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1.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38668694

RESUMO

An extremely stable megavolt (MV) level DC voltage source is the key foundation for many scientific instruments, and the need for accurate measurement and long-term real-time monitoring of its output voltage is increasingly urgent. The utilization of conventional resistive voltage dividers for measurements introduces leakage currents, resulting in considerable measurement errors. The non-contact generating voltmeter (GVM) sensor based on electric field measurement has a simple structure and a low cost, making it expected to be an effective solution. Currently, most research on GVM sensors focuses on the measurement of weak electric fields at kV/m levels with significant interference. In this paper, an improved high-precision non-contact GVM sensor was designed. A DC voltage test platform was built, and the effects of the sampling resistor and motor rotation speed on the measurement results were discussed. The relative combined uncertainty of the improved GVM sensor reached 0.042%, which satisfied the urgent need for MV level DC voltage source measurement. The improved GVM sensor can provide an effective reference for measuring the output voltage of a metal-enclosed MV level DC voltage source or the potential of a suspended electrode.

2.
Front Psychiatry ; 15: 1279266, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352653

RESUMO

Objective: Potential causal associations between psychiatric disorders and irritable bowel syndrome have been demonstrated in observational studies; however, these studies are susceptible to underlying confounding and reverse causation biases. We aimed to assess the causal effects of psychiatric disorders on irritable bowel syndrome (IBS) and the potential mediators from a genetic perspective by conducting a Mendelian randomization (MR) study with mediation analysis. Method: Genetic instruments associated with psychiatric disorders, potential mediators, and IBS were obtained from large-scale genome-wide association studies (GWAS). Three MR methods - the inverse-variance weighted (IVW) method, MR-Egger method, and weighted median method, were used to investigate causal association estimates. Heterogeneity among different genetic instrumental variables (IVs) was assessed using Q tests. Additionally, the MR-PRESSO and MR-Pleiotropy methods were used to verify horizontal pleiotropy and detect outliers that might bias the results, which were removed from further analysis. Consequently, we used MR mediation analysis to investigate potential mediators in the causal associations between psychiatric disorders and IBS. Results: MR provided evidence of the causal effects of genetically predicted broad depression, major depressive disorder (MDD), anxiety disorder, post-traumatic stress disorder (PTSD), and schizophrenia on IBS. The results of MR mediation analysis demonstrated that the reduction in acetate levels mediated 12.6% of the effects of broad depression on IBS; insomnia mediated 16.00%, 16.20%, and 27.14% of the effects of broad depression, MDD, and PTSD on IBS, respectively; and the increase in blood ß-hydroxybutyrate levels mediated 50.76% of the effects of schizophrenia on IBS. Conclusion: Our study confirmed the brain-gut axis involvement and potential modulators in the pathophysiology of psychiatric disorder-induced IBS from a genetic perspective, and suggests potential therapeutic targets for the disrupted brain-gut axis.

3.
Rev Sci Instrum ; 93(12): 124702, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36586935

RESUMO

A reliable and repeatable triggering technology for a megavolt gap switch with a low working coefficient η is an urgent need and a research focus. In this study, a novel method of hybrid plasma injection (HPI) driven by pulsed discharge inside a capillary was first proposed. The HPI actuator adopted a metal-polytetrafluoroethylene (PTFE)-stacked capillary, in which severe ablation could generate a hybrid plasma containing gas and metal vapor ionized component ejected outward from the nozzle. The HPI actuator could perform repeatedly with an extremely strong plasma injection and triggering ability and, thus, provided a solution for megavolt ultrafast bypass switches (UFBPSs). The evolution and the trigger properties of the HPI actuator were investigated, and the influence of the stacked material (Al, Zn, and Sn) and its proportion (3/15, 7/15, and 10/15) was studied, followed by the performance degradation in multi-shot. It was found that stacking chemically active and low-ionization-energy aluminum in a proportion of 7/15 strongly enhanced the HPI, with an initial velocity of 1200 m/s and a maximum height of 7.5 cm in 0.5 MPa SF6. In repeated operations, the HPI actuator performance degraded obviously due to capillary expansion and deformation, and the lifetime was tens of magnitude. Finally, the optimized HPI actuator was used to trigger a 7 cm-0.5 MPa SF6 gap, with a breakdown voltage of ∼1.5 MV. When a 100 kV DC voltage was applied (η < 7%), the gap was successfully and continuously triggered for 27 shots with the trigger delay ranging from 301 to 670 µs, indicating that the HPI actuator could effectively and repeatedly trigger megavolt-magnitude SF6 gaps at a very low η and was a good solution for megavolt UFBPSs.

