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Infection with drug-resistant bacteria poses a significant threat to human health. Judicious use of antibiotics could reduce the likelihood of bacterial resistance, which can be evaluated through antibiotic susceptibility testing (AST). This paper focuses on the application of a needle-like nanocapillary tip filled with chitosan (CS)/polyethylene pyrrolidone (PVP) hydrogel based on its specific pH-sensitive properties. The gel-filled nanocapillary has the potential to be used for electrical pH detection with a sensitivity of 3.06 nA/pH and a linear range from 7.3 to 4.3. Such sensitivity for pH measurement could be extended for monitoring of bacterial (such as Escherichia coli and Streptococcus salivarius) growth because of the relationship between pH and bacterial growth. Bacterial growth curves obtained using the hydrogel-filled nanocapillary showed good agreement with the OD600 method. Moreover, this device could be applied for rapid AST for tetracycline and norfloxacin on E. coli with minimum inhibitory concentrations of 2 and 0.125 µg/mL, respectively. This study expands the application of the hydrogel-based nanocapillary for bacterial research by monitoring changes in pH values.
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Antibacterianos , Quitosano , Escherichia coli , Hidrogeles , Pruebas de Sensibilidad Microbiana , Quitosano/química , Quitosano/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Hidrogeles/química , Hidrogeles/farmacología , Concentración de Iones de Hidrógeno , Povidona/química , Povidona/farmacologíaRESUMEN
Understanding the fundamentals and applications of chirality relies substantially on the amplification of chirality through hierarchical assemblies involving various weak interactions. However, a notable challenge remains for metal clusters chiral assembly driven by halogen bonding, despite their promising applications in lighting, catalysis, and biomedicine. Here, we used halogen bonding-driven assembly to achieve a hierarchical degree of achiral emissive Au2Cu2 clusters. From single crystals to one-dimensional ribbons and then to helixes, the morphologies were primarily modulated by intermolecular halogen bonding that evoked by achiral or/and chiral iodofluorobenzene (IFBs) molecules. Concomitantly, the luminescence and circularly polarized luminescence (CPL) changed a lot, ultimately leading to a substantial increase in the luminescence dissymmetry g-factor (glum) of 0.036 in the supramolecular helix. This work opens an avenue for hierarchical assemblies using predesigned metal clusters as building blocks though directional halogen bonding. This achievement marks a noteworthy advancement in the field of nanosized inorganic functional blocks.
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Metallophilic interactions, which are ubiquitous among d10 metal complexes with linear coordination geometries, can direct one-dimensional assembly. However, the ability of these interactions to manipulate chirality at the hierarchical level largely remains unknown. In this work, we unveiled the role of Au···Cu metallophilic interactions in directing the chirality of multicomponent assemblies. N-heterocyclic carbene-Au(I) complexes bearing amino acid residues formed chiral co-assemblies with [CuI2]- anions via Au···Cu interactions. These metallophilic interactions changed the molecular packing modes of the co-assembled nanoarchitectures from lamellar to columnar chiral packing. This transformation initiated the emergence, inversion, and evolution of supramolecular chirality, thereby affording helical superstructures, depending on the geometry of building units. In addition, the Au···Cu interactions altered the luminescence properties and induced the emergence and amplification of circularly polarized luminescence. This work, for the first time, revealed the role of Au···Cu metallophilic interactions in modulating supramolecular chirality, paving the way for the construction of functional chiroptical materials based on d10 metal complexes.
