Publications by authors named "Wei-Hua Zhang"

128 Publications

A Fast and Efficient Approach to Obtaining High-Purity Glioma Stem Cell Culture.

Front Genet 2021 6;12:639858. Epub 2021 Jul 6.

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Glioma is the most common and malignant primary brain tumor. Patients with malignant glioma usually have a poor prognosis due to drug resistance and disease relapse. Cancer stem cells contribute to glioma initiation, progression, resistance, and relapse. Hence, quick identification and efficient understanding of glioma stem cells (GSCs) are of profound importance for therapeutic strategies and outcomes. Ideally, therapeutic approaches will only kill cancer stem cells without harming normal neural stem cells (NSCs) that can inhibit GSCs and are often beneficial. It is key to identify the differences between cancer stem cells and normal NSCs. However, reports detailing an efficient and uniform protocol are scarce, as are comparisons between normal neural and cancer stem cells. Here, we compared different protocols and developed a fast and efficient approach to obtaining high-purity glioma stem cell by tracking observation and optimizing culture conditions. We examined the proliferative and differentiative properties confirming the identities of the GSCs with relevant markers such as Ki67, SRY-box containing gene 2, an intermediate filament protein member nestin, glial fibrillary acidic protein, and s100 calcium-binding protein (s100-beta). Finally, we identified distinct expression differences between GSCs and normal NSCs including cyclin-dependent kinase 4 and tumor protein p53. This study comprehensively describes the features of GSCs, their properties, and regulatory genes with expression differences between them and normal stem cells. Effective approaches to quickly obtaining high-quality GSCs from patients should have the potential to not only help understand the diseases and the resistances but also enable target drug screening and personalized medicine for brain tumor treatment.
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http://dx.doi.org/10.3389/fgene.2021.639858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291338PMC
July 2021

sp. nov., isolated from Indian Ocean marine sediment.

Int J Syst Evol Microbiol 2021 Jul;71(7)

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, PR China.

A novel Gram-stain-positive, catalase-positive, oxidase-negative, aerobic, non-motile, rod-shaped bacterium, designated strain YIM M12148, was isolated from a marine sediment sample collected from the Indian Ocean. The strain grew optimally at 28 °C, pH 8.0 and in the presence of 1-3 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM M12148 belongs to the genus , with the highest sequence similarity to NBRC 15706 (96.12 %). The cell-wall sugars of strain YIM M12148 were rhamnose, ribose, glucose and mannose. The predominant isoprenoid quinones were MK-8 and MK-9. The polar lipids consisted of major amounts of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unknown phospholipid and one unknown lipid. Major fatty acids (>5 % of the total) of the novel isolate were anteiso-C, iso-C, iso-C and anteiso-C. The genomic DNA G+C content of strain YIM M12148 was 67.15 mol%. On the basis of genotypic and phenotypic data, it is apparent that strain YIM M12148 represents a novel species of the genus , for which the name sp. nov. is proposed. The type strain is YIM M12148 (=KCTC 29660=DSM 29154).
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http://dx.doi.org/10.1099/ijsem.0.004906DOI Listing
July 2021

Case Report: A Variant Non-ketotic Hyperglycinemia With Mutations: Manifestation of Deficiency of Activities of the Respiratory Chain Enzymes.

Front Genet 2021 13;12:605778. Epub 2021 May 13.

Neurology Department, National Center for Children's Health China, Beijing Children Hospital Affiliated to Capital Medical University, Beijing, China.

Variant non-ketotic hyperglycinaemia (NKH) is a rare disorder characterized by variable clinical, biochemical, and imaging features. The variant form of NKH is rare and characterized by variable clinical, biochemical and imaging features. Herein, we report a girl with variant NKH with two mutations in glutaredoxin 5 (), which has been described in only three patients. The clinical and biochemical phenotypes of the patient are also described. She suffered from developmental regression associated with spasticity, developmental delay, anemia and optic atrophy. The mitochondrial leukoencephalopathy was used to designate these disorders. An increased T2 signal from the medulla oblongata to the C6 spinal region was also observed on spinal cord MRI. Tandem mass analysis of a dried blood sample revealed elevated levels of glycine. The patient has two compound heterozygous mutations (c.151_153 del AAG and c.196C>T) in the gene. The c.196C>T mutation led to a stop codon (p.Q66Ter). Activities of mitochondrial respiratory chain (MRC) complexes II+III in the patient's fibroblasts were abnormal. We present the case of a girl with variant NKH who manifested spasticity and bilateral cavitating leukoencephalopathy. The patient had a deficiency of a respiratory chain enzyme, and this is the first report. Genetic testing is important for physicians to evaluate suspected variant NKH patients and to provide proper genetic counseling.
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http://dx.doi.org/10.3389/fgene.2021.605778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155699PMC
May 2021

A comparison between 18F-FDG PET/CT and classical physical examination package for cancer screening in asymptomatic Chinese patients.

