Publications by authors named "Zhilei Zhang"

24 Publications

  • Page 1 of 1

A joint method for the screening of pharmacological chaperones for phenylalanine hydroxylase.

Org Biomol Chem 2021 Jun 11. Epub 2021 Jun 11.

The affiliated Obstetrics and Gynecology Hospital with Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Center of Genetic Medicine, Nanjing 210004, Jiangsu, P.R. China.

Phenylalanine hydroxylase (PAH) deficiency (PAHD) is an autosomal recessive disorder that causes severe injury to the nervous system, the treatment of which mainly depends on dietary therapy. The limited treatment options for PAHD are an incentive to develop new methods to identify more efficient therapeutic drugs, such as agonists which could improve PAH activity. In this study, we aimed to establish a rapid and convenient method for the screening and verification of PAH agonists. We compared fluorospectrophotometry and tandem mass spectrometry for detection of enzymatic formation of tyrosine, finding that the latter was a more sensitive method. We optimized immunoprecipitation purification conditions and measurement conditions of PAH activity. The optimal ratio between PAH protein and magnetic beads was 500 μg protein per 20 μL beads, and the optimized conditions for the detection of PAH enzymatic activity included the presence of 75 μM coenzyme ((6R)-l-erythro-5,6,7,8-tetrahydrobiopterin) and 30 min reaction time. Based on virtual screening, we screened ten candidate agonists from the FDA drug library. Three of these (nefopam, fluocinonide, and risperidone) were found to activate the enzyme in a dose-dependent manner (0.1-10 μM) by the joint method. We tested the efficacy of the three agonists on three PAH mutations (p.I65T, p.H107R, and p.D101N) that influence enzyme activity, and found that risperidone could specifically activate D101N-mutated enzyme. In conclusion, we established a joint method that is highly reliable, cost-effective, labor-saving, and time-saving. And we also found a specific agonist for D101N-mutated PAH by this joint method which may assist the development of clinical treatment for PAHD patients with different enzyme deficiencies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1ob00638jDOI Listing
June 2021

Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population.

Orphanet J Rare Dis 2021 May 12;16(1):214. Epub 2021 May 12.

Genetic Medicine Center, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, 123 Tianfei St., Qinhuai District, Nanjing, 210004, People's Republic of China.

Background: Hyperphenylalaninemia (HPA) is the most common amino acid metabolic disease involving phenylalanine hydroxylase (PAH, OMIM*612,349) deficiency or coenzyme tetrahydrobiopterin (BH4) deficiency. Patients with severe HPA often have a difficult life. Early diagnosis of HPA before the development of symptoms is possible via neonatal screening, facilitating appropriate treatment and reducing mortality and disability rates. This study revealed the prevalence, mutational and phenotypic spectrum, and prognosis of HPA by neonatal screening from January 2001 to September 2020 in Nanjing, Jiangsu Province, China.

Methods: Through a retrospective analysis of the information available in the neonatal screening database, the clinical presentations, laboratory data, molecular characteristics and treatment follow-up data of HPA patients detected by neonatal screening were evaluated.

Results: We diagnosed 181 patients with HPA from 1 to 957 newborns, giving an incidence of 1:6873. Among these patients, 177 were identified as PAH deficient and four patients were BH4 deficient. The average current age of the patients was 6.38 years old. The most common mutations of PAH were c.728 C > A/ p.Arg243Gln (13.83 %), c.158G > A/ p.Arg53His (9.57 %), c.611 A > G/ p.Tyr204Cys (7.44 %), and c.721 C > T/ p.Arg241Cys (6.38 %).

Conclusions: This study revealed the prevalence, phenotype-genotype, and prognosis of HPA in China and contributes to the updating of PAHD data for China and worldwide. Our study not only expanded the spectrum of phenotypes and genotype but also provided a valuable tool for improved genetic counseling and management of future cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-021-01846-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114530PMC
May 2021

MiR-124-3p Suppresses Prostatic Carcinoma by Targeting PTGS2 Through the AKT/NF-κB Pathway.

Authors:
Zhilei Zhang

Mol Biotechnol 2021 Jul 24;63(7):621-630. Epub 2021 Apr 24.

Department of Urologic Surgery, Shengli Hospital of Dongying, No.107 Beier Road, Dongying District, Dongying, 257000, Shandong, China.

