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1.
Cardiorenal Med ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740015

RESUMO

INTRODUCTION: Cardiorenal syndrome encompasses a range of disorders involving both the heart and kidneys, wherein dysfunction in one organ may induce dysfunction in the other, either acutely or chronically. This study conducted a literature search on cardiorenal syndrome from January 1, 2003, to September 8, 2023. Meanwhile, a quantitative analysis of the developmental trajectory, research hotspots and evolutionary trends in the field of cardiorenal syndrome through bibliometric analysis and knowledge mapping. SUMMARY: The field of cardiorenal syndrome exhibits promising potential to grow and is emerging as a prominent research area. Future endeavours should prioritise a comprehensive understanding of the field and foster multi-centre co-operation among different countries and regions. KEY MESSAGES: The annual publication trend analysis revealed a consistent annual increase in cardiorenal syndrome literature over the last 20 years. The IL6, REN and INS genes were identified as the current research hotspots.

2.
Angew Chem Int Ed Engl ; 63(20): e202402642, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38453641

RESUMO

Conjugated polymers (CPs) with low crystallinity are promising candidates for application in organic thermoelectrics (OTEs), particularly in flexible devices, because the disordered structures of these CPs can effectively accommodate dopants and ensure robust resistance to bending. However, n-doped CPs usually exhibit poor thermoelectric performance, which hinders the development of high-performance thermoelectric generators. Herein, we report an n-type CP (ThDPP-CNBTz) comprising two acceptor units: a thiophene-flanked diketopyrrolopyrrole and a cyano-functionalized benzothiadiazole. ThDPP-CNBTz shows a low LUMO energy level of below -4.20 eV and features low crystallinity, enabling high doping efficiency. Moreover, the dual-acceptor design enhances polaron delocalization, resulting in good thermoelectric performance. After n-doping, ThDPP-CNBTz exhibits an average electrical conductivity (σ) of 50.6 S cm-1 and a maximum power factor (PF) of 126.8 µW m-1 K-2, which is among the highest values reported for solution-processed n-type CPs to date. Additionally, a solution-processed flexible OTE device based on doped ThDPP-CNBTz exhibits a maximum PF of 70 µW m-1 K-2; the flexible device also shows remarkable resistance to bending strain, with only a marginal change in σ after 600 bending cycles. The findings presented in this work will advance the development of n-type CPs for OTE devices, and flexible devices in particular.

3.
Urol Oncol ; 42(5): 144-154, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38485644

RESUMO

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Adenocarcinoma/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Proliferação de Células
4.
Sci Rep ; 14(1): 4667, 2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409247

RESUMO

This study analyzed the effects of the Dark Tetrad (narcissism, Machiavellianism, psychopathy, sadism) and self-concealment on social appearance anxiety. Empirical investigations on which personality traits influence social appearance anxiety are yet missing. In this study, a sample of N = 1186 Chinese students performed a questionnaire-based survey assessing different personality facets and social appearance anxiety tendencies. Measures included the Narcissistic Personality Inventory, the Levenson Self-Report Psychopathy Scale, the Machiavellian Personality Scale, the Short Sadistic Impulse Scale, the Self-concealment Scale, and the Social Appearance Anxiety Scale. The results of the multiple regression analysis showed that psychopathy, Machiavellianism, sadism, and self-concealment positively predicted social appearance anxiety and narcissism negatively predicted social appearance anxiety. Machiavellianism, psychopathy, sadism, and self-concealment were positive predictors of social appearance anxiety, whereas narcissism was a negative predictor. These findings provide insight into the complex nature of the Dark Tetrad and their influence on social appearance anxiety.


Assuntos
Transtorno da Personalidade Antissocial , Personalidade , Humanos , Maquiavelismo , Transtornos da Personalidade , Narcisismo , Ansiedade
5.
Macromol Rapid Commun ; 45(1): e2300245, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37278130