Chin Med J (Engl) 2021 Jan 28;134(7):873-875. Epub 2021 Jan 28.

Department of Nuclear Medicine, First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.

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http://dx.doi.org/10.1097/CM9.0000000000001376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104175PMC
January 2021

[Human dental pulp stem cells conditioned medium protects genioglossus myoblast from cobalt chloride-induced hypoxia injury through AMPK/PGC-1α pathway].

Shanghai Kou Qiang Yi Xue 2020 Dec;29(6):573-579

Shanghai Stomatological Hospital, Fudan University. Shanghai 200001, China.

Purpose: To study the effect of hypoxia induced by cobalt chloride (CoCl2) on viability and oxidative stress of genioglossus myoblast, and to explore the mechanism of the protective effect of conditioned medium (CM) on human dental pulp stem cells (hDPSCs).

Methods: The hDPSCs were isolated and cultured, and the conditioned medium was prepared by ultrafiltration concentration. Mouse genioglossus myoblasts were isolated and divided into control group, CM group, CoCl2 group and CoCl2+CM group. The cell viability of genioglossus myoblasts was detected by CCK-8. The intracellular and mitochondrial ROS levels were evaluated by DCFH-DA and MitoSOX, respectively. The expression level of mitochondria-related genes in NRF-1 and NRF-2 were analyzed by real-time PCR. The expression of PGC-1α, p-AMPK and total AMPK protein was detected by Western blot. Statistical analysis was performed using SPSS 22.0 software package.

Results: The proliferation of genioglossus myoblasts was significantly decreased after 200 μmol/L CoCl2 treatment for 24 h (P<0.05), and the levels of reactive oxygen species (ROS) were significantly increased in intracellular and mitochondria (P<0.05). Compared with CoCl2 group, the proliferation ability of hDPSCs-CM was dramatically raised (P<0.05), and the intracellular and mitochondrial ROS content was remarkably decreased(P<0.05). hDPSCs-CM up-regulated the protein expression levels of pAMPK and PGC-1α in genioglossus myoblasts and mitochondrial downstream effectors of PGC-1α, including mRNA expression levels of NRF-1, NRF-2 (P<0.05).

Conclusions: Human dental pulp stem cells conditioned medium can alleviate hypoxia injury induced by CoCl2 in genioglossus myoblasts, and its mechanism may be related to AMPK/PGC-1α signaling pathway.
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December 2020

Novel Fluorinated 7-Hydroxycoumarin Derivatives Containing an Oxime Ether Moiety: Design, Synthesis, Crystal Structure and Biological Evaluation.

Molecules 2021 Jan 12;26(2). Epub 2021 Jan 12.

Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China.

A series of fluorinated 7-hydroxycoumarin derivatives containing an oxime ether moiety have been designed, synthesized and evaluated for their antifungal activity. All the target compounds were determined by H-NMR, C-NMR, FTIR and HR-MS spectra. The single-crystal structures of compounds , , and were further confirmed using X-ray diffraction. The antifungal activities against (), (), (), (), () and () were evaluated in vitro. The preliminary bioassays showed that some of the designed compounds displayed the promising antifungal activities against the above tested fungi. Strikingly, the target compounds and exhibited outstanding antifungal activity against at 100 μg/mL, with the corresponding inhibition rates reached 90.1 and 85.0%, which were better than the positive control Osthole (83.6%) and Azoxystrobin (46.5%). The compound was identified as the promising fungicide candidate against with the EC values of 5.75 μg/mL, which was obviously better than Osthole (33.20 μg/mL) and Azoxystrobin (64.95 μg/mL). Meanwhile, the compound showed remarkable antifungal activities against with the EC values of 28.96 μg/mL, which was better than Osthole (67.18 μg/mL) and equivalent to Azoxystrobin (21.34 μg/mL). The results provide a significant foundation for the search of novel fluorinated 7-hydroxycoumarin derivatives with good antifungal activity.
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http://dx.doi.org/10.3390/molecules26020372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828289PMC
January 2021

Mechanisms of Renal-Splenic Axis Involvement in Acute Kidney Injury Mediated by the α7nAChR-NF-κB Signaling Pathway.

Inflammation 2021 Apr 3;44(2):746-757. Epub 2020 Nov 3.

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No.23 Youzheng Street, Harbin, 150001, China.

