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1.
Nano Lett ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468149

RESUMO

Recently, MnBi2Te4 has been demonstrated to be an intrinsic magnetic topological insulator and the quantum anomalous Hall (QAH) effect was observed in exfoliated MnBi2Te4 flakes. Here, we used molecular beam epitaxy (MBE) to grow MnBi2Te4 films with thickness down to 1 septuple layer (SL) and performed thickness-dependent transport measurements. We observed a nonsquare hysteresis loop in the antiferromagnetic state for films with thickness greater than 2 SL. The hysteresis loop can be separated into two AH components. We demonstrated that one AH component with the larger coercive field is from the dominant MnBi2Te4 phase, whereas the other AH component with the smaller coercive field is from the minor Mn-doped Bi2Te3 phase. The extracted AH component of the MnBi2Te4 phase shows a clear even-odd layer-dependent behavior. Our studies reveal insights on how to optimize the MBE growth conditions to improve the quality of MnBi2Te4 films.

2.
Genome Med ; 13(1): 146, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493320

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood. METHODS: We applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments. RESULTS: Our analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function. CONCLUSIONS: We portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

3.
J Pharmacol Exp Ther ; 378(3): 276-286, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34253647

RESUMO

Our previous studies have shown that cathepsin L (CTSL) is involved in the ability of tumors to resist ionizing radiation (IR), but the specific mechanisms responsible for this remain unknown. We report here that mutant p53 (mut-p53) is involved in IR-induced transcription of CTSL. We found that irradiation caused activation of CTSL in mut-p53 cell lines, whereas there was almost no activation in p53 wild-type cell lines. Additionally, luciferase reporter gene assay results demonstrated that IR induced the p53 binding region on the CTSL promoter. We further demonstrated that the expression of p300 and early growth response factor-1 (Egr-1) was upregulated in mut-p53 cell lines after IR treatment. Accordingly, the expression of Ac-H3, Ac-H4, AcH3K9 was upregulated after IR treatment in mut-p53 cell lines, whereas histone deacetylase (HDAC) 4 and HDAC6 were reciprocally decreased. Moreover, knockdown of either Egr-1 or p300 abolished the binding of mut-p53 to the promoter of CTSL. Chromatin immunoprecipitation assay results showed that the IR-activated transcription of CTSL was dependent on p300. To further delineate the clinical relevance of interactions between Egr-1/p300, mut-p53, and CTSL, we accessed primary tumor samples to evaluate the relationships between mut-p53, CTSL, and Egr-1/p300 ex vivo. The results support the notion that mut-p53 is correlated with CTSL transcription involving the Egr-1/p300 pathway. Taken together, the results of our study revealed that p300 is an important target in the process of IR-induced transcription of CTSL, which confirms that CTSL participates in mut-p53 gain-of-function. SIGNIFICANCE STATEMENT: Transcriptional activation of cathepsin L by ionizing radiation required the involvement of mutated p53 and Egr-1/p300. Interference with Egr-1 or p300 could inhibit the expression of cathepsin L induced by ionizing radiation. The transcriptional activation of cathepsin L by p300 may be mediated by p53 binding sites on the cathepsin L promoter.

4.
Zhongguo Zhong Yao Za Zhi ; 46(1): 125-129, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645061

RESUMO

This study was to investigate the chemical constituents from the aerial parts of Thymus przewalskii. The chemical consti-tuents were separated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and semi-prepared HPLC, and their structures were determined by physicochemical properties and spectroscopic data. Four flavanones were isolated from the ethanol extract of the aerial parts of T. przewalskii, and identified as(2S)-5,6-dihydroxy-7,8,4'-trimethoxyflavanone(1), 5,4'-dihydroxy-6,7-dimethoxyflavanone(2),(2S)-5,4'-dihydroxy-7,8-dimethoxyflavanone(3), sakuranetin(4), respectively. Compound 1 was a new compound and its configuration was determined by CD spectrum, compound 3 was natural product which was isolated for the first time and their configurations were determined by CD spectra. Compound 2 was isolated from the genus Thymus for the first time and compound 4 was isolated from T. przewalskii for the first time. Furthermore, cytotoxicity test was assayed for the four flavanones. They exhibited weak cytotoxicity against human lung cancer cells(A549), with the IC_(50) from 74.5 to 135.6 µmol·L~(-1).


