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1.
Autoimmunity ; : 1-11, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533429

RESUMO

Exosomes isolated from mesenchymal stem cells (MSC) had shown beneficial effect on acute lung injury (ALI). However, the effective components in MSC-derived exosomes need further investigation. ALI mice model was established by lipopolysaccharide (LPS) injection. In vitro inflammatory model was established by LPS stimulation of MLE-12 cells. The cell proliferation was evaluated by EdU assay. TUNEL and Annexin V/PI were applied to evaluate the apoptosis of tissue and cell respectively. HE staining was performed to evaluate the lung injury. Transmission electronic microscope was used to observe isolated exosomes. Level of cytokines, MDA, KGF were determined by ELISA kit. Direct interaction of miR-132-3p and TRAF6 were verified by dual luciferase assay. The level of mRNA or proteins were determined by qRT-PCR or western blots respectively. TRAF6 was upregulated while miR-132-3p was downregulated in LPS-stimulated ALI model. MiR-132-3p negatively regulated TRAF6 by direct binding. MiR-132-3p potentiated proliferation and suppressed apoptosis of LPS-induced MLE-12 cells at least partly dependent on targeting TRAF6. Treatment of exosome alleviated the LPS-induced ALI in mice and LPS-induced inflammatory response in MLE-12 cells. Moreover, overexpression of miR-132-3p promoted the protective effect of exosomes in LPS-induced MLE-12 cells injury and LPS-induced ALI. Mechanically, it was suggested that miR-132-3p inactivated PI3K/Akt signalling via targeting TRAF6. In the present study, our results indicated that miR-132-3p mediated protective effect of MSC-derived exosomes on LPS-induced ALI. Exosomal miR-132-3p ameliorated LPS-induced ALI via targeting TRAF6 and inactivating PI3K/Akt signalling.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34499729

RESUMO

BACKGROUND: The increasing use of colistin causes a serious breach in our last line of defence against MDR Gram-negative pathogens. Our previous study showed that CpxR overexpression increases the susceptibility of acrB and cpxR double-deleted Salmonella enterica serovar Typhimurium to colistin. OBJECTIVES: To identify the mechanism of CpxAR and efflux pumps that synergistically enhance the susceptibility of S. Typhimurium to colistin. METHODS: A series of cpxR- and tolC-deleted mutants and a cpxR-complemented strain from a multidrug-susceptible standard strain of S. Typhimurium (JS) were generated in our previous study. Herein, we investigated the susceptibility of these strains to colistin through the broth microdilution method, time-kill curves and survival assays. Growth curves were measured by OD600 in LB broth, tryptone-soy broth (TSB) and M9-glucose (0.2%) minimal media. Finally, molecular mechanisms underlying the mode of action were elucidated by transcriptomic analysis. RESULTS: We found that in contrast to JS (0.8 mg/L), the MIC of colistin for JSΔtolC::kan showed a 16-fold decrease (0.05 mg/L). Notably, JSΔcpxRΔtolC and JSΔcpxRΔtolC/pcpxR were associated with a 256-fold decrease (0.0031 mg/L) compared with JS. Growth curves identified that JSΔcpxRΔtolC and JSΔcpxRΔtolC/pcpxR displayed a markedly lower growth rate and poorer adaptability. In addition, time-kill curves and survival assays showed that JSΔcpxRΔtolC and JSΔcpxRΔtolC/pcpxR were more susceptible to colistin. Lastly, double deletion of cpxR and tolC enhanced oxidative damage through promoting oxidative phosphorylation, the tricarboxylic acid (TCA) cycle and trimethylamine N-oxide (TMAO) respiration. CONCLUSIONS: Our findings revealed that double deletion of cpxR and tolC significantly increases the susceptibility of S. Typhimurium to colistin.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34508611

