L66, F67, D68 and L81 on two β-sheets (B-sheet and C-sheet) that depended on the integrity of VP2. Random parings of heavy and light chains of the IgGs confirmed that the heavy chain is predominantly involved in binding to antigen. The light chain of porcine IgG contributes to the binding affinity toward an antigen and may function as a support platform for antibody stability. In summary, this study is the first to reveal the conserved antigenic profile of FMDV recognized by porcine B cells and provides a novel method for analysing the antibody response against FMDV in its natural hosts (i.e. pigs) at the clonal level.
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http://dx.doi.org/10.1099/jgv.0.001608DOI Listing
July 2021

Investigation of the Mechanism of Complement System in Diabetic Nephropathy via Bioinformatics Analysis.

J Diabetes Res 2021 24;2021:5546199. Epub 2021 May 24.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072 Sichuan, China.

Objectives: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients.

Methods: GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN.

Results: There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN.

Conclusions: We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.
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http://dx.doi.org/10.1155/2021/5546199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169258PMC
May 2021

Hierarchical Self-Assembly of Nanowires on the Surface by Metallo-Supramolecular Truncated Cuboctahedra.

J Am Chem Soc 2021 Apr 13;143(15):5826-5835. Epub 2021 Apr 13.

College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.

Parastichy, the spiral arrangement of plant organs, is an example of the long-range apparent order seen in biological systems. These ordered arrangements provide scientists with both an aesthetic challenge and a mathematical inspiration. Synthetic efforts to replicate the regularity of parastichy may allow for molecular-scale control over particle arrangement processes. Here we report the packing of a supramolecular truncated cuboctahedron (TCO) into double-helical (DH) nanowires on a graphite surface with a non-natural parastichy pattern ascribed to the symmetry of the TCOs and interactions between TCOs. Such a study is expected to advance our understanding of the design inputs needed to create complex, but precisely controlled, hierarchical materials. It is also one of the few reported helical packing structures based on Platonic or Archimedean solids since the discovery of the Boerdijk-Coxeter helix. As such, it may provide experimental support for studies of packing theory at the molecular level.
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http://dx.doi.org/10.1021/jacs.1c00625DOI Listing
April 2021

Based on Network Pharmacology Tools to Investigate the Molecular Mechanism of Cordyceps sinensis on the Treatment of Diabetic Nephropathy.

J Diabetes Res 2021 5;2021:8891093. Epub 2021 Feb 5.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072 Sichuan, China.

Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis.

Materials And Methods: In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN.

Results: Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes.

Conclusions: Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.
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http://dx.doi.org/10.1155/2021/8891093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884116PMC
February 2021

A High Proportion of Novel ACAN Mutations and Their Prevalence in a Large Cohort of Chinese Short Stature Children.

J Clin Endocrinol Metab 2021 Jun;106(7):e2711-e2719

Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Context: Aggrecan, encoded by the ACAN gene, is the main proteoglycan component in the extracellular cartilage matrix. Heterozygous mutations in ACAN have been reported to cause idiopathic short stature. However, the prevalence of ACAN pathogenic variants in Chinese short stature patients and clinical phenotypes remain to be evaluated.

Objective: We sought to determine the prevalence of ACAN pathogenic variants among Chinese short stature children and characterize the phenotypic spectrum and their responses to growth hormone therapies.

Patients And Methods: Over 1000 unrelated short stature patients ascertained across China were genetically evaluated by next-generation sequencing-based test.

Result: We identified 10 novel likely pathogenic variants and 2 recurrent pathogenic variants in this cohort. None of ACAN mutation carriers exhibited significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect is estimated to be 1.2% in the whole cohort; it increased to 14.3% among those with advanced bone age and to 35.7% among those with both advanced bone age and family history of short stature. Nonetheless, 5 of 11 ACAN mutation carries had no advanced bone age. Two individuals received growth hormone therapy with variable levels of height SD score improvement.

Conclusion: Our data suggest that ACAN mutation is 1 of the common causes of Chinese pediatric short stature. Although it has a higher detection rate among short stature patients with advanced bone age and family history, part of affected probands presented with delayed bone age in Chinese short stature population. The growth hormone treatment was moderately effective for both individuals.
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http://dx.doi.org/10.1210/clinem/dgab088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208663PMC
June 2021

Sensitivity of SARS-CoV-2 to different temperatures.

Animal Model Exp Med 2020 Dec 29;3(4):316-318. Epub 2020 Dec 29.

Key Laboratory of Human Disease Comparative Medicine Chinese Ministry of Health Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases Institute of Laboratory Animal Science Chinese Academy of Medical Sciences and Comparative Medicine Center Peking Union Medical College Beijing China.

This study was designed to investigate the sensitivity of SARS-CoV-2 to different temperatures, to provide basic data and a scientific basis for the control of COVID-19 epidemic. The virus was dispersed in 1 mL basal DMEM medium at a final concentration of 10 TCID/mL and then incubated at 4, 22, 30, 35, 37, 38, 39 and 40°C for up to 5 days. The infectivity of residual virus was titrated using the Vero E6 cell line. The results showed that the virus remained viable for 5 days at 4°C, and for 1 day only at 22 and 30°C. We found that the infectivity of the virus was completely lost after less than 12 hours at 37, 38 and 39°C, while at 40°C, the inactivation time of the virus was rapidly reduced to 6 hours. We show that SARS-CoV-2 is sensitive to heat, is more stable at lower temperatures than higher temperature, remains viable for longer at lower temperatures, and loses viability rapidly at higher temperatures.
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http://dx.doi.org/10.1002/ame2.12141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824962PMC
December 2020

Characterization of Genome-Wide DNA Methylation and Hydroxymethylation in Mouse Arcuate Nucleus of Hypothalamus During Puberty Process.

