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1.
Sci Total Environ ; : 174835, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39025148

RESUMEN

The increasing prevalence of zinc pollution in marine ecosystems, primarily from industrial sources, has become a global environmental concern. This study addresses zinc toxicity in Chinese coastal waters, emphasizing the importance of considering environmental factors like salinity and temperature in establishing water quality criteria (WQC). Data collected from various marine regions underwent meticulous analysis, incorporating salinity corrections to derive more precise criteria values. The short-term water quality criteria for the Bohai Sea, Yellow Sea, East China Sea, and South China Sea were 94.0, 77.6, 84.2, and 118 µg/L under the salinity correction, respectively, and the long-term criteria was 4.10 µg/L. Ecological risk assessments employing diverse methodologies revealed varying levels of risk across sea areas, underscoring the nuanced nature of zinc pollution's impact on marine ecosystems. Greater acute and chronic risk of zinc ions observed in the Yellow Sea region. These findings highlight the necessity for tailored management strategies to safeguard local marine life against zinc-induced environmental threats. These findings underscore the imperative need for tailored management strategies to protect local marine life from the environmental threats posed by zinc.

2.
ACS Macro Lett ; 13(7): 882-888, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38953383

RESUMEN

We report a "grafting to" method for stably grafting high-molecular-weight polymer brushes on both active and inert surfaces using tadpole-like single-chain particles (TSCPs) with an interactive "head" as grafting units. The TSCPs can be efficiently synthesized through intrachain cross-linking one block of a diblock copolymer; the "head" is the intrachain cross-linked single-chain particle, and the "tail" is a linear polymer chain that has a contour length up to micrometers. When grafted to a surface, the "head", integrating numerous interacting groups, can synergize multiple weak interactions with the surface, thereby enabling stable grafting of the "tail" on both active and traditionally challenging inert surfaces. Because the structural parameters and composition of the "heads" and "tails" can be separately adjusted over a wide range, the interactivity of the "heads" with the surface and properties of the brushes can be controlled orthogonally, accomplishing surface brushes that cannot be achieved by existing methods.

3.
Front Vet Sci ; 11: 1395327, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887536

RESUMEN

Equine influenza (EI) is a severe infectious disease that causes huge economic losses to the horse industry. Spatial epidemiology technology can explore the spatiotemporal distribution characteristics and occurrence risks of infectious diseases, it has played an important role in the prevention and control of major infectious diseases in humans and animals. For the first time, this study conducted a systematic analysis of the spatiotemporal distribution of EI using SaTScan software and investigated the important environmental variables and suitable areas for EI occurrence using the Maxent model. A total of 517 occurrences of EI from 2005 to 2022 were evaluated, and 14 significant spatiotemporal clusters were identified. Furthermore, a Maxent model was successfully established with high prediction accuracy (AUC = 0.920 ± 0.008). The results indicated that annual average ultraviolet radiation, horse density, and precipitation of the coldest quarter were the three most important environmental variables affecting EI occurrence. The suitable areas for EI occurrence are widely distributed across all continents, especially in Asia (India, Mongolia, and China) and the Americas (Brazil, Uruguay, USA, and Mexico). In the future, these suitable areas will expand and move eastward. The largest expansion is predicted under SSP126 scenarios, while the opposite trend will be observed under SSP585 scenarios. This study presents the spatial epidemiological characteristics of EI for the first time. The results could provide valuable scientific insights that can effectively inform prevention and control strategies in regions at risk of EI worldwide.

