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1.
Appl Environ Microbiol ; 87(10)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33674440

RESUMO

We investigated the prevalence and transmission of NDM-producing Enterobacteriaceae in fecal samples of geese and environmental samples from a goose farm in southern China. The samples were cultivated on MacConkey agar plates supplemented with meropenem. Individual colonies were examined for bla NDM, and bla NDM-positive bacteria were characterized based on whole-genome sequencing (WGS) data from the Illumina and Oxford Nanopore Technologies (ONT) platforms. Of 117 samples analyzed, the carriage rates for New Delhi metallo-ß-lactamase (NDM)-positive Enterobacteriaceae were 47.1, 18, and 50% in geese, inanimate environments (sewage, soil, fodder, and dust), and mouse samples, respectively. Two variants (bla NDM-1 and bla NDM-5, in 4 and 40 isolates, respectively) were found among 44 bla NDM-positive Enterobacteriaceae; these variants belonged to eight species, and Escherichia coli was the most prevalent (50%). WGS analysis revealed that bla NDM coexisted with diverse antibiotic resistance genes (ARGs). Population structure analysis showed that most E. coli and Enterobacter sp. isolates were highly heterogeneous, while most Citrobacter sp. and P. stuartii isolates possessed extremely high genetic similarities. In addition, bla NDM-5-positive ST4358/ST48 E. coli isolates were found to be clonally spread between geese and the environment and were highly genetically similar to those reported from ducks, farm environments, and humans in China. Plasmid analysis indicated that IncX3 pHNYX644-1-like (n = 40) and untypeable pM2-1-like plasmids (n = 4) mediated bla NDM spread. pM2-1-like plasmids possessed diverse ARGs, including bla NDM-1, the arsenical and mercury resistance operons, and the maltose operon. Our findings revealed that the goose farm is a reservoir for NDM-positive Enterobacteriaceae The bla NDM contamination of wild mice and the novel pM2-1-like plasmid described here likely adds to the risk for dissemination of bla NDM and associated resistance genes.IMPORTANCE Carbapenem-resistant bacteria, in particular NDM-producing Enterobacteriaceae, have become a great threat to global public. These bacteria have been found not only in hospital and community environments but also among food animal production chains, which are recognized as reservoirs for NDM-producing Enterobacteriaceae However, the dissemination of NDM-producing bacteria in waterfowl farms has been less well explored. Our study demonstrates that the horizontal spread of bla NDM-carrying plasmids and the partial clonal spread of bla NDM-positive Enterobacteriaceae contribute to the widespread contamination of bla NDM in the goose farm ecosystem, including mice. Furthermore, we found a novel and transferable bla NDM-1-carrying multidrug resistance (MDR) plasmid that possessed multiple environmental adaptation-related genes. The outcomes of this study contribute to a better understanding of the prevalence and transmission of bla NDM-carrying Enterobacteriaceae among diverse niches in the farm ecosystem.

2.
Sci Total Environ ; 771: 144828, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33545481

RESUMO

Overuse of antibiotics in animal husbandry has led to an increase of antibiotic resistance microorganisms as well as antibiotic-resistance genes (ARGs). Duck farming in China is practiced on a large and diverse scale and the overuse of antibiotics in this field is gaining attention recently. We evaluated the diversity of ARGs from five duck farms using a functional metagenomic approach and constructed five libraries. A total of seventy-six resistant determinants were identified, of which sixty-one were gene variants or novel genes. The novel genes contained five ß-lactamase-encoding genes designated as blaDWA1, blaDWA2, blaDWA3, blaDWA4 and blaDWB1, respectively, and two genes conferring resistance to fosfomycin designated as fosA-like1 and fosA-like2. Three of the five ß-lactamase-encoding genes were further identified as extended-spectrum ß-lactamases (ESBL) that can hydrolyze both penicillins and cephalosporins. Besides, two of the five ß-lactamase-encoding genes were associated with mobile genetic elements, indicating a high potential for transfer of the genes to other bacterial hosts. The two novel fosA-like genes were able to increase the MICs of the test Escherichia coli strain from 2 µg/mL to as high as 256 µg/mL(up to 128-fold increase). Our study provides a reference for ARGs prevalence in duck farm wastes and implies that they are an important resistome reservoir, especially for novel ARGs with high spread potential.