4.
Front Nutr ; 9: 977556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003835

RESUMO

Hyaluronan (HA) is a mucopolysaccharide that naturally exists in all living organisms as the main component of the extracellular matrix. Over the last 30 years, HA has been used as the main ingredient in cosmetic products, eye drops, and medicinal products. It is also taken orally as a health supplement. However, the physiological effect of the ingested HA is not clear. In the current study, the interaction between HA and gut microbiota, and the potential prebiotic effects were investigated. HA was used to treat the C57BL/6 mice for 15 consecutive days, then fecal genomic DNA was extracted from fecal samples for 16S rRNA amplicon sequencing. The results showed that HA could significantly change the composition of gut microbiota (GM), e.g., increased the relative abundance of beneficial bacteria, including short-chain fatty acids (SCFAs)-producing bacteria and xylan/cellulose-degrading bacteria, whereas decreased the relative abundance of potential pathogens including sulfate-reducing bacteria (SRB), inflammation and cancer-related bacteria. The rotarod test was used to evaluate the anti-fatigue effects of HA in C57BL/6 mice. The results showed that HA could lengthen the mice's retention time on the accelerating rotarod. HA increased the concentration of glycogen and superoxide dismutase (SOD) in mice's muscle and liver, whereas decreased the serum concentration of malondialdehyde (MDA). Moreover, the metabolic products of Desulfovibrio vulgaris (MPDV), the model SRB bacteria, showed cytotoxic effects on H9c2 cardiomyocytes in a dosage-dependent manner. MPDV also caused mitochondrial damage by inducing mitochondrial fragmentation, depolarization, and powerless ATP production. Taken together, we show that HA possesses significant prebiotic and anti-fatigue effects in C57BL/6 mice.

5.
Pharmacol Res ; 176: 106082, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35032662

RESUMO

Patchouli Essential Oil (PEO) has been used as a scent for various healing purposes since the ancient Egyptian period. The primary source of the oil is Pogostemon cablin (PC), a medicinal plant for treating gastrointestinal symptoms. However, the pharmacological function has not been addressed. Here, we report the cancer prevention and gut microbiota (GM) modulating property of PEO and its derivatives patchouli alcohol (PA) and pogostone (PO) in the ApcMin /+ colorectal cancer mice model. We found that PEO, PA, and PO significantly reduced the tumor burden. At the same time, it strengthened the epithelial barrier, evidenced by substantially increasing the number of the goblet and Paneth cells and upregulation of tight junction and adhesion molecules. In addition, PEO, PA, and PO shifted M1 to M2 macrophage phenotypes and remodeled the inflammatory milieu of ApcMin /+ mice. We also found suppression of CD4+CD25+ and stimulation CD4+ CD8+ cells in the spleen, blood, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) of the treated mice. The composition of the gut microbiome of the drug-treated mice was distinct from the control mice. The drugs stimulated the short-chain fatty acids (SCFAs)-producers and the key SCFA-sensing receptors (GPR41, GPR43, and GPR109a). The activation of SCFAs/GPSs also triggered the alterations of PPAR-γ, PYY, and HSDCs signaling mediators in the treated mice. Our work showed that PEO and its derivatives exert potent anti-cancer effects by modulating gut microbiota and improving the intestinal microenvironment of the ApcMmin /+ mice.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Óleos Voláteis/uso terapêutico , Pogostemon , Animais , Antineoplásicos Fitogênicos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/microbiologia , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Óleos Voláteis/farmacologia , Nódulos Linfáticos Agregados/efeitos dos fármacos , Baço/efeitos dos fármacos
6.
Rev Sci Instrum ; 92(10): 104701, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34717402