This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.
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http://dx.doi.org/10.1007/s10753-020-01374-yDOI Listing
April 2021

[Biological characteristics of periodontal ligament stem cells modified by platelet derived growth factor BB].

Shanghai Kou Qiang Yi Xue 2020 Aug;29(4):343-349

Shanghai Stomatological Hospital, Fudan University. Shanghai 200001, China.

Purpose: To investigate the biological characteristics of human periodontal stem cells (hPDLSCs) modified with platelet derived growth factor BB(PDGFBB) gene, and to explore its influence on proliferation, migration and osteogenic induction of hPDLSCs.

Methods: hPDLSCs were isolated and amplified, and immunofluorescence staining was performed to identify cell surface markers and osteogenic differentiation ability. hPDLSCs were transfected with PDGFBB gene by lentivirus vector, and the effects on cell proliferation and migration were detected by CCK-8 and scratch test after transfection. Real-time PCR was performed to analyze the mRNA expression levels of osteogenic and angiogenic genes in hPDLSCs cells transfected with PDGFBB gene. Statistical analysis was performed using SPSS 22.0 software package.

Results: hPDLSCs were successfully obtained by tissue mass culture and finite dilution method. Compared with the blank virus group and non-transfected group, the proliferation and migration ability of the cells in the transfection group were significantly increased, and the mRNA expression levels of OPN, COL-1 and VEGF were significantly up-regulated(P<0.05).

Conclusions: Lentiviral vector can transfer PDGFBB gene into hPDLSCs in vitro and obtain continuous and stable expression. PDGFBB can promote proliferation and migration of hPDLSCs cells and up-regulate expression of osteogenic and angiogenic genes.
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August 2020

[Effect of NUDT21 on Alternative Splicing of Transcripts in K562 Cells].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Oct;28(5):1504-1509

Department of Hematology, The First Hospital of Shanxi Medical University,Taiyuan 030001, Shanxi Province, China,E-mail:

Objective: To explore the effect of nudix hydrolase 21 (NUDT 21) on alternative splicing of transcripts in leukemia K562 cells.

Methods: The K562 cell line was used as the research objects. The NUDT 21 was knocked-down by lentivirus vector, then the expression of transcripts before and after interference was determined by transcriptome sequencing (RNA seq). The bioinformatics methods including GO analysis and KEGG pathway analysis were used to analyze the changes of differentially expressed genes and 3' alternative splicing, then these changes were confirmed by qPCR.

Results: After the NUDT 21 in K562 cells was knoced-down, the differentially expressed genes showed that 5 196 were up-regulated, 3 917 were down-regulated. GO analysis and KEGG pathway analysis showed that the very differentially expressed transcripts mainly related with cell adhesion and differentiation, hematopoietic cell lines and autoimmunity. There were 436 significant alternative splicing, which mainly involved in the regulation of some biological processes such as cell proliferation and metabolism. The ERBB2, MAPK kinase MKNK2, G protein-coupled receptor GRK6, eukaryotic translation elongation factor EEF1B2, cyclin L2 CCNL2, mitotic checkpoint protein BUB3 were changed by 3' alternative splicing. Among them the expression of variant 1 of ERBB2 mRNA decreased and variant 4 increased.

Conclusion: NUDT21 influences the cell biological function at a higher level by variously regulating ways, including 3' end APA.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.05.013DOI Listing
October 2020

Clinical Characteristics and Outcome Analysis of 94 Children With Brain Abscess in Beijing: A Single-center Retrospective Study.

Pediatr Infect Dis J 2021 02;40(2):109-115

From the Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Infectious Diseases.

Background: There are limit studies about pediatric brain abscess in China. The aim of this study was to analyze clinical characteristics and outcomes of pediatric brain abscess in recent years in China.

Methods: The clinical information of children with brain abscess hospitalized in Beijing Children's Hospital between January 1, 2007 and December 31, 2016 were retrospectively reviewed.

Results: Ninety-four children were enrolled in this study. A Streptococcus milleri group (13.8%) was identified as the most common causative organisms, followed by Staphylococcus aureus (6.4%). The overall mortality was 21.6%, with 50.0% of deaths happening in the first week after diagnosis. Long-term outcomes of 74 patients were assessed with Glasgow Outcome Scale-Extended Pediatric Reversion: 50 patients with a score of 1-2 (favorable outcome) and 24 patients with a score of 3-8 (unfavorable outcome). Patients with multiple abscesses (P = 0.029) and intraventricular rupture of brain abscess/hydrocephalus (P = 0.024) had higher risk of unfavorable outcomes.

