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1.
J Cell Mol Med ; 28(7): e18221, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38509759

RESUMO

Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 µM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy.


Assuntos
Glioma , Naftalenos , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Apoptose , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Serina-Treonina Quinases TOR/metabolismo , Naftalenos/farmacologia
2.
Biomed Chromatogr ; 37(6): e5613, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36849133

RESUMO

Fluvoxamine is a selective serotonin reuptake inhibitor commonly used for various types of depression. The purpose of this study was to evaluate the pharmacokinetics and bioequivalence of fluvoxamine maleate tablets orally on an empty stomach and after a meal in healthy adult Chinese subjects and to preliminarily evaluate their safety. A single-center, randomized, open-label, two-drug, two-period, crossover, single-dose trial protocol was designed. Sixty healthy Chinese participants were enrolled and randomly classified into fasting (n = 30) and fed groups (n = 30). Each week, subjects took fluvoxamine maleate tablets 50 mg orally once as a test preparation or as a reference preparation on an empty stomach/after meals. To evaluate the bioequivalence of test and reference tables, the concentration of fluvoxamine maleate in the plasma of the subjects at different time points after administration was detected by liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters including the maximum plasma drug concentration (Cmax ), the time to reach maximum concentration (Tmax ), the area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t ) and the area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞ ) were calculated. Our data revealed that the 90% confidence intervals of the geometric mean ratio of the test or reference drugs for the Cmax , AUC0-t and AUC0-∞ fell within the acceptance range for bioequivalence (92.30-102.77%). The absorption, measured by AUC, did not show a significant difference between the two groups. There were no suspected serious adverse reactions or serious adverse events over the entire trial. Our results demonstrated that the test and reference tablets were bioequivalent under fasting and fed conditions.


Assuntos
Fluvoxamina , Adulto , Humanos , Área Sob a Curva , China , Estudos Cross-Over , População do Leste Asiático , Jejum , Fluvoxamina/farmacocinética , Voluntários Saudáveis , Comprimidos , Espectrometria de Massas em Tandem , Equivalência Terapêutica
3.
Mol Psychiatry ; 26(12): 7363-7371, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385597

RESUMO

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.


Assuntos
Transtorno Depressivo Maior , Encéfalo , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética/métodos , Vias Neurais , Tamanho da Amostra
4.
Bipolar Disord ; 24(4): 400-411, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34606159

RESUMO

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
BMC Health Serv Res ; 22(1): 399, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35346179

RESUMO

BACKGROUND: During the coronavirus disease 2019 (COVID-19) containment, primary health care (PHC) facilities inChina played an important role in providing both healthcare and public care services to community populations. The tasks of COVID-19 containment facilitated by PHC facilities were different among different regions and during different periods of COVID-19 pandemic. We sought to investigate the gaps on task participation, explore existing problems and provide corresponding solutions. METHODS: Semi-structured face-to-face interviews with COVID-19 prevention and control management teams of PHC facilities were conducted. Purposive stratified sampling was used and 32 team members of 22 PHC facilities were selected from Wuhan (as high-risk city), Shanghai (as medium-risk city) and Zunyi (as low-risk city). Framework analysis was employed to analyze the transcribed recordings. RESULTS: The main tasks of PHC facilities during the early period of the pandemic included assisting in contact tracing and epidemiological investigation, screening of populations at high-risk at travel centers/internals, house-by-house, or pre-examination/triage within PHC facilities; at-home/ centralized quarantine management; the work of fever sentinel clinics. Further analyses revealed the existing problems and suggestions for improvement or resolutions. Regular medical supply reserves were recommended because of the medical supply shortage during the pre-outbreak period. Temporarily converted quarantine wards and centralized quarantine centers could be used to deal with pressures on patients' treatment and management of the febrile patients. Only after strict evaluation of nucleic acid testing (NAT) results and housing conditions, decision on quarantine at-home or centralized quarantine centers could be made. Settings of fever sentinel clinics at PHC facilities allowed fever patients with no COVID-19 infection risks for treatment without being transferred to fever clinics of the designed secondary hospitals. Psychological intervention was sometimes in need and really helped in addressing individuals' mental pressures. CONCLUSIONS: During the COVID-19 containment, PHC facilities in China were responsible for different tasks and several problems were encountered in the working process. Accordingly, specific and feasible suggestions were put forward for different problems. Our findings are highly beneficial for healthcare teams and governments in handling similar situations.


Assuntos
COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Cidades , Humanos , Pandemias/prevenção & controle , Atenção Primária à Saúde
6.
Proc Natl Acad Sci U S A ; 116(18): 9078-9083, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30979801

RESUMO

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.


Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Mapeamento Encefálico/métodos , China , Conectoma/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Vias Neurais/fisiopatologia , Descanso/fisiologia
7.
Reproduction ; 162(1): 83-94, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33983895

RESUMO

Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, can significantly improve the reprogramming efficiency of somatic cells. However, whether TSA has a detrimental effect on other kinds of embryos is largely unknown because of the lack of integrated analysis of the TSA effect on natural fertilized embryos. To investigate the effect of TSA on mouse embryo development, we analyzed preimplantation and post-implantation development of in vivo, in vitro fertilized, and parthenogenetic embryos treated with TSA at different concentrations and durations. In vivo fertilized embryos appeared to be the most sensitive to TSA treatment among the three groups, and the blastocyst formation rate decreased sharply as TSA concentration and treatment time increased. TSA treatment also reduced the livebirth rate for in vivo fertilized embryos from 56.59 to 38.33% but did not significantly affect postnatal biological functions such as the pups' reproductive performance and their ability for spatial learning and memory. Further analysis indicated that the acetylation level of H3K9 and H4K5 was enhanced by TSA treatment at low concentrations, while DNA methylation appeared to be also disturbed by TSA treatment only at high concentration. Thus, our data indicates that TSA has different effects on preimplantation embryonic development depending on the nature of the embryo's reproductive origin, the TSA concentration and treatment time, whereas the effect of TSA at the indicated concentration on postnatal function was minor.


Assuntos
Blastocisto/citologia , Embrião de Mamíferos/citologia , Desenvolvimento Embrionário , Ácidos Hidroxâmicos/farmacologia , Aprendizagem/fisiologia , Memória/fisiologia , Reprodução , Acetilação , Animais , Animais Recém-Nascidos , Blastocisto/efeitos dos fármacos , Metilação de DNA , Implantação do Embrião , Transferência Embrionária , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Fertilização in vitro , Inibidores de Histona Desacetilases/farmacologia , Histonas/química , Histonas/genética , Histonas/metabolismo , Masculino , Camundongos , Técnicas de Transferência Nuclear , Gravidez
8.
Trop Med Int Health ; 26(11): 1419-1426, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34370367

RESUMO

OBJECTIVES: Human toxocariasis is a widespread zoonosis for which a chemotherapy decision and therapy effectiveness are difficult to determine. We aimed to investigate the kinetic profile of clinical and laboratory findings and treatment outcome of patients with toxocariasis in Vietnam. METHODS: The prospective study was conducted between October 2017 and June 2019. The diagnosis of toxocariasis was established based on clinical, laboratory (eosinophilia, raised IgE concentration) and serological (positive Toxocara IgG ELISA) evaluation as well as the exclusion of another helminthic co-infection. The patients were followed up after seven days, then one, three and six months after chemotherapy by thiabendazole. RESULTS: The study involved 80 patients with a mean age of 41.6 ± 15.2 years of whom 58.8% were female. At three and six months after chemotherapy, most patients demonstrated resolution of clinical signs and symptoms, eosinophil count and IgE concentration but not in the proportion of IgG seropositivity. Skin lesions and eosinophilia resolved earlier than the other symptoms (one month after treatment). About four-fifths of the patients were "cured" after three and six months of follow-up; 33.8% showed side effects to thiabendazole therapy but no severe events were reported. The most common adverse reaction was neurologic symptoms followed by gastrointestinal or skin manifestations which lasted as long as 4 days. CONCLUSIONS: In toxocariasis patients, cutaneous manifestations and eosinophilia resolve more rapidly than other clinical and laboratory findings while IgG titre has a very slow kinetic after therapy. Thiabendazole seems to be a potential alternative for the treatment of human toxocariasis.


Assuntos
Toxocaríase/diagnóstico , Adolescente , Adulto , Idoso , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Anticorpos Anti-Helmínticos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tiabendazol/administração & dosagem , Tiabendazol/uso terapêutico , Toxocara/imunologia , Toxocaríase/sangue , Toxocaríase/tratamento farmacológico , Toxocaríase/epidemiologia , Vietnã/epidemiologia , Adulto Jovem , Zoonoses/diagnóstico , Zoonoses/tratamento farmacológico
9.
Childs Nerv Syst ; 37(2): 671-676, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32588176

RESUMO

Pineal region is deep located and tightly connected with surrounding important nerves, blood vessels, and other critical structure. Tumors in the regions are more commonly observed in children with complex pathology, difficult surgery, and poor prognosis. However, excision surgery on large tumor in the pineal region and extending into the third ventricle is characterized by high difficulty and uneasy treatment. Related experience and knowledge about excising large tumor in children pineal region which extending into the third ventricle by transcallosal-lateral ventricle-choroid fissure approach was described in the paper. Clinical data of 15 children patients with large tumors in pineal region which extending into the third ventricle treated by our group from 2011 to 2015 was retrospectively analyzed (< 15 years of age, tumor size > >3 × 3 × 3 cm3). Fifteen cases underwent tumor excision with surgery by transcallosal-lateral ventricle-choroid fissure approach including 11 male patients and 4 female patients with average age of 9.1 years and tumor volume from 3 × 3 × 3 to 5 × 6 × 7 cm3. They were assessed according to postoperative clinical symptom remission rate, blood loss during surgery, tumor removal rate, postoperative recurrence rate, etc. as indicators. Five cases belonged to germ cell tumors, 4 for teratoma, 1 for malignant teratoma, 2 for glioma, 2 for meningioma, and 1 for pineocytoma. Surgical total excision rate was 100%, while the mean intraoperative blood loss was about 300 ml. No case was dead due to surgery, and all cases had good postoperative recovery. Children patients are characterized by less blood than adults, larger volume size during surgery treatment, poor postoperative anti-infectious ability, etc. High requirements are proposed on surgery treatment, by long-term clinical exploration and experience accumulation. Our group believes that surrounding structures such as veins and dome are stretched and stimulated rarely in excision of children in large and medium tumor in pineal region which extending into the third ventricle by transcallosal-lateral ventricle-choroid fissure approach; thereby, the tumor can be completely excised, and larger veins and other important structures can be well-preserved with fewer complications, high full cut rate, and rapid recovery.


Assuntos
Neoplasias Encefálicas , Neoplasias do Ventrículo Cerebral , Neoplasias Meníngeas , Glândula Pineal , Pinealoma , Terceiro Ventrículo , Adulto , Criança , Corioide , Feminino , Humanos , Ventrículos Laterais/diagnóstico por imagem , Ventrículos Laterais/cirurgia , Masculino , Recidiva Local de Neoplasia , Glândula Pineal/diagnóstico por imagem , Glândula Pineal/cirurgia , Pinealoma/diagnóstico por imagem , Pinealoma/cirurgia , Estudos Retrospectivos , Terceiro Ventrículo/diagnóstico por imagem , Terceiro Ventrículo/cirurgia
10.
Blood ; 130(20): 2161-2170, 2017 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-28972010

RESUMO

Congenital hypothyroidism (CH) is one of the most prevalent endocrine diseases, for which the underlying mechanisms remain unknown; it is often accompanied by anemia and immunodeficiency in patients. Here, we created a severe CH model together with anemia and T lymphopenia to mimic the clinical features of hypothyroid patients by ethylnitrosourea (ENU) mutagenesis in Bama miniature pigs. A novel recessive c.1226A>G transition of the dual oxidase 2 (DUOX2) gene was identified as the causative mutation. This mutation hindered the production of hydrogen peroxide (H2O2) and thus contributed to thyroid hormone (TH) synthesis failure. Transcriptome sequencing analysis of the thymuses showed that Krüppel-like factor 9 (KLF9) was predominantly downregulated in hypothyroid mutants. KLF9 was verified to be directly regulated by TH in a TH receptor (TR)-dependent manner both in vivo and in vitro. Furthermore, knockdown of klf9 in zebrafish embryos impaired hematopoietic development including erythroid maturation and T lymphopoiesis. Our findings suggest that the TR-KLF9 axis is responsible for the hematopoietic dysfunction and might be exploited for the development of novel therapeutic interventions for thyroid diseases.


Assuntos
Hipotireoidismo Congênito/fisiopatologia , Modelos Animais de Doenças , Hematopoese , Fatores de Transcrição Kruppel-Like/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Suínos , Hormônios Tireóideos/fisiologia , Animais , Hipotireoidismo Congênito/genética , Oxidases Duais/genética , Etilnitrosoureia , Regulação da Expressão Gênica , Genes Recessivos , Peróxido de Hidrogênio/metabolismo , Redes e Vias Metabólicas , Mutagênese Sítio-Dirigida , Mutação , Timo , Sequenciamento do Exoma , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
11.
Cell Mol Life Sci ; 75(24): 4619-4628, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30259067

RESUMO

Insulin-like growth factor 2 (IGF2) is an important growth factor, which promotes growth and development in mammals during fetal and postnatal stages. Using CRISPR-Cas9 system, we generated multiple founder pigs containing 12 different mutant alleles around a regulatory element within the intron 3 of IGF2 gene. Crossing two male founders passed four mutant alleles onto F1 generation, and these mutations abolished repressor ZBED6 binding and rendered this regulatory element nonfunctional. Both founders and F1 animals showed significantly faster growth, without affecting meat quality. These results indicated that editing IGF2 intron 3-3072 site using CRISPR-Cas9 technology improved meat production in Bama pigs. This is the first demonstration that editing non-coding region can improve economic traits in livestock.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Fator de Crescimento Insulin-Like II/genética , Íntrons , Sequências Reguladoras de Ácido Nucleico , Suínos/genética , Alelos , Criação de Animais Domésticos/métodos , Animais , Cruzamento/métodos , Feminino , Genótipo , Masculino , Carne/análise , Mutação , Fenótipo
12.
Int J Mol Sci ; 20(18)2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31540158

RESUMO

The mediator complex is an essential link between transcription factors and RNA polymerase II, and mainly functions in the transduction of diverse signals to genes involved in different pathways. Limited information is available on the role of soybean mediator subunits in growth and development, and their participation in defense response regulation. Here, we performed genome-wide identification of the 95 soybean mediator subunits, which were unevenly localized on the 20 chromosomes and only segmental duplication events were detected. We focused on GmMED16-1, which is highly expressed in the roots, for further functional analysis. Transcription of GmMED16-1 was induced in response to Phytophthora sojae infection. Agrobacterium rhizogenes mediated soybean hairy root transformation was performed for the silencing of the GmMED16-1 gene. Silencing of GmMED16-1 led to an enhanced susceptibility phenotype and increased accumulation of P. sojae biomass in hairy roots of transformants. The transcript levels of NPR1, PR1a, and PR5 in the salicylic acid defense pathway in roots of GmMED16-1-silenced transformants were lower than those of empty-vector transformants. The results provide evidence that GmMED16-1 may participate in the soybean-P. sojae interaction via a salicylic acid-dependent process.


Assuntos
Estudo de Associação Genômica Ampla , Glycine max/genética , Glycine max/parasitologia , Interações Hospedeiro-Parasita/genética , Complexo Mediador/metabolismo , Phytophthora/fisiologia , Mapeamento Cromossômico , Cromossomos de Plantas , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Phytophthora/classificação , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Subunidades Proteicas , Transcriptoma
13.
Zhongguo Zhong Yao Za Zhi ; 44(18): 4000-4008, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31872737

RESUMO

Agarwood is a traditional and precious medicinal material and natural spice in China and other southeast Asian countries.As the head of all spices,agarwood has many pharmacological activities such as analgesia,antidiarrheal,anti-inflammatory and antibacterial effects. Due to its high price and scarce resources,there were just a few previous studies on it,mainly focusing on the chemical compositions of the agarwood essential oil and solvent extract mixture. The components of agarwood oils obtained by supercritical extraction and steam distillation were analyzed by using Gas Chromatography-Mass Spectrometer( GC-MS),and then the agarwood oils compositions and contents were compared between the traditional extraction method and the recently emerging supercritical extraction method. Antioxidant experiments of scavenging DPPH,ABTS,hydroxyl radical,total reducing power and MIC experiments of five kinds of tester strains such as staphylococcus aureus were combined to illustrate the differences between these two kinds of agarwood oils in terms of antioxidant and bacteriostatic activities. The results showed that the main components of agarwood oil were sesquiterpenoids( 68. 68%) in steam distillation extraction method,but sesquiterpenoids( 23. 78%) and chromones( 29. 42%) in supercritical extraction method. Fourteen common components included benzyl acetone,α-santalol,γ-eudesmol,agarospirol and guaiol etc. The antioxidant activity and inhibitory MIC of agarwood oils in supercritical extraction method were better than those in steam distillation method,and the inhibitory effect of agarwood oil on the growth of bacillus subtilis was found for the first time.


