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1.
Lipids Health Dis ; 23(1): 177, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851716

RESUMO

BACKGROUND: Exposure to different concentration levels of fatty acids (FAs) may have an impact on depression. However, previous studies using individual FAs may not reflect the performance of mixtures of various FAs, and the associations of FA patterns with depression remain unclear. METHODS: We conducted the cross-sectional analysis in 792 adults aged 18 and older with available serum FAs and depression screening data in the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The serum concentrations of thirty FAs were measured using gas chromatography-mass spectrometry and their percentage compositions were subsequently calculated. Depression was defined as the Patient Health Questionnaire-9 score ≥ 10. We employed principal component analysis to derive serum FA patterns. We examined the association between these patterns and depression in the overall population and various subgroups through survey-weighted logistic regression. RESULTS: Four distinct patterns of serum FAs were identified: 'high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); low docosatetraenoic acid (DTA) and docosapentaenoic acid (DPA) n-6', 'high long-chain saturated FA and long chain FA', 'low median-chain saturated FA and myristoleic acid' and 'low capric acid and lauric acid; high gamma-linolenic acid (GLA) and stearidonic acid (SDA)' pattern. Individuals in the high tertile of 'high EPA and DHA; low DTA and DPA n-6' pattern score had 0.46 (95% CI: 0.22, 0.93) lower odds of developing depression compared to individuals in the lowest tertile after adjusting for confounders such as age, sex, physical activity and total energy intake, etc. The odds ratio (OR) of depression was increased in the population with the highest tertile of 'low capric acid and lauric acid; high GLA and SDA' pattern (OR: 2.45, 95% CI: 1.24, 4.83). In subgroup analyses, we observed that the association between 'high EPA and DHA; low DTA and DPA n-6' and depression persisted among specific demographic and lifestyle subgroups, including females, non-Mexican Americans, non-obese, those aged over 60 years, smokers and drinkers. Similarly, 'low capric acid and lauric acid; high GLA and SDA' showed stable associations in female, non-Mexican Americans and smokers. CONCLUSIONS: Serum FA patterns are associated with depression, and their relationships vary across sex, race, BMI, age, smoking and drinking subgroups, highlighting the importance of considering specific FA patterns within these demographic and lifestyle categories. Utilization of combined FA administration may serve as a mitigation measure against depression in these specific populations.


Assuntos
Depressão , Ácidos Graxos , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Depressão/sangue , Depressão/epidemiologia , Adulto , Pessoa de Meia-Idade , Ácidos Graxos/sangue , Estudos Transversais , Estados Unidos/epidemiologia , Ácidos Decanoicos/sangue , Ácido Eicosapentaenoico/sangue , Idoso , Ácidos Graxos Insaturados/sangue , Adulto Jovem , Adolescente , Análise de Componente Principal
2.
Food Sci Nutr ; 11(12): 7555-7564, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38107103

RESUMO

Dietary intake is considered as a crucial factor affecting mental health symptoms, particularly depression and anxiety symptoms, especially in the case of pregnant women. This study explored the role of dietary intake in depression and anxiety symptoms of pregnant women and provided evidence for primary care interventions. We enrolled 806 pregnant women in their third trimester from 14 communities in Hengyang City, Hunan Province, China, from July 2019 to September 2019. The Chinese version of the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder questionnaire-7 (GAD-7) were used to assess depression and anxiety symptoms. Dietary intake, demographic characteristics, BMI, and pregnancy characteristics were collected using a self-designed, structural questionnaire. A covariate-adjusted logistic regression was conducted to examine the relationship between mental health symptoms and dietary intake. The prevalence of anxiety and depression symptoms in our population were 7.7% (95% CI: 5.9%-9.5%) and 9.2% (95% CI: 7.2%-11.2%), respectively. Women consuming eggs and egg products once a week (OR: 3.688, 95% CI: 1.476-9.215) were more likely to have depression symptom than consumed eggs and egg products once or more per day. Consuming green leafy vegetable <2-3 times per month had a significantly greater risk for depression symptoms than consuming the same once or more per day (OR: 3.450, 95% CI: 1.145-10.393). Women who consumed eggs and egg products 2-3 times a week had an increased likelihood of experiencing anxiety symptoms (OR: 2.253, 95% CI: 1.049-4.837). Anxiety symptoms in women consuming green leafy vegetables <2-3 times per month probably increased by 3.988 times (95% CI: 1.327-11.985) compared with women consuming the same once or more per day. Consuming salted and smoked food <2-3 times per month was protective against anxiety symptoms (OR: 0.181, 95% CI: 0.040-0.828) than consuming the same every day. Implementing interventions to promote healthy dietary among pregnant women is crucial due to its association with mental health. However, future researches are warranted to confirm the reliability and causal association obtained in this study.

