Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ChemSusChem ; 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32662564

RESUMO

The efficient valorization of lignin could dictate the success of the 2nd generation biorefinery. Lignin, accounting for on average a third of the lignocellulosic biomass, is the most promising candidate for sustainable production of value-added phenolics. However, the structural alteration induced during lignin isolation is often depleting its potential for value-added chemicals. Recently, catalytic reductive depolymerization of lignin has appeared to be a promising and effective method for its valorization to obtain phenolic monomers. The present study systematically summarizes the far-reaching and state-of-the-art lignin valorization strategies during different stages, including conventional catalytic depolymerization of technical lignin, emerging reductive catalytic fractionation of protolignin, stabilization strategies to inhibit the undesired condensation reactions, and further catalytic upgrading of lignin-derived monomers. Finally, the potential challenges for the future researches on the efficient valorization of lignin and possible solutions are proposed.

2.
J Hazard Mater ; 402: 123490, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32712365

RESUMO

Catalytic hydrogenolysis of lignin to obtain value-added phenolic chemicals is a sustainable and cost-effective strategy for the efficient valorization of biomass derived wastes. Herein, an innovative approach by using a single-step microwave assisted depolymerization of lignin from birch sawdust without external hydrogen in the mixture of water-alcohol (methanol, ethanol, isopropanol) co-solvents over commercial catalysts (Pd/C, Pt/C, Ru/C) was investigated. A 65 wt% yield of phenolic monomers was obtained based on 43.8 wt% of delignification (190 °C, 3 h). The solid residues retained 92.0 wt% of cellulose and 57.3 wt% of hemicellulose, which could be further used for fermentation or in the pulp industry. Analysis of the lignin oil revealed that in-situ hydrogen generated from methanol decomposition promoted the hydrogenolysis of ßO4 ether linkage and selective hydrogenation of unsaturated side-chains of phenolic monomers. This work introduces new perspectives for the efficient and cost-effective production of value-added phenolic compounds from lignin in agro-industrial wastes without external hydrogen assisted by microwave heating.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32620370

RESUMO

AIM: This study aimed to compare the effectiveness of a 3D-printed ear splint with that of a conventional thermoplastic ear splint after microtia reconstruction. METHODS: Patients who underwent ear elevation surgery with postauricular fascia coverage between October 2017 and October 2018 were included. They were randomly divided into the experimental group (3D-printed ear splint) and the control group (thermoplastic ear splint) and underwent routine postoperative rehabilitation and antiscar therapy. Splint therapy was initiated 4 weeks postoperatively and continued until 24 weeks postoperatively. The evaluated indices were the Vancouver scar scale score (VSS score), cranioauricular distance, patient compliance, complications (dermatitis, skin ulcers, skin necrosis), and patient satisfaction. A two-group t-test was carried out to compare all variables except patient satisfaction, which was compared using the Mann-Whitney U-test; p < 0.05 was considered significant. RESULTS: Twenty patients were included in each group. At 4 weeks postoperatively, the VSS score (p = 0.748) and cranioauricular distance (p = 0.647) showed no significant differences between the groups. At 24 weeks postoperatively, the mean VSS scores were 4.85 ± 1.46 and 6.25 ± 1.74 (p = 0.009), the mean cranioauricular distances were 15.80 ± 1.82 mm and 13.95 ± 1.93 mm (p = 0.004), and the patient satisfaction scores were 4.5 ± 0.51 and 3.7 ± 0.47 (p < 0.001) in the experimental group and the control group, respectively, all showing significant differences. Two patients in each group exhibited skin irritation or skin ulcers, which resolved after 6 months of follow-up. CONCLUSION: The application of 3D-printed ear splints provides better inhibition of scar contracture, better maintenance of ear projection and higher patient satisfaction than conventional ear splints following ear elevation surgery in microtia patients. Therefore, 3D-printed ear splints should be preferred over conventional ear splints whenever possible.

