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1.
J Sci Food Agric ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606621

RESUMO

BACKGROUND: 10-Hydroxy-cis-12-octadecenoic acid (10-HOE, 10-OH C18:1), an emerging functional fatty acid, has anti-fungal and anti-inflammatory effects. 10-HOE is synthesized by bacterial 10-linoleic acid hydratase (10-LHT) with linoleic acid as the substate. However, the characterization of 10-LHT and its targeted synthesis of 10-HOE have been rarely reported. In this study, the recombinant 10-LHT from Lactiplantibacillus plantarum ZS2058 was characterized, and the biocatalysis of 10-HOE using crude enzyme was optimized. RESULTS: The recombinant 10-LHT catalyzed the conversion of linoleic acid (C18:2) to 10-HOE as identified using gas chromatography-mass spectrometry (GC-MS). It showed a molecular weight of about 70 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and was a flavin adenine dinucleotide (FAD)-dependent enzyme. The activity of 10-LHT was optimal at pH 6.5 and 25 °C, and it was pH-stable but thermo-sensitive. The optimal condition for the 10-HOE biosynthesis using crude enzyme was 5 g L-1 linoleic acid (C18:2), 148.0 U mL-1 10-LHT, 0.05 mmol L-1 FAD, 2% methanol and 100 mmol L-1 sodium chloride at 25 °C and pH 6.5. A conversion yield of 47.8 ± 1.5% and the corresponding 10-HOE concentration of 2.4 ± 0.1 g L-1 were achieved at 48 h under the optimal reaction conditions. CONCLUSION: This work achieved the highest conversion yield of 10-HOE with the highest substrate concentration, and provides some useful information for the industrial production of 10-HOE. © 2021 Society of Chemical Industry.

2.
Adv Healthc Mater ; : e2101346, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34624168

RESUMO

Selectively inducing lysosomal membrane permeabilization (LMP) is a promising strategy for cancer therapy. But integrating alkaline phosphatase (ALP)-instructed self-assembly and lysosome-targeting to induce LMP for selective killing cancer cells was not reported. Herein, we rationally designed a pyrene-peptide conjugate Py-Phe-Phe-Glu-Tyr(H2 PO3 )-Gly-lyso (Py-Yp-Lyso) and demonstrated its lysosome-targeting cytotoxicity on cancer cells, together with its pyrene (Py) excimer fluorescence turning "on" at 480 nm. In vitro results showed that, Py-Yp-Lyso was efficiently dephosphorylated by ALP to yield Py-Phe-Phe-Glu-Tyr-Gly-lyso (Py-Y-Lyso) which self-assembled into nanofibers. Cell experiments verified that, after taken up by HeLa cells, the excimer fluorescence of Py-Yp-Lyso assemblies was turned "on" and the assemblies specifically targeted the lysosomes, inducing LMP and ultimate cancer cell death. In vivo experiments indicated that Py-Yp-Lyso had the highest inhibition effect towards HeLa tumors among the four compounds studied. We anticipate to apply Py-Yp-Lyso to treat cancers in clinic in the future. This article is protected by copyright. All rights reserved.

3.
J Phys Chem Lett ; : 10262-10269, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652163

RESUMO

Spin-dependent charge transmission or the so-called chirality-induced spin selectivity (CISS) effect was demonstrated in self-assembled chiral coordinated monolayers. Distinct from the previous CISS phenomenon observed mainly on pure biomolecules, here we expanded this effect to the coordinated complex of chiral biomolecules and metal cations, specifically, cysteine-Cu2+-alanine (Cys/Cu/Ala), in which the complex itself was redox-active. However, the coordinated self-assembled monolayers of cysteine-Cu2+-cysteine did not show any spin-dependent effect. In addition, this phenomenon was explained by developing a theoretical model with spin-orbit coupling. The alanine molecules contributed to multiple transport pathways, leading to experimentally observable spin polarization. Finally, this CISS effect in Cys/Cu/Ala complex was demonstrated to amplify the sensing signal. The enantioselective discrimination efficiency could be improved by controlling the orientation of the external magnetic field.