MiR-124-3p had shown its tumor-regulatory properties in different cancers, but its potential roles in prostatic carcinoma had not been clearly understood. This study aimed to explore the roles of miR-124-3p in the regulation of prostatic carcinoma. The expression levels of PTGS2 and miR-124-3p were detected in prostatic carcinoma tissues and cultivated cell lines with qRT-PCR, immunohistochemistry and western blot, respectively. The interaction between miR-124-3p and PTGS2 was verified by the dual-luciferase reporter assay. Western blot, MTT, colony formation and flow cytometry assays were performed to evaluate the mediatory roles of miR-124-3p in prostatic carcinoma cells and the involvement of molecular pathways. Both prostatic carcinoma tissues and cells expressed a lower level of miR-124-3p and a higher level of PTGS2. PTGS2 was confirmed to be a target of miR-124-3p. MiR-124-3p suppressed cell viability, proliferation, migration, invasion and enhanced apoptosis of prostatic carcinoma cells by directly sponging PTGS2 to inhibit the AKT/NF-κB pathway. These findings provided information that miR-124-3p exerted anti-tumor effects in prostatic carcinoma by targeting PTGS2 to inactivate the AKT/NF-κB pathway. MiR-124-3p might have the potential to become an emerging therapeutic target for the treatment of prostatic carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12033-021-00326-7DOI Listing
July 2021

Prognostic significance of preoperative neutrophil-to-lymphocyte ratio in papillary renal cell carcinoma patients after receiving curative surgery based on a retrospective cohort.

BMC Urol 2021 Mar 22;21(1):43. Epub 2021 Mar 22.

Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: Inflammatory response biomarkers have been studied as promising prognostic factors in renal cell carcinoma, but few studies have focused on papillary renal cell carcinoma (PRCC). This study was performed to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in PRCC patients.

Methods: In total, 122 postoperative PRCC patients selected from 366 non-clear cell renal cell carcinoma patients were enrolled from our institution between 2012 and 2020. The optimal cutoff value of the NLR was assessed by receiver operating characteristic (ROC) curve analysis, and the Kaplan-Meier method and Cox's proportional hazards regression models were performed to analyze the association of the NLR with overall survival (OS). In addition, the potential of tumor-node-metastasis (TNM) stage, the NLR and an NLR-TNM system to predict survival were compared with ROC curves, and clinical usefulness of the predicting models were assessed by decision curve analysis.

Results: A threshold value of 2.39 for the NLR for OS analysis was determined by ROC curve analysis. An NLR ≥ 2.39 was associated with a more advanced TNM stage (P < 0.01) and larger tumors (P < 0.05) than a low NLR, as well as pathological subtype II (P < 0.05), and the patients with a high NLR also exhibited significantly worse overall survival outcomes (P < 0.05). The NLR was determined to be a significant independent prognostic indicator by univariable and multivariable analyses (HR = 5.56, P < 0.05). Furthermore, TNM stage and the NLR were integrated, and the area under the curve (AUC) of for the NLR-TNM system was larger than that of for the TNM system when predicting overall survival (0.84 vs 0.73, P = 0.04). Decision curve analysis also demonstrated a better clinical value for the NLR-TNM model to predict the prognosis.

Conclusion: A high preoperative NLR was associated with poor clinical and pathologic parameters in patients with PRCC; moreover, the NLR was also an independent prognostic factor for the OS of patients with PRCC. The NLR-TNM system, which was a model that integrated the NLR with TNM staging, could improve the ability to predict overall survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12894-021-00805-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983378PMC
March 2021

Two cases of hand, foot and mouth disease caused by enterovirus A71 after vaccination.

Int J Infect Dis 2021 Mar 15;108:190-197. Epub 2021 Mar 15.

Institute of Paediatrics, The Kunming Children's Hospital of Kunming Medical University, Kunming, PR China; Yunnan Key Laboratory of Children's Major Disease Research, Kunming, PR China. Electronic address:

Background: Enterovirus A71 (EVA71) is one of the main pathogens causing hand, foot and mouth disease (HFMD). In China, the proportion of cases of HFMD caused by EVA71 is known to be significantly lower following EVA71 vaccination; however, infection with EVA71 can still occur after vaccination.

Methods: The complete genomic sequences of EVA71-KM18A and KM18B (from two rare cases of EVA71 infection following vaccination) were obtained. Phylogenetic analysis, nucleotide mutation analysis, recombinant analysis and comparative analysis of amino acid mutations were performed.

Results: Phylogenetic analysis determined that the EVA71 strains belonged to the C4a subgenotype. The KM18A and KM18B strains were highly similar to the vaccine strains. For the KM18B strain, there were some obvious homologous recombination signals in the 5'non-coding region, region 2A, region 2C and region 3D. Amino acid mutations were observed in the SP55 (position 729) and 71-6 (position 500) conformational neutralizing epitopes of the KM18A and KM18B strains.

Conclusions: These amino acid mutations may affect the SP55 and 71-6 conformational neutralizing epitopes and change their spatial conformation, thereby weakening vaccine effectiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.03.039DOI Listing
March 2021

Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

BMC Cancer 2021 Feb 12;21(1):152. Epub 2021 Feb 12.

Organ Transplant Center, The Affiliated Hospital of Qingdao University, Haier Road No. 59, Qingdao, 266000, Laoshan District, China.

