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1.
Int J Biol Macromol ; 256(Pt 2): 128233, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38040166

ABSTRACT

In this work, we report an environmentally friendly renewable nanocomposite magnetic lignin-based palladium nanoparticles (Fe3O4-lignin@Pd-NPs) for efficient wastewater treatment by decorating palladium nanoparticles without using any toxic reducing agents on the magnetic lignin abstracted from Poplar. The structure of composite Fe3O4-lignin@Pd-NPs was unambiguously confirmed by XRD, SEM, TEM, EDS, FTIR, and Zeta potential. After systematic evaluation of the use and efficiency of the composite to remove toxic organic dyes in wastewater, some promising results were observed as follows: Fe3O4-lignin@Pd-NPs exhibits highly active and efficient performance in the removal of toxic methylene blue (MB) (up to 99.8 %) wastewater in 2 min at different concentrations of MB and different pH values. Moreover, except for toxic MB, the other organic dyes including Rhodamine B (RhB), Rhodamine 6G (Rh6G), and Methyl Orange (MO) can also be removed efficiently by the composite. Finally, the easily recovered composite Fe3O4-lignin@Pd-NPs exhibits well stability and reusability, and catalytic efficiency is maintained well after ten cycles. In conclusion, the lignin-based magnetism Pd composite exhibits powerful potential practical application in industrial wastewater treatment.


Subject(s)
Metal Nanoparticles , Nanocomposites , Water Purification , Lignin , Metal Nanoparticles/chemistry , Palladium/chemistry , Wastewater , Coloring Agents
2.
Article in English | WPRIM (Western Pacific) | ID: wpr-1007910

ABSTRACT

OBJECTIVE@#This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.@*METHODS@#We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( n = 113,154) and MDD ( n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.@*RESULTS@#The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.@*CONCLUSION@#This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.


Subject(s)
Humans , Depressive Disorder, Major/genetics , Depression , Genome-Wide Association Study , Mendelian Randomization Analysis , Risk Factors , Serotonin Plasma Membrane Transport Proteins
3.
EMBO Mol Med ; 15(11): e17611, 2023 11 08.
Article in English | MEDLINE | ID: mdl-37691516

ABSTRACT

Cingulin (CGN) is a cytoskeleton-associated protein localized at the apical junctions of epithelial cells. CGN interacts with major cytoskeletal filaments and regulates RhoA activity. However, physiological roles of CGN in development and human diseases are currently unknown. Here, we report a multi-generation family presenting with autosomal dominant non-syndromic hearing loss (ADNSHL) that co-segregates with a CGN heterozygous truncating variant, c.3330delG (p.Leu1110Leufs*17). CGN is normally expressed at the apical cell junctions of the organ of Corti, with enriched localization at hair cell cuticular plates and circumferential belts. In mice, the putative disease-causing mutation results in reduced expression and abnormal subcellular localization of the CGN protein, abolishes its actin polymerization activity, and impairs the normal morphology of hair cell cuticular plates and hair bundles. Hair cell-specific Cgn knockout leads to high-frequency hearing loss. Importantly, Cgn mutation knockin mice display noise-sensitive, progressive hearing loss and outer hair cell degeneration. In summary, we identify CGN c.3330delG as a pathogenic variant for ADNSHL and reveal essential roles of CGN in the maintenance of cochlear hair cell structures and auditory function.


Subject(s)
Deafness , Hearing Loss , Animals , Humans , Mice , Cytoskeletal Proteins , Deafness/genetics , Hair Cells, Auditory/metabolism , Hearing/physiology , Hearing Loss/genetics , Hearing Loss/metabolism
4.
Int J Gen Med ; 16: 203-209, 2023.
Article in English | MEDLINE | ID: mdl-36699343

ABSTRACT

Purpose: To investigate the prevalence and influencing factors of symptomatic dry eye disease (DED) in Chinese coal workers. Methods: The prevalence of symptomatic DED in coal workers was investigated by using the questionnaire of Ocular Surface Disease Index (OSDI) and the influencing factors were explored. Results: The prevalence of symptomatic DED was 50.7% in coal workers. Of the influencing factors of symptomatic DED, the level of dust exposure had an odds ratio (OR) of 1.26, the time of dust exposure had an OR of 1.02, and the age had an OR of 1.03. Conclusion: There was a high morbidity of symptomatic DED among coal workers and the level and the time of dust exposure and the age of coal workers had important effects.

