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1.
Small ; : e2400468, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38516967

RESUMEN

Alloy-type antimony (Sb) and conversion-type molybdenum (Mo) anodes have attracted extensive attention in the application of lithium-ion batteries (LIBs) owing to their high theoretical capacity. In this study, Sb2MoO6 nanowires are prepared via a hydrothermal method and assessed their thermal behavior upon heat treatment, observing an intriguing transformation from nanowire to Sb2O3/MoOx nanosheets. To enhance structure stability, the Sb2MoO6 nanowires are successfully coated with a polyphosphazene layer (referred to as PZS@Sb2MoO6), which not only preserved the nanowires form but also yielded N/S co-doped carbon-coated SbPO4/MoOx (NS-C@SbPO4/MoOx) nanowires following annealing in an inert environment. This composite benefits from the stable PO4 3- anion that serve as a buffer against volume expansion and form a Li3PO4 matrix during cycling, both of which substantially bolster ion transport and cycle endurance. Doping with heteroatoms introduces numerous oxygen vacancies, augmenting the number of electrochemically active sites, and carbon integration considerably enhances the electronic conductivity of the electrode and alleviates the volume-change-induced electrode pulverization. Employed as anode materials in LIBs, the NS-C@SbPO4/MoOx electrode exhibits remarkable cycling performance (449.8 mA h g-1 at 1000 mA g-1 over 700 cycles) along with superior rate capability (394.2 mA h g-1 at 2000 mA g-1).

2.
Acta Pharmacol Sin ; 45(6): 1252-1263, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38360931

RESUMEN

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.


Asunto(s)
Adenocarcinoma del Pulmón , Antineoplásicos , Neoplasias Pulmonares , Proteínas de Fusión Oncogénica , Compuestos Organofosforados , Inhibidores de Proteínas Quinasas , Pirimidinas , Humanos , Compuestos Organofosforados/uso terapéutico , Compuestos Organofosforados/farmacología , Pirimidinas/uso terapéutico , Pirimidinas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Animales , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Pronóstico , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Lactamas/uso terapéutico , Carbazoles/uso terapéutico , Carbazoles/farmacología , Sulfonas/uso terapéutico , Sulfonas/farmacología , Crizotinib/uso terapéutico , Crizotinib/farmacología , Línea Celular Tumoral , Piperidinas/uso terapéutico , Piperidinas/farmacología , Femenino , Ratones , Inflamación/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Pirazoles/uso terapéutico , Pirazoles/farmacología , Masculino , Quinasa de Linfoma Anaplásico/genética , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/metabolismo , Proliferación Celular/efectos de los fármacos , Mutación , Aminopiridinas/uso terapéutico , Aminopiridinas/farmacología
3.
J Cell Mol Med ; 27(13): 1820-1835, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37248957

RESUMEN

Inflammation and ferroptosis crosstalk complexly with immune microenvironment of hepatocellular carcinoma (HCC), thus affecting the efficacy of immunotherapy. Herein, our aim was to identify the inflammation-associated ferroptosis (IAF) biomarkers for contributing HCC. A total of 224 intersecting DEGs identified from different inflammation- and ferroptosis-subtypes were set as IAF genes. Seven of them including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 were used for construction of a risk model which classified HCC patients into two groups (high and low risk). HCC patients in the high-risk group exhibited shorter survival rate and higher immune score, and were predicted to have higher respond rate in immune checkpoint inhibition (ICI) therapy. Levels of the seven genes were significantly changed in HCC tissues in comparison to adjacent tissues. After inserting the gene expression into the risk model, we found that the risk model exhibited the higher diagnostic value for distinguish HCC tissues compared each single gene. Furthermore, HCC tissues from our research group with high-risk score exhibited more cases of microsatellite instability (MSI), heavier tumour mutational burden (TMB), higher expression level of PDL1 and cells with CD8. Knockdown of APOA5 reduced HCC cell proliferation combining with elevating inflammation and ferroptosis levels. In conclusion, we considered APOA5 maybe a novel target for suppressing HCC via simultaneously elevating inflammation and ferroptosis levels, and signature constructed by seven IAF genes including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 can act as a biomarker for optimising the diagnosis, prognosis evaluation and immunotherapy options in HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Ferroptosis/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Inmunoterapia , Inflamación/genética , Microambiente Tumoral/genética , Arildialquilfosfatasa
4.
Pak J Med Sci ; 39(6): 1584-1588, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37936757