4.
J Hazard Mater ; 399: 123055, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32526445

RESUMO

With the aim to develop optimized biochar with minimal contaminants, it is important significance to broaden the understanding of biochar. Here, we disclose for the first time, a highly toxic substance (metal cyanide, MCN, such as KCN or NaCN) in biochar. The cyanide ion (CN-) content in biochar can be up to 85,870 mg/kg, which is determined by the inherent metal content and type in the biomass with K and Na increasing and Ca, Mg and Fe decreasing its formation. Density functional theory (DFT) analysis shows that unstable alkali oxygen-containing metal salts such as K2CO3 can induce an N rearrangement reaction to produce for example, KOCN. The strong reducing character of the carbon matrix further converts KOCN to KCN, thus resulting biochar with high risk. However, the stable Mg, Ca and Fe salts in biomass cannot induce an N rearrangement reaction due to their high binding energies. We therefore propose that high valent metal chloride salts such as FeCl3 and MgCl2 could be used to inhibit the production of cyanide via metal interactive reaction. These findings open a new point of view on the potential risk of biochar and provide a mitigation solution for biochar's sustainable application.

5.
Theranostics ; 10(13): 5879-5894, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483425

RESUMO

Rationale: Interleukin 22 (IL-22) is an epithelial survival cytokine that is at present being explored as therapeutic agents for acute and chronic liver injury. However, its molecular basis of protective activities remains poorly understood. Methods: Here we demonstrate that IL-22 inhibits the deteriorating metabolic states induced by stimuli in hepatocytes. Utilizing cell biological, molecular, and biochemical approaches, we provide evidence that IL-22 promotes oxidative phosphorylation (OXPHOS) and glycolysis and regulates the metabolic reprogramming related transcriptional responses. Results: IL-22 controls metabolic regulators and enzymes activity through the induction of AMP-activated protein kinase (AMPK), AKT and mammalian target of rapamycin (mTOR), thereby ameliorating mitochondrial dysfunction. The upstream effector lncRNA H19 also participates in the controlling of these metabolic processes in hepatocytes. Importantly, amelioration of liver injury by IL-22 through activation of metabolism relevant signaling and regulation of mitochondrial function are further demonstrated in cisplatin-induced liver injury and steatohepatitis. Conclusions: Collectively, our results reveal a novel mechanism underscoring the regulation of metabolic profiles of hepatocytes by IL-22 during liver injury, which might provide useful insights from the bench to the clinic in treating and preventing liver diseases.

6.
Appl Microbiol Biotechnol ; 104(13): 5889-5898, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356198

RESUMO

Acetaminophen (APAP) overdose can lead to acute, severe kidney injury, which has recently attracted considerable attention among researchers and clinicians. Unfortunately, there are no well-established treatments for APAP-induced renal injury, and the molecular mechanism of APAP-induced kidney injury is still unclear. Herein, we explored the protective effects of interleukin (IL)-22 on APAP-induced renal injury and the underlying molecular basis. We found that IL-22 could significantly alleviate the accumulation of reactive oxygen species (ROS) and ameliorate mitochondrial dysfunction, reducing APAP-induced renal tubular epithelial cell (TEC) death in vitro and in vivo. Furthermore, IL-22 could downregulate the APAP-induced NLRP3 inflammasome activation and mature IL-1ß release in kidney injury. Additionally, the APAP-mediated upregulation of the serum levels of IL-18, TNF-α, IL-6, and IL-1ß was obviously decreased, suggesting IL-22 has inhibitory effects on inflammatory responses. Conclusively, our study demonstrated that IL-22 exerted ameliorative effects on APAP-induced kidney injury by alleviating mitochondrial dysfunction and NLRP3 inflammasome activation, suggesting that IL-22 represents a potential therapeutic approach to treat APAP-induced kidney injury. KEY POINTS: • IL-22 could ameliorate APAP that triggered oxidative stress and mitochondrial dysfunction. • IL-22 could reduce APAP that caused inflammatory responses. Graphical abstract.

