Publications by authors named "Leilei Wang"

142 Publications

[Genetic study of a child carrying a maternally derived unbalanced 46,Y,der(X)t(X;Y)(p22;q11) chromosomal translocation].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Apr;38(4):376-379

Lianyungang Maternal and Child Health Care Hospital, Lianyungang, Jiangsu 222000, China.

Objective: To explore the genetic basis for a child featuring short stature, saddle nose, cryptorchidism and mental retardation.

Methods: The child and his parents were subjected to G-banded karyotyping and chromosomal microarray analysis (CMA).

Results: The child was found to have a 46,Y,der(X)t(X;Y)(p22;q11)mat karyotype. CMA has revealed a 8.3 Mb deletion at Xp22.33p22.31 and a 43.3 Mb duplication at Yq11.221qter. His mother had a karyotype of 46,X,der(X)t(X;Y)(p22;q11). His father had a normal karyotype.

Conclusion: The child has carried an unbalanced translocation der(X)t(X;Y) (p22;q11) derived from his mother. His clinical phenotype has correlated with the size and position of X chromosome deletion. Compared with the females, abnormal phenotypes such as mental retardation and growth retardation of male carriers are more severe.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200321-00188DOI Listing
April 2021

Advances in biotechnological production of β-alanine.

World J Microbiol Biotechnol 2021 Apr 5;37(5):79. Epub 2021 Apr 5.

Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Department of Biochemical Engineering, School of Chemical Engineering and Technology, SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, 300072, People's Republic of China.

β-Alanine (3-aminopropionic acid) is the only naturally occurring β-type amino acid. Although it is not incorporated into proteins, it has important physiological functions in the metabolism of animals, plants and microorganisms. Furthermore, it has attracted great interest due to its wide usage as a precursor of many significant industrial chemicals for medicine, feed, food, environmental applications and other fields. With the depletion of fossil fuels and concerns regarding environmental issues, biological production of β-alanine has attracted more attention relative to chemical methods. In this review, we first summarize the pathways through which natural microorganisms synthesize β-alanine. Then, the current research progress in the biological synthesis of β-alanine is also elaborated. Finally, we discuss the main problems and challenges in optimizing the biological pathways, offering perspectives on promising new biological approaches.
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http://dx.doi.org/10.1007/s11274-021-03042-1DOI Listing
April 2021

IT-SVO: Improved Semi-Direct Monocular Visual Odometry Combined with JS Divergence in Restricted Mobile Devices.

Sensors (Basel) 2021 Mar 12;21(6). Epub 2021 Mar 12.

School of Mechanical Engineering, Guizhou University, Guiyang 550025, China.

Simultaneous localization and mapping (SLAM) has a wide range for applications in mobile robotics. Lightweight and inexpensive vision sensors have been widely used for localization in GPS-denied or weak GPS environments. Mobile robots not only estimate their pose, but also correct their position according to the environment, so a proper mathematical model is required to obtain the state of robots in their circumstances. Usually, filter-based SLAM/VO regards the model as a Gaussian distribution in the mapping thread, which deals with the complicated relationship between mean and covariance. The covariance in SLAM or VO represents the uncertainty of map points. Therefore, the methods, such as probability theory and information theory play a significant role in estimating the uncertainty. In this paper, we combine information theory with classical visual odometry (SVO) and take Jensen-Shannon divergence (JS divergence) instead of Kullback-Leibler divergence ( divergence) to estimate the uncertainty of depth. A more suitable methodology for SVO is that explores to improve the accuracy and robustness of mobile devices in unknown environments. Meanwhile, this paper aims to efficiently utilize small portability for location and provide a priori knowledge of the latter application scenario. Therefore, combined with SVO, JS divergence is implemented, which has been realized. It not only has the property of accurate distinction of outliers, but also converges the inliers quickly. Simultaneously, the results show, under the same computational simulation, that SVO combined with JS divergence can more accurately locate its state in the environment than the combination with divergence.
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http://dx.doi.org/10.3390/s21062025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998773PMC
March 2021

Construction of a prognostic value model in papillary renal cell carcinoma by immune-related genes.

Medicine (Baltimore) 2021 Mar;100(12):e24903

Department of Pharmacy, Traditional Chinese Medical Hospital of Huangdao District, Qingdao, P.R. China.

Abstract: Papillary renal cell carcinoma (PRCC) is the second most common type of renal carcinoma following clear cell renal cell carcinoma, and the role of immune-related genes (IRGs) in tumorigenesis and metastasis is evident; its prognostic value in PRCC remains unclear. In this study, we downloaded the gene expression profiles and clinical data of patients with PRCC from The Cancer Genome Atlas (TCGA) database and obtained IRGs from the ImmPort database. A total of 371 differentially expressed IRGs (DEIRGs) were discovered between PRCC and normal kidney tissues. Prognostic DEIRGs (PDEIRGs) were identified by univariate Cox regression analysis. Then, we screened the four most representative PDEIRGs (IL13RA2, CCL19, BIRC5, and INHBE) and used them to construct a risk model to predict the prognosis of patients with PRCC. This model precisely stratified survival outcome and accurately identified mutation burden in PRCC. Thus, our results suggest that these four PDEIRGs are available prognostic predictors for PRCC. They could be used to assess the prognosis and to guide individualized treatments for patients with PRCC.
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http://dx.doi.org/10.1097/MD.0000000000024903DOI Listing
March 2021

Imaging of Vulva Syringoma With Reflectance Confocal Microscopy.

Front Med (Lausanne) 2021 24;8:649438. Epub 2021 Feb 24.

Department of Pathology, St. Vincent Evansville Medical Center, Evansville, IN, United States.