RESUMEN

Objective: To investigate the correlations between APACHE-II score and pressure parameters of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) and their value in prognostic evaluation. Methods: This was a retrospective study. The clinical data of 79 patients with ARDS treated in Shengzhou Hospital of Traditional Chinese Medicine from April 2020 to April 2022 were analyzed retrospectively. According to whether their APACHE-II scores were higher than 15, they were divided into low score group (n= 20) and high score group (n= 59). The plateau pressure (Pplat), driving pressure(ΔP) and mean airway pressure (Pmean) were compared. The correlation between APACHE-II score and pressure parameters of mechanical ventilation was analyzed. Based on the follow-up of 28-d survival, their Pplat, ΔP, Pmean and APACHE-II scores were compared. The value of APACHE-II score and pressure parameters in the prognostic evaluation of ARDS patients was analyzed. Results: Pplat, ΔP and Pmean in the low score group were significantly lower than those in the high score group(P<0.05). Pplat, ΔP, Pmean and APACHE-II score in the survival group were significantly lower than those in the control group(P<0.05). APACHE-II score showed significantly positive correlations with Pplat, ΔP and Pmean. The AUC of Pmean, Pplat, ΔP and APACHE-II score in predicting the prognosis and diagnosis of ARDS patients was 0.761, 0.833, 0.754 and 0.832, respectively. Conclusion: APACHE-II score of ARDS patients shows significantly positive correlations with pressure parameters of mechanical ventilation, and has diagnostic value for the prognosis of ARDS patients.

5.
Acta Pharmacol Sin ; 43(4): 1013-1023, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34267347

RESUMEN

Hyperactive signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in human triple-negative breast cancer (TNBC) and gastric cancer, leading to uncontrolled tumor growth, resistance to chemotherapy, and poor prognosis. Thus, inhibition of STAT3 signaling is a promising therapeutic approach for both TNBC and gastric cancer, which have high incidences and mortality and limited effective therapeutic approaches. Here, we report a small molecule, WZ-2-033, capable of inhibiting STAT3 activation and dimerization and STAT3-related malignant transformation. We present in vitro evidence from surface plasmon resonance analysis that WZ-2-033 interacts with the STAT3 protein and from confocal imaging that WZ-2-033 disrupts HA-STAT3 and Flag-STAT3 dimerization in intact cells. WZ-2-033 suppresses STAT3-DNA-binding activity but has no effect on STAT5-DNA binding. WZ-2-033 inhibits the phosphorylation and nuclear accumulation of pY705-STAT3 and consequently suppresses STAT3-dependent transcriptional activity and the expression of STAT3 downstream genes. Moreover, WZ-2-033 significantly inhibited the proliferation, colony survival, migration, and invasion of TNBC cells and gastric cancer cells with aberrant STAT3 activation. Furthermore, administration of WZ-2-033 in vivo induced a significant antitumor response in mouse models of TNBC and gastric cancer that correlated with the inhibition of constitutively active STAT3 and the suppression of known STAT3 downstream genes. Thus, our study provides a novel STAT3 inhibitor with significant antitumor activity in human TNBC and gastric cancer harboring persistently active STAT3.


Asunto(s)
Neoplasias Gástricas , Neoplasias de la Mama Triple Negativas , Animales , Línea Celular Tumoral , Proliferación Celular , Xenoinjertos , Humanos , Ratones , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología
6.
J Nanobiotechnology ; 20(1): 405, 2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36064371

RESUMEN

BACKGROUND: Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown. RESULTS: NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis. CONCLUSIONS: The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury.


