Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 256
Filtrar
1.
Environ Pollut ; 276: 116688, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33611196

RESUMO

As drug abuse has become increasingly serious, carbamazepine (CBZ) is discharged into the aquatic environment with municipal sewage, causing potential harm to aquatic organisms. Here, we utilized zebrafish, an aquatic vertebrate model, to comprehensively evaluate the hepatotoxicity of CBZ. The larvae were exposed to 0.07, 0.13, and 0.26 mmol/L CBZ from 72 hpf to 144 hpf, and the adults were exposed to 0.025, 0.05, and 0.1 mmol/L CBZ for 28 days. The substantial changes were observed in the size and histopathology of livers, indicating that CBZ induced severe hepatoxicity in the larvae and adults. Oil red O staining demonstrated CBZ exposure caused severe lipid accumulation in the livers of both larvae and adults. Furthermore, CBZ exposure facilitated hepatocyte apoptosis through TUNEL staining, which was caused by rising ROS content. Subsequently, down-regulation of genes related to the Wnt pathway in exposure groups indicated that CBZ inhibited the development of liver via the Wnt/ß-catenin signaling pathway. In conclusion, CBZ induced severe hepatotoxicity by promoting lipid accumulation, generating excessive ROS production, and inhibiting the Wnt/ß-catenin signaling pathway in zebrafish. The results reveal the occurrence of CBZ-induced hepatotoxicity in zebrafish and clarify its mechanism of action, which potentially illustrate environmental concerns associated with CBZ exposure.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33401753

RESUMO

Infectious diseases have caused some of the most feared plagues and greatly harmed human health. However, despite the qualitative understanding that the occurrence and diffusion of infectious disease is related to the environment, the quantitative relations are unknown for many diseases. Zika virus (ZIKV) is a mosquito-borne virus that poses a fatal threat and has spread explosively throughout the world, impacting human health. From a geographical perspective, this study aims to understand the global hotspots of ZIKV as well as the spatially heterogeneous relationship between ZIKV and environmental factors using exploratory special data analysis (ESDA) model. A geographically weighted regression (GWR) model was used to analyze the influence of the dominant environmental factors on the spread of ZIKV at the continental scale. The results indicated that ZIKV transmission had obvious regional and seasonal heterogeneity. Population density, GDP per capita, and landscape fragmentation were the dominant environmental factors affecting the spread of ZIKV, which indicates that social factors had a greater influence than natural factors on the spread of it. As SARS-CoV-2 is spreading globally, this study can provide methodological reference for fighting against the pandemic.


Assuntos
Infecção por Zika virus , Animais , Humanos , Mosquitos Vetores , Análise Espaço-Temporal , Zika virus , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissão
3.
Theriogenology ; 159: 77-86, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33113448

RESUMO

Coenzyme Q10 (CoQ10) is essential to many fundamental biological processes. However, the effect of CoQ10 on meiotic maturation of pig oocytes still remains elusive. In the present study we aimed to understand the effects of CoQ10 on porcine oocyte maturation, by supplementing different concentrations of CoQ10 (25, 50 and 100 µM) into the maturation medium. We showed that CoQ10 at 50 µM had better capacity to promote the nuclear maturation of pig oocytes derived from both small and large antral follicles. Though the cleavage and blastocyst rates of parthenotes stayed stable, 50 µM CoQ10 treatment could accelerate the development of parthenotes to blastocyst stage, and increase the average cell number of blastocyst. For cumulus-oocyte complexes from large antral follicles categorized by the brilliant cresyl blue (BCB) test, 50 µM CoQ10 treatment could specifically promote the nuclear maturation of poor-quality oocytes in the BCB-negative group. Mitochondrial function of oocytes treated by 50 µM CoQ10 could be boosted, through increasing the levels of mitochondrial membrane potential, ATP production and CoQ6, and changing the pattern of mitochondrial distribution as well. Moreover, 50 µM CoQ10 treatment suppressed the level of reactive oxygen species and reduced the percentage of oocytes with early apoptosis signal. Taken together, CoQ10 could improve the meiotic maturation of pig oocytes, especially for poor-quality oocytes, mainly through enhancing mitochondrial function and suppressing oxidative stress to reduce apoptosis.

