ABSTRACT
Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.
Subject(s)
Humans , Polymorphism, Single Nucleotide , Malaria , Capillary Resistance , Artemisinins , Genes , Molecular ConformationABSTRACT
Introduction: Quincke´s Scholarship deals with themes related to neuroinmunology and the complement system. Objective: Describe the most recent advances of the Vll Edition of Quincke´s Scholarship. Methods: Publications pertaining to Quincke´s Scholarship were selected and revised from the work group of the Central Lab of Cerebrospinal fluid (LABCEL). Results: The principal topic was the C1q protein; initiator of the clasic complement pathway. From the analisis of the molecular concentration of this protein, its transference and the correlations between the concentration of C1q protein in cerebrospinal fluid (LCR) and the quotient of albumin (QAlb) between LCR and plasma it is hypothesized that an intratecal synthesis of the C1q in patients with a disfunction of the blood-brain barrier. The most recently discovered pathway in the activation of the complement is the lectin pathway. The diffusion of the MASP-3 protein from blood to LCR is proof that the MASP-3 is synthesized in the leptomeninges. The reibergram is useful to evaluate the inmune response in patients with: neurological manifestations caused by the dengue virus, and patients with multiple sclerosis. Conclusions: The Vll Edition of Quincke´s Scholarship dealt with C1q protein and recently discovered themes of the lectin pathway and the use of the reibergram(AU)
Subject(s)
Humans , Cerebrospinal Fluid/microbiology , Molecular ConformationABSTRACT
OBJECTIVE@#To identify a novel human leukocyte antigen (HLA) B allele in a Chinese Han individual and construct its three-dimensional structure.@*METHODS@#The initial HLA genotyping was performed by PCR-sequence-based typing (PCR-SBT). The ambiguous allele was confirmed with single-strand DNA sequencing. The DNA sequence was analyzed to identify the difference between the novel allele and its closest matching allele. Finally, the three-dimensional molecular structure of the novel allele was constructed using a Swiss-Model.@*RESULTS@#One allele of the subject at the HLA-B locus was B*44:03:01, whilst the other was a novel allele which differed from the closest matching allele B*51:01:01:01 by nucleotide (nt) 329 A to C in exon 2, resulting in an amino acid change at codon 86 (p.Asn86Thr).@*CONCLUSION@#A novel HLA-B allele has been identified and officially named as HLA-B*51:159 by the WHO Nomenclature Committee for Factors of the HLA System. The three-dimensional structure of B*51:159 was simulated.
Subject(s)
Humans , Alleles , Asian People , Base Sequence , HLA-B Antigens , Chemistry , Genetics , Molecular Conformation , Sequence Analysis, DNAABSTRACT
Resumen Justificación y objetivo: la leucemia mieloide crónica constituye un paradigma de reversión de neoplasia con un tratamiento específico basado en los inhibidores de tirosina quinasa. Aunque la situación epidemiológica ha sido estudiada en países primermundistas, los estudios en Latinoamérica son escasos. Con el fin de actualizar la situación real de la LMC en la región centroamericana, el estudio pretende describir la epidemiología de la leucemia mieloide crónica en Costa Rica. Métodos: se evaluaron 133 pacientes con la enfermedad, mediante monitoreo hematológico y molecular. Se analizó la respuesta de estos casos a tratamiento conforme a las siguientes variables: respuesta hematológica, respuesta molecular y supervivencia global, libre de evento, progresión, así como la prevalencia de mutaciones que confieren resistencia al tratamiento. Resultados: la respuesta hematológica completa fue del 97,7%, y la molecular mayor, a los 12 meses, fue del 43,4%. El seguimiento recomendado por la guía European LeukemiaNet se alcanzó solo en un 68,4% de los pacientes en el primer año, bajando al 57,7%, posteriormente. Un total de 92 pacientes alcanzó respuesta molecular mayor en algún momento; de ellos, el 87,0% conservó respuesta. La supervivencia libre de evento a 3 años fue del 65,7%, libre de progresión del 92,2% y global del 89,2%. La mutación más frecuente encontrada en el gen ABL fue la T315I. Conclusión: el tratamiento de la leucemia mieloide crónica en Costa Rica presenta una eficacia comparable a lo reportado en otros países, con una respuesta molecular mayor inferior a lo esperado, debido a dificultades de acceso al medicamento y monitoreo de la enfermedad.
