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1.
Carbohydr Polym ; 227: 115296, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590872

RESUMO

Cutaneous chronic wounds are characterized by an impaired wound healing which may lead to infection. To surmount this problem, a novel quaternary ammonium chitosan nanoparticles (TMC NPs)/chitosan (CS)composite sponge with asymmetric wettability surfaces was successfully prepared. The optimum concentrations of TMC NPs and CS were 0.2 mg/mL and 2.0%, respectively. The incorporated TMC NPs could improve the antibacterial activity of the CS sponge. Asymmetric modification enables the CS sponge to have hydrophobic outer surface and hydrophilic inner surface. The hydrophobic surface of the sponge shows waterproof and anti-adhesion contaminant properties, whereas the hydrophilic surface preserves water-absorbing capability and efficiently inhibits the growth of bacteria. More importantly, in vivo chronic wound healing model evaluation reveals that TMC NPs/CS composite sponge promotes the wound healing and accelerates re-epithelialization and angiogenesis. And in vivo anti-infection test shows the TMC NPs/CS composite sponge could effectively prevent wound infection. These findings demonstrate that TMC NPs/CS composite sponge is a promising dressing material for chronic wounds.

2.
Physiol Meas ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703212

RESUMO

Detecting discomfort status of infants is particularly clinically relevant. Late treatment on discomfort infants can lead to adverse problems such as abnormal brain development, central nervous system damage and changes in responsiveness of the neuroendocrine and immune systems to stress at maturity. In this study, we exploit deep Convolutional Neural Network (CNN) algorithms to address the problem of discomfort detection for infants by analyzing their facial expressions. A dataset of 55 videos about facial expressions, recorded from 24 infants, is used in our study. Given the limited available data for training, we employ a pre-trained CNN model, which is followed by fine-tuning the networks using a public dataset with labeled facial expressions (the Shoulder-Pain dataset). The CNNs are further refined with our data of infants. Using a twofold cross-validation, we achieve an Area Under the Curve (AUC) value of 0.96, which is substantially higher than the results without any pre-training steps (AUC=0.77). Our method also achieves better results than the existing methods based on handcrafted features. By fusing individual frame results, the AUC is further improved from 0.96 to 0.98. The proposed system has great potential for continuous discomfort and pain monitoring in clinical practice.

3.
Nanotechnology ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675732

RESUMO

Flexible photodetector shows great potential applications in intelligent wearable devices, health monitoring, and biological sensing. In this work, single crystal ß-tellurium nanowires were grown on flexible muscovite by molecular beam epitaxy, constructing high-density ordered nanomesh structure. The prepared photodetectors based on tellurium nanomesh exhibit excellent mechanical flexibility, fast response in a broad range from ultraviolet to near-infrared, and good photosensitivity. We found that the flexible photodetectors with Shottky contact drastically suppressed dark current, while the response speed was lowered in comparison to the devices with ohmic contact, as holes would take long time to tunnel through the Shottky barrier between metal and p-type Te. Moreover, photoresponse of flexible Shottky photodetectors can be modulated by piezoelectricity of tellurium, and pronounced photocurrent increase after many times of bend. Under external stress, polarization charges could tune Shottky barrier height of the metal/tellurium, resulting in variation of photocurrent. The research not only explores the broadband photoresponse and piezoelectric effect of tellurium nanomesh, but also promotes the integration and development of broadband flexible optoelectronic devices.