4.
Zhen Ci Yan Jiu ; 45(11): 868-74, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33269829

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture(EA) on miR-34a-5p, silent mating type information regulation 2 homolog-1 (SIRT1) and nuclear factor-κB subunit p65 (NF-κB p65) in the trigeminal ganglion of rats with migraine, so as to explore the mechanisms of EA underlying prevention of migraine. METHODS: Male SD rats were randomly divi-ded into normal, sham operation, model, EA, and EA plus EX527(a SIRT1 inhibitor) groups, with 10 rats in each group. The rat model of migraine was established by electrical stimulation of the trigeminal ganglion. Before modeling, EA was applied at "Waiguan"(TE5) and "Fengchi"(GB20) for 20 min each time, once a day for 5 consecutive days, and intraperitoneal injection of EX527 (5 mg/kg) every day simultaneously. Serum prostaglandin E2 (PGE2) and calcitonin gene-related peptide (CGRP) concentrations were measured by enzyme-linked immunosorbent assay. The levels of miR-34a-5p, SIRT1 and interleukin-1ß (IL-1ß) mRNA,and protein expression of SIRT1, IL-1ß, NF-κB p65, NF-κB Ac-p65 and cyclooxygenase-2 (COX2) in trigeminal ganglia were detected by real-time quantitative PCR and Western blot, separately. RESULTS: The serum concentrations of PGE2 and CGRP, the expression of miR-34a-5p, IL-1ß mRNA and protein, NF-κB p65, NF-κB Ac-p65 and COX2 protein expression in the trigeminal ganglion were remarkably increased (P<0.05), while the SIRT1 mRNA and protein decreased (P<0.05) in the model group in contrast to the normal group. Following EA intervention, the serum PGE2 and CGRP concentrations, miR-34a-5p expression, IL-1ß mRNA and protein, NF-κB p65, NF-κB Ac-p65 and COX2 protein expression were significantly down-regulated (P<0.05), and SIRT1 mRNA and protein significantly up-regulated (P<0.05). Compared with the EA group, the serum concentrations of PGE2 and CGRP, IL-1ß mRNA and protein, NF-κB p65, NF-κB Ac-p65 and COX2 protein expressions increased (P<0.05), and SIRT1 protein decreased (P<0.05) in the EA plus EX527 group. CONCLUSION: In migraine rats, EA can inhibit miR-34a-5p expression in the trigeminal ganglion, increase SIRT1 expression, down-regulate IL-1ß/COX2 inflammation signals, reduce PGE2 synthesis, and thus redue CGRP released from the peripheral terminals, which may be one of the mechanisms of EA in preventing migraine.

5.
Soft Matter ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33325974

RESUMO

In recent years, hydrogel, as a stretchable, transparent, ionic conductor, has attracted considerable attention and its integration with various materials has enabled new functions: hydrogel ionotronics. These hybrid systems rely on both mobile ions and mobile electrons. However, coupling of ions and electrons brings a new challenge: electrochemical breakdown. Here, we study the breakdown behaviors of a typical ionotronic system-a hydrogel-elastomer device at high DC voltage, which consists of three elements: hydrogel, dielectric elastomer, and metal. We develop a phase diagram of the possible failure modes through theory and experiment, and find a new failure mode, electrochemical breakdown, caused by ion-electron exchange at the metal-hydrogel interface. Our experiments show that the breakdown voltage of the dielectric elastomer decreases when the capacitance of the electrical double layer formed at the metal-hydrogel interface is below a certain value. It is found that the failure mode and its transition are determined by three material properties: the electrical breakdown strength of the dielectric elastomer, the capacitance of the metal-hydrogel interface per unit area, and the electrochemical window of the hydrogel electrolyte. These findings will guide the characterization and improvement of the reliability of hydrogel ionotronic devices.

