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1.
Water Res ; 169: 115205, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31670086

RESUMO

The release of silver nanomaterials (AgNMs) from extensive use poses potential risks to human health and ecological environments. Although previous studies have reported the negative effects of AgNMs on various microorganisms, little is known about the response of bacteria under the exposure of AgNMs at the cellular level. Here, we report the multiple responses of Pseudomonas aeruginosa PAO1 (PAO1) under the exposure of two types of AgNMs, including spherical silver nanoparticles (AgNPs) and fibrous silver nanorods (AgNRs), by physiological experiments, microscopy, synchrotron-based X-ray Absorption Spectroscopy (XAS), flow cytometry and genome-wide RNA sequencing. Our results demonstrated that the exposure to both types of AgNMs could inhibit the growth of PAO1, accompanied by the overproduction of oxidative stress and inducing cell membrane damage. Transmission electron microscopy revealed the roughened cell membrane under both AgNMs treatment. In addition, both AgNMs repressed the expression of quorum sensing and metal efflux-related genes in PAO1, but stimulated denitrification, glycerol and amino acid metabolisms, SOS response and pyocin overproduction of PAO1. Compared to AgNRs, AgNPs exposure showed a much lower threshold concentration to trigger the inhibitory effect and induced greater transcriptional responses of PAO1. This study suggested that AgNMs could cause multiple effects on the proliferation, metabolism, virulence and pathogenesis of PAO1, which might further affect the corresponding environmental microbial communities. Overall, our findings offer insights into the interactions between AgNMs and bacteria at the molecular level.

2.
Math Biosci Eng ; 16(5): 4908-4922, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31499696

RESUMO

Steganography poses a serious challenge to forensics because investigators cannot identify even traces of secret messages embedded using a steganographer. Contrarily, the objective of locating steganalysis is to locate the embedded message, which should help extract the secret message. In this paper, a methodology of locating steganalysis using quantitative steganalysis is presented for multiple stego images with embedded messages along the same embedding path. Three typical quantitative steganalysis methods are applied to the methodology to locate the messages embedded using LSB re-placement. Experimental results show that the presented methods can reliably estimate the embedding positions, which verifies the validity of the presented methodology. The presented methodology points out a new use of quantitative steganalysis, and further demonstrates that it is necessary to design more precise quantitative steganalysis methods.

3.
J Biomed Nanotechnol ; 15(10): 2045-2058, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462370

RESUMO

Combining photodynamic therapy (PDT) and chemotherapy can improve anti-cancer efficacy. In this study, a novel copolymer PTPP combining thioketal and protoporphyrin was synthesized and tested for antitumor activity. Self-assembled PTPP micelles loaded with doxorubicin (DOX) showed uniform size, narrow particle size distribution and greater antitumor activity in vivo and in vivo than DOX-loaded micelles made from the commonly used material mPEG-PCL. Under laser irradiation, the photosensitizing protoporphyrin of DOX/PTPP produces abundant reactive oxygen species (ROS) that directly kill tumor cells as well as destroy the micelles themselves, leading to drug release. The ROS and DOX then act synergistically against the tumors. These ROS-responsive, laser-sensitive polymeric micelles may be useful for combining PDT and chemotherapy.


Assuntos
Espécies Reativas de Oxigênio/química , Doxorrubicina , Liberação Controlada de Fármacos , Micelas , Fotoquimioterapia , Polímeros
4.
Water Sci Technol ; 79(10): 1947-1955, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31294711

RESUMO

Developing substrate with carbon release properties is helpful to enhance nitrogen removal in low C/N ratio wastewater treatment. In this study, substrates with and without adding carbon source and microorganism were prepared to treat the drainage effluent from a wastewater treatment plant (WWTP), the difference in nitrogen removal were investigated. The results showed that adding a carbon source and microorganism to substrates could not only increase the amount of chemical oxygen demand (COD) released, but also enhance the adsorption capacities of NH4+-N and NO3--N. The carbon release process followed the first-order kinetic equation. A nitrogen removal model consisting of four phases of diffusion, adsorption, assimilation and transformation was proposed. In the short term, nitrogen was mainly removed by adsorption; adding microorganism contributed to enhance nitrification and denitrification. In the long-term, nitrogen removal performances were similar whether microorganism was added or not, and microbial species on the surface of substrates were similar. This work suggested when using substrate to treat wastewater for nitrogen removal, preparing a substrate with excellent property for biofilm formation was the most important factor.


