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1.
Hepatology ; 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30820969

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD-induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogen-activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.

2.
Cell Cycle ; 17(18): 2230-2242, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30244637

RESUMO

MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs which can bind to completely or partially complementary sequences in the 3'UTR of target mRNAs, therefore degrading the mRNA or repressing translation. We previously reported that miR-378 played a role in estradiol production via suppression of aromatase translation in porcine granulosa cells and could affect oocyte maturation in vitro by inhibiting cumulus cell expansion. However, the role of miR-378 on ovary development in vivo is unknown. The current study aimed to uncover the molecular mechanism of miR-378 in regulating mouse follicular development via micro-injection of CMV-miR-378 lentivirus into the bursa of mouse ovary. The results showed that CMV-miR-378 lentivirus transduction in the mouse ovaries resulted in reduced ovary size, extended oestrous cycle (6-7 d in miR-378 overexpression group and 4-5 dyas in GFP control group) due to continuous oestrum, decreased percentage of oocytes in vitro maturation rate (IVM 60.8% vs. 89.4% in GFP control), increased apoptosis rate (Bax/Bcl2 in mRNA and protein level), decreased expression of genes associated with gap junction, such as connexin 43 (Cx-43) and connexin (Cx-37) and decreased expression of genes associated with follicular development, such as BMP15 and GDF9. Moreover, the number of pups/litter was consistently lower in the miR-378 group in each batch of the paired breeding. Our data suggest that miR-378 alters gene expression in cumulus cells and indirectly influences oocyte maturation competency, possibly via inhibition of oocyte-cumulus interaction or induction of apoptosis.

3.
Med Sci Monit ; 24: 4876-4881, 2018 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-30006997

RESUMO

BACKGROUND The objectives of the present study were to examine the intra- and inter-operator reliability of the MyotonPRO device in quantifying the stiffness of the Achilles tendon and the device's ability to examine the modulation in stiffness of the Achilles tendon during ankle joint flexion. MATERIAL AND METHODS Twenty asymptomatic participants (10 males and 10 females; mean age: 25.0±3.1 years) were recruited for this study. The stiffness of the Achilles tendon was quantified using the MyotonPRO device. RESULTS The results revealed excellent intra- and inter-operator reliability for quantifying Achilles tendon stiffness with the ankle joint in a neutral position and detected a 13.9% increase in stiffness of the Achilles tendon between 0° and 30° of ankle joint flexion. The minimal detectable change (MDC) in tendon stiffness was 45 Newton/meter (N/m). CONCLUSIONS Our findings indicated that the MyotonPRO device is a feasible method to quantify the stiffness of the Achilles tendon and monitor its changes. Thus, it is an essential tool to use to examine the modulation in the stiffness of the Achilles tendon due to pathology or interventions for future studies.


Assuntos
Tendão do Calcâneo/fisiologia , Artrometria Articular/instrumentação , Adulto , Articulação do Tornozelo , Fenômenos Biomecânicos/fisiologia , Feminino , Humanos , Masculino , Amplitude de Movimento Articular/fisiologia , Reprodutibilidade dos Testes
4.
Chaos ; 28(5): 051102, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29857681

RESUMO

Dealing with the protection of critical infrastructures, many game-theoretic methods have been developed to study the strategic interactions between defenders and attackers. However, most game models ignore the interrelationship between different components within a certain system. In this paper, we propose a simultaneous-move attacker-defender game model, which is a two-player zero-sum static game with complete information. The strategies and payoffs of this game are defined on the basis of the topology structure of the infrastructure system, which is represented by a complex network. Due to the complexity of strategies, the attack and defense strategies are confined by two typical strategies, namely, targeted strategy and random strategy. The simulation results indicate that in a scale-free network, the attacker virtually always attacks randomly in the Nash equilibrium. With a small cost-sensitive parameter, representing the degree to which costs increase with the importance of a target, the defender protects the hub targets with large degrees preferentially. When the cost-sensitive parameter exceeds a threshold, the defender switches to protecting nodes randomly. Our work provides a new theoretical framework to analyze the confrontations between the attacker and the defender on critical infrastructures and deserves further study.