6.
Sensors (Basel) ; 20(21)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138177

RESUMO

Downward surface solar radiation (Rs) plays a dominant role in determining the climate and environment on the Earth. However, the densely distributed ground observations of Rs are usually insufficient to meet the increasing demand of the climate diagnosis and analysis well, so it is essential to build a long-term accurate Rs dataset. The extremely randomized trees (ERT) algorithm was used to generate Rs using routine meteorological observations (2000-2015) from the Climate Data Center of the Chinese Meteorological Administration (CDC/CMA). The estimated Rs values were validated against ground measurements at the national scale with an overall correlation coefficient value of 0.97, a mean bias of 0.04 Wm-2, a root-mean-square-error value of 23.12 Wm-2, and a mean relative error of 9.81%. It indicates that the estimated Rs from the ERT-based model is reasonably accurate. Moreover, the ERT-based model was used to generate a new daily Rs dataset at 756 CDC/CMA stations from 1958 to 2015. The long-term variation trends of Rs at 454 stations covering 46 consecutive years (1970-2015) were also analyzed. The Rs in China showed a significant decline trend (-1.1 Wm-2 per decade) during 1970-2015. A decreasing trend (-2.8 Wm-2 per decade) in Rs during 1970-1992 was observed, followed by a recovery trend (0.23 Wm-2 per decade) during 1992-2015. The recovery trends at individual stations were found at 233 out of 454 stations during 1970-2015, which were mainly located in southern and northern China. The new Rs dataset would substantially provide basic data for the related studies in agriculture, ecology, and meteorology.

7.
Neurobiol Aging ; 98: 63-77, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33254080

RESUMO

Synaptic failure underlies cognitive impairment in Alzheimer's disease (AD). Cumulative evidence suggests a strong link between mitochondrial dysfunction and synaptic deficits in AD. We previously found that oligomycin-sensitivity-conferring protein (OSCP) dysfunction produces pronounced neuronal mitochondrial defects in AD brains and a mouse model of AD pathology (5xFAD mice). Here, we prevented OSCP dysfunction by overexpressing OSCP in 5xFAD mouse neurons in vivo (Thy-1 OSCP/5xFAD mice). This approach protected OSCP expression and reduced interaction of amyloid-beta (Aß) with membrane-bound OSCP. OSCP overexpression also alleviated F1Fo ATP synthase deregulation and preserved mitochondrial function. Moreover, OSCP modulation conferred resistance to Aß-mediated defects in axonal mitochondrial dynamics and motility. Consistent with preserved neuronal mitochondrial function, OSCP overexpression ameliorated synaptic injury in 5xFAD mice as demonstrated by preserved synaptic density, reduced complement-dependent synapse elimination, and improved synaptic transmission, leading to preserved spatial learning and memory. Taken together, our findings show the consequences of OSCP dysfunction in the development of synaptic stress in AD-related conditions and implicate OSCP modulation as a potential therapeutic strategy.

8.
BMC Pulm Med ; 20(1): 276, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097022

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) characterized by the airway and lung inflammation, is a leading cause of morbidity and mortality worldwide, especially among smokers over 40 years of age and individuals exposed to biomass smoke. Although the detailed mechanisms of this disease remain elusive, there is feasible evidence that protein posttranslational modifications (PTMs) may play a role in its pathoetiology. We thus conducted studies to dissect the effect of cigarette smoke extracts (CSE) on the change of SUMOylated substrates in human bronchial epithelial cells (HBEs). METHODS: Samples were collected in HBEs with or without 24 h of CSE insult and then subjected to Western-blot and LC-MS/MS analysis. Subsequently, bioinformatic tools were used to analyze the data. The effect of SUMOylation on cytochrome P450 1A1 (CYP1A1) was evaluated by flow cytometry. RESULTS: It was noted that CSE stimulated HBEs to undergo a SUMOylation turnover as evidenced by the changes of SUMOylated substrates and SUMOylation levels for a particular substrate. The SUMOylated proteins are relevant to the regulation of biological processes, molecular function and cellular components. Particularly, CSE stimulated a significant increase of SUMOylated CYP1A1, a critical enzyme involved in the induction of oxidative stress. CONCLUSIONS: Our data provide a protein SUMOylation profile for better understanding of the mechanisms underlying COPD and support that smoking induces oxidative stress in HBEs, which may predispose to the development of COPD in clinical settings.