5.
Org Lett ; 24(45): 8283-8288, 2022 11 18.
Article in English | MEDLINE | ID: mdl-36331137

ABSTRACT

In this work, we successfully explored an unexpected dehydrogenation triggered by Pd/Cu-catalyzed C(sp3)-H arylation and intramolecular C-N coupling of amides to synthesize the bioactive 1,2-dihydroquinoline scaffold with good regioselectivity and good compatibility of functional groups. This strategy provides an alternative route to realize molecular complexity and diversity from simple and readily available molecules via multiple C-H bond activation. Preliminary mechanistic studies demonstrated that ß,γ-dehydrogenation is triggered by the arylation of the C(sp3)-H bond and the intramolecular C-N coupling.


Subject(s)
Amides , Palladium , Amides/chemistry , Palladium/chemistry , Catalysis , Molecular Structure
6.
Int J Ophthalmol ; 15(10): 1619-1626, 2022.
Article in English | MEDLINE | ID: mdl-36262859

ABSTRACT

AIM: To analyze concentrations of vascular endothelial growth factor (VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy (PDR) patients pre-treated with intravitreal anti-VEGF injections (IVI) at different time periods prior to pars plana vitrectomy (PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative IVI. METHODS: The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDR-related complications (PDR group) and 21 eyes with non-diabetic ocular disease (control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3d after IVI (3-day group); 5d after IVI (5-day group); 7 or more days after IVI (≥7-day group); and no IVI. Vitreous fluid samples (0.5-1.0 mL) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor (bFGF), periostin (PN), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression analysis. RESULTS: PDR eyes without IVI had significantly higher VEGF, bFGF, PN, and IL-6 concentrations than non-diabetic eyes (all P<0.05), and had a significantly higher concentration of VEGF (P<0.05) and a significantly lower concentration of IL-8 (P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, bFGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups (all P<0.05); meanwhile there was no significant difference in TNF-α among groups (P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of bFGF and PN. The degree of vitreoretinal fibrosis was significantly higher in the ≥7-day group compared to the 3-day (P=0.015) and 5-day group (P=0.039), and vitreoretinal fibrosis correlated significantly with concentrations of bFGF, PN, IL-6, and IL-8 (all P<0.05). Univariate ordinal logistic regression analysis showed that bFGF was an independent risk factor for the severity of vitreoretinal fibrosis in PDR patients pre-treated with IVI. CONCLUSION: The vitreous concentrations of VEGF, bFGF, PN, IL-6, and IL-8 change after pretreatment with IVI before PPV in PDR patients. The degree of vitreoretinal fibrosis is higher in patients with a longer time between IVI treatment and PPV, which may be related to the angio-fibrosis switch. The results suggest that PPV should be performed 5d after IVI administration in PDR patients.