To investigate the application of reflectance confocal microscopy (RCM) imaging in diagnosis of vulva syringoma. Patients with lesions suspicious of syringoma on vulva were enrolled in the study. After informed consent was taken, the lesions were photographed and imaged with RCM. The features of the lesion in confocal images were then analyzed and compared with the biopsy findings for histology correlation. Eleven cases in total were included in the study. The typical RCM features observed in syringoma are the presence of round to oval high refractive, and relatively monomorphous mass of varying sizes in the superficial and middle dermis, usually surrounded with 1-2 layers of light-dark line structures, which were further confirmed by histological evaluation. Ten cases showed classic features of syringoma and 1 case exhibited milia in RCM images. Syringoma has distinct features in RCM imaging, which correlates well with histological findings, highlighting the potential role of RCM in the diagnosis and differential diagnosis of vulva syringoma.
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http://dx.doi.org/10.3389/fmed.2021.649438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959786PMC
February 2021

An IncP-2 plasmid sublineage associated with dissemination of among carbapenem-resistant .

Emerg Microbes Infect 2021 Dec;10(1):442-449

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

IMP-45, a variant of IMP-9, is one of the dominant metallo-β-lactamases (MBLs) in clinical carbapenem-resistant (CRPA) isolates in China. The aim of this study was to investigate the distribution and mechanism of dissemination of . MBL genes were detected by PCR in 173 non-duplicate CRPA isolates collected from Hospital HS in Shanghai and 605 isolates from a multicenter surveillance of in China. In total, 17 IMP-45-producers (14 from Hospital HS and 3 from other hospitals) were identified. Molecular typing identified an outbreak of 11 IMP-45-producing ST508 CRPA in the ICU of Hospital HS. Conjugation assays and whole genome sequencing were conducted among IMP-45-producers. Genomic comparison revealed that 16 -carrying plasmids (9 from this study and 7 from GenBank) shared a similar backbone with IncP-2 -carrying plasmid pOZ176 but lacked -- region. gene was presented in pOZ176, -carrying plasmids (17 from this study and 7 from GenBank) and 15 megaplasmids from GenBank. Phylogenetic analysis of showed that most -carrying plasmids were clustered into a sublineage separate from the one containing pOZ176. This IncP-2 plasmid sublineage contributed to the dissemination of among genetically diverse and recruited multiple resistance genes during its evolution.
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http://dx.doi.org/10.1080/22221751.2021.1894903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971254PMC
December 2021

Circ_0004872 promotes platelet-derived growth factor-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs via miR-513a-5p/TXNIP axis.

Vascul Pharmacol 2021 Feb 13:106842. Epub 2021 Feb 13.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

The proliferation, migration and dedifferentiation of vascular smooth muscle cells (VSMCs) exert crucial roles in atherosclerosis (AS) progression. The aim of our study was to explore the influences of circular RNA 0004872 (circ_0004872) in platelet-derived growth factor-BB (PDGF-BB)-induced AS cell model and investigate the underlying mechanisms. Real-time quantitative polymerase chain reaction (RT-qPCR) was implemented for the expression detection of circ_0004872, mitogen-activated protein kinase 1 (MAPK1) messenger RNA (mRNA), microRNA-513a-5p (miR-513a-5p) and thioredoxin interacting protein (TXNIP). Cell proliferation was analyzed via Cell Counting Kit 8 (CCK8) assay. Cell migration was assessed via wound healing assay and transwell migration assay. Western blot assay was used to measure the expression of alpha smooth muscle actin (α-SMA), osteopontin (OPN), calponin and TXNIP. Dual-luciferase reporter assay and RNA-pull down assay were used for confirmation of interaction between miR-513a-5p and circ_0004872 or TXNIP. Circ_0004872 expression was elevated in PDGF-BB-induced human aortic vascular smooth muscle cells (HA-VSMCs) and carotid plaque tissues. Circ_0004872 silencing alleviated PDGF-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs. MiR-513a-5p bound to circ_0004872, and circ_0004872 knockdown-induced effects in PDGF-BB-treated HA-VSMCs were largely attenuated by the silencing of miR-513a-5p. MiR-513a-5p bound to the 3' untranslated region (3'UTR) of TXNIP, and miR-513a-5p overexpression-mediated effects were counteracted by the transfection of pcDNA-TXNIP in PDGF-BB-induced HA-VSMCs. TXNIP was modulated by circ_0004872/miR-513a-5p signaling cascade in HA-VSMCs. Circ_0004872 accelerated PDGF-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs through enhancing TXNIP level via sponging miR-513a-5p.
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http://dx.doi.org/10.1016/j.vph.2021.106842DOI Listing
February 2021

Down-regulation of the Sp1 transcription factor by an increase of microRNA-4497 in human placenta is associated with early recurrent miscarriage.

Reprod Biol Endocrinol 2021 Feb 12;19(1):21. Epub 2021 Feb 12.

Clinical Center of Reproductive Medicine, Lianyungang Maternal and Child Health Hospital, Kangda College of Nanjing Medical University, 222000, Lianyungang, Jiangsu, China.

Background: The pathophysiological mechanism of recurrent miscarriage (RM) is unclear. The goals of this study were to determine the role of microRNA-4497 overexpression in placental villus tissues in early RM; To identify the potential target mRNAs of miRNA-4497; And to investigate the microRNA-4497-mediated regulatory mechanisms in placental trophoblasts.

Methods: Bioinformatics analysis was performed to identify the candidate target genes of miRNA-4497. The protein expression of Sp1 transcription factor (SP1), chemokine (C-X-C motif) receptor 5 (CXCR5) and bone morphogenetic protein 8a (BMP8A) were determined in the villus tissues of the RM and normal groups by Western blotting and immunohistochemistry. Cultured 293T cells were co-transfected with the miRNA-4497 agomir or luciferase reporter vectors containing the wild-type or mutant 3'-UTRs of the target mRNAs to verify the regulatory role of miRNA-4497.

Results: Bioinformatics analysis suggested that SP1, CXCR5 and BMP8A mRNAs are potential targets of miRNA-4497. The expression of SP1, CXCR5 and BMP8A proteins in the chorionic villus tissues of RM placentas were significantly decreased compared to those in the normal controls. Moreover, SP1 protein levels were inversely correlated with the levels of miRNA-4497 in the placentas of RM patients and normal controls. The expression of SP1 mRNA and protein were down-regulated in HTR-8/SVneo cells after forced overexpression of the miRNA-4497 agomir. The results of the co-transfection assay showed that mutation of the miRNA-4497-binding sites in the 3'-untranslated region (3'-UTR) of SP1 led to a recovery of luciferase activity upon overexpression of miRNA-4497, suggesting that SP1 could be a direct target of miRNA-4497.