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Objective: In order to analyze the clinical characteristics of epileptic seizures in children with acute lymphoblastic leukemia (ALL) during treatment. Methods: The clinical and imaging data of children diagnosed as ALL with epilepsy seizures from January 2013 to December 2020 were retrospectively analyzed. Results: A total of 2217 children with ALL were admitted during the study, of whom 229 (10.33%) had epileptic seizures after ALL treatment. Among them, 45 (19.65%) were in the high-risk group and 184 (80.35%) were in the low-risk group. Epileptic seizures mainly occurred in the induction remission period (24.02%), maintenance treatment period (25.33%) and after bone marrow transplantation (21.40%). The common causes were MTX-related demyelinating encephalopathy (34.06%) and reversible posterior encephalopathy syndrome (PRES) (25.3%). The first symptom was mainly convulsion (34.50%). The first attack had a comprehensive attack and partial attack. Most patients stop themselves. 30 cases (13.10%) had acute recurrence of epilepsy (recurrence within 3 months after the first attack), and 49 cases (25.76%) had neurological dysfunction after follow-up. 36 cases developed symptomatic epilepsy. Among the 130 children who completed the follow-up, 78 (60.00%) had no obvious neurological sequelae, and 52 (40.0%) had neurological sequelae. Among the 52 cases, there were 34 cases of mild sequelae and 18 cases of severe sequelae, including 8 cases of epilepsy combined with cognitive impairment. Conclusion: Epileptic seizure is a common neurological complication during ALL treatment. The etiology and associated manifestations of the first epileptic seizure are diverse. Early neuroimaging and EEG examination are helpful for early diagnosis and treatment.
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BACKGROUND: Short stature is defined as height below 2 standard deviations of the population with the same age, gender. This study is aimed to assess the characteristics of body composition in preschool children with short stature. METHODS: Anthropometric measurements and body composition were assessed in 68 preschool children aged 3 to 6 years old with short stature and 68 normal controls matched on age and gender. Height, weight and body composition (total body water, protein, minerals, body fat mass, fat-free mass, soft lean mass, skeletal muscle mass, and bone mineral contents) in the two groups were measured and compared. RESULTS: The total body water, protein, minerals, body fat mass, fat-free mass, soft lean mass, skeletal muscle mass, and bone mineral contents were lower in preschool children with short stature than controls (P < 0.05). Body mass index and fat mass index did not differ between groups. Fat-free mass index was significantly lower in short stature group than controls (t = 2.17, P = 0.03). Linear regression analysis showed that there was a positive correlation between height and fat-free mass index [ß, 1.99 (0.59, 3.39), P = 0.01], a negative correlation between height and body fat percentage [ß, - 0.20 (- 0.38, - 0.01), P = 0.04]. The proportions of fat-free mass in the upper limbs were significantly lower (Right,t = - 2.78,Left t = - 2.76, P < 0.05, respectively) in short stature, although body fat distribution was not. CONCLUSIONS: The fat-free mass such as protein and bone minerals is lower in preschool children with short stature, suggesting the monitoring of fat-free mass for early identification and intervention.
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Composición Corporal , Estatura , Composición Corporal/fisiología , Estatura/fisiología , Índice de Masa Corporal , Densidad Ósea , Estudios de Casos y Controles , Niño , Preescolar , HumanosRESUMEN
The application of plastic film mulching can greatly improve dryland productivity, while the release of toxic phthalate esters (PAEs) from the plastic film has generated concern. This study investigated the effects of mulched plastic film and residual plastic film on the PAE concentrations in the soil-crop system and assessed the risks to people eating crop products. The PAEs concentration in the 0-25 cm soil layer of plastic mulched farmland was 0.45-0.81 mg/kg, while the average PAEs concentration of 0.37-0.73 mg/kg in non-mulched farmland decreased by 19%. The PAEs concentration in mulched soil reached the highest in July, being 0.80-0.84 mg/kg, while in the non-mulched soil, the PAEs also appeared and gradually decreased from May at 0.62-0.74 mg/kg to October, and the PAEs concentrations were almost the same in the mulched and non-mulched soils at the harvest time in October at 0.37-0.44 mg/kg. With the amounts of residual film in farmland increasing from 0 kg/ha to 2700 kg/ha (equivalent to the total amount of residual film after 60 years of continuous plastic film mulching), the PAEs concentrations were no significant changes, being 0.54-0.93 mg/kg. Maize (Zea mays L.) roots could absorb and accumulate PAEs, and the bio-concentration factor (BCF) was 1.6-2.3, and the average PAEs concentrations in stems, leaves, and grains were 79%-80% of those in roots at 0.77-1.47 mg/kg. For the ingestion of maize grains or potato (Solanum tuberosum L.) tubers grown in plastic film mulched farmland or farmland containing residual film of 450-2700 kg/ha, the hazard index (HI) were less than 1, the carcinogenic risks (CRs) were 2.5 × 10-7-2.2 × 10-6, and the estrogenic equivalences were 6.17-17.73 ng E2/kg. This study provides important data for the risk management of PAEs in farmlands.
