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1.
Opt Lett ; 46(21): 5360-5363, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724475

RESUMO

We propose a novel framework for the systematic design of lensless imaging systems based on the hyperuniform random field solutions of nonlinear reaction-diffusion equations from pattern formation theory. Specifically, we introduce a new class of imaging point-spread functions (PSFs) with enhanced isotropic behavior and controllable sparsity. We investigate PSFs and modulated transfer functions for a number of nonlinear models and demonstrate that two-phase isotropic random fields with hyperuniform disorder are ideally suited to construct imaging PSFs with improved performances compared to PSFs based on Perlin noise. Additionally, we introduce a phase retrieval algorithm based on non-paraxial Rayleigh-Sommerfeld diffraction theory and introduce diffractive phase plates with PSFs designed from hyperuniform random fields, called hyperuniform phase plates (HPPs). Finally, using high-fidelity object reconstruction, we demonstrate improved image quality using engineered HPPs across the visible range. The proposed framework is suitable for high-performance lensless imaging systems for on-chip microscopy and spectroscopy applications.

2.
Sensors (Basel) ; 21(15)2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34372460

RESUMO

Due to the COVID-19 virus being highly transmittable, frequently cleaning and disinfecting facilities is common guidance in public places. However, the more often the environment is cleaned, the higher the risk of cleaning staff getting infected. Therefore, strong demand for sanitizing areas in automatic modes is undoubtedly expected. In this paper, an autonomous disinfection vehicle with an Ultraviolet-C (UVC) lamp is designed and implemented using an ultra-wideband (UWB) positioning sensor. The UVC dose for 90% inactivation of the reproductive ability of COVID-19 is 41.7 J/m2, which a 40 W UVC lamp can achieve within a 1.6 m distance for an exposure time of 30 s. With this UVC lamp, the disinfection vehicle can effectively sterilize in various scenarios. In addition, the high-accuracy UWB positioning system, with the time difference of arrival (TDOA) algorithm, is also studied for autonomous vehicle navigation in indoor environments. The number of UWB tags that use a synchronization protocol between UWB anchors can be unlimited. Moreover, this proposed Gradient Descent (GD), which uses Taylor method, is a high-efficient algorithm for finding the optimal position for real-time computation due to its low error and short calculating time. The generalized traversal path planning procedure, with the edge searching method, is presented to improve the efficiency of autonomous navigation. The average error of the practical navigation demonstrated in the meeting room is 0.10 m. The scalability of the designed system to different application scenarios is also discussed and experimentally demonstrated. Hence, the usefulness of the proposed UWB sensor applied to UVC disinfection vehicles to prevent COVID-19 infection is verified by employing it to sterilize indoor environments without human operation.


Assuntos
COVID-19 , Desinfecção , Algoritmos , Humanos , Projetos de Pesquisa , SARS-CoV-2
4.
Free Radic Biol Med ; 172: 578-589, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34242792

RESUMO

Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), which is characterized by GSH depletion, oxidative stress and mitochondrial dysfunction. However, the specific mechanism of APAP-induced ALF remains to be clarified. In this study, we demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) aggravated APAP-induced ALF associated with excess lipid peroxidation, which was reversed by lipid peroxidation inhibitor (ferrostatin-1). Meanwhile, IDO1 deficiency effectively decreased the accumulation of reactive nitrogen species. Additionally, IDO1 deficiency prevented against APAP-induced liver injury through suppressing the activation of macrophages, thereby reduced their iron uptake and export, eventually reduced iron accumulation in hepatocytes through transferrin and transferrin receptor axis. In summary, our study confirmed that APAP-induced IDO1 aggravated ALF by triggering excess oxidative and nitrative stress and iron accumulation in liver. These results offer new insights for the clinical treatment of ALF or iron-dysregulated liver diseases in the future.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Dioxigenases , Falência Hepática Aguda , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dioxigenases/metabolismo , Hepatócitos , Ferro/metabolismo , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
5.
Front Pharmacol ; 12: 687394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305600

