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1.
Cardiovasc Res ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782769

RESUMO

AIMS: Overactivated B cells secrete pathological antibodies, which in turn accelerate the formation of abdominal aortic aneurysms (AAAs). Hyperhomocysteinemia (HHcy) aggravates AAA in mice; however, the underlying mechanisms remain largely elusive. In this study, we further investigated whether homocysteine (Hcy)-activated B cells produce antigen-specific antibodies that ultimately contribute to AAA formation. METHODS AND RESULTS: ELISA assays showed that HHcy induced the secretion of anti-beta 2 glycoprotein I (anti-ß2GPI) antibody from B cells both in vitro and in vivo. Mechanistically, Hcy increased the accumulation of various lipid metabolites in B cells tested by LC-MS/MS, which contributed to elevated anti-ß2GPI IgG secretion. By using the Toll-like receptor 4 (TLR4)-specific inhibitor TAK-242 or TLR4-deficient macrophages, we found that culture supernatants from Hcy-activated B cells and HHcy plasma IgG polarized inflammatory macrophages in a TLR4-dependent manner. In addition, HHcy markedly increased the incidence of elastase- and CaPO4-induced AAA in male BALB/c mice, which was prevented in µMT mice. To further determine the importance of IgG in HHcy-aggravated AAA formation, we purified plasma IgG from HHcy or control mice and then transferred the IgG into µMT mice, which were subsequently subjected to elastase- or CaPO4-induced AAA. Compared with µMT mice that received plasma IgG from control mice, µMT mice that received HHcy plasma IgG developed significantly exacerbated elastase- or CaPO4-induced AAA accompanied by increased elastin degradation, MMP2/9 expression, and anti-ß2GPI IgG deposition in vascular lesions, as shown by immunofluorescence histochemical staining. CONCLUSION: Our findings reveal a novel mechanism by which Hcy-induced B cell-derived pathogenic anti-ß2GPI IgG might, at least in part, contribute to HHcy-aggravated chronic vascular inflammation and AAA formation. TRANSLATIONAL PERSPECTIVE: HHcy is an independent risk factor for cardiovascular diseases in which B cell secretion of IgG antibodies play a key role. However, whether the antigen specific antibody production is changed during HHcy-accelerated AAA remains unclear. Our results provided the first evidence supporting the important role of activated B cell-derived anti-ß2GPI IgG in HHcy-aggravated chronic vascular inflammation and AAA formation. It sheds new light on understanding pathogenesis of HHcy-accelerated AAA. In addition, anti-ß2GPI IgG may be a potential diagnostic marker and therapeutic target for HHcy-related vascular injury.

2.
BMC Pregnancy Childbirth ; 19(1): 408, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703641

RESUMO

BACKGROUND: Incarceration of the gravid uterus is a rare obstetric disorder that contributes to pregnancy-related complications. To understand its clinical characteristics and managements, we have reviewed the etiology, risk factors, clinical characteristics and current treatments of an incarcerated gravid uterus based on 162 cases reported in the English language literature, including our patient. CASE PRESENTATION: A 25-year-old primigravida, with a history of lymphatic tuberculosis, infertility due to blocked fallopian tubes and received in vitro fertilization. The patient presented with urine retention and lower abdominal pain in the early second trimester. Uterine incarceration was diagnosed based on pelvic examination and abdominal ultrasound. A Foley catheter was placed and manual reposition was successful. No episode of retention was experienced after the further enlargement of the uterus and its ascent. A healthy infant was delivered vaginally on 38th week of pregnancy. CONCLUSIONS: Uterine incarceration due to pelvic adhesions is rare and, because of it non-specific clinical presentations, is often misdiagnosed. Abdominal ultrasound is instrumental for the diagnosis because it can directly image the disturbed uterine and pelvic anatomy. There are limited treatment options for uterine incarceration, but definitive diagnosis allows procedures to treat and to reduce severe complications of uterine incarceration.

3.
Front Physiol ; 10: 1236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632289

RESUMO

Preeclampsia is a common obstetric complication associated with pregnancy and it endangers lives of the mother and the infant. The histopathological changes associated with preeclampsia include systemic endothelial dysfunction, persistent inflammatory state, and coagulation and fibrinolysis dysregulations. Preeclampsia is considered to be caused by the systemic vasoconstriction of small arteries and disruption of the endothelial integrity, resulting in hypertension, proteinuria, and multiple organ dysfunction. However, mediators that trigger or propagate the pathology of preeclampsia remain poorly defined. Syncytiotrophoblast-derived extracellular vesicles (SDEVs) are increasingly recognized as a key mediator for the development of preeclampsia, but the underlying mechanisms through which these SDEVs are released and induce systemic responses are not fully understood. This review focuses on multiple roles of SDEVs in the pathogenesis of preeclampsia.