7.
Ying Yong Sheng Tai Xue Bao ; 33(1): 229-238, 2022 Jan.
Article in Chinese | MEDLINE | ID: mdl-35224945

ABSTRACT

In this study, triazine-degrading strain SB5 was isolated and screened from the activated sludge contaminated with atrazine by enrichment culture technology. Based on its morphology and 16S rRNA gene analysis, strain SB5 was initially identified as Paenarthrobacter sp. It contained the atrazine-degrading genes trzN, atzB, and atzC. The addition of glucose, sucrose, sodium citrate, yeast extract and peptone to the culture medium significantly increased the biomass and atrazine degradation efficiency of strain SB5. The addition of (NH4)2SO4 and NH4Cl inhibited the biomass of strain SB5, but did not affect its degradation efficiency for atrazine. The addition of starch did not affect the biomass of strain SB5, but significantly inhibited its degradation for atrazine. Strain SB5 showed good atrazine tolerance and atrazine degradation ability in the temperature range of 4-42 ℃, initial pH of 4-10 and initial concentration of 50-1000 mg·L-1. Using 100 mg·L-1 atrazine as the sole carbon source, the strain SB5 degraded 100% of atrazine within 36 h under the optimal conditions of 37 ℃ and initial pH 8.0. The results of degradation spectrum analysis showed that strain SB5 had a good degradation effect on the six triazine herbicides (simazine, terbuthylazine, propazine, cyanazine, ametryn and prometryn) at an initial concentration of 100 mg·L-1, and the degradation rates were 86.4%, 92%, 98.6%, 95.6%, 100% and 99.2% after 48 h of incubation, respectively. The results demonstrated that SB5 was an efficient and broad-spectrum degradation strain. The strain SB5 further enriched the strain resources for atrazine biodegradation, and its high-efficient and broad-spectrum degradation characteristics for triazine herbicides showed a potential application value in the development of bioremediation technology for the pollution of triazine herbicides.


Subject(s)
Atrazine , Herbicides , Atrazine/analysis , Atrazine/metabolism , Biodegradation, Environmental , Herbicides/analysis , Herbicides/metabolism , RNA, Ribosomal, 16S , Soil Microbiology
8.
Front Cell Dev Biol ; 9: 728352, 2021.
Article in English | MEDLINE | ID: mdl-34621745

ABSTRACT

In the mammalian cochlea, spiral ganglion neurons (SGNs) relay the acoustic information to the central auditory circuits. Degeneration of SGNs is a major cause of sensorineural hearing loss and severely affects the effectiveness of cochlear implant therapy. Cochlear glial cells are able to form spheres and differentiate into neurons in vitro. However, the identity of these progenitor cells is elusive, and it is unclear how to differentiate these cells toward functional SGNs. In this study, we found that Sox2+ subpopulation of cochlear glial cells preserves high potency of neuronal differentiation. Interestingly, Sox2 expression was downregulated during neuronal differentiation and Sox2 overexpression paradoxically inhibited neuronal differentiation. Our data suggest that Sox2+ glial cells are potent SGN progenitor cells, a phenotype independent of Sox2 expression. Furthermore, we identified a combination of small molecules that not only promoted neuronal differentiation of Sox2- glial cells, but also removed glial cell identity and promoted the maturation of the induced neurons (iNs) toward SGN fate. In summary, we identified Sox2+ glial subpopulation with high neuronal potency and small molecules inducing neuronal differentiation toward SGNs.

9.
Nature ; 587(7832): 139-144, 2020 11.
Article in English | MEDLINE | ID: mdl-33116310

ABSTRACT

Zygotic genome activation (ZGA) is the first transcription event in life1. However, it is unclear how RNA polymerase is engaged in initiating ZGA in mammals. Here, by developing small-scale Tn5-assisted chromatin cleavage with sequencing (Stacc-seq), we investigated the landscapes of RNA polymerase II (Pol II) binding in mouse embryos. We found that Pol II undergoes 'loading', 'pre-configuration', and 'production' during the transition from minor ZGA to major ZGA. After fertilization, Pol II is preferentially loaded to CG-rich promoters and accessible distal regions in one-cell embryos (loading), in part shaped by the inherited parental epigenome. Pol II then initiates relocation to future gene targets before genome activation (pre-configuration), where it later engages in full transcription elongation upon major ZGA (production). Pol II also maintains low poising at inactive promoters after major ZGA until the blastocyst stage, coinciding with the loss of promoter epigenetic silencing factors. Notably, inhibition of minor ZGA impairs the Pol II pre-configuration and embryonic development, accompanied by aberrant retention of Pol II and ectopic expression of one-cell targets upon major ZGA. Hence, stepwise transition of Pol II occurs when mammalian life begins, and minor ZGA has a key role in the pre-configuration of transcription machinery and chromatin for genome activation.


