RESUMO
Oral tranexamic acid (TA) has been an effective treatment for melasma with unclear mechanism. The present study aimed to demonstrate the effect of TA on melanogenesis via regulation of TGF-ß1 expression in keratinocytes. We firstly determined the expression level of TGF-ß1 in TA-treated keratinocyte-conditioned medium (KCM). Then, the mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1) of human epidermal melanocytes (NHEMs) in the presence of TA-treated KCM were evaluated via RT-PCR and western blot analysis. Moreover, melanin content and tyrosinase activity were quantified. TGF-ß1 gene was knocked down by small interfering RNA (siRNA) in keratinocytes. The mRNA and protein levels of TGF-ß1 in keratinocytes were significantly increased after TA treatment. Melanin contents, tyrosinase activity, protein and mRNA levels of TYR, MITF and TRP-1 were downregulated in NHEMs in the presence of TA-treated KCM. Knockdown of TGF-ß1 in keratinocytes could attenuate the inhibitory effect of TA-treated KCM on melanogenesis. TA could stimulate TGF-ß1 expression in keratinocytes, which further inhibits melanogenesis through the paracrine signalling.
Assuntos
Ácido Tranexâmico , Meios de Cultivo Condicionados/farmacologia , Humanos , Queratinócitos/metabolismo , Melaninas/metabolismo , Melanócitos/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , RNA Mensageiro/metabolismo , Ácido Tranexâmico/metabolismo , Ácido Tranexâmico/farmacologia , Fator de Crescimento Transformador beta1/metabolismoRESUMO
The accurate segmentation of retinal vascular is of great significance for the diagnosis of diseases such as diabetes, hypertension, microaneurysms and arteriosclerosis. In order to segment more deep and small blood vessels and provide more information to doctors, a multi-scale joint optimization strategy for retinal vascular segmentation is presented in this paper. Firstly, the Multi-Scale Retinex (MSR) algorithm is used to improve the uneven illumination of fundus images. Then, the multi-scale Gaussian matched filtering method is used to enhance the contrast of the retinal images. Optimized by the Particle Swarm Optimization (PSO) algorithm, Otsu algorithm (OTSU) multi-threshold segmentation is utilized to segment the retinal image extracted by the multi-scale matched filtering method. Finally, the image is post-processed, including binarization, morphological operation and edge-contour removal. The test experiments are implemented on the DRIVE and STARE datasets to evaluate the effectiveness and practicability of the proposed method. Compared with other existing methods, it can be concluded that the proposed method can segment more small blood vessels while ensuring the integrity of vascular structure and has a higher performance. The proposed method has more obvious targets, a higher contrast, more plentiful detailed information, and local features. The qualitative and quantitative analysis results show that the presented method is superior to the other advanced methods.
Assuntos
Algoritmos , Vasos Retinianos , Fundo de Olho , Processamento de Imagem Assistida por Computador , Distribuição Normal , Vasos Retinianos/diagnóstico por imagemRESUMO
This study experimentally investigated the effects of hydrogen direct injection on combustion and the cycle-by-cycle variations in a spark ignition n-butanol engine under lean burn conditions. For this purpose, a spark ignition engine installed with a hydrogen and n-butanol dual fuel injection system was specially developed. Experiments were conducted at four excess air ratios, four hydrogen fractions(φ(ð»2)) and pure n-butanol. Engine speed and intake manifold absolute pressure (MAP) were kept at 1500 r/min and 43 kPa, respectively. The results indicate that the θ0-10 and θ10-90 decreased gradually with the increase in hydrogen fraction. Additionally, the indicated mean effective pressure (IMEP), the peak cylinder pressure (Pmax) and the maximum rate of pressure rise ((dP/dφ)max) increased gradually, while their cycle-by-cycle variations decreased with the increase in hydrogen fraction. In addition, the correlation between the (dP/dφ)max and its corresponding crank angle became weak with the increase in the excess air coefficient (λ), which tends to be strongly correlated with the increase in hydrogen fraction. The coefficient of variation of the Pmax and the IMEP increased with the increase in λ, while they decreased obviously after blending in the hydrogen under lean burn conditions. Furthermore, when λ was 1.0, a 5% hydrogen fraction improved the cycle-by-cycle variations most significantly. While a larger hydrogen fraction is needed to achieve the excellent combustion characteristics under lean burn conditions, hydrogen direct injection can promote combustion process and is beneficial for enhancing stable combustion and reducing the cycle-by-cycle variations.
