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1.
BMC Cardiovasc Disord ; 23(1): 80, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36765270

RESUMO

BACKGROUND: The home treatment of elderly patients with chronic heart failure (CHF) is often accompanied by malnutrition, which increases the risk of re-hospitalisation and affects the prognosis. Therefore, how to effectively improve the nutritional self-management of patients is a current focus of medical research. This study aims to test the effect of home-based nutritional intervention method on improving the nutritional status of elderly patients with CHF. METHODS: A total of 90 hospitalised elderly patients with CHF were randomly divided into the experimental group (n = 45) and the control group (n = 45). The patients in both groups were given standardised drug therapy and their nutritional status was evaluated using a body composition analyser prior to discharge (protein, body fat percentage, visceral fat area, skeletal muscle, upper arm muscle circumference, left lower limb and right lower limb muscle mass), with the cardiopulmonary function evaluated using a six-minute walk test and the metabolic equivalents method. The control group was given general nutrition education and routine dietary guidance from cardiac rehabilitation nurses, while the experimental group was given an individualised nutrition prescription by dietitians based on the evaluation results, according to which one-to-one food exchange dietary intervention training was given until the patients mastered the process. RESULTS: The nutritional indexes at the end of the study were significantly higher in the experimental group than in the control group and were higher than those before the intervention (P < 0.05). The muscle circumference of the upper arm, the muscle mass of the left lower limb and the right lower limb had no statistical significance following the intervention compared to the control group and before the intervention (P > 0.05). The cardiopulmonary function indexes were significantly better in the experimental group at the end of the study than before the intervention and were better than those in the control group, with statistically significant differences (P < 0.05), while no significant changes were observed in the control group before and after the intervention (P > 0.05). CONCLUSION: The home-based nutritional intervention method of food exchange portions can effectively improve the nutritional status of elderly patients with CHF, with the distribution of visceral fat more reasonable and the cardiopulmonary function and exercise endurance improved.


Assuntos
Insuficiência Cardíaca , Desnutrição , Humanos , Idoso , Estado Nutricional , Avaliação Nutricional , Desnutrição/diagnóstico , Desnutrição/terapia , Dieta , Doença Crônica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia
2.
Br J Nutr ; : 1-26, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35440346

RESUMO

Thyroid cancer (TC) incidence has increased greatly during the past decades with a few established risk factors, while no study is available that has assessed the association of the Chinese Health Dietary Index (CHDI) with TC. We conducted a 1:1 matched case-control study in two hospitals in Shanghai, China. Diet quality scores were calculated according to CHDI using a validated and reliable food-frequency questionnaire. Conditional logistic regression analysis and Restricted cubic spline (RCS) analysis was used to reveal potential associations between CHDI score and thyroid cancer risk. A total of 414 pairs of historically confirmed TC patients and healthy controls were recruited from November 2012 to December 2015. The total score of cases and controls were 67.5 and 72.8, respectively (p < 0.001). The median score of total vegetables, fruit, diary, dark green and orange vegetables, fish, shellfish and mollusk, soybean, and whole grains, dry bean and tuber in cases was significantly lower than those in controls. Compared to the reference group (≤60 points), the average (60∼80 points) and high (≥80 points) levels of the CHDI score were associated with a reduced risk of TC (OR: 0.40, 95% Cl: 0.26∼0.63 for 60∼80 points; OR: 0.22, 95% Cl: 0.12∼0.38 for ≥80 points). In age-stratified analyses, the favorable association remained significant among participants who younger than 50 years old. Our data suggested that high diet quality as determined by CHDI was associated with lower risk of TC.

