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1.
World J Gastroenterol ; 25(40): 6107-6115, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686766

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been widely used in pediatric patients with cholangiopancreatic diseases. AIM: To evaluate the efficacy, safety, and long-term follow-up results of ERCP in symptomatic pancreaticobiliary maljunction (PBM). METHODS: A multicenter, retrospective study was conducted on 75 pediatric patients who were diagnosed with PBM and underwent therapeutic ERCP at three endoscopy centers between January 2008 and March 2019. They were divided into four PBM groups based on the fluoroscopy in ERCP. Their clinical characteristics, specific ERCP procedures, adverse events, and long-term follow-up results were retrospectively reviewed. RESULTS: Totally, 112 ERCPs were performed on the 75 children with symptomatic PBM. Clinical manifestations included abdominal pain (62/75, 82.7%), vomiting (35/75, 46.7%), acholic stool (4/75, 5.3%), fever (3/75, 4.0%), acute pancreatitis (47/75, 62.7%), hyperbilirubinemia (13/75, 17.3%), and elevated liver enzymes (22/75, 29.3%). ERCP interventions included endoscopic sphincterotomy, endoscopic retrograde biliary or pancreatic drainage, stone extraction, etc. Procedure-related complications were observed in 12 patients and included post-ERCP pancreatitis (9/75, 12.0%), gastrointestinal bleeding (1/75, 1.3%), and infection (2/75, 2.7%). During a mean follow-up period of 46 mo (range: 2 to 134 mo), ERCP therapy alleviated the biliary obstruction and reduced the incidence of pancreatitis. The overall effective rate of ERCP therapy was 82.4%; seven patients (9.3%) were lost to follow-up, eight (11.8%) re-experienced pancreatitis, and eleven (16.2%) underwent radical surgery, known as prophylactic excision of the extrahepatic bile duct and hepaticojejunostomy. CONCLUSION: ERCP is a safe and effective treatment option to relieve biliary or pancreatic obstruction in symptomatic PBM, with the characteristics of minor trauma, fewer complications, and repeatability.

2.
Ital J Pediatr ; 45(1): 116, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462301

RESUMO

BACKGROUND: Immunocompromised (IC) patients have an increased risk of refractory diarrhea. Fecal microbiota transplantation (FMT) is a safe and effective therapy for infection-related diarrhea which are mainly mediated by the loss of the microbial colonization, although there is concern that IC patients may be at higher risk of infectious complications related to FMT. And reports of FMT in IC children are limited. CASE PRESENTATION: We describe two cases of FMT in IC children with refractory diarrhea. One IC child had polyendocrinopathy, enteropathy, X-linked syndrome and the other child had graft-versus-host disease. Both of the children had a long course of diarrhea and no response to traditional treatment. FMT was performed on both patients via nasojejunal tubes under guidance of gastroduodenoscopy. After FMT, the patients achieved remission of symptoms and neither of them had related infectious complications. Microbiota analysis showed that FMT resulted in reconstruction of a diverse microbiota. CONCLUSIONS: Use of FMT is safe and effective in treatment of refractory diarrhea in IC children with a damaged microbiota.

3.
Chemosphere ; 235: 58-69, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31255766

RESUMO

In this study, ultrafiltration membrane fouling was alleviated by hydrophilic modification and coagulation pretreatment. A polydopamine (PDA) layer was used as a bridge to introduce the nano titanium dioxide (TiO2) onto the polysulfone (PSf) membranes, forming a hydrophilic modified layer. A relationship model was established between the coagulation efficiencies and floc properties and membrane fouling of the modified PSf membranes during the coagulation/ultrafiltration (C-UF) process. The combination styles of flocculants, poly dimethyldiallylammonium chloride (PDMDAAC) and polyaluminum chloride (PAC) were used in C-UF hybrid process. The characterization results indicated that the hydrophilicity was significantly enhanced in the modified PSf membranes. Scanning electron microscopy (SEM) tests proved that the PDA layer could be tightly bound to TiO2 by coordination bond onto PSf membrane surface. In the acidic conditions, more TiO2 nano-particles were adhered on the PDA particles surface as the pH of (NH4)2TiF6 solution was increased, which resulted in higher hydrophilicity of membranes. In addition, the C-UF tests exhibited that the coagulation efficiency was greatly improved in the PAC/PDMDAAC system, and the PSf membrane modified by PDA/TiO2 in UF tests significantly reduced the membrane fouling, this was partially due to the formation of TiO2 modified coating with higher hydrophilicity.