4.
Drug Des Devel Ther ; 13: 2911-2922, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695323

RESUMO

Purpose: Postoperative delirium is a serious and common complication, it occurs in 13-50% of elderly patients after major surgery, and presages adverse outcomes. Emerging literature suggests that dexmedetomidine sedation in critical care units (intensive care unit) is associated with reduced incidence of delirium. However, few studies have investigated whether postoperative continuous infusion of dexmedetomidine could safely decrease the incidence of delirium in elderly patients admitted to general surgical wards after noncardiac surgery. Patients and methods: This double-blind, randomized, placebo-controlled trial was conducted in patients aged 65 years or older undergoing major elective noncardiac surgery without a planned ICU stay. Eligible patients were randomly assigned to receive either dexmedetomidine (0.1 µg/kg/h) or placebo (0.9% normal saline) immediately after surgery though patient-controlled intravenous analgesia device. The primary outcome was the incidence of delirium during the first 5 postoperative days. Secondary outcomes included postoperative subjective pain scores and subjective sleep quality. The study dates were from January 2018 to January 2019. Results: A total of 557 patients were randomly assigned to receive either dexmedetomidine (n=281) or placebo (n=276). The incidence of postoperative delirium had no difference between the dexmedetomidine and placebo groups (11.7% [33 of 281] vs 13.8% [38 of 276], P=0.47). Compared with placebo group, patients in dexmedetomidine group reported significant lower numerical rating score pain scores at 3, 12, 24, and 48 hrs after surgery (all P<0.05) and significant improved Richards Campbell Sleep Questionnaire results during the first 3 postoperative days (all P<0.0001). Dexmedetomidine-related adverse events were similar between the two groups. Conclusion: Postoperative continuous infusion of dexmedetomidine did not decrease the incidence of postoperative delirium in elderly patients admitted to general surgical wards after elective noncardiac surgery.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31580705

RESUMO

Objectives: Large sample and high-quality evidence to evaluate the preliminary safety of the mobilizations and massage for cervical vertigo are not yet available. Thus, the present study aimed to investigate the comparative effectiveness and preliminary safety of Shi-style cervical mobilizations (SCM) compared with traditional massage (TM) in cervical vertigo patients. Design: A prospective, multicenter, open-label, randomized, controlled clinical trial with a 1:1 allocation ratio. Settings: Five academic medical centers. Subjects: A total of 360 adult patients with a diagnosis of cervical vertigo. Interventions: The patients were randomly allocated to either an SCM (n = 180) or TM (n = 180) group. The patients were treated during six sessions over 2 weeks. The primary outcome was the Dizziness Handicap Inventory (DHI) total scale score, and secondary outcomes included the DHI subscales, Chinese version of the Short-Form 36 Health Survey (CSF-36), and adverse events (AEs). Outcomes were assessed in the short term at 2 weeks, 1 month, and 3 months, and in the intermediate term at 6 months after randomization. Results: Significant changes were observed from the baseline in the DHI total scale and subscales at 2 weeks and 1, 3, and 6 months in both groups (all p < 0.05). However, the differences between the two groups were not significant (all p > 0.05). Furthermore, we noted significant changes from the baseline in SF-36 scores at 2 weeks in both groups (all p < 0.05), whereas CSF-36 scores were not significantly higher in the SCM group (all p > 0.05) compared with the TM group. No serious AEs were reported in either of the two groups. Conclusions: No differences in outcomes were detected between the SCM and TM groups in terms of treatment of cervicogenic dizziness. Efficacy trials are required to determine whether the improvement observed for each treatment was causally related to the interventions.

6.
Clin Exp Rheumatol ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31573475

RESUMO

OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

7.
Small ; : e1904255, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588685

RESUMO

As an essential member of 2D materials, MXene (e.g., Ti3 C2 Tx ) is highly preferred for energy storage owing to a high surface-to-volume ratio, shortened ion diffusion pathway, superior electronic conductivity, and neglectable volume change, which are beneficial for electrochemical kinetics. However, the low theoretical capacitance and restacking issues of MXene severely limit its practical application in lithium-ion batteries (LIBs). Herein, a facile and controllable method is developed to engineer 2D nanosheets of negatively charged MXene and positively charged layered double hydroxides derived from ZIF-67 polyhedrons into 3D hollow frameworks via electrostatic self-assembling. After thermal annealing, transition metal oxides (TMOs)@MXene (CoO/Co2 Mo3 O8 @MXene) hollow frameworks are obtained and used as anode materials for LIBs. CoO/Co2 Mo3 O8 nanosheets prevent MXene from aggregation and contribute remarkable lithium storage capacity, while MXene nanosheets provide a 3D conductive network and mechanical robustness to facilitate rapid charge transfer at the interface, and accommodate the volume expansion of the internal CoO/Co2 Mo3 O8 . Such hollow frameworks present a high reversible capacity of 947.4 mAh g-1 at 0.1 A g-1 , an impressive rate behavior with 435.8 mAh g-1 retained at 5 A g-1 , and good stability over 1200 cycles (545 mAh g-1 at 2 A g-1 ).

