RESUMO
Accurate regulation of innate immunity is necessary for the host to efficiently respond to invading pathogens and avoid excessive harmful immune pathology. Here we identified OTUD3 as an acetylation-dependent deubiquitinase that restricts innate antiviral immune signaling. OTUD3 deficiency in mice results in enhanced innate immunity, a diminished viral load, and morbidity. OTUD3 directly hydrolyzes lysine 63 (Lys63)-linked polyubiquitination of MAVS and thus shuts off innate antiviral immune response. Notably, the catalytic activity of OTUD3 relies on acetylation of its Lys129 residue. In response to virus infection, the acetylated Lys129 is removed by SIRT1, which promptly inactivates OTUD3 and thus allows timely induction of innate antiviral immunity. Importantly, acetyl-OTUD3 levels are inversely correlated with IFN-ß expression in influenza patients. These findings establish OTUD3 as a repressor of MAVS and uncover a previously unknown regulatory mechanism by which the catalytic activity of OTUD3 is tightly controlled to ensure timely activation of antiviral defense.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Imunidade Inata , Influenza Humana/imunologia , Proteases Específicas de Ubiquitina/fisiologia , Células A549 , Acetilação , Adulto , Animais , Enzimas Desubiquitinantes/metabolismo , Feminino , Células HEK293 , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , UbiquitinaçãoRESUMO
The objective of this study was to analyze differences in birth weight and overweight/obesity in a Shanghai twin cohort. We also wanted to study their association and explore possible risk factors for the discordance of overweight/obesity within twins. This was an internal case-control study designed for twins. The 2012 Shanghai Twin Registration System baseline survey data of a total of 3417 twin pairs were statistically analyzed using SPSS22 software. Results show that the body mass index (BMI) of the Shanghai twin population increased with age. Twins with a high birth weight had a higher BMI and a higher rate of overweight and obesity; 0- to 6-year-old twins, male twins and dizygotic (DZ) twins had higher rates of overweight/obesity than other groups. The greater the discordant birth weight rate of twins, the more obvious the difference in BMI (p < .05). There was a significant difference in overweight/obesity between twins with a relative difference of birth weight ≥15% in DZ twins (p < .05). DZ twins, male twins and 0- to 6-year-old twins were more likely to be discordant in overweight/obese than others. The discordant birth weight within twins was not a risk factor for discordant overweight/obesity. However, attention should be paid to childhood obesity, and appropriate interventions should be made at the appropriate time. Genetics may play an important role in the occurrence and development of overweight/obesity. In conclusion, discordant growth and development in the uterus early in life may not lead to discordant weight development in the future.
Assuntos
Obesidade Infantil , Peso ao Nascer , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Sobrepeso/epidemiologia , Sobrepeso/genética , Obesidade Infantil/epidemiologia , Obesidade Infantil/genética , Gêmeos Dizigóticos/genéticaRESUMO
This study aimed to develop a Chinese Healthy Eating Index for School-age Children (CHEI-SC), apply it in the 2011 China Health and Nutrition Survey (CHNS) to assess dietary quality, and compared it with our former developed index named CHEI. Data of 3-day 24-hour diet recalls and household food inventory survey from 1600 school-age children in CHNS-2011 were used to develop the CHEI-SC, using the methods of standard portion size, energy-density-based approach, and least restrictive approach. The CHEI-SC included 19 components with a total score (T-score) ranging from 0 to 100. The investigated children had a median score of 49.6. Children with a higher T-score were more likely to have higher social economic status (SES), higher level of urbanisation, fewer family size, and regularly attending school. The CHEI-SC was able to assess dietary quality of Chinese school-age children, was sensitive to demographics, and more comprehensive and accurate than the CHEI.
Assuntos
Dieta Saudável , Inquéritos Nutricionais , Adolescente , Criança , China , Humanos , Tamanho da Porção , Fatores SocioeconômicosRESUMO
Methionine is one of the most hydrophobic, redox-sensitive, and one of the only two sulfur-containing amino acids on protein. Because of these biochemical properties, the methionine residue plays a central role in a variety of biological processes, such as metal coordination, antioxidant stress, and aging. However, studies on the molecular functions of methionine are much less common than the other primary sulfur-containing amino acid, cysteine. The limited number of publications on methionine-related studies is partially due to the lack of tools for methionine modification. Methionine bioconjugation offers a new strategy to decipher the biological function of methionine and expands the toolbox for protein functionalization in the context of the application, such as synthesizing proteins with novel properties and producing new biomaterials. The purpose of this Perspective is to highlight the biochemical properties and functions of methionine, list recent progress in the development of methionine bioconjugation reagents, and briefly demonstrate the application of these reagents on polypeptides, proteins, and proteomes.