RESUMO

Aiming at developing a megavolt ultrafast bypass switch (UFBPS) that operates at a very low working coefficient, an enhanced plasma injection (EPI) method was proposed, which ejected high-density plasmas up to several centimeters in height in a high-pressure SF6 and thus has an extremely strong triggering ability. The EPI method employed a thin polytetrafluoroethylene microcavity embedded inside the ground electrode and a metal wire electrically exploded inside the microcavity, generating a high-density metal vapor plasma that was rapidly ejected outward from the nozzle and inducing a breakdown of the residual gas gap. In this study, the ejected plasma properties by EPI and main influencing factors were examined and the EPI triggering ability was experimentally verified. The results showed that EPI evolution presented three stages: ellipsoid-shaped, mushroom-shaped, and dissipation stages. In 0.5-MPa SF6, when the trigger energy was 960 J and the exploded aluminum wire was 300 µm in radius, the EPI maximum height reached over 9 cm within 0.7 ms, with an initial evolution velocity >800 m/s. Then, an EPI cavity array was set to repetitively trigger a 10 cm-magnitude SF6 gas gap at 0.5 MPa, with a theoretical breakdown voltage >2 MV. The gas gap was successfully triggered with an average trigger delay of 538 µs when a DC 100 kV voltage (undervoltage ratio <5%) was applied. These results indicated that EPI was an effective method for triggering megavolt-magnitude high-pressure SF6 gas gaps at a low undervoltage ratio and meeting the submillisecond trigger requirement of the UFBPS.

7.
ACS Sens ; 6(6): 1990-2001, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34044533

RESUMO

Hydrogel is a unique family of biocompatible materials with growing applications in chemical and biological sensors. During the past few decades, various hydrogel-based optical ion sensors have been developed aiming at point-of-care testing and environmental monitoring. In this Perspective, we provide an overview of the research field including topics such as photonic crystals, DNAzyme cross-linked hydrogels, ionophore-based ion sensing hydrogels, and fluoroionophore-based optodes. As the different sensing principles are summarized, each strategy offers its advantages and limitations. In a nutshell, developing optical ion sensing hydrogels is still in the early stage with many opportunities lying ahead, especially with challenges in selectivity, assay time, detection limit, and usability.


Assuntos
DNA Catalítico , Hidrogéis , Monitoramento Ambiental , Óptica e Fotônica , Testes Imediatos
8.
Pharmacol Res ; 168: 105587, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33798737

RESUMO

We previously reported the neuroprotective effects of icariin in rat cortical neurons. Here, we present a study on icariin's anti-aging effect in 24-month aged mice by treating them with a single daily dose of 100 mg/kg of icariin for 15 consecutive days. Icariin treatment improved motor coordination and learning skills while lowered oxidative stress biomarkers in the serum, brain, kidney, and liver of the aged mice. In addition, icariin improved the intestinal integrity of the aged mice by upregulating tight junction adhesion molecules and the Paneth and goblet cells, along with the reduction of iNOS and pro-inflammatory cytokines (IL-1ß, TNF-α, IL-2 and IL-6, and IL-12). Icariin treatments also significantly upregulated aging-related signaling molecules, Sirt 1, 3 & 6, Pot1α, BUB1b, FOXO1, Ep300, ANXA3, Calb1, SNAP25, and BDNF in old mice. Through gut microbiota (GM) analysis, we observed icariin-associated improvements in GM composition of aged mice by reinstating bacteria found in the young mice, while suppressing some bacteria found in the untreated old mice. To clarify whether icariin's anti-aging effect is rooted in the GM, we performed fecal microbiota transfer (FMT) from icariin-treated old mice to the old mice. FMT-recipients exhibited similar improvements in the rotarod score and age-related biomarkers as observed in the icariin-treated old mice. Equal or better improvement on the youth-like features was noticed when aged mice were FMT with feces from young mice. Our study shows that both direct treatments with icariin and fecal transplant from the icariin-treated aged mice produce similar anti-aging phenotypes in the aged mice. We prove that GM plays a pivotal role in the healing abilities of icariin. Icariin has the potentials to be developed as a medicine for the wellness of the aged adults.