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Ácidos Ftálicos , Contaminantes del Suelo , Agricultura , China , Ésteres , Humanos , Plásticos , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisisRESUMEN
BACKGROUND: Some long non-coding RNAs (lncRNAs) have been found to contribute to cisplatin resistance. Here, we identified a novel lncRNA that was downregulated in cisplatin-resistant to ovarian cancer (OC) cells and aimed to examine the contribution of LINC01508 to cisplatin resistance in OC cells. METHODS: Differences in the lncRNA expression profile between OV2008 and C13K cells were assessed by lncRNA expression microarray. The expression of LINC01508 in ovarian epithelial cells, four OC cells, and OC, benign ovary tumor and normal ovary, cisplatin-resistant and non-resistant OC specimens were evaluated by quantitative real-time polymerase chain reaction (qPCR). The role of LINC01508 in OC cisplatin-resistant was evaluated by cell counting kit-8 (CCK-8), flow cytometry, colony formation, wound healing, Transwell, and tumor growth inhibition study in vivo. The clinical associations of LINC01508 in OC were evaluated using correlation analysis. The effects of verteporfin (VP) on cisplatin were explored to reveal the function of the hippo-YAP pathway on the cisplatin tolerance of C13K. RESULTS: LINC01508 was downregulated in cisplatin-resistant OC cells and platinum-resistant OC tissue (p<0.01). LINC01508 downregulation was correlated with tumor size, residual tumor, and platinum resistance. The overexpression of LINC01508 improves in vitro and in vivo sensitivity to cisplatin while predicts the poor overall survival which need further follow-up research. The increased level of LINC01508 could suppress the cisplatin resistance of OC cells through the inhibition of the hippo-YAP pathway. CONCLUSIONS: The study proposes that dysregulation of LINC01508 expression results in resistance of OC to cisplatin through the inhibition of the hippo-YAP pathway.
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Cisplatino , Resistencia a Antineoplásicos , Neoplasias Ováricas , ARN Largo no Codificante/genética , Apoptosis , Línea Celular Tumoral , Cisplatino/farmacología , Regulación hacia Abajo , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Vía de Señalización Hippo , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de SeñalRESUMEN
Phthalate esters (PAEs) are potentially dangerous chemicals in plastic film mulched fields; however, few studies have investigated how to reduce their concentrations in plastic film and soil. In this study, the effects of solar radiation, mechanical tension, and soil burial on PAEs concentrations in polyethylene (PE) film and degradable film were investigated, and the half-lives of di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) in soil also studied. PAEs concentrations in polyethylene films were about twice those in the degradable films; however, PAEs concentrations in all experimental films were similar after 1-year of field exposure. Mechanical tension had no effect on the PAEs concentrations of polyethylene films, but increased the detected concentrations of PAEs in degradable films by 34%-120%. After 4-years of burial, the PAEs concentrations in films decreased by 79.2%-98.0%, and mechanical tension promoted the reductions. However, there was little difference in PAEs concentrations between the buried soils with and without films, indicating the released PAEs reduced quickly in soil. Also, the half-lives of DBP and DEHP were 2.4-4.6 days and 18.5-41.4 days, respectively. Overall, the results presented herein provide reasonable approaches to reduce the concentrations of PAEs in plastic films and soils.
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The widespread use of polyethylene (PE) mulch films has led to a significant accumulation of plastic waste in agricultural soils. The biodegradation of plastic waste by microorganisms promises to provide a cost-effective and environmentally-friendly alternative for mitigating soil plastic pollution. A large number of microorganisms capable of degrading PE have been reported, but degradation may be further enhanced by the cooperative activity of multiple microbial species. Here, two novel strains of Arthrobacter sp. and Streptomyces sp. were isolated from agricultural soils and shown to grow with PE film as a sole carbon source. Arthrobacter sp. mainly grew in the suspension phase of the culture, and Streptomyces sp. formed substantial biofilms on the surface of the PE film, indicating that these strains were of different metabolic types and occupied different microenvironments with contrasting nutritional access. Individual strains were able to degrade the PE film to some extent in a 90-day inoculation experiment, as indicated by decreased hydrophobicity, increased carbonyl index and CO2 evolution, and the formation of biofilms on the film surface. However, a consortium of both strains had a much greater effect on these degradation properties. Together, these results provide new insights into the mechanisms of PE biodegradation by a microbial consortium composed of different types of microbes with possible metabolic complementarities.