RESUMO

Inflammation and apoptosis of vascular endothelial cells play a key role in the occurrence and development of atherosclerosis (AS), and the AMPK/mTOR/Nrf2 signaling pathway plays an important role in alleviating the symptoms of AS. Geniposide combined with notoginsenoside R1 (GN combination) is a patented supplement for the prevention and treatment of AS. It has been proven to improve blood lipid levels and inhibit the formation of AS plaques; however, it is still unclear whether GN combination can inhibit inflammation and apoptosis in AS by regulating the AMPK/mTOR/Nrf2 signaling pathway and its downstream signals. Our results confirmed that the GN combination could improve blood lipid levels and plaque formation in ApoE -/- mice fed with a high-fat diet (HFD), inhibit the secretion of serum inflammatory factors and oxidative stress factors. It also decreased the expression of pyrin domain containing protein 3 (NLRP3) inflammasome-related protein and Bax/Bcl2/caspase-3 pathway-related proteins. At the same time, the GN combination could also inhibit the H2O2-induced inflammatory response and apoptosis of human umbilical vein endothelial cells (HUVECs), which is mainly related to the activation of the AMPK/mTOR pathway by GN combination, which in turn induces the activation of Nrf2/HO-1 signal. In addition, the above phenomenon could be significantly reversed by dorsomorphin. Therefore, our experiments proved for the first time that the GN combination can effectively inhibit AS inflammation and apoptosis by activating the AMPK/mTOR/Nrf2 signaling pathway to inhibit the NLRP3 inflammasome and Bax/Bcl2/caspase-3 pathway.

6.
Front Pharmacol ; 12: 616409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33716743

RESUMO

Alcoholic liver disease (ALD) has become a heavy burden on health worldwide. Ginsenoside Rb1 (GRb1), extracted from Panax quinquefolium L., has protective effects on many diseases, but the effect and mechanisms of GRb1 on ALD remain unknown. This study aimed to investigate the protective effects of GRb1 on ALD and to discover the potential mechanisms. Zebrafish larvae were exposed to 350 mM ethanol for 32 h to establish a model of acute alcoholic liver injury, and the larvae were then treated with 6.25, 12.5, or 25 µM GRb1 for 48 h. The human hepatocyte cell line was stimulated by 100 mM ethanol and meanwhile incubated with 6.25, 12.5, and 25 µM GRb1 for 24 h. The lipid changes were detected by Oil Red O staining, Nile Red staining, and triglyceride determination. The antioxidant capacity was assessed by fluorescent probes in vivo, and the expression levels of inflammatory cytokines were detected by immunohistochemistry, immunofluorescence, and quantitative real-time PCR. The results showed that GRb1 alleviated lipid deposition in hepatocytes at an optimal concentration of 12.5 µM in vivo. GRb1 reversed the reactive oxygen species accumulation caused by alcohol consumption and partially restored the level of glutathione. Furthermore, GRb1 ameliorated liver inflammation by inhibiting neutrophil infiltration in the liver parenchyma and downregulating the expression of nuclear factor-kappa B pathway-associated proinflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß. This study revealed that GRb1 has a protective effect on alcohol-induced liver injury due to its resistance to lipid deposition as well as antioxidant and anti-inflammatory actions. These findings suggest that GRb1 may be a promising candidate against ALD.

7.
Aging (Albany NY) ; 13(5): 6592-6605, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707345

RESUMO

Acute hepatic damage is a severe condition characterized by inflammation and oxidative stress, which is a serious threat to people's life and health. But there are few effective treatments for acute liver injury. Therefore, safe and effective therapeutic approaches for preventing acute liver damage are urgently needed. Lupeol is a natural compound, which has significant antioxidant and anti-inflammatory properties in liver disease. However, the protective mechanism of lupeol against acute liver injury remains unclear. Here, zebrafish and mutant mice were utilized to investigate the protective effects of lupeol against lipopolysaccharide (LPS)/ D-galactosamine(D-GalN) -induced liver injury and the underlying mechanisms. We found that pretreatment with lupeol attenuated the LPS/D-GalN-induced liver injury by decreasing the infiltration of inflammatory cells and reducing pro-inflammatory cytokines. We also demonstrated that lupeol could protect injured liver from oxidative stress by downregulating the expression of TGFß1 and upregulating Nrf2. Notably, our experimental results provided the support that lupeol effectively protected against LPS/D-GalN-induced acute liver injury via suppression of inflammation response and oxidative stress, which were largely dependent on the upregulation of the Nrf2 pathway via downregulating TGFß1.