Background: The goal of this study is to disclose the clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

Methods: A total of 86 Chinese patients were enrolled in this study. A panel of 579 pan-cancer genes was sequenced for the qualified samples from these patients. Driver genes, actionability, and tumor mutational burden were inferred and compared to a cohort of Western patients.

Results: Totally, 36 and 12 driver genes were identified in the Chinese and Western cohorts, respectively. Of them, seven driver genes (IDH1, KRAS, TP53, BAP1, PBRM1, ARID1A, and NRAS) were shared by the two cohorts. Four driver genes (SPTA1, ARID2, TP53, and GATA1) were found significantly correlated with the tumor mutational burden. For both cohorts, half of the patients had actionable mutations. The two cohorts shared the most actionable genes but differed much in their frequency. Though KRAS mutations were at the first and second actionable rank respectively for the Chinese and Western populations, they were still at a relatively low level of actionable evidence.

Conclusions: The study on the clinical significance of genomic alterations directs the future development of precision medicine for intrahepatic cholangiocarcinoma treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-07792-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879680PMC
February 2021

Neonatal Screening and Genotype-Phenotype Correlation of 21-Hydroxylase Deficiency in the Chinese Population.

Front Genet 2020 22;11:623125. Epub 2021 Jan 22.

Genetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that leads to impaired cortisol biosynthesis. 21-hydroxylase deficiency (21-OHD) is the most common type of CAH. Severe cases of 21-OHD may result in death during the neonatal or infancy periods or sterility in later life. The early detection and timely treatment of 21-OHD are essential. This study aimed to summarize the clinical and genotype characteristics of 21-OHD patients detected by neonatal screening in Nanjing, Jiangsu province of China from 2000 to 2019. Through a retrospective analysis of medical records, the clinical presentations, laboratory data, and molecular characteristics of 21-OHD patients detected by neonatal screening were evaluated. Of the 1,211,322 newborns who were screened, 62 cases were diagnosed with 21-OHD with an incidence of 1:19858. 58 patients were identified with the classical salt-wasting type (SW) 21-OHD and four patients were identified with simple virilizing type (SV) 21-OHD. Amongst these patients, 19 cases patients accepted genetic analysis, and another 40 cases were received from other cities in Eastern China. Eighteen different variants were found in the gene. The most frequent variants was c.293-13A/C>G (36.29%). The most severe clinical manifestations were caused by large deletions or conversions of . This study suggested that neonatal screening effectively leads to the early diagnosis of 21-OHD and reduces fatal adrenal crisis. Our data provide additional information on the occurrence and genotype-phenotype correlation of 21-OHD in the Chinese population which can be used to better inform treatment and improve prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.623125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862715PMC
January 2021

Circ_LDLR Knockdown Suppresses Progression of Hepatocellular Carcinoma via Modulating miR-7/RNF38 Axis.

Cancer Manag Res 2021 13;13:337-349. Epub 2021 Jan 13.

Department of Hepatobiliary Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, Hebei, People's Republic of China.

Background: Hepatocellular carcinoma (HCC) is a horrible malignancy derived from liver. Circular RNAs (circRNAs) act important roles in the pathogenesis and progression of human diseases, including HCC. The current assay intended to investigate the function of circRNA low-density lipoprotein receptor (circ_LDLR) in HCC and clarify the underlying mechanism.

Materials And Methods: Expression of circ_LDLR, microRNA (miR)-7 and ring finger protein 38 (RNF38) was determined by quantitative real-time PCR (qRT-PCR) or Western blot analysis. Flow cytometry was used to detect cell cycle distribution and apoptosis. Cell colony formation ability and viability were examined by colony formation and methyl thiazolyl tetrazolium (MTT) assays, respectively. Levels of cell proliferation and epithelia-mesenchymal transition (EMT) biomarker proteins were analyzed via Western blot assay. Cell migration and invasion were monitored by Transwell assay, and target relationship between miR-7 and circ_LDLR or RNF38 was validated by dual-luciferase reporter assay. Xenograft model was established to explore the role of circ_LDLR in vivo.

Results: Expression of circ_LDLR and RNF38 was upregulated, but miR-7 expression was downregulated in HCC tissues and cells. Circ_LDLR knockdown significantly inhibited cell proliferation, migration, invasion and EMT in HCC cells. Circ_LDLR acted as a sponge of miR-7, and interference of miR-7 could attenuate circ_LDLR knockdown-induced inhibitory effects on malignant behaviors of HCC cells. Besides, miR-7 also repressed cell proliferation and metastasis of HCC cells, by targeting RNF38. Depletion of circ_LDLR could suppress tumor growth in vivo.