Conclusions: An increased miRNA-4497 level in the placental villus tissues associated with recurrent miscarriage may down-regulate SP1 expression. The negative regulation of SP1 by miRNA-4497 may potentially contribute to the pathogenesis of recurrent miscarriage through promotion of trophoblast apoptosis. These findings provide novel information on the regulation of placental trophoblast apoptosis, and could be useful for the development of new therapeutic strategies for better management of recurrent miscarriage.
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http://dx.doi.org/10.1186/s12958-021-00701-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879516PMC
February 2021

[Application of chromosomal microarray analysis in prenatal diagnosis of pregnant women with advanced age].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Feb;38(2):101-107

Laboratory of Genetics, Lianyungang Maternal and Child Health Care Hospital, Lianyangang, Jiangsu 222000, China.

Objective: To assess the value of chromosomal microarray analysis (CMA) for the detection of fetal anomalies among pregnant women with advanced age.

Methods: CMA results of 562 cases, in addition with the outcome of pregnancy and neonatal follow-up were reviewed.

Results: Among the 562 amniotic fluid samples, 73 cases (12.99%) of fetal chromosomal abnormalities were detected, which included 21 cases (3.73%) of chromosomal aneuploidies and 52 cases (9.25%) of copy number variations (CNVs). The latters included 27 cases of pathological CNVs (4.80%), 4 cases of possible pathogenic CNVs (0.71%) and 42 cases of variants with unknown clinical significance (7.47%). Compared with those under 35, the detection rate of fetal chromosomal aneuploidies for women with advanced age was higher under the indications of voluntary test, abnormal ultrasonic structures, abnormal ultrasonic soft index and risks indicated by non-invasive prenatal testing (NIPT). No significant difference was found in the detection rate of CNVs between those ≥35 and <35 and between those with age factor only and with additional indications (P> 0.05). 552 cases (98.22%) of pregnant women have completed the followed up. Among 31 women with pathological and possible pathogenic fetal CNVs detected by CMA, 25 had terminated the pregnancy, 6 (19.35%) have delivered without obvious abnormality. 41 pregnant women with fetal CNVs of unknown clinical significance have completed the follow up, among whom 3 had terminated the pregnancy, 1 newborn was found with malformation after birth, which yielded an abnormal pregnancy rate of 9.76%. 480 pregnant women with negative CMA results have completed the follow up, among whom 5 (1.04%) had abnormal pregnancy or delivered a child with birth defect.

Conclusion: There is a certain difference between the outcome of pregnancy predicted by CMA testing and the actual outcome. The pregnancies with fetal CNVs with unknown clinical significance detected by CMA have a high adverse rate, which should attract clinical attention. CMA testing should be recommended for pregnant women with advanced age regardless of whether they have other symptoms. CMA combined with other detection methods is the trend for prenatal diagnosis.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200323-00195DOI Listing
February 2021

The Differential Diagnosis of Hypopigmented Mycosis Fungoides and Vitiligo With Reflectance Confocal Microscopy: A Preliminary Study.

Front Med (Lausanne) 2020 11;7:609404. Epub 2021 Jan 11.

Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

To investigate the role of reflectance confocal microscopy (RCM) in the differential diagnosis of hypopigmented mycosis fungoides (HMF) and vitiligo. Cases with persistent hypopigmented patches, suspicious of early stage vitiligo, or HMF were imaged with RCM. The melanin contents and inflammatory conditions of the epidermis and superficial dermis of the lesions were compared with the same layers of the adjacent skin, and then, the imaged lesions were biopsied and analyzed by histology. 15 cases were enrolled in this study, and based on the RCM findings, there was just slight or moderate reduction of melanin but no melanin absence in the basal cell layer of HMF lesions. The finding of monomorphous weakly refractile, oval to round cells on the basis of vesicle-like dark space was clearly elucidated in the epidermis of the lesions by RCM, which indicates the Pautrier's microabscesses on histopathology. Among those 15 cases, 13 cases were identified as HMF, and the other two cases were vitiligo, based on RCM findings, which were confirmed by histology analysis. The RCM findings correlated well with histology results in the screening of HMF, which indicates the RCM is an important tool in the early detection and differential diagnosis of HMF.
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http://dx.doi.org/10.3389/fmed.2020.609404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829195PMC
January 2021

Immature defense mechanisms mediate the relationship between childhood trauma and onset of bipolar disorder.

J Affect Disord 2021 01 15;278:672-677. Epub 2020 Oct 15.

Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, PR China. Electronic address:

Background: Accumulating evidence has converged to suggest that childhood trauma may contribute to bipolar disorder (BD). This study aimed to investigate the patterns of childhood trauma among patients with bipolar I (BD-I) and bipolar II (BD-II) disorders, according to DSM-IV and in contrast with healthy volunteers. We also explored whether the relationship between childhood trauma and onset of bipolar disorder is mediated by immature defense mechanisms.

Methods: Participants were patients with BD-I (n=44) and BD-II (n = 42), and healthy controls (HCs, n = 43). Childhood traumatic experiences and defense mechanisms were assessed by the Childhood Trauma Questionnaire (CTQ) and the Defense Style Questionnaire (DSQ), respectively.

Results: BD patients experienced more severe childhood trauma than HCs. Physical neglect sub-score and total score of the CTQ had both direct and indirect effects on the diagnosis of BD-I, and an immature defense style mediated the indirect effects. The diagnosis of BD-II was mainly related to the physical neglect and emotional abuse subs-core and total score of the CTQ, as mediated by the immature defense mechanisms. BD-I and BD-II significantly differed in the emotional abuse sub-score of the CTQ.