Assuntos
Flavanonas , Cromatografia Líquida de Alta Pressão , Humanos
5.
Nat Commun ; 12(1): 1313, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637730

RESUMO

To increase the reliability and success rate of drug discovery, efforts have been made to increase the C(sp3) fraction and avoid flat molecules. sp3-Rich enantiopure amines are most frequently encountered as chiral auxiliaries, synthetic intermediates for pharmaceutical agents and bioactive natural products. Streamlined construction of chiral aliphatic amines has long been regarded as a paramount challenge. Mainstream approaches, including hydrogenation of enamines and imines, C-H amination, and alkylation of imines, were applied for the synthesis of chiral amines with circumscribed skeleton structures; typically, the chiral carbon centre was adjacent to an auxiliary aryl or ester group. Herein, we report a mild and general nickel-catalysed asymmetric reductive hydroalkylation to effectively convert enamides and enecarbamates into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamide or enecarbamate to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C-C bond formation via alkyl electrophiles.

6.
Nano Lett ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404255

RESUMO

We report compelling evidence of an emergent topological Hall effect (THE) from chiral bubbles in a two-dimensional uniaxial ferromagnet, V-doped Sb2Te3 heterostructure. The sign of THE signal is determined by the net curvature of domain walls in different domain configurations, and the strength of THE signal is correlated with the density of nucleation or pinned bubble domains. The experimental results are in good agreement with the integrated linear transport and Monte Carlo simulations, corroborating the emergent gauge field at chiral magnetic bubbles. Our findings not only reveal a general mechanism of THE in two-dimensional ferromagnets but also pave the way for the creation and manipulation of topological spin textures for spintronic applications.

7.
Nature ; 588(7838): 419-423, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33328665

RESUMO

A quantum anomalous Hall (QAH) state is a two-dimensional topological insulating state that has a quantized Hall resistance of h/(Ce2) and vanishing longitudinal resistance under zero magnetic field (where h is the Planck constant, e is the elementary charge, and the Chern number C is an integer)1,2. The QAH effect has been realized in magnetic topological insulators3-9 and magic-angle twisted bilayer graphene10,11. However, the QAH effect at zero magnetic field has so far been realized only for C = 1. Here we realize a well quantized QAH effect with tunable Chern number (up to C = 5) in multilayer structures consisting of alternating magnetic and undoped topological insulator layers, fabricated using molecular beam epitaxy. The Chern number of these QAH insulators is determined by the number of undoped topological insulator layers in the multilayer structure. Moreover, we demonstrate that the Chern number of a given multilayer structure can be tuned by varying either the magnetic doping concentration in the magnetic topological insulator layers or the thickness of the interior magnetic topological insulator layer. We develop a theoretical model to explain our experimental observations and establish phase diagrams for QAH insulators with high, tunable Chern number. The realization of such insulators facilitates the application of dissipationless chiral edge currents in energy-efficient electronic devices, and opens up opportunities for developing multi-channel quantum computing and higher-capacity chiral circuit interconnects.

8.
Phys Rev Lett ; 125(12): 126801, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33016726

RESUMO

Doping a topological insulator (TI) film with transition metal ions can break its time-reversal symmetry and lead to the realization of the quantum anomalous Hall (QAH) effect. Prior studies have shown that the longitudinal resistance of the QAH samples usually does not vanish when the Hall resistance shows a good quantization. This has been interpreted as a result of the presence of possible dissipative conducting channels in magnetic TI samples. By studying the temperature- and magnetic-field-dependence of the magnetoresistance of a magnetic TI sandwich heterostructure device, we demonstrate that the predominant dissipation mechanism in thick QAH insulators can switch between nonchiral edge states and residual bulk states in different magnetic-field regimes. The interactions between bulk states, chiral edge states, and nonchiral edge states are also investigated. Our Letter provides a way to distinguish between the dissipation arising from the residual bulk states and nonchiral edge states, which is crucial for achieving true dissipationless transport in QAH insulators and for providing deeper insights into QAH-related phenomena.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1668-1673, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067971

