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1.
ACS Nano ; 18(22): 14595-14604, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38758185

RESUMEN

Defect engineering and nitrogen doping being effective strategies for modulating the surface chemical state of the carbon matrix have been widely explored to promote the catalytic activity in the territory of electrochemical energy storage and conversion devices. However, the controllable synthesis of carbon material with high-density specific defects and high nitrogen doping is still full of challenges. Here, we first synthesize one-dimensional necklace-like nitrogen-doped carbon nanochains (N-CNCs) with abundant defects on carbon fiber paper (CFP) by chemical vapor deposition (CVD) method. The resultant nanostructures are a bunch of interconnected carbon spheres with a hollow structure at the internode and present the complete one-dimensional nanochain configuration. Specifically, the N-CNCs with a corrugated surface possesses high content of sp3 defects (31.2%) and nitrogen (23.6 at %). Combining finite element analysis and experimental results, it reveals that the robust shear field generated by etching gas releasing from thermal decomposition of melamine in situ modulates the CVD process via changing the size and force environment of the metal catalyst droplets for formation of N-CNCs. Benefiting from the high ratio of sp3/sp2 and nitrogen doped on the surface, the N-CNCs@CFP displays a superior electrocatalytic performance for CO2RR, delivering CO Faradaic efficiency of 95.9% and a current density of 23.2 mA cm-2 at -0.86 V vs RHE. This work provides promising synthesis strategy and some inspirations for construction of ultradense and specific defects coupling with nitrogen doping sites into carbon materials to achieve high-efficiency electrocatalysis applications.

2.
Brief Bioinform ; 25(1)2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-38113075

RESUMEN

Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.


Asunto(s)
Antineoplásicos , Polifarmacología , Proteínas Serina-Treonina Quinasas , Descubrimiento de Drogas
3.
Chin J Nat Med ; 21(11): 842-851, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38035939

RESUMEN

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 µmol·L-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Antineoplásicos/química , Células A549 , Apoptosis , Línea Celular Tumoral , Proliferación Celular
4.
J Med Internet Res ; 25: e52444, 2023 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-37988147

RESUMEN

As wearable devices, which allow individuals to track and self-manage their health, become more ubiquitous, the opportunities are growing for researchers to use these sensors within interventions and for data collection. They offer access to data that are captured continuously, passively, and pragmatically with minimal user burden, providing huge advantages for health research. However, the growth in their use must be coupled with consideration of their potential limitations, in particular, digital inclusion, data availability, privacy, ethics of third-party involvement, data quality, and potential for adverse consequences. In this paper, we discuss these issues and strategies used to prevent or mitigate them and recommendations for researchers using wearables as part of interventions or for data collection.


Asunto(s)
Exactitud de los Datos , Dispositivos Electrónicos Vestibles , Humanos , Recolección de Datos , Privacidad , Investigadores
5.
BMC Med ; 21(1): 388, 2023 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-37814306

RESUMEN

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Glucemia , Hipoglucemiantes/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Método Doble Ciego , Resultado del Tratamiento
6.
Front Microbiol ; 14: 1157601, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37323895