Asunto(s)
Insuficiencia Cardíaca , Lesiones Cardíacas , Nanopartículas , Sepsis , Animales , Insuficiencia Cardíaca/metabolismo , Hierro , Ratones , Miocardio/metabolismo , Sepsis/metabolismo
7.
BMC Surg ; 22(1): 216, 2022 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-35658934

RESUMEN

BACKGROUND: Pubic ramus fracture was an injury of anterior pelvic ring, the anterior pelvic ring plays an important role in maintaining the stability of the pelvis. The purpose of this study was to investigate the effect and indication of percutaneous retrograde pubic screw fixation assisted by hollow pedicle finder for pubic ramus fractures. METHODS: The clinical data of 68 patients with pubic ramus fracture treated with cannulated screw from March 2008 to March 2020 were retrospectively analyzed. According to the surgical methods, they were divided into traditional surgery group (32 cases in group A, with traditional retrograde pubic screw fixation) and modified surgery group (36 cases in group B, with percutaneous retrograde pubic screw fixation assisted by hollow open circuit device). Operation time, blood loss, incision length, screw length and complications were recorded and compared between the two groups. On the second day after surgery, the maximum fracture displacement over plain radiographs, entrance radiographs and exit radiographs of the pelvis was evaluated according to Matta criteria to evaluate the postoperative fracture reduction. Majeed score was used to evaluate the hip function at 12 months after surgery. RESULTS: The operations were successfully completed in both groups. The operation time, blood loss and incision length in group B were significantly less than those in group A (P < 0.05). There was no significant difference in screw length between the two groups (t = 0.797, P = 0.431). All patients were followed up for 8-38 months (mean 21.8 months). There were no vascular and nerve injury, fracture of internal fixator, screw entry into joint cavity, fracture nonunion and other complications in both groups. The fracture healing time of the two groups was 23.1 ± 2.1 weeks in group A while 22.7 ± 2.1 weeks in group B, respectively, and there was no statistical difference in the fracture healing time between the two groups (P > 0.05). In group A, there were 3 cases of incision infection, 1 case of incision fat liquefaction and 2 cases of lower extremity deep venous thrombosis, and the complication rate was 18.8%. There was only 1 case of lower extremity deep vein thrombosis in group B, and the complication rate was 2.8%, which was significantly lower than that in group A. The fracture in one case after surgery was found to be displaced in group A and no fracture was found in group B. There was no significant difference between the two groups in Matta imaging evaluation on the next day after surgery and Majeed function evaluation at 12 months after surgery (P > 0.05). CONCLUSION: Percutaneous retrograde pubic ramus screw fixation assisted by hollow pedicle finder is effective in the treatment of pelvic pubic ramus fracture. It has the advantages of less incision, shorter operation time, less blood loss and lower incidence of complications compared with traditional methods. However, correct surgical indications should be required when we apply this surgical method.


Asunto(s)
Fracturas Óseas , Huesos Pélvicos , Fracturas de la Columna Vertebral , Tornillos Óseos , Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Humanos , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
8.
Biotechnol Bioeng ; 118(12): 4643-4654, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34436762

RESUMEN

Enzyme engineering toward catalytic-tetrad residues usually results in activity loss. Unexpectedly, we found that a directed evolution campaign yielded a beneficial residue A100 in KmCR (a carbonyl reductase from Kluyveromyces marxianus ZJB14056), which is a residue of catalytic tetrad and conserved according to multiple sequence alignment. Inspired by this finding, we performed saturation mutagenesis on all the four residues of catalytic tetrad of KmCR. A number of variants with improved enzymatic activities were obtained. Among them, the variant KmCR_A100S exhibited increased catalytic efficiency (kcat /KM = 47.3 s-1 ·mM-1 ), improved stereoselectivity (from moderate selectivity (deP = 66.7%) to strict (S)-selectivity (deP > 99.5%)), and extended substrate scope, compared to those of KmCR_WT. In silico analysis showed that a relay system was rebuilt in KmCR via the beneficial residue S100. Furthermore, comparison of 11 protein engineering campaigns indicated that the beneficial position is easily overlooked due to the long distance (>10 Å) from ketone substrates. Since CRs share similar catalytic mechanism, the knowledge gained from this study has universal significance to CR engineering.


