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1.
BMC Musculoskelet Disord ; 22(1): 846, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610813

RESUMO

BACKGROUND: The treatment for intertrochanteric femoral fractures (IFF) among the elderly has been a controversial topic. Hemiarthroplasty (HA) and proximal femoral nail antirotation (PFNA) have their own advantages in the management of IFF. Hence, this study aims to compare and analyze differences in the effectiveness of both procedures on IFF among the elderly. METHODS: Overall, 99 patients (81.09 ± 8.29 years; 68 women) underwent HA or PFNA from January 2016 to May 2020. IFF were classified according to the Arbeitsgemeins für Osteosynthesefragen (AO) classification. The difference in underlying diseases, the American Society of Anesthesiologists (ASA) grade, Singh index, Harris scores, surgical time, intraoperative bleeding, postoperative blood test results, postoperative number of days to partially bearing weight, and survival outcomes were analyzed. Postoperative follow-ups were performed every 3 months. RESULTS: There was no significant difference in the AO classification, underlying diseases, ASA grade, Singh index, surgical time, and survival outcomes of the HA (45 patients) group and PFNA group (54 patients). The HA group was associated with earlier partial weight-bearing (HA: 4 [2 ~ 4.5] days, PFNA: 10 [8~14] days). It also had a higher total Harris score than the PFNA group at the 6-month follow-up visit (HA: 86.8 [81.90 ~ 90.23], PFNA: 83.48 [75.13 ~ 88.23]). Harris scores decreased more in patients aged ≥90 years in the PFNA group than in the HA group. The postoperative stress recovery rate in the HA group was faster based on postoperative blood test results. CONCLUSIONS: PFNA and HA have good therapeutic effects in the treatment of IFF. The advantages of HA were reflected in short-term weight bearing, faster recovery from stress, and better joint function in the long term. This advantage is more obvious in the patient population aged over 90 years. Therefore, we suggest that surgeons should consider the benefit of HA in the treatment of IFF among the elderly. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000035814. Registered 17 August 2020, https://www.chictr.org.cn/showproj.aspx?proj=57083.


Assuntos
Hemiartroplastia , Fraturas do Quadril , Idoso , Idoso de 80 Anos ou mais , Pinos Ortopédicos , Estudos de Casos e Controles , Feminino , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Humanos , Masculino , Estudos Retrospectivos
2.
Nano Lett ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647747

RESUMO

The involvement between electron transfer (ET) and catalytic reaction at the electrocatalyst surface makes the electrochemical process challenging to understand and control. Even ET process, a primary step, is still ambiguous because it is unclear how the ET process is related to the nanostructured electrocatalyst. Herein, locally enhanced ET current dominated by mass transport effect at corner and edge sites bounded by {111} facets on single Au triangular nanoplates was clearly imaged. After decoupling mass transport effect, the ET rate constant of corner sites was measured to be about 2-fold that of basal {111} plane. Further, we demonstrated that spatial heterogeneity of local inner potential differences of Au nanoplates/solution interfaces plays a key role in the ET process, supported by the linear correlation between the logarithm of rate constants and the potential differences of different sites. These results provide direct images for heterogeneous ET, which helps to understand and control the nanoscopic electrochemical process and electrode design.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34542277

RESUMO

Bi0.42Sb1.58Te3 + x wt % Cu1.8S (x = 0, 0.03, 0.05, and 0.1) bulk materials with enhanced thermoelectric and mechanical properties were fabricated by a solid-state reaction and spark plasma sintering. The thermoelectric properties, such as electrical transport properties and thermal conductivity, are highly dependent on the Cu1.8S content. The highest value of ZT obtained for Bi0.42Sb1.58Te3 with 0.05 wt % Cu1.8S is 1.23 at 373 K, and an optimistic average ZT of 1.2 is achieved at temperatures in the range of 323-448 K, which is 34% higher than that of the pristine sample. The highly enhanced ZT of the doped sample is attributed to the increased electrical conductivity and reduced lattice thermal conductivity caused by the effective element doping and the multiscale phonon scattering by quantities of point defects, twin boundaries, and nanopores. Further, the hardness obtained for this sample is 1.02 GPa, which is increased by 16% in comparison with that of the pristine sample. The conversion efficiency of the doped sample is also significantly higher than that of the pristine sample. Therefore, Cu1.8S is considered to be a promising dopant for enhancing the thermoelectric and mechanical properties of Bi-Sb-Te-based thermoelectric materials.