7.
J Hazard Mater ; 393: 122446, 2020 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-32155525

RESUMO

In this study, lincomycin residue (LR, a type of antibiotic mycelial residue) derived hydrochar samples (LR-HCs) were obtained from hydrothermal carbonization (HTC), and pyrolysis applied to these LR-HCs to produce activated pyrolyzed samples (LR-APs). Transformation of phosphorus (P) and nitrogen (N) species during HTC and pyrolysis was of primary interest and characterized by several techniques. Nitrogen content of dry LR was calculated by elemental analysis, being 7.91 wt. %, decreasing to 2.51 after HTC and 1.12 wt. % after concesutive HTC and pyrolysis. FT-IR analysis provided evidence for amine groups in LR samples. XPS analysis described N species (Pyridinic-N, Amine-N, Protein-N, Pyrrolic-N, and Quaternary-N) and P species (ortho-P/pyro-P and Ar-P) in LR samples, effectively. Sequential extraction showed that the HTC and pyrolysis changed the proportion of the P species from labile (P-NaHCO3 and P-NaOH) to stable ones (P-residue). Utilization and suitability of as-prepared LR-HCs and LR-APs for heavy metal Pb (II) immobilization show promising results. To help understand immobilization process, kinetic (pseudo-1st-order and pseudo-2nd-order) and isotherm (Freundlich) models were tested and verified. Results confirmed that P and N species were transformed during HTC and pyrolysis and that these processes lead to an advantageous effect on Pb (II) removal from solution.

8.
J Hazard Mater ; 388: 122037, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31951992

RESUMO

Thiol-modified rice straw biochar (RS) was prepared by an esterification reaction with ß-mercaptoethanol and used for the remediation of Cd and Pb polluted soils. Modified biochar was characterized through elemental analysis, BET analysis, FE-SEM, FT-IR and XPS. These analytical results revealed that thiol groups were successfully grafted onto the surface of the biochar and were involved in metal ion complexation. Batch sorption experiments indicated that Cd2+ and Pb2+ sorption onto RS described well by a pseudo second order kinetic model and a Langmuir isotherm. The maximum adsorption capacities for Cd2+ and Pb2+, in the single-metal systems, were 45.1 and 61.4 mg g-1, respectively. In the binary-metal systems, RS selectively adsorbed Cd2+ over Pb2+. Cd2+ and Pb2+ were removed mainly through surface complexation. In the soil incubation experiments (28 days), RS reduced the available Cd by 34.8-39.2 %; while, RS reduced the available Pb by 8.6 %-11.1 %. This research demonstrates RS as a potentially effective amendment for the remediation of heavy metal polluted soils.

9.
J Hazard Mater ; 384: 121466, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31679891

RESUMO

Organic phosphorus is an important source of eutrophication. In this study, to understand the mechanism of organophosphorus photodegradation, humic acid-Fe3+ (HA-Fe3+) complexes were prepared as a sensitizer, and glyphosate (GP) was used as a substrate for photodegradation. The effects of the initial GP concentration, HA concentration, Fe3+ concentration and microbial factors on photodegradation were investigated. The initial concentrations of GP, HA and Fe3+ could significantly affect the degradation rate of GP. Phosphate is the main product of GP photodegradation. Based on the identification of the active species in the reaction process, t-butanol was found to have the most significant inhibitory effect on the degradation. The reaction rate after t-butanol treatment was reduced from 0.017 to 0.003. This confirmed that OH was the main oxidant in the system, which was also demonstrated by EPR spectroscopy. A possible mechanism of GP photodegradation sensitized by HA-Fe3+ complexes was revealed for the first time. The HA-Fe3+ complexes in the reaction system were photodegraded and oxidized to finally produce OH, which promotes GP photodegradation. This study facilitates understanding the phosphorus cycle in a water environment and provides a scientific basis for the restoration of eutrophic lakes.

10.
Carcinogenesis ; 41(3): 345-357, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31175354

RESUMO

Hepatocellular carcinoma (HCC), one of the most lethal malignancies worldwide, has limited efficient therapeutic options. Here, we first demonstrated that simultaneously targeting poly (ADP-ribose) polymerase (PARP) and autophagy could evoke striking synergistic lethality in HCC cells. Specifically, we found that the PARP inhibitor Niraparib induced cytotoxicity accompanied by significant autophagy formation and autophagic flux in HCC cells. Further experiments showed that Niraparib induced suppression of the Akt/mTOR pathway and activation of the Erk1/2 cascade, two typical signaling pathways related to autophagy. In addition, the accumulation of reactive oxygen species was triggered, which was involved in Niraparib-induced autophagy. Blocking autophagy by chloroquine (CQ) in combination with Niraparib further enhanced cytotoxicity, induced apoptosis and inhibited colony formation in HCC cells. Synergistic inhibition was also observed in Huh7 xenografts in vivo. Mechanistically, we showed that autophagy inhibition abrogated Niraparib-induced cell-cycle arrest and checkpoint activation. Cotreatment with CQ and Niraparib promoted the formation of γ-H2AX foci while inhibiting the recruitment of the homologous recombination repair protein RAD51 to double-strand break sites. Thus, the present study developed a novel promising strategy for the management of HCC in the clinic and highlighted a potential approach to expand the application of PARP inhibitors.