Conclusion: Depletion of circ_LDLR restrained HCC cell proliferation, metastasis and tumorigenesis through the regulation on miR-7/RNF38 axis, affording a promising therapeutic target for HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S275003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813465PMC
January 2021

CircLRRK1 targets miR-223-3p to inhibit the proliferation, migration and invasion of trophoblast cells by regulating the PI3K/AKT signaling pathway.

Placenta 2021 01 7;104:110-118. Epub 2020 Dec 7.

Department of Gynaecology, Qingdao Women and Children's Hospital, Qingdao, 266011, Shandong, China. Electronic address:

Introduction: Many studies have shown that circular RNAs (circRNAs) are related to the occurrence of preeclampsia (PE). However, the role of circLRRK1 in the progression of PE is unclear.

Methods: The identification and localization of circLRRK1 were verified by Actinomycin D (ActD) assay, Ribonuclease R (RNase R) digestion assay and subcellular localization assay. Moreover, the proliferation of trophoblast cells was detected by 3-(45)-dimethylthiahiazo (-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and colony formation assay. Furthermore, the migration and invasion of trophoblast cells were determined by wound healing assay and transwell assay. Meanwhile, Western blot (WB) analysis was used to examine the protein levels of migration markers and PI3K/AKT signaling pathway markers. In addition, the interaction between circLRRK1 and miR-223-3p was confirmed by dual-luciferase reporter assay and biotin-labeled RNA pull-down assay.

Results: Our results showed that circLRRK1 was significantly highly expressed in PE patients. Silenced circLRRK1 could markedly enhance the proliferation, migration and invasion of trophoblast cells. Additionally, we found that circLRRK1 could target miR-223-3p. MiR-223-3p overexpression also promoted the proliferation, migration and invasion of trophoblast cells. The rescue experiments revealed that miR-223-3p inhibitor could reverse the promoting effect of circLRRK1 silencing on the proliferation, migration and invasion of trophoblast cells. Furthermore, circLRRK1 silencing could activate the PI3K/AKT signaling pathway by targeting miR-223-3p.

Discussion: CircLRRK1 could suppress the proliferation, migration and invasion of trophoblast cells by regulating the PI3K/AKT signaling pathway via targeting miR-223-3p, suggesting that circLRRK1 might be a potential biomarker for the treatment of PE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.placenta.2020.12.003DOI Listing
January 2021

Effect of Taijiquan Exercise on Rehabilitation of Male Amphetamine-Type Addicts.

Evid Based Complement Alternat Med 2020 19;2020:8886562. Epub 2020 Nov 19.

Chinese Wushu Research Center, Shanghai University of Sport, Shanghai 200438, China.

Taijiquan is a traditional Chinese sport that is classified as a moderate exercise. Recent studies have evaluated the effectiveness of Taijiquan in substance abuse rehabilitation. . To test the rehabilitation effect of Taijiquan exercise in patients with amphetamine (ATS) drug dependence. . The effect of Taijiquan intervention was tested by parallel control experiment: Taijiquan group ( = 38) and control group ( = 38). The factors between the experimental groups were the group (Taijiquan group and the control group), and the factors within the group were the test time (before and after intervention). Repeated measurement analysis of variance was used to compare the two groups, and the factors that may affect the results were included in the covariance. . Taijiquan exercise promoted the balance control ability of ATS dependent patients ( = 0.014,  = 0.064), increased the overall sense of health ( = 0.029,  = 0.100), vitality ( = 0.030,  = 0.056), and mental health ( = 0.016,  = 0.061), improved trait anxiety ( = 0.028,  = 0.053), and reduced drug craving ( = 0.048,  = 0.048). . Taijiquan exercise is beneficial to the physical and mental recovery of dependent patients, and the physical and mental benefits of exercise may have an effect on drug craving, which is of the most important significance for addicts to quit drugs and prevent relapse. The study is registered on the Chinese Clinical Trial Registry (No. ChiCTR1800015777).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8886562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690993PMC
November 2020

Hydrazinocurcumin and 5-fluorouracil enhance apoptosis and restrain tumorigenicity of HepG2 cells via disrupting the PTEN-mediated PI3K/Akt signaling pathway.

Biomed Pharmacother 2020 Sep 17;129:109851. Epub 2020 Jun 17.

Department of Hepatobiliary Surgery, Fourth Hospital of Hebei Medical University Tumor Hospital of Hebei Province, Shijiazhuang 050011, PR China. Electronic address:

