RESUMEN
The wastewater treatment processes (WTP) on pig farms are heavily contaminated by antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) play an important role in shaping ARG profiles. Here we first employed metagenomic sequencing to follow the diversities and shifts of ARG associated mobile genetic elements (AAMGEs) including insertion sequences (ISs) and plasmids along the WTP for three pig farms in southeast China. The IS average relative abundance rose from the initial pig feces source to the wastewater storage lagoon (WSL) but decreased in the influent and rose in the effluent of the anaerobic digestor (AD). In contrast, plasmids were eliminated rapidly along this process. These results indicated that the AD reduced plasmid copies while IS abundance increased. We found a great diversity ISs, including IS91, ISNCY, IS630 and IS701, were large contributors to the transfer of multi-drug resistance. In addition, the tetracycline resistance genes co-occurred with a greater diversity of ISs than other ARG classes and this likely contributed to the high abundance of tetracycline resistance genes we found. The transfer of ARGs mediated by MGEs along the WTP of pig farms was a key contributor for the ARGs persistence in the environment of pig farms. Collectively, our findings demonstrated different fates for ISs and plasmids along the WTP for pig farms and suggested that AAMGE monitoring served as an important role in controlling ARGs in pig waste.
Asunto(s)
Antibacterianos , Purificación del Agua , Animales , Antibacterianos/farmacología , Farmacorresistencia Microbiana/genética , Granjas , Genes Bacterianos , Secuencias Repetitivas Esparcidas , Porcinos , Aguas ResidualesRESUMEN
We determined the longitudinal persistence of ceftiofur-resistant Escherichia coli from a chicken breeding farm in China. A total of 150 samples were collected from 5 breeding periods in a flock of layer hens, and the prevalence of ceftiofur-resistant E. coli fluctuated across the 5 chicken breeding stages: eggs, 3.33%; growing period, 100%; early laying period, 36.7%; peak laying period, 66.7% and late laying period, 80%. The most prevalent ceftiofur resistance genes were blaCTX-M-55, blaCMY and blaNDM, and ST101 was the most prevalent and persistent sequence type across the breeding periods. Our results indicated that this breeder flock was heavily contaminated by ST101 ceftiofur-resistant E. coli and that its presence should be intensively monitored on chicken farms.
RESUMEN
FLT3-ITD mutations occur in approximately 30% of acute myeloid leukemia (AML) and are associated with a poor outcome. Currently available FLT3 inhibitors have in vitro but limited clinical activity in FLT3-ITD AML. Reports have shown that an arsenic trioxide (ATO)/all-trans-retinoic acid (ATRA) combination improves prognosis in acute promyelocytic leukemia, especially with FLT3-ITD, and ATO or ATRA alone enhances apoptosis in FLT3-ITD AML cells treated with FLT3 inhibitors, providing a rationale to investigate the role of ATO/ATRA in FLT3-ITD AML. Here, we demonstrate that an ATO/ATRA combination selectively exerts synergistic cytotoxicity against FLT3-ITD AML cell lines (MV4;11/MOLM-13). The signaling pathways affected by ATO/ATRA include FLT3/STAT5/MYC, FLT3/STAT5/E2F1, FLT3/ERK/ATF5 and FLT3/AKT/ATF5.ATF5 may function as an oncogene in FLT3-ITD AML. Our findings provide experimental evidence that supports further exploration of ATO/ATRA in FLT3-ITD AML in vivo and warrants a clinical evaluation of regimens comprising an ATO/ATRA combination.
Asunto(s)
Trióxido de Arsénico , Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Tretinoina , Apoptosis/efectos de los fármacos , Trióxido de Arsénico/farmacología , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Tretinoina/farmacología , Tirosina Quinasa 3 Similar a fms/efectos de los fármacosRESUMEN
Idiopathic pulmonary fibrosis is known as a life-threatening disease with high mortality and limited therapeutic strategies. In addition, the molecular mechanism by which pulmonary fibrosis developed is not fully understood. Asiatic acid (AA) is a triterpenoid, isolated from Centella asiatica, exhibiting efficient anti-inflammatory and anti-oxidative activities. In our study, we attempted to explore the effect of Asiatic acid on bleomycin (BLM)-induced pulmonary fibrosis in mice. The findings indicated that pre-treatment with Asiatic acid inhibited BLM-induced lung injury and fibrosis progression in mice. Further, Asiatic acid down-regulates inflammatory cells infiltration in bronchoalveolar lavage fluid (BALF) and pro-inflammatory cytokines expression in lung tissue specimens induced by BLM. Also, Asiatic acid apparently suppressed transforming growth factor-beta 1 (TGF-ß1) expression in tissues of lung, accompanied with Collagen I, Collagen III, α-SMA and matrix metalloproteinase (TIMP)-1 decreasing, as well as Smads and ERK1/2 inactivation. Of note, Asiatic acid reduces NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome. The findings indicated that Asiatic acid might be an effective candidate for pulmonary fibrosis and inflammation treatment.
