49 results on '"Dai HQ"'
Search Results
2. Radical scavenging activity of novel phenolic glycosides from Citrullus lanatus
- Author
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Adebayo, AH, primary, Song, FH, additional, Liu, XT, additional, Dai, HQ, additional, Huang, P, additional, Zhang, JY, additional, and Zhang, LX, additional
- Published
- 2014
- Full Text
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3. A gene cluster encoding a nonribosomal peptide synthetase-like enzyme catalyzes γ-aromatic butenolides.
- Author
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Meng QZ, Wang XZ, Dai HQ, Assani I, Zhang MT, Zhao PP, Li LF, Yin X, Qi J, Pan Y, Zhang LX, and Xia XK
- Subjects
- Molecular Structure, Animals, Zebrafish, Peptide Synthases genetics, Multigene Family, 4-Butyrolactone analogs & derivatives, 4-Butyrolactone pharmacology, 4-Butyrolactone chemistry, Aspergillus enzymology, Aspergillus chemistry, Aspergillus genetics
- Abstract
Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds ( 1 - 11 ), including two γ -aromatic butenolides ( γ -AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ -butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.
- Published
- 2024
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4. Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.
- Author
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Liu YQ, Xu YW, Zheng ZT, Li D, Hong CQ, Dai HQ, Wang JH, Chu LY, Liao LD, Zou HY, Li EM, Xie JJ, and Fang WK
- Subjects
- Humans, Phosphorylation, Protein Kinase D2, Cell Line, Tumor, Cell Proliferation physiology, Serine, Cell Movement physiology, Gene Expression Regulation, Neoplastic, Desmoglein 2 genetics, Desmoglein 2 metabolism, Esophageal Squamous Cell Carcinoma metabolism, Esophageal Neoplasms pathology
- Abstract
Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)
- Published
- 2024
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5. When does paternalistic control positively relate to job satisfaction and citizenship behavior in Taiwan? The role of follower expectation.
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Wang AC, Tsai CY, Wang SB, and Dai HQ
- Abstract
Although prior research predicts mainly that followers expect leaders to exert less paternalistic control (such as emphasis on discipline, didactic instruction, and belittling followers), we argue that such an expectation may not be stable overtime or across settings. Based on the connectionist perspectives of implicit leadership theories, we propose a follower expectation model of paternalistic control, in which followers compare their perceived with expected levels of paternalistic control. Two inconsistent conditions-insufficient and excessive control-are identified, and the consistency between perceived and expected paternalistic control is predicted to relate to favorable follower outcomes. We examine this model by conducting two daily experience sampling studies in Taiwan. Our findings indicate that insufficient control is as unfavorable as excessive control in lowering followers' job satisfaction and citizenship behavior, and this pattern is particularly salient in terms of emphasis on discipline and the belittling of followers. A supplemental, qualitative analysis additionally demonstrated the conditions under which the expectation-perception consistency regarding belittling followers relates to favorable follower responses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
- Published
- 2023
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6. Mesoscale sequence feature modulates AID activity in antibody diversification.
- Author
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Li J and Dai HQ
- Subjects
- Antibodies
- Published
- 2023
- Full Text
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7. Contribution of the IGCR1 regulatory element and the 3' Igh CTCF-binding elements to regulation of Igh V(D)J recombination.
- Author
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Liang Z, Zhao L, Ye AY, Lin SG, Zhang Y, Guo C, Dai HQ, Ba Z, and Alt FW
- Subjects
- Animals, Mice, Immunoglobulin Variable Region genetics, Immunoglobulin Variable Region metabolism, Precursor Cells, B-Lymphoid metabolism, Chromatin metabolism, V(D)J Recombination genetics, Regulatory Sequences, Nucleic Acid
- Abstract
Immunoglobulin heavy chain variable region exons are assembled in progenitor-B cells, from V
H , D, and JH gene segments located in separate clusters across the Igh locus. RAG endonuclease initiates V(D)J recombination from a JH -based recombination center (RC). Cohesin-mediated extrusion of upstream chromatin past RC-bound RAG presents Ds for joining to JH s to form a DJH -RC. Igh has a provocative number and organization of CTCF-binding elements (CBEs) that can impede loop extrusion. Thus, Igh has two divergently oriented CBEs (CBE1 and CBE2) in the IGCR1 element between the VH and D/JH domains, over 100 CBEs across the VH domain convergent to CBE1, and 10 clustered 3' Igh -CBEs convergent to CBE2 and VH CBEs. IGCR1 CBEs segregate D/JH and VH domains by impeding loop extrusion-mediated RAG-scanning. Downregulation of WAPL, a cohesin unloader, in progenitor-B cells neutralizes CBEs, allowing DJH -RC-bound RAG to scan the VH domain and perform VH -to-DJH rearrangements. To elucidate potential roles of IGCR1-based CBEs and 3' Igh -CBEs in regulating RAG-scanning and elucidate the mechanism of the ordered transition from D-to-JH to VH -to-DJH recombination, we tested effects of inverting and/or deleting IGCR1 or 3' Igh -CBEs in mice and/or progenitor-B cell lines. These studies revealed that normal IGCR1 CBE orientation augments RAG-scanning impediment activity and suggest that 3' Igh -CBEs reinforce ability of the RC to function as a dynamic loop extrusion impediment to promote optimal RAG scanning activity. Finally, our findings indicate that ordered V(D)J recombination can be explained by a gradual WAPL downregulation mechanism in progenitor-B cells as opposed to a strict developmental switch.- Published
- 2023
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8. Contribution of the IGCR1 regulatory element and the 3 'Igh CBEs to Regulation of Igh V(D)J Recombination.
- Author
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Liang Z, Zhao L, Yongxin Ye A, Lin SG, Zhang Y, Guo C, Dai HQ, Ba Z, and Alt FW
- Abstract
Immunoglobulin heavy chain variable region exons are assembled in progenitor-B cells, from V
H , D, and JH gene segments located in separate clusters across the Igh locus. RAG endonuclease initiates V(D)J recombination from a JH -based recombination center (RC). Cohesin-mediated extrusion of upstream chromatin past RC-bound RAG presents Ds for joining to JH s to form a DJH -RC. Igh has a provocative number and organization of CTCF-binding-elements (CBEs) that can impede loop extrusion. Thus, Igh has two divergently oriented CBEs (CBE1 and CBE2) in the IGCR1 element between the VH and D/JH domains, over 100 CBEs across the VH domain convergent to CBE1, and 10 clustered 3' Igh -CBEs convergent to CBE2 and VH CBEs. IGCR1 CBEs segregate D/JH and VH domains by impeding loop extrusion-mediated RAG-scanning. Down-regulation of WAPL, a cohesin unloader, in progenitor-B cells neutralizes CBEs, allowing DJH -RC-bound RAG to scan the VH domain and perform VH-to-DJH rearrangements. To elucidate potential roles of IGCR1-based CBEs and 3' Igh -CBEs in regulating RAG-scanning and elucidate the mechanism of the "ordered" transition from D-to-JH to VH -to-DJH recombination, we tested effects of deleting or inverting IGCR1 or 3' Igh -CBEs in mice and/or progenitor-B cell lines. These studies revealed that normal IGCR1 CBE orientation augments RAG-scanning impediment activity and suggest that 3' Igh -CBEs reinforce ability of the RC to function as a dynamic loop extrusion impediment to promote optimal RAG scanning activity. Finally, our findings indicate that ordered V(D)J recombination can be explained by a gradual WAPL down-regulation mechanism in progenitor B cells as opposed to a strict developmental switch., Significance Statement: To counteract diverse pathogens, vertebrates evolved adaptive immunity to generate diverse antibody repertoires through a B lymphocyte-specific somatic gene rearrangement process termed V(D)J recombination. Tight regulation of the V(D)J recombination process is vital to generating antibody diversity and preventing off-target activities that can predispose the oncogenic translocations. Recent studies have demonstrated V(D)J rearrangement is driven by cohesin-mediated chromatin loop extrusion, a process that establishes genomic loop domains by extruding chromatin, predominantly, between convergently-oriented CTCF looping factor-binding elements (CBEs). By deleting and inverting CBEs within a critical antibody heavy chain gene locus developmental control region and a loop extrusion chromatin-anchor at the downstream end of this locus, we reveal how these elements developmentally contribute to generation of diverse antibody repertoires.- Published
- 2023
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9. Novel Sulfonylurea Derivatives as Potential Antimicrobial Agents: Chemical Synthesis, Biological Evaluation, and Computational Study.
- Author
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Meng FF, Shang MH, Wei W, Yu ZW, Liu JL, Li ZM, Wang ZW, Wang JG, and Dai HQ
- Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide health threat and has already tormented humanity during its long history, creating an urgent need for the development of new classes of antibacterial agents. In this study, twenty-one novel sulfonylurea derivatives containing phenyl-5-vinyl and pyrimidinyl-4-aryl moieties were designed and synthesized, among which, nine compounds exhibited inhibitory potencies against Gram-positive bacterial strains: MRSA (Chaoyang clinical isolates), S. aureus ATCC6538, vancomycin-resistant Enterococci -309 (VRE-309), and Bacillus subtilis ATCC 6633. Especially, 9i and 9q demonstrated inhibitory activities against the four bacterial strains with minimum inhibitory concentrations (MICs) of 0.78-1.56 μg/mL, and quite a few of other MRSA clinical strains with MICs of 0.78 μg/mL, superior to those of the positive controls vancomycin (MIC of 1 μg/mL) and methicillin (MIC of >200 μg/mL). This is the very first time that sulfonylurea derivatives have been identified as promising inhibitors against different MRSA clinical isolates. In addition, all the MIC values of the synthesized compounds against Candida albicans were greater than 100 μg/mL. Since the reported anti- Candida activities of sulfonylureas were due to acetohydroxyacid synthase (AHAS) inhibition, the molecular target against MRSA for the target sulfonylureas was thought to be a different mode of action. Density functional theory (DFT) calculations were finally performed to understand the structure-activity relationships, based on which, significant differences were observed between their HOMO maps for compounds with strong antibacterial activities and weak anti-MRSA effects. The present results hence provide valuable guidance for the discovery of novel agents to treat bacterial infections, especially against MRSA.