4.
FASEB J ; 33(11): 12780-12799, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31480861

RESUMO

Intercellular communication between lymphocytes plays a fundamental role in numerous immune responses. Previously, we demonstrated that hyperhomocysteinemia (HHcy) induced T cell intracellular glycolytic-lipogenic reprogramming and IFN-γ secretion via pyruvate kinase muscle isozyme 2 (PKM2) to accelerate atherosclerosis. Usually, B cells partially obtain help from T cells in antibody responses. However, whether PKM2 activation in T cells regulates B cell antibody production is unknown. Extracellular vesicles (EVs) are important cellular communication vehicles. Here, we found that PKM2 activator TEPP46-stimulated T-cell-derived EVs promoted B-cell IgG secretion. Conversely, EVs secreted from PKM2-null T cells were internalized into B cells and markedly inhibited B-cell mitochondrial programming, activation, and IgG production. Mechanistically, lipidomics analyses showed that increased ceramides in PKM2-activated T-cell EVs were mainly responsible for enhanced B cell IgG secretion induced by these EVs. Finally, quantum dots (QDs) were packaged with PKM2-null T cell EVs and anti-CD19 antibody to exert B-cell targeting and inhibit IgG production, eventually ameliorating HHcy-accelerated atherosclerosis in vivo. Thus, PKM2-mediated EV ceramides in T cells may be an important cargo for T-cell-regulated B cell IgG production, and QD-CD19-PKM2-null T cell EVs hold high potential to treat B cell overactivation-related diseases.-Yang, J., Dang, G., Lü, S., Liu, H., Ma, X., Han, L., Deng, J., Miao, Y., Li, X., Shao, F., Jiang, C., Xu, Q., Wang, X., Feng, J. T-cell-derived extracellular vesicles regulate B-cell IgG production via pyruvate kinase muscle isozyme 2.

5.
Materials (Basel) ; 12(11)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163666

RESUMO

Tannic acid (TA), a high-molecular-weight polyphenol, is used as a hemostasis spray and unguent for trauma wound remedy in traditional medical treatment. However, the use of tannic acid on a large-area wound would lead to absorption poisoning. In this work, a TA coating was assembled on a quartz/silicon slide, or medical gauze, via chelation interaction between TA and Fe3+ ions and for further use as a hemostasis dressing. Protein adsorption on the TA coating was further investigated by fluorescence signal, ellipsometry analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The adsorbed bovine serum albumin (BSA), immunoglobulin G (IgG) and fibrinogen (Fgn) on the TA coating was in the manner of monolayer saturation adsorption, and fibrinogen showed the largest adsorption. Furthermore, we found the slight hemolysis of the TA coating caused by the lysed red blood cells and adsorption of protein, especially the clotting-related fibrinogen, resulted in excellent hemostasis performance of the TA coating in the blood clotting of an animal wound. Thus, this economic, environmentally friendly, flexible TA coating has potential in medical applications as a means of preparing novel hemostasis materials.