Assuntos
Envelhecimento/efeitos dos fármacos , Flavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Células Caliciformes/efeitos dos fármacos , Intestinos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Junções Íntimas/efeitos dos fármacos
10.
Pharmacol Res ; 159: 104809, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32502642

RESUMO

Microbiome therapy has attracted a keen interest from both research and business sectors. Our lab has been applying this "second genome" platform to assess the functionality of herbal medicines with fulfilling results. In this study, we applied this platform to assess the potential cancer-preventive effects of three selected adaptogenic plants. The flower buds from these plants were used to constitute Preparations SL and FSP according to the receipts of two commonly consumed Chinese medicinal decoctions for gastrointestinal discomfort. Preparation SL contains Sophorae japonica and Lonicerae Japonicae, and Preparation FSP contains Sophorae japonica and Gardenia Jasminoides. SL and FSP extracts significantly (p < 0.001) lowered the polyp burden, as well as the expressions of oncogenic signaling molecules, such as MAPK/ERK, PI3K/AKT, and STAT3 in ApcMin/+ mice. The inflamed gut was alleviated by shifting M1 to M2 macrophage phenotypes and the associated immune cytokines. The other remarkable change was on the extracellular tight junction protein complex, where the occludin, ZO-1, ICAM-1, E-cadherin were significantly (p < 0.05) upregulated while the N-cadherin and ß-catenin were downregulated in the treated mice. The above physiological changes in the gut epithelial barrier were companied with the changes in gut microbiome. The 16S Sequencing data revealed a marked decrease in the potential pathogens (especially Helicobacter species and hydrogen sulfide producing-bacteria) and the increase in beneficial bacteria (especially for species from the genera of Akkermansia, Barnesiella, Coprococcus, Lachnoclostridium, and Ruminococcus). The majority of which were the short-chain fatty acids (SCFAs) producers. Meanwhile SCFAs-sensing G protein-coupled receptors (GPCRs), including GPR41, GPR43, and GPR109a were also significantly upregulated. In a recent report, we proved that the bacteria-derived SCFAs plays an essential role to the anti-cancer effects of the mushroom polysaccharides and saponins in ApcMin/+ mice. In this study, we further demonstrated that butyrate treatment could enhance the extracellular tight junction protein complex as effective as the treatments with SL and FSP to the ApcMin/+ mice. Our findings provide strong evidence of the vital role of the SCFA-producers and their metabolites to the cancer-preventive properties of the SL and FSP preparations.


Assuntos
Anticarcinógenos/farmacologia , Bactérias/efeitos dos fármacos , Neoplasias Colorretais/prevenção & controle , Ácidos Graxos/metabolismo , Flores/química , Microbioma Gastrointestinal , Mucosa Intestinal/efeitos dos fármacos , Pólipos Intestinais/prevenção & controle , Magnoliopsida/química , Junções Íntimas/efeitos dos fármacos , Animais , Anticarcinógenos/isolamento & purificação , Bactérias/metabolismo , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Citocinas/metabolismo , Gardenia/química , Genes APC , Interações Hospedeiro-Patógeno , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Pólipos Intestinais/imunologia , Pólipos Intestinais/metabolismo , Pólipos Intestinais/microbiologia , Lonicera/química , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Sophora/química , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo
11.
Future Microbiol ; 15: 591-600, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32490694

RESUMO

Aim: Here, we hypothesize that dysbiotic gut microbiota might contribute to the development of Kawasaki disease (KD), a pediatric disease with unknown etiology. This is the second report on gut microbiota composition in KD patients. Materials & results: 16S amplicon sequencing was performed on fecal DNA samples and revealed predominance of bacterial pathogens, such as Fusobacterium, Neisseria, Shigella and Streptococcus, in the gut of KD patients, but absent or suppressed after immunoglobulin/antibiotics therapy. In addition, beneficial bacteria propagated after the therapy. Conclusion: We conclude that prevalence of Fusobacteria, Shigella and Streptococcus might contribute to KD pathogenesis.


Assuntos
Microbioma Gastrointestinal , Síndrome de Linfonodos Mucocutâneos/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Pré-Escolar , DNA Bacteriano/genética , Fezes/microbiologia , Feminino , Humanos , Lactente , Masculino , RNA Ribossômico 16S/genética
12.
Front Pharmacol ; 10: 1229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680986