- Published
- 2023
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10. Physical oral care prevents ventilator-associated pneumonia in Vietnam: A prospective interventional study.
- Author
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Saito S, Thao PTN, Ishikane M, Xuan PT, Kutsuna S, Dai HQ, Ohtsu H, Kimura T, Kiyohara H, Shimada Y, Maruoka Y, Thuy PTP, Phu TT, Phuong HK, Tra TT, Duy NLM, Ohara H, Kurosu H, Son NT, and Ohmagari N
- Subjects
- Chlorhexidine therapeutic use, Humans, Incidence, Intensive Care Units, Prospective Studies, Respiration, Artificial adverse effects, Vietnam epidemiology, Pneumonia, Ventilator-Associated drug therapy, Pneumonia, Ventilator-Associated epidemiology, Pneumonia, Ventilator-Associated prevention & control
- Abstract
Background: Ventilator-associated pneumonia (VAP) has emerged as a critical issue in the intensive care unit (ICU) because of its high burden on patients and medical staff. Here, we examined the potential for reducing VAP incidence through physical oral care interventions without any medication., Methods: This prospective interventional study compared VAP incidence during an 8-month baseline period (usual oral care) and a 9-month intervention period (physical oral care with sponge brush) among patients who received mechanical ventilation for >48 h in a tertiary care hospital in Vietnam from 2017 to 2019. Physical oral care was provided by general ICU nurses who had been trained by dentists and infection control nurses. VAP was diagnosed using the Clinical Pulmonary Infection Score., Results: In total, 423 patients were enrolled in the baseline group and 454 patients were enrolled in the intervention group; 303 and 300 patients, respectively, were included in the analysis. Two hundred thirty-eight VAP episodes were identified: 135 (44.6%) during the baseline period and 103 (34.3%) during the intervention period. Univariate analysis revealed significant reduction of VAP occurrence in the intervention period (odds ratio = 0.65; 95% confidence interval = 0.47-0.90; P = 0.010). The incidences of VAP per 1000 ventilator-days were 63.4 (135/2128) during the baseline period and 48.4 (103/2128) during the intervention period (P = 0.038)., Conclusions: Physical oral care without any medication (e.g., chlorhexidine) reduced VAP incidence in the ICU. This method could be used to reduce VAP incidence, particularly in countries with limited medical resources., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2022
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11. Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy.
- Author
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Zhou J, Feng J, Wu Y, Dai HQ, Zhu GZ, Chen PH, Wang LM, Lu G, Liao XW, Lu PZ, Su WJ, Hooi SC, Ye XP, Shen HM, Peng T, and Lu GD
- Subjects
- Humans, Sorafenib pharmacology, Sorafenib therapeutic use, Mitophagy, Glucose, Niacinamide pharmacology, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular pathology, Chemoembolization, Therapeutic, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use
- Abstract
Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC., (© 2022. The Author(s).)
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- 2022
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12. An antibody from single human V H -rearranging mouse neutralizes all SARS-CoV-2 variants through BA.5 by inhibiting membrane fusion.
- Author
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Luo S, Zhang J, Kreutzberger AJB, Eaton A, Edwards RJ, Jing C, Dai HQ, Sempowski GD, Cronin K, Parks R, Ye AY, Mansouri K, Barr M, Pishesha N, Williams AC, Vieira Francisco L, Saminathan A, Peng H, Batra H, Bellusci L, Khurana S, Alam SM, Montefiori DC, Saunders KO, Tian M, Ploegh H, Kirchhausen T, Chen B, Haynes BF, and Alt FW
- Subjects
- Humans, Mice, Animals, Spike Glycoprotein, Coronavirus genetics, Angiotensin-Converting Enzyme 2, Membrane Fusion, Antibodies, Viral, Antibodies, Neutralizing, Epitopes, Receptors, Antigen, B-Cell, SARS-CoV-2, COVID-19
- Abstract
SARS-CoV-2 Omicron subvariants have generated a worldwide health crisis due to resistance to most approved SARS-CoV-2 neutralizing antibodies and evasion of vaccination-induced antibodies. To manage Omicron subvariants and prepare for new ones, additional means of isolating broad and potent humanized SARS-CoV-2 neutralizing antibodies are desirable. Here, we describe a mouse model in which the primary B cell receptor (BCR) repertoire is generated solely through V(D)J recombination of a human V
H 1-2 heavy chain (HC) and, substantially, a human Vκ1-33 light chain (LC). Thus, primary humanized BCR repertoire diversity in these mice derives from immensely diverse HC and LC antigen-contact CDR3 sequences generated by nontemplated junctional modifications during V(D)J recombination. Immunizing this mouse model with SARS-CoV-2 (Wuhan-Hu-1) spike protein immunogens elicited several VH 1-2/Vκ1-33-based neutralizing antibodies that bound RBD in a different mode from each other and from those of many prior patient-derived VH 1-2-based neutralizing antibodies. Of these, SP1-77 potently and broadly neutralized all SARS-CoV-2 variants through BA.5. Cryo-EM studies revealed that SP1-77 bound RBD away from the receptor-binding motif via a CDR3-dominated recognition mode. Lattice light-sheet microscopy-based studies showed that SP1-77 did not block ACE2-mediated viral attachment or endocytosis but rather blocked viral-host membrane fusion. The broad and potent SP1-77 neutralization activity and nontraditional mechanism of action suggest that it might have therapeutic potential. Likewise, the SP1-77 binding epitope may inform vaccine strategies. Last, the type of humanized mouse models that we have described may contribute to identifying therapeutic antibodies against future SARS-CoV-2 variants and other pathogens.- Published
- 2022
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13. Role of Cell-Cell Junctions in Oesophageal Squamous Cell Carcinoma.
- Author
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Xu QR, Du XH, Huang TT, Zheng YC, Li YL, Huang DY, Dai HQ, Li EM, and Fang WK
- Subjects
- Humans, Adherens Junctions metabolism, Intercellular Junctions metabolism, Biomarkers metabolism, Esophageal Squamous Cell Carcinoma metabolism, Esophageal Neoplasms metabolism
- Abstract
Cell-cell junctions comprise various structures, including adherens junctions, tight junctions, desmosomes, and gap junctions. They link cells to each other in tissues and regulate tissue homeostasis in critical cellular processes. Recent advances in cell-cell junction research have led to critical discoveries. Cell-cell adhesion components are important for the invasion and metastasis of tumour cells, which are not only related to cell-cell adhesion changes, but they are also involved in critical molecular signal pathways. They are of great significance, especially given that relevant molecular mechanisms are being discovered, there are an increasing number of emerging biomarkers, targeted therapies are becoming a future therapeutic concern, and there is an increased number of therapeutic agents undergoing clinical trials. Oesophageal squamous cell carcinoma (ESCC), the most common histological subtype of oesophageal cancer, is one of the most common cancers to affect epithelial tissue. ESCC progression is accompanied by the abnormal expression or localisation of components at cell-cell junctions. This review will discuss the recent scientific developments related to the molecules at cell-cell junctions and their role in ESCC to offer valuable insights for readers, provide a global view of the relationships between position, construction, and function, and give a reference for future mechanistic studies, diagnoses, and therapeutic developments.
- Published
- 2022
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14. The role of chromatin loop extrusion in antibody diversification.
- Author
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Zhang Y, Zhang X, Dai HQ, Hu H, and Alt FW
- Subjects
- B-Lymphocytes metabolism, Chromatin genetics, Chromatin metabolism, Humans, Immunoglobulin Heavy Chains genetics, Immunoglobulin Heavy Chains metabolism, Immunoglobulin Variable Region genetics, V(D)J Recombination
- Abstract
Cohesin mediates chromatin loop formation across the genome by extruding chromatin between convergently oriented CTCF-binding elements. Recent studies indicate that cohesin-mediated loop extrusion in developing B cells presents immunoglobulin heavy chain (Igh) variable (V), diversity (D) and joining (J) gene segments to RAG endonuclease through a process referred to as RAG chromatin scanning. RAG initiates V(D)J recombinational joining of these gene segments to generate the large number of different Igh variable region exons that are required for immune responses to diverse pathogens. Antigen-activated mature B cells also use chromatin loop extrusion to mediate the synapsis, breakage and end joining of switch regions flanking Igh constant region exons during class-switch recombination, which allows for the expression of different antibody constant region isotypes that optimize the functions of antigen-specific antibodies to eliminate pathogens. Here, we review recent advances in our understanding of chromatin loop extrusion during V(D)J recombination and class-switch recombination at the Igh locus., (© 2022. Springer Nature Limited.)
- Published
- 2022
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15. TET enzymes regulate skeletal development through increasing chromatin accessibility of RUNX2 target genes.
- Author
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Wang L, You X, Ruan D, Shao R, Dai HQ, Shen W, Xu GL, Liu W, and Zou W
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- 5-Methylcytosine metabolism, Animals, Core Binding Factor Alpha 1 Subunit genetics, Core Binding Factor Alpha 1 Subunit metabolism, Cytosine metabolism, DNA Methylation, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Mammals genetics, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Chromatin, Dioxygenases metabolism
- Abstract
The Ten-eleven translocation (TET) family of dioxygenases mediate cytosine demethylation by catalyzing the oxidation of 5-methylcytosine (5mC). TET-mediated DNA demethylation controls the proper differentiation of embryonic stem cells and TET members display functional redundancy during early gastrulation. However, it is unclear if TET proteins have functional significance in mammalian skeletal development. Here, we report that Tet genes deficiency in mesoderm mesenchymal stem cells results in severe defects of bone development. The existence of any single Tet gene allele can support early bone formation, suggesting a functional redundancy of TET proteins. Integrative analyses of RNA-seq, Whole Genome Bisulfite Sequencing (WGBS), 5hmC-Seal and Assay for Transposase-Accessible Chromatin (ATAC-seq) demonstrate that TET-mediated demethylation increases the chromatin accessibility of target genes by RUNX2 and facilities RUNX2-regulated transcription. In addition, TET proteins interact with RUNX2 through their catalytic domain to regulate cytosine methylation around RUNX2 binding region. The catalytic domain is indispensable for TET enzymes to regulate RUNX2 transcription activity on its target genes and to regulate bone development. These results demonstrate that TET enzymes function to regulate RUNX2 activity and maintain skeletal homeostasis., (© 2022. The Author(s).)