Front Genet 2020 14;11:626536. Epub 2020 Dec 14.

Shanghai Center for Systems Biomedicine, Ministry of Education Key Laboratory for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process. Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation. A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty. Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process.
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http://dx.doi.org/10.3389/fgene.2020.626536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768033PMC
December 2020

The novel function of miR-3195 for mutant PROK2 (c.223-4C>A) degradation.

Authors:
Shasha Zhou Pin Li

Cell Biol Int 2021 Feb 10;45(2):404-410. Epub 2020 Nov 10.

Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.

Kallmann syndrome (KS) is a rare human genetic disorder characterized by hypogonadotropic hypogonadism with the reduction or absence of olfactory sense. Mutations in multiple genes, including chemokine prokineticin-2 (PROK2), are considered to contribute to the abnormal migration of gonadotropin-releasing hormone neurons in the embryonic stage. However, the mechanisms of the different inheritance modes of KS have not been comprehensively determined. In this article, we present the case of one KS patient with the same mutation in PROK2 (c.223-4C>A) as his mother. RNA sequencing analysis of his leukocytes showed a new transcript of PROK2, which contained a partial intron (192 bp) compared to those of his parents. Furthermore, we observed that hsa-miR-3195 was expressed at low levels in his and his father's sera compared to his mother's. Unexpectedly, hsa-miR-3195 was also identified to specifically target the 192 bp intron of the aberrant PROK2 transcript of this patient. We determined that high expression of hsa-miR-3195 could efficiently target aberrant PROK2 and stabilize the normal function of PROK2 in vitro, which provided a probable explanation for the different phenotypes of the patient and his mother with the same genotype.
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http://dx.doi.org/10.1002/cbin.11496DOI Listing
February 2021

Photochromism and Fluorescence Switch of Furan-Containing Tetraarylethene Luminogens with Aggregation-Induced Emission for Photocontrolled Interface-Involved Applications.

ACS Appl Mater Interfaces 2020 Sep 1;12(37):42410-42419. Epub 2020 Sep 1.

Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, People's Republic of China.

It is extremely challenging to design photocontrolled molecular switches with absorption and fluorescence dual-mode outputs that are suited for a solid surface and interface. Herein, we report a group of furan-containing tetraarylethene derivatives with unique photophysical behavior of aggregation-induced emission (AIE) and distinct photochemical reaction-triggered photochromic behaviors by combining a photoactive furan or benzofuran group and an AIE-active triphenylethene molecule. The introduction of a furyl or benzofuryl group into the AIE luminogen endows the molecules with significant reversible photochromism and solid-state fluorescence. The coloration and decoloration of these molecules can be switched by respective irradiation of UV and visible light in a reversible way, and the photochromic changes are accompanied by a switch-on and switch-off of the solid-state fluorescence. It is revealed that the photocontrolled cyclization and cycloreversion reactions are responsible for the reversible photochromism and fluorescence switching based on experimental data and theoretical analysis. Both the position and conjugation of the introduced photoactive units have significant influence on the color and strength of the photochromism, and the simultaneous occurrence of photoinduced fluorescence change in the solid state is perfectly suited for surface-involved applications. The demonstrations of dual-mode signaling in photoswitchable patterning on a filter paper and anti-counterfeiting of an anti-falsification paper strongly highlight the unique advantage of these photochromic molecules with an aggregation-induced emission characteristic in various practical applications. This work proposes a general strategy to design photochromic molecules with AIE activity by introducing photoactive functionals into an AIEgen and demonstrates incomparable advantage in dual-mode signaling and multifunctional applications of these molecules.
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http://dx.doi.org/10.1021/acsami.0c12603DOI Listing
September 2020

Mechanistic Investigation of a Self-Assembling Peptide against .

Langmuir 2020 08 12;36(33):9800-9809. Epub 2020 Aug 12.

Centre for Bioengineering and Biotechnology, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China.

Because of their distinctive mode of action in targeting bacterial cell membranes, antimicrobial peptides (AMPs) are increasingly regarded as a potential candidate for the development of novel antibiotics to combat the wide spread of bacterial resistance. To date, understanding of the exact molecular process by which AMPs act on the real bacterial envelope remains challenging. Simultaneously, the aggregated state of AMPs upon interaction with bacterial envelopes is still elusive. Previously, we have demonstrated that the potent antibacterial activity of a designed surfactant-like peptide Ac-AK-NH benefited greatly from its high self-assembling ability and appropriate self-assembled morphologies and sizes. By using high-resolution atomic force microscopy, we here not only follow the variations of the cell envelope in the presence of Ac-AK-NH but also characterize the peptide aggregates on the bacterial surface as well as on the substrate surface. The results, together with those from fluorescence, zeta potential, circular dichroism, and scanning electron microscopy measurements, indicate that both the positively charged peptide monomers and self-assembled nanostructures can directly act on the negatively charged bacterial surface, followed by their insertion into the bacterial membrane, the formation of surface nanopores, and membrane lysis. The mechanism of Ac-AK-NH against is thus consistent with the detergent-like mode of action. This work enhances our mechanistic understanding of the antibacterial behaviors of self-assembling peptides that will be valuable in exploring their biomedical applications.
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http://dx.doi.org/10.1021/acs.langmuir.0c01311DOI Listing
August 2020

Crop Load Influences Growth and Hormone Changes in the Roots of "Red Fuji" Apple.