RESUMO
With the continuous progress of development, deep learning has made good progress in the analysis and recognition of images, which has also triggered some researchers to explore the area of combining deep learning with hyperspectral medical images and achieve some progress. This paper introduces the principles and techniques of hyperspectral imaging systems, summarizes the common medical hyperspectral imaging systems, and summarizes the progress of some emerging spectral imaging systems through analyzing the literature. In particular, this article introduces the more frequently used medical hyperspectral images and the pre-processing techniques of the spectra, and in other sections, it discusses the main developments of medical hyperspectral combined with deep learning for disease diagnosis. On the basis of the previous review, tne limited factors in the study on the application of deep learning to hyperspectral medical images are outlined, promising research directions are summarized, and the future research prospects are provided for subsequent scholars.
Assuntos
Aprendizado Profundo , Diagnóstico por ImagemRESUMO
The unbalanced charge transport is always a key influencing factor on the device performance of quantum dot light-emitting diodes (QLEDs), particularly for the blue QLEDs due to their large optical band gap. Here, a method of electron transport layer (ETL) doping was developed to regulate the energy levels and the carrier mobility of the ETL, which resulted in more balanced charge injection, transport and recombination in the blue emitting CdZnS/ZnS core/shell QLEDs. Consequently, an enhanced performance of blue QLEDs was achieved by modulating the charge balance through ETL doping. The maximum external quantum efficiency and luminance was dramatically increased from 2.2% to 7.3% and from 3786 cd m-2to 9108 cd m-2, respectively. The results illustrate that charge transport layer doping is a simple and effective strategy to regulate the charge injection barrier and carrier mobility of QLEDs.
RESUMO
To get more obvious target information and more texture features, a new fusion method for the infrared (IR) and visible (VIS) images combining regional energy (RE) and intuitionistic fuzzy sets (IFS) is proposed, and this method can be described by several steps as follows. Firstly, the IR and VIS images are decomposed into low- and high-frequency sub-bands by non-subsampled shearlet transform (NSST). Secondly, RE-based fusion rule is used to obtain the low-frequency pre-fusion image, which allows the important target information preserved in the resulting image. Based on the pre-fusion image, the IFS-based fusion rule is introduced to achieve the final low-frequency image, which enables more important texture information transferred to the resulting image. Thirdly, the 'max-absolute' fusion rule is adopted to fuse high-frequency sub-bands. Finally, the fused image is reconstructed by inverse NSST. The TNO and RoadScene datasets are used to evaluate the proposed method. The simulation results demonstrate that the fused images of the proposed method have more obvious targets, higher contrast, more plentiful detailed information, and local features. Qualitative and quantitative analysis results show that the presented method is superior to the other nine advanced fusion methods.
Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Simulação por Computador , Imageamento por Ressonância Magnética , Fenômenos FísicosRESUMO
Metastasis is the main cause of the lethality of prostate cancer. Class I phosphatidylinositol 3-kinases (PI3Ks), which contain 4 isoforms, α, ß, δ, and γ, are known to play important roles in cell growth, migration, invasion, and so on. However, the respective role of each PI3K isoform in cancer cell migration and invasion remains unknown. In a study that aimed to elucidate the respective role of the 4 PI3K isoforms, we investigated the change in migratory and invasive ability of DU145 cells after treatment with each PI3K isoform-specific inhibitor. Both migration and invasion of DU145 cells were potently blocked by each of the PI3Kß inhibitors (GSK2636771 and TGX221) and PI3Kδ inhibitors (CAL101 and IC87114) while not obviously affected by PI3Kα inhibitor BYL719 or PI3Kγ inhibitor AS252424. Furthermore, knocking down PI3Kß or PI3Kδ isoform led to a significant decrease in migration of DU145. The results suggest that PI3Kß and PI3Kδ play key roles in prostate cancer cell migration, while PI3Kα and PI3Kγ might be redundant. Oral administration of GSK2636771 (100 mg/kg) and CAL101 (30 mg/kg) inhibited tumor growth in bone, an experimental model by intratibia injection of DU145 cells, with improved bone structure and bone mineral density analyzed by micro-computed tomography. Tissue staining indicated reduction of metastatic DU145 cells and osteoclasts in the bones of GSK2636771- and CAL101-treated mice compared to the untreated group. In summary, our results indicated the distinct roles of 4 PI3K isoforms in the migration of prostate cancer DU145 cells, and they demonstrated the in vitro and in vivo antimetastatic effect of PI3K-isoform specific inhibitors, most of which are in clinical trials.-Zhang, Z., Liu, J., Wang, Y., Tan, X., Zhao, W., Xing, X., Qiu, Y., Wang, R., Jin, M., Fan, G., Zhang, P., Zhong, Y., Kong, D. Phosphatidylinositol 3-kinase ß and δ isoforms play key roles in metastasis of prostate cancer DU145 cells.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Metástase Neoplásica , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Humanos , Concentração Inibidora 50 , Integrina beta1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica/prevenção & controle , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Microtomografia por Raio-XRESUMO
What is the central question of this study? Does Danzhi Qing'e (DZQE) regulate lipid metabolism and improve ovarian function in a rat model of perimenopausal hyperlipidaemia, and could this effect be mediated through the AMPK pathway? What is the main finding and its importance? We revealed that DZQE is a pharmacotherapy that could activate the AMPK pathway to improve ovarian function and lipid metabolism during perimenopause complicated with hyperlipidaemia syndrome in an animal model. Thus, this study provides a novel therapeutic option for treating perimenopausal syndrome and highlights the therapeutic potential of DZQE in perimenopausal rats. Menopause is an important event in a woman's life. During perimenopause, accompanied by development of osteoporosis and dyslipidaemia, ovarian function gradually declines. Dyslipidaemia is a risk factor for cardiovascular disorders, cerebrovascular disease and breast cancer in postmenopausal women. All of these contribute to impairment of liver function, particularly fatty liver disease, because liver dysfunction is associated with ovarian dysfunction and hyperlipidaemia. The aim of this study was to define a therapeutic approach to improve ovarian function and attenuate lipid accumulation in order to prevent perimenopause-induced ovarian dysfunction and hyperlipidaemia. Four-week-old female Wistar rats were injected i.p. with 4-vinylcyclohexene diepoxide (4-VCD) and fed with a high-fat diet (HFD) to serve as a model of perimenopause complicated with hyperlipidaemia. The 4-VCD induces perimenopause, while the HFD causes hyperlipidaemia. Five days after administration of 4-VCD, the 4-VCD + HFD-treated rats were assessed daily for oestrous cycle stage by vaginal cytology. Rats were then assigned into groups, in which 2.5, 5.0 or 10.0 g kg-1 Danzhi Qing'e (DZQE) or estradiol valerate was administered intragastrically for 8 weeks. Expression levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen and testosterone measured by enzyme-linked immunosorbent assay served as biomarkers for perimenopause and ovarian dysfunction. The expression levels of AMPK and acetyl-CoA carboxylase in the liver were determined with Western blotting, and aspartate aminotransferase and alanine aminotransferase were analysed using an automated biochemical analyser to examine liver function. The DZQE improved ovarian function by upregulating oestrogen and testosterone concentrations in serum and downregulating FSH and LH serum concentrations. Moreover, DZQE reduced serum concentrations of triglyceride, total cholesterol and low-density lipoprotein in a dose-dependent manner to regulate lipid levels during perimenopause. Furthermore, DZQE increased AMPK at both the transcriptional and translational levels and decreased the expression of SREBP-1c gene as well as its downstream target gene, fatty acid synthase. Danzhi Qing'e improved dyslipidaemia during menopause and also had an effect on liver function. Danzhi Qing'e is an effective Chinese herbal compound, which improves ovarian function and lipid metabolism in perimenopause complicated with hyperlipidaemia at least in part through the AMPK pathway.