Assuntos
Antibacterianos , Patos , Animais , Antibacterianos/farmacologia , China , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , beta-Lactamases/genética
3.
Vet Microbiol ; 253: 108954, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33373881

RESUMO

The recent emergence of plasmid-mediated tigecycline resistance gene tet(X) has challenged the clinical effectiveness of tigecycline as a last-resort treatment option. During 2017-2018, 336 fecal samples from sick ducks, pigs, chickens and geese in Guangdong, China, were screened for tet(X)-positive Acinetobacter baumannii strains. Their activities on tetracyclines were determined by microbiological degradation and mass spectrometry, followed by susceptibility testing, sequence typing, gene transfer, molecular location and genomic DNA sequencing analyses. A total of 10 tet(X)-positive A. baumannii strains were isolated from ducks and chickens, including eight plasmid-borne tet(X5)-positive and two chromosomal tet(X6)-positive isolates. All of them exhibited good degradation activities on tetracyclines by hydroxylation at C11a and were multidrug-resistant to tigecycline, tetracycline, florfenicol, ciprofloxacin and trimethoprim/sulfamethoxazole. Genetically, they belonged to two sequence types (ST355, n = 8; ST1980, n = 2) that were consistent with their pulsotypes, revealing a clonal spread of ST355 A. baumannii. An ISCR2- or IS26-mediated tet(X) transposition structure, homologous to those of clinical A. baumannii strains, was also identified and ISCR2 could transfer tet(X5) into the recipient Acinetobacter baylyi ADP1 at a frequency of (1.8 ± 0.3)×10-6. Therefore, more efforts are needed to evaluate the clinical impact of these tigecycline resistance genes.

4.
Genome Med ; 12(1): 111, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287863

RESUMO

BACKGROUND: The recent emergence and dissemination of high-level mobile tigecycline resistance Tet(X) challenge the clinical effectiveness of tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens. Although tet(X) has been found in various bacterial species, less is known about phylogeographic distribution and phenotypic variance of different genetic variants. METHODS: Herein, we conducted a multiregional whole-genome sequencing study of tet(X)-positive Acinetobacter isolates from human, animal, and their surrounding environmental sources in China. The molecular and enzymatic features of tet(X) variants were characterized by clonal expression, microbial degradation, reverse transcription, and gene transfer experiments, while the tet(X) genetic diversity and molecular evolution were explored by comparative genomic and Bayesian evolutionary analyses. RESULTS: We identified 193 tet(X)-positive isolates from 3846 samples, with the prevalence ranging from 2.3 to 25.3% in nine provinces in China. The tet(X) was broadly distributed in 12 Acinetobacter species, including six novel species firstly described here. Besides tet(X3) (n = 188) and tet(X4) (n = 5), two tet(X5) variants, tet(X5.2) (n = 36) and tet(X5.3) (n = 4), were also found together with tet(X3) or tet(X4) but without additive effects on tetracyclines. These tet(X)-positive Acinetobacter spp. isolates exhibited 100% resistance rates to tigecycline and tetracycline, as well as high minimum inhibitory concentrations to eravacycline (2-8 µg/mL) and omadacycline (8-16 µg/mL). Genetic analysis revealed that different tet(X) variants shared an analogous ISCR2-mediated transposon structure. The molecular evolutionary analysis indicated that Tet(X) variants likely shared the same common ancestor with the chromosomal monooxygenases that are found in environmental Flavobacteriaceae bacteria, but sequence divergence suggested separation ~ 9900 years ago (7887 BC), presumably associated with the mobilization of tet(X)-like genes through horizontal transfer. CONCLUSIONS: Four tet(X) variants were identified in this study, and they were widely distributed in multiple Acinetobacter spp. strains from various ecological niches across China. Our research also highlighted the crucial role of ISCR2 in mobilizing tet(X)-like genes between different Acinetobacter species and explored the evolutionary history of Tet(X)-like monooxygenases. Further studies are needed to evaluate the clinical impact of these mobile tigecycline resistance genes.