Asunto(s)
Oxidorreductasas de Alcohol , Dominio Catalítico/genética , Ingeniería de Proteínas/métodos , Oxidorreductasas de Alcohol/química , Oxidorreductasas de Alcohol/genética , Oxidorreductasas de Alcohol/metabolismo , Biocatálisis , Escherichia coli/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Kluyveromyces/enzimología , Kluyveromyces/genética , Simulación del Acoplamiento Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4488-4496, 2021 Sep.
Artículo en Zh | MEDLINE | ID: mdl-34581054

RESUMEN

This study focused on the ameliorative effects of gypenosides(GPS) on insulin sensitivity and inflammatory factors in rats with type 2 diabetes mellitus(T2 DM) and explored their possible molecular mechanisms. After the successful establishment of T2 DM model, diabetic rats were randomly divided into four groups, including model group, GPS groups(200, 100 mg·kg~(-1)) and metformin group(100 mg·kg~(-1)), with healthy rats serving as the control. After 6-week intragastric administration, fasting blood glucose(FBG) and oral glucose tolerance were examined. The levels of insulin, C-peptide, tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), interleukin-6(IL-6) and C-reactive protein(CRP) in serum were examined. Then the homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index(ISI) were calculated. The protein expression levels of phosphorylated insulin receptor substrate-1(p-IRS-1) and phosphorylated protein kinase B(p-Akt) in skeletal muscle were measured by Western blot, as well as those of phosphorylated inhibitor of nuclear factor-κB(NF-κB) kinase ß(p-IKKß), phosphorylated alpha inhibitor of NF-κB(p-IκBα) and phosphorylated p65 subunit of NF-κB(p-p65) in adipose tissue. The relative expression levels of glucose transporter 4(GLUT4) mRNA in skeletal muscle and NF-κB mRNA in adipose tissue were measured by qRT-PCR, and the morphological changes of pancreatic tissue were observed. Compared with the model group, the GPS groups witnessed significant decrease in FBG, marked amelioration of impaired oral glucose tolerance and significant increase in ISI. Further, the high-dose GPS group saw significantly reduced HOMA-IR, TNF-α, IL-1ß and CRP, significantly increased expression levels of p-IRS-1(Tyr), p-Akt and GLUT4, and markedly inhibited p-IRS-1(Ser), p-IKKß, p-IκBα, p-p65 and NF-κB. The concentration of CRP and the expression levels of p-IRS-1(Ser), p-IKKß, p-IκBα and NF-κB were remarkably reduced in the low-dose GPS group. However, GPS was found less effective in the regulation of serum insulin, C-peptide and IL-6 levels and the alleviation of pancreatic islet injury. The results indicated that GPS can reduce FBG and improve insulin sensitivity in diabetic rats possibly by regulating the NF-κB signaling pathway, inhibiting inflammation, and thereby regulating the expression of key proteins in the insulin signaling pathway.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Gynostemma , Insulina , FN-kappa B/genética , FN-kappa B/metabolismo , Extractos Vegetales , Ratas , Transducción de Señal
10.
Plant Cell Environ ; 43(11): 2699-2711, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32816352

RESUMEN

Abscisic acid (ABA) signaling is a vital plant signaling pathway for plant responses to stress conditions. ABA treatment can alter global gene expression patterns and cause significant phenotypic changes. We investigated the responses to ABA treatment during flowering in Arabidopsis thaliana. Dipping the flowers of CARK3 T-DNA mutants in ABA solution, led to less reduction of pollen fertility than in the wild type plants (Col-0). We demonstrated that PMEIL, a gene located downstream of CARK3, directly affects pollen fertility. Due to the close arrangement of CARK3 and PMEIL, CARK3 expression represses transcription of PMEIL in an ABA-dependent manner through transcriptional interference. Our study uncovers a molecular mechanism underlying ABA-mediated pollen sterility and provides an example of how transcriptional interference caused by close arrangement of genes may mediate stress responses during plant reproduction.


Asunto(s)
Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Reguladores del Crecimiento de las Plantas/fisiología , Infertilidad Vegetal/genética , Polen/genética , Proteínas Serina-Treonina Quinasas/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/fisiología , Orden Génico/genética , Orden Génico/fisiología , Germinación , Péptidos y Proteínas de Señalización Intracelular/fisiología , Reguladores del Crecimiento de las Plantas/metabolismo , Infertilidad Vegetal/fisiología , Polen/fisiología , Proteínas Serina-Treonina Quinasas/fisiología
11.
Electrophoresis ; 41(10-11): 902-908, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32090356

