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1.
Acta Biochim Biophys Sin (Shanghai) ; 52(12): 1325-1336, 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33210714

RESUMO

During acute myocardial infarction, endoplasmic reticulum (ER) stress-induced autophagy and apoptosis have been shown as important pathogeneses of myocardial reconstruction. Importantly, hydrogen sulfide (H2S), as a third endogenous gas signaling molecule, exerts strong cytoprotective effect on anti-ER stress, autophagy regulation and antiapoptosis. Here, we showed that H2S treatment inhibits apoptosis by regulating ER stress-autophagy axis and improves myocardial reconstruction after acute myocardial infarction. We found that H2S intervention improved left ventricle function, reduced glycogen deposition in myocardial tissue mesenchyme, and inhibited apoptosis. Moreover, the expressions of fibrosis indicators (Col3a1 and Col1a2), ER stress-related proteins (CHOP and BIP/ERP78), autophagy-related proteins (Beclin and ATG5), apoptosis protein (Bax), as well as fibrosis protein Col4a3bp were all decreased after treatment with H2S. H2S administration also maintained MMP/TIMP balance. Mechanistically, H2S activated the PI3K/AKT signaling pathway. In addition, H2S treatment also reduced the expressions of ER stress-related proteins, autophagy-related proteins, and apoptins in in vitro experiments. Interestingly, activation of ER stress-autophagy axis could reverse the inhibitory effect of H2S on myocardial apoptosis. Altogether, these results suggested that exogenous H2S suppresses myocardial apoptosis by blocking ER stress-autophagy axis, which in turn reverses cardiac remodeling after myocardial infarction.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Animais , Linhagem Celular , Cistationina gama-Liase/metabolismo , Modelos Animais de Doenças , Fibrose/metabolismo , Fibrose/patologia , Coração/efeitos dos fármacos , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
2.
Zhongguo Zhong Yao Za Zhi ; 42(4): 725-730, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28959844

RESUMO

This study was aimed to explore the effects of Buzhong Yiqi decoction on the expression levels of Bad, NF-κB, caspase-9, Survivin, and mTOR in nude mice with A549/DDP transplantation tumors.Sixty BALB/C mice were randomly divided into blank control group, tumor-bearing control group, cisplatin group and Buzhong Yiqi decoction of high, medium and low doses+cisplatin groups (hereinafter referred to as the high,medium and low combined groups). A549/DDP cells (concentration of 5×106 cells/mL)were cultured and inoculated in various groups, then the tumor-forming situations were observed. Corresponding treatment was given in all groups. Fourteen days later, immunohistochemistry and Real-time PCR methods were used to detect the expression levels of Bad, NF-κB, caspase-9, Survivin, mTOR protein and mRNA in tumors.Results showed that Buzhong Yiqi decoction combined with cisplatin could reduce the volume of transplanted tumors, and there was significant difference between medium combined group and high combined group(P<0.05). As compared with the tumor-bearing control group, the expression levels of Bad, NF-κB, Survivin and mTOR were significantly reduced in medium and high combined groups(P<0.05); the protein and mRNA expression levels of caspase-9 were gradually increased in medium combined and high combined groups(P<0.05), with statistical difference with tumor-bearing control group(P<0.05). There were statistical difference in mRNA expression of Bad, NF-κB and caspase-9 between medium combined group, high combined group and cisplatin group, low-combined group, tumor-bearing control group(P<0.05), but there was no statistical difference between cisplatin group, low-combined group, and tumor-bearing control group. In addition, there was no statistical difference between medium combined group and high combined group in protein and mRNA expression levels of various factors. Experimental results showed that Buzhong Yiqi decoction combined with cisplatin can inhibit the growth of A549/DDP transplanted tumors, and the mechanism may be associated with regulating Bad, NF-κB, caspase-9, Survivin, and mTOR levels as well as promoting apoptosis.