Abstract Background and aim: Chronic myeloid leukemia is a paradigm of reversion of neoplasia with a specific treatment based on tyrosine kinase inhibitors. Although the epidemiological situation has been studied in first world countries, studies in Latin American countries are scarce. In order to update the real situation of the chronic myeloid leukemia in our Central American region, this study aims to describe the epidemiology of chronic myeloid leukemia in Costa Rica. Methods: 133 patients with the disease were evaluated through hematological and molecular monitoring. The response of these cases to treatment was analyzed by the following variables: haematological response, molecular response and overall survival, event-free, progression, as well as the prevalence of mutations that confer resistance to treatment. Results: The complete haematological response was 97.7% and the molecular response greater than 12 months was 43.4%. The follow-up recommended by the European LeukemiaNet guideline was reached in only 68.4% of the patients in the first year, decreasing to 57.7% later on. A total of 92 patients achieved a higher molecular response at some point, of which 87.0% retained a response. The 3-year event-free survival was 65.7%, progression free of 92.2% and overall of 89.2%. The most frequent mutation found in the ABL gene was T315I. Conclusion: The treatment of chronic myeloid leukemia in Costa Rica presents an efficacy comparable to that reported in other countries, with a lower molecular response than expected due to difficulties in accessing medication and monitoring the disease.
Subject(s)
Infant , Child, Preschool , Child , Adolescent , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myeloid , Costa Rica , Protein Kinase Inhibitors , Molecular ConformationABSTRACT
Two cyclopeptides, celogentin L (1) and its epimer lyciumin A (2) were firstly isolated from Celosia argentea L.. The planar structures of the two compounds were fully determined by spectroscopic data, including 1D-, 2D-NMR, and HR-ESI/MS. The absolute configurations of amino acid components were assigned via chiral-phase HPLC analyses after acid hydrolysis. Furthermore, the configuration of C-N linkage at the glycine Cα was elucidated by extensive analyses of 2D-NMR and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cytotoxicity of the two compounds against human alveolar epithelial A549, hepatocellular carcinoma HepG2, and cervical cancer Hela cell lines was assayed. Although both of them were inactive in these cells, the present findings add new facets for the chemistry of Celosia argentea.
Subject(s)
Humans , A549 Cells , Cell Survival , Celosia , Chemistry , Chemistry Techniques, Analytical , HeLa Cells , Hep G2 Cells , Molecular Conformation , Molecular Structure , Peptides, Cyclic , Chemistry , Toxicity , Seeds , Chemistry , StereoisomerismABSTRACT
Two cyclopeptides, celogentin L (1) and its epimer lyciumin A (2) were firstly isolated from Celosia argentea L.. The planar structures of the two compounds were fully determined by spectroscopic data, including 1D-, 2D-NMR, and HR-ESI/MS. The absolute configurations of amino acid components were assigned via chiral-phase HPLC analyses after acid hydrolysis. Furthermore, the configuration of C-N linkage at the glycine Cα was elucidated by extensive analyses of 2D-NMR and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cytotoxicity of the two compounds against human alveolar epithelial A549, hepatocellular carcinoma HepG2, and cervical cancer Hela cell lines was assayed. Although both of them were inactive in these cells, the present findings add new facets for the chemistry of Celosia argentea.
Subject(s)
Humans , A549 Cells , Cell Survival , Celosia , Chemistry , Chemistry Techniques, Analytical , HeLa Cells , Hep G2 Cells , Molecular Conformation , Molecular Structure , Peptides, Cyclic , Chemistry , Toxicity , Seeds , Chemistry , StereoisomerismABSTRACT
OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable. .
OBJETIVO: Investigar a relação entre o volume do tumor após a quimioterapia pré-operatória (VTPOS) e antes da quimioterapia pré-operatória (VTPRE) com sobrevida geral aos dois e cinco anos e tempo de vida. MÉTODOS: A amostra foi composta por pacientes consecutivos avaliados de 1989 a 2009, em um serviço de onco-hematologia. Os dados clínicos, histológicos e volumétricos foram coletados a partir dos registros médicos. Para análise, usaram-se os testes qui-quadrado, Kaplan-Meier, log-rank e regressão de Cox. RESULTADOS: A amostra foi composta de 32 pacientes, 53,1% do sexo masculino, com mediana de idade ao diagnóstico de 43 meses. Houve associação significativa entre VTPOS >500 mL e a diferença entre o VTPRE e VTPOS (p=0,015) e os tipos histológicos de risco (p=0,008). Verificou-se também uma associação entre a diferença entre o VTPRE e VTPOS e o tumor de predomínio estromal (p=0,037). Quando se avaliou o VTPOS de todos os pacientes, sem um ponto de corte definido, observou-se associação dessa variável com o tempo de vida (p=0,013), isto é, para cada aumento de 10 mL no VTPOS houve um aumento médio de 2% no risco de morte. CONCLUSÕES: Embora os resultados indiquem que o VTPOS poderia ser considerado um preditor isolado de mau prognóstico, independentemente do ponto de corte sugerido na literatura, mais estudos são necessários para substituir a histologia e estadiamento pelo tamanho do tumor como melhor variável prognóstica. .