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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is seriously affecting the general health due to its high prevalence and associated risk of liver-related consequences and extrahepatic chronic complications. New drugs are urgently needed for the treatment of NAFLD. The purpose of this meta-analysis is to assess the efficacy of incretin-based therapies in patients with NAFLD. METHODS: We will search 4 databases for relative studies: PubMed, Cochrane Library, Embase, and Web of Science databases and identified all reports of randomized controlled trials (RCTs) published from inception to July 2020. Two authors will independently scan the searched articles, extract the data from included articles, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Fixed-effects model or random-effects model will be used to calculate pooled estimates of weighted mean difference (WMD) with 95% confidence intervals (CIs) or odds ratio (OR) with 95% CIs. RESULTS: This systematic review aims to examine the effect of incretin-based therapies on liver histology, liver fat content, liver enzymes, and adverse events in patients with NAFLD. CONCLUSIONS: These findings will provide guidance to clinicians and patients on the use of incretin-based therapies for NAFLD.
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Incretinas/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Humanos , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
OBJECTIVES: To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS: In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to < 0.0001). Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively. CONCLUSION: FibroTouch has a high success rate and good reliability in staging liver fibrosis in patients with CHB.
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Diagnóstico por Imagen de Elasticidad , Hepatitis B Crónica , Adulto , Biopsia , Hepatitis B Crónica/patología , Humanos , Hígado/patología , Cirrosis Hepática/patología , Estudios Prospectivos , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis, which is considered as the hepatic manifestation of metabolic syndrome, has a great prevalence all over the world. New drugs are urgently needed for the treatment of NAFLD. This review will be to assess the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on liver-related outcomes (liver histology and liver enzymes) in patients with NAFLD. METHODS: We will search 5 databases for relative studies: Medline, the Cochrane Library, EMBASE, Web of Science, and ClinicalTrials.gov and identified all reports of randomized controlled trials published prior to July 2020. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Fixed-effects model or random-effects model will be used to calculate pooled estimates of weighted mean difference with 95% confidence intervals. RESULTS: This systematic review aims to examine the effect of n-3 PUFAs on liver histology and liver enzymes in patients with NAFLD. CONCLUSIONS: These findings will provide guidance to clinicians and patients on the use of n-3 PUFAs for NAFLD. ETHICS AND DISSEMINATION: This study is a protocol for a systematic review of n-3 PUFAs as a treatment of NAFLD patients. This review will be published in a journal and disseminated in print by peer-review. SYSTEMATIC REVIEW REGISTRATION: INPLASY202050008.
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Ácidos Grasos Omega-3/uso terapéutico , Metaanálisis como Asunto , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Ácidos Grasos Omega-3/efectos adversos , Humanos , Hígado/enzimología , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/enzimología , Enfermedad del Hígado Graso no Alcohólico/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Hepatic fibrosis is a pathophysiological process, which causes excessive extracellular matrix (ECM) deposition resulting from persistent liver damage. Myofibroblasts are the core cells that produce ECM. It is known that epithelial-mesenchymal transition (EMT) is not a simple transition of cells from the epithelial to mesenchymal state. Instead, it is a process, in which epithelial cells temporarily lose cell polarity, transform into interstitial cell-like morphology, and acquire migration ability. Hepatocytes, hepatic stellate cells, and bile duct cells are the types of intrahepatic cells found in the liver. They can be transformed into myofibroblasts via EMT and play important roles in the development of hepatic fibrosis through a maze of regulations involving various pathways. The aim of the present study is to explore the relationship between the relevant regulatory factors and the EMT signaling pathways in the various intrahepatic cells.