Hydrazinocurcumin (HZC), a curcumin analogue, serves as a tumor suppressor in breast cancer and lung cancer. In this study, we investigate the role and mechanism of HZC in regulating HepG2 cell apoptosis and tumorigenicity, and its synergistic effects with 5-fluorouracil (5-Fu). HepG2 cells were treated with HZC and/or 5-Fu to analyze the possible synergistic effects on cell proliferation, apoptosis and cell cycle distribution in vitro using EdU staining, Hoechst staining and flow cytometry, respectively. For mechanistic investigation we used pic, a phosphatase and tensin homolog (PTEN) inhibitor, and in other studies assessed the expression pattern of PTEN and PI3K/Akt signaling pathway-related genes. Additionally, we tested in vivo effects of HZC and 5-Fu treatment on growth of HepG2 cell tumors in nude mice. We found that HZC or 5-Fu induced apoptosis and repressed proliferation of HepG2 cells by upregulating the expression of PTEN and disrupting the PI3K/Akt signaling pathway activation. Moreover, HZC had a higher pro-apoptotic effect than 5-Fu. HZC and 5-Fu induced HepG2 cell apoptosis and inhibited their tumorigenicity in vivo. Inhibition of PTEN expression activated the PI3K/Akt signaling pathway and reversed the protective effects of HZC or 5-Fu. Thus, HZC and 5-Fu increase PTEN, which blocks the PI3K/Akt signaling pathway, ultimately inducing HepG2 cell apoptosis. Importantly, the synergistic combination of HZC and 5-Fu may present promising strategy for the treatment of HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2020.109851DOI Listing
September 2020

A study of zederone for the inhibition on ovarian cancer cell proliferation through mTOR/p70s6K signalling pathway.

J BUON 2020 Mar-Apr;25(2):785-791

Department of Obstetrics and Gynecology, the third affiliated Hospital of Zhengzhou University and Henan Province Women's and Children's Hospital, Zhengzhou 450000, P.R. China.

Purpose: To investigate the inhibitory effect of Zederone (Zed) on the proliferation of human ovarian cancer cell line SK-OV-3 (SKOV3) and to explore the possible mechanism.

Methods: Cell Counting Kit-8 (CCK-8) assay was performed to detect the inhibitory effect of different concentrations of Zed on the proliferation of SKOV3 cells; the effect of Zed on the morphology of SKOV3 cells was observed; flow cytometry was performed to investigate the effect of Zed on the cycle phase distribution of SKOV3 cells; Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and western blot were performed to detect the effects of Zed on the expression of mTOR, p70s6K, p-PI3K and p-Akt at mRNA and protein level in SKOV3 cells, respectively.

Results: Zed could effectively inhibit the proliferation of SKOV3 cells in vitro and change cell morphology. Flow cytometry indicated that Zed arrested SKOV3 cells at G1 phase. qRT-PCR revealed that Zed downregulated the mRNA levels of mTOR and p70s6K. However, western blot demonstrated that Zed could downregulate the protein expressions of mTOR, and phosphorylated p70 S6 kinase (p-p70s6K) in SKOV3 cells, but had no significant influences on p-PI3K and p-Akt proteins.

Conclusion: In conclusion, Zed can significantly inhibit the proliferation of human ovarian cancer SKOV3 cells, and this regulation may be mediated by the inhibition of mTOR/p70s6K signal pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2021

Author Correction: Role of HDAC9-FoxO1 Axis in the Transcriptional Program Associated with Hepatic Gluconeogenesis.

Sci Rep 2020 May 28;10(1):8989. Epub 2020 May 28.

Jiangsu Province Key Lab of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-66085-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253407PMC
May 2020

Construction of PDDA functionalized black phosphorus nanosheets/BiOI Z-scheme photocatalyst with enhanced visible light photocatalytic activity.

J Colloid Interface Sci 2020 Sep 27;576:34-46. Epub 2020 Apr 27.

School of Resources and Environmental Engineering, Shandong University of Technology, 255049 Zibo, PR China. Electronic address:

The use of black phosphorus (BP) nanosheets has attracted much attention in the area of photocatalysis owing to the thickness-tunable bandgap and high carrier mobility. In order to improve the stability of BP nanosheets, poly dimethyldiallyl ammonium chloride (PDDA) is used to passivate the BP nanosheets and change its surface properties. The present study concerns the development of a facile electrostatic assembly method for the construction of a Z-scheme system consisting of PDDA-functionalized BP nanosheets and layered BiOI in order to enhance visible light adsorption and promote electron-hole separation. The morphology, structure and photoelectrochemical properties of the composites are thoroughly characterized and the photocatalytic performances of all the samples were assessed under visible light irradiation. The 5-F-BP/BiOI exhibits excellent photocatalytic activity with removal efficiencies of 97.6% and 90.0% for methylene blue (MB) and tetracycline (TC), respectively. Superoxide radicals (·O) were found to be the main organic decomposition products according to species trapping experiments. The photocatalyst presents favorable stability after three catalytic cycles. This study provides new insights into the design of highly efficient Z-scheme photocatalysts based on functionalized BP nanosheets in order to meet environmental demands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2020.04.103DOI Listing
September 2020

Hydrazinocurcumin Induces Apoptosis of Hepatocellular Carcinoma Cells Through the p38 MAPK Pathway.

Clin Transl Sci 2020 Feb 26. Epub 2020 Feb 26.