Conclusions: Physical neglect sub-score and total score of the CTQ were associated with the diagnosis of BD (both BD-I and BD-II), as mediated by an immature defense style. Furthermore, emotional abuse might be an important risk factor for BD-II compared to BD-I. These findings may inform risk reduction and psychosocial intervention strategies to prevent and treat patients with bipolar disorders.
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http://dx.doi.org/10.1016/j.jad.2020.10.029DOI Listing
January 2021

The effect of prophylactic rewarming on postoperative nausea and vomiting among patients undergoing laparoscopic hysterectomy: a prospective randomized clinical study.

Sao Paulo Med J 2020 Sep-Oct;138(5):414-421

MD. Anesthesiologist, Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Ouhai Area, Wenzhou City, Zhejiang Province, China.

Background: Postoperative nausea and vomiting (PONV) is a common complication from general anesthesia that impacts on postoperative recovery.

Objective: To evaluate prophylactic rewarming following general anesthesia, so as to decrease the incidence of PONV among patients undergoing laparoscopic hysterectomy.

Design And Setting: Prospective randomized clinical study at a hospital in China.

Methods: Sixty-two patients were randomly assigned into two groups. The forced air warming (FAW) group received pre-warmed Ringer's solution with FAW until the end of surgery. The control group received Ringer's solution without FAW. The pre-warmed Ringer's solution was stored in a cabinet set at 40 °C. The FAW tube was placed beside the patient's shoulder with a temperature of 43 °C.

Results: Sixty patients completed the study. The FAW group showed significant differences versus the controls regarding temperature. At 6, 24 and 48 hours postoperatively, the incidences of PONV were 53.3%, 6.7% and 3.3% in the FAW group versus 63.3%, 30% and 3.3% in the controls. VAS scores were significantly lower in the FAW group than in the controls at 24 hours (P= 0.035). Forty-item questionnaire total scores in the FAW group were significantly higher than in the controls. The physical independence and pain scores at 24 hours and emotional support and pain scores at 48 hours in the FAW group were higher than in the controls (P < 0.05). There was no difference in hemodynamics or demographics between the two groups (P > 0.05).

Conclusions: Prophylactic rewarming relieved PONV and improved the quality of postoperative recovery.

Chinese Clinical Trial Register (chictr): ChiCTR-IOR-17012901.
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http://dx.doi.org/10.1590/1516-3180.2020.0059.R2.06072020DOI Listing
January 2021

Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice.

Commun Biol 2020 Oct 8;3(1):556. Epub 2020 Oct 8.

Department of Microbiology & Immunology, School of Medicine, New York Medical College, Valhalla, NY, 10595, USA.

Macrophage scavenger receptor 1 (MSR1) mediates the endocytosis of modified low-density lipoproteins and plays an important antiviral role. However, the molecular mechanism underlying MSR1 antiviral actions remains elusive. We report that MSR1 activates autophagy to restrict infection of Chikungunya virus (CHIKV), an arthritogenic alphavirus that causes acute and chronic crippling arthralgia. Msr1 expression was rapidly upregulated after CHIKV infection in mice. Msr1 knockout mice had elevated viral loads and increased susceptibility to CHIKV arthritis along with a normal type I IFN response. Induction of LC3 lipidation by CHIKV, a marker of autophagy, was reduced in Msr1 cells. Mechanistically, MSR1 interacted with ATG12 through its cytoplasmic tail and this interaction was enhanced by CHIKV nsP1 protein. MSR1 repressed CHIKV replication through ATG5-ATG12-ATG16L1 and this was dependent on the FIP200-and-WIPI2-binding domain, but not the WD40 domain of ATG16L1. Our results elucidate an antiviral role for MSR1 involving the autophagic function of ATG5-ATG12-ATG16L1.
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http://dx.doi.org/10.1038/s42003-020-01285-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545163PMC
October 2020

Uncovering the protective mechanism of Taohong Siwu decoction against diabetic retinopathy via HIF-1 signaling pathway based on network analysis and experimental validation.

BMC Complement Med Ther 2020 Oct 6;20(1):298. Epub 2020 Oct 6.

The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Pudong, Shanghai, 200137, China.

Background: Diabetic retinopathy (DR) is a common and serious microvascular complication of diabetes. Taohong Siwu decoction (THSWD), a famous traditional Chinese medicine (TCM) prescription, has been proved to have a good clinical effect on DR, whereas its molecular mechanism remains unclear. Our study aimed to uncover the core targets and signaling pathways of THSWD against DR.

Methods: First, the active ingredients of THSWD were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database. Second, the targets of active ingredients were identified from ChemMapper and PharmMapper databases. Third, DR associated targets were searched from DisGeNET, DrugBank and Therapeutic Target Database (TTD). Subsequently, the common targets of active ingredients and DR were found and analyzed in STRING database. DAVID database and ClueGo plug-in software were used to carry out the gene ontology (GO) and KEGG enrichment analysis. The core signaling pathway network of "herb-ingredient-target" was constructed by the Cytoscape software. Finally, the key genes of THSWD against DR were validated by quantitative real-time PCR (qRT-PCR).

Results: A total of 2340 targets of 61 active ingredients in THSWD were obtained. Simultaneously, a total of 263 DR-associated targets were also obtained. Then, 67 common targets were found by overlapping them, and 23 core targets were identified from protein-protein interaction (PPI) network. Response to hypoxia was found as the top GO term of biological process, and HIF-1 signaling pathway was found as the top KEGG pathway. Among the key genes in HIF-1 pathway, the mRNA expression levels of VEGFA, SERPINE1 and NOS2 were significantly down-regulated by THSWD (P < 0.05), and NOS3 and HMOX1 were significantly up-regulated (P < 0.05).

Conclusion: THSWD had a protective effect on DR via regulating HIF-1 signaling pathway and other important pathways. This study might provide a theoretical basis for the application of THSWD and the development of new drugs for the treatment of DR.
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http://dx.doi.org/10.1186/s12906-020-03086-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542117PMC
October 2020

Experimental study on co-combustion of low rank coal semicoke and oil sludge by TG-FTIR.

Waste Manag 2020 Oct 12;116:91-99. Epub 2020 Aug 12.

Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China. Electronic address:

Co-combustion was proposed as an effective and complementary means for the co-treatment of low rank coal semicoke (LRCS) and oil sludge. The combustion, kinetics and gaseous pollutants emission characteristics during co-combustion of LRCS and oil sludge were investigated by thermogravimetric analyzer coupled with Fourier transform infrared spectrometer (TG-FTIR). Results showed oil sludge had more complex weight loss characteristics than LRCS. Proper addition of oil sludge could effectively improve the ignition, burnout and comprehensive combustion performance of blends and 60% was a recommended oil sludge blend ratio. High heating rates could also enhance the combustion performance of blends. The activation energy determined by Coats-Redfern method gradually decreased with the increase of oil sludge blend ratio. DAEM kinetic analysis results showed the maximum activation energy of 113.4 kJ/mol was obtained when conversion rate was 0.4 due to the poor ignition performance of LRCS. All of the CO, CO, NOx and SO emission gradually decreased with the increasing oil sludge blend ratio. LRCS had suppression effect on NOx emission during co-combustion while oil sludge was just the opposite. The low sulfur release rate of oil sludge resulted in the decreasing SO emission of blends although oil sludge had promotion effect on SO emission.
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http://dx.doi.org/10.1016/j.wasman.2020.08.007DOI Listing
October 2020

Human umbilical cord mesenchymal stem cell-derived exosome-mediated transfer of microRNA-133b boosts trophoblast cell proliferation, migration and invasion in preeclampsia by restricting SGK1.

Cell Cycle 2020 08 28;19(15):1869-1883. Epub 2020 Jun 28.

Department of Obstetric and Gynecology, Shengjing Hospital of China Medical University , Shengyang, Liaoning, China.

Objective: Exosomes have been documented to function in human diseases, yet their transfer of microRNA (miRNA) in preeclampsia (PE) has seldom been reported. This study intends to discuss the role of miR-133b derived from exosomes in human umbilical cord mesenchymal stem cells (hUC-MSCs) in trophoblast cell development in PE.

Methods: Placentas from PE patients and normal pregnant women were collected. The hUC-MSCs and their exosomes were obtained and identified. Trophoblast cell HPT-8 and HTR8-S/Vneo were obtained and co-cultured with hUC-MSCs-derived exosomes that had been transfected with different miR-133b plasmids. MiR-133b and glucocorticoid-regulated kinase 1 (SGK1) expression in placental tissues and HPT-8 and HTR8-S/Vneo cells was determined. HTR8-S/Vneo and HPT-8 cell proliferation, cell cycle distribution, apoptosis rate, migration and invasion were detected.

Results: MiR-133b was down-regulated and SGK1 was up-regulated in placental tissues of PE patients. MiR-133b expression was inversely related to SGK1 expression in HTR8-S/Vneo and HPT-8 cells co-cultured with hUC-MSC-derived exosomes. Exosomes promoted HTR8-S/Vneo and HPT-8 cell proliferation, migration and invasion abilities, cell cycle entry and inhibited apoptosis. Elevated exosome-derived miR-133b from hUC-MSCs boosted HTR8-S/Vneo and HPT-8 cell proliferation, cell cycle progression, migration and invasion and limited cell apoptosis. MiR-133b targeted SGK1.

Conclusion: Collectively, we demonstrate that miR-133b is down-regulated and SGK1 is up-regulated in PE, and miR-133b derived from exosomes in hUM-MSCs facilitates trophoblast cell proliferation, migration and invasion in PE via constraining SGK1.
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http://dx.doi.org/10.1080/15384101.2020.1769394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469539PMC
August 2020

The differential diagnosis of syringoma and milia based on the imaging of reflectance confocal microscopy.

Skin Res Technol 2020 Nov 14;26(6):951-953. Epub 2020 Jun 14.

Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

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http://dx.doi.org/10.1111/srt.12879DOI Listing
November 2020

New insights into the mechanism of storage protein biosynthesis in wheat caryopsis under different nitrogen levels.

Protoplasma 2020 Sep 13;257(5):1289-1308. Epub 2020 May 13.

Jiangsu Key Laboratory of Crop Genetics and Physiology/Co-Innovation Center for Modern Production Technology of Grain Crops, Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou, 225009, China.

Effect of different nitrogen levels (0, 150, and 300 kg hm) at booting stage on storage protein biosynthesis and processing quality of wheat was investigated using microstructural and ultrastructural observation, RNA sequencing, and quality analysis in this study. The results showed that the storage protein genes encoding ω- and γ-gliadin and low molecular weight glutenin subunit were upregulated at N150, and the genes encoding α- or β-gliadin and avenin-like protein were upregulated at N300. Two nitrogen levels induced expression of some interesting regulating genes, such as USE1, STX1B_2_3, SEC23, SEC24, SEC61A, HSP A1_8, HSP20, and HSP90B/TRA1. These regulatory genes were enriched in the KEGG pathway protein export, SNARE interactions in vesicular transport, and protein processing in endoplasmic reticulum. The amount, morphology, and accumulation pattern of protein body in four different endosperm regions in developing caryopsis show different response to N150 and N300, of which N300 had greater influence than N150. N150 and N300 both enhanced the contents of protein components, endosperm fullness, grain hardness, and parameters of processing quality, with the latter showing a greater degree of influence. Contrary to the accumulation pattern of protein body, N300 reduced the ratio of the amount of starch granules to the area ratio of protein body to starch granule. Results suggested that the difference of different nitrogen levels affecting storage protein biosynthesis might be through affecting the expression of the encoding and regulating gene of storage protein.
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http://dx.doi.org/10.1007/s00709-020-01489-xDOI Listing
September 2020

Metal-Free Trifluoroalkylation of Quinoxalin-2(1)-ones with Unactivated Alkenes and Langlois' Reagent.

J Org Chem 2020 06 11;85(11):6888-6896. Epub 2020 May 11.

School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165, China.