4.
Int J Mol Sci ; 22(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34502550

RESUMO

The ionotropic GABAA receptor (GABAAR) has been proven to be an important target of atypical antipsychotics. A novel series of imidazo [1,2-a]-pyridine derivatives, as selective positive allosteric modulators (PAMs) of α1-containing GABAARs with potent antipsychotic activities, have been reported recently. To better clarify the pharmacological essentiality of these PAMs and explore novel antipsychotics hits, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking, pharmacophore modeling, and molecular dynamics (MD) were performed on 33 imidazo [1,2-a]-pyridines. The constructed 3D-QSAR models exhibited good predictive abilities. The dockings results and MD simulations demonstrated that hydrogen bonds, π-π stackings, and hydrophobic interactions play essential roles in the binding of these novel PAMs in the GABAAR binding pocket. Four hit compounds (DS01-04) were then screened out by the combination of the constructed models and computations, including the pharmacophore model, Topomer Search, molecular dockings, ADME/T predictions, and MD simulations. The compounds DS03 and DS04, with higher docking scores and better predicted activities, were also found to be relatively stable in the binding pocket by MD simulations. These results might provide a significant theoretical direction or information for the rational design and development of novel α1-GABAAR PAMs with antipsychotic activities.

5.
Water Sci Technol ; 84(5): 1079-1089, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34534107

RESUMO

Dewatered sewage sludge (DSS) and anaerobically digested sludge (ADS) were pyrolyzed at 550 °C to investigate the characteristics of derived biochar and evaluate the risk of heavy metals (Cr, Ni, Cu, As, Cd, and Pb). The results showed that the pH value of the biochar derived from DSS (DSS-C) was slightly lower than that of the biochar derived from ADS (ADS-C), while DSS-C presented relatively higher specific surface area and total pore volume. DSS-C also showed higher H/C and lower O/C ratios than ADS-C, indicating a higher aromatic condensation and a lower polarity. Total concentrations of Cr, Ni, Cu, As, Cd, and Pb in DSS and ADS increased significantly after pyrolysis owing to the thermal decomposition of organic matter in the sludge, with corresponding rise of the Nemerow pollution index (NPI) of the biochars compared with the raw sludge. In addition, the sequential extraction procedure (BCR) analysis revealed that the pyrolysis process promoted the transformation of heavy metals from bio-available fractions to stable fractions. The potential environmental risk of heavy metals decreased from moderate and extremely high levels in the DSS and ADS to low risk and moderate levels in DSS-C and ADS-C after pyrolysis, respectively.


Assuntos
Metais Pesados , Esgotos , Carvão Vegetal , Medição de Risco
6.
J Microbiol ; 59(9): 854-860, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34382147

RESUMO

Extraintestinal pathogenic Escherichia coli (ExPEC) is an important zoonotic pathogen that places severe burdens on public health and animal husbandry. There are many pathogenic factors in E. coli. The type VI secretion system (T6SS) is a nano-microbial weapon that can assemble quickly and inject toxic effectors into recipient cells when danger is encountered. T6SSs are encoded in the genomes of approximately 25% of sequenced Gram-negative bacteria. When these bacteria come into contact with eukaryotic cells or prokaryotic microbes, the T6SS assembles and secretes associated effectors. In the porcine ExPEC strain PCN033, we identified four classic rearrangement hotspot (Rhs) genes. We determined the functions of the four Rhs proteins through mutant construction and protein expression. Animal infection experiments showed that the Δrhs-1CT, Δrhs-2CT, Δrhs-3CT, and Δrhs-4CT caused a significant decrease in the multiplication ability of PCN033 in vivo. Cell infection experiments showed that the Rhs protein is involved in anti-phagocytosis activities and bacterial adhesion and invasion abilities. The results of this study demonstrated that rhs1, rhs3, and rh4 plays an important role in the interaction between PCN033 and host cell. Rhs2 has contribution to cell and mice infection. This study helps to elucidate the pathogenic mechanism governing PCN033 and may help to establish a foundation for further research seeking to identify potential T6SS effectors.


Assuntos
Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/metabolismo , Doenças dos Suínos/microbiologia , Animais , Aderência Bacteriana , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Escherichia coli Extraintestinal Patogênica/genética , Escherichia coli Extraintestinal Patogênica/metabolismo , Feminino , Intestinos/microbiologia , Camundongos , Família Multigênica , Suínos
7.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360886