Assuntos
Anti-Inflamatórios/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Triterpenos Pentacíclicos/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Modelos Animais de Doenças , Regulação para Baixo , Galactosamina/toxicidade , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Regulação para Cima , Peixe-Zebra
8.
Cell Death Dis ; 12(1): 16, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414436

RESUMO

Liver fibrosis is a course of chronic liver dysfunction, can develop into cirrhosis and hepatocellular carcinoma. Inflammatory insult owing to pathogenic factors plays a crucial role in the pathogenesis of liver fibrosis. Indoleamine 2,3-dioxygenase 1 (IDO1) can affect the infiltration of immune cells in many pathology processes of diseases, but its role in liver fibrosis has not been elucidated completely. Here, the markedly elevated protein IDO1 in livers was identified, and dendritic cells (DCs) immune-phenotypes were significantly altered after BDL challenge. A distinct hepatic population of CD11c+DCs was decreased and presented an immature immune-phenotype, reflected by lower expression levels of co-stimulatory molecules (CD40, MHCII). Frequencies of CD11c+CD80+, CD11c+CD86+, CD11c+MHCII+, and CD11c+CD40+ cells in splenic leukocytes were reduced significantly. Notably, IDO1 overexpression inhibited hepatic, splenic CD11c+DCs maturation, mature DCs-mediated T-cell proliferation and worsened liver fibrosis, whereas above pathological phenomena were reversed in IDO1-/- mice. Our data demonstrate that IDO1 affects the process of immune cells recruitment via inhibiting DCs maturation and subsequent T cells proliferation, resulting in the promotion of hepatic fibrosis. Thus, amelioration of immune responses in hepatic and splenic microenvironment by targeting IDO1 might be essential for the therapeutic effects on liver fibrosis.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cirrose Hepática/enzimologia , Cirrose Hepática/patologia , Animais , Ductos Biliares/enzimologia , Ductos Biliares/patologia , Ductos Biliares/cirurgia , Diferenciação Celular/fisiologia , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
J Ethnopharmacol ; 266: 113436, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33011372

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dingxin Recipe (DXR) is a traditional Chinese medicine formula that has been reported to be effective and safe treatment for cardiovascular diseases, such as arrhythmias, coronary heart disease. Dingxin Recipe IV (DXR IV) was further improved from the DXR according to the traditional use. However, the mechanism of DXR IV in atherosclerosis is unclear. AIM OF THE STUDY: This study aimed to illustrate whether DXR IV improve atherosclerosis through modulating the lipid metabolism and gut microbiota in atherosclerosis mice. MATERIALS AND METHODS: 40 male ApoE-/- mice were fed on HFD for 12 weeks and were then treated with DXR IV (1.8, 0.9, or 0.45 g/kg/d) for another 12 weeks. The decroation of DXR IV contains four traditional Chinese medicines: the dried rhizome of Coptis chinensis Franch. (15.09%), the root of Salvia miltiorrhiza Bunge (28.30%), the seed of Ziziphus jujuba Mill. (37.74%) and the fruiting body of Ganoderma lucidum (Leyss.ex Fr.) Karst. (18.87%). 8 male c57BL/6 mice fed a normal diet served as control group. The atherosclerotic plaque was quantified by oil-red O staining and masson trichrome staining. Mice feces were collected. The gut micobiota were detected by 16S rRNA gene sequencing and fecal metabolites were analyzed by 1H NMR spectroscopy. The effect of DXR IV on blood lipids (TG, TC, LDL-C, HDL-C) was investigated. The lipid metabolism related genes were determined by RT-qPCR and western blotting respectively. RESULTS: DXR IV exerted the anti-atherosclerosis effect by inhibiting the excessive cholesterol deposition in aorta and regulating the level of TG, TC, LDL-C and HDL-C. The composition of gut microbiota was changed. Interestingly, the relative abundance of Muribaculaceae and Ruminococcaceae increased after DXR IV administration, whereas the abundance of Erysipelotrichaceae decreased, which have been beneficial to lipid metabolism. Nine potential metabolic biomarkers, including acetate, butyrate, propionate, alanine, succinate, valerate, xylose, choline, glutamate, were identified, which were related to fatty acid metabolism. Further, the pathway of fatty acid was detected by the RT-qPCR and western blotting. Compared with model group, the level of LXR-α and SREBP1 decreased significantly in DXR IV group while LXR-ß, SREBP2 showed no statistical significance. It indicated that DXR IV modulated lipid metabolism by LXR-α/SREBP1 but not LXRß and SREBP2. CONCLUSIONS: DXR IV exhibits potential anti-atherosclerosis effect, which is closely related to lipid metabolism and the gut microbiota. This study may provide novel insights into the mechanism of DXR IV on atherosclerosis and a basis for promising clinical usage.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Receptores X do Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/prevenção & controle , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
10.
Front Endocrinol (Lausanne) ; 11: 601956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281750