RESUMO

OBJECTIVES: To characterize a novel MDR efflux pump gene cluster tnfxB3-tmexCD3-toprJ1b carried by Proteus spp. and Pseudomonas aeruginosa strains from chickens. METHODS: Antimicrobial susceptibility testing, conjugation and WGS were performed to characterize tnfxB3-tmexCD3-toprJ1b-positive isolates. Cloning and reverse transcription-quantitative PCR were performed to investigate the function of tnfxB3-tmexCD3-toprJ1b. RESULTS: The WGS data revealed that a novel efflux pump gene cluster, tnfxB3-tmexCD3-toprJ1b, was identified on the chromosome of the Proteus cibarius strain SDQ8C180-2T, where an SXT/R391-family integrative and conjugative element (ICE) was found to co-carry tet(X6) and tnfxB3-tmexCD3-toprJ1b. Further retrospective analysis found two other tnfxB3-tmexCD3-toprJ1b variants in a Proteus mirabilis isolate and a P. aeruginosa isolate, respectively. tmexCD3-toprJ1b and its variants increased the MICs of tigecycline (8-fold) and other antibiotics (2-8-fold) in Escherichia coli host strains. The TNfxB3 protein down-regulated the expression of the tmexCD3-toprJ1b operon. Moreover, genetic-context analyses showed that tnfxB3-tmexCD3-toprJ1b together with adjacent integrase genes appeared to compose a transferable module 'int1-like+int2-like+hp1+hp2+ISCfr1+tnfxB3-tmexCD3-toprJ1b', which was inserted into the umuC-like gene of this ICE. Further analysis of the tnfxB3-tmexCD3-toprJ1b-harbouring sequences deposited in GenBank revealed similar transferable modules inserted into umuC-like genes in plasmids or chromosomes of Klebsiella pneumoniae, Pseudomonas spp. and Aeromonas spp., implying that these modules could be transferred across different bacterial species. CONCLUSIONS: To the best of our knowledge, this is the first identification of a novel tigecycline gene cluster, tmexCD3-toprJ1b, which co-exists with tet(X6) within an ICE. More attention should be paid to the co-transfer of these two tigecycline resistance determinants via an ICE to other Gram-negative bacteria.

4.
Mol Cell Biochem ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34346000

RESUMO

Acute lung injury (ALI) is a fatal inflammatory response syndrome. LncRNA XIST (XIST) is a lung cancer-related gene and participates in pneumonia. However, whether XIST participates in lipopolysaccharides (LPS)-induced ALI remains unclear. LPS-induced inflammation model was constructed in vitro, then cell viability, cytokines, cell apoptosis, protein, and mRNA expressions were individually detected by cell counting kit-8, enzyme-linked immunosorbent assay and flow cytometry, Western blot, and qRT-PCR. A dual-luciferase reporter assay confirmed the relationships among XIST, miR-132-3p, and MAPK14. Furthermore, inflammation and conditions after knockdown of XIST were assessed by hematoxylin and eosin staining, lung wet-to-dry weight ratio, PaO2/FiO2 ratio, and malondialdehyde (MDA) contents using LPS-induced in vivo model. Our findings indicated that the LPS challenge decreased cell viability, increased cell apoptosis, and caused secretions of pro-inflammatory cytokines. Noticeably, LPS significantly upregulated XIST, MAPK14, and downregulated miR-132-3p. Mechanistically, XIST acted as a molecular sponge to suppress miR-132-3p, and MAPK14 was identified as a target of miR-132-3p. Functional analyses demonstrated that XIST silencing remarkably increased cell survival and alleviated cell death and lung injury through decreasing TNF-α, IL-1ß, IL-6, accumulation of inflammatory cells, alveolar hemorrhage, MDA release, and increased PaO2/FiO2 ratio, as well as upregulating Bcl-2, and downregulating Bax, MAPK14, and p-extracellular signal-regulated kinases ½. In contrast, inhibition of the miR-132-3p antagonized the effects of XIST silencing. In conclusion, inhibition of XIST exhibited a protective role in LPS-induced ALI through modulating the miR-132-3p/MAPK14 axis.