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- 2022
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16. Sesquiterpenes and polyphenols with glucose-uptake stimulatory and antioxidant activities from the medicinal mushroom Sanghuangporus sanghuang.
- Author
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Zhang JJ, Chen BS, Dai HQ, Ren JW, Zhou LW, Wu SH, and Liu HW
- Subjects
- Antioxidants pharmacology, Basidiomycota, Glucose, Humans, Molecular Docking Simulation, SARS-CoV-2, Agaricales, Polyphenols pharmacology, Sesquiterpenes pharmacology, COVID-19 Drug Treatment
- Abstract
A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites (1-14) including eight sesquiterpenoids (1-8) and six polyphenols (9-14). Compounds 1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 μmol·L
-1 , respectively. Compounds 9-12 also showed good cellular antioxidant activities with CAA50 values of 12.23, 23.11, 5.31 and 16.04 μmol·L-1 , respectively. Molecular docking between COVID-19 Mpro and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds. This work provides new insights for the potential role of the medicinal mushroom S. sanghuang as drugs and functional foods., (Copyright © 2021 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)- Published
- 2021
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17. Inhibition of starch digestion: The role of hydrophobic domain of both α-amylase and substrates.
- Author
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Liu QZ, Zhang H, Dai HQ, Zhao P, Mao YF, Chen KX, and Chen ZX
- Subjects
- Digestion, Enzyme Inhibitors chemistry, Hydrophobic and Hydrophilic Interactions, Poloxamer chemistry, Protein Domains, Spectrometry, Fluorescence, Spectroscopy, Fourier Transform Infrared, Starch chemistry, alpha-Amylases antagonists & inhibitors, alpha-Amylases metabolism, Poloxamer pharmacology, Starch pharmacokinetics, alpha-Amylases chemistry
- Abstract
The physicochemical mechanism of starch digestion is very complicated since it may be affected by the non-valence interactions of the amylase inhibitor with the substrate or the enzyme. The role of hydrophobic interaction in the process of starch digestion is not clear. In this study, pluronics (PLs) with different hydrophobicity were used as model amphiphilic compounds to study their inhibition on starch digestion using multi-spectroscopic methods. The results showed that the hydrophobic nature of PLs changed starch structure, but it had a greater effect on the structure of α-amylase by exposing more tryptophan residues and increasing α-helix and β-sheet contents. Further investigation by using different chain-length fatty acids confirmed the results. The finding in this study is informative to design and fabricate α-amylase inhibitors for controlling starch digestion at the molecular level., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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18. Corrigendum: Quercetin Induces Apoptosis Via Downregulation of VEGF/Akt Signaling Pathway in Acute Myeloid Leukemia Cells.
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Shi H, Li XY, Chen Y, Zhang X, Wu Y, Wang ZX, Chen PH, Dai HQ, Feng J, Chatterjee S, Li ZJ, Huang XW, Wei HQ, Wang J, Lu GD, and Zhou J
- Abstract
[This corrects the article DOI: 10.3389/fphar.2020.534171.]., (Copyright © 2021 Shi, Li, Chen, Zhang, Wu, Wang, Chen, Dai, Feng, Chatterjee, Li, Huang, Wei, Wang, Lu and Zhou.)
- Published
- 2021
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19. Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma.
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Li ZJ, Dai HQ, Huang XW, Feng J, Deng JH, Wang ZX, Yang XM, Liu YJ, Wu Y, Chen PH, Shi H, Wang JG, Zhou J, and Lu GD
- Subjects
- Animals, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols pharmacology, Artesunate administration & dosage, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Drug Synergism, Ferroptosis drug effects, Humans, Lipid Peroxidation drug effects, Liver Neoplasms pathology, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Oxidative Stress drug effects, Sorafenib administration & dosage, Xenograft Model Antitumor Assays, Artesunate pharmacology, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Sorafenib pharmacology
- Abstract
Sorafenib is the first-line medication for advanced hepatocellular carcinoma (HCC), but it can only extend limited survival. It is imperative to find a combination strategy to increase sorafenib efficacy. Artesunate is such a preferred candidate, because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms. In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms. We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7, SNU-449, and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice. The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic. Compared with the treatment with artesunate or sorafenib alone, combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis, which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate, but not by inhibitors of other types of cell death (z-VAD, necrostatin-1 and belnacasan). In Huh7 cells, we demonstrated that the combined treatment induced oxidative stress and lysosome-mediated ferritinophagy, two essential aspects of ferroptosis. Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in HCC treatment. The combined treatment can be easily translated into clinical applications.
- Published
- 2021
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20. Loop extrusion mediates physiological Igh locus contraction for RAG scanning.
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Dai HQ, Hu H, Lou J, Ye AY, Ba Z, Zhang X, Zhang Y, Zhao L, Yoon HS, Chapdelaine-Williams AM, Kyritsis N, Chen H, Johnson K, Lin S, Conte A, Casellas R, Lee CS, and Alt FW
- Subjects
- Animals, B-Lymphocytes cytology, B-Lymphocytes enzymology, Cell Line, Cells, Cultured, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, Down-Regulation, Endonucleases deficiency, Endonucleases genetics, G1 Phase Cell Cycle Checkpoints, High-Throughput Nucleotide Sequencing, Homeodomain Proteins genetics, Mice, Mice, Inbred C57BL, Proteins genetics, Proteins metabolism, V(D)J Recombination genetics, B-Lymphocytes metabolism, DNA-Binding Proteins metabolism, Endonucleases metabolism, Homeodomain Proteins metabolism, Immunoglobulin Heavy Chains genetics, Nucleic Acid Conformation
- Abstract
RAG endonuclease initiates Igh V(D)J recombination in progenitor B cells by binding a J
H -recombination signal sequence (RSS) within a recombination centre (RC) and then linearly scanning upstream chromatin, presented by loop extrusion mediated by cohesin, for convergent D-RSSs1,2 . The utilization of convergently oriented RSSs and cryptic RSSs is intrinsic to long-range RAG scanning3 . Scanning of RAG from the DJH -RC-RSS to upstream convergent VH -RSSs is impeded by D-proximal CTCF-binding elements (CBEs)2-5 . Primary progenitor B cells undergo a mechanistically undefined contraction of the VH locus that is proposed to provide distal VH s access to the DJH -RC6-9 . Here we report that an inversion of the entire 2.4-Mb VH locus in mouse primary progenitor B cells abrogates rearrangement of both VH -RSSs and normally convergent cryptic RSSs, even though locus contraction still occurs. In addition, this inversion activated both the utilization of cryptic VH -RSSs that are normally in opposite orientation and RAG scanning beyond the VH locus through several convergent CBE domains to the telomere. Together, these findings imply that broad deregulation of CBE impediments in primary progenitor B cells promotes RAG scanning of the VH locus mediated by loop extrusion. We further found that the expression of wings apart-like protein homologue (WAPL)10 , a cohesin-unloading factor, was low in primary progenitor B cells compared with v-Abl-transformed progenitor B cell lines that lacked contraction and RAG scanning of the VH locus. Correspondingly, depletion of WAPL in v-Abl-transformed lines activated both processes, further implicating loop extrusion in the locus contraction mechanism.- Published
- 2021
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21. ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma.
- Author
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Feng J, Lu PZ, Zhu GZ, Hooi SC, Wu Y, Huang XW, Dai HQ, Chen PH, Li ZJ, Su WJ, Han CY, Ye XP, Peng T, Zhou J, and Lu GD
- Subjects
- Animals, Biomarkers, Tumor metabolism, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Coenzyme A Ligases genetics, Ferroptosis drug effects, Gene Knockout Techniques, Humans, Liver Neoplasms diagnosis, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Mice, Inbred BALB C, Prognosis, Xenograft Model Antitumor Assays, Mice, Antineoplastic Agents therapeutic use, Carcinoma, Hepatocellular drug therapy, Coenzyme A Ligases metabolism, Liver Neoplasms drug therapy, Sorafenib therapeutic use
- Abstract
Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC
50 values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.- Published
- 2021
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22. Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells.
- Author
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Shi H, Li XY, Chen Y, Zhang X, Wu Y, Wang ZX, Chen PH, Dai HQ, Feng J, Chatterjee S, Li ZJ, Huang XW, Wei HQ, Wang J, Lu GD, and Zhou J
- Abstract
Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myeloid leukemia is less studied, and the underlying mechanisms still largely unknown. This study aimed to explore the specific target and potential mechanism of quercetin-induced cell death in AML. First, we found that quercetin induces cell death in the form of apoptosis, which was caspase dependent. Second, we found that quercetin-induced apoptosis depends on the decrease of mitochondria membrane potential (MMP) and Bcl-2 proteins. With quantitative chemical proteomics, we observed the downregulation of VEGFR2 and PI3K/Akt signaling in quercetin-treated cells. Consistently, cell studies also identified that VEGFR2 and PI3K/Akt signaling pathways are involved in the action of quercetin on mitochondria and Bcl-2 proteins. The decrease of MMP and cell death could be rescued when PI3K/Akt signaling is activated, suggesting that VEGFR2 and PI3K/Akt exert as upstream regulators for quercetin effect on apoptosis induction in AML cells. In conclusion, our findings from this study provide convincing evidence that quercetin induces cell death via downregulation of VEGF/Akt signaling pathways and mitochondria-mediated apoptosis in AML cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Shi, Li, Chen, Zhang, Wu, Wang, Chen, Dai, Feng, Chatterjee, Li, Huang, Wei, Wang, Lu and Zhou.)
- Published
- 2020
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23. CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning.