RESUMO

Background: The association between normal range thyroid function and offspring birth weight has been postulated, but evidence from observational studies is prone to be confounded. We conducted a two-sample Mendelian randomization (MR) study to explore the causal effects of maternal thyroid stimulating hormone (TSH) and free thyroxine (FT4) on birth weight. Methods: We utilized public shared summary-level statistics from European-ancestry genome wide association studies. We obtained 40 and 21 single nucleotide polymorphisms as instrumental variables, which were associated with TSH and FT4 levels at genome-wide significance (P < 5 × 10-8). Partitioned maternal effects on birth weight were retrieved from datasets contributed by the Early Growth Genetics Consortium. Inverse-variance weighted method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. Results: Genetically determined normal range thyroid function was not causally associated with offspring birth weight. Each one standard deviation (SD) increase in maternal TSH was associated with 0.002 SD higher of birth weight (95% confidence interval [CI], -0.021 to 0.025; P = 0.87). Similarly, change in birth weight was -0.001 SD (95% CI, -0.031 to 0.029; P = 0.94) per one SD higher in maternal FT4. Consistent results were yielded via additional MR methods. Sensitivity analyses demonstrated no presence of horizontal pleiotropy or heterogeneity. Conclusion: This MR study did not identify a causality between normal range thyroid function and offspring birth weight in the Europeans.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Análise da Randomização Mendeliana , Mães/estatística & dados numéricos , Glândula Tireoide/fisiologia , Tireotropina/farmacologia , Tiroxina/farmacologia , Causalidade , Feminino , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Polimorfismo de Nucleotídeo Único , Valores de Referência , Testes de Função Tireóidea
11.
Am J Chin Med ; 48(8): 1821-1840, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33308094

RESUMO

Macrophage autophagy defect is closely related to the progression of atherosclerosis (AS) and is regulated by the triggering receptor expressed on myeloid cell 2 (TREM2). TREM2 is a key factor in the development of Alzheimer's disease (AD), the deficiency of which leads to anomalous autophagy in microglia. However, the role of TREM2 in the autophagy of plaque macrophages is still unclear. Geniposide (GP) can inhibit AS progression and enhance macrophage autophagy, although the underlying mechanisms remain unknown. We found that high-fat diet (HFD) feeding significantly increased TREM2 levels and inhibited autophagy in the macrophages of ApoE[Formula: see text] mice. TREM2 overexpression in RAW264.7 macrophages decreased autophagy via activation of mTOR signaling. GP inhibited the progression of AS in ApoE[Formula: see text] mice, reinforced macrophage autophagy, and downregulated TREM2 by inhibiting mTOR signaling. Taken together, augmenting the autophagy levels in plaque macrophages by inhibiting the TREM2/mTOR axis can potentially impede atherosclerotic progression. The promising therapeutic effects of GP seen in this study should be validated in future trials, and the underlying mechanisms have to be elucidated in greater detail.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Iridoides/farmacologia , Iridoides/uso terapêutico , Macrófagos/fisiologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Fitoterapia , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo
12.
Clin Sci (Lond) ; 134(19): 2549-2563, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-32975280