Assuntos
Metionina/química , Peptídeos/química , Proteínas/química , Proteoma/química , Alquilação , Indicadores e Reagentes/química , OxirreduçãoRESUMO
BACKGROUND: Epoxide hydrolase can regioselectively catalyze the oxirane ring-opening hydrolysis of rac-epoxides producing the corresponding chiral diols. In our laboratory, a gene named pveh1 encoding an EH from Phaseolus vulgaris was cloned. Although the directed modification of PvEH1 was carried out, the mutant PvEH1Y3 showed a limited degree of enantioconvergence towards racemic (rac-) m-chlorostyrene oxide (mCSO). RESULTS: PvEH1 and PvEH1Y3 were combinatively subjected to laboratory evolution to further enhance the enantioconvergence of PvEH1Y3 towards rac-mCSO. Firstly, the substrate-binding pocket of PvEH1 was identified using a CAVER 3.0 software, and divided into three zones. After all residues in zones 1 and 3 were subjected to leucine scanning, two E. coli transformants, E. coli/pveh1Y149L and /pveh1P184L, were selected, by which rac-mCSO was transformed into (R)-m-chlorophenyl-1,2-ethanediol (mCPED) having 55.1% and 27.2% eep. Secondly, two saturation mutagenesis libraries, E. coli/pveh1Y149X and /pveh1P184X (X: any one of 20 residues) were created at sites Y149 and P184 of PvEH1. Among all transformants, both E. coli/pveh1Y149L (65.8% αS and 55.1% eep) and /pveh1P184W (66.6% αS and 59.8% eep) possessed the highest enantioconvergences. Finally, the combinatorial mutagenesis was conducted by replacements of both Y149L and P184W in PvEH1Y3, constructing E. coli/pveh1Y3Z2, whose αS reached 97.5%, higher than that (75.3%) of E. coli/pveh1Y3. In addition, the enantioconvergent hydrolysis of 20 mM rac-mCSO was performed by E. coli/pveh1Y3Z2, giving (R)-mCPED with 95.2% eep and 97.2% yield. CONCLUSIONS: In summary, the enantioconvergence of PvEH1Y3Z2 was successfully improved by laboratory evolution, which was based on the study of substrate-binding pocket by leucine scanning. Our present work introduced an effective strategy for the directed modification of enantioconvergence of PvEH1.
Assuntos
Evolução Molecular Direcionada , Epóxido Hidrolases/genética , Phaseolus/enzimologia , Escherichia coli , Genes de Plantas , Modelos Moleculares , Mutagênese Sítio-Dirigida , Phaseolus/genética , Transformação BacterianaRESUMO
Based on the results of previous data mining,the mechanism of high frequency use of Tibetan medicine in the treatment of high altitude polycythemia(HAPC) was analyzed in this study by network pharmacology. The author obtained the high frequency use data on Tibetan medicine Terminalia chebula,Aucklandia lappa,Crocus sativus and Myristica fragrans for the treatment of HAPC by data mining in the previous period. The first five main active ingredients of each high frequency Tibetan medicine were screened out by reviewing comprehensive literature and TCMSP database. The potential targets of each medicine were screened by PharmMapper and Drug Bank database,and then the targets were imported into MAS 3. 0 database to obtain the corresponding path information. The KEGG database was used for path annotation and GO function enrichment analysis. Finally,Cystoscope 3. 4. 0 software was used to construct " compound-target-path" network for four high-frequency Tibetan medicines. Among them,the target points of four herbs related to HAPC were 16(T. chebula),20(A. lappa),20(C. sativus),and 15(M. fragrans). The common target points included BHMT,F2,ADH5,AKR1 C2,GSK3 B,INSR and PDE4 B,involving pathways related to T. chebula(17),A. lappa(17),C. sativus(24) and M. fragrans(14),and the common pathway was metabolism of xenobiotics by cytochrome P450. The results showed that high-frequency Tibetan medicine had common pathways and targets in treating HAPC,such as T. chebula,A. lappa,C. sativus and M. fragrans.The medicines could reduce hemoglobin and enhance immunity by mediating cell proliferation and oxidative stress,exerting anti-inflammatory effects and participating in regulating blood vessels,showing therapeutic effects for HAPC. In this study,the multi-component,multi-target and multi-pathway mechanism of Tibetan medicine in preventing and treating HAPC was analyzed from the information level,providing a useful reference for further study of Tibetan medicine in preventing and treating plateau diseases from the multi-dimensional perspective.