4.
NPJ Syst Biol Appl ; 5: 20, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312514

RESUMO

Cancer cells with heterogeneous mutation landscapes and extensive functional redundancy easily develop resistance to monotherapies by emerging activation of compensating or bypassing pathways. To achieve more effective and sustained clinical responses, synergistic interactions of multiple druggable targets that inhibit redundant cancer survival pathways are often required. Here, we report a systematic polypharmacology strategy to predict, test, and understand the selective drug combinations for MDA-MB-231 triple-negative breast cancer cells. We started by applying our network pharmacology model to predict synergistic drug combinations. Next, by utilizing kinome-wide drug-target profiles and gene expression data, we pinpointed a synergistic target interaction between Aurora B and ZAK kinase inhibition that led to enhanced growth inhibition and cytotoxicity, as validated by combinatorial siRNA, CRISPR/Cas9, and drug combination experiments. The mechanism of such a context-specific target interaction was elucidated using a dynamic simulation of MDA-MB-231 signaling network, suggesting a cross-talk between p53 and p38 pathways. Our results demonstrate the potential of polypharmacological modeling to systematically interrogate target interactions that may lead to clinically actionable and personalized treatment options.

5.
J Am Chem Soc ; 141(27): 10590-10594, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31188590

RESUMO

Herein, we report a novel carbothermal welding strategy to prepare atomically dispersed Pd sites anchored on a three-dimensional (3D) ZrO2 nanonet (Pd1@ZrO2) via two-step pyrolysis, which were evolved from isolated Pd sites anchored on linker-derived nitrogen-doped carbon (Pd1@NC/ZrO2). First, the NH2-H2BDC linkers and Zr6-based [Zr6(µ3-O)4(µ3-OH)4]12+ nodes of UiO-66-NH2 were transformed into amorphous N-doped carbon skeletons (NC) and ZrO2 nanoclusters under an argon atmosphere, respectively. The NC supports can simultaneously reduce and anchor the Pd sites, forming isolated Pd1-N/C sites. Then, switching the argon to air, the carbonaceous skeletons are gasified and the ZrO2 nanoclusters are welded into a rigid and porous nanonet. Moreover, the reductive carbon will result in abundant oxygen (O*) defects, which could help to capture the migratory Pd1 species, leaving a sintering-resistant Pd1@ZrO2 catalyst via atom trapping. This Pd1@ZrO2 nanonet can act as a semi-homogeneous catalyst to boost the direct synthesis of indole through hydrogenation and intramolecular condensation processes, with an excellent turnover frequency (1109.2 h-1) and 94% selectivity.

6.
Chemosphere ; 231: 349-356, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132541

RESUMO

Ultrafiltration (UF) technology is considered an efficient water treatment method. In recent years, researchers have been committed to enhancing the treatment efficiency of UF and alleviating membrane fouling. An effective method is to achieve this is through the use of coagulation as a pre-treatment to UF; however, during a long term operation, membrane fouling can occur due to the residual organic matters and the generation of microorganisms. In this study, we combine coagulation and ozonation as a pre-treatment of UF and compare four types of pre-treatment: coagulation, ozonation, coagulation followed by ozonation (C-O) and ozonation followed by coagulation (O-C). Results showed that ozonation alone did not perform well. Both combinations of coagulation and ozonation enhanced the organic matter removal efficiency, although membrane fouling was lowest following the C-O pre-treatment as the microbial load was reduced. While a slight increase in the yield of disinfection by-products was observed with the addition of ozonation, the concentration remained below the Chinese standard for tap water quality (100 µg/L).