3.
Int J Clin Pract ; 2022: 7025811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936062

RESUMO

Objective: The present study aims to (1) analyze the clinical characteristics and related influencing factors of knee bone infarction in systemic lupus erythematosus (SLE) and (2) improve the understanding of SLE complicated with knee bone infarction. Methods: The data of patients with SLE complicated with knee bone infarction were retrospectively analysed; patients with SLE during the same period who matched in age, gender, and disease duration were selected as control subjects, with a 1 : 1 ratio with the SLE group. The clinical data were collected to analyze the risk factors for SLE complicated with knee bone infarction. Results: In a total of 36 (6.4%) of 563 patients aged 19-33 (25.8 ± 4.8) years who had SLE during the same period, the disease was complicated with knee bone infarction. The diagnosis of knee bone infarction was made at an SLE duration of 7-65 (26.2 ± 15.7) months. During the SLE course, knee bone infarction occurred within 1 year in 6 cases (16.7%), within 1-5 years in 28 cases (77.8%), and in >5 years in 2 cases (5.6%). Raynaud's phenomenon incidence and anti-nRNP antibody positivity were significantly higher in the knee bone infarction group than in the control group (P < 0.01 and P < 0.05, respectively). The cumulative glucocorticoid dose at 1, 3, and 6 months was significantly higher in the knee bone infarction group than in the control group (P < 0.05). SLE complicated with knee necrosis had a statistically significant rank correlation with Raynaud's phenomenon (r = 0.445, P < 0.001), anti-nRNP antibody (r = 0.309, P=0.008), and renal injury (r = 0.252, P=0.032). The multivariate analysis of SLE complicated with knee bone infarction showed that Raynaud's phenomenon was an independent influencing factor for the complicated knee bone infarction in SLE patients (OR = 4.938, P=0.004), and the probability of SLE complicated with knee bone infarction in Raynaud's phenomenon positive patients was 4.938 times that of Raynaud's phenomenon negative patients. Conclusions: The risk of knee bone infarction was relatively high in patients with SLE within a 5-year disease course and in young patients. The risk factors were Raynaud's phenomenon, anti-nRNP antibody positivity, and early high-dose glucocorticoid therapy.


Assuntos
Lúpus Eritematoso Sistêmico , Doença de Raynaud , Glucocorticoides/uso terapêutico , Humanos , Infarto/complicações , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Doença de Raynaud/complicações , Doença de Raynaud/epidemiologia , Estudos Retrospectivos
4.
Bioconjug Chem ; 32(9): 2032-2042, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469136

RESUMO

Bacterial biofilm, as a natural and renewable material, is a promising architecture for enzyme immobilization. In this study, we have demonstrated the feasibility of an Escherichia coli biofilm to immobilize a self-assembly multienzyme complex by the covalent interaction between a peptide SpyTag and its protein partner SpyCatcher. The SpyTag-labeled biofilm is displayed on the surface of E. coli by overexpressing the recombinant CsgA-SpyTag, in which CsgA is capable of forming biofilms. This SpyTag bearing biofilm is used to bind with SpyCatcher bearing synthetic mini-scaffoldin, which also contains a carbohydrate-binding module 3 (CBM3), and four different cohesins from different microorganisms. CBM3 was used to bind with cellulose, while the four different cohesins were used to recruit four dockerin-containing cascade enzymes, which were subsequently applied to convert starch to myo-inositol. Compared to the free enzyme mixture, the biofilm-immobilized enzyme complex exhibited a 4.28 times increase in initial reaction rate in producing myo-inositol from 10 g/L maltodextrin (a derivative of starch). Additionally, this biofilm-immobilized enzyme complex showed much higher recycle ability than the enzyme complex which was immobilized on a regenerated amorphous cellulose (RAC) system. In conclusion, the biofilm-mediated immobilization of the enzymatic biosystem provides a promising strategy to increase the reaction rate and enhance the stability of an in vitro enzymatic biosystem, exhibiting high potential to improve the efficiency of an in vitro biosystem.