Assuntos
Adenilato Quinase/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Perimenopausa/efeitos dos fármacos , Acetil-CoA Carboxilase/metabolismo , Animais , Cicloexenos/farmacologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Ratos , Ratos Wistar , Compostos de Vinila/farmacologiaRESUMO
As typical nano metarials in near infrared waveband, PbSe Quantum Dots have a very large exciton Bohr radius of 46 nm and a small band gap of 0.28 eV at room temperature. PbSe QDs have very unique properties, such as the quantum confined optical property, and which possess high photoluminescence (PL) quantum yield (QY) with size dependent tunable wavelength emissions. By analyzing the luminescence spectrum of PbSe Quantum Dots, a method through adjusting the particle size of PbSe Quantum Dots (QDs) to match gas absorption spectrum was presented in this paper. 4.6 and 6.1 nm PbSe QDs were synthesized and deposited on the GaN chip to fabricate the NIR QDs light sources. The PbSe QDs-UV glue composites thickness was determined to be 48.0 and 671.5 µm for 6.1 and 4.6 nm PbSe QDs. The NIR QDs were used to detect the C2H2 and NH3 gas. The experiments show that the PL spectrum of 4.6 nm NIR QDs can cover the entire absorption spectrum of C2H2 gas (from 1 500 to 1 550 nm) and the PL spectrum of 6.1 nm NIR QDs can cover the entire absorption spectrum of NH3 gas (from 1 900 to 2 060 nm). By changing the quantum size of QDs, the PL peak of the NIR QDS light source can be adjusted to cover the absorption peak of different gases. The matching method presented in this paper is efficient and feasible, which has great application potential in gas detection.
RESUMO
Perimenopause is an important period in women's lives, in which they experience a series of physiological changes. Current animal models of perimenopause fail to adequately replicate this particular stage in female life, while current in vitro models are too simplistic and cannot account for systemic effects. Neither the naturally-ageing animal model, nor the ovariectomised animal model, mimic the natural transitional process that is the menopause. In vivo and in vitro studies have confirmed that the occupational chemical, 4-vinylcyclohexene diepoxide (VCD), can cause selective destruction of the ovarian primordial and primary follicles of rats and mice by accelerating the apoptotic process, which successfully mimics the perimenopausal state in women. However, it is the in vivo VCD-induced rodent perimenopausal models that are currently the most widely used in research, rather than any of the available in vitro models. Studies on the mechanisms involved have found that VCD induces ovotoxicity via interference with the c-kit/kit ligand and apoptotic signalling pathways, among others. Overall, the VCD-induced perimenopausal animal models have provided some insight into female perimenopause, but they are far from ideal models of the human situation.
