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1.
Sci Rep ; 13(1): 1932, 2023 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-36732582

RESUMEN

The human facial skeleton consists of multiple segments and causes difficulty during analytic processes. We developed image analysis software to quantify the amount of injury and validate the smooth curvature of the surface after facial bone reduction surgery. Three-dimensional computed tomography images of facial bone were obtained from 40 patients who had undergone open reduction surgery to treat unilateral zygomaticomaxillary fractures. Analytic software was developed based on the discrete curvature of a triangular mesh model. The discrete curvature values were compared before and after surgery using two regions of interest. For the inferior orbital rim, the weighted average of curvature changed from 0.543 ± 0.034 to 0.458 ± 0.042. For the anterior maxilla, the weighted average of curvature changed from 0.596 ± 0.02 to 0.481 ± 0.031, showing a significant decrement (P < 0.05). The curvature was further compared with the unaffected side using the Bray-Curtis similarity index (BCSI). The BCSI of the inferior orbital rim changed from 0.802 ± 0.041 to 0.904 ± 0.015, and that for the anterior maxilla changed from 0.797 ± 0.029 to 0.84 ± 0.025, demonstrating increased similarity (P < 0.05). In computational biology, adequate analytic software is crucial. The newly developed software demonstrated significant differentiation between pre- and postoperative curvature values. Modification of formulas and software will lead to further advancements.


Asunto(s)
Fracturas Craneales , Mallas Quirúrgicas , Humanos , Maxilar/cirugía , Tomografía Computarizada por Rayos X/métodos
2.
Front Microbiol ; 13: 1005415, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36601396

RESUMEN

Polyurethane (PU), currently replacing existing synthetic materials worldwide, is a synthetic polymer derived from polyols, isocyanates, and a chain extender added by condensation reactions. PU wastes which are difficult to recycle, are commonly discarded in landfills and flow into ecosystems, thereby causing serious environmental problems. In recent years, insect-associated microbes have become a promising, eco-friendly strategy as an alternative to plastic recycling. This study aimed to evaluate the potential of Serratia sp. HY-72 strain isolated from the intestine of the Asian mantis (Hierodula patellifera) for PU degradation. The 65 kDa family I.3 lipase which degrades PU was identified and characterized, with a specific activity of 2,883 U mg-1. The bacterial filtrates and the recombinant lipase degraded Impranil (a colloidal polyester-PU dispersion, 100 g l-1) by 85.24 and 78.35% after 72 h incubation, respectively. Fourier transform infrared spectroscopy analysis revealed changes in Impranil functional groups, with decreased C=O functional group and aliphatic chain signals, and increased N-H bending with C-N stretching and C-O stretching. The current study also revealed that the HY-72 strain biodegraded the commercial PU foams (polyester- and polyether- PU) with 23.95 and 10.95% weight loss after 2 weeks, respectively with changes in surface morphology and structure such as cracks, roughness, and surface roughening. Altogether, this is one of the few studies reporting biodegradation of PU by the insect-associated microbe. These findings suggest that the insect-associated microbe could be a promising resource for biodegradation and recycling of plastic waste.

3.
Front Microbiol ; 12: 715241, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34475865

RESUMEN

A new formulation, nanoprebiotics [e.g., phthalyl pullulan nanoparticles (PPNs)], was demonstrated to enhance the antimicrobial activity of probiotics [e.g., Lactobacillus plantarum (LP)] in vitro through intracellular stimulation better than that by backbone prebiotics, which are commonly used. In this study, we aimed to investigate whether this combination would exert distinct effects as synbiotics in vivo. Synbiotics combinations of LP, pullulan, and PPNs were used as experimental treatments in a dysbiosis-induced murine model, and their restorative effect was assessed using pathogen Escherichia coli K99 challenge. Our results showed that the E. coli infection was suppressed markedly in the experimental group fed with synbiotics containing PPNs. In addition, the decrease in serum endotoxin level after synbiotics treatment suggested the reinforcement of the gut barrier. Comparison of treatment groups, including a normal control group, showed that synbiotics containing PPNs increased microbial diversity, which is a representative parameter of healthy status. Furthermore, distinct from probiotics treatment alone, synbiotics showed additive effects of enrichment of several well-known beneficial bacteria such as Lactobacillus, Bifidobacterium, and other butyrate-producing bacteria including Faecalibacterium. Collectively, our results indicate that synbiotics containing PPNs are effective at restoring gut dysbiosis, suppressing pathogenic infection, and increasing microbial diversity, suggesting that synbiotics with nanoprebiotics have the potential to be a novel strategy for ameliorating gut dysbiosis and infectious diseases.

