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1.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970561

RESUMO

From the perspective of market classification of Cnidii Fructus, this paper revealed the scientific connotation of evaluating the quality grade of Cnidii Fructus by its appearance traits. Thirty batches of Cnidii Fructus in different grades were selected as the research objects. The canonical correlation analysis and principal component analysis(PCA) were used to explore the measurement values of 15 appearance traits and intrinsic content indexes. The results of correlation analysis showed that except the aspect ratio, the 5 appearance trait indexes(length, width, 1 000-grain weight, broken grain weight proportion, and chroma) and 9 internal content indexes(the content of moisture, total ash, acid insoluble ash, osthole, imperatorin, 5-methoxy psoralen, isopimpinellin, xanthotoxin, and xanthotol) showed significant correlation to varying degrees. In addition, there was a significant positive correlation between the first typical variable U_1 composed of appearance traits and the first typical variable V_1 composed of internal content indexes(CR_1=0.963, P<0.01). The results of PCA showed that the classification results of appearance traits for 30 batches of Cnidii Fructus were consistent with the actual information of the samples. Under the same analysis conditions, 30 batches of Cnidii Fructus were reclassified by 9 groups of internal content indexes, and the analysis results were consistent. From the classification standard of the appearance traits of the system study, the statistical results of 6 appearance traits of Cnidii Fructus showed a correlation with grades. There was a good correlation between the appearance and the internal content of Cnidii Fructus, and the appearance quality effectively predicted the level of the internal content. There is a certain scientific basis for the quality classification of Cnidii Fructus by main appearance traits. Appearance classification can replace quality grading to realize the "quality evaluation through morphological identification" of Cnidii Fructus.


Assuntos
Frutas , Fenótipo , Análise de Componente Principal , Grupos Populacionais
2.
Chinese Journal of Epidemiology ; (12): 713-719, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985552

RESUMO

Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ2 test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.


Assuntos
Humanos , COVID-19 , Estudos Retrospectivos , SARS-CoV-2 , China , Ácidos Nucleicos
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985514

RESUMO

Objectives: To study the association between metals mixture exposure and DNA oxidative damage using mixture analysis methods, and to explore the most significant exposure factors that cause DNA oxidative damage. Methods: Workers from steel enterprises were recruited in Shandong Province. Urinary metals were measured by using the inductively coupled plasma mass spectrometry method. The level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined by using the ultra-high performance liquid chromatography-mass spectrometry method. Bayesian kernel machine regression (BKMR), elastic net regression and quantile g-computation regression were used to analyze the association between urinary metals and urinary 8-OHdG. Results: A total of 768 subjects aged (36.15±7.40) years old were included in the study. BKMR, elastic net regression and quantile g-computation all revealed an overall positive association between the mixture concentration and increased urinary 8-OHdG. The quantile g-computation results showed that with a 25% increase in metal mixtures, the urinary 8-OHdG level increased by 77.60%. The elastic net regression showed that with a 25% increase in exposure risk score, the urinary 8-OHdG level increased by 26%. The BKMR summarized the contribution of individual exposures to the response, and selenium, zinc, and nickel were significant contributors to the urinary 8-OHdG elevation. Conclusion: Exposure to mixed metals causes elevated levels of DNA oxidative damage, and selenium, zinc, and nickel are significant exposure factors.


Assuntos
Humanos , Adulto , Níquel/toxicidade , Selênio , Teorema de Bayes , Metais/toxicidade , 8-Hidroxi-2'-Desoxiguanosina , Estresse Oxidativo/fisiologia , Zinco , Dano ao DNA
4.
Chemosphere ; 307(Pt 3): 135932, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35940414

RESUMO

Phthalic acid esters (PAEs) are commonly used as plasticizer and are emerging concern worldwide for potent adverse effects of aquatic organisms. Certain PAEs were often detected in different environmental matrices but related toxicity data were still lacking to support their risk assessment. The study investigated the acute toxicity of Diisobutyl phthalate (DiBP) and Di-n-octyl phthalate (DnOP) using 6 Chinese resident aquatic organisms from 3 phyla and 6 species and constructed the species sensitivity distribution (SSD) models for ecological risk assessment. Lethal concentration 50% (LC50) ranges of DiBP and DnOP were 4.89-21.45 mg/L and 1.45-1200 mg/L, respectively. The derived acute and chronic predicted no-effect concentrations (PNECs) based on log-normal model of water were 0.54 and 0.04 mg/L for DiBP and 0.23 and 0.05 mg/L for DnOP, respectively. The ERA for DiBP and DnOP in the surface water and sediment of China was conducted. Water samples of Haihe Rive (RQ = 0.41) and Hun River (RQ = 0.16) of DiBP showed medium risk. And sediment samples of Yellow River (RQ = 0.71) and Chao Hu Lake (RQ = 0.42) of DiBP showed medium risk. Meanwhile, the above water and sediment samples (RQ<0.1) of DnOP showed low risk.