RESUMO

A series of thienoisoindigo (TIG)-based conjugated polymers (CPs) with high molecular weights are synthesized by direct arylation polycondensation (DArP) by using TIG derivatives as CBr monomer and multi-halogenated thiophene derivatives, i.e., (E)-1,2-bis(3,4-difluorothien-2-yl)ethene (4FTVT), (E)-1,2-bis(3,4-dichlorothien-2-yl)ethene (4ClTVT), 3,3',4,4'-tetrafluoro-2,2'-bithiophene (4FBT), and 3,3',4,4'-tetrachloro-2,2'-bithiophene (4ClBT), as CH monomers. Density functional theory (DFT) calculations reveal the high selectivity between α-CH bonds in 4FTVT, 4ClTVT, 4FBT, and 4ClBT and ß-CH bonds in TIG CBr monomer. All four resulting CPs exhibit low optical bandgaps of ca. 1.20 eV and ambipolar transport characteristics with both electron and hole mobility above 0.1 cm2  V-1  s-1 as elaborated with organic thin-film transistors (OTFTs). The polymer TIG-4FTVT delivers the best device performance. With this polymer, n-channel OTFTs with electron mobility up to 1.67 cm2  V-1  s-1 and p-channel OTFTs with hole mobility up to 0.62 cm2  V-1  s-1 are fabricated by modifying source/drain electrodes with polyethylenimine ethoxylated (PEIE) and MoO3 , respectively, to selectively inject electrons and holes.


Assuntos
Etilenos , Polímeros , Polímeros/química , Tiofenos/química , Elétrons
6.
Int J Mol Sci ; 24(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37569764

RESUMO

Cyanobacterial harmful algal blooms (CyanoHABs) pose significant threats to human health and natural ecosystems worldwide, primarily caused by water eutrophication, increased surface water temperature, and co-occurring microorganisms. Urgent action is needed to develop an eco-friendly solution to effectively curb the proliferation of CyanoHABs. Sophorolipids (SLs) are fully biodegradable biosurfactants synthesized by Starmerella bombicola. They can be classified into lactone and acid types. The lactone type displays strong antimicrobial activity, while the acid type exhibits good solubility, which make them ideal agents for mitigating CyanoHABs. Nevertheless, the broad utilization of SLs are hindered by their expensive production costs and the absence of effective genetic editing tools in the native host. In this study, we constructed recombinant strains capable of producing either acidic or lactonic SLs using the CRISPR-Cas9 gene editing system. The yields of acidic and lactonic SLs reached 53.64 g/L and 45.32 g/L in a shaking flask, respectively. In a 5 L fermenter, acidic SLs reached 129.7 g/L using low-cost glucose and rapeseed oil as substrates. The addition of 5 mg/L lactonic SLs effectively degraded cyanobacteria within 30 min, and a ratio of 8.25:1.75 of lactonic to acidic SLs showed the highest degradation efficiency. This study offers a safe and promising solution for CyanoHABs treatment.


Assuntos
Cianobactérias , Proliferação Nociva de Algas , Humanos , Ecossistema , Cianobactérias/genética , Lactonas
7.
Macromol Rapid Commun ; 44(23): e2300393, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37640284

RESUMO

3,4-Difluorothiophene-substituted aryls, i.e., 1,4-bis(3,4-difluorothiophen-2-yl)-benzene (Ph-2FTh), 1,4-bis(3,4-difluorothiophen-2-yl)-2,5-difluorobenzene (2FPh-2FTh), and 4,7-bis(3,4-difluorothiophen-2-yl)-2,1,3-benzothiadiazole (BTz-2FTh), are synthesized as C─H monomers for the synthesis of conjugated polymers (CPs) via direct arylation polycondensation (DArP) with diketopyrrolopyrrole (DPP) and isoindigo (IID) derivatives as C─Br monomers. The Gibbs free energies of activation for direct arylation (ΔG298 K , kcal mol-1 ) for α─C─H bonds of thiophene moieties as calculated by density functional theory (DFT) are 14.3, 16.5, and 16.4 kcal mol-1 for Ph-2FTh, 2FPh-2FTh and BTz-2FTh, respectively, meaning that inserting an electron-deficient unit in 3,3',4,4'-tetrafluoro-2,2'-bithiophene (4FBT, ΔG298K : 14.6 kcal mol-1 ) may cause a reactivity decrease of the C─H monomers. Photophysical and semiconducting properties of the resulting six CPs (i.e., DPP-Ph, DPP-2FPh, DPP-BTz, 2FIID-Ph, 2FIID-2FPh, and 2FIID-BTz) are characterized in detail. DPP-based CPs show ambipolar transport properties while IID-based ones exhibited n-type behavior owing to the deeper frontier molecular orbital energy levels of IID-based CPs. With source/drain electrodes modified with polyethylenimine ethoxylated, n-channel organic thin-film transistors with maximum electron mobility of 0.40, 0.54, 0.29, 0.05, 0.16, and 0.01 cm2 V-1 s-1 for DPP-Ph, DPP-2FPh, DPP-BTz, 2FIID-Ph, 2FIID-2FPh, and 2FIID-BTz, respectively, are fabricated. DPP-2FPh exhibits the best device performance due to the good film morphology and the highest intermolecular packing order.


