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1.
J Chromatogr A ; : 460915, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-32008824

RESUMO

Considering the huge difference of biological toxicity, it is extremely significant to recognize the exact content of arsenic species in actual samples. In this paper, a novel pretreatment technique for the efficient extraction of arsenic species from herbal samples is developed by dual-frequency ultrasound-assisted enzymatic digestion (DUED). The preservation of arsenic original form, reduction of the actual analysis time, environmental friendliness and free-interference in subsequent detection make this method over the traditional method such as wet digestion, ashing and some solvent extraction technologies. The combination of DUED and atomic fluorescence spectrometry realize the speciation analysis of arsenic in traditional Chinese medicine. The optimizations of experimental parameters have been achieved, and the potential mechanism is discussed. The experimental data showed that cellulase is suitable for the digestion of herbal matrix than α-amylase and papain. Ultrasound can significantly increase the rate of enzymatic hydrolysis of biological molecules, especially under dual-frequency ultrasound irradiation. The highest relative extraction efficiency can be obtained by combining 40 kHz ultrasonic bath (UB) with 20 kHz ultrasonic probe (UP). Two certified reference materials [CRMs, GBW(E)090066 and GBW(E)090067] and four practical herbs were used to evaluate the accuracy and practicability of the method. Inorganic arsenic, including trivalent arsenic and pentavalent arsenic, was the main species in the four herbal samples.

2.
ACS Nano ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31999429

RESUMO

The development of highly efficient electrocatalysts to reduce overpotentials is vital for accelerating the sluggish oxygen evolution reaction (OER) processes. Herein, we demonstrate ultrathin heterogeneous nanosheets as a promising OER electrocatalyst, which are composed of ultrafine CoFeOx nanoparticles and a monolayered CoN4-based metal-organic framework (MOF) matrix. The embedding of such inorganic nanoparticles in the MOF lattice creates metal Co sites located at the CoFeOx/MOF interfaces. Structural characterization and analysis indicated a higher valence and changed 3d electronic configuration for the interfacial Co in contrast to the CoN4 sites. Furthermore, theoretical calculations reveal the high activity of interfacial Co sites for OER. Electrochemical studies confirm that the ultrathin heterogeneous nanosheets deposited on carbon cloth can achieve an excellent electrocatalytic OER performance with a low overpotential of 232 mV at a current density of 10 mA cm-2 with good stability. This work provides insights on the development of ultrathin OER heterocatalysts with highly active interfaces of inorganic units and MOFs.

3.
Sci Total Environ ; 714: 136697, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31982745

RESUMO

Climate change is exacerbating environmental pollution from crop production. Spatially and temporally explicit estimates of life-cycle environmental impacts are therefore needed for suggesting location and time relevant environmental mitigations strategies. Emission factors and process-based mechanism models are popular approaches used to estimate life-cycle environmental impacts. However, emission factors are often incapable of describing spatial and temporal heterogeneity of agricultural emissions, whereas process-based mechanistic models, capable of capturing the heterogeneity, tend to be very complicated and time-consuming. Efficient prediction of life-cycle environmental impacts from agricultural production is lacking. This study develops a rapid predictive model to quantify life-cycle global warming (GW) and eutrophication (EU) impacts of corn production using a novel machine learning approach. We used the boosted regression tree (BRT) model to estimate future life-cycle environmental impacts of corn production in U.S. Midwest counties under four emissions scenarios for years 2022-2100. Results from BRT models indicate that the cross-validation (R2) for predicting life cycle GW and EU impacts ranged from 0.78 to 0.82, respectively. Furthermore, results show that future life-cycle GW and EU impacts of corn production will increase in magnitude under all four emissions scenarios, with the highest environmental impacts shown under the high-emissions scenario. Moreover, this study found that changes in precipitation and temperature played a significant role in influencing the spatial heterogeneity in all life-cycle impacts across Midwest counties. The BRT model results indicate that machine learning can be a useful tool for predicting spatially and temporally explicit future life-cycle environmental impacts associated with corn production under different climate scenarios.