6.
Cell Death Dis ; 12(7): 631, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145212

RESUMO

Bone marrow-derived mesenchymal stem cells (BM-MSCs), the common progenitor cells of adipocytes and osteoblasts, have been recognized as the key mediator during bone formation. Herein, our study aim to investigate molecular mechanisms underlying circular RNA (circRNA) AFF4 (circ_AFF4)-regulated BM-MSCs osteogenesis. BM-MSCs were characterized by FACS, ARS, and ALP staining. Expression patterns of circ_AFF4, miR-135a-5p, FNDC5/Irisin, SMAD1/5, and osteogenesis markers, including ALP, BMP4, RUNX2, Spp1, and Colla1 were detected by qRT-PCR, western blot, or immunofluorescence staining, respectively. Interactions between circ_AFF4 and miR-135a-5p, FNDC5, and miR-135a-5p were analyzed using web tools including TargetScan, miRanda, and miRDB, and further confirmed by luciferase reporter assay and RNA pull-down. Complex formation between Irisin and Integrin αV was verified by Co-immunoprecipitation. To further verify the functional role of circ_AFF4 in vivo during bone formation, we conducted animal experiments harboring circ_AFF4 knockdown, and born samples were evaluated by immunohistochemistry, hematoxylin and eosin, and Masson staining. Circ_AFF4 was upregulated upon osteogenic differentiation induction in BM-MSCs, and miR-135a-5p expression declined as differentiation proceeds. Circ_AFF4 knockdown significantly inhibited osteogenesis potential in BM-MSCs. Circ_AFF4 stimulated FNDC5/Irisin expression through complementary binding to its downstream target molecule miR-135a-5p. Irisin formed an intermolecular complex with Integrin αV and activated the SMAD1/5 pathway during osteogenic differentiation. Our work revealed that circ_AFF4, acting as a sponge of miR-135a-5p, triggers the promotion of FNDC5/Irisin via activating the SMAD1/5 pathway to induce osteogenic differentiation in BM-MSCs. These findings gained a deeper insight into the circRNA-miRNA regulatory system in the bone marrow microenvironment and may improve our understanding of bone formation-related diseases at physiological and pathological levels.


Assuntos
Células da Medula Óssea/metabolismo , Diferenciação Celular , Fibronectinas/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese , RNA Circular/metabolismo , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Animais , Células Cultivadas , Feminino , Fibronectinas/genética , Humanos , Transplante de Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , MicroRNAs/genética , RNA Circular/genética , Transdução de Sinais
7.
Zool Res ; 42(4): 461-468, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34156173

RESUMO

During a 2018 antimicrobial resistance surveillance of Escherichia coli isolates from diarrheal calves in Xinjiang Province, China, an unexpectedly high prevalence (48.5%) of fosfomycin resistance was observed. This study aimed to reveal the determinants of fosfomycin resistance and the underlying transmission mechanism. Polymerase chain reaction (PCR) screening showed that all fosfomycin-resistant E. coli carried the fosA3 gene. Pulsed-field gel electrophoresis (PFGE) and southern blot hybridization revealed that the 16 fosA3-positive isolates belonged to four different PFGE patterns (i.e., A, B, C, D). The fosA3 genes of 11 clonally related strains (pattern D) were located on the chromosome, while others were carried by plasmids. Whole-genome and long-read sequencing indicated that the pattern D strains were E. coli O101: H9-ST10, and the pattern C, B, and A strains were O101: H9-ST167, O8: H30-ST1431, and O101: H9 with unknown ST, respectively. Among the pattern C strains, the bla CTX-M-14 gene was co-localized with the fosA3 gene on the F18: A-: B1 plasmids. Interestingly, phylogenetic analysis based on core genome single nucleotide polymorphisms (cgSNPs) showed that the O101: H9-ST10 strains were closely related to a Australian-isolated Chroicocephalus-origin E. coli O101: H9-ST10 strain producing CTX-M-14 and FosA3, with a difference of only 11 SNPs. These results indicate possible international dissemination of the high-risk E. coli clone O101: H9-ST10 by migratory birds.