4.
Vet Res Commun ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874832

RESUMEN

Mastitis is one of the most serious diseases that threatens the health of dairy animals. The somatic cell count (SCC) in milk is widely used to monitor mastitis. This study aimed to reveal the diversity of microorganisms in buffalo milk with high somatic cell count (SCC ≥ 3 × 105 cells/mL, n = 30) and low somatic cell count (SCC ≤ 5 × 104 cells/mL, n = 10), and identify the dominant bacteria that cause mastitis in a local buffalo farm. We also investigated the potential method to treat bacterial mastitis. The V3-V4 region of 16 S rDNA was sequenced. Results showed that, compared to the milk with low SCC, the high SCC samples showed lower microbial diversity, but a high abundance of bacteria and operational taxonomic units (OTUs). By in vitro isolation and culture, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae were found to be the leading pathogens, which is consistent with the 16 S rDNA sequencing data. We further isolated 3 of the main pathogens and established a pathogen detection method based on ELISA. In addition, the antibacterial effects of 10 antimicrobials and 15 Chinese herbal extracts were also investigated. Results showed that the microbial has developed tolerance to several of the antimicrobials. While the water extracts of Chinese herbal medicine such as Galla Chinensis, Coptis chinensis Franch, Terminalia chebula Retz, and Sanguisorba officinalis L can effectively inhibit the growth of main pathogens. This study provides novel insight into the microbial diversity in buffalo milk and a reference for the prevention, diagnosis, and treatment of mastitis.

5.
ACS Omega ; 9(10): 11925-11941, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38496984

RESUMEN

Despite the previous preparation of aconine hydrochloride monohydrate (AHM), accurate determination of the crystal's composition was hindered by severely disordered water molecules within the crystal. In this study, we successfully prepared a new dihydrate form of the aconine hydrochloride [C25H42NO9+Cl-·2(H2O), aconine hydrochloride dihydrate (AHD)] and accurately refined all water molecules within the AHD crystal. Our objective is to elucidate both water-chloride and water-water interactions in the AHD crystal. The crystal structure of AHD was determined at 136 K using X-ray diffraction and a multipolar atom model was constructed by transferring charge-density parameters to explore the topological features of key short contacts. By comparing the crystal structures of dihydrate and monohydrate forms, we have observed that both AHD and AHM exhibit identical aconine cations, except for variations in the number of water molecules present. In the AHD crystal, chloride anions and water molecules serve as pivotal connecting hubs to establish three-dimensional hydrogen bonding networks and one-dimensional hydrogen bonding chain; both water-chloride and water-water interactions assemble supramolecular architectures. The crystal packing of AHD exhibits a complete reversal in the stacking order compared to AHM, thereby emphasizing distinct disparities between them. Hirshfeld surface analysis reveals that H···Cl- and H···O contacts play a significant role in constructing the hydrogen bonding network and chain within these supramolecular architectures. Furthermore, topological analysis and electrostatic interaction energy confirm that both water-chloride and water-water interactions stabilize supramolecular architectures through electrostatic attraction facilitated by H···Cl- and H···O contacts. Importantly, these findings are strongly supported by the existing literature evidence. Consequently, navigating these water-chloride and water-water interactions is imperative for ensuring storage and safe processing of this pharmaceutical compound.

6.
Aquat Toxicol ; 270: 106883, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38503038

RESUMEN

The escalating use of silver nanoparticles (AgNPs) across various sectors for their broad-spectrum antimicrobial capabilities, has raised concern over their potential ecotoxicological effects on aquatic life. This study explores the impact of AgNPs (50 µg/L) on the marine clam Ruditapes philippinarum, with a particular focus on its gills and digestive glands. We adopted an integrated approach that combined in vivo exposure, biochemical assays, and transcriptomic analysis to evaluate the toxicity of AgNPs. The results revealed substantial accumulation of AgNPs in the gills and digestive glands of R. philippinarum, resulting in oxidative stress and DNA damage, with the gills showing more severe oxidative damage. Transcriptomic analysis further highlights an adaptive up-regulation of peroxisome-related genes in the gills responding to AgNP-induxed oxidative stress. Additionally, there was a noteworthy enrichment of differentially expressed genes (DEGs) in key biological processes, including ion binding, NF-kappa B signaling and cytochrome P450-mediated metabolism of xenobiotics. These insights elucidate the toxicological mechanisms of AgNPs to R. philippinarum, emphasizing the gill as a potential sensitive organ for monitoring emerging nanopollutants. Overall, this study significantly advances our understanding of the mechanisms driving nanoparticle-induced stress responses in bivalves and lays the groundwork for future investigations into preventing and treating such pollutants in aquaculture.