11.
Biomaterials ; 227: 119570, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670032

RESUMO

Excessive release of interleukin-1ß (IL-1ß) is well-known to provoke cascades of inflammatory responses thus contributing to the pathogenesis of alcohol-induced steatohepatitis (ASH), but the cellular mechanism that regulates IL-1ß release during ASH remains unclear. Herein, we identified that gasdermin D (GSDMD) membrane pore is critical in mediating IL-1ß hypersecretion from chronic ethanol or acetaldehyde-stimulated macrophages. Deletion of GSDMD reduced IL-1ß release and ameliorated alcoholic steatohepatitis in vivo. These findings uncovered a novel mechanism regarding the IL-1ß release in ASH, and also indicated the therapeutic potential of IL-1ß blockade. Interleukin-1 receptor antagonist (IL-1Ra) is protective to ASH by blocking IL-1ß, but it has a short biological half-life (4-6 h) and lower liver concentrations. Thus, we constructed a therapeutic plasmid pVAX1-IL-1Ra-ApoAI (pVAX1-IA) encoding IL-1Ra anchored to the liver-targeting protein apolipoprotein A-I (ApoAI), and developed hepatocyte-specific nanobiologics (Glipo-pVAX1-IA) by galactose functionalization for local and prolonged expression of IL-1Ra in liver. Data presented here showed that Glipo-pVAX1-IA facilitated efficient uptake of gene cargos by hepatocytes. The biodistribution studies confirmed a predominant hepatocytes internalization, but a minimal kupffer cells uptake of Glipo-pVAX1-IA following intravenous injection. The locally secreted IL-1Ra attenuated alcohol-induced steatohepatisis and infiltration of inflammatory cells. Together, our results unraveled the critical role of GSDMD membrane pore in IL-1ß hypersecretion and highlighted the hepatocyte-specific Glipo-pVAX1-IA nanobiologics as a promising therapeutic strategy for ASH.

12.
Water Res ; 168: 115199, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655439

RESUMO

The critical challenge of hydrothermal liquefaction (HTL) for bio-oil production from biomass is the production of large amounts of aqueous products (HTL-AP) with high organic contents. The present study investigated the anaerobic digestion (AD) performances of HTL-AP under both thermophilic and mesophilic conditions, and molecular and metabolic analysis were conducted to provide insights into the different performances. The results showed that thermophilic AD had lower COD removal efficiency compared to mesophilic AD (45.0% vs. 61.6%). Liquid chromatography coupled with organic carbon detection and organic nitrogen (LC-OCD-OND) analysis showed that both high molecular weight (HMW) and low molecular weight (LMW) compounds were degraded to some extent and more LMW acids (LMWA) and recalcitrant aromatic compounds were degraded in the mesophilic reactor, which was the main reason of higher COD removal efficiency. Phenyl compounds (e.g. phenol and 2 methoxyphenol), furans and pyrazines were the recalcitrant chemicals detected through GC-MS analysis. Fourier transform ion cyclone resonance mass spectrometry (FT-ICR-MS) analysis demonstrated the complexity of HTL-AP and the proportions of phenolic or condensed aromatic compounds increased especially in the thermophilic effluents. Metabolites analysis showed that the reasons contributing to the differences of mesophilic and thermophilic AD were not only related to the degradation of organic compounds (e.g. benzoate degradation via CoA ligation) in HTL-AP but also related to the microbial autogenesis (e.g. fatty acid biosynthesis) as well as the environmental information processing. In addition, the enrichment of Mesotoga, responsible for the high degradation efficiency of LMWA, and Pelolinea, involved in the degradation of phenyl compounds, were found in mesophilic reactor, which was consistent with higher removal of corresponding organics.