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Medicina Tradicional Tibetana , Policitemia , Mineração de Dados , Quinase 3 da Glicogênio Sintase , Humanos , Medicina Tradicional ChinesaRESUMO
This study using traditional Chinese medicine inheritance support software(TCMISS) to analyze the prescription rules of Tibetan medicine containing Terminalia chebula in the Encyclopedia of Chinese Medicine-Tibetan Medicine, Tibetan Medicine Composition Preparation of Modern Research and Clinical Application and Common Interpretation of Tibetan Medicine and so on. TCMISS(V2.5) was used to build a prescription database of Tibetan medicine containing T. chebula.The software statistical statement module, association rules and improved mutual information method and other data mining technologies were adopted to analyze the common herbs, combination rules and core combination of prescriptions containing T. chebula.Total 502 prescriptions containing T. chebula were analyzed and 14 common herbal combinations were summarized, whose ingredients mostly had the functions of clearing heat and detoxicating, promoting blood circulation and stopping pain, warming the middle-jiao and promoting the circulation of Qi. Prescriptions containing T. chebula were commonly used to treat 640 kinds of diseases, there are 22 kinds with high frequency(≥12) in which the representative "Tripa" disease, antiquated febrile symptoms, food poisoning had the highest frequency.T. chebula had different therapeutic effects through different compatibility.The complex composing and medication regularities of Tibetan medicine containing T. chebula have been clarified by TCMISS. That will provide reference for the clinical application of T. chebula and the new development.
Assuntos
Medicamentos de Ervas Chinesas/química , Medicina Tradicional Tibetana , Terminalia/química , Mineração de Dados , Humanos , Medicina Tradicional Chinesa , SoftwareRESUMO
OBJECTIVE: This study was designed to evaluate the prevalence of thyroid nodules (TNs) and its relationship with urine iodine concentrations (UICs) after the regional rapid economic growth and lifestyle changes. METHODS: A cross-sectional survey was conducted in the general population aged 15-69 years. A questionnaire regarding general and personal characteristics and relevant information was administered. Ultrasonography of the thyroid was performed, and serum triiodothyronine (T3), tetraiodothyronine (T4), serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and TSH receptor antibody (TRAb) levels were measured for each individual subject. RESULTS: The prevalence rates of TNs in the whole population, females and males were 27.76%, 34.04%, and 21.60%, respectively. The prevalence of multiple nodules increased with age, whereas the prevalence peaks differed between males and females. The median UICs in the whole population and females with non-TNs were higher than those of subjects with TNs (P=0.0035, P=0.0068). The median UICs in subjects with a single TN were higher than those in subjects with multiple TNs (P=0.0164, P=0.0127). The result showed a U-shaped curve relationship between UIC and prevalence of TNs. The prevalence of TNs was the lowest when the UIC was 140-400 µg/L. CONCLUSION: The prevalence of TNs was nearly 30% and increased with age. The relationship between UIC and prevalence of TNs is U-shaped, with an increase in risk when the UIC was <140 µg/L and >400 µg/L. Very low or high UIC levels need attention and correction.
Assuntos
Iodo/urina , Estado Nutricional , Nódulo da Glândula Tireoide/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Nódulo da Glândula Tireoide/induzido quimicamente , Adulto JovemRESUMO
Tibetan medicine "Dida" isoccasionally misused due to its complex origins, which ultimately affects its clinical efficacy. The accurate name, origin, property, and efficacy of "Dida"are highly important for its further research and development. In the present study, by viewing the classic Tibetan medicine and modern literature, and combining the clinical practice of Tibetan medicine, the origins, properties and the clinic effects of "Dida" were defined. "Dida" originated from multiple plant species of Swertia, Gentianopsis, Halenia, Lomatogonium, Comastoma(Gentianaceae), Hedyotis (Saxifragaceae) and Erysimum (Cruciferae). The medicinal properties of "Dida" is mainly bitter and cold. It has been commonly used to treat febrile diseases and hepatic and gall diseases. This study suggested that the relevant herbalogical study, species identification and pharmacological effects of "Dida" should be taken based on the Tibetan medicine theories and clinical practice. Thus the medicine can be better used and ensure its safety and quality simultaneously.
Assuntos
Medicamentos de Ervas Chinesas/química , Gentianaceae/química , Hedyotis/química , Plantas Medicinais/química , Swertia/química , Pesquisa Biomédica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional TibetanaRESUMO
The purpose of our study was to assess drinking status in middle school students and to understand the associated factors. The adjusted drinking rates were 50.9%, 39.8%, and 15.1% for lifetime, past-year, and current drinking, respectively. Multivariable logistic regression revealed the following variables positively related to drinking during the past year: family income, maternal educational level, family members who drink, parents who support drinking, best friends who drink, friends who encourage drinking, frequently attending friends' parties, smoking, and actuation trend (P<0.05). The main risk factors were friends (OR=6.77, 95% CI: 6.17, 7.43) and smoking (OR=4.70, 95% CI: 3.44, 6.43). These results contribute to obtaining the potential associated factors and aid in targeted intervention into the drinking behavior of middle school students.
Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Adolescente , China , Coleta de Dados , Família , Feminino , Amigos , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Fatores de Risco , Fumar , Fatores SocioeconômicosRESUMO
Dietary selenium intake within the normal physiological range is critical for various supporting biological functions. However, the effect of nano-selenium on biological mechanism of goblet cells associated with autophagy is largely unknown.The purpose of this study was to investigate the effect of nano-selenium on the mucosal immune-defense mechanism of goblet cells (GCs) in the small intestine of laying hens.The autophagy was determined by using specific markers. Nano-selenium-treated group of immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) results indicated the strong positive immune signaling of microtubule-associated light chain (LC3) within the mucosal surface of the small intestine. However, weak expression of LC3 was observed in the 3-methyladenine autophagy inhibitor (3-MA) group. IHC and IF staining results showed the opposite tendency for LC3 of sequestosome 1 (P62/SQSTM1). P62/SQSTM1 showed strong positive immune signaling within the mucosal surface of the small intestine of the 3-MAgroup, and weak immune signaling of P62/SQSTM1 in the nano-selenium-treated group. Moreover, pinpointing autophagy was involved in the mucosal production and enrichment of mucosal immunity of the GCs. The morphology and ultrastructure evidence showed that the mucus secretion of GCs was significantly increased after nano-selenium treatment confirmed by light and transmission electron microscopy. Besides that, immunostaining of IHC, IF and WB showed that autophagy enhanced the secretion of Mucin2 (Muc2) protein in nano-selenium-treated group. This work illustrates that the nano-selenium particle might enhance the mucosal immune-defense mechanism via the protective role of GCs for intestinal homeostasis through autophagy.
Assuntos
Células Caliciformes , Selênio , Animais , Feminino , Células Caliciformes/metabolismo , Proteína Sequestossoma-1/metabolismo , Selênio/farmacologia , Selênio/metabolismo , Galinhas/metabolismo , Autofagia , Intestino Delgado/metabolismoRESUMO
PURPOSE: The present meta-analysis aimed at assessing the effectiveness and safety of tranexamic acid (TXA) in reducing blood loss and transfusion in spinal surgery. METHODS: Systematic searches of all studies published through March 2012 were identified from PubMed, EMBase, Cochrane library, Science Direct, and other databases. Only randomized controlled trials (RCTs) were included in the present study. Two independent reviewers searched and assessed the literature. Mean difference (MD) of blood loss and blood transfusions, risk ratios (RR) of transfusion rate and of deep vein thrombosis rate in the TXA-treated group versus placebo group were pooled throughout the study. The meta-analysis was conducted by RevMan 5.1 software. RESULTS: Six placebo-controlled RCTs encompassing 411 patients met the inclusion criteria for our meta-analysis. The use of TXA significantly reduced both total blood loss [MD = -285.35, 95 % CI (-507.03 to -63.67), P = 0.01] as well as the number of patients requiring blood transfusion [RR = 0.71, 95 % CI (0.54-0.92), P = 0.01]. None of the patients in the treatment group had deep-vein thrombosis (DVT) or pulmonary embolism. CONCLUSIONS: Intravenous use of TXA for patients undergoing spinal surgery is effective and safe. It reduces total blood loss and the need for blood transfusion, particularly in the using of high dosage of TXA (≥ 15 mg/kg), yet does not increase the risk of postoperative DVT. Due to the limitation of the quality of the evidence currently available, high-quality RCTs are required.