Assuntos
Doenças dos Bovinos/microbiologia , Charadriiformes/microbiologia , Diarreia/veterinária , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/metabolismo , Escherichia coli/classificação , Migração Animal , Animais , Antibacterianos/farmacologia , Austrália , Bovinos , Doenças dos Bovinos/epidemiologia , China/epidemiologia , Diarreia/epidemiologia , Diarreia/microbiologia , Farmacorresistência Bacteriana , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , beta-Lactamases/genética
8.
Scand J Gastroenterol ; 56(8): 914-919, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34165373

RESUMO

PURPOSE: To evaluate the effect of AMD3100 treatment to cholangiocarcinoma by analyzing the relationship between them, and provide experimental evidence for whether AMD3100 can become a clinical treatment drug for cholangiocarcinoma. MATERIALS AND METHODS: Cholangiocarcinoma RBE cell lines were used in this study. MTT cell proliferation test was used for evaluating the effect of gemcitabine and AMD3100 to cell. CXCR4, N-cadherin, VEGF-C and MMP-9 were detect by RT-PCR and western. Transwell was used for evaluating the invasion effect. RESULTS: We demonstrated that as the concentration of gemcitabine increasing from 0.33, 3.33 to 33.33 uM, the cell survival rate was 76.65%, 71.40%, 52.25%, respectively. RT-PCR and Western blot that gemcitabine could affect the expression of CXCR4 protein and the level of mRNA transcription in a dose-dependent manner. N-cadherin VEGF-C, MMP-9 mRNA transcription level showed a significant upward trend in gemcitabine group. In Transwell test, the number of cells in the gemcitabine group was significantly higher than that in the no-medication group (p < .05), the AMD3100 group and the combination group of gemcitabine and AMD3100, the difference between the no-medication group and the AMD3100 monotherapy group was not significant, and the combination group was between them. CONCLUSIONS: This study showed that gemcitabine significantly inhibited the growth of cholangiocarcinoma RBE cells in a dose-dependent manner, and gemcitabine can affect the expression of CXCR4, N-cadherin, VEGF-C, MMP-9 protein and mRNA. Cell invasion and metastasis-related factors decreased after AMD3100 combined with gemcitabine.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Benzilaminas , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CXCL12 , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Ciclamos , Desoxicitidina/análogos & derivados , Humanos , Invasividade Neoplásica , Receptores CXCR4/genética
9.
Eur J Radiol ; 141: 109820, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34139574

RESUMO

OBJECTIVES: Imaging features of positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT and pathological changes in benign solitary schwannoma were retrospectively analyzed, and the factors associated with high uptake of fluorodeoxyglucose (FDG) were examined. METHODS: The PET/CT, contrast-enhanced CT, and pathological results of 58 cases of benign solitary schwannomas confirmed by surgery or biopsy were retrospectively analyzed. The association of each variable with the maximum standardized uptake value (SUVmax) was evaluated. RESULTS: The SUVmax of the 58 benign schwannoma cases was 4.1 ± 2.1 (1.5-11.1). When the locations of schwannomas were divided into gastrointestinal system/heart/abdominal and pelvic cavities/thoracic wall (type-1 locations) and other sites (type-2 locations), the schwannoma location was significantly correlated with the SUVmax (r = 0.538, p = 0.000). The SUVmax values were 5.8 ± 2.4 and 3.3 ± 1.5, respectively (p = 0.000). Peritumoral lymphoid cuffs were observed in 7 cases, 4 of which were tumors of gastrointestinal origin, accounting for 80 % of the gastrointestinal schwannomas (4/5). The presence of peritumoral lymphoid cuffs was significantly correlated with the SUVmax (r = 0.456, p = 0.000). The location of the schwannoma was significantly correlated with the presence of peritumoral lymphoid cuffs (r = 0.640, p = 0.000). We found that a peritumoral lymphoid cuff is strongly correlated with the presence of regional lymphadenopathy. Among the 7 cases showing peritumoral lymphoid cuffs, 5 cases had the presence of peritumoral enlarged lymph nodes. The degree of enhancement was significantly correlated with the SUVmax (r = 0.556, p = 0.000). CONCLUSIONS: Benign schwannomas originating from the gastrointestinal system/heart/abdominal location and showing the presence of peritumoral lymphoid cuffs or moderate and significant enhancement on contrast-enhanced CT were significantly associated with high FDG uptake. An accurate understanding of the factors associated with high FDG uptake can help reduce the misdiagnosis rate.