Subject(s)
Animals , Humans , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Macrocyclic Compounds/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Diterpenes/chemistry , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Euphorbia/chemistry , Macrocyclic Compounds/chemistry , Macrocyclic Compounds/isolation & purification , Molecular Conformation , Phenotype , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
OBJECTIVE: To investigate the association between physical inactivity and anthropometric measures in schoolchildren from Paranavaí-Parana, Brazil. METHODS: Cross-sectional survey, carried out in July and August 2013. Sample of 566 students (287 boys and 279 girls) from 6th to 9th grade, aged 10 to 14 years, from public and private schools of Paranavaí - PR, Southern Brazil. The variables analyzed were: time of weekly physical activity through a questionnaire (physical inactivity <300 minutes/week), body mass index (BMI) and waist circumference (WC). In the statistical analysis, the U Mann-Whitney and Student's t tests were used for comparison between genders. To identify factors associated with insufficient levels of physical activity, univariate and multivariate logistic regression analysis was applied and expressed in Odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: There was an association between physical inactivity and anthropometric measurements for BMI (p<0.001) and WC (p<0.001), with a prevalence rate of 56.1% and 52.7% of inactive adolescents, respectively. In the multivariate analysis, there was significant association of physical inactivity and overweight (OR 1.8, 95%CI: 1.1-3.0) and with increased waist circumference (OR 2.8, 95%CI: 1.4-3.8). CONCLUSIONS: Inadequate levels of physical activity is a determining factor for overweight and abdominal adiposity. Accordingly, preventive measures should be taken, especially in schools, emphasizing the importance of exercise for body composition control and weight reduction. .
OBJETIVO: Investigar a associação entre a inatividade física e medidas antropométricas em escolares de Paranavaí, Paraná, Brasil. MÉTODOS: Pesquisa com delineamento transversal, feita em julho e agosto de 2013. Amostra composta por 566 escolares (287 meninos e 278 meninas), de 10 a 14 anos, do 6° ao 9° ano da rede pública e privada de Paranavaí (PR). As variáveis analisadas foram: tempo de atividade física semanal, por meio de questionário (inatividade física: < 300 min/semanal), índice de massa corporal (IMC) e circunferência de cintura (CC). Na análise estatística foram usados os testes U de Mann-Whitney e t de Student para comparar os sexos. Para verificar os fatores associados ao nível insuficiente de atividade física aplicou-se o modelo de regressão logística binária univariada e multivariada, expressa em odds ratio (OR), e intervalo de confiança de 95% (IC95%). RESULTADOS: Houve associação entre inatividade física e as medidas antropométricas para IMC (p<0,001) e CC (p<0,001), com prevalências de 56,1% e 52,7% de inativos, respectivamente. Na análise multivariada, foram observadas associações significativas de inatividade física nos alunos que apresentaram excesso de peso (OR 1,8; IC95%: 1,1-3,0) e circunferência de cintura aumentada (OR 2,2; IC95%: 1,4-3,8). CONCLUSÕES: Nível inadequado de atividade física é fator determinante no excesso de peso e na adiposidade abdominal. Nesse sentido, medidas preventivas devem ser tomadas, principalmente nas escolas, e enfatizar-se a importância do exercício físico no controle da composição corporal e redução do pesoe. .
Subject(s)
Fluorescence Resonance Energy Transfer , Lipid Bilayers/chemistry , Membrane Proteins/chemistry , Peptides/chemistry , Polycyclic Compounds/chemistry , Models, Molecular , Molecular Conformation , Spectrophotometry, InfraredABSTRACT
OBJECTIVE: To review the current literature concerning the effects of physical exercise on several metabolic variables related to childhood obesity. DATA SOURCE: A search was performed in Pubmed/MEDLINE and Web of Science databases. The keywords used were as follows: Obesity, Children Obesity, Childhood Obesity, Exercise and Physical Activity. The online search was based on studies published in English, from April 2010 to December 2013. DATA SYNTHESIS: Search queries returned 88,393 studies based on the aforementioned keywords; 4,561 studies were selected by crossing chosen keywords. After applying inclusion criteria, four studies were selected from 182 eligible titles. Most studies found that aerobic and resistance training improves body composition, lipid profile and metabolic and inflammatory status of obese children and adolescents; however, the magnitude of these effects is associated with the type, intensity and duration of practice. CONCLUSIONS: Regardless of the type, physical exercise promotes positive adaptations to childhood obesity, mainly acting to restore cellular and cardiovascular homeostasis, to improve body composition, and to activate metabolism; therefore, physical exercise acts as a co-factor in fighting obesity. .