- Author
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Ba Z, Lou J, Ye AY, Dai HQ, Dring EW, Lin SG, Jain S, Kyritsis N, Kieffer-Kwon KR, Casellas R, and Alt FW
- Subjects
- Animals, Cell Line, Chromatin genetics, Chromatin metabolism, DNA-Binding Proteins metabolism, Female, G1 Phase, Genes, Immunoglobulin Heavy Chain genetics, Humans, Indoleacetic Acids metabolism, Male, Mice, Mice, Inbred C57BL, Precursor Cells, B-Lymphoid immunology, Precursor Cells, B-Lymphoid metabolism, Transcription, Genetic, Cohesins, CCCTC-Binding Factor metabolism, Cell Cycle Proteins metabolism, Chromosomal Proteins, Non-Histone metabolism, V(D)J Recombination genetics
- Abstract
The RAG endonuclease initiates Igh locus V(D)J recombination in progenitor (pro)-B cells
1 . Upon binding a recombination centre-based JH , RAG scans upstream chromatin via loop extrusion, potentially mediated by cohesin, to locate Ds and assemble a DJH -based recombination centre2 . CTCF looping factor-bound elements (CBEs) within IGCR1 upstream of Ds impede RAG scanning3-5 ; however, their inactivation allows scanning to proximal VH s, where additional CBEs activate rearrangement and impede scanning any further upstream5 . Distal VH utilization is thought to involve diffusional access to the recombination centre following large-scale Igh locus contraction6-8 . Here we test the potential of linear RAG scanning to mediate distal VH usage in G1-arrested v-Abl pro-B cell lines9 , which undergo robust D-to-JH but little VH -to-DJH rearrangements, presumably owing to lack of locus contraction2,5 . Through an auxin-inducible approach10 , we degraded the cohesin component RAD2110-12 or CTCF12,13 in these G1-arrested lines. Degradation of RAD21 eliminated all V(D)J recombination and interactions associated with RAG scanning, except for reecombination centre-located DQ52-to-JH joining, in which synapsis occurs by diffusion2 . Remarkably, while degradation of CTCF suppressed most CBE-based chromatin interactions, it promoted robust recombination centre interactions with, and robust VH -to-DJH joining of, distal VH s, with patterns similar to those of 'locus-contracted' primary pro-B cells. Thus, downmodulation of CTCF-bound scanning-impediment activity promotes cohesin-driven RAG scanning across the 2.7-Mb Igh locus.- Published
- 2020
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24. Direct analysis of brain phenotypes via neural blastocyst complementation.
- Author
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Dai HQ, Liang Z, Chang AN, Chapdelaine-Williams AM, Alvarado B, Pollen AA, Alt FW, and Schwer B
- Subjects
- Animals, Blastocyst, Cell Differentiation, Chimera, Female, Male, Mice, Organogenesis, Phenotype, Brain embryology, Brain Mapping methods, Mouse Embryonic Stem Cells physiology
- Abstract
We provide a protocol for generating forebrain structures in vivo from mouse embryonic stem cells (ESCs) via neural blastocyst complementation (NBC). We developed this protocol for studies of development and function of specific forebrain regions, including the cerebral cortex and hippocampus. We describe a complete workflow, from methods for modifying a given genomic locus in ESCs via CRISPR-Cas9-mediated editing to the generation of mouse chimeras with ESC-reconstituted forebrain regions that can be directly analyzed. The procedure begins with genetic editing of mouse ESCs via CRISPR-Cas9, which can be accomplished in ~4-8 weeks. We provide protocols to achieve fluorescent labeling of ESCs in ~2-3 weeks, which allows tracing of the injected, ESC-derived donor cells in chimeras generated via NBC. Once modified ESCs are ready, NBC chimeras are generated in ~3 weeks via injection of ESCs into genetically programmed blastocysts that are subsequently transferred into pseudo-pregnant fosters. Our in vivo brain organogenesis platform is efficient, allowing functional and systematic analysis of genes and other genomic factors in as little as 3 months, in the context of a whole organism.
- Published
- 2020
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25. Distinct effects of anti-diabetic medications on liver cancer risk and patient survival.
- Author
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Chen PH, Zhu GZ, Li L, Chen Y, Dai HQ, Su WJ, Wu Y, and Zhou J
- Subjects
- Female, Humans, Liver Neoplasms mortality, Male, Metformin pharmacology, Risk Factors, Survival Analysis, Diabetes Mellitus, Type 2 drug therapy, Liver Neoplasms drug therapy, Metformin therapeutic use
- Abstract
Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease worldwide. Multiple types of cancer, particularly liver cancer, are closely associated with T2DM. As a result, there is growing interest in investigating whether anti-diabetic medications could lower cancer risks in the population and even prolong patient survival among those with concurrent cancer. There are many types of anti-diabetic medications available in the clinic. The present study reviewed how different anti-diabetic drugs affect cancer risk and patient survival. On the one hand, multiple retrospective studies have shown that the different anti-diabetic medications have distinct effects on cancer risks. Insulin-raising drugs, including exogenous insulin, increased cancer risks, while drugs potentiating insulin sensitivity like metformin reduced cancer risks. On the other hand, the effects of anti-diabetic medications on patient survival are relatively less studied, except limited reports in liver cancer and pancreatic cancer. It seems that metformin could extend overall survival in patients of early-stage cancer. In contrast in the advanced cancer with metastasis, metformin has no effect or even worsens cancer mortality. It is yet unknown whether these distinct effects of metformin are attributable to the severity of the cancer staging or to the drug interactions between metformin and other medications. This question warrants reconsideration of the current clinical practice in the control of T2DM. Future large-scale prospective studies are needed to resolve this.
- Published
- 2020
26. New meroterpenoid compounds from the culture of mushroom Panus lecomtei.
- Author
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Wang SX, Zhao RL, Guo C, Chen BS, Dai HQ, Liu GQ, and Liu HW
- Subjects
- China, Molecular Structure, Terpenes isolation & purification, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Bacteria drug effects, Plant Extracts chemistry, Polyporales chemistry, Terpenes chemistry
- Abstract
Two new meroterpenoid compounds (1 and 2) together with five known meroterpenoid derivatives (3-7) were isolated from solid culture of mushroom Panus lecomtei. The structures of new compounds were confirmed by the analysis of NMR and HR-ESI-MS spectroscopic data. The biosynthetic pathway of 1-7 was postulated. All isolated compounds were evaluated for antibacterial activities against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Bacillus Calmette-Guérin. Compound 3 exhibited weak antibacterial activity against Bacillus Calmette-Guérin with the inhibition rate of 83.6% at 100 μmol·L
-1 . Other compounds showed no antibacterial activities against all tested pathogens at 100 μmol·L-1 ., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)- Published
- 2020
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27. Synergistic interaction between exogenous and endogenous emulsifiers and its impact on in vitro digestion of lipid in crowded medium.
- Author
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Wang SZ, Dai HQ, Chen KX, Li J, and Chen ZX
- Subjects
- Caprylates metabolism, Digestion, Emulsions chemistry, Emulsions pharmacokinetics, Hydrolysis, Lipase chemistry, Lipase metabolism, Lipids chemistry, Polyethylene Glycols, Polysorbates chemistry, Sodium Cholate chemistry, Soybean Oil metabolism, Temperature, Triglycerides metabolism, Emulsifying Agents pharmacokinetics, Lipids pharmacokinetics, Polysorbates pharmacokinetics, Sodium Cholate pharmacokinetics
- Abstract
Control of lipid digestibility by various food components has received great attention in recent decades. However, there is limited literature on investigating the synergistic effect of exogenous emulsifiers and endogenous sodium cholate (SC) on lipid digestion in a simulated physiological crowded medium. In this work, the synergistic interaction of Tween80 and SC according to the regular solution theory, and the hydrolysis of lipid emulsions containing tricaprylin, glyceryltrioleate or soybean oil in crowding medium was studied. The results show that emulsions stabilized by a combination of Tween80 and SC showed higher digestion rate and transformation than those with Tween80 or SC. The digestion rate could be increased by polyethylene glycols (PEGn) with varying crowding degree. The denaturation temperature of the lipase was increased in macromolecular crowded medium. This work allows for better understanding of the interaction between the amphiphiles and the macromolecular crowding effect on lipase digestion in the physiological environment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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28. Histone deacetylases up-regulate C/EBPα expression through reduction of miR-124-3p and miR-25 in hepatocellular carcinoma.
- Author
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Hu XX, Feng J, Huang XW, Lu PZ, Wang ZX, Dai HQ, Deng JH, Ye XP, Peng T, Hooi SC, Zhou J, and Lu GD
- Subjects
- Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms metabolism, Liver Neoplasms pathology, Up-Regulation, CCAAT-Enhancer-Binding Protein-alpha genetics, Carcinoma, Hepatocellular genetics, Histone Deacetylases metabolism, Liver Neoplasms genetics, MicroRNAs genetics
- Abstract
Background: CCAAT enhancer binding protein α (C/EBPα), as an important transcription factor involved in cell proliferation, differentiation and metabolism, was up-regulated in primary hepatocellular carcinoma (HCC) and predicted poorer prognosis. In this study, we explored how histone deacetylases (HDACs) up-regulated C/EBPα in HCC., Methods: The protein expressions of HDAC1, HDAC2 were associated with C/EBPα by immunohistochemistry staining in a HCC tissue microarray. HCC cells were then treated with HDAC inhibitors or siRNAs to determine the roles of miR-124-3p and miR-25 in the regulation of C/EBPα mRNA expression., Results: Both HDAC1 and HDAC2 proteins were significantly associated with C/EBPα. Inhibition of HDAC by either pharmacological inhibitors or siRNAs decreased C/EBPα mRNA expression in dose-dependent manners in HCC cells. HDAC inhibitors reduced C/EBPα mRNA stability as shown by pmiRGLO luciferase reporter assays. HDAC inhibition consistently induced miR-124-3p and miR-25 expression. Conversely, blockage of miR-124-3p and/or miR-25 by treatment with specific synthetic inhibitors abolished C/EBPα reduction. More importantly, C/EBPα mRNA stability could be rescued by site-directed mutations of miR-124-3p or miR-25 recognition sites in the C/EBPα 3'UTR sequence. In summary, HDAC may up-regulate C/EBPα expression through miR-124-3p and miR-25 in HCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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29. Neural blastocyst complementation enables mouse forebrain organogenesis.