Assuntos
Bactérias , Reatores Biológicos , Anaerobiose , Biocombustíveis , Biomassa , Temperatura
13.
J Immunother Cancer ; 7(1): 346, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829270

RESUMO

BACKGROUND: Inhibitors targeting VEGF and VEGFR are commonly used in the clinic, but only a subset of patients could benefit from these inhibitors and the efficacy was limited by multiple relapse mechanisms. In this work, we aimed to investigate the role of innate immune response in anti-angiogenic therapy and explore efficient therapeutic strategies to enhance efficacy of anti-angiogenic therapy against non-small cell lung cancer (NSCLC). METHODS: Three NSCLC tumor models with responses to VEGF inhibitors were designed to determine innate immune-related underpinnings of resistance to anti-angiogenic therapy. Immunofluorescence staining, fluorescence-activated cell sorting and immunoblot analysis were employed to reveal the expression of immune checkpoint regulator CD47 in refractory NSCLC. Metastatic xenograft models and VEGFR1-SIRPα fusion protein were applied to evaluate the therapeutic effect of simultaneous disruption of angiogenetic axis and CD47-SIRPα axis. RESULTS: Up-regulation of an innate immunosuppressive pathway, CD47, the ligand of the negative immune checkpoint regulator SIRPα (signal regulatory protein alpha), was observed in NSCLC tumors during anti-angiogenic therapy. Further studies revealed that CD47 upregulation in refractory lung tumor models was mediated by TNF-α/NF-κB1 signal pathway. Targeting CD47 could trigger macrophage-mediated elimination of the relapsed NSCLC cells, eliciting synergistic anti-tumor effect. Moreover, simultaneously targeting VEGF and CD47 by VEGFR1-SIRPα fusion protein induced macrophages infiltration and sensitized NSCLC to angiogenesis inhibitors and CD47 blockade. CONCLUSIONS: Our research provided evidence that CD47 blockade could sensitize NSCLC to anti-angiogenic therapy and potentiate its anti-tumor effects by enhancing macrophage infiltration and tumor cell destruction, providing novel therapeutics for NSCLC by disrupting CD47/SIRPα interaction and angiogenetic axis.

14.
Front Immunol ; 10: 2277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616439

RESUMO

Aristolochic acid nephropathy (AAN), as a rapidly progressive interstitial nephropathy due to excessive ingestion of aristolochia herbal medications, has recently raised considerable concerns among clinicians and researchers as its underlying pathogenic mechanisms are largely unclear. In the current study, we identified NLRP3 inflammasome activation as a novel pathological mechanism of AAN. We found that NLRP3 inflammasome was aberrantly activated both in vivo and in vitro after AA exposure. Blockade of IL-1ß and NLRP3 inflammasome activation by IL-1Ra significantly attenuated renal tubular injury and function loss in AA-induced nephropathy. Moreover, NLRP3 or Caspase-1 deficiency protected against renal injury in the mouse model of acute AAN, suggesting that the NLRP3 signaling pathway was probably involved in the pathogenesis of AAN. We also found that administration of IL-22 could markedly attenuate renal tubular injury in AAN. Notably, IL-22 intervention significantly alleviated renal fibrosis and dysfunction in AA-induced nephropathy. Furthermore, IL-22 largely inhibited renal activation of NLRP3 inflammasome in AA-induced nephropathy. These results indicated that IL-22 ameliorated renal tubular injury in AAN through suppression of NLRP3 inflammasome activation. In summary, this study identified renal activation of NLRP3 inflammasome as a novel mechanism underlying the pathogenesis of AAN, thus providing a potential therapeutic strategy for AAN based on suppression of NLRP3 inflammasome activation.

15.
Sensors (Basel) ; 19(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514461

RESUMO

Underwater structural damage inspection has mainly relied on diver-based visual inspection, and emerging technologies include the use of remotely operated vehicles (ROVs) for improved efficiency. With the goal of performing an autonomous and robotic underwater inspection, a novel Tactile Imaging System for Underwater Inspection (TISUE) is designed, prototyped, and tested in this paper. The system has two major components, including the imaging subsystem and the manipulation subsystem. The novelty lies in the imaging subsystem, which consists of an elastomer-enabled contact-based optical sensor with specifically designed artificial lighting. The completed TISUE system, including optical imaging, data storage, display analytics, and a mechanical support subsystem, is further tested in a laboratory experiment. The experiment demonstrates that high-resolution and high-quality images of structural surface damage can be obtained using tactile 'touch-and-sense' imaging, even in a turbid water environment. A deep learning-based damage detection framework is developed and trained. The detection results demonstrate the similar detectability of five damage types in the obtained tactile images to images obtained from regular (land-based) structural inspection.