RESUMO

Acute lung injury (ALI) is a life-threatening disease without effective pharmacotherapies, so far. Forsythia suspensa is frequently used in the treatment of lung infection in traditional Chinese medicine. In search for natural anti-inflammatory components, the activity and the underlying mechanism of Forsythoside A (FA) from Forsythia suspensa were explored. In the present paper, BALB/c mice and murine RAW 264.7 cells were stimulated by LPS to establish inflammation models. Data showed that FA inhibited the production of TNF-α and IL-6 and the activation of STAT3 in LPS-stimulated RAW 264.7 cells. Additionally, FA increased the expression level of microRNA-124 (miR-124). Furthermore, the inhibitory effect of FA on STAT3 was counteracted by the treatment of miR-124 inhibitor. Critically, FA ameliorated LPS-induced ALI pathological damage, the increase in lung water content and inflammatory cytokine, cells infiltration and activation of the STAT3 signaling pathway in BALB/c mice. Meanwhile, FA up-regulated the expression of miR-124 in lungs, while administration with miR-124 inhibitor attenuated the protective effects of FA. Our results indicated that FA alleviates LPS-induced inflammation through up-regulating miR-124 in vitro and in vivo. These findings indicate the potential of FA and miR-124 in the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Glicosídeos/farmacologia , MicroRNAs/genética , Substâncias Protetoras/farmacologia , Regulação para Cima/genética , Animais , Glicosídeos/química , Inflamação/genética , Inflamação/patologia , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , Modelos Biológicos , Substâncias Protetoras/química , Células RAW 264.7 , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos
13.
Free Radic Biol Med ; 160: 178-190, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-32771520

RESUMO

Liver fibrosis can develop into liver cirrhosis and hepatocellular carcinoma substantially without effective available treatment currently due to rarely characterized molecular pathogenesis. Indoleamine 2,3-dioxygenase 1(IDO1) can be detected on antigen-presenting cells (APCs) and modulates various immune responses. However, the role of IDO1 in the regulation of dendritic cells (DCs) during liver fibrosis is rarely reported. Here, we found that hepatic IDO1 was up-regulated during CCL4-induced liver fibrosis, which accompanied by a significant decrease in the frequencies of CD11c+CD80+, CD11c+CD86+, CD11c+CD40+ and CD11c+MHCII+ cells and a reduction in the subsequent T cell proliferation rate, whereas these changes were reversed significantly in IDO1-/- mice. Overexpressing IDO1 by adeno-associated viral vector serotype 9 (AAV9) significantly inhibited the maturation status of DCs, worsened fibrosis. In vitro studies showed that significantly elevated CD80, CD86, CD40 and MHCII expression were observed in BMDCs derived from IDO1-/- mice. Moreover, the maturation of BMDCs derived from WT mice were significantly increased after stimulated with IDO1 inhibitor (1-methyl- D -tryptophan). Nuclear factor E2-related factor 2 (Nrf2), a key regulator of the cellular adaptive response to oxidative insults and inflammation, exhibited a markedly decrease in the liver of WT fibrotic mice, nevertheless, knockout of IDO1 enhanced the protein level of Nrf2. Moreover, the expression of IDO1 and Nrf2 exhibited inverse colocalization pattern suggesting that ectopically expressed IDO1 down-regulated Nrf2. Additionally, up-regulation of IDO1 was also observed in the livers of Nrf2-/- fibrotic mice. Taken together, these data uncovered mutual antagonism between IDO1 and Nrf2 on the maturation status of DCs during hepatic fibrosis.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase , Cirrose Hepática , Fator 2 Relacionado a NF-E2 , Animais , Células Dendríticas , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Cirrose Hepática/genética , Camundongos , Fator 2 Relacionado a NF-E2/genética , Triptofano
14.
Front Pharmacol ; 11: 748, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536866