8.
Environ Res ; 179(Pt A): 108769, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31574450

RESUMO

Excessive nitrogen (N) input is one of the most important causative factors of lake eutrophication, which has aroused increasing public attention in past decades. Estrogen contamination is also an increasing environmental problem in aquatic systems around the world. Although both substances usually co-exist in aquatic ecosystems, many researches have only investigated the influences of either N or estrogen individually on sediment bacterial community and nitrous oxide (N2O) emission. Knowledge regarding the combined effects of N and estrogen is still very limited. In this study, a 30-day laboratory incubation experiment was performed to examine the impacts of different N sources (ammonium and nitrate) combined with 17ß-estradiol (E2) on sediment bacterial community. High-throughput 16S rRNA gene sequencing technique was used and N2O emission was measured. The results revealed that the relative abundances of Proteobacteria and Bacteroidetes were higher in nitrate treatment than ammonium treatment. Compared to N treatments, N and E2 combined treatments showed higher relative abundances of Proteobacteria, Bacteroidetes, and Firmicutes, but lower relative abundances of Chloroflexi, Acidobacteria, and Actinobacteria over entire incubation period. At the genus level, the relative abundances of genera Flavobacterium, Pseudomonas, Arenimonas, Novosphingobium, Massilia, Aquabacterium, and Bacillus were enhanced by N treatments and especially N and E2 combined treatments, compared to sediment without addition of N and E2. However, the relative abundances of Sporacetigenium, Gaiella, Desulfatiglans, Nitrospira, and Haliangium were decreased in N treatments. Apart from the changes in bacterial community structure, N2O emission was also influenced by different treatments. Nitrate exerted a more significant positive effect on N2O emission than ammonium, and the cumulative emission of N2O was highest in nitrate and E2 combined treatment. Very low abundances of ammonia monooxygenase (amoA) gene and hydroxylamine oxidase (hao) gene were observed in sediments compared to other genes involved in N cycles (such as nitrate reductase (narG and napA) genes, nitrite reductase (nirB, nirK, and nrfA) genes, and nitric oxide reductase (norB) gene), implying that denitrification rather than nitrification played an important role in sediments. The abundances of napA, nirK, and norB were higher in N and E2 combined treatments, indicating that E2 might provide a carbon source for denitrifiers. Moreover, decrease in the abundance of nitrous oxide reductase (nosZ) gene during the denitrifying process in N and E2 combined treatment might be an important reason for increases of N2O emission. These results indicated that alterations of the bacterial community structure due to the co-existence of N and E2 could also change the abundances of genes involved in N cycle.

10.
Cell Prolif ; : e12708, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642557

RESUMO

OBJECTIVES: Due to the instability of microRNAs, the applications of microRNA are currently limited. Thus, we utilized tetrahedral framework nucleic acids and a targeted microRNAs to form a stable nanocomposite to explore whether this nanocomposite can promote apoptosis of tumour cells. MATERIALS AND METHODS: In our study, the survivin gene, which is expressed only in tumour cells and embryonic cells, was selected as the target gene; miRNA-214-3p, which can reduce the expression of survivin, was modified onto tetrahedral framework nucleic acid, thereby producing a reduction in the expression of survivin upon intracellular delivery and eventually leading to tumour cell apoptosis. RESULTS: By comparing the stability of microRNAs with that of microRNA-tetrahedral framework nucleic acid, we proved the superiority of this carrier system. The results of flow cytometry showed that after treated with this complex, the ratio of A549 cells in both late and early period of apoptosis in miRNA-214-3p-tetrahedral framework nucleic acid group had doubled and the cell cycle in the G2-M phase had declined. The decrease in the expression of anti-apoptotic protein and the increase in the expression of pro-apoptotic protein indicate that the ability of this complex to function in cells also makes it attractive as a new targeted therapy for cancer. CONCLUSION: The unique expression of survivin in tumour cells and embryonic cells makes microRNA-tetrahedral framework nucleic acid a new targeted therapy. In addition, due to the functional diversity of microRNAs, this delivery system approach can be applied to a wide variety of fields, such as targeted therapy and tissue regeneration.