3.
BMC Pregnancy Childbirth ; 22(1): 695, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085019

RESUMO

BACKGROUND: Existing evidence highlights that exposure to secondhand smoke (SHS) is a risk factor for pregnant women's health and is possibly affected by individual characteristics. This study aimed to explore the effect of individual socioeconomic status (SES) on SHS exposure among pregnant women in the third trimester and the interaction effect of age. METHODS: A total of 678 nonsmoking pregnant women with a median age of 29.0 years from 14 communities in a medium-sized city were recruited for this survey. Exposure to SHS was defined as the self-reported smoking habit of a spouse/partner. Individual SES characteristics consisted of marital status, educational attainment, employment and per capita monthly income. RESULTS: There were 238 (35.1%) participants who suffered from SHS exposure. Compared to the pregnant women who were employed, those who were unemployed were more likely to suffer from SHS exposure (OR = 1.572, 95% CI: 1.013-2.441). Participants who had a high school or technical secondary school education were more likely to be exposed to SHS than those with a college education or above (OR = 1.601, 95% CI: 1.029-2.449). Advanced age was a protective factor for participants with a college education or above (OR = 0.939, 95% CI: 0.884-0.997), but age increased the risk of SHS exposure among women who had unstable marriages (OR = 1.256, 95% CI: 1.019-1.549). CONCLUSION: Exposure to SHS was very common among pregnant women in the third trimester. Pregnant women with a low SES and an older age should be considered a key population for the implementation of public health interventions.


Assuntos
Gestantes , Poluição por Fumaça de Tabaco , Adulto , Estudos Transversais , Feminino , Humanos , Renda , Gravidez , Classe Social , Poluição por Fumaça de Tabaco/efeitos adversos
4.
Front Public Health ; 10: 751985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223720

RESUMO

BACKGROUND: The prevalence of functional limitations is relatively high among the middle-aged and older adults. However, the contribution of functional limitations to subsequent incident cardiovascular diseases (CVD) and death is unclear. This study aims to examine the association between functional limitations and incident CVD and all-cause mortality among the middle-aged and older adults. METHODS: This is a nationally representative prospective cohort study. Participants were middle-aged and older Chinese adults from The China Health and Retirement Longitudinal Study. Functional limitations were measured using activities of daily living (ADL) scale and instrumental activities of daily living (IADL) scale. Incident CVD and death were recorded at followed-up from June 1, 2011, up until August 31, 2018. Cox proportional hazards model was used to assess the association between functional limitations and incident CVD and all-cause mortality. RESULTS: A total of 11,013 participants were included in this study. During the 7 years of follow-up, 1,914 incident CVD and 1,182 incident deaths were identified. Participants with functional limitations were associated with a 23% increased risk of incident CVD (HR, 1.23, 95% CI:1.08,1.39) after adjusting for age, gender, residential area, marital status, education, smoking, alcohol drinking, sleep duration, nap duration, depression symptoms, social participation, history of hypertension, diabetes, dyslipidemia, use of hypertension medications, diabetes medications, and lipid-lowering therapy. Moreover, participants with functional limitations were associated with a 63% increased risk of all-cause mortality (HR,1.63, 95%CI: 1.41,1.89) after adjusting for potential confounders. CONCLUSIONS: Functional limitations were significantly associated with subsequent incident CVD and death among the middle-aged and older Chinese adults.