Assuntos
Ácidos Ftálicos , Poluentes Químicos da Água , Organismos Aquáticos , China , Dibutilftalato/análogos & derivados , Dibutilftalato/toxicidade , Ésteres , Etilaminas , Ácidos Ftálicos/toxicidade , Plastificantes/toxicidade , Medição de Risco , Rios , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
5.
J Biomed Nanotechnol ; 18(4): 1052-1063, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35854453

RESUMO

Glioblastoma, the most common tumor in the brain, has witnessed very little clinical progress over the last decades. Exploring and discovering new therapeutic strategies for glioblastoma has become a critical problem. Harmine (HM), belonging to the beta-carboline alkaloid, is a natural product and isolated from the seeds of Peganum harmala L., which own notable antitumor activity in vitro. However, the poor water solubility and less selectivity of HM severely limit its clinical use. For enhancing its selective ability to tumor cells, we fabricated a kind of protein nanoparticles (BSA-HM NPs), composed of the modified bovine serum albumin (BSA) and HM. It was substantiated through in vitro and in vivo experiment that BSA-HM NPs could predominantly accumulate in tumor tissues and exhibited remarkably enhanced antitumor efficacy. This study provides a promising strategy to improve the bioavailability and avoid side effects of HM as antitumor agents by choosing BSA as carriers.


Assuntos
Antineoplásicos , Glioblastoma , Nanopartículas , Antineoplásicos/farmacologia , Glioblastoma/tratamento farmacológico , Harmina/farmacologia , Humanos , Soroalbumina Bovina
6.
Environ Res ; 214(Pt 2): 113849, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35843282

RESUMO

Androgens are released by humans and livestock into the environment and which cause potent endocrine disruptions even at nanogram per liter levels. In this article, we reviewed updated research results on the structure, source, distribution characteristics and the fate of androgens in ecological systems; and emphasized the potential risk of androgens in aquatic organism. Androgens have moderately solubility in water (23.6-58.4 mg/L) and moderately hydrophobic (log Kow 2.75-4.40). The concentration of androgens in surface waters were mostly in ng/L ranges. The removal efficiencies of main wastewater treatment processes were about 70-100%, except oxidation ditch and stabilization ponds. Sludge adsorption and microbial degradation play important role in the androgens remove. The conjugated androgens were transformed into free androgens in environmental matrices. Global efforts to provide more toxicity data and establish standard monitoring methods need a revisit. Of the day available, there is an urgent need for comprehensive consideration of the impact of androgens on the environment and ecology.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Androgênios/toxicidade , Organismos Aquáticos , Monitoramento Ambiental , Humanos , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Purificação da Água/métodos
7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-940324

RESUMO

In this paper, through consulting relevant records in materia medica, medical and prescription books, and combining with modern literature, the name, origin, producing area, collection and processing of Gentianae Macrophyllae Radix in famous classical formulas from The Catalogue of Ancient Famous Classical Formulas (The First Batch) was systematically sorted out and textual research was carried out, in order to provide a basis for the development of the famous classical formulas containing Gentianae macrophyllae Radix. After textual research, it was found that Gentianae Macrophyllae Radix was the rectification of name in the past dynasties. In addition, there were other names such as Qinjiao, Qingua and Qinzhua. Gentiana macrophylla, G. straminea, G. dahurica and G. siphonantha were the main origin of this herb in ancient literature. Among them, G. macrophylla is the mainstream. In the Southern and Northern dynasties, G. straminea and G. macrophylla produced in northern Sichuan were recommended as the best. In the early Tang dynasty, G. macrophylla from the Liupan Mountain area at the border of Shanxi and Gansu provinces was the mainstream. During the Northern Song dynasty, G. siphonantha from Linxia and Qilian Mountain of Gansu province and G. macrophylla from eastern Shaanxi province were two new producing areas. In the Ming and Qing dynasties, the abundant base and production areas of Gentianae Macrophyllae Radix were gradually formed. In the past dynasties, harvesting was carried out in spring and autumn, and stored mainly by aeration drying or shade drying treatment. The processing methods are mainly the raw products after the net selection, cutting and drying, in addition to the frying, processing with wine and milk. G. macrophylla is recommended as the first choice for the herbal medicine involved in the famous classical formulas. Among them, wild products produced in Gansu and Shaanxi are the best, and raw products are recommended to be used. At the same time, it is suggested that G. siphonantha should be added to the subsequent edition of Chinese Pharmacopoeia as one of origins of Gentianae Macrophyllae Radix.