Front Plant Sci 2020 26;11:665. Epub 2020 May 26.

College of Horticulture, Hebei Agricultural University, Baoding, China.

Crop load has a substantial impact on growth of the aerial and belowground parts of apple trees. Here, we examined the effects of different crop loads on growth and hormone levels in apple roots. A crop load of 1.5 (T1.5) fruits per cm trunk cross-sectional area (TCSA) treatment resulted in lower root growth vigor, while non-fruiting (T0) and T0.4 conditions showed higher root growth vigor. In all treatments, dead roots increased in length 90 days after full bloom (DAFB), whereas live roots were more abundant at about 50 and 170 DAFB, showing a bimodal curve. During each root growth peak, levels of cytokinins (CTKs), indole acetic acid (IAA), and gibberellic acid (GA) were higher. Moreover, hormone levels gradually decreased with increasing crop load within each peak. Root turnover tended to decrease with decreasing crop load. These findings indicate that root growth and hormone contents were positively correlated during the fruit growth phase, and that the negative impact of crop load on root growth may have been caused by hormone level decreases.
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http://dx.doi.org/10.3389/fpls.2020.00665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265680PMC
May 2020

Clustering-Triggered Ultralong Room-Temperature Phosphorescence of Organic Crystals through Halogen-Mediated Molecular Assembly.

J Phys Chem Lett 2020 Jul 11;11(13):4962-4969. Epub 2020 Jun 11.

Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, People's Republic of China.

To achieve efficient room-temperature phosphorescence of organic materials with ultralong lifetime, it is imperative to resolve the dilemma that the introduction of heavy atoms simultaneously improves emission efficiencies and shortens the emission lifetimes. Herein, we report a new molecular design approach for halogenated luminogens with a methylene bridge to avoid the lifetime shortening induced by heavy halogens and propose a general molecular engineering strategy to realize efficient and ultralong room-temperature phosphorescence via halogen-mediated molecular clustering. The halogenated N-benzylcarbazole derivatives show distinct photophysical behaviors depending on different physical states, including single-molecule state and cluster state. Their crystals demonstrate the halogen-dependent emission duration of room-temperature phosphorescence upon excitation. Experimental data and theoretical analysis indicate that halogen-regulated molecular clustering in the crystal is responsible for the generation of efficient ultralong room-temperature phosphorescence, and halogen-dominated molecular engineering favors the promotion of the intersystem crossing process and the following triplet emissions.
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http://dx.doi.org/10.1021/acs.jpclett.0c01272DOI Listing
July 2020

Dual Mode of Anti-Biofilm Action of G3 against .

ACS Appl Mater Interfaces 2020 Jun 15;12(25):27866-27875. Epub 2020 Jun 15.

Centre for Bioengineering and Biotechnology, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China.

Oral biofilms, formed by multiple microorganisms and their extracellular polymeric substances, seriously affect people's life. The emergence of the resistance of biofilms to conventional antibiotics and their side effects on the oral cavity have posed a great challenge in the treatment of dental diseases. Recently, antimicrobial peptides have been recognized as promising alternatives to conventional antibiotics due to their broad antibacterial spectrum, high antibacterial activity, and specific mechanism. However, the research of their anti-biofilm behaviors is still in its infancy, and the underlying mechanism remains unclear. In this study, we investigated the anti-biofilm activities of a designed helical peptide (G3) against (), one of the primary causative pathogens of caries. The results indicated that G3 inhibited biofilm formation by interfering with different stages of biofilm development. At the initial stage, G3 inhibited the bacterial adhesion by decreasing the bacterial surface charges, hydrophobicity, membrane integrity, and adhesion-related gene transcription. At the later stage, G3 interacted with extracellular DNA to destabilize the 3D architecture of mature biofilms and thus dispersed them. The high activity of G3 against biofilms, along with its specific modes of action, endows it great application potential in preventing and treating dental plaque diseases.
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http://dx.doi.org/10.1021/acsami.0c00771DOI Listing
June 2020

Implication of Broadly Neutralizing Bovine Monoclonal Antibodies in the Development of an Enzyme-Linked Immunosorbent Assay for Detecting Neutralizing Antibodies against Foot-and-Mouth Disease Virus Serotype O.

J Clin Microbiol 2019 12 22;57(12). Epub 2019 Nov 22.