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Transdiferenciación Celular , Transición Epitelial-Mesenquimal , Cirrosis Hepática/patología , Hígado/patología , Animales , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/patología , Linaje de la Célula , Fibrosis , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patología , Transducción de SeñalRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in reproductive-aged women. In addition to the reproductive consequences, PCOS is also characterized by a metabolic disorder, which may play a part in the etiology of anovulation and has important implications for long-term health as well. Vitamin D deficiency is prevalent in PCOS and there is a close relationship between metabolic dysfunction and vitamin D status in women with PCOS. The purpose of this systematic analysis is to evaluate the effect of vitamin D supplementation on serum lipid profiles in patients with PCOS. METHODS: We will search five databases for relative studies: Medline, the Cochrane Library, EMBASE, Web of Science, and ClinicalTrials.gov and identified all reports of randomized controlled trials published prior to July 2020. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Fixed-effects model or random-effects model was used to calculate pooled estimates of weighted mean difference (WMD) with 95% confidence intervals. RESULTS: This review will be to assess the effect of vitamin D supplementation on serum lipid profiles in patients with PCOS. The results of the study will be published in a scientific journal after peer-review. CONCLUSIONS: These findings will provide guidance to clinicians and patients on the use of vitamin D for PCOS with dyslipidemia. ETHICS AND DISSEMINATION: This study is a protocol for a systematic review of vitamin D as a treatment of dyslipidemia in PCOS patients. SYSTEMATIC REVIEW REGISTRATION: INPLASY202050007.
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Dislipidemias/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones , Vitamina D/administración & dosificación , Vitaminas/administración & dosificación , Dislipidemias/sangre , Dislipidemias/complicaciones , Femenino , Humanos , Metaanálisis como Asunto , Síndrome del Ovario Poliquístico/sangre , Revisiones Sistemáticas como Asunto , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
The aim of this paper was to investigate the effect and mechanism of paeonol on peritoneal macrophage M1 polarization in mice, explore whether the intervention action is related to the down-regulation of miR-155 and the inhibition of downstream JAK1-STAT1 pathway, and provide a new idea for the molecular mechanism of paeonol against atherosclerosis(AS). Lipopolysaccharide(LPS) and interferon-γ(IFN-γ) were used to stimulate macrophages for 24 hours to establish the M1 polarization model, and paeonol was given 24 hours before co-stimulation to provide a pre-protective effect on cells. CCK-8 assay was used to detect the cells damage induced by LPS and IFN-γ co-stimulation; flow cytometry was used to detect the expression of M1 surface markers F4/80 and CD86. ELISA was used to detect the secretion of interleukin 6(IL-6) and tumor necrosis factor-α(TNF-α) in supernatant. RT-qPCR was used to detect the expression of miR-155, and Western blot was used to detect the protein expression at JAK1-STAT1-SOCS1 pathway. The results showed that LPS and IFN-γ had no obvious damage to the cells at the optimal concentration, but they induced macrophages polarized to M1, resulted in high expression of M1 type marker factors F4/80 and CD86 on the cell surface, and increased secretion of IL-6 and TNF-α on the cell surface(P<0.05 or P<0.01). Paeonol significantly reduced the LPS and IFN-γ-induced high expression of F4/80 and CD86, the secretion of inflammatory factors IL-6 and TNF-α(P<0.05 or P<0.01), decreased the expression level of miR-155, significantly down-regulated the protein phosphorylation level of JAK1-STAT1 and up-regulated the protein expression of SOCS1(P<0.01) in RAW264.7 cells. The results showed that paeonol could inhibit M1 polarization of macrophages by down-regulating cell surface marker factors and inflammatory factors secreted by cells, which may be related to the down-regulation of miR-155 expression and the inhibition JAK1-STAT1 pathway activation.