8.
Eur J Histochem ; 65(3)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34494412

RESUMO

Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.


Assuntos
Diferenciação Celular/fisiologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/fisiologia , Tendões/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Ratos Sprague-Dawley , Lesões do Manguito Rotador/metabolismo , Células-Tronco/fisiologia , Tendões/citologia
9.
Orthop Surg ; 13(6): 1755-1764, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34351052

RESUMO

To determine the outcome and differences between arthroscopic hip surgery and conservative therapy in patients suffering from femoroacetabular impingement syndrome, we searched articles from PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov using a Boolean search algorithm. Only randomized controlled trials comparing arthroscopic hip surgery and conservative therapy were included in this meta-analysis of femoroacetabular impingement syndrome management. Two authors determined eligibility, extracted the needed data and assessed the risk of bias of eligible studies independently. Then we meta-analyzed three articles to assess pooled estimate size (ES) and 95% confidence interval for Hip Outcome Score of activities of daily living (HOS ADL subscale), Hip Outcome Score sport (HOS sports subscale) and International Hip Outcome Tool (iHOT-33) analyses were performed by using STATA version 14.0 MP (STATA, College Station, TX, USA) with the principal summary measures are mean between group difference, sample size, and standard deviation. We collected 52 articles in total after removing duplicates and screened by titles and abstracts. A total of three RCTs were included finally. There was definite evidence of additional benefit of arthroscopic hip surgery against conservative therapy in the field of improving quality of life (three trials, 575 participants, ES = 2.109, 95% CI: 1.373 to 2.845, I2  = 42.8%, P = 0.000) and activity of daily living (two trials, 262 participants, ES = 9.220, 95% CI: 5.931 to 12.508, I2  = 16.5%, P = 0.000). However, no significant difference could be seen in sports function improvement (two trials, ES = 7.562, 95% CI: -2.957 to 18.082, I2  = 60.1%, P = 0.159). In conclusion, this meta-analysis suggests that arthroscopic hip surgery provided essential benefit compared with conservative therapy in improving activity of daily living and quality of life.


Assuntos
Artroscopia/métodos , Tratamento Conservador/métodos , Terapia por Exercício/métodos , Impacto Femoroacetabular/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários
10.
Ann Transl Med ; 9(9): 768, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34268381

RESUMO

BACKGROUND: The purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced. METHODS: Mice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties. RESULTS: Glycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone specific alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups. CONCLUSIONS: The glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.

11.
Acta Pharmaceutica Sinica ; (12): 3353-3361, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-906835

RESUMO

italic>Aconitum pendulum is a Tibetan medicine that is rich in bioactive compounds such as aconitine-type C19-diterpenoid alkaloids. To investigate the key enzymes in the aconitine biosynthesis pathway, roots, leaves and flowers of Aconitum pendulum were subjected to a high-throughput transcriptomic sequencing analysis by Illumina HiSeqTM2000. Trinity de novo assembly yielded 47 264 unigenes with an average length of 1 140 bp and N50 of 1 678 bp, of which 30 231 unigenes (63.96%) were annotated. In the KEGG database, 542 unigenes were implicated in 17 secondary metabolic pathways; the analysis showed that 44 genes encoded 20 key enzymes in the diterpene skeleton of aconitine biosynthesis and 12 BAHD acyltransferase genes were related to the acetylation modification, with differential expression among three organs. For example, ApTPS8 was the only committed enzyme in the upstream aconitine biosynthetic pathway. The high expression level of ApTPS8 in root indicated that it is the main tissue for the production of precursors of diterpene alkaloids. Consistent with the accumulation of aconitine, we propose that ApBAHD1/2/8 is involved in the biosynthesis of 2-hydroxyaconitine, dehydrated 14-benzoylaconitine, 8-O-methyl-14-benzoylaconine, benzoyldeoxyaconitine and benzoylaconitine, and ApBAHD10 is involved in the biosynthesis of acontine, lucidusculine, 14-O-acetylneoline and 14-O-acetylvirescenin. Comparative transcriptome analysis of A. pendulum and A. carmichaeli indicates significant gene loss in the family of diterpene synthases and acyltransferases in A. pendulum, which is in accordance with the significantly fewer type and quantity of aconitine compounds in this species. Therefore, A. pendulum has proved to be an ideal material for the study of the aconitine biosynthesis pathway. This work provides basic scientific data for further study of aconitine biosynthesis, the discussion of molecular mechanisms of toxicity, and the synthesis of genuine medicinal materials.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-905824

RESUMO

Objective:To investigate academic publications of students of the full-time master of public health (professional degree, MPH) program and explore their research capacity. Methods:A total of 160 students of the full-time MPH program admitted from 2010 through 2014 were included in the study. Their academic publications were retrieved for analysis. Results:The average number of academic publications was 1.35. Moreover, 10.2% of the students had academic publications in Chinese journals, and 12.5% had publications in SCI-indexed English journals. Type of disciplines, province they were from, and economic status of their family were determined to be significantly associated with academic publications in SCI-indexed journals. Conclusion:Students of the full-time MPH program have research capacity; however, they have achieved relatively few academic publications of high quality. Establishment of a teaching and training program is warranted in both practice and research for students in full-time MPH programs in universities.

13.
Chinese Medical Journal ; (24): 1669-1675, 2020.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-827559

RESUMO

BACKGROUND@#Certain hemophilia patients are unable to cooperate with or afford magnetic resonance imaging (MRI) examinations. The purpose of our study was to explore the value of multislice spiral computed tomography (MSCT) in evaluating hemophilic arthropathy (HA).@*METHODS@#Thirty-eight patients with 73 joints of HA were consecutively selected from January 2016 to May 2018 for this prospective study. All 73 joints were examined by X-ray, CT, and MRI within 2 days. The MRI scores of the joints were determined by the International Prophylaxis Study Group (IPSG) standard. The CT findings were quantified according to the IPSG standard, except for cartilage injury, which was quantified by joint space narrowing using the X-ray Pettersson score. The CT and MRI scores were compared by the paired Wilcoxon signed-rank test. The correlations between the CT score of joint space narrowing and MRI score of cartilage injury and the total CT and MRI scores were analyzed by Spearman rank correlation. The kappa test was used to compare the consistency of CT and MRI scores.@*RESULTS@#MRI was superior to CT based on the scores for small amount of effusion (P  0.05), and there was a high degree of consistency between the two scores (kappa > 0.81). The consistency between the Pettersson scores of joint space narrowing on CT and the IPSG scores of cartilage injury on MRI was high (kappa = 0. 774, P < 0.05).@*CONCLUSION@#The image scores of MSCT are generally consistent with MRI except for mild synovitis, which can be used as an alternative for the evaluation of HA.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-837841

RESUMO

Objective To summarize the clinical features and imaging findings of six coronavirus disease 2019 (COVID-19) patients, so as to provide evidences for early diagnosis and clinical intervention. Methods Six COVID-19 patients with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were enrolled from the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine from Jan. 1 to Feb. 22, 2020. The epidemiological history, clinical manifestations, imaging data and laboratory indicators were retrospectively analyzed. Results All six patients had a clear travel or residence history in Wuhan. Four patients had fever, three had cough, two had upper respiratory tract symptoms such as runny nose and sore throat, and two had systemic symptoms such as headache and muscle ache. Chest computed tomography (CT) showed that all the six patients had abnormal manifestations in bilateral lungs, and the lower lung lesions were more common than the upper lung lesions. The main manifestations were multiple ground-glass opacities, consolidation shadows, crazy paving sign and different degrees of fibrosis in lateral field of bilateral lungs. Chest CT examination later after onset showed lung consolidation and severe fibrosis. Conclusion The imaging of COVID-19 has special characteristics. Combined with the epidemiological history, clinical manifestations and the detection of SARS-CoV-2 nucleic acid, COVID-19 can be effectively diagnosed in the early stage.