State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot-and-Mouth Disease Reference Laboratory of China, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China

Vaccination with inactivated vaccines is still the main measure to control foot-and-mouth disease (FMD) in areas where the disease is endemic, and the level of neutralizing antibody in vaccinated animals is directly related to their protection against virus challenge. Currently, neutralizing antibody is mainly detected using the virus neutralization test (VNT) based on cell culture, which is laborious and time-consuming and requires restrictive biocontainment facilities. In this study, two broadly neutralizing antibodies (bnAbs), E46 and F128, were successfully produced using techniques for the isolation of single B cells from peripheral blood mononuclear cells (PBMCs) from bovines sequentially immunized with three topotypes of foot-and-mouth disease virus (FMDV) serotype O. Based on these bnAbs, a blocking enzyme-linked immunosorbent assay (ELISA) for detecting neutralizing antibodies (NA-ELISA) against FMDV serotype O was developed. The specificity and sensitivity of the test were estimated to be 99.21% and 100%, respectively. A significant correlation ( < 0.01) was observed between the NA-ELISA titers and the VNT titers for all sera from vaccinated animals and for all tested strains, suggesting that the NA-ELISA could detect neutralizing antibodies against FMDV serotype O strains of wide antigenic and molecular diversity and could be used for the evaluation of protective immunity.
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http://dx.doi.org/10.1128/JCM.01030-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879294PMC
December 2019

Microvesicles derived from human Wharton's Jelly mesenchymal stem cells ameliorate acute lung injury partly mediated by hepatocyte growth factor.

Int J Biochem Cell Biol 2019 07 14;112:114-122. Epub 2019 May 14.

Department of Urology, Henan Provincial People's Hospital, Zhengzhou, China. Electronic address:

Several studies have highlighted the underlying role of mesenchymal stem cells microvesicles (MSC-MVs) in acute lung injury (ALI). Hepatocyte growth factor (HGF) derived from MSC-MVs is partly involved in their therapeutic effects; however, the detailed mechanism remains unclear. MVs were isolated from human Wharton's Jelly MSCs. The rat model of ALI was established by intratracheal instillation of bleomycin (BLM). A co-culture model of alveolar epithelial cells or pulmonary endothelial cells and MSC-MVs was utilized. Total protein content in bronchoalveolar lavage fluid (BALF) was determined by bicinchoninic acid method. White blood cell (WBC) and neutrophil in BALF were counted. ELISA was used for the determination of cytokines and HGF in BALF. Apoptosis was determined by TUNEL assay and Annexin V-FITC/PI staining as well as caspase-3 activity detection. HE and Masson staining of lung tissues was used for histopathology analysis. The expression of HGF and proteins involved in the PI3K/AKT/mTOR pathway were measured by quantitative Real-Time PCR (qRT-PCR) and western blotting. Treatment with MSC-MVs significantly inhibited BLM-induced apoptosis and fibrosis in lung tissues and PI3K/AKT/mTOR activation, which was reversed by HGF mRNA deficient MVs. Intriguingly, these effects were completely abrogated by PI3K inhibitor. The therapeutic effect of MSC-MVs in ALI was partly mediated through HGF mRNA.
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http://dx.doi.org/10.1016/j.biocel.2019.05.010DOI Listing
July 2019

Sirtuin 1 alleviates diabetic neuropathic pain by regulating synaptic plasticity of spinal dorsal horn neurons.

Pain 2019 05;160(5):1082-1092

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.

Accumulating evidence has demonstrated that the enhanced synaptic plasticity of nociceptive interneurons in the spinal dorsal horn is the basis of central sensitization in neuropathic pain. Our previous results demonstrated that sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, alleviates neuropathic pain in type 2 diabetes mellitus rats. SIRT1 has also been reported to regulate synaptic plasticity in different brain neurons. However, the role of SIRT1 in synaptic plasticity of spinal dorsal horn neurons remains unknown. In this study, we found that in the spinal dorsal horn of diabetic neuropathic pain (DNP) rats and db/db mice, decreased SIRT1 expression was accompanied by enhanced structural synaptic plasticity. The levels of postsynaptic density protein 95 (PSD-95), growth-associated protein 43 (GAP43), and synaptophysin increased in the spinal dorsal horn of DNP rats and db/db mice and in high glucose-cultured primary spinal neurons. Upregulation of spinal SIRT1 by SIRT1 activator SRT1720 relieved pain behavior, inhibited the enhanced structural synaptic plasticity in rats and db/db mice with DNP, and decreased the levels of synapse-associated proteins in DNP rats, db/db mice, and high glucose-cultured spinal neurons. SIRT1-shRNA induced pain behavior and enhanced structural synaptic plasticity in normal rats and increased synapse-associated proteins levels in normal rats and spinal neurons. Intrathecal injection of AAV-Cre-EGFP into SIRT1 mice also induced pain behavior and enhanced synaptic plasticity of the spinal dorsal horn neurons. These results suggest that SIRT1 plays an important role in the progression of DNP by regulating synaptic plasticity of spinal dorsal horn neurons.
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http://dx.doi.org/10.1097/j.pain.0000000000001489DOI Listing
May 2019

Functional analysis of the UL24 protein of suid herpesvirus 1.

Virus Genes 2019 Feb 26;55(1):76-86. Epub 2018 Nov 26.

Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 518, Ziyue Road, Minhang District, Shanghai, 200241, China.