Assuntos
Caspase 9/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Proteínas Inibidoras de Apoptose/metabolismo , NF-kappa B/metabolismo , Proteínas Repressoras/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo , Células A549 , Animais , Antineoplásicos , Apoptose , Cisplatino/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Survivina
3.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(10): 1250-5, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25509271

RESUMO

OBJECTIVE: To analyze the reversal effect of Buzhong Yiqi Decoction (BYD) on multidrug resistance of human adenocarcinoma of lung cell line A549/DDP, and to study its effect on the expression of survivin by using serum pharmacological methods in vitro. Methods Totally 24 SD rats were divided into the high, medium and low dose groups, and the blank control group by randomized controlled method. The high dose BYD containing serum (1. 134 g/mL, 2 mL), the middle dose BYD containing serum (0.576 g/mL, 2 mL), and the low dose BYD containing serum (0.284 g/mL, 2 mL) were prepared. The inhibitory effects of different dose and concentrations BYD on the proliferation of A549 and A549/DDP cells were detected by MTT assay, and the drug resistance reversal fold was calculated. The expression of Survivin in the two cell strains were detected respectively by immunohistochemical assay, Western blot, and immunofluorescence method. RESULTS: BYD containing serum showed obvious inhibitory effect on the growth of A549 and 549/DDP. The inhibition rates of 10% dose groups were higher than those of 5% dose groups. Besides, it gradually increased along with increased concentrations. Compared with 10% blank control group, the inhibition rate increased in 10% middle and low dose groups (P <0.05). After acted with 10% middle dose BYD containing serum, IC50, of A549 and A549/DDP were both reduced (P <0.05), reversal fold (RF) both increased. Its reversal ratio on A549/DDP cells was 2. 46, decreasing the resistance of A549/DDP to DDP. Compared with A549 in the same group, the expression of Survivin was detected to decrease by immunocytochemical assay, Western blot, and immunofluorescence method (P<0.05). Compared with 10% blank control group, the inhibition rate decreased in 10% middle dose group (P <0. 05). CONCLUSIONS: 10% middle dose BYD containing serum could significantly inhibit the apoptosis of A549 and A549/DDP. Besides, it could moderately reverse the multidrug resistance of A549/DDP cells to DDP possibly through reducing the intracellular expression of Survivin and enhancing the sensitivity 549/DDP to chemotherapeutics.


Assuntos
Adenocarcinoma/metabolismo , Cisplatino/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas Associadas aos Microtúbulos/farmacologia , Ratos
4.
Zhongguo Zhong Yao Za Zhi ; 39(10): 1869-73, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25282897

RESUMO

OBJECTIVE: To explore the effect of Buzhong Yiqi decoction on PI3K/AKT signaling pathway in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor. METHOD: Totally 60 nude mice were randomly divided into the blank control group, the tumor-bearing control group, the cisplatin group, the low-dose Buzhong Yiqi decoction group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. After the corresponding interventions, efforts were made to measure the transplanted tumor volume and calculate the tumor inhibiting rate. The immunohistochemical method and real time PCR were used to detect the expression of PI3K and AKT level in nude mice spleen, stomach and lung. RESULT: Buzhong Yiqi decoction of different concentrations combined with cisplatin could inhibit the growth of the transplanted tumor, with the strongest inhibitory effect in the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. All of the expressions of PI3K and AKT protein and gene in the spleen, stomach and lung increased, with the most significant increase in the tumor-bearing group. Along with the increase of the concentration of cisplatin and Buzhong Yiqi decoction, the expressions of PI3K and AKT gradually reduced. Compared with the tumor-bearing control group, there were statistical differences in spleen and stomach tissues (P < 0.05). Compared with the cisplatin group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group showed statistical differences (P < 0.05), but without statistical difference compared with the blank control group. CONCLUSION: Among nude mice with lung adenocarcinoma transplantation tumor, the PI3K and AKT protein and gene expressions in spleen, stomach and lung tissues increased, which might indicated the effect of cisplatin and Buzhong Yiqi decoction in reducing PI3K and AKT expressions and the relations between the reduction degree and the concentrations of Buzhong Yiqi decoction. Cisplatin combined with Buzhong Yiqi decoction could decrease the PI3K and AKT protein and gene expression in spleen, stomach and lung, and make the pathway closer to normal, so as to protect the functions of spleen, stomach and lung, there may be target spots of Buzhong Yiqi decoction in PI3K/AKT signal pathway.