Assuntos
Doenças Cardiovasculares , Hipertensão , Atividades Cotidianas , Idoso , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Estudos de Coortes , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos
5.
J Sep Sci ; 45(9): 1538-1549, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35182112

RESUMO

Herein, an improved method for detecting the endocrine-disrupting chemicals in milk is presented, which is based on high performance liquid chromatography tandem mass spectrometry, coupled with a quick, effective, and safe method. The linearity of the proposed method was in the range of 0.05-100 µg/L, and all correlation coefficients were ≥0.9973. At three concentration levels, the spiked recoveries ranged from 77.7 to 107.5%, relative standard deviations ranged from 0.2 to 14.6%, limits of quantitation ranged from 0.1 to 40 µg/kg, limits of detection ranged from 0.03 to 13.3 µg/kg. The proposed method for the identification and quantitation of 26 endocrine disruptors present in milk is not only easy, fast, and cost-efficient but also provides a reference for the detection of various endocrine disruptors in milk and other dairy products.


Assuntos
Disruptores Endócrinos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Disruptores Endócrinos/análise , Leite/química , Espectrometria de Massas em Tandem/métodos
6.
J Sep Sci ; 45(2): 432-440, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34716661

RESUMO

High-performance liquid chromatography-tandem mass spectrometry coupled with the quick, easy, cheap, effective, rugged and safe method was established for the qualitative and quantitative detections of 20 mycotoxins in milk. The linear range of this method was 0.01-10 µg/L and the correlation coefficients were all greater than or equal to 0.9933. At three levels of addition, the spiked recoveries ranged from 80.00 to 112.50%, relative standard deviations were 2.67-14.97%, limits of quantitation were 0.02-4.00 µg/kg, and limits of detection were 0.007-1.300 µg/kg. This developed procedure for the identification and quantitation of mycotoxins provided prospective support for quality regulation.


Assuntos
Micotoxinas , Animais , Cromatografia Líquida de Alta Pressão/métodos , Leite/química , Micotoxinas/análise , Estudos Prospectivos , Espectrometria de Massas em Tandem/métodos
7.
BMJ Open ; 10(9): e038511, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873680

RESUMO

OBJECTIVES: To evaluate the prevalence of depressive symptoms and its influencing factors in late pregnancy. DESIGN: Cross-sectional study. SETTING: Fourteen community in urban areas of Hengyang City. PARTICIPANTS: The study conducted from July to October 2019, and surveyed 813 women in late pregnancy who lived in urban areas of Hengyang for more than 6 months, signed an informed consent and were without cognitive disorders, severe mental illnesses or other serious diseases. MEASURES: Perinatal depression symptoms were evaluated using the Patient Health Questionnaire-9, and perinatal anxiety symptoms were evaluated using the Generalised Anxiety Disorder-7 Scale. Sociodemographic variables, obstetric characteristics, lifestyle behaviours, family factors, social support, sleep quality and self-efficacy were obtained through structured questionnaires. RESULTS: The prevalence of depression symptoms among pregnant women in late pregnancy was 9.2% (95% CI 7.2%-11.2%). Protective factor: age between 25 and 29 years (OR=0.398; 95% CI 0.16-0.991). RISK FACTORS: a normal relationship with her mother-in-law (OR=5.309; 95% CI 1.122-4.184), artificial insemination (OR=4.339; 95% CI 1.492-12.623), no exercise during pregnancy (OR=2.666; 95% CI 1.177-6.039), low self-efficacy (OR=4.253; 95% CI 1.518-11.916), low social support (OR=2.371; 95% CI 1.206-4.661), poor sleep quality (OR=2.134; 95% CI 1.131-4.027), existence of anxiety symptoms (OR=17.654; 95% CI 8.494-36.689). CONCLUSION: The prevalence of depression symptoms is lower than that in developing countries, but due to the large population base of China, the problem should still be taken seriously. To prevent mental disorders of pregnant women, early screening for mental disorders, promotion of healthy lifestyles, mental healthcare during pregnancy and improved family and social support should be implemented during pregnancy nursing.