A KSO-mediated three-component protocol has been developed for the construction of 3-trifluoroalkylated quinoxalin-2(1)-ones under metal-free conditions. The present reaction could be accomplished through the trifluoroalkylation of quinoxalin-2(1)-ones with unactivated alkenes and Langlois' reagent (CFSONa), which provided a highly attractive approach to access a series of biologically important 3-trifluoroalkylated quinoxalin-2(1)-ones.
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http://dx.doi.org/10.1021/acs.joc.9b03505DOI Listing
June 2020

LncRNA LINC00313 Knockdown Inhibits Tumorigenesis and Metastasis in Human Osteosarcoma by Upregulating FOSL2 through Sponging miR-342-3p.

Yonsei Med J 2020 May;61(5):359-370

Department of Orthopedics, The Sixth Affiliated Hospital of Xinjiang Medical University, Xinjiang, China.

Purpose: Osteosarcoma (OS) is the most common primary bone tumor, with high morbidity in infants and adolescents. Long noncoding RNA LINC00313 has been found to modulate papillary thyroid cancer tumorigenesis and to be dysregulate in lung cancer. However, the role of LINC00313 in OS has not yet been addressed.

Materials And Methods: We evaluated mRNA and protein expression using real-time quantitative PCR and Western blotting. Cell proliferation was evaluated using MTT; apoptosis and autophagy were assessed with flow cytometry, Western blotting, and/or GFP-LC3 assay. Transwell assay was conducted to measure cell migration and invasion. Potential target sites for LINC00313 and miR-342-3p were predicted with starBase v.2.0 and TargetScan Human, and verified using luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. In vivo, xenogeneic tumors were induced with U2OS and MG-63 cells, separately.

Results: LINC00313 was upregulated and miR-342-3p was downregulated in OS tissues and cells. High expression of LINC00313 was associated with shorter overall survival. FOSL2 downregulation and miR-342-3p overexpression suppressed cell proliferation and migratory and invasive abilities while promoting apoptosis and autophagy, all of which were consistent with the effects of LINC00313 knockdown. miR-342-3p, sponged by LINC00313, inversely modulated FOSL2 by targeting MG-63 cells, and FOSL2 expression was positively controlled by LINC00313. LINC00313 knockdown suppressed tumor growth in vivo.

Conclusion: LINC00313 is upregulated in OS, and LINC00313 knockdown plays a vital anti-tumor role in OS cell progression through a miR-342-3p/FOSL2 axis. Our study suggests that LINC00313 may be a novel, promising biomarker for diagnosis and prognosis of OS.
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http://dx.doi.org/10.3349/ymj.2020.61.5.359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214116PMC
May 2020

Molecular Characteristics and Antimicrobial Susceptibility Profiles of Clinical Isolates in Shanghai, China.

Infect Drug Resist 2020 29;13:247-256. Epub 2020 Jan 29.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Purpose: To investigate molecular characteristics and antimicrobial susceptibility profiles of clinical isolates of in Shanghai, China.

Methods: isolates were collected in a university-affiliated hospital in 2012-2015 and 2017-2018. They were re-identified to species level by 16S rRNA gene and species-specific gene sequencing. Antimicrobial susceptibility testing, screening for metallo-beta-lactamase production, identification of antimicrobial resistance genes and pulsed-field gel electrophoresis (PFGE) were performed.

Results: Among 52 isolates, was the most prevalent species (67.3%), followed by (26.9%). High carriage rates of , and genes were consistent with the poor in vitro activity of most β-lactams including carbapenems. Nevertheless, β-lactamase inhibitors increased susceptibility rates significantly for cefoperazone and piperacillin. Susceptibility rates for minocycline, tigecycline, rifampin and levofloxacin were 100%, 78.8%, 76.9% and 71.2%, respectively. Ser83Ile or Ser83Arg substitution in the DNA gyrase A unit was associated with resistance to fluoroquinolones. MIC/MIC values of vancomycin and linezolid were 16/16 mg/L and 16/32 mg/L, respectively. Molecular typing showed twenty-one different types of PFGE and more than one indistinguishable isolates were observed in each of the eight subtypes.

Conclusion: Tetracyclines, tigecycline, β-lactam/β-lactamase inhibitor combinations, rifampin and fluoroquinolones demonstrated high rates of in vitro activity against clinical isolates of . Both genetic diversity and clonality were observed from this health-care facility. Our report provides potential alternative treatment options for infections.
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http://dx.doi.org/10.2147/IDR.S240963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996224PMC
January 2020

[Genetic analysis of a case of mosaic trisomy 21 associated with autism spectrum disorder].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Feb;37(2):190-194

Laboratory of Genetics, Lianyungang Maternal and Child Health Care Hospitial, Lianyuangang, Jiangsu 222000, China.

Objective: To explore the genetic basis for a child with autism spectrum disorder (ASD) and congenital heart disease.

Methods: G-banded chromosomal karyotyping was carried out for the patient and his parents. The child was also subjected to whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq). The result was validated by chromosomal microarray analysis (CMA).

Results: The karyotype of the patient and his parents were normal. No significant genetic variation was found by WES. However, CNV-seq has discovered a 47, XY, +21 [10%]/46,XY [90%] mosaicism in the patient. The result was confirmed by CMA.

Conclusion: In addition to Down syndrome, low proportion mosaic trisomy 21 is also associated with ASD. WES and CNV-seq can enable accurate diagnosis for patient with unexplained ASD.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.02.023DOI Listing
February 2020

Target delivering paclitaxel by ferritin heavy chain nanocages for glioma treatment.

J Control Release 2020 07 12;323:191-202. Epub 2019 Dec 12.