4.
J Integr Med ; 18(6): 455-458, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32891598

RESUMEN

On May 25, 2019, the World Health Assembly approved the eleventh revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), containing a chapter on traditional medicine. This means that the traditional East Asian medicine (TEAM) is now officially recognized as a part of mainstream medical practice. However, the patterns presented in the ICD-11 traditional medicine chapter are only the tip of the iceberg of TEAM clinical practice, and it will be necessary to supplement and upgrade the contents. In order to implement this, objectification and standardization of TEAM must be premised, and grafting with proper modern science and technology is imperative. Pattern Identification and Prescription Expert-11 (PIPE-11), which is a TEAM clinical decision support system, adopts vastly from clinical literature on pattern identification and the prescription. By adopting the rule-based reasoning method, the way of diagnosis and prescription by a TEAM practitioner in actual clinical practice is implemented as it is. PIPE-11 could support to improve both the accuracy of medical diagnosis and the reliability of the medical treatment of TEAM in clinical practices. In the field of research, it might facilitate the usage for reliable reference for symptoms and signs retrieval and patient simulation. In the field of education, it can provide a high level of training for learning pattern identification and prescription, and further be used to reinforce skills of diagnosis and prescription by providing self-simulation methods. Therefore, PIPE-11 as a digital application is expected to support the traditional medicine chapter of ICD-11 to successfully contribute to the improvement of human health.


Asunto(s)
Clasificación Internacional de Enfermedades , Medicina Tradicional , Aplicaciones Móviles , Sistemas de Apoyo a Decisiones Clínicas , Humanos , Reproducibilidad de los Resultados
5.
Integr Cancer Ther ; 19: 1534735420908334, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32070150

RESUMEN

In 2019, the World Health Assembly approved the International Classification of Diseases, 11th Revision (ICD-11), which included a traditional medicine chapter. This means that traditional medicine (TM) is incorporated into the mainstream medicine of the world. For TM to contribute to human health, the role of ICD-11, chapter 26 (ICD-11-26), is important. Since the ICD-11-26 is "a union set of harmonized traditional medicine conditions of the Chinese, Japanese, and Korean classifications," it is advisable to supplement the essential patterns while maintaining the already adopted patterns. The ICD-11-26 was originated from the World Health Organization International Standard Terminologies on Traditional Medicine in the Western Pacific Region (WHO-IST), and the WHO-IST is the world's most authoritative TM standard terminology system with an emphasis on traditional and conventional expression. In addition, it includes patterns that are widely used in TM clinical practice and have representative prescriptions at the same time. Therefore, future revisions of ICD-11-26 should make WHO-IST the main reference. Based on this spirit, this proposed revision is a modification of ICD-11-26's structure, order, and expression (English translation) with more essential patterns.


