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1.
Int J Toxicol ; 43(4): 357-367, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38477622

RESUMO

In silico modeling offers an opportunity to supplement and accelerate cardiac safety testing. With in silico modeling, computational simulation methods are used to predict electrophysiological interactions and pharmacological effects of novel drugs on critical physiological processes. The O'Hara-Rudy's model was developed to predict the response to different ion channel inhibition levels on cardiac action potential duration (APD) which is known to directly correlate with the QT interval. APD data at 30% 60% and 90% inhibition were derived from the model to delineate possible ventricular arrhythmia scenarios and the marginal contribution of each ion channel to the model. Action potential values were calculated for epicardial, myocardial, and endocardial cells, with action potential curve modeling. This study assessed cardiac ion channel inhibition data combinations to consider when undertaking in silico modeling of proarrhythmic effects as stipulated in the Comprehensive in Vitro Proarrhythmia Assay (CiPA). As expected, our data highlight the importance of the delayed rectifier potassium channel (IKr) as the most impactful channel for APD prolongation. The impact of the transient outward potassium channel (Ito) inhibition on APD was minimal while the inward rectifier (IK1) and slow component of the delayed rectifier potassium channel (IKs) also had limited APD effects. In contrast, the contribution of fast sodium channel (INa) and/or L-type calcium channel (ICa) inhibition resulted in substantial APD alterations supporting the pharmacological relevance of in silico modeling using input from a limited number of cardiac ion channels including IKr, INa, and ICa, at least at an early stage of drug development.


Assuntos
Potenciais de Ação , Simulação por Computador , Canais Iônicos , Miócitos Cardíacos , Potenciais de Ação/efeitos dos fármacos , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Canais Iônicos/efeitos dos fármacos , Canais Iônicos/metabolismo , Canais Iônicos/fisiologia , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia
2.
Int J Phytoremediation ; 26(4): 569-578, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37684742

RESUMO

To promote the selenium (Se) uptakes in fruit trees under Se-contaminated soil, the effects of water extract of Fagopyrum dibotrys (D. Don) Hara straw on the Se accumulation in peach seedlings under selenium-contaminated soil were studied. The results showed that the root biomass, chlorophyll content, activities of antioxidant enzymes, and soluble protein content of peach seedlings were increased by the F. dibotrys straw extract. The different forms of Se (total Se, inorganic Se, and organic Se) were also increased in peach seedlings following treatment with the F. dibotrys straw extract. The highest total shoot Se content was treated by the 300-fold dilution of F. dibotrys straw, which was 30.87% higher than the control. The F. dibotrys straw extract also increased the activities of adenosine triphosphate sulfurase (ATPS), and adenosine 5'-phosphosulfate reductase (APR) in peach seedlings, but decreased the activity of serine acetyltransferase (SAT). Additionally, correlation and grey relational analyses revealed that chlorophyll a content, APR activity, and root biomass were closely associated with the total shoot Se content. Overall, this study shows that the water extract of F. dibotrys straw can promote Se uptake in peach seedlings, and 300-fold dilution is the most suitable concentration.


The water extract of Fagopyrum dibotrys (D. Don) Hara straw promoted the selenium (Se) uptake in peach seedlings under selenium-contaminated soil. The concentration of F. dibotrys straw extract showed a quadratic polynomial regression relationship with the total root and shoot Se. Furthermore, chlorophyll a content, APR activity, and root biomass were closely associated with the total shoot Se. This study shows that water extract of F. dibotrys straw can promote Se uptake in peach seedlings, and 300-fold dilution is the most suitable concentration.


Assuntos
Fagopyrum , Prunus persica , Selênio , Biodegradação Ambiental , Clorofila A/análise , Fagopyrum/metabolismo , Prunus persica/metabolismo , Plântula/química , Selênio/metabolismo , Solo , Água/análise
3.
Exp Cell Res ; 406(2): 112763, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358524

RESUMO

MCL1 is an anti-apoptotic BCL2 family member that is often overexpressed in various malignant tumors. However, few reports have described the role of MCL1 in squamous cell carcinoma (SqCC) derived from airways including the lung. In this study, we examined whether MCL1 could be a novel druggable target for airway-derived SqCC, for which effective molecular targeted drugs are unavailable. We searched the Kaplan-Meier Plotter database and found that high MCL1 mRNA expression was significantly associated with shorter survival in patients with lower airway (lung) or upper airway (head and neck) derived SqCC. We also explored the Expression Atlas database and learned that authentic lung SqCC cell lines expressing both TP63 and KRT5 mRNA were extremely sparse among the publicly available "lung SqCC cell lines", with an exception being HARA cells. HARA cells were highly dependent on MCL1 for survival, and MCL1-depleted cells were not able to grow, and even declined in number, upon docetaxel (DTX) exposure in vitro and in vivo. Similar in vitro experimental findings, including those in a 3D culture model, were also obtained using Detroit 562 pharyngeal SqCC cells. These findings suggested that combined treatment with MCL1 silencing plus DTX appears highly effective against airway-derived SqCC.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Docetaxel/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Apoptose , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Phytochem Anal ; 33(4): 517-532, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35144310

RESUMO

INTRODUCTION: The diterpenoids are the most important active constituents that contribute to the pharmacological efficacy of Isodon serra (Maxim.) Hara. Clinical studies have revealed that diterpenoids possess multiple features, e.g. antitumour, antitubercular and anti-ischemic activities. Therefore, the identification and detection of diterpenoids may be equally important for understanding the pharmacological basis of diterpenoids and enhancing the product quality control of I. serra. OBJECTIVES: The purpose of this study was to develop a practical analysis approach of rapid characterisation using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) for the structure characterisation of the ent-kaurane diterpenoids from I. serra. METHODOLOGY: The analytical strategy was as follows: first, ent-kaurane diterpenoids were detected by a novel on-line data acquisition approach, i.e. sequential window acquisition of all theoretical fragment-ion spectra (SWATH). Second, the MS of eight ent-kaurane diterpenoids was explored, and their mass spectrum cleavage pathways were summarised and determined. Finally, the methanol extract of I. serra was studied using SWATH and identified by extracted ion chromatography (XIC). RESULTS: Compared to the traditional information-dependent acquisition (IDA) method, SWATH significantly improved the hit rate of ent-kaurane diterpenoids. With support from UHPLC separation and specific detection by tandem mass spectrometry (MS/MS), 48 ent-kaurane diterpenoids were successfully characterised and classified as ent-kaurane diterpenoids from a complex matrix. CONCLUSIONS: These combined qualitative methods were used to provide a potential approach for the characterisation of traditional Chinese medicine (TCM) and its preparations. Meanwhile, the SWATH provided a novel and reliable method for the structural characterisation of ent-kaurane diterpenoids from other complicated TCMs.


Assuntos
Diterpenos do Tipo Caurano , Diterpenos , Isodon , Cromatografia Líquida de Alta Pressão , Diterpenos/análise , Diterpenos do Tipo Caurano/análise , Isodon/química , Espectrometria de Massas em Tandem/métodos
5.
Anal Biochem ; 629: 114297, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34217704

RESUMO

Genuine regional drugs have played a vital role in clinical use for a long time. There are differences in traditional Chinese medicines (TCM) from different regions based on their chemical composition. Differences in chemical composition may lead to deviations in therapeutic effects. To our knowledge, to date, there are no effective methods for distinguishing genuine regional drugs based on the differences in their chemical composition. Therefore, establishing an analytical platform for distinguishing the compounds used in TCM from various geographical locations is essential. In this work, an integrated platform based on UPLC-Q-TOF-MS/MS combined with plant metabolomics approach was established for comprehensively distinguishing genuine regional drugs. Isodon rubescens (Hemsl.) Hara, a widely used herbal medicine of China, was chosen for this study and 24 samples from four geographical locations in China were collected. A total of 60 ent-kaurane diterpenoids were tentatively identified, and then the samples from four geographical origins were distinguished using PCA (principal component analysis) and PLS-DA (partial least squares discrimination analysis). Different compounds were identified among the samples collected from the four geographical locations, and 12 of them were regarded as marker compounds responsible for the distinction. Our study highlights the essence and predictive ability of metabolomics in detecting minute differences in the same varieties of TCM samples based on the levels and compositions of their metabolites. These results showed that the analysis using UHPLC-Q-TOF-MS/MS combined with metabolomics could be applied to distinguish the geographical origins and varieties of TCM.


Assuntos
Biomarcadores/análise , Diterpenos/análise , Medicamentos de Ervas Chinesas/análise , Isodon/química , Cromatografia Líquida de Alta Pressão , Análise dos Mínimos Quadrados , Medicina Tradicional Chinesa , Metabolômica , Análise Multivariada , Análise de Componente Principal , Espectrometria de Massas em Tandem
6.
Plant Dis ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33944581

RESUMO

Severe disease with leaf spots and necrotic symptoms were observed in Adenophora triphylla var. japonica (Regel) Hara (A. triphylla) during the survey in July 2020 on a field in Andong, Gyeongbuk province, Korea. It is a highly valued medicinal plant used to treat various diseases, including cough, cancer, and obesity. The infected plants initially showed spots with halo lesions, at later stages, enlarged and spread to the leaves, which the lesions becoming yellowing and chlorotic (Fig. 1). In some areas, disease incidence was up to 15% of the plants. The symptomatic samples were collected from A. triphylla and cut into 4 to 5 mm squares, surface-sterilized in 1% sodium hypochlorite for 1 min, rinsed three times, and macerated in sterile distilled water (SDW). They were spread onto nutrient agar (NA) plates and incubated at 28°C for 3 days. The representative bacterial strains selected for identification showed fluorescent colonies on King's medium B (KB). Fifteen isolates from independent samples were subjected to biochemical and pathogenicity tests. The isolates induced a hypersensitive reaction in tobacco leaves, gave a reaction in the anaerobe respiratory test, and were negative for levan, oxidase, arginine dihydrolase, gelatin hydrolysis, aesculin hydrolysis, and starch hydrolysis. The isolated strains presented the following LOPAT profile: - - + - +. The Biolog GN2 microplate and the Release 4.20 system putatively found the isolate to exhibit 93% similarity with the bacterium, Pseudomonas viridiflava. Likewise, analysis of FAME profiles using the Microbial identification system (Sherlock version 3.1) also characterized the representative bacterial strain as P. viridiflava with 87% similarity. The genomic DNA of the isolate was extracted, and the 16S rDNA sequence was amplified with a universal bacterial primer set (27F and 1492R). The sequence was submitted to GenBank under the accession number MT975233. BLASTn analysis yielded 99.79% identity with P. viridiflava strain RT228.1b (accession no. AY604846.1) and 99.72% similarity with P. viridiflava KNOX249.1b strain (accession no. AY604848.1). Phylogenetic dendrogram constructed from the comparative analysis of 16S rDNA gene sequences showing the relationship between P. viridiflava GYUN274 and related Pseudomonas species (Fig. 2). Pathogenicity tests were conducted three times on seedling of A. triphylla by spraying 50 ml of bacterial suspensions of a 24-h culture in KB medium (108 CFU/ml). The leaves inoculated with SDW alone did not develop symptoms; however, the plants treated with isolated bacterial suspensions developed halo and blight symptoms similar to those observed in the field 7 days post-inoculation. Finally, Koch's postulates were verified by re-isolating P. viridiflava from all symptomatic tissues and determined to be morphologically identical to the original isolates. To our knowledge, this is the first report of leaf blight disease of A. triphylla caused by P. viridiflava in Korea. Based on the observed symptoms, and identification by morphological characteristics, molecular data, and pathogenicity against the host plant, the proper control measures can be identified in future studies.

7.
BMC Ophthalmol ; 20(1): 349, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859176

RESUMO

BACKGROUND: Drainage of exudative retinal detachment may be necessary for either therapeutic or diagnostic purposes (or both). Here, we describe an external drainage technique for non-resolving vision-threatening exudative retinal detachment which combines the advantages of internal drainage (widefield viewing and intraocular pressure control using continuous anterior chamber infusion) with those of external drainage (drainage of sub-retinal fluid without vitrectomy). CASE PRESENTATION: To illustrate this technique, we present a 13-year-old girl with macula-off exudative retinal detachment secondary to Vogt-Koyanagi-Harada syndrome, which was unresponsive to aggressive medical management. External drainage was undertaken using widefield viewing and chandelier illumination. Intraocular pressure was maintained with an anterior chamber infusion. Near-complete drainage of sub-retinal fluid was achieved, and retinal reattachment was maintained at 6 months postoperatively, with a corresponding improvement in visual acuity from 20/63 to 20/40. CONCLUSIONS: External drainage under chandelier-assisted viewing at the surgical microscope with anterior chamber infusion offers the ergonomic and optical advantages of the surgical microscope and widefield visualisation, continuous IOP control and drainage of sub-retinal fluid without the need for pars plana vitrectomy.


Assuntos
Descolamento Retiniano , Adolescente , Câmara Anterior , Drenagem , Feminino , Humanos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Líquido Sub-Retiniano , Vitrectomia
8.
Acta Cardiol Sin ; 35(6): 641-648, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31879517

RESUMO

BACKGROUND: p-Cresylsulfate (PCS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease. Previous studies have indicated that serum total PCS levels are significantly increased in the presence of abnormal corrected QT (QTc) intervals, and that they are associated with QTc prolongation. However, the QTc prolongation effect of PCS remains unclear. The current study aimed to investigate the arrhythmogenic effect of PCS using in vitro experiments and computer simulation. METHODS: The arrhythmogenic effect of PCS was evaluated by incubating H9c2 rat ventricular cardiomyocytes in vitro with increasing concentrations of PCS. Electrophysiological studies and mathematical computer simulations were performed. RESULTS: in vitro, the delayed rectifier potassium current (IK ) was significantly decreased in a dose-dependent manner after treatment with PCS. The modulation of PCS on IK was through regulation of the phosphorylation of the major potassium ion channel protein Kv2.1. In computer simulations, the decrease in IK induced by PCS prolonged the action potential duration (APD) and sped up the re-entrant wave, which is known to be a trigger mechanism for lethal ventricular arrhythmias. CONCLUSIONS: PCS significantly downregulated the phosphorylation of the IK channel protein Kv2.1 and IK current activity, which increased the cardiomyocyte APD. This was observed both in vitro and in the computer O'Hara-Rudy dynamic human ventricular model. These findings suggest that PCS may play a key role in the development of cardiac arrhythmias.

9.
Cancer Sci ; 109(1): 112-120, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29095550

RESUMO

Suppression of bone metastasis can improve patient quality of life. Current drugs for bone metastasis have been shown to prolong progression-free survival but not overall survival; therefore, other potential therapeutic targets for bone metastasis should be investigated. Cell-surface antigens, such as CD24, have been recently shown to be involved in the metastasis of various cancers. However, whether CD24 plays a role in bone metastasis of lung cancer remains unknown. To observe metastasis of lung cancer cells by imaging technology, we introduced a near-infrared fluorescent protein, iRFP720, into a bone-seeking subclone established from lung cancer cells, HARA-B4 cells. The anchorage-independent growth of these cells was then evaluated by colony formation assays. We also compared cancer cell tropism to bone tissue with HARA-B4 cells in the presence or absence of CD24 by cell adhesion assays. To clarify the role of CD24 in bone metastasis, we intracardially injected CD24-knockdown HARA-B4 cells into mice and monitored metastasis through detection of iRFP720 using an in vivo imaging system. CD24-knockdown HARA-B4 cells in vitro showed reduced anchorage-independent growth and cancer cell tropism to bone. Bone metastasis was diminished in mice inoculated with CD24-knockdown HARA-B4 cells, which was rescued by add-back of CD24 in cells. Our findings indicate that iRFP720 is effective for in vivo imaging analysis of bone metastasis and that downregulation of CD24 suppresses bone metastasis of lung cancer cells. These findings collectively indicate that CD24 may be considered a promising new therapeutic candidate for the prevention of bone metastasis of lung cancer.


Assuntos
Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Antígeno CD24/metabolismo , Regulação para Baixo , Neoplasias Pulmonares/metabolismo , Animais , Neoplasias Ósseas/genética , Antígeno CD24/genética , Adesão Celular , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Proteínas Luminescentes/metabolismo , Neoplasias Pulmonares/genética , Camundongos , Células NIH 3T3 , Transplante de Neoplasias
10.
J Neural Transm (Vienna) ; 125(1): 3-7, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29124338

RESUMO

We describe a unique interaction between the very advanced German medicine and the ambitious Japanese medicine at the end of the 19th century and some of their protagonists. The Japanese sent some of their brightest young doctors to Germany where they not only studied medicine but also contributed to medical progress in Germany. Most went to Berlin, but before coming to Germany, in Japan they had to learn not only the German language but also German medicine as students of prominent German doctors in Japan. Both groups complemented each other in this cooperation to the benefit of all.


Assuntos
Pesquisa Biomédica/história , História da Medicina , Pessoal de Laboratório/história , Médicos/história , Berlim , História do Século XIX , História do Século XX , Humanos , Japão
11.
Cult Med Psychiatry ; 40(3): 450-74, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26848985

RESUMO

In Japan, the first half of the twentieth century saw a remarkable revival of concern with the cultivation of the belly, with a variety of belly-cultivation techniques, particularly breathing exercise and meditative sitting, widely practiced for improving health and treating diseases. This article carefully examines some practitioners' experiences of belly-cultivation practice in attempting to understand its healing effects for them within their life histories and contemporary intellectual, social and cultural contexts. It shows that belly-cultivation practice served as a medium for some practitioners to reflect on and retell their life stories, and that the personal charisma of certain masters and the communities developing around them provided practitioners with a valuable sense of belonging in an increasingly industrialized and urbanized society. Moreover, these belly-cultivation techniques provided an embodied way for some to explore and affirm their sense of self and develop individual identity. While they were increasingly promoted as cultural traditions capable of cultivating national character, they also served as healing practices by inspiring practitioners with a sense of collective identity and purpose. With these analyses, this article sheds light on the complicated meanings of belly-cultivation for practitioners, and provides illustrative examples of the multitude of meanings of the body, bodily cultivation and healing.


Assuntos
Exercícios Respiratórios/métodos , Terapias Complementares/métodos , Neurastenia/terapia , Exercícios Respiratórios/história , Terapias Complementares/história , História do Século XX , Humanos , Japão/etnologia , Neurastenia/etnologia , Neurastenia/história
12.
Toxicol Ind Health ; 31(1): 60-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23235995

RESUMO

The purpose of this article was to investigate the levels of metals, cadmium, lead, and zinc, in Western reef heron (Egretta gularis) (n = 15) in order to (1) examine the sex-related variation in trace metal accumulation and (2) determine the significant differences between the metal concentrations in the kidney, liver, and pectoral muscle. Bird samples were collected from throughout the Hara biosphere reserve of southern Iran, during November and December 2010 and the concentration of metals were measured using a Shimadzu AA 680 flame atomic absorption spectrophotometer. The overall cadmium, lead and zinc concentrations means were measured as 0.8 ± 0.1, 3.4 ± 1.1, and 29.4 ± 12.9 µg/g for kidney; 0.7 ± 0.1, 2.2 ± 0.5, and 65.9 ± 20.7 µg/g for liver; and 0.2 ± 0.1, 2.2 ± 0.7, and 17.6 ± 12.9 µg/g for pectoral muscle, respectively. The results showed that with the exception of cadmium in liver, there were no significant differences between males and females (t test, p > 0.05). In the contrast, the results indicated metal concentrations differed significantly in kidneys, livers, and pectoral muscles among tissues in Western reef heron (one-way analysis of variance, p < 0.001).


Assuntos
Aves , Poluentes Ambientais/análise , Metais Pesados/análise , Análise de Variância , Animais , Poluentes Ambientais/metabolismo , Feminino , Irã (Geográfico) , Rim/química , Fígado/química , Masculino , Metais Pesados/metabolismo , Músculo Esquelético/química , Distribuição Tecidual
13.
Toxicol Ind Health ; 30(1): 64-72, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22740619

RESUMO

This study determined the concentration of heavy metals (Al, Cr, Cu, and Zn) in water and sediments at nine sites in the Hara biosphere reserve of southern Iran during the summer and winter 2010. Determination of Al, Cr, Cu, and Zn in water was carried out by graphite furnace atomic absorption spectrometer (Shimadzu, AA 610s) and in sediment by flame atomic absorption spectrometer (Perkin Elmer, AA3030). Results showed that the heavy metal concentrations in the water samples decreased in the sequence of Zn > Al > Cu > Cr, while in sediment samples were Cr > Zn > Cu > Al. Data analysis indicated that with the exception of Al, there was a Pearson's correlation coefficient between pH and Cu, Zn, and Cr at α = 0.01, 0.05, and 0.001 in sediment (in winter), respectively. There were also significant differences between heavy metals of Cr, Cu, and Zn during the two seasons (p < 0.001) in the water and sediment.


Assuntos
Água Doce/química , Sedimentos Geológicos/química , Metais Pesados/análise , Poluentes Químicos da Água/análise , Análise de Variância , Concentração de Íons de Hidrogênio , Irã (Geográfico) , Árvores
14.
Phytochemistry ; 225: 114171, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38844058

RESUMO

Seven undescribed abietane diterpenoids [abietamethinols A-G (1-7)] were isolated from the twigs and leaves of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic methods including 2D NMR, and they were further confirmed by X-ray crystallographic data. Lophanic acid was considered as the precursor of 1-7 in the biosynthesis pathway hypothesis. These compounds were evaluated for their cytotoxic, anti-bacterial and anti-AIV (avian influenza virus) activities. Compound 5 showed 42.9% inhibitory activity against the cancer cell line SMMC-7721 at the concentration of 40 µM, 3 and 4 could inhibit the bacterial growth of Streptococcus sobrinus by 55.3% and 63.2% at the concentrations of 148.6 and 141.9 µM, respectively, and 4 was demonstrated with antiviral activity against AIV with the inhibitory effect of 68.4% at 25 µM.


Assuntos
Abietanos , Antibacterianos , Antineoplásicos Fitogênicos , Antivirais , Isodon , Testes de Sensibilidade Microbiana , Abietanos/farmacologia , Abietanos/química , Abietanos/isolamento & purificação , Humanos , Antivirais/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Isodon/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Folhas de Planta/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Conformação Molecular , Vírus da Influenza A/efeitos dos fármacos
15.
Front Pharmacol ; 15: 1284371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881872

RESUMO

Background: Cynanchum paniculatum (Bunge) Kitag. ex H.Hara, a member of the Asclepiadaceae family, has a rich history as a traditional Chinese medicinal plant used to treat digestive disorders. However, its potential anti-cancer effects in pancreatic cancer remain largely unexplored. Aim: This study delves into the intricate anti-pancreatic cancer mechanisms of C. paniculatum (Bunge) Kitag. ex H.Hara aqueous extract (CPAE) by elucidating its role in apoptosis induction and the inhibition of invasion and migration. Methods: A comprehensive set of methodologies was employed to assess CPAE's impact, including cell viability analyses using MTT and colony formation assays, flow cytometry for cell cycle distribution and apoptosis assessment, scratch-wound and Matrigel invasion assays for migration and invasion capabilities, and immunoblotting to measure the expression levels of key proteins involved in apoptosis and metastasis. Additionally, a murine xenograft model was established to investigate CPAE's in vivo anti-cancer potential. Results: CPAE exhibited time- and dose-dependent suppression of proliferation and colony formation in pancreatic cancer cells. Notably, CPAE induced apoptosis and G2/M phase arrest, effectively activating the caspase-dependent PARP pathway. At non-cytotoxic doses, CPAE significantly curtailed the metastatic abilities of pancreatic cells, effectively suppressing epithelial-mesenchymal transition (EMT) and downregulating the TGF-ß1/Smad2/3 pathway. In vivo experiments underscored CPAE's ability to inhibit tumor proliferation. Conclusion: This study illuminates the multifaceted anti-proliferative, pro-apoptotic, anti-invasive, and anti-migratory effects of CPAE, both in vitro and in vivo. CPAE emerges as a promising herbal medicine for pancreatic cancer treatment, with its potential mediated through apoptosis induction via the caspase-dependent PARP pathway and MET suppression via the TGF-ß1/Smad2/3 signaling pathway at non-cytotoxic doses. These findings advocate for further exploration of CPAE's therapeutic potential in pancreatic cancer.

16.
Front Physiol ; 15: 1374355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638275

RESUMO

Torsades de pointes (TdP) is a type of ventricular arrhythmia that can lead to sudden cardiac death. Drug-induced TdP has been an important concern for researchers and international regulatory boards. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative was proposed that integrates in vitro testing and computational models of cardiac ion channels and human cardiomyocyte cells to evaluate the proarrhythmic risk of drugs. The TdP risk classification performance using only a single TdP metric may require some improvements because of information limitations and the instability of generalizing results. This study evaluates the performance of TdP metrics from the in silico simulations of the Tomek-O'Hara Rudy (ToR-ORd) ventricular cell model for classifying the TdP risk of drugs. We utilized these metrics as an input to an artificial neural network (ANN)-based classifier. The ANN model was optimized through hyperparameter tuning using the grid search (GS) method to find the optimal model. The study outcomes show an area under the curve (AUC) value of 0.979 for the high-risk category, 0.791 for the intermediate-risk category, and 0.937 for the low-risk category. Therefore, this study successfully demonstrates the capability of the ToR-ORd ventricular cell model in classifying the TdP risk into three risk categories, providing new insights into TdP risk prediction methods.

17.
Phytochemistry ; 210: 113642, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36933879

RESUMO

Detailed phytochemical investigation on the traditional Chinese medicine Swertia pseudochinensis Hara led to the isolation of ten undescribed secoiridoids and fifteen known analogs. Their structures were elucidated by extensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS). Selected isolates were assayed for their anti-inflammatory and antibacterial activities, and moderate anti-inflammatory activity via inhibiting the secretion of cytokines IL-6 and TNF-α in macrophages RAW264.7 induced by LPS were observed. Antibacterial activity against Staphylococcus aureus was not found at 100 µM.


Assuntos
Medicamentos de Ervas Chinesas , Swertia , Medicina Tradicional Chinesa , Swertia/química , Iridoides/química , Medicamentos de Ervas Chinesas/farmacologia , Anti-Inflamatórios/farmacologia , Estrutura Molecular
18.
Genes (Basel) ; 14(4)2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-37107678