Assuntos
Nitrogênio , Eliminação de Resíduos Líquidos , Águas Residuárias , Biodegradação Ambiental , Carbono , Desnitrificação , Microbiologia da Água
5.
Biophys Chem ; 253: 106213, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31276987

RESUMO

The interaction event between programmed death receptor-1 (PD-1) and its ligand (PD-L1) functions as an essential immune checkpoint against cytotoxic T effector cell activation. Previously, a number of small-molecule inhibitors and antibody drugs have been successfully developed to block the PD1/PDL1 signaling axis for breast cancer immunotherapy. Here, we attempt to directly disrupt the formation of PD-1/PD-L1 complex by using a self-inhibitory peptide (SIP) strategy. In the procedure, the complex crystal structure is examined systematically with energetic analysis and alanine scanning. Two double-stranded segments I and II in PD-L1 active finger are identified as hotspot regions; they directly interact with the amphipathic pocket of PD-1 to form the complex system. The segments are derived from PD-L1 to define two SIP peptides, namely, DS-I and DS-II, which are thought to have capability of rebinding at the complex interface, thus disrupting PD-1/PD-L1 interaction as a new immune checkpoint blockade. A further analysis reveals that the free linear DS-I and DS-II peptides are highly flexible without protein context support, which would incur a large entropy penalty (unfavorable indirect readout effect) when rebinding to PD-1. Next, intramolecular cyclization is applied to constraining the intrinsically disordered conformation of free DS-II peptide into native ordered double-stranded configuration, which can be substantiated by molecular dynamics simulation and circular dichroism spectroscopy. Several cyclized counterparts of linear DS-II peptide are designed and their affinities to PD-1 are determined using fluorescence polarization assays. As might be expected, three designed cyclic peptides DS-II[c111-127], ΔDS-II[c111-127] and ΔDS-II[c110-128] exhibit considerably increased potency (Kd = 28.0 ±â€¯4.2, 17.5 ±â€¯3.1 and 11.6 ±â€¯2.3 µM, respectively) relative to linear DS-II peptide (Kd = 109 ±â€¯15 µM).


Assuntos
Antígeno B7-H1/imunologia , Neoplasias da Mama/terapia , Imunoterapia , Peptídeos/imunologia , Receptor de Morte Celular Programada 1/imunologia , Antígeno B7-H1/química , Neoplasias da Mama/imunologia , Dicroísmo Circular , Ciclização , Feminino , Humanos , Simulação de Dinâmica Molecular , Peptídeos/síntese química , Peptídeos/química , Receptor de Morte Celular Programada 1/química , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Linfócitos T Citotóxicos/imunologia
6.
Water Sci Technol ; 79(9): 1639-1647, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31241469