11.
Food Funct ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31664275

RESUMO

Nobiletin (NBT), a citrus flavonoid, has been associated with various health benefits. Herein, we investigated the chemopreventive actions of NBT and its metabolites in a pulmonary carcinogenesis mouse model and human lung cancer cells. In 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-treated mice, the oral administration of NBT significantly suppressed lung tumorigenesis as evidenced by reduced tumor volume compared to the control mice. NBT also greatly attenuated cell proliferation in the lung of NNK-treated mice. Our previous study has identified three major metabolites of NBT, namely, 3'-demethylnobiletin (M1), 4'-demethylnobiletin (M2), and 3',4'-didemethylnobiletin (M3). In this study, we further determined the inhibitory effects of NBT and its metabolites on human non-small cell lung cancer (NSCLC) cells and the underlying mechanisms of action. Interestingly, we found that M2 and M3 exerted much stronger growth inhibition on both H460 and H1299 cells, compared to their parent compound NBT. Flow cytometry and western blotting analysis revealed that M2 and M3 caused significant cell cycle arrest and cellular apoptosis and profoundly modulated multiple proteins associated with cell proliferation and cell death, including p21, cyclin B1, CDK1, cyclin D1, CDK6, CDK4, Bax, cleaved caspase-1, and cleaved PARP. Overall, our results demonstrated that the oral administration of NBT significantly inhibited lung carcinogenesis in mice, and these chemopreventive effects could be attributed to its metabolites that showed potent anti-cancer effects.

12.
J Cell Physiol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637717

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by vascular remodeling, endothelial cell (EC) dysfunction, and inflammation. The roles of microRNAs have received much critical attention. Thus, this study was attempted to show the biological function of miR-181a/b-5p (miR-181a/b) in monocrotaline (MCT)-induced PAH. Here, rats injected with MCT were used as PAH models. The expression of miR-181a/b and its effect on PAH pathologies were examined using miR-181a/b overexpression lentivirus. A luciferase reporter analysis was performed to measure the relationships between miR-181a/b and endocan. Additionally, primary rat pulmonary arterial endothelial cells (rPAECs) treated with tumor necrosis factor-α (TNF-α) were employed to further validate the regulatory mechanism of miR-181a/b in vitro. Our results showed that miR-181a/b expression was reduced in PAH, and its upregulation significantly attenuated the short survival period, right ventricular systolic pressure and mean pulmonary artery pressure increments, right ventricular remodeling, and lung injury. Furthermore, the increase of intercellular cell adhesion molecule-1 (ICAM1) and vascular cell adhesion molecule-1 (VCAM1) in PAH rats was inhibited by miR-181a/b overexpression. Similarly, our in vitro results showed that inducing miR-181a/b suppressed TNF-α-stimulated increase of ICAM1 and VCAM1 in rPAECs. Importantly, the increased expression of endocan in PAH model or TNF-α-treated rPAECs was restored by miR-181a/b upregulation. Further analysis validated the direct targeting relationships between miR-181a/b and endocan. Collectively, this study suggests that miR-181a/b targets endocan to ameliorate PAH symptoms by inhibiting inflammatory states, shedding new lights on the prevention and treatment of PAH.

13.
J Mater Chem B ; 7(40): 6232-6237, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31566630

RESUMO

Nanozymes have been extensively investigated to imitate protein enzymes in biomimetic chemistry and the identification of the active site is believed to be the pre-requisite before one can effectively regulate their activity. Herein, ultrathin NiCo LDH nanosheets are synthesized via a fast co-precipitation at room temperature and can be stably dispersed in water without any additives of surfactants or organic solvents. By tuning the ratio between Ni and Co in LDH nanosheets, the activity is tuned and their peroxidase-like activity is determined by Co sites that show higher affinity to both 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) due to the strong Lewis acidity of Co3+ and the low redox potential of Co3+/Co2+. Together with their small crystallite size, ultra-thin thickness and tunable composition, NiCo LDH is used as a nanozyme for highly sensitive colorimetric detection of H2O2 and the limit of detection (LOD) reaches 0.48 µM.