RESUMO

Xanthine oxidase (XO) is an important target for the effective treatment of hyperuricemia-associated diseases. A series of novel 2-substituted 6-oxo-1,6-dihydropyrimidine-5-carboxylic acids (ODCs) as XO inhibitors (XOIs) with remarkable activities have been reported recently. To better understand the key pharmacological characteristics of these XOIs and explore more hit compounds, in the present study, the three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, pharmacophore modeling, and molecular dynamics (MD) studies were performed on 46 ODCs. The constructed 3D-QSAR models exhibited reliable predictability with satisfactory validation parameters, including q2 = 0.897, R2 = 0.983, rpred2 = 0.948 in a CoMFA model, and q2 = 0.922, R2 = 0.990, rpred2 = 0.840 in a CoMSIA model. Docking and MD simulations further gave insights into the binding modes of these ODCs with the XO protein. The results indicated that key residues Glu802, Arg880, Asn768, Thr1010, Phe914, and Phe1009 could interact with ODCs by hydrogen bonds, π-π stackings, or hydrophobic interactions, which might be significant for the activity of these XOIs. Four potential hits were virtually screened out using the constructed pharmacophore model in combination with molecular dockings and ADME predictions. The four hits were also found to be relatively stable in the binding pocket by MD simulations. The results in this study might provide effective information for the design and development of novel XOIs.


Assuntos
Ácidos Carboxílicos/química , Inibidores Enzimáticos/química , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/química , Desenho de Fármacos , Inibidores Enzimáticos/uso terapêutico , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hiperuricemia/tratamento farmacológico , Estrutura Molecular , Ligação Proteica , Relação Quantitativa Estrutura-Atividade
8.
Trials ; 22(1): 557, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419131

RESUMO

BACKGROUND: Recruitment of fibromyalgia populations into long-term clinical trials involving exercise interventions is a challenge. We evaluated the cost and randomization yields of various recruitment methods used for a fibromyalgia trial in an urban setting. We also investigated differences in participant characteristics and exercise intervention adherence based on recruitment source. METHODS: We recruited individuals with fibromyalgia in the greater Boston area to a randomized controlled trial (RCT) using six recruitment strategies: newspaper advertisements, web advertisements, flyers, clinic referrals, direct mailing to patients in a clinic database, and word of mouth. We used the American College of Rheumatology 1990 and 2010 diagnostic criteria to screen and enroll participants. During an initial phone call to an interested participant, the study staff asked how they heard about the study. In this study, we compared the cost and yield of the six recruitment strategies as well as baseline characteristics, adherence, and attendance rates of participants across strategies. RESULTS: Our recruitment resulted in 651 prescreens, 272 screening visits, and 226 randomized participants. Advertisements in a local commuter newspaper were most effective, providing 113 of 226 randomizations, albeit high cost ($212 per randomized participant). Low-cost recruitment strategies included clinical referrals and web advertisements, but they only provided 32 and 16 randomizations. Community-based strategies including advertisement and flyers recruited a more racially diverse participant sample than clinic referrals and mailing or calling patients. There was no evidence of difference in adherence among participants recruited from various strategies. CONCLUSIONS: Newspaper advertisement was the most effective and most expensive method per randomized participant for recruiting large numbers of individuals with fibromyalgia in an urban setting. Community-based strategies recruited a more racially diverse cohort than clinic-based strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01420640 . Registered on 19 August 2011.


Assuntos
Fibromialgia , Boston , Exercício Físico , Fibromialgia/diagnóstico , Fibromialgia/terapia , Humanos , Seleção de Pacientes , Projetos de Pesquisa , Estados Unidos
9.
Oxid Med Cell Longev ; 2021: 5552530, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221234

RESUMO

As reported in our previous study, cinaciguat can improve implant osseointegration in type 2 diabetes mellitus (T2DM) rats by reactivating type 2 cGMP-dependent protein kinase (PKG2), but the downstream mechanisms remain unclear. In the present study, we investigated the favorable effect of cinaciguat on primary rat osteoblast, which was cultivated on titanium disc under vitro T2DM conditions (25 mM glucose and 200 µM palmitate), and clarified the therapeutic mechanism by proteomic analysis. The results demonstrated that T2DM medium caused significant downregulation of PKG2 and induced obvious osteoblast dysfunction. And overexpression of PKG2 by lentivirus and cinaciguat could promote cell proliferation, adhesion, and differentiation, leading to decreased osteoblasts injury. Besides, proteomic analysis revealed the interaction between PKG2 and phospholipase Cß1 (PLCß1) in the cinaciguat addition group, and we further verified that upregulated PKG2 by cinaciguat could inhibit the activation of PLCß1, then relieve intracellular calcium overload, and suppress endoplasmic reticulum (ER) stress to ameliorate osteoblast functions under T2DM condition. Collectively, these findings provided the first detailed mechanisms responsible for cinaciguat provided a favorable effect on promoting osseointegration in T2DM and demonstrated a new insight that diabetes mellitus-induced the aberrations in PKG2-PLCß1-Ca2+-ER stress pathway was one underlying mechanism for poor osseointegration.

