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1.
Qual Life Res ; 33(1): 207-218, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37824058

RESUMO

OBJECTIVE: To investigate the effects of systemic lupus erythematosus (SLE) on health-related quality of life (HRQOL), the relationship between disease activity and HRQOL, and potential factors affecting HRQOL in Chinese SLE patients. METHODS: This study recruited 1568 patients and 2610 controls to explore the effects of SLE on HRQOL. The association between disease activity and HRQOL, and the influencing factors of HRQOL were determined in 1568 patients. Then, we prospectively followed 1096 patients to explore the association between reduced disease activity and improved HRQOL, and the influencing factors of improved HRQOL. The Short-Form 36 (SF-36) and SLE disease activity index (SLEDAI) were used to evaluate HRQOL and disease activity. RESULTS: Chinese SLE patients had lower HRQOL than controls in all domains (P < 0.001), especially in role-physical (RP) and role-emotional (RE). Compared with SLE patients from outside China, the HRQOL of Chinese patients appeared to be higher in mental component summary (MCS) but lower in RP and RE. SLEDAI was negatively correlated with HRQOL, which was validated using the results of a follow-up study, where SLEDAI reduction was positively associated with HRQOL improvements (P < 0.05). Furthermore, personality, life nervous and experiences of adverse life events may influence HRQOL and HRQOL improvements. CONCLUSION: SLE significantly affected the HRQOL of Chinese patients, especially in RP and RE. Disease activity was negatively correlated with HRQOL. We also found for the first time some factors affecting HRQOL, which can be regarded as the basis for improving the HRQOL of SLE patients.


Assuntos
Lúpus Eritematoso Sistêmico , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Seguimentos , Índice de Gravidade de Doença , Inquéritos e Questionários , Lúpus Eritematoso Sistêmico/psicologia , China
2.
Rheumatology (Oxford) ; 61(6): 2652-2662, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-34718439

RESUMO

OBJECTIVE: To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with SLE susceptibility, glucocorticoid (GC) efficacy and prognosis. METHODS: Our study was done in two stages. First, we performed whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and GC efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis. RESULTS: In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all PBH < 0.05). We confirmed that T16362C was related to efficacy of GCs (PBH = 0.014). Significant associations were detected between T16362C and T16519C and the efficacy of GCs in females with SLE (PBH < 0.05). In the prognosis study, variants A4833G (PBH = 0.003) and G14569A (PBH = 9.744 × 10-4) substantially increased SLE relapse risk. Female patients harbouring variants T5108C and T16362C were more prone to relapse (PBH < 0.05). Haplotype analysis showed that haplogroup G was linked with SLE susceptibility (PBH = 0.001) and prognosis (PBH = 0.013). Moreover, mtDNA variant-environment interactions were observed. CONCLUSION: We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GC efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GC efficacy. Our findings provide important information for future understanding of the occurrence and development of SLE.


Assuntos
Glucocorticoides , Lúpus Eritematoso Sistêmico , DNA Mitocondrial/genética , Feminino , Predisposição Genética para Doença , Glucocorticoides/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Recidiva
3.
Lupus ; 31(14): 1735-1743, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36194484

RESUMO

OBJECTIVE: Our present study intended to examine the associations of RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) with susceptibility, glucocorticoids (GCs) efficacy, anxiety, depression, and health-related quality of life (HRQoL) in Chinese systemic lupus erythematosus (SLE) patients. METHODS: Initially, 1000 participants (500 SLE cases and 500 controls) were recruited for the case-control study. Then, 429 cases who received GCs were followed through 12 weeks to explore GCs efficacy, depression, anxiety, and HRQoL. We selected the iMLDR technique for genotyping: RPEL1: rs4917385 (G/T) and miR-1307: rs7911488 (A/G). RESULTS: The minor G allele of rs7911488 reduced the risk of SLE (p = .024). Four haplotypes consisting of rs4917385 and rs7911488 were associated with SLE susceptibility (p < .025). Both rs4917385 and rs7911488 were associated with anxiety symptoms and physical function (PF) in SLE patients (p < .025). The rs4917385 was associated with depression and its improvement. No statistical significance was found between RPEL1 and miR-1307 gene polymorphisms with GCs efficacy. Meanwhile, additive interaction analysis showed a significant association between RPEL1 and miR-1307 gene polymorphisms with tea consumption in anxiety. CONCLUSION: RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) might be related to SLE susceptibility in Chinese population. Additionally, the two polymorphisms were possibly associated with depression, anxiety, and HRQoL in Chinese SLE population.