Assuntos
Biofilmes , Enzimas Imobilizadas , Inositol , Amido
5.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3511-3517, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893538

RESUMO

To explore the population characteristics and clinical application characteristics of patients with cerebral hemorrhage treated with Xingnaojing Injection in real world. The model was established by Apriori algorithm, and the general information and medication information of 8 369 patients with cerebral hemorrhage treated with Xingnaojing Injection were analyzed by using Clementine 12.0 in the databases of information systems of 33 class Ⅲ grade A hospitals in China. The results showed that among the 8 369 patients with cerebral hemorrhage treated with Xingnaojing Injection, the median age was 59 years old. And the male to female ratio was about 1.74∶1. Most of them did manual labor(31.26%), and were hospitalized in winter(27.46%), especially during the Cold Dew(5.1%). The majority of the patients were in a stable condition(50.94%), and preferred neurosurgery department(48.82%). 29.03% of patients were hospitalized for 15-28 days, and 42.47% of patients spent 10 000-50 000 Yuan of hospitalization expenses. The single dose of Xingnaojing Injection was 10-20 mL at most(46.03%). And the course of medication was mostly 3 days or less(68.60%). Lidocain was the most frequently used Western medicine in drug combination(5.05%), and Huayu Tongmai Ji was the most frequently used traditional Chinese medicine in drug combination(10.73%). The most frequently used one type of traditional Chinese medicine combined with one type of Western medicine was Huayu Tongmai Ji + Dexamethasone(8.08%). The most frequently used two Western medicines in drug combination were Omeprazole + Dexamethasone(5.07%). Prilosec + Dexamethasone + Lidocaine(3.35%) were three Western drugs with the most frequent combination. When the dosage was 10-20 mL and the number of days of treatment was > 15 days, the largest number of the patients was cured and improved(44.78%, 45.85%). The results showed that cerebral hemorrhage patients treated with Xingnaojing Injection were mostly middle-aged and elderly people, with more males than females. Brain hemorrhage often occurred in winter and spring. Xingnaojing Injectiont was often combined with glucocorticoids, proton pump inhibitors and cardiovascular drugs to prevent cerebral hemorrhage complications. The clinical medication met the guidelines for the treatment of cerebral hemorrhage. Some patients had over-treatment use, which can provide a reference for clinicians in treating cerebral hemorrhage.


Assuntos
Medicamentos de Ervas Chinesas , Idoso , Hemorragia Cerebral , China , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade
6.
Neurochem Res ; 44(4): 930-946, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30661230

RESUMO

Exercise has been regarded as an effective rehabilitation strategy to facilitate motor and cognitive functional recovery after stroke, even though the complex effects associated with exercise-induced repair of cerebral ischemic injury are not fully elucidated. The enhancement of angiogenesis and neurogenesis, and the improvement of synaptic plasticity following moderate exercise are conducive to functional recovery after ischemic damage. Our previous studies have confirmed the angiogenesis and neurogenesis through the caveolin-1/VEGF pathway in MCAO rats. As an essential neurotrophic factor, BDNF has multiple effects on ischemic injury. In this study, we attempted to determine an additional mechanism of treadmill exercise-mediated motor and cognitive functional recovery through the caveolin-1/VEGF pathway associated with BDNF in the ischemic penumbra of MCAO mice. We found that mice exposed to treadmill exercise after the MCAO operation showed a significant up-regulation in expression of caveolin-1, VEGF, BDNF, synapsin I and CYFIP1 proteins, numbers of cells positive for BrdU/CD34, BDNF, BrdU/NeuN, BrdU/Synapsin I and CYFIP1 expression were increased, which support the reduction in neurological deficit and infarction volume, as well as improved synaptic morphology and spatial learning abilities, compared with the non-exercise mice. However, the caveolin-1 inhibitor, daidzein, resulted in increase in neurological deficit and infarction volume. The selective VEGFR2 inhibitor, PD173074, significantly induced larger infarction volume and neurological injury, and decreased the expression of BDNF in the ischemic penumbra. These findings indicate that exercise improves angiogenesis, neurogenesis and synaptic plasticity to ameliorate motor and cognitive impairment after stroke partially through the caveolin-1/VEGF pathway, which is associated with the coregulator factor, BDNF.