10.
Future Microbiol ; 16: 721-729, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34223787

RESUMO

Aim: This study aims to develop a subunit vaccine with high cross-protection for Streptococcus suis. Materials & methods: Four-week-old female BALB/c mice were first immunized with a single and mixed protein. Various indicators, such as antibody titers and various cytokine levels, were further analyzed. Results: The results showed that purified recombinant proteins IF-2 and 1022 had a good protective effect against lethal doses of S. suis serotype 2 and S. suis serotype 9. This study showed immunization with recombinant proteins. Conclusion: IF-2 and 1022 can enhance cross-protection against S. suis serotypes 2 and 9.

11.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198513

RESUMO

BACKGROUND: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. METHODS: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC50 of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time-kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. RESULTS: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. CONCLUSIONS: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection.


Assuntos
Antibacterianos/uso terapêutico , Lipoglicopeptídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/fisiologia , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Imunossupressão , Espaço Intracelular/microbiologia , Lipoglicopeptídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Células THP-1
12.
Anal Chem ; 93(29): 9970-9973, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34264075

RESUMO

Urokinase-type plasminogen activator (uPA) is a cell-secreted serine protease and plays a significant role in numerous biological processes. Overexpression of uPA has been proved to be relevant to some malignant tumors as well as poor prognosis. However, bioluminescence (BL) probes for selectively sensing uPA activity have not been reported up to now. Herein, we designed a BL probe, GGR-AmLuc, to detect uPA in vitro and sense uPA both inside cells and in tumors. In vitro studies demonstrated that GGR-AmLuc was able to selectively detect uPA with a limit of detection (LOD) of 1.37 µg/L. Moreover, GGR-AmLuc was successfully applied to image uPA in living subjects with excellent sensitivity. We anticipate that probe GGR-AmLuc could be applied for highly sensitive diagnosis of cancers overexpressing uPA and provide guidance for cancer treatment in the near future.


Assuntos
Neoplasias , Ativador de Plasminogênio Tipo Uroquinase , Humanos , Neoplasias/diagnóstico por imagem , Receptores de Ativador de Plasminogênio Tipo Uroquinase
13.
J Integr Plant Biol ; 63(9): 1620-1631, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34331750

RESUMO

The creation of new soybean varieties has been limited by genomic duplication and redundancy. Efficient multiplex gene editing and large chromosomal segment deletion through clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems are promising strategies for overcoming these obstacles. CRISPR/Cpf1 is a robust tool for multiplex gene editing. However, large chromosomal excision mediated by CRISPR/Cpf1 has been reported in only a few non-plant species. Here, we report on CRISPR/LbCpf1-induced large chromosomal segment deletions in soybean using multiplex gene targeting. The CRISPR/LbCpf1 system was optimized for direct repeat and guide RNA lengths in crispr RNA (crRNA) array. The editing efficiency was evaluated using LbCpf1 driven by the CaMV35S and soybean ubiquitin promoter. The optimized system exhibited editing efficiencies of up to 91.7%. Our results showed eight gene targets could be edited simultaneously in one step when a single eight-gRNA-target crRNA array was employed, with an efficiency of up to 17.1%. We successfully employed CRISPR/LbCpf1 to produce small fragments (<1 Kb) and large chromosomal segment deletions (10 Kb-1 Mb) involving four different gene clusters in soybean. Together, these data demonstrate the power of the CRISPR/LbCpf1 platform for multiplex gene editing and chromosomal segment deletion in soybean, supporting the use of this technology in both basic research and agricultural applications.