Conclusions: Brain abscess is a serious disease with high mortality in children; more aggressive treatments should be considered in the first week of diagnosis because of high risk of death, and for patients with multiple brain abscesses and intraventricular rupture of brain abscess/hydrocephalus because of their higher risk of unfavorable.
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http://dx.doi.org/10.1097/INF.0000000000002933DOI Listing
February 2021

Psychometric properties of the Clinically Useful Depression Outcome Scale supplemented with DSM-5 Mixed subtype questionnaire in Chinese patients with mood disorders.

J Affect Disord 2021 01 30;279:53-58. Epub 2020 Sep 30.

Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Mental Disorder's Management of Zhejiang Province, No. 79, Qingchun Road, Hangzhou 310003, China. Electronic address:

Background: With the modification of DSM-5 mixed features specifier, a brief scale to screen mixed features in patients with mood disorders is needed in clinical practice. This study aimed to explore the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with DSM-5 Mixed subtype (CUDOS-M-C) for the Chinese patients with mood disorders.

Methods: Overall, 300 patients with major depressive episode were recruited. All participants were assessed using CUDOS-M-C, Young Mania Rating Scale, Hamilton Anxiety Scale and Montgomery-Asberg Depression Rating Scale. The receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cut-off values of CUDOS-M-C score. The reliability and validity of CUDOS-M-C were examined using Cronbach's alpha, intraclass correlation coefficient (ICC) and principal component analysis (PCA).

Results: The results of PCA indicated two-factor structure as the best solution for CUDOS-M-C, which explained 54.82% of cumulative variance. The Cronbach's alpha was 0.892 and the ICC was 0.853. The area under the ROC curve of the CUDOS-M-C for participants with mixed depression was 0.927 (p<0.001) and the suitable cut-off value was 8, with a sensitivity of 91.6% and specificity of 79.9%.

Limitations: Most of the patients were recruited from eastern China and further research with larger sample is warranted. And this study did not perform confirmatory factor analysis to identify the generalization of factor structure of CUDOS-M-C. Besides, the study performed the test-retest reliability of CUDOS-M-C and further analysis is needed to ascertain the patient's post-treatment changes.

Conclusion: The CUDOS-M-C demonstrated to have satisfactory psychometric properties as a self-report scale, and could be applied to screen patients with mixed depression in clinical practice.
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http://dx.doi.org/10.1016/j.jad.2020.09.117DOI Listing
January 2021

A Woman in Her 40s With Dilated Cardiomyopathy and Abdominal Contractions.

JAMA Cardiol 2020 09;5(9):1062

Key Laboratory of Cardiovascular Disease of Yunnan Province, Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, China.

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http://dx.doi.org/10.1001/jamacardio.2020.2563DOI Listing
September 2020

[Clinical effect of tacrolimus in the treatment of myasthenia gravis in children].

Zhongguo Dang Dai Er Ke Za Zhi 2020 Sep;22(9):964-969

Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

Objective: To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG).

Methods: A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment.

Results: After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05).

Conclusions: Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499454PMC
September 2020

Visible Light-Driven α-Alkylation of -Aryl tetrahydroisoquinolines Initiated by Electron Donor-Acceptor Complexes.

Org Lett 2020 Sep 9;22(18):7290-7294. Epub 2020 Sep 9.

Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China.

The visible light-driven α-alkylation of -aryl tetrahydroisoquinolines was initiated through electron donor-acceptor complex photochemistry. The reaction can proceed smoothly without the addition of any photocatalysts, transition-metal catalysts, or additional oxidants. The proposed mechanism was supported by various mechanistic studies, and the reactive open-shell alkyl radicals were generally produced from an alkylamine and underwent radical coupling for alkylating a wide range of -aryl tetrahydroisoquinolines.
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http://dx.doi.org/10.1021/acs.orglett.0c02631DOI Listing
September 2020

Clinical phenotypes, genotypes and treatment in Chinese dystonia patients with KMT2B variants.

Parkinsonism Relat Disord 2020 08 9;77:76-82. Epub 2020 Jun 9.

Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. Electronic address:

Background: KMT2B-related dystonia is a recently discovered hereditary dystonia that mostly occurs in childhood. This dystonia usually progresses to generalized dystonia with cervical, cranial, pharynx and larynx involvement. Our study summarizes genotype-phenotype features and deep brain stimulation (DBS) efficacy observed with KMT2B-related dystonia patients in China.

Methods: We identified 20 patients with KMT2B variations from dystonia samples with a gene panel and whole exome sequencing. Genetic, clinical and treatment analyses of these patients with KMT2B mutations were further conducted.