4.
Curr Drug Metab ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34468296

RESUMO

BACKGROUND: Gelsemium elegans Benth(G. elegans) is a well-known toxic plant. Alkaloids are main active components of G. elegans. Currently, the metabolism of several alkaloids, such as gelsenicine, koumine, and gelsemine, has been widely studied. However, as one of the most important alkaloids in G. elegans, the metabolism of humantenine has not been studied yet. METHODS: In order to elaborate on the in vitro metabolism of humantenine, a comparative analysis of its metabolic profile in human, pig, goat and rat liver microsomes was carried out using high-performance chromatography/quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS) for the first time. RESULTS: Totally, ten metabolites of humantenine were identified in liver microsomes from human (HLMs), pig (PLMs), goat (GLMs) and rat (RLMs) based on the accurate MS/MS spectra. Five metabolic pathways of humantenine, including demethylation, dehydrogenation, oxidation, dehydrogenation and oxidation, and demethylation and oxidation, were proposed in this study. There were qualitative and quantitative species differences in the metabolism of humantenine among the four species. CONCLUSIONS: The in vitro metabolism of humantenine in HLMs, PLMs, GLMs and RLMs was studied by a sensitive and specific detection method based on HPLC/QqTOF-MS. The results indicated that there were species-related differences in the metabolism of humantenine. This work might be of great significance for the further research and explanation of species differences in terms of toxicological effects of G. elegans.

5.
Waste Manag ; 134: 220-230, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34454188

RESUMO

The heterogeneous Fenton-like process with bimetallic chelated magnetic chitosan aerogel (Cu-Fe@CTS) as catalyst was applied to treat pre-coagulated leachate nanofiltration concentrate. The process conditions were optimized by Box-Behnken Design (BBD) and the maximum UV254 removal reached 96.06% under the conditions of temperature 87.62 °C, oxidant dosage 0.2395 mol/L and catalyst dosage 1 g/L. The TOC concentration was reduced from 847.5 to 99.7 mg/L and COD concentration was reduced from 1625 to 464 mg/L. The three-dimensional (3D) fluorescence analysis showed that most of Fulvic acid-like (FA-like) was removed. The adsorption experiment showed that the catalyst reached the adsorption balanced after 60 min and the corresponding FA adsorption removal reached 14.1%. The addition of Tert-butanol (TBA) reduced the FA removal by 59.4%, indicating that the hydroxyl radicals (OH) was the main active species. Experiments of the OH capture at different pH showed that the Fenton-like system produced more OH at pH of 4, at which the maximum FA removal was 96.61%, while the FA removal still reached 94.26% at pH of 7. The OH capture at different temperature showed that the Fenton-like system produced more OH at 90 °C. KI and TBA shielding experiments showed that OH was produced on the catalyst surface rather than being produced by catalysis of free metal ions in the solution.


Assuntos
Peróxido de Hidrogênio , Poluentes Químicos da Água , Catálise , Ferro , Oxirredução , Poluentes Químicos da Água/análise
6.
Molecules ; 26(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34443301

RESUMO

Staphylococcus saprophyticus, the food-borne bacteria present in dairy products, ready-to-eat food and environmental sources, has been reported with antibiotic resistance, raising concerns about food microbial safety. The antimicrobial resistance of S. saprophyticus requires the development of new strategies. Light- and photosensitizer-based antimicrobial photodynamic inactivation (PDI) is a promising approach to control microbial contamination, whereas there is limited information regarding the effectiveness of PDI on S. saprophyticus biofilm control. In this study, PDI mediated by natural bioactive compound (curcumin) associated with LED was evaluated for its potential to prevent and disrupt S. saprophyticus biofilms. Biofilms were treated with curcumin (50, 100, 200 µM) and LED fluence (4.32 J/cm2, 8.64 J/cm2, 17.28 J/cm2). Control groups included samples treated only with curcumin or light, and samples received neither curcumin nor light. The action was examined on biofilm mass, viability, cellular metabolic activity and cytoplasmic membrane integrity. PDI using curcumin associated with LED exhibited significant antibiofilm activities, inducing biofilm prevention and removal, metabolic inactivation, intracellular membrane damage and cell death. Likewise, scanning electronic microscopy observations demonstrated obvious structural injury and morphological alteration of S. saprophyticus biofilm after PDI application. In conclusion, curcumin is an effective photosensitizer for the photodynamic control of S. saprophyticus biofilm.