Subject(s)
Gene Expression Regulation, Developmental/genetics , Genome/genetics , RNA Polymerase II/metabolism , Zygote/metabolism , Alleles , Animals , Chromatin/genetics , Chromatin/metabolism , Embryo, Mammalian/cytology , Embryo, Mammalian/enzymology , Embryo, Mammalian/metabolism , Epigenome/genetics , Female , Male , Maternal Inheritance/genetics , Mice , Mice, Inbred C57BL , Oocytes/enzymology , Oocytes/metabolism , Promoter Regions, Genetic/genetics , RNA Polymerase II/genetics , Zygote/cytology , Zygote/enzymology
10.
J Med Case Rep ; 14(1): 199, 2020 Oct 23.
Article in English | MEDLINE | ID: mdl-33092626

ABSTRACT

BACKGROUND: The choroid is the most common site for intraocular tumor metastasis because of its abundant vascular supply. However, choroidal metastasis in penile cancer is highly unusual. Here, we report the first case of diagnosis of choroidal metastasis at presentation in a patient with penile squamous cell carcinoma. CASE PRESENTATION: A 43-year-old Asian man with a 3-year history of penile cancer presented with metastasis in the right intraocular sites. Magnetic resonance imaging showed hyperintensity in the T1-weighted images and hypointensity in the T2-weighted images of the right eye. After enucleation of his right eye, histopathological analysis led to a diagnosis of metastatic, moderately differentiated penile squamous cell carcinoma. CONCLUSIONS: Penile cancer typically occurs as penile squamous cell carcinoma, and its most common metastatic sites are the inguinal lymph nodes. Hemorrhagic transfer of tumor cells is extremely rare, especially to intraocular sites. Intraocular metastatic tumors have a unique presentation on imaging, as observed on magnetic resonance imaging and histopathological analysis. This novel finding of intraocular metastasis in penile squamous cell carcinoma is of great significance to optic surgeons and oncologists as it has new implications in the diagnosis of and timely intervention for penile cancer metastasis.


Subject(s)
Carcinoma, Squamous Cell , Penile Neoplasms , Adult , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/surgery , Humans , Lymph Nodes , Magnetic Resonance Imaging , Male , Penile Neoplasms/diagnostic imaging , Penile Neoplasms/surgery
12.
J Hazard Mater ; 377: 113-123, 2019 09 05.
Article in English | MEDLINE | ID: mdl-31154198

ABSTRACT

Although many literatures have reported that biomass materials had been used for water treatment, most of the biomass materials were directly used for adsorbing toxic or organic substances. In this research, modified pine bark and corn straw were used to prepare the high-efficiency and low-cost activated sludge immobilized materials. By treating phenol wastewater and ordinary organic wastewater, various factors influencing the treatment effect were investigated. The results showed that the immobilized biological carriers had good effects on the treatment of two kinds of wastewater. The removal efficiency of the phenol wastewater reached 100% in 24 h, and the removal efficiency of ordinary organic wastewater reached 95.5% in 96 h. The results of microbial community analysis showed that the abundance of the immobilized carrier and that of the original sludge was similar. But when treating different wastewater, the number and proportion of microorganisms were significantly different.


Subject(s)
Microbiota , Waste Disposal, Fluid/methods , Bacteria , Biodegradation, Environmental , Biological Oxygen Demand Analysis , Biomass , Bioreactors , DNA, Bacterial/chemistry , Hydrogen-Ion Concentration , Particle Size , Phenols/chemistry , Pinus , Plant Bark , Sewage , Temperature , Wastewater , Zea mays
13.
J Cell Sci ; 131(3)2018 02 02.
Article in English | MEDLINE | ID: mdl-29361524