RESUMO

Background: Malignant melanoma is an extremely aggressive and metastatic cancer, and highly resistant to conventional therapies. Signal transducer and activator of transcription 3 (STAT3) signaling promotes melanoma development and progression, which has been validated as an effective target in melanoma treatment. Natural naphthoquinone shikonin is reported to exert anti-melanoma effects. However, the underlying mechanisms have not been fully elucidated. Purpose: This study aims to evaluate the anti-melanoma activities of shikonin and explore the involvement of STAT3 signaling in these effects. Methods: Zebrafish tumor model was established to evaluate the anti-human melanoma effects of shikonin in vivo. MTT assay and colony formation assay were employed to investigate the anti-proliferative effects of shikonin on human melanoma A375 and A2058 cells. Flow cytometry was used to analyze cell cycle distribution and apoptosis induction. Wound healing assay and Transwell chamber assay were conducted to examine the cell migratory and invasive abilities. Immunofluorescence assay was used to observe F-actin, Tubulin, and STAT3 localization. Western blotting was used to determine the expression levels of proteins associated with apoptosis and key proteins in the STAT3 signaling pathway. Immunoblotting was performed in DSS cross-linked cells to determine the homo-dimerization of STAT3. Gelatin zymography was employed to evaluate the enzymatic activity of MMP-2 and MMP-9. Transient transfection was used to overexpress STAT3 in cell models. Results: Shikonin suppressed melanoma growth in cultured cells and in zebrafish xenograft models. Shikonin induced melanoma cells apoptosis, inhibited cell migration and invasion. Mechanistic study indicated that shikonin inhibited the phosphorylation and homo-dimerization of STAT3, thus reduced its nuclear localization. Further study showed that shikonin decreased the levels of STAT3-targeted genes Mcl-1, Bcl-2, MMP-2, vimentin, and Twist, which are involved in melanoma survival, migration, and invasion. More importantly, overexpression of constitutively active STAT3 partially abolished the anti-proliferative, anti-migratory, and anti-invasive effects of shikonin. Conclusion: The anti-melanoma activity of shikonin is at least partially attributed to the inhibition on STAT3 signaling. These findings provide new insights into the anti-melanoma molecular mechanisms of shikonin, suggesting its potential in melanoma treatment.

15.
Opt Express ; 28(8): 11618-11633, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32403669

RESUMO

In this paper, we employ the emerging paradigm of physics-informed neural networks (PINNs) for the solution of representative inverse scattering problems in photonic metamaterials and nano-optics technologies. In particular, we successfully apply mesh-free PINNs to the difficult task of retrieving the effective permittivity parameters of a number of finite-size scattering systems that involve many interacting nanostructures as well as multi-component nanoparticles. Our methodology is fully validated by numerical simulations based on the finite element method (FEM). The development of physics-informed deep learning techniques for inverse scattering can enable the design of novel functional nanostructures and significantly broaden the design space of metamaterials by naturally accounting for radiation and finite-size effects beyond the limitations of traditional effective medium theories.

16.
Opt Lett ; 45(8): 2371-2374, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32287235

RESUMO

We design and characterize compact phase-modulated axilens devices that combine efficient point focusing and grating selectivity within four-level phase mask configurations. Specifically, we select and characterize in detail two device configurations designed for long-wavelength infrared (LWIR) operation in the $ 6\,\,\unicode{x00B5}{\rm m}\! -\! 12\,\,\unicode{x00B5}{\rm m} $6µm-12µm wavelength range. These devices are ideally suited for monolithic integration atop the substrate layers of infrared focal plane arrays (IR-FPAs) for use in multiband LWIR photodetection. We systematically study their focusing efficiency, spectral response, and crosstalk ratio, and we demonstrate a single-component microspectrometer. Our design method leverages the Rayleigh-Sommerfeld (RS) diffraction theory that is validated numerically using the finite element method (FEM). The proposed devices are broadband and polarization insensitive and add fundamental spectroscopic capabilities to miniaturized optical components for a number of applications in LWIR detection and spectroscopy.