Assuntos
Purificação da Água/métodos , Desinfecção , Membranas Artificiais , Ozônio , Ultrafiltração/métodos , Qualidade da Água
7.
Cardiovasc Diabetol ; 18(1): 56, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039789

RESUMO

BACKGROUND: Myocardial energetic efficiency (MEE), is a strong predictor of CV events in hypertensive patient and is reduced in patients with diabetes and metabolic syndrome. We hypothesized that severity of insulin resistance (by HOMA-IR) negatively influences MEE in participants from the Strong Heart Study (SHS). METHODS: We selected non-diabetic participants (n = 3128, 47 ± 17 years, 1807 women, 1447 obese, 870 hypertensive) free of cardiovascular (CV) disease, by merging two cohorts (Strong Heart Study and Strong Heart Family Study, age range 18-93). MEE was estimated as stroke work (SW = systolic blood pressure [SBP] × stroke volume [SV])/"double product" of SBP × heart rate (HR), as an estimate of O2 consumption, which can be simplified as SV/HR ratio and expressed in ml/sec. Due to the strong correlation, MEE was normalized by left ventricular (LV) mass (MEEi). RESULTS: Linear trend analyses showed that with increasing quartiles of HOMA-IR patients were older, more likely to be women, obese and hypertensive, with a trend toward a worse lipid profile (all p for trend < 0.001), progressive increase in LV mass index, stroke index and cardiac index and decline of wall mechanics (all p < 0.0001). In multivariable regression, after adjusting for confounders, and including a kinship coefficient to correct for relatedness, MEEi was negatively associated with HOMA-IR, independently of significant associations with age, sex, blood pressure, lipid profile and central obesity (all p < 0.0001). CONCLUSIONS: Severity of insulin resistance has significant and independent negative impact on myocardial mechano-energetic efficiency in nondiabetic individual from a population study of American Indians. Trial registration number NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134 , Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988.

8.
PLoS Comput Biol ; 15(5): e1006752, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31107860

RESUMO

High-throughput drug screening has facilitated the discovery of drug combinations in cancer. Many existing studies adopted a full matrix design, aiming for the characterization of drug pair effects for cancer cells. However, the full matrix design may be suboptimal as it requires a drug pair to be combined at multiple concentrations in a full factorial manner. Furthermore, many of the computational tools assess only the synergy but not the sensitivity of drug combinations, which might lead to false positive discoveries. We proposed a novel cross design to enable a more cost-effective and simultaneous testing of drug combination sensitivity and synergy. We developed a drug combination sensitivity score (CSS) to determine the sensitivity of a drug pair, and showed that the CSS is highly reproducible between the replicates and thus supported its usage as a robust metric. We further showed that CSS can be predicted using machine learning approaches which determined the top pharmaco-features to cluster cancer cell lines based on their drug combination sensitivity profiles. To assess the degree of drug interactions using the cross design, we developed an S synergy score based on the difference between the drug combination and the single drug dose-response curves. We showed that the S score is able to detect true synergistic and antagonistic drug combinations at an accuracy level comparable to that using the full matrix design. Taken together, we showed that the cross design coupled with the CSS sensitivity and S synergy scoring methods may provide a robust and accurate characterization of both drug combination sensitivity and synergy levels, with minimal experimental materials required. Our experimental-computational approach could be utilized as an efficient pipeline for improving the discovery rate in high-throughput drug combination screening, particularly for primary patient samples which are difficult to obtain.

9.
Nucleic Acids Res ; 47(W1): W43-W51, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31066443

RESUMO

Drug combination therapy has the potential to enhance efficacy, reduce dose-dependent toxicity and prevent the emergence of drug resistance. However, discovery of synergistic and effective drug combinations has been a laborious and often serendipitous process. In recent years, identification of combination therapies has been accelerated due to the advances in high-throughput drug screening, but informatics approaches for systems-level data management and analysis are needed. To contribute toward this goal, we created an open-access data portal called DrugComb (https://drugcomb.fimm.fi) where the results of drug combination screening studies are accumulated, standardized and harmonized. Through the data portal, we provided a web server to analyze and visualize users' own drug combination screening data. The users can also effectively participate a crowdsourcing data curation effect by depositing their data at DrugComb. To initiate the data repository, we collected 437 932 drug combinations tested on a variety of cancer cell lines. We showed that linear regression approaches, when considering chemical fingerprints as predictors, have the potential to achieve high accuracy of predicting the sensitivity of drug combinations. All the data and informatics tools are freely available in DrugComb to enable a more efficient utilization of data resources for future drug combination discovery.

