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1.
Proc Natl Acad Sci U S A ; 120(20): e2220353120, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37155875

RESUMEN

Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females.


Asunto(s)
Neuropéptidos , Estrés Psicológico , Animales , Femenino , Ratones , Giro del Cíngulo , Privación Materna , Neuropéptidos/metabolismo , Receptores de Orexina/genética , Orexinas/genética , Orexinas/metabolismo
2.
Yi Chuan ; 45(10): 922-932, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37872114

RESUMEN

This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.


Asunto(s)
Genoma , Modelos Genéticos , Porcinos/genética , Animales , Fenotipo , Genómica/métodos , Genotipo , Polimorfismo de Nucleótido Simple
3.
J Gene Med ; 22(7): e3182, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32166848

RESUMEN

BACKGROUND: Hepatoblastoma is a rare malignancy originating from pluripotent stem cells with unknown etiology. An understanding of the etiology in pediatric hepatoblastoma has been hampered by the unavailability of sufficient patient samples. To date, only a few epidemiological studies with small sample sizes have been performed investigating risk factors for hepatoblastoma. TP53 and pri-miR-34b/c genes are implicated in the tumorigenesis, yet the role of their polymorphisms in hepatoblastoma susceptibility remains unknown. METHODS: We conducted a seven-center case-control study to explore the genetic variants predisposing to hepatoblastoma susceptibility. In our study, we genotyped two functional polymorphisms, the TP53 rs1042522 C>G (Arg72Pro) and miR-34b/c rs4938723 T>C, in 313 cases and 1446 controls using the TaqMan method. RESULTS: Single loci analysis showed that neither TP53 rs1042522 C>G, nor miR-34b/c rs4938723 T>C significantly modified hepatoblastoma risk. In the stratification analysis, we identified that the miR-34b/c rs4938723 TC/CC genotypes were associated with a decreased risk in patients with clinical stages III + IV hepatoblastoma (adjusted odds ratio = 0.53, 95% confidence interval = 0.33-0.84, P=0.007] compared to the rs4938723 TT genotype. Subsequent analysis further showed that the combination of TP53 and miR-34b/c variant genotypes had no impact on susceptibility hepatoblastoma. CONCLUSIONS: Taken together, TP53 rs1042522 C>G and miR-34b/c rs4938723 T>C may not confer hepatoblastoma susceptibility. These findings may aid in our understanding of the genetic etiology of hepatoblastoma.


Asunto(s)
Predisposición Genética a la Enfermedad , Hepatoblastoma/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple , Proteína p53 Supresora de Tumor/genética , Factores de Edad , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Estadificación de Neoplasias , Oportunidad Relativa , Factores de Riesgo , Factores Sexuales
4.
Bioconjug Chem ; 31(1): 51-63, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31830418

RESUMEN

The traditional antibiotics have specific intracellular targets and disinfect in chemical ways, and the drug-resistance induced by the antibiotics has grown into an emerging threat. It is urgent to call for novel strategies and antibacterial materials to control this situation. Herein, we report a class of silver-decorated nanocomposite AgNPs@PCL-b-AMPs as potent nanoantibiotic, constructed by ring-opening polymerization of the monomers ε-caprolactone, Z-Lys-N-carboxyanhydrides (NCAs), and Phe-NCAs, then decorated with AgNPs, and characterized by SEM, TEM, and DLS. The biological assays revealed that the nanocomposite possessed strong antibacterial efficacy against both Gram-positive and Gram-negative bacteria including clinical isolated bacteria MRSA, VRE, P. aeruginosa, and K. pneumonia, exhibiting a MIC value range in 2-8 µg/mL. Importantly, the S. aureus and P. aeruginosa treated with the nanocomposite did not show drug-resistance even after 21 passages. Also, in vivo anti-infective assays showed that the nanocomposite was able to effectively kill bacteria in the infected viscera of mice. The study of the sterilization mechanism showed that the nanocomposite exhibited a multimodal antimicrobial mechanism, including irreversibly damaging the membrane structure, making the leakage of intracellular ions and subsequently inducing generation of the reactive oxygen species (ROS), ultimately sterilizing the bacteria. The nanocomposite exhibits effective broad-spectrum antibacterial properties and shows low toxicity to the mammalian cells/animal. Overall, the AgNPs@PCL-b-AMPs gained in this work show great potential as a highly promising antibacterial material for biomedical applications including drug-resistant bacterial infection.


