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In addition to topography and climate, biogeographic dispersal has been considered to influence plant diversity in the Himalaya-Hengduan Mountains (HHM), yet, the mode and tempo of sky island dispersal and its influence on species richness has been little explored. Through phylogenetic analysis of Gaultheria ser. Trichophyllae, a sky island alpine clade within the HHM, we test the hypothesis that dispersal has affected current local species richness. We inferred the dynamics of biogeographic dispersal with correlation tests on direction, distance, occurrence time, and regional species richness. We found that G. ser. Trichophyllae originated at the end of the Miocene and mostly dispersed toward higher longitudes (eastward). In particular, shorter intra-regional eastward dispersals and longer inter-regional westward dispersals were most frequently observed. We detected a prevalence of eastward intra-region dispersals in both glacial periods and interglacials. These dispersals may have been facilitated by the reorganization of paleo-drainages and monsoon intensification through time. We suggest that the timing of dispersal corresponding to glacial periods and the prevalence of intra-region dispersal, rather than dispersal frequency, most influenced the pattern of species richness of G. ser. Trichophyllae. This study facilitates a more comprehensive understanding of biodiversity in the sky islands within the HHM.
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Biodiversidade , Filogenia , China , Filogeografia , Ilhas , Dispersão VegetalRESUMO
Objective: To prospectively determine the median effective dose (ED50) of propofol for inhibiting a response to laryngeal mask airway (LMA) insertion when combined with different doses of esketamine in female patients. Methods: A total of 58 female patients (aged 20-60 years, ASAâ -â ¡) scheduled for elective hysteroscopy were enrolled and randomly divided into 2 groups, one of which was administered 0.2 mg/kg of esketamine (K1 group, n = 28) and the other 0.3 mg/kg of esketamine (K2 group, n = 30). The 2 groups received the corresponding doses of esketamine intravenously, followed by an intravenous injection of propofol (injection time was 30 s). The initial dose of propofol was 2 mg/kg, and the dose ratio of propofol in the adjacent patients was 0.9. If a positive reaction occurred due to LMA insertion, the dose ratio in the next patient was increased by 1 gradient; if not, the dose ratio was decreased by 1 gradient. The ED50, 95 % effective dose (ED95) and 95 % confidence interval (CI) of propofol for inhibiting a response to LMA insertion in the 2 esketamine groups were calculated using probit analysis. Results: The ED50 of propofol for inhibiting a response to LMA insertion in female patients was 1.95 mg/kg (95 % CI, 1.82-2.08 mg/kg) in the K1 group and 1.60 mg/kg (95 % CI, 1.18-1.83 mg/kg) in the K2 group. The ED95 of propofol for inhibiting a response to LMA insertion in female patients was 2.22 mg/kg (95 % CI, 2.09-2.86 mg/kg) in the K1 group and 2.15 mg/kg (95 % CI, 1.88-3.09 mg/kg) in the K2 group. Conclusion: Propofol combined with 0.3 mg/kg of esketamine has low ED50 and ED95 effective doses for inhibiting an LMA insertion response in female patients undergoing hysteroscopy and surgery. There were no significant adverse effects, but the additional dose of propofol and airway pressure were significantly higher than those in the group administered 0.2 mg/kg of esketamine. Based on the results, we recommend the combination of propofol with 0.2 mg/kg esketamine for optimal conditions during LMA insertion in women undergoing hysteroscopy.
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BACKGROUND: The application of calcium phosphate (CaP)-based bone substitutes plays an important role in periodontal regeneration, implant dentistry and alveolar bone reconstruction. The incorporation of strontium (Sr) into CaP-based bone substitutes appears to improve their biological properties, but the reported in vivo bone repair performance is inconsistent among studies. Herein, we conducted a systematic review and meta-analysis to investigate the in vivo performance of Sr-doped materials. METHODS: We searched PubMed, EMBASE (via OVIDSP), and reference lists to identify relevant animal studies. The search, study selection, and data extraction were performed independently by two investigators. Meta-analyses and sub-group analyses were conducted using Revman version 5.4.1. The heterogeneity between studies were assessed by I2. Publication bias was investigated through a funnel plot. RESULTS: Thirty-five studies were finally enrolled, of which 16 articles that reported on new bone formation (NBF) were included in the meta-analysis, covering 31 comparisons and 445 defects. The overall effect for NBF was 2.25 (95% CI 1.61-2.90, p < 0.00001, I2 = 80%). Eight comparisons from 6 studies reported the outcomes of bone volume/tissue volume (BV/TV), with an overall effect of 1.42 (95% CI 0.65-2.18, p = 0.0003, I2 = 75%). Fourteen comparisons reported on the material remaining (RM), with the overall effect being -2.26 (95% CI - 4.02 to - 0.50, p = 0.0009, I2 = 86%). CONCLUSIONS: Our study revealed that Sr-doped calcium phosphate bone substitutes improved in vivo performance of bone repair. However, more studies are also recommended to further verify this conclusion.