Assuntos
Isquemia Encefálica/metabolismo , Caveolina 1/biossíntese , Cognição/fisiologia , Condicionamento Físico Animal/métodos , Recuperação de Função Fisiológica/fisiologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Isquemia Encefálica/terapia , Caveolina 1/antagonistas & inibidores , Cognição/efeitos dos fármacos , Teste de Esforço/métodos , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/terapia , Injeções Subcutâneas , Isoflavonas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Destreza Motora/efeitos dos fármacos , Destreza Motora/fisiologia , Pirimidinas/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
7.
Bioorg Med Chem Lett ; 29(9): 1060-1064, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30857748

RESUMO

Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14) (q13;q32), resulting in the overexpression of cyclin-D1. The progression of MCL is an interaction of multitarget and multilink regulation. It has been proven that Bruton's tyrosine kinase (BTK) is commonly overexpressed in MCL, which makes it a focus of targeted therapy for MCL. Irreversible inhibitors usually have great potency, rapid onset of inhibition and long duration of drug action. Herein, structural modification via an open-loop strategy based on lead compound ibrutinib (IBN) was performed, leading to a series of pyrazole derivatives. Compounds 19c, 19'c, 21c and 21'c showed potent effect in MCL cells with IC50 values lower than 1 µM, and a more than 3-28-fold increase in antiproliferative activity compared with IBN.


Assuntos
Antineoplásicos/química , Desenho de Fármacos , Pirazóis/química , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia/metabolismo , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Meia-Vida , Humanos , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Microssomos Hepáticos/metabolismo , Pirazóis/metabolismo , Pirazóis/farmacologia , Relação Estrutura-Atividade
8.
Bioorg Chem ; 89: 102943, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31031018

RESUMO

Bruton's tyrosine kinase (BTK) is a key regulator of B-cell receptor (BCR) signaling pathway and takes effect in the regulation of B-cell activation, survival, proliferation and differentiation. It has been proved that BTK is commonly overexpressed in mantle cell lymphoma (MCL), which makes it a focus of targeted therapy for MCL. Our studies yielded a novel series of pyrazolopyrimidine derivatives capable of potent inhibition of BTK. Notably, 12a showed higher selectivity against BTK and exhibited robust antiproliferative effects in both mantle cell lymphoma cell lines and primary patient tumor cells. Low micromolar doses of 12a induced strong cell apoptosis in Jeko-1 and Z138 cells.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Desenho de Fármacos , Inibidores de Proteínas Quinases/química , Pirimidinas/química , Tirosina Quinase da Agamaglobulinemia/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Estrutura Terciária de Proteína , Pirazóis/química , Pirimidinas/metabolismo , Pirimidinas/farmacologia , Relação Estrutura-Atividade
9.
Metab Eng ; 42: 168-174, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28624535

RESUMO

Fructose 1,6-diphosphate (FDP) is a widely used medicine and is also a precursor of two important three-carbon phosphates - glyceraldehyde 3-phosphate (GA3P) and dihydroxyacetone phosphate (DHAP) for the biosynthesis of numerous fine chemicals. An in vitro synthetic cofactor-free enzymatic pathway comprised of four hyperthermophilic enzymes was designed to produce FDP from starch and pyrophosphate. All of four hyperthermophilic enzymes (i.e., alpha-glucan phosphorylase from Thermotaga maritima, phosphoglucomutase from Thermococcus kodakarensis, glucose 6-phosphate isomerase from Thermus thermophilus, and pyrophosphate phosphofructokinase from T. maritima) were overexpressed in E. coli BL21(DE3) and purified by simple heat precipitation. The optimal pH and temperature of one-pot biosynthesis were 7.2 and 70°C, respectively. The optimal enzyme ratios of αGP, PGM, PGI and PFK were 2:2:1:2 in terms of units. Via step-wise addition of new substrates, up to 125 ± 4.6mM FDP was synthesized after 7-h reaction. This de novo ATP-free enzymatic pathway comprised of all hyperthermophilic enzymes could drastically decrease the manufacturing costs of FDP and its derivatives GA3P and DHAP, better than those catalyzed by ATP-regeneration cascade biocatalysis, the use of mesophilic enzymes, whole cell lysates, and microbial cell factories.