Assuntos
Complicações na Gravidez , Gestantes , Adulto , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários
8.
BMJ Open ; 10(8): e036557, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32759246

RESUMO

OBJECTIVE: To explore the prevalence of depressive symptoms among women in late pregnancy, and assess mediating effect of self-efficacy in the association between family functions and the antenatal depressive symptoms. DESIGN: Community-based, cross-sectional study was conducted among women during the third trimester of pregnancy. SETTING: This study was conducted among pregnant women registered at community health service centres of urban Hengyang City, China from July to October 2019. PARTICIPANTS: 813 people were selected from 14 communities by multi-staged cluster random sampling method. MAIN OUTCOME MEASURES: The Family Adaptation Partnership Growth Affection and Resolve Index, the General Self-efficacy Scale and Patient Health Questionnaire were used to access family functions, self-efficacy and antenatal depression symptoms, respectively. RESULTS: In this study, 9.2% pregnant women reported the symptoms of antenatal depression (95 CI% 7.2% to 11.2%). After adjustment, the results showed that severe family dysfunction (adjusted OR, AOR 3.67; 95% CI 1.88 to 7.14) and low level of self-efficacy (AOR 3.16; 95% CI 1.37 to 7.27) were associated with antenatal depressive symptoms (p<0.05). Furthermore, self-efficacy level partially mediated the association between family functions and antenatal depressive symptoms(ß=-0.05, 95% CI -0.07 to -0.03, p<0.05) and the mediating effect accounted for 17.09% of the total effect. CONCLUSIONS: This study reported 9.2% positive rates of antenatal depression symptoms among women in the third trimester of pregnancy in Hengyang city, China. The mediating effect of self-efficacy on the association between family functions and antenatal depression symptoms among women in the third trimester of pregnancy was found in this study, which provide a theoretical basis to maternal and child health personnel to identify high-risk pregnant women and take targeted intervention for them.


Assuntos
Complicações na Gravidez , Gestantes , Criança , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários
9.
BMC Public Health ; 20(1): 620, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370810

RESUMO

BACKGROUND: With the increased vulnerability during pregnancy, domestic violence (DV) is a serious threat to the physical and mental health of pregnant women, making it a significant issue in public health initiatives. In China, family is of great significance to pregnant women, but few scholars have focused specifically on the relationship between the family factors of pregnant women and DV. This study aimed to explore the prevalence and association between family factors and DV among women in late pregnancy, to provide evidence for the prevention of domestic violence during pregnancy. METHODS: A cross-sectional survey was conducted from July-October, 2019 among pregnant women in urban communities of Hengyang City, Hunan Province, China. A total of 813 participants were included by a multi-staged cluster random sampling method. DV was assessed by the Abuse Assessment Screen Questionnaire (AAS). A multivariate binary logistic regression model was used to evaluate the relationship between family factors and DV. RESULTS: Ultimately, 127 (15.62%) participants were identified as victims of DV. After adjustment, the potential risk factors of DV were tensions between their mother-in-law and other family members (OR: 2.85; 95% CI: 1.29 to 6.30 and OR: 3.30; 95% CI: 1.57 to 6.93), medium household debt (OR: 2.17; 95% CI: 1.18 to 4.00), middle and low family APGARI (OR: 2.01; 95% CI: 1.30 to 3.13 and OR: 4.01; 95% CI: 2.09 to 7.69). CONCLUSIONS: In summary, women in late pregnancy were at higher risk of DV in the family with tensions, medium household debt and family dysfunction, which may help medical personnel intervene in cases of domestic violence against pregnant women in a reasonable and timely manner.