Department of Hepatobiliary Surgery, Fourth Hospital of Hebei Medical University Tumor Hospital of Hebei Province, Shijiazhuang, China.

Hydrazinocurcumin (HZC), a synthetic derivative of curcumin (CUR), has been documented to show anticancer potential in impeding tumor growth in several cancers, including hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms remain unclear. This study aimed to explore the function and underlying mechanisms of HZC on HCC cells, which may involve the p38 mitogen activated protein kinase (MAPK) pathway. HZC was first purified and identified. HepG2 cells were then subjected to treatment with HZC or CUR of different concentrations and p38 MAPK signaling inhibitor (SB203580) to verify their effects on HCC cell apoptosis and proliferation. Furthermore, the functional relevance between HZC and the p38 MAPK pathway in HCC was examined. It was observed that 40 μM HZC exhibited the best pro-apoptosis effect in HCC cells. HZC was found to inhibit HCC cell proliferation and promote apoptosis, the effect of which was stronger than 5-fluorouracil (5-FU). More importantly, the anti-oncogenic effect of HZC and 5-FU was implicated with activation of the p38 MAPK pathway. In vivo experimental results showed that HZC inhibited tumor growth more effectively than 5-FU through the p38 MAPK pathway. These results provide evidence that HZC exerted anti-oncogenic and pro-apoptosis effects in HCC cells through activation of the p38 MAPK pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cts.12765DOI Listing
February 2020

Analysis of five cases of hypermethioninemia diagnosed by neonatal screening.

J Pediatr Endocrinol Metab 2020 Jan;33(1):47-52

Center of Genetic Medicine, The Affiliated Obstetrics and Gynecology Hospital with Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Background Hypermethioninemia is a group of diseases with elevated plasma methionine (Met) caused by hereditary and non-hereditary factors, although it could also be caused by administration of the amino acid Met. Among these, the disease caused by methionine adenosyltransferase (MAT) I/III deficiency is the most common, and is characterized by persistent, isolated hypermethioninemia as well as slightly elevated homocysteine. S-adenosylmethionine is the product of Met, which can be used as a direct methyl donor of many substances, such as choline and nucleotide, and essential in the development of the body. Among the patients, most have no symptoms, and a small number have central nervous system complications with high levels of plasma Met, including mental retardation, cognitive impairment and special breathing odor. Methods In this study, five cases of MAT I/III deficiency were diagnosed and retrospectively analyzed among 220,000 newborns. Patients with high Met levels received a Met-restricted diet treatment. Results and conclusions MAT I/III deficiency is a common reason for Met elevation in neonatal screening by tandem mass spectrometry (MS/MS), which needs long-term follow-up except for these patients with explicitly benign mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpem-2019-0285DOI Listing
January 2020

Note: Development of sTGC strip front-end readout prototype for ATLAS new small wheel upgrade.

Rev Sci Instrum 2018 Dec;89(12):126104

State Key Laboratory of Particle Detection and Electronics, University of Science and Technology of China, Hefei 230026, China.

This note presents the development of front-end electronics prototype for A Toroidal LHC ApparatuS (ATLAS) New Small Wheel (NSW) detector small-strip Thin Gap Chamber (sTGC) to be used for level-1 triggering and precision muon tracking at the Large Hadron Collider. The sTGC front-end electronics must deal with a large number of strip channels with very limited space constraint, large dynamic range of charge readout with low noise, simultaneous fast trigger, and precision readout data movement. The prototype uses custom radiation-tolerant application specific integrated circuits, optimized layout, power, and ESD protection networks to realize the above stringent requirements. The electronic test indicates that the front-end channel has a dynamic range of 900 pC and inherent noise of 0.19 fC. The sTGC cosmic ray test verified the precision charge measurement of the prototype, reconstructed the muon track, and measured the performance of sTGC. The NSW trigger chain test verified the trigger processing and 4.8 Gbps transmission of the prototype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/1.5055906DOI Listing
December 2018

miR-122-5p Inhibits the Proliferation, Invasion and Growth of Bile Duct Carcinoma Cells by Targeting ALDOA.

Cell Physiol Biochem 2018 17;48(6):2596-2606. Epub 2018 Aug 17.

Department of Radiation Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background/aims: Bile duct cancer, although not among the most common tumors, still accounts for more and more worldwide deaths each year. By attempting to verify an overexpression of ALDOA in cholangiocarcinoma tissues and cells and explore the underlying molecular mechanism regulated by miR-122-5p, this study was designed to provide a potential molecular target in bile duct cancer treatment.