4.
Talanta ; 209: 120553, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892094

RESUMO

Using ultrasound (US) to reduce the agglomeration of magnetic materials has attracted many researchers' attention in the field of magnetic solid phase extraction (MSPE). This paper showed that even the simple magnetic material (Fe3O4@AuNPs) can stimulate excellent arsenic (As) enrichment performance with the assistance of US. Compared with stirring dispersion, the extraction efficiencies of Fe3O4@AuNPs for 0.2 µg L-1 As(III) and As(V) improved by a factor of about 6.2- and 5.7-times with ultrasonic agitation, respectively. Importantly, when the ultrasonic frequency and power are varied within a certain range, the extraction efficiency was increased by about 50% and 130%, respectively. This effect of ultrasonic frequency and power on the enrichment of arsenic by magnetic materials has never been reported. The number, dispersion uniformity and energy released by the bursting of cavitation bubbles under different conditions are considered to be the main reasons for the above phenomena. Additionally, the As(III) or As(V) can be converted into a gaseous product by in-situ slurry chemical hydride generation (SCHG) technology, and the material adsorbed by the material can be effectively removed, thereby ensuring that the complex is repeated at least 5 times or more. Under the optimized conditions, the whole enrichment process can be shortened from ~1 h to several minutes in the presence of US. At the same time, the linear calibration range was 0.01-3.0 µg L-1 documenting that this US-assisted dispersive MSPE method coupled with a sensitive spectral detector (e.g. atomic fluorescence spectrometer, AFS) is suitable for analysis of inorganic As in natural water samples. The content of arsenic in five kinds of natural water samples ranged from 34 ng L-1 to 2.3 µg L-1.

5.
J Ethnopharmacol ; : 112537, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31901455

RESUMO

PURPOSE: This paper aimed to study the active compounds of Astragali Radix (AR) in the treatment of adriamycin nephropathy (AN) by a combination of network pharmacology and transcriptomics. METHODS: The chemical compounds of AR were screened out by text mining and database searching. Pharm Mapper was used to predict the targets of these chemical compounds. Potential targets of AN were screened by integrating the data from network pharmacology with known transcriptomics analysis results of kidney tissue. Compound-active target-potential target interactions networks were constructed so as to illustrate the relationship between compounds and targets, and obtain the chemical compounds directly related to potential targets of AN. The formula of compound contribution index (CI) based on algorithm was used to screen the active compounds of AR in the treatment of AN. In addition, we established an adriamycin-induced cell damage model with MPC5 cell, and used MTT assay, trypan blue dyeing and western blot analyses to validate the pharmacodynamic effect of the active compounds. RESULTS: 27 chemical compounds and 376 targets in AR were obtained by network pharmacology. Through Compound-active target-potential target interactions networks analysis, 22 compounds and 9 active targets as well as 130 potential targets were linked through 282 edges. The CI of every chemical compounds was further calculated by formula, the first four chemical compounds, including astragaloside IV, formononetin, quercetin and calycosin, whose cumulative contribution rate reached 87.28%, were considered to be active compounds. The results of MTT and trypan blue staining indicate that four active compounds had the significant protective effect on adriamycin-induced cell damage with MPC5 cell. Western blot result showed that four active compounds could significantly increase the expression of podocin protein in MPC5 cell. CONCLUSION: The active compounds of AR in the treatment of AN were successfully identified by using a network pharmacology and transcriptomics approach. This approach is expected to be beneficial to the study of the pharmacodynamic material basis of traditional Chinese medicine (TCM) in treating specific diseases.