Asunto(s)
Clasificación Internacional de Enfermedades , Medicina Tradicional , Pautas de la Práctica en Medicina/clasificación , Humanos , Clasificación Internacional de Enfermedades/normas , Clasificación Internacional de Enfermedades/tendencias , Medicina Tradicional/métodos , Medicina Tradicional/normas , Estándares de Referencia , Terminología como Asunto , Organización Mundial de la Salud
6.
Brain Behav ; 9(3): e01235, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30761781

RESUMEN

INTRODUCTION: Experimental studies and clinical observations have shown that stress can damage hepatic tissue both directly and indirectly. Many studies have partially revealed the contributors of stress-induced liver injury; however, the whole process has not yet been uncovered. This review aims to summarize the mechanisms that have been proposed to be involved. METHODS: A literature search was conducted using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) in its entirety up to March 2018, and analyzed the animal-derived mechanistic studies on stress-induced liver injury. RESULTS: The liver is the organ that meets and filters a mass of alien material, and then maintains immune tolerance under physiological conditions. Under stress conditions, however, immune tolerance is interrupted, which results in the induction of inflammation in the liver. Contributors to this process can be categorized as follows: hypoxia-reoxygenation, over-activation of Kupffer cells and oxidative stress, influx of gut-derived lipopolysaccharide and norepinephrine, and over-production of stress hormones and activation of the sympathetic nerve. CONCLUSIONS: Psychological stress is associated with a variety of pathological conditions resulting in liver injury through multiple systems, including the sympathetic nervous and adrenocortical system. Mechanistic understanding of this phenomenon is important for the clinical practice of managing patients with hepatic disorders and should be explored further in the future.


Asunto(s)
Hepatopatías , Estrés Psicológico , Animales , Humanos , Hepatopatías/etiología , Hepatopatías/inmunología , Hepatopatías/psicología , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología
7.
Phytomedicine ; 41: 24-32, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29519316

RESUMEN

BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) has increased by 15-39% worldwide, but no pharmaceutical therapeutics exists. HYPOTHESIS/PURPOSE: This study investigated anti-hepatosteatotic effect of CGplus (a standardized herbal composition of Artemisia iwayomogi, Amomum xanthioides, and Salvia miltiorrhiza) and its underlying mechanisms in a tunicamycin-induced NASH model. METHODS: C57/BL6J male mice were orally administrated CGplus (50, 100, or 200 mg/kg), dimethyl dimethoxy biphenyl dicarboxylate (DDB, 50 mg/kg) or distilled water daily for 5 days. 18 h after a single injection of tunicamycin (ip, 2 mg/kg), the parameters for hepatic steatosis and inflammation were measured. RESULTS: Pretreatment with CGplus significantly attenuated the accumulation of triglycerides and total cholesterol as well as lipid peroxidation, evidenced by quantitative and histopathological analyses in liver tissues. The elevations of serum aspartate transaminase, alanine transaminase and lactate dehydrogenase were significantly ameliorated by CGplus. Also, it normalized the altered activities of pro- (TNF-α, IL-1ß and IL-6), anti-inflammatory (IL-10) cytokines and lipid metabolism-related molecules in protein and gene expression analyses. CONCLUSION: Our data present experimental evidence for the potential of CGplus as an herbal therapeutic against NAFLD and NASH. Its underlying mechanisms may involve the modulations of pro- and anti-inflammatory cytokines, but further study is required especially for the actions of CGplus on lipid metabolisms.


Asunto(s)
Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Sustancias Protectoras/farmacología , Tunicamicina/efectos adversos , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Citocinas/metabolismo , Modelos Animales de Enfermedad , Metabolismo de los Lípidos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Triglicéridos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
8.
Artículo en Inglés | MEDLINE | ID: mdl-29234397