Asunto(s)
Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Nanopartículas del Metal , Poliésteres/farmacología , Plata/farmacología , Animales , Antibacterianos/química , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Poliésteres/química , Poliésteres/uso terapéutico , Plata/química , Plata/uso terapéutico
5.
J Cell Biochem ; 120(1): 658-670, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30203578

RESUMEN

Emerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole-genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non-cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region-5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection.


Asunto(s)
Neoplasias de la Mama/genética , Metilación de ADN/genética , Detección Precoz del Cáncer , Genoma Humano/genética , Proteínas de Homeodominio/genética , Factor I del Crecimiento Similar a la Insulina/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Factores de Transcripción/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , Metilación de ADN/efectos de los fármacos , Bases de Datos de Ácidos Nucleicos , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células MCF-7 , Persona de Mediana Edad , Ftalimidas/farmacología , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismo , Transcriptoma/genética , Triptófano/análogos & derivados , Triptófano/farmacología , Regulación hacia Arriba/genética
6.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2124-2130, 2019 May.
Artículo en Zh | MEDLINE | ID: mdl-31355571

RESUMEN

The Shenghua Decoction recorded in Fu Qing Zhu's Gynaecology,is a commonly used postpartum prescription,widely used in treating postpartum and gynecological diseases. However,its mechanism of action in treating lower abdominal pain remains unclear. In this paper,network pharmacology was used to explore the mechanism of Shenghua Decoction in the treatment of lower abdomen pain,so as to provide data support for better clinical application of Shenghua Decoction. The drug targets of lower abdominal pain and Shenghua Decoction were retrieved in SymMap. String and Cytoscape were adopted for enrichment analysis to construct the disease-drug-target biological network. Relevant gene search results showed that there were 400 targets in Shenghua Decoction,11 of which coincided with the disease genes of lower abdomen pain. In String analysis,18 gene interactions were obtained. Gene modularizationbased analysis results indicated that one module containing six genes was obtained after modularization processing. Furthermore,there were 170 enrichment results of biological process,2 enrichment results of molecular function and 30 enrichment results of KEGG pathways in String enrichment analysis. Shenghua Decoction may play a role in treating lower abdomen pain through neuro-endocrine-immune,metabolism and other means. Its mechanism may be achieved by accelerating the repair and growth of endometrial tissue cells,improving microcirculation,promoting endometrial cell renewal and inflammation subsidence,and accelerating uterine involution; at the same time,it can regulate the autoimmunity,regulate and control the function of some natural immune cells in the process of antiinfection by using signaling pathway,supplement the vital energy,and induce elimination of pathogens from the body,thereby achieving the effect of treating lower abdomen pain.


Asunto(s)
Dolor Abdominal/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Femenino , Ginecología , Humanos , Transducción de Señal
7.
Environ Microbiol ; 19(7): 2806-2818, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28557308

RESUMEN

High proportions of hypothetical proteins exist in genomic databases of fungi, including putative secretory proteins (PSPs) likely involved in fungal invasion and virulence. Here we characterize one of many PSPs revealed in the previous transcriptome of Beauveria bassiana (a fungal insect pathogen) infecting a global lepidopteran pest and name it vacuole-localized protein 4 (VLP4) because this small, domain-lacking protein (22.96 kDa) was specifically localized in the vacuoles of hyphal cells. Deletion of VLP4 resulted in repression of almost all genes acting in autophagy and central development pathways. Consequently, the deletion mutant formed no autophagosome in hyphal vacuoles and displayed severe defects in aerial conidiation. conidial hydrophobicity to the insect surface, and secretion of cuticle-degrading Pr1 proteases required for normal cuticle infection. Blastospore formation was inhibited in the submerged mutant culture mimic to insect haemolymph, and formation of hyphal bodies in vivo was delayed. The fungal virulence was attenuated in the absence of VLP4. These phenotypic defects were well restored by targeted gene complementation. Our findings unveil a vital role of VLP4 in B. bassiana and call attention to many more PSPs for new insights into the interactions of fungal insect pathogens with insects.


Asunto(s)
Autofagia/fisiología , Beauveria/genética , Beauveria/patogenicidad , Proteínas Fúngicas/genética , Factores de Virulencia/genética , Animales , Autofagia/genética , Hifa/metabolismo , Insectos/microbiología , Esporas Fúngicas/metabolismo , Virulencia/genética
8.
Fungal Genet Biol ; 105: 8-15, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28552321

RESUMEN

Cyclophilin B (CypB) was previously revealed as one of many putative secretory proteins in the transcriptome of Beauveria bassiana infection to a lepidopteran pest. Here we show a main localization of CypB in hyphal cell walls and septa and its essential role in the in vitro and in vivo asexual cycles of the fungal insect pathogen. Deletion of cypB reduced colony growth by 16-42% on two rich media and 30 scant media with different carbon or nitrogen sources. The deletion mutant suffered a delayed conidiation on a standard medium and a final 47% reduction in conidial yield, accompanied with drastic transcript depression of several key genes required for conidiation and conidial maturation. The mutant conidia required 10h longer to germinate 50% at optimal 25°C than wild-type conidia. Intriguingly, cultivation of the mutant conidia in a trehalose-peptone broth mimic to insect hemolymph resulted in 83% reduction in blastospore yield but only slight decrease in biomass level, indicating severe defects in transition of hyphae to blastospores. LT50 for the deletion mutant against Galleria mellonella larvae through normal cuticle infection was prolonged to 7.4d from a wild-type estimate of 4.7d. During colony growth, additionally, the deletion mutant displayed hypersensitivity to Congo red, menadione, H2O2 and heat shock but increased tolerance to cyclosporine A and rapamycin. All of changes were restored by targeted gene complementation. Altogether, CypB takes part in sustaining normal growth, aerial conidiation, conidial germination, dimorphic transition, stress tolerance and pathogenicity in B. bassiana.


Asunto(s)
Beauveria/crecimiento & desarrollo , Ciclofilinas/fisiología , Beauveria/genética , Beauveria/patogenicidad , Ciclofilinas/genética , Ciclofilinas/aislamiento & purificación , Mutagénesis , Reproducción Asexuada , Estrés Fisiológico , Virulencia
9.
J Hand Surg Am ; 41(9): e263-6, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27497801

RESUMEN

PURPOSE: To compare the outcomes and complications of open reduction and internal fixation using precontoured versus noncontoured plates for the treatment of midshaft clavicle fractures. METHODS: Open reduction and internal fixation using was performed on 130 patients with a midshaft clavicle fracture. Precontoured plates were used in 69 cases (group A) and noncontoured plates in 61 cases (group B). RESULTS: The average follow-up in both groups was approximately 21 months. There was a significant difference between the 2 groups in mean surgery duration and blood loss, although Disabilities of the Arm, Shoulder, and Hand and Constant-Murley Shoulder scores at final follow-up were similar. Plate removal was required in 44.9% (31 of 69) of the precontoured group and 65.6% (40 of 61) of the noncontoured group. The indication was prominence of the hardware in 27.5% (19 of 69) of the precontoured group and 54.1% (33 of 61) of the noncontoured. In both groups, body mass index was lower in patients requiring implant removal because of hardware prominence. A higher proportion of females in both groups required implant removal. CONCLUSIONS: Precontoured plates are associated with a lower rate of hardware removal. Body mass index and gender may be factors that influence the rate of hardware removal. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Asunto(s)
Placas Óseas , Clavícula/cirugía , Fijación Interna de Fracturas/efectos adversos , Fracturas Óseas/cirugía , Adulto , Clavícula/lesiones , Femenino , Fijación Interna de Fracturas/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
10.
Zhongguo Zhong Yao Za Zhi ; 40(23): 4573-84, 2015 Dec.
Artículo en Zh | MEDLINE | ID: mdl-27141666

RESUMEN

There are 250 species of Zanthoxylum (Rutaceae) in the world. This genus distributed in tropical and subtropical regions. Alkaloids are the major and representative ingredients in these plants including quinolines, isoquinolines, and amide alkaloids, with such biological activities as anti-tumor, anti-inflammatory, analgesic, anti-virus, anti-platelet aggregation, anti-bacteria and anti- oxidant. These species have been used for a long time to treat toothache, urinary and venereal diseases, lumbago and rheumatism. This review summarizes the chemical constituents and pharmacological activities from the Z. sppplants, in an effort to the systematic research and application of the alkaloids of this genus.


Asunto(s)
Alcaloides/química , Alcaloides/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Zanthoxylum/química , Animales , Humanos , Estructura Molecular
11.
Glycobiology ; 24(7): 638-48, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24727441

RESUMEN

O-Mannosylation dependent on the protein O-mannosyltransferase (Pmt) family is an essential post-translational modification process in eukaryotes, but their connection to the biocontrol potential of a filamentous entomopathogen against arthropod pests is not understood. Here, we characterized the functions of three Pmt orthologues (Pmt1, Pmt2 and Pmt4) in the Pmt family of Beauveria bassiana and found that they were positive, but differential, regulators of the fungal growth, conidiation, multi-stress tolerance and virulence. Three Pmt2 knockdown mutants (ΔPmt2 was lethal), ΔPmt1 and ΔPmt4 grew 20-79% slower on nutrition-rich and limited media. Their conidial yields on a standard medium were reduced by 17-62%, accompanied with delayed germination. All the mutants became significantly less tolerant to most stresses of cell wall perturbation, high osmolarity, oxidation, wet heat and UV-B irradiation during colony growth and conidial germination and lost virulence by 53-62% via cuticle infection, although their virulence via hemocoel injection was not affected. Strikingly, these phenotypic defects were accompanied with remarkable cell wall damage, including thinner cell wall, lower conidial hydrophobicity and altered cell wall composition. All the changes were well restored to wild-type levels by targeted Pmt1 or Pmt4 complementation. Our results indicate for the first time that Pmt1, Pmt2 and Pmt4 are all required for the full biocontrol potential of B. bassiana despite differential contributions.


Asunto(s)
Antifúngicos/farmacología , Beauveria/enzimología , Proteínas Fúngicas/metabolismo , Manosiltransferasas/metabolismo , Animales , Beauveria/efectos de los fármacos , Beauveria/genética , Beauveria/patogenicidad , Pared Celular/efectos de los fármacos , Pared Celular/genética , Proteínas Fúngicas/genética , Manosiltransferasas/genética , Mariposas Nocturnas/microbiología , Mutación , Oxidantes/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Esporas Fúngicas/genética , Esporas Fúngicas/crecimiento & desarrollo , Virulencia/genética
12.
Environ Microbiol ; 16(7): 2316-28, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24725588

RESUMEN

Phytochromes (Phy) in filamentous fungi are Group VIII histidine kinases that share a unique N-terminal photosensory core, but their functions are largely unknown. Here we show that Beauveria bassiana Phy (Bbphy) is functionally vital for growth, conidiation and multistress tolerance of the fungal entomopathogen lacking sexual stage. Colony growth of ΔBbphy was significantly slower in a nutrition-rich medium but faster in several minimal media. Conidial yield of ΔBbphy in the rich medium increased at the fitted rate of 3.4 × 10(7) conidia h(-1) white light in the light/dark cycles of 0:24 to 16:8 h, decreased greatly in the short-, long- and full-day cycles of red/far-red light, but was unaffected under full-day blue light. Moreover, ΔBbphy showed higher osmosensitivity, increased antioxidant capability, and decreased conidial thermotolerance and UV-B resistance, accompanied with downregulation of Hog1 phosphorylation and of four Hog1-related genes under osmotic stress, and upregulation of five superoxide dismutases and four catalases under oxidative stress. All the changes were restored by the gene complementation. Taken together, Bbphy controls conidiation by responding to daylight length and red/far-red light and regulates multistress responses perhaps because of an involvement in Hog1 pathway. Our findings highlight diverse functions of Bbphy in B. bassiana.


Asunto(s)
Beauveria/efectos de la radiación , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica/efectos de la radiación , Fitocromo/genética , Proteínas Quinasas/genética , Antioxidantes/metabolismo , Beauveria/genética , Beauveria/metabolismo , Catalasa/genética , Catalasa/metabolismo , Proteínas Fúngicas/metabolismo , Eliminación de Gen , Histidina Quinasa , Luz , Presión Osmótica , Estrés Oxidativo , Fosforilación , Fitocromo/metabolismo , Proteínas Quinasas/metabolismo , Esporas Fúngicas/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Virulencia/genética
13.
Zhong Yao Cai ; 37(6): 1093-5, 2014 Jun.
Artículo en Zh | MEDLINE | ID: mdl-25470975

RESUMEN

OBJECTIVE: To study the clinical effect of Dengzhanhua injection and Xiongqin injection combined with Xuesaitong to treat the elderly patients with acute cerebral infarction. METHODS: From March 2012 to March 2013,140 patients with acute cerebral infarction elderly patients were treated, as research subjects were randomly divided into two groups, the observation group and the control group,70 cases in each group. The control group were treated using Xuesaitong;The observation group using Dengzhanhua injection and Xiongqin injection combined with Xuesaitong. The changes of cerebral blood flow,plasma viscosity and platelet adhesion rate were com- pared before and after the treatment; Nerve function and living abilities of the two groups were recorded and compared; Cure rate of the two groups were compared. RESULTS: The cerebral blood flow,plasma viscosity and platelet adhesion rate had improved to some extent af- ter treatment both of the two groups, the degree of improvement in the observation group was significantly better than the control group (P <0. 01) ;Nerve function and living abilities of the observation group was significantly better than the control group(P <0. 05) ;Cure rate in the observation group was significantly higher than the control group(P <0. 01). CONCLUSION: Using Dengzhanhua injection and Xiongqin injection combined with Xuesaitong to treat elderly patients with acute cerebral infarction has significantly high curative rate, which can significantly improve patients' cerebral blood flow,plasma viscosity,platelet adhesion rate,nerve function and life skills.


Asunto(s)
Infarto Cerebral/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides , Humanos , Fitoterapia
14.
Acta Crystallogr C ; 69(Pt 5): 467-70, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23629892

RESUMEN

The title compound, poly[[µ4-5-carboxy-4-carboxylato-2-(pyridin-4-yl)-1H-imidazol-1-ido]disilver(I)], [Ag2(C10H5N3O4)]n, was synthesized by reacting silver nitrate with 2-(pyridin-4-yl)-1H-imidazole-4,5-dicarboxylic acid (H3PyIDC) under hydrothermal conditions. The asymmetric unit contains two crystallographically independent Ag(I) cations and one unique HPyIDC(2-) anion. Both Ag(I) cations are three-coordinated in distorted T-shaped coordination geometries. One Ag(I) cation is coordinated by one N and two O atoms from two HPyIDC(2-) anions, while the other is bonded to one O and two N atoms from two HPyIDC(2-) anions. It is interesting to note that the HPyIDC(2-) group acts as a µ4-bridging ligand to link the Ag(I) cations into a three-dimensional framework, which can be simplified as a diamondoid topology. The thermal stability and photoluminescent properties of the title compound have also been studied.

15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 30(6): 697-700, 2013 Dec.
Artículo en Zh | MEDLINE | ID: mdl-24327150

RESUMEN

OBJECTIVE: To analyze the status of HLA-DPA1 and DPB1 matching for unrelated donor-recipient pairs matched at high-resolution allele level for HLA-A, B, C, DRB1 and DQB1 loci. METHODS: A total of 76 unrelated donor-recipient pairs matching at allele level for HLA-A, B, C, DRB1 and DQB1 loci were subjected to HLA-DPA1 and DPB1 sequence-based typing (SBT). HLA-DPA1and DPB1 matching status at high-resolution allelic level was also analyzed. RESULTS: The allelic identity ratio for single HLA-DPA1 and DPB1 were 17.1% and 9.2%, respectively. HLA-DPA1 and DPB1 allelic identity ratio were both very low. The majority of unrelated donor-recipient pairs (73.7%) had an incompatibility at 1 HLA-DPA1 allele, 9.2% of pairs had an incompatibility at 2 DPA1 alleles. As for the high-polymorphic HLA-DPB1 gene, 57.9% of studied donor-recipient pairs had an incompatibility at 1 HLA-DPB1 allele, almost 1/3 (32.9%) of them were completely incompatible. When HLA-DPA1 and DPB1 genes were analyzed together, the donor-recipient pairs matched at 2/4 was the most common (51.4%), 4/4 allelic complete matched pairs accounted for 5.6%, and 0/4 matched pairs accounted for 8.3%. CONCLUSION: Our results indicated that the ratio of HLA-DPA1 and DPB1 complete match in the unrelated donor-recipient pairs matching at allelic level for HLA-A, B, C, DRB1 and DQB1 loci were very low. The effect of HLA-DPA1 and DPB1 matching status on clinical unrelated stem cell transplantation still needs to be elucidated.


Asunto(s)
Cadenas alfa de HLA-DP/genética , Cadenas beta de HLA-DP/genética , Cadenas beta de HLA-DQ/genética , Antígenos de Histocompatibilidad Clase I/genética , Donante no Emparentado , Alelos , Prueba de Histocompatibilidad/métodos , Humanos , Trasplante/métodos
16.
Int J Pharm ; 647: 123497, 2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-37827390

RESUMEN

Olaparib (OLA) is the first PARP inhibitor worldwide used for the treatment of ovarian cancer. However, the oral absorption of OLA is extremely limited by its poor solubility. Herein, pharmaceutical cocrystallization strategy was employed to optimize the physicochemical and pharmacokinetic properties. Four cocrystals of OLA with oxalic acid (OLA-OA), malonic acid (OLA-MA), fumaric acid (OLA-FA) and maleic acid (OLA-MLA) were successfully discovered and characterized. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the formation of cocrystals rather than salts, and the possible hydrogen bonding patterns were analyzed through molecular surface electrostatic potential calculations. The in vitro and in vivo evaluations indicate that all of the cocrystals demonstrate significantly improved dissolution performance, oral absorption and tabletability compared to pure OLA. Among them, OLA-FA exhibit sufficient stability and the most increased Cmax and AUC0-24h values that were 11.6 and 6.1 times of free OLA, respectively, which has great potential to be developed into the improved solid preparations of OLA.


Asunto(s)
Piperazinas , Cristalización/métodos , Fenómenos Químicos , Solubilidad , Difracción de Rayos X
17.
ACS Omega ; 7(34): 29909-29922, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36061679

RESUMEN

The overuse of antibiotics exacerbates the development of antibiotic-resistant bacteria, threatening global public health, while most traditional antibiotics act on specific targets and sterilize through chemical modes. Therefore, it is a desperate need to design novel therapeutics or extraordinary strategies to overcome resistant bacteria. Herein, we report a positively charged nanocomposite PNs-Cur with a hydrodynamic diameter of 289.6 nm, which was fabricated by ring-opening polymerization of ε-caprolactone and Z-Lys-N-carboxyanhydrides (NCAs), and then natural curcumin was loaded onto the PCL core of PNs with a nanostructure through self-assembly, identified through UV-vis, and characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Especially, the self-assembly dynamics of PNs was simulated through molecular modeling to confirm the formation of a core-shell nanostructure. Biological assays revealed that PNs-Cur possessed broad-spectrum and efficient antibacterial activities against both Gram-positive and Gram-negative bacteria, including drug-resistant clinical bacteria and fungus, with MIC values in the range of 8-32 µg/mL. Also, in vivo evaluation showed that PNs-Cur exhibited strong antibacterial activities in infected mice. Importantly, the nanocomposite did not indeed induce the emergence of drug-resistant bacterial strains even after 21 passages, especially showing low toxicity regardless of in vivo or in vitro. The study of the antibacterial mechanism indicated that PNs-Cur could indeed destruct membrane potential, change the membrane potential, and cause the leakage of the cytoplasm. Concurrently, the released curcumin further plays a bactericidal role, eventually leading to bacterial irreversible apoptosis. This unique bacterial mode that PNs-Cur possesses may be the reason why it is not easy to make the bacteria susceptible to easily produce drug resistance. Overall, the constructed PNs-Cur is a promising antibacterial material, which provides a novel strategy to develop efficient antibacterial materials and combat increasingly prevalent bacterial infections.

18.
Ecol Evol ; 12(3): e8714, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35356559

RESUMEN

Understanding the impacts and constraints of climate change on the geographical distribution of wild Akebia trifoliata is crucial for its sustainable management and economic development as a medicinal material or fruit. In this study, according to the first-hand information obtained from field investigation, the distribution and response to climate change of A. trifoliata were studied by the MaxEnt model and ArcGIS. The genetic diversity and population structure of 21 natural populations of A. trifoliata were studied by simple sequence repeat (SSR) markers. The results showed that the most important bioclimatic variable limiting the distribution of A. trifoliata was the Mean Temperature of Coldest Quarter (bio11). Under the scenarios SSP1-2.6 and SSP2-4.5, the suitable area of A. trifoliata in the world will remain stable, and the suitable area will increase significantly under the scenarios of SSP3-7.0 and SSP5-8.5. Under the current climate scenario, the suitable growth regions of A. trifoliata in China were 79.9-122.7°E and 21.5-37.5°N. Under the four emission scenarios in the future, the geometric center of the suitable distribution regions of Akebia trifoliata in China will move to the north. The clustering results of 21 populations of A. trifoliata analyzed by SSR markers showed that they had a trend of evolution from south to north.

19.
Cancer Innov ; 1(1): 70-79, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38089451

RESUMEN

Background: Glioma is one of the central nervous system (CNS) tumors in children, accounting for 80% of malignant brain tumors. Nucleotide excision repair (NER) is a vital pathway during DNA damage repair progression. Xeroderma pigmentosum group D (XPD) or excision repair cross-complementing group 2 (ERCC2) is a critical factor in the NER pathway, playing an indispensable role in the DNA repair process. Therefore, the genetic variants in XPD may be associated with carcinogenesis induced by defects in DNA repair. Methods: We are the first to conduct a multi-center case-control study to investigate the correlation between XPD gene polymorphisms and pediatric glioma risk. We chose three single nucleotide polymorphisms and genotyped them using the TaqMan assay. Results: Although there is no significant association of these genetic variations with glioma susceptibility, the stratified analysis revealed that in the subtype of astrocytic tumors, the rs13181 TG/GG genotype enhanced glioma risk than the TT genotype, and carriers with two to three genotypes also elevated the tumor risk than 0-1 genotypes. Conclusion: In conclusion, our findings provided an insight into the impact of XPD genetic variants on glioma risk.

20.
Curr Med Sci ; 42(4): 797-802, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35819658

RESUMEN

OBJECTIVE: Gliomas are the most common tumors in the central nervous system. The cancer susceptibility candidate 15 (CASC15) gene has been reported to be a susceptibility gene for several types of cancer. No studies have been carried out on the predisposing effect of CASC15 gene single nucleotide polymorphisms (SNPs) on glioma risk. METHODS: In order to determine whether CASC15 gene SNPs are involved in glioma susceptibility, the first association study in a relatively large sample, which consisted of 171 patients and 228 healthy controls recruited from China, was performed. The contribution of SNPs (rs6939340 A>G, rs4712653 T>C and rs9295536 C>A) to the risk of glioma was evaluated by multinomial logistic regression, based on the calculation of the odds ratio (OR) and 95% confidence interval (CI). RESULTS: In the single locus and combined analysis, it was revealed that the genetic risk score had no significant associations between CASC15 gene SNPs and glioma risk. However, in the stratified analysis, a significant decrease in risk of glioma was observed in subjects of <60 months old with the rs4712653 TT genotype, when compared to those with the CC/CT genotype (OR=0.12, 95% CI=0.02-0.91, P=0.041). CONCLUSION: The present study provides referential evidence on the association between the genetic predisposition of the CASC15 gene and glioma risk in Chinese children. However, more well-designed case-control studies and functional experiments are needed to further explore the role of CASC15 gene SNPs.


Asunto(s)
Glioma , Pueblo Asiatico/genética , Preescolar , Predisposición Genética a la Enfermedad , Genotipo , Glioma/genética , Humanos , Polimorfismo de Nucleótido Simple/genética
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