The UL24 homologous genes are conserved in alphaherpesviruses. However, the proximity of the UL24 gene and the UL23 gene encoding for thymidine kinase (TK) in the genome of suid herpesvirus 1 (SuHV-1) makes it difficult to mutate UL24 without affecting the expression of the TK gene, and thus functional studies of the UL24 gene have lagged behind. In this study, CRISPR/Cas9 and homologous recombination were adopted to generate UL24 and TK mutant viruses. Deletion of either the UL24 or the TK gene resulted in significantly reduced SuHV-1 replication and spread capacity in Vero cells. However, UL24-deleted virus still maintained a certain degree of lethality in mice, while TK-deleted viruses completely lost their lethality in mice. Similarly, neurovirulence of UL24-deleted virus in mice was not significantly affected compared to parental virus. In comparison, infection with the TK-deleted viruses resulted in significantly reduced neurovirulence and complete loss of lethality. In addition, and for the first time, viral UL24 protein was found to be expressed late during SuHV-1 infection; enhanced green fluorescence protein (eGFP) labeled UL24 protein was shown to be localized in the nucleus via heterologous expression. In conclusion, the UL24 gene of SuHV-1 encodes a nuclear-localized viral protein and acts as a minor virulence-associated factor compared to the TK gene.
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http://dx.doi.org/10.1007/s11262-018-1619-3DOI Listing
February 2019

Temperature Difference Triggering Controlled Growth of All-Inorganic Perovskite Nanowire Arrays in Air.

Small 2018 Oct 12;14(41):e1803010. Epub 2018 Sep 12.

State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.

All-inorganic perovskites have attracted increasing worldwide interest due to its significantly improved stability in atmospheric environment compared to organic-inorganic hybrid perovskites, which renders it infinitely applicable in many fields such as electronics, optoelectronics, and energy storage. However, all-inorganic perovskites have to confront the challenges from fabrication before their wide utilization in the aforementioned applications. Liquid-phase synthesis holds the advantage of mass production and easy modulation of composition but with the deficiencies of relatively low crystallinity and disordered products. Interestingly, gas-phase growth has complementary characteristics compared to the liquid-phase method. In this work, it is proposed that a novel temperature difference triggers growth strategy to integrate the merits of the liquid- and gas-phase methods, and the feasibility of this strategy via a simple lab-use hot plate is demonstrated. High quality all-inorganic perovskites, cesium lead halide (CsPbX ) nanowire arrays, can be epitaxially grown as in a gas-phase method, but at the same time, the composition of products can be easily modulated by predesigning the recipe of precursors as in the liquid-phase method on a large scale. Notably, the as-fabricated CsPbX perovskite nanowire arrays demonstrate excellent stability and good optoelectronic properties in air. It is believed that this novel strategy can strikingly prompt the development of perovskites fabrication and applications in future.
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http://dx.doi.org/10.1002/smll.201803010DOI Listing
October 2018

Temperature dependence of Raman responses of few-layer PtS.

Nanotechnology 2018 Dec 25;29(50):505709. Epub 2018 Sep 25.

State Key Laboratory of Material Processing and Die and Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology (HUST), 430074, Wuhan, People's Republic of China.

Platinum disulfide (PtS) is a newly emerging 2D material, which possesses relatively high carrier mobility, a widely tunable band gap from 0.25 to 1.6 eV, and ultra-high air stability, showing a potential in electronics and optoelectronics. Here, for the first time, we study the temperature-dependent Raman spectra on PtS with different thicknesses. It was found that with the temperature increase from 80 to 298 K, the [Formula: see text] and [Formula: see text] modes of all samples show linear softening. Moreover, the linear softening with temperature of PtS is much smaller than other 2D transition metal dichalcogenides, which could be attributed to the stronger interlayer coupling in PtS. Our work gives fundamental temperature-dependent vibrational information of PtS, which will be useful in future PtS-based electronic devices.
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http://dx.doi.org/10.1088/1361-6528/aae41fDOI Listing
December 2018

In situ formed nanoparticle-assisted growth of large-size single crystalline h-BN on copper.

Nanoscale 2018 Sep;10(37):17865-17872

State Key Laboratory of Material Processing and Die and Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, P. R. China.

h-BN is a widely used ultrathin insulator that can be synthesized in a controllable manner by chemical vapor deposition, similar to the growth of graphene. However, it is challenging to grow large-size single crystalline h-BN because of the ambiguous understanding of its growth mechanism. In this study, we propose a novel in situ formed nanoparticle-assisted growth strategy for large-size single crystalline h-BN growth on conventional polycrystalline copper. We found that the areal nucleation density of h-BN can be suppressed from ∼105 nuclei per mm2 to ∼102 nuclei per mm2 by the in situ formed nanoparticles that were introduced by pre-oxidation. Thus, single crystalline h-BN with lateral length of up to ∼102 μm was readily synthesized. Furthermore, for first time we discovered that the areal nucleation density of h-BN initially decreases and then increases under extreme annealing conditions, indicating that there is a competition-induced limit for suppressing the nucleation of h-BN on copper. This mechanism is universal for h-BN and graphene synthesis, which probably paves the way for large-size graphene/h-BN heterostructures synthesis in the future.
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http://dx.doi.org/10.1039/c8nr05722bDOI Listing
September 2018

Generation and characterization of UL41 null pseudorabies virus variant in vitro and in vivo.