RESUMEN

Mangrove rhizosphere soils host diverse Actinobacteria tolerant to numerous stresses and are inevitably capable of exhibiting excellent biological activity by producing impressive numbers of bioactive natural products, including those with potential medicinal applications. In this study, we applied an integrated strategy of combining phylogenetic diversity, biological activities, and biosynthetic gene clusters (BGCs) screening approach to investigate the biotechnological importance of Actinobacteria isolated from mangrove rhizosphere soils from Hainan Island. The actinobacterial isolates were identifified using a combination of colony morphological characteristics and 16S rRNA gene sequence analysis. Based on the results of PCR-detected BGCs screening, type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected. Crude extracts of 87 representative isolates were subjected to antimicrobial evaluation by determining the minimum inhibitory concentration of each strain against six indicator microorganisms, anticancer activities were determined on human cancer cell lines HepG2, HeLa, and HCT-116 using an MTT colorimetric assay, and immunosuppressive activities against the proliferation of Con A-induced T murine splenic lymphocytes in vitro. A total of 287 actinobacterial isolates affiliated to 10 genera in eight families of six orders were isolated from five different mangrove rhizosphere soil samples, specififically, Streptomyces (68.29%) and Micromonospora (16.03%), of which 87 representative strains were selected for phylogenetic analysis. The crude extracts of 39 isolates (44.83%) showed antimicrobial activity against at least one of the six tested indicator pathogens, especially ethyl acetate extracts of A-30 (Streptomyces parvulus), which could inhibit the growth of six microbes with MIC values reaching 7.8 µg/mL against Staphylococcus aureus and its resistant strain, compared to the clinical antibiotic ciproflfloxacin. Furthermore, 79 crude extracts (90.80%) and 48 (55.17%) of the isolates displayed anticancer and immunosuppressive activities, respectively. Besides, four rare strains exhibited potent immunosuppressive activity against the proliferation of Con A-induced T murine splenic lymphocyte in vitro with an inhibition rate over 60% at 10 µg/mL. Type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected in 49.43, 66.67, and 88.51% of the 87 Actinobacteria, respectively. Signifificantly, these strains (26 isolates, 29.89%) harbored PKS I, PKS II, and NRPS genes in their genomes. Nevertheless, their bioactivity is independent of BGCs in this study. Our findings highlighted the antimicrobial, immunosuppressive, and anticancer potential of mangrove rhizosphere Actinobacteria from Hainan Island and the biosynthetic prospects of exploiting the corresponding bioactive natural product.

7.
J Cheminform ; 15(1): 57, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37287071

RESUMEN

Three-dimensional (3D) conformations of a small molecule profoundly affect its binding to the target of interest, the resulting biological effects, and its disposition in living organisms, but it is challenging to accurately characterize the conformational ensemble experimentally. Here, we proposed an autoregressive torsion angle prediction model Tora3D for molecular 3D conformer generation. Rather than directly predicting the conformations in an end-to-end way, Tora3D predicts a set of torsion angles of rotatable bonds by an interpretable autoregressive method and reconstructs the 3D conformations from them, which keeps structural validity during reconstruction. Another advancement of our method over other conformational generation methods is the ability to use energy to guide the conformation generation. In addition, we propose a new message-passing mechanism that applies the Transformer to the graph to solve the difficulty of remote message passing. Tora3D shows superior performance to prior computational models in the trade-off between accuracy and efficiency, and ensures conformational validity, accuracy, and diversity in an interpretable way. Overall, Tora3D can be used for the quick generation of diverse molecular conformations and 3D-based molecular representation, contributing to a wide range of downstream drug design tasks.

8.
Mediators Inflamm ; 2023: 7123568, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37124060

RESUMEN

Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment for stomach adenocarcinoma (STAD), but only a minority of patients benefit from it. It is believed that the poor therapeutic efficacy is attributed to the complex tumor immune microenvironment (TIM) of STAD. Therefore, elucidating the specific regulatory mechanism of TIM in STAD is critical. Previous study suggests that GRP176 may be involved in regulating the pace of circadian behavior, and its role in tumors has not been reported. In this study, we first found that GPR176 was highly expressed in STAD and negatively correlated with patient prognosis. Next, we investigated the relationship between GPR176 and clinical characteristics, and the results showed that the stage is closely related to the level of GPR176. In addition, our further analysis found that GRP176 expression level was significantly correlated with chemotherapeutic drug sensitivity and ICI response. KEGG and GO analyses showed that GPR176 might be involved in stromal remodeling of STAD. Furthermore, we analyzed the association between GPR176 expression and immune implication, and the results revealed that GPR176 was negatively related to the infiltration of various immune cells. Interestingly, GPR176 induced the conversion of TIM while reducing the tumor immune burden (TMB). The expression of GRP176 is closely related to the level of various immunomodulators. Moreover, we performed univariate and multivariate regression analyses on the immunomodulators and finally obtained 4 genes (CRCR4, TNSF18, PDCD1, and TGFB1). Then, we constructed a GRP176-related immunomodulator prognostic model (GRIM) based on the above 4 genes, which was validated to have good predictive power. Finally, we developed a nomogram based on the risk score of GRIM and verified its accuracy. These results suggested that GPR176 is closely related to the prognosis and TIM of STAD. GPR176 may be a new potential target for immunotherapy in STAD.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Pronóstico , Biomarcadores , Adenocarcinoma/genética , Neoplasias Gástricas/genética , Adyuvantes Inmunológicos , Microambiente Tumoral
9.
Mediators Inflamm ; 2023: 7992140, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152370