Asunto(s)
Bivalvos , Nanopartículas del Metal , Contaminantes Químicos del Agua , Animales , Antioxidantes/metabolismo , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Plata/análisis , Contaminantes Químicos del Agua/toxicidad , Bivalvos/metabolismo , Branquias
7.
Toxics ; 11(10)2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37888712

RESUMEN

Aquatic life criteria (ALC) serve as the scientific foundation for establishing water quality standards, and in China, significant strides have been made in the development of freshwater ALC. This comprehensive review traces the evolution of China's WQC, focusing on the methodological advancements and challenges in priority pollutants selection, test organism screening, and standardized ecotoxicity testing protocols. It also provides a critical evaluation of quality assurance measures, data validation techniques, and minimum data requirements essential for ALC assessments. The paper highlights China's technical guidelines for deriving ALC, and reviews the published values for typical pollutants, assessing their impact on environmental quality standards. Emerging trends and future research avenues are discussed, including the incorporation of molecular toxicology data and the development of predictive models for pollutant toxicity. The review concludes by advocating for a tiered WQC system that accommodates China's diverse ecological regions, thereby offering a robust scientific basis for enhanced water quality management.

8.
Sci Total Environ ; 905: 166690, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-37704150

RESUMEN

Water quality criteria (WQC) for zinc oxide nanoparticles (ZnO NPs) are crucial due to their extensive industrial use and potential threats to marine organisms. This study conducted toxicity tests using marine organisms in China, revealing LC50 or EC50 values for ZnO NPs ranging from 0.36 to 95.6 mg/L across seven species, among which the salinity lake crustacean zooplankton Artemia salina exhibited the highest resistance, while diatom Phaeodactylum tricornutum the most sensitive. Additionally, the EC10 or maximum acceptable toxicant concentration (MATC) values for ZnO NPs were determined for five species, ranging from 0.03 to 2.82 mg/L; medaka Oryzias melastigma demonstrated the highest tolerance, while mysis shrimp Neomysis awatschensis the most sensitive. Based on the species sensitivity distribution (SSD) method, the derived short-term and long-term WQC for ZnO NPs were 138 µg/L and 8.37 µg/L, respectively. These values were further validated using the sensitive species green algae Chlorella vulgaris, confirming effective protection. There is no environmental risk observed in Jiaozhou Bay, Yellow River Estuary and Laizhou Bay in the northern coastal seas of China. This study provides important reference data for the establishment of water quality standards for nanoparticles.


Asunto(s)
Chlorella vulgaris , Diatomeas , Nanopartículas , Contaminantes Químicos del Agua , Óxido de Zinc , Óxido de Zinc/toxicidad , Organismos Acuáticos , Nanopartículas/toxicidad , Agua de Mar , Medición de Riesgo , China , Contaminantes Químicos del Agua/toxicidad
9.
Front Microbiol ; 14: 1071603, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37275170

RESUMEN

Modifying and transforming natural antibacterial products is a novel idea for developing new efficacious compounds. Phillygenin has an inhibitory effect on H. pylori. The aim of the present study was to prepare a phillygenin derivative (PHI-Der) through demethylation and hydroxylation. The minimum inhibitory concentration of 18 strains of H. pylori from different sources was 8-32 µg/mL in vitro, and the activity increased 2-8 times than that of phillygenin. PHI-Der could significantly inhibit the colonization of H. pylori in vivo, reduce the inflammatory response, and promote the repair of inflammatory damage. Further, we used SwissTargetPrediction to predict that its main targets are ALOX5, MCL1, and SLC6A4, and find that it can inhibit bacterial biofilm formation and reduce bacterial infection of cells. It can enhance the intracellular oxidative capacity of H. pylori to inhibit H. pylori growth. Further, it could prevent the oxidation of H. pylori-infected cells and reduce the inflammatory response, which plays a role in protection. In conclusion, compared to phillygenin, PHI-Der had better antibacterial activity and was more effective in treating H. pylori infection. It has characteristics of high safety, specificity, resistance to drug resistance and better antibacterial activity than phillygenin, it's a good antioxidant for host cells.