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Hemorragia/tratamento farmacológico , Doenças da Coluna Vertebral/cirurgia , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/efeitos adversos , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Protein post-translational modifications play central roles in regulating protein functions. Lysine threonylation is a newly discovered reversible post-translational modification. However, the biological effect of lysine threonylation on proteins remains largely elusive. Here we report a chemical biology approach for site-specific incorporation of Nε-threonyllysine into proteins with high efficiency and investigate the biological effect of lysine threonylation on Aurora kinase A. Using this unnatural amino acid mutagenesis approach, we find that threonylation of Lys162 of Aurora kinase A inhibits its kinase activity both in vitro and in vivo and that the inhibitory effect can be reversed by the deacetylase Sirtuin 3, which removes the threonylated group from the lysine. Additionally, threonylation of Aurora kinase A makes its substrate p53 more stable in the cell. Therefore, our study demonstrates that site-specific lysine threonylation is a powerful method for probing the biological effect of protein threonylation.
Assuntos
Aurora Quinase A , Lisina , Treonina , Aminoácidos/metabolismo , Aurora Quinase A/metabolismo , Lisina/química , Fosforilação , Processamento de Proteína Pós-Traducional , Treonina/química , Treonina/metabolismoRESUMO
Protein post-translational modification (PTM) regulates nearly every aspect of cellular processes in eukaryotes. However, the identification of new protein PTMs is very challenging. Here, using genetically encoded unnatural amino acids as chemical probes, we report the identification and validation of a previously unreported form of protein PTM, aminoacylated lysine ubiquitination, in which the modification occurs on the α-amine group of aminoacylated lysine. We identify more than 2,000 ubiquitination sites on all 20 aminoacylated lysines in two human cell lines. The modifications can mediate rapid protein degradation, complementing the canonical lysine ubiquitination-mediated proteome degradation. Furthermore, we demonstrate that the ubiquitin-conjugating enzyme UBE2W acts as a writer of aminoacylated lysine ubiquitination and facilitates the ubiquitination event on proteins. More broadly, the discovery and validation of aminoacylated lysine ubiquitination paves the way for the identification and verification of new protein PTMs with the genetic code expansion strategy.
Assuntos
Lisina , Processamento de Proteína Pós-Traducional , Humanos , Lisina/química , Ubiquitinação , Proteoma/genética , Proteoma/metabolismo , Código Genético , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
PURPOSE: Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC. MATERIALS AND METHODS: Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed. RESULTS: APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor ß signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations. CONCLUSION: APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.
Assuntos
Polipose Adenomatosa do Colo , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Prognóstico , Neoplasias Colorretais/patologia , MutaçãoRESUMO
OBJECTIVE: This study aimed to determine whether the prevalence of thyroid nodules (TNs) increased due to modern lifestyles or other factors, despite the advances in screening and diagnostic tools. METHODS: This study included 3474 pairs of participants, who were matched by gender and age (±3 years) from two cross-sectional sampling surveys: (1) the program on the iodine nutritional status and related health status of residents in Shanghai in 2009; (2) the thyroid disease screening program for adults in Shanghai between 2017 and 2018. The prevalence of TNs and thyroid diseases in 2009 and 2017-2018 were compared, and the potential risk factors of TNs were detected. RESULTS: The prevalence of TNs in 2009 was 28.9%: 22.5% in males and 34.5% in females. In 2017, this increased to 43.8%: 37.9% in males and 49.1% in females. The prevalence of TNs significantly increased from 2009 to 2017 (odds ratio, 1.486; 95% confidence interval, 1.238-1.786). In addition, female gender, thyroid disease history, and age were the main risk factors for TNs after adjusting for confounders in the logistic regression across the time period. CONCLUSION: The prevalence of TNs significantly increased across nearly 10 years in Shanghai.
Assuntos
Nódulo da Glândula Tireoide , Adulto , Masculino , Humanos , Feminino , China/epidemiologia , Prevalência , Estudos Transversais , Fatores de RiscoRESUMO
BACKGROUND: Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis. We hypothesized that pericytes, a group of pluripotent cells that maintain vascular integrity and tension, are protective against sepsis via regulating vascular reactivity and permeability. METHODS: We conducted a series of in vivo experiments using wild-type (WT), platelet-derived growth factor receptor beta (PDGFR-ß)-Cre + mT/mG transgenic mice and Tie2-Cre + Cx43flox/flox mice to examine the relative contribution of pericytes in sepsis, either induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) challenge. In a separate set of experiments with Sprague-Dawley (SD) rats, pericytes were depleted using CP-673451, a selective PDGFR-ß inhibitor, at a dosage of 40 mg/(kg·d) for 7 consecutive days. Cultured pericytes, vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were used for mechanistic investigations. The effects of pericytes and pericyte-derived microvesicles (PCMVs) and candidate miRNAs on vascular reactivity and barrier function were also examined. RESULTS: CLP and LPS induced severe injury/loss of pericytes, vascular hyporeactivity and leakage (P < 0.05). Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization (P < 0.05). Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels (P < 0.05). Additionally, PCMVs transferred miR-145 and miR-132 to VSMCs and VECs, respectively, exerting a protective effect on vascular reactivity and barrier function after sepsis (P < 0.05). miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2 (Sphk2)/sphingosine-1-phosphate receptor (S1PR)1/phosphorylation of myosin light chain 20 pathway, whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways. CONCLUSIONS: Pericytes are protective against sepsis through regulating vascular reactivity and barrier function. Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.
Assuntos
MicroRNAs , Sepse , Animais , Camundongos , Ratos , Permeabilidade Capilar/fisiologia , Conexina 43/metabolismo , Células Endoteliais/metabolismo , Lipopolissacarídeos/farmacologia , MicroRNAs/farmacologia , Pericitos/metabolismo , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To evaluate the effectiveness of unilateral versus bilateral pedicle screw fixation in lumbar spinal fusion. METHODS: Studies on comparison between unilateral and bilateral pedicle screw fixation in lumbar spinal fusion were identified from Medline, EMBASE, Cochrane CENTRAL (Third Quarter 2011), ScienceDirect, OVID, SpringerLink and The China Biological Medicine Database, and searched several related journals by hand. The included trials were screened out according to the criterion of inclusion and exclusion. The quality of included trials was evaluated. Data were extracted by two reviewers independently. RevMan 5.1.1 was used for data analysis. RESULTS: Seven studies involving 480 patients were included, 246 in unilateral group, and 234 in bilateral group. The results of meta-analysis indicated that statistically significant difference were observed between the two fixation procedures in mean operation time (MD = -24.39, 95%CI: -33.16 to 15.61, P < 0.01), the amount of bleeding (MD = -118.73, 95%CI: -143.43 to -94.03, P < 0.01). There were no difference in inpatient stay, fusion rate, complication rate and excellent and good rate. CONCLUSIONS: Both unilateral and bilateral pedicle screw fixation are effective in lumbar spinal fusion. To compare with bilateral fixation, unilateral fixation can shorten operation time, reduce amount of bleeding and medical expenses. And there is a similar effect of inpatient stay, fusion rate, complication rate and excellent and good rate.
Assuntos
Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Parafusos Ósseos , Humanos , Fixadores Internos , Resultado do TratamentoRESUMO
Using three pipe clamp solenoid valves to replace the traditional six-port valve for sample quota, a set of multi-channel flow injection analyzer was designed in the present paper. The authors optimized optimum instrumental testing condition, and realized determination and analysis of total dissolved nitrogen in seawaters. The construction of apparatus is simple and it has the potential to be used for analysis of total dissolved nitrogen. The sample throughput of total dissolved nitrogen was 27 samples per hour. The linear range of total dissolved nitrogen was 50.0-1 000.0 microgN x L(-3) (r > or = 0.999). The detection limit was 7.6 microgN x L(-3). The recovery of total dissolved nitrogen was 87.3%-107.2%. The relative standard deviation for total dissolved nitrogen was 1.35%-6.32% (n = 6). After the t-test analysis, it does not have the significance difference between this method and national standard method. It is suitable for fast analysis of total dissolved nitrogen in seawater.