Assuntos
Escherichia coli , Frutosedifosfatos/biossíntese , Engenharia Metabólica , Proteínas Arqueais/biossíntese , Proteínas Arqueais/genética , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Frutosedifosfatos/genética , Thermococcus/enzimologia , Thermococcus/genética , Thermotoga maritima/enzimologia , Thermotoga maritima/genética , Thermus thermophilus
10.
Neurochem Res ; 42(2): 389-397, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27747480

RESUMO

Using a model of middle cerebral artery occlusion (MCAO), we have previously demonstrated that treadmill exercise promotes angiogenesis in the ischemic penumbra through caveolin-1/VEGF signaling pathways. However, the function of caveolin-1/VEGF signaling in neurogenesis after MCAO has not been determined. In this study, we aimed to investigate the potential of treadmill exercise to promote neurogenesis after MCAO and whether caveolin-1/VEGF signaling pathways are involved. After MCAO, rats were subjected to a program of treadmill exercise. Daidzein (a specific inhibitor of caveolin-1 protein expression, 0.4 mg/kg) was used to confirm the effect of caveolin-1/VEGF signaling on exercise-mediated neurogenesis. We found that the total protein expression of both caveolin-1 and VEGF was increased by exercise and consistent with the improved neurological recovery, decreased infarct volumes and increased 5-bromo-2'-deoxyuridine (BrdU) in the ipsilateral Subventricular zone (SVZ), as well as increased numbers of BrdU/DCX and BrdU/Neun-positive cells in the peri-infarct region. Furthermore, we observed that the treadmill exercise-induced increased VEGF expression, improved neurological recovery, decreased infarct volumes, increased BrdU/DCX and BrdU/Neun-positive cells were significantly inhibited by the caveolin-1 inhibitor. Our results indicate that treadmill exercise improves neurological recovery in ischemic rats, possibly by enhancement of SVZ-derived neural stem cell (NSC) proliferation, migration and differentiation in the penumbra. Moreover, caveolin-1/VEGF signaling is involved in exercise-mediated NSC migration and neuronal differentiation.


Assuntos
Isquemia Encefálica/metabolismo , Caveolina 1/biossíntese , Teste de Esforço , Neurogênese/fisiologia , Condicionamento Físico Animal/fisiologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/patologia , Proliferação de Células/fisiologia , Proteína Duplacortina , Teste de Esforço/métodos , Masculino , Condicionamento Físico Animal/métodos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia
11.
Med Sci Monit ; 23: 4004-4013, 2017 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-28821706

RESUMO

BACKGROUND To identify the effect of apigenin on cognitive deficits of rats after cerebral ischemia and reperfusion injury, and to investigate the potential molecular mechanisms. MATERIAL AND METHODS The rats were given sodium butyrate (NaB) or apigenin (20 or 40 mg/kg) for 28 days. Cognition was investigated by the Morris water maze (MWM) test. On day 28, the rats were euthanized and their hippocampal brain regions were used to identify biochemical and neurochemical alterations. The content of histone deacetylase (HDAC) was measured by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to determine the levels of BDNF, phosphorylated cAMP response element-binding protein (pCREB), acetylated H3, and acetylated H4. The mRNA expressions of brain-derived neurotrophic factor (BDNF) and synapsin-I (Syn-I) were examined by polymerase chain reaction (PCR). RESULTS The rats with chronic administration of apigenin (20 and 40 mg/kg) showed better performance in the MWM task than the model rats; there was no significant difference between the apigenin-treated and NaB-treated rats. At the higher apigenin dose of 40 mg/kg, the HDAC content was decreased, the BDNF level was markedly increased, and acetylated H3 and acetylated H4 expressions and Syn-I expressions in the hippocampus was upregulated compared with the model group. Apigenin at 20 mg/kg did not show reversal of the neurochemical alterations. CONCLUSIONS The improvement effect of apigenin on cognitive impairments after cerebral ischemia and reperfusion injury may involve multiple mechanisms, such as the inhibition of HDAC, induction of BDNF and Syn-I expression, and regulation of histone acetylation.