Assuntos
Polímeros , Pirróis , Gravidez , Humanos , Feminino , Polímeros/química , Pirróis/química , Cetonas , Tiofenos/química
8.
Angew Chem Int Ed Engl ; 62(20): e202219262, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-36917081

RESUMO

n-Type conjugated polymers (CPs) are crucial in the applications of organic electronics. Direct coupling of electron-deficient C-H monomer via selective C-H activation, namely C-H/C-H oxidative direct arylation polycondensation (Oxi-DArP), is an ideal approach toward such CPs. Herein, Oxi-DArP is firstly adopted to synthesize a high-performance n-type CP using a newly developed monomer, i.e., 3,6-di(thiazol-5-yl)-diketopyrrolopyrrole (Tz-5-DPP). Tz-5-DPP based homopolymer PTz-5-DPP with a molecular weight of 22 kDa has been synthesized via Oxi-DArP. After n-doping, PTz-5-DPP films exhibited electric conductivity values up to 8 S cm-1 and power factors (PFs) up to 106 µW m-1 K-2 . Notably, this PF value is the highest for n-type polymer thermoelectric materials to date. The Oxi-DArP synthesis and the excellent n-type performance of the polymer make this work an important step toward the straightforward and sustainable preparation of high-performance n-type polymer semiconductors.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36361460

RESUMO

Negative emotions caused by break-up are the key work of university students' psychological intervention. It is important to explore the specific factors of break-up distress for university students' psychological intervention. Therefore, we investigated 869 university students to examine the effect of Machiavellianism and psychological capital on break-up distress, as well as its gender difference. The results indicated that high Machiavellians experience more break-up distress. Moreover, through structural equation models, we found that as for female university students, psychological capital mediated the relationship between Machiavellianism and break-up distress. However, as for male university students, the mediation effect was not significant. It means that for female university students, psychological capital acted as the mechanism to connect Machiavellianism and break-up distress.


Assuntos
Maquiavelismo , Angústia Psicológica , Feminino , Humanos , Masculino
10.
ACS Synth Biol ; 11(4): 1497-1509, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35294186

RESUMO

Gene editing technology plays an extremely significant role in synthetic biology and metabolic engineering. Traditional genetic manipulation methods, such as homologous recombination, however, are inefficient, time-consuming, and barely feasible when disrupting multiple genes simultaneously. Starmerella bombicola, a nonconventional yeast that overproduces sophorolipids, lacks convenient genetic tools for engineering strains. Here, we developed an efficient CRISPR-Cas9 genome editing technology by combining molecular element mining and expression system optimization for S. bombicola. This CRISPR-Cas9 system improved the efficiency of gene-integration/target gene-introducing disruption by homology-directed repair and realized the multi-gene simultaneous disruptions. Based on this CRISPR-Cas9 system, we also further constructed an engineered strain via the in vivo assembly of multiple DNA fragments (10 kb) that can produce acid-type sophorolipids. These results showed that the CRISPR-Cas9 system may be an efficient and convenient strategy to perform genetic manipulation in S. bombicola.


Assuntos
Sistemas CRISPR-Cas , Saccharomycetales , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Saccharomycetales/genética , Leveduras/genética
11.
Cell Cycle ; 20(23): 2531-2546, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34724861