10.
World J Gastroenterol ; 29(18): 2818-2835, 2023 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-37274067

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) is the main pathogen that causes a variety of upper digestive diseases. The drug resistance rate of H. pylori is increasingly higher, and the eradication rate is increasingly lower. The antimicrobial resistance of H. pylori is an urgent global problem. It has been confirmed that Banxia Xiexin decoction (BXXXT) demonstrates the effects of treating gastrointestinal diseases, inhibiting H. pylori and protecting gastric mucosa. The purpose of the present study is to further explore the therapeutic effects of BXXXT on drug-resistant H. pylori. AIM: To confirm that BXXXT demonstrates therapeutical effects in vivo and in vitro on gastritis mice with drug-resistant H. pylori and explain its mechanism to provide an experimental basis for promoting the application of BXXXT. METHODS: The aqueous extract of BXXXT was gained by water decocting method. The inhibitory effect of the aqueous extract on H. pylori was detected by dilution in vitro; drug-resistant H. pylori cells were used to build an acute gastritis model in vivo. Thereafter, the model mice were treated with the aqueous extract of BXXXT. The amount of H. pylori colonization, the repair of gastric mucosal damage, changes of inflammatory factors, apoptosis, etc., were assessed. In terms of mechanism exploration, the main medicinal compositions of BXXXT aqueous extract and the synergistic bacteriostatic effects they had demonstrated were analyzed using mass spectrometry; the immune function of peripheral blood cells such as CD3+ T and CD4+ T of mice with gastritis before and after treatment with BXXXT aqueous extract was detected using a flow cytometry; the H. pylori transcriptome and proteome after treatment with BXXXT aqueous extract were detected. Differently expressed genes were screened and verification was performed thereon with knockout expression. RESULTS: The minimum inhibitory concentration of BXXXT aqueous extract against H. pylori was 256-512 µg/mL. A dose of 28 mg/kg BXXXT aqueous extract treatment produced better therapeutical effects than the standard triple therapy did; the BXXXT aqueous extract have at least 11 ingredients inhibiting H. pylori, including berberine, quercetin, baicalin, luteolin, gallic acid, rosmarinic acid, aloe emodin, etc., of which berberine, aloe emodin, luteolin and gallic acid have a synergistic effect; BXXXT aqueous extract was found to stimulate the expressions of CD3+ T and CD4+ T and increase the number of CD4+ T/CD8+ T in gastritis mice; the detection of transcriptome and proteome, quantitative polymerase chain reaction, Western blotting and knockout verification revealed that the main targets of BXXXT aqueous extract are CFAs related to urea enzymes, and CagA, VacA, etc. CONCLUSION: BXXXT aqueous extract could demonstrate good therapeutic effects on drug-resistance H. pylori in vitro and in vivo and its mechanism comes down to the synergistic or additional antibacterial effects of berberine, emodin and luteolin, the main components of the extract; the extract could activate the immune function and enhance bactericidal effects; BXXXT aqueous extract, with main targets of BXXXT aqueous extract related to urease, virulence factors, etc., could reduce the urease and virulence of H. pylori, weaken its colonization, and reduce its inflammatory damage to the gastric mucosa.


Asunto(s)
Berberina , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Ratones , Animales , Ureasa/metabolismo , Berberina/farmacología , Luteolina/metabolismo , Luteolina/farmacología , Luteolina/uso terapéutico , Proteoma/metabolismo , Mucosa Gástrica/microbiología , Infecciones por Helicobacter/microbiología , Proteínas Bacterianas/genética
11.
Plant Sci ; 327: 111547, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36462682

RESUMEN

The brown planthopper (BPH; Nilaparvata lugens) is a piercing-sucking insect pest specific to rice plants and may cause severe declines in rice yields. Therefore, it is of great theoretical significance and practical application value to elucidate the molecular mechanism of rice resistance to BPH. Previous studies have shown that an ethylene (ET) signaling pathway gene, OsEBF1, positively regulates BPH resistance in rice. OsEBF1 is an E3 ligase that mediates the degradation of another ET pathway gene, OsEIL1. OsEBF2 is the homologous gene of OsEBF1, and the sequence identity between the two genes is 78.5%. Our results indicated that OsEBF2 can directly interact with OsEIL1 and positively regulate rice resistance to BPH. More importantly, there were no obvious differences in agronomic traits between WT and OsEBF2OE transgenic lines. The resistance mechanism of the OsEBF2 gene may be to reduce the content of ET in rice by inhibiting the expression of ethylene response factor genes. This study revealed that OsEBF2 is an F-box protein that positively regulates the rice resistance to BPH and can be used as an effective target gene for rice BPH resistance breeding.