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Activación de Macrófagos , MicroARNs , Acetofenonas , Animales , Macrófagos , Ratones , Factor de Transcripción STAT1RESUMEN
OBJECTIVE: Recurrent seizures can cause brain damage and affect the cognitive outcome, particularly in developing children. We aimed to determine the effects of recurrent seizures on the expression of gamma-aminobutyric acid A receptor (GABAAR) α1 and γ2 subunit and neurodevelopment in immature rats. The role of the GABAAR agonist clonazepam and antagonist/partial agonist flumazenil in seizure-induced brain injury was also studied. METHODS: Recurrent seizures (RS) were induced by flurothyl inhalation in immature rats. Clonazepam (CZP) and flumazenil (FMZ) were administered to modulate GABAAR subunit expression in different experimental groups. Neurobehavioral changes and GABAAR α1 and γ2 subunit expression were studied. RESULTS: Inhalation of flurothyl for five days triggered RS and caused reflex delay, inability to adapt to new environments in adulthood, and deficits in long-term learning and memory ability in rats. Down-regulation of GABAAR α1 and γ2 subunits occurred after seizure onset and persisted for a long time. CZP treatment decreased the expression of GABAAR α1 and γ2 subunits and delayed neurodevelopment of the immature rats, whereas FMZ did not show any significant effects. CONCLUSIONS: Changes in GABAAR α1 and γ2 subunit expression and neurodevelopment were related to recurrent seizures and administration of CZP. Thus, GABAAR α1 and γ2 subunits likely play a significant role in the development of immature rats with RS and provide a novel target for therapeutic intervention.
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Lesiones Encefálicas/tratamiento farmacológico , Epilepsia Generalizada/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Receptores de GABA-A/metabolismo , Convulsiones/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Lesiones Encefálicas/metabolismo , Epilepsia Generalizada/metabolismo , Femenino , Flurotilo/farmacología , Hipocampo/metabolismo , Masculino , Ratas Wistar , Convulsiones/tratamiento farmacológico , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
BACKGROUND: Several reports indicated that the expression of Yes-associated protein (YAP) was associated with multi-drug resistance. Acidic microenvironment increased by the overexpression of vacuolar-ATPase (V-ATPase) was also observed in tumor growth and drug resistance. We hypothesize that proton pump inhibitors (PPIs), currently used in the anti-acid treatment of peptic disease, could inhibit the acidification of the tumor microenvironment and increase the sensitivity of tumor cells to cytotoxic agents. Thus, our objective is to explore the reversal of drug resistance by the inhibition of YAP through specific PPIs in the epithelial ovarian carcinoma (EOC) cells. . RESULTS: We found that V-ATPase D1 was a positive regulator of YAP. Sub-lethal doses of the proton pump inhibitor esomeprazole (EMSO) in combination with paclitaxel (PTX) increased the PTX sensitivity in PTX-resistant EOC cells, as compared to PTX single treatments by inhibiting YAP and reserving pH gradient created by the V-ATPase D1. Moreover, sub-lethal doses of EMSO combined with PTX decreased autophagy and improved caspases independent apoptosis of PTX-resistant EOC cells. CONCLUSIONS: These results suggested that sub-lethal doses of esomeprazole reverse YAP-mediated PTX resistance through the inhibiting of both YAP expression and acidic tumor microenvironment created by the V-ATPase D1. Therefore, we think the use of PPIs represents a promising strategy to improve the effectiveness of anti-EOC.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/farmacología , Inhibidores de la Bomba de Protones/uso terapéutico , Factores de Transcripción/metabolismo , Carcinoma Epitelial de Ovario/metabolismo , Línea Celular Tumoral , Esomeprazol/uso terapéutico , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Microambiente Tumoral/efectos de los fármacos , ATPasas de Translocación de Protón Vacuolares/metabolismo , Proteínas Señalizadoras YAPRESUMEN
Hematopoietic stem cells (HSCs) aging is associated with hematopoietic dysfunction and diseases. Our previous study showed that lead exposure induced a functional decline in HSCs. Allicin, a chemical extracted from the garlic (Allium sativum L.), has been reported to have antioxidative and anti-inflammatory effects. However, the biological activities of allicin on lead-induced toxicity, especially in the hematopoietic system, remain unclear. Here, we found that lead exposure elicited aging phenotypes in HSCs, including perturbed cell quiescence, disabled self-renewal function and colony-forming ability, and myeloid-biased differentiation, all of which contributed to significant hematopoietic disorders in mice. Intragastric administration of allicin substantially ameliorated lead-induced HSCs aging phenotypes in vivo Lead exposure induced a peroxide condition in HSCs leading to DNA damage, which reduced expression of the glycolytic enzyme pyruvate kinase M2 isoform (PKM2), a phenotype which was significantly ameliorated by allicin treatment. These findings suggested that allicin alleviated lead-induced HSCs aging by up-regulating PKM2 expression; thus, it could be a natural herb for preventing lead toxicity.