Key Laboratory of Drug Targeting and Drug Delivery Systems under Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address:

Glioma is one of the most common aggressive brain malignancies, but the treatment of glioma is still far from satisfying. The efficiency of chemotherapy - the major choice of glioma treatment - is severely limited by low chemotherapeutic agents delivery across blood-brain barrier (BBB) and low tumor retention. Therefore, a safe and effective drug delivery system to help chemotherapy agents traverse the BBB and accumulate at tumor sites is urgently needed. Paclitaxel (PTX) is one of the most common and effective chemotherapy agent, however, it suffers from extremely low solubility and BBB penetration ability. Herein, we developed endogenous human ferritin heavy chain nanocage (HFn) as PTX carrier, which could specifically bind to widely overexpressed transferrin receptor 1 (TfR1) on BBB and glioma cells. We propose that this binding may help PTX cross the BBB and enhance its tumor accumulation. PTX-loaded HFn (HFn-PTX) was prepared and exhibited satisfactory targeting effect in Bend.3 and C6 cells in vitro. In vivo tissue biodistribution assay also demonstrated that HFn-PTX could indeed promote the accumulation of PTX in the brain. HFn-PTX exhibited the best anti-tumor effect with median survival time of 30 days, significantly longer than that of free PTX (14 days) and physiological saline group (13 days). In summary, we have designed and fabricated an effective delivery system for PTX to treat glioma. We also provided evidences that Transferrin (Tf) could not prevent the binding of HFn to TfR1 nor consequent TfR1-mediated HFn uptake, providing a clue for future research.
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http://dx.doi.org/10.1016/j.jconrel.2019.12.010DOI Listing
July 2020

3-Methylcrotonyl-CoA carboxylase deficiency newborn screening in a population of 536,008: is routine screening necessary?

J Pediatr Endocrinol Metab 2019 Dec;32(12):1321-1326

The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.

Objective To evaluate whether 3-methylcrotonyl-CoA carboxylase deficiency (3-MCCD) should be routinely screened in newborns. Methods Dried blood spots (DBS) were collected and analyzed by tandem mass spectrometry (TMS). Blood samples were collected from infants with positive 3-MCCD results. Targeted sequencing was performed using the extended panel for inherited metabolic diseases to detect 306 genes. The sequencing libraries were quantified and used for massively parallel sequencing on the Illumina HiSeq 2500 platform. Results A total of 536,008 infants underwent newborn screening (NBS) and 14 cases of 3-MCCD were diagnosed. The incidence of 3-MCCD in Jiangsu province was 1:38,286. During the last 3 years of follow-up, none of the subjects with 3-MCCD exhibited obvious clinical symptoms. Only two children had mild feeding difficulties and vomiting. Eleven patients had complex variants of the MCCC1 gene, and three patients had mutations in MCCC2. In total, 17 types of MCCC1 or MCCC2 variants were found, and c.639 + 2t > a was the most common mutation. Conclusions As far as the current results are concerned, 3-MCCD may be benign in Jiangsu province. However, additional investigations and a longer follow-up period are necessary to decide whether NBS of 3-MCCD is necessary or not.
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http://dx.doi.org/10.1515/jpem-2018-0536DOI Listing
December 2019

Femtosecond laser direct writing of diffraction grating and its refractive index change in chalcogenide AsSe film.

Opt Express 2019 Oct;27(21):30090-30101

Chalcogenide glasses possess novel optical property in infrared range, which make them ideal candidates for photonic devices by laser direct writing. Precisely control of the refractive index manipulation in the material is the key to achieve high quality optical devices. In this work, diffraction gratings in chalcogenide AsSe thin films were fabricated with femtosecond laser direct writing and its refractive index change was carefully studied. Grating diffraction efficiency was measured from visible to near-infrared light by using multiple single-wavelength lasers and a supercontinuum laser. Clear diffraction patterns and high diffraction efficiency indicated the good optical quality of the prepared gratings. Results show that the grating with period of 5 µm inscribed under pulse energy of 30 nJ demonstrated a 1st-order diffraction efficiency of 30% at 808 nm testing wavelength, due to the changes of refractive index and absorption. The relationship of the change of refractive index and absorption coefficient of film under different laser irradiation intensity is carefully studied. The maximum refractive index change was estimated to be 0.087 at 808 nm.
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http://dx.doi.org/10.1364/OE.27.030090DOI Listing
October 2019

Phospho‑regulation of Cdc14A by polo‑like kinase 1 is involved in β‑cell function and cell cycle regulation.

Mol Med Rep 2019 Nov 9;20(5):4277-4284. Epub 2019 Sep 9.

Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

The objective of the present study was to investigate the effects of polo‑like kinase 1 (PLK1) and the phosphorylation of human cell division cycle protein 14A (Cdc14A) by PLK1 on β‑cell function and cell cycle regulation. Mouse β‑TC3 cells were incubated with small interfering RNA (siRNA) to knock down the expression of PLK1. Cell cycle analysis was performed using flow cytometry, and cell proliferation and apoptosis was determined. Insulin secretion was evaluated by a radioimmunoassay under both low and high glucose conditions. Mouse β‑TC3 cells were transfected with a wild type or a non‑phosphorylatable Cdc14A mutant (Cdc14AS351A/363A; Cdc14AAA) to investigate whether the phosphorylation of Cdc14A is involved in cellular regulation of PLK1 under high glucose conditions. It was found that PLK1 siRNA significantly promoted cellular apoptosis, inhibited cell proliferation, decreased insulin secretion and reduced Cdc14A expression under both low and high glucose conditions. Cdc14A overexpression promoted β‑TC3 cell proliferation and insulin secretion, while Cdc14AAA overexpression inhibited cell proliferation and insulin secretion under high glucose conditions. PLK1 siRNA partially reversed the proliferation‑promoting effects of Cdc14A and further intensified the inhibition of proliferation by Cdc14AAA under high glucose conditions. Similarly, Cdc14A overexpression partially reversed the insulin‑inhibiting effects of PLK1 siRNA, while Cdc14AAA overexpression showed a synergistic inhibitory effect on insulin secretion with PLK1 siRNA under high glucose conditions. In conclusion, PLK1 promoted cell proliferation and insulin secretion while inhibiting cellular apoptosis in β‑TC3 cell lines under both low and high glucose conditions. In addition, the phospho‑regulation of Cdc14A by PLK1 may be involved in β‑TC3 cell cycle regulation and insulin secretion under high glucose conditions.
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http://dx.doi.org/10.3892/mmr.2019.10653DOI Listing
November 2019

Exosome-like nanoplatform modified with targeting ligand improves anti-cancer and anti-inflammation effects of imperialine.

J Control Release 2019 10 1;311-312:104-116. Epub 2019 Sep 1.

Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, College of Polymer Science and Engineering, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.

Currently, most anti-cancer therapies are still haunted by serious and deleterious adverse effects. Here, we report a highly biocompatible tumor cell-targeting delivery systems utilizing exosome-like vesicles (ELVs) that delivers a low-toxicity anti-cancer agent imperialine against non-small cell lung cancer (NSCLC). First, we introduced a novel micelle-aided method to efficiently load imperialine into intact ELVs. Then, integrin α3β1-binding octapeptide cNGQGEQc was modified onto ELV platform for tumor targeting as integrin α3β1 is overexpressed on NSCLC cells. This system not only significantly improved imperialine tumor accumulation and retention, but also had extremely low systemic toxicity both in vitro and in vivo. Our discoveries offer new ways to utilize ELV more efficiently for both drug loading and targeting. The solid pharmacokinetics improvement and extraordinary safety of this system also highlight possibilities of alternative long course cancer therapies using similar strategies.
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http://dx.doi.org/10.1016/j.jconrel.2019.08.037DOI Listing
October 2019

Construction of a sp /sp Carbon Interface in 3D N-Doped Nanocarbons for the Oxygen Reduction Reaction.

Angew Chem Int Ed Engl 2019 Oct 18;58(42):15089-15097. Epub 2019 Sep 18.

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

The development of highly efficient metal-free carbon electrocatalysts for the oxygen reduction reaction (ORR) is one very promising strategy for the exploitation and commercialization of renewable and clean energy, but this still remains a significant challenge. Herein, we demonstrate a facile approach to prepare three-dimensional (3D) N-doped carbon with a sp /sp carbon interface derived from ionic liquids via a simple pyrolysis process. The tunable hybrid sp and sp carbon composition and pore structures stem from the transformation of ionic liquids to polymerized organics and introduction of a Co metal salt. Through tuning both composition and pores, the 3D N-doped nanocarbon with a high sp /sp carbon ratio on the surface exhibits a superior electrocatalytic performance for the ORR compared to that of the commercial Pt/C in Zn-air batteries. Density functional theory calculations suggest that the improved ORR performance can be ascribed to the existence of N dopants at the sp /sp carbon interface, which can lower the theoretical overpotential of the ORR.
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http://dx.doi.org/10.1002/anie.201907915DOI Listing
October 2019

μ-Opioid receptor signalling via PI3K/Akt pathway ameliorates lipopolysaccharide-induced acute respiratory distress syndrome.

Exp Physiol 2019 10 22;104(10):1555-1561. Epub 2019 Jul 22.

Department of Neurosurgery, Cangzhou Central Hospital, Xinhua West Road, Cangzhou, 061000, Hebei, China.

New Findings: What is the central question of this study? The aim was to investigate the role of μ-opioid receptors in acute respiratory distress syndrome and whether their protective effect is mediated via the PI3K/Akt signalling pathway. What is the main finding and its importance? Our findings show that activation of μ-opioid receptors ameliorates lung injury, and the effects are reversed by the PI3K inhibitor, wortmannin.

Abstract: The main pathology of acute respiratory distress syndrome (ARDS) is the accumulation of inflammatory cells in the lung and increased permeability of vascular endothelial cells. The μ-opioid receptor (MOR) is a G-protein-coupled receptor, which stimulates angiogenesis and vascular endothelial cell proliferation. In addition, the MOR inhibits cell apoptosis via the PI3K/Akt signalling pathway. In this study, we aimed to explore the contribution of the MOR in ARDS and whether its effects are mediated via PI3K/Akt signalling. An ARDS model was established by intratracheal instillation of 5 mg kg lipopolysaccharide (LPS). Lung injury was confirmed by Haematoxylin and Eosin staining, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity and vascular cell adhesion molecule 1 expression. Lung inflammation was determined by assessment of interleukin-1β and tumour necrosis factor-α concentrations. The protein level of p-Akt was detected by western blot. Endomorphin-1-activated MORs attenuated LPS-induced lung injury, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity, interleukin-1β and tumour necrosis factor-α levels and vascular cell adhesion molecule 1 expression, and elevated LPS-induced decreased p-Akt expression. However, the protective effect of MOR activation on lung injury was reversed by the PI3K inhibitor, wortmannin. In conclusion, MOR involvement in LPS-induced ARDS is via the PI3K/Akt pathway.
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http://dx.doi.org/10.1113/EP087783DOI Listing
October 2019

Inhibition of Ubc9-Induced CRMP2 SUMOylation Disrupts Glioblastoma Cell Proliferation.

J Mol Neurosci 2019 Nov 2;69(3):391-398. Epub 2019 Jul 2.

Department of Emergency, Cangzhou Central Hospital, Xinhua West Road, Cangzhou, 061000, Hebei, China.

Glioblastoma (GBM) is the most aggressive astrocytoma. Despite maximum treatment, the GBM usually recurs and the patient survival is poor. Thus, understanding the molecular mechanism of GBM progression will be meaningful to ameliorate this situation. In this study, collapsin response mediator protein 2 (CRMP2) and Ubc9 protein levels were evaluated in three GBM cell lines. Sumoylated CRMP2 were enriched and immunoprecipitated using SUMO1 and IgG antibodies. CRMP2-K374A mutant was generated by site-direct mutagenesis. All indicated constructs were transfected into GL15 cells, and the corresponding proliferation-promoting effect was assessed through cell proliferation ratio. The t-CSM peptide was used to disturb Ubc9-CRMP2 interaction. CRMP2 is expressed in all tested GBM cell lines. The Ubc9 protein levels are positively correlated with CRMP2 level, and both can promote GBM cell proliferation. Blocking CRMP2 SUMOylation through SUMOylation-incompetent mutant or small peptide suppresses CRMP2-induced GBM cell proliferation. This study demonstrates that the CRMP2 SUMOylation exists widely in GBM cells and drives glioblastoma proliferation. CRMP2 SUMOylation inhibition can significantly suppress GBM proliferation in vitro.
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http://dx.doi.org/10.1007/s12031-019-01368-yDOI Listing
November 2019