5.
Cell Death Dis ; 9(5): 452, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29670080

RESUMO

Although it is becoming increasingly evident that maternal starvation during pregnancy can have permanent effects on a range of physiological processes in the offspring, scant information is available about the consequence of such condition for oogenesis and hence for lifetime reproductive success of progeny in mammals. In the present study, we address this topic by starving pregnant mice at the time of ovarian differentiation (12.5 days post coitum (dpc)) for three consecutive days and analyzed the consequence first on the survival of the fetal oocytes and their capability to progress throughout the stages of meiotic prophase I (MPI) and then on the postnatal folliculogenesis of the offspring. The results showed that maternal starvation increased apoptosis in the fetal ovaries, resulting in reduction of the oocyte number. Moreover, MPI progression was slowed down in the surviving oocytes and the expression of DNA repair players in the starved ovaries increased. Transcriptome analysis identified 61 differentially expressed genes between control and starved ovaries, the most part of these being involved in metabolic processes. A significant decrease in the percentage of oocytes enclosed in primordial follicles and the expression of oocyte genes critically involved in folliculogenesis such as Nobox, Lhx8 and Sohlh2 in the 3 days post partum (dpp) starved ovaries were found. Finally, at the time of juvenile period (21 dpp), the number of oocytes and antral follicles resulted significantly lower in the ovaries of the offspring from starved mothers in comparison to controls. Our findings support the notion that maternal starvation can affect ovary development in the offspring that could adversely affect their reproductive success in the adult life.

6.
Toxicol Appl Pharmacol ; 329: 9-17, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28552778

RESUMO

Zearalenone (ZEA) is a mycotoxin produced by fusarium graminearum. It can cause abnormal reproductive function by acting as an environmental estrogen. Research has traditionally focused on acute and chronic injury on mammalian reproductive capacity after ZEA treatment. Little research has been done studying the effects of ZEA exposure on early oogenesis. In this study, we investigate the effects of ZEA exposure on meiotic entry, DNA double-strand breaks (DSBs), and primordial follicle assembly during murine early oogenesis. The results show that ZEA exposure significantly decreased the percentage of diplotene stage germ cells, and made more germ cells remain at zygotene or pachytene stages. Moreover, the mRNA expression level of meiosis-related genes was significantly reduced after ZEA treatment. ZEA exposure significantly increased DNA-DSBs at the diplotene stage. Meanwhile, DNA damage repair genes such as RAD51 and BRCA1 were activated. Furthermore, maternal exposure to ZEA significantly decreased the number of primordial follicles in newborn mouse ovaries. In conclusion, ZEA exposure impairs mouse female germ cell meiotic progression, DNA-DSBs, and primordial follicle assembly.


Assuntos
Disruptores Endócrinos/toxicidade , Estrogênios não Esteroides/toxicidade , Meiose/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Quebras de DNA de Cadeia Dupla , Reparo do DNA/efeitos dos fármacos , Feminino , Prófase Meiótica I/efeitos dos fármacos , Camundongos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Óvulo/metabolismo , Óvulo/patologia , Gravidez , Rad51 Recombinase/metabolismo , Medição de Risco , Proteínas Supressoras de Tumor/metabolismo
7.
Toxicol Appl Pharmacol ; 317: 33-40, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28089945

RESUMO

Zearalenone (ZEA) is an estrogenic mycotoxin mainly produced as a secondary metabolite by numerous species of Fusarium. Previous work showed that ZEA had a negative impact on domestic animals with regard to reproduction. The adverse effects and the mechanisms of ZEA on mammalian ovarian folliculogenesis remain largely unknown, particularly its effect on primordial follicle formation. Thus, we investigated the biological effects of ZEA exposure on murine ovarian germ cell cyst breakdown and primordial follicle assembly. Our results demonstrated that newborn mouse ovaries exposed to 10 or 30µM ZEA in vitro had significantly less germ cell numbers compared to the control group. Moreover, the presence of ZEA in vitro increased the numbers of TUNEL and γH2AX positive cells within mouse ovaries and the ratio of mRNA levels of the apoptotic genes Bax/Bcl-2. Furthermore, ZEA exposure reduced the mRNA of oocyte specific genes such as LIM homeobox 8 (Lhx8), newborn ovary homeobox (Nobox), spermatogenesis and oogenesis helix-loop-helix (Sohlh2), and factor in the germline alpha (Figlα) in a dose dependent manner. Exposure to ZEA led to remarkable changes in the Lhx8 3'-UTR DNA methylation dynamics in oocytes and severely impaired folliculogenesis in ovaries after transplantation under the kidney capsules of immunodeficient mice. In conclusion, ZEA exposure impairs mouse primordial follicle formation in vitro.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Estrogênios não Esteroides/toxicidade , Proteínas com Homeodomínio LIM/biossíntese , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Fatores de Transcrição/biossíntese , Zearalenona/toxicidade , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação para Baixo/fisiologia , Feminino , Regulação da Expressão Gênica , Proteínas com Homeodomínio LIM/antagonistas & inibidores , Camundongos , Camundongos SCID , Folículo Ovariano/crescimento & desenvolvimento , Fatores de Transcrição/antagonistas & inibidores
8.
Onco Targets Ther ; 9: 1545-57, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27051295