14.
J Exp Bot ; 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31618418

RESUMO

Cell viability requires the maintenance of intracellular homeostasis through the unfolded protein response mediated by receptors localized on the endoplasmic reticulum (ER) membrane. The receptor IRE1 mediates not only various adaptive outputs but also programmed cell death (PCD) under varying stress levels. However, little is known about the mechanism by which the same receptors trigger different responses in plants. Arabidopsis Golgi anti-apoptotic protein 1 (GAAP1) and GAAP3 resist PCD upon ER stress and negatively modulate the adaptive response of the IRE1-bZIP60 pathway through IRE1 association. To elucidate the mechanism underlying the anti-PCD activity of GAAPs, we attempted to isolate interactors of GAAPs by yeast two-hybrid screening. Membrane-associated progesterone receptor 3 (MAPR3) was isolated as one of the factors interacting with GAAP. Mutations in GAAP1/GAAP3 and/or MAPR3 enhanced the sensitivity of seedlings to ER stress. Whole-transcriptome analysis combined with quantitative reverse transcription-PCR and cellular analysis showed that regulated IRE1-dependent decay (RIDD) and autophagy were impaired in mutants mapr3, gaap1mapr3, and gaap3mapr3. MAPR3, GAAP1, and GAAP3 interacted with IRE1B as determined by protein interaction assays. These data suggest that the interaction of GAAP1/GAAP3 with MAPR3 mitigates ER stress to some extent through regulating IRE10-mediated RIDD and autophagy.

15.
Nat Commun ; 10(1): 4599, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601813

RESUMO

Host-guest interactions are of central importance in many biological and chemical processes. However, the investigation of the formation and decomplexation of host-guest systems at the single-molecule level has been a challenging task. Here we show that the single-molecule conductance of organoplatinum(II) metallocycle hosts can be enhanced by an order of magnitude by the incorporation of a C60 guest molecule. Mechanically stretching the metallocycle-C60 junction with a scanning tunneling microscopy break junction technique causes the release of the C60 guest from the metallocycle, and consequently the conductance switches back to the free-host level. Metallocycle hosts with different shapes and cavity sizes show different degrees of flexibility to accommodate the C60 guest in response to mechanical stretching. DFT calculations provide further insights into the electronic structures and charge transport properties of the molecular junctions based on metallocycles and the metallocycle-C60 complexes.

16.
ACS Appl Mater Interfaces ; 11(44): 41118-41126, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31612699

RESUMO

The recovery of rare single circulating tumor cells (CTCs) from patients has great potential to facilitate the study of cell heterogeneity and cancer metastasis, which may promote the development of individualized cancer immunotherapy. Herein, a versatile single-cell recovery approach that utilizes an acoustic droplet-induced enzyme responsive platform for the capture and on-demand release of single CTCs is proposed. The platform combines a multifunctional enzyme-responsive gelatin nanoparticle (GNP)-decorated substrate (GNP-chip) for specific capture with an acoustic droplet positioning technique to realize on-demand release of single CTCs. The acoustic droplet dispenser is employed to generate oxidized alginate microdroplets containing the MMP-9 enzyme (OA-MMP-9) with controllable size and precise positioning upon the cell-attached GNP-chip, allowing controlled cell-surface biodegradation under enzymatic reactions followed by calcium chloride (CaCl2) solution treatment to form single-cell encapsulated calcium alginate hydrogels. Benefitting from the existence of hydrogels, the released cells could be efficiently recovered by microcapillary. Results demonstrate that the encapsulated cells maintain good cell morphology in the hydrogels, which allow further single-cell nucleic acid analysis. As a proof-of-concept platform, this approach enables reliable and efficient retrieval of single CTCs and holds the potential for versatility in single-cell analysis systems.

17.
EBioMedicine ; 48: 301-315, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31594750

RESUMO

BACKGROUND: Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma. METHODS: The Apcmin/+ mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography. FINDINGS: The Apcmin/+mice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of ß-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased. INTERPRETATION: Gut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apcmin/+mice, suggesting that a new strategy to target gut microbiota against CRC could be noted. FUND: The study was supported by the National Natural Science Foundation of China, Tianjin Research Programme of Application Foundation and Advanced Technology of China, and China Postdoctoral Science Foundation.