6.
World J Clin Cases ; 7(8): 940-950, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31119139

RESUMO

BACKGROUND: Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as the QT interval, Tpeak-to-Tend (Tpe) interval and Tpe/QT ratio, are associated with cardiac diastolic function in the healthy Chinese population. AIM: To assess the relationship between ventricular repolarization variables and cardiac diastolic function in apparently healthy Chinese individuals. METHODS: This was a community-based cross-sectional study conducted in Shenyang, China. A total of 414 healthy subjects aged 35-91 years were enrolled. All subjects underwent standard 12-lead electrocardiography (ECG) and comprehensive echocardiography. ECG enabled the measurement of QT and Tpe intervals and Tpe/QT ratio. echocardiographic parameters, such as the ratio of mitral early diastolic inflow velocity (E) and late diastolic inflow velocity (A), E-wave deceleration time, left atrial volume (LAV) and LAV index, were measured to assess diastolic function. E/A < 0.75 was considered to indicate reduced diastolic function. ECG and echocardiography results were analyzed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations. RESULTS: Ventricular repolarization variables, such as the QTc interval (393.59 ± 26.74 vs 403.86 ± 33.56; P < 0.001), Tpe interval (72.68 ± 12.41 vs 77.26 ± 17.86; P < 0.01), Tpec interval (76.36 ± 13.53 vs 83.32 ± 21.25; P < 0.001) and Tpe/QT ratio (0.19 ± 0.03 vs 0.20 ± 0.04; P < 0.01), were significantly different between the normal diastolic function group and the reduced diastolic function group. Significant associations were found between repolarization variables and diastolic function. After adjusting for all other possible confounders, the QTc and Tpec intervals were significantly associated with the E/A ratio (P = 0.008; P = 0.010). In men, the QTc interval was associated with abnormal diastolic function, and compared to the third QTc tertile, in the second QTc tertile, the odds ratio was 0.257 (95%CI: 0.102-0.649; P = 0.004). CONCLUSION: Repolarization variables are associated with cardiac diastolic function even in healthy people. Moderate levels of the QTc interval exert a protective effect on diastolic dysfunction in men.

7.
Eur J Clin Microbiol Infect Dis ; 38(2): 233-239, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30467614

RESUMO

The purpose of this study was to investigate the risk factors and pregnancy outcomes for aerobic vaginitis (AV) in late pregnancy. A total of 624 pregnant women who were treated in the perinatal unit at Tianjin Medical University General Hospital and 365 nonpregnant women who were evaluated at a health management center from January 2015 to June 2016 were recruited for this case-control study. A questionnaire covering personal hygiene habits and sociodemographic factors was administered to pregnant women to analyze risk factors for AV. Bacterial vaginosis, AV, vulvovaginal candidiasis, and Trichomonas vaginitis were scored according to standardized definitions. Pregnancy outcomes were followed up and recorded. The chi-square test and univariate and multivariate logistic regression analyses were used for statistical evaluation. The prevalence of vaginal infection in pregnant and nonpregnant women were 27.9% and 15.3%, respectively (P < 0.05). AV was identified more frequently in pregnant women than in nonpregnant women (4.2% vs. 1.4%; P < 0.05). A history of vaginal infection within 1 year (odds ratio [OR] = 3.219, 95% confidence interval [CI] 1.103-9.346) and external hemorrhoids (OR = 11.233, 95% CI 4.647-27.155) were independent risk factors for AV during pregnancy. A higher incidence of premature rupture of membranes (PROM) was significantly associated with AV (P < 0.05). AV is common in late pregnancy. Clinicians should pay more attention to vaginal microbiota evaluations during pregnancy.


Assuntos
Bactérias Aeróbias/isolamento & purificação , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Vaginite/diagnóstico , Vaginite/epidemiologia , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Gravidez , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Prevalência , Fatores de Risco , Inquéritos e Questionários , Vagina/microbiologia , Vagina/parasitologia
8.
Menopause ; 26(5): 546-553, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30516715

RESUMO

OBJECTIVES: Changes in serum protein levels of fibroblast growth factor 23 (FGF23) and Klotho resulting from bone metabolism are still controversial. The purpose of this study was to observe the relationship between FGF23 and Klotho serum proteins and lumbar spine bone mineral density (LBMD) in northern Chinese postmenopausal women. METHODS: This was a community-based cross-sectional study carried out in Shenyang, a northern Chinese city. The study included 355 postmenopausal women with an average age of 62.92 ±â€Š8.78 years. FGF23 and Klotho serum proteins were measured using a sandwich enzyme immunoassay. LBMD was examined using dual-energy X-ray absorptiometry. Pearson's correlation and regression analyses were performed to investigate the associations among them. RESULTS: The LgKlotho was positively correlated with LBMD (r = 0.105). There was a linear relationship between LgKlotho serum levels and LBMD (P = 0.007) after adjusting for BMI, and the relationship still existed after adjustments for many confounding variables (P = 0.045), including age, BMI, systolic blood pressure, diastolic blood pressure, total protein, total bilirubin, high-density lipoprotein cholesterol, fasting blood glucose, serum calcium, estimated glomerular filtration rate, serum uric acid, estradiol, cigarette smoking, alcohol consumption, milk intake, calcium and vitamin D supplements, physical exercise, and fracture history in postmenopausal women. FGF23 serum levels were, however, not significantly associated with LBMD. CONCLUSIONS: Klotho was positively correlated with LBMD, and there was a linear relationship between Klotho serum protein levels and LBMD; however, the levels of serum Klotho were not independently associated with reduced LBMD in northern Chinese postmenopausal women. Moreover, serum FGF23 levels were not significantly related to LBMD in this sample population.