6.
Anal Chem ; 92(1): 662-667, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31834784

RESUMO

The continuous detection of hydrogen sulfide (H2S) is significant for revealing its role in the neuron protection and diagnosis of various diseases. In this study, a Prussian blue analog nanocubes (PBA NCs)-based oxidase-like mimic was synthesized and designed for continuous H2S monitoring in a visible light absorption-based online optical detection platform (OODP). A specific chemical reaction between H2S and the PBA NCs induce a decreasing oxidase-like activity of the PBA NCs, generating lower amounts of oxidized products of 3,3'5,5'-tetramethylbenzidine (TMB) and increasing the light intensity. By coupling the microdialysis techniques with OODP, excellent linearity in the range of 0.1-20 µM H2S with a limit of detection of 33 nM and outstanding stability, reproducibility, and specificity in the response to H2S were exhibited. By using this OODP, near real-time response and continuous H2S measurements in the brains of living rats were successfully achieved. This new idea of integrating enzyme-like mimics with specific chemical reactions to form an online optical detection platform for continuous monitoring of neurochemical in the brain may be highly meaningful for thoroughly understanding the function of the brain.

7.
ACS Appl Mater Interfaces ; 12(2): 2171-2179, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31872997

RESUMO

Solar steam generation is regarded as a perspective technology, due to its potentials in solar light absorption and photothermal conversion for seawater desalination and water purification. Although lots of steam generation systems have been reported to possess high conversion efficiencies recently, researches of simple, cost-effective, and sustainable materials still need to be done. Here, inspired by natural young sunflower heads' property increasing the temperature of dish-shaped flowers by tracking the sun, we used 3D-structured carbonized sunflower heads as an effective solar steam generator. The evaporation rate and efficiency of these materials under 1 sun (1 kW m-2) are 1.51 kg m-2 h-1 and 100.4%, respectively, beyond the theoretical limit of 2D materials. This high solar efficiency surpasses all other biomass-based materials ever reported. It is demonstrated that such a high capability is mainly attributed to the 3D-structured top surface, which could reabsorb the lost energy of diffuse reflection and thermal radiation, as well as provide enlarged water/air interface for steam escape. 3D-structured carbonized sunflower heads provide a new method for the future design and fabrication of high-performance photothermal devices.

8.
Chem Commun (Camb) ; 55(96): 14534-14537, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31740902

RESUMO

Fe-N/C single atom catalysts (SACs) exhibit peroxidase-like, oxidase-like, catalase-like, and glutathione peroxidase-like activity. Fe-N/C SACs are successfully applied to control the intracellular H2O2 level. This study not only explores the types of SACs mimicking enzymes but also provides opportunities for SACs in biomedical and other bioengineering applications.


Assuntos
Materiais Biomiméticos/química , Carbono/química , Ferro/química , Nitrogênio/química , Espécies Reativas de Oxigênio/química , Materiais Biomiméticos/metabolismo , Materiais Biomiméticos/farmacologia , Catalase/química , Catalase/metabolismo , Catálise , Sobrevivência Celular/efeitos dos fármacos , Glutationa Peroxidase/química , Glutationa Peroxidase/metabolismo , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Oxirredução , Porfirinas/química , Espécies Reativas de Oxigênio/metabolismo
9.
Cancer Res ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723000

RESUMO

Anti-VEGF therapy prolongs recurrence-free survival in patients with glioblastoma but does not improve overall survival. To address this discrepancy, we investigated immunologic resistance mechanisms to anti-VEGF therapy in glioma models. A screening of immune-associated alterations in tumors after anti-VEGF treatment revealed a dose-dependent upregulation of regulatory T cell (Treg) signature genes. Enhanced numbers of Tregs were observed in spleens of tumor-bearing mice, and later in tumors after anti-VEGF treatment. Elimination of Tregs with CD25 blockade prior to anti-VEGF treatment restored IFN-γ production from CD8+ T cells and improved antitumor response from anti-VEGF therapy. The treated tumors overexpressed the glutamate/cystine antiporter SLC7A11/ xCT which led to elevated extracellular glutamate in these tumors. Glutamate promoted Treg proliferation, activation, suppressive function, and metabotropic glutamate receptor 1 (mGlutR1) expression. We propose that VEGF blockade coupled with glioma-derived glutamate induces systemic and intratumoral immunosuppression by promoting Treg overrepresentation and function, which can be pre-emptively overcome through Treg depletion for enhanced antitumor effects.