Results: We summarized the genotype and phenotypic characteristics of KMT2B-related patients in China, including 16 sporadic patients and 3 pedigrees (including 4 patients). Thirty-five percent (7/20) of patients had been published previously. The age of onset was between 1 month and 24 years (average 6.90 ± 5.72 years). Sixty-five percent (13/20) of patients had onset from lower limbs. Upper limbs or larynx accounted for 15% (3/20) and 20% (4/20) of patients, respectively. In the same family, male patients tended to have more severe symptoms than female patients. Carriers of KMT2B variants may present with nonmotor symptoms without dystonia. Abnormal endocrine metabolism could also be seen in our patients, including advanced bone age that had never been reported previously. Nine of our patients underwent DBS surgery. The mean follow-up time was 4.9 (range 1.3-16) months after DBS, and perceptible improvement of clinical symptoms were observed.

Conclusions: The genotypic and phenotypic spectra of Chinese KMT2B-related dystonia patients were further expanded. DBS surgery might be the preferred option for severe KMT2B-related dystonia patients till now.
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http://dx.doi.org/10.1016/j.parkreldis.2020.06.002DOI Listing
August 2020

Effects of agomelatine and mirtazapine on sleep disturbances in major depressive disorder: evidence from polysomnographic and resting-state functional connectivity analyses.

Sleep 2020 11;43(11)

Beijing Key laboratory of Drug Dependence, National Institute on Drug Dependence, Peking University, Beijing, China.

To investigate effects of agomelatine and mirtazapine on sleep disturbances in patients with major depressive disorder. A total of 30 depressed patients with sleep disturbances, 27 of which completed the study, took agomelatine or mirtazapine for 8 weeks. Subjective scales were administered, and polysomnography was performed at baseline and at the end of week 1 and 8. Functional magnetic resonance imaging was performed at baseline and at the end of week 8. Compared with baseline, scores on the Hamilton Depression Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Sleep Dysfunction Rating Scale, and Insomnia Severity Index after 8 weeks of treatment significantly decreased in both groups, with no significant differences between groups, accompanied by significant increases in total sleep time, sleep efficiency, and rapid eye movement (REM) sleep and significant decrease in wake after sleep onset. Mirtazapine treatment increased N3 sleep at week 1 compared with agomelatine treatment, but this difference disappeared at week 8. The increases in the percentage and duration of N3 sleep were positively correlated with increases in connectivity between right dorsal lateral prefrontal cortex (dlPFC) and right precuneus and between left posterior cingulate cortex and right precuneus in both groups, respectively. Functional connectivity (FC) between right dlPFC and left precuneus in mirtazapine group was higher compared with agomelatine group after 8 weeks of treatment. These findings indicated that both agomelatine and mirtazapine improved sleep in depressed patients, and the effect of mirtazapine was greater than agomelatine with regard to rapidly increasing N3 sleep and gradually improving FC in the brain.
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http://dx.doi.org/10.1093/sleep/zsaa092DOI Listing
November 2020

Primary solitary fibrous tumour in the pulmonary artery: a case report.

J Int Med Res 2020 03;48(3):300060520911273

Department of Cardiovascular Medicine, the First Hospital of Jilin University, Changchun, China.

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http://dx.doi.org/10.1177/0300060520911273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254594PMC
March 2020

Neurologic Manifestations as Initial Clinical Presentation of Familial Hemophagocytic Lymphohistiocytosis Type2 Due to Mutation in Chinese Pediatric Patients.

Front Genet 2020 4;11:126. Epub 2020 Mar 4.

Neurology Department, National Center for Children's Health China, Beijing Children Hospital affiliated to Capital Medical University, Beijing, China.

Familial hemophagocytic lymphohistiocytosis Type 2 (FHL2) associated central nervous system (CNS) involvement is less understood in children, especially when considering neurologic manifestations as part of the initial presentation. We conducted a retrospective review of the clinical manifestations and genetic abnormality of four Han Chinese children with FHL2 who were patients at the neurology department of Beijing Children's Hospital from November 2015 to October 2018. These four patients initially manifested CNS symptoms in their disease presentation, and all four patients were misdiagnosed as having ademyelinating disease, such as acute disseminated encephalomyelitis and multiple sclerosis. Given these misdiagnoses, it is important that general physicians and pediatricians maintain awareness of the possibility of FHL2 as a differential diagnosis. These four cases included neurologic manifestations including seizures, ataxia, spasticity, gait disorder, and coma. Bilateral abnormal signals in the cerebrum, including in white matter, gray matter, and junctions were discovered. Enhanced magnetic resonance imaging (MRI) in these patients showed spot or ring enhancement and/or hemorrhage. These patients all possessed a compound heterozygote mutation gene. Whole exome sequencing analysis revealed seven different mutations (three novel mutations) spread over the gene and a heterozygous missense mutation c.1349C > T [p.T450M] that was present in two patients. Three novel mutations, c.634T > C[p.Y212H], c.1083_1094del[p.361_364del], and c.1306G > T [p.D436Y], were discovered and through analysis were discovered to be deleterious. Neurologic manifestations were the initial symptoms of FHL2 in these patients in addition to the expected leukopenia and hepatosplenomegaly. Whole exome sequencing of for patients with similar presentations would facilitate prompt and accurate diagnosis and treatment.
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http://dx.doi.org/10.3389/fgene.2020.00126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064636PMC
March 2020