14.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206143

RESUMO

Primary liver cancer accounts for the third most deadly type of malignant tumor globally, and approximately 80% of the cases are hepatocellular carcinoma (HCC), which highly relies on the activity of hypoxia responsive pathways to bolster its metastatic behaviors. MicroRNA-29a (MIR29A) has been shown to exert a hepatoprotective effect on hepatocellular damage and liver fibrosis induced by cholestasis and diet stress, while its clinical and biological role on the activity hypoxia responsive genes including LOX, LOXL2, and VEGFA remains unclear. TCGA datasets were retrieved to confirm the differential expression and prognostic significance of all genes in the HCC and normal tissue. The Gene Expression Omnibus (GEO) dataset was used to corroborate the differential expression and diagnostic value of MIR29A. The bioinformatic identification were conducted to examine the interaction of MIR29A with LOX, LOXL2, and VEGFA. The suppressive activity of MIR29A on LOX, LOXL2, and VEGF was verified by qPCR, immunoblotting, and luciferase. The effect of overexpression of MIR29A-3p mimics in vitro on apoptosis markers (caspase-9, -3, and poly (ADP-ribose) polymerase (PARP)); cell viability and wound healing performance were examined using immunoblot and a WST-1 assay and a wound healing assay, respectively. The HCC tissue presented low expression of MIR29A, yet high expression of LOX, LOXL2, and VEGFA as compared to normal control. Serum MIR29A of HCC patients showed decreased levels as compared to that of normal control, with an area under curve (AUC) of 0.751 of a receiver operating characteristic (ROC) curve. Low expression of MIR29A and high expression of LOX, LOXL2, and VEGFA indicated poor overall survival (OS). MIR29A-3p was shown to target the 3'UTR of LOX, LOXL2, and VEGFA. Overexpression of MIR29A-3p mimic in HepG2 cells led to downregulated gene and protein expression levels of LOX, LOXL2, and VEGFA, wherein luciferase reporter assay confirmed that MIR29A-3p exerts the inhibitory activity via directly binding to the 3'UTR of LOX and VEGFA. Furthermore, overexpression of MIR29A-3p mimic induced the activity of caspase-9 and -3 and PARP, while it inhibited the cell viability and wound healing performance. Collectively, this study provides novel insight into a clinical-applicable panel consisting of MIR29, LOX, LOXL2, and VEGFA and demonstrates an anti-HCC effect of MIR29A via comprehensively suppressing the expression of LOX, LOXL2, and VEGFA, paving the way to a prospective theragnostic approach for HCC.


Assuntos
Aminoácido Oxirredutases/genética , Carcinoma Hepatocelular/genética , MicroRNAs/genética , Proteína-Lisina 6-Oxidase/genética , Fator A de Crescimento do Endotélio Vascular/genética , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Transdução de Sinais/genética
15.
Sci Rep ; 11(1): 14879, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290308

RESUMO

The removal and chemical speciation changes of heavy metals in the sewage sludge during the single bioleaching and combined bioleaching/Fenton-like processes were compared in this study. The improvement in the dewaterability of the treated sludge was also investigated. The single bioleaching led to a removal of Zn, Cu, Cd, Cr, Mn, Ni, As and Pb of 67.28%, 50.78%, 64.86%, 6.32%, 56.15%, 49.83%, 20.78% and 10.52% in 10 days, respectively. The chemical speciation analysis showed that the solubilization of heavy metals in mobile forms (exchangeable/acid soluble and reducible forms) and oxidizable form was the main reason for their removal. Subsequent Fenton-like treatment was carried out at different bioleaching stages when the bioleached sludge dropped to certain pH values (4.5, 4.0 and 3.0), by adding H2O2 at different dosages. The highest removal ratio of Zn, Cu, Cd, Cr, Mn and Ni could reach 75.53%, 52.17%, 71.91%, 11.63%, 66.29% and 65.19% after combined bioleaching/Fenton-like process, respectively, with appropriate pH and H2O2 dosages in less than 6 days. The solubilization efficiencies of these heavy metals in mobile forms were further improved by Fenton-like treatment. The removal efficiencies of As and Pb decreased due to their transformation into insoluble forms (mostly residual fraction) after Fenton treatment. The capillary suction times (CST) of the raw sludge (98.7 s) decreased by 79.43% after bioleaching and 87.44% after combined process, respectively.

16.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072443

RESUMO

As an important zoonotic pathogen, Streptococcus suis (S. suis) infection has been reported to be a causative agent for variety of diseases in humans and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which is commonly seen in cases of severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of death. This calls for development of new strategies to avert the damage caused by STSLS. In this study, we found for the first time that Baicalein, combined with ampicillin, effectively improved severe S. suis infection. Further experiments demonstrated that baicalein significantly inhibited the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. Cell-based assays revealed that Baicalein did not exert toxic effects and conferred protection in S. suis-infected cells. Interestingly, compared with ampicillin alone, Baicalein combined with ampicillin resulted in a higher survival rate in mice severely infected with S. suis. At the same time, we found that baicalein can be combined with meropenem against MRSA. In conclusion, these results indicate that baicalein has a good application prospect.