5.
Sci Total Environ ; : 143654, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33277010

RESUMO

Vast reservoirs of antibiotic resistance genes (ARG) are discharged into the environment via pig manure. We used metagenomic analysis to follow the distribution and shifts of ARGs and their bacterial hosts along wastewater treatment in three large pig farms. The predominating ARGs potentially encoded resistance to tetracycline (28.13%), aminoglycosides (23.64%), macrolide-lincosamide-streptogramin (MLS) (12.17%), sulfonamides (11.53%), multidrug (8.74%) and chloramphenicol (6.18%). The total relative ARG abundance increased along the treatment pathway prior to anaerobic digestion that had a similar degradative capacity for different ARGs and these ARGs were reduced by about 25% after digestion, but ARGs enriched erratically in manured soils. Distinctive ARG distribution patterns were found according to the three sample locations; feces, soil and wastewater and the differences were primarily due to the tetracycline ARGs (feces > wastewater > soil), sulfonamide ARGs (soil > wastewater > feces) and MLS ARGs (feces > wastewater > soil). Metagenomic assembly-based host analyses indicated the Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes were primary ARG carriers. The Streptococcaceae increased the abundance of multidrug, MLS and aminoglycoside ARGs in feces; Moraxellaceae were the primary contributors to the high abundance of multidrug ARGs in wastewater; the Comamonadaceae led to the higher abundance of bacA in wastewater and soil than feces. We found a high level of heterogeneity for both ARGs and ARG-hosts in the wastewater treatment system and in the agricultural soils for these pig farms.

6.
Bioorg Chem ; 105: 104398, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33137559

RESUMO

A series of novel pleuromutilin derivatives containing piperazine ring, 1, 2, 3-triazoles and secondary amines on the side chain of C14 were synthesized under mild conditions via click reaction. The in vitro antibacterial activities of the synthesized derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, ATCC 29213 ,144 and AD3) and one strain of Escherichia coli (ATCC 25922) were evaluated by the broth dilution method. Among these derivatives, 22-[2-(4-((4-nitrophenyl piperazine)methyl)-1,2,3-triazol-1-yl)-1-(piperazine-1-yl) ethyl-1-one] deoxy pleuromutilin (compound 59) showed the most prominent in vitro antibacterial effect against MRSA (MIC = 1 µg/mL). Furthermore, compound 59 displayed more rapid bactericidal kinetic than tiamulin time-kill studies and possessed a longer PAE than tiamulin against MRSA in vitro. In addition, in vivo antibacterial activities of compound 59 against MRSA were further evaluated employing thigh infection model. And compound 59 (-8.89 log10 CFU/mL) displayed superior activities than tiamulin. Compound 59 was further evaluated in CYP450 inhibition assay and the results showed that it exhibited low to moderate inhibitory effects on CYP1A2, CYP2E1, CYP2D6 and CYP3A4 enzymes. The PK properties of compound 59 were then measured. The half-life (t1/2), clearance rate (Cl) and the area under the plasma concentration time curve (AUC0→∞) of compound 59 were 0.74 h, 0.29 L/h/kg and 46.28 µg·h/mL, respectively.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33020156

RESUMO

Alternative therapeutic options are urgently needed against multidrug-resistant E. coli infections, especially in situations of pre-existing tigecycline and colistin resistances. Here, we investigated synergistic activity of the antiretroviral drug zidovudine in combination with tigecycline or colistin against E. coli harboring tet(X) and mcr-1 in vitro and in a murine thigh infection model. Zidovudine and tigecycline/colistin combinations achieved synergistic killing and significantly decreased bacterial burdens by >2.5 log10cfu/g in thigh tissues compared to each monotherapy.