RESUMEN

Liver hepatocellular carcinoma (LIHC) is a highly lethal malignant tumor originating from the digestive system, which is a serious threat to human health. In recent years, immunotherapy has shown significant therapeutic effects in the treatment of LIHC, but only for a minority of patients. The basement membrane (BM) plays an important role in the occurrence and development of tumors, including LIHC. Therefore, this study is aimed at establishing a risk score model based on basement membrane-related genes (BMRGs) to predict patient prognosis and response to immunotherapy. First, we defined three patterns of BMRG modification (C1, C2, and C3) by consensus clustering of BMRG sets and LIHC transcriptome data obtained from public databases. Survival analysis showed that patients in the C2 group had a better prognosis, and Gene Set Variation Analysis (GSVA) revealed that the statistically significant pathways were mainly enriched in the C2 group. Moreover, we performed Weighted Correlation Network Analysis (WGCNA) on the above three subgroups and obtained 179 intersecting genes. We further applied function enrichment analyses, and the results demonstrated that they were mainly enriched in metabolism-related pathways. Furthermore, we conducted the LASSO regression analysis and obtained 4 BMRGs (MPV17, GNB1, DHX34, and MAFG) that were significantly related to the prognosis of LIHC patients. We further constructed a prognostic risk score model based on the above genes, which was verified to have good predictive performance for LIHC prognosis. In addition, we analyzed the correlation between the risk score and the tumor immune microenvironment (TIM), and the results showed that the high-risk scoring group tended to be in an immunosuppressed status. Finally, we investigated the relationship between the risk score and LIHC immune function. The results demonstrated that the risk score was closely related to the expression levels of multiple immune checkpoints. Patients in the low-risk group had significantly higher IPS scores, and patients in the high-risk group had lower immune escape and TIDE score. In conclusion, we established a novel risk model based on BMRGs, which may serve as a biomarker for prognosis and immunotherapy in LIHC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas/genética , Membrana Basal , Pronóstico , Microambiente Tumoral , ARN Helicasas
10.
Chem Commun (Camb) ; 59(22): 3261-3264, 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36815681

RESUMEN

A quasi-homogenized miniemulsion system enabled by carbon quantum dot solid nanoparticles for biphasic catalysis is proposed, which breaks existing limits for an immiscibly biphasic system and overcomes issues for large-sized solid particle-stabilized emulsion droplets. The presented Pickering miniemulsion features pH-responsive behavior, finally triggering facile product separation and catalyst recycling in one reaction vessel.

11.
J Pharm Biomed Anal ; 226: 115238, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36645985

RESUMEN

Ormosia hosiei Hemsl. et Wils. is an economical and medicinal plant, increasingly cultivated in China; however, its branches and leaves are often pruned as waste. This is the first study focused on the phytochemical profiles and antioxidant, anti-α-glucosidase, anti-tyrosinase, and anti-neuroinflammatory activities of the branches and leaves of O. hosiei. Herein, thirty-seven characteristic compounds were identified by UPLC-MS/MS and twelve were detected for the first time in O. hosiei. Twenty-seven phenolics were further quantified and significant differences in phenolic compositions between the branches and leaves of O. hosiei were observed. The ethanol extracts exhibited promising antioxidant, anti-α-glucosidase, anti-tyrosinase, and anti-neuroinflammatory effects, and the bioactivities significantly correlated with total phenolic content and twelve individual phenolics. Naringin, genistein, vitexin, vitexin-2-O-rhamnoside, syringaresinol and syringaresinol-4-O-ß-D-glucopyranoside can be considered potential quality markers of O. hosiei. Our results provided solid evidence that the branches and leaves of O. hosiei deserve more attention and exploitation, considering the potential to be developed as functional foods or herbal medicines.