RESUMO

Exosomes mediate the interaction between cancer cells and their microenvironment, and play a key role in tumor development. Although exosomes can package lncRNAs to mediate extracellular communication, the role of exosomal lncRNA AY927529 in prostate cancer (PCa) remains unclear. Exosomes were extracted from normal human prostatic epithelial cell lines (BPH-1 and RWPE-1) and PCa cell lines (VCaP and LNCaP, DU145, PC3) by ultrahigh speed centrifugation. Results of Western blot indicated that Alix, HSC70 and TSGl01 protein levels were upregulated in exosomes derived from PCa cells. LncAY927529 level was upregulated in PCa cells and exosomes derived from PCa patient serum and human PCa cells. CCK-8, Transwell and Flow cytometry assays demonstrated that bone marrow stromal cell line (ST2) conditioned medium (ST2-CM), treated with exosomes derived from PCa cells with high lncAY927529 level, promoted proliferation and invasion of PC3 and DU145 cells, and inhibited cell apoptosis. RT-qPCR assay indicated that lncAY927529 level was downregulated in PC3 and DU145 cells, exosomes derived from PCa cells (PCa-Exo) and ST2-CM treated with PCa-Exo with low expression of lncAY927529, and overexpression of lncAY927529 had the opposite results. In addition, Western blot assay showed that the autophagy related protein LC3II level was increased in ST2 cells treated with exosomes derived from DU145 cells with high expression of lncAY927529, and LC3I protein level was decreased. CXCL14 acted as a RNA-binding protein of lncAY927529, and exosome-mediated lncAY927529 positively regulated CXCL14 levels in ST2 cells. In general, exosome-mediated lncAY927529 could promote PCa cell proliferation and invasion by regulating bone microenvironment, suggesting that exosomal lncAY927529 may be a potential molecular diagnostic marker of PCa.


Assuntos
Exossomos , MicroRNAs , Hiperplasia Prostática , Neoplasias da Próstata , RNA Longo não Codificante , Osso e Ossos/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Exossomos/genética , Exossomos/metabolismo , Humanos , Masculino , MicroRNAs/genética , Próstata , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Microambiente Tumoral/genética
12.
BMC Cancer ; 21(1): 1022, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525951

RESUMO

BACKGROUND: Eukaryotic translation initiation factors (eIFs) are the key factors to synthesize translation initiation complexes during the synthesis of eukaryotic proteins. Besides, eIFs are especially important in regulating the immune function of tumor cells. However, the effect mechanism of eIFs in prostate cancer remains to be studied, which is precisely the purpose of this study. METHODS: In this study, three groups of prostate cancer cells were investigated. One group had its eIF5B gene knocked down; another group had its Programmed death 1 (PD-L1) overexpressed; the final group had its Wild-type p53-induced gene 1 (Wig1) overexpressed. Genetic alterations of the cancer cells were performed by plasmid transfection. The expression of PD-L1 mRNA was detected by quantitative real-time PCR (qRT-PCR), and the expressions of PD-L1 and eIF5B proteins were observed by western blot assays. Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Transwell martrigel were used to investigated cell proliferation, apoptosis, migration and invasion, respectively. The effect of peripheral blood mononuclear cells (PBMCs) on tumor cells was observed, and the interaction between eIF5B and Wig1 was revealed by co-immunoprecipitation (CoIP) assay. Finally, the effects of interference with eIF5B expression on the growth, morphology, and immunity of the tumor, as well as PD-L1 expression in the tumor, were verified by tumor xenograft assays in vivo. RESULTS: Compared with normal prostate epithelial cells, prostate cancer cells revealed higher expressions of eIF5B and PD-L1 interference with eIF-5B expression can inhibit the proliferation, migration, invasion and PD-L1 expression of prostate cancer cells. Meanwhile, the cancer cell group with interference with eIF5B expression also demonstrated greater, apoptosis and higher vulnerability to PBMCs. CoIP assays showed that Wig1 could bind to eIF5B in prostate cancer cells, and its overexpression can inhibit the proliferation, migration, invasion and PD-L1 expression of cancer cells while promoting apoptosis. Moreover, interference with eIF5B expression can inhibit tumor growth, destroy tumor morphology, and suppress the proliferation of tumor cells. CONCLUSION: eIF5B can promote the expression of PD-L1 by interacting with Wig1. Besides, interference with eIF5B expression can inhibit the proliferation, migration, invasion and immunosuppressive response of prostate cancer cells. This study proposes a new target, eIF5B, for immunotherapy of prostate cancer.