Assuntos
Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/farmacologia , Fotoquimioterapia , Staphylococcus saprophyticus/fisiologia , Biofilmes/efeitos dos fármacos , Contagem de Colônia Microbiana , Curcumina/farmacologia , Staphylococcus saprophyticus/citologia , Staphylococcus saprophyticus/efeitos dos fármacos , Staphylococcus saprophyticus/ultraestrutura
7.
Oxid Med Cell Longev ; 2021: 6614574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457117

RESUMO

Inflammatory reactions mediated by the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to non-small-cell lung cancer (NSCLC) progression, particularly in patients with bacterial infections. Salidroside (SAL) has recently been shown to suppress lipopolysaccharide- (LPS-) induced NSCLC proliferation and migration, but its mechanism of action remains unclear. It has been shown that SAL improves metabolic inflammation in diabetic rodents through AMP-activated protein kinase- (AMPK-) dependent inhibition of the NLRP3 inflammasome. However, whether the NLRP3 inflammasome is regulated by SAL in NSCLC cells and how its underlying mechanism(s) can be determined require clarification. In this study, human lung alveolar basal carcinoma epithelial (A549) cells were treated with LPS, and the effects of SAL on cell proliferation, migration, AMPK activity, reactive oxygen species (ROS) production, and NLRP3 inflammasome activation were investigated. We found that LPS induction increases the proliferation and migration of A549 cells which was suppressed by SAL. Moreover, SAL protected A549 cells against LPS-induced AMPK inhibition, ROS production, and NLRP3 inflammasome activation. Blocking AMPK using Compound C almost completely suppressed the beneficial effects of SAL. In summary, these results indicate that SAL suppresses the proliferation and migration of human lung cancer cells through AMPK-dependent NLRP3 inflammasome regulation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glucosídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fenóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Proliferação de Células , Humanos , Inflamassomos/metabolismo , Lipopolissacarídeos/farmacologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Transdução de Sinais , Células Tumorais Cultivadas
8.
Artigo em Inglês | MEDLINE | ID: mdl-34433122

RESUMO

Humantenirine is an active oxindole alkaloid extracted from Gelsemium elegans Benth (G. elegans). In the present study, the metabolites of humantenirine in liver microsomes were first identified by HPLC/QqTOF-MS. Then, the metabolic profile and tissue distribution after oral administration in rats were further investigated. A total of seven metabolites were identified in vitro, and five metabolites in vitro were found in vivo. Moreover, a Ⅱ-phase metabolite was identified first in vivo. The results indicated that humantenirine could be metabolized widely. The parent drug and its metabolites were distributed widely in various tissues and highly in the liver and pancreas. However, the parent drug and its metabolites had low peak intensities in plasma. The elimination of humantenirine occurred rapidly as well, the most unconverted forms of which were found in the kidney. Metabolic pathways, including demethylation, dehydrogenation, oxidation and glucuronidation, were proposed. The present findings may provide a basis for the study of pharmacokinetic characteristics and will contribute to the evaluation of the pharmacology and toxicity of G. elegans.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34235851

RESUMO

The role of solution aggregates on the charge transport process of conjugated polymers in electronic devices has gained increasing attention; however, the correlation of the charge carrier mobilities between the solution aggregates and the solid-state films remains elusive. Herein, three polymers, FBDOPV-2T, FBDOPV-2F2T, and FBDOPV-4F2T, are designed and synthesized with distinct aggregation behavior in solution. By combining contact-free ultrafast terahertz (THz) spectroscopy and field-effect transistor measurements, we track the charge carrier mobility of the aggregates of these polymers from the solution to the thin-film state. Remarkably, the mobility of these three polymers is found to follow nearly the same trend (FBDOPV-2T>FBDOPV-2F2T≫FBDOPV-4F2T) in both solutions and thin-film states. The quantitative mobility correlation indicates that the charge transport properties of solution aggregates play a critical role in determining the thin-film charge transport properties and final device performance. Our results highlight the importance of investigating and controlling solution aggregation structures towards efficient organic electronic devices.