9.
Transbound Emerg Dis ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33119963

RESUMO

Lumpy skin disease (LSD) is a viral disease of cattle caused by LSD virus (LSDV). This disease poses a significant threat to stockbreeding and is listed as one of bovine notifiable diseases by OIE. Before 2019, LSD has not been reported in China. The first LSD outbreak was determined in China on August 3, 2019. Since then, a total of 7 LSD outbreaks have been reported in other 6 provinces in China, infecting 91 and killing 7 cattle. As of now, LSDV was detected in western and eastern China and also in Taiwan Island outside Mainland China. LSD is undoubtedly an emerging threat to the cattle industry in China.

10.
Research (Wash D C) ; 2020: 2505619, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029586

RESUMO

Highly stretchable and transparent ionic conducting materials have enabled new concepts of electronic devices denoted as iontronics, with a distinguishable working mechanism and performances from the conventional electronics. However, the existing ionic conducting materials can hardly bear the humidity and temperature change of our daily life, which has greatly hindered the development and real-world application of iontronics. Herein, we design an ion gel possessing unique traits of hydrophobicity, humidity insensitivity, wide working temperature range (exceeding 100°C, and the range covered our daily life temperature), high conductivity (10-3~10-5 S/cm), extensive stretchability, and high transparency, which is among the best-performing ionic conductors ever developed for flexible iontronics. Several ion gel-based iontronics have been demonstrated, including large-deformation sensors, electroluminescent devices, and ionic cables, which can serve for a long time under harsh conditions. The designed material opens new potential for the real-world application progress of iontronics.

11.
ChemMedChem ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32964625

RESUMO

Since the initial discovery as nicotinic acetylcholine receptor ligands, the 3-alkoxyisoxazole scaffold has now been shown as a versatile platform for the development of potent σ1 and σ2 receptor ligands. Herein we report a further SAR exploration on the 3-alkoxyisoxazole scaffold with the aim of obtaining potent σ2 receptor ligands. Various substitutions on the benzene ring and the basic amino regions resulted in a total of 21 compounds that were tested for their binding affinities to σ2 receptor. In particular, compound 51 was identified as one of the most potent σ2 ligands within the series with a K i value of 7.9 nM, and demonstrated potent anti-proliferative effects on the both osteosarcoma cell lines 143B and MOS-J (IC 50 values of 0.89 and 0.71 µM, respectively), compared to siramesine (IC 50 values of 1.81 and 2.01 µM). Moreover, compound 51 inhibited the clonal formation of the osteosarcoma 143B cells at 1 µM concentration, corresponding to half the dose required of siramesine for similar effects. The general cytotoxicity profile of compound 51 was assessed in a number of normal cell lines, including HaCaT, HAF, and LO2 cells. Furthermore, FACS analysis showed that compound 51 likely inhibits the osteosarcoma cell growth by disruption of the cell cycle and promotion of cell apoptosis.

12.
Theriogenology ; 157: 449-457, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32882647

RESUMO

Oocytes of better quality and developmental competence are highly demanded, which is affected by many intrinsic and external factors, including environmental pollutants. We have previously demonstrated that 7, 12-dimethylbenz [a]anthracene (DMBA) reduces the developmental competence of porcine oocytes, by desynchronizing nuclear and ooplasmic maturation. However, the underlying molecular mechanism remains obscure. Here we performed single cell RNA-seq to study the transcriptome changes in DMBA-treated porcine MII oocytes, and identified 19 protein-coding genes and 156 novel long non-coding RNAs (lncRNAs) with abundance to be significantly different (P < 0.05), which enriched in signaling pathways such as glycosphingolipid biosynthesis, nicotine addiction, basal transcription factors and nucleotide excision repair. RT-qPCR on oocyte pools confirmed ornithine aminotransferase (Oat) and serine/arginine-rich splicing factor 4 (Srsf4) to be significantly up- and down-regulated, respectively (P < 0.05). Treating porcine COCs with MAPK and PLC pathway inhibitors suppressed DMBA's effects on increasing PB1 extrusion rate. In addition, DMBA co-incubation with 250 µM vitamin C derivative (l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) and 100 µM co-enzyme Q10 (CoQ10) could significantly reduce the DMBA-induced high ROS level, and partially alleviate the DMBA-induced high PB1 rate, whereas the cleavage and blastocyst rates of parthenotes derived from treated mature oocytes remained to be low. Collectively, our findings indicate that single cell RNA-seq can help reveal the dynamics of molecular signaling pathways for porcine oocytes treated by DMBA, and supplement of anti-oxidative reagents could not sufficiently rescue DMBA-induced defects of porcine oocytes.