Assuntos
Neurilemoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Humanos , Neurilemoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(5): 456-459, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34020733

RESUMO

OBJECTIVE: To study the epidemiological features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Shijiazhuang, China. METHODS: Based on the information officially announced on the official website of the Health Commission of Hebei Province, epidemiological data were collected from 133 children, aged 0-18 years, who were diagnosed with SARS-CoV-2 infection in Shijiazhuang from January 2 to January 30, 2021. A statistical analysis was performed for general status, regional distribution, presence or absence of clusters, and results of SARS-CoV-2 nucleic acid tests. RESULTS: Among the 133 children with SARS-CoV-2 infection, there were 65 boys and 68 girls, with a male/female ratio of 0.96:1. The youngest age of onset was 3 months and 7 days, and the mean age of onset was (9±5) years. Of all the 133 children, 90(67.7%) were the first confirmed case of SARS-CoV-2 infection among their family members. Of all the children, 108(81.2%) came from the Gaocheng District in Shijiazhuang, among whom 38(28.6%) were from Xiaoguozhuang Village where the first patient with a confirmed diagnosis lived. SARS-CoV-2 nucleic acid test at week 2 after the outbreak showed positive results in 88 children (66.2%), and only 5 children had clinical symptoms before positive SARS-CoV-2 results were obtained. Of all the 133 children, 19(14.3%) were found positive in the first SARS-CoV-2 nucleic acid test after the outbreak, and 70(52.6%) had positive results for ≥4 times. There were 98 school students with infection, among whom 74(75.5%) were the first confirmed case in their family, and among 35 non-school students, 16(45.7%) were the first confirmed case in their family (P < 0.05). CONCLUSIONS: Among the children confirmed with SARS-CoV-2 infection in Shijiazhuang, there is a high proportion of children who are the first confirmed case in their family, and the children are mainly distributed in the rural areas of Gaocheng. Most of these children are students, so the prevention and control of cluster infection in schools should be taken seriously. There are often no symptoms before SARS-CoV-2 nucleic acid test, with a low positive rate of the first nucleic acid test, which increases the difficulty of early discovery of the epidemic.


Assuntos
COVID-19 , SARS-CoV-2 , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Instituições Acadêmicas
11.
Nucleic Acids Res ; 49(7): 3981-3996, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33721023

RESUMO

The plasmid-encoded colistin resistance gene mcr-1 challenges the use of polymyxins and poses a threat to public health. Although IncI2-type plasmids are the most common vector for spreading the mcr-1 gene, the mechanisms by which these plasmids adapt to host bacteria and maintain resistance genes remain unclear. Herein, we investigated the regulatory mechanism for controlling the fitness cost of an IncI2 plasmid carrying mcr-1. A putative ProQ/FinO family protein encoded by the IncI2 plasmid, designated as PcnR (plasmid copy number repressor), balances the mcr-1 expression and bacteria fitness by repressing the plasmid copy number. It binds to the first stem-loop structure of the repR mRNA to repress RepA expression, which differs from any other previously reported plasmid replication control mechanism. Plasmid invasion experiments revealed that pcnR is essential for the persistence of the mcr-1-bearing IncI2 plasmid in the bacterial populations. Additionally, single-copy mcr-1 gene still exerted a fitness cost to host bacteria, and negatively affected the persistence of the IncI2 plasmid in competitive co-cultures. These findings demonstrate that maintaining mcr-1 plasmid at a single copy is essential for its persistence, and explain the significantly reduced prevalence of mcr-1 following the ban of colistin as a growth promoter in China.