Assuntos
Apigenina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/psicologia , Acetilação , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ácido Butírico/farmacologia , Transtornos Cognitivos/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Histona Desacetilases/metabolismo , Histonas/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/psicologia , Acidente Vascular Cerebral/metabolismo
12.
J Struct Biol ; 193(3): 206-211, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26719223

RESUMO

The cold-adapted xylanases can catalyze at low temperature and hold great potential in food industry applications. Here we describe the first crystal structure of a cold-adapted glycoside hydrolase (GH) family 10 xylanase XynGR40 and its complex with xylobiose at 2.15 and 2.50Å resolution. The enzyme folds into a typical GH10 (ß/α)8 TIM-barrel, with E132 and E243 serving as the catalytic residues. The xylobiose was observed to occupy the -1 and -2 subsites. Structural comparison with a thermophilic GH10 xylanase highlighting various parameters that may explain the cold adaptation features were analyzed. Synergistic effects of the increased exposure of hydrophobic residues, the higher flexibility of substrate-binding residues, more flexible loops, and the ratios of special amino acid residues, may result in the cold adaptation of XynGR40.


Assuntos
Adaptação Fisiológica , Dissacarídeos/química , Endo-1,4-beta-Xilanases/química , Conformação Proteica , Sítios de Ligação , Catálise , Temperatura Baixa , Cristalografia por Raios X , Dissacarídeos/metabolismo , Endo-1,4-beta-Xilanases/genética , Endo-1,4-beta-Xilanases/metabolismo , Microbioma Gastrointestinal , Interações Hidrofóbicas e Hidrofílicas , Especificidade por Substrato
13.
Angew Chem Int Ed Engl ; 55(15): 4721-4, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-26922900

RESUMO

We report the first X-ray structure of the unique "head-to-middle" monoterpene synthase, lavandulyl diphosphate synthase (LPPS). LPPS catalyzes the condensation of two molecules of dimethylallyl diphosphate (DMAPP) to form lavandulyl diphosphate, a precursor to the fragrance lavandulol. The structure is similar to that of the bacterial cis-prenyl synthase, undecaprenyl diphosphate synthase (UPPS), and contains an allylic site (S1) in which DMAPP ionizes and a second site (S2) which houses the DMAPP nucleophile. Both S-thiolo-dimethylallyl diphosphate and S-thiolo-isopentenyl diphosphate bind intact to S2, but are cleaved to (thio)diphosphate, in S1. His78 (Asn in UPPS) is essential for catalysis and is proposed to facilitate diphosphate release in S1, while the P1 phosphate in S2 abstracts a proton from the lavandulyl carbocation to form the LPP product. The results are of interest since they provide the first structure and structure-based mechanism of this unusual prenyl synthase.


Assuntos
Dimetilaliltranstransferase/metabolismo , Monoterpenos/metabolismo , Monoterpenos Acíclicos , Cristalografia por Raios X , Dimetilaliltranstransferase/química , Modelos Moleculares , Relação Estrutura-Atividade
14.
Angew Chem Int Ed Engl ; 54(51): 15478-15482, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26768532

RESUMO

Structures of the iridoid synthase nepetalactol synthase in the presence of NAD(+) , NADPH or NAD(+) /10-oxogeranial were solved. The 10-oxogeranial substrate binds in a transoid-O1-C3 conformation and can be reduced by hydride addition to form the byproduct S-10-oxo-citronellal. Tyr178 Oζ is positioned 2.5 Šfrom the substrate O1 and provides the second proton required for reaction. Nepetalactol product formation requires rotation about C1-C2 to form the cisoid isomer, leading to formation of the cis-enolate, together with rotation about C4-C5, which enables cyclization and lactol production. The structure is similar to that of progesterone-5ß-reductase, with almost identical positioning of NADP, Lys146(147), Tyr178(179), and F342(343), but only Tyr178 and Phe342 appear to be essential for activity. The transoid 10-oxogeranial structure also serves as a model for ß-face hydride attack in progesterone 5ß-reductases and is of general interest in the context of asymmetric synthesis.