Assuntos
Violência Doméstica/estatística & dados numéricos , Relações Familiares/psicologia , Gestantes/psicologia , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Saúde Mental , Gravidez , Prevalência , Fatores de Risco , Inquéritos e Questionários , População Urbana
10.
Int J Biol Macromol ; 79: 49-55, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25934110

RESUMO

When not incorporated into the casein micelle, isolated κ-casein spontaneously forms amyloid fibrils under physiological conditions, and is a convenient model for researching generic aspects of fibril formation. Ginsenosides have recently attracted much research interest because of the effects on aging diseases, which are always associated with amyloid fibril formation, for example, Alzheimer's, Parkinson's, and Huntington's diseases. In addition, the mechanism remains unclear that ginsenosides exert the effects against aging diseases. To address these aspects, we have investigated the ability of ginsenoside Rb1, Rc, Rg1, and Re influencing fibril formation by RCMκ-casein (reduced and carboxymethylated κ-casein), with the methods of Thioflavin T fluorescence assay, transmission electron microscopy (TEM), and intrinsic fluorescence spectroscopy. The results showed that ginsenoside Rb1 and Rg1 inhibited obviously RCMκ-CN fibrillation in both the initial rate and final level of ThT fluorescence. On the contrary, ginsenoside Re had a few effect on promoting RCMκ-CN fibril formation, proved by thick and larger fibrils observed frequently in TEM. While Rc did not influence RCMκ-CN fibrillation. It is demonstrated that Rg1 prevent RCMκ-CN fibril formation by stabilising RCMκ-CN in its native like state. Additional chemical structure difference of ginsenosides and the effects on fibril formation are also implicated.


Assuntos
Amiloide/antagonistas & inibidores , Caseínas/química , Ginsenosídeos/química , Amiloide/química , Benzotiazóis , Microscopia Eletrônica de Transmissão , Modelos Químicos , Estabilidade Proteica , Soluções , Espectrometria de Fluorescência , Relação Estrutura-Atividade , Tiazóis
11.
J Med Chem ; 57(17): 7342-54, 2014 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-25156906

RESUMO

Triterpene saponins are a major group of active components in natural products with nonspecific antiviral activities, while T20 peptide (enfuvirtide), which contains a helix zone-binding domain (HBD), is a gp41-specific HIV-1 fusion inhibitor. In this paper, we report the design, synthesis, and structure-activity relationship (SAR) of a group of hybrid molecules in which bioactive triterpene sapogenins were covalently attached to the HBD-containing peptides via click chemistry. We found that either the triterpenes or peptide part alone showed weak activity against HIV-1 Env-mediated cell-cell fusion, while the hybrids generated a strong cooperative effect. Among them, P26-BApc exhibited anti-HIV-1 activity against both T20-sensitive and -resistant HIV-1 strains and improved pharmacokinetic properties. These results suggest that this scaffold design is a promising strategy for developing new HIV-1 fusion inhibitors and possibly novel antiviral therapeutics against other viruses with class I fusion proteins.


Assuntos
Proteína gp41 do Envelope de HIV/farmacologia , Inibidores da Fusão de HIV/farmacologia , Fragmentos de Peptídeos/farmacologia , Sapogeninas/farmacologia , Sequência de Aminoácidos , Antivirais/síntese química , Antivirais/química , Antivirais/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Enfuvirtida , Proteína gp41 do Envelope de HIV/química , Proteína gp41 do Envelope de HIV/genética , Inibidores da Fusão de HIV/química , HIV-1/efeitos dos fármacos , Humanos , Modelos Químicos , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Estrutura Secundária de Proteína , Sapogeninas/química , Relação Estrutura-Atividade
12.
Eur J Med Chem ; 82: 341-6, 2014 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-24927054

RESUMO

Discovery of new drugs for the treatment of AIDS that possess unique structures associated with novel mechanisms of action are of great importance due the rapidity with which drug-resistant HIV-1 strains evolve. Recently we reported on a novel class of DNA duplex-based HIV-1 fusion inhibitors modified with hydrophobic groups. The present study describes a new category of hairpin fusion inhibitor DNA duplexes bearing a 3 nucleotide loop located at either the hydrophobic or hydrophilic end. The new loop structures were designed to link 2 separate duplex-forming oligodeoxynucleotides (ODNs) to make helix-assembly easier and more thermally stable resulting in a more compact form of DNA duplex based HIV-1 fusion inhibitors. A series of new hairpin duplexes were tested for anti-HIV-1 cell-cell membrane fusion activity. In addition, Tm, CD, fluorescent resonance energy transfer assays, and molecular modeling analyses were carried out to define their structural activity relationships and possible mechanisms of action.