17.
Biomed Chromatogr ; 34(6): e4817, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32112425

RESUMO

Folium Camelliae Nitidissimae (jinhuacha in Chinese, JHC) is a kind of caffeine-less tea with antioxidant, antitumor and antibacterial effects. Studies on the chemical profiles and hepatoprotective effects of JHC extracts have not been systematically conducted so far. This study comprehensively investigated the compound profiles of JHC extract by ultrafast liquid chromatography with quadrupole time-of-flight tandem mass spectrometry. We also determined JHC's hepatoprotective effects against CCl4 -induced liver injury in mice. A JHC extract was administered orally to mice at 1.95 and 7.80 g/kg body weight once daily for 14 consecutive days prior to CCl4 treatment. Eighty-four compounds including flavonoids, organic acids, catechins, coumarins, phenylpropanol, amino acids, anthraquinones, saponins and nucleosides in JHC extract were authentically identified or tentatively identified by comparing MS information and retention times with those of authentic standards or available references. JHC administration significantly decreased elevated levels of aspartate aminotransferase and alanine aminotransferase in mouse serum, inhibited hepatic malondialdehyde formation and enhanced glutathione and superoxide dismutase activities in the liver of CCl4 -treated mice. The histological observations also further supported the results. These results demonstrate that JHC contains various chemical compounds and its hepatoprotective effects against CCl4 -induced liver injury correlated with decreasing lipid oxidation are significant.


Assuntos
Camellia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Medicamentos de Ervas Chinesas , Substâncias Protetoras , Animais , Tetracloreto de Carbono/efeitos adversos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/análise , Flavonoides/química , Flavonoides/farmacologia , Fígado/efeitos dos fármacos , Camundongos , Substâncias Protetoras/análise , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Espectrometria de Massas em Tandem
18.
Free Radic Biol Med ; 152: 668-679, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31945497

RESUMO

Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, the molecular mechanisms of ferroptosis in acute immune hepatitis (AIH) are largely unknown. In this study, we investigated the classical ferroptotic events in the livers of mice with concanavalin A (ConA) to induce AIH. The dramatically upregulated gene indoleamine 2, 3-dioxygenase 1 (IDO1) was identified with AIH, and its role in generation of ferroptosis and reactive nitrogen species (RNS) was assessed both in vitro and in vivo by genetic deletion or pharmacologic inhibition of IDO1. We observed that ferroptosis contributed to the ConA-induced hepatic damage, which was confirmed by the therapeutical effects of ferroptosis inhibitor (ferrostatin-1). Noteworthy, upregulation of hepatic IDO1 and nitrative stress in ConA-induced hepatic damage were also remarkably inhibited by the ferroptosis abolishment. Additionally, IDO1 deficiency contributed to ferroptosis resistance by activating solute carrier family 7 member 11 (SLC7A11; also known as xCT) expression, accompanied with the reductions of murine liver lesions and RNS. Meanwhile, IDO inhibitor 1-methyl tryptophan alleviated murine liver damage with the reduction of inducible nitric oxide synthase and 3-nitrotyrosine expression. Consistent with the results in vivo, hepatocytes-specific knockdown of IDO1 led to ferroptosis resistance upon exposure to ferroptosis-inducing compound (Erastin) in vitro, whereas IDO1 overexpression aggravated the classical ferroptotic events, and the RNS stress. Overall, these results revealed a novel molecular mechanism of ferroptosis with the key feature of nitrative stress in ConA-induced liver injury, and also identified IDO1-dependent ferroptosis as a potential target for the treatment of AIH.