ABSTRACT

The key cyclin-dependent kinase Cdk1 (Cdc2) promotes irreversible mitotic entry, mainly by activating the phosphatase Cdc25 while suppressing the tyrosine kinase Wee1. Wee1 needs to be downregulated at the onset of mitosis to ensure rapid activation of Cdk1. In human somatic cells, one mechanism of suppressing Wee1 activity is mediated by ubiquitylation-dependent proteolysis through the Skp1/Cul1/F-box protein (SCF) ubiquitin E3 ligase complex. This mechanism is believed to be conserved from yeasts to humans. So far, the best-characterized human F-box proteins involved in recognition of Wee1 are ß-TrCP (BTRCP) and Tome-1 (CDCA3). Although fission yeast Wee1 was the first identified member of its conserved kinase family, the F-box proteins involved in recognition and ubiquitylation of Wee1 have not been identified in this organism. In this study, our screen using Wee1-Renilla luciferase as the reporter revealed that two F-box proteins, Pof1 and Pof3, are required for downregulating Wee1 and are possibly responsible for recruiting Wee1 to SCF. Our genetic analyses supported a functional relevance between Pof1 and Pof3 and the rate of mitotic entry, and Pof3 might play a major role in this process.


Subject(s)
Cell Cycle Proteins/metabolism , F-Box Proteins/metabolism , Mitosis , Nuclear Proteins/metabolism , Protein-Tyrosine Kinases/metabolism , Proteolysis , Schizosaccharomyces pombe Proteins/metabolism , Schizosaccharomyces/cytology , Schizosaccharomyces/metabolism , Mutant Proteins/metabolism , Mutation/genetics , Protein Binding , Protein Stability
14.
Int J Gynaecol Obstet ; 137(2): 145-149, 2017 May.
Article in English | MEDLINE | ID: mdl-28170083

ABSTRACT

OBJECTIVE: To compare E6/E7 mRNA and HPV DNA assays for evaluating women with atypical cells of undetermined significance (ASCUS). METHODS: The present prospective study enrolled patients with ASCUS undergoing HPV testing at Third Affiliated Hospital of Zhengzhou University, China, between September 1, 2013, and January 31, 2016. Patients with positive HPV DNA test results underwent screening by E6/E7 mRNA assay, and the accuracy of HPV DNA and E6/E7 mRNA testing were compared, with histology used for definitive diagnoses. RESULTS: In total, 591 patients with ASCUS underwent HPV DNA screening, with 455 and 136 having positive and negative results, respectively; 252 patients with positive results and 66 with negative results underwent biopsy and histology testing and were included in the study. The sensitivity of the E6/E7 mRNA assay was similar to that of HPV DNA testing (88.2%, 95% confidence interval [CI] 77.6-94.4 vs 90.7%, 95%CI 81.2-95.9; P=0.636) for the detection of cervical intraepithelial neoplasia grade 2+, and the specificity was higher (36.4%, 95%CI 29.6-43.9 vs 24.3%, 95%CI 19.1-30.3; P=0.006). The area under the receiver operating characteristic curve was greater for E6/E7 mRNA testing compared with HPV DNA testing (0.658 vs 0.588). CONCLUSION: The higher specificity of the E6/E7 mRNA assay means it could be a promising technique in the management of women with ASCUS.


Subject(s)
DNA, Viral/analysis , Papillomaviridae/genetics , Papillomavirus Infections/virology , RNA, Viral/analysis , Uterine Cervical Dysplasia/virology , Adult , China , Disease Progression , Female , Humans , Papillomavirus Infections/pathology , Prospective Studies , ROC Curve , Sensitivity and Specificity , Women's Health , Uterine Cervical Dysplasia/pathology
15.
Chinese Journal of Nursing ; (12): 1055-1058, 2017.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-662595

ABSTRACT

According to the professional characteristics of the operating room,on the basis of basic principles of hierarchical management and post management of nursing department,taking clinical needs as guiding ideology,combined with the development needs of surgical departments,we developed the operating room nursing staff management model,and set up 23 jobs.We adjusted it accordingly in practice,and constantly optimized nurses' career plan by providing clinical,teaching,research,management and other multi-channel development direction,meanwhile provided better quality care for patients.

16.
Chinese Journal of Nursing ; (12): 1055-1058, 2017.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-660380

ABSTRACT

According to the professional characteristics of the operating room,on the basis of basic principles of hierarchical management and post management of nursing department,taking clinical needs as guiding ideology,combined with the development needs of surgical departments,we developed the operating room nursing staff management model,and set up 23 jobs.We adjusted it accordingly in practice,and constantly optimized nurses' career plan by providing clinical,teaching,research,management and other multi-channel development direction,meanwhile provided better quality care for patients.