15.
Acta Pharmaceutica Sinica ; (12): 54-59, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-780577

RESUMO

The coagulation VIII factor (FVIII) contains eight pairs of disulfide bonds, which are involved in maintaining its structure and function. It has been demonstrated that the disulfide bond between Cys1899/Cys1903 of the A3 domain in the light chain impedes secretion. In our previous work, an engineered inter-chain disulfide in the B domain-deleted FVIII (BDD-FVIII) promoted heterodimer assembly and secretion of separately expressed heavy and light chains. In this study, we constructed two BDD-FVIII variants, one of which contains an engineered inter-chain disulfide bond (F8C) between Met662 > Cys and Asp1828 > Cys mutations and another contains an endogenous A3 domain with a disrupted disulfide bond from F8C (F8CG) by replacement of Cys1899 and Cys1903 with Gly in F8C. We explored their function and secretion. By transducing F8C and F8CG into HEK293 and COS-7 cells, the formation of disulfide bonds and the secretion and coagulation activity of the two variants in the culture media and their binding affinity for von Willebrand factor (vWF) could be observed. The results show that variants F8C and F8CG are mainly the disulfide bonded heavy and light chain dimer, while the wild type BDD-FVIII (F8) is dominated by the easily dissociated heavy and light chain dimer. The secretion and activity of F8C was significantly higher than that of F8, while the secretion and activity of F8CG was significantly higher than that of F8C. The vWF binding of the two variants is similar to F8. This indicates that the BDD-FVIII variant F8CG may be attractive molecule for protein replacement and as a transgene in gene-therapy strategies. These findings are encouraging for future studies targeting disulfide bond elimination for further enhancement of FVIII secretion.

16.
Biochem Biophys Res Commun ; 515(2): 352-358, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31153636

RESUMO

Obesity-associated insulin resistance is a forerunner of type 2 diabetes. Macrophages reside within adipose tissue (ATMs) have been reported to regulate insulin sensitivity through secreting miRNAs containing exosomes. Here, we show that miR-29a is increased in obese ATMs derived exosomes (ATMs-Exos) and can be transferred into adipocytes, myocytes and hepatocytes causing insulin resistance in vitro and in vivo. Administration of obese ATMs-Exos impairs insulin sensitivity of lean mice. While knockdown miR-29a level in obese ATM-Exos blunts this effect. PPAR-δ is identified to function as downstream target of miR-29a in regulating insulin resistance. PPAR-δ agonist GW501516 partially rescued the insulin resistance induced by miR-29a. Taken together, these findings suggest that ATMs derived exosomal miR-29a could regulate obesity-associated insulin resistance, which may serve as a potential therapeutic target for obesity-associated type 2 diabetes.


Assuntos
Tecido Adiposo/metabolismo , Resistência à Insulina/fisiologia , Macrófagos/metabolismo , MicroRNAs/metabolismo , Obesidade/metabolismo , Adipócitos/metabolismo , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Exossomos/genética , Exossomos/metabolismo , Técnicas de Silenciamento de Genes , Hepatócitos/metabolismo , Técnicas In Vitro , Resistência à Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Células Musculares/metabolismo , Obesidade/complicações , Obesidade/genética , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/metabolismo , Tiazóis/farmacologia
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-743722

RESUMO

Objective: To analyze the effects of different doses of flurbiprofen and other analgesic drugs on the postoperative analgesia in the Enhanced Recovery After Surgery (ERAS) . Methods: 98 patients with jaw cysts or multiple impact teeth were retrospectively analyzed. Patients were divided into 3 groups by the drug scheme: flurbiprofen 250 mg + 0. 9% NS to 100 ml (group Ⅰ, n =32), sulfentanil 100 μg + azasetron 20 mg + 0. 9% NS to 100 ml (group Ⅱ, n = 34), flurbiprofen 200 mg + sulfentanil 50 μg + azasetron 20 mg + 0. 9% NS to 100 ml (group Ⅲ, n = 32) . Analgesic effects were evaluated at 3 h, 1 d and 2 d after surgery with Wong-Baker expression scale and numeric rating scale (NRS) . Questionnaire survey was also used to evaluate degree of satisfaction on analgesia. Results: Analgesia effective rate of group Ⅰ, Ⅱ and Ⅲ was 40. 62%, 67. 65% and 68. 75% respectively (P <0. 05) . Degree of satisfaction on analgesia of group Ⅰ, Ⅱ and Ⅲ was 71. 87%, 58. 82% and 93. 75% respectively (P < 0. 05) .Conclusion: Flurbiprofen combined with sulfentanil has good analgesic effects and low side effects in the maxillofacial surgery of jaw cysts and multiple impact teeth.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-817660