Assuntos
Antígeno B7-H1/metabolismo , Fatores de Iniciação em Eucariotos/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Apoptose/genética , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Fatores de Iniciação em Eucariotos/genética , Citometria de Fluxo , Inativação Gênica , Genes p53/fisiologia , Humanos , Imunoprecipitação , L-Lactato Desidrogenase/metabolismo , Leucócitos Mononucleares/imunologia , Linfócitos do Interstício Tumoral , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transfecção/métodos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
ACS Macro Lett ; 10(4): 419-425, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35549230

RESUMO

Direct arylation of 2,7-dibromofluorene with n-octyl, 6-diethoxylphosphorylhexyl, 6-(N,N-diethylamino)hexyl or 6-bromohexyl side chains and 1,2,4,5-tetrafluorobenzene (TFB) were conducted to investigate the effect of side chain functional groups on the coupling, and the resulting TFB-substituted fluorene derivatives were used as C-H monomers for the synthesis of water/alcohol soluble conjugated polymers (WSCPs) by direct arylation polycondensation (DArP). The direct arylation and DArP of the monomers carrying phosphonate and amino groups went on smoothly in typical DArP conditions, that is, Pd(OAc)2/PtBu2Me-HBF4/base/DMAc and Pd2(dba)3·CHCl3/P(o-MeOPh)3/pivalic acid/base/THF, and high molecular weight polymers with these groups were successfully synthesized. However, for fluorene-monomers with bromohexyl side chains, the target products could not be obtained from the above conditions but could be prepared in the absence of carboxylic acid additives in low polar solvents. With the above DArP-made polymers as cathode interfacial layers, high performance organic solar cells (OSCs) were successfully fabricated.

14.
BMC Cancer ; 20(1): 555, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539763

RESUMO

BACKGROUND: Prostate cancer (PC), a common malignant tumor, is the second-leading cause of cancer death among American men. Its successful treatment greatly relies on the early diagnose. Engrailed-2 (EN2) has been confirmed being existed with a high level in the urine of PC patients. In this study, to explore the application of EN2 in PC, we detected the immunohistochemical staining difference and EN2 expression level between benign prostatic hyperplasia (BPH) and PC. METHODS: We developed a monoclonal antibody against the helix 3 in EN2 and confirmed its specificity with Western blotting (WB) and immunofluorescence detecting the subcellular localization of endogenous and exogenous EN2 in three PC cell lines (LNCap, PC3, and DU145). We conducted immunohistochemical staining using this homemade antibody, and RT-PCR to detect the expression of EN2 in 25 PC and 25 BPH cases, and analyzed the correlation of EN2 expression and PC clinical staging. RESULTS: The results of WB and immunofluorescence showed our homemade EN2 monoclonal antibody could specifically bind endogenous and exogenous EN2 protein in three different PC cell lines. Endogenous EN2 was generally expressed in the cytoplasm and exogenous EN2 mostly existed in the nucleus of these cell lines. Immunohistochemical staining in PC had extremely stronger signals than that in BPH, suggesting a higher EN2 expression level in PC, which was confirmed by RT-PCR. Interestingly, the stained areas in BPH tissues were mainly in nucleus and cytoplasm, while in PC tissues were mainly on cytomembrane. Moreover, the expression level of EN2 was positively correlated with the PC clinical staging. CONCLUSION: Using our homemade EN2 antibody, we have found different staining patterns and expression level of EN2 in BPH and PC,which may be helpful to predict prostatic disease progression.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Próstata/patologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/diagnóstico , Idoso , Biomarcadores Tumorais/análise , Linhagem Celular Tumoral , Progressão da Doença , Perfilação da Expressão Gênica , Proteínas de Homeodomínio/análise , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/análise , Prognóstico , Neoplasias da Próstata/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Microbiol Res ; 169(9-10): 749-58, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24680501

RESUMO

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes serious diseases in pigs and humans. GdpP protein is a recently discovered specific phosphodiesterase that degrades cyclic diadenosine monophosphate (c-di-AMP). It is widely distributed among the firmicutes phylum and altered expression of GdpP is associated with several phenotypes in various bacterial strains. We investigated the role of GdpP in physiology and virulence in SS2. An in-frame mutant of gdpP was constructed using homologous recombination and bacterial growth, biofilm formation, hemolytic activity, cell adherence and invasion, expression of virulence factors, and virulence were evaluated. Disruption of gdpP increased intracellular c-di-AMP level and affected growth and increased biofilm formation of SS2. Simultaneously, the gdpP mutant strain exhibited a significant decrease in hemolytic activity and adherence to and invasion of HEp-2 cells compared with the parental strain. Quantitative reverse transcriptase polymerase chain reaction indicated significantly reduced expression of the known virulence genes cps2, sly, fpbs, mrp, ef and gdh in the gdpP mutant. In murine infection models, the gdpP mutant strain was attenuated, and impaired bacterial growth was observed in specific organs. All these findings revealed a significant contribution of gdpP and its substrate (c-di-AMP) to the biology and virulence of SS2.