Assuntos
Substitutos Ósseos , Fosfatos de Cálcio , Animais , Substitutos Ósseos/uso terapêutico , Osso e Ossos , Fosfatos de Cálcio/uso terapêutico , Humanos , Estrôncio/uso terapêuticoRESUMO
BACKGROUND: High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown. OBJECTIVE: The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated. DESIGN, PARTICIPANTS AND INTERVENTION: This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone. MAIN OUTCOME MEASURES: The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3. RESULTS: A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/µL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups. CONCLUSION: STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only. TRIAL REGISTRATION: This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.
Assuntos
Intervenção Coronária Percutânea , Difosfato de Adenosina , Angina Instável/induzido quimicamente , Animais , Biomarcadores , Clopidogrel , Citocromo P-450 CYP2C19/genética , Medicamentos de Ervas Chinesas , Galectina 3 , Humanos , Molécula 1 de Adesão Intercelular , Masculino , Camundongos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
Gaultheria nummularioides D.Don 1825 (Ericaceae) is a traditional Chinese medicinal plant used to treat rheumatoid arthritis. The complete chloroplast genome of G. nummularioides has been sequenced and assembled. The genome is 176,207 bp in total with one large single copy (LSC: 107,726 bp), one small single copy (SSC: 3,389 bp), and two inverted repeat regions (IRa and IRb; each 32,546 bp). The chloroplast genome encoded a total of 110 unique genes; the GC content of these genes is 36.6%. The results based on phylogenetic analysis of the complete chloroplast genome suggests that G. nummularioides diverged later than G. praticola, the sister relationship between G. nummularioides and the clade comprising G. fragrantissima Wall. 1820 and G. hookeri C.B. Clarke 1882 was strongly supported. This study provides additional information on the genetic diversity of G. nummularioides, its closely related taxa, and further exploration of chloroplast genomes in the Ericaceae family.
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Artrite Reumatoide , Ericaceae , Gaultheria , Genoma de Cloroplastos , Genoma de Cloroplastos/genética , FilogeniaRESUMO
Anesthetic management for patients of pseudomyxoma peritonei (PMP) is challenging. This case report describes a patient of PMP with high intra-abdominal pressure. Intubation was performed in lateral position; the intraabdominal pressure was relieved slowly to prevent significant hemodynamic changes. Additionally, positive pressure ventilation was performed to reduce the risk of re-expansion pulmonary edema. During the operation, transfusion and infusion therapy was performed with target-mediated fluid therapy according to stroke volume variation (SVV) and cardiac index (CI) and blood gas analysis.
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Laggera pterodonta (DC.) Benth, a folk herb widely distributes in southwest China, especially in Yunnan Province, demonstrates anti-pathogenic microorganisms, anti-inflammatory, inhibition of Helicobacter pylori activities in vitro et al. Interestingly, previous studies have shown that pterodontic acid (1), a eudesmane-type sesquiterpene isolated from L. pterodonta (DC.), displays excellent selective antiviral activity to H1N1 subtype of influenza A virus. At the same time, our group also discovered that the antiviral activity of 1 was relatively close to that activity of post-marketed ribavirin. Therefore, we consider that the synthesis of pterodontic acid (1) derivatives and evaluation of their anti-influenza A virus (H1N1) activities is of potential clinical significance. In this manuscript, a series of pterodontic acid derivatives were prepared and demonstrated significantly improved anti-influenza A virus (H1N1) activities, providing more opportunities for the treatment of respiratory viral diseases.