OBJETIVO: Revisar a literatura atual a respeito dos efeitos do exercício físico sobre diferentes variáveis metabólicas da obesidade infantil. FONTES DE DADOS: A pesquisa foi feita nas bases de dados Pubmed e Web of Science. Os descritores usados foram: obesity, children obesity, childhood obesity, exercise e physical activity. A pesquisa eletrônica foi feita com base nos estudos publicados de abril de 2010 a dezembro de 2013, em idioma inglês. SÍNTESE DOS DADOS: O rastreamento dos estudos com os descritores encontrou 88.393. Após cruzamento entre os descritores, obtiveram-se 4.561. Desses, depois da análise dos títulos, foram cogitados 182 relevantes referências, submetidos então aos critérios de inclusão/exclusão, e totalizaram, no fim, 39. A maioria dos estudos relacionou a prática de exercícios físicos aeróbicos e resistidos à melhoria da composição corporal, à regulação do perfil lipídico e metabólico e ao estado inflamatório de crianças e adolescentes obesos. Entretanto, a magnitude dos efeitos está associada ao tipo, à intensidade e à duração da prática. CONCLUSÕES: O exercício físico, independentemente do tipo, mostra-se capaz de promover adaptações positivas sobre a obesidade infantil, principalmente por atuar na restauração da homeostase celular e sistema cardiovascular, na melhoria da composição corporal e também aumento da ativação metabólica. .
Subject(s)
Animals , Male , Mice , Eating/drug effects , Opioid Peptides/pharmacology , Receptors, Opioid/agonists , Dose-Response Relationship, Drug , Electric Stimulation , Injections, Intraventricular , Ligands , Molecular Conformation , Opioid Peptides/administration & dosage , Opioid Peptides/chemistry , Structure-Activity RelationshipABSTRACT
O presente artigo tem por objetivo avaliar associação entre fatores de risco cardiovascular (FRCV) e indicadores antropométricos em amostra de base populacional de universitários de São Luís/MA. Estudo transversal com 968 universitários, mediana de 22 anos. Glicemia, triglicerídeos (TGL), HDL-c, tabagismo, consumo de álcool, sedentarismo, síndrome metabólica (SM–critérios do Joint Interim Statement) e resistência insulínica (RI), foram associados e correlacionados com os indicadores antropométricos Índice de Massa Corporal (IMC), Circunferência da Cintura (CC), Relação Cintura Quadril (RCQ) e Relação Cintura Altura (RCA). Encontraram-se associações entre TGL, HAS, SM e maiores valores de todas as variáveis antropométricas. RI associou-se a maiores valores IMC e RCA em homens e mulheres. Baixo HDL-c foi associado a maiores valores de todas as variáveis antropométricas em mulheres. Consumo de álcool associou-se a valores mais elevados de IMC e CC em mulheres e RCQ e RCA em homens. Fumo associou-se a maiores valores de RCA em ambos os sexos. Sedentarismo foi associado a maiores valores de RCQ apenas em homens. As correlações mais altas foram estabelecidas para mulheres entre TGL e IMC, CC, RCQ e RCA. Os indicadores que mais se associaram aos FRCV foram IMC, CC e RCA em mulheres e RCQ e RCA em homens.
The article aims to evaluate the relation between cardiovascular risk factors (CVRF) and anthropometric indicators in a sample of university students from São Luís-MA, Brazil. It is a cross-sectional study conducted with 968 university students, with median age of 22. Glycemia, triglycerides, HDL-c, smoking, alcohol consumption, physical inactivity, metabolic syndrome (Joint Interim Statement criteria) and insulin resistance (IR), were associated and correlated with anthropometric indicators such as BMI, WC, WHR and WHtR. Associations were found between TGL, SH, SM and higher values of all anthropometric variables. The RI was associated with higher BMI values and WHtR in men and women. The low HDL-c was associated with higher values of all anthropometric variables in women. Consumption of alcohol was associated with higher values of BMI and WC in women and WHR in men and WHtR. Smoking was associated with higher values of WHtR in both sexes. Physical inactivity was associated with higher values of WHR in men only. The highest correlations were established for women between TGL and BMI CC, WHR and WHtR. The indicators most associated with CVRF were BMI, WC and WHtR in females and WHR and WHtR in men.