10.
J Colloid Interface Sci ; 602: 426-436, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34144301

RESUMO

Inspired by the interfacial catalysis of lipase, Herein, the hydrophobic ZIF-L coated with polydimethylsiloxane (PDMS) were prepared by chemical vapor deposition (CVD) and used to immobilize lipase from Aspergillus oryzae (AOL) for biodiesel production. The results showed that the PDMS coating enhanced the stability of ZIF-8 and ZIF-L in PBS. Immobilization efficiency of AOL on PDMS-modified ZIF-L was 96% under optimized conditions. The resultant immobilized lipase (AOL@PDMS-ZIF-L) exhibited higher activity recovery (430%) than AOL@ZIF-L. Meanwhile, compared with free lipase, the AOL@PDMS-ZIF-L exhibited better storage stability and thermal stability. After 150 days of storage, the free lipase retained only 20% of its original activity of hydrolyzing p-NPP, while the AOL@PDMS-ZIF-L still retained 90% of its original activity. The biodiesel yield catalyzed from soybean oil by free lipase was only 69%, However, the biodiesel yield by AOL@PDMS-ZIF-L reached 94%, and could still be maintained at 85% even after 5 consecutive cycles. It is believed that this convenient and versatile strategy has great promise in the important fields of immobilized lipase on MOF for biodiesel production.


Assuntos
Lipase , Estruturas Metalorgânicas , Biocombustíveis , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Lipase/metabolismo
11.
Nanomicro Lett ; 13(1): 56, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34138258

RESUMO

The development of microwave absorption materials (MAMs) is a considerable important topic because our living space is crowed with electromagnetic wave which threatens human's health. And MAMs are also used in radar stealth for protecting the weapons from being detected. Many nanomaterials were studied as MAMs, but not all of them have the satisfactory performance. Recently, metal-organic frameworks (MOFs) have attracted tremendous attention owing to their tunable chemical structures, diverse properties, large specific surface area and uniform pore distribution. MOF can transform to porous carbon (PC) which is decorated with metal species at appropriate pyrolysis temperature. However, the loss mechanism of pure MOF-derived PC is often relatively simple. In order to further improve the MA performance, the MOFs coupled with other loss materials are a widely studied method. In this review, we summarize the theories of MA, the progress of different MOF-derived PC­based MAMs, tunable chemical structures incorporated with dielectric loss or magnetic loss materials. The different MA performance and mechanisms are discussed in detail. Finally, the shortcomings, challenges and perspectives of MOF-derived PC­based MAMs are also presented. We hope this review could provide a new insight to design and fabricate MOF-derived PC-based MAMs with better fundamental understanding and practical application.

12.
J Food Biochem ; : e13820, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34132394

RESUMO

Oxidative stress-associated mitochondrial dysfunction has been identified as a major mechanism in multiple neurodegenerative diseases. This study aims to investigate the cytoprotective effects of piceatannol on ROS-mediated PC-12 cells damage and related mitochondrial dysfunction. Piceatannol treatment could significantly attenuate PC-12 cells oxidative damage and ROS-mediated cells apoptosis. Moreover, pretreatment with piceatannol effectively decreased mitochondrial membrane depolarization, cleaved-caspase 3, and increased Bcl-2 and Bcl-2/Bax compared with control H2 O2 group. Meanwhile, piceatannol treatment improved mitochondrial respiration function which led to an enhancement in the maximal respiration and spare respiratory capacity. Further mechanisms analysis showed that the protein expression of SIRT3 and its downstream protein FOXO3a were significantly increased after piceatannol addition in a dose-dependent manner. Whereas the cytoprotective role of piceatannol was markedly abolished by the SIRT3 inhibitor 3-TYP, suggesting that SIRT3/FOXO3a signaling pathway played a vital role in mediating the neuronal cytoprotective effects of piceatannol. PRACTICAL APPLICATIONS: The results of our study provide a novel insight that piceatannol could be potentially used as a promising bioactive component against oxidative damage and neurocyte apoptosis. The findings may provide theoretical basis for brain health of piceatannol consumption in some extent.