Virol J 2018 08 2;15(1):119. Epub 2018 Aug 2.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 518, Ziyue Road, Minhang District, Shanghai, 200241, People's Republic of China.

Background: The alphaherpesvirus virion host shutoff (vhs) gene, UL41, can induce degradation of host mRNAs and shut off host protein synthesis. The roles of vhs in HSV-1 and HSV-2 have been studied extensively in previous studies, however, relatively little is known about the vhs protein of PRV.

Methods: A novel method combining CRISPR/Cas9 and Gibson assembly was developed to generate UL41 null PRV variant. The properties of UL41 null PRV in vitro and in vivo were further characterized. And the vhs activity of UL41 protein of PRV variant was evaluated by luciferase assay, Western-blot and RT-qPCR.

Results: Gibson assembly based on homologous recombination can accomplish one-step insertion of viral DNA fragments into donor plasmids efficiently (> 80%). Cas9/gRNA further largely enhanced the efficiency of homologous recombination. Using this method we were able to rapidly generate the UL41 null and revertant viruses of PRV variant. Compared to wild type (JS-2012), the UL41 null virus showed significantly smaller plaques and lower titers in Vero cells and impaired lethality and neuroinvasion in mice. Further the UL41 protein from different PRV strains exhibited unequal vhs activity in vitro, which of JS-2012 showed significantly weaker vhs activity than that of European-American strains. In addition UL41 null virus can also significantly decrease the expression of host genes during the early period of infection, which suggests other viral factors may be also involved in host shutoff.

Conclusions: CRISPR/Cas9 combined with Gibson assembly efficiently generated UL41 null PRV. Compared to wild type, UL41 null PRV showed impaired both replication capability in vitro and neuroinvasion in vivo. Further UL41 protein of PRV variant showed significantly weaker vhs activity than that of PRV SC (European-American-like strain), suggesting the deficiency of vhs activity by the PRV variant UL41 protein.
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http://dx.doi.org/10.1186/s12985-018-1025-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090798PMC
August 2018

The heat shock protein 40 LeDnaJ regulates stress resistance and indole-3-acetic acid biosynthesis in Lentinula edodes.

Fungal Genet Biol 2018 09 10;118:37-44. Epub 2018 Jul 10.

Institute of Applied Mycology, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Agro-Microbial Resource Comprehensive Utilization, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei, China. Electronic address:

DnaJ proteins, termed heat shock proteins based on their molecular weight, function as molecular chaperones that play critical roles in regulating organism growth and development as well as adaptation to the environment. However, little has been reported on their gene function in higher basidiomycetes. Here, the heat shock protein 40 (LeDnaJ) gene was cloned and characterized from Lentinula edodes. RNA interference was used to explore the function of LeDnaJ in response to heat stress and Trichoderma atroviride. Integration of the target gene into the L. edodes genome was confirmed by Southern blot analysis, and the silence efficiency of LeDnaJ was analyzed by qRT-PCR. The results revealed that LeDnaJ silence caused defects in mycelial growth and resistance to heat stress and T. atroviride, but increased the mycelial density compared with the wild type (WT) strain S606. Additionally, the IAA content showed a more than 10-fold increase in the WT after heat stress, but an about two-fold increase in the two LeDnaJ RNAi transfortants (LeDnaJ-i-6 and LeDnaJ-i-8). Previous study has shown that enhanced IAA (indole-3-acetic acid) content enhanced the thermotolerance of the heat-sensitive strain YS3357. In this study, it was documented that IAA amendments could partly restore the resistance to T. atroviride and thermotolerance of the two LeDnaJ RNAi transformants. Overall, LeDnaJ is nvolved in fungal growth, T. atroviride resistance, and thermotolerance by regulating the IAA biosynthesis in L. edodes.
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http://dx.doi.org/10.1016/j.fgb.2018.07.002DOI Listing
September 2018

Adjuvant chemotherapy after surgery can improve clinical outcomes for patients with IB2-IIB cervical cancer with neoadjuvant chemotherapy followed by radical surgery.

Sci Rep 2018 04 24;8(1):6443. Epub 2018 Apr 24.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

The aim of the study is to evaluate the efficacy of postoperative treatments based on pathological response for cervical cancer patients who received neoadjuvant chemotherapy (NACT) followed by radical surgery. Firstly, a total of 756 cervical squamous cell cancer (SCC) patients with FIGO IB2-IIB were included in this retrospective study. Then data from a prospective cohort of 393 patients was employed for further validation. Overall survival (OS) and disease-free survival (DFS) were assessed. In the retrospective study, SCC patients who accepted adjuvant chemotherapy after radical surgery had a relatively better OS than those who received no therapy (P = 0.08, HR = 0.57). The result was more noticeable in the prospective cohort study (P = 0.006, HR = 0.28). In the combined analysis, adjuvant chemotherapy improved clinical outcomes compared with no therapy (P = 0.002 and 0.04 for OS and DFS). Particularly for patients with extra-cervical residual disease, adjuvant chemotherapy improved OS (log-rank P = 0.008, 0.004 and 0.001 in the retrospective, prospective and combined studies). Optimal response patients had good outcomes even without therapy. Our study indicates that adjuvant chemotherapy can benefit clinical outcomes for SCC patients with NACT followed by radical surgery, especially those with extra-cervical residual disease. For optimal response patients, there may be no need for further treatment. This finding needs to be validated in more future studies.
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http://dx.doi.org/10.1038/s41598-018-24413-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915525PMC
April 2018

Tunneling Diode Based on WSe /SnS Heterostructure Incorporating High Detectivity and Responsivity.