Assuntos
Ferroptose , Hepatite , Animais , Hepatócitos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Camundongos
19.
J Ethnopharmacol ; 249: 112427, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778782

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liang-Ge-San (LGS) is a traditional Chinese medicine formula that commonly used in acute inflammatory diseases. However, the anti-inflammatory effects and the underlying mechanisms of LGS are not fully studied. AIM OF THE STUDY: This study aims to investigate the anti-inflammatory activity and explore the underlying mechanisms of LGS in zebrafish and cell inflammation models. MATERIALS AND METHODS: LPS-induced zebrafish inflammation model was established by LPS-yolk microinjection. The protective effect of LGS on zebrafish injected with LPS was observed using survival analysis. Infiltration of inflammatory cells was determined by H&E staining assay. Expression levels of key inflammatory cytokines TNF-α and IL-6 were measured by q-PCR assay. Recruitment of neutrophils and macrophages were observed by fluorescence microscopy, SB staining and NR staining. In vitro anti-inflammatory effects of LGS were evaluated on LPS-stimulated RAW 264.7 cells. The generation of IL-6 and TNF-α was detected by ELISA. The protein expression levels of JNK, p-JNK (Thr183/Tyr185), Nur77 and p-Nur77 (Ser351) were determined by Western blotting. Finally, two additional inflammatory models in zebrafish, which were induced by CuSO4 or tail fin injury, were also established and the recruitment of neutrophils and macrophages were observed for the determination of the anti-inflammatory activity of LGS. RESULTS: LGS protected zebrafish against LPS-induced death and dose-dependently inhibited LPS-induced acute inflammatory response in zebrafish, as indicated by increased survival rate, reduced infiltration of inflammatory cells, decreased recruitment of macrophages and neutrophils, and downregulated expression levels of TNF-α and IL-6. Additionally, LGS inhibited the secretion of TNF-α and IL-6, increased the expression of Nur77, and reduced the expression of p-Nur77 (Ser351) and p-JNK (Thr183/Tyr185) in LPS-stimulated RAW 264.7 cells. The anti-inflammatory action of LGS was also observed in another two zebrafish inflammation models, which was supported by the inhibition on neutrophils and macrophages recruitment. CONCLUSION: The present study demonstrates that LGS possesses anti-inflammatory activity in zebrafish inflammation models and LPS-stimulated RAW 264.7 cells, which is related to the inhibition on p-JNK and p-Nur77. This finding provides a pharmacological basis for LGS in the control of inflammatory disorder.


Assuntos
Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Doença Aguda/terapia , Animais , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/imunologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/imunologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Peixe-Zebra
20.
Free Radic Biol Med ; 148: 151-161, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31877357

RESUMO

Ferroptosis is a new regulated cells death manner defined as results of iron-dependent accumulation of lipid peroxidation. However, the specific mechanisms of regulating ferroptosis remain unclear. In our present study, we demonstrated that Caveolin-1 (Cav-1) played a central role in protecting hepatocytes against ferroptosis in autoimmunity-mediated hepatitis (AIH). The down-regulated Cav-1 in liver tissues, accompanied by ferroptotic events and RNS production, were contributed to the outcome of ConA-induced hepatic damage, which were rescued by ferrostatin-1 (an inhibitor of ferroptosis) in vivo and in vitro. Additionally, Cav-1 deficiency aggravated ConA-induced hepatocellular death and ferroptosis associated with excessive nitrogen stress response. Short hairpin RNA of Cav-1 in hepatocytes promoted ferroptosis and nitrative stress in response to erastin in vitro, which was ameliorated by Cav-1 over-expression. Meanwhile, administration of the iNOS inhibitor (1400W) or ONOO- scavenger (Fe-TMPyP), diminished reactive nitrogen species (RNS), remarkably reduced hepatocytes ferroptosis and attenuated ConA-induced liver damage. Furthermore, immune inhibition by gadolinium chloride (GdCl3), a well-known Kupffer cell depletor, elevated hepatic Cav-1 but inhibited ferroptosis and nitrative stress under ConA exposure. In conclusion, these data revealed a novel molecular mechanism of ferroptosis with the Cav-1 regulation was essential for pathogenesis of ConA-induced hepatitis. Downstream of Cav-1, RNS-mediated ferroptosis was a pivotal step that drives the execution of acute immune-mediated hepatic damage.


Assuntos
Ferroptose , Caveolina 1/genética , Hepatócitos , Peroxidação de Lipídeos , Nitrogênio
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