RESUMO

OBJECTIVE: To investigate the difference of clinical characteristics between young patients(age≤40 years old) and middle-older patients(age>40 years old) with the myeloproliferative neoplasms(MPN). METHODS: The clinical data (gene mutations, peripheral blood routine examinations, imaging examination and past history) of 269 MPN patients was collected and analyzed. RESULTS: In essential thrombocythemia (ET) group, the proportion of triple-negative type in young patients was higher than that in middle-older group, while the peripheral white blood cell(WBC) and platelets(PLT) counts in the first visit were lower. In polycythemia vera (PV) group, the total detection rate of JAK2V617F (80.65%) was lower than that of other research reports. Young patients with PV showed the lower JAK2V617F rate and lower WBC count, compared with the middle-older aged patients. Both CALR and MPL mutations were not found in PV patients. There was only 1 primary myelofibrosis (PMF) patient aged <40 years old. 91.67% of the patients merged splenomegaly and this rate was higher than that of ET or PV patients. It was found that there were a diagnosed familial MPN family and an undiagnosed family, and the youngest patient was only 8 years old. The second-generation gene sequencing detection for them was not carried out. CONCLUSION: Age is an important reference index in the assessment of risks. The MPN patients with different age and types show much difference in gene mutations, peripheral blood cell counts, thrombotic events and sizes of spleen. The onset ages of patients with familial MPN trends to be generational younger.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Adulto , Idoso , Criança , Cromossomos , Humanos , Janus Quinase 2/genética , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Trombocitemia Essencial/genética
10.
Front Pharmacol ; 11: 559, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457605

RESUMO

The current clinical guidelines on post-traumatic stress disorder (PTSD) recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) of drugs. However, there is uncertainty about the efficacy of other drugs and selecting which treatments work best for which patients. This meta-analysis evaluated efficacy and acceptability of pharmaceutical management for adults with PTSD. Randomized-controlled trials, which reported active comparators and placebo-controlled trials of pharmaceutical management for adults with PTSD, from the Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and ISIWeb of Science, were searched until June 21, 2019. In terms of efficacy, all active drugs demonstrated superior effect than placebo (SMD = -0.33; 95% CI, -0.43 to -0.23). The medications were superior to placebo in reducing the symptom of re-experiencing, avoidance, hyperarousal, depression, and anxiety. For acceptability, medicine interventions for PTSD showed no increase in all-cause discontinuation compared with placebo. Nevertheless, in terms of safety, medicine interventions indicated a higher risk of adverse effect compared with placebo (RR = 1.47, 95% CI: 1.24 to 1.75). Compared with placebo, the SSRIs and atypical antipsychotics drugs had significant efficacy whether in patients with severe or extremely severe PTSD status. However, only atypical antipsychotics (SMD = -0.29, 95% CI: -0.48 to -0.10) showed superior efficacy than placebo in veterans. Medication management could be effective in intervention of PTSD, which demonstrated a sufficient improvement in the core symptoms. This meta-analysis supports the status of SSRIs and SNRIs as recommended pharmacotherapy. However, patients with different clinical characteristics of PTSD should consider individualized drug management.

11.
Acta Pharmacol Sin ; 41(4): 508-515, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32123301

RESUMO

Olanzapine is an antipsychotic drug used to treat patients with schizophrenia due to its lower incidence of extrapyramidal symptoms. Previous studies have shown that olanzapine activates AMP-activated protein kinase (AMPK), and induce autophagy in SH-SY5Y cell line. In this study, we investigated whether olanzapine protected against rotenone-induced neurotoxicity in PC12 cells. We showed that treatment with olanzapine increased the phosphorylation of AMPK in both dose- and time-dependent manners in PC12 cells. In addition, olanzapine activated autophagy and increased autophagic vacuoles. Furthermore, olanzapine pretreatment could protect PC12 cells from rotenone-induced apoptosis. Besides, olanzapine pretreatment could suppress the rotenone-induced depolarization of mitochondrial potential and thus protect the cells. Moreover, pretreatment with specific AMPK inhibitor compound C or with autophagy inhibitor 3-methyladenine impaired the protective effect of olanzapine on rotenone-treated PC12 cells. In summary, our results show for the first time that olanzapine ameliorates rotenone-induced injury by activating autophagy through AMPK pathway.