Subject(s)
Cysteine Proteases/metabolism , Cysteine Proteinase Inhibitors/chemical synthesis , Cysteine Proteinase Inhibitors/pharmacology , Drug Design , Norwalk virus/enzymology , Chemistry Techniques, Synthetic , Crystallography, X-Ray , Cysteine Proteinase Inhibitors/chemistry , Dose-Response Relationship, Drug , Models, Molecular , Molecular Conformation , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Podophyllotoxone (1) was isolated from the roots of Dysosma versipellis. The structure was determined by spectroscopic analysis in combination with single-crystal X-ray analysis. The absolute configuration of compound 1 was assigned based on the Flack parameter. It showed significant inhibitory activities against human prostate cancer cells PC3 and DU145 with IC50 values being 14.7 and 20.6 μmol·L(-1), respectively. It also arrested the cells at G2/M phase. Tubulin polymerization assay showed that it inhibited the tubulin polymerization in a dose-dependent manner, and molecular docking analysis revealed a different binding mode with tubulin as compared with those known tubulin inhibitors.
Subject(s)
Humans , Male , Antineoplastic Agents , Chemistry , Pharmacology , Berberidaceae , Chemistry , Cell Line, Tumor , Dose-Response Relationship, Drug , G2 Phase , Hydrogen Bonding , Molecular Conformation , Molecular Docking Simulation , Phytotherapy , Plant Extracts , Chemistry , Pharmacology , Plant Roots , Chemistry , Podophyllotoxin , Chemistry , Pharmacology , Polymerization , Prostatic Neoplasms , Drug Therapy , Tubulin , Tubulin Modulators , PharmacologyABSTRACT
Molecular imprinting technique (MIT) involves the synthesis of polymer in the presence of a template to produce complementary binding sites in terms of its size, shape and functional group orientation. Such kind of polymer possesses specific recognition ability towards its template molecule. Despite the rapid development of MIT over the years, the majority of the template molecules that have been studied are small molecules, while molecular imprinting of proteins remains a significant yet challenging task due to their large size, structural flexibility and complex conformation. This review, we summarized the research findings over the past years, and discussed the nano-reinforcing materials used to prepare molecular imprinting of proteins and the perspective of these nano-reinforcing materials.
Subject(s)
Binding Sites , Molecular Conformation , Molecular Imprinting , Nanostructures , Chemistry , Polymers , Chemistry , Proteins , ChemistryABSTRACT
Almost all pre-miRNAs in eukaryotic cytoplasm are recognized and processed into double-stranded microRNAs by the endonuclease Dicer protein comprising of multiple domains. As a key player in the small RNA induced gene silencing pathway, the major domains of Dicer are conserved among different species with the exception of the N-terminal components. Human Dicer's N-terminal domain has been shown to play an auto-inhibitory function of the protein's dicing activity. Such an auto-inhibition can be released when the human Dicer protein dimerizes with its partner protein, such as TRBP, PACT through the N-terminal DExH/D (ATPase-helicase) domain. The typical feature of a pre-miRNA contains a terminal loop and a stem duplex, which bind to human Dicer's DExH/D (ATPase-helicase) domain and PAZ domain respectively during the dicing reaction. Here, we show that pre-miRNA's terminal loop can regulate human Dicer's enzymatic activity by interacting with the DExH/D (ATPase-helicase) domain. We found that various editing products of pre-miR-151 by the ADAR1P110 protein, an A-to-I editing enzyme that modifies pre-miRNAs sequence, have different terminal loop structures and different activity regulatory effects on human Dicer. Single particle electron microscopy reconstruction revealed that pre-miRNAs with different terminal loop structures induce human Dicer's DExH/D (ATPase-helicase) domain into different conformational states, in correlation with their activity regulatory effects.
Subject(s)
Humans , Base Pairing , Base Sequence , DEAD-box RNA Helicases , Chemistry , Genetics , MicroRNAs , Chemistry , Genetics , Molecular Conformation , Molecular Sequence Data , Protein Structure, Tertiary , RNA Editing , Genetics , Ribonuclease III , Chemistry , GeneticsABSTRACT
En las sociedades industrializadas se está reflexionando cada vez más sobre el impacto de la inseguridad alimentaria, entendida como la dificultad para asegurar la accesibilidad de una parte de la población a los recursos alimentarios suficientes para garantizar su subsistencia y bienestar. Con base en datos recogidos a partir de una investigación en curso en España, este artículo discute, por un lado, si la actual crisis económica está revirtiendo algunas de las tendencias positivas que el sistema agroalimentario industrial había favorecido, como la disminución de las diferencias sociales en el consumo y el derecho a la alimentación. Por otro lado, reflexiona acerca de la creciente precarización en las estrategias alimentarias y en el estado de salud de la población, así como sobre la necesidad de considerar la desigualdad social como variable explicativa de las diversas maneras de alimentarse.