Assuntos
Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/fisiologia , Escherichia coli/genética , Plasmídeos , Proteínas de Ligação a RNA/fisiologia , Antibacterianos/farmacologia , Colistina/farmacologia
12.
Zhen Ci Yan Jiu ; 46(1): 69-72, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33559429

RESUMO

OBJECTIVE: To explore the excitatory effect of the sensory cortex through somatic electroacupuncture (EA) stimulation at Taichong (LR3). METHODS: Ten healthy volunteer men ranging in age from 20 to 50 years were enrolled in this study. EA (2 Hz, a tolerable strength) was applied to the left LR3. Before and after EA, the somatosensory evoked potential (SEP) from the Cz' area of the scalp was recorded by electrical stimulation of the bilateral dorsal penile nerves and the indentation behind the medial malleolus of the foot, termed as the pudendal SEP (PSEP) and lower extremity SEP (LSEP), respectively. RESULTS: The amplitude of the left LSEP induced by stimulation of the left medial malleolus was significantly increased after EA (P < 0.05), but there were no significant changes in the latency of LSEP and PSEP, and the amplitude of right LSEP evoked by stimulation of the left medial malleolus, and that of the PSEP. CONCLUSION: EA at LR3 increases the excitability of the contralateral cerebral sensory cortex (lower extremity area), but has no effect on the adjacent sensory cortex (genital area).


Assuntos
Eletroacupuntura , Adulto , Córtex Cerebral , Estimulação Elétrica , Potenciais Somatossensoriais Evocados , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-33495220

RESUMO

We recently identified a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, tmexCD1-toprJ1, in Klebsiella pneumoniae that conferred resistance to multiple antimicrobials, including tigecycline. While homologs of tmexCD1-toprJ1 were found encoded in many other bacterial species in GenBank, their functions and transfer mechanisms remain unknown. This study identified another mobile gene cluster, tmexCD2-toprJ2, co-occurring on both a plasmid (pHNNC189-2) and the chromosome of a clinical Raoultella ornithinolytica isolate, strain NC189, producing KPC-2, NDM-1, and RmtC. tmexCD2-toprJ2 shares high similarity at the nucleotide level with tmexCD1-toprJ1, with 98.02%, 96.75%, and 99.93% identities to tmexC1, tmexD1, and toprJ1, respectively. Phylogenetic analysis revealed that tmexCD2-toprJ2 may have originated from the chromosome of a Pseudomonas species. The expression of tmexCD2-toprJ2 in an Escherichia coli strain resulted in an 8-fold increase in the tigecycline MIC and decreased susceptibility to other antimicrobials. Genetic context analyses demonstrated that tmexCD2-toprJ2, together with the adjacent hypothetical site-specific integrase genes, was possibly captured and mobilized by a XerD-like tyrosine recombinase system, forming a putative transposition unit (xerD-like-int3-like-thf2-ybjD-umuD-ΔumuC1-int1-like-int2-like-hp1-hp2-tnfxB2-ISBvi2-tmexCD2-toprJ2-ΔumuC1), which was inserted into umuC-like genes in both the NC189 plasmid pHNNC189-2 and the chromosome. Since tmexCD1-toprJ1 and tmexCD2-toprJ2 could confer multidrug resistance, the spread of these gene clusters, associated with the new recombinase system, calls for more attention.