10.
Cell Cycle ; 18(13): 1513-1522, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31135266

RESUMO

L755S, a HER2 kinase domain mutation, is the most common HER2 mutation in breast cancer associated with resistance to anti-HER2 trastuzumab treatment. Here, we showed that HER2-L755S confers hyperactivation of MAPK and PI3K/AKT/mTOR pathways and resistance to both reversible and irreversible HER2 tyrosine kinase inhibitors. We further demonstrated that the HER2 TKIs in combination with MEK inhibitor, AZD6244, or PI3K inhibitor, GDC0941, yield robust killing in HER2-L755S cancer cells, indicating a novel targeted strategy to overcome HER2-L755S resistance to anti-HER2 treatment.

11.
J Ethnopharmacol ; 239: 111896, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31028858

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis rhizoma (CR) is the dried rhizome of the ranunculaceous plant CR. For decades in China, this plant has been used to treat hypertension, hyperlipidemia, and chronic diarrhea and has been officially included in the Chinese Pharmacopoeia. The present paper presents a review of the pharmacokinetics of CR. AIM OF THE STUDY: The pharmacokinetic studies and differences of 10 alkaloids among Coptis deltoidea C. Y. cheng et Hsiao, Coptis chinensis Franch and Coptis teeta Wall. Are seldom reported. This study is the first to determine corydaline, dehydrocorydaline, tetrahydropalmatine, palmatine, magnoflorine, jatrorrhizine, berberine, worenine, berberrubine, and coptisine, which adopted an ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, simultaneously. MATERIALS AND METHODS: Chromatographic separation was performed within 8 min by using an Agilent SB-C18 column (150 mm × 2.1 mm, 1.8 µm) with gradient mobile phase consisting of 0.3% acetic acid water (v/v) and acetonitrile at a flow rate of 0.3 mL/min. Multiple reaction monitoring mode was used to detect the tandem mass spectrum in the positive ionization mode by electrospray ionization source. RESULTS: The method was fully validated to be linear over a wide concentration (r > 0.9916), and the linear concentration range was 0.195-2260 ng/mL. Intra- and interday precisions were below 14.19% and 18.56% for the 10 analytes, respectively. The accuracy ranged from -9.30% to 6.31%. The extraction recovery of the 10 alkaloids and internal standard ranged from 79.76% to 95.37%. Pharmacokinetic comparative study showed that the Cmax and AUC0-∞ values of dehydrocorydaline, tetrahydropalmatine, palmatine, magnoflorine, jatrorrhizine, berberine, worenine, berberrubine, and coptisine increased significantly (p < 0.05), which was different for beagles after oral administration. The results can help determine the mechanism of action and guide clinical application of these three extracts. CONCLUSION: This validated method was successfully applied for the pharmacokinetics study of beagle plasma after oral administration of three CR extract types.

12.
Zhongguo Zhong Yao Za Zhi ; 44(2): 364-371, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30989959

RESUMO

To investigate the " drug-guide" effect of Achyranthes bidentata saponins( ABS) and geniposide( GE) in the treatment on adjuvant arthritis( AA) rats. A UHPLC-MS/MS method for the quantitative determination of GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa in rat blood and joint dialysate was established. After single or combined administration with ABS and GE was given to AA rat model,a microdialysis sampling method for rat joint cavity and jugular vein blood vessels was established to collect microdialysis samples. Waters Acquity HSS C_(18) column was used to separate the above four components,with mobile phase as acetonitrile-0. 1% formic acid water as mobile phase for gradient elution. ESI source was adopted for mass spectra in a negative ion scanning mode. Multiple reaction monitoring( MRM) mode was applied to detect the above four components. The methodological results showed that GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa demonstrated a good linear relationship within the concentration ranges of 2-4 000,16-4 096,14-3 584,23-5 888 µg·L-1 respectively. The precision,accuracy,stability and matrix effect of these four ingredients reached the requirements of quantitative analysis of biological samples. The pharmacokinetic results demonstrated that the combined administration of ABS and GE( 60 mg·kg~(-1)+60 mg·kg~(-1)) can increase the degree of GE in joint cavity distribution,and the AUCjoint/AUCplasmwere twice of that of single administration of GE( 60 mg·kg~(-1)),which indicated that ABS might played a vital role in GE's distribution to joint cavity. Moreover,there was no significant difference between the distribution trend of total three ABS and GE in rats. The pharmacodynamics results showed that the combined administration of ABS and GE has stronger effects on paw swelling,arthritis index and synovial pathomorphology of AA rats than single administration of GE,which suggested that ABS might improve GE's anti-inflammatory effect in AA rats. Based on the above results,ABS has a targeting effect in increasing GE's concentration in joint cavity,with a synergy in efficacy.