Adv Mater 2018 Feb 8;30(7). Epub 2018 Jan 8.

State Key Laboratory of Material Processing and Die and Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology (HUST), Wuhan, 430074, P. R. China.

van der Waals (vdW) heterostructures based on atomically thin 2D materials have led to a new era in next-generation optoelectronics due to their tailored energy band alignments and ultrathin morphological features, especially in photodetectors. However, these photodetectors often show an inevitable compromise between photodetectivity and photoresponsivity with one high and the other low. Herein, a highly sensitive WSe /SnS photodiode is constructed on BN thin film by exfoliating each material and manually stacking them. The WSe /SnS vdW heterostructure shows ultralow dark currents resulting from the depletion region at the junction and high direct tunneling current when illuminated, which is confirmed by the energy band structures and electrical characteristics fitted with direct tunneling. Thus, the distinctive WSe /SnS vdW heterostructure exhibits both ultrahigh photodetectivity of 1.29 × 10 Jones (I /I ratio of ≈10 ) and photoresponsivity of 244 A W at a reverse bias under the illumination of 550 nm light (3.77 mW cm ).
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http://dx.doi.org/10.1002/adma.201703286DOI Listing
February 2018

Bisphenol A deteriorates egg quality through HDAC7 suppression.

Oncotarget 2017 Nov 28;8(54):92359-92365. Epub 2017 Sep 28.

Department of Assisted Reproduction, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, People's Republic of China.

Bisphenol A (BPA), a synthetic substance of endocrine disrupter, widely distributes in environment and can affect the health of ovarian follicles, thereby impacting the fertilization ability and pregnancy rate. However, the underlying mechanisms regarding how BPA disrupts the egg quality have not been fully revealed. In this study, we determine that BPA treated female mice display the decreasing HDAC7 expression in ovary and eggs compared to control. Moreover, the global levels of H3K9 and H4K16 acetylation abnormally increase after BPA treatment and recover partially upon HDAC7 compensation. Collectively, our study reveals that BPA deteriorates egg quality through HDAC7 suppression.
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http://dx.doi.org/10.18632/oncotarget.21308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696187PMC
November 2017

Single-base methylome analysis reveals dynamic epigenomic differences associated with water deficit in apple.

Plant Biotechnol J 2018 02 22;16(2):672-687. Epub 2017 Sep 22.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Horticulture, Northwest A&F University, Yangling, Shaanxi, China.

Cytosine methylation is an essential feature of epigenetic regulation and is involved in various biological processes. Although cytosine methylation has been analysed at the genomic scale for several plant species, there is a general lack of understanding of the dynamics of global and genic DNA methylation in plants growing in environments challenged with biotic and abiotic stresses. In this study, we mapped cytosine methylation at single-base resolution in the genome of commercial apple (Malus x domestica), and analysed changes in methylation patterns associated with water deficit in representative drought-sensitive and drought-tolerant cultivars. We found that the apple genome exhibits ~54%, ~38% and ~8.5% methylation at CG, CHG and CHH sequence contexts, respectively. We additionally documented changes in gene expression associated with water deficit in an attempt to link methylation and gene expression changes. Global methylation and transcription analysis revealed that promoter-unmethylated genes showed higher expression levels than promoter-methylated genes. Gene body methylation appears to be positively correlated with gene expression. Water deficit stress was associated with changes in methylation at a multitude of genes, including those encoding transcription factors (TFs) and transposable elements (TEs). These results present a methylome map of the apple genome and reveal widespread DNA methylation alterations in response to water deficit stress. These data will be helpful for understanding potential linkages between DNA methylation and gene expression in plants growing in natural environments and challenged with abiotic and biotic stresses.
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http://dx.doi.org/10.1111/pbi.12820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787839PMC
February 2018

DNA methylation of METTL7A gene body regulates its transcriptional level in thyroid cancer.

Oncotarget 2017 May;8(21):34652-34660

Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200040, People's Republic of China.

DNA methylation is the best-studied epigenetic mechanism for regulating gene transcription and maintaining genome stability. Current research progress of transcriptional regulation by DNA methylation mostly focuses on promoter region where hypomethylated CpG islands are present transcriptional activity, as hypermethylated CpG islands generally result in gene repression. Recently, the DNA methylation patterns across the gene body (intragenic methylation) have increasingly attracted attention towards their role in transcriptional regulation and efficiency, due to the improvement of numerous genome-wide DNA methylation profiling studies. However, the function and mechanism of gene body methylation is still unclear. In this study, we revealed that the methylation level of METTL7A, a seldom studied gene, was downregulated in thyroid cancer compared to normal thyroid cells in vivo and in vitro. Moreover, we determined the methylation level of one CpG site at the exon of the METTL7A gene body impacted the transcriptional activity. Through generating a mutation of this CpG site (CG to CC) of METTL7A exogenous vector artificially in vitro, we observed higher RNA polymerase II recruitment and a declined enrichment of methyl-CpG binding protein-2 in gene body of METTL7A, in papillary thryoid cancer cells (BCPAP) compared to normal thryoid cells. Finally, we revealed that EZH2, a subunit of polycomb repressor complex 2, dominant in thyroid cancer, might be responsible for regulating gene body methylation of METTL7A. Our study depicted the DNA methylation patterns and the transcriptional regulatory mechanism of the gene body in thyroid cancer. Furthermore, this study provides new insight into potential future avenues, for therapies targeting cancer.
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http://dx.doi.org/10.18632/oncotarget.16147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470999PMC
May 2017

Genome-wide association study identifies four SNPs associated with response to platinum-based neoadjuvant chemotherapy for cervical cancer.