Aging Induced p53/p21 in Genioglossus Muscle Stem Cells and Enhanced Upper Airway Injury.

Stem Cells Int 2020 4;2020:8412598. Epub 2020 Mar 4.

Oral Biomedical and Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai 200001, China.

Aging of population brings related social problems, such as muscle attenuation and regeneration barriers with increased aging. Muscle repair and regeneration depend on muscle stem cells (MuSCs). Obstructive sleep apnea (OSA) rises in the aging population. OSA leads to hypoxia and upper airway muscle injury. However, little is known about the effect of increasing age and hypoxia to the upper airway muscle. The genioglossus (GG) is the major dilator muscle to keep the upper airway open. Here, we reported that muscle fiber and MuSC function declined with aging in GG. Increasing age also decreased the migration and proliferation of GG MuSCs. p53 and p21 were high expressions both in muscle tissue and in GG MuSCs. We further found that hypoxia inhibited GG MuSC proliferation and decreased myogenic differentiation. Then, hypoxia enhanced the inhibition effect of aging to proliferation and differentiation. Finally, we investigated that hypoxia and aging interact to form a vicious circle with upregulation of p53 and p21. This vicious hypoxia plus aging damage accelerated upper airway muscle injury. Aging and hypoxia are the major damage elements in OSA patients, and we propose that the damage mechanism of hypoxia and aging in GG MuSCs will help to improve upper airway muscle regeneration.
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http://dx.doi.org/10.1155/2020/8412598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073476PMC
March 2020

Transcatheter closure of a huge pulmonary arteriovenous fistula.

Rev Esp Cardiol (Engl Ed) 2020 Sep 24;73(9):765. Epub 2020 Feb 24.

Key Laboratory of Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, China.

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http://dx.doi.org/10.1016/j.rec.2020.01.006DOI Listing
September 2020

Diversity-oriented synthesis and antifungal activities of novel pimprinine derivative bearing a 1,3,4-oxadiazole-5-thioether moiety.

Mol Divers 2021 Feb 13;25(1):205-221. Epub 2020 Feb 13.

Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing, 210095, China.

Based on the strategy of diversity-oriented synthesis and the structures of natural product pimprinine and streptochlorin, two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized under the optimized reaction conditions. Biological assays conducted at Syngenta showed the designed derivatives displayed an altered pattern of biological activity, of which 5h was identified as the most promising compound with strong activity against Pythium dissimile and also a broad antifungal spectrum in primary screening. Further structural optimization of pimprinine and streptochlorin derivatives is well under way, aiming to discover synthetic analogues with improved antifungal activity. Two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized through diversity-oriented synthesis strategy under the optimized conditions. Biological assays showed the designed derivatives exhibited potential activity.
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http://dx.doi.org/10.1007/s11030-020-10048-8DOI Listing
February 2021

Hypoxia-Induced ROS Contribute to Myoblast Pyroptosis during Obstructive Sleep Apnea via the NF-B/HIF-1 Signaling Pathway.

Oxid Med Cell Longev 2019 11;2019:4596368. Epub 2019 Dec 11.

Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200001, China.