Assuntos
Cicloexenos/toxicidade , Folículo Ovariano/efeitos dos fármacos , Perimenopausa , Compostos de Vinila/toxicidade , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Ratos , Transdução de SinaisRESUMO
BACKGROUND: There is no standardized and effective treatment modality for Riehl's melanosis. AIMS: To compare the efficacy and safety of oral tranexamic acid (TXA) combined with intense pulsed light (IPL) versus TXA alone in the treatment of refractory Riehl's melanosis. METHODS: A prospective study of 28 subjects with refractory Riehl's melanosis and Fitzpatrick Skin Types III or IV was conducted. All subjects received oral TXA 500 mg daily and 11 of them were treated in combination with monthly IPL therapy for 6 months. The primary outcome measure was mean melanin index (MI), erythema index (EI) and acquired dermal macular hyperpigmentation area and severity index (DPASI). The Physician Global Assessment (PGA) and patient satisfaction scale were documented. RESULTS: After treatment, DPASI, mean MI, and EI were significantly reduced in both groups. The group treated with combination therapy showed better improvement according to MI (p = 0.0032) and DPASI (p = 0.00468). PGA and patient satisfaction scale showed superior efficacy in the combination group. No significant difference was observed in treatment-related side effects. CONCLUSION: The combination of oral TXA and IPL proves to be a safe and satisfactory treatment strategy for refractory Riehl's melanosis.
Assuntos
Antifibrinolíticos , Terapia de Luz Pulsada Intensa , Melanose , Satisfação do Paciente , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/efeitos adversos , Melanose/terapia , Melanose/tratamento farmacológico , Melanose/diagnóstico , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Administração Oral , Resultado do Tratamento , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Terapia de Luz Pulsada Intensa/efeitos adversos , Terapia de Luz Pulsada Intensa/métodos , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/efeitos adversos , Índice de Gravidade de DoençaRESUMO
Photobiomodulation (PBM) using 830 nm light-emitting diode (LED) benefits tissue regeneration, wound healing and neural stimulation. However, there is not much exploration of its effect on melanocytes and ex vivo skin model. This study aims to investigate the mechanism behind the anti-melanogenic activity of 830 nm LED and provides evidence for its activity in human ex vivo skin model. Our results showed that 830 nm LED at fluences ranging from 5 to 20 J/cm2 inhibited melanosome maturation and reduced melanin content, tyrosinase activity and melanogenesis-related proteins. 830 nm LED inhibited the phosphorylation of AKT and its downstream FOXO3a, leading to nuclear translocation of FOXO3a. Furthermore, FOXO3a knockdown and AKT activator like SC79 could reverse the melanogenesis inhibition phenotype induced by 830 nm LED. In human ex vivo skin model, Fontana-Masson staining revealed a decrease in epidermal basal pigmentation after 830 nm LED irradiation. Taken together, 830 nm LED demonstrated the anti-melanogenic activity via FOXO3a.
RESUMO
Oxidative stress represents an imbalance between the generation of reactive oxygen and nitrogen species and the ability of antioxidant systems to decompose those products. Oxidative stress is implicated in the pathogenesis of hyperpigmentation, hypopigmentation, melanoma, and other skin diseases. Regulatory networks involving oxidative stress and related pathways are widely represented in hypopigmentation diseases, particularly vitiligo. However, there is no complete review into the role of oxidative stress in the pathogenesis of hyperpigmentation disorders, especially regarding associations involving oxidative stress and cellular signaling pathways. Here, we review oxidative and antioxidant systems, oxidative stress-induced signal transduction mechanisms, and effects of antioxidant drugs used in preclinical and clinical settings in hyperpigmentation disorders.
Assuntos
Hiperpigmentação/tratamento farmacológico , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo , Humanos , Hiperpigmentação/patologiaRESUMO
BACKGROUND: Robust evidence regarding the efficacy of topical tranexamic acid (TA) on melasma in Chinese population is lacking. OBJECTIVE: To evaluate the efficacy and safety of 1.8% liposomal TA and microneedling with 5% TA solution on melasma. METHODS: Sixty melasma patients were enrolled and randomized to receive 1.8% liposomal TA twice daily, microneedling with 5% TA solution weekly or 2% hydroquinone every night. Objective and subjective assessments were obtained at baseline, 4, 8, and 12 weeks. RESULTS: 27.8% of patients of liposomal TA group, 33.3% of microneedling with TA solution group, and 30.0% of hydroquinone group were recognized as "more than 50% improvement." At the endpoint, the melanin index (MI) in all treatment groups was significantly decreased, while the improvement of MI in microneedling with TA solution group and hydroquinone group is higher than liposomal TA group. The erythema index (EI) was significantly diminished in liposomal TA group and microneedling with TA solution group. Dermatoscopy and reflectance confocal microscopy revealed decreased brown granules in all groups and reduced telangiectasia in liposomal TA group and microneedling with TA solution group. CONCLUSION: 1.8% liposomal TA and microneedling with 5% TA solution are both effective and safe on melasma.