Methods: Western blot and immunohistochemistry were performed to detect the ALDOA protein level in duct carcinoma tissues. The transfection efficiency was confirmed by western blot and/or RT-qPCR assay. The proliferation of bile duct carcinoma cells was determined by MTT and colony formation assay. The invasion ability of bile duct carcinoma cells was evaluated with Transwell invasion assay. Flow cytometry detected cell apoptosis of bile duct carcinoma cells. The miRNAs which modulate ALDOA were filtrated from bioinformatics software and clinical specimens. The target relationship was confirmed by dual luciferase reporter assay. Furthermore, a xenograft model was completed to verify the impact of miRNA on inhibition growth of bile duct carcinoma cells.

Results: ALDOA was found up-regulated in bile duct carcinoma tissues and cells. Knockdown of ALDOA promoted the apoptosis of cells and inhibited the proliferation and invasion of bile duct carcinoma cells. Bioinformatics and clinical specimens indicated the negative correlation and targeted regulation between miR-122-5p and ALDOA. By down-regulating ALDOA, overexpression of miR-122-5p appeared to promote cell apoptosis and significantly inhibit cell proliferation, invasion in vitro and suppress the tumor growth in vivo.

Conclusion: miR-122-5p inhibited proliferation and invasion of bile duct carcinoma cells and promoted cell apoptosis by targeting ALDOA expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000492702DOI Listing
September 2018

Suppressor of cytokine signalling-2 limits IGF1R-mediated regulation of epithelial-mesenchymal transition in lung adenocarcinoma.

Cell Death Dis 2018 04 1;9(4):429. Epub 2018 Apr 1.

Jiangsu Province Key Lab of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, China.

Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma, is the leading cause of death from lung malignancies and has a poor prognosis due to metastasis. Suppressor of cytokine signalling-2 (SOCS2), a feedback inhibitor of cytokine signalling, has been shown to be involved in growth control. Here, we show that SOCS2 were significantly downregulated in tumour foci in NSCLC patients. The expression levels of SOCS2 significantly correlated with clinical stage, lymph node metastasis, histological subtype and survival time. In particular, the decreased expression of SOCS2 significantly associated with advanced pathological stage, lymph node metastasis and shorter overall survival in lung adenocarcinoma patients. In vivo animal results showed that overexpressed SOCS2 attenuated the metastatic characteristics of lung adenocarcinoma, including by inhibiting the epithelial-mesenchymal transition (EMT). Further functional studies indicated that insulin-like growth factor 1 (IGF1)-driven migratory and invasive behaviours of lung adenocarcinoma cells can be partially suppressed by exogenous SOCS2 expression. Investigations into the mechanism of action revealed that SOCS2 inhibits EMT by inactivating signal transducer and activator of transcription 3 (STAT3) and STAT5 via the competitive binding of SOCS2 to the STAT binding sites on IGF1R. Altogether, our results reveal an important role for SOCS2 dysregulation in the pathogenicity of lung adenocarcinoma, suggest its potential use as a biomarker for diagnosing lung adenocarcinoma, and paves the way to develop novel therapy targets as the axis of SOCS2-IGF1R-STAT in lung adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-018-0457-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861121PMC
April 2018

Role of HDAC9-FoxO1 Axis in the Transcriptional Program Associated with Hepatic Gluconeogenesis.

Sci Rep 2017 07 21;7(1):6102. Epub 2017 Jul 21.

Jiangsu Province Key Lab of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, China.

Histone deacetylase 9 (HDAC9) regulates hepatic gluconeogenesis by deacetylating Forkhead box O 1 (FoxO1). HDAC9 upregulation is involved in hepatitis C virus (HCV)-associated exaggerated gluconeogenesis. Herein, we found in addition to FoxO1, HDAC9 also regulates other gluconeogenic transcription factors, including peroxisomeproliferator-activated receptor-γ coactivator-1α (PGC-1α), cyclic AMP-responsive element-binding protein (CREB), and glucocorticoid receptor (GR). Unlike FoxO1, which is regulated by post-translational modification responses to HDAC9, HDAC9 regulates PGC-1α, CREB and GR by altering gene expression. Similar to PGC-1α, CREB and GR were found to be novel regulatory targets of FoxO1 by examination of the FoxO1 binding site in their promoter. PGC-1α, CREB and GR were upregulated in response to HDAC9 via FoxO1 deacetylation. These findings indicate that HDAC9-FoxO1 signalling contributes to gluconeogenesis by modulating the expression of gluconeogenic transcription factors. In particular, metabolic profiling demonstrated a clear shift towards gluconeogenesis metabolism, and HDAC9-FoxO1 signalling can be strongly induced to upregulate gluconeogenic transcription factors following HCV infection. The positive correlation between HDAC9 and gluconeogenic transcription factor expression levels in the livers of both HCV-infected patients and normal individuals further emphasizes the clinical relevance of these results. Thus, HDAC9-FoxO1 signalling axis is involved in regulating gluconeogenic transcription factors, gluconeogenesis, and HCV-induced type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-06328-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522426PMC
July 2017

Anomalous but massive removal of two organic dye pollutants simultaneously.