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Envejecimiento/genética , Células Madre Hematopoyéticas/efectos de los fármacos , Piruvato Quinasa/genética , Ácidos Sulfínicos/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/patología , Animales , Antioxidantes/farmacología , Proliferación Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Disulfuros , Regulación del Desarrollo de la Expresión Génica , Células Madre Hematopoyéticas/metabolismo , Humanos , Ratones , Isoformas de Proteínas/genéticaRESUMEN
Although high mortality of lung cancer is greatly due to distant metastasis, the mechanism of this metastasis remains unclear. Here, we investigate in lung cancer that SOX30 is sharply under-expressed in metastatic tumors compared with non-metastatic tumors, and suppresses plenty of metastasis related processes or pathways. SOX30 strongly inhibits tumor cell metastasis in vitro and in vivo. Sox30 deficiency promotes lung metastasis in Sox30-/- mice and this uncontrollable lung-metastasis is re-inhibited upon Sox30 re-expression. Mechanistically, SOX30 diminishes Wnt-signaling via directly transcriptional repressing ß-catenin or interacting with ß-catenin to compete with TCF for binding to ß-catenin. The carboxyl-terminus of SOX30 is required for attenuating ß-catenin transcriptional activity, whereas the amino-terminus of SOX30 is required for its interaction with ß-catenin protein. Enhance of ß-catenin attenuates the anti-metastatic role of SOX30. Moreover, Sox30 deficiency promotes tumor metastasis and reduces survival of mice. In addition, nuclear SOX30 expression is closely associated with metastasis and represents a favorable independent prognostic biomarker of lung cancer patients. Altogether, these results highlight an important role and mechanism of SOX30 in lung cancer metastasis, providing a potential therapeutic target for anti-metastasis.
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Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/metabolismo , Factores de Transcripción SOX/metabolismo , Transcripción Genética , Proteínas Supresoras de Tumor/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismo , Células A549 , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Metástasis de la Neoplasia , Factores de Transcripción SOX/genética , Proteínas Supresoras de Tumor/genética , beta Catenina/genéticaRESUMEN
To evaluate the soil quality in the main cotton growing regions of Xinjiang, 11 soil quality indices were measured in representative locations: Hami, Bole, Changji, Shihezi, Aksu, Kashgar and Kuitun. The indices included soil pH, salt, organic matter, total N, available P and available K for soil physicochemical properties, and Cr, Cu, Zn, As, and Pb for soil heavy metal pollution. Based on these indices, a comprehensive soil quality index (SQI) was developed to analyze the soil quality in the cotton fields of Xinjiang. The results showed that the soils in Xinjiang's cotton fields were alkaline, with an average pH of 7.87. The soils were mildly saline, with an average salt content of 3.44 g·kg-1. Soil organic matter and total N concentrations were generally low, whereas available P and available K concentrations were relatively high. Soil available P concentrations were significantly higher than that of the second national soil survey, whereas soil pH, salt content, organic matter, and total N were less. Soil available K was greater in some regions but lower in others compared with the second national soil survey. The average heavy metal concentrations were as follows: Cr, 45.88 mg·kg-1; Cu, 40.66 mg·kg-1; Zn, 68.30 mg·kg-1; As, 12.88 mg·kg-1; and Pb, 16.68 mg·kg-1. These values were all below the national standards. However, the Cu, Zn, and As concentrations were greater than the background values in Xinjiang, indicating the accumulation of those elements in the soils. When the Nemerow comprehensive pollution index (PN) of heavy metals was less than 0.5, the comprehensive soil quality improved as the soil physicochemical properties improved. Soil organic matter, total N, Cu, Zn, As and Pb were the main variables affecting soil quality in the main cotton cropping regions of Xinjiang. The cotton growing areas in Xinjiang generally had medium soil quality. Changji and Kuitun had the highest SQI (0.52) whereas Aksu had the lowest value (0.31). Soil quality was generally highest in northern Xinjiang, followed by western area, and then southern area.