Assuntos
Antibacterianos , Família Multigênica , Antibacterianos/farmacologia , Enterobacteriaceae , Família Multigênica/genética , Filogenia , Tigeciclina/farmacologia
14.
Plasmid ; 114: 102555, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33472047

RESUMO

To analyze characteristics and underlying evolutionary processes of IncC and IncI1 plasmids in a multidrug-resistant avian E. coli strain, antibiotic susceptibility testing, PCR, conjugation assays, and next-generation sequencing were performed. The type 1 IncC plasmid pEC009.1 harbored three antimicrobial resistance regions including ISEcp1-blaCMY-2-blc-sugE, ARI-B resistance island, and ARI-A island that was a mosaic multidrug resistance region (MRR) comprised of a class 1 integron with cassette array |aac(6')-II(aacA7)|qacE∆1|sul1|, IS26-mphR(A)-mrx-mph(A)-IS26, IS26-fosA3-IS26, and mercury resistance cluster merRTPABDE. It is the first report of three different size circular forms derived from IS26-mphR(A)-mrx-mph(A)-IS26-fosA3-IS26 in ARI-A of type 1 IncC plasmid. In IncI1/ST136 pEC009.2, the truncated transposon Tn1722 carrying blaTEM-1b, rmtB, aac(3)-IId(aacC2d), and a class 1 integron with cassette array |dfrA12|orfF|aadA2|, inserted into the plasmid backbone generating 5-bp direct repeats (DRs, TATAA) at the boundaries of the region, which was highly similar to that of other IncI1 plasmids, and differed by the arrangements of resistance determinants. Comparison among two epidemic plasmid lineages showed complex MRRs respectively located in the specific position in type 1 IncC and IncI1/ST136 plasmids with conserved backbones, and these have evolved via multiple events involved in mobile elements-mediated loss and gain of resistance genes and accessory genes. Strains harboring these plasmids may serve as a reservoir for antibiotic resistance genes, thereby contributing to the rapid spread of resistance genes and posing a public health threat.

15.
Chin J Integr Med ; 27(5): 384-387, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33420901

RESUMO

From the perspective view of Chinese medicine, the Gan (Liver) meridian of Foot-Jueyin starts from the great toe, running upward along the medial side of the thigh to the perineal area, where it curves around the external genitalia and goes up to the lower abdomen. In clinical practice, acupoints in the feet of the Gan meridian of Foot-Jueyin are used to treat the genitourinary and external genitalia diseases. Studies have shown that reproductive system diseases have specific pathological reactions in the places (radial side of tibia and foot) where Gan meridian of Foot-Jueyin passes by. Why does this happen? In this article, we begin by briefly reviewing the evidences linking foot and genitalia. We then explore the potential mechanism of the relationship between genitals and the Gan meridian of Foot-Jueyin. The brain cerebral cortex is characterized by cortical interactions. Numerous studies show that different cerebral cortex function areas (especially the adjacent areas) are overlapping and interact with each other. Finally, we presume that there is a specific connection between the feet and the genitals. Physiologically in the cortical homunculus, the genital area lies adjacent or overlapped to the foot areas, the two areas may interact with each other. The functional reorganization between different areas of the cerebral cortex under pathological conditions may be the underlying mechanism of the relationship between the feet and the genitals.

16.
Microb Drug Resist ; 27(6): 809-815, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33216688

RESUMO

The occurrence and characterization of carbapenemase-producing Enterobacteriaceae from companion animals in Guangzhou, China, are investigated. Six isolates (2.3%, 6/257) were positive for blaNDM-5, that is, one Enterobacter cloacae, one Citrobacter freundii, and four Escherichia coli. Three E. coli isolates obtained from the same animal hospital were ST410 and showed identical pulse field gel electrophoresis pattern, resistance profiles, and resistance genes. blaNDM-5 was located on IncX3 (n = 5) and IncK2 (n = 1) plasmid, respectively. The presence of carbapenemase-producing Enterobacteriaceae among companion animals needs continued surveillance.