18.
Free Radic Biol Med ; 145: 187-197, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31574344

RESUMO

Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway is associated with ischemic heart diseases (IHD). 7,8-dihydroxyflavone (7,8-DHF), BDNF mimetic, is a potent agonist of TrkB. We aimed to investigate the effects and the underlying mechanisms of 7,8-DHF on cardiac ischemia. Myocardial ischemic mouse model was induced by ligation of left anterior descending coronary artery. 7,8-DHF (5 mg/kg) was administered intraperitoneally two days after ischemia for four weeks. Echocardiography, HE staining and transmission electron microscope were used to examine the function, histology and ultrastructure of the heart. H9c2 cells were treated with hydrogen peroxide (H2O2), 7,8-DHF or TrkB inhibitor ANA-12. The effects of 7,8-DHF on cell viability, mitochondrial membrane potential (MMP) and mitochondrial superoxide generation were examined. Furthermore, mitochondrial fission and protein expression of mitochondrial dynamics (Mfn2 [mitofusin 2], OPA1 [optic atrophy 1], Drp1 [dynamin-related protein 1] and Fis-1 [fission 1]) was detected by mitotracker green staining and western blot, respectively. 7,8-DHF attenuated cardiac dysfunction and cardiomyocyte abnormality of myocardial ischemic mice. Moreover, 7,8-DHF increased cell viability and reduced cell death accompanied by improving MMP, inhibiting mitochondrial superoxide and preventing excessive mitochondrial fission of H2O2-treated H9c2 cells. The cytoprotective effects of 7,8-DHF were antagonized by ANA-12. Mechanistically, 7,8-DHF repressed OMA1-dependent conversion of L-OPA1 into S-OPA1, which was abolished by Akt inhibitor. In conclusion, 7,8-DHF protects against cardiac ischemic injury by inhibiting the proteolytic cleavage of OPA1. These findings provide a novel pharmacological effect of 7,8-DHF on mitochondrial dynamics and a new potential target for IHD.

19.
Biomed Pharmacother ; 118: 109161, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545223

RESUMO

This study investigated the value of using ultrasound-targeted microbubble destruction (UTMD) to deliver an IL-8 monoclonal antibody to inhibit the inflammatory response and increase plaque stability in a rabbit model of atherosclerosis (AS). An abdominal aortic atherosclerotic plaque model was established in sixty 4-week-old male New Zealand rabbits. The rabbits were fed a high-fat diet for 12 weeks. On the 12th week, the abdominal aorta was subjected to both balloon-induced mechanical injury and bovine serum albumin-induced immunological injury. After these injuries were established, the rabbits were fed a high-fat diet for 8 additional weeks. On the 20th week, the rabbits were divided into three groups: the pretreatment (PT) group, the control group, and the IL-8 group. The ultrasonic parameters and histological data associated with the plaques from the PT group were acquired on the 20th week after targeted contrast-enhanced ultrasonography (CEUS) was performed. The rabbits in the IL-8 and control groups received targeted CEUS and UTMD every 2 weeks. A targeted contrast agent carrying IL-8 monoclonal antibody was used for the IL-8 group, whereas normal saline was used for the control group. The rabbits in these two groups underwent the same procedure four times beginning during the 20th week. On the 26th week after UTMD, ultrasonic parameters and histological data were collected. The peak intensity (PI), microvessel density (MVD), and macrophage count of the PT group were significantly higher than those of both the control and IL-8 groups (P < 0.05). Additionally, these three parameters were higher in the control group than in the IL-8 group (P < 0.05). The two-dimensional (2D) ultrasonic parameters, including the maximum thickness of the plaque and the intima-media thickness (IMT), did not differ significantly among the three groups (P > 0.05). PI, MVD, and macrophage count were positively correlated with each other (r=0.564, r=0.6034, and r=0.536, respectively; P<0.05). UTMD-delivered IL-8 monoclonal antibodies alleviate inflammation within atherosclerotic plaques. UTMD is a novel and effective method for plaque stabilization.

20.
Dalton Trans ; 48(38): 14256-14260, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31528971

RESUMO

NiMo bimetallic phosphide was synthesized from its corresponding oxidic precursor in a 1 : 1 CH4 : CO2 gas mixture for the first time. The in situ synthesized NiMoP phase in the feed for CH4-CO2 reforming can exhibit a higher activity compared to the one prepared in H2.

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