Assuntos
Melanose , Ácido Tranexâmico , Administração Cutânea , Humanos , Hidroquinonas/efeitos adversos , Melanose/tratamento farmacológico , Ácido Tranexâmico/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: 585 nm light-emitting diodes have been proven to suppress melanogenesis in melanocytes. However, whether LEDs will influence normal human epidermal keratinocytes (NHEKs) and paracrine effect of LEDs-irradiated NHEKs in melanogenesis remains unknown. OBJECTIVE: To elucidate the possible mechanisms in vitro of anti-melanogenic activity of 585 nm LEDs on paracrine effect of NHEKs and its exosomes. METHODS: NHEKs irradiated with different fluences of 585 nm LEDs were evaluated the cell viability by CCK8 assay. Irradiated medium of NHEKs was co-cultured with melanocytes. Melanin content, tyrosinase activity and melanogenic enzymes activities were detected. Exosomes from NHEKs medium were isolated and characterized by electron microscopy and nanoparticle tracking analysis. The expression changes of H19 and its encoded exosomal miR-675 were analyzed. RESULTS: Irradiation with 585 nm LEDs from 0 J/cm2 to 20 J/cm2 had no cytotoxic effect on NHEKs. After co-cultured with irradiated medium of NHEKs, melanin content and tyrosinase activity were reduced and the melanogenic activities were downregulated on both mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1). H19 and its derived exosomal miR-675 from NHEKs, which has been proven relevant to melanogenesis, were significantly upregulated after irradiation. Furthermore, H19 knockdown and miR-675 inhibition in NHEKs could attenuate the inhibition effect of 585 nm LEDs on melanogenesis. CONCLUSIONS: This study demonstrated that 585 nm LEDs could inhibit melanogenesis via the up-regulation of H19 and its derived exosomal miR-675 from NHEKs, which was considered as a novel paracrine factor in regulating melanogenesis.
Assuntos
Hiperpigmentação/terapia , Terapia com Luz de Baixa Intensidade/instrumentação , Melaninas/biossíntese , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Células Cultivadas , Técnicas de Cocultura , Exossomos/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Hiperpigmentação/genética , Queratinócitos/citologia , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Melanócitos/metabolismo , Glicoproteínas de Membrana/metabolismo , MicroRNAs/antagonistas & inibidores , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Oxirredutases/metabolismo , Comunicação Parácrina/genética , Comunicação Parácrina/efeitos da radiação , Cultura Primária de Células , RNA Longo não Codificante/genética , Semicondutores , Regulação para Cima/genética , Regulação para Cima/efeitos da radiaçãoRESUMO
Astragaloside IV is one of the main active ingredients isolated from Astragalus membranaceus. Here we confirmed its protective effect against cardiac ischemia-reperfusion (I/R) injury and aimed to investigate the potential molecular mechanisms involved. Pretreatment of ex vivo and in vivo I/R-induced rat models by astragaloside IV significantly prevented the ratio of myocardium infarct size, systolic and diastolic dysfunction, and the production of creatine kinase and lactate dehydrogenase. Metabolic analyses showed that I/R injury caused a notable reduction of succinate and elevation of lysophospholipids, indicating excessive reactive oxygen species (ROS) generation driven by succinate's rapid reoxidization and glycerophospholipid degradation. Molecular validation mechanistically revealed that astragaloside IV stimulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) released from Kelch-like ECH-associated protein 1 (Keap1) and translocated to the nucleus to combine with musculoaponeurotic fibrosarcoma (Maf) to initiate the transcription of antioxidative gene heme oxygenase-1 (HO-1), which performed a wide range of ROS scavenging processes against pathological oxidative stress in the hearts. As expected, increasing succinate and decreasing lysophospholipid levels were observed in the astragaloside IV-pretreated group compared with the I/R model group. These results suggested that astragaloside IV ameliorated myocardial I/R injury by modulating succinate and lysophospholipid metabolism and scavenging ROS via the Nrf2 signal pathway.