16.
Carbohydr Polym ; 223: 115043, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31426995

RESUMO

Microwave-assisted hydrothermal extraction of non-structural carbohydrates and hemicelluloses from tobacco biomass was investigated. Non-structural carbohydrates extraction was optimized by an Optimal design. The maximum yields for the leaf and stem were 118.57 mg/g and 120.33 mg/g biomass, respectively. The extracted stem residue was further treated for hemicelluloses extraction. A temperature of 200 °C without holding was proved to be the most efficient condition to produce a hemicelluloses yield of 105.15 mg/g. GPC results showed that the Mw values of precipitated hemicelluloses decreased from 143.5 kDa to 13.25 kDa with increasing temperature and holding time, while the un-precipitated fraction were ranging from 11.83 to 4.88 kDa. Monosaccharide analysis revealed that hemicelluloses extracted at lower temperature are heterogeneous compositional type, including xylan, glucuronoxylan and xylanglucan, while the ratio of xylose increased significantly (up to 72.64%) with increasing temperature. The developed microwave-assisted hydrothermal extraction process opens new avenues for a sustainable tobacco-based biorefinery.


Assuntos
Biomassa , Monossacarídeos/isolamento & purificação , Polissacarídeos/isolamento & purificação , Tabaco/química , Calefação , Temperatura Alta , Micro-Ondas , Peso Molecular , Monossacarídeos/análise , Monossacarídeos/química , Folhas de Planta/química , Caules de Planta/química , Polissacarídeos/análise , Polissacarídeos/química , Extração em Fase Sólida/métodos
17.
Cell Death Dis ; 10(9): 626, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427566

RESUMO

Lung adenocarcinoma (LUAD), which comprises over 50% of all cases of non-small-cell lung cancer, has a poor prognosis and requires novel therapeutic approaches. The sonic Hedgehog (Shh) pathway, which plays a crucial role in differentiation, proliferation, and survival of cancer cells, is likely to be activated in LUADs, suggesting the Shh pathway as a potential therapeutic target for LUAD treatment. In this study, we reported that vismodegib, an inhibitor of the Shh pathway, only elicited minor antitumor efficacy in A549 and NCI-H1975 LUAD cells as well as in the xenograft tumors, with overexpressed GLI2 and increased autophagic activity. The aberrant autophagy in LUAD cells was further confirmed by the three main stages of autophagic flux, including the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes. Furthermore, inhibition of autophagy by siRNA against ATG5 or ATG7 rescued the sensitivity of A549 and NCI-H1975 LUAD cells to vismodegib in vitro. Meanwhile, administration of the pharmaceutical inhibitor of autophagy, chloroquine, contributed to the enhanced anti-LUAD efficacy of vismodegib in vivo, probably through overproduction of ROS, acceleration of apoptosis, and suppression of GLI2 in LUAD tissues. In summary, our research revealed that downregulating autophagy facilitated the anti-LUAD efficacy of the Shh pathway suppression, thus highlighting a potential approach for LUAD therapy via simultaneously targeting the Shh signaling and autophagy pathway.

18.
Bioresour Technol ; 289: 121734, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323713

RESUMO

From the perspective of waste utilization, the invasive species, Eupatorium adenophorum was used to prepare biochar, which was then loaded with iron/nickel bimetals. Compared with pure biochar, the biochar-loaded nano-iron/nickel bimetals have a significant effect on the removal of 2,4,6-trichlorophenol (2,4,6-TCP) from water, and their degradation rate can be increased by 39.7%-71.6% under different conditions. Several factors can influence the removal of 2,4,6-TCP, including the load ratio, pH of the solution, concentration of 2,4,6-TCP, and coexisting ions in water (HCO3-, SO42-, NO3-). Based on the density functional model (DET), Ni can activate H2 (produced in the reaction between nano-Fe and H2O) to convert to H*, which can then substitute Cl. The activation energy is 109.5 kJ/mol, indicating the reaction is easy to take place.