RESUMEN

The combination of Artemisia iwayomogi and Curcuma longa radix is frequently prescribed for liver diseases in TKM. However, the synergic effects of the two herbs on nonalcoholic steatohepatitis (NASH) have not yet been studied. Therefore, we investigated the anti-NASH effects of the water extract of A. iwayomogi (AI), C. longa radix (CL), and combination of the two herbs (ACE). Hepatic steatosis and NASH were induced in HepG2 cells by treatment with palmitic acid (PA, for 6 h) with/without pretreatment of ACE (25 or 50 µg/mL), AI (50 or 100 µg/mL), CL (50 or 100 µg/mL), curcumin (5 µg/mL), or scopoletin (5 µg/mL). The PA treatment (200 µM) drastically altered intracellular triglyceride levels, total cholesterol, and expression levels of genes related to lipid metabolism (CD36, SREBP1c, PPAR-γ, and PPAR-α), whereas pretreatment with ACE significantly attenuated these alterations. ACE also protected HepG2 cells from PA- (300 µM-) induced endoplasmic reticulum (ER) stress and apoptosis and attenuated the related key molecules including GRP78, eIF2, and CHOP, respectively. In conclusion, we found synergic effects of A. iwayomogi and C. longa on NASH, supporting the clinical potential for fatty liver disorders. In addition, modulation of ER stress-relative molecules would be involved in its underlying mechanism.

10.
Neoplasia ; 19(3): 145-153, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28142087

RESUMEN

Anaplastic thyroid carcinoma (ATC) although rare is the most deadly form of thyroid cancer. The fatality rate for ATC is high-pitched, the survival rate at 1 year after diagnosis is <20%. Control of ATC is severely hard and widespread with unpredictability. We Previous proved that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. Herein, the goal of this study was to investigate the anti-tumor activities of a HDAC inhibitor, HNHA alone and in combination with sorafenib in ATC cells in vitro and in vivo and to explore its effects on apoptotic cell death pathways. Three ATC cell lines were exposed to sorafenib in the presence or absence of HNHA, and cell viability was determined by MTT assay. Effects of combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell lines xenograft model was used to examine the anti-tumor activity in vivo. Our data showed that HNHA and sorafenib synergistically decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as proved by the cleavage of caspase-3 and DNA fragmentation. HNHA and sorafenib combination was reduced anti-apoptotic factor in ATC. Thus, combination therapy with HNHA and sorafenib significantly decreased vessel density, and most significantly reduced tumor volume and increased survival in ATC xenografts. These results propose that HNHA in combination with sorafenib has significant anti-cancer activity in preclinical models, potentially suggesting a new clinical approach for patients of advanced thyroid cancer type.

11.
J Acupunct Meridian Stud ; 9(2): 49-57, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27079225

RESUMEN

Obesity is the state of excessive body fat accumulation and is mainly caused by consuming more calories than are burned through physical activity. Herbal acupuncture (HA), also known as pharmacopuncture, has been increasingly used in clinics of Korean medical to alleviate obesity. This review analyzed four clinical studies and 16 animal studies on the effectiveness of HA as a treatment for obesity. Clinical evidence suggests that various kinds of HA might be beneficial for treating obesity; however, further investigations with well-designed, evidence-based, randomized clinical trials are needed. Animal studies support the idea that HA might be beneficial for the treatment of obesity and provide possible mechanisms, such as anti-inflammation, antioxidation, modulating lipid metabolism and so on, to explain the effect of HA on obesity. This review, based on the evidence collected, suggests that HA could have a beneficial effect for alleviating obesity by modulating inflammation, oxidative stress, lipid metabolism, leptin, and the insulin signal.


Asunto(s)
Puntos de Acupuntura , Obesidad/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Animales , Humanos , Insulina/metabolismo , Obesidad/metabolismo
12.
BMC Cancer ; 15: 1003, 2015 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-26698299