RESUMO

Micro-polluted river water is characterized as having limited biodegradability, low carbon to nitrogen ratio and little organic carbon supply, all of which makes it hard to further purify. Two bench scale constructed wetlands (CWs) with a horizontal subsurface flow mode were set up in the laboratory to evaluate their feasibility and efficiency on denitrification with and without corn cobs as external carbon sources. Micro-polluted river water was used as feed solution. The CW without corn cobs substrates possessed a good performance in removing chemical oxygen demand (COD, <40 mg/L) and ammonia nitrogen (NH3-N, <0.65 mg/L), but less efficiency in removing total nitrogen (TN) and nitrate nitrogen (NO3-N). In marked contrast, the CW with 1% (w/w) corn cobs substrates as external carbon sources achieved a significant improvement in the removal efficiency of TN (increased from 34.2% to 71.9%) and NO3-N (increased from 19% to 71.9%). The incorporation of corn cobs substrates did not cause any obvious increase in the concentrations of COD and NH3-N in the effluent. This improvement in the denitrification efficiency was owing to the released organic carbon from corn cobs substrates, which facilitated the growth of abundant microbes on the surface and pores of the substrate. The open area of the used corn chips is larger than that of the pristine ones, and corn cobs can continue to provide a carbon fiber source for denitrification.


Assuntos
Recuperação e Remediação Ambiental/métodos , Nitrogênio/análise , Poluentes da Água/análise , Áreas Alagadas , Carbono , Desnitrificação , Rios , Eliminação de Resíduos Líquidos/métodos , Zea mays
7.
Chin J Traumatol ; 22(4): 196-201, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31235287

RESUMO

PURPOSE: Undisplaced subtle ligamentous Lisfranc injuries are easy to miss or underestimate, and many cases are treated without surgical fixation. It has not yet widely known whether conservative treatment for undisplaced subtle ligamentous Lisfranc injuries may lead to a poor outcome. The purpose of this study is to compare the outcomes of conservative versus surgical management (percutaneous position screw) of undisplaced subtle ligamentous Lisfranc injury. METHODS: We analysed 61 cases in this retrospective study, including 38 males and 23 females. Forty-one patients were managed conservatively, while 20 patients received surgical treatment involving minimal invasive percutaneous position screw. American orthopaedic foot &ankle society (AOFAS), foot function index (FFI, including FFI disability, FFI pain score and activity limitation scale) scores, Maryland foot score and short form-36 (SF-36) were recorded and compared after a follow-up of 10-16 months (average 12.3). RESULTS: Patients in the surgical management group had higher scores in all evaluation methods (p < 0.05). The complications in the conservative management group had higher incidence, mainly including secondary diastasis (34.1% vs. 5.0%), joint stiffness after 3 months (82.9% vs. 0%), and secondary arthrodesis (12.2% vs. 0%). The highest rate of complication in surgical management group was temporary forefoot pain (55.0%). CONCLUSION: The results of this study suggest that the outcomes of the surgical management with percutaneous position screw fixation are better than the conservative management to treat undisplaced subtle ligamentous Lisfranc injuries. This study can serve as a resource for orthopaedic surgeons in recognizing and managing such injuries.

8.
Int J Med Sci ; 16(4): 494-500, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171899

RESUMO

Aim: Sulfasalazine (SSZ) displayed anti-cancer activities. Vitamin E succinate (VES) could inhibit cell growth in various cancer cells. However, chemical therapies were often not useful for triple-negative breast cancer cells (TNBCs) treatment. Here, this study investigated the anti-cancer effects and the mechanisms on TNBCs under combination treatment with SSZ and VES. Methods: Cell viability was analyzed by using the MTT assay. The H2O2 levels were determined by using lucigenin-amplified chemiluminescence method. In addition, caspase and MAPs signals were studied by using western blotting. Results: Low-dose VES antagonized the SSZ-induced cytotoxicity effects while high-dose VES promoted the SSZ-induced cytotoxicity effects on TNBCs. In addition, SSZ alone treatment activated both caspase-3 and ERK signals, however, VES alone treatment only activated JNK signals. On the other hand, activation of caspase-3, JNK, and ERK were found in SSZ plus VES-treated cells. Conclusion: Combined SSZ and VES has synergistic or antagonistic cytotoxic effects depending on VES concentration. In addition, different cytotoxic signals are induced on SSZ-treated, VES-treated and SSZ plus VES-treated cells.