Assuntos
Ansiedade , Depressão , Lúpus Eritematoso Sistêmico , MicroRNAs , Humanos , Ansiedade/genética , Ansiedade/diagnóstico , Estudos de Casos e Controles , China/epidemiologia , Depressão/genética , Depressão/diagnóstico , Predisposição Genética para Doença , Glucocorticoides/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/psicologia , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Qualidade de Vida
4.
Scott Med J ; 67(3): 109-120, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35686317

RESUMO

BACKGROUND AND AIMS: This updated meta-analysis aimed to further quantify the risk of endometrial, ovarian, and breast cancer in patients with polycystic ovary syndrome (PCOS), thus providing updated and more reliable estimates. METHODS AND RESULTS: We identified relevant articles by searching electronic databases of PubMed, Embase, Web of Science, and Chinese Biological Medical Literature (CBM) published up to March 20, 2021. The pooled effect estimates and their 95% confidence intervals (CIs) were calculated using the random-effect model or the fixed-effect model. A total of 26 eligible studies were included. We found that PCOS was significantly associated with endometrial cancer (odds ratios [OR]: 3.66, 95%CI: 2.05-6.54, P < 0.001), but not with ovarian or breast cancer (OR: 1.23, 95%CI: 0.99-1.53, P = 0.059; OR: 0.94, 95%CI: 0.78-1.14, P = 0.551, respectively). However, in subgroups of high-quality studies, cohort studies, younger women (54 years or less or premenopausal), and studies with unadjusted body mass index (BMI), PCOS patients had a significantly higher risk of ovarian cancer. CONCLUSION: These results indicated that PCOS is a significant risk factor for endometrial cancer independent of BMI, but not for breast cancer. PCOS may increase the risk of ovarian cancer in younger women.


Assuntos
Neoplasias da Mama , Neoplasias do Endométrio , Neoplasias Ovarianas , Síndrome do Ovário Policístico , Neoplasias da Mama/complicações , Neoplasias da Mama/etiologia , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/etiologia , Feminino , Humanos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Fatores de Risco
5.
BMC Med Educ ; 21(1): 183, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766012

RESUMO

BACKGROUND: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. METHOD: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career. RESULTS: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career. CONCLUSION: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.


Assuntos
Psiquiatria , Estudantes de Medicina , Escolha da Profissão , China , Feminino , Humanos , Psiquiatria/educação , Faculdades de Medicina , Inquéritos e Questionários
6.
Nanotechnology ; 30(34): 345202, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30840935

RESUMO

The excellent conductive surface electronic states of topological insulators make them suitable candidates for the next generation optoelectronic devices. Moreover, their unique semiconducting properties are favorable for building heterojunctions with other semiconductors. Here, we fabricated a low cost and broadband self-powered photodetector based on Sb2Te3 and Si. The photolithography and thermal evaporation technique were combined to fabricate a series of asymmetric planar Sb2Te3 electrodes on the surface of an n-type silicon substrate. An obvious asymmetrical current voltage curve occurred under dark conditions, which is ascribed to the asymmetry of each electrode. During the photodetection test, self-powered photodetection was obtained upon 940 nm light irradiation. Moreover, the photodetector exhibited fast and broadband photodetection from 365 nm to 940 nm with a response time less than 40 ms.

7.
Biosci Biotechnol Biochem ; 83(12): 2375-2385, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31392932

RESUMO

Carotenoids have good biological activity in antioxidant, anti-aging and scavenging harmful free radicals. In this study, we screened a strain that produced carotenoids, and selected a stress condition which significantly improved carotenoids content. The strain was identified as Phaffia rhodozyma PR106. Active oxygen generator TiO2 was the most significant factor to the carotenoids content of the P. rhodozyma. The content of carotenoids was 54.45 mg/g at 500 mg/L TiO2, which was about 1.25 times of the control and the proportion of carotenoids also changed from 1:9:16 to 1:8.5:12. Further, we determined the reactive oxygen species (ROS) in YEPD medium and P. rhodozyma, found that the ROS (H2O2, O2-, and HO•) was significantly increased at 500 mg/L TiO2 in YEPD medium compared with the control, but increased in P. rhodozyma under 1000 mg/L TiO2 treated. These results suggested that the increase in carotenoids was related to ROS in P. rhodozyma.


Assuntos
Basidiomycota/metabolismo , Carotenoides/metabolismo , Estresse Oxidativo , Biomassa , Vias Biossintéticas , Peróxido de Hidrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Titânio/química
8.
BMC Complement Altern Med ; 19(1): 147, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234859

RESUMO

BACKGROUND: Ethanol withdrawal (EtOHW) anxiety is a crucial risk factor for alcoholic relapse. The neuropeptide nociceptin/orphanin FQ (N/OFQ) acts upon its receptor (NOP) to antagonize corticotropin-releasing factor (CRF) and elicit anxiolytic actions. Semen Ziziphi Spinosae (SZS), a prototypical hypnotic-sedative herb in Oriental medicine, exhibits anxiolytic effects during nicotine withdrawal by improving amygdaloid CRF/CRF1 receptor (CRFR1) signaling. Therefore, we evaluated the effects of SZS on EtOHW anxiety and the involvement of amygdaloid CRF/CRFR1 and N/OFQ/NOP pathways. METHODS: Male Sprague Dawley rats received intraperitoneal injections of 2 g/kg EtOH (20% v/v) once daily for 28 d followed by a 3-d withdrawal. During EtOHW, the rats were given once-daily intragastric treatments of a methanol extract of SZS (MESZS, 60 or 180 mg/kg/d). Anxiety-like behaviors were measured with the open field (OF) and elevated plus maze (EPM) tests, and plasma corticosterone (CORT) levels were examined by an enzyme-linked immunosorbent assay. mRNA and protein expression levels of the neuropeptides and their receptors were determined by quantitative polymerase chain reaction and Western blot assays. RESULTS: MESZS increased the distance traveled in the center zone of the OF and dose-dependently elongated the duration of staying in the center zone in EtOHW rats. MESZS increased both the number of entries into and the time spent in the open arms of the EPM by EtOHW rats. And, MESZS inhibited the over secretion of plasma CORT during EtOHW. EtOHW enhanced CRF and CRFR1 gene and protein expression in the central nucleus of the amygdala (CeA), which were inhibited by 180 mg/kg/d MESZS. EtOHW increased amygdaloid NOP mRNA and protein expression but spared N/OFQ mRNA expression, and 180 mg/kg/d MESZS further promoted these increases. Additionally, a post-MESZS intra-CeA infusion of either CRF or the selective NOP antagonist UFP-101 abolished the expected anxiolytic effect of 180 mg/kg/d MESZS. CONCLUSIONS: These results suggest that MESZS ameliorates EtOHW anxiety by improving both CRF/CRFR1 and N/OFQ/NOP transmissions in the CeA.


Assuntos
Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Núcleo Central da Amígdala/efeitos dos fármacos , Etanol/efeitos adversos , Neuropeptídeos/metabolismo , Síndrome de Abstinência a Substâncias/complicações , Ziziphus/química , Animais , Ansiedade/etiologia , Ansiedade/genética , Ansiedade/metabolismo , Núcleo Central da Amígdala/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo
9.
Nanotechnology ; 29(27): 275201, 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29595523

RESUMO

Graphene-structure WSe2 nano-films (NFMs) were prepared by magnetron sputtering and vacuum selenization. The as synthesized WSe2 NFMs were characterized using various techniques such as SEM, XRD and EDS. Our work provides a simple and effective method to prepare WSe2 NFMs. We have observed the high photo responsivity of WSe2 NFMs up to 10 A W-1, which is 40% higher than the previously reported data. Our photoelectrochemical tests demonstrate that WSe2 NFMs have excellent photoelectric properties, indicating that NFMs have a wide application potentialsin solar cells and optoelectronic devices.

10.
Nanotechnology ; 29(16): 165706, 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29384501

RESUMO

Graphene-ZnO (GZO) nanocomposites were synthesized by a modified solvothermal method, and characterized by transmission electron microscopy, x-ray diffraction, Raman spectra, and UV-vis absorption spectra. The controllable nonlinear optical (NLO) properties of as-prepared GZO nanocomposites were tested by an open-aperture Z-scan method with 1030 nm fs laser pulses; the tested results showed that there were five-photon absorption (5PA) at 46.8 GW cm-2, 3PA at 28.1 GW cm-2, 2PA at 18.7 GW cm-2, and a vital change from saturable absorption (SA) to reverse SA (RSA) with the increase of incident intensity. This was the first time that 5PA was found in GZO nanocomposites at such a low intensity, 46.8 GW cm-2. The tunable NLO property from SA to RSA and controllable multi-photon absorption provided a facile approach for their applications in optical, optoelectronic devices, and information storage.

11.
Bioorg Med Chem ; 26(14): 4254-4263, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30054192

RESUMO

With the purpose of identifying novel selective κ opioid receptor (KOR) antagonists as potential antidepressants from nepenthone analogues, starting from N-nor-N-cyclopropylmethyl-nepenthone (SLL-020ACP), a highly selective and potent KOR agonist, a series of 7ß-methyl-nepenthone analogues was conceived, synthesized and assayed on opioid receptors based on the concept of hybridization. According to the pharmacological results, the functional reversal observed in orvinol analogues by introduction of 7ß-methyl substituent could not be reproduced in nepenthone analogues. Alternatively, introduction of 7ß-methyl substituent was associated with substantial loss of both subtype selectivity and potency but not efficacy for nepenthone analogues, which was not found in 7ß-methyl orvinol analogues. Surprisingly, SLL-603, a 7ß-methyl analogue of SLL-020ACP, was identified to be a KOR full agonist. The possible molecular mechanism for the heterogeneity in activity cliff was also investigated. In conclusion, 7ß-methyl substituent was a structural locus associated with activity cliff and demonstrated as a pharmacological heterogeneity between nepenthone and orvinol analogues that warrants further investigations.


Assuntos
Morfinanos/farmacologia , Receptores Opioides kappa/agonistas , Animais , Células CHO , Células Cultivadas , Cricetulus , Relação Dose-Resposta a Droga , Modelos Moleculares , Estrutura Molecular , Morfinanos/síntese química , Morfinanos/química , Relação Estrutura-Atividade
12.
BMC Complement Altern Med ; 17(1): 493, 2017 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-29145840

RESUMO

BACKGROUND: We previously reported that a methanol extract of Glycyrrhizae radix (MEGR) blocked methamphetamine-induced locomotor sensitization and conditioned place preference in rats. In the present study, the effects of MEGR on repeated nicotine-induced locomotor sensitization and enhanced extracellular dopamine (DA) release in the nucleus accumbens (Nacc) were evaluated. METHODS: Male Sprague-Dawley rats received repeated administrations of nicotine (0.4 mg/kg, subcutaneous) or saline twice a day for 7 d and were challenged with nicotine 4 d after the last daily dosing. During the 4-d withdrawal period, the rats were treated once a day with MEGR (60 or 180 mg/kg/d). Extracellular DA levels were measured by in vivo microdialysis, the malondialdehyde levels and the activities of superoxide dismutase and catalase in the Nacc were biochemically evaluated, and the expression of antioxidant proteins was confirmed by Western blot assays. All data were assessed with analysis of variance tests followed by post-hoc comparison tests and p values <0.05 were considered statistically significant. RESULTS: The expression of repeated nicotine-induced locomotor sensitization was dose-dependently attenuated by MEGR, and 180 mg/kg/d MEGR significantly inhibited augmented accumbal DA release induced by a direct local challenge of nicotine. Moreover, 180 mg/kg/d MEGR reversed increases in malondialdehyde production, decreases in superoxide dismutase and catalase activities, and the reduced expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1 in the nicotine-sensitized Nacc. CONCLUSIONS: These results suggest that MEGR inhibited nicotine-induced locomotion and dopaminergic sensitization via antioxidant action.


Assuntos
Glycyrrhiza , Nicotina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Dopamina/metabolismo , Interações Ervas-Drogas , Locomoção/efeitos dos fármacos , Masculino , Metanol , Núcleo Accumbens/química , Núcleo Accumbens/metabolismo , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley
13.
Zhongguo Zhong Yao Za Zhi ; 42(15): 2989-2994, 2017 Aug.
Artigo em Zh | MEDLINE | ID: mdl-29139268

RESUMO

Models were established in mice with warfarin sodium method, and their bleeding time and hemostasis time were measured by tail cutting method and slide method respectively. Rats were administered for 15 consecutive days to measure their recalcification time, plasma viscosity, platelet adhesion rate, platelet aggregation rate and other blood indexes. As compared with the blank group, the bleeding time was prolonged in model groupn(P<0.05). As compared with the model group, the results showed that the positive vitamin K, the leaching type water decoction and the sediment type decoction could significantly shorten the bleeding time (P<0.01); positive vitamin K significantly (P<0.01) shortened clotting time, and the leaching type water decoction, the sediment type water decoction and the sediment type powder could also shorten the clotting time (P<0.05). As compared with blank group, low dose, medium dose of leaching type water decoction, medium dose of powder, high dose of sediment type decoction and low dose of drug residues could reduce plasma viscosity (P<0.05), and high dose of leaching powder and low dose of water decoction could significantly reduce (P<0.01) plasma viscosity. As compared with blank group, Limonitum leaching type decoction high dose group could significantly reduce the platelet adhesion rate (P<0.05), while sediment type water decoction could significantly increase the platelet adhesion rate (P<0.05); the high dose of leaching type water decoction, high dose of drug residues, low dose of leaching type powder and low dose of drug residues could decrease the platelet aggregation rate (P<0.05), while high dose of leaching type water decoction and high dose of the powder could increase the platelet aggregation rate (P<0.05). Analysis of mineral compositions was conducted by polarized light microscopy and X-ray diffraction (XRD). The results of the both methods showed that Limonitum mineral compositions contained goethite, quartz, and kaolinite, and sedimentary type also contained illite and albite. Sediment type of Limonitum showed better hemostatic effect, which may be related to the high content of goethite and illite.


Assuntos
Medicamentos de Ervas Chinesas/química , Hemostáticos/farmacologia , Plumbaginaceae/química , Animais , Hemostasia , Camundongos , Minerais , Agregação Plaquetária , Ratos
14.
Zhong Yao Cai ; 39(1): 155-9, 2016 Jan.
Artigo em Zh | MEDLINE | ID: mdl-30080018

RESUMO

Objective: To study the intervention effect of Chloriti Lapis in PTZ-kindled epileptic rat. Methods: Rats were kindled by pentylenetetrazol( PTZ),and successful kindled model were administered with drugs, then taken out the hippocampus of the brain. HE staining method was used to observe lesion in hippocampus, immunohistochemical method was used to test protein expression of nNOS, xanthine oxidase method was used to measure the activity of T-SOD, thiobarbituric acid method was used to measure the content of MDA,and phosphorus determination method was used to detect the activities of Na+,K+-ATPase and Ca2 +,Mg2 +-ATPase. Results: Each group of Chloriti Lapis( powder group, dregs group and decoction group) decreased the lesion grade, MDA content,nNOS protein expression, while increased the T-SOD activities, Na+,K+-ATPase and Ca2 +,Mg2 +-ATPase activities in the hippocampu of rats. Conclusion: Chloriti Lapis have antiepileptic effects, the mechanism may be related to increasing brain antioxidant activities, eliminating free radicals, protecting membrane function, maintaining dynamic balance of ion concentration in the braiofn rat, inhibiting brain abnormalities discharge, and ultimately achieve the goal of epilepsy treatment.