RESUMEN

BACKGROUND: Thyroid cancer has been indicated to have a higher global proportion of DNA methylation and a decreased level of histone acetylation. Previous studies showed that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. The goal of this research was to study the endoplasmic reticulum (ER) stress-mediated actions of the dominant histone deacetylase (HDAC) inhibitor, N-hydroxy-7-(2-naphthylthio) hepatonomide (HNHA), in thyroid cancer and to explore its effects on apoptotic cell death pathways. METHODS: Experiments were achieved to conclude the effects of HNHA in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) cell lines and xenografts, as compared with two other established HDAC inhibitors (SAHA; suberoylanilide hydroxamic acid and TSA; trichostatin A). RESULTS: Apoptosis, which was induced by all HDAC inhibitors, was particularly significant in HNHA-treated cells, where noticeable B-cell lymphoma-2 (Bcl-2) suppression and caspase activation were observed both in vitro and in vivo. HNHA increased Ca(2+) release from the ER to the cytoplasm. ER stress-dependent apoptosis was induced by HNHA, suggesting that it induced caspase-dependent apoptotic cell death in PTC and ATC. PTC and ATC xenograft studies demonstrated that the antitumor and pro-apoptotic effects of HNHA were greater than those of the established HDAC inhibitors. These HNHA activities reflected its induction of caspase-dependent and ER stress-dependent apoptosis on thyroid cancer cells. CONCLUSIONS: The present study indicated that HNHA possibly provide a new clinical approach to thyroid cancers, including ATC.


Asunto(s)
Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Naftalenos/farmacología , Neoplasias de la Tiroides/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Caspasas/metabolismo , Línea Celular Tumoral , Retículo Endoplásmico/metabolismo , Humanos , Inmunohistoquímica , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias de la Tiroides/metabolismo
13.
Toxicol Res ; 31(1): 61-8, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25874034

RESUMEN

The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency.

15.
Phytother Res ; 28(9): 1374-82, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24638915

RESUMEN

The fruit of hassaku (Citrus hassaku Hort. ex Tanaka) is locally known as phalsak in Korea. Recently, the fruit extract has been known to exhibit in vivo preventive effects against UVB-induced pigmentation, antiallergic activity, and enhancement of blood fluidity. However, the exact mechanisms of how supercritical extracts of phalsak peel (SEPS) inhibits tumor metastasis and invasion are still not fully understood. We found that SEPS could downregulate the constitutive expression of both CXCR4 and HER2 in human breast cancer MDA-MB-231 cells as compared with other cells. SEPS also suppressed matrix metalloproteinase-9 (MMP-9) expression and its enzymatic activity under non-cytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the SEPS-induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, suppression of NF-κB activity, and inhibition of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by SEPS correlated with the inhibition of CXCL12-stimulated invasion of MDA-MB-231 cells. Overall, our results indicate, for the first time, that SEPS can suppress CXCR4 and MMP-9 expressions through blockade of NF-κB activation and thus has the potential to suppress metastasis of breast cancer.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Citrus/química , Metaloproteinasa 9 de la Matriz/metabolismo , Extractos Vegetales/farmacología , Receptores CXCR4/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Femenino , Frutas/química , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica , Factor de Transcripción ReIA/metabolismo
16.
ACS Nano ; 8(3): 2318-27, 2014 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-24484512

RESUMEN

Field effect transistors (FETs), incorporating metal-oxide nanofibers as the active conductive channel, have the potential for driving the widespread application of nanowire or nanofiber FETs-based electronics. Here we report on low voltage FETs with integrated electrospun In2O3-ZnO-ZnGa2O4 composite fiber channel layers and high-K dielectric (MgO)0.3-(Bi1.5Zn1.0Nb1.5O7)0.7 gate insulator and compare their performance against FETs utilizing conductive single phase, polycrystalline ZnO or In2O3 channel layers. The polycrystalline In2O3-ZnO-ZnGa2O4 composite fibers provide superior performance with high field effect mobility (∼7.04 cm2 V(-1) s(-1)), low subthreshold swing (390 mV/dec), and low threshold voltage (1.0 V) combined with excellent saturation, likely resulting from the effective blocking of high current-flow through the In2O3 and ZnO nanocrystallites by the insulating spinel ZnGa2O4 phase. The microstructural evolution of the individual In2O3, ZnO, and ZnGa2O4 phases in composite fibers is clearly observed by high resolution TEM. A systematic examination of channel area coverage, ranging from single fiber to over 90% coverage, demonstrates that low coverage results in relatively low current outputs and reduced reproducibility which we attribute to the difficulty in positioning fibers and fiber length control. On the other hand, those with ∼80% coverage exhibited high field effect mobility, high on/off current ratios (>10(5)), and negligible hysteresis following 15 sweep voltage cycles. A special feature of this work is the application of the FETs to modulate the properties of complex polycrystalline nanocomposite channels.