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Antivirais/farmacologia , Asteraceae/química , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Antivirais/síntese química , China , Cães , Células Madin Darby de Rim Canino , Estrutura Molecular , Sesquiterpenos/síntese químicaRESUMO
Self-assembled vesicles with structured (tetrahedral order with strong hydrogen bonds) interstitial water are reported. The vesicles, known as MCsome, are assembled from metal carbonyl compounds, FpR (Fp = (Cp)Fe(PPh3)(CO)(CO-), Cp = cyclopentadiene, R = C3Bithiophene, C6Pyrene or C6) with the Fp heads exposed to water. The R groups are surrounded by the interstitial water with the hydrogen bonding strength variable depending on the hydrophobicity of R groups. The structure of the interstitial water is responsible for the integrity of the membrane and swelling behavior of the vesicles. This constructional role of water opens new concepts for the creation of aqueous assemblies with water-mediated functions.
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Both Aconitum hemsleyanum and Aconitum geniculatun have abundant contents of yunaconitine (1). Yunaconitine (1) has similar skeleton to crassicauline A (3); the only difference between them is that 1 contains a α-hydroxyl group at C-3. Our team attempts to convert 1 into 3 because 3 owns pharmacological activity. There are two steps to achieve the transformation above: firstly, use dehydration reaction to transform yunaconitine (1) into dehydroyunaconitine (2); secondly, use hydrogen reduction to acquire crassicauline A (3). Compared with other methods, this one below is more suitable for production application and more concise; moreover, the cost is lower with higher yield.
Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/patologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia , Terapia Trombolítica/métodos , Vitamina D/análogos & derivados , Idoso , Isquemia Encefálica/tratamento farmacológico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento , Vitamina D/sangueRESUMO
Mutations in the mitochondrial alanyl-transfer (t)RNA synthetase 2 (AARS2; OMIM 612035) have been linked to leukoencephalopathy recently. Until now, there have been only 13 cases reported in the literature. Hence, the clinical and genetic characteristics of this disease are not fully understood. Here, we reported an adolescence-onset male leukoencephalopathy patient characterized by progressive limb tremor at the age of 17 years. He had no signs of a cardiomyopathy. Magnetic resonance imaging scanning demonstrated severe cerebellar atrophy and white matter abnormalities involving descending tracts. Focused exome sequencing revealed he had novel compound heterozygous mutations in AARS2 gene (c.2265dupA; p.Arg756fs and c.650C>T; p.Pro217Leu). The patient was diagnosed with AARS2 mutation-related leukodystrophy (AARS2-L). We report a case with novel AARS2 gene mutations with developed striking cerebellar atrophy and leukoencephalopathy, which helps to further understand the clinical and genetic heterogeneity of AARS2-L.
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Alanina-tRNA Ligase/genética , Doenças Cerebelares/genética , Leucoencefalopatias/genética , Mutação , Adolescente , Alanina-tRNA Ligase/metabolismo , Atrofia , Sequência de Bases , Doenças Cerebelares/diagnóstico por imagem , Doenças Cerebelares/patologia , Expressão Gênica , Heterozigoto , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/patologia , Imageamento por Ressonância Magnética , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Substância Branca/patologia , Sequenciamento do ExomaRESUMO
Human breast milk is widely recognized as the best source of nutrients for healthy growth and development of infants; it contains a diverse microbiota. Here, we characterized the diversity of the microbiota in the breast milk of East Asian women and assessed whether delivery mode influenced the microbiota in the milk of healthy breast-feeding mothers. We profiled the microbiota in breast milk samples collected from 133 healthy mothers in Taiwan and in six regions of mainland China (Central, East, North, Northeast, South, and Southwest China) by using 16S rRNA pyrosequencing. Lactation stage (months postpartum when the milk sample was collected) and maternal body mass index did not influence the breast milk microbiota. Bacterial composition at the family level differed significantly among samples from the seven geographical regions. The five most predominant bacterial families were Streptococcaceae (mean relative abundance: 24.4%), Pseudomonadaceae (14.0%), Staphylococcaceae (12.2%), Lactobacillaceae (6.2%), and Oxalobacteraceae (4.8%). The microbial profiles were classified into three clusters, driven by Staphylococcaceae (abundance in Cluster 1: 42.1%), Streptococcaceae (Cluster 2: 48.5%), or Pseudomonadaceae (Cluster 3: 26.5%). Microbial network analysis at the genus level revealed that the abundances of the Gram-positive Staphylococcus, Streptococcus, and Rothia were negatively correlated with those of the Gram-negative Acinetobacter, Bacteroides, Halomonas, Herbaspirillum, and Pseudomonas. Milk from mothers who had undergone Caesarian section (C-section group) had a significantly higher abundance of Lactobacillus (P < 0.05) and a higher number of unique unclassified operational taxonomic units (OTUs) (P < 0.001) than that from mothers who had undergone vaginal delivery (vaginal group). These findings revealed that (i) geographic differences in the microbial profiles were found in breast milk from mothers living in Taiwan and mainland China, (ii) the predominant bacterial families Streptococcaceae, Staphylococcaceae, and Pseudomonadaceae were key components for forming three respective clusters, and (iii) a significantly greater number of unique OTUs was found in the breast milk from mothers who had undergone C-section than from those who had delivered vaginally.
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Folate-mediated one-carbon metabolism is an important therapeutic target of human diseases. We extensively investigated how gene-nutrient interactions may modulate human cancer risk in 2 major folate metabolic genes, MTHFR and GNMT. The biochemical impacts of MTHFR and GNMT on methyl group supply, global DNA methylation, nucleotide biosynthesis, DNA damage, and partitioning of the folate dependent 1-carbon group were carefully studied. The distinct model systems used included: EB virus-transformed lymphoblasts expressing human MTHFR polymorphic genotypes; liver-derived GNMT-null cell-lines with and without GNMT overexpression; and HepG2 cells with stabilized inhibition of MTHFR using shRNA, GNMT wildtype, heterozygotous (GNMT(het)) and knockout (GNMT(nul)) mice. We discovered that the MTHFR TT genotype significantly reduces folate-dependent remethylation under folate restriction, but it assists purine synthesis when folate is adequate. The advantage of de novo purine synthesis found in the MTHFR TT genotype may account for the protective effect of MTHFR in human hematological malignancies. GNMT affects transmethylation kinetics and S-adenosylmethionine (adoMet) synthesis, and facilitates the conservation of methyl groups by limiting homocysteine remethylation fluxes. Restoring GNMT assists methylfolate-dependent reactions and ameliorates the consequences of folate depletion. GNMT expression in vivo improves folate retention and bioavailability in the liver. Loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. The systematic series of studies gives new insights into the underlying mechanisms by which MTHFR and GNMT may participate in human tumor prevention.
Assuntos
Carbono/metabolismo , Metilação de DNA , Ácido Fólico/metabolismo , Glicina N-Metiltransferase/metabolismo , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Neoplasias/metabolismo , Nucleotídeos/biossíntese , Animais , Dano ao DNA , Genótipo , Glicina N-Metiltransferase/genética , Células Hep G2 , Homocisteína/metabolismo , Humanos , Fígado/metabolismo , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Camundongos , Camundongos Knockout , Neoplasias/genética , Estado Nutricional , Purinas/metabolismo , S-Adenosilmetionina/biossíntese , Uracila/metabolismoRESUMO
Glycine N-methyltransferase (GNMT) is a folate binding protein commonly diminished in human hepatoma yet its role in tumor development remains to be established. GNMT binds to methylfolate but is also inhibited by it; how such interactions affect human carcinogenesis is unclear. We postulated that GNMT plays a role in folate-dependent methyl group homeostasis and helps maintain genome integrity by promoting nucleotide biosynthesis and DNA repair. To test the hypothesis, GNMT was over-expressed in GNMT-null cell lines cultured in conditions of folate abundance or restriction. The partitioning of folate dependent 1-carbon groups was investigated using stable isotopic tracers and GC/MS. DNA damage was assessed as uracil content in cell models, as well as in Gnmt wildtype (Gnmt(+/+)), heterozygote (Gnmt(+/-)) and knockout (Gnmt(-/-)) mice under folate deplete, replete, or supplementation conditions. Our study demonstrated that GMMT 1) supports methylene-folate dependent pyrimidine synthesis; 2) supports formylfolate dependent purine syntheses; 3) minimizes uracil incorporation into DNA when cells and animals were exposed to folate depletion; 4) translocates into nuclei during prolonged folate depletion. In conclusion, loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. To our best knowledge, the role of GNMT in folate dependent 1-carbon transfer in nucleotide biosynthesis has never been investigated. The present study gives new insights into the underlying mechanism by which GNMT can participate in tumor prevention/suppression in humans.
Assuntos
Carcinoma Hepatocelular/patologia , Dano ao DNA , Ácido Fólico/farmacologia , Glicina N-Metiltransferase/fisiologia , Hepatócitos/patologia , Neoplasias Hepáticas/patologia , Fígado/patologia , Adenosina/metabolismo , Animais , Radioisótopos de Carbono , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Metilação de DNA , Suplementos Nutricionais , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Hepatócitos/metabolismo , Homocisteína/metabolismo , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Camundongos , Camundongos Knockout , Antígenos de Histocompatibilidade Menor , Transporte Proteico , Purinas/metabolismo , Pirimidinas/metabolismo , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Tetra-Hidrofolatos , Uracila/metabolismoRESUMO
Varicocele, a cause of male infertility, occurs in nearly 40% of infertile males. It has been postulated that varicoceles may cause sperm DNA damage. Sperm DNA integrity has been recognized as one of the important determinants of normal fertilization and embryo growth in natural and assisted conception. Eighty-three human studies were identified after an extensive literature search involving the role of varicoceles in sperm DNA damage. Of the 83 studies, 12 were selected that measured similar types of reactive sperm DNA damage. Seven studies determined the damage of sperm DNA in varicocele-associated patients and six studies evaluated the efficacy of varicocelectomy. One study was a duplicate because both outcomes were included. Data were analysed using RevMan software. The overall estimate showed that patients with varicoceles have significantly higher sperm DNA damage than controls, with a mean difference of 9.84% (95% CI 9.19 to 10.49; P<0.00001). A varicocelectomy can improve sperm DNA integrity, with a mean difference of -3.37% (95% CI -4.09 to -2.65; P<0.00001). In conclusion, there is increased sperm DNA damage in patients with varicoceles and varicocelectomy may be a possible treatment; however, more studies with appropriate controls are needed to confirm this finding. A varicocele is an important cause of male infertility and occurs in nearly 40% of infertile males. The recent understanding of the effect of varicoceles in male reproduction has led some researchers to postulate varicoceles as the possible cause of sperm DNA damage. Eighty-three human studies were identified after an extensive literature search involving the role of varicoceles in sperm DNA damage. Of the 83 studies, 12 were selected that measured similar types of reactive sperm DNA damage by a similar method. Seven studies determined the damage of sperm DNA in varicocele-associated patients and six studies evaluated the efficacy of varicocelectomy. One study was a duplicate because both outcomes were included. The data were then entered in the RevMan software for analysis. The overall estimate showed that patients with varicoceles have significantly higher sperm DNA damage than controls, with a mean difference of 9.84% (95% CI 9.19 to 10.49; P<0.00001). A varicocelectomy can improve sperm DNA integrity, with a mean difference of -3.37% (95% CI -4.09 to -2.65; P<0.00001). Based on the results, it can be concluded that there is increased sperm DNA damage in patients with varicoceles and that varicocelectomy may be a possible treatment; however, more studies with appropriate controls are needed to confirm this finding.
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Dano ao DNA , Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Espermatozoides/metabolismo , Varicocele/diagnóstico , Varicocele/cirurgia , Fragmentação do DNA , Humanos , Masculino , Microcirurgia/métodos , Contagem de Espermatozoides , Motilidade dos Espermatozoides/genética , Resultado do Tratamento , Varicocele/complicações , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Glycine N-methyltransferase (GNMT) is a major hepatic enzyme that converts S-adenosylmethionine to S-adenosylhomocysteine while generating sarcosine from glycine, hence it can regulate mediating methyl group availability in mammalian cells. GNMT is also a major hepatic folate binding protein that binds to, and, subsequently, may be inhibited by 5-methyltetrafolate. GNMT is commonly diminished in human hepatoma; yet its role in cellular folate metabolism, in tumorigenesis and antifolate therapies, is not understood completely. In the present study, we investigated the impacts of GNMT expression on cell growth, folate status, methylfolate-dependent reactions and antifolate cytotoxicity. GNMT-diminished hepatoma cell lines transfected with GNMT were cultured under folate abundance or restriction. Folate-dependent homocysteine remethylation fluxes were investigated using stable isotopic tracers and gas chromatography/mass spectrometry. Folate status was compared between wild-type (WT), GNMT transgenic (GNMT(tg)) and GNMT knockout (GNMT(ko)) mice. In the cell model, GNMT expression increased folate concentration, induced folate-dependent homocysteine remethylation, and reduced antifolate methotrexate cytotoxicity. In the mouse models, GNMT(tg) had increased hepatic folate significantly, whereas GNMT(ko) had reduced folate. Liver folate levels correlated well with GNMT expressions (r = 0.53, P = 0.002); and methionine synthase expression was reduced significantly in GNMT(ko), demonstrating impaired methylfolate-dependent metabolism by GNMT deletion. In conclusion, we demonstrated novel findings that restoring GNMT assists methylfolate-dependent reactions and ameliorates the consequences of folate depletion. GNMT expression in vivo improves folate retention and bioavailability in the liver. Studies on how GNMT expression impacts the distribution of different folate cofactors and the regulation of specific folate dependent reactions are underway.