Assuntos
Antibacterianos/química , Antioxidantes/química , Destilação/métodos , Óleos Voláteis/química , Óleos de Plantas/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , China , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Vapor , Thymelaeaceae/química , Madeira/química
14.
Eur J Clin Pharmacol ; 74(1): 61-67, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28975417

RESUMO

PURPOSE: The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. METHODS: This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. RESULTS: All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUCt) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. CONCLUSIONS: These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about the ingestion of grapefruit juice.


Assuntos
Citrus paradisi , Interações Alimento-Droga , Sucos de Frutas e Vegetais , Piperazinas/sangue , Piperidinas/sangue , Adulto , Área Sob a Curva , Disponibilidade Biológica , Citocromo P-450 CYP3A/metabolismo , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Humanos , Intestinos/enzimologia , Masculino , Piperazinas/administração & dosagem , Piperidinas/administração & dosagem , Adulto Jovem
15.
Hum Genet ; 136(11-12): 1463-1475, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29094203

RESUMO

Human Waardenburg syndrome 2A (WS2A) is a dominant hearing loss (HL) syndrome caused by mutations in the microphthalmia-associated transcription factor (MITF) gene. In mouse models with MITF mutations, WS2A is transmitted in a recessive pattern, which limits the study of hearing loss (HL) pathology. In the current study, we performed ENU (ethylnitrosourea) mutagenesis that resulted in substituting a conserved lysine with a serine (p. L247S) in the DNA-binding domain of the MITF gene to generate a novel miniature pig model of WS2A. The heterozygous mutant pig (MITF +/L247S) exhibits a dominant form of profound HL and hypopigmentation in skin, hair, and iris, accompanied by degeneration of stria vascularis (SV), fused hair cells, and the absence of endocochlear potential, which indicate the pathology of human WS2A. Besides hypopigmentation and bilateral HL, the homozygous mutant pig (MITF L247S/L247S) and CRISPR/Cas9-mediated MITF bi-allelic knockout pigs both exhibited anophthalmia. Three WS2 patients carrying MITF mutations adjacent to the corresponding region were also identified. The pig models resemble the clinical symptom and molecular pathology of human WS2A patients perfectly, which will provide new clues for better understanding the etiology and development of novel treatment strategies for human HL.


Assuntos
Modelos Animais de Doenças , Etilnitrosoureia/toxicidade , Perda Auditiva/genética , Fator de Transcrição Associado à Microftalmia/genética , Mutação , Síndrome de Waardenburg/genética , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Feminino , Perda Auditiva/induzido quimicamente , Perda Auditiva/patologia , Humanos , Masculino , Fator de Transcrição Associado à Microftalmia/antagonistas & inibidores , Mutagênese , Mutagênicos/toxicidade , Homologia de Sequência , Suínos , Porco Miniatura , Síndrome de Waardenburg/induzido quimicamente , Síndrome de Waardenburg/patologia
16.
Med Sci Monit ; 22: 2431-8, 2016 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-27404044

RESUMO

BACKGROUND The purpose of the study was to analyze the risk factors for failed extubation in subjects submitted to infratentorial craniotomy. MATERIAL AND METHODS Patients aged over 18 years who received infratentorial craniotomy for brain tumor resection were consecutively included in this study. Perioperative variables were collected and analyzed. Univariate analyses and multiple logistic regression were used to derive factors related to failed extubation. Patients had follow-up care until either out of hospital or death. RESULTS Throughout the course of the study, 2118 patients were eligible and 94 (4.4%) suffered from extubation failure at some point during their hospital stay. Five factors were recognized as independent risk factors for postoperative failed extubation: craniotomy history, preoperative lower cranial nerve dysfunction, tumor size, tumor position, and maximum change in blood pressure (BP) during the operation. Failed extubation was related to a higher incidence rate of pneumonia, mortality, unfavorable Glasgow Outcome Scale score, longer stay in the neuro-intensive care unit (ICU) and hospitalization, and higher hospitalization costs compared with successful extubation. CONCLUSIONS History of craniotomy, preoperative lower cranial nerve dysfunction, tumor size, tumor position, and maximum change in BP during the operation were independent risk factors related to postoperative failed extubation in patients submitted to infratentorial craniotomy. Extubation failure raises the incidences of postoperative pneumonia, mortality, and higher hospitalization costs, and prolongs neuro-ICU and postoperative length of stay.


Assuntos
Extubação/métodos , Craniotomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Extubação/mortalidade , Extubação/estatística & dados numéricos , China/epidemiologia , Craniotomia/efeitos adversos , Craniotomia/mortalidade , Craniotomia/estatística & dados numéricos , Feminino , Humanos , Neoplasias Infratentoriais/epidemiologia , Neoplasias Infratentoriais/cirurgia , Unidades de Terapia Intensiva , Intubação Intratraqueal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
17.
Yao Xue Xue Bao ; 51(8): 1202-8, 2016 08.
Artigo em Chinês | MEDLINE | ID: mdl-29897713

RESUMO

Recently, more and more attentions of drug development are placed to macromolecules, such as monoclonal antibodies, proteins, etc. It has become one of the most promising areas in drug research and development in 21st Century. In terms of the structure and the ADMET (absorption, distribution, metabolism, excretion and toxicity), macromolecules is different from small molecule drugs, which lead to a distinct modeling strategy. The characterization of biologics ADMET processes and its application in the PK model selection of macromolecules are reviewed in this paper.


Assuntos
Anticorpos Monoclonais/farmacocinética , Produtos Biológicos/farmacocinética , Preparações Farmacêuticas
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(10): 3243-8, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30246947

RESUMO

With concentrated phosphoric acid as catalyst and various organic solvents as liquefying agents, corn stalk powder was liquefied into bio-oil in an autoclave, under the condition of 170 ℃. Analysis was conducted to throw light on the liquefying effects of three different agents; they are glycerol triacetate with ethylene carbonate, glycerol with ethylene carbonate and polyethylene glycol with ethylene carbonate(6∶1 ω/ω), and the properties of the biomass liquefaction oil products. FT-IR was applied to examine raw material and residues, whose chemical compositions were further analyzed with the use of GC-MS. The results of experiments indicated that the liquefaction yield of polyethylene glycol was 97.84%, the yield of glycerol triacetate was 80.20%, the yield of glycerol were36.97%. FT-IR analysis showed that the functional groups of cellulose, hemicelluloses and lignin was disappeared and liquefaction is best when polyethylene glycol with ethylene carbonate was used as the liquefaction agent. GC-MS analysis showed that the oil composition produced in this way is complex, contains organic acids and ketones, alcohols and ethers, aromatic, sugars and esters compounds.

19.
Nature ; 461(7260): 86-90, 2009 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-19672241

RESUMO

Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat. It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells. However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, fertile live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.


Assuntos
Células-Tronco Pluripotentes/fisiologia , Poliploidia , Técnicas Reprodutivas , Animais , Blastocisto/citologia , Blastocisto/fisiologia , Desdiferenciação Celular/fisiologia , Linhagem Celular , Linhagem da Célula , Reprogramação Celular , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Feminino , Fibroblastos/citologia , Perfilação da Expressão Gênica , Teste de Complementação Genética , Masculino , Camundongos , Camundongos SCID , Células-Tronco Pluripotentes/citologia , Gravidez , Taxa de Sobrevida , Teratoma
20.
Opt Express ; 22(25): 30748-55, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25607023

RESUMO

We report the size effects on the metal-insulator phase transition of vanadium dioxide (VO2) nanowires prepared by chemical vapor deposition. The phase transition temperature can be tuned from 67 °C in the bulk VO2 to as low as 29°C by reducing the diameter of VO2 nanowires to nanoscale. Temperature-dependent Raman spectra display a clear dynamic picture on the metal-insulator phase transition process of the VO2 nanowires. Whilst, Raman study shows no remarkable strain effect on the phase transition behaviors of our samples. The increasing surface defect density with reducing nanowire size facilitates the decreasing phase transition temperature. In addition, the polarized-photocurrent effect was observed, resulting from the anisotropy of the photoresponse and also caused by the reduced dimensionality.Our results indicate that size of VO2 nanostructures can dominate their thermoelectric and photoelectrical properties.

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