9.
Org Biomol Chem ; 17(2): 257-263, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30357229

RESUMO

Bi-valent/specific antibodies are coming to the forefront of therapeutic and diagnostic applications for extending the functions of conventional antibodies. Nanobodies as building blocks, due to their small sizes, are prone to synthesizing these homo/hetero-dimers. However, the classical C-terminus to N-terminus (C-N) ligation manner for generating the dimer results in the inhibition of the antigen-binding capacity of the bivalent/specific antibodies. In this study, we designed and constructed several C-terminus to C-terminus (C-C) linked bivalent and bispecific nanobodies against the human ß2-microglobulin via freezing, overcoming the biological function-disrupt raised by the C-N ligation. The nanobody modified by the formylglycine generating enzyme was ligated to a hydrazide or aminooxy bi-functionalized linker. During the process, we discovered that freezing significantly improved the efficiency of hydrazone or oxime formation between the linker and nanobodies, which could not take place at room temperature. By freezing from -10 to -20 °C, up to 50% yield of bivalent nanobodies was achieved within 24 h. The C-C linked nanobody-fusions maintained almost all of its binding activity and exhibited an increase by two orders of magnitudes in affinity kinetics, demonstrating the superiority of C-C over the C-N linking approach.

10.
Clin Exp Hypertens ; 41(6): 524-530, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30183401

RESUMO

Preeclampsia (PE) occurs specifically during pregnancy characterized by new-onset hypertension. The pathogenesis of PE was complicated, and inflammation may be central to the pathogenesis of PE. Ferulic acid (FA) is recognized to prevent cell damage and apoptosis induced by oxidative stress and inflammation. In our study, we used NG-nitro-l-arginine methyl ester (L-NAME)-induced rat model of PE to investigate whether FA improved PE and its possible mechanism. We found that FA significantly reduced blood pressure, urine volume, and urinary protein level in rats with PE. Meanwhile, FA decreased L-NAME induced higher expression of circulating TNF-α、IL-6、IL-1ß and PlGF, it reduced placental TNF-α and NF-κB p65. Furthermore, FA rescued L-NAME induced decreasing expression of IL-4 and IL-10 expression in the circulation and placenta of rats. FA also ameliorated placental apoptosis in L-NAME induced rats by increasing Bcl-2 whereas decreasing Bax expression in placenta. It suggested FA as a potential candidate for the treatment of various disorders including L-NAME induced preeclampsia in rats through decreasing placental inflammation and apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Inflamação/tratamento farmacológico , Placenta/metabolismo , Pré-Eclâmpsia/tratamento farmacológico , Prenhez , Animais , Anti-Hipertensivos/farmacologia , Citocinas/sangue , Feminino , Inflamação/sangue , NG-Nitroarginina Metil Éster/efeitos adversos , Estresse Oxidativo , Placenta/patologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/fisiopatologia , Gravidez , Ratos
11.
Enzyme Microb Technol ; 120: 36-42, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30396397

RESUMO

A facile and economical method was established for the oriented immobilization of biotin ligase (BirA) on Co3+-NTA sepharose through H2O2 oxidation of Co2+ and His-tag. His-tag of the BirA were designed at both N-terminal (His-BirA) and C-terminal (BirA-His), respectively. Immobilization of the His-BirA was performed, realized to 92.85% using by 10 mM H2O2 without compromising catalytic activity. Because amounts of ions on matrix were far more than that of the immobilized BirA, EDTA should be used to remove residual ions before catalyzing, while it should be limited to lower than 30 mM, and imidazole ranging from 50 to 250 mM could be added in the catalytic system. When 10 mM EDTA and 50 mM imidazole were used, over 90% of substrates were obtained from the matrix. Moreover, the His-BirA showed higher immobilization rate than the BirA-His, while both of them appeared high catalytic abilities at pH ranging from 6.5 to 9.0, indicating versatile options in the biotinylation of proteins with different pH stabilities. Under the best catalytic conditions, the both immobilized His-BirA and BirA-His exhibited the same activity as the free. When the enzyme was incubated at different pH (pH 3.0, 4.0, 5.0, 10.0 and 11.0) and temperature (40 °C, 50 °C and 60 °C), the immobilized His-BirA showed less pH-sensitive, overall preferable thermo-stability than the free, making it a more desirable option for storage and transportation. More importantly, the reusability of the immobilized His-BirA implied a promising value in industrialization.