This article analyzes the reasons why food insecurity in Spain must increasingly be understood as lack of access to sufficient food resources to guarantee the survival and wellbeing of part of the population. Using data collected in an ongoing research project, two possible causes for this are explored. First, it is argued that certain positive developments that seemed firmly established, such as recognition of the right to an adequate diet and the leveling out of social differences in food consumption, are now being reversed by the current economic crisis. Second, the analysis focuses on strategies people in precarious circumstances use to obtain food, their relationship to health, and the need to take social inequality into consideration as an explanatory variable in accounting for different ways of procuring daily sustenance.
Subject(s)
Cathepsin B/chemistry , Cysteine Proteinase Inhibitors/chemistry , Dipeptides/chemistry , Leucine/analogs & derivatives , Binding Sites , Cathepsin B/antagonists & inhibitors , Cathepsin B/metabolism , Computer Simulation , Cysteine Proteinase Inhibitors/metabolism , Hydrogen Bonding , Leucine/chemistry , Leucine/metabolism , Models, Molecular , Molecular Conformation , Monte Carlo Method , Structure-Activity RelationshipABSTRACT
OBJECTIVES: to analyze the Pelvic Floor Muscle Strength (PFMS) of pregnant women with one or more vaginal or cesarean deliveries; to compare the PFMS of these with pregnant women with the PFMS of primiparous women. METHODS: cross-sectional study with women up to 12 weeks pregnant, performed in Itapecerica da Serra, São Paulo state, from December 2012 to May 2013. The sample consisted of 110 pregnant women with one or more vaginal deliveries or cesarean sections and 110 primigravidae. The PFMS was evaluated by perineometry (Peritron(tm)) and vaginal digital palpation (modified Oxford scale). RESULTS: the average PFMS in pregnant women with a history of vaginal delivery or cesarean section was 33.4 (SD=21.2) cmH2O. From the Oxford scale, 75.4% of the pregnant women with previous vaginal or cesarean deliveries presented grade ≤ 2, and 5.5% grade ≥ 4; among the primiparae, 39.9% presented grade ≤ 2, and 50.9% grade ≥ 4, with a statistically significant difference (p<0.001). From the perineometry, there was no statistically significant difference between the PFMS and age, type of delivery, parity, body mass index, and genitourinary tract symptoms, however, there was a statistically significant difference between the pregnant women with and without a history of episiotomy (p=0.04). In the palpation, none of the variables showed a statistically significant difference. CONCLUSION: pregnancy and childbirth can reduce the PFMS. .
OBJETIVOS: analisar a força muscular do assoalho pélvico de gestantes com um ou mais partos normais ou cesarianas; comparar a a força muscular do assoalho pélvico dessas gestantes com a de primigestas. MÉTODO: estudo transversal com gestantes até 12 semanas de gravidez, realizado em Itapecerica da Serra, SP, de dezembro de 2012 a maio de 2013. A amostra foi composta por 110 gestantes, com um ou mais partos normais ou cesarianas e 110 primigestas. A força muscular do assoalho pélvico foi avaliada pela perineometria e palpação digital vaginal (Escala de Oxford modificada). RESULTADOS: a média da força muscular do assoalho pélvico em gestantes com antecedentes de parto normal ou cesariana foi 33,4 (desvio-padrão=21,2) cmH2O. Pela escala de Oxford, 75,4% das gestantes com partos ou cesarianas anteriores apresentaram grau ≤2 e 5,5%, grau ≥4; entre as primigestas, 39,9% apresentaram grau ≤2 e 50,9%, grau ≥4, com diferença estatisticamente significante (p<0,001). Pela perineometria, não houve diferença estatisticamente significante entre a força muscular do assoalho pélvico e idade, tipo de parto, paridade, índice de massa corpórea e sintomas do trato geniturinário, mas houve entre as gestantes com e sem antecedente de episiotomia (p=0,04). Na palpação, nenhuma das variáveis mostrou diferença estatisticamente significante. CONCLUSÃO: a gravidez e o parto podem reduzir a força muscular do assoalho pélvico. .