9.
Environ Int ; 129: 478-487, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31158594

RESUMO

The spread of antibiotic resistance has become a major concern for public health. As emerging contaminants, various metallic nanoparticles (NPs) and ionic heavy metals have been ubiquitously detected in various environments. Although previous studies have indicated NPs and ionic heavy metals could exhibit co-selection effects for antibiotic resistance, little is known about whether and how they could promote antibiotic resistance spread via horizontal gene transfer across bacterial genera. This study, we report both CuO NPs and copper ions (Cu2+) could stimulate the conjugative transfer of multiple-drug resistance genes. When exposing bacteria to CuO NPs or Cu2+ at environmental-relevant and sub-inhibitory concentrations (e.g., 1-100 µmol/L), conjugation frequencies of plasmid-encoded antibiotic resistance genes across genera (i.e., from Escherichia coli to Pseudomonas putida) were significantly enhanced (p < 0.05). The over-production of reactive oxygen species played a crucial role in promoting conjugative transfer. Genome-wide RNA and protein sequencing suggested expressional levels of genes and proteins related to oxidative stress, cell membrane permeability, and pilus generation were significantly up-regulated under CuO NPs and Cu2+ exposure (p < 0.05). This study provides insights in the contributions of NPs and heavy metals on the spread of antibiotic resistance.


Assuntos
Bactérias/efeitos dos fármacos , Cobre/química , Farmacorresistência Bacteriana/genética , Transferência Genética Horizontal , Nanopartículas Metálicas/química , Plasmídeos/genética , Bactérias/genética , Cobre/farmacologia , Metais Pesados/química , Metais Pesados/farmacologia
10.
J Cardiothorac Surg ; 14(1): 60, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30871612

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a common complication after radical surgery of esophageal cancer. The aim of this study was to explore AF risk factors after radical surgery of esophageal carcinoma. METHOD: The data of 335 patients with esophageal cancer who were admitted in our hospital from January 2014 to August 2016 for the first time were retrospectively analyzed. We retrieved the papers in some data banks using the search terms including English and Chinese search terms, and obtained 13 factors which were mentioned in more than 6 papers. The 13 factors including age, gender, history of smoking, history of hypertension, history of peripheral vascular disease, history of cardiac stents or angina pectoris, preoperative pulmonary infection, preoperative brain natriuretic peptide (BNP) level, preoperative left ventricular diastolic dysfunction, operative method, lesion location, intraoperative blood transfusion, adhesion between lymph nodes and pericardium, underwent univariate and multivariate analyses. RESULTS: Of the 335 patients with esophageal cancer, 48 had AF within one week after operation. Univariate analysis indicated that the age (OR: 4.89; CI: 2.53-9.47, P: 0.000), gender (OR: 2.26; CI: 1.17-4.37, P: 0.013), history of peripheral vascular disease (OR: 2.29; CI: 1.06-4.92, P: 0.030), history of cardiac stents or angina pectoris (OR: 27.30; CI: 12.44-59.91, P: 0.000), preoperative BNP level (OR: 27.13; CI: 10.97-67.06, P: 0.000), preoperative left ventricular diastolic dysfunction (OR: 2.22; CI: 1.19-4.14, P: 0.012), operative method (OR: 2.09; CI: 1.002-4.380, P: 0.046), intraoperative blood transfusion (OR: 20.24; CI: 8.39-48.82, P: 0.000), and adhesion between lymph nodes and pericardium were risk factors (OR: 2.05; CI: 1.08-3.87, P: 0.024). Furthermore, multivariate analysis displayed that advanced age (OR: 5.044; CI: 1.748-14.554, P: 0.003), male (OR: 6.161; CI: 2.143-17.715, P: 0.001), history of cardiac stents or angina pectoris (OR: 48.813; CI: 13.674-174.246, P: 0.000), preoperative BNP > 100 (OR: 41.515; CI: 9.380-183.732, P: 0.000), open surgery (OR: 3.357; CI: 1.026-10.983, P: 0.045), intraoperative blood transfusion (OR: 58.404; CI: 10.777-316.509, P: 0.000), and adhesion between lymph nodes and pericardium (OR: 3.954; CI: 1.364-11.459, P: 0.011) were risk factors which could increase the incidence of postoperative AF. CONCLUSION: We should pay attention to the above risk factors in order to reduce the incidence of postoperative AF.