RESUMO

Pogostemon cablin (Blanco) Benth (PC) is a Chinese medicinal plant traditionally used for the treatment of gastrointestinal symptoms. To investigate the prebiotic effect of patchouli essential oil (PEO) and its derived compounds through the modulation of gut microbiota (GM). C57BL/6J mice were treated with the PEO and three active components of PEO, i.e. patchouli alcohol (PA), pogostone (PO) and ß-patchoulene (ß-PAE) for 15 consecutive days. Fecal samples and mucosa were collected for GM biomarkers studies. PEO, PA, PO, and ß-PAE improve the gut epithelial barrier by altering the status of E-cadherin vs. N-cadherin expressions, and increasing the mucosal p-lysozyme and Muc 2. Moreover, the treatments also facilitate the polarization of M1 to M2 macrophage phenotypes, meanwhile, suppress the pro-inflammatory cytokines. Fecal microbial DNAs were analyzed and evaluated for GM composition by ERIC-PCR and 16S rRNA amplicon sequencing. The GM diversity was increased with the treated groups compared to the control. Further analysis showed that some known short chain fatty acids (SCFAs)-producing bacteria, e.g. Anaerostipes butyraticus, Butytivibrio fibrisolvens, Clostridium jejuense, Eubacterium uniforme, and Lactobacillus lactis were significantly enriched in the treated groups. In addition, the key SCFAs receptors, GPR 41, 43 and 109a, were significantly stimulated in the gut epithelial layer of the treated mice. By contract, the relative abundance of pathogens Sutterlla spp., Fusobacterium mortiferum, and Helicobacter spp. were distinctly reduced by the treatments with PEO and ß-PAE. Our findings provide insightful information that the microbiota/host dynamic interaction may play a key role for the pharmacological activities of PEO, PA, PO, and ß-PAE.

13.
Pharmacol Res ; 148: 104448, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31499195

RESUMO

The incidence of colorectal cancer (CRC) is alarming among younger peoples. While no effective chemopreventive drug available in the market, researchers have been searching for alternative strategies against CRC that are in demand. Therefore, we tested the cancer-preventive properties of Ganoderma lucidum (Lingzhi) polysaccharides (GLP), along with the saponins extracted from Gynostemma pentaphyllum (GpS), an herbal tea with prebiotic-like effects. Here, we report that saponins from Gynostemma pentaphyllum (GpS) and polysaccharides from Ganoderma lucidum (GLP together with GpS) profoundly improved the inflamed gut barrier of ApcMin/+ mice by reducing polyps, shifting colonic M1 to M2 macrophages, positively reverting E-cadherin/N-cadherin ratio, and downregulating oncogenic signaling molecules. The treatments also markedly promoted short-chain fatty acids (SCFAs)-producing bacteria and abridged sulfate-reducing bacteria in a time-dependent manner. G-protein coupled-receptors were significantly stimulated in the treated mice, accompanied by the modulated expressions of histone deacetylases, anti-cancer gut hormone PYY, and PPAPγ. These findings suggest that some of the herbal medicinal foods could modulate the relationship between the host and the gut microbiota (GM) to exert their beneficial properties to the host. Our study also implicates that these dietary mushroom polysaccharides and the Gp saponins have the potential to be developed as new preventive medicines against CRC.


Assuntos
Agaricales/química , Neoplasias Colorretais/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Gynostemma/química , Polissacarídeos/farmacologia , Saponinas/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Bactérias/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Camundongos , Prebióticos/administração & dosagem , RNA Ribossômico 16S/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Anal Chem ; 91(16): 10390-10394, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31339689

RESUMO

Demand for rapid quantitation of polyions such as heparin and protamine are ever growing. Previous paper-based and polymeric optical and electrochemical sensing devices required more than several hours for signal stabilization. Therefore, signals were acquired with fixed sample exposure time modes, which was time-consuming and technically demanding. We present here for the first time the optical detection of protamine and heparin in equilibrium mode with emulsified nanospheres. The method significantly shortens the response time from hours to typically less than 10 s and offers tunable, sensitive, and colorimetric detection within the clinically relevant range (10 to 100 mg/L) for heparin. The improved characteristics are attributable to the small size of the nanospheres (ca. 50 nm in diameter) as well as the reversible recognition at the nanoscale liquid-liquid interface. Detection of the anticoagulant heparin was also successfully demonstrated in human blood serum background.