Assuntos
Apocynaceae/enzimologia , Iridoides/química , Ligases/química , Monoterpenos/química , NADP/química , NAD/química , Monoterpenos Acíclicos , Modelos Moleculares , Estrutura Molecular
15.
Br J Haematol ; 165(5): 649-58, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24601943

RESUMO

The CpG island methylator phenotype (CIMP) is an epigenetic phenomenon and plays an important role in tumourigenesis in various cancers. The identification of aberrant DNA methylation can be exploited for early diagnosis and risk assessment of patients. We identified a CIMP in myelodysplastic syndrome (MDS). Genes were screened for hypermethylation and transcription downregulation through genome-wide DNA methylation profiling and gene expression microarrays. Methylation-specific, real-time, and bisulfite-sequencing polymerase chain reaction were performed to validate selected genes. The hypermethylation of genes as a diagnostic tool for the detection of MDS was evaluated. Kaplan-Meier survival analysis and Cox regression were performed. A draft of an MDS CIMP was established and revised to 6 genes after validation in 20 patients and 20 controls. Further large-scale analysis showed that the majority of 211 MDS patients were hypermethylated in 6 genes. The area under the curve of CIMP was 0·9768 (95% confidence interval 0·9609-0·9928). A combination of 5 or more of the methylated genes showed a specificity of 95% and sensitivity of 91% for the diagnosis of MDS. We found CIMP positivity to be a significantly unfavourable prognostic factor for MDS. These results indicate that the newly established CIMP may improve diagnostic accuracy and prognosis assessment in MDS.


Assuntos
Ilhas de CpG/genética , Metilação de DNA , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Idoso , Estudos de Casos e Controles , Feminino , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Estudo de Associação Genômica Ampla , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , RNA Mensageiro/genética , Sensibilidade e Especificidade
16.
Molecules ; 19(12): 19718-31, 2014 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-25438082

RESUMO

In an attempt to improve the antitumor activity and reduce the side effects of irinotecan (2), novel prodrugs of SN-38 (3) were prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage. The synthesized compounds completely generated SN-38 in pH 7.4 buffer or in human plasma, while remaining stable under acidic conditions. All prodrug compounds demonstrated much greater in vitro antitumor activities against HeLa cells and SGC-7901 cells than irinotecan. The most active compounds, 5h, 7c, 7d, and 7f, exhibited IC50 values that were 1000 times lower against HeLa cells and 30 times lower against SGC-7901 cells than those of irinotecan, and the inhibitory activities of these prodrugs against acetylcholinesterase (AchE) were significantly reduced, with IC50 values more than 6.8 times greater than that of irinotecan. In addition, compound 5e exhibited the same level of tumor growth inhibitory activity as irinotecan (CPT-11) in a human colon xenograft model in vivo.


Assuntos
Camptotecina/análogos & derivados , Pró-Fármacos/síntese química , Pró-Fármacos/farmacologia , Animais , Camptotecina/síntese química , Camptotecina/química , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Irinotecano , Camundongos Nus , Pró-Fármacos/química , Pró-Fármacos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Reprod Sci ; 31(1): 99-106, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37612521

RESUMO

As a public health problem, premature ovarian insufficiency leads to infertility or sub-fertility. In addition to premature ovarian insufficiency (POI) increases the lifetime risk of bone fragility, cardiovascular disease, and cognitive impairment. To investigate the effects of environmental pollutants on the occurrence of POI and explore its mechanism, we conducted a computer search for articles published in electronic databases by December 13, 2022. Three reviewers independently examined all included studies and scored the qualities of included studies using the Newcastle-Ottawa Scale criteria. In this meta-analysis, eight clinical studies as well as ten preclinical findings showed a pooled OR of 2.331 and 95% CI of 1.968-2.760. This confirms that environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI. In addition, it is demonstrated from the results of this study that signaling pathway of calcium and PI3K Akt and Xpnpep2, Col1, Col3, Col4, Cx43, Egr3, Tff1, and Ptgs2 genes may all be involved in the process. Environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI.