8.
Front Cell Infect Microbiol ; 10: 583341, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102258

RESUMO

The emergence and spread of the novel mobile Tet(X) tetracycline destructases confer high-level tigecycline and eravacycline resistance in Escherichia coli and Acinetobacter spp. and pose serious threats to human and animal health. Therefore, a rapid and robust Tet(X) detection assay was urgently needed to monitor the dissemination of tigecycline resistance. We developed a rapid and simple assay to detect Tet(X) producers in Gram-negative bacteria based on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). This MALDITet(X) test was based on the inactivation of tigecycline by a Tet(X)-producing strain after a 3-h incubation of bacterial cultures with tigecycline. Culture supernatants were analyzed using MALDI-TOF MS to identify peaks corresponding to tigecycline (586 ± 0.2 m/z) and a tigecycline metabolite (602 ± 0.2 m/z). The results were calculated using the MS ratio [metabolite/(metabolite + tigecycline)]. The sensitivity of the MALDITet(X) test with all 216 test strains was 99.19%, and specificity was 100%. The test can be completed within 3 h. Overall, the MALDITet(X) test is an accurate, rapid, cost-effective method for the detection of Tet(X)-producing E. coli and Acinetobacter spp. by determining the unique peak of an oxygen-modified derivative of tigecycline.

9.
Front Microbiol ; 11: 1919, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013731

RESUMO

The chemotherapeutic options for methicillin-resistant Staphylococcus aureus (MRSA) infections are limited. Due to the multiple resistant MRSA, therapeutic failure has occurred frequently, even using antibiotics belonging to different categories in clinical scenarios, very recently. This study aimed to investigate the interactions between 11 antibiotics representing different mechanisms of action against MRSA strains and provide therapeutic strategies for clinical infections. Susceptibilities for MRSA strains were determined by broth microdilution or agar dilution according to CLSI guideline. By grouping with each other, a total of 55 combinations were evaluated. The potential synergism was detected through drug interaction assays and further investigated for time-killing curves and an in vivo neutropenic mouse infection model. A total of six combinations (vancomycin with rifampicin, vancomycin with oxacillin, levofloxacin with oxacillin, gentamycin with oxacillin, clindamycin with oxacillin, and clindamycin with levofloxacin) showed synergistic activity against the MRSA ATCC 43300 strain. However, antibacterial activity against clinical isolate #161402 was only observed when vancomycin combined with oxacillin or rifampicin in time-killing assays. Next, therapeutic effectiveness of vancomycin/oxacillin and vancomycin/rifampicin was verified by an in vivo mouse infection model inoculated with #161402. Further investigations on antimicrobial synergism of vancomycin plus oxacillin and vancomycin plus rifampicin against 113 wild-type MRSA strains were evidenced by combined antibiotic MICs and bacterial growth inhibition and in vitro dynamic killing profiles. In summary, vancomycin/rifampicin and vancomycin/oxacillin are the most potential combinations for clinical MRSA infection upon both in vitro and in vivo tests. Other synergetic combinations of levofloxacin/oxacillin, gentamycin/oxacillin, clindamycin/oxacillin, and clindamycin/fosfomycin are also selected but may need more assessment for further application.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33057710