Assuntos
Antibacterianos/farmacologia , Flavanonas/farmacologia , Infecções Estreptocócicas/microbiologia , Streptococcus suis/efeitos dos fármacos , Animais , Antibacterianos/química , Citocinas/biossíntese , Modelos Animais de Doenças , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Flavanonas/química , Hemólise/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/metabolismo , Infecções Estreptocócicas/patologia , Relação Estrutura-Atividade
18.
Curr Pharm Des ; 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082675

RESUMO

BACKGROUND: Neuronal cell apoptosis is associated with radiation exposure. It is urgent to study the radiation protection of hippocampal neurons. OBJECTIVE: The purpose of this study was to investigate the protective effect of anthocyanins on radiation and its potential mechanism. MATERIALS AND METHODS: The irradiation was carried out at room temperature with 4-Gy dose. Anthocyanins were intraperitoneally administered to rats prior to radiation exposure. The immunohistology and survival of neurons within the hippocampi,neuroprotective effects of anthocyanin,mean ROS accumulation and SIRT3 expression by Western Blot and qRTPCR were performed. RESULTS: Anthocyanins inhibit radiation-induced apoptosis by activating SIRT3. SIRT3 mRNA increased 24 hours after anthocyanin performed, accompanied by an increase in SIRT3 protein and activity. CONCLUSIONS: Anthocyanin can effectively resist radiation-induced oxidation and support its role in scavenging cellular reactive oxygen species. The results showed that anthocyanin protected hippocampal neurons from apoptosis through the activity of SIRT3 after irradiation.

19.
Int J Biol Macromol ; 181: 1207-1223, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33971233

RESUMO

The basic leucine zipper (bZIP) family is one of the largest families of transcription factors (TFs) in plants and is responsible for various functions, including regulating development and responses to abiotic/biotic stresses. However, the roles of bZIPs in the regulation of responses to drought stress and salinity stress remain poorly understood in Jatropha curcas L., a biodiesel crop. In the present study, 50 JcbZIP genes were identified and classified into ten groups. Cis-element analysis indicated that JcbZIP genes are associated with abiotic stress. Gene expression patterns and quantitative real-time PCR (qRT-PCR) showed that four JcbZIP genes (JcbZIPs 34, 36, 49 and 50) are key resistance-related genes under both drought and salinity stress conditions. On the basis of the results of cis-element and phylogenetic analyses, JcbZIP49 and JcbZIP50 are likely involved in responses to drought and salinity stress; moreover, JcbZIP34 and JcbZIP36 might also play important roles in seed development and response to abiotic stress. These findings advance our understanding of the comprehensive characteristics of JcbZIP genes and provide new insights for functional validation in the further.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Secas , Jatropha/genética , Estresse Salino/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/genética , Genoma de Planta/genética , Jatropha/crescimento & desenvolvimento , Filogenia , Proteínas de Plantas/genética , Sementes/crescimento & desenvolvimento , Estresse Fisiológico/genética
20.
J Genet ; 1002021.
Artigo em Inglês | MEDLINE | ID: mdl-34057149

RESUMO

Jatropha curcas has recently emerged as an important bioenergy plant which is an ideal alternative for fossil fuels. It is particularly significant to analyse the codon usage bias (CUB) and further evaluate the intraspecific genetic divergence of three J. curcas in Asia, considering its potential economic benefits and various utilities. In the present study, the patterns of CUB were systematically compared, and the factors shaping CUB were identified in all three genomes of J. curcas. Our observations indicate that the preference for A/T nucleotides and A/T ending codons was present in all the three genomes. Moreover, 11 identical high-frequency codons as well as the optimal expression receptor Nicotiana tabacum were confirmed. Besides, it was observed that CUB resulted from the combined effects of natural selection and mutation pressure, while the natural selection was the determining factor. Eventually, similarity indices based on relative synonymous codon usage (RSCU) values implied low intraspecific genetic divergence in three Asian J. curcas. This study provides useful clues for improving the expression level of exogenous genes and optimizing breeding programmes by molecular-assisted breeding in J. curcas.


Assuntos
Uso do Códon , Genoma de Planta , Jatropha/classificação , Jatropha/genética , Mutação , Melhoramento Vegetal , Proteínas de Plantas/genética , Deriva Genética , Seleção Genética
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