13.
Transl Vis Sci Technol ; 10(4): 24, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34004000

RESUMO

Purpose: This study sought to perform automated segmentation of 11 retinal layers and Stargardt-associated features on spectral-domain optical coherence tomography (SD-OCT) images and to analyze differences between normal eyes and eyes diagnosed with Stargardt disease. Methods: Automated segmentation was accomplished through application of the deep learning-shortest path (DL-SP) framework, a shortest path segmentation approach that is enhanced by a deep learning fully convolutional neural network. To compare normal eyes and eyes diagnosed with Stargardt disease, various retinal layer thickness and intensity feature maps associated with the outer retinal layers were generated. Results: The automated DL-SP approach achieved a mean difference within a subpixel accuracy range for all layers when compared to manually traced layers by expert graders. The algorithm achieved mean and absolute mean differences in border positions for Stargardt features of -0.11 ± 4.17 pixels and 1.92 ± 3.71 pixels, respectively. In several of the feature maps generated, the characteristic Stargardt features of flecks and atrophic-appearing lesions were readily visualized. Conclusions: To the best of our knowledge, this is the first automated algorithm for 11 retinal layer segmentation on OCT in eyes with Stargardt disease, and, furthermore, the feature differences found between eyes diagnosed with Stargardt disease and normal eyes may inform new insights and the better understanding of retinal characteristic morphologic changes caused by Stargardt disease. Translational Relevance: The automated algorithm's performance and the feature differences found using the algorithm's segmentation support the future applications of SD-OCT for the quantitative monitoring of Stargardt disease.


Assuntos
Aprendizado Profundo , Algoritmos , Humanos , Retina/diagnóstico por imagem , Doença de Stargardt , Tomografia de Coerência Óptica
14.
Sci Total Environ ; 780: 146631, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34030310

RESUMO

Currently used foam agent HCFC-141b was undergoing phased out worldwide with the implementation of the Montreal Protocol. HFO-1234ze was proposed as replacement in polyurethane (PU) foam industry with shorter atmospheric lifetime. This paper calculated historical and future emissions of HCFC-141b and HFO-1234ze till 2050, used GEOS-Chem under two HFO-1234ze emission scenarios to track its atmospheric process and distribution, and to assess its potential environmental effects. Results showed that annual HCFC-141b emissions for 2015, 2019 and 2050 were 12.6 Gg/yr, 21.0 Gg/yr and 7.6 Gg/yr, respectively and emissions of HFO-1234ze would reach 124.4 Gg/yr by 2050. Under Scenario I with HFO-1234ze emissions of 12.6 Gg/yr as input, annual mixing ratios of HFO-1234ze and its products CF3CHO and HCOF were 10.47, 2.68 and 1.74 pptv for China, and were 0.55, 0.18 and 0.1 pptv globally, respectively, suggesting the regional aggregation of these substances in emission areas. HCOF were removed from atmosphere by depositions, with total deposition rates of 22.06 g km-1 y-1 in CH, and 1.15 g km-1 y-1 in globe. Under Scenario II with HFO-1234ze emissions of 124.4 Gg/yr as input, annual mixing ratios of HFO-1234ze, CF3CHO and HCOF, along with HCOF total deposition rates were 102.98 26.36 and 17.17 pptv and 217 g km-1 y-1 in China, respectively, increased linearly to HFO-1234ze emissions change. The mixing ratios of HFO-1234ze and HCOF were too small to exert significant effects on current atmosphere burden and circulation, while CF3CHO might potentially involve in aminolysis reaction under future emissions of HFO-1234ze.

15.
Front Cell Infect Microbiol ; 11: 609722, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791234

RESUMO

Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization.


Assuntos
Probióticos , Administração Oral , Trato Gastrointestinal , Trânsito Gastrointestinal , Intestinos
16.
Biomed Pharmacother ; 137: 111284, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33561641