Asunto(s)
Extractos Vegetales , Plantas Medicinales , Extractos Vegetales/química , Antioxidantes/química , Cromatografía Liquida , Espectrometría de Masas en Tándem , Fitoquímicos/análisis , Fenoles/análisis , Glucosidasas , Hojas de la Planta/química
12.
Nat Prod Res ; 37(8): 1321-1327, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34933632

RESUMEN

Two new cytisine-like alkaloids, hositisines C (1) and D (2), were isolated from the seeds of Ormosia hosiei along with four known compounds, (-)-tinctorine (3), ß-adenosine (4), 2'-deoxyadenosine (5), and 7, 2', 4'-trihydroxy-5-methoxyisoflavanone (6). Their structures were established using extensive spectroscopic techniques (UV, IR, CD, HRESIMS, 1 D and 2 D NMR). In the cytotoxic activity, compounds 1-3 and 5-fluorouracil (positive control) displayed inhibitory effects against HepG2 cells, exhibiting IC50 values of 44.52 ± 7.83 µM, 111.49 ± 12.76 µM, 127.72 ± 18.67 µM, and 16.37 ± 3.82 µM.


Asunto(s)
Alcaloides , Fabaceae , Estructura Molecular , Fabaceae/química , Alcaloides/química , Quinolizinas/farmacología , Azocinas/farmacología , Semillas/química
13.
Nat Prod Res ; 37(15): 2486-2492, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35289695

RESUMEN

Two new bibenzyls (1 and 2) were isolated from the pseudobulbs of Pleione grandiflora (Rolfe) Rolfe along with six known compounds, including isoarundinin I (3), isoarundinin II (4), bulbocodin D (5), batatasin III (6), 5,3'-dihydroxy- 4-(p-hydroxybenzyl)-3-methoxybibenzyl (7) and shancigusin F (8). Their structures were established on the basis of spectroscopic methods. These compounds showed potent DPPH free radical scavenging effects with IC50 values ranging from 49.72 ± 0.35 µM to 65.41 ± 0.49 µM.


Asunto(s)
Bibencilos , Medicamentos Herbarios Chinos , Orchidaceae , Antioxidantes/farmacología , Bibencilos/química , Estructura Molecular , Medicamentos Herbarios Chinos/química , Orchidaceae/química
14.
Adv Mater ; 35(14): e2209652, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36575967

RESUMEN

Carbon-hybridized hydroxides (CHHs) have been intensively investigated for uses in the energy conversion/storage fields. Nevertheless, the intrinsic structure-activity relationships between carbon and hydroxides within CHHs are still blurry, which hinders the fine modulation of CHHs in terms of practical applications to some degree. This review aims to figure out the intrinsic role of carbon materials in CHHs with a focus on the interface chemistry and the engineering strategy in-between two components. The fundamental effects of the carbon materials in enhancing the charge/mass transfer kinetics are first analyzed, particularly the extra electron pathways for fast charge transfer and the anchoring sites for boosting the mass transfer. Subsequently, the surface-guided/confined effects of carbon materials in CHHs to modify the morphology and tailor the hydroxides, and functional heterojunction for regulating the inner electronic structure are decoupled. The methods to efficiently construct a stable yet robust solid-solid heterointerface are summarized, including oxygen functional groups engrafting, topological defective sites construction and heteroatom incorporation to activate the inert carbon surface. The smart CHHs in some typical energy applications are demonstrated. Additionally, the methodologies that can reveal the hybridization electron configuration between two components are summed up. At last, the perspective and challenges faced by the CHHs for energy-related applications are outlined.

15.
Angew Chem Int Ed Engl ; 62(4): e202216321, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36414544

RESUMEN

Electrocatalytic synthesis of aldehydes from alcohols exhibits unique superiorities as a promising technology, in which cascade reactions are involved. However, the cascade reactions are severely limited by the low selectivity resulting from the peroxidation of aldehydes in a traditional liquid-solid system. Herein, we report a novel liquid-liquid-solid system to regulate the selectivity of benzyl alcohol electrooxidation. The selectivity of benzaldehyde increases 200-fold from 0.4 % to 80.4 % compared with the liquid-solid system at a high current density of 136 mA cm-2 , which is the highest one up to date. In the tri-phase system, the benzaldehyde peroxidation is suppressed efficiently, with the conversion of benzaldehyde being decreased from 87.6 % to 3.8 %. The as-produced benzaldehyde can be in situ extracted to toluene phase and separated from the electrolyte to get purified benzaldehyde. This strategy provides an efficient way to efficiently enhance the selectivity of electrocatalytic cascade reactions.