RESUMO

We mined the literature for proteomics data to examine the occurrence and metastasis of prostate cancer (PCa) through a bioinformatics analysis. We divided the differentially expressed proteins (DEPs) into two groups: the group consisting of PCa and benign tissues (P&b) and the group presenting both high and low PCa metastatic tendencies (H&L). In the P&b group, we found 320 DEPs, 20 of which were reported more than three times, and DES was the most commonly reported. Among these DEPs, the expression levels of FGG, GSN, SERPINC1, TPM1, and TUBB4B have not yet been correlated with PCa. In the H&L group, we identified 353 DEPs, 13 of which were reported more than three times. Among these DEPs, MDH2 and MYH9 have not yet been correlated with PCa metastasis. We further confirmed that DES was differentially expressed between 30 cancer and 30 benign tissues. In addition, DEPs associated with protein transport, regulation of actin cytoskeleton, and the extracellular matrix (ECM)-receptor interaction pathway were prevalent in the H&L group and have not yet been studied in detail in this context. Proteins related to homeostasis, the wound-healing response, focal adhesions, and the complement and coagulation pathways were overrepresented in both groups. Our findings suggest that the repeatedly reported DEPs in the two groups may function as potential biomarkers for detecting PCa and predicting its aggressiveness. Furthermore, the implicated biological processes and signaling pathways may help elucidate the molecular mechanisms of PCa carcinogenesis and metastasis and provide new targets for clinical treatment.

9.
Blood Press Monit ; 20(4): 221-4, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25714995

RESUMO

OBJECTIVE: This study aimed to validate the fully automated Pangao PG-800B68 upper-arm device according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010. MATERIALS AND METHODS: Sequential measurements of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were obtained in 33 participants using the standard mercury sphygmomanometer and the test device. The ESH-IP revision 2010 was followed precisely and 99 pairings of test device and reference blood pressure measurements were obtained for analysis. RESULTS: The number of blood pressure differences within 5, 10, and 15 mmHg was 76, 95, and 98, respectively, for SBP and 79, 96, and 99, respectively, for DBP. The device achieved all the required criteria of the ESH-IP revision 2010 with a device-observer difference of -0.03±4.64 mmHg for SBP and -0.64±4.50 mmHg for DBP. CONCLUSION: According to the validation results on the basis of the ESH-IP revision 2010, the Pangao PG-800B68 can be recommended for clinical use and self-measurement in adults.


Assuntos
Monitores de Pressão Arterial/normas , Adulto , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Guias de Prática Clínica como Assunto
10.
Chin Med J (Engl) ; 128(5): 602-9, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25698190

RESUMO

BACKGROUND: Previous studies have indicated that the cognitive deficits in patients with Alzheimer's disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific. METHODS: Resting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and "small-world" property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz, and 0.11-0.25 Hz). RESULTS: At lower-frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz), the global efficiency, the CC and the "small-world" properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11-0.25 Hz), the CpL was much longer, and the "small-world" property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD. CONCLUSIONS: This study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.


Assuntos
Doença de Alzheimer/diagnóstico , Encéfalo/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
11.
J Mater Sci Mater Med ; 26(2): 81, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25634138

RESUMO

Eutectic melting bonding (EMB) method is a useful technique for fabricating bioactive coatings with relatively high crystallinity and bonding strength with substrate on titanium substrates. Using the EMB method, hydroxyapatite/Ti2Ni coatings were prepared on the surface of Ti-6Al-4V at a relatively low temperature (1,050 °C) in a vacuum furnace. The coatings were then characterized in terms of phase components, microstructure, bonding strength and cytotoxicity. The results showed that the coatings were mainly composed of HAp and Ti2Ni, and the thickness of the coatings was approximately 300 µm. X-ray diffraction analysis showed that the coatings exhibited relatively high crystallinity. The tensile bonding strength between the coatings and the substrates was 69.68±5.15 MPa. The coatings had a porous and rough surface which is suitable for cell attachment and filopodia growth. The cell culture study showed that the number of MG-63 cells increased, and the cell morphology changed with the incubation time. This study showed that the EMB method can be utilized as a potentially powerful method to obtain high quality hydroxyapatite coatings with desired mechanical and biocompatibility properties on Ti-alloy substrates.


Assuntos
Materiais Revestidos Biocompatíveis/química , Durapatita/química , Níquel/química , Titânio/química , Ligas/química , Biotecnologia , Adesão Celular , Linhagem Celular , Temperatura Alta , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Resistência à Tração , Termodinâmica , Difração de Raios X
12.
PLoS One ; 8(9): e73186, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24019905