17.
PLoS One ; 9(1): e87062, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24489834

RESUMEN

Impaired ethanol metabolism can lead to various alcohol-related health problems. Key enzymes in ethanol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); however, neuroendocrine pathways that regulate the activities of these enzymes are largely unexplored. Here we identified a neuroendocrine system involving Corazonin (Crz) neuropeptide and its receptor (CrzR) as important physiological regulators of ethanol metabolism in Drosophila. Crz-cell deficient (Crz-CD) flies displayed significantly delayed recovery from ethanol-induced sedation that we refer to as hangover-like phenotype. Newly generated mutant lacking Crz Receptor (CrzR(01) ) and CrzR-knockdown flies showed even more severe hangover-like phenotype, which is causally associated with fast accumulation of acetaldehyde in the CrzR(01) mutant following ethanol exposure. Higher levels of acetaldehyde are likely due to 30% reduced ALDH activity in the mutants. Moreover, increased ADH activity was found in the CrzR(01) mutant, but not in the Crz-CD flies. Quantitative RT-PCR revealed transcriptional upregulation of Adh gene in the CrzR(01) . Transgenic inhibition of cyclic AMP-dependent protein kinase (PKA) also results in significantly increased ADH activity and Adh mRNA levels, indicating PKA-dependent transcriptional regulation of Adh by CrzR. Furthermore, inhibition of PKA or cAMP response element binding protein (CREB) in CrzR cells leads to comparable hangover-like phenotype to the CrzR(01) mutant. These findings suggest that CrzR-associated signaling pathway is critical for ethanol detoxification via Crz-dependent regulation of ALDH activity and Crz-independent transcriptional regulation of ADH. Our study provides new insights into the neuroendocrine-associated ethanol-related behavior and metabolism.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Etanol/metabolismo , Neuronas/metabolismo , Neuropéptidos/metabolismo , Receptores de Neuropéptido/metabolismo , Acetaldehído/metabolismo , Alcohol Deshidrogenasa/genética , Alcohol Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa/metabolismo , Alelos , Animales , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/enzimología , Etanol/farmacología , Genes Reporteros , Masculino , Mutación/genética , Neuronas/efectos de los fármacos , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcripción Genética
18.
Br J Pharmacol ; 171(21): 4820-30, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24467283

RESUMEN

BACKGROUND AND PURPOSE: Activation of hepatic stellate cells (HSCs) is a crucial step in the pathogenesis of hepatic fibrosis. Histone deacetylase (HDAC) is an attractive target in liver fibrosis because it plays a key role in gene expression and cell differentiation. We have developed a HDAC inhibitor, N-hydroxy-7-(2-naphthylthio)heptanomide (HNHA), and investigated the anti-fibrotic activity of HNHA in vitro and in vivo. EXPERIMENTAL APPROACH: We investigated the anti-fibrotic effect of HNHA on mouse and human HSC activation in vitro and in the liver of bile duct-ligated (BDL) rats in vivo using cell proliferation assays, cell cycle analysis, biochemical assay, immunohistochemistry and Western blots. Liver pathology was assessed with histochemical techniques. KEY RESULTS: HNHA inhibited proliferation and arrested the cell cycle via p21 induction in HSCs. In addition, HNHA induced apoptosis of HSCs, which was correlated with reduced COX-2 expression, NF-κB activation and cell death signals. HNHA restored liver function and decreased the accumulation of extracellular matrix in the liver via suppression of HSC activation in BDL rats in vivo. HNHA administration also increased survival in BDL rats. CONCLUSIONS AND IMPLICATIONS: HNHA improved liver function, suppressed liver fibrosis and increased survival of BDL rats, accompanied by reduction of cell growth, activation and survival of HSCs. These findings show that HNHA may be a potent anti-fibrosis agent against hepatic fibrosis because of its multi-targeted inhibition of HSC activity in vivo and in vitro.