Assuntos
Inibidores da Fusão de HIV/farmacologia , HIV-1/efeitos dos fármacos , Ácidos Nucleicos Heteroduplexes/farmacologia , Oligodesoxirribonucleotídeos/química , Transferência Ressonante de Energia de Fluorescência , Inibidores da Fusão de HIV/síntese química , Inibidores da Fusão de HIV/química , HIV-1/metabolismo , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Estrutura Molecular , Ácidos Nucleicos Heteroduplexes/síntese química , Ácidos Nucleicos Heteroduplexes/química , Oligodesoxirribonucleotídeos/síntese química
13.
AIDS ; 28(9): 1251-60, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24625369

RESUMO

OBJECTIVE: To investigate the effect of mutations in a highly conserved buried polar area on the function of HIV-1 gp41. DESIGN: During HIV-1 entry, a six helical bundle (6-HB) formation between the C-terminal and N-terminal heptad repeat (CHR and NHR) of gp41 provides energy for virus cell membrane fusion. In 6-HB, residues at a and d (a-d) positions of CHR directly interact with NHR and are buried. They are considered critical residues for 6-HB stability and for anti-HIV-1 activity of CHR-derived peptides (C-peptides). Most of a-d residues in CHR are hydrophobic, as buried hydrophobic residues facilitate protein stability. However, HIV-1 gp41 CHR contains a highly conserved polar area with four successive buried a-d polar residues: S649/Q652/N656/E659. We mutated these buried polar residues to hydrophobic residues, either Leu or Ile, and studied its effect on the gp41 NHR-CHR interactions and anti-HIV activities of the C-peptides. METHODS: We measured the C-peptide mutants' ability to form 6-HB with NHR, thermal stability of the 6-HBs and C-peptides' inhibitory activity against both T20-sensitive and resistant HIV-1 strains. RESULTS: All the mutated C-peptides retained their ability to form stable 6-HB with NHR and strongly inhibited HIV-1 replication. Strikingly, S649L and E659I mutations endow C-peptide with a significantly enhanced activity against T20-resistant HIV-1 strains. CONCLUSION: The highly conserved buried a-d polar residues in HIV-1 gp41 CHR can be mutated as a means of developing new fusion inhibitors against drug-resistant HIV-1 strains. The concept can also be utilized to design fusion inhibitors against other viruses with similar mechanisms.


Assuntos
Fármacos Anti-HIV/metabolismo , Proteína gp41 do Envelope de HIV/genética , Proteína gp41 do Envelope de HIV/metabolismo , Mutação de Sentido Incorreto , Peptídeos/metabolismo , Sequência de Aminoácidos , Fármacos Anti-HIV/farmacologia , Análise Mutacional de DNA , Proteína gp41 do Envelope de HIV/química , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Peptídeos/farmacologia , Ligação Proteica , Conformação Proteica , Estabilidade Proteica , Internalização do Vírus
14.
Chem Commun (Camb) ; 49(94): 11086-8, 2013 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-24141661

RESUMO

Systematic exchange of amino acid residues of similar physicochemical properties maintains specific coiled-coil interaction between two heptad repeats of HIV-1 gp41, as well as the biological activity of related peptide fusion inhibitors. This exchangeability can greatly degenerate sequence space of peptides thus making ab initio design of coiled-coil interaction feasible.


Assuntos
Aminoácidos , Fenômenos Químicos , Proteína gp41 do Envelope de HIV/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Sequência de Aminoácidos , Dados de Sequência Molecular , Engenharia de Proteínas , Sequências Repetitivas de Aminoácidos
15.
Antimicrob Agents Chemother ; 57(10): 4963-70, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23896466

RESUMO

Discovery of new drugs for the treatment of AIDS typically possessing unique structures associated with novel mechanisms of action has been of great importance due to the quick drug-resistant mutations of HIV-1 strains. The work presented in this report describes a novel class of DNA duplex-based HIV-1 fusion inhibitors. Hydrophobic groups were introduced into a DNA duplex skeleton either at one end, at both ends, or in the middle. These modified DNA duplexes inhibited fusion between HIV-1 and human cell membranes at micro- or submicromolar concentrations. Respective inhibitors adopted an aptamer pattern instead of a base-pairing interaction pattern. Structure-activity relationship studies of the respective DNA duplexes showed that the rigid and negatively charged DNA skeletons, in addition to the presence of hydrophobic groups, were crucial to the anti-HIV-1 activity of these compounds. A fluorescent resonance energy transfer (FRET)-based inhibitory assay showed that these duplex inhibitors interacted with the primary pocket in the gp41 N-terminal heptad repeat (NHR) instead of interacting with the lipid bilayers.


Assuntos
Membrana Celular/química , DNA/química , DNA/farmacologia , Inibidores da Fusão de HIV/química , Inibidores da Fusão de HIV/farmacologia , HIV-1/química , HIV-1/efeitos dos fármacos , Linhagem Celular , Dicroísmo Circular , Transferência Ressonante de Energia de Fluorescência , Humanos , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Relação Estrutura-Atividade
16.
Chem Commun (Camb) ; 48(94): 11579-81, 2012 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-23093045

RESUMO

Specific interactions were introduced between an artificial heptad repeat peptide template and HIV-1 gp41 for fusion inhibitor design, using a structure based rational design strategy. The designed peptides are nonhomologous with naturally occurring peptide and protein sequences, specifically interact with HIV-1 gp41, and show strong anti-HIV activity.


Assuntos
Fármacos Anti-HIV/farmacologia , Desenho de Fármacos , HIV-1/fisiologia , Peptidomiméticos/farmacologia , Internalização do Vírus/efeitos dos fármacos , Sequência de Aminoácidos , Fármacos Anti-HIV/química , Proteína gp41 do Envelope de HIV/química , HIV-1/efeitos dos fármacos , Dados de Sequência Molecular , Peptidomiméticos/química , Sequências Repetitivas de Aminoácidos
17.
Bioorg Med Chem Lett ; 21(19): 5762-4, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21873060

RESUMO

The Hotoda's sequence substituted with TBDPS via 5'-end nucleobase existed as parallel quadruplex structure and exhibited inhibitory activities in an HIV-1 envelop proteins mediated cell-cell fusion assay. This result demonstrated that the 5'-aromatic groups of the Hotoda's sequence are allowed to have a large spatial freedom and remain to be optimized for its role in the binding to HIV-1 envelop proteins.


Assuntos
Fusão Celular , Quadruplex G , Inibidores da Fusão de HIV/síntese química , Inibidores da Fusão de HIV/farmacologia , HIV-1/efeitos dos fármacos , Produtos do Gene env do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Sequência de Aminoácidos , Composição de Bases , Inibidores da Fusão de HIV/química , Inibidores da Fusão de HIV/metabolismo , HIV-1/fisiologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Fusão de Membrana , Ligação Proteica , Relação Estrutura-Atividade , Produtos do Gene env do Vírus da Imunodeficiência Humana/química , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(5): 1417-21, 2010 May.
Artigo em Chinês | MEDLINE | ID: mdl-20672646

RESUMO

To meet the requirements of outdoor field mineral analysis and remote sensing ground verification spectral analysis, the wide-range fiber spectral instrument covering 400 nm-2 500 nm was developed. The present article illustrates the design of the optical, mechanical and electrical parts of the instrument. The optical system utilizes grating horizontal-reflecting light route to implement the full coverage of the spectrum. Three line-array sensors are intercrossed in three directions on the spectrum surface to sense different spectrum ranges. CPLD device generates the sampling and driving temporal logic signals to the three line-array photoelectrical devices. Fourteen bits high speed AD converts the analog signals into digital ones. USB 2.0 is used for communication. The final results demonstrate that while implementing the measurement of wide spectrum, the instrument is improved in size, spectrum resolving power, signal quality and measuring speed. Ideal spectrum data were acquired.

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