Assuntos
Ageratina , Poluentes Químicos da Água , Purificação da Água , Carvão Vegetal , Clorofenóis , Ferro , Níquel , Água
19.
Appl Microbiol Biotechnol ; 103(12): 4825-4838, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31053913

RESUMO

Arginase I has been documented to impair T cell function and attenuate cellular immunity, however, there is little evidence to reveal the effect of arginase I on macrophage function. Recently, recombinant human arginase I (rhArg) has been developed for cancer therapy and is in clinical trial for hepatocellular carcinoma, whereas the potential immunosuppression induced by rhArg limited its therapeutic efficacy. To improve the clinical outcome of rhArg, addressing the immune suppression appears to be particularly important. In this study, we found that rhArg attenuated macrophage functions, including inhibiting macrophage cell proliferation, nitric oxide (NO) and reactive oxygen species (ROS) production, cytokine secretion, MHC-II surface expression, and phagocytosis, thereby inducing immunosuppression in lipopolysaccharides (LPS)/interferon-γ (IFN-γ)-activated macrophages. Notably, we observed that rhArg downregulated autophagy in activated macrophages. Moreover, application of trehalose (an autophagy inducer) significantly restored the impaired immune function in activated macrophages, suggesting the essential role of autophagy in rhArg-induced immunosuppression. To further illustrate the effect of autophagy in immunosuppression, we then observed the effect of 3-MA (an autophagy inhibitor) on the immune function of macrophages. As expected, inhibiting autophagy by 3-MA attenuated immune functions in activated macrophages. Collectively, this study elucidated that rhArg induced immunosuppression in activated macrophages via inhibiting autophagy, providing potential strategy to ameliorate the immune suppression which is of great significance to cancer therapy and facilitating the development of rhArg as a potential therapy for malignant carcinomas.


Assuntos
Arginase/imunologia , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Imunossupressores/farmacologia , Macrófagos/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Arginase/genética , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Citocinas/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Neoplasias Hepáticas/terapia , Macrófagos/patologia , Camundongos , Óxido Nítrico/metabolismo , Fagocitose/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/imunologia , Trealose/farmacologia
20.
ACS Appl Mater Interfaces ; 11(5): 4842-4857, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30628769

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is now a leading cause of chronic liver disease, and there is currently no available treatment strategy. Interleukin-22 (IL-22) has been recognized as a promising agent for alleviating NAFLD, but the efficacy of IL-22 is far from satisfactory because safe dose of IL-22 elicited limited improvement, whereas higher concentration might induce serious side effects and off-target toxicities. Thus, targeted and sustained expression of IL-22 in the liver is necessary. To meet the challenge, we elaborately developed a novel polymetformin carrier by conjugating biguanide to chitosan, termed chitosan-metformin (CM), which could exert advanced gene delivery efficiency and possess intrinsic therapeutic efficacy from metformin for NAFLD. CM accompanied with penetratin and DSPE-PEG2000 could self-assemble to form stable nanocomplexes with IL-22 gene via electrostatic interaction. This nanoparticle (CDPIA) exerted desirable particle size at ∼100 nm, fine morphology, and efficient cellular internalization. Furthermore, CDPIA also demonstrated a unique superiority in endosomal escape capacity and satisfactory biocompatibility as well as predominant liver accumulation. Most importantly, CDPIA distinctly alleviated hepatic steatosis, restored insulin sensitivity, and improved metabolic syndrome in high-fat-diet-fed mice model. This liver-targeted delivery of IL-22 activated STAT3/Erk1/2 and Nrf2/SOD1 signaling transductions as well as modulated lipid-metabolism-related gene expression. These findings altogether demonstrated that the polymetformin and penetratin-based hybrid nanoparticles could be exploited as a novel safe and efficient strategy for the improvement of NAFLD.


Assuntos
Peptídeos Penetradores de Células/química , Técnicas de Transferência de Genes , Interleucinas/genética , Nanopartículas/química , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Peptídeos Penetradores de Células/farmacocinética , Quitosana/química , Quitosana/farmacocinética , Dieta Hiperlipídica , Modelos Animais de Doenças , Células Hep G2 , Humanos , Interleucinas/metabolismo , Masculino , Metformina/química , Metformina/farmacocinética , Camundongos , Camundongos Endogâmicos C57BL
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA