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BACKGROUND: Clinacanthus nutans (for abbreviation thereafter) is often used as medicine in the form of fresh juice in the folk to treat many kinds of cancers, including renal cell carcinoma (RCC). It is speculated that its active ingredient may have heat sensitivity, but there are currently no reports on this aspect. Therefore, based on the folk application for fresh juice of C nutans, this study used metabonomics and network pharmacology to explore the material basis and mechanism of action of C nutans against RCC. METHODS: Firstly, untargeted metabolomics profiling was performed by Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to screen the metabolites down-regulated by heat in the extract of C nutans. Secondly, we collected the targets of metabolites in the Swiss Target Prediction platform. In addition, the targets of RCC were obtained in the GeneCards database. The "component-target-disease" network was established by Cytoscape3.9.0 software. Then we constructed a protein-protein interaction network in the STRING network platform to screen core targets. The gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis of core targets were carried out to predict the relevant pathway of C nutans in the treatment of RCC. Finally, the molecular docking verification of the core targets were carried out. RESULTS: In this study, 35 potential active ingredients and 125 potential targets were obtained. And the core targets were Cellular tumor antigen p53, Signal transducer and activator of transcription 3, and so on. Then, 48 biological processes, 30 cell components, and 36 molecular functions were obtained by gene ontology enrichment analysis. Besides, 44 pathways were obtained by Kyoto encyclopedia of genes and genomes enrichment analysis, including Pathway in cancer, PI3K-Akt signal pathway, P53 signal pathway, and so on. The docking model between the core target and its corresponding components was stable. CONCLUSION: This research is based on the folk application of C nutans, showed its potential active ingredients by metabonomics, and predicted the potential mechanism of C nutans in the treatment of RCC by network pharmacology. It provides new references for follow-up research and new drug development.
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Carcinoma de Células Renales , Medicamentos Herbarios Chinos , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Farmacología en Red , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Neoplasias Renales/tratamiento farmacológico , Medicina Tradicional ChinaRESUMEN
The Oriental rat snake Ptyas mucosa is a common non-venomous snake of the colubrid family, spanning most of South and Southeast Asia. P. mucosa is widely bred for its uses in traditional medicine, scientific research, and handicrafts. Therefore, genome resources of P. mucosa could play an important role in the efficacy of traditional medicine and the analysis of the living environment of this species. Here, we present a highly continuous P. mucosa genome with a size of 1.74 Gb. Its scaffold N50 length is 9.57 Mb, and the maximal scaffold length is 78.3 Mb. Its CG content is 37.9%, and its gene integrity reaches 86.6%. Assembled using long-reads, the total length of the repeat sequences in the genome reaches 735 Mb, and its repeat content is 42.19%. Finally, 24,869 functional genes were annotated in this genome. This study may assist in understanding P. mucosa and supporting medicinal research.
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ETHNOPHARMACOLOGICAL RELEVANCE: The capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. AIM OF THE STUDY: The study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. MATERIALS AND METHODS: Biochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. RESULTS: We confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. CONCLUSIONS: Our study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.
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Hiperlipidemias , Fosfatidilinositol 3-Quinasas , Ratones , Humanos , Animales , Proteínas Proto-Oncogénicas c-akt , LDL-Colesterol , Flavonoides/farmacología , Flavonoides/uso terapéutico , Hiperlipidemias/metabolismo , Lípidos/uso terapéutico , Triglicéridos , Serina-Treonina Quinasas TORRESUMEN
OBJECTIVE: To observe and compare the efficacy and safety of electroacupuncture and antidepressants in the treatment of poststroke depression (PSD) using a meta-analysis method. METHODS: The VIP, CNKI, Wanfang, CMB, Embase, PubMed, and Cochrane databases were searched. All randomized controlled trials (RCT) on electroacupuncture treatment of PSD were searched and further screened. Meta-analysis was performed on electroacupuncture and western medicine for PSD to explore the difference in efficacy between electroacupuncture and western medicine for PSD. RESULTS: Nineteen RCTs were included in the meta-analysis. Compared with the Western medicine group, the meta-analysis showed no significant changes in Hamilton Depression Scale (HAMD) scores between the electroacupuncture group and the antidepressant group (P > 0.05). The number of adverse events in the electroacupuncture group was less than that in the antidepressant group. CONCLUSION: Compared with antidepressants, electroacupuncture is not less effective in improving depression symptoms in PSD patients with greater safety.
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Antidepresivos/uso terapéutico , Depresión/terapia , Electroacupuntura/métodos , Accidente Cerebrovascular/psicología , Depresión/etiología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Rehabilitación de Accidente Cerebrovascular/métodos , Rehabilitación de Accidente Cerebrovascular/psicologíaRESUMEN
Objectives: Dendrobium officinale polysaccharide (DOP) is the main active ingredient in a valuable traditional Chinese medicine, which exerts several pharmacological activities including hepatoprotection and hypoglycemic effects. However, the effects of DOP on obesity-associated insulin resistance (IR) and lipid metabolism remain unknown. This study aimed to investigate the role of DOP in IR and abnormal lipid metabolism in obese mice. Methods: IR models were established using 3T3-L1 adipocytes, C2C12 myocytes, and primary cultured hepatocytes exposed to palmitate acid. After treatment with DOP, insulin-stimulated glucose uptake, glucose release, and AKT phosphorylation was detected. Fasting blood glucose, fasting serum insulin, the glucose tolerance test (GTT), and the insulin tolerance test (ITT) were measured to evaluate IR of obese mice. Lipid analysis was conducted to evaluate the effects of DOP on lipid metabolism in obese mice. Results: In vitro, DOP treatment ameliorated palmitic acid-induced IR in adipocytes, myocytes, and hepatocytes. DOP regulated cellular insulin sensitivity via the peroxisome proliferator-activated receptor-γ (PPAR-γ). Furthermore, administration of DOP significantly reduced the IR and visceral adipose tissue (VAT) inflammation of diet-induced obese (DIO) and the genetically-induced obesity mice (ob/ob) mouse models. In addition, DOP treatment attenuated the high-fat diet (HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing HDL-C levels. Conclusion: DOP could improve obesity-associated IR and abnormal lipid metabolism through its activities on PPAR-γ, and may serve as a potential therapeutic agent for obesity-associated insulin resistance and lipid metabolism disorder.
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ETHNOPHARMACOLOGICAL RELEVANCE: Rheum palmatum L; Astragalus membranaceus (Fisch.), is referred to as 'Dahuang, Huangqi' in China. As an important medicinal plant, the rhizome of rhubarb and astragalus is traditionally used in the treatment of kidney diseases associated with renal failure, inflammation and tumors. AIM OF THE STUDY: This study aimed to investigate the effect of a drug-containing serum of rhubarb-astragalus capsules (composed of rhubarb and astragalus) and to elucidate its mechanism in the epithelial-mesenchymal transformation of renal tubular epithelial cells. MATERIALS AND METHODS: Epithelial-mesenchymal transformation (EMT) of HK-2 cells was induced by TGF-ß1, and rhubarb-astragalus and losartan drug-containing serum from rats, as well as SB203580 (a specific inhibitor of p38 MAPK), were used. High-performance liquid chromatography analysis was performed to determine the main components of the drug-containing serum of rhubarb-astragalus from rats. Western blotting and immunofluorescence analysis were used to determine the levels of protein expression, and real-time quantitative PCR analysis was used to detect the levels of gene expression. RESULTS: The drug-containing serum of rhubarb-astragalus contained emodin (0.36 µg/ml) and danthraquinone (0.96 µg/ml). Rhubarb-astragalus significantly decreased the protein expression levels of α-SMA, FN, vimentin and N-cadherin in HK-2 cells that were increased by TGF-ß1, while it significantly increased the E-cadherin protein expression level that was decreased by TGF-ß1. Rhubarb-astragalus also significantly decreased the protein expression levels of TGF-ß1 and p38 MAPK and the mRNA expression levels of α-SMA, vimentin, TGF-ß1, p38 MAPK, Smad2 and Smad3 in HK-2 cells that were increased by TGF-ß1. It is worth noting that SB203580 (a p38 MAPK inhibitor) had similar effects as rhubarb-astragalus in this study. CONCLUSION: The drug-containing serum of rhubarb-astragalus can inhibit EMT in HK-2 cells by downregulating the TGF-ß1/p38 MAPK/Smad2/3 pathway.
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Planta del Astrágalo , Células Epiteliales/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Rheum , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Emodina/administración & dosificación , Emodina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Imidazoles/farmacología , Túbulos Renales/citología , Masculino , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína smad3/genética , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Pigeonpea (Cajanus cajan (L.) Millsp) leaves (PL) are widely used for treating avascular necrosis of the femoral head. PL has an ideal effect on bone angiogenesis in patients with hormone-induced avascular necrosis of the femoral head and could promote the repair of blood vessels in the necrotic femoral head. Angiogenesis is beneficial to the treatment of myocardial ischemia. PL can be used to treat ischemic heart disease; however, no studies have examined whether it could protect the myocardium against ischemia injury via promoting angiogenesis. AIM: The present study aimed to investigate whether PL could encourage angiogenesis on hypoxic human umbilical vein endothelial cells (HUVECs) and whether estrogen receptor (ER-α), protein kinase B (Akt), and vascular endothelial growth factor (VEGF) (the ischemia injury salvage kinase pathway, phosphoinositide-3 kinase (PI3K)) are involved in this effect. METHODS: A hypoxic HUVEC model was established by culture in the hypoxia incubator. The proliferation ability of HUVECs was determined by the 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method, the migration rate of HUVECs was inspected by the Transwell method, the tube formation was evaluated by the Matrigel method, and the expression of PI3K, phosphorylated Akt (p-Akt), and VEGF was detected by Western blotting. RESULTS: The proliferation, migration, and tube formation were promoted by the PL extract on hypoxic HUVECs, and the hypoxia-induced downstream signaling was counteracted, leading to increased expression of PI3K, p-Akt, and VEGF in HUVECs. CONCLUSIONS: The current findings showed that the PL extracts encourage angiogenesis. In addition, the above effects could be mediated via ER-α and PI3K/Akt/VEGF pathways.
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Cajanus/química , Proliferación Celular/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta/química , Movimiento Celular/efectos de los fármacos , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Fulvestrant/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Oxígeno , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/química , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Side effects of chemotherapy are burning questions for physicians and patients involved in cancers. Ganoderma lucidum is a widely consumed traditional Chinese medicine and edible mushroom with multiple functional properties. The present study aims to investigate the potential of polysaccharides from spore of G. lucidum (SGP) on small intestinal barrier function recovery against paclitaxel (PTX) challenge in a breast cancer mice model and IEC-6 cell line. The 4T1 tumor-bearing mice were treated with PTX together with four-week daily oral administration of SGP. Results indicated that combination of PTX and SGP reversed body weight lost and remolded the histology of small intestine, accompanied with promoted proliferation but suppressed apoptosis in intestinal cells. Intestinal barrier function was enhanced by the combination as indicated by reduced endotoxemia and the up-regulation of tight junction proteins, including Zonula occludens-1 (ZO-1), E-cadherin, ß-catenin and Occludin. The protection of SGP was further confirmed in IEC-6 cells affected by PTX in vitro. The combination treatment prevented PTX-induced apoptosis in IEC-6 by inhibiting microtubule polymerization, and the aforementioned tight junction proteins were also upregulated. These findings suggest a promising protective effect of SGP against small intestinal barrier injury caused by PTX, highlighting its clinical implication against the chemotherapy side effects.
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Antineoplásicos Fitogénicos/toxicidad , Apoptosis/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Microtúbulos/efectos de los fármacos , Paclitaxel/toxicidad , Polisacáridos/farmacología , Reishi/química , Esporas Fúngicas/química , Animales , Antineoplásicos Fitogénicos/antagonistas & inhibidores , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Femenino , Humanos , Mucosa Intestinal/citología , Ratones , Ratones Endogámicos BALB C , Paclitaxel/antagonistas & inhibidores , Polisacáridos/química , Proteínas de Uniones Estrechas/biosíntesis , Pérdida de Peso/efectos de los fármacosRESUMEN
Evidences showed that chronic stress (CS) can aggravate the situation of nonalcoholic fatty liver disease (NAFLD). Vitexin is one of the major components in hawthorn, which is widely used to reduce blood lipid. This study was aimed to explore the therapeutic effects and potential mechanisms of vitexin on chronic stress mice with high-fat diet (CSHFD). The results showed that 5-week vitexin administration (40 mg/kg, i.g.) could obviously reduce hepatic fat deposition, alleviate lipid metabolism, and inhibit liver inflammation in CSHFD mice. In addition, vitexin significantly reduced hepatic macrophage infiltration, obviously down-regulated the mRNA and protein expressions of hepatic SREBP-1c, FAS, ACC. Moreover, we also found that vitexin treatment could significantly inhibit the expressions of TLR4/NF-κB signaling in CSHFD mice. This results suggested that vitexin could ameliorate chronic stress combined with high-fat diet induced NAFLD, and its mechanisms is closely related to inhibit TLR4/NF-κB signaling and reduce fatty acid synthesis proteins.
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Antiinflamatorios/uso terapéutico , Apigenina/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Apigenina/farmacología , Citocinas/sangre , Citocinas/inmunología , Dieta Alta en Grasa , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/patología , Masculino , Ratones Endogámicos C57BL , FN-kappa B/inmunología , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Estrés Fisiológico , Receptor Toll-Like 4/inmunologíaRESUMEN
BACKGROUND: Dextrorotatory borneol (D-borneol), a cyclic monoterpene, is widely used in traditional Chinese medicine as an efficient topical analgesic drug. Fresh leaves of Cinnamomum trees, e.g., C. burmannii and C. camphor, are the main sources from which D-borneol is extracted by steam distillation, yet with low yields. Insufficient supply of D-borneol has hampered its clinical use and production of patent remedies for a long time. Biological synthesis of D-borneol offers an additional approach; however, mechanisms of D-borneol biosynthesis remain mostly unresolved. Hence, it is important and necessary to elucidate the biosynthetic pathway of D-borneol. RESULTS: Comparative analysis on the gene expression patterns of different D-borneol production C. burmannii samples facilitates elucidation on the underlying biosynthetic pathway of D-borneol. Herein, we collected three different chemotypes of C. burmannii, which harbor different contents of D-borneol.A total of 100,218 unigenes with an N50 of 1,128 bp were assembled de novo using Trinity from a total of 21.21 Gb clean bases. We used BLASTx analysis against several public databases to annotate 45,485 unigenes (45.38%) to at least one database, among which 82 unigenes were assigned to terpenoid biosynthesis pathways by KEGG annotation. In addition, we defined 8,860 unigenes as differentially expressed genes (DEGs), among which 13 DEGs were associated with terpenoid biosynthesis pathways. One 1-deoxy-D-xylulose-5-phosphate synthase (DXS) and two monoterpene synthase, designated as CbDXS9, CbTPS2 and CbTPS3, were up-regulated in the high-borneol group compared to the low-borneol and borneol-free groups, and might be vital to biosynthesis of D-borneol in C. burmannii. In addition, we identified one WRKY, two BHLH, one AP2/ERF and three MYB candidate genes, which exhibited the same expression patterns as CbTPS2 and CbTPS3, suggesting that these transcription factors might potentially regulate D-borneol biosynthesis. Finally, quantitative real-time PCR was conducted to detect the actual expression level of those candidate genes related to the D-borneol biosynthesis pathway, and the result showed that the expression patterns of the candidate genes related to D-borneol biosynthesis were basically consistent with those revealed by transcriptome analysis. CONCLUSIONS: We used transcriptome sequencing to analyze three different chemotypes of C. burmannii, identifying three candidate structural genes (one DXS, two monoterpene synthases) and seven potential transcription factor candidates (one WRKY, two BHLH, one AP2/ERF and three MYB) involved in D-borneol biosynthesis. These results provide new insight into our understanding of the production and accumulation of D-borneol in C. burmannii.
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Motor recovery of wrist and fingers is still a great challenge for chronic stroke survivors. The present study aimed to verify the efficiency of motor imagery based brain-computer interface (BCI) control of continuous passive motion (CPM) in the recovery of wrist extension due to stroke. An observational study was conducted in 26 chronic stroke patients, aged 49.0 ± 15.4 years, with upper extremity motor impairment. All patients showed no wrist extension recovery. A 24-channel highresolution electroencephalogram (EEG) system was used to acquire cortical signal while they were imagining extension of the affected wrist. Then, 20 sessions of BCI-driven CPM training were carried out for 6 weeks. Primary outcome was the increase of active range of motion (ROM) of the affected wrist from the baseline to final evaluation. Improvement of modified Barthel Index, EEG classification and motor imagery pattern of wrist extension were recorded as secondary outcomes. Twenty-one patients finally passed the EEG screening and completed all the BCI-driven CPM trainings. From baseline to the final evaluation, the increase of active ROM of the affected wrists was (24.05 ± 14.46)Ë. The increase of modified Barthel Index was 3.10 ± 4.02 points. But no statistical difference was detected between the baseline and final evaluations (P > 0.05). Both EEG classification and motor imagery pattern improved. The present study demonstrated beneficial outcomes of MI-based BCI control of CPM training in motor recovery of wrist extension using motor imagery signal of brain in chronic stroke patients.
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Encéfalo/fisiología , Imágenes en Psicoterapia , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/complicaciones , Articulación de la Muñeca , Adulto , Anciano , Interfaces Cerebro-Computador , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Recuperación de la Función , MuñecaRESUMEN
The further development of fishery resources is a hotspot in the development of the fishery industry. However, how to develop aquatic animal resources deeply is a key point to be solved in the fishery industry. Over the past decades, numerous aquatic animals have gained great attention in the development and utilization of their bioactive molecules which are of therapeutic applications as nutraceuticals and pharmaceuticals. Recent research revealed that aquatic animals are composed of many vital moieties, such as polysaccharides and proteins, which provide health benefits beyond basic nutrition. In particular, aquatic animal polysaccharides are gaining worldwide popularity owing to their high content, ease of extraction, specific structure, few side effects, prominent therapeutic potential and incorporation in functional foods and dietary supplements. Thus, tremendous research on the isolation, identification and bioactivities of polysaccharides has been carried out. This review presents comprehensive viewpoints on extraction, separation, purification, structural characterization and bioactivity of various polysaccharides from aquatic animals, such as sea cucumber, abalone, oyster and mussels. In addition, this review profiled a brief knowledge on both current challenges and future scope in aquatic animal polysaccharides field. The review will be a direction of deep processing in fishery resources, which is a hotspot, but technical bottleneck. Furthermore, the review could be served as a useful reference material for further investigation, production and application of polysaccharides from aquatic animals in functional foods and therapeutic agents.
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Polisacáridos/aislamiento & purificación , Alimentos Marinos/análisis , Animales , Bivalvos , Suplementos Dietéticos , Alimentos Funcionales , Gastrópodos , Ostreidae , Polisacáridos/química , Polisacáridos/farmacología , Pepinos de MarRESUMEN
Melastoma dodecandrum, the only creeping species in the Melastoma genus, serves as a medicinal herb in southeast China. It belongs to the huge family Melastomataceae, which contains over 5000 species worldwide. In this study, we used next-generation sequencing to determine the complete chloroplast genome sequences of M. dodecandrum, which is a circular molecule of 156,611 bp in length. After annotation, we identified 131 putative genes in total, comprised of 85 protein-coding genes, 38 transfer RNA genes and 8 ribosomal RNA genes. Genome structure, GC content, repeat sequences and codon usage were investigated to gain a comprehensive understanding of this genome. Furthermore, we conducted comparative genome analyses between the M. dodecandrum genome and that of four other Melastomataceae species. Additionally, a phylogenetic analysis was performed based on available chloroplast genomes of Melastomataceae species and several Myrtaceae species, revealing the taxonomic relationships between M. dodecandrum and related species. In conclusion, our study represents the first look into the complete chloroplast genome of M. dodecandrum, providing abundant information for further studies such as species identification, taxonomy and phylogenetic resolution of Melastomataceae species.
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Dendrobium officinale protocorms (DOPs) are a specific developmental stage of Dendrobium officinale KIMURA et MIGO, which is used in folk medicine to ease skin issues, such as wrinkles and erythema. The purpose of the current study was to evaluate the effect of DOPs on UV irradiation-induced skin damage in bc_nu hairless mice, using matrixyl as a positive control. Hairless mice were randomly separated into 6 groups (8 mice per group). The normal control group received solvent and was not exposed to UV irradiation, while the model control group received solvent and was exposed to UV irradiation. The positive control group was subjected to UV irradiation and then received a 10 mg/mL formulation of matrixyl. The DOPs-treated groups received a transdermal application of a DOPs formulation after 4 weeks of UV irradiation. Relevant indicators, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS) and matrix metalloproteinases (MMPs), were then used to evaluate the ability of DOPs to repair photodamage. The results indicated that DOPs significantly reduced erythema and protected the skin from dryness and therefore exhibits a significant anti-photoaging effect. In addition, the expression of CAT, SOD, and GSH-Px increased while TBARS and MMPs levels decreased in DOPs-treated mice. This demonstrated that DOPs can inhibit photodamage in the skin of hairless mice. DOPs could be used as a potential therapeutic agent to protect the skin against UV-induced photoaging.
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Dendrobium , Fármacos Dermatológicos/uso terapéutico , Protectores contra Radiación/uso terapéutico , Envejecimiento de la Piel/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Animales , Catalasa/metabolismo , Eritema/tratamiento farmacológico , Eritema/metabolismo , Glutatión Peroxidasa/metabolismo , Masculino , Metaloproteinasas de la Matriz/metabolismo , Ratones Pelados , Fitoterapia , Piel/efectos de los fármacos , Piel/metabolismo , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Lycium chinense Mill, an important Chinese herbal medicine, is widely used as a dietary supplement and food. Here the chloroplast (CP) genome of L. chinense was sequenced and analyzed, revealing a size of 155,756 bp and with a 37.8% GC content. The L. chinense CP genome comprises a large single copy region (LSC) of 86,595 bp and a small single copy region (SSC) of 18,209 bp, and two inverted repeat regions (IRa and IRb) of 25,476 bp separated by the single copy regions. The genome encodes 114 genes, 16 of which are duplicated. Most of the 85 protein-coding genes (CDS) had standard ATG start codons, while 3 genes including rps12, psbL and ndhD had abnormal start codons (ACT and ACG). In addition, a strong A/T bias was found in the majority of simple sequence repeats (SSRs) detected in the CP genome. Analysis of the phylogenetic relationships among 16 species revealed that L. chinense is a sister taxon to Lycium barbarum. Overall, the complete sequence and annotation of the L. chinense CP genome provides valuable genetic information to facilitate precise understanding of the taxonomy, species and phylogenetic evolution of the Solanaceae family.
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BACKGROUND: Gitelman syndrome (GS) is an inherited autosomal recessive renal tubular disorder characterized by low levels of potassium and magnesium in the blood, decreased excretion of calcium in the urine, and elevated blood pH. GS is caused by an inactivating mutation in the SLC12A3 gene, which is located on the long arm of chromosome 16 (16q13) and encodes a thiazide-sensitive sodium chloride cotransporter (NCCT). CASE PRESENTATION: A 45-year-old man with Graves' disease complicated by paroxysmal limb paralysis had a diagnosis of thyrotoxic periodic paralysis for 12 years. However, his serum potassium level remained low despite sufficiently large doses of potassium supplementation. Finally, gene analysis revealed a homozygous mutation in the SLC12A3 gene. After his thyroid function gradually returned to normal, his serum potassium level remained low, but his paroxysmal limb paralysis resolved. CONCLUSIONS: GS combined with hyperthyroidism can manifest as frequent episodes of periodic paralysis; to date, this comorbidity has been reported only in eastern Asian populations. This case prompted us to more seriously consider the possibility of GS associated with thyroid dysfunction.
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Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/genética , Mutación/genética , Síndrome de Gitelman/complicaciones , Enfermedad de Graves/complicaciones , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Miembro 3 de la Familia de Transportadores de Soluto 12/genéticaRESUMEN
Respiratory viral infections cause mild to severe diseases, such as common cold, bronchiolitis and pneumonia and are associated with substantial burden for society. To test new molecules for shortening, alleviating the diseases or to develop new therapies, relevant human in vitro models are mandatory. MucilAir™, a human standardized air-liquid interface 3D airway epithelial culture holds in vitro specific mechanisms to counter invaders comparable to the in vivo situation, such as mucus production, mucociliary clearance, and secretion of defensive molecules. The objective of this study was to test the relevance of such a model for the discovery and validation of antiviral drugs. Fully differentiated 3D nasal epithelium cultures were inoculated with picornaviruses, a coronavirus and influenza A viruses in the absence or in the presence of reference antiviral drugs. Results showed that, rupintrivir efficiently inhibits the replication of respiratory picornaviruses in a dose dependent manner and prevents the impairment of the mucociliary clearance. Similarly, oseltamivir reduced the replication of influenza A viruses in a dose dependent manner and prevented the impairment of the epithelial barrier function and cytotoxicity until 4 days of infection. In addition we found that Rhinovirus B14, C15 and influenza A(H1N1) induce significant increase of ß Defensins 2 and Cathelicidin release with different time course. These results reveal that a large panel of epithelial functions is modified upon viral infection and validate MucilAir™ as a pertinent tool for pre-clinical antiviral drug testing.
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Antivirales/aislamiento & purificación , Evaluación Preclínica de Medicamentos/métodos , Epitelio/inmunología , Epitelio/fisiología , Inmunidad Innata , Técnicas de Cultivo de Órganos/métodos , Antivirales/farmacología , Coronavirus/efectos de los fármacos , Humanos , Virus de la Influenza A/efectos de los fármacos , Modelos Biológicos , Picornaviridae/efectos de los fármacos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Virosis/tratamiento farmacológico , Replicación Viral/efectos de los fármacosRESUMEN
BACKGROUND AND PURPOSE: Effective anti-respiratory syncytial virus (RSV) agents are still not available for clinical use. Current major targets are virus surface proteins, such as a fusion protein involved in viral entry, but agents effective after RSV infection is established are required. Here we have investigated the effects of late therapeutic intervention with a novel inhaled RSV polymerase inhibitor, PC786, on RSV infection in human airway epithelium. EXPERIMENTAL APPROACH: Air liquid interface-cultured bronchial or small airway epithelium was infected with RSVA2. PC786 was applied apically or basolaterally once daily following peak virus load on Day 3 post inoculation. Apical wash was collected daily for determination of viral burden by PCR and plaque assay (primary endpoints) and biomarker analyses. The effects were compared with those of ALS-8112, an anti-RSV nucleoside analogue, and GS-5806, a fusion-protein inhibitor, which were treated basolaterally. KEY RESULTS: Late intervention with GS-5806 did not show significant anti-viral effects, but PC786 produced potent, concentration-dependent inhibition of viral replication with viral load falling below detectable limits 3 days after treatment commenced in airway epithelium. These effects were superior to those of ALS-8112. PC786 showed inhibitory activities against RSV-induced increases of CCL5, IL-6, double-strand DNA and mucin. The effects of PC786 were also confirmed in small airway epithelium. CONCLUSION AND IMPLICATIONS: Late therapeutic intervention with the RSV polymerase inhibitor, PC786, reduced the viral burden quickly in human airway epithelium. Thus, PC786 demonstrates the potential to be an effective therapeutic agent to treat active RSV infection.
Asunto(s)
Antivirales/farmacología , Epitelio/efectos de los fármacos , Mucosa Respiratoria/efectos de los fármacos , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Compuestos de Espiro/farmacología , Antivirales/química , Benzamidas , Benzazepinas , ARN Polimerasas Dirigidas por ADN/antagonistas & inhibidores , ARN Polimerasas Dirigidas por ADN/metabolismo , Relación Dosis-Respuesta a Droga , Epitelio/metabolismo , Epitelio/virología , Células HeLa , Humanos , Pruebas de Sensibilidad Microbiana , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/virología , Infecciones por Virus Sincitial Respiratorio/metabolismo , Compuestos de Espiro/química , Relación Estructura-Actividad , Replicación Viral/efectos de los fármacosRESUMEN
Polysaccharide, as a promising candidate to meet the medication requirement of ulcerative colitis (UC), is increasingly attracting extensive interest. Dendrobium officinale has been widely used to treat gastrointestinal sickness in the clinical treatment of Traditional Chinese Medicine. However, it remains largely unknown whether polysaccharides (DOPS) from Dendrobium officinale can treat UC. The purpose of this paper is to confirm therapeutic action of DOPS to UC and explored its underlying mechanisms. We noted that DOPS could dramatically improve clinical signs and symptoms, decrease mortality, alleviate colonic pathological damage, and reestablish the balance of pro- and anti-inflammatory cytokines in DSS-induced acute UC mice. Moreover, DOPS treatment could also markedly suppress the activation of NLRP3 inflammasome and ß-arrestin1 in vivo and in vitro. This study showed that DOPS possesses appreciable therapeutic effect to treat experimental acute UC mice. Its mechanism could be related to inhibition of NLRP3 inflammasome and ß-arrestin1 signaling pathways.
Asunto(s)
Antiinflamatorios/química , Colitis Ulcerosa/tratamiento farmacológico , Dendrobium/química , Medicamentos Herbarios Chinos/química , Polisacáridos/química , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Línea Celular , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Transducción de Señal , beta-Arrestina 1/metabolismoRESUMEN
A novel series of benzodihydrofuran derivatives was developed as potent MEK inhibitors through scaffold hopping based on known clinical compounds. Further SAR exploration and optimization led to another benzofuran series with good oral bioavailability in rats. One of the compounds EBI-1051 (28d) demonstrated excellent in vivo efficacy in colo-205 tumor xenograft models in mouse and is suitable for pre-clinical development studies for the treatment of melanoma and MEK associated cancers. Compared to AZD6244, EBI-1051 showed superior potency in some cancer cell lines such as colon-205, A549 and MDA-MB-231.