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5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Ácido Fólico/metabolismo , Glicina N-Metiltransferase/metabolismo , Fígado/metabolismo , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Animais , Glicina N-Metiltransferase/genética , Células Hep G2 , Homocisteína/metabolismo , Humanos , Fígado/enzimologia , Metilação , Camundongos , Camundongos TransgênicosRESUMO
OBJECTIVE: To investigate the effect of focal irrigation with mild hypothermic artificial cerebral spinal fluid on the spinal ischemia/reperfusion injury. METHODS: Eighteen health male New Zealand white rabbits were randomly divided into three groups: normal control group (Group NC), spinal ischemia-reperfusion group (Group SIR) and focal irrigation with mild hypothermic artificial cerebral spinal fluid group (Group FI). The rabbits in Group SIR and Group FI were subjected to spinal ischemia/reperfusion injury by clamping the infrarenal abdominal aorta. The rabbits in Group FI received focal irrigation with 25 degrees C artificial cerebral spinal fluid during the spinal ischemia period. The mean arterial pressure (MAP) and cerebral spinal fluid pressure (CSFP) were continuously measured during the ischemic/reperfusion processes. The neurological conditions of the rabbits were assessed at 24 h, 48 h and 72 h after reperfusions. The spinal cords were harvested 72 h after reperfusions for histological analysis. RESULTS: The MAP and CSFP in Group NC remained stable. The MAP in Group SIR and Group FI decreased continuously in the first 30 min of spinal ischemia period and 30 min after reperfusion. The CSFP in Group SIR increased continuously in the first 10 min of spinal ischemia and was higher than the baseline and those in Group NC. The CSFP in Group FI decreased to 3.8 mmHg (1 mmHg = 0.1333 kPa) at the beginning of spinal ischemia, and remained at 3-5 mmHg until 20 min after reperfusions. Group FI had better neurological outcomes and less severe pathological changes than Group SIR measured at 72 h after ischemia/reperfusion. CONCLUSION: Focal irrigation with mild hypothermic artificial cerebral spinal fluid can decrease CSFP during spinal ischemia/reperfusion and protect spinal cords against ischemia/reperfusion injuries.
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Líquido Cefalorraquidiano/química , Hipotermia Induzida/métodos , Isquemia/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Medula Espinal/irrigação sanguínea , Animais , Masculino , Perfusão , Coelhos , Distribuição Aleatória , Medula Espinal/patologiaRESUMO
To increase drug concentration in the head through intranasal administration, we have investigated the excised animal nasal mucosa permeability and nasal toxicity of the baicalin drug carrier systems, such as baicalin liposomes, beta-cyclodextrin inclusion compound, and phospholipid complex. A transport of baicalin drug carrier systems through nasal mucosa was simulated in diffusion chamber in vitro, and swine, caprine and rabbit nasal mucosa was used, the concentration of drug in the receptor was determined by HPLC. By taking the apparent permeability coefficients as evaluation standard, investigated the isolated animal nasal mucosa permeability of different baicalin drug systems was investigated for screening the best baicalin drug carrier system through nasal cavity administration. Toxicity of baicalin and its phospholipids complex on toad palate mucosal cilia movement and rats nasal mucosa long-term toxicity were studied in vivo. The apparent permeability coefficient of three kinds of baicalin drug carrier systems was better than that of baicalin (P < 0.05), and its lag-time was obviously shortened. At the same time, the apparent permeability coefficient of phospholipid complex was higher than those of other two drug carrier systems (P < 0.05). The results showed that the baicalin phospholipids complex nasal mucosa permeability was obviously superior to the other two drug systems. Baicalin phospholipids complex had no toxicity to ciliary movement, and had no irritation to rat nasal mucosa. The results show that baicalin phospholipid complex was the best baicalin drug carrier system, it could significantly enhance the permeability of baicalin across nasal mucosa, had no toxicity to nasal mucosa, and could be used for intranasal administration.
Assuntos
Portadores de Fármacos/farmacocinética , Flavonoides/farmacocinética , Mucosa Nasal/metabolismo , Fosfolipídeos/farmacocinética , Administração Intranasal , Animais , Bufo bufo , Portadores de Fármacos/toxicidade , Sistemas de Liberação de Medicamentos , Feminino , Flavonoides/administração & dosagem , Flavonoides/toxicidade , Cabras , Lipossomos/farmacocinética , Lipossomos/toxicidade , Masculino , Mucosa Nasal/efeitos dos fármacos , Palato/efeitos dos fármacos , Permeabilidade , Fosfolipídeos/toxicidade , Coelhos , Distribuição Aleatória , Ratos , Suínos , beta-Ciclodextrinas/farmacocinética , beta-Ciclodextrinas/toxicidadeRESUMO
ZnO-Al(2)O(3) composites with different Zn/Al molar ratios (R) have been prepared using zinc-aluminium layered double hydroxides (LDHs) Zn( R )Al-CO(3) as precursor. The samples were characterized by XRD, ICP, EDX, EPR and FT-IR. The results show that ZnO is highly dispersed in all of the ZnO-Al(2)O(3) composites. Bactericidal experiments against Staphylococcus aureus ATCC 6538 and Bacillus subtilis var. niger ATCC 9372 were carried out by contacting the bacteria and spores with the ZnO-Al(2)O(3) composites. The composites all showed high bactericidal activity against Staphylococcus aureus ATCC 6538, and the bactericidal efficiency against Bacillus subtilis var. niger ATCC 9372 increased with increasing content of ZnO. The mechanism of bactericidal activity of ZnO-Al(2)O(3) has also been investigated. It is suggested that highly active O(2) (-) and *OH species generated on the surface of ZnO-Al(2)O(3) particles react with the peptide linkages in the cell walls of bacteria or spores resulting in their destruction.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/química , Bacillus/efeitos dos fármacos , Bacillus/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Óxido de Zinco/administração & dosagem , Óxido de Zinco/química , Sobrevivência Celular/efeitos dos fármacos , Hidróxidos/química , Teste de Materiais , NanoestruturasRESUMO
OBJECTIVE: To reveal the mechanism of propofol aortic infusion in protecting ischemia-reperfusion spinal cords through detecting the IL-6 levels in the spinal cords and observing the neurological functioning. METHODS: Fifty six healthy New Zealand White rabbits were randomly allocated into three groups, 4 in the control group, 26 in the Saline infusion group and 26 in the Propofol infusion group. The spinal cord ischemia was induced by infrarenal aorta occlusion for 30 minutes. Propofol were infused through aorta distal to the occlude sites of the rabbits in the Propofol infusion group continuously with a pump at a rate of 50 mg/kg x 30 min. The same volume of Saline were infused in the same way and at the same rate to the rabbits in the Saline infusion group. The lumbar segments of 4-6 spinal cords were harvested and the IL-6 were examined 0 hour or 2 hours after reperfusion. The spinal cords of the rabbits in the control group were harvested right after anesthesia. Forty eight hours after reperfusion, the neurological functioning of the rabbits was assessed with the Tarlov scale system and the normal motor neurons of anterior horn of the lumbar segments of 4-6 spinal cords were counted. RESULTS: The IL-6 levels of the rabbits in the Saline infusion group were significant higher than those in the control group and the Propofol infusion group (P < 0.05). There was no significant difference in the IL-6 level between the Propofol infusion group and the control group (P > 0.05). A significant increase of IL-6 in the rabbits in the Saline infusion group and the Propofol infusion group 2 hours after reperfusion was observed (P < 0.05). The rabbits in the Propofol infusion group had less paraplegia (30%) and more normal neurons (8.4) than those in the Saline infusion group (80% and 1.9, respectively) (P < 0.05). CONCLUSION: Occlusion of aorta increases IL-6 in the injured spinal cords. Propofol aortic infusion can decrease the IL-6 level and improve the neurological functioning, which is perhaps associated with the inflammatory inhibition effect of Propofol.