OBJETIVOS: analizar la Fuerza Muscular del Suelo Pélvico (FMSP) de embarazadas con uno o más partos normales o cesáreas; comparar la FMSP de estas embarazadas con la FMSP de primigestas. MÉTODO: estudio transversal con embarazadas hasta 12 semanas de embarazo, realizado en Itapecerica de la Serra, SP, de diciembre de 2012 a mayo de 2013. La muestra fue de 110 embarazadas con uno o más partos normales o cesáreas y 110 primigestas. La FMSP fue evaluada por la perineometría (Peritron(tm)) y palpación digital vaginal (escala de Oxford modificada). RESULTADOS: el promedio de la FMSP en embarazadas con antecedentes de parto normal o cesárea fue 33,4 (de=21,2) cmH2O. Por la escala de Oxford, 75,4% de las embarazadas con partos o cesáreas anteriores presentaron grado ≤ 2 y 5,5%, grado ≥ 4; entre las primigestas, 39,9% presentaron grado ≤ 2 y 50,9%, grado ≥ 4, con diferencia estadísticamente significativa (p<0,001). Por la perineometría, no hubo diferencia estadísticamente significativa entre la FMSP y edad, tipo de parto, número de partos anteriores, índice de masa corporal y síntomas del tracto genitourinario, pero hubo entre las embarazadas con y sin antecedente de episiotomía (p=0,04). En la palpación, ninguna de las variables mostró diferencia estadísticamente significativa. CONCLUSIÓN: el embarazo y el parto pueden reducir la FMSP. .
Subject(s)
Calcium , Calmodulin , Calpain , Binding Sites , Calcium/pharmacology , Calmodulin/antagonists & inhibitors , Calpain/antagonists & inhibitors , Calpain/metabolism , Fluorescent Dyes , Felodipine/pharmacology , In Vitro Techniques , Imidazoles/pharmacology , Leucine/analogs & derivatives , Leucine/pharmacology , Molecular Conformation , Naphthalenesulfonates/pharmacology , Spectrometry, FluorescenceABSTRACT
Investigar molecularmente la deficiencia en los genes de reparo de DNA (MMR) asociados al síndrome de Lynch. Materiales y métodos: Realizar los análisis de inmunohistoquímica e inestabilidad de microsatélites (MSI) en 5 familias con sospecha de síndrome de Lynch de acuerdo a los criterios clínicos de Amsterdam y/o Bethesda, atendidos en el Hospital Nacional Almanzor Aguinaga Asenjo de la ciudad de Chiclayo (Lambayeque-Perú) durante 2007-2010. Resultados. La falta de expresión de las proteínas MLH1/PMS2 y una alta MSI (MSI-H) fueron observados en un paciente de sexo masculino de 60 años diagnosticado con adenocarcinoma de grado I. Adicionalmente, se realizó el análisis mutacional puntual en el gen BRAF (V600E) a fin de descartar que se trate de un caso esporádico de cáncer colorrectal. La ausencia de mutación en el gen analizado asociado a los resultados moleculares del tumor, sugiere la caracterización de este paciente como sospecha de síndrome de Lynch. Conclusiones: Es el primer estudio molecular reportado en la población peruana y demuestra la importancia del análisis molecular en familias con sospecha de cáncer colorrectal hereditario a fin de ofrecer posibilidades de vigilancia y seguimiento que han demostrado reducir la morbilidad y la mortalidad del cáncer colorrectal así como contribuir a la caracterización a nivel genética y clínica de este tipo de cáncer en la población peruana...
To investigate the molecular deficiency in MMR genes associated to Lynch syndrome. Material and methods: Immunohistochemical and microsatellite instability (MSI) analysis were performed in 5 families with suspected Lynch syndrome according to the clinical criteria, Amsterdam and/or Bethesda that had been treated at the Hospital Nacional Almanzor Aguinaga Asenjo (Lambayeque-Peru) during 2007-2010. Results: The absence of expression of MLH1/PMS2 and high MSI (MSI-H) were observed in a male patient aged 60 with adenocarcinoma grade I. In addition, the point mutational analysis was performed in BRAF (V600E) to rule that it is a sporadic case of colorectal cancer. The absence of mutation in BRAF together with the molecular analysis suggests the suspicion as a Lynch syndrome. Conclusions: It is the first molecular study reported in the Peruvian population and demonstrates the importance of molecular analysis in families with suspected hereditary colorectal cancer in order to provide possibilities of surveillance and monitoring that have been shown to reduce morbidity and mortality of colorectal cancer. The present study contributes to the genetic and clinical characterization of the Lynch syndrome in the Peruvian population...