- Author
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Chang AN, Liang Z, Dai HQ, Chapdelaine-Williams AM, Andrews N, Bronson RT, Schwer B, and Alt FW
- Subjects
- Animals, Chimera embryology, Chimera genetics, DNA-Binding Proteins deficiency, Doublecortin Domain Proteins, Female, Genetic Complementation Test, Germ Cells metabolism, Hippocampus anatomy & histology, Hippocampus cytology, Hippocampus embryology, Hippocampus physiology, Male, Mice, Mice, Transgenic, Microtubule-Associated Proteins deficiency, Mouse Embryonic Stem Cells cytology, Mouse Embryonic Stem Cells metabolism, Neocortex anatomy & histology, Neocortex cytology, Neocortex embryology, Neocortex physiology, Neurons cytology, Neurons metabolism, Neuropeptides deficiency, Phenotype, Prosencephalon anatomy & histology, Prosencephalon physiology, Blastocyst cytology, Blastocyst metabolism, Organogenesis, Prosencephalon cytology, Prosencephalon embryology
- Abstract
Genetically modified mice are commonly generated by the microinjection of pluripotent embryonic stem (ES) cells into wild-type host blastocysts
1 , producing chimeric progeny that require breeding for germline transmission and homozygosity of modified alleles. As an alternative approach and to facilitate studies of the immune system, we previously developed RAG2-deficient blastocyst complementation2 . Because RAG2-deficient mice cannot undergo V(D)J recombination, they do not develop B or T lineage cells beyond the progenitor stage2 : injecting RAG2-sufficient donor ES cells into RAG2-deficient blastocysts generates somatic chimaeras in which all mature lymphocytes derive from donor ES cells. This enables analysis, in mature lymphocytes, of the functions of genes that are required more generally for mouse development3 . Blastocyst complementation has been extended to pancreas organogenesis4 , and used to generate several other tissues or organs5-10 , but an equivalent approach for brain organogenesis has not yet been achieved. Here we describe neural blastocyst complementation (NBC), which can be used to study the development and function of specific forebrain regions. NBC involves targeted ablation, mediated by diphtheria toxin subunit A, of host-derived dorsal telencephalic progenitors during development. This ablation creates a vacant forebrain niche in host embryos that results in agenesis of the cerebral cortex and hippocampus. Injection of donor ES cells into blastocysts with forebrain-specific targeting of diphtheria toxin subunit A enables donor-derived dorsal telencephalic progenitors to populate the vacant niche in the host embryos, giving rise to neocortices and hippocampi that are morphologically and neurologically normal with respect to learning and memory formation. Moreover, doublecortin-deficient ES cells-generated via a CRISPR-Cas9 approach-produced NBC chimaeras that faithfully recapitulated the phenotype of conventional, germline doublecortin-deficient mice. We conclude that NBC is a rapid and efficient approach to generate complex mouse models for studying forebrain functions; this approach could more broadly facilitate organogenesis based on blastocyst complementation.- Published
- 2018
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30. CTCF-Binding Elements Mediate Accessibility of RAG Substrates During Chromatin Scanning.
- Author
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Jain S, Ba Z, Zhang Y, Dai HQ, and Alt FW
- Subjects
- Animals, Cell Line, DNA, Intergenic genetics, DNA, Intergenic metabolism, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, Immunoglobulin Heavy Chains genetics, Immunoglobulin Heavy Chains metabolism, Immunoglobulin Variable Region genetics, Immunoglobulin Variable Region metabolism, Mice, Mice, Inbred C57BL, Models, Molecular, Mutagenesis, Protein Sorting Signals, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell metabolism, RNA, Guide, CRISPR-Cas Systems, CCCTC-Binding Factor metabolism, Chromatin metabolism, Homeodomain Proteins metabolism, V(D)J Recombination
- Abstract
RAG endonuclease initiates antibody heavy chain variable region exon assembly from V, D, and J segments within a chromosomal V(D)J recombination center (RC) by cleaving between paired gene segments and flanking recombination signal sequences (RSSs). The IGCR1 control region promotes DJ
H intermediate formation by isolating Ds, JH s, and RCs from upstream VH s in a chromatin loop anchored by CTCF-binding elements (CBEs). How VH s access the DJH RC for VH to DJH rearrangement was unknown. We report that CBEs immediately downstream of frequently rearranged VH -RSSs increase recombination potential of their associated VH far beyond that provided by RSSs alone. This CBE activity becomes particularly striking upon IGCR1 inactivation, which allows RAG, likely via loop extrusion, to linearly scan chromatin far upstream. VH -associated CBEs stabilize interactions of D-proximal VH s first encountered by the DJH RC during linear RAG scanning and thereby promote dominant rearrangement of these VH s by an unanticipated chromatin accessibility-enhancing CBE function., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
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31. TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling.
- Author
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Dai HQ, Wang BA, Yang L, Chen JJ, Zhu GC, Sun ML, Ge H, Wang R, Chapman DL, Tang F, Sun X, and Xu GL
- Subjects
- 5-Methylcytosine metabolism, Animals, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Methyltransferase 3A, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, Dioxygenases deficiency, Dioxygenases genetics, Embryo, Mammalian embryology, Embryo, Mammalian enzymology, Embryo, Mammalian metabolism, Enhancer Elements, Genetic genetics, Epigenesis, Genetic, Female, Male, Mesoderm embryology, Mesoderm metabolism, Mice, Oxidation-Reduction, Promoter Regions, Genetic genetics, Proto-Oncogene Proteins deficiency, Proto-Oncogene Proteins genetics, DNA Methyltransferase 3B, DNA Methylation genetics, DNA-Binding Proteins metabolism, Dioxygenases metabolism, Gastrulation genetics, Left-Right Determination Factors metabolism, Nodal Protein metabolism, Proto-Oncogene Proteins metabolism, Signal Transduction genetics
- Abstract
Mammalian genomes undergo epigenetic modifications, including cytosine methylation by DNA methyltransferases (DNMTs). Oxidation of 5-methylcytosine by the Ten-eleven translocation (TET) family of dioxygenases can lead to demethylation. Although cytosine methylation has key roles in several processes such as genomic imprinting and X-chromosome inactivation, the functional significance of cytosine methylation and demethylation in mouse embryogenesis remains to be fully determined. Here we show that inactivation of all three Tet genes in mice leads to gastrulation phenotypes, including primitive streak patterning defects in association with impaired maturation of axial mesoderm and failed specification of paraxial mesoderm, mimicking phenotypes in embryos with gain-of-function Nodal signalling. Introduction of a single mutant allele of Nodal in the Tet mutant background partially restored patterning, suggesting that hyperactive Nodal signalling contributes to the gastrulation failure of Tet mutants. Increased Nodal signalling is probably due to diminished expression of the Lefty1 and Lefty2 genes, which encode inhibitors of Nodal signalling. Moreover, reduction in Lefty gene expression is linked to elevated DNA methylation, as both Lefty-Nodal signalling and normal morphogenesis are largely restored in Tet-deficient embryos when the Dnmt3a and Dnmt3b genes are disrupted. Additionally, a point mutation in Tet that specifically abolishes the dioxygenase activity causes similar morphological and molecular abnormalities as the null mutation. Taken together, our results show that TET-mediated oxidation of 5-methylcytosine modulates Lefty-Nodal signalling by promoting demethylation in opposition to methylation by DNMT3A and DNMT3B. These findings reveal a fundamental epigenetic mechanism featuring dynamic DNA methylation and demethylation crucial to regulation of key signalling pathways in early body plan formation.
- Published
- 2016
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32. Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicans.
- Author
-
Li WR, Shi QS, Dai HQ, Liang Q, Xie XB, Huang XM, Zhao GZ, and Zhang LX
- Subjects
- Allyl Compounds pharmacology, Antifungal Agents pharmacology, Candida albicans genetics, Cell Death, Gene Expression Regulation, Fungal drug effects, Genes, Fungal drug effects, Microbial Sensitivity Tests, Sequence Analysis, RNA, Sulfides pharmacology, Allyl Compounds pharmacokinetics, Antifungal Agents pharmacokinetics, Candida albicans drug effects, RNA, Fungal drug effects, Sulfides pharmacokinetics
- Abstract
The antifungal activity, kinetics, and molecular mechanism of action of garlic oil against Candida albicans were investigated in this study using multiple methods. Using the poisoned food technique, we determined that the minimum inhibitory concentration of garlic oil was 0.35 μg/mL. Observation by transmission electron microscopy indicated that garlic oil could penetrate the cellular membrane of C. albicans as well as the membranes of organelles such as the mitochondria, resulting in organelle destruction and ultimately cell death. RNA sequencing analysis showed that garlic oil induced differential expression of critical genes including those involved in oxidation-reduction processes, pathogenesis, and cellular response to drugs and starvation. Moreover, the differentially expressed genes were mainly clustered in 19 KEGG pathways, representing vital cellular processes such as oxidative phosphorylation, the spliceosome, the cell cycle, and protein processing in the endoplasmic reticulum. In addition, four upregulated proteins selected after two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) analysis were identified with high probability by mass spectrometry as putative cytoplasmic adenylate kinase, pyruvate decarboxylase, hexokinase, and heat shock proteins. This is suggestive of a C. albicans stress responses to garlic oil treatment. On the other hand, a large number of proteins were downregulated, leading to significant disruption of the normal metabolism and physical functions of C. albicans.
- Published
- 2016
- Full Text
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33. Synthesis and evaluation of isatin-β-thiosemicarbazones as novel agents against antibiotic-resistant Gram-positive bacterial species.
- Author
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Zhang XM, Guo H, Li ZS, Song FH, Wang WM, Dai HQ, Zhang LX, and Wang JG
- Subjects
- Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Dose-Response Relationship, Drug, Isatin chemistry, Microbial Sensitivity Tests, Molecular Structure, Structure-Activity Relationship, Thiosemicarbazones chemistry, Anti-Bacterial Agents pharmacology, Isatin pharmacology, Methicillin-Resistant Staphylococcus aureus drug effects, Thiosemicarbazones pharmacology, Vancomycin-Resistant Enterococci drug effects
- Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) have caused an increasing mortality rate, which means that antibiotic resistance is becoming an important health issue. In the course to screen new agents for resistant bacteria, we identified that a series of isatin-β-thiosemicarbazones (IBTs) could inhibit the growth of MRSA and VRE. This was the first time that the "familiar" IBT compounds exhibited significant anti Gram-positive pathogen activity. Against a clinical isolated MRSA strain, 20 of the 51 synthesized compounds showed minimum inhibitory concentration (MIC) data of 0.78 mg/L and another 12 novel compounds had MICs of 0.39 mg/L. Moreover, these compounds also inhibited Enterococcus faecalis and VRE at similar levels, indicating that IBTs might have different mode of action compared with vancomycin. For these IBTs, comparative field analysis (CoMFA) models were further established to understand the structure-activity relationships in order to design new compounds from steric and electrostatic contributions. This work has suggested that IBTs can be considered as potential lead compounds to discover antibacterial inhibitors to combat drug resistance., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)
- Published
- 2015
- Full Text
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34. Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition in somatic cell reprogramming.