16.
Int J Prosthodont ; 2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36484666

RESUMEN

PURPOSE: To evaluate the accuracy of intraoral scanners by comparing the marginal fit of 70 all-ceramic crowns fabricated from both conventional impressions and intraoral scans. MATERIALS AND METHODS: A total of 70 posterior teeth requiring single-crown restorations randomly underwent either intraoral scanning or conventional impression-taking followed by laboratory scanning of the casts in a parallel-group RCT. Subsequently, 70 monolithic all-ceramic crowns were CAD/CAM fabricated; only the impression technique differed. Marginal fit, internal fit, adjustment time required for insertion and occlusal contacts, and visual analog scale (VAS) scores assessing dentists' satisfaction with all of the crowns were clinically evaluated by a blinded and calibrated examiner. Data were analyzed using independent-samples t test and likelihood ratio test or Fisher exact test. All tests were performed with α = .05. RESULTS: The mean marginal fit with intraoral scanning (57.94 ± 22.51 µm) was better than with diagnostic cast scanning (82.98 ± 21.72 µm). The difference was statistically significant (P = .000). The differences in internal fit, adjustment time for crown insertion and occlusal contacts, and VAS scores were also significant, and the secondary outcomes were in favor of intraoral scanning. CONCLUSION: Within the limitations of this clinical trial, CAD/CAM-fabricated single-tooth restorations in the posterior region produced by an intraoral scanning technique using TRIOS was found to be a more accurate and efficient alternative to restorations based on conventional impressions in combination with the laboratory scanning technique.

17.
J Chromatogr A ; 1683: 463550, 2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36219969

RESUMEN

Mussel-inspired catechol-amine co-deposition is an effective modification strategy for various materials. In this work, polyvinylidene fluoride (PVDF) membrane was employed as the carrier for α-glucosidase immobilization. By virtue of the co-polymerization of tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) and the hydrolysis of APTES, a hierarchical layer-colloidal nanospheres coating was decorated on the surface of PVDF membrane. Subsequently, α-glucosidase was covalently bound to the modified PVDF membrane through Schiff base reaction and Michael addition reaction between the residual quinine groups in the coating and the amino groups in enzyme molecules. Several parameters affecting the immobilization procedure were investigated thoroughly. The morphology and functional groups of the prepared composite were characterized by scanning electron microscopy (SEM), Fourier transform infrared-Attenuated total reflectance spectroscopy (FTIR-ATR), and X-ray photoelectron spectroscopy (XPS). Combined with capillary electrophoresis (CE) analysis, the performance, enzyme reaction kinetics and inhibition kinetics of PVDF-immobilized α-glucosidase were studied. The immobilized enzyme exhibited the enhanced tolerance to temperature and pH value. In addition, it possessed good reusability maintaining 77.1% of initial relative activity after 11 recycles, and batch-to-batch reproducibility with RSD of 4.3% (n = 10). The Michaelis-Menten constant (Km) of immobilized enzyme was calculated to be 4.16 mM, and IC50 value of acarbose was 0.10 µM. Finally, the PVDF-immobilized α-glucosidase was applied to screening potential inhibitors from 13 kinds of traditional Chinese medicines (TCMs), among which Sanguisorba Radix exhibited the strongest inhibitory activity. The positive results suggested that TA/APTES co-deposition was a simple and mild functionalization method for chemically inert polymer membrane and the proposed screening method was a reliable approach for discovering enzyme inhibitors from TCMs.


Asunto(s)
Enzimas Inmovilizadas , alfa-Glucosidasas , alfa-Glucosidasas/metabolismo , Enzimas Inmovilizadas/metabolismo , Taninos/química , Polímeros , Bases de Schiff , Acarbosa , Reproducibilidad de los Resultados , Quinina , Concentración de Iones de Hidrógeno , Propilaminas , Inhibidores Enzimáticos , Catecoles
18.
J Ethnopharmacol ; 295: 115455, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35697192