Assuntos
Poluentes Ambientais , Infertilidade , Menopausa Precoce , Metais Pesados , Insuficiência Ovariana Primária , Feminino , Humanos , Poluentes Ambientais/efeitos adversos , Fosfatidilinositol 3-Quinases , Insuficiência Ovariana Primária/induzido quimicamente , Preparações Farmacêuticas
18.
Pediatr Emerg Care ; 29(1): 39-42, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23283261

RESUMO

BACKGROUND: Fractures are reported to complicate anterior shoulder dislocations in up to 50% of adults. For this reason, prereduction and postreduction radiographs are recommended for the routine evaluation of shoulder dislocations in all patients. To date, few data have been reported as to the incidence of fractures or as to the value of prereduction x-rays in pediatric patients with anterior shoulder dislocations. OBJECTIVES: The objectives of this study were to estimate the incidence of fractures associated with anterior shoulder dislocation in pediatric patients and to examine the value of prereduction radiographs for these patients. METHODS: This was a retrospective review of records for pediatric patients who presented to an emergency department (ED), received a diagnosis of anterior shoulder dislocation, and had at least 1 set of shoulder x-rays. RESULTS: Of 119 patients who met criteria for inclusion in the study, 3 patients (3%) had a fracture identified; 6 patients (5%) had a possible fracture identified. Except for 1 patient with an avulsion fracture who was transferred without a reduction attempt or further x-rays, all patients had their dislocation reduced uneventfully in the ED. CONCLUSIONS: In our sample of pediatric patients with anterior shoulder dislocations due to low-energy injury mechanisms, plain radiography identified a lower incidence of fractures than those reported from adult studies. Pediatric patients with anterior shoulder dislocations clinically apparent after clinical evaluation may not benefit from prereduction radiographs. Forgoing prereduction x-rays might expedite definitive pain relief for patients, lower cost and radiation exposure, and decrease ED length of stay.


Assuntos
Luxação do Ombro/diagnóstico por imagem , Fraturas do Ombro/diagnóstico por imagem , Adolescente , Distribuição de Qui-Quadrado , Criança , Feminino , Humanos , Incidência , Masculino , Medição da Dor , Radiografia , Estudos Retrospectivos , Luxação do Ombro/epidemiologia , Fraturas do Ombro/epidemiologia , Adulto Jovem
19.
Zhonghua Yi Xue Za Zhi ; 93(39): 3104-10, 2013 Oct 22.
Artigo em Chinês | MEDLINE | ID: mdl-24417987

RESUMO

OBJECTIVE: To assess the efficacy and safety of aranidipine versus retard-released felodipine in Chinese patients with mild-to-moderate essential hypertension. METHODS: This was a multicenter, randomized, double-blind, placebo and active antihypertensive drug parallel-controlled study. After 2 weeks of placebo run-in period, 315 patients at 6 centers with diastolic blood pressure (DBP) between 95 to 109 mm Hg (1 mm Hg = 0.133 kPa) while systolic blood pressure (SBP) below 180 mm Hg were randomized to receive aranidipine 5-20 mg/d (n = 126) or retard-released felodipine 5-10 mg/d (n = 126) for 12 weeks. Others (n = 63) received placebo for 4 weeks. Their blood pressures were evaluated at baseline and the end of Weeks 4, 8 and 12. RESULTS: After a 12-week treatment, SBP decreased from 148.8 ± 10.7 mm Hg to (132.8 ± 11.2) mm Hg while DBP dropped from ( 98.4 ± 2.8) mm Hg to (83.9 ± 7.5) mm Hg. There were significant differences with the baseline values (P < 0.0001). After a 4-week treatment, the reductions of SBP in aranidipine and retard-released felodipine groups were (12.1 ± 11.0) mm Hg and (12.2 ± 11.2) mm Hg while the reductions of DBP in two groups (11.8 ± 6.9) mm Hg and (12.1 ± 7.9) mm Hg respectively. The reductions of SBP and DBP in two groups were (2.3 ± 8.4) mm Hg and (4.0 ± 5.1) mm Hg and they were significantly superior to that in placebo group (P < 0