- Author
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Hu X, Zhang L, Mao SQ, Li Z, Chen J, Zhang RR, Wu HP, Gao J, Guo F, Liu W, Xu GF, Dai HQ, Shi YG, Li X, Hu B, Tang F, Pei D, and Xu GL
- Subjects
- Animals, Blotting, Western, Cell Differentiation, Cell Lineage, Cells, Cultured, Dioxygenases, Embryo, Mammalian cytology, Embryo, Mammalian metabolism, Embryonic Stem Cells metabolism, Epigenesis, Genetic, Fibroblasts cytology, Fibroblasts metabolism, Flow Cytometry, Gene Expression Regulation, Immunoenzyme Techniques, Induced Pluripotent Stem Cells metabolism, Mice, Mice, Knockout, MicroRNAs physiology, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Cellular Reprogramming, DNA Glycosylases physiology, DNA Methylation, DNA-Binding Proteins physiology, Embryonic Stem Cells cytology, Epithelial-Mesenchymal Transition, Induced Pluripotent Stem Cells cytology, Proto-Oncogene Proteins physiology
- Abstract
Tet-mediated DNA oxidation is a recently identified mammalian epigenetic modification, and its functional role in cell-fate transitions remains poorly understood. Here, we derive mouse embryonic fibroblasts (MEFs) deleted in all three Tet genes and examine their capacity for reprogramming into induced pluripotent stem cells (iPSCs). We show that Tet-deficient MEFs cannot be reprogrammed because of a block in the mesenchymal-to-epithelial transition (MET) step. Reprogramming of MEFs deficient in TDG is similarly impaired. The block in reprogramming is caused at least in part by defective activation of key miRNAs, which depends on oxidative demethylation promoted by Tet and TDG. Reintroduction of either the affected miRNAs or catalytically active Tet and TDG restores reprogramming in the knockout MEFs. Thus, oxidative demethylation to promote gene activation appears to be functionally required for reprogramming of fibroblasts to pluripotency. These findings provide mechanistic insight into the role of epigenetic barriers in cell-lineage conversion., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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35. ABC transporters coupled with the elevated ergosterol contents contribute to the azole resistance and amphotericin B susceptibility.
- Author
-
Ren B, Dai HQ, Pei G, Tong YJ, Zhuo Y, Yang N, Su MY, Huang P, Yang YZ, and Zhang LX
- Subjects
- Drug Synergism, Fluphenazine pharmacology, ATP-Binding Cassette Transporters metabolism, Amphotericin B pharmacology, Antifungal Agents pharmacology, Azoles pharmacology, Candida albicans drug effects, Drug Resistance, Fungal, Ergosterol metabolism
- Abstract
Most screening approaches produce compounds that target survival genes and are likely to generate resistance over time. Simply having more drugs does not address the potential emergence of resistance caused by target mutation, drug efflux pumps over-expression, and so on. There is a great need to explore new strategies to treat fungal infections caused by drug-resistant pathogens. In this study, we found that azole-resistant Candida albicans with CaCDR1 and CaCDR2 over-expression is hypersensitive against amphotericin B (AmB) by our high throughput synergy screening (HTSS). In contrast, Δcdr1 and Δcdr2 knockout strains were resistant to AmB. Moreover, clinical isolates with increased expression of CaCDR1 and CaCDR2 demonstrated susceptibility to AmB, which can also synergize with the efflux pumps inducer fluphenazine (FPZ). Finally, the increased drug susceptibility to AmB in azole-resistant C. albicans with drug efflux pumps over-expression was consistent with the elevated expression of CaERG11 and its associated ergosterols in clinical isolates. Our data implies that the level of ergosterol contents determines the susceptibility to azoles and AmB in C. albicans. Deep understanding of the above mechanisms would offer new hope to treat drug-resistant C. albicans.
- Published
- 2014
- Full Text
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36. Salinibacillus xinjiangensis sp. nov., a halophilic bacterium from a hypersaline lake.
- Author
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Yang N, Ren B, Liu ZH, Dai HQ, Wang J, Zhou YG, Song FH, and Zhang LX
- Subjects
- Bacillaceae genetics, Bacillaceae isolation & purification, Bacterial Typing Techniques, Base Composition, China, DNA, Bacterial genetics, Diaminopimelic Acid chemistry, Fatty Acids chemistry, Molecular Sequence Data, Phosphatidylglycerols chemistry, RNA, Ribosomal, 16S genetics, Salinity, Sequence Analysis, DNA, Sodium Chloride chemistry, Vitamin K 2 analogs & derivatives, Vitamin K 2 chemistry, Bacillaceae classification, Lakes microbiology, Phylogeny
- Abstract
A Gram-positive, endospore-forming, rod-shaped bacterium, designated isolate J4(T), was isolated from a neutral saline lake sample from Xinjiang Uyghur Autonomous Region, China, and subjected to a polyphasic taxonomic investigation. Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain J4(T) is most closely related to Salinibacillus aidingensis 25-7(T) (with 96.7 % similarity), Salinibacillus kushneri 8-2(T) (96.5 %), Ornithinibacillus scapharcae TW25(T) (96.4 %), Salirhabdus euzebyi CVS-14(T) (96.4 %) and Ornithinibacillus californiensis MB-9(T) (96.2 %). Chemotaxonomic analysis showed menaquinone-7 (MK-7) to be the major isoprenoid quinone of strain J4(T); diphosphatidylglycerol and phosphatidylglycerol were the major cellular polar lipids and the cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid. The major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The genomic DNA G+C content of strain J4(T) was determined to be 36.2 mol%. Strain J4(T) was positive for catalase activity and negative for oxidase activity. Strain J4(T) was observed to grow at 25-50 °C (optimal 35-42 °C), pH 6.5-8.0 (optimal 7.0-7.5) and in media containing 1-21 % (w/v) NaCl (optimal 9-12 %). Based on these data, strain J4(T) represents a novel species of the genus Salinibacillus and the name Salinibacillus xinjiangensis sp. nov. is proposed. The type strain is J4(T) ( = CGMCC 1.12331(T) = JCM 18732(T)).
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- 2014
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37. Ophiobolins P-T, five new cytotoxic and antibacterial sesterterpenes from the endolichenic fungus Ulocladium sp.
- Author
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Wang QX, Bao L, Yang XL, Liu DL, Guo H, Dai HQ, Song FH, Zhang LX, Guo LD, Li SJ, and Liu HW
- Subjects
- Anti-Bacterial Agents chemistry, Anti-Bacterial Agents isolation & purification, Antineoplastic Agents chemistry, Antineoplastic Agents isolation & purification, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Bacillus subtilis drug effects, Biological Products chemistry, Biological Products therapeutic use, Hep G2 Cells, Humans, KB Cells, Methicillin-Resistant Staphylococcus aureus drug effects, Microbial Sensitivity Tests, Molecular Structure, Mycobacterium bovis drug effects, Sesterterpenes chemistry, Sesterterpenes isolation & purification, Anti-Bacterial Agents pharmacology, Ascomycota chemistry, Bacteria drug effects, Biological Products pharmacology, Lichens chemistry, Neoplasms drug therapy, Sesterterpenes pharmacology
- Abstract
Five ophiobolane sesterterpenes, ophiobolins P-T, and three known compounds, 6-epi-21,21-O-dihydroophiobolin G, 6-epi-ophiobolin G and 6-epi-ophiobolin K, were isolated from the acetone extract of the endolichenic fungus Ulocladium sp. by using OSMAC method. Their structures were elucidated on the basis of spectroscopic analysis. The absolute configuration of the 18,19-diol moieties in ophiobolin Q was assigned using the Frelek's method. The cytotoxic effects on KB and HepG2 cell lines, antibacterial activity against Bacillus subtilis, methicillin-resistant Staphylococcus aureus, and Bacille Calmette-Guerin were evaluated for all isolated compounds. Ophiobolin T and 6-epi-ophiobolin G exhibited the most potent cytotoxic activity against HepG2 with IC₅₀ of 0.24 and 0.37 μM, respectively. In antibacterial assay, ophiobolins P and T showed moderate antibacterial activity against B. subtilis and meticillin-resistant S. aureus. Ophiobolin T also displayed moderate antibacterial activity against the Bacille Calmette-Guerin strain., (© 2013.)
- Published
- 2013
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38. Antioxidant activity and components of a traditional Chinese medicine formula consisting of Crataegus pinnatifida and Salvia miltiorrhiza.
- Author
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Chen CY, Li H, Yuan YN, Dai HQ, and Yang B
- Subjects
- Chemistry, Pharmaceutical, Chromatography, High Pressure Liquid, Phenols analysis, Antioxidants analysis, Crataegus chemistry, Drugs, Chinese Herbal analysis, Salvia miltiorrhiza chemistry
- Abstract
Background: The aims of this study were to evaluate the antioxidant activity and to identify the antioxidant components of a traditional Chinese medicine formula consisting of a combination of Shanzha (the fruit of Crataegus pinnatifida Bge. var. major N.E.Br., SZ) and Danshen (the root of Salvia miltiorrhiza Bge., DS). This medicine is extensively used to treat cardiovascular disease., Methods: Twelve samples extracted and fractionated from SZ, DS and the formula (SZ+DS) were analyzed. The concentrations of eight phenolic compounds were determined by high performance liquid chromatography. Oxygen radical absorbance capacity (ORAC) assay and 1,1-diphenyl-2-picrylhydrazyl assay were conducted to explore the antioxidant activities of the samples and of the 15 phenolic compounds detected. Correlation analysis of the antioxidant activity of herb samples and their phenolic components was performed., Results: The main phenolic component in all SZ+DS samples was salvianolic acid B, which exhibited strong antioxidant activity (ORAC value: 16.73 ± 2.53, IC50 value: 8.80 ± 0.06 μM) compared with the other phenolic compounds. For all samples, there was a positive relationship between their total phenolic components and their antioxidant activities., Conclusions: Phenolic compounds were the bioactive components of the herb samples, and salvianolic acid B was identified as the main bioactive compound in the SZ+DS formula.