10.
J Mater Chem B ; 7(48): 7704-7712, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31754682

RESUMO

Hydrogen peroxide (H2O2) is the main product of enzymatic reactions and plays an important role in biological processes. The detection of H2O2 inside organisms or cells is critical. Here, we report a nickel-iron Prussian blue analogue nanocube doped with molybdenum disulfide and Au nanoparticles (Au@PBA(Ni-Fe):MoS2) as an electrochemical sensing material for the stable detection of H2O2 in neutral solutions for a long time. First, the Prussian blue analogue (PBA(Ni-Fe)) is synthesized by a simple charge-assembly technology, and then etched into PBA(Ni-Fe):MoS2 hollow nanocubes by a high-temperature hydrothermal reaction. Finally, Au nanoparticles are reduced inside the PBA(Ni-Fe):MoS2in situ to generate Au@PBA(Ni-Fe):MoS2 nanocubes. Ni-doping enhances the nanocube's stability in neutral solutions; as a result, the sensor can maintain a stable current response towards H2O2 reduction for more than 1 h. The sensing material can meet the needs of a long-time test. The introduction of Au enhances the electron transfer efficiency, which endows the sensor with good reduction ability for H2O2 at 0 V over a wide linear range (0.5-200 µM and 210-3000 µM) and with a low detection limit (0.23 µM (S/N = 3)), which fulfills the requirements for the detection of H2O2 in a biological system. The sensor can sense H2O2 released from cells stimulated by ascorbic acid. Au@PBA(Ni-Fe):MoS2 provides good guidance for the future development of efficient biosensors to be applied in cell biology.

11.
World J Gastroenterol ; 25(38): 5838-5849, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31636476

RESUMO

BACKGROUND: Prolonged postoperative ileus (PPOI) is one of the common complications in gastric cancer patients who underwent gastrectomy. Evidence on the predictors of PPOI after gastrectomy is limited and few prediction models of nomogram are used to estimate the risk of PPOI. We hypothesized that a predictive nomogram can be used for clinical risk estimation of PPOI in gastric cancer patients. AIM: To investigate the risk factors for PPOI and establish a nomogram for clinical risk estimation. METHODS: Between June 2016 and March 2017, the data of 162 patients with gastrectomy were obtained from a prospective and observational registry database. Clinical data of patients who fulfilled the criteria were obtained. Univariate and multivariable logistic regression models were performed to detect the relationship between variables and PPOI. A nomogram for PPOI was developed and verified by bootstrap resampling. The calibration curve was employed to detect the concentricity between the model probability curve and ideal curve. The clinical usefulness of our model was evaluated using the net benefit curve. RESULTS: This study analyzed 14 potential variables of PPOI in 162 gastric cancer patients who underwent gastrectomy. The incidence of PPOI was 19.75% in patients with gastrectomy. Age older than 60 years, open surgery, advanced stage (III-IV), and postoperative use of opioid analgesic were independent risk factors for PPOI. We developed a simple and easy-to-use prediction nomogram of PPOI after gastrectomy. This nomogram had an excellent diagnostic performance [area under the curve (AUC) = 0.836, sensitivity = 84.4%, and specificity = 75.4%]. This nomogram was further validated by bootstrapping for 500 repetitions. The AUC of the bootstrap model was 0.832 (95%CI: 0.741-0.924). This model showed a good fitting and calibration and positive net benefits in decision curve analysis. CONCLUSION: We have developed a prediction nomogram of PPOI for gastric cancer. This novel nomogram might serve as an essential early warning sign of PPOI in gastric cancer patients.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1463-1468, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607299