Assuntos
Achyranthes/química , Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Iridoides/farmacocinética , Microdiálise , Ratos , Reprodutibilidade dos Testes , Saponinas/farmacocinética , Espectrometria de Massas em Tandem
13.
Nat Commun ; 10(1): 1617, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30962421

RESUMO

Clear-cell carcinomas (CCCs) are a histological group of highly aggressive malignancies commonly originating in the kidney and ovary. CCCs are distinguished by aberrant lipid and glycogen accumulation and are refractory to a broad range of anti-cancer therapies. Here we identify an intrinsic vulnerability to ferroptosis associated with the unique metabolic state in CCCs. This vulnerability transcends lineage and genetic landscape, and can be exploited by inhibiting glutathione peroxidase 4 (GPX4) with small-molecules. Using CRISPR screening and lipidomic profiling, we identify the hypoxia-inducible factor (HIF) pathway as a driver of this vulnerability. In renal CCCs, HIF-2α selectively enriches polyunsaturated lipids, the rate-limiting substrates for lipid peroxidation, by activating the expression of hypoxia-inducible, lipid droplet-associated protein (HILPDA). Our study suggests targeting GPX4 as a therapeutic opportunity in CCCs, and highlights that therapeutic approaches can be identified on the basis of cell states manifested by morphological and metabolic features in hard-to-treat cancers.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma de Células Renais/patologia , Glutationa Peroxidase/metabolismo , Neoplasias Renais/patologia , Proteínas de Neoplasias/metabolismo , Idoso , Animais , Apoptose/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Sistemas CRISPR-Cas/genética , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Glutationa Peroxidase/genética , Células HEK293 , Humanos , Ferro/metabolismo , Neoplasias Renais/genética , Peroxidação de Lipídeos/genética , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Gastrointest Surg ; 23(11): 2111-2118, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30895428

RESUMO

PURPOSE: To evaluate the survival benefit of combining radiotherapy with surgery in locally advanced esophageal squamous cell carcinoma (ESCC) patients aged over 65. METHODS: Using the SEER database, we selected patients age ≥ 65 years that were diagnosed as locally advanced ESCC during 2004-2013. Cancer-specific survival (CSS) was examined using the Kaplan-Meier analysis and compared by the log-rank test. Univariable and multivariable Cox proportional hazard models were established to identify possible prognostic factors. RESULTS: A total of 972 cases were included in the study. For surgical patients aged 65-79 years, 74 patients (32.9%) were treated by surgery alone and 122 patients (54.2%) had received additional neoadjuvant radiotherapy (NRT). NRT + surgery was associated with improved CSS comparing with surgery alone (HR, 0.58; 95%CI, 0.39 to 0.85; P = 0.005). In subgroup analysis, NRT was associated with improved CSS for patients aged 65-74 years (2-year CSS 56.6% versus 39.6%, P = 0.026). No significant differences of progonosis was observed for different treatment groups in 75-79 years patients (P = 0.972). CONCLUSIONS: In this SEER-based study, the addition of neoadjuvant radiotherapy before surgery was associated with improved CSS for locally advanced ESCC patients aged 65 to 74 years.