RESUMEN

The polyethyleneimine (PEI)-based antigen delivery system has been proved valuable for therapeutic vaccines. However, the previous bulk mixing method is not ideal to prepare PEI-base antigen- containing nanoparticles. The wide-size distribution and poor reproducibility limit its further application. In this research, we developed a microfluidic method to prepare nanopolyplexes on chips with Tesla structure to improve the fabrication. The structure and bioactivity of protein were not hampered by the shearing force in microfluidics. Comparison between physiochemical parameters suggested that the polyplexes prepared by Tesla chips were more uniform than those prepared by bulk mixing and non-Tesla chips. The reproducibility was improved obviously. The preparation was not influence much by the operating parameters such as flow rates, reagents concentration, and switching of inlets. The results indicated that it was a robust and reliable method. The data that were obtained from BMDC model demonstrated that the nanopolyplexes with optimal weight ratio had higher antigen cross-presentation efficiency than those in free antigen group. In conclusion, Tesla structured microfluidics offers a better method over bulk mixing in the preparation of PEI-based antigen-containing nanopolyplexes. It greatly expands the scope of our study and increases the potential of PEI-based antigen delivery system.


Asunto(s)
Portadores de Fármacos/química , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/métodos , Nanopartículas/química , Animales , Antígenos/química , Línea Celular , Masculino , Ratones , Ratones Endogámicos C57BL , Tamaño de la Partícula , Polietileneimina/química
13.
Arch Environ Contam Toxicol ; 75(3): 464-475, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30027305

RESUMEN

Mangrove wetlands are important coastal ecosystems in tropical and subtropical regions, and mangrove sediments and tissues often are the pollutant sinks due to their high organic matter contents. Polycyclic aromatic hydrocarbons (PAHs) in the mangrove sediments and tissues of nine species from three typical mangrove wetlands of Hainan Island were studied. The average concentration of PAHs in all mangrove tissues was 403 ng g-1 dw, with PAHs concentrations in leaf, branch, root, and fruit of 566, 335, 314, and 353 ng g-1 dw, respectively. PAHs levels were much higher in leaf than in other mangrove tissues, which may be caused partly by atmospheric deposition of PAHs. The dominant individual PAH compounds in mangrove tissues were phenanthrene (41.3%), fluoranthene (14.7%), and pyrene (11.4%), while in sediments were naphthalene (73.4%), phenanthrene (3.9%), and pyrene (3.6%), respectively. The biota-sediment accumulation factors of PAH congeners in the mangrove wetlands showed different patterns, with the most predominant of phenanthrene. The cycling of PAHs in the mangrove wetlands of Hainan Island also were estimated, and the results showed that the standing accumulation, the annual absorption, the annual net retention, the annual return, and the turnover period in all mangrove tissues of the community were 2228 µg m-2, 869 µg m-2 a-1, 206 µg m-2 a-1, 663 µg m-2 a-1, and 3.4 a, respectively. These results indicated that mangroves are playing an important role in retaining PAHs.


Asunto(s)
Plantas/química , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Químicos del Agua/análisis , Humedales , Biota , China , Ecosistema , Monitoreo del Ambiente/métodos , Sedimentos Geológicos , Fenantrenos/análisis , Fenantrenos/farmacocinética , Plantas/efectos de los fármacos , Plantas/metabolismo , Hidrocarburos Policíclicos Aromáticos/farmacocinética , Pirenos/análisis , Pirenos/farmacocinética , Contaminantes Químicos del Agua/farmacocinética
14.
Antimicrob Agents Chemother ; 60(10): 6207-15, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27503640

RESUMEN

EDP-239, a novel hepatitis C virus (HCV) inhibitor targeting nonstructural protein 5A (NS5A), has been investigated in vitro and in vivo EDP-239 is a potent, selective inhibitor with potency at picomolar to nanomolar concentrations against HCV genotypes 1 through 6. In the presence of human serum, the potency of EDP-239 was reduced by less than 4-fold. EDP-239 is additive to synergistic with other direct-acting antivirals (DAAs) or host-targeted antivirals (HTAs) in blocking HCV replication and suppresses the selection of resistance in vitro Furthermore, EDP-239 retains potency against known DAA- or HTA-resistant variants, with half-maximal effective concentrations (EC50s) equivalent to those for the wild type. In a phase I, single-ascending-dose, placebo-controlled clinical trial, EDP-239 demonstrated excellent pharmacokinetic properties that supported once daily dosing. A single 100-mg dose of EDP-239 resulted in reductions in HCV genotype 1a viral RNA of >3 log10 IU/ml within the first 48 h after dosing and reductions in genotype 1b viral RNA of >4-log10 IU/ml within 96 h. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.).