Assuntos
Biotinilação/métodos , Carbono-Nitrogênio Ligases/metabolismo , Complexos de Coordenação/metabolismo , Enzimas Imobilizadas/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimologia , Histidina/química , Proteínas Repressoras/metabolismo , Sefarose/química , Carbono-Nitrogênio Ligases/química , Catálise , Cobalto/química , Complexos de Coordenação/química , Enzimas Imobilizadas/química , Proteínas de Escherichia coli/química , Peróxido de Hidrogênio/química , Microesferas , Ácido Nitrilotriacético/química , Proteínas Repressoras/química
12.
Medicine (Baltimore) ; 97(51): e13735, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572514

RESUMO

BACKGROUND: laparoscopic cholecystectomy (LC) has become the gold standard surgery for benign gallbladder diseases. Metal clips are conventionally used to secure the cystic duct and artery, while monopolar electrocautery (ME) predominates during laparoscopic dissection. ultrasonic scalpel (US) has already been explored for sealing the cystic duct and artery as a sole instrument, which has been regarded as a reasonable alternative to clips. The aim of this study was to investigate the safety and effectiveness of US versus clips for securing the cystic duct during LC. METHODS: We identified eligible studies in PubMed, Medline, Cochrane Library, Embase, and SpringerLink up to 1st May 2018, together with the reference lists of original studies. Meta-analysis was conducted using STATA 14.0. Q-based chi-square test and the I statistics were utilized to assess heterogeneity among the included studies. A P-value below .05 was set for statistical significance. Forest plots of combined Hazard ratios (HRs) with 95% confidence intervals (CIs) were also generated. RESULTS: Eight studies met eligibility criteria in this meta-analysis eventually. A total of 1131 patients were included, of whom 529 were contained in the US group, compared to 602 in the clips group, which showed a significant difference (P = .025) without substantial statistical heterogeneity (I = 0.0%). No statistical significance was revealed regarding age (I = 0.0%, P = .957), and sex (I = 0.0%, P = .578) between both groups. The operative time and hospital stay in the US group were significantly shorter than that in the clips group, with I = 95.0%, P = .000 and I = 72.8%, P = .005, respectively. Concerning conversion (I = 48.6%, P = .084), perforation (I = 12.0%, P = .338), along with bile leakage (I = 0.0% P = .594), and overall morbidity (I = 19.1%, P = .289), comparison between both groups exhibited no statistical significance. CONCLUSIONS: US enabled shorter operative time and hospital stay during LC, compared with clips. Additionally, US was comparable to clips regarding conversion, perforation, along with bile leakage and overall morbidity. Therefore, our meta-analysis concluded that US is clinically superior to the conventional clips in some aspects, or is at least as safe and effective as them, concerning closure of the cystic duct and artery.


Assuntos
Colecistectomia Laparoscópica/instrumentação , Ducto Cístico/cirurgia , Instrumentos Cirúrgicos , Doenças da Vesícula Biliar/cirurgia , Humanos , Metais , Ultrassom
13.
Micromachines (Basel) ; 9(12)2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30477232

RESUMO

In this paper, a direct pre-bonding technology after alignment of the chip is presented to avoid the post-misalignment problem caused by the transferring process from an alignment platform to a heating oven. An alignment system with a high integration level including a microscope device, a vacuum device, and an alignment device is investigated. To align the chip, a method of 'fixing a chip with microchannels and moving a chip with nanochannels' is adopted based on the alignment system. With the alignment system and the assembly method, the micro/nanofluidic chip was manufactured with little time and low cost. Furthermore, to verify the performance of the chip and then confirm the practicability of the device, an ion enrichment experiment is carried out. The results demonstrate that the concentration of fluorescein isothiocyanate (FITC) reaches an enrichment value of around 5 µM and the highest enrichment factor is about 500-fold. Compared with other devices, an alignment system presented in this paper has the advantages of direct pre-bonding and high integration level.