RESUMO

OBJECTIVES: To determine the dissemination and molecular characteristics of NDM-producing Escherichia coli strains from duck farms in south-east coastal China and their threats to human health. METHODS: A total of 232 NDM-producing E. coli were recovered from 1505 samples collected from 25 duck farms and their surrounding environments in five provinces in China. Resistance genes were confirmed using PCR. Genomic characteristics of the carbapenemase-producing isolates were determined by WGS and bioinformatic analysis. RESULTS: The rate of NDM-positive E. coli detected in samples from the five provinces ranged from 3.7% to 28.5%. There was substantial variation in the prevalence of NDM-positive E. coli from different duck farms in each province studied. Three variants (blaNDM-1, blaNDM-4 and blaNDM-5) were found in 232 NDM-positive E. coli; blaNDM-5 (94.8%, 220/232) was the most prevalent. WGS analysis indicated that ST746, ST48, ST1011 and ST167 E. coli isolates were prevalent in the current study and poultry was likely the primary reservoir for NDM-positive ST746 and ST48 E. coli in China. Phylogenomic analysis showed that NDM-positive E. coli isolates from ducks were closely related to those of human origin. In addition, WGS analysis further revealed that blaNDM co-existed with other antibiotic resistance genes, conferring resistance to nine classes of antimicrobials. CONCLUSIONS: This study revealed that ducks farm in China are an important reservoir for NDM-positive E. coli and STs of the isolates showed obvious distinctive diversities in geographical distribution. The distribution and spread of NDM-positive E. coli in duck farms poses a threat to public health.

11.
Antimicrob Agents Chemother ; 64(12)2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-32928734

RESUMO

We determined in vivo efficacy and target PK/PD exposures of antofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in the murine pneumonia model. The mean plasma free drug area under the concentration-time curve/MIC (fAUC/MIC) targets associated with stasis and 1-log10 and 2-log10 kill effects were 8.93, 19.2, and 48.1, respectively, for S. pneumoniae, whereas they were 30.5, 55.4, and 115.8, respectively, for S. aureus The fAUC/MIC targets in murine lung epithelial lining fluids (ELF) for the same endpoints were nearly 2-fold higher than those in plasma.

12.
Infect Genet Evol ; 86: 104531, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32891878

RESUMO

Stenotrophomonas maltophilia is emerging as a significant cause of human and animal disease worldwide. A total of 3400 samples were collected from animal farms and adjacent environments in China. The blaL1 and blaL2 genes were identified using whole genome sequence analyses and examined by phylogenetics. Isolates were also tested for susceptibility to 18 antibiotics. We isolated 118 strains of S. maltophilia from 3400 samples. The positive rates of blaL1 and blaL2 genes were 75% (89/118) and 22% (26/118) and we identified 11 L1 and 6 L2 amino acid sequence variants. S. maltophilia has at least two inducible ß-lactamases (L1 and L2) that can hydrolyze almost all classes of ß-lactams and these genes are suspected to confer carbapenem resistance. This represents a significant public health threat especially for hospitalized patients. We conducted a molecular surveillance study on the prevalence and characteristics of the blaL1 and blaL2 genes of S. maltophilia.

13.
Front Med (Lausanne) ; 7: 364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850887

RESUMO

Objectives: There is an urgent need for accurate and fast diagnostic tests to identify carbapenemase-producing bacteria. Here we used Bacillus stearothermophilus as an indicator strain in the format of the carbapenem inactivation method (CIM) procedure to develop a rapid carbapenemase phenotype detection method: CIMB.S. Methods: The CIMB.S test was derived from the mCIM, where B. stearothermophilus replaced Escherichia coli as the indicator strain. The test bacteria were incubated in the presence of imipenem for 30 min, and then, aliquots were placed on colorimetric plates, and incubation was continued for 3.5 h at 60°C. We examined 134 clinical strains to evaluate the CIMB.S performance. Results: The CIMB.S can be completed in 4 h, and we successfully identified 38/39 (97.4%) carbapenemase-producing Enterobacteriaceae, including 17/18 (94.4%) carbapenemase-producing Pseudomonas aeruginosa and 18/19 (94.7%) carbapenemase-producing Acinetobacter baumannii. All non-carbapenemase producers we tested were negative and included Enterobacteriaceae (n = 36), P. aeruginosa (n = 17), and A. baumannii (n = 5). Conclusions: The CIMB.S test is a rapid carbapenemase phenotype detection method requiring only 4 h of total work time and displays high sensitivity and specificity.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32631827