18.
Int J Chron Obstruct Pulmon Dis ; 15: 3051-3061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262584

RESUMO

Introduction: Currently, there is a lack of evidence on the utilization of high-flow nasal cannula (HFNC) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) accompanied by hypercapnic respiratory failure. We aimed to explore the efficacy and safety of HFNC compared with conventional oxygen therapy (COT) in such patients. Methods: This was a prospective, randomized, controlled trial. Patients with AECOPD with a baseline arterial blood gas pH ≥7.35, PaO2 <60 mmHg, and PaCO2 >45 mmHg were enrolled. The primary endpoint was treatment failure, which needs mechanical ventilation. Results: A total of 320 patients were randomized to either the HFNC group (n = 160) or the COT group (n = 160). Sixteen (10.0%) patients in the HFNC group had treatment failure during hospitalization, which was significantly lower than the COT group figure of 31 (19.4%) patients (p = 0.026). Twenty-four hours after recruitment, the PaCO2 of the HFNC group was lower than that of the COT group (54.1 ± 9.79 mmHg vs 56.9 ± 10.1 mmHg, p = 0.030). PaCO2 higher than 59 mmHg after HFNC for 24 h was identified as an independent risk factor for treatment failure [OR 1.078, 95% CI 1.006-1.154, p = 0.032]. Conclusion: In AECOPD patients with acute compensated hypercapnic respiratory failure, HFNC improved the prognosis compared with COT. Therefore, HFNC might be considered for first-line oxygen therapy in select patients. Trial Registration Number: ClinicalTrials.Gov: NCT02439333.


Assuntos
Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Cânula , Humanos , Ventilação não Invasiva/efeitos adversos , Oxigenoterapia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia
19.
Front Microbiol ; 11: 588658, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162965

RESUMO

Rapid dissemination of the plasmid-born polymyxin resistance gene mcr-1 poses a critical medical challenge. MCR-1 expression is tightly controlled and imposes a fitness cost on the bacteria. We used growth studies and metabolomics to examine growth and metabolic changes within E. coli TOP10 at 8 and 24 h in response to different levels of expression of mcr-1. Induction of mcr-1 greatly increased expression at 8 h and markedly reduced bacterial growth; membrane disruption and cell lysis were evident at this time. At 24 h, the expression of mcr-1 dramatically declined with restored growth and membrane integrity, indicating regulation of mcr-1 expression in bacteria to maintain membrane homeostasis. Intermediates of peptide and lipid biosynthesis were the most commonly affected metabolites when mcr-1 was overexpressed in E. coli. Cell wall biosynthesis was dramatically affected with the accumulation of lipids including fatty acids, glycerophospholipids and lysophosphatidylethanolamines, especially at 8 h. In contrast, levels of intermediate metabolites of peptides, amino sugars, carbohydrates and nucleotide metabolism and secondary metabolites significantly decreased. Moreover, the over-expression of mcr-1 resulted in a prolonged reduction in intermediates associated with pentose phosphate pathway and pantothenate and CoA biosynthesis. These findings indicate that over-expression of mcr-1 results in global metabolic perturbations that mainly involve disruption to the bacterial membrane, pentose phosphate pathway as well as pantothenate and CoA biosynthesis.

20.
World J Gastrointest Oncol ; 12(9): 1065-1072, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33005299

RESUMO

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) amplification is a molecular driver for a subset of colorectal cancers (CRCs) and one of the major causes of anti-epidermal growth factor receptor (EGFR) treatment failure. Compared to dual anti-HER2 treatments, which have been shown to be effective in HER2-positive metastatic CRC patients, single-agent anti-HER2 therapy is rarely used to treat CRC. CASE SUMMARY: Herein, we report a case of RAS/BRAF-wild-type metastatic CRC that was identified as HER2-positive through circulating tumor DNA (ctDNA) testing by next-generation sequencing following the failure of two lines of therapy. Subsequently, the patient was given lapatinib monotherapy that led to a partial response with a progression-free survival of 7.9 mo. Moreover, serial ctDNA detection was used to monitor the efficacy of lapatinib. The aberration of HER2 copy number disappeared when radiographic assessment revealed a partial response. However, a high level of HER2 amplification was detected again at the time of disease progression. Finally, a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression, which may explain the acquired resistance to lapatinib. CONCLUSION: This is the first case report of HER2-positive RAS/BRAF wild-type metastatic CRC patient responding to lapatinib monotherapy. It highlights that ctDNA testing is an effective and feasible approach to evaluate the efficacy of anti-HER2 therapy.

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