Assuntos
Anticoagulantes/sangue , Colorimetria/métodos , Heparina/sangue , Protaminas/análise , Clorofórmio/química , Emulsões , Humanos , Nanosferas , Tamanho da Partícula , Compostos de Amônio Quaternário/química , Sensibilidade e Especificidade
15.
Phytomedicine ; 60: 153008, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31288940

RESUMO

BACKGROUND: Melanogenesis is a physiological process of melanin production in response to UV exposure, which is modulated through multi-signaling pathways including cAMP/PKA, Wnt/ß-catenin and MAPK signaling cascades. HYPOTHESIS/PURPOSE: The present study aims to investigate the molecular mechanism of hyperpigmentation induced by Gynostemma pentaphyllum saponins. STUDY DESIGN/METHODS: In this study, we investigated the melanogenic effects of triterpenoid saponins of Gynostemma pentaphyllum (GpS), a medicinal plant. Two mouse melanogenic cell lines B16 and B16F10 were employed for the current study. RESULTS: The results showed that non-toxic doses of GpS markedly increased melanin formation in both B16 and B16F10 cells. Western blot analysis showed that GpS treatment significantly up-regulated the expression levels of the key melanogenic proteins, including tyrosinase (TYR), microphthalmia-associated transcription factor (MITF), TRP-1 and TRP-2 in a dose-dependent manner. The phospho-CREB, which is the downstream target of PKA is also elevated upon GpS treatment. We further observed that H89, a PKA inhibitor, attenuated the GpS induced tyrosinase activity, melanin content, the expression of phospho-CREB. In addition to the cAMP/PKA signaling pathway, GpS treatment also up-regulated the ß-catenin of the Wnt signaling pathway which is involved in the transcriptional activation of MITF in melanogensis. We further demonstrated that treatment with GpS markedly enhance mRNA expression of MITF, along with the downstream target molecules, TYR, TRP-1 and TRP-2. Knock-down MITF with siMITF inhibited the expression of MITF mRNA by 63%, and the melanin content was reduced 70% in the siMITF-transfected cells compared to untransfected or scramble siRNA control cells. CONCLUSION: These findings demonstrated strong melanogenic activities of GpS, and the MITF is essential for the melanogenesis stimulated by GpS.


Assuntos
Gynostemma/química , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Saponinas/farmacologia , Via de Sinalização Wnt , Animais , Linhagem Celular Tumoral , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Técnicas de Silenciamento de Genes , Oxirredutases Intramoleculares/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Oxirredutases/metabolismo , Regulação para Cima
16.
Rev Sci Instrum ; 89(3): 035113, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29604770

RESUMO

Microparticle initiated pre-firing of high pressure gas switches for fast linear transformer drivers (FLTDs) is experimentally and theoretically verified. First, a dual-electrode gas switch equipped with poly-methyl methacrylate baffles is used to capture and collect the microparticles. By analyzing the electrode surfaces and the collecting baffles by a laser scanning confocal microscope, microparticles ranging in size from tens of micrometers to over 100 µm are observed under the typical working conditions of FLTDs. The charging and movement of free microparticles in switch cavity are studied, and the strong DC electric field drives the microparticles to bounce off the electrode. Three different modes of free microparticle motion appear to be responsible for switch pre-firing. (i) Microparticles adhere to the electrode surface and act as a fixed protrusion which distorts the local electric field and initiates the breakdown in the gap. (ii) One particle escapes toward the opposite electrode and causes a near-electrode microdischarge, inducing the breakdown of the residual gap. (iii) Multiple moving microparticles are occasionally in cascade, leading to pre-firing. Finally, as experimental verification, repetitive discharges at ±90 kV are conducted in a three-electrode field-distortion gas switch, with two 8 mm gaps and pressurized with nitrogen. An ultrasonic probe is employed to monitor the bounce signals. In pre-firing incidents, the bounce is detected shortly before the collapse of the voltage waveform, which demonstrates that free microparticles contribute significantly to the mechanism that induces pre-firing in FLTD gas switches.