Sci Rep 2017 01 25;7:41103. Epub 2017 Jan 25.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

To identify genomic markers associated with the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. A total of 596 patients with stage IA2-IIIB cervical cancer were enrolled in this study. One single nucleotide polymorphism (SNP) (rs6812281, per allele OR = 2.37, P = 9.0 × 10) located at 4q34.3 reached GWAS significance (P < 5.0 × 10). Another three SNPs, rs4590782 (10q26.2, P = 1.59 × 10, per allele OR = 0.48), rs1742101 (14q32.11, P = 7.11 × 10, per allele OR = 0.52), and rs1364121 (16q23.3, P = 3.15 × 10, per allele OR = 1.98), exhibited strong evidence of associations with response to neoadjuvant chemotherapy. Patients with a C allele (CT + CC) of rs4590782 had better 5-year overall survival rates (82.9% vs. 75.8%, P = 0.083) and 5-year disease-free survival rate (80.8% vs. 72.7%, P = 0.021) than those without a C allele. Our findings help to characterize the genetic etiology of the response to neoadjuvant chemotherapy in patients with cervical cancer.
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http://dx.doi.org/10.1038/srep41103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264598PMC
January 2017

Association between vascular endothelial growth factor expression and lymph node metastasis in cervical cancer: A meta-analysis.

J Obstet Gynaecol Res 2016 Oct 23;42(10):1310-1316. Epub 2016 Jun 23.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aim: The expression of vascular endothelial growth factor (VEGF) by cancer cells has been identified as a factor that is associated with lymph node metastasis (LNM) in some cancers, but an accurate description of the relation between VEGF and LNM in cervical cancer is lacking. We conducted a concurrent meta-analysis to investigate this issue.

Methods: We searched PubMed and EMBASE for articles addressing the association between VEGF and cervical cancer. We used stata 12.0 and calculated the crude odds ratios (OR) and corresponding 95% confidence intervals (CI). Heterogeneity between the studies included was assessed by Cochran's Q-test.

Results: Overall, 16 relevant studies with 426 cases and 751 controls were included in our study. The results demonstrated that cervical cancer patients with VEGF-positive expression had a 2.87-fold higher risk of LNM than patients without VEGF-positive expression (95%CI = 1.85-4.44, P < 0.001). Furthermore, subgroup analysis by ethnicity revealed that VEGF-positive expression could increase the risk of LNM in cervical cancer among Asian populations (OR = 2.55, 95%CI = 1.61-4.03, P < 0.001) and Caucasian populations (OR = 8.81, 95%CI = 2.78-27.88, P < 0.001). Moreover, subgroup analysis by country revealed that VEGF-positive expression could increase the risk of LNM in cervical cancer among Chinese populations (OR = 3.38, 95%CI = 2.18-5.25, P < 0.001) but not among Korean populations (P = 0.84) or Japanese populations (P = 0.06). Subgroup analysis based on sample size proved that VEGF-positive expression was statistically associated with LNM in a large sample group.

Conclusion: Our study revealed that VEGF-positive expression is related with higher risk of LNM in cervical cancer.
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http://dx.doi.org/10.1111/jog.13064DOI Listing
October 2016

Optimal pathological response indicated better long-term outcome among patients with stage IB2 to IIB cervical cancer submitted to neoadjuvant chemotherapy.

Sci Rep 2016 06 21;6:28278. Epub 2016 Jun 21.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.

The role of pathological response in long-term outcome is still unclear in cervical cancer patients treated with neoadjuvant chemotherapy (NACT) in China. This study aimed to investigate the effect of optimal pathologic response (OPR) on survival in the patients treated with NACT and radical hysterectomy. First, 853 patients with stage IB2-IIB cervical cancer were included in a retrospective analysis; a Cox proportional hazards model was used to investigate the relationship between pathological response and disease-free survival (DFS). In the retrospective database, 64 (7.5%) patients were found to have achieved an OPR (residual disease <3 mm stromal invasion); in the multivariate Cox model, the risk of death was much greater in the non-OPR group than in the OPR group (HR, 2.61; 95%CI, 1.06 to 6.45; P = 0.037). Next, the role of OPR was also evaluated in a prospective cohort of 603 patients with cervical cancer. In the prospective cohort, 56 (9.3%) patients were found to have achieved an OPR; the log-rank tests showed that the risk of recurrence was higher in the non-OPR patients than in the OPR group (P = 0.05). After combined analysis, OPR in cervical cancer was found to be an independent prognostic factor for DFS.
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http://dx.doi.org/10.1038/srep28278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915007PMC
June 2016
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