RESUMO

OBJECTIVE: To investigate the transcriptional regulation of transcription factor MZF-1 on acute monocytic leukemia-related gene MLAA-34. METHODS: The effect of MZF-1 on the transcriptional activity of MLAA-34 gene promoter was analyzed by luciferase reporter gene detection system and site-directed mutation technique. The EMSA and ChIP assay were used to verify whether MZF-1 directly and specifically binds to the core region of MLAA-34 promoter. The over-expression vector and interference vector of MZF-1 were constructed to transfect U937 cells, and RT-PCR and Western blot were used to detect the transcription and expression changes of MLAA-34 gene. RESULTS: The transcription factor MZF-1 had a regulatory effect on MLAA-34 gene expression, and the relative luciferase activity was decreased after MZF-1 binding point mutation (P<0.01). EMSA and ChIP experiments demonstrated that MZF-1 could directly bind to MLAA-34 promoter and play a regulatory role. In the over-expression test, the increase of MZF-1 could up-regulate the expression of MLAA-34 (P<0.05). In the interference test, the decrease of MZF-1 could down-regulate the expression of MLAA-34 (P<0.05). CONCLUSION: Transcription factor MZF-1 can bind to the transcriptional regulatory region on the promoter of MLAA-34 gene and promote the transcription of MLAA-34 gene in acute monocytic leukemia.


Assuntos
Antígenos de Neoplasias/genética , Proteínas Reguladoras de Apoptose/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Leucemia Monocítica Aguda , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Fator 1-alfa Nuclear de Hepatócito , Humanos , Regiões Promotoras Genéticas , Transcrição Genética
13.
J Cell Mol Med ; 23(12): 8314-8327, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31576676

RESUMO

Endothelial barrier dysfunction is a critical pathophysiological process of sepsis. Impaired endothelial cell migration is one of the main reasons for endothelial dysfunction. Statins may have a protective effect on endothelial barrier function. However, the effect and mechanism of statins on lipopolysaccharide (LPS)-induced endothelial barrier dysfunction remain unclear. Simvastatin (SV) was loaded in nanostructured lipid carriers to produce SV nanoparticles (SV-NPs). Normal SV and SV-NPs were used to treat human umbilical vein vascular endothelial cells (HUVECs) injured by LPS. Barrier function was evaluated by monitoring cell monolayer permeability and transendothelial electrical resistance, and cell migration ability was measured by a wound healing assay. LY294002 and imatinib were used to inhibit the activity of PI3K/Akt and platelet-derived growth factor receptor (PDGFR) ß. IQ-GTPase-activating protein 1 (IQGAP1) siRNA was used to knockdown endogenous IQGAP1, which was used to verify the role of the PDGFRß/PI3K/Akt/IQGAP1 pathway in SV/SV-NPs-mediated barrier protection in HUVECs injured by LPS. The results show that SV/SV-NPs promoted the migration and decreased the permeability of HUVECs treated with LPS, and the efficacy of the SV-NPs exceeded that of SV significantly. LY294002, imatinib and IQGAP1 siRNA all suppressed the barrier protection of SV/SV-NPs. SV/SV-NPs promoted the secretion of platelet-derived growth factor-BB (PDGF-BB) and activated the PDGFRß/PI3K/Akt/IQGAP1 pathway. SV preparations restored endothelial barrier function by restoring endothelial cell migration, which is involved in the regulation of the PDGFRß/PI3K/Akt/IQGAP1 pathway and PDGF-BB secretion. As an appropriate formulation for restoring endothelial dysfunction, SV-NPs may be more effective than SV.

14.
Int Angiol ; 38(5): 365-371, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31566320

RESUMO

BACKGROUND: To assess the efficacy and safety of Orchid drug-coated balloon (DCB) for treatment of femoropopliteal (FP) artery in-stent restenosis (ISR) in Chinese patients. METHODS: The study is a prospective, single center, single-blinded, randomized controlled trial (RCT) that randomized (1:1) 74 patients to DCB group (N.=38) and PTA group (N.=36). The primary efficacy endpoint was primary patency of the target lesion at 12 months. Second efficacy endpoint included clinically-driven target-lesion revascularization (CD-TLR) and ABI change at 12 months. The primary safety endpoint included peri-operative death at 30 days, all-cause death, major amputation, and other major adverse events (MAEs) at 12 months. The primary functional endpoint included Walking Impairment Questionnaire (WIQ), quality-of-life measures (EQ-5D) and 6-minute walking test (6MWT). RESULTS: The DCB group had higher primary patency (87.9% vs. 51.6%; P=0.001) and lower rates of CD-TLR (6.1% vs. 35.5%; P=0.003) than the PTA group at 12 months. There were no peri-operative deaths, and no major amputations at 12 months in two groups. There were 1(2.6%) in the DCB group and 2 (5.6%) in the PTA group of all-cause deaths (P=0.524). CONCLUSIONS: Results from the study showed superior treatment effect with Orchid DCB versus PTA for the treatment of FP ISR, and without an apparent difference in safety.