13.
Onco Targets Ther ; 13: 8223-8232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884300

RESUMO

Background: New evidence suggests that histidine triad nucleotide-binding protein 1 (Hint1) exerts a tumor suppressor effect in various human tumors, such as colorectal cancer and gastric cancer. However, it has not been reported whether Hint1 is involved in the occurrence and development of osteosarcoma (OS). Materials and Methods: The present study investigated the role of Hint1 in human OS cells by using cell lines, including 143B, U2OS, KHOS-240S, Saos-2 and MG-63. Cell proliferation and apoptosis were detected by flow cytometry. Results: The present result revealed that Hint1 is downregulated in these cell lines. The overexpression of Hint1 by adenovirus transfection in 143B and MG63 cell lines suppressed the proliferation and cell cycle, and increased the cell apoptosis. Mechanically, it was found that Hint1 downregulated the cyclin D1 expression via FOXO1 inhibition. Furthermore, FOXO1 overexpression in the 143B and MG63 cell lines significantly blurred the effects of Hint1 on cellular proliferation and apoptosis. Conclusion: The present study indicates that Hint1 inhibits the development of OS by regulating FoxO1-cyclin D1, suggesting that Hint1 may be a new method for the treatment of OS.

14.
Neuroreport ; 31(15): 1104-1110, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32925607

RESUMO

Mitochondrial dysfunction has been repeatedly identified to be hallmark brain pathology underlying neuronal stress in Alzheimer's disease. As a result, mitochondrial medicine for the treatment of Alzheimer's disease has received increasing recognition. Idebenone (IDB) is a synthetic analog of Coenzyme Q10 (CoQ10) carrying antioxidizing property. Previous clinical trials reported a conflicting disease-modifying effect of IDB on Alzheimer's disease patients. However, whether IDB is preventive against amyloid beta (Aß)-induced mitochondrial and neuronal stress has not been comprehensively investigated. In this study, we adopted an in-vitro setting by using primary cultured cortical neurons for the test. Neurons were pretreated with IDB prior to Aß exposure. IDB pretreatment significant prevented neurons from Aß-induced collapse of mitochondrial bioenergetics and perturbations of the protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling. Importantly, the treatment of IDB alone demonstrated an indiscernible side effect on the measured mitochondrial function, PKA/CREB signaling and neuronal viability. Therefore, our findings in together show a preventive effect of IDB against Aß-mediated mitochondrial and neuronal injury. The use of IDB may hold potential to reduce the risk of Alzheimer's disease as a preventive strategy.