Assuntos
Fármacos Neuroprotetores/farmacologia , Olanzapina/farmacologia , Rotenona/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células PC12 , Ratos , Rotenona/toxicidade , Células Tumorais Cultivadas
12.
Nat Mater ; 19(7): 732-737, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32015537

RESUMO

The quantum anomalous Hall (QAH) effect is a consequence of non-zero Berry curvature in momentum space. The QAH insulator harbours dissipation-free chiral edge states in the absence of an external magnetic field. However, the topological Hall (TH) effect, a hallmark of chiral spin textures, is a consequence of real-space Berry curvature. Here, by inserting a topological insulator (TI) layer between two magnetic TI layers, we realized the concurrence of the TH effect and the QAH effect through electric-field gating. The TH effect is probed by bulk carriers, whereas the QAH effect is characterized by chiral edge states. The appearance of the TH effect in the QAH insulating regime is a consequence of chiral magnetic domain walls that result from the gate-induced Dzyaloshinskii-Moriya interaction and occurs during the magnetization reversal process in the magnetic TI sandwich samples. The coexistence of chiral edge states and chiral spin textures provides a platform for proof-of-concept dissipationless spin-textured spintronic applications.

13.
Science ; 367(6473): 64-67, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31896711

RESUMO

A quantum anomalous Hall (QAH) insulator coupled to an s-wave superconductor is predicted to harbor chiral Majorana modes. A recent experiment interprets the half-quantized two-terminal conductance plateau as evidence for these modes in a millimeter-size QAH-niobium hybrid device. However, non-Majorana mechanisms can also generate similar signatures, especially in disordered samples. Here, we studied similar hybrid devices with a well-controlled and transparent interface between the superconductor and the QAH insulator. When the devices are in the QAH state with well-aligned magnetization, the two-terminal conductance is always half-quantized. Our experiment provides a comprehensive understanding of the superconducting proximity effect observed in QAH-superconductor hybrid devices and shows that the half-quantized conductance plateau is unlikely to be induced by chiral Majorana fermions in samples with a highly transparent interface.

14.
Food Funct ; 11(1): 200-210, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31845693

RESUMO

Selenium (Se) is an essential trace element for living organisms and plays diverse biological roles. Endometritis is a common reproductive disorder in dairy cows, causing huge economic losses. In this study, we explored the effects of Se on lipopolysaccharide (LPS)-induced endometritis in mice and expounded its underlying mechanism of action. We validated the anti-inflammatory effects of Se in vivo by establishing a mouse model of endometriosis induced by LPS. Se significantly reversed the LPS-induced uterine histopathological changes, MPO activity and inflammatory cytokine levels in vivo. Simultaneously, TLR4 and its downstream signaling pathways, lipid rafts and cholesterol levels in the tissues were also attenuated by Se under LPS stimulation. In addition, the molecular mechanism of the Se anti-inflammatory effect was clarified in mouse endometrial epithelial cells. Se inhibited TLR4-mediated NF-κB and IRF3 signal transduction pathways to reduce the production of inflammatory factors. We found that Se promoted the consumption of cholesterol to suppress the lipid rafts coming into being and inhibited the TLR4 positioning to the lipid raft to prevent the inflammatory response caused by LPS. Meanwhile, Se activated the LxRα-ABCA1 pathway to cause the outflow of cholesterol in cells. The anti-inflammatory effect of Se was disrupted by silencing LxRα. In conclusion, Se exerted anti-inflammatory effects most likely by the LxRα-ABCA1 pathway activation, which inhibited lipid rafts by depleting cholesterol and ultimately impeded the migration of TLR4 to lipid rafts.


Assuntos
Colesterol/metabolismo , Endometrite/tratamento farmacológico , Microdomínios da Membrana/metabolismo , Selênio/farmacologia , Receptor 4 Toll-Like/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Animais , Endometrite/induzido quimicamente , Feminino , Lipopolissacarídeos , Receptores X do Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
15.
Acta Pharmacol Sin ; 40(11): 1394-1403, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31444477