15.
ACS Appl Mater Interfaces ; 11(43): 40564-40574, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566943

RESUMO

The fabrication of metal-organic framework (MOF)-based macro-materials is considered as a promising strategy toward the practical applications of powdered MOF crystals. In this study, selective laser sintering (SLS), an advanced three-dimensional (3D) powder printing technique, has been employed to fabricate MOF-polymer mixed matrix films (MMFs) by using thermoplastic polyamide 12 (PA12) powder as the matrix material and five types of MOFs including ZIF-67, NH2-MIL-101(Al), MOF-801, HKUST-1, and ZIF-8 crystals as the fillers. A three-layer HKUST-1-PA12 complex with a grid pattern is fabricated to demonstrate the printability of 3D MOF-polymer structure. Single-layer MMFs with grid patterns are printed by using the five types of MOF fillers with different mass loadings to study their free-standing characteristic, thickness, specific surface area, hydrophilia, water permeate flux, and mechanical stability. The methylene blue (MB) adsorption tests are conducted using the NH2-MIL-101(Al)-PA12 MMFs with different grid patterns to exemplify the applications of the MMFs for water purification. It is confirmed that the MOF components retain their high maximum adsorption capacity, and the printed MMFs can be conveniently regenerated for cyclic utilization. This work provides an insight into the utilization of advanced 3D printing technology to manufacture macro-MOF-polymer materials for practical applications.

16.
Opt Express ; 27(15): 21667-21676, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510239

RESUMO

A continuously deformative space possesses trivial or nontrivial topological characteristics depending on the associated homotopy groups associated with spaces describing the physical processes. Moreover, the interaction of spatial warping and structural symmetry always presents fantastic phenomena, especially in the systems with unique symmetrical properties such as quasicrystals. Here, we propose a quasi-periodic structure (QPS) with topological defects. The analytical expression of the corresponding Fourier spectrum is derived, which reflects the combined effects of topological structure and quasi-translational symmetry. Light-matter interaction therein brings unusual diffraction characteristics with exotic evolution of orbital angular momentum (OAM). Long-range correlation of QPS resulted in multi-fractal and pairwise distribution of optical singularities. A general conservation law of OAM is revealed. A liquid crystal photopatterned QPS is fabricated to demonstrate the above characteristics. Dynamic reconfigurable manipulation of optical singularities is achieved. Our approach offers the opportunity to manipulate OAM with multiple degrees of freedom, which has promising applications in multi-channel quantum information processing and high-dimensional quantum state generation.

17.
Biomed Pharmacother ; 118: 109131, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545226

RESUMO

Berberine and metformin, both established pharmaceutical agents with herbal origins, have incidental beneficial effects on multiple diseases, including diabetes. These effects have been speculated to occur via the gut microbiome. In this study, we administered either berberine or metformin to db/db mice and investigated changes in body weight, food intake, and blood glucose levels. Fresh stool samples were analyzed using 16 s rDNA high-throughput sequencing to evaluate the gut microbiome. Short-chain fatty acids (SCFA) in the stool were quantified using gas chromatography. The expression of NF-κB signaling pathway and tight junction (ZO1 and occludin) proteins in the intestinal epithelium was determined using qPCR and western blotting. The intestinal barrier structure was examined using transmission electron microscopy and serum lipopolysaccharide (LPS) was measured using a commercial kit. Both berberine and metformin reduced food intake, body weight, and blood glucose and HbA1c levels. Both treatments effectively restored the intestinal SCFA content, reduced the level of serum LPS, relieved intestinal inflammation, and repaired intestinal barrier structure. Intervention with metformin or berberine modified the gut microbiome in db/db mice, increasing the number of SCFA-producing bacteria (e.g., Butyricimonas, Coprococcus, Ruminococcus) and reducing opportunistic pathogens (e.g., Prevotella, Proteus). An increased abundance of other probiotics including Lactobacillus and Akkermansia was also observed. Berberine and metformin can modulate the composition of the gut microbiome and reduce body weight, blood glucose levels, and intestinal inflammation in db/db mice, which demonstrates their effectiveness in the reduction of diabetic complications in this model.