Assuntos
Epilepsia , Animais , Antioxidantes , Encéfalo , Hipocampo , Minerais , Pentilenotetrazol , Ratos , ATPase Trocadora de Sódio-Potássio
15.
Org Biomol Chem ; 13(20): 5656-73, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-25895552

RESUMO

A novel series of 1-(pyrrolidin-1-ylmethyl)-2-[(3-oxo-indan)-formyl]-1,2,3,4-tetrahydroisoquinoline derivatives maj-3a-maj-3u were synthesized and evaluated in vitro for their binding affinity at κ-opioid receptors. Maj-3c displayed the highest affinity for κ-opioid receptors (Ki = 0.033 nM) among all the compounds evaluated. Furthermore, all four stereoisomers of compound 3c were prepared, and (1S,18S)-3c was identified as the most potent (Ki = 0.0059 nM) κ-opioid receptor agonist among the four stereoisomers. Maj-3c produced significant antinociception (ED50 = 0.000406 mg kg(-1)) compared to U-50,488H and original BRL 52580 in the acetic acid writhing assay, but its strong sedative effect (ED50 = 0.000568 mg kg(-1)) observed in the mouse rotation test reduced its druggability. To minimize the central nervous system side effects, a series of hydroxyl-containing analogs of maj-3c were synthesized, and maj-11a was found to be a potent κ-opioid receptor agonist (Ki = 35.13 nM). More importantly, the dose for the sedative effect (ED50 = 9.29 mg kg(-1)) of maj-11a was significantly higher than its analgesic dose (ED50 = 0.392 mg kg(-1)), which made it a promising peripheral analgesic candidate compound with weak sedative side effects.


Assuntos
Analgésicos/química , Analgésicos/farmacologia , Descoberta de Drogas , Indanos/química , Indanos/farmacologia , Sistema Nervoso Periférico/efeitos dos fármacos , Receptores Opioides kappa/agonistas , Receptores Opioides mu/metabolismo , Tetra-Hidroisoquinolinas/química , Ácido Acético/metabolismo , Analgésicos/farmacocinética , Animais , Indanos/farmacocinética , Masculino , Camundongos , Medição da Dor , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Tetra-Hidroisoquinolinas/farmacocinética , Tetra-Hidroisoquinolinas/farmacologia , Distribuição Tecidual
16.
Acta Pharmacol Sin ; 36(5): 565-71, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25816912

RESUMO

AIM: To characterize the pharmacological profiles of a novel κ-opioid receptor agonist MB-1C-OH. METHODS: [(3)H]diprenorphine binding and [(35)S]GTPγS binding assays were performed to determine the agonistic properties of MB-1C-OH. Hot plate, tail flick, acetic acid-induced writhing, and formalin tests were conducted in mice to evaluate the antinociceptive actions. Forced swimming and rotarod tests of mice were used to assess the sedation and depression actions. RESULTS: In [(3)H]diprenorphine binding assay, MB-1C-OH did not bind to µ- and δ-opioid receptors at the concentration of 100 µmol/L, but showed a high affinity for κ-opioid receptor (Ki=35 nmol/L). In [(35)S]GTPγS binding assay, the compound had an Emax of 98% and an EC50 of 16.7 nmol/L for κ-opioid receptor. Subcutaneous injection of MB-1C-OH had no effects in both hot plate and tail flick tests, but produced potent antinociception in the acetic acid-induced writhing test (ED50=0.39 mg/kg), which was antagonized by pretreatment with a selective κ-opioid receptor antagonist Nor-BNI. In the formalin test, subcutaneous injection of MB-1C-OH did not affect the flinching behavior in the first phase, but significantly inhibited that in the second phase (ED50=0.87 mg/kg). In addition, the sedation or depression actions of MB-1C-OH were about 3-fold weaker than those of the classical κ agonist (-)U50,488H. CONCLUSION: MB-1C-OH is a novel κ-opioid receptor agonist that produces potent antinociception causing less sedation and depression.


Assuntos
Analgésicos Opioides/farmacologia , Comportamento Animal/efeitos dos fármacos , Isoquinolinas/farmacologia , Limiar da Dor/efeitos dos fármacos , Dor/prevenção & controle , Receptores Opioides kappa/agonistas , Vigília/efeitos dos fármacos , Analgésicos Opioides/metabolismo , Analgésicos Opioides/toxicidade , Animais , Ligação Competitiva , Células CHO , Cricetulus , Depressão/induzido quimicamente , Depressão/metabolismo , Depressão/psicologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Isoquinolinas/metabolismo , Ligantes , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Dor/metabolismo , Dor/fisiopatologia , Dor/psicologia , Ligação Proteica , Ratos , Receptores Opioides kappa/genética , Receptores Opioides kappa/metabolismo , Transfecção
17.
Zhongguo Zhong Yao Za Zhi ; 40(16): 3249-55, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26790302

RESUMO

OBJECTIVE: To study the differences in the toxicity of vinegar-processed Kansui Radix on normal and cancerous ascites model rats. METHOD: Normal and cancerous ascites model rats were taken as the research objects and orally administered with different doses of vinegar-processed Kansui Radix for 7 d. Pathological sections were prepared to observe the damages in liver, stomach, intestinal tissues in rats and detect the impacts on serum, liver, stomach and intestinal tissues and the oxidative damage index. RESULT: Compared with the blank group, all of normal administration groups and model groups showed significant damages in liver, stomach and intestinal tissues. Compared with the model groups, all of normal administration groups revealed notable alleviation in damages. Compared with the blank group, the model groups showed significant increases in AST, ALT and MDA in serum and liver (P < 0.01) and a significant decrease in GSH in serum and liver, stomach, intestinal tissues (P < 0.01). Compared with the blank group, the results showed significant decreases in ALT, AST in serum and ALT in liver in model low, medium and high dose groups and AST activity in liver tissues in the normal high dose group (P < 0.05, P < 0.01); significant decreases in GSH in serum and stomach tissues in normal low, medium and high dose groups and GSH content in liver and intestinal tissues in normal medium and high dose groups (P < 0.05, P < 0.01); notable rises in MDA in liver tissues in normal low, medium and high dose groups and MDA content in serum and stomach and intestinal tissues in normal medium and high dose groups (P < 0.05, P < 0.01). Compared with model groups, data revealed significant decreases in ALT, AST in serum in model low, medium and high dose groups, AST in liver tissues of model medium and high dose groups and ALT activity in liver in the model high dose group (P < 0.05, P < 0.01); significant increases in GSH content in serum and stomach tissues of model low, medium and high dose groups, GSH in liver tissues in model medium and high dose groups and GSH in intestinal tissues in the high dose groups (P < 0.05, P < 0.01); and notable declines in MDA content in serum in model low, medium and high dose groups, MDA in liver tissues of model medium and high dose groups and MDA in stomach and intestinal tissues the high dose group (P < 0.05, P < 0.01). CONCLUSION: According to the study, vinegar-processed Kansui Radix showed a significant lower toxicity liver, stomach, and intestines of cancerous ascites model rats, which provided a basis for clinical safe application of vinegar-processed Kansui Radix based on symptom-based prescription theory.


Assuntos
Química Farmacêutica/métodos , Medicamentos de Ervas Chinesas/química , Euphorbia/química , Neoplasias/tratamento farmacológico , Ácido Acético/química , Animais , Prescrições de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/toxicidade , Euphorbia/toxicidade , Intestinos/efeitos dos fármacos , Intestinos/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/química , Raízes de Plantas/toxicidade , Ratos , Ratos Sprague-Dawley
18.
Opt Express ; 22(1): 177-82, 2014 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-24514979

RESUMO

Silver nanoparticles synthesized in a synthetic sapphire matrix were fabricated by ion implantation using the metal vapor vacuum arc ion source. The optical absorption spectrum of the Ag: Al2O3 composite material has been measured. The analysis of the supercontinuum spectrum displayed the nonlinear refractive property of this kind of sample. Nonlinear optical refraction index was identified at 800 nm excitation using the Kerr-lens autocorrelation (KLAC) technique. The spectrum showed that the material possessed self-defocusing property (n(2) = -1.1 × 10(-15) cm(2)W). The mechanism of nonlinear refraction has been discussed.