14.
Exp Gerontol ; 112: 97-102, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30219349

RESUMO

BACKGROUND: Studies have suggested that Helicobacter pylori (Hp) infection is associated with atherosclerotic process, while the relationship between pepsinogens, gastrin and atherosclerosis is unknown. AIM: The aim of the study was to observe association of Hp infection on atherosclerotic parameters and blood pressure, and explore the relationship between atherosclerotic parameters, blood pressure and gastric biomarkers in a healthy population. METHODS: 395 subjects were chosen and received physical examinations, carotid artery ultrasound, peripheral atherosclerosis measurement, and testing of serum pepsinogen (PG) I and II, Hp antibody, and gastrin-17 (G-17) levels. Analyses were conducted by Student's t-test, ANOVA, Pearson correlation, multiple linear regression and binary logistic regression. RESULTS: In Hp-infected subjects, right carotid intima media thickness (R-CIMT) were higher (P = 0.027) and left ankle brachial index were higher in 45-64 years compared to 35-44 years group (P = 0.039, P = 0.016). Hp-IgG, PGI and G-17 respectively positively correlated with CIMT, pulse wave velocity and systolic blood pressure (P = 0.044, P = 0.013, P = 0.021). The unadjusted OR in subjects with elevated CIMT for quartile IV of PGI was 3.542 (95% CI, 1.491-8.411), the adjusted OR was 2.916 (95% CI, 1.035-8.216). The unadjusted OR in subjects with elevated CIMT for quartile III of G-17 was 4.351 (95% CI, 1.670-11.336) and for quartile IV was 3.108 (95% CI, 1.149-8.406), the adjusted OR for quartile III was 4.962 (95% CI, 1.515-16.258). CONCLUSIONS: Hp infection, higher levels of PGI and G-17 may contribute to atherosclerotic process by influencing atherosclerotic parameters and blood pressure in a healthy population, the influence on CIMT was most significant.


Assuntos
Aterosclerose/epidemiologia , Gastrinas/sangue , Infecções por Helicobacter/sangue , Pepsinogênios/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/sangue , Biomarcadores/sangue , Espessura Intima-Media Carotídea , China/epidemiologia , Estudos Transversais , Feminino , Voluntários Saudáveis , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco
15.
Lipids Health Dis ; 17(1): 186, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30111317

RESUMO

The extensive performance of splenectomy worldwide for patients suffered from splenic trauma has given rise to high risks of postoperative complications, which has been attracting increasing attention in recent years. Nowadays the spleen is regarded as a versatile organ of the human body, invested with various excellent properties. The spleen has been recognized to take a great part in lipid metabolism. While removal of the spleen intends to alter lipid values, especially with an elevated LDL, splenic autotransplantation is able to normalize these lipid alterations. What is more, conservative surgical procedures like subtotal or partial splenectomy, could as well, afford a correction of dyslipidemia. At the same time, clinically, splenectomy demonstrates a high rate of atherosclerosis (AS), whereas non-surgical treatment after splenic trauma shows unchanged propagation of AS. Based on the intimate relationship between serum lipids and AS, the lipid changes modulated by splenectomy are believed to be responsible for the development of AS. Therefore, a "splenic factor" is most likely present in the regulation of lipidation and AS. Several theories have been postulated to elucidate the possible mechanism involved, among which most are primarily based on its forceful natural immune function, that is to say, the mononuclear phagocytic system.However, the accurate mechanisms behind this mysterious phenomenon still remain unclear so far. Of importance, lipid fractions should be monitored consecutively in case of inevitable splenectomy.


Assuntos
Aterosclerose/metabolismo , Metabolismo dos Lipídeos , Baço/metabolismo , Baço/cirurgia , Esplenectomia , Aterosclerose/sangue , Aterosclerose/genética , Humanos , Lipídeos/sangue , MicroRNAs/genética , MicroRNAs/metabolismo
16.
Neurobiol Dis ; 117: 15-27, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29859317