- Published
- 2013
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39. Synthesis and evaluation of novel sulfenamides as novel anti Methicillin-resistant Staphylococcus aureus agents.
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Shang JL, Guo H, Li ZS, Ren B, Li ZM, Dai HQ, Zhang LX, and Wang JG
- Subjects
- Anti-Bacterial Agents chemistry, Microbial Sensitivity Tests, Molecular Structure, Sulfamerazine chemistry, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents pharmacology, Methicillin-Resistant Staphylococcus aureus drug effects, Sulfamerazine chemical synthesis, Sulfamerazine pharmacology
- Abstract
A total of 29 novel sulfenamide compounds were synthesized, spectroscopically characterized and evaluated in vitro for antimicrobial activity against various infectious pathogens. Compounds 1b and 2c exhibited potent inhibition against clinical Methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentration (MIC) values of 1.56 μg/mL., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
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40. Identification of blapsins A and B as potent small-molecule 14-3-3 inhibitors from the insect Blaps japanensis.
- Author
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Yan YM, Dai HQ, Du Y, Schneider B, Guo H, Li DP, Zhang LX, Fu H, Dong XP, and Cheng YX
- Subjects
- 14-3-3 Proteins chemistry, Animals, Antineoplastic Agents isolation & purification, Antineoplastic Agents pharmacology, COS Cells, Chlorocebus aethiops, Chromans isolation & purification, Chromans pharmacology, Enzyme-Linked Immunosorbent Assay, Ethanol, Magnetic Resonance Spectroscopy, Phenylacetates isolation & purification, Phenylacetates pharmacology, Solvents, Structure-Activity Relationship, Tissue Extracts chemistry, 14-3-3 Proteins antagonists & inhibitors, Antineoplastic Agents chemistry, Chromans chemistry, Coleoptera chemistry, Phenylacetates chemistry
- Abstract
In this study, we report three novel naturally occurring compounds, blapsins A (1) and B (2), and blapsamide (3) from the ethanol extract of the stink beetle, Blaps japanensis. The structures of these compounds were determined using spectroscopic methods. Compound 3 is a phenolic compound bearing a formamido group in the structure. Functional studies revealed that compounds 1 and 2 potently inhibited 14-3-3 protein-protein interactions (PPIs) with IC(50) values of 9.2 and 10.0 μM as determined by an ELISA assay, and 2.0 and 2.5 μM in an FP assay, respectively. These compounds represent the first example of natural small-molecule 14-3-3 inhibitors., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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41. Polyketides with antimicrobial activity from the solid culture of an endolichenic fungus Ulocladium sp.
- Author
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Wang QX, Bao L, Yang XL, Guo H, Yang RN, Ren B, Zhang LX, Dai HQ, Guo LD, and Liu HW
- Subjects
- Antifungal Agents chemistry, Bacteria drug effects, Biphenyl Compounds chemistry, Candida albicans drug effects, Free Radical Scavengers chemistry, Free Radical Scavengers pharmacology, Molecular Structure, Picrates chemistry, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Antifungal Agents pharmacology, Ascomycota chemistry, Polyketides chemistry, Polyketides pharmacology
- Abstract
Two new polyketides, 7-hydroxy-3, 5-dimethyl-isochromen-1-one (1) and 6-hydroxy-8-methoxy-3a-methyl-3a,9b-dihydro-3H-furo[3,2-c]isochromene-2,5-dione (2), along with eleven known compounds, 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (3), 7-hydroxy-3-(2-hydroxy-propyl)-5-methyl-isochromen-1-one (4), rubralactone (5), isoaltenuene (6), altenuene (7), dihydroaltenuenes A (8), altenusin (9), alterlactone (10), 6-O-methylnorlichexanthone (11), norlichexanthone (12), and griseoxanthone C (13) were isolated from the culture of the endolichenic fungus Ulocladium sp. Compound 2 was obtained as a racemate with an unprecedented chemical skeleton. The NMR data assignments for 3 and 4 were achieved for the first time. Compounds 1-13 were screened for their antimicrobial and radical scavenging activities. Compound 1 showed some antifungal activity against Candida albicans SC 5314 with IC(50) of 97.93 ± 1.12 μM. Compounds 11-13 showed strong activity against Bacillus subtilis with IC(50) in the range of 1-5 μM. Compound 12 significantly inhibited the growth of methicillin-resistant Staphylococcus aureus with IC(50) of 20.95 ± 1.56 μM. Compounds 9 and 10 showed strong radical scavenging activity in comparison with vitamin C. The plausible biosynthetic pathways for compounds 1, 2, and 4-8 were discussed., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
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42. Antioxidant flavonoids from the seed of Oroxylum indicum.
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Yan RY, Cao YY, Chen CY, Dai HQ, Yu SX, Wei JL, Li H, and Yang B
- Subjects
- Antioxidants isolation & purification, Flavonoids isolation & purification, Glycosides isolation & purification, Seeds chemistry, Antioxidants chemistry, Bignoniaceae chemistry, Flavonoids chemistry, Glycosides chemistry, Plant Extracts chemistry
- Abstract
Three new flavonoid glycosides (1-3) and nineteen known compounds (4-22) were isolated from the aqueous ethanolic extract of the seed of Oroxylum indicum. The structures of 1-3 were elucidated on the basis of spectroscopic analysis. Antioxidant activities of all the isolated compounds were evaluated using a DPPH and an ORAC assay. Compounds 3, 5-7, 9 and 12 exhibited potent antioxidant activity in the DPPH assay, while compounds 3-15 showed potent antioxidant capacity in the ORAC assay, and seven antioxidant flavonoids (4-6, 8, 9, 11, 12) were detected as the main ingredients in the methanolic extract of seed of O. indicum using an HPLC analysis., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
- Full Text
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43. Chemical constituents from endophytic fungus Fusarium oxysporum.
- Author
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Wang QX, Li SF, Zhao F, Dai HQ, Bao L, Ding R, Gao H, Zhang LX, Wen HA, and Liu HW
- Subjects
- Anti-Bacterial Agents pharmacology, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Biological Products pharmacology, Biological Products therapeutic use, Cell Line, Tumor, Humans, Phytotherapy, Piperidones chemistry, Piperidones pharmacology, Pyridones pharmacology, Pyridones therapeutic use, Anti-Bacterial Agents isolation & purification, Antineoplastic Agents isolation & purification, Biological Products chemistry, Fusarium chemistry, Methicillin-Resistant Staphylococcus aureus drug effects, Neoplasms drug therapy, Piperidones isolation & purification, Pyridones isolation & purification
- Abstract
A new oxysporidinone analogue (1) and a new 3-hydroxyl-2-piperidinone derivative (2), along with the known compounds (-)-4,6'-anhydrooxysporidinone (3), (+)-fusarinolic acid (4), gibepyrone D (5), beauvercin (6),cerevisterol (7), fusaruside (8), and (2S,2'R,3R,3'E,4E,8E)-1-O-D-glucopyranosyl-2-N-(2'-hydroxy-3'-octadecenoyl)-3-hydroxy-9-methyl-4,8-sphingadienine (9) were isolated from Fusarium oxysporum. Compounds 1-9 were evaluated for cytotoxicity using the MTT method against cancer cell lines, PC-3, PANC-1, and A549. Beauvericin showed cytotoxicity against PC-3, PANC-1, and A549 with IC(50) value of 49.5 ± 3.8, 47.2 ± 2.9, and 10.4 ± 1.6μM, respectively. Beauvericin also exhibited anti-bacterial activity towards methicillin-resistant Staphylococcus aureus (MIC=3.125 μg/mL) and Bacillus subtilis (MIC=3.125 μg/mL)., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
- Full Text
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44. Yuhushiella deserti gen. nov., sp. nov., a new member of the suborder Pseudonocardineae.
- Author
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Mao J, Wang J, Dai HQ, Zhang ZD, Tang QY, Ren B, Yang N, Goodfellow M, Zhang LX, and Liu ZH
- Subjects
- Actinomycetales chemistry, Actinomycetales genetics, Base Composition, Carbohydrates analysis, China, Cluster Analysis, DNA, Bacterial chemistry, DNA, Bacterial genetics, DNA, Ribosomal chemistry, DNA, Ribosomal genetics, Diaminopimelic Acid analysis, Molecular Sequence Data, Muramic Acids analysis, Mycolic Acids analysis, Phospholipids analysis, Phylogeny, Quinones analysis, RNA, Ribosomal, 16S genetics, Sequence Analysis, DNA, Actinomycetales classification, Actinomycetales isolation & purification, Soil Microbiology
- Abstract
A thermotolerant, Gram-stain-positive, aerobic, sporangium-forming actinomycete, strain RA45(T), was isolated from a desert region in Xinjiang Uigur Autonomous Region, north-western China. Comparative analysis of the 16S rRNA gene sequence and phenotypic characterization revealed that strain RA45(T) belonged phylogenetically to the family Pseudonocardiaceae of the suborder Pseudonocardineae. Strain RA45(T) showed more than 5 % 16S rRNA gene sequence divergence from recognized species of genera in the family Pseudonocardiaceae, forming a distinct lineage within the evolutionary radiation occupied by the genera Amycolatopsis, Prauserella, Thermocrispum, Saccharomonospora, Saccharopolyspora and Sciscionella, but distinct from each of them. The affiliation to the family was supported by the presence of suborder- and family-specific 16S rRNA signature nucleotides, a DNA G+C content of 69.9 mol%, the presence of meso-diaminopimelic acid, ribose, arabinose, glucose and galactose, which are characteristic components of cell-wall chemotype IV of actinomycetes, the presence of menaquinone MK-9(H₄) as the major respiratory lipoquinone, a lack of mycolic acids and the presence of an N-acetylated type of muramic acid. However, strain RA45(T) differed from known genera of the family in its polar lipid composition: the major phospholipids were phosphatidylethanolamine, phosphatidylinositol mannosides, phosphatidylmethylethanolamine, diphosphatidylglycerol, phospholipids of unknown structure and phospholipids of unknown structure containing glucosamine (phospholipid type IV). Based on its morphological, chemotaxonomic and phylogenetic characteristics, strain RA45(T) is considered to represent a novel species of a new genus in the family Pseudonocardiaceae, for which the name Yuhushiella deserti gen. nov., sp. nov. is proposed. The type strain of Yuhushiella deserti is RA45(T) (=CGMCC 4.5579(T) =JCM 16584(T)).