RESUMO

Combating plasmid-mediated carbapenem resistance is essential to control and prevent the dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Here, we conducted a proof-of-concept study to demonstrate that CRISPR-Cas9-mediated resistance gene and plasmid curing can effectively resensitize CRE to carbapenems. A novel CRISPR-Cas9-mediated plasmid-curing system (pCasCure) was developed and electrotransferred into various clinical CRE isolates. The results showed that pCasCure can effectively cure bla KPC, bla NDM, and bla OXA-48 in various Enterobacteriaceae species of Klebsiella pneumoniae, Escherichia coli, Enterobacter hormaechei, Enterobacter xiangfangensis, and Serratia marcescens clinical isolates, with a >94% curing efficiency. In addition, we also demonstrated that pCasCure can efficiently eliminate several epidemic carbapenem-resistant plasmids, including the bla KPC-harboring IncFIIK-pKpQIL and IncN pKp58_N plasmids, the bla OXA-48-harboring pOXA-48-like plasmid, and the bla NDM-harboring IncX3 plasmid, by targeting their replication and partitioning (parA in pKpQIL) genes. However, curing the bla OXA-48 gene failed to eliminate its corresponding pOXA-48-like plasmid in clinical K. pneumoniae isolate 49210, while further next-generation sequencing revealed that it was due to IS1R-mediated recombination outside the CRISPR-Cas9 cleavage site resulting in bla OXA-48 truncation and, therefore, escaped plasmid curing. Nevertheless, the curing of carbapenemase genes or plasmids, including the truncation of bla OXA-48 in 49210, successfully restore their susceptibility to carbapenems, with a >8-fold reduction of MIC values in all tested isolates. Taken together, our study confirmed the concept of using CRISPR-Cas9-mediated carbapenemase gene and plasmid curing to resensitize CRE to carbapenems. Further work is needed to integrate pCasCure in an optimal delivery system to make it applicable for clinical intervention.

15.
Ginekol Pol ; 91(6): 301-307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32627150

RESUMO

OBJECTIVES: Human papillomavirus (HPV) ranks the first cause of cervical cancer. Cervical cancer has high prevalence rates in women around the world. The HPV-E7 oncoprotein is expressed in cervical cancer and is a target of developing immunotherapies against HPV-associated tumors. However, the antigenicity of this protein is low. Due to this reason, potent adjuvants are required to enhance its therapeutic efficacy. This preliminary study aims to evaluate whether lymphotoxin (LT) could act as an effective immune adjuvant for HPV infection in mice models. MATERIAL AND METHODS: Intranasal immunization was used to explore the effect of HPV-E7 and/or LT immune response. After the third intranasal immunization, the titer for the HPV-E7 antibody was detected in serum and vaginal washing fluid. Also, we assessed the expression of chemokine ligand 13 (CXCL13) and Peripheral Node Addressin (PNAd) in the lymph nodes after intranasal immunization with immunohistochemical analysis. RESULTS: compared to HPV-E7 immunization, intranasal immunization with HPV-E7 plus LT significantly increased HPV-E7-specific serum IgG and vaginal IgA titers. Furthermore, the combined use of HPV-E7 and LT strongly induced E7-specific CTL responses. CONCLUSIONS: LT can be effective for intranasal immunized HPV-E7 to improve E7-specific immune responses to HPV infection. It is new approach to eradicate chronic HPV infection capable of inducing an effective anti-infection method.

16.
Antimicrob Agents Chemother ; 64(10)2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32660996

RESUMO

The mobile colistin resistance gene mcr-3 has globally disseminated since it was first reported in 2017 in Escherichia coli In vitro mobilization assays in this study demonstrate the functionality of the composite transposon structure ISKpn40-mcr-3.11-dgkA-ISKpn40 in wild-type and recA - E. coli strains. These transpositions generated 4-bp duplications at the target sites. This is the first report demonstrating the mobility of the mcr-3.11 gene by transposition.