Tissue hypoxia caused by upper airway collapse is a main cause of excessive oxidative stress and systemic inflammation in obstructive sleep apnea (OSA) patients. Increased reactive oxygen species (ROS) and inflammatory responses affect cell survival and ultimately contribute to tissue injury. In the present study, we proposed that the induction of ROS by hypoxia, as an intrinsic stress, activates myoblast pyroptosis in OSA. We found increased cell death and abnormal expression of pyroptosis markers in the skeletal muscle of OSA mice. In vitro studies showed hypoxia-induced pyroptotic death of C2C12 myoblasts, as evidenced by the activation of caspase-1 and gasdermin D (GSDMD). Hypoxia induced ROS overproduction and accumulation in myoblasts. More importantly, applying N-acetylcysteine (NAC), an ROS scavenger, rescued cell swelling, downregulated the inflammatory response, and prevented pyroptotic death in hypoxia-cultured myoblasts. Hypoxia stimulation promoted NF-B P65 phosphorylation and HIF-1 nuclear translocation. Moreover, hypoxia increased the nuclear level of cleaved caspase-1 and GSDMD. NAC inhibited hypoxia-induced variations in the HIF-1 and NF-B signaling pathway. Taken together, our results determined that hypoxia-induced ROS contribute to myoblast pyroptosis. Therefore, our findings suggest that ROS may be a potential therapeutic target for ameliorating hypoxia-induced cell death and tissue injury, especially in OSA and hypoxia-related diseases.
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http://dx.doi.org/10.1155/2019/4596368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927050PMC
June 2020

[Migration and Source Analysis of Heavy Metals in Vertical Soil Profiles of the Drylands of Xiamen City].

Huan Jing Ke Xue 2019 Aug;40(8):3764-3773

Key Laboratory of Environmental Monitoring, Fujian Province University, Xiamen 361024, China.

The concentrations of eight heavy metal elements (V, Cr, Co, Ni, Cu, Zn, Sr, and Pb) and the isotopic composition of Pb and Sr were determined in vertical soil profiles of the drylands of Xiamen City using ICP-MS and TIMS. The vertical distributions and leaching migration patterns of the heavy metals were also analyzed. The results showed that most of the heavy metals (except for Sr) were not enriched relative background values at most profile depths, which indicated that heavy metal content is less affected by exogenous sources. The migration coefficients of Sr were greater than 0 throughout the entire soil profile; Zn and Co were enriched in the surface soil; and Cr, Ni, and Cu were depleted throughout the profile. V and Pb were less influenced by external activities. Sr and Pb showed clear vertical migration characteristics, and the migration depth of Sr was greater than that of Pb. Factor analysis showed that the heavy metals mainly originated from natural sources, followed by agricultural activities, transportation, and other complex anthropogenic activities. Enrichment factor analysis showed that Sr was affected by exogenous sources to varying extents. The isotopic composition analysis of Pb and Sr showed that Pb was mainly derived from the parent material, whereas Sr was interpreted as deriving from both the parent material and anthropogenic activities, and tended to migrate to the subsurface soil horizons (30-70 cm).
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http://dx.doi.org/10.13227/j.hjkx.201901227DOI Listing
August 2019

Synthesis of 3-Acyl-isoxazoles and Δ-Isoxazolines from Methyl Ketones, Alkynes or Alkenes, and tert-Butyl Nitrite via a Csp-H Radical Functionalization/Cycloaddition Cascade.

Org Lett 2019 Jul 13;21(13):5096-5100. Epub 2019 Jun 13.

Jiangsu Key Laboratory of Pesticide Science , College of Sciences, Nanjing Agricultural University , Nanjing 210095 , China.

A novel metal-free tandem Csp-H bond functionalization of ketones and 1,3-dipolar cycloaddition has been developed. An efficient approach to a variety of oxazole and isoxazoline derivatives is demonstrated using the 1,3-dipolar cycloaddition of alkynes and alkenes to nitrile oxides generated by reactions of methyl ketones with tert-butyl nitrite. This new protocol provides access to a variety of isoxazolines with diverse functionalities. An isoxazole generated in this way was found to have significant antifungal activity.
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http://dx.doi.org/10.1021/acs.orglett.9b01683DOI Listing
July 2019

Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis.

Front Genet 2019 25;10:370. Epub 2019 Apr 25.

Department of Neurology, National Centre for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Neuronal Ceroid Lipofuscinoses (NCLs) are progressive degenerative diseases mainly affect brain and retina. They are characterized by accumulation of autofluorescent storage material, mitochondrial ATPase subunit C, or sphingolipid activator proteins A and D in lysosomes of most cells. Heterogenous storage material in NCLs is not completely disease-specific. Most of CLN proteins and their natural substrates are not well-characterized. Studies have suggested variants of Late-Infantile NCLs (LINCLs) include the major type CLN2 and minor types CLN5, CLN6, CLN7, and CLN8. Therefore, combination of clinical and molecular analysis has become a more effective diagnosis method. We studied 4 late-infantile NCL siblings characterized by seizures, ataxia as early symptoms, followed by progressive regression in intelligence and behavior, but mutations are located in different genes. Symptoms and progression of 4 types of LINCLs are compared. Pathology of LINCLs is also discussed. We performed Nest-Generation Sequencing on these phenotypically similar families. Three novel variants c.1551+1insTGAT in TPP1, c.244G>T in CLN6, c.554-5A>G in MFSD8 were identified. Potential outcome of the mutations in structure and function of proteins are studied. In addition, we observed some common and unique clinical features of Chinese LINCL patient as compared with those of Western patients, which greatly improved our understanding of the LINCLs.
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http://dx.doi.org/10.3389/fgene.2019.00370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494930PMC
April 2019

Molecular characterization of a new recombinant brassica yellows virus infecting tobacco in China.