Assuntos
Fosfatos de Dinucleosídeos/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Streptococcus suis/enzimologia , Streptococcus suis/fisiologia , Estruturas Animais/microbiologia , Animais , Aderência Bacteriana , Biofilmes/crescimento & desenvolvimento , Modelos Animais de Doenças , Regulação para Baixo , Deleção de Genes , Perfilação da Expressão Gênica , Bactérias Gram-Positivas , Hemólise , Células Hep G2 , Hepatócitos/microbiologia , Humanos , Camundongos , Diester Fosfórico Hidrolases/genética , Sorogrupo , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/patologia , Streptococcus suis/classificação , Streptococcus suis/patogenicidade , Fatores de Virulência/biossíntese
16.
Wei Sheng Wu Xue Bao ; 52(2): 141-5, 2012 Feb 04.
Artigo em Chinês | MEDLINE | ID: mdl-22586990

RESUMO

The holin-lysin two-step lysis system widely exists in double stranded DNA bacteriophages for the release of progeny bacteriophage from an infected bacterial cell at the final stage of phage infection. Lambda bacteriophage is a prototype for studying holin. The S gene in Lambda bacteriophage has a dual-start motif and encodes holin S105 and antiholin S107. Here, we reviewed the progress in topological structure of holin from Lambda bacteriophage and its formation of membrane lethal holes. We also discussed the potential of the holin in the control of bacterial infection.


Assuntos
Bacteriófago lambda/química , Proteínas Virais/química , Proteínas Virais/fisiologia , Bacteriófago lambda/genética
17.
Curr Microbiol ; 65(1): 28-34, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22526567

RESUMO

Development of novel antibacterial agents is required to control infection with multidrug-resistant Streptococcus suis. HolSMP and LySMP, the holin and lysin of S. suis serotype 2 bacteriophage, named SMP, are responsible for lysis of host cells and release of progeny phage. HolSMP and LySMP expressed in Escherichia coli BL21(DE3) exerted efficient activity at 37 °C, pH 5.2, with addition of 0.8 % ß-mercaptoethanol. Lytic spectra of purified HolSMP, LySMP or HolSMP + LySMP mixture were investigated. HolSMP, exhibiting a narrow lytic spectrum, was effective against Staphylococcus aureus and Bacillus subtilis, which were insensitive to LySMP. Moreover, HolSMP was identified as a promising antibacterial agent which was able to extend the spectrum of LySMP. The data suggest that combined use of holin and lysin could be a candidate strategy for resolution of drug resistance.


Assuntos
Antibacterianos/farmacologia , Enzimas/farmacologia , Fagos de Streptococcus/enzimologia , Proteínas Virais/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Bacillus subtilis/efeitos dos fármacos , Enzimas/química , Enzimas/isolamento & purificação , Enzimas/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Fagos de Streptococcus/química , Fagos de Streptococcus/genética , Proteínas Virais/química , Proteínas Virais/isolamento & purificação , Proteínas Virais/metabolismo
18.
Virol J ; 9: 70, 2012 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-22436471

RESUMO

BACKGROUND: Holins are a group of phage-encoded membrane proteins that control access of phage-encoded endolysins to the peptidoglycan, and thereby trigger the lysis process at a precise time point as the 'lysis clock'. SMP is an isolated and characterized Streptococcus suis lytic phage. The aims of this study were to determine the holin gene, HolSMP, in the genome of SMP, and characterized the function of holin, HolSMP, in phage infection. RESULTS: HolSMP was predicted to encode a small membrane protein with three hydrophobic transmembrane helices. During SMP infections, HolSMP was transcribed as a late gene and HolSMP accumulated harmlessly in the cell membrane before host cell lysis. Expression of HolSMP in Escherichia coli induced an increase in cytoplasmic membrane permeability, an inhibition of host cell growth and significant cell lysis in the presence of LySMP, the endolysin of phage SMP. HolSMP was prematurely triggered by the addition of energy poison to the medium. HolSMP complemented the defective λ S allele in a non-suppressing Escherichia coli strain to produce phage plaques. CONCLUSIONS: Our results suggest that HolSMP is the holin protein of phage SMP and a two-step lysis system exists in SMP.