17.
Bioessays ; 42(8): e2000014, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32567703

RESUMO

Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next-generation tetracycline that is the final line of defense against severe infections by pan-drug-resistant bacterial pathogens. Unfortunately, this last-resort antibiotic has been challenged by the recent emergence of the mobile Tet(X) orthologs that can confer high-level tigecycline resistance. As it is reviewed here, these novel tetracycline destructases represent a growing threat to the next-generation tetracyclines, and a basic framework for understanding the molecular epidemiology and resistance mechanisms of them is presented. However, further large-scale epidemiological and functional studies are urgently needed to better understand the prevalence and dissemination of these newly discovered Tet(X) orthologs among Gram-negative bacteria in both human and veterinary medicine.

18.
Medicine (Baltimore) ; 99(25): e20623, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569192

RESUMO

INTRODUCTION: Pathological scar is the abnormal manifestation of skin fiber hyperplasia caused by the failure of normal healing after skin damage. At present, there are many clinical treatments for pathological scars. However, there is no cure for clinically effective pathological scars with high recurrence rate. In this study, we will use a combination of Chinese and western medicine treatment methods to evaluate the clinical efficacy and related indicators of young and middle-aged female patients who meet pathological scars, looking for an objective and effective treatment method for pathological scars. METHODS/DESIGN: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for pathological scars. The untreated pathological scars of the enrolled patients will be used as blank controls. The intervention group will be given conventional western medicine treatment and combined Chinese and western medicine treatment. The assessment of scar area, color, hardness, thickness, itching, and pain was recorded for 8 weeks of treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of traditional Chinese medicine for patients with pathological scars. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000032187, Registered on April 22, 2020.


Assuntos
Cicatriz/terapia , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
19.
Medicine (Baltimore) ; 99(26): e20790, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590760

RESUMO

INTRODUCTION: Hypertrophic scars are a common disease in plastic surgery, which is the reaction of skin connective tissue to trauma beyond the normal range. Although scholars around the world have explored the tissue structure and formation mechanism of HS for decades, they are not satisfactory the result of. No effective treatment has been found. Therefore, the search for safe and effective treatments for HS has always been the focus of medical attention and research. Acupuncture therapy has a definite effect on HS and has unique advantages. METHODS/DESIGN: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for HS. The untreated HS of the enrolled patients will be used as blank controls. The intervention group will be given acupuncture treatment. The assessment of scar area, color, hardness, thickness, itching and pain will be recorded for 30 days of treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of Acupuncture for patients with HS. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000032624, Registered on 04 May 2020.


Assuntos
Terapia por Acupuntura/métodos , Cicatriz Hipertrófica , Adulto , Cicatriz Hipertrófica/diagnóstico , Cicatriz Hipertrófica/fisiopatologia , Cicatriz Hipertrófica/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Projetos de Pesquisa , Resultado do Tratamento
20.
Oxid Med Cell Longev ; 2020: 9820168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377314

RESUMO

Acute renal injury has an incidence of 25%-30% in patients with tumors who are treated with cisplatin and in patients for whom no specific drugs are available for treatment. Amifostine is the only FDA-approved chemoprotective drug; however, its clinical application is limited because of side effects. The small-molecule antioxidant XH-003, an acute radiation syndrome- (ARS-) protective drug independently developed in our laboratory, with 100% intellectual property rights, overcomes the side effects of amifostine but retains its high efficacy. In this study, XH-003 showed a chemoprotective effect similar to that of amifostine. A mechanistic study showed that XH-003 could significantly reduce cisplatin-induced increases in serum creatinine and urea nitrogen, increase the activity of antioxidant enzymes (SOD, CAT, and GSH-Px), reduce oxidative stress and tissue inflammation, and alleviate renal tissue damage by blocking the activity of the mitochondrial apoptosis pathway. Most importantly, XH-003 could reduce the accumulation of cisplatin in renal tissue by regulating the expression of proteins involved in cisplatin uptake and excretion, such as organic cation transporter 2 and MRP2. Moreover, in an in vivo xenotransplantation model, XH-003 did not interfere with the antitumor effect of cisplatin. These data provide strong evidence that the ARS-protective agent has a great potential for protecting against chemotherapy-induced toxicity. Thus, XH-003 can be considered in antitumor therapy.

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