J Hazard Mater 2016 Nov 22;318:54-60. Epub 2016 Jun 22.

Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 100083, China. Electronic address:

A one-pot method to remove two organic dye contaminants and alkali simultaneously from alkaline wastewater was developed by forming Zn-Al layered double hydroxide (ZnAl-LDH). Using this process, not only alkali but also methyl orange (MO), an anionic contaminant was totally removed from wastewater. In addition, cationic contaminant, methylene blue (MB) was also removed effectively while maintaining the high removal efficiency of MO. The removal efficiency of MO was almost 100% and the pH of the treated wastewater decreased from 12 to 7.38. The charge-limited removal process, molecular arrangement of the contaminants in LDHs, and the anomalous removal mechanism were analyzed experimentally and through simulation. After MO accumulated in the interlayers of LDH by electrostatic interaction, MB entered and trapped by hydrophobic interaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2016.06.044DOI Listing
November 2016

Promotion of breast cancer cells MDA-MB-231 invasion by di(2-ethylhexyl)phthalate through matrix metalloproteinase-2/-9 overexpression.

Environ Sci Pollut Res Int 2016 May 6;23(10):9742-9. Epub 2016 Feb 6.

Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China.

Di(2-ethylhexyl)phthalate (DEHP) is an estrogenic chemical that is widely used in polyvinyl products. We aimed to determine the mechanisms behind the effects of DEHP on ERα-negative breast cancer cells MDA-MB-231 invasion and matrix metalloproteinases-2/-9 (MMP-2/-9) up-regulation in this study. Transwell assay indicated that DEHP exposure (>50 μg/ml) significantly enhanced the invasion ability of MDA-MB-231 cells. Quantitative real-time PCR (qPCR) and western blotting revealed that MMP-2/-9 is overexpressed in mRNA and protein levels after DEHP treatment. Gelatin zymography consistently demonstrated that DEHP exposure also enhances the activity of MMP-2/-9. Immunofluorescence assay showed that DEHP could accelerate NF-kappaB (NF-κB) subunits-p65 translocation into the nucleus, which is confirmed by western blotting assay, suggesting that the ratio of nuclear/cytosolic level of p65 was significantly increased. Furthermore, the invasion and MMP-2/-9 overexpression of MDA-MB-231 cells after DEHP-treated were reversed by the NF-κB chemical inhibitor JSH-23 via drug inhibition assay. This study suggested that DEHP could promote ERα-negative breast cancer cells MDA-MB-231 invasion through activating NF-κB and MMP-2/-9 overexpression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-016-6158-7DOI Listing
May 2016

Synthesis, characterization and cytotoxicity of mixed-ligand complexes of palladium(II) with 2, 2'-biquinoline/1, 4-diaminobutane and 4-toluenesulfonyl-L-amino acid dianion.

Eur J Med Chem 2011 Nov 30;46(11):5711-6. Epub 2011 Aug 30.

College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, China.

Seven new palladium(II) complexes (1-7) with 4-toluenesulfonyl-L-amino acid dianion and 2, 2'-biquinoline (bqu)/1,4-diaminobutane (dab) have been synthesized and characterized by elemental analysis, IR, (1)H NMR, and mass spectra techniques. Crystal structure of the complex (7) has been determined by X-ray diffraction analysis. The cytotoxicity was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The results indicate that the complexes exert cytotoxic effects with selectivity against tested carcinoma cell lines, but their cytotoxicity is less than that of cisplatin. It suggests that all the amino acids, N-containing ligands and metal ions have important effect on cytotoxicity, but the IC(50) values do not show definite correlation with variation of amino acids, N-containing ligands and metal ions, the cytotoxicity of complexes is related to tumor cell species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2011.08.037DOI Listing
November 2011

[Study of multi-factor cognition evoked by binocular disparity].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2003 Dec;20(4):679-85

Department of Biological Science and Technology, Zhejiang University, Hangzhou 310027.

It is the aim of studies in cognitive process to understand how the impressive cognitive capacity of the human mind is uninterruptedly developed and how the process is controlled. We have been focusing attention on the central question with stereoscopic research. A multi-channel EEG data acquisition system is constructed for cognition studies which not only works perfectly in the EEG collection and signal processing of stereoscopic visual evoked potentials(VEP) but also is suitable for investigative and clinical use. We have identified the fact that the processing of stereoscopic depth information is done in the cortical advance functional areas with labeled characteristic signaling of the depth related VEP and the results were shown to be of no difference when compared with the ones of other investigations. We believe, the stereoscopic depth cognition is both a dynamic multi-factor processing process and a consequence of depth perception in advanced cortical areas through biological feedback to the whole process of visual signal processing. It is our novel and significant supposition in the psychophysical study, and the experimental results of the VEP are presented in this article.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2003