Asunto(s)
Inhibidores de Histona Desacetilasas/uso terapéutico , Ácidos Hidroxámicos/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Naftalenos/uso terapéutico , Actinas/metabolismo , Animales , Conductos Biliares/cirugía , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Ciclooxigenasa 2/metabolismo , Células Estrelladas Hepáticas/citología , Células Estrelladas Hepáticas/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ácidos Hidroxámicos/farmacología , Ligadura , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Naftalenos/farmacología , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo
19.
Phytother Res ; 28(3): 423-31, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23686889

RESUMEN

The oncogenic PI3K/Akt/mammalian target of rapamycin (mTOR) signaling axis and its downstream effector, the ribosomal protein S6 kinase 1 (S6K1) play a key role in mediating cell survival in various tumor cells. Here, we investigated the effects of brassinin (BSN), a phytoalexin first identified as a constituent of cabbage, on the PI3K/Akt/mTOR/S6K1 activation, cellular proliferation, and apoptosis in PC-3 human prostate cancer. BSN exerted a significant dose-dependent cytotoxicity and reduced constitutive phosphorylation of Akt against androgen-independent PC-3 cells as compared to androgen-dependent LNCaP cells. Moreover, knockdown of androgen receptor (AR) by small interfering RNA enhanced the potential effect of BSN on induction of apoptosis in LNCaP cells. BSN clearly suppressed the constitutive activation of PI3K/Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, TUNEL staining, loss of mitochondrial membrane potential, down-regulation of antiapoptotic and proliferative proteins, activation of caspase-3, and cleavage of PARP. Additionally, BSN could block broad-spectrum inhibition of PI3K/Akt/mTOR/S6K1 axes, and aberrant Akt activation by pcDNA3-myr-HA-Akt1 plasmid could not prevent the observed suppressive effect of BSN on constitutive mTOR activation. Finally, overexpression of Bcl-2 also attenuated BSN-mediated apoptosis in PC-3 cells. Taken together, our findings suggest that BSN can interfere with multiple signaling cascades involved in tumorigenesis and might be provided as a potential therapeutic candidate for both the prevention and treatment of prostate cancer.


Asunto(s)
Apoptosis/efectos de los fármacos , Indoles/farmacología , Neoplasias de la Próstata/metabolismo , Transducción de Señal/efectos de los fármacos , Tiocarbamatos/farmacología , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo , Humanos , Masculino , Potencial de la Membrana Mitocondrial , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Poli(ADP-Ribosa) Polimerasas/metabolismo , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Proteínas Quinasas S6 Ribosómicas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
20.
Int Rev Neurobiol ; 111: 67-90, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24215918

RESUMEN

The discovery of adult neurogenesis was a turning point in the field of neuroscience. Adult neurogenesis offers an enormous possibility to open a new therapeutic paradigm of neurodegenerative diseases and stroke. Recently, several studies suggested that acupuncture may enhance adult neurogenesis. Acupuncture has long been an important treatment for brain diseases in the East Asia. The scientific mechanisms of acupuncture treatment for the diseases, such as Alzheimer's disease, Parkinson's disease, and stroke, have not been clarified yet; however, the neurogenic effect of acupuncture can be a possible reason. Here, we have reviewed the studies on the effect of stimulation at various acupoints for neurogenesis, such as ST36 and GV20. The suggested mechanisms are also discussed including upregulation of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, basic fibroblast growth factor and neuropeptide Y, and activation of the function of primo vascular system.


Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura , Encéfalo/fisiología , Neurogénesis/fisiología , Adulto , Animales , Humanos , Enfermedades Neurodegenerativas/metabolismo
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