Assuntos
Lisofosfolipídeos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Animais , Lisofosfolipídeos/farmacologia , Masculino , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio , Saponinas/farmacologia , Ácido Succínico , Triterpenos/farmacologiaRESUMO
BACKGROUND: Up till now, there is no standardized and satisfactory treatment strategy for Riehl's melanosis. OBJECTIVE: In this pilot study, we evaluated the efficacy and safety of a novel combination therapy with oral administration of tranexamic acid (TA) and Glycyrrhizin compound for recalcitrant Riehl's melanosis. METHODS: Ten patients with Riehl's melanosis were recruited in this study. After elimination of potential contraindication, all patients were treated with 500 mg TA together with 150 mg Glycyrrhizin compound per day orally for 3 months, followed by 500 mg TA per day orally alone for another 3 months. Lesions were imaged by reflectance confocal microscopy (RCM), dermatoscopy, and VISIA® Complexion Analysis System monthly. Mexameter was adopted to evaluate Melanin Index (MI) and Erythema Index (EI). Clinical outcome scores were given by both physicians and patients. RESULTS: Seven out of ten patients received "marked improvement", while two received "moderate improvement" and one "minimal improvement" at the final visit. Both mean MI and EI were significantly decreased compared with baselines. Furthermore, RCM and dermatoscopy analyses confirmed the improvement of pigmentation and erythema with decreased pigment granules and telangiectatic vessels. CONCLUSION: Oral administration of TA in combination with Glycyrrhizin compound may be an effective therapy for Asian patients with recalcitrant Riehl's melanosis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antifibrinolíticos/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Melanose/tratamento farmacológico , Ácido Tranexâmico/uso terapêutico , Administração Oral , Adulto , Dermoscopia , Quimioterapia Combinada/efeitos adversos , Humanos , Melanose/diagnóstico por imagem , Microscopia Confocal , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: The lethality of prostate cancer is mainly due to metastasis. Inhibition of metastasis is expected to be a promising approach for prostate cancer therapy. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is reported to be closely involved in cell growth, migration, etc. Objective: The study investigated the antimetastatic activities of pan-PI3K inhibitor ZSTK474 on DU145 cells. METHODS: 1. The In vitro effect of ZSTK474 on the migration, invasion and adhesion of DU145 cells was determined with Transwell migration assay and wound healing assay, Tranwell invasion assay and adhesion assay, respectively. 2. In vitro effect of ZSTK474 on the signal proteins in DU145 cells was determined with Western blot analysis and ELISA. 3. Moreover, the In vivo antimetastatic effect of ZSTK474 was evaluated with MicroCT and histology analysis. RESULTS: ZSTK474 potently attenuated the capability of migration, invasion and adhesion of DU145 cells, negatively regulated Girdin, Integrinß1 and matrix metalloproteinases (MMPs). In addition, the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are known to be related to angiogenesis and metastasis, was also inhibited. Oral administration of ZSTK474 (200 mg/kg) ameliorated in vivo bone metastasis of DU145 cells, with improved bone structure and bone mineral density (BMD). Tissue staining indicated a reduction in metastatic DU145 cells and osteoclasts in the bones of ZSTK474-treated mice, compared with the non-treated group. CONCLUSION: Our result demonstrated the antimetastatic activity of ZSTK474 on prostate cancer DU145 cells, suggesting the potential application in prostate cancer patients.