Asunto(s)
Hemípteros , Oryza , Animales , Etilenos/metabolismo , Hemípteros/fisiología , Oryza/metabolismo , Fitomejoramiento
12.
Nanotechnology ; 31(47): 475706, 2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-32674089

RESUMEN

The electrical properties of individual multiwall carbon nanotubes (CNTs) filled with Fe3C nanowires (Fe-CNTs) grown by chemical vapor deposition were investigated. The individual Fe-CNTs were measured by two-probe configuration in a scanning electron microscope, in which one probe was used to contact one end of the nanotubes and the other varied its contact position to measure the resistance along the Fe-CNTs. The data suggest that the ferromagnetic nanowires and the CNTs were well connected into a conduction network, and the resistance of the individual Fe-CNTs decreased as the filling rate increased. Analysis shows that the encapsulated ferromagnetic nanowires played a profound part in determining the electrical behavior of individual Fe-CNTs. The results may be useful for understanding of electronic transport of individual Fe-CNTs and applications based on individual Fe-CNTs.

13.
Hepatol Res ; 49(6): 695-704, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30811072

RESUMEN

AIM: To assess the level of hepatic oxidative damage and its correlation with clinical severity in biliary atresia (BA), and to understand BA mitochondrial gene sequencing. METHODS: Forty-eight BA patients and 28 control subjects (20 hepatoblastoma and 8 cholestasis patients) were enrolled. Hepatic oxidative damage was assessed by the expression of oxidation and antioxidant genes, and the correlation between oxidative damage and BA incidence, liver inflammation, and fibrosis was evaluated. Moreover, 8-hydroxyguanine (8-OHdG), mitochondrial DNA (mtDNA) copy number, and mitochondrial gene sequences were determined to evaluate oxidative mtDNA damage in BA. RESULTS: The expression of oxidation gene cytochrome b-245 beta chain (CYBB) in BA was significantly increased and patients with a higher CYBB expression had the higher risk of BA incidence, liver inflammation, and cirrhosis. However, the expression of antioxidant genes was significantly decreased, and glutathione S-transferase alpha 1 (GSTA1) negatively correlated with BA incidence and cirrhosis. When GSTA1 mRNA expression was <0.5487, the sensitivity was 80.85% and the specificity was 80% for BA diagnosis. Moreover, 8-OHdG was increased, whereas mtDNA copy number was significantly decreased in BA. Using mitochondrial gene sequencing, 10 mutation sites were identified, and one family showed a maternal inheritance in genetic loci 15 326. CONCLUSIONS: In BA, oxidative damage positively correlated with BA incidence, liver inflammation, and cirrhosis. GSTA1 could be a novel diagnostic indicator. Genetic loci 15 326 could be a maternal genetic mutation site. Taken together, antioxidation therapy after Kasai surgery might have great potential in relieving liver inflammation and fibrosis in BA patients.