RESUMO

Cathepsin L (CTSL), a cysteine protease, is responsible for the degradation of a variety of proteins. It is known to participate in neuronal apoptosis associated with abnormal cell cycle. However, the mechanisms underlying CTSL-induced cell apoptosis remain largely unclear. We reported here that rotenone caused an activation of CTSL expression in PC-12 cells, while knockdown of CTSL by small interfering RNAs or its inhibitor reduced the rotenone-induced cell cycle arrest and apoptosis. Moreover, elevation of CTSL and increased-apoptosis were accompanied by induction of B-Myb, a crucial cell cycle regulator. We found that B-Myb was increased in rotenone-treated PC-12 cells and knockdown of B-Myb ameliorated rotenone-stimulated cell apoptosis. Further analysis demonstrated that CTSL influenced the expression of B-Myb as suppression of CTSL activity led to a decreased B-Myb expression, whereas overexpression of CTSL resulted in B-Myb induction. Reduction of B-Myb in CTSL-overexpressing cells revealed that regulation of cell cycle-related proteins, including cyclin A and cyclin B1, through CTSL was mediated by the transcription factor B-Myb. In addition, we demonstrated that the B-Myb target, Bim, and its regulator, Egr-1, which was also associated with CTSL closely, were both involved in rotenone-induced apoptosis in PC-12 cells. Our data not only revealed the role of CTSL in rotenone-induced neuronal apoptosis, but also indicated the involvement of B-Myb in CTSL-related cell cycle regulation.


Assuntos
Apoptose/fisiologia , Catepsina L/fisiologia , Proteínas de Ciclo Celular/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteína 11 Semelhante a Bcl-2/metabolismo , Ciclo Celular/fisiologia , Ciclina A/metabolismo , Ciclina B1/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Células PC12 , Ratos , Rotenona/farmacologia
16.
Nano Lett ; 19(5): 2945-2952, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-30942075

RESUMO

Inducing magnetic orders in a topological insulator (TI) to break its time reversal symmetry has been predicted to reveal many exotic topological quantum phenomena. The manipulation of magnetic orders in a TI layer can play a key role in harnessing these quantum phenomena toward technological applications. Here we fabricated a thin magnetic TI film on an antiferromagnetic (AFM) insulator Cr2O3 layer and found that the magnetic moments of the magnetic TI layer and the surface spins of the Cr2O3 layers favor interfacial AFM coupling. Field cooling studies show a crossover from negative to positive exchange bias clarifying the competition between the interfacial AFM coupling energy and the Zeeman energy in the AFM insulator layer. The interfacial exchange coupling also enhances the Curie temperature of the magnetic TI layer. The unique interfacial AFM alignment in magnetic TI on AFM insulator heterostructures opens a new route toward manipulating the interplay between topological states and magnetic orders in spin-engineered heterostructures, facilitating the exploration of proof-of-concept TI-based spintronic and electronic devices with multifunctionality and low power consumption.

17.
CNS Neurosci Ther ; 25(9): 911-921, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30955240

RESUMO

AIMS: Our laboratory previously reported that olanzapine treatment inhibited growth of glioma cell lines and hypothesized that autophagy may be involved in the proliferation inhibitory effects of olanzapine. However, the mechanisms of olanzapine-contributed autophagy activation are unclear. METHODS: The inhibitory effects of olanzapine on glioma cells were evaluated by CCK8 assay, Hoechst 33258 staining and annexin V-FITC/PI staining. Western blotting, nuclear separation techniques, and immunofluorescence assays were used to investigate the relationship between the inhibition of NF-κB and autophagy activation by olanzapine. RESULTS: In this work, we verified that olanzapine increased autophagic flux and autophagic vesicles. In addition, we confirmed that autophagy was related to NF-κB inhibition in cancer progression, especially with the nuclear translocation of p65. Furthermore, we demonstrated that autophagy induced by olanzapine could be impaired with TNFα cotreatment. We also found that olanzapine had an inhibitory effect on T98 cells with positive MGMT protein expression, which may involve the inhibition of MGMT through effects on NF-κB. CONCLUSIONS: Our findings identify a pathway by which olanzapine induces autophagy by depressing NF-κB in a glioma cell line, providing evidence which supports the use of olanzapine as a potential anticancer drug.


Assuntos
Autofagia/efeitos dos fármacos , Glioma/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Olanzapina/toxicidade , Inibidores de Captação de Serotonina/toxicidade , Antineoplásicos/toxicidade , Autofagia/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Glioma/patologia , Humanos
18.
J Mater Chem B ; 7(11): 1855-1866, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255048