15.
Cell Death Differ ; 26(11): 2179-2193, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30770877

RESUMO

It was found in this study that long intergenic non-protein coding RNA 346 (LINC00346) was an lncRNA aberrantly expressed in gastric cancer (GC) based on multiple Gene Expression Omnibus (GEO) databases of GC cohorts. The LINC00346 gene was recurrently amplified and upregulated in GC, and its expression was positively correlated with poor pathologic stage, large tumor size, and poor prognosis. In addition, the oncogenic transcription factors KLF5 and MYC could bind to the LINC00346 promoter and enhance its expression. Gene Set Enrichment Analysis (GSEA) in the GEO datasets revealed that cell cycle and focal adhesion genes were enriched in patients with high LINC00346 expression. In vitro and in vivo assays of LINC00346 alterations revealed a complex integrated phenotype affecting cell growth, migration and invasion. Strikingly, high-throughput sequencing analysis after LINC00346 alterations highlighted alterations in cell cycle and focal adhesion pathways in GC cells. Mechanistically, argonaute 2 (Ago2) was recruited by LINC00346, which functioned as a molecular sponge for miR-34a-5p by antagonizing its ability to repress CD44, NOTCH1, and AXL protein translation. Taken together, our findings support a model in which the KLF5, MYC/LINC00346/miR-34a-5p cross-talk served as critical effectors in GC tumorigenesis and progression, suggesting a new therapeutic direction in the treatment of GC.

16.
Acta Biomater ; 86: 280-290, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616077

RESUMO

Recently, novel approaches for the delivery of therapeutic antibodies have attracted much attention, especially sustained release formulations. However, sustained release formulations capable of carrying a high antibody load remain a challenge for practical use. In this study, a novel injectable hydrogel composed of maleimide-modified γ-polyglutamic acid (γ-PGA-MA) and thiol end-functionalized 4-arm poly(ethylene glycol) (4-arm PEG-SH) was developed for the subcutaneous delivery of trastuzumab. γ-PGA-MA and 4-arm PEG-SH formed a hydrogel through thiol-maleimide reactions, which had shear-thinning properties and reversible rheological behaviors. Moreover, a high content of trastuzumab (>100 mg/mL) could be loaded into this hydrogel, and trastuzumab demonstrated a sustained release over several weeks through electrostatic attraction. In addition, trastuzumab released from the hydrogel had adequate stability in terms of its structural integrity, binding bioactivity, and antiproliferative effect on BT-474 cells. Pharmacokinetic studies demonstrated that trastuzumab-loaded hydrogel (Her-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, and 10 mg/mL trastuzumab) and trastuzumab/Zn-loaded hydrogel (Her/Zn-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, 5 mM ZnCl2, and 10 mg/mL trastuzumab) could lower the maximum plasma concentration (Cmax) than the trastuzumab solution. Furthermore, Her/Zn-hydrogel-10 was better able to release trastuzumab in a controlled manner, which was ascribed to electrostatic attraction and formation of trastuzumab/Zn nanocomplexes. In a BT-474 xenograft tumor model, Her-hydrogel-10 had a similar tumor growth-inhibitory effect as that of the trastuzumab solution. By contrast, Her/Zn-hydrogel-10 exhibited a superior tumor growth-inhibitory capability due to the functionality of Zn. This study demonstrated that this hydrogel has potential as a carrier for the local and systemic delivery of proteins and antibodies. STATEMENT OF SIGNIFICANCE: Recently, novel sustained-release formulations of therapeutic antibodies have attracted much attention. However, these formulations should be able to carry a high antibody load owing to the required high dose, and these formulations remain a challenge for practical use. In this study, a novel injectable chemically cross-linked hydrogel was developed for the subcutaneous delivery of trastuzumab. This novel hydrogel possessed ideal characteristics of loading high content of trastuzumab (>100 mg/mL), sustained release of trastuzumab over several weeks, and maintaining adequate stability of trastuzumab. In vivo studies demonstrated that a trastuzumab-loaded hydrogel possessed the ability of controlled release of trastuzumab and maintained antitumor efficacy same as that of trastuzumab. These results implied that a γ-PGA-MA and 4-arm PEG-SH-based hydrogel has great potential in serving as a carrier for the local or systemic delivery of therapeutic proteins or antibodies.

17.
Chem Commun (Camb) ; 55(16): 2285-2288, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30694288

RESUMO

Herein, we report a heterogeneous single iron atom catalyst exhibiting excellent peroxidase, oxidase and catalase enzyme-like activities (defined as single atom enzymes, SAEs), exceeding those of Fe3O4 nanozymes by a factor of 40. Our findings open up a new family of artificial materials that mimic natural enzymes.