Asunto(s)
Antivirales/farmacología , Bencimidazoles/farmacología , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Valina/análogos & derivados , Proteínas no Estructurales Virales/antagonistas & inhibidores , Animales , Antivirales/farmacocinética , Carbamatos , Línea Celular , Evaluación Preclínica de Medicamentos/métodos , Farmacorresistencia Viral/efectos de los fármacos , Farmacorresistencia Viral/genética , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Humanos , Imidazoles/farmacología , Masculino , Pirrolidinas , ARN Viral/sangre , Valina/farmacología , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Replicación Viral/efectos de los fármacos
15.
Clin Lab ; 62(4): 553-61, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27215073

RESUMEN

BACKGROUND: Assessment of immunoglobulin A (IgA) antibody responses to Epstein-Barr virus (EBV) antigen is important for the early diagnosis of nasopharyngeal carcinoma (NPC). EBV glycoprotein gp42 has been shown to play an essential role in membrane fusion with B cells. The aim of the present study was to assess whether the antibodies to EBV glycoprotein gp42 in serum could be a novel marker for diagnosis of NPC. METHODS: EBV glycoprotein gp42 expressed in the recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to gp42 in serum. The blood samples were obtained from 406 participants (n = 208 patients with NPC and 198 healthy controls). Receiver operating characteristics (ROC) was used to calculate diagnostic accuracy. RESULTS: The ROC curves showed that IgA-gp42 ELISA had a sensitivity of 76.4%, specificity of 78.3% and an area under the curve (AUC) of 0.856 (95% CI, 0.82 - 0.891) to diagnose NPC. Furthermore, gp42 maintained diag- nostic capacity in NPC patients who were IgA-viral capsid antigen (VCA) negative (87.5%, 64.1% and 0.844 [95% CI, 0.776 - 0.912]). Combining gp42 and VCA improved the diagnostic capacity compared with the individual tests (89.9%, 94.4% and 0.973 [95% CI, 0.959 - 0.9871). CONCLUSIONS: The EBV glycoprotein complex gp42 acts as a novel biomarker for diagnosis of NPC and improves identification of patients with VCA-negative NPC.


Asunto(s)
Anticuerpos Antivirales/sangre , Glicoproteínas/inmunología , Neoplasias Nasofaríngeas/diagnóstico , Proteínas Virales/inmunología , Adulto , Biomarcadores , Proteínas de la Cápside/análisis , Carcinoma , Femenino , Humanos , Inmunoglobulina A/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/virología , Curva ROC
16.
Environ Geochem Health ; 38(1): 39-49, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25588738

RESUMEN

Bioaccumulation and trophic transfer of mercury (Hg) both in the natural marine ecosystem and the mariculture ecosystem were studied at Daya Bay, a subtropical bay in Southern China. Averaged Hg concentrations in sediment, phytoplankton, macrophyte, shrimp, crab, shellfish, planktivorous fish, carnivorous fish, farmed pompano, farmed snapper, compound feed and trash fish were 0.074, 0.054, 0.044, 0.098, 0.116, 0.171, 0.088, 0.121, 0.210, 0.125, 0.038 and 0.106 µg g(-1) dw, respectively. These Hg levels were at the low-middle ends of the global range. Positive correlation between Hg concentrations in farmed fish and fish weights/sizes was observed, whereas no clear correlation between Hg concentrations and lipid contents was found. Hg concentrations followed macrophyte < phytoplankton < sediment < planktivorous fish < shrimp < crab < carnivorous fish < shellfish, and commercial feed < trash fish < farmed fish. Hg was biomagnified along the marine food chain in the ecosystem of Daya Bay. Hg levels in the farmed fish were higher than those in the wild fish primarily because of the higher Hg level in fish feed and the smaller size of marine wild fish.