15.
BMJ Paediatr Open ; 2(1): e000339, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30397671

RESUMEN

OBJECTIVE: To validate a three-step protocol that assesses the clinical risk associated with using blood glucose monitoring systems (BGMS) in neonates for the management of dysglycaemia. METHOD: The three-step validation approach included confirmation of the accuracy of the reference method using National Institute of Standards and Technology (NIST) glucose standards, assessment of analytical risk performed on whole blood collected from paediatric patients routinely tested for glucose and a clinical risk assessment performed using heel stick capillary samples collected from 147 new-born babies and neonates admitted to intensive care. BGMS glucose measurements were compared with the NIST aligned laboratory reference method. RESULTS: The accuracy of the laboratory reference method was confirmed with the NIST standards. Specificity studies demonstrated that the accuracy of one of the BGMS was affected, particularly, in the hypoglycaemic range, by known interference factors including haematocrit, ascorbic acid, lactose, galactose, N-acetylcysteine and glutathione. The accuracy of the other BGMS was unaffected. The clinical performance of this BGMS in neonates met the system accuracy criteria of Clinical and Laboratory Standards Institute (CLSI) POCT 12-A3 standard for evaluating hospital BGMS with 95.1% of glucose measurements within±0.67 mmol/L for samples ≤5.55 mmol/L and 95.6% within±12.5% for samples>5.55 mmol/L. CONCLUSIONS: This three-step validation protocol provides a challenging approach for determining the accuracy and reliability of BGMS for managing dysglycaemia in neonates. StatStrip BGMS achieved analytical and clinical performance criteria confirming its suitability for use in neonates. We advocate that this validation approach should be considered for performance evaluations of both BGMS and continuous glucose monitoring systems going forward.

16.
Hortic Res ; 5: 48, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30181888

RESUMEN

Cymbidium has been artificially domesticated for centuries in Asia, which produced numerous cultivated varieties. Flowers with stamenoid tepals or those with multiple tepals have been found in different species of Cymbidium; however, the molecular basis controlling the formation of these phenotypes is still largely unknown. Previous work demonstrated that AGAMOUS/AG lineage MADS genes function in floral meristem determinacy as well as in reproductive organs development in both dicots and monocots, indicating a possible relationship with the origin of two flower varieties in Cymbidium. Here, we characterized and analyzed two AG lineage paralogues, CsAG1 and CsAG2, from Cymbidium sinense, both of which were highly expressed in the gynostemium column of a standard C. sinense. Interestingly, we detected ectopic expression of CsAG1 rather than CsAG2 in all floral organs of a stamenoid-tepal variety and significant down-regulation of CsAG1 in a variety with multiple tepals. Over-expression of CsAG1 in wild type Arabidopsis resulted in petal-to-stamen homeotic conversion, suggesting a conserved C-function of CsAG1 in the development of Cymbidium flower. Altogether, our results supported a hypothesis that disruption of a single AG-like factor would be associated with the formation of two domesticated varieties in C. sinense.

17.
Plant Cell Physiol ; 59(10): 2064-2074, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-29986119

RESUMEN

An orchid flower exhibits a zygomorphic corolla with a well-differentiated labellum. In Cymbidium sinense, many varieties with peloric or pseudopeloric flowers have been bred during centuries of domestication. However, little is known about the molecular basis controlling orchid floral zygomorphy and the origin of these varieties. Here, we studied the floral morphogenesis of C. sinense and transcriptome-wide enriched differentially expressed genes among different varieties. The floral zygomorphy of C. sinense is established in the early developmental process. Out of 27 MIKCC-MADS factors, we found two homeotic MADS genes whose expression was down-regulated in peloric varieties but up-regulated in pseudopeloric varieties. CsAP3-2 expressed in the inner floral organs co-operates with a labellum-specific factor CsAGL6-2, asymmetrically promoting the differentiation of inner tepals. Interestingly, we detected exon deletions on CsAP3-2 in peloric varieties, indicating that loss of B-function results in the origin of peloria. Additional petaloid structures developed when we ectopically expressed these genes in Arabidopsis, suggesting their roles in floral morphogenesis. These findings indicate that the interplay among MADS factors would be crucial for orchid floral zygomorphy, and mutations in these factors may have maintained during artificial selection.


Asunto(s)
Orchidaceae/genética , Proteínas de Plantas/metabolismo , Transcriptoma/genética , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Filogenia , Fitomejoramiento , Proteínas de Plantas/genética
18.
Pharmazie ; 70(2): 110-6, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25997251

RESUMEN

Taspoglutide has elicited a long-lasting glycemic control effect with favorable body weight loss. The objective of this study was to develop a quantitative model to delineate the net efficacy of taspoglutide on body weight (WT) loss from the response of placebo in type 2 diabetes patients, and further find pharmacodynamic potency of taspoglutide for half of maximum reduction response of WT. Several PD data about taspoglutide treatments for type 2 diabetes patients were digitalized from the published papers. The model based metaanalysis (MBMA) study for WT loss was performed with Monolix 4.3 software. The MBMA successfully described the effects of placebo and taspoglutide on the pharmacological index of WT loss in clinical trials. The pharmacodynamic potency (41.7 pmol/l) produced 50% of maximum response of WT (-1.85 kg) from the responses of placebo (-1.33 kg). The longitudinal MBMA could be utilized to quantitatively describe the efficacy of taspoglutide on body weight loss and may lead to a clinical guideline for treatment of type 2 diabetes patients in the future.


Asunto(s)
Péptidos/farmacología , Pérdida de Peso/efectos de los fármacos , Algoritmos , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Modelos Estadísticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos
19.
J Pharmacol Sci ; 127(2): 170-80, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25727954

RESUMEN

A hybrid pharmacokinetic/pharmacodynamic (PK/PD) model with extended-release (ER) process and target mediated drug disposition (TMDD) was developed for exenatide ER to account for its complex absorption process and glucagon-like peptide 1 receptor (GLP-1R)-mediated non-linear PK behaviors along with its influences to fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Using hybrid PK/PD model, simulations were done to explore the potential dosing regimens which could achieve likelihood of more pharmacodynamic exposure with respect to FPG and HbA1c over a much shorter period compared with the currently used treatment protocol. The mean PK/PD data about exenatide ER for type 2 diabetes mellitus (T2DM) were digitized from the publications, and the hybrid PK/PD model was performed using the Monolix 4.3 program. The plasma concentration-time and FPG/HbA1c-time profiles for exenatide ER subcutaneously administrated to patients with T2DM were well described by this hybrid model. Monte Carlo simulation was applied to mimic the PK profiles when higher loading dose 7.5 and 5.0 mg exenatide ER were subcutaneously administrated with different dosing intervals at the first 3 weeks of 30-week treatment. Two potentially optimizing schedules could improve the likelihood of achieving much more FPG and HbA1c exposures than currently used clinical treatment protocol.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Metaanálisis como Asunto , Péptidos/administración & dosificación , Péptidos/farmacocinética , Ponzoñas/administración & dosificación , Ponzoñas/farmacocinética , Glucemia , Preparaciones de Acción Retardada , Diabetes Mellitus Tipo 2/sangre , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Exenatida , Ayuno , Hemoglobina Glucada/metabolismo , Humanos , Inyecciones Subcutáneas , Modelos Biológicos , Método de Montecarlo
20.
Zhongguo Zhong Yao Za Zhi ; 39(17): 3371-5, 2014 Sep.
Artículo en Chino | MEDLINE | ID: mdl-25522631

RESUMEN

OBJECTIVE: To investigate the regulation of Cha Gan Beng Ga on the activity of biomarker PGC-1α in vivo and in vitro, and lay the foundation for studying the efficacy result of Cha Gan Beng Ga on xenograft tumor model and extracting active constituents. METHOD: (1) The coarse powder of Cha Gan Beng Ga was extracted with 70% ethanol solution through heating and refluxing, and finally was used to freeze dry powder. (2) 50 mg x kg(-1) of freeze-dried power was orally administrated to KM and C57BL/6J mice once daily, lasting for 5 consecutive days; different concentrations of extracted materials was given to non-small cell lung cells A549. (3) The expression level of PGC-1α mRNA was quantitatively determined in lung tissue of mice and non-small cell lung cells A549. RESULT: The expression levels of PGC-1α in lung tissue of different mice strains had an increasing tendency. Furthermore, the expression levels of PGC-1α in non-small cell lung cells A549 also had an increasing tendency, showing dose and time-dependent relationships. CONCLUSION: Mongolian Medicine Cha Gan Beng Ga could induce the over-expression of PGC-1α mRNA in lung tissue of mice and in non-small cell lung cells A549. The present results will lay foundation for studying the efficacy result of antitumor and active constitutes in future.


Asunto(s)
Aconitum/química , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Medicina Tradicional Mongoliana , Extractos Vegetales/farmacología , Factores de Transcripción/genética , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos C57BL , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo
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