RESUMO

Pathogenesis-related proteins, often used as molecular markers of disease resistance in plants, can enable plants to obtain systemic resistance. In this study, a gene encoding a pathogenesis-related protein was identified via RNA-seq sequencing analysis performed at different stages of soybean seedling development. Because the gene sequence showed the highest similarity with PR1L sequence in soybean, the gene was named GmPR1-9-like (GmPR1L). GmPR1L was either overexpressed or silenced in soybean seedlings through Agrobacterium-mediated transformation to examine the resistance of soybean to infection caused by Cercospora sojina Hara. The results revealed that GmPR1L-overexpressing soybean plants had a smaller lesion area and improved resistance to C. sojina infection, whereas GmPR1L-silenced plants had low resistance to C. sojina infection. Fluorescent real-time PCR indicated that overexpression of GmPR1L induced the expression of genes such as WRKY, PR9, and PR14, which are more likely to be co-expressed during C. sojina infection. Furthermore, the activities of SOD, POD, CAT, and PAL were significantly increased in GmPR1L-overexpressing soybean plants after seven days of infection. The resistance of the GmPR1L-overexpressing lines OEA1 and OEA2 to C. sojina infection was significantly increased from a neutral level in wild-type plants to a moderate level. These findings predominantly reveal the positive role of GmPR1L in inducing resistance to C. sojina infection in soybean, which may facilitate the production of improved disease-resistant soybean cultivars in the future.


Assuntos
Ascomicetos , Ascomicetos/genética , Glycine max/genética , Doenças das Plantas/genética , Cercospora , Anticorpos
19.
Environ Sci Pollut Res Int ; 30(17): 48962-48971, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36763266

RESUMO

Molybdenum (Mo) sourced mainly from artificial activities is an emerging environmental concern whose remediation is seldom reported. This study screened the Mo-enriched macrophyte Vallisneria natans (Lour.) Hara due to its high enrichment factor (10.25). Phytoremediation (V. natans) and microorganism-assisted phytoremediation (V. natans-Serratia marcescens A2) efficiency were compared. S. marcescens A2 improved phytoremediation in the early stage, however, it reduced the total Mo removal rate by 8.42%. Further experiments were conducted to investigate the environmental factors (light intensity and overlying water flow rate) on the phytoremediation by V. natans. The optimal phytoremediation performance was achieved under a high overlying water flow rate (0.022 cm·s-1) with intense light (60 µmol·m-2·s-1) conditions. In addition, increasing the light intensity or flow rate increased the microbial communities' diversity in the sediment. Notably, the abundance of norank_f__Bacteroidetes_vadinHA17, related to Mo release in sediments, increased by 147.96% at optimal conditions. This study illustrated that the phytoremediation of Mo-contaminated sediments by V. natans is of practical potential.


Assuntos
Hydrocharitaceae , Poluentes Químicos da Água , Molibdênio , Biodegradação Ambiental , Poluentes Químicos da Água/análise , Água
20.
Foods ; 11(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35564064

RESUMO

We developed a vegetable alternative to meat patties using Aruncus dioicus var. kamtschaticus Hara (A. dioicus) and used it to generate basic data for the alternative meat market by comparing nutritional and microbiological components with commercially available vegetable and meat patties. Nutrient analysis, microbiological analysis, chromaticity, and texture analysis were performed on substitute meat patties (SMPs) with A. dioicus and commercially available vegetable and animal patties. Among sugars, the contents of fructose and maltose were respectively high in commercial meat patties (CMPs) and SMPs. SMPs were low in saturated and trans-fat, and high in ω-3 fatty acids. The contents (in descending order) of leucine > phenylalanine > threonine > isoleucine were high in SMPs and commercial vegetable patties (CVPs). Qualitative and quantitative findings of Escherichia coli (E. coli) and Staphylococcus aureus were all negative. Our SMPs had high lightness (L*), low redness (a*), and low yellowness (b*). The hardness, chewiness, and resilience of our SMPs were lower than those of other vegetable and animal patties. Considering our results, the method of manufacturing SMPs developed in the present study allows meat to be flavored without significant nutritional differences compared with commercially available CMPs. Our findings provide a base for studies on future meat alternatives.

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