- Published
- 2011
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45. Antituberculosis agents and an inhibitor of the para-aminobenzoic acid biosynthetic pathway from Hydnocarpus anthelminthica seeds.
- Author
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Wang JF, Dai HQ, Wei YL, Zhu HJ, Yan YM, Wang YH, Long CL, Zhong HM, Zhang LX, and Cheng YX
- Subjects
- 4-Aminobenzoic Acid chemistry, Biosynthetic Pathways drug effects, Candida albicans drug effects, Cells, Cultured, Magnetic Resonance Spectroscopy, Microbial Sensitivity Tests, Molecular Structure, 4-Aminobenzoic Acid antagonists & inhibitors, Antitubercular Agents chemistry, Antitubercular Agents pharmacology, Mycobacterium tuberculosis drug effects, Salicaceae chemistry, Seeds chemistry
- Abstract
Investigation on the extracts of Hydnocarpus anthelminthica seeds led to the isolation of three new compounds, anthelminthicins A-C (1-3, resp.), and two known ones, namely chaulmoogric acid (4) and ethyl chaulmoograte (5). Their structures were determined mainly by using spectroscopic techniques. The absolute configuration at the cyclopentenyl moiety of compound 2 was rationalized by quantum calculations. Base hydrolysis, followed by optical-rotation comparison, allowed assignment of the configuration of chaulmoogric-acid moiety of compounds 3 and 5. Biological assays revealed that compounds 1-5 significantly inhibit Mycobacterium tuberculosis (MTB) growth with MIC values of 5.54, 16.70, 4.38, 9.82, and 16.80 microM, respectively. Compound 3 was found to inhibit the pathway between chorismate and para-aminobenzoic acid (pAba) with a MIC value of 11.3 microM, representing a new example of pAba inhibitor isolated from a natural source. All compounds were not toxic to Candida albicans SC5314 at a concentration up to 100 microM.
- Published
- 2010
- Full Text
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46. Verrucosispora sediminis sp. nov., a cyclodipeptide-producing actinomycete from deep-sea sediment.
- Author
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Dai HQ, Wang J, Xin YH, Pei G, Tang SK, Ren B, Ward A, Ruan JS, Li WJ, and Zhang LX
- Subjects
- DNA, Bacterial genetics, DNA, Ribosomal genetics, Micromonosporaceae genetics, Micromonosporaceae metabolism, Molecular Sequence Data, Phylogeny, RNA, Ribosomal, 16S genetics, Dipeptides metabolism, Geologic Sediments microbiology, Micromonosporaceae classification, Micromonosporaceae isolation & purification, Seawater microbiology
- Abstract
An actinomycete, designated MS426T, the culture broth of which showed potent antimicrobial activity, was isolated from a deep-sea sediment sample of the South China Sea. An almost-complete sequence of the 16S rRNA gene of strain MS426T was determined and aligned with those of representatives of the family Micromonosporaceae available in public databases. Phylogenetic trees were inferred by using three algorithms. Strain MS426T formed a branch adjacent to Verrucosispora lutea YIM 013T in a distinct cluster occupied only by strains of the genus Verrucosispora. Strain MS426T was distinguishable from the type strains of the two described Verrucosispora species by using a combination of chemical and morphological markers and by DNA-DNA relatedness. On the basis of these genotypic and phenotypic differences, the novel antimicrobial strain with pharmaceutical potential represents a novel species, for which the name Verrucosispora sediminis sp. nov. is proposed. The type strain is MS426T (=CGMCC 4.3550T =JCM 15670T).
- Published
- 2010
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47. Amycolatopsis marina sp. nov., an actinomycete isolated from an ocean sediment.
- Author
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Bian J, Li Y, Wang J, Song FH, Liu M, Dai HQ, Ren B, Gao H, Hu X, Liu ZH, Li WJ, and Zhang LX
- Subjects
- Actinomycetales chemistry, Actinomycetales genetics, Actinomycetales isolation & purification, China, DNA, Bacterial analysis, DNA, Ribosomal Spacer analysis, Genes, rRNA, Molecular Sequence Data, Nucleic Acid Hybridization, Phylogeny, RNA, Ribosomal, 16S genetics, RNA, Ribosomal, 23S genetics, Sequence Analysis, DNA, Species Specificity, Actinomycetales classification, Geologic Sediments microbiology, Seawater microbiology
- Abstract
A Gram-positive, aerobic, non-motile actinobacterium, designated strain Ms392A(T), was isolated from an ocean-sediment sample collected from the South China Sea. The isolate contained chemical markers that supported chemotaxonomic assignment to the genus Amycolatopsis. On the basis of an analysis of 16S rRNA gene sequence similarities, strain Ms392A(T) represents a novel subclade within the genus Amycolatopsis, with Amycolatopsis palatopharyngis 1BDZ(T) as its closest phylogenetic neighbour (99.4 % similarity). However, DNA-DNA hybridization demonstrated that strain Ms392A(T) was distinct from A. palatopharyngis AS 4.1729(T) (48.6 % relatedness). The polyphasic analysis demonstrated that the ocean isolate can be clearly distinguished from recognized species of the genus Amycolatopsis. Therefore, strain Ms392A(T) represents a novel species of the genus Amycolatopsis, for which the name Amycolatopsis marina sp. nov. is proposed. The type strain is Ms392A(T) (=CGMCC 4.3568(T) =NBRC 104263(T)).
- Published
- 2009
- Full Text
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48. [Changes of electroencephalographic background patterns and serum neuron specific enolase levels in neonates with hypoxic-ischemic encephalopathy].
- Author
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Dai HQ and Luo YH
- Subjects
- Electroencephalography, Female, Humans, Hypoxia-Ischemia, Brain blood, Hypoxia-Ischemia, Brain mortality, Infant, Newborn, Male, Prognosis, Hypoxia-Ischemia, Brain physiopathology, Phosphopyruvate Hydratase blood
- Abstract
Objective: To examine electroencephalographic (EEG) background patterns and serum neuron specific enolase (NSE) levels in neonates with hypoxic-ischemic encephalopathy (HIE) in order to study their roles in assessing clinical progress, severity and prognosis in children with HIE., Methods: A total of 58 neonates with HIE, including 38 cases of mild, 12 cases of moderate and 8 cases of severe HIE, were enrolled. Thirty normal neonates were used as the control group. Serum NES levels were measured by radioimmunoassay 12-24 hrs and 7-10 days after birth. EEG examination was performed 24 hrs-18 days of age (early stage) and 28-30 days of age (convalescence stage). The neonates with HIE were followed-up, with a duration of 6 months to 3 years., Results: Fifty-five neonates with HIE (94.8%) showed EEG abnormalities in the early stage, but only 2 patients (6.7%) in the control group (p<0.01). EEG background patterns abnormalities in the early stage were found in 90.0% (18/20) of moderate-severe HIE neonates. The proportion was significantly higher than that in the mild HIE group [5.2% (2/38); p<0.01]. Thirteen (72.2%) out of 18 patients with early EEG background patterns abnormalities had poor outcomes. Serum levels of NES in the HIE group were significantly higher than those in the control group 12-24 hrs after birth (p<0.01). EEG background patterns abnormalities and increased serum levels of NES 12-24 hrs after birth were consistent with the clinical grading of HIE. Most of neonates [87.5% (7/8)] who showed abnormal EEG background patterns at the convalescence stage had neurological sequelae., Conclusions: EEG background patterns and serum NSE levels may be useful in assessment of disease severity and neurological outcome in children with HIE.
- Published
- 2009
49. Observation on the effect of Salvia miltiorrhiza injection in treating traumatic hyphema and the opportune time for its application.
- Author
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Zhang L, Ren L, Zhang J, and Dai HQ
- Subjects
- Adolescent, Adult, Child, Female, Humans, Injections, Male, Middle Aged, Prospective Studies, Retrospective Studies, Time Factors, Treatment Outcome, Drugs, Chinese Herbal therapeutic use, Hyphema complications, Hyphema drug therapy, Phytotherapy, Salvia miltiorrhiza metabolism, Wounds and Injuries complications, Wounds and Injuries drug therapy
- Abstract
Objective: To observe the effect of Salvia miltiorrhiza Injection (SMI) in treating traumatic hyphema (TH) and the opportune time for its application., Methods: A retrospective study was conducted in 174 patients with TH (all with a single eye wounded), of whom 92 patients were treated with dicynone and 82 with SMI, and their status of recurrent or aggravated hemorrhage within 5 days after trauma were analyzed. Further, a prospective study was conducted in 76 TH patients (all with a single eye wounded), who were treated with dicynone though they had hyphema 5 days after treatment. After the dicynone medication was discontinued, 39 of them were treated with SI, but 37 were not. The status of hyphema absorption was observed., Results: The retrospective study showed that the number of cases with recurrent or aggravated bleeding in the SMI-treatment group was much more than that in the dicynonetreated group (Z=-2.531, P=0.011). On the other hand, the prospective study showed that the status of hyphema absorption among the SMI-treated patients was significantly better than in those untreated with SMI (Z=-2.642, P=0.008)., Conclusion: SMI shows an effect of promoting the absorption of TH, and SMI treatment is worthy of being spread in clinical practice. For safety considerations, it is suitable to apply the treatment 5 days after trauma.
- Published
- 2008
- Full Text
- View/download PDF
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