RESUMO

The purpose of this study is to explore the changes in functional brain networks of AD patients using complex network theory. In this study, resting-state fMRI datasets of 10 AD patients and 11 healthy controls were collected. Time series of 90 brain regions were extracted from the fMRI datasets after preprocessing. Pearson correlation method was used to calculate the correlation coefficient between any two time series. Then, a wide threshold range was selected to transform the adjacency matrix to a binary matrix under a different threshold. The topology parameters of each binary network were calculated, and all of them were then averaged within a group. During the evolution, node betweenness and the Euclidean distance between the nodes were set as control factors. Each binary network of healthy controls underwent evolution of 100 steps in accordance with the evolution rules. Then, the topology parameters of the evolution network were calculated. Finally, support vector machine (SVM) was used to classify the network topology parameters of the evolution network and to determine whether evolution results matched the datasets from AD patients. We found there were differing degrees of decline in global efficiency, clustering coefficient, number of edges and transitivity in AD patients compared with healthy controls. The topology parameters of the evolution network tended toward those of the AD group. The results of SVM classification of the evolution network show that the evolution network had a greater probability to be classified as an AD patients group. A new biological marker for diagnosis of AD was provided through comparison of topology parameters between AD patients and healthy controls. The study of network evolution strategies enriched the method of brain network evolution. The use of SVM to classify the results of network evolution provides an objective criteria for determining evolution results.


Assuntos
Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Idoso , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa , Máquina de Vetores de Suporte
13.
Zhonghua Yu Fang Yi Xue Za Zhi ; 47(10): 949-53, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24378138

RESUMO

OBJECTIVE: To investigate the prevalence of dyslipidemia among the Uyghur, Kazakh, and Han adults in Xinjiang Region and to analyze the features of distribution. METHODS: 3625 Uygur residents, 1773 males and 1852 females, aged (42.89 ± 15.95) years old, 4148 Kazakh residents, 1649 males and 2499 females, aged (44.14 ± 13.27) years old, and 3733 Han residents, 1563 males and 2170 females, aged (49.66 ± 12.24) years old, were selected by stratified cluster random sampling method in year 2010, 11 506 adults in total. Questionnaire and physical examination were conducted, including fasting venous blood samples to test the levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C). RESULTS: The levels of TG, TC, HDL-C and LDL-C were separately (1.31 ± 1.03), (4.44 ± 1.20), (1.41 ± 0.62), and (2.44 ± 0.81) mmol/L in the Uygur adults; separately (1.24 ± 0.99), (4.55 ± 1.31), (1.41 ± 0.62), and (2.40 ± 0.87) mmol/L in the Kazakh adults; and (1.62 ± 1.34), (4.60 ± 1.10), (1.16 ± 0.68), and (2.23 ± 0.93) mmol/L in the Han adults, respectively. The general prevalence of dyslipidemia in the Uygur, Kazakh, and Han adults were 42.4% (1537/3625), 31.6% (1311/4148), and 30.2% (1127/3733) respectively; while the age-standardized prevalence were separately 42.4%, 31.8%, and 28.2%. The prevalence of dyslipidemia in the Uygur adults was significantly higher than it of the Kazakh and Han adults, with statistical significance (χ(2) = 179.87, P < 0.01). The standardized prevalence of dyslipidemia in the Uygur males was 52.6%, significantly higher than it of the Kazakh and Han males (35.4% and 33.2%), with statistical significance (χ(2) = 159.19, P < 0.01). The prevalence of hypertriglyceridemia among the Han adults was 17.3%, which was significantly higher than it among the Uyghur and Kazakh adults (χ(2) = 172.55, P < 0.01). The prevalence of hypercholesterolemia in Kazakh (6.9%) was higher than it in Uygur (5.2%), with statistical significance (χ(2) = 10.20, P < 0.01). The prevalence of low HDL-C hyperlipidemia in the above 3 ethnic were 33.6%, 20.8% and 11.1%, respectively; while Uygur was the highest (χ(2) = 552.82, P < 0.01), followed by Kazakh, which was higher than Han (χ(2) = 138.01, P < 0.01). There was no significant difference in the prevalence of high LDL-C hyperlipidemia among the adults of the 3 ethnics. CONCLUSION: The prevalence of dyslipidemia among the Uygur, Kazakh, and Han adults in Xinjiang were all higher than the national average prevalence, the distribution of dyslipidemia varied with ethnicity, age and sex.


Assuntos
Dislipidemias/etnologia , Dislipidemias/epidemiologia , Grupos Étnicos , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(2): 422-6, 2011 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-21510395

RESUMO

From 0.5 to 5.0 generation PAMAM dendrimers were synthesized with ethylenediamine core by Michael addition reaction and aminolysis reaction two repeated steps. The structure of dendrimers were confirmed by FTIR 1H NMR 13C NMR MS and all of these measurements showed that they were successfully synthesized. Furthermore, The authors studied the UV and fluorescence properties of different generation dendrimers. Because of diffenent terminal groups, it was found that the whole generation and half generation show different ultraviolet absorption peaks and the intensity of ultraviolet absorption is closely related to the molecular skeleton. There is no traditional fluorescence emission groups, but PAMAM dendrimers show the peculiar phenomenon. In this paper we detailedly studied the factors which affect PAMAM dendrimers fluorescence properties.

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