Assuntos
Adenocarcinoma/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Baço/enzimologia , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/efeitos dos fármacos , Baço/efeitos dos fármacos
5.
iScience ; 27(4): 109321, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38558936

RESUMO

Doxorubicin induces myocardial injury and fibrosis. Still, no effective interventions are available. AP39 is an H2S donor that explicitly targets mitochondria. This study investigated whether AP39 could improve doxorubicin-induced myocardial fibrosis. Doxorubicin induced significant myocardial fibrosis while suppressing mitophagy-related proteins and elevating pyroptosis-related proteins. Conversely, AP39 reverses these effects, enhancing mitophagy and inhibiting pyroptosis. In vitro experiments revealed that AP39 inhibited H9c2 cardiomyocyte pyroptosis, improved doxorubicin-induced impairment of mitophagy, reduced ROS levels, ameliorated the mitochondrial membrane potential, and upregulated AMPK-ULK1-FUNDC1 expression. In contrast, AMPK inhibitor (dorsomorphin) and ULK1 inhibitor (SBI-0206965) reversed AP39 antagonism of doxorubicin-induced FUNDC1-mediated impairment of mitophagy and secondary cardiomyocyte pyroptosis. These results suggest that mitochondria-targeted H2S can antagonize doxorubicin-induced pyroptosis and impaired mitophagy in cardiomyocytes via AMPK-ULK1-FUNDC1 and ameliorated myocardial fibrosis and remodeling.

6.
Adv Mater ; 36(14): e2312425, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38146671

RESUMO

2D transition metal dichalcogenides (TMDCs) are considered as promising materials in post-Moore technology. However, the low photoluminescence quantum yields (PLQY) and single carrier polarity due to the inevitable defects during material preparation are great obstacles to their practical applications. Here, an extraordinary defect engineering strategy is reported based on first-principles calculations and realize it experimentally on WS2 monolayers by doping with IIIA atoms. The doped samples with large sizes possess both giant PLQY enhancement and effective carrier polarity modulation. Surprisingly, the high PL emission maintained even after one year under ambient environment. Moreover, the constructed p-n homojunctions shows high rectification ratio (≈2200), ultrafast response times and excellent stability. Meanwhile, the doping strategy is universally applicable to other TMDCs and dopants. This smart defect engineering strategy not only provides a general scheme to eliminate the negative influence of defects, but also utilize them to achieve desired optoelectronic properties for multifunctional applications.

7.
ACS Appl Mater Interfaces ; 15(19): 23573-23582, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37141554

RESUMO

Artificial synapse networks capable of massively parallel computing and mimicking biological neural networks can potentially improve the processing efficiency of existing information technologies. Semiconductor devices functioning as excitatory and inhibitory synapses are crucial for developing intelligence systems, such as traffic control systems. However, achieving reconfigurability between two working modes (inhibitory and excitatory) and bilingual synaptic behavior in a single transistor remains challenging. This study successfully mimics a bilingual synaptic response using an artificial synapse based on an ambipolar floating gate memory comprising tungsten selenide (WSe2)/hexagonal boron nitride (h-BN)/ molybdenum telluride (MoTe2). In this WSe2/h-BN/MoTe2 structure, ambipolar semiconductors WSe2 and MoTe2 are inserted as channel and floating gates, respectively, and h-BN serves as the tunneling barrier layer. Using either positive or negative pulse amplitude modulations at the control gate, this device with bipolar channel conduction produced eight distinct resistance states. Based on this, we experimentally projected that we could achieve 490 memory states (210 hole-resistance states + 280 electron-resistance states). Using the bipolar charge transport and multistorage states of WSe2/h-BN/MoTe2 floating gate memory, we mimicked reconfigurable excitatory and inhibitory synaptic plasticity in a single device. Furthermore, the convolution neural network formed by these synaptic devices can recognize handwritten digits with an accuracy of >92%. This study identifies the unique properties of heterostructure devices based on two-dimensional materials as well as predicts their applicability in advanced recognition of neuromorphic computing.

8.
Front Optoelectron ; 15(1): 41, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36637698

RESUMO

Two-dimensional (2D) transition metal dichalcogenides (TMDs) have attracted extensive attention due to their unique electronic and optical properties. In particular, TMDs can be flexibly combined to form diverse vertical van der Waals (vdWs) heterostructures without the limitation of lattice matching, which creates vast opportunities for fundamental investigation of novel optoelectronic applications. Here, we report an atomically thin vertical p-n junction WSe2/MoS2 produced by a chemical vapor deposition method. Transmission electron microscopy and steady-state photoluminescence experiments reveal its high quality and excellent optical properties. Back gate field effect transistor (FET) constructed using this p-n junction exhibits bipolar behaviors and a mobility of 9 cm2/(V·s). In addition, the photodetector based on MoS2/WSe2 heterostructures displays outstanding optoelectronic properties (R = 8 A/W, D* = 2.93 × 1011 Jones, on/off ratio of 104), which benefited from the built-in electric field across the interface. The direct growth of TMDs p-n vertical heterostructures may offer a novel platform for future optoelectronic applications.

9.
Fundam Res ; 2(3): 405-411, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-38933404

RESUMO

Understanding the fundamental charge carrier dynamics is of great significance for photodetectors with both high speed and high responsivity. Devices based on two-dimensional (2D) transition metal dichalcogenides can exhibit picosecond photoresponse speed. However, 2D materials naturally have low absorption, and when increasing thickness to gain higher responsivity, the response time usually slows to nanoseconds, limiting their photodetection performance. Here, by taking time-resolved photocurrent measurements, we demonstrated that graphene/MoTe2 van der Waals heterojunctions realize a fast 10 ps photoresponse time owing to the reduced average photocurrent drift time in the heterojunction, which is fundamentally distinct from traditional Dirac semimetal photodetectors such as graphene or Cd3As2 and implies a photodetection bandwidth as wide as 100 GHz. Furthermore, we found that an additional charge carrier transport channel provided by graphene can effectively decrease the photocurrent recombination loss to the entire device, preserving a high responsivity in the near-infrared region. Our study provides a deeper understanding of the ultrafast electrical response in van der Waals heterojunctions and offers a promising approach for the realization of photodetectors with both high responsivity and ultrafast electrical response.

10.
iScience ; 24(9): 103031, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34541467

RESUMO

Ultrathin hexagonal GaTe, with relatively high charge density, holds great potential in the field of optoelectronic devices. However, the thermodynamical stability limits it fabrications as well as applications. Here, by introducing two-dimensional MoS2 as the substrate, we successfully realized the phase-controlled synthesis of ultrathin h-GaTe, leading to high-quality h-GaTe/MoS2 heterostructures. Theoretical calculation studies reveal that GaTe with hexagonal phase is more thermodynamically stable on MoS2 templates, which can be attributed to the strain stretching and the formation energy reduction. Based on the achieved p-n heterostructures, optoelectronic devices are designed and probed, where remarkable photoresponsivity (32.5 A/W) and fast photoresponse speed (<50 µs) are obtained, indicating well-behaved photo-sensing behaviors. The study here could offer a good reference for the controlled growth of the relevant materials, and the achieved heterostructure will find promising applications in future integrated electronic and optoelectronic devices and systems.

11.
Technol Health Care ; 29(S1): 195-209, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33682759

RESUMO

OBJECTIVE: We waimed to investigate whether H2S can relieve the myocardial fibrosis caused by doxorubicin through Keap1-Nrf2. METHODS: Sprague-Dawley (SD) rats were randomly divided into four groups: normal control group (Control); DOX model group (DOX); H2S intervention model group (DOX+H2S); H2S control group (H2S). DOX and DOX+H2S group were injected with doxorubicin (3.0 mg/kg/time) intraperitoneally. Both of the Control group and H2S groups were given normal saline in equal volume, 2 weeks later, DOX+H2S and H2S group were controlled with NaHS (56 µmol/kg/d) through the abdominal cavity, while the Control and DOX group were injected with normal saline of the same dosage intraperitoneally. RESULTS: Myocardial injury and myocardial cell apoptosis were significantly increased, the H2S content in myocardial tissue was remarkably down-regulated, the expression levels of MDA, Keap1, caspase-3, caspase-9, TNF-α, IL1ß, MMPs and TIMP-1 in rat myocardial tissue was significantly up-regulated (P< 0.05), and the expression levels of GSH, NQO1, Bcl-2 were down-regulated compared with those of control group. The above results can be reversed by the DOX+H2S group. There is no statistically significant difference between the Control group and the H2S control group. CONCLUSIONS: These results suggest that H2S can improve DOX-induced myocardial fibrosis in rats, and the keap1/Nrf2 signaling pathway, oxidative stress, inflammation, and apoptosis may be involved in the mechanism.


Assuntos
Doxorrubicina , Fator 2 Relacionado a NF-E2 , Animais , Apoptose , Fibrose , Proteína 1 Associada a ECH Semelhante a Kelch , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
12.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33649809

RESUMO

The present study aimed to determine the role and regulatory mechanism of hydrogen sulfide (H2S) in the amelioration of doxorubicin­induced myocardial fibrosis in rats. It is hypothesized that the PI3K/AKT/mTOR signaling pathway is regulated to inhibit endoplasmic reticulum stress (ERS) and autophagy to reduce myocardial fibrosis. A total of 40 adult male Sprague Dawley rats were randomly divided into 4 groups (n=10/group). The 4 groups included the normal control group (control group), model group [doxorubicin (Dox) group], H2S intervention model group (H2S+Dox group) and H2S control group (H2S group). The model used in the present study was constructed by administering intraperitoneal injections of doxorubicin (3.0 mg/kg every other day; total of 6 injections). In addition, the intervention factor, NaHS and the donor of H2S, was also administered by intraperitoneal injection (56 µmol/kg/day), which lasted a month. Pathological changes in the rats were observed using Masson staining and transmission electron microscopy, while the protein expression levels of MMPs/TIMPs, transforming growth factor­ß1, cystathionine lyase and PI3K/AKT/mTOR, which are autophagy­related and ERS­related proteins were detected in myocardial tissues using western blot analysis. The gene expression levels of collagen type I α­2 chain and collagen type III α­1 chain were detected using reverse transcription­quantitative PCR and the quantification of myocardial H2S content was performed using ELISA. In the Dox group compared with that in the control group, myocardial fibers were significantly disordered, while the protein expression levels of ERS­related and autophagy­related proteins were increased markedly, and the expression levels of PI3K/AKT/mTOR proteins were reduced markedly. The aforementioned changes were markedly reversed following H2S intervention, which indicated that H2S exerts a positive protective effect on doxorubicin­induced myocardial fibrosis. The protective mechanism of H2S intervention in myocardial fibrosis is hypothesized to be associated with the inhibition of overactivation of the ER and that of autophagy via upregulation of the PI3K/AKT/mTOR pathway.


Assuntos
Sulfeto de Hidrogênio/farmacologia , Miocárdio/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Colágeno/genética , Doxorrubicina , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibrose/induzido quimicamente , Fibrose/metabolismo , Fibrose/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Masculino , Microscopia Eletrônica de Transmissão , Miocárdio/patologia , Miocárdio/ultraestrutura , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1
13.
Adv Mater ; 33(27): e2101036, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34057257

RESUMO

Multifunctional reconfigurable devices, with higher information capacity, smaller size, and more functions, are urgently needed and draw most attention in frontiers in information technology. 2D semiconductors, ascribing to ultrathin body and easy electrostatic control, show great potential in developing reconfigurable functional units. This work proposes a novel double-gate field-effect transistor architecture with equal top and bottom gate (TG and BG) and realizes flexible optimization of the subthreshold swing (SS) and threshold voltage (VTH ). While the TG and BG are used simultaneously, as a single gate to drive the transistor, ultralow average SS value of 65.5 mV dec-1 can be obtained in a large current range over 104 , enabling the application in high gain inverter. While one gate is used to initialize the channel doping, full logic swing inverter circuit with high noise margin (over 90%) is demonstrated. Such device prototype is further extended for designing reconfigurable logic applications and can be dynamically switched and well maintained between binary and ternary logics. This study provides important concept and device prototype for future multifunctional logic applications.

14.
Planta Med ; 76(5): 433-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19830654

RESUMO

Luteolin, a naturally occurring polyphenol flavonoid, has demonstrated some beneficial modulation toward the endothelium. This study aims to investigate the effects of luteolin on lysophosphatidylcholine (LPC)-induced apoptosis, a key event in the pathogenesis of atherosclerosis, in endothelial cells. Luteolin reduced not only LPC-induced cell death but also lactate dehydrogenase (LDH) leakage. Luteolin inhibition of LPC-induced apoptosis in endothelial cells demonstrated its protection against the cytotoxicity of LPC. LPC-induced apoptosis is characterized by a calcium-dependent mitochondrial pathway, involving calcium influx, activation of calpains, cytochrome C release and caspases activation. Luteolin reduced calcium influx. It also inhibited calpains activation and prevented the release of cytochrome C from mitochondrion. The inhibition of cytochrome C release by luteolin blocked the activation of caspase-3 and thus prevented subsequent endothelial cell apoptosis. These results suggested that luteolin inhibits LPC-induced apoptosis in endothelial cells through the blockage of the calcium-dependent mitochondrial pathway.


Assuntos
Apoptose/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Luteolina/farmacologia , Lisofosfatidilcolinas/antagonistas & inibidores , Cálcio/metabolismo , Calpaína/antagonistas & inibidores , Calpaína/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Inibidores de Caspase , Caspases/metabolismo , Células Endoteliais/metabolismo , Ativação Enzimática/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Lisofosfatidilcolinas/toxicidade , Redes e Vias Metabólicas/efeitos dos fármacos , Mitocôndrias/metabolismo
15.
Front Pharmacol ; 11: 1150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903815

RESUMO

Stress aging of myocardial cells participates in the mechanism of myocardial fibrosis (MF). Previous studies have shown that hydrogen sulfide (H2S) can improve MF, however the specific internal mechanism remains still unclear. Therefore, this study aims to explore whether H2S can improve myocardial cell aging induced by high glucose and myocardial fibrosis in diabetic rats by activating autophagy through SIRT6/AMPK. We observed that HG (high glucose, 33 mM) induced down-regulation of endogenous H2S-producing enzyme CSE protein expression, increased cell senescence, down-regulation of autophagy-related proteins Beclin1, Atg5, Atg12, Atg16L1, and inhibition of SIRT6/AMPK signaling pathway in H9c2 cardiomyocytes. H2S (NaHS: 400 µM) could up-regulate CSE protein expression, inhibit cell senescence, activate autophagy and SIRT6/AMPK signaling pathway. On the contrary, no above phenomena was achieved upon addition of CSE inhibitor PAG (dl-propargylglycine: mmol/L). In order to further elucidate the relationship between H2S and SIRT6/AMPK signaling pathway, dorsomorphin dihydrochloride (Dor), an inhibitor of AMPK signaling pathway, was added to observe the reversal of H2S's inhibitory effect on myocardial cell aging. At the same, streptozotocin (STZ; 40 mg/kg) was injected intraperitoneally to build an animal model of diabetic SD rats. The results showed that myocardial collagen fibers were significantly deposited, myocardial tissue senescent cells were significantly increased and the expression of CSE protein was down-regulated, while SIRT6/AMPK signaling pathway and cell autophagy were significantly inhibited. H2S-treated (NaHS; 56 µmol/kg) could significantly reverse the above phenomenon. In conclusion, these findings suggest that exogenous H2S can inhibit myocardial cell senescence and improve diabetic myocardial fibrosis by activating CSE and autophagy through SIRT6/AMPK signaling pathway.

16.
Sci Bull (Beijing) ; 65(23): 2007-2013, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36659059

RESUMO

The newly emerged two-dimensional (2D) semiconducting materials, owning to the atomic thick nature and excellent optical and electrical properties, are considered as potential candidates to solve the bottlenecks of traditional semiconductors. However, the realization of high performance 2D semiconductor-based field-effect transistors (FETs) has been a longstanding challenge in 2D electronics, which is mainly ascribing to the presence of significant Schottky barrier (SB) at metal-semiconductor interfaces. Here, an additional contact gate is induced in 2D ambipolar FET to realize near ideal reconfigurable FET (RFET) devices without restrictions of SB. Benefitting from the consistently high doping of contact region, the effective SB height can be maintained at ultra-small value during all operation conditions, resulting in the near ideal subthreshold swing (SS) values (132 mV/decade for MoTe2 RFET and 67 mV/decade for WSe2 RFET) and the relatively high mobility (28.6 cm2/(V s) for MoTe2 RFET and 89.8 cm2/(V s) for WSe2 RFET). Moreover, the flexible control on the doping polarity of contact region enables the remodeling and switching of the achieved unipolar FETs between p-type mode and n-type mode. Based on such reconfigurable behaviors, high gain complementary MoTe2 inverters are further realized. The findings in this work push forward the development of high-performance 2D semiconductor integrated devices and circuits.

17.
Nanoscale ; 12(11): 6480-6488, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32154546

RESUMO

van der Waals (vdWs) heterostructures, combining different two-dimensional (2D) layered materials with diverse properties, have been demonstrated to be a very promising platform to explore a new physical phenomenon and realize various potential applications in atomically thin electronic and optoelectronic devices. Here, we report the controlled growth of vertically stacked ß-In2Se3/MoS2 vdWs heterostructures (despite the existence of large lattice mismatching ∼29%) through a typical two-step chemical vapor deposition (CVD) method. The crystal structure of the achieved heterostructures is characterized by transmission electron microscopy, where evident Moiré patterns are observed, indicating well-aligned lattice orientation. Strong photoluminescence quenching is obeserved in the heterostructure, revealing effective interlayer charge transfer at the interface. Electrical devices are further constructed based on the achieved heterostructures, which have a high on/off ratio and a typical rectifying behavior. Upon laser irradiation, the devices show excellent photosensing properties. A high responsivity of 4.47 A W-1 and a detectivity of 1.07 × 109 Jones are obtained under 450 nm laser illumination with a bias voltage of 1 V, which are much better than those of heterostructures grown via CVD. Most significantly, the detection range can be extended to near-infrared due to the relatively small bandgap nature of ß-In2Se3. With 830 nm laser illumination, the devices also show distinct photoresponses with fast response speed even when operating at room temperature. The high-quality ß-In2Se3/MoS2 heterostructures broaden the family of the 2D layered heterostructure system and should have significant potential applications in high-performance broadband photodetectors.

18.
Microbiol Res ; 169(2-3): 179-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23890723

RESUMO

A glutathione S-transferase (GST) gene from Antarctic sea-ice bacteria Pseudoalteromonas sp. ANT506 (namely PsGST), was cloned and expressed in Escherichia coli. The open reading frame of PsGST comprised 654 bp encoding a protein of 217 amino acids with a calculated molecular size of 24.3 kDa. The rPsGST possesses the conserved amino acid defining the binding sites of glutathione (G-site) and substrate binding pocket (H-site) in GST N_3 family. PsGST was expressed in E. coli and the recombinant PsGST (rPsGST) was purified by Ni-affinity chromatography with a high specific activity of 74.21 U/mg. The purified rPsGST showed maximum activity at 40 °C and exhibited 14.2% activity at 0 °C. It was completely inactivated at 50 °C for 40 min. These results indicated that rPsGST was a typical cold active GST with low thermostability. The enzyme was little affected by H2O2 and Triton X-100, and 50.2% of the remaining activity was detected in the presence of high salt concentrations (2M NaCl). The enzymatic Km values for CDNB and GSH was 0.22 mM and 1.01 mM, respectively. These specific enzyme properties may be related to the survival environment of Antarctic sea ice bacteria.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Clonagem Molecular , Glutationa Transferase/química , Glutationa Transferase/genética , Camada de Gelo/microbiologia , Pseudoalteromonas/enzimologia , Sequência de Aminoácidos , Regiões Antárticas , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Estabilidade Enzimática , Glutationa Transferase/isolamento & purificação , Glutationa Transferase/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Dados de Sequência Molecular , Pseudoalteromonas/química , Pseudoalteromonas/genética , Pseudoalteromonas/isolamento & purificação , Alinhamento de Sequência , Especificidade por Substrato
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