RESUMO

The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated inflammatory response has emerged as a prominent contributor to the pathophysiological processes of traumatic brain injury (TBI). Recently, a potent, selective, small-molecule NLRP3 inflammasome inhibitor, MCC950, was described. Here, we investigated the effect of MCC950 on inflammatory brain injury and long-term neurological outcomes in a mouse model of TBI. Male C57/BL6 mice were subjected to TBI using the controlled cortical impact injury (CCI) system. Western blotting, flow cytometry, and immunofluorescence assays were utilized to analyze post-traumatic NLRP3 inflammasome expression and determine its cellular source. We found that NLRP3 inflammasome expression was significantly increased in the peri-contusional cortex and that microglia were the primary source of this expression. The effects of MCC950 on mice with TBI were then determined using post-assessments including analyses of neurological deficits, brain water content, traumatic lesion volume, neuroinflammation, blood-brain barrier (BBB) integrity, and cell death. MCC950 treatment resulted in a better neurological outcome after TBI by alleviating brain edema, reducing lesion volume, and improving long-term motor and cognitive functions. The therapeutic window for MCC950 against TBI was as long as 6 h. Furthermore, the neuroprotective effect of MCC950 was associated with reduced microglial activation, leukocyte recruitment, and pro-inflammatory cytokine production. In addition, MCC950 preserved BBB integrity, alleviated TBI-induced loss of tight junction proteins, and attenuated cell death. Notably, the efficacy of MCC950 was abolished in microglia-depleted mice. These results indicate that microglia-derived NLRP3 inflammasome may be primarily involved in the inflammatory response to TBI, and specific NLRP3 inflammasome inhibition using MCC950 may be a promising therapeutic approach for patients with TBI.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sulfonas/uso terapêutico , Animais , Modelos Animais de Doenças , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamassomos/biossíntese , Inflamassomos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Sulfonas/farmacologia , Fatores de Tempo , Resultado do Tratamento
17.
Redox Biol ; 17: 386-399, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29860106

RESUMO

The adaptive immune system plays a critical role in hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Recent studies suggest that HHcy aggravates atherosclerosis with elevated oxidative stress and reduced S-nitrosylation level of redox-sensitive protein residues in the vasculature. However, whether and how S-nitrosylation contributes to T-cell-driven atherosclerosis remain unclear. In the present study, we report that HHcy reduced the level of protein S-nitrosylation in T cells by inducing S-nitrosoglutathione reductase (GSNOR), the key denitrosylase that catalyzes S-nitrosoglutathione (GSNO), which is the main restored form of nitric oxide in vivo. Consequently, secretion of inflammatory cytokines [interferon-γ (IFN-γ) and interleukin-2] and proliferation of T cells were increased. GSNOR knockout or GSNO stimulation rectified HHcy-induced inflammatory cytokine secretion and T-cell proliferation. Site-directed mutagenesis of Akt at Cys224 revealed that S-nitrosylation at this site was pivotal for the reduced phosphorylation at Akt Ser473, which led to impaired Akt signaling. Furthermore, on HHcy challenge, as compared with GSNOR+/+ApoE-/- littermate controls, GSNOR-/-ApoE-/- double knockout mice showed reduced T-cell activation with concurrent reduction of atherosclerosis. Adoptive transfer of GSNOR-/- T cells to ApoE-/- mice fed homocysteine (Hcy) decreased atherosclerosis, with fewer infiltrated T cells and macrophages in plaques. In patients with HHcy and coronary artery disease, the level of plasma Hcy was positively correlated with Gsnor expression in peripheral blood mononuclear cells and IFN-γ+ T cells but inversely correlated with the S-nitrosylation level in T cells. These data reveal that T cells are activated, in part via GSNOR-dependent Akt denitrosylation during HHcy-induced atherosclerosis. Thus, suppression of GSNOR in T cells may reduce the risk of atherosclerosis.


Assuntos
Aldeído Oxirredutases/genética , Apolipoproteínas E/genética , Aterosclerose/genética , Hiper-Homocisteinemia/genética , Proteínas Proto-Oncogênicas c-akt/genética , Imunidade Adaptativa/genética , Idoso , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Feminino , Humanos , Hiper-Homocisteinemia/metabolismo , Hiper-Homocisteinemia/patologia , Interferon gama/genética , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Oxirredução , Estresse Oxidativo/genética , Fosforilação/genética , S-Nitrosoglutationa/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
18.
Biomed Pharmacother ; 99: 791-797, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29710477

RESUMO

Systemic lupus erythematosus (SLE) is a severe autoimmune disease and the pathogenesis remains incompletely understood. This study aimed to investigate the role of miR-125b in the pathogenesis of SLE and explore the underlying mechanism. Compared to healthy controls, the expression of miR-125b decreased in peripheral blood mononuclear cells (PBMCs) of SLE patients. In addition, PBMCs exposed to ultraviolet B had lower miR-125b level compared to those unexposed to radiation. We identified UV radiation resistance associated gene (UVRAG) as a target of miR-125b. Jurkat cells treated with miR-125b-5p agomir showed reduced levels of ATG7, Beclin-1 and LC3 II and decreased autophagy. In contrast, Jurkat cells treated with miR-125b-5p antagomir showed increased levels of ATG7, Beclin-1 and LC3 II and increased autophagy. Furthermore, Jurkat cells transfected with UVRAG expression vector showed higher expression of ATG7, Beclin-1 and LC3 II and increased autophagy. Conversely, cells transfected with UVRAG siRNA had lower expression of ATG7, Beclin-1 and LC3 II and decreased autophagy. Taken together, our data demonstrate that Ultraviolet B radiation can downregulate miR-125b-5p and increase UVRAG expression and autophagy activity in PBMCs of SLE patients. These findings help explain how ultraviolet B exacerbates SLE and suggest that UVRAG is a potential therapeutic target for SLE.