17.
J Virol Methods ; 224: 35-41, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26297960

ABSTRACT

HPV-16 L1 methylation and E6/E7 mRNA have suggested that they had close relationship with cervical neoplastic progression. This study aimed to evaluate the clinical performance of the HPV-16 L1 methylation assay and E6/E7 mRNA test for detecting high-grade cervical lesions (CIN2+). A total of 81 women with liquid-based cytology (LBC) samples, histological results, and positive HPV-DNA test for HPV type 16 only were included in this study. HPV-16 L1 methylation and E6/E7 mRNA levels were measured using methylation-sensitive high resolution melting (MS-HRM) analysis and Quantivirus®HPV E6/E7 RNA 3.0 assay (bDNA), respectively, in the same residue of LBC samples. The current date showed a positive correlation between the HPV-16 L1 methylation and the E6/E7 mRNA levels. The L1 methylation and mRNA levels both increased with disease severity. The mRNA test method showed higher sensitivity and NPV (98.0 and 91.7% vs. 89.8 and 80.8%), while lower specificity and PPV (34.4 and 69.6% vs. 65.6 and 80.0%), than the L1 methylation assay for detecting histology-confirmed CIN2+. When using the detection method of mRNA test combined with L1 methylation assay, we obtained a sensitivity of 89.8% and a specificity of 71.9%. These findings suggest that assessment of HPV-16 L1 methylation testing combined with E6/E7 mRNA testing may be a promising method for the triage of women with HPV type 16 only.


Subject(s)
Capsid Proteins/genetics , DNA Methylation , Human papillomavirus 16/isolation & purification , Oncogene Proteins, Viral/genetics , RNA, Messenger/analysis , RNA, Viral/analysis , Squamous Intraepithelial Lesions of the Cervix/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adult , Aged , Female , Humans , Middle Aged , Sensitivity and Specificity , Transition Temperature
18.
Biomed Pharmacother ; 73: 116-22, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26211591

ABSTRACT

Platinum-based drugs have been widely used for the treatment of malignant tumors. However, their applications are limited by severe side effects for their lack of selectivity for cancer cells. The development of antibody drug conjugates (ADCs) have provided a platform to reduce drug toxicity and improve drug efficacy. Here we describe a nover conjugate comprising of Herceptin (an anti-HER2 antibody) and platinum drug via a cathepsin B cleavable dipetide for enhancing drug accumulation and HER2-positive cancer cell specific delivery. This conjugate is believed to be cleaved by cathepsin B, leading to a 1,6-elimination reaction and activation of drug release. Herceptin-Pt(II) is evaluated to have approximately loaded with 6.4 moles platinum drugs per mole of antibody. We demonstrate that Herceptin-Pt(II) retain high and selective binding affinity for HER2 protein and HER2-positive SK-BR-3 cancer cells. The in vitro cytotoxicity tests indicate that Herceptin-Pt(II) exhibits much higher cytotoxicity than oxaliplatin against SK-BR-3 cells. More importantly, Herceptin-Pt(II) shows no obvious inhibition against the growth of both MCF-7 and MDA-MB-231 cells, which express lower levels of HER2. Furthermore, compared with free oxaliplatin, Herceptin significantly improved the cellular uptake of platinum drugs in SK-BR-3 cells. In summary, Herceptin-platinum (II) conjugate is a remarkable and potent platform for efficient and cancer cell specific delivery.


Subject(s)
Antineoplastic Agents/chemical synthesis , Drug Delivery Systems/methods , Platinum Compounds/chemical synthesis , Trastuzumab/chemistry , Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Cell Line, Tumor , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical/methods , Female , Humans , MCF-7 Cells , Platinum Compounds/administration & dosage , Trastuzumab/administration & dosage , Treatment Outcome
19.
Clin Biochem ; 48(13-14): 855-9, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25982893

ABSTRACT

OBJECTIVE: Methylation-sensitive high-resolution melting (MS-HRM) is a new technique for DNA methylation analysis, but it is rarely used for the detection of viral DNA methylation. In this study, we investigated the HPV-16L1 gene methylation that is detected by MS-HRM as a potential biomarker for prognosing cervical dysplasia and cancer. DESIGN AND METHODS: A total of 114 HPV-16 infected patients (normal (17), CIN1 (25), CIN2 (29), CIN3 (32), SCC (11)) who underwent liquid-based cytology test and biopsy were included in this study. 17 cases with HPV-16 infection and negative cytologic and histologic results served as the control group. The HPV-16L1 gene methylation statuses of these samples were investigated using a methylation-sensitive high-resolution melting (MS-HRM) assay after bisulfite modification. RESULTS: The HPV-16L1 gene methylation statuses of all the 114 specimens were successfully detected by MS-HRM, and we observed increasing methylation levels in severe lesions, as determined using histologic assays. In addition, the methylation levels of CIN2+ (CIN2, CIN3 and SCC) were significantly higher than that of CIN2- (normal and CIN1, P<0.001). When taking CIN2+ as the reference, our HPV-16L1 DNA methylation assay achieved 91.7% sensitivity and 59.5% specificity, respectively. CONCLUSIONS: The results of the present work demonstrated that HPV-16L1 gene methylation was closely associated with cervical precancerosis and cancer. Moreover, using MS-HRM to detect HPV-16L1 gene methylation may be a powerful assay for the triage of HPV-16-positive females, which could identify patients with high risk of invasive cancer.


Subject(s)
DNA Methylation/genetics , Nucleic Acid Denaturation/genetics , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/genetics , Adult , Aged , Capsid Proteins/genetics , DNA, Viral/genetics , Female , Fluorescence , Humans , Linear Models , Middle Aged , Neoplasm Grading , Oncogene Proteins, Viral/genetics , Prognosis , Reference Standards , Uterine Cervical Neoplasms/pathology
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-332394

ABSTRACT

<p><b>OBJECTIVE</b>To understand the HA1 genetic variation characterization of influenza virus subtype H3N2 circulated from 2001 to 2006 in Liaoning local area.</p><p><b>METHODS</b>Viral RNA was extracted and transcribed into cDNA by reverse transcriptase and amplified by PCR. The product of PCR was purified by QIAgen purification kits,and sequenced by ABI 3100avant. The sequence data were analyzed phylogenetically by Sequence software with epidemic records. Finally, the phylogenetic trees were drawn according to deduced amino acid sequences of influenza virus H3N2 from 2000 to 2006 in the NCBI database.</p><p><b>RESULTS</b>The seven HA1domain sequences of H3N2 influenza viruses circulated from 2001 to 2006 in Liaoning local area had been analyzed. Compared with WHO 2004-2006 H3N2 vaccine A/California/7/2004, 12 bases had changed, 4 positions had amino acid substitution in 62 * > E, 182 T > 1,224 S > A,225 C > Y. 224 and 225 are RBS (Receptor binding site). The homology is lower than 98%. Phylogenetic tree showed Liaoning H3N2 2006 strains and Zhejiang 2005 strains were similar to WHO Northern hemisphere winter 2006-2007 Vaccine A/Wisconsin/67/2005 (H3N2)-like virus and grouped together to form an independent cluster even though several bases were still different.</p><p><b>CONCLUSION</b>The HA1 domain of HA gene of influenza viruses (H3N2) isolated from 2001-2006 in Liaoning local area showed base mutation, amino acid sequence difference compared to A/California/7/2004 (2005-2006 vaccine), suggesting it might be the main cause leading to the spread of influenza. The sequence analysis showed Liaoning 2006 H3N2 strains were similar to those from Southern area which suggested that further surveullance should be conducted to monitor the virus mutation in circulation.</p>


Subject(s)
Humans , Cell Line , China , Epidemiology , Hemagglutinin Glycoproteins, Influenza Virus , Chemistry , Genetics , Influenza A Virus, H3N2 Subtype , Chemistry , Classification , Genetics , Influenza, Human , Epidemiology , Virology , Molecular Sequence Data , Mutation , Phylogeny , Population Surveillance , Protein Structure, Tertiary
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