17.
Sci Rep ; 7(1): 12552, 2017 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-28970547

RESUMO

Studies showed that manipulation of gut microbiota (GM) composition through the treatment of prebiotics could be a novel preventive measure against colorectal cancer (CRC) development. In this study, for the first time, we assessed the non-toxic doses of the triterpene saponins (ginsenoside-Rb3 and ginsenoside-Rd) - as prebiotics - that effectively reinstated the dysbiotic-gut microbial composition and intestinal microenvironment in an ApcMin/+ mice model. Rb3 and Rd effectively reduced the size and the number of the polyps that accompanied with the downregulation of oncogenic signaling molecules (iNOS, STAT3/pSTAT3, Src/pSrc). Both the compounds improved the gut epithelium by promoting goblet and Paneth cells population and reinstating the E-cadherin and N-Cadherin expression. Mucosal immunity remodeled with increased in anti-inflammatory cytokines and reduced in pro-inflammatory cytokines in treated mice. All these changes were correlating with the promoted growth of beneficial bacteria such as Bifidobacterium spp., Lactobacillus spp., Bacteroides acidifaciens, and Bacteroides xylanisolvens. Whereas, the abundance of cancer cachexia associated bacteria, such as Dysgonomonas spp. and Helicobacter spp., was profoundly lower in Rb3/Rd-treated mice. In conclusion, ginsenosides Rb3 and Rd exerted anti-cancer effects by holistically reinstating mucosal architecture, improving mucosal immunity, promoting beneficial bacteria, and down-regulating cancer-cachexia associated bacteria.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Ginsenosídeos/administração & dosagem , Pólipos/tratamento farmacológico , Prebióticos/administração & dosagem , Animais , Bacteroides/efeitos dos fármacos , Bacteroides/crescimento & desenvolvimento , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/crescimento & desenvolvimento , Caderinas/genética , Microambiente Celular/efeitos dos fármacos , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/patologia , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Pólipos/patologia , Fator de Transcrição STAT3/genética , Saponinas/administração & dosagem , Triterpenos/administração & dosagem , Quinases da Família src/genética
18.
Molecules ; 21(11)2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27879670

RESUMO

Icariin, an ingredient in the medicinal herb Epimedium brevicornum Maxim (EbM), has been considered as a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). Hyperhomocysteinaemia is a risk factor for AD and other associated neurological diseases. In this study we aim to investigate whether icariin can reverse homocysteine (Hcy)-induced neurotoxicity in primary embryonic cultures of rat cortical neurons. Our findings demonstrated that icariin might be able restore the cytoskeleton network damaged by Hcy through the modulation of acetyl-α-tubulin, tyrosinated-α-tubulin, and phosphorylation of the tubulin-binding protein Tau. In addition, icariin downregulated p-extracellular signal-regulated kinase (ERK) which is a kinase targeting tau protein. Furthermore, icariin effectively restored the neuroprotective protein p-Akt that was downregulated by Hcy. We also applied RT² Profiler PCR Arrays focused on genes related to AD and neurotoxicity to examine genes differentially altered by Hcy or icariin. Among the altered genes from the arrays, ADAM9 was downregulated 15 folds in cells treated with Hcy, but markedly restored by icariin. ADAM family, encoded α-secreatase, plays a protective role in AD. Overall, our findings demonstrated that icariin exhibits a strong neuroprotective function and have potential for future development for drug treating neurological disorders, such as AD.


Assuntos
Embrião de Mamíferos/citologia , Flavonoides/farmacologia , Homocisteína/efeitos adversos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas ADAM/genética , Animais , Células Cultivadas , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Modelos Biológicos , Neurônios/citologia , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
19.
Rev Sci Instrum ; 87(3): 035103, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27036815

RESUMO

At present, conducting standard lightning impulse (LI) tests in the field for gas-insulated switchgear (GIS) equipment is difficult because of the high capacitance of the test equipment and large circuit inductance of traditional impulse devices, which leads to a wavefront time T(f) ≥ 2.5 µs. A novel fully enclosed, compact standard LI generator for testing ultra-high-voltage-class GIS equipment with high capacitance is presented to solve the problem of T(f) exceeding the standard during LI voltage tests for actual large-sized equipment. The impulse generator is installed in a metal vessel filled with SF6 or SF6/N2 gas mixture at a pressure of 0.3-0.5 MPa, providing a more compact structure and a lower series inductance. A newly developed conical voltage sensor is used to accurately measure the output voltage waveform. Two test modes (via bushing docking and direct docking) for the GIS test based on the impulse generator are introduced. Calculation results show that the impulse generator can generate an LI test waveform following the present IEC standard for the test of equipment with capacitance >10,000 pF.

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