Asunto(s)
Bahías/química , Cadena Alimentaria , Sedimentos Geológicos/análisis , Mercurio/metabolismo , Contaminantes Químicos del Agua/metabolismo , Animales , Animales Salvajes/metabolismo , Acuicultura , China , Monitoreo del Ambiente , Mercurio/análisis , Contaminantes Químicos del Agua/análisis
17.
Chemosphere ; 359: 142324, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38740339

RESUMEN

Seawater warming, ocean acidification and chemical pollution are the main threats to coral growth and even survival. The legacy persistent organic contaminants (POCs), such as polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), and the emerging contaminants, including polybrominated diphenyl ethers (PBDEs), dechlorane plus (DPs) and novel brominated flame retardants (NBFRs) were studied in corals from Luhuitou fringing reef in Sanya Bay and Yongle atoll in Xisha Islands, the South China Sea (SCS). Total average concentrations of ∑16PAHs, ∑23OCPs, ∑34PCBs, ∑8PBDEs, ∑2DPs and ∑5NBFRs in 20 coral species (43 samples) from the SCS were 40.7 ± 34.6, 5.20 ± 5.10, 0.197 ± 0.159, 3.30 ± 3.70, 0.041 ± 0.042 and 36.4 ± 112 ng g-1 dw, respectively. PAHs and NBFRs were the most abundant compounds and they are likely to be dangerous pollutants for future coral growth. Compared to those found in other coral reef regions, these pollutants concentrations in corals were at low to median levels. Except for PBDEs, POCs in massive Porites were significantly higher than those in branch Acropora and Pocillopora (p < 0.01), as large, closely packed corals may be beneficial for retaining more pollutant. The current study contributes valuable data on POCs, particularly for halogenated flame retardants (HFRs, including PBDEs, DPs and NBFRs), in corals from the SCS, and will improve our knowledge of the occurrence and fate of these pollutants in coral reef ecosystems.


Asunto(s)
Antozoos , Monitoreo del Ambiente , Retardadores de Llama , Éteres Difenilos Halogenados , Hidrocarburos Clorados , Contaminantes Orgánicos Persistentes , Bifenilos Policlorados , Hidrocarburos Policíclicos Aromáticos , Agua de Mar , Contaminantes Químicos del Agua , Animales , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Químicos del Agua/análisis , China , Éteres Difenilos Halogenados/análisis , Retardadores de Llama/análisis , Agua de Mar/química , Bifenilos Policlorados/análisis , Hidrocarburos Clorados/análisis , Plaguicidas/análisis , Arrecifes de Coral , Océanos y Mares
18.
Sci Rep ; 14(1): 9182, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649422

RESUMEN

In order to obtain high yield pomelo peel pectin with better physicochemical properties, four pectin extraction methods, including hot acid extraction (HAE), microwave-assisted extraction (MAE), ultrasound-assisted extraction, and enzymatic assisted extraction (EAE) were compared. MAE led to the highest pectin yield (20.43%), and the lowest pectin recovery was found for EAE (11.94%). The physicochemical properties of pomelo peel pectin obtained by different methods were also significantly different. Pectin samples obtained by MAE had the highest methoxyl content (8.35%), galacturonic acid content (71.36%), and showed a higher apparent viscosity, thermal and emulsion stability. The pectin extracted by EAE showed the highest total phenolic content (12.86%) and lowest particle size (843.69 nm), showing higher DPPH and ABTS scavenging activities than other extract methods. The pectin extracted by HAE had the highest particle size (966.12 nm) and degree of esterification (55.67%). However, Fourier-transform infrared spectroscopy showed that no significant difference occurred among the different methods in the chemical structure of the extracted pectin. This study provides a theoretical basis for the industrial production of pomelo peel pectin.