Subject(s)
Humans , Male , Molecular Conformation , Colorectal Neoplasms, Hereditary NonpolyposisABSTRACT
The non-proteinogenic amino acids — phenylglycine (PG) and hydroxyphenylglycine (HPG) are crucial components of certain peptidic natural products and are important for the preparation of various medicines. In this, study, the conformation of model dipeptides Ac-X-NHMe of PG, p-HPG and 3, 5-di-hydroxyphenylglycine (3, 5-DHPG) was studied both in R and S form by quantum mechanical (QM) and molecular dynamics approaches. On the energy scale, the conformational states of these molecules in both the R and S were found to be degenerate by QM studies, stabilized by non-covalent interactions like carbonyl--carbonyl interactions, carbonyl-lp··π (aromatic ring) interactions etc. These interactions disappeared/weakened due to interaction of water molecules with carbonyl groups of backbone in simulation and water was found to interact with the aromatic ring through Ow-H··π or Owlp··π interactions. The degeneracy of conformational states was lifted in favor of R-form of PG and DHPG and water molecules interactions with aromatic ring led to non-planarity of the aromatic ring. In simulation studies, irrespective of the starting geometry, the , values for the R form correspond to inverse b/inverse collagen region and for the S-form, the , values correspond to b/collagen region i.e., adopt single conformation. The obtained results were in conformity with the CD spectroscopic data on D-PG and D-p-HPG. The conformational behavior of the unusual amino acids might be of great help in designing of bioactive peptides/peptide based drugs to be realized in single conformation – an essential requirement.
Subject(s)
Benzene/chemistry , Computer Simulation , Glycine/analogs & derivatives , Glycine/chemistry , Models, Chemical , Molecular Conformation , Molecular Dynamics Simulation , Quantum TheoryABSTRACT
Total RNA was isolated from Siraitia grosvenorii fruit by the method of modified Trizol, according to S. grosvenorii fruit characteristics of rich phenols, polysaccharide, oil and proteins. The OD260/280, OD260/230, RNA integrity (RIN) and yield of the total RNA with this method were 2.01, 2.02, 9.50 and 260 mirog.g-1, respectively. The open reading frame (ORF) of dehydroascorbate reductase (DHAR), named as SgDHAR, was cloned by rapid amplification of cDNA ends (RACE) and RT-PCR method from S. grosvenorii. The GenBank accession number for this gene is KC907731. The SgDHAR gene contains a full-length cDNA of 1,252 bp including ORF of 819 bp and encodes a predicted protein of 272 amino acids. The molecular mass is 30.217 7 kD and the isoelectric point is 8.76. Homology comparison showed that it shared 87% nucleotide sequence homology with Cucumis sativus. Expression patterns using qRT-PCR analysis showed that SgDHAR was mainly expressed in fruit and stem, followed by flower, and was lowest in root, while the expression level was 6.83 times in triploid. T than that in diploid. Therefore, SgDHAR gene may be involved in abortion of triploid seedless S. grosvenorii.
Subject(s)
Amino Acid Sequence , Base Sequence , Cloning, Molecular , Cucurbitaceae , Chemistry , Genetics , DNA, Complementary , Genetics , Flowers , Chemistry , Genetics , Fruit , Chemistry , Genetics , Molecular Conformation , Open Reading Frames , Oxidoreductases , Genetics , Metabolism , Phylogeny , Plant Roots , Chemistry , Genetics , Plant Stems , Chemistry , Genetics , Plants, Medicinal , Chemistry , Genetics , Protein Structure, Secondary , RNA, PlantABSTRACT
During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed.
Subject(s)
Aging , Arthritis, Rheumatoid , Blood Proteins , Cardiomyopathies , Cataract , Cell Membrane , Collagen , Diabetes Complications , Diabetes Mellitus , Fibrinogen , Free Radicals , Gene Expression , Globulins , Glucose , Inflammation , Molecular Conformation , Nucleic Acids , Osteoporosis , Oxidative StressABSTRACT
Riboflavin [vitamin B[2]] belongs to a group of respiratory enzymes that occur widely in animals and plants participating in vital oxidation- reduction processes in the body. A computational study was conducted on riboflavin by ArgusLab 4.0.1 to obtain the most active conformation of riboflavin and to analyze its excited-state properties. The best conformation of riboflavin was found to be -199.2173 kcal/mol which is the minimum potential energy calculated by geometry convergence function by ArgusLab software; performed according to Hartree-Fock calculation method. Electronic transition states [ground and excited], were also calculated and visualized by semi-empirical ZINDO method by ArgusLab from which molecular properties such as energies, wave function and dipole moments were established. All the results obtained from geometry optimization and excited-state properties lead us to delineate the active sites with charged groups of riboflavin to interact with the receptors. Such types of investigations are significant for drug -receptor interactions