RESUMO

@#【Objective】To investigate whether bone marrow mesenchymal stem cells(BMSC)over-expressing FoxM1genecanattenuatelipopolysaccharide(LPS)-inducedapoptosisofalveolarepithelialcells,andexploreitspossi⁃ blemechanism.【Methods】SDratBMSCwereisolatedandculturedbywholebonemarrowadherencemethod.FoxM1 genewasoverexpressedinBMSCbylentiviraltransfection.TheexpressionofthetargetgeneFoxM1wasverifiedbyWestern blot.ApoptosisofA549cellswasmeasuredbyTUNELandflowcytometry.Andthemulti-factorlevelofsupernatantin BMSC-A549co-culturesystemwasdetectedbyMilliplexmethod.【Results】TUNELandflowcytometryconfirmedthat theapoptosisrateofA549inducedbyLPSdecreasedafterco-culturewithBMSCoverexpressingFoxM1,andthediffer⁃ encewasstatisticallysignificant(P <0.05).MilliplexassayshowedthatthelevelsofIL-13,IL-21,IL-23,MIP-1a, MIP-1bandinBMSCoverexpressing FoxM1 geneandA549co-culturesystemweresignificantlyincreased,whilethe MIP-3alevelissignificantlyreduced.【Conclusion】BMSCoverexpressingFoxM1genecanattenuateLPS-inducedapop⁃ tosisofalveolarepithelialcells.BMSCmayplayananti-apoptoticrolebychangingthelevelsofinflammation-related cytokinesreleasedbyA549cells.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-701076

RESUMO

AIM:To investigate the protective effect of basic fibroblast growth factor(bFGF)on the heart of mice with myocardial infarction and its mechanism.METHODS:The model of myocardial infarction was established by the ligation of left anterior descending artery of C57/B6 mice(8~12 weeks old)after lateral thoracotomy.The mice were divided into sham operation group ,myocardial infarction group and bFGF administration group.bFGF at 0.5μg was intra-peritoneally injected on alternate days after myocardial infarction for 7 d.Cardiac Doppler ultrasonography was used to de-tect cardiac function after myocardial infarction for 28 d,and left ventricular end-diastolic diameter ,left ventricular end-systolic diameter,left ventricular ejection fraction and left ventricular shortening fraction(LVFS)were used to evaluate cardiac function.After myocardial infarction for 28 d,the mice were sacrificed and the hearts were collected for preparing pathological sections.The degrees of myocardial fibrosis and angiogenesis in the myocardial infarction area were observed. Western blot was used to detect the indicators of angiogenesis.RESULTS:The results of Masson staining showed that bF-GF administration significantly reduced myocardial fibrosis at 28 d after myocardial infarction.Cardiac ultrasound data showed that cardiac functions in myocardial infarction group were poorer than those in sham group ,and bFGF administration significantly improved cardiac functions.Immunofluorescence staining showed that neovascularization in myocardial infarc -tion area of bFGF administration group was more than that in myocardial infarction group.The results of Western blot showed that bFGF activated AKT/HIF-1α/VEGF signaling pathway.CONCLUSION:Intraperitoneal injection of bFGF reduces myocardial fibrosis and improves cardiac function in myocardial infarction mice.bFGF may promote angiogenesis by activating AKT/HIF-1α/VEGF signaling pathway.

20.
Military Medical Sciences ; (12): 110-113, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-694327

RESUMO

Objective To compare the effects of three different methods for extracting short RNA-DNA hybrids, including the TRI reagent method , the phenol saturated with water method and the phenol saturated with Tris buffer method in order to facilitate studies on the biological function of RNA-DNA hybrids .Methods Short RNA fragments modifiedwith FAM at the 5′end and those modified with Cy 5 at the 5′end were synthesized .RNA and DNA fragments were annealed to form RNA-DNA hybrids.They were extracted with the above-mentioned 3 methods respectively .The extracted products were analyzed with electrophoresis .Results and Conclusion Short RNA-DNA hybrids can be extracted by the phenol saturated with water method and by the phenol saturated with Tris buffer method .The results can help study the function of short RNA-DNA hybrids .

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