Asunto(s)
Bleomicina/farmacología , Inflamación/tratamiento farmacológico , Triterpenos Pentacíclicos/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Líquido del Lavado Bronquioalveolar/citología , Línea Celular , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Citocinas/metabolismo , Humanos , Inflamación/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Oxidative stress has been reported to play an important role in children with primary nephrotic syndrome (PNS). However, the results of previous studies are controversial. METHODS: Forty children with steroid-sensitive nephrotic syndrome (SSNS) and 20 age- and sex-matched healthy controls were enrolled. Patients were followed-up for 12-18 months and divided into three subgroups: frequent relapse (n = 10), non-frequent relapse (n = 12), and non-relapse (n = 18). The plasma levels of advanced oxidation protein products (AOPP), malondialdehyde (MDA), and superoxide dismutase (SOD) were tested in controls and patient group at first presentation and after 4 weeks of steroid treatment. RESULTS: Patients had higher AOPP and MDA levels but lower SOD compared with controls. AOPP levels were significantly higher in the frequent relapse subgroup compared with the non-frequent relapse and non-relapse subgroups, respectively. No significant differences were found in the plasma levels of MDA and SOD among the three subgroups. AOPP >87.55 µmol/l before steroid treatment and AOPP >78.5 µmol/l after 4-week steroid treatment were positively correlated with the relapse frequency in patients with SSNS. CONCLUSIONS: Children with SSNS have oxidative stress. The plasma levels of AOPP before and after 4-week steroid treatment may predict whether patients with SSNS will relapse frequently.
Asunto(s)
Productos Avanzados de Oxidación de Proteínas/sangre , Síndrome Nefrótico/sangre , Síndrome Nefrótico/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Esteroides/uso terapéutico , Adolescente , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Malondialdehído/sangre , Síndrome Nefrótico/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Superóxido Dismutasa/sangre , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Catheter-related infection (CRI) is associated with increased all-cause mortality and morbidity in hemodialysis patients and may be reduced by using antimicrobial lock solutions. But the safety of long-term use of antimicrobial lock still needs to be defined. METHODS: Patients with a new inserted permanent tunneled cuffed hemodialysis catheter were randomly assigned to an antibiotic lock solution of gentamicin (4 mg/ml) heparin (G group) or heparin alone (H group). RESULTS: A total of 140 patients were enrolled in this study. CRI rates were 0.06/1,000 catheter-days for the G group versus 0.67 in the H group (p = 0.014). The risk of CRI was 10.54 higher in patients with a heparin-alone locked catheter (p = 0.025) than that with gentamicin. The serum-measured gentamicin levels were very low. CONCLUSIONS: Gentamicin lock solution reduces CRI and improves catheter survival rates in hemodialysis patients. It is relatively safe in strictly catheter-restricted antibiotic lock solution therapy.
Asunto(s)
Infecciones Relacionadas con Catéteres/prevención & control , Catéteres de Permanencia/efectos adversos , Gentamicinas/administración & dosificación , Heparina/administración & dosificación , Diálisis Renal/métodos , Adulto , Anciano , Femenino , Gentamicinas/sangre , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Diálisis Renal/instrumentaciónRESUMEN
OBJECTIVE: To investigate the serotonin reuptake transporter (SERT) genetic polymorphisms in the 5-hydroxytryptamine (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 among Chinese people, and their relationship to the pathogenesis of irritable bowel syndrome (IBS); and to investigate the impact of SERT genotypes on the efficacy of 5-HT(4) receptor agonist tegaserod in constipation predominant type (C-IBS) patients. METHODS: PCR was used to detect the genetic polymorphisms in 87 patients with IBS confirmed with Rome II criteria and 96 healthy subjects, then 41 C-IBS patients received tegaserod 6 mg twice daily for 4 weeks. Each patient recorded his or her symptoms in a diary. Efficacy was assessed by patient's experience of overall symptoms and severity of constipation before and after the treatment. RESULTS: The 5-HTTLPR genotypes frequencies were: S/S 52.9%, S/L 31.0%, L/L 16.1% in IBS patients; and S/S 57.3%, S/L 35.4%, L/L 7.3% in control. VNTRs genotypes were STin2.10/10: 2.3%, STin2.12/10: 17.2%, STin2.12/12: 80.5% in IBS patients; and STin2.10/10: 2.1%, STin2.12/10: 11.4%, STin2.12/12: 86.5% in control. There was no significant difference in the two genotypes frequencies between IBS and control groups (P > 0.05). However, the allele frequency of the L/L genotype was significantly higher in the C-IBS group than in control (25.0% vs 7.3%, P < 0.05). The clinical responder rates of tegaserod in S/S (85.0%) and S/L (70.0%) genotypes differed significantly from that (36.4%) in L/L genotype (P < 0.05). The scores of Subject's Global Assessment of relief after treatment were: S/S 1.35 +/- 0.81, S/L 1.70 +/- 0.95 vs L/L 2.27 +/- 0.45 (P < 0.05). All other variables for assessment of efficacy including stool frequency, stool consistency and sensation of bowel complete evacuation in L/L genotype were also significantly poorer than those in S/S and S/L (P < 0.05). CONCLUSIONS: 5-HTTLPR and VNTRs genetic polymorphisms existed in Chinese people. In general, the genotypes were not involved in the pathogenesis of IBS. However people with L/L genotype were vulnerable for development of C-IBS. The 5-HTTLPR genetic polymorphisms influenced the efficacy of tegaserod treatment in C-IBS patients with L/L being poorer than S/S and S/L genotypes.