Assuntos
Autofagia/genética , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Proteínas Supressoras de Tumor/genética , Adulto , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Células Jurkat , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/efeitos da radiação , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Raios Ultravioleta , Adulto Jovem
19.
Brain Res ; 1698: 1-10, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29842860

RESUMO

Early brain injury (EBI) plays a pivotal role in the prognosis of patients with subarachnoid haemorrhage (SAH). Dexmedetomidine (DEX), a highly selective α2 receptor agonist, is reported to exert multiple protective effects in many neurological diseases. This study was designed to investigate whether DEX had neuroprotective functions in EBI after SAH, and to explore the possible mechanisms. The SAH model was established by an endovascular perforation in adult male Sprague-Dawley (SD) rats. DEX (25 µg/kg) or vehicle was administered intraperitoneally 2 h after SAH. Neurological deficits, brain oedema, inflammation, BBB damage, and cell apoptosis at 24 h after SAH were evaluated. Additionally, the expression of components of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway, and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome were also assessed. We demonstrated that DEX treatment improved neurological scores, alleviated brain oedema, reduced the permeability of the blood-brain barrier (BBB), and up-regulated the expression of tight junction proteins. DEX treatment could reduce the neutrophil infiltration, microglial activation, and pro-inflammatory factor release. In addition, DEX alleviated cell apoptosis at 24 h after SAH. Notably, DEX could also suppress the activation of the TLR4/NF-κB pathway and the NLRP3 inflammasome. These findings suggested that treatment with DEX after SAH attenuated SAH-induced EBI, partially through the suppression of the TLR4/NF-κB pathway and the NLRP3 inflammasome.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Dexmedetomidina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hemorragia Subaracnóidea/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Edema Encefálico/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/fisiopatologia , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/fisiopatologia , Receptor 4 Toll-Like/metabolismo
20.
Food Funct ; 9(5): 2962-2969, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29748675

RESUMO

Our previous study showed that catechin controlled rats' body weights and changed gut microbiota composition when supplemented into a high-fructo-oligosaccharide (FOS) diet. This experiment is devised to further confirm the relationship between specific bacteria in the colon and body weight gain, and to investigate how specific bacteria impact body weight by changing the expression of colonic epithelial cells. Forty obese rats were divided into four groups: three catechin-supplemented groups with a high-FOS diet (100, 400, and 700 mg kg-1 d-1 catechin, orally administered) and one group with a high-FOS diet only. Food consumption and body weights were recorded each week. After one month of treatment, rats' cecal content and colonic epithelial cells were individually collected and analyzed with MiSeq and gene expression profiling techniques, respectively. Results identified some specific bacteria at the genus level-including the increased Parabacteroides sp., Prevotella sp., Robinsoniella sp., [Ruminococcus], Phascolarctobacterium sp. and an unknown genus of YS2, and the decreased Lachnospira sp., Oscillospira sp., Ruminococcus sp., an unknown genus of Peptococcaceae and an unknown genus of Clostridiales in rats' cecum-and eight genes-including one downregulated Pla2g2a and seven upregulated genes: Apoa1, Apoa4, Aabr07073400.1, Fabp4, Pik3r5, Dgat2 and Ptgs2 of colonic epithelial cells-that were due to the consumption of catechin. Consequently, various biological functions in connection with energy metabolism in colonic epithelial cells were altered, including fat digestion and absorption and the regulation of lipolysis in adipocytes. In conclusion, catechin induces host weight loss by altering gut microbiota and gene expression and function in colonic epithelial cells.


Assuntos
Catequina/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Oligossacarídeos/metabolismo , Perda de Peso/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/microbiologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Suplementos Nutricionais/análise , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Humanos , Masculino , Obesidade/genética , Obesidade/metabolismo , Ratos , Ratos Sprague-Dawley
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