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Euscaphis konishii Hayata is a traditional medicinal plant in China, and its leaves are usually used to make dishes for hepatic or gastrointestinal issues by Chinese She nationality. Pharmacological analysis showed that E. konishii leaves contain high levels of flavonoids and chromones with favorable anti-hepatoma effect. AIM OF THE STUDY: The extract from E. konishii leaves was detected to evaluate its chemical composition, and the alcoholic liver injury mice model was adopted to elucidate its hepatoprotective effects. MATERIALS AND METHODS: The total leaf extract from E. konishii was separated by polyamide column to get the flavonoid and chromone-rich extract (FCE). Single compounds from FCE was purified by gel and Sephadex LH-20 chromatography and analyzed by nuclear magnetic resonance (NMR). The chemical component of FCE was confirmed and quantified by HPLC-MS. The OH·, O2-, DPPH and ABTS + free radical assays were adopted to estimate the antioxidant activity of FCE in vitro. The alcohol-fed model mice were established to assess the hepatoprotective capacity of FCE in vivo, through biochemical determination, histopathological analysis, mitochondrial function measurement, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) detection and Western blot determination. RESULTS: 8 flavonoids and 2 chromones were recognized in the FCEextract by both NMR and HPLC-MS. FCE represented strong free radicals scavenging activity in vitro. With oral administration, FCE (50, 100 and 200 mg/kg) dose-dependently decreased the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) in alcohol-fed mice. FCE gradually reduced the malondialdehyde (MDA) content, increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the alcohol-treated liver tissues. FCE also alleviated the hepatic inflammation, inhibited the hepatocyte apoptosis and lessened the alcohol-induced histological alteration and lipid accumulation in the liver tissues. FCE administration inhibited the overexpression of endoplasmic reticulum (ER) chaperones signaling and unfolded protein response (UPR) pathways to defense the ER-induced apoptosis. Pretreatment with FCE also restored the mitochondrial membrane potentials andadenosine triphosphate (ATP) levels, which in turn suppressed the Cytochrome C release and mitochondria-induced apoptosis. CONCLUSIONS: FCE conferred great protection against alcoholic liver injury, which might be associated with its viability through suppressing reactive oxygen species (ROS) stress and hepatocyte apoptosis.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Flavonoides , Alanina Transaminasa , Animales , Antioxidantes/farmacología , Aspartato Aminotransferasas , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cromonas/farmacología , Femenino , Flavonoides/farmacología , Flavonoides/uso terapéutico , Hígado , Ratones , Estrés Oxidativo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
19.
Angew Chem Int Ed Engl ; 61(30): e202115885, 2022 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-35524649

RESUMEN

Pickering emulsions are particle-stabilized surfactant-free dispersions composed of two immiscible liquid phases, and emerge as attractive catalysis platform to surpass traditional technique barrier in some cases. In this review, we have comprehensively summarized the development and the catalysis applications of Pickering emulsions since the pioneering work in 2010. The explicit mechanism for Pickering emulsions will be initially discussed and clarified. Then, summarization is given to the design strategy of amphiphilic emulsion catalysts in two categories of intrinsic and extrinsic amphiphilicity. The progress of the unconventional catalytic reactions in Pickering emulsion is further described, especially for the polarity/solubility difference-driven phase segregation, "smart" emulsion reaction system, continuous flow catalysis, and Pickering interfacial biocatalysis. Challenges and future trends for the development of Pickering emulsion catalysis are finally outlined.

20.
ChemSusChem ; 15(7): e202102473, 2022 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-35146937

RESUMEN

Widely pH-stable emulsions configured by solid emulsifiers with high chemical stabilities and anti-corrosion properties under strong acid or alkaline conditions are highly sought after for practical and wide application of Pickering interfacial catalysis. Herein, a unique strategy was reported for synthesis of a widely pH-stable and novel emulsifier by passivating the pH-responsive sites on graphene oxide nanoribbon (GONR) surface using ionic liquid (IL). The suitable wettability of GONR-IL was derived from the positive binding energy between IL and water, which ensured the stability of the emulsion in a wide pH range. Benefiting from the passivated surface chemistry of GONR, the emulsion microreactor stabilized by GONR-IL exhibited a remarkable stability over a wide range of pH values. A GONR-IL-supported Pd catalyst stabilized at the toluene-water interface achieved an excellent emulsion catalytic activity for benzyl alcohol oxidation (conversion of 92 %), which was exceedingly higher than that of Pd/GONR (<1 %), Pd/CNTs-IL (51 %), or Pd/GO-IL (8 %).


Asunto(s)
Alcohol Bencilo , Emulsionantes , Emulsionantes/química , Emulsiones/química , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Agua/química
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