RESUMO

Rapid and effective hemostasis for a noncompressible hemorrhage is the key to control bleeding and reduce mortality. Chitosan (CS) has been widely used as a popular hemostatic dressing; however, irregularly shaped wounds present in emergencies limit the performance of CS powder. To improve the hemostatic effect of CS, we modified it with poly(vinyl alcohol) (PVA), a fast-swelling sponge triggered by water. The novel synthetic PVA-CS was prepared by cross-linking PVA and CS during foaming and crosslinking reactions. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction were utilized to analyze the characteristics of PVA-CS. In vitro, the swelling ratio and blood clotting ability were evaluated in different groups with various weight ratios or degrees of deacetylation of the CS, and the cytocompatibility and cell attachment on the material were analyzed by human dermal fibroblast (HDF) cell testing. In vivo, the hemostatic effects were evaluated in Sprague-Dawley rats and Bama miniature pigs in a femoral artery hemorrhage model or gunshot wound experiment. PVA-CS presents robust mechanical strength, rapid water-triggered swelling and a fast absorption speed. As compared with gauze and PVA, which are widely used in first aid, PVA-CS sponges showed an improved blood clotting ability and increased blood cell and platelet adhesion and activation. The PVA-CS sponges also showed high biocompatibility in cell viability, cell proliferation and cell attachment bioassays. Furthermore, in vivo evaluation of the PVA-CS sponges revealed excellent hemostatic performance and enhanced wound healing with increased re-epithelialization and decreased granulation tissues. The results of this study strongly support the use of these composite sponges for noncompressible hemorrhage in acute trauma and ballistic injuries.


Assuntos
Bandagens , Materiais Revestidos Biocompatíveis , Hidrogéis , Cicatrização , Ferimentos por Arma de Fogo/terapia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Células Cultivadas , Quitosana/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Artéria Femoral/lesões , Fibroblastos , Hemostáticos/química , Hemostáticos/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Álcool de Polivinil/química , Ratos , Ratos Sprague-Dawley , Suínos
19.
Genomics ; 111(1): 50-58, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29288711

RESUMO

Heimuer, Auricularia heimuer, is one of the most famous traditional Chinese foods and medicines, and it is the third most important cultivated mushroom worldwide. The aim of this study is to develop genomic resources for A. heimuer to furnish tools that can be used to study its secondary metabolite production capability, wood degradation ability and biosynthesis of polysaccharides. The genome was obtained from single spore mycelia of the strain Dai 13782 by using combined high-throughput Illumina HiSeq 4000 system with the PacBio RSII long-read sequencing platform. Functional annotation was accomplished by blasting protein sequences with different public available databases to obtain their corresponding annotations. It is 49.76Mb in size with a N50 scaffold size of 1,350,668bp and encodes 16,244 putative predicted genes. This is the first genome-scale assembly and annotation for A. heimuer, which is the third sequenced species in Auricularia.


Assuntos
Agaricales/genética , Basidiomycota/genética , Genoma Fúngico , Análise de Sequência de DNA , Sequenciamento Completo do Genoma , Basidiomycota/metabolismo , Bases de Dados de Proteínas , Carpóforos/genética , Micélio/genética , Polissacarídeos/biossíntese , Metabolismo Secundário , Esporos/genética , Sequências de Repetição em Tandem
20.
Zhongguo Zhong Yao Za Zhi ; 43(20): 4069-4073, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30486532

RESUMO

Diketo aldehyde (DKA),one of the most important impurities in dihydroartemisinin,was synthesized through reaction between dihydroartemisinin and anhydrous ferrous bromide under a N2 atmosphere, and an HPLC method was established for the determination of DKA in bulk drug and in DHA tablet. DKA was prepared from dihydroartemisinin in the presence of FeBr2.The chromatographic separation was achieved through an Agilent Eclise XDB-C18 column (4.6 mm×250 mm,5 µm), and the optimal mobile phase consisted of acetonitrile and water in the ratio of 37:63 at flow rate of 1.0 mL·min⁻¹.The detection was carried out at 216 nm, and column temperature was 15 °C.The injection volume was 40 µL.The method featured a good linearity (r=0.999 9),precision (1.0%),repeatability (1.3%),stability (DKA standards RSD=1.0% and in tablet form instability),recovery (92.88%),limits of detection (0.20 mg·L⁻¹) ,and limits of quantification (0.78 mg·L⁻¹). The result show that the content of DKA in bulk drug was 0.086 7%-2.622 9%, and the content of DKA in tablet was 0.068 3%-0.615 1%.


Assuntos
Aldeídos/análise , Artemisininas/análise , Artemisininas/normas , Contaminação de Medicamentos , Cromatografia Líquida de Alta Pressão
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