15.
Sensors (Basel) ; 20(17)2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32846961

RESUMO

Ocean latent heat flux (LHF) is an essential variable for air-sea interactions, which establishes the link between energy balance, water and carbon cycle. The low-latitude ocean is the main heat source of the global ocean and has a great influence on global climate change and energy transmission. Thus, an accuracy estimation of high-resolution ocean LHF over low-latitude area is vital to the understanding of energy and water cycle, and it remains a challenge. To reduce the uncertainties of individual LHF products over low-latitude areas, four machine learning (ML) methods (Artificial Neutral Network (ANN), Random forest (RF), Bayesian Ridge regression and Random Sample Consensus (RANSAC) regression) were applied to estimate low-latitude monthly ocean LHF by using two satellite products (JOFURO-3 and GSSTF-3) and two reanalysis products (MERRA-2 and ERA-I). We validated the estimated ocean LHF using 115 widely distributed buoy sites from three buoy site arrays (TAO, PIRATA and RAMA). The validation results demonstrate that the performance of LHF estimations derived from the ML methods (including ANN, RF, BR and RANSAC) were significantly better than individual LHF products, indicated by R2 increasing by 3.7-46.4%. Among them, the LHF estimation using the ANN method increased the R2 of the four-individual ocean LHF products (ranging from 0.56 to 0.79) to 0.88 and decreased the RMSE (ranging from 19.1 to 37.5) to 11 W m-2. Compared to three other ML methods (RF, BR and RANSAC), ANN method exhibited the best performance according to the validation results. The results of relative uncertainty analysis using the triangle cornered hat (TCH) method show that the ensemble LHF product using ML methods has lower relative uncertainty than individual LHF product in most area. The ANN was employed to implement the mapping of annual average ocean LHF over low-latitude at a spatial resolution of 0.25° during 2003-2007. The ocean LHF fusion products estimated from ANN methods were 10-30 W m-2 lower than those of the four original ocean products (MERRA-2, JOFURO-3, ERA-I and GSSTF-3) and were more similar to observations.

16.
Biochem Biophys Res Commun ; 529(2): 314-320, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32703429

RESUMO

Mitochondria play an essential role in maintaining intraneuronal calcium homeostasis. Mitochondrial calcium uniporter (MCU) is a determined major brain mitochondrial calcium entry pathway. Activated MCU-mediated mitochondrial calcium overloading has been linked with brain mitochondrial pathology in disease conditions. Cyclophilin D (CypD)-mediated mitochondrial permeability transition (mPT) favors mitochondrial calcium efflux. The physiological function of CypD-mediated mPT has received increasing recognition. However, the regulatory role of CypD-mediated mPT in brain mitochondrial calcium dynamics in response to mitochondrial calcium accumulation via MCU has not been comprehensively studied. Here, by adopting purified brain mitochondria, we have determined an effect of CypD and CypD-mediated mPT against mitochondrial calcium overloading. In addition, blockade of CypD pharmaceutically or genetically blunts brain mitochondrial MCU's sensitivity to its inhibitor. Therefore, our findings suggest that CypD-mediated mPT is a mitochondrial compensatory response to MCU-mediated excess mitochondrial calcium accumulation. Moreover, CypD may potentially modulate MCU function in calcium-stressed mitochondria.

17.
World J Clin Cases ; 8(10): 1848-1858, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32518774

RESUMO

BACKGROUND: Receptor interacting protein kinase 1 (RIPK1)-mediated cell death, including apoptosis and necroptosis, belongs to programmed cell death. It has been reported that RIPK1-mediated necroptosis exists in lesions of cerebral hemorrhage (CH). Electroacupuncture, a treatment derived from traditional Chinese medicine, could improve neurological impairment in patients with brain injury. AIM: To investigate the protective role of cross electro-nape acupuncture (CENA) in CH, and clarify the potential mechanism. METHODS: CH rat models were established, and CENA was applied to the experimental rats. Neurological functions and encephaledema were then measured. Necrotic cells in the brain of rats with CH were evaluated by propidium iodide staining. Necroptosis was assessed by immunofluorescence. Activation of the necroptosis-related pathway was detected by western blot. Extraction of brain tissue, cerebrospinal fluid and serum samples was conducted to measure the expression and secretion of inflammatory cytokines by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: The necroptotic marker p-MLKL was detectable in the brains of rats with CH. Next, we found that CENA could ameliorate neurological functions in rat models of CH. Moreover, the upregulation of RIPK1-mediated necroptosis-related molecules in the brains of rats with CH were inhibited by CENA. Further investigation revealed that CENA partially blocked the interaction between RIPK1 and RIPK3. Finally, in vivo assays showed that CENA decreased the expression of the inflammatory cytokines tumor necrosis factor-α, interleukin-6 and interleukin-8 in CH rat models. CONCLUSION: These findings revealed that CENA exerts a protective role in CH models by inhibiting RIPK1-mediated necroptosis.