Assuntos
Bacteriólise , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fagos de Streptococcus/genética , Fagos de Streptococcus/fisiologia , Proteínas Virais/genética , Proteínas Virais/metabolismo , Sequência de Aminoácidos , Clonagem Molecular , Escherichia coli/genética , Expressão Gênica , Dados de Sequência Molecular , Streptococcus suis/virologia
19.
Appl Environ Microbiol ; 77(23): 8272-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21984241

RESUMO

Bacterial biofilms are crucial to the pathogenesis of many important infections and are difficult to eradicate. Streptococcus suis is an important pathogen of pigs, and here the biofilm-forming ability of 32 strains of this species was determined. Significant biofilms were completely formed by 10 of the strains after 60 h of incubation, with exopolysaccharide production in the biofilm significantly higher than that in the corresponding planktonic cultures. S. suis strain SS2-4 formed a dense biofilm, as revealed by scanning electron microscopy, and in this state exhibited increased resistance to a number of antibiotics (ampicillin, amoxicillin, ciprofloxacin, kanamycin, and rifampin) compared to that of planktonic cultures. A bacteriophage lysin, designated LySMP, was used to attack biofilms alone and in combination with antibiotics and bacteriophage. The results demonstrated that the biofilms formed by S. suis, especially strains SS2-4 and SS2-H, could be dispersed by LySMP and with >80% removal compared to a biofilm reduction by treatment with either antibiotics or bacteriophage alone of less than 20%; in addition to disruption of the biofilm structure, the S. suis cells themselves were inactivated by LySMP. The efficacy of LySMP was not dose dependent, and in combination with antibiotics, it acted synergistically to maximize dispersal of the S. suis biofilm and inactivate the released cells. These data suggest that bacteriophage lysin could form part of an effective strategy to treat S. suis infections and represents a new class of antibiofilm agents.


Assuntos
Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Mucoproteínas/metabolismo , Fagos de Streptococcus/enzimologia , Streptococcus suis/efeitos dos fármacos , Streptococcus suis/crescimento & desenvolvimento , Proteínas Virais/metabolismo , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Microscopia Eletrônica de Varredura , Mucoproteínas/isolamento & purificação , Streptococcus suis/ultraestrutura , Proteínas Virais/isolamento & purificação
20.
Curr Microbiol ; 62(2): 458-64, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20697714

RESUMO

The prevalence and nature of Shiga toxin (Stx)-producing Escherichia coli (STEC) and Stx phage were investigated in 720 swine fecal samples randomly collected from a commercial breeding pig farm in China over a 1-year surveillance period. Eight STEC O157 (1.1%), 33 STEC non-O157 (4.6%), and two stx-negative O157 (0.3%) isolates were identified. Fecal filtrates were screened directly for Stx phages using E. coli K-12 derivative strains MC1061 as indicator, yielding 15 Stx1 and 57 Stx2 phages. One Stx1 and eight Stx2 phages were obtained following norfloxacin induction of the eight field STEC O157 isolates. All Stx1 phages had hexagonal heads with long tails, while Stx2 phages had three different morphologies. Notably, most of field STEC O157 isolates released more free phages and Stx toxin after induction with ciprofloxacin. Furthermore, upon infection with the recombinant phage ΦMin27(Δstx::cat), E. coli laboratory strains produced both lysogenic and lytic phage, whereas two of the eight O157 STEC isolates produced only lysogens. The lysogens from laboratory strains produced infectious particles similar to ΦMin27. Similarly, the lysogens from the STEC O157 isolates released Stx phage too, although free ΦMin27(Δstx::cat) particles were not detected. Collectively, our results reveal that breeding pig farms could be important reservoirs for Stx phages and that residual antibacterial agents may enhance the release of Stx phages and the expression of Stx.


Assuntos
Colífagos/isolamento & purificação , Microbiologia Ambiental , Escherichia coli O157/virologia , Fezes/virologia , Lisogenia , Toxina Shiga/genética , Proteínas Virais/genética , Animais , Animais Domésticos , Antibacterianos/metabolismo , China , Colífagos/genética , Escherichia coli K12/virologia , Escherichia coli O157/isolamento & purificação , Norfloxacino/metabolismo , Suínos , Ensaio de Placa Viral , Ativação Viral
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