Asunto(s)
Citrus , Ácidos Hexurónicos , Pectinas , Pectinas/química , Pectinas/aislamiento & purificación , Citrus/química , Viscosidad , Tamaño de la Partícula , Microondas , Espectroscopía Infrarroja por Transformada de Fourier , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Fraccionamiento Químico/métodos , Fenómenos Químicos , Frutas/química , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Fenoles/análisis , Fenoles/química , Fenoles/aislamiento & purificación , Esterificación
19.
Adv Healthc Mater ; 13(5): e2302868, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37925607

RESUMEN

Burn wound healing continues to pose significant challenges due to excessive inflammation, the risk of infection, and impaired tissue regeneration. In this regard, an antibacterial, antioxidant, and anti-inflammatory nanocomposite (called HPA) that combines a nanosystem using hexachlorocyclotriphosphazene and the natural polyphenol of Phloretin with silver nanoparticles (AgNPs) is developed. HPA effectively disperses AgNPs to mitigate any toxicity caused by aggregation while also showing the pharmacological activities of Phloretin. During the initial stage of wound healing, HPA rapidly releases silver ions from its surface to suppress bacterial activity. Moreover, these nanoparticles are pH-sensitive and degrade efficiently in the acidic infection microenvironment, gradually releasing Phloretin. This sustained release of Phloretin helps scavenge overexpressed reactive oxygen species in the infected microenvironment area, thus reducing the upregulation of pro-inflammatory cytokines. The antibacterial activity, free radical clearance, and regulation of inflammatory factors of HPA through in vitro experiments are validated. Additionally, its effects using an infectious burn mouse model in vivo are evaluated. HPA is found to promote collagen deposition and epithelialization in the wound area. With its synergistic antibacterial, antioxidant, and anti-inflammatory activities, as well as favorable biocompatibilities, HPA shows great promise as a safe and effective multifunctional nanoplatform for burn injury wound dressings.


Asunto(s)
Antiinfecciosos , Quemaduras , Nanopartículas del Metal , Infección de Heridas , Ratones , Animales , Plata/farmacología , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Antibacterianos/farmacología , Infección de Heridas/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Quemaduras/tratamiento farmacológico , Floretina
20.
Acad Radiol ; 31(5): 1792-1798, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38307790

RESUMEN

RATIONALE AND OBJECTIVES: To identify the risk factors for contrast media (CM) extravasation and provide effective guidance for reducing its incidence. MATERIALS AND METHODS: We observed adult inpatients (n = 38 281) who underwent intravenous contrast-enhanced computed tomography between January 1, 2018, and December 31, 2022. Risk factors for CM extravasation were evaluated using univariate and multivariate logistic regression. RESULTS: Among the 38 281 inpatients who underwent enhanced computed tomography angiography, 3885 received peripherally inserted central venous catheters (PICCs) and 34 396 received peripheral short catheters. In 3885 cases of PICCs, no CM extravasation occurred, but in five cases, ordinary PICCs that are unable to withstand high pressure were mistakenly used; three of those patients experienced catheter rupture, and eventually, all five patients underwent unplanned extubation. Among 34 396 cases of peripheral short catheters, 224 (0.65%) had CM extravasation. Female sex (odds ratio [OR]=1.541, 95% confidence interval [CI]: 1.111-2.137), diabetes (OR=2.265, 95% CI: 1.549-3.314), venous thrombosis (OR=2.157, 95% CI: 1.039-4.478), multi-site angiography (OR=9.757, CI: 6.803-13.994), and injection rate ≥ 3 mL/s (OR=6.073, 95% CI: 4.349-8.481) were independent risk factors for CM extravasation. Due to peripheral vascular protection measures in patients with malignant tumor, there was a low incidence of CM extravasation (OR=0.394, 95% CI: 0.272-0.570). CONCLUSION: Main risk factors for CM extravasation are female, diabetes, venous thrombosis, multi-site angiography, and injection rate ≥ 3 mL/s. However, patients with malignant tumor have a low incidence of CM extravasation. CLINICAL IMPACT: Analysis of these risk factors can help reduce the incidence of CM extravasation.


Asunto(s)
Medios de Contraste , Extravasación de Materiales Terapéuticos y Diagnósticos , Humanos , Extravasación de Materiales Terapéuticos y Diagnósticos/prevención & control , Extravasación de Materiales Terapéuticos y Diagnósticos/epidemiología , Extravasación de Materiales Terapéuticos y Diagnósticos/diagnóstico por imagen , Femenino , Masculino , Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos , Factores de Riesgo , Persona de Mediana Edad , Anciano , Adulto , Angiografía por Tomografía Computarizada/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano de 80 o más Años , Estudios de Cohortes , Incidencia
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