18.
Front Plant Sci ; 11: 578, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477389

RESUMO

Carotenoids are ubiquitous precursors of important metabolites including hormones, such as strigolactones (SLs) and abscisic acid (ABA), and signaling and regulatory molecules, such as the recently discovered zaxinone. Strigolactones and ABA are key regulators of plant growth and development, adaptation to environmental changes and response to biotic and abiotic stress. Previously, we have shown that zaxinone, an apocarotenoid produced in rice by the enzyme zaxinone synthase (ZAS) that is common in mycorrhizal plants, is required for normal rice growth and development, and a negative regulator of SL biosynthesis. Zaxinone is also formed in Arabidopsis, which lacks ZAS, via an unknown route. In the present study, we investigated the biological activity of zaxinone in Arabidopsis, focusing on its effect on SL and ABA biosynthesis. For this purpose, we quantified the content of both hormones and determined the levels of related transcripts in Arabidopsis (Arabidopsis thaliana), roots upon zaxinone treatment. For SL quantification, we also employed Striga seed germination bioassay. Results obtained show that zaxinone application to hydroponically grown Arabidopsis seedlings enhanced transcript levels of key biosynthetic genes of both hormones, led to higher root ABA and SL (methyl carlactonoate, MeCLA) content, and increased SL release, even under sufficient phosphate supply. Using the SL insensitive (max2-1) and the ABA deficient (aba1-6, aba2-1, and nced3) mutants, we also show that zaxinone application reduced hypocotyl growth and that this effect is caused by increasing ABA content. Our results suggest that zaxinone is a regulatory metabolite also in Arabidopsis, which triggers the biosynthesis of both carotenoid-derived hormones, SLs and ABA, in roots. In the non-mycotrophic plant Arabidopsis, zaxinone does not increase growth and may be perceived as a stress signal, while it acts as a growth-promoting metabolite and suppressor of SL biosynthesis in rice.

19.
Biomicrofluidics ; 14(3): 034107, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32477446

RESUMO

State of the art acoustofluidics typically treat micro-particles in a multi-wavelength range due to the scale limitations of the established ultrasound field. Here, we report a spatial selective acoustofluidic device that allows trapping micro-particles and cells in a wavelength scale. A pair of interdigital transducers with a concentric-arc shape is used to compress the beam width, while pulsed actuation is adopted to localize the acoustic radiation force in the wave propagating direction. Unlike the traditional usage of geometrical focus, the proposed device is designed by properly superposing the convergent section of two focused surface acoustic waves. We successfully demonstrate a single-column alignment of 15-µm polystyrene particles and double-column alignment of 8-µm T cells in a wavelength scale. Through proof-of-concept experiments, the proposed acoustofluidic device shows potential applications in on-chip biological and chemical analyses, where localized handing is required.

20.
Acta Biomater ; 112: 14-28, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32531395

RESUMO

Vaccine is one of the most effective strategies for preventing and controlling infectious diseases and some noninfectious diseases, especially cancers. Adjuvants and carriers have been appropriately added to the vaccine formulation to improve the immunogenicity of the antigen and induce long-lasting immunity. However, there is an urgent need to develop new all-purpose adjuvants because some adjuvants approved for human use have limited functionality. Graphene oxide (GO), widely employed for the delivery of biomolecules, excels in loading and delivering antigen and shows the potentiality of activating the immune system. However, GO aggregates in biological liquid and induces cell death, and it also exhibits poor biosolubility and biocompatibility. To address these limitations, various surface modification protocols have been employed to integrate aqueous compatible substances with GO to effectively improve its biocompatibility. More importantly, these modifications render functionalized-GO with superior properties as both carriers and adjuvants. Herein, the recent progress of physicochemical properties and surface modification strategies of GO for its application as both carriers and adjuvants is reviewed. STATEMENT OF SIGNIFICANCE: Due to its unique physicochemical properties, graphene oxide is widely employed in medicine for purposes of photothermal treatment of cancer, drug delivery, antibacterial therapy, and medical imaging. Our work describes the surface modification of graphene oxide and for the first time summarizes that functionalized graphene oxide serves as a vaccine carrier and shows significant adjuvant activity in activating cellular and humoral immunity. In the future, it is expected to be introduced into vaccine research to improve the efficacy of vaccines.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA