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Objective: To compare the effects of artesunate (Art) and fuzheng huayu decoction on mitochondrial autophagy in the treatment of schistosomiasis liver fibrosis. Methods: Eighty C57BL/6 female mice were randomly divided into healthy control group, infection group, Art treatment group and Fuzheng Huayu Decoction treatment group, with 20 mice in each group. Mice in the infection group and treatment group were infected with 16 Schistosoma japonicum cercariae. After 6 weeks, praziquantel (300 mg/kg) was used for 2 days to kill the worms. The Art treatment group was treated with intraperitoneal injection of 100 mg/kg/day, while the Fuzheng Huayu Decoction treatment group was fed 16g of fuzheng huayu decoction per 1kg per day. After 6 weeks, fresh liver tissues of the four groups were collected. Masson staining and Western blot were used to observe the succinate dehydrogenase subunit A (SDHA) and malate dehydrogenase (MDH2), citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and target of rapamycin 1 (mTORC1) pathway involved in mitochondrial tricarboxylic acid cycle in liver tissues. The relative expression levels of adenylate activated protein kinase (AMPK) and mitochondrial autophagy pathway kinase (PINK1) were detected. Liver tissue samples were extracted from each group to detect the mitochondrial oxygen consumption rate. Two-way ANOVA was used to compare the significance and difference between two sets of samples. Results: Masson staining showed that the infection group mice had significantly higher liver fibrosis area than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group mice had lower liver fibrosis area than the infection group. Western blot analysis showed that the infection group (0.82 ± 0.05) had significantly lower relative expression of SDHA protein than the healthy control group (1.00 ± 0.05) (t = 11.23, P = 0.0035), while the Art treatment group (0.73 ± 0.05) had significantly higher relative expression of SDHA protein than the infection group (t = 10.79, P = 0.0073). However, there was no significant change in Fuzheng Huayu Decoction treatment group (0.98±0.05) (t = 1.925, P = 0.1266). The relative expression of p-AMPK protein was significantly higher in the infection group (1.15 ±0.05) than in the healthy control group (0.98 ± 0.07, t = 12.18, P = 0.0029), and the expression of p-AMPK in the Art treatment group (0.50 ± 0.05) was significantly lower than the infection group (t = 11.78, P = 0.0032). The relative protein expression of AMPK was significantly lower in the infection group (0.80 ± 0.05) than in the healthy control group (1.00 ± 0.05, t = 10.53, P = 0.0046). The expression of AMPK was significantly lower in the Art treatment group (0.54 ± 0.05) than in the infection group (T = 13.98, P = 0.0036). The relative expression of p-mTORC1 protein (0.93 ± 0.08) was not significantly different in the infection group than in the healthy control group (t = 2.28, P = 0.065), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1 protein than the infection group (t = 10.58, P = 0.029). The expression of p-mTORC1/ m-TORC1 was not significantly different in the infection group (0.98 ± 0.03) than in the healthy control group (0.97 ± 0.03, t = 0.98, P = 0.085), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1/ m-TORC1 than the infection group (t = 14.58, P = 0. 009). The relative protein expression of PINK1 was significantly lower in the infection group (0.55 ± 0.05) than in the healthy control group (1.00 ± 0.03, t = 13.49, P = 0.0011), while the Art treatment group (1.21 ± 0.05, t = 9.98, P = 0.0046) and Fuzheng Huayu Decoction treatment group (1.31 ±0.35, t = 6.98, P = 0.027) had significantly higher relative protein expression of PINK1 than the infection group. Mitochondrial function tests showed that after adding substrate complex II, the oxygen consumption of the infection group was lower than the healthy control group, while the Art treatment group and the Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. The oxygen consumption was significantly lower after adding the substrate complex III in the infection group than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. Conclusion: Art can alleviate schistosomiasis liver fibrosis by inhibiting AMPK/mTORC1 signaling pathway activity and enhancing mitochondrial oxygen consumption, autophagy and SDHA expression.
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Medicamentos Herbarios Chinos , Esquistosomiasis , Animales , Artesunato , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Cirrosis Hepática/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , MitocondriasRESUMEN
The Macau Baimahang Hospital (Hospital de S. Rafael), took more than 400 years from 1569 to 1975 to develop as a comprehensive western medicine hospital , and is believed to be one of the earliest western medicine hospitals in China. Up to now, very little has been written about it as most of the records are kept in Macao, and few materials are recorded in Chinese. The author will review the archives and literature comprehensively with field work, in order to provide reference for further research.
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Hospitales , China , MacaoRESUMEN
According to all the reports about "eliminating the four pests" in Nanfang Daily and Guangzhou Daily between 1949 and 1959, this paper reviews the formation and development of "eliminating four pests" movement in Guangzhou. The movement started from 1949, and its first stage ended in 1952. The focus of the movement was to improve the appearance and environment of Guangzhou. From 1952 to 1956, the Patriotic Public Health Campaign started, and reached its climax around 1958, yet the movement has moved from pragmatism to radicalism. In the 10 years of "eliminating the four pests" , the movement has greatly improved the public health in Guangzhou and played a positive role in improving the physical health of the people in Guangzhou. However, excessive activities such as wiping out sparrows have also caused serious ecological disasters and poor harvests.
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BACKGROUND: Vitamin D is important for maintaining physiological functions including cognition and its deficiency is associated with the occurrence of cognitive impairment. This study was to explore the association between preoperative vitamin D status and the occurrence of postoperative cognitive dysfunction (POCD) in elderly patients undergoing major surgery. METHODS: This was a predefined exploratory sub-analysis of one-centre data from a randomized controlled trial. In all, 123 elderly (≥ 65 years) patients who were scheduled to undergo major cancer surgery were recruited. Serum 25-hydroxyvitamin D concentration was measured before surgery. In total, 59 nonsurgical control subjects with comparable age and education level were also enrolled. A battery of neuropsychological tests was administered the day before and the 7th day after surgery in patients or at the same time interval in control subjects. POCD was diagnosed according to the ISPOCD1 definition. RESULTS: 71.5% (88/123) of elderly patients had vitamin D deficiency (serum 25-hydroxyvitamin D concentration < 12 ng/ml) before surgery; 24.4% (30/123) of them developed cognitive dysfunction at 1 week after surgery. After adjusting for confounding factors, high preoperative serum 25-hydroxyvitamine D concentration was related to a decreased risk of POCD (odds ratio [OR]: 0.829, 95% confidence interval [CI]: 0.708-0.971; P = 0.020), whereas preoperative vitamin D deficiency was associated with an increased risk of POCD (OR: 8.427, 95% CI: 1.595-44.511; P = 0.012). CONCLUSIONS: Vitamin D deficiency is prevalent in elderly patients undergoing major cancer surgery and increases the risk of early POCD development. Whether prophylactic vitamin D supplementation can reduce POCD in the elderly deserves further study.
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Disfunción Cognitiva/etiología , Neoplasias/cirugía , Complicaciones Posoperatorias/etiología , Deficiencia de Vitamina D/complicaciones , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Neoplasias/sangre , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
Menkes disease (MD) is a lethal disorder characterized by severe neurological symptoms and connective tissue abnormalities; and results from malfunctioning of cuproenzymes, which cannot receive copper due to a defective intracellular copper transporting protein, ATP7A. Early parenteral copper-histidine supplementation may modify disease progression substantially but beneficial effects of long-term treatment have been recorded in only a few patients. Here we report on the eldest surviving MD patient (37 years) receiving early-onset and long-term copper treatment. He has few neurological symptoms without connective tissue disturbances; and a missense ATP7A variant, p.(Pro852Leu), which results in impaired protein trafficking while the copper transport function is spared. These findings suggest that some cuproenzymes maintain their function when sufficient copper is provided to the cells; and underline the importance of early initiated copper treatment, efficiency of which is likely to be dependent on the mutant ATP7A function.
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ATPasas Transportadoras de Cobre/metabolismo , Cobre/uso terapéutico , Síndrome del Pelo Ensortijado/tratamiento farmacológico , Síndrome del Pelo Ensortijado/enzimología , Adolescente , Adulto , Preescolar , Humanos , Lactante , Recién Nacido , Masculino , Transporte de ProteínasRESUMEN
The objective of this study was to assess whether vitamin D (VD) treatment alters the overall all-cause and cardiovascular mortalities in a chronic kidney disease (CKD) population. We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials without language restriction, until the publication date of 22 February 2016. All related literatures that compared VD treatment with non-VD treatment and reported the mortality of patients with CKD (including those undergoing dialysis) were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated by using the random- and fixed-effects models. Randomised controlled trials (RCTs) that used the intention-to-treat principle and observational studies (OSs) were analysed separately. For this study, 38 studies involving 223 429 patients (17 RCTs, n=1819 and 21 OSs, n=221610) were included. In the OSs, VD treatment was significantly associated with reductions in both all-cause and cardiovascular mortalities; however, such significant association was not found in the RCTs. The existing RCTs do not provide sufficient or precise evidence that VD supplementation affects the mortality of patients with CKD, although subsets of patients that could potentially benefit from VD treatment can be identified by using the existing data from the RCTs. Nevertheless, large-size RCTs are needed in the future to assess any potential differences in survival prospectively.
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Suplementos Dietéticos , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/mortalidad , Vitamina D/administración & dosificación , Humanos , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Vitamina D/sangreRESUMEN
OBJECTIVE: The present planned to elucidate the mechanistic role zinc supplementation in the modulation of p53 post-translational acetylation, the activity of cyclooxygenase-2 (COX-2) along with other biophysical parameters during benzo(a)pyrene (BP) induced lung carcinogenesis in mice. MATERIALS AND METHODS: The mice were segregated into four groups viz., normal control, BP treated, BP + zinc and zinc alone treated. Lung carcinogenesis was induced by a single intra-peritoneal (IP) injection of BP (100 mg/kg body weight). Zinc was supplemented to mice at dose levels of 227 mg/kg body weight in drinking water. All the treatments were continued for 20 weeks. RESULTS: The BP caused a significant rise in the expression of p53. On the other hand, protein expressions of acetylated (lys382)-p53 were significantly decreased, following BP treatment. Also, a significant decrease was observed in the enzyme activities of caspase 3 and caspase 9. Moreover, BP treatment brought about a significant increase in the activity of COX-2. Supplementation of zinc to BP treated mice stimulated acetylation of p53 as observed by an increase in the protein expression of acetylated (lys382)-p53. Also, the enzyme activities of caspase 3 and caspase 9 showed a significant elevation upon zinc supplementation. On the other hand, the zinc supplementation brought about moderation in the expression of enzymatic activity of COX-2 which was restored within the normal limits. Further, BP treatment recorded increased 3H-thymidine uptake as well as enhanced 14C-glucose uptake and its turnover which were reduced significantly following simultaneous treatment with zinc. CONCLUSIONS: The treatment with zinc has the potential to modulate p53 acetylation to stimulate apoptosis against experimentally induced lung carcinogenesis.
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Neoplasias Pulmonares/prevención & control , Zinc/metabolismo , Animales , Benzo(a)pireno , Carcinogénesis/metabolismo , Pulmón/metabolismo , Neoplasias Pulmonares/metabolismo , RatonesRESUMEN
BACKGROUND: Antioxidants protect spermatozoa against cell damage during cryopreservation. OBJECTIVE: To investigate whether melatonin supplement in the extender may improve the quality of cryopreserved mouse sperm. METHODS: Kunming mice sperm frozen in extender R18S3 (18% (w/v) rafï¬nose and 3% (w/v) skim milk) supplemented with melatonin were thawed and evaluated. RESULTS: Mouse spermatozoa were cryopreserved in the freezing extender R18S3 that contained melatonin at 0, 0.125, 0.25 and 0.5 mg/mL melatonin. The extender without melatonin supplement was associated with increased formation of reactive oxygen species (ROS) and decreased sperm motility. Melatonin supplement at 0.125 mg/mL significantly increased the progressive motility of sperm in comparison to other melatonin concentration or control. The percentage of thawed viable sperm with ROS was lower in the melatonin-treated groups than in untreated group. Melatonin supplement also increased antiapoptotic gene Bcl-xl expression in the thawed sperm. CONCLUSION: Supplement of 0.125 mg/mL melatonin could reduce oxidative damage and apoptosis.
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Criopreservación/métodos , Crioprotectores/farmacología , Melatonina/farmacología , Preservación de Semen/métodos , Espermatozoides , Animales , Apoptosis/efectos de los fármacos , Criopreservación/instrumentación , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Análisis de Semen , Preservación de Semen/instrumentación , Motilidad Espermática/efectos de los fármacos , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMEN
Soil contains a large amount of phosphorus, but plants cannot absorb most of this phosphorus effectively. Low inorganic phosphorus has been singled out as a major constraint that leads to a perpetually low Zea mays (maize) grain yield. The fundamental approach to solving this problem is to screen new genes of low phosphorous (LP) tolerance. Consequently, the exploration and utilization of LP-tolerant genes are of great significance in plants. The maize inbred line 178 is an inbred LP-tolerant line. In the current study, the expression of this inbred line was induced under the stress of LP conditions. We applied cDNA-amplified fragment length polymorphism to screen LP-tolerant genes and obtained and sequenced 78 differentially expressed gene fragments. Their functions were predicted via bioinformatic analysis. There were no function annotations for 8 differentially expressed fragments. Nine genes exhibited high homology to Arabidopsis thaliana and Oryza sativa genes involved in phosphorus metabolism. This study lays a good foundation for further cloning and verification of the genes involved in phosphorus metabolism in maize.
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Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Raíces de Plantas/genética , Polimorfismo Genético , Zea mays/genética , ADN Complementario/genética , Regulación de la Expresión Génica de las Plantas , Fósforo/química , Fósforo/metabolismo , Proteínas de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Suelo/química , Estrés Fisiológico/genética , Zea mays/crecimiento & desarrollo , Zea mays/metabolismoRESUMEN
The calcium-dependent protein kinases (CDPKs) are unique enzymes found only in plants, green algae, ciliates and apicomplexan parasites. In this study, a novel CDPK gene of Eimeria tenella, designed EtCDPK3, was cloned using rapid amplification of cDNA ends (RACE) based on the expressed sequence tag (EST). The entire cDNA of EtCDPK3 contained 1637 nucleotides encoding 433 amino acids and the deduced EtCDPK3 protein had canonical characteristic domains identified in other CDPKs, including a well-conserved amino-terminal kinase domain and a carboxy-terminal calmodulin-like structure with 4 EF-hand motifs for calcium binding. The expression profiles of the EtCDPK3 gene in different development stages were investigated by real-time quantitative PCR. Messenger RNA levels from the EtCDPK3 gene were higher in sporozoites than in other stages (unsporulated oocysts, sporulated oocysts and merozoites). Western blot analysis showed that rabbit antiserum against recombinant EtCDPK3 could recognize a native 49 kDa protein band of parasite. Indirect immunofluorescent antibody labelling revealed dispersed localization of EtCDPK3 during the first schizogony and intense specific staining. EtCDPK3 was located at the apical end of the sporozoites after early infection of DF-1 cells and the protein was highly expressed. Inhibition of EtCDPK3 function using specific antibodies reduced the ability of E. tenella to invade host cells. These results suggested that EtCDPK3 may be involved in invasion and survival of the parasite intracellular stages of E. tenella. Because this kinase family is absent from hosts, it represents a valid target that could be exploited for chemotherapy against Eimeria spp.
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Coccidiosis/parasitología , Eimeria tenella/enzimología , Proteínas Quinasas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , Embrión de Pollo , ADN Complementario/química , ADN Complementario/genética , ADN Protozoario/química , ADN Protozoario/genética , Eimeria tenella/genética , Eimeria tenella/fisiología , Sueros Inmunes , Masculino , Datos de Secuencia Molecular , Filogenia , Proteínas Quinasas/metabolismo , Estructura Terciaria de Proteína , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , ARN Protozoario/genética , Conejos , Alineación de Secuencia , Análisis de Secuencia de ADN , EsporozoítosRESUMEN
The efficacy of conjugated linoleic acid (CLA) in diet supplements for milk fat reduction is well documented in several species. However, the mechanisms by which fatty acids regulate mammary lipogenesis remain largely unknown, especially with regard to gene expression of enzyme and regulators. In this study, 8 Holstein dairy cows in their mid-lactation period were randomly divided into 2 groups. Control cows received a Ca salt of palm oil fatty acid dietary supplement, and those in the CLA group were fed Ca salts of CLA (Ca-CLA), all in a dose of approximately 200 gâcow(-1)âday(-1) for 14 days. The milk yield was recorded daily, and protein, lactose, and fat in the milk were quantified every 3 days for 2 weeks. Fatty acids in the milk were analyzed with gas-liquid chromatography. Measurement of messenger RNA levels of the main lipogenic genes of lipoprotein lipase, acetyl-coenzyme A (CoA) carboxylase, fatty acid synthase, stearoyl-CoA desaturase, and transcription factors such as sterol response element binding protein 1 (SREBP1) and peroxisome proliferator-activated receptor γ was performed in biopsy samples of mammary tissue on the last day. The results indicated that dietary Ca-CLA caused a continuous reduction of milk fat (P < 0.01) with no effect on milk yield, milk protein, and lactose. The fatty acid profile in the milk from the CLA group differed from that from controls, and the yield of milk fatty acid decreased (P < 0.01) with Ca-CLA supplementation. The depressed expression of lipogenic genes (lipoprotein lipase, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase) demonstrated inhibition of fatty acid de novo synthesis and uptake in the mammary gland of the CLA group. Furthermore, the gene expression of transcription factor SREBP1 was also downregulated (P < 0.01), but peroxisome proliferator-activated receptor γ was unchanged, suggesting that SREBP1 may play a key role in the regulation of lipogenic gene expression in the lactating mammary gland.
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Bovinos/fisiología , Ácidos Linoleicos Conjugados/administración & dosificación , Lipogénesis/genética , Glándulas Mamarias Animales/metabolismo , Leche/metabolismo , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Animales , Suplementos Dietéticos , Represión Enzimática , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Ácidos Grasos/metabolismo , Femenino , Expresión Génica , Lactancia , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismoRESUMEN
The cytoplasmic male sterility (CMS) line FuCMS5A and its restorer line FuHui9 were crossed to produce a segregating F(2) population for pollen fertility assay and the genetic mapping of restorer-of-fertility (Rf) gene. Results showed that the individual F(2) plants were fertile or semi-fertile based on their pollen fertility characteristics. The average ratios of viable pollen were 96.90% and 50.00% for each class of individuals. The segregation of F(2) plants showed a good fit to a 1:1 ratio, which reflects a typical heredity pattern of gametophytic CMS with fertility restorer being controlled by a single dominant gene. Using bulk segregation analysis (BSA) and genetic mapping, the Rf gene was mapped on molecular linkage group J (chromosome 16), between the simple sequence repeat (SSR) makers BARCSOYSSR-16-1064 and BARCSOYSSR-16-1082 with the distances of 0.59 and 0.83 cM, respectively. Four SSR markers (BARCSOYSSR-16-1070, Sctt011, BARCSOYSSR-16-1076 and BARCSOYSSR-16-1077) were cosegregating with this Rf gene in the mapping population. These makers will greatly facilitate the maker assisted selection procedures in CMS breeding programs and it lays a foundation for further map-base cloning of the Rf gene.
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Citoplasma/genética , Genes de Plantas/genética , Glycine max/genética , Infertilidad Vegetal/genética , Cruzamiento , Mapeo Cromosómico , Citoplasma/fisiología , Flores/genética , Flores/fisiología , Ligamiento Genético , Marcadores Genéticos/genética , Repeticiones de Microsatélite , Polen/genética , Polen/fisiología , Glycine max/fisiologíaRESUMEN
Field-grown Echinacea purpurea plants showing necrosis, leaf roll, yellow mosaic, and mosaic symptoms in leaves were collected in June 2010 in Huairou, Beijing, China. ELISAs of extracts of four samples showed that one sample with mosaic symptoms had a positive reaction with Broad bean wilt virus 2 (BBWV-2) monoclonal antibody provided by Professor X. P. Zhou (1). The monoclonal antibody recognized the 44.7 kD coat protein subunit of BBWV-2. We used Chenopodium quinoa as an assay species to isolate the virus by sap transmissions and to maintain the virus strain. Sap from infected C. quinoa, when inoculated onto indicator plant species, induced the following symptoms: C. quinoa: local lesions in inoculated leaves, systemic chlorotic mottle in upper leaves, deformation, and apical necrosis; C. amaranticolor: chlorotic local lesions, systemic mosaic and leaf distortion; Nicotiana benthamiana: systemic mosaic; Gomphrena globosa: local purple spots in inoculated leaves and systemic infection in upper leaves; Tetragonia expansa: local lesions, but no symptoms of systemic infection; Physalis floridana: systemic mosaic. No symptoms were observed on Capsicum annuum, Datura stramonium, N. glutinosa, or N. tabacum cv. White Burley. To confirm BBWV-2 infection, total RNAs extracted from infected C. quinoa leaves were reverse transcripted to cDNA using oligo-dT primer (T17V). The primer pair Fab5'R1F (5'-AAATATTAAAACAAACAGCTTTCGTT-3') and Fab5'R1R (5'-TTCAAAGCTCGTGCCATNTYATTKGC-3') for specific detection of the Fabavirus genus (2) was used for PCR analysis. The amplified fragment is between the 5'-terminal non-translatable region (NTR) and the beginning of the coding region of RNA1. Amplicons of approximately the expected size (~391 bp) were produced from the virus-infected C. quinoa and a BBWV-2 positive control (ATCC PV131, PV0537). Amplicons of approximately the expected size (~350 bp) were produced from the BBWV-1 positive control (ATCC PV132). However, no such amplicons were observed from healthy C. quinoa plants and water control. The 391-bp amplicons of RNA1 obtained from the infected C. quinoa were cloned and sequenced. Comparison with sequences of other BBWV-2 isolates showed that the isolate we obtained (No. JX070674) had approximately 99% nt identity (98% amino acid identity) with Chinese BBWV-2 isolate BC (No. FJ485686.1) (3). As an ornamental and medicinal plant, E. purpurea is widely cultivated in northern China. Up until now, Tomato ring spot virus, Tobacco rattle virus, Cucumber mosaic virus, and Tomato spotted wilt virus have been detected or isolated from E. purpurea in the world (4). To our knowledge, this is the first report of BBWV-2 infecting E. purpurea in China. BBWV-2-infected E. purpurea may have less secondary metabolites, which could influence the quality and therapeutic efficacy of this herbal medicine. References: (1) L. Qing et al. Acta Microbiologica Sinica 40:166, 2000. (2) R. M. Ferrer et al. J. Virol. Methods 144:156, 2007. (3) C. Sui et al. Plant Dis. 93:844, 2009. (4) B. Dikova. Bulgarian J. Agric. Sci. 17:306, 2011.
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UNLABELLED: Ovariectomized (OVX) rats with tibial fracture received vehicle, ZA, PTH, or ZA plus PTH treatment for 4 and 8 weeks. Bone metabolism, callus formation, and the mass of undisturbed bone tissue were evaluated by serum analysis, histology, immunohistochemistry, radiography, micro-computerized tomography, and biomechanical test. INTRODUCTION: Previous studies have demonstrated the effect of ZA or PTH on osteoporotic fracture healing. However, reports about effects of ZA plus PTH on callus formation of osteoporotic fracture were limited. This study was designed to investigate the impact of combined treatment with ZA and PTH on fracture healing in OVX rats. METHODS: Twelve weeks after bilateral ovariectomy, all rats underwent unilateral transverse osteotomy on tibiae. Animals then randomly received vehicle, ZA (1.5 µg/kg weekly), PTH (60 µg/kg, three times a week), or ZA plus PTH until death at 4 and 8 weeks. The blood and bilateral tibiae of rats were harvested for evaluation. RESULTS: All treatments increased callus formation and strength other than the control; ZA + PTH showed the strongest effects on percent bone volume (BV/TV), trabecular thickness, total fluorescence-marked callus area, and biomechanical strength. Additionally, inhibited RANKL and enhanced osteoprotegerin expression were observed in the ZA + PTH group. But no difference in bone mineral density and BV/TV of the contralateral tibiae was observed between treated groups. CONCLUSION: Findings in this study suggested an additive effect of ZA and PTH on fracture healing in OVX rats, and this additive effect was specific to callus formation, not to undisturbed bone tissue.
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Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Curación de Fractura/efectos de los fármacos , Imidazoles/uso terapéutico , Fracturas Osteoporóticas/tratamiento farmacológico , Hormona Paratiroidea/uso terapéutico , Animales , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Callo Óseo/diagnóstico por imagen , Callo Óseo/efectos de los fármacos , Difosfonatos/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Quimioterapia Combinada , Femenino , Imidazoles/farmacología , Fracturas Osteoporóticas/fisiopatología , Osteoprotegerina/sangre , Hormona Paratiroidea/farmacología , Ligando RANK/sangre , Ratas , Ratas Sprague-Dawley , Fracturas de la Tibia/tratamiento farmacológico , Fracturas de la Tibia/fisiopatología , Microtomografía por Rayos X/métodos , Ácido ZoledrónicoRESUMEN
The objective was to determine whether adding L-carnitine in IVM/IVC medium enhanced maturation and developmental competence of porcine oocytes in vitro. Oocyte maturation rates did not differ significantly among groups supplemented with 0, 0.25, 0.5, or 1 mg/mL of L-carnitine added during IVM (although 2 mg/mL of L-carnitine reduced maturation rate). Compared with control oocytes, those treated with 0.5 mg/mL of L-carnitine during IVM had greater (P < 0.05) rates of blastocyst formation after parthenogenetic activation, and these blastocysts had less (P < 0.05) apoptosis. Adding 0.5 mg/mL of L-carnitine during IVM also significantly reduced intracellular reactive oxygen species (ROS), and increased glutathione (GSH) concentrations. With or without glucose supplementation, 0.5 mg/mL of L-carnitine in the IVM medium significantly hastened nuclear maturation of oocytes. Moreover, supplementing the IVM medium with either glucose or L-carnitine increased (P < 0.05) percentages of oocytes that reached the metaphase II (MII) stage, relative to a control group. Final maturation rates in IVM medium containing either glucose or L-carnitine were not significantly different. Adding L-carnitine (0 to 2 mg/mL) to IVC medium for activated porcine oocytes did not significantly affect development. However, 0.5 mg/mL of L-carnitine in IVC medium significantly reduced reactive oxygen species levels and apoptosis in activated blastocysts, although glutathione concentrations were not significantly altered. In conclusion, adding L-carnitine during IVM/IVC improved developmental potential of porcine oocytes, and also the quality of parthenogenetic embryos, probably by accelerating nuclear maturation, and preventing oxidative damage and apoptosis.
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Carnitina/farmacología , Oocitos/efectos de los fármacos , Oocitos/fisiología , Partenogénesis/efectos de los fármacos , Sus scrofa , Animales , Apoptosis/efectos de los fármacos , Blastocisto/fisiología , Núcleo Celular/fisiología , Técnicas de Cultivo de Embriones/veterinaria , Femenino , Glucosa/farmacología , Glutatión/análisis , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos/química , Oogénesis/efectos de los fármacos , Especies Reactivas de Oxígeno/análisisRESUMEN
Hybrid sterility hinders the exploitation of the heterosis displayed by japonica × indica rice hybrids. The variation in pollen semi-sterility observed among hybrids between the japonica recipient cultivar and each of two sets of chromosome segment substitution lines involving introgression from an indica cultivar was due to a factor on chromosome 5 known to harbor the gene S24. S24 was fine mapped to a 42 kb segment by analyzing a large F(2) population bred from the cross S24-NIL × Asominori, while the semi-sterility shown by the F(1) hybrid was ascribable to mitotic failure at the early bicellular pollen stage. Interestingly, two other pollen sterility genes (f5-Du and Sb) map to the same region (Li et al. in Chin Sci Bull 51:675-680, 2006; Wang et al. in Theor Appl Genet 112:382-387, 2006), allowing a search for candidate genes in the 6.4 kb overlap between the three genes. By sequencing the overlapped fragment in wild rice, indica cultivars and japonica cultivars, a protein ankyrin-3 encoded by the ORF2 was identified as the molecular base for S24. A cultivar Dular was found to have a hybrid-sterility-neutral allele, S24-n, in which an insertion of 30 bp was confirmed. Thus, it was possible to add one more case of molecular bases for the hybrid sterility. No gamete abortion is caused on heterozygous maternal genotype with an impaired sequence from the hybrid-sterility-neutral genotype. This result will be useful in understanding of wide compatibility in rice breeding.
Asunto(s)
Genes de Plantas/genética , Hibridación Genética/genética , Oryza/genética , Infertilidad Vegetal/genética , Polen/genética , Mapeo Cromosómico , Regulación de la Expresión Génica de las Plantas , Genotipo , Mutagénesis Insercional , Oryza/fisiología , Fenotipo , Polen/clasificación , Polen/fisiología , Polimorfismo Genético/genéticaRESUMEN
OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and economic modelling. DATA SOURCES: The Cochrane Incontinence Group Specialised Register, electronic databases and the websites of relevant professional organisations and manufacturers, and the following databases: CINAHL, EMBASE, BIOSIS, Science Citation Index and Social Science Citation Index, Current Controlled Trials, ClinicalTrials.gov and the UKCRN Portfolio Database. STUDY SELECTION: The study comprised three distinct elements. (1) A survey of 188 women with SUI to identify outcomes of importance to them (activities of daily living; sex, hygiene and lifestyle issues; emotional health; and the availability of services). (2) A systematic review and meta-analysis of non-surgical treatments for SUI to find out which are most effective by comparing results of trials (direct pairwise comparisons) and by modelling results (mixed-treatment comparisons - MTCs). A total of 88 randomised controlled trials (RCTs) and quasi-RCTs reporting data from 9721 women were identified, considering five generic interventions [pelvic floor muscle training (PFMT), electrical stimulation (ES), vaginal cones (VCs), bladder training (BT) and serotonin-noradrenaline reuptake inhibitor (SNRI) medications], in many variations and combinations. Data were available for 37 interventions and 68 treatment comparisons by direct pairwise assessment. Mixed-treatment comparison models compared 14 interventions, using data from 55 trials (6608 women). (3) Economic modelling, using a Markov model, to find out which combinations of treatments (treatment pathways) are most cost-effective for SUI. DATA EXTRACTION: Titles and abstracts identified were assessed by one reviewer and full-text copies of all potentially relevant reports independently assessed by two reviewers. Any disagreements were resolved by consensus or arbitration by a third person. RESULTS: Direct pairwise comparison and MTC analysis showed that the treatments were more effective than no treatment. Delivering PFMT in a more intense fashion, either through extra sessions or with biofeedback (BF), appeared to be the most effective treatment [PFMT extra sessions vs no treatment (NT) odds ratio (OR) 10.7, 95% credible interval (CrI) 5.03 to 26.2; PFMT + BF vs NT OR 12.3, 95% CrI 5.35 to 32.7]. Only when success was measured in terms of improvement was there evidence that basic PFMT was better than no treatment (PFMT basic vs NT OR 4.47, 95% CrI 2.03 to 11.9). Analysis of cost-effectiveness showed that for cure rates, the strategy using lifestyle changes and PFMT with extra sessions followed by tension-free vaginal tape (TVT) (lifestyle advice-PFMT extra sessions-TVT) had a probability of greater than 70% of being considered cost-effective for all threshold values for willingness to pay for a QALY up to 50,000 pounds. For improvement rates, lifestyle advice-PFMT extra sessions-TVT had a probability of greater than 50% of being considered cost-effective when society's willingness to pay for an additional QALY was more than 10,000 pounds. The results were most sensitive to changes in the long-term performance of PFMT and also in the relative effectiveness of basic PFMT and PFMT with extra sessions. LIMITATIONS: Although a large number of studies were identified, few data were available for most comparisons and long-term data were sparse. Challenges for evidence synthesis were the lack of consensus on the most appropriate method for assessing incontinence and intervention protocols that were complex and varied considerably across studies. CONCLUSIONS: More intensive forms of PFMT appear worthwhile, but further research is required to define an optimal form of more intensive therapy that is feasible and efficient for the NHS to provide, along with further definitive evidence from large, well-designed studies.
Asunto(s)
Modelos Económicos , Incontinencia Urinaria de Esfuerzo/terapia , Inhibidores de Captación Adrenérgica/economía , Inhibidores de Captación Adrenérgica/uso terapéutico , Biorretroalimentación Psicológica , Análisis Costo-Beneficio , Terapia por Estimulación Eléctrica/economía , Terapia por Ejercicio/economía , Terapia por Ejercicio/métodos , Femenino , Humanos , Estilo de Vida , Cadenas de Markov , Diafragma Pélvico/fisiología , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Inhibidores Selectivos de la Recaptación de Serotonina/economía , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Estrés Psicológico/etiología , Cabestrillo Suburetral/economía , Resultado del Tratamiento , Reino Unido/epidemiología , Incontinencia Urinaria de Esfuerzo/economía , Incontinencia Urinaria de Esfuerzo/epidemiología , Incontinencia Urinaria de Esfuerzo/psicologíaRESUMEN
The relationship between pollen germination and the dynamic organization of the actin cytoskeleton during pollen germination is a central theme in plant reproductive biology research. Maize (Zea mays) pollen grains were implanted with 30 keV argon ion (Ar(+)) beams at doses ranging from 0.78 x 10(15) to 13 x 10(15) ions/cm(2). The effects of low-energy ion implantation on pollen germination viability and the dynamic organization of the actin cytoskeleton during pollen germination were studied using confocal laser scanning microscopy. Maize pollen germination rate increased remarkably with Ar(+) dose, in the range from 3.9 x 10(15) to 6.5 x 10(15) ions/cm(2); the germination rate peaked at an Ar(+) dose of 5.2 x 10(15) ions/cm(2). When the implantation dose exceeded 7.8 x 10(15) ions/cm(2), the rate of pollen germination decreased sharply. The actin filaments assembled in pollen grains implanted with 5.2 x 10(15) ions/cm(2) Ar(+) much earlier than in controls. The actin filaments organized as longer parallel bundles and extended into the emerging pollen tube in treated pollen grains, while they formed random and loose fine bundles and were gathered at the pollen aperture in the control. The reorganization of actin cytoskeleton in the pollen implanted with 9.1 x 10(15) ions/cm(2) Ar(+) was slower than in controls. There was a positive correlation between pollen germination and the dynamic organization of the actin cytoskeleton during pollen germination. Ion implantation into pollen did not cause changes in the polarization of actin filaments and organelle dynamics in the pollen tubes. The effects of Ar(+) implantation on pollen germination could be mediated by changes in the polymerization and rearrangement of actin polymers.
Asunto(s)
Actinas/metabolismo , Argón/farmacología , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Germinación/efectos de los fármacos , Polen/fisiología , Zea mays/fisiología , Citoesqueleto de Actina/efectos de los fármacos , Citoesqueleto de Actina/metabolismo , Iones , Microscopía Confocal , Polen/citología , Polen/efectos de los fármacos , Tubo Polínico/citología , Tubo Polínico/efectos de los fármacos , Tubo Polínico/crecimiento & desarrollo , Zea mays/citología , Zea mays/efectos de los fármacosRESUMEN
UNLABELLED: Systemic treatment with strontium ranelate (SR) was performed on ovariectomized (OVX) rats with fractured tibiae. Callus quality was assessed by radiographic, histological, micro-computerized tomography, and biomechanical examinations at 4 and 8 weeks after fracture. Results revealed that systemic applied SR promoted osteoporotic fracture healing. INTRODUCTION: Several studies have demonstrated the dual effect of SR on osteoporotic and undisturbed bone. However, reports of their effect on osteoporotic fracture healing are limited. This study was designed to investigate the effects of SR on bone regeneration in OVX rats with fractured tibiae. METHODS: Three months after being OVX, female Sprague-Dawley rats accepted bilateral osteotomy on proximal tibiae fixed with intramedullary wires and were divided into two groups: OVX and OVX + SR (625 mg/kg/day). Callus quality was evaluated at 4 and 8 weeks postfracture. RESULTS: Compared with OVX group, SR treatment significantly increased bone formation, BMD, biomechanical strength, and improved microstructural properties of the callus. The ultimate load was increased by 211.0% and 61.4% (p<0.01), and the total bone volume of callus by 74.8% and 79.3% (p<0.01) at 4 and 8 weeks postfracture, respectively. SR treatment also promoted healing progress with increased osteogenesis at 4 weeks; more mature and tightly arranged woven or lamellar bone at 8 weeks across the fracture gap in histological analysis. CONCLUSION: This study suggests that systemic treatment with strontium ranelate could promote tibial fracture healing in OVX rats.