18.
Int J Med Sci ; 16(8): 1149-1156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523178

RESUMO

Background Sepsis, a leading cause of death in intensive care units, is generally associated with vascular dysfunction. However, its pathophysiological process has not been fully clarified, lacking in-depth knowledge of its pathophysiological process may hinder the improvement of diagnosis and therapy for sepsis. Hence, as the key parts of the vascular wall, the interaction between endothelial cells (ECs) and smooth muscle cells (SMCs) under septic situation need to be further studied. Methods ECs and SMCs were co-cultured using Transwell plates. Lipopolysaccharide (LPS) was used to induce sepsis. A scratch-wound assay was used to assess cell migration, and western blotting was used to assess the level of redifferentiation of SMCs as well as the expression of PDGFR-ß and IQGAP1. Results Co-culture with ECs reduced the redifferentiation of SMCs induced by LPS (10 µg/ml), which was characterized by increased migration ability and decreased expression of contractile proteins (e.g., SM22 and α-SMA). The production of TNF-α could decrease the level of PDGFR-ß in SMCs. Treatment of SMCs with the PDGFR-ß inhibitor imatinib (5 µM) was able to counteract LPS-induced SMC redifferentiation and reduce IQGAP1 protein expression, especially when SMCs were co-cultured with ECs. Conclusion The phenotype of vascular SMCs co-cultured with ECs was modulated by IQGAP1 through the PDGFR-ß pathway, which may lead to vascular remodeling and homeostasis in LPS-induced intravascular injury. This pathway could be a novel target for the treatment of vascular damage.


Assuntos
Músculo Liso Vascular/citologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo , Técnicas de Cocultura , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Humanos , Lipopolissacarídeos/toxicidade , Músculo Liso Vascular/efeitos dos fármacos , Fenótipo , Sepse/metabolismo , Sepse/patologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
19.
Int J Biol Sci ; 15(9): 1846-1860, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523187

RESUMO

Pancreatic disease, including pathologies such as acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic cancer (PC), is a complicated and dangerous clinical condition involving the disruption of exocrine or endocrine function. PC has one of the highest mortality rates among cancers due to insufficient diagnosis in early stages. Furthermore, efficient treatment options for the disease etiologies of AP and CP are lacking. Thus, the identification of new therapeutic targets and reliable biomarkers is required. As essential couriers in intercellular communication, exosomes have recently been confirmed to play an important role in pancreatic disease, but the specific underlying mechanisms are unknown. Herein, we summarize the current knowledge of exosomes in pancreatic disease with respect to diagnosis, molecular mechanisms, and treatment, proposing new ideas for the study of pancreatic disease.

20.
Nat Commun ; 10(1): 4016, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488817

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy targeting solid tumors has stagnated as a result of tumor heterogeneity, immunosuppressive microenvironments, and inadequate intratumoral T cell trafficking and persistence. Early (≤3 days) intratumoral presentation of CAR T cells post-treatment is a superior predictor of survival than peripheral persistence. Therefore, we have co-opted IL-8 release from tumors to enhance intratumoral T-cell trafficking through a CAR design for maximal antitumor activity in solid tumors. Here, we demonstrate that IL-8 receptor, CXCR1 or CXCR2, modified CARs markedly enhance migration and persistence of T cells in the tumor, which induce complete tumor regression and long-lasting immunologic memory in pre-clinical models of aggressive tumors such as glioblastoma, ovarian and pancreatic cancer.


Assuntos
Glioblastoma/imunologia , Imunoterapia Adotiva , Interleucina-8/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8B/metabolismo , Linfócitos T/imunologia , Animais , Antígenos de Neoplasias/imunologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Camundongos Endogâmicos NOD , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
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