Assuntos
Fibrilação Atrial/etiologia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Neoplasias Esofágicas/cirurgia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
11.
Biosci Rep ; 39(4)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30886066

RESUMO

Background. A relationship between matrix metalloproteinase-1 (MMP-1)-1607 (rs1799750) gene polymorphism and osteoarthritis (OA) susceptibility was reported in the Bioscience Reports journal; however, these results were inconsistent. To evaluate the specific relationship, we used a meta-analysis study to clarify the controversy. Methods. The relevant articles were retrieved on 20 October 2018 from PubMed, Elsevier, Springer, Ebase (Ovid), and Google Scholar. The number of alleles and genotypes for MMP-1 was obtained. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between MMP-1-1607 (rs1799750) 1G/2G promoter polymorphism and OA, while the Egger's test was used to assess heterogeneity among studies and publication bias. All statistical analyses were conducted using STATA 12.0 software. Results. A total of six case-control studies covering 1133 cases and 1119 controls were included in the final meta-analysis. There was no significant association between MMP-1-1607 1G/2G promoter polymorphism and OA in all genetic models (2G versus 1G: OR = 1.12, 95% CI = 0.78-1.60; 1G/2G versus 1G/1G: OR = 0.73, 95% CI = 0.32-1.67; 2G/2G versus 1G/1G: OR = 1.31, 95% CI = 0.57-2.98; the recessive model: OR = 1.23, 95% CI = 0.63-2.41; and the dominant model: OR = 1.25, 95% CI = 0.79-1.97). We obtained similar results for the subgroup analysis using ethnicity and type of disease. Conclusion. We systematically investigated the association between MMP-1-1607 (rs1799750) 1G/2G polymorphism and OA susceptibility; however, the results show no correlation.

12.
Environ Int ; 125: 65-74, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30710801

RESUMO

The widespread use of CuO nanoparticles (NPs) results in their continuous release into the environment, which could pose risks to public health and to microbial ecosystems. Following consumption, NPs will initially enter into sewer systems and interact with and potentially influence sewer microbial communities. An understanding of the response of microbes in sewers, particularly sulfate-reducing bacteria (SRB), to the CuO NPs induced stress is important as hydrogen sulfide produced by SRB can cause sewer corrosion and odour emissions. In this study, we elucidated how the anabolic and catabolic processes of a model SRB, Desulfovibrio vulgaris Hidenborough (D. vulgaris), respond to CuO NPs. Physiological analyses indicated that the exposure of the culture to CuO NPs at elevated concentrations (>50 mg/L) inhibited both its anabolic and catabolic activities, as revealed by lowered cell proliferation and sulfate reduction rate. The antibacterial effects of CuO NPs were mainly attributed to the overproduction of reactive oxygen species. Transcriptomic analysis indicated that genes encoding for flagellar assembly and some genes involved in electron transfer and respiration were down-regulated, while genes for the ferric uptake regulator (Fur) were up-regulated. Moreover, the CuO NPs exposure significantly up-regulated genes involved in protein synthesis and ATP synthesis. These results suggest that CuO NPs inhibited energy conversion, cell mobility, and iron starvation to D. vulgaris. Meanwhile, D. vulgaris attempted to respond to the stress of CuO NPs by increasing protein and ATP synthesis. These findings offer new insights into the bacterial-nanoparticles interaction at the transcriptional level, and advance our understanding of impacts of CuO NPs on SRB in the environment.


Assuntos
Cobre/toxicidade , Desulfovibrio vulgaris/efeitos dos fármacos , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidade , Desulfovibrio vulgaris/genética , Desulfovibrio vulgaris/metabolismo , Oxirredução , Sulfatos/metabolismo , Transcriptoma/efeitos dos fármacos
13.
Chin J Traumatol ; 22(2): 120-124, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30744942

RESUMO

Bosworth ankle fracture-dislocation is rare, known to be an irreducible type of ankle injury, with a high incidence of complication. We present two cases of even rarer variants of Bosworth ankle fracture-dislocation. The first case is a type of supination external rotation adduction, and the second case is a type of supination external rotation adduction. These types have not been described before. In both of the cases we failed to achieve close reduction, and therefore proceeded with emergency surgeries, with open reduction and internal fixation. Both of the cases were performed with a postero-lateral approach to reduce the dislocations, and fix the fractures successfully. Unfortunately in one of the cases, acute compartment syndrome developed post-surgically. However, both cases showed good functional outcomes.


Assuntos
Fraturas do Tornozelo/cirurgia , Traumatismos do Tornozelo/cirurgia , Fratura-Luxação/cirurgia , Fixação Interna de Fraturas/métodos , Redução Aberta/métodos , Doença Aguda , Fraturas do Tornozelo/fisiopatologia , Traumatismos do Tornozelo/fisiopatologia , Síndromes Compartimentais , Fratura-Luxação/fisiopatologia , Humanos , Masculino , Complicações Pós-Operatórias , Recuperação de Função Fisiológica , Rotação , Supinação , Resultado do Tratamento , Adulto Jovem
14.
Comput Biol Chem ; 78: 290-296, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30605854

RESUMO

Human epidermal growth factor receptor 2 (ErbB2) is an attractive therapeutic target for metastatic breast cancer. The kinase has been clinically observed to harbor a gatekeeper mutation T798M in its active site, which causes acquired resistance to the first-line targeted breast cancer therapy with small-molecule tyrosine kinase inhibitors. Previously, several theories have been proposed to explain the molecular mechanism of gatekeeper mutation-caused drug resistance, such as blocking of inhibitor binding and increasing of ATP affinity. In the current study, the direct binding of three wild type-selective inhibitors (Lapatinib, AEE788 and TAK-285) and two wild type-sparing inhibitors (Staurosporine and Bosutinib) to the wild-type ErbB2 and its T798M mutant are investigated in detail by using rigorous computational analysis and binding affinity assay. Substitution of the polar threonine with a bulky methionine at residue 798 can impair and improve the direct binding affinity of wild type-selective and wild type-sparing inhibitors, respectively. Hindrance effect is responsible for the affinity decrease of wild type-selective inhibitors, while additional nonbonded interactions contribute to the affinity increase of wild type-sparing inhibitors, thus conferring selectivity to the inhibitors for mutant over wild type. The binding affinity of Staurosporine and Bosutinib to ErbB2 kinase domain is improved by 11.9-fold and 2.1-fold upon T798M mutation, respectively. Structural analysis reveals that a nonbonded network of S-π contact interactions (for Staurosporine) or an S-involving halogen bond (for Bosutinib) forms with the sulfide group of mutant Met798 residue.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Estrutura Molecular , Mutação , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade
15.
Environ Int ; 121(Pt 2): 1217-1226, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30389380

RESUMO

BACKGROUND: Antibiotic resistance poses an increasing threat to public health. Horizontal gene transfer (HGT) promoted by antibiotics is recognized as a significant pathway to disseminate antibiotic resistance genes (ARGs). However, it is unclear whether non-antibiotic, anti-microbial (NAAM) chemicals can directly promote HGT of ARGs in the environment. OBJECTIVES: We aimed to investigate whether triclosan (TCS), a widely-used NAAM chemical in personal care products, is able to stimulate the conjugative transfer of antibiotic multi-resistance genes carried by plasmid within and across bacterial genera. METHODS: We established two model mating systems, to investigate intra-genera transfer and inter-genera transfer. Escherichia coli K-12 LE392 carrying IncP-α plasmid RP4 was used as the donor, and E. coli K-12 MG1655 or Pseudomonas putida KT2440 were the intra- and inter-genera recipients, respectively. The mechanisms of the HGT promoted by TCS were unveiled by detecting oxidative stress and cell membrane permeability, in combination with Nanopore sequencing, genome-wide RNA sequencing and proteomic analyses. RESULTS: Exposure of the bacteria to environmentally relevant concentrations of TCS (from 0.02 µg/L to 20 µg/L) significantly stimulated the conjugative transfer of plasmid-encoded multi-resistance genes within and across genera. The TCS exposure promoted ROS generation and damaged bacterial membrane, and caused increased expression of the SOS response regulatory genes umuC, dinB and dinD in the donor. In addition, higher expression levels of ATP synthesis encoding genes in E. coli and P. putida were found with increased TCS dosage. CONCLUSIONS: TCS could enhance the conjugative ARGs transfer between bacteria by triggering ROS overproduction at environmentally relevant concentrations. These findings improve our awareness of the hidden risks of NAAM chemicals on the spread of antibiotic resistance.

16.
Biomed Res Int ; 2018: 7356173, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30327780

RESUMO

Diabetes has become the third most serious threat to human health, after cancer and cardiovascular disease. Notably, Lactobacillus brevis is the most common species of LAB that produces γ-aminobutyric acid (GABA). The aim of this study is to clarify the effect of time, strain types, antibiotic concentrations, different levels of pH, and intestinal juices in aerobic or anaerobic conditions and the effect of interactions between these factors on the potential properties of KLDS 1.0727 and KLDS 1.0373, furthermore, antagonistic activity against foodborne pathogens. Moreover, another aim is to study the capability of KLDS 1.0727 and KLDS 1.0373 strains as gad gene carriers to express GABA that reduce the risk of type 1 diabetes in C57BL/6 mice as diabetic models. The obtained results exhibited the surprising tolerance of Lactobacillus brevis strains in vitro digestion models mimicking the conditions of the gastrointestinal tract, further, large antagonistic activity against foodborne pathogeneses. In vivo results displayed the significant effect on glucose level reduction, blood plasma, and histological assays of mice organs. As recommended, the use of Lactobacillus brevis strains should be widely shared in the market as a natural source of GABA in pharmaceutical and food applications.

17.
ISME J ; 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30291330

RESUMO

Antibiotic resistance is a severe global threat for public health, causing around 700,000 deaths per year. Horizontal gene transfer (HGT) is one of the most significant pathways to disseminate antibiotic resistance. It is commonly acknowledged that sub-minimum inhibition concentrations of antibiotics are major contributors in promoting antibiotic resistance through HGT. Pharmaceuticals are occurring in our environments at increased levels, yet little is known whether non-antibiotic pharmaceuticals cause or accelerate the dissemination of antibiotic resistance. Here, we report for the first time that the antiepileptic drug, carbamazepine, promotes conjugative transfer of antibiotic resistance genes. It was seen that environmentally relevant concentrations of carbamazepine (e.g., 0.05 mg/L) significantly enhanced the conjugative transfer of multiresistance genes carried by plasmid within and across bacterial genera. The underlying mechanisms of the enhanced HGT were revealed by detecting oxidative stress and cell membrane permeability, in combination with MinION DNA sequencing, genome-wide RNA sequencing, and proteomic analysis. Carbamazepine induced a series of acute responses, including increased levels of reactive oxygen species, the SOS response; increased cell membrane permeability, and pilus generation. Expressional levels of genes related to these processes were significantly upregulated during carbamazepine exposure. Given that HGT occurs widely among different species in various environments, these findings are an early warning for a wide assessment of the roles of non-antibiotic pharmaceuticals in the spread of antibiotic resistance.

18.
J Cell Biochem ; 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30216493

RESUMO

Cardiac fibrosis is known to be present in dilated cardiomyopathy (DCM) and it predicts the occurrence of sudden death and congestive heart failure. The aim of our study is to investigate the expression of microRNA-132 (miR-132) and its effect on cardiocyte proliferation, apoptosis, and cardiac fibrosis by binding to phosphatase and tensin homolog (PTEN) through the phosphateidylinositol 3-kinase (PI3K)/protein kinase (Akt) signal transduction pathway in DCM rats. DCM rat models induced by doxorubicin were established and confirmed by an ultrasonic cardiogram. Epithelial cells were treated with inhibitors, activators, and small interfering RNAs to identify the mechanisms by which miR-132 controls cardiocyte activity and cardiac fibrosis. Angiotensin II (Ang II) and aldosterone (ALD) expressions were detected by an enzyme-linked immunosorbent assay. The relationship between PTEN and miR-132 was verified by a dual-luciferase reporter assay. Cell proliferation and apoptosis were tested by the MTT assay and flow cytometry. PTEN was determined to be the target gene of miR-132. Rat models of DCM exhibited a lower level of miR-132, PI3K, Akt, B-cell lymphoma 2, collagen I, and collagen III, but a higher level of PTEN, Bcl-2-associated X protein, and proliferating cell nuclear antigen as well as inflammatory response (Ang II and ALD), accompanied by declined cardiocyte proliferation and elevated apoptosis and cardiac fibrosis. Upregulated miR-132 or silenced PTEN activated the PI3K/Akt pathway, thus facilitating cardiocyte proliferation and repressing cardiocyte apoptosis and cardiac fibrosis, as well as inflammatory responses. Downregulated miR-132 reversed this tendency. These findings indicate that miR-132 activates the PI3K/Akt pathway by inhibiting PTEN expression, thus facilitating cardiocyte proliferation and inhibiting apoptosis and cardiac fibrosis in DCM rats.

19.
BMC Ecol ; 18(1): 31, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30189862

RESUMO

BACKGROUND: During electricity generation of nuclear power plant, heat energy cannot be completely converted into electrical energy, and a part of it is lost in the form of thermal discharge into the environment. The thermal discharge is harmful to flora and fauna leading to environmental deterioration, biological diversity decline, and even biological extinction. RESULTS: The present study investigated the influence of thermal discharge from a nuclear power plant on the growth and development of Pacific oyster Crassostrea gigas which is widely used as bio indicator to monitor environmental changes. The growth of soft part and the gonad development of oysters were inhibited due to thermal discharge. During winter season, temperature elevation caused by thermal discharge promoted the growth of oyster shells. During summer season, the growth rate of oysters in thermal discharge area was significantly lower than that of the natural sea area. CONCLUSIONS: The results of this study provided a better understanding of assessing the impact of thermal discharge on the marine ecological environment and mariculture industry. It also provided a scientific basis for defining a safe zone for aquaculture in the vicinity of nuclear power plants.

20.
Saudi J Biol Sci ; 25(5): 975-981, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30108450

RESUMO

Prostate cancer is the second most common cancer in men worldwide. This study focused to clarify the roles of Metadherin (MTDH) and miR-342-3p in prostate cancer. We identified that MTDH was up-regulated and miR-342-3p was down-regulated in the prostate tissues, and there is an inverse correlation between MTDH and miR-342-3p. Functional studies revealed that miR-342-3p directly targets MTDH via binding to the 3' untranslated regions (UTRs) in the prostate cancer cells. Moreover, we also found MTDH overexpression in DU145 and PC3 cells inhibited apoptosis. Subsequently, miR-342-3p has been revealed to reverse the MTDH effect on the cellular apoptosis in the further studies. Our results indicate that MTDH repress apoptosis of prostate cancer in vitro and provides a new strategy for human prostate cancer therapy in the future.

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