Virus Genes 2019 Apr 29;55(2):253-256. Epub 2019 Jan 29.

Tobacco Research Institute, Chinese Academy of Agricultural Sciences, Qingdao, 266101, People's Republic of China.

Brassica yellows virus (BrYV), prevalently distributed throughout mainland China and South Korea while triggering serious diseases in cruciferous crops, is proposed to be a new species in the genus Polerovirus within the family Luteoviridae. There are three distinct genotypes (BrYV-A, BrYV-B and BrYV-C) reported in cabbage and radish. Here, we describe a new BrYV isolate infecting tobacco plants in the field, which was named BrYV-NtabQJ. The complete genome sequence of BrYV-NtabQJ is 5741 nt in length, and 89% of the sequence shares higher sequence identities (about 90%) with different BrYV isolates. However, it possesses a quite divergent region within ORF5, which is more close to Beet western yellows virus (BWYV), Beet mild yellowing virus (BMYV) and Beet chlorosis virus (BChV). A significant recombination event was then detected among BrYV-NtabQJ, BrYV-B Beijng isolate (BrYV-BBJ) and BWYV Leonurus sibiricus isolate (BWYV-LS). It is proposed that BrYV-NtabQJ might be an interspecific recombinant between BrYV-BBJ and BWYV-LS, and the recombination might result in the successful aphid transmission of BrYV from cruciferous crops to tobacco. And it also poses new challenges for BrYV diagnosis and the vegetable production.
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http://dx.doi.org/10.1007/s11262-019-01636-4DOI Listing
April 2019

Design, synthesis and antifungal activities of novel pyrrole- and pyrazole-substituted coumarin derivatives.

Mol Divers 2019 Nov 29;23(4):915-925. Epub 2019 Jan 29.

Jiangsu Key Laboratory of Pesticide, College of Sciences, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.

We synthesized a series of novel pyrrole- and pyrazole-substituted coumarin derivatives and evaluated their antifungal activity against six phytopathogenic fungi in vitro. The primary assay results demonstrated that some designed compounds displayed potent activities. Among them, compounds 5g, 6a, 6b, 6c, 6d and 6h exhibited more effective control than Osthole against Cucumber anthrax and Alternaria leaf spot. Furthermore, compound 5g displayed stronger antifungal activity against Rhizoctorzia solani (EC = 15.4 µg/mL) than positive control Osthole (EC = 67.2 µg/mL).
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http://dx.doi.org/10.1007/s11030-019-09920-zDOI Listing
November 2019

Comparison of the inhibition potential of parthenolide and micheliolide on various UDP-glucuronosyltransferase isoforms.

Xenobiotica 2019 Oct 25;49(10):1158-1163. Epub 2019 Apr 25.

a Department of Colorectal Surgery , Tianjin Union Medical Center , Tianjin , China.

Parthenolide (PTL) and micheliolide (MCL) are sesquiterpene lactones with similar structures, and both of them have been reported to exhibit multiple biochemical and pharmacological activities. This study aims to investigate the inhibition of these two compounds on the activity of UDP-glucuronosyltransferases (UGTs). incubation mixture for recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition kinetics (including inhibition type and parameters) were determined, and docking was employed to elucidate the inhibition difference between PTL and MCL on UGT1A1. MCL showed no inhibition toward all the UGT isoforms, and PTL showed strong inhibition toward UGT1A1. The half-maximal inhibitory concentration (IC) of PTL on the activity of UGT1A1 was determined to be 64.4 μM. Inhibition kinetics determination showed that PTL exerted noncompetitive inhibition toward UGT1A1, and the inhibition kinetic constant () was determined to be 12.1 μM. docking method has been employed to show that hydrogen bonds between PTL and the activity cavity of UGT1A1 contributed to the stronger inhibition of PTL on the activity of UGT1A1 than MCL. In conclusion, PTL can more easily induce drug-drug interaction (DDI) with clinical drugs mainly undergoing UGT1A1-catalyzed glucuronidation.
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http://dx.doi.org/10.1080/00498254.2018.1544383DOI Listing
October 2019
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