Assuntos
Algoritmos , Óxido de Alumínio/química , Lentes , Nanopartículas Metálicas/química , Refratometria/instrumentação , Refratometria/métodos , Prata/química , Desenho de Equipamento , Análise de Falha de Equipamento , Teste de Materiais/instrumentação , Teste de Materiais/métodos , Nanopartículas Metálicas/ultraestrutura , Dinâmica não Linear
19.
Arterioscler Thromb Vasc Biol ; 33(2): e31-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23220274

RESUMO

OBJECTIVE: Cell-surface localization and intracellular trafficking are essential for the function of ATP-binding cassette transporter A-1 (ABCA1). However, regulation of these activities is still largely unknown. Brefeldin A, an uncompetitive inhibitor of brefeldin A-inhibited guanine nucleotide-exchange proteins (BIGs), disturbs the intracellular distribution of ABCA1, and thus inhibits cholesterol efflux. This study aimed to define the possible roles of BIGs in regulating ABCA1 trafficking and cholesterol efflux, and further to explore the potential mechanism. METHODS AND RESULTS: By vesicle immunoprecipitation, we found that BIG1 was associated with ABCA1 in vesicles preparation from rat liver. BIG1 depletion reduced surface ABCA1 on HepG2 cells, and inhibited by 60% cholesterol release. In contrast, BIG1 overexpression increased surface ABCA1 and cholesterol secretion. With partial restoration of BIG1 through overexpression in BIG1-depleted cells, surface ABCA1 was also restored. Biotinylation and glutathione cleavage revealed that BIG1 small interfering RNA dramatically decreased the internalization and recycling of ABCA1. This novel function of BIG1 was dependent on the guanine nucleotide-exchange activity and achieved through activation of ADP-ribosylation factor 1. CONCLUSIONS: BIG1, through its ability to activate ADP-ribosylation factor 1, regulates cell-surface levels and function of ABCA1, indicating a transcription-independent mechanism for controlling ABCA1 action.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Membrana Celular/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Fator 1 de Ribosilação do ADP/metabolismo , Transportador 1 de Cassete de Ligação de ATP , Animais , Apolipoproteína A-I/metabolismo , Biotinilação , Colesterol/metabolismo , Glutationa/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Células HeLa , Células Hep G2 , Humanos , Imunoprecipitação , Lipoproteínas LDL/metabolismo , Fígado/metabolismo , Masculino , Transporte Proteico , Interferência de RNA , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Transfecção
20.
Zhongguo Zhong Yao Za Zhi ; 39(7): 1311-4, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-25011274

RESUMO

Coronary artery disease (CAD) is one of the leading causes of death. Safflower attracts great attention owing to its anti-ischemia/reperfusion injury effect. Ninety-three patients with CAD were included and randomized into safflower treatment group, PCI group and control group. Low-dose dobutamine stress echocardiography (DSE) was performed to measure end-systolic volume (ESV), end-diastolic volume (EDV), left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) to determine the recovery of hibernating myocardium and cardiac function in all patients before treatment and after 3-month follow-up. The study was to investigate the effects of safflower on hibernating myocardial revascularization and cardiac function. It was found that LVEF was significantly improved, while the ESV and WMSI were significantly reduced after 2-week treatment in safflower and PCI treatment groups. No significant differences were found between safflower and PCI treatment groups in ESV, EDV, WMSI and LVEF after treatment Safflower injection effectively improved hibernating myocardial function.


Assuntos
Carthamus tinctorius/química , Doença da Artéria Coronariana/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Miocárdio Atordoado/tratamento farmacológico , Idoso , Doença da Artéria Coronariana/fisiopatologia , Feminino , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica , Miocárdio Atordoado/fisiopatologia , Miocárdio Atordoado/cirurgia , Recuperação de Função Fisiológica
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