Assuntos
Materiais Biomiméticos/química , Compostos Férricos/química , Nanoestruturas/química , Peroxidase/metabolismo , Catálise , Concentração de Íons de Hidrogênio , Modelos Moleculares , Conformação Molecular
18.
Chemosphere ; 215: 214-226, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30317092

RESUMO

In this work, four alkaline lignin (AL) based flocculants with distinct molecular weight, chain architectures and charge densities (denoted as AL-g-DMC1, AL-g-DMC2, AL-GTA1 and AL-GTA2) were prepared from paper mill sludge, which were designed via graft copolymerization of dimethyl diallyl ammonium chloride (DMC) or etherification of 2, 3-epoxypropyl trimethyl ammonium chloride (GTA). The characteristics of the aforementioned flocculants were evaluated by a series of analysis technologies, which essentially confirmed the successful introduction of quaternary ammonium groups onto the AL. The flocculation performances of the four synthesized lignin-based polymers as the coagulant aids for PAC were investigated in disperse dye (DY) wastewater treatment, and the effects of dosages, initial pH, coexisting ions, humic acid (HA) or kaolin particles were also studied. The results indicated that branched copolymers with high molecular weight like AL-g-DMC1 and AL-g-DMC2 exerted excellent color removals and satisfactory floc properties in comparison with linear polymers with low molecular weight (AL-GTA1 and AL-GTA2). Furthermore, AL-g-DMC1 and AL-g-DMC2 exhibited remarkable tolerance on pH alteration and coexisting ions owing to their strong bridging action.


Assuntos
Águas Residuárias/química , Purificação da Água/métodos , Corantes/isolamento & purificação , Floculação , Lignina/química , Peso Molecular , Polímeros/química , Esgotos/química , Poluentes Químicos da Água/isolamento & purificação
19.
J Environ Sci (China) ; 75: 318-324, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30473297

RESUMO

Coagulation-ultrafiltration (C-UF) is widely used for surface water treatment. With the removal of pollutants, the characteristics of organic matter change and affect the final treatment efficiency and the development of membrane fouling. In this study, we built a dynamic C-UF set-up to carry out the treatment of micro-polluted surface water, to investigate the characteristics of dissolved organic matter from different units. The influences of poly aluminum chloride and poly dimethyldiallylammonium chloride (PDMDAAC) on removal efficiency and membrane fouling were also investigated. Results showed that the dosage of PDMDAAC evidently increased the UV254 and dissolved organic carbon removal efficiencies, and thereby alleviated membrane fouling in the C-UF process. Most hydrophobic bases (HoB) and hydrophobic neutral fractions could be removed by coagulation. Similarly, UF was good at removing HoB compared to hydrophilic substances (HiS) and hydrophobic acid (HoA) fractions. HiS and HoA fractions with low molecule weight accumulated on the surface of the membrane, causing the increase of transmembrane pressure (TMP). Membrane fouling was mainly caused by a removable cake layer, and mechanical cleaning was an efficient way to decrease the TMP.


Assuntos
Ultrafiltração/métodos , Poluentes da Água/análise , Purificação da Água/métodos , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Poluição da Água
20.
Sensors (Basel) ; 18(11)2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30424483

RESUMO

An aerosol electrometer with enhanced detection limit was developed for measuring the collected particles electrical current ranging from -50 pA to 50 pA with no range switching necessary. The detection limit was enhanced by suppressing the electric current measurement noise and improving the detection efficiency. A theoretical model for the aerosol electrometer has been established to investigate the noise effect factors and verified experimentally. The model showed that the noise was a function of ambient temperature, and it was affected by the characteristics of feedback resistor and operational amplifier simultaneously. The Faraday cup structure of the aerosol electrometer was optimized by adopting a newly designed cup-shaped metal filter which increased the surface area of the cup; thus the particle interception efficiency was improved. The aerosol electrometer performance-linearity, noise and the particle detection efficiency, were evaluated experimentally. When compared with TSI-3068B, a 99.4% ( R 2 ) statistical correlation was achieved. The results also showed that the root mean square noise and the peak-to-peak noise were 0.31 fA and 1.55 fA, respectively. The particle detection efficiency was greater than 99.3% when measuring particle diameter larger than 7.0 nm.

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