RESUMO

BACKGROUND: Gelsemium elegans (G. elegans) is a flowering plant of the Loganiaceae family, which had been used in traditional Chinese herb medicine for many years for the treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers, anxiety and cancer. Acute toxicity of the plant severely limits the application and development of G. elegans; however, long-term toxicity of exposure to G. elegans has not been illuminated. PURPOSE: This study is a comprehensive observation of the effects of long-term exposure (21 days at 70 mg/kg) to G. elegans in rats. METHODS AND RESULTS: The histopathological examination showed only a mild glial cell proliferation in the brain, and no lesions were observed in other organs. No abnormal changes in the biochemical parameters were observed that would have significant effects. The identification and analysis of absorbed natural ingredients showed that the active ingredients of the G. elegans could distribute to various tissues, and six compounds were identified in the brain, suggesting that they could cross the blood-brain barrier. Based on the intestinal content metabolomics, the tryptophan (Trp) biosynthesis, bile acid synthesis and bile secretion pathways have attracted our attention. Plasma metabolomic results showed that uric acid (UA) was significantly increased. The results of the brain metabolomic tests showed that the level of pyridoxal (PL) was decreased; considering the expression levels of the related enzymes, it was hypothesized that the level of pyridoxal 5'-phosphate (PLP) was decreased. PLP was important for the regulation of the neuronal γ-aminobutyric acid (GABA)/glutamate (Glu) interconversion and therefore neuronal excitability. The data of the study suggested that toxic reaction caused by G. elegans was due to a disruption of the balance of the neurotransmitter GABA/Glu transformation. CONCLUSIONS: Overall, G. elegans did not cause significant toxic reaction in the rats after long-term exposure. The results were significant for the future clinical applications of G. elegans and suggested that G. elegans could be potentially developed as a drug. The study provided a scientific basis for investigation of the mechanisms of toxicity and detoxification.


Assuntos
Encéfalo/efeitos dos fármacos , Gelsemium/toxicidade , Neuroglia/efeitos dos fármacos , Extratos Vegetais/toxicidade , Testes de Toxicidade Crônica , Administração Oral , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Proliferação de Células/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica , Neuroglia/metabolismo , Neuroglia/patologia , Extratos Vegetais/administração & dosagem , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo , Ácido gama-Aminobutírico/metabolismo
17.
Aging Cell ; 20(2): e13306, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33450132

RESUMO

Osteoarthritis (OA) is a heterogeneous disease that is extremely hard to cure owing to its complex regulation network of pathogenesis, especially cartilage degeneration. FBXO21 is a subunit of ubiquitin E3 ligases that degrades P-glycoprotein and EID1 by ubiquitination and activates the JNK and p38 pathways; however, its role in OA remains unknown. Here, the main objective of this study was to evaluate the potential effects and mechanism of FBXO21 in OA degeneration, we revealed that FBXO21 is upregulated in the cartilage of patients with OA, aging, and monosodium iodoacetate-induced OA rats, and chondrocytes treated with interleukin-1ß, tumor necrosis factor-α, and lipopolysaccharide. Moreover, the in vivo and in vitro knockdown of FBXO21 suppressed OA-related cartilage degeneration, as evidenced by activated autophagy, upregulated anabolism, alleviated apoptosis, and downregulated catabolism. In contrast, its overexpression promoted OA-related cartilage degeneration. In addition, using mass spectrometry and co-immunoprecipitation assay, we demonstrated that the downstream mechanism of FBXO21 inhibits autophagy by interacting with and phosphorylating ERK. Furthermore, FBXO21 alleviated anabolism and enhanced apoptosis and catabolism by inhibiting autophagy in rat chondrocytes. Interestingly, for its upstream mechanism, JUNB promoted FBXO21 expression by directly targeting the FBXO21 promoter, thus further accelerating cartilage degeneration in SW1353 cells and rat chondrocytes. Overall, our findings reveal that the JUNB-FBXO21-ERK axis regulates OA apoptosis and cartilage matrix metabolism by inhibiting autophagy. Therefore, FBXO21 is an attractive target for regulating OA pathogenesis, and its knockdown may provide a novel targeted therapy for OA.


Assuntos
Autofagia , Cartilagem Articular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas F-Box/metabolismo , Osteoartrite/metabolismo , Fatores de Transcrição/metabolismo , Idoso , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
18.
Phytomedicine ; 82: 153414, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33461143

RESUMO

BACKGROUD: Dihydromyricetin (DMY), a natural flavonoid compound from the leaves of the Chinese medicinal herb Vitis heyneana, has been shown to have the potential to combat chemoresistance by inhibiting Nrf2/MRP2 signaling in colorectal cancer (CRC) cells. However, the precise underlying molecular mechanism and its therapeutic target are not well understood. PURPOSE: Our study aims to investigate the effects of DMY on multidrug resistance (MDR), and elucidate the underlying mechanisms. STUDY DESIGN: In vitro, HCT116/OXA and HCT8/VCR cells were employed as our MDR models. The cells were treated with DMY (50 µM) or MK-571 (50 µM) plus oxaliplatin (OXA) (10 µM) or vincristine (VCR) (10 µM) for 48 h. In vivo, we used BALB/c mice as a CRC xenograft mouse model. BALB/c mice were given DMY (100 mg/kg), OXA (5 mg/kg) and DMY (100 mg/kg) combined with OXA (5 mg/kg) via intraperitoneal route every 2 days per week for 4 weeks. METHODS: We used MTT and colony forming assays to detect DMY's ability to reverse MDR. Flow cytometric analysis was used to detect apoptosis. Immunocytochemistry was used to detect the localization of Nrf2 and NF-κB/p65. Western blot, qRT-PCR and reporter gene assays were employed to measure the protein and gene transcriptional levels (MRP2, Nrf2, NF-κB/p65). Moreover, chromatin immunoprecipitation (ChIP) assay was used to investigate the endogenous promoter occupancy of NF-κB/p65. Finally, immunohistochemistry and TUNEL staining were used to detect protein expression and apoptosis in vivo. RESULTS: DMY restored chemosensitivity (OXA and VCR) by inhibiting both MRP2 expression and its promoter activity in HCT116/OXA and HCT8/VCR cell lines. Furthermore, DMY could inhibit NF-κB/p65 expression, reducing NF-κB/p65 translocation to the nucleus to silence Nrf2 signaling, which is necessary for MRP2 expression. Overexpressing NF-κB/p65 expression reduced the reversal effect of DMY. In addition, NF-κB/p65 regulated Nrf2 expression by directly binding to its specific promoter region and activating its transcription. Finally, we proved that the combination of OXA and DMY has a synergistic tumor suppression effect in vivo. CONCLUSION: Our study provided a novel mechanism of DMY boosted chemosensitivity in human CRC. The downstream signals of DMY, NF-κB or Nrf2 could also be potential targets for the treatment of CRC.


Assuntos
Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Flavonóis/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Animais , Apoptose/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias Colorretais/tratamento farmacológico , Células HCT116 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Vincristina/farmacologia
19.
Angew Chem Int Ed Engl ; 60(9): 4594-4598, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33241615

RESUMO

High-spin conjugated radicals have great potential in magnetic materials and organic spintronics. However, to obtain high-spin conjugated radicals is still quite challenging due to their poor stability. We report the successful synthesis and isolation of a stable triplet conjugated diradical, 10,12-diaryldiindeno[1,2-b:2',1'-e]pyrazine (m-DIP). With the m-xylylene analogue skeleton containing electron-deficient sp2 -nitrogen atoms, m-DIP displays significant aromatic character within its pyrazine ring and its spin density mainly delocalizes on the meta-pyrazine unit, making it a triplet ground state conjugated diradical. Our work provides an effective "spin density tuning" strategy for stable high-spin conjugated radicals.

20.
Int J Biol Macromol ; 166: 601-610, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33130266

RESUMO

The Phenylketonuria (PKU) is an inborn defect of phenylalanine (Phe) metabolism, in which Phe accumulated in the blood causing alterations at the central nervous system. Therefore, the detection of PKU is very important for the early diagnosis of PKU patients. However, existing tests for PKU are time-consuming and require high-resource laboratories. In this study, a novel paper-based biosensor based on phenylalnine ammonia lyase (PAL) hybrid nanoflowers was constructed that provides a semi-quantitative output of the concentration of Phe from urine samples. PAL@Ca3(PO4)2 hybrid nanoflowers (PAL@NF) were first prepared using PAL and Ca2+. Synthesis conditions of the PAL@NF on the formation of the PAL@NF were optimized. The PAL@NF exhibited 90% activity recovery under optimal condition. Compared with free PAL, the PAL@NF displayed good storage stability and increased tolerance to proteolysis. After five consecutive operating cycles, the PAL@NF still retained 73% of its initial activity, indicating excellent reusability. Furthermore, the paper-based biosensor was able to detect Phe concentration in urine samples, and exhibited good linearity to the Phe concentrations in the range from 60 to 2400 µM and the response time was only about 10 min. Therefore, the paper-based biosensor can be a promising candidate as a biosensor for the detection of PKU.


Assuntos
Técnicas Biossensoriais/métodos , Nanopartículas/química , Papel , Fenilalanina Amônia-Liase/metabolismo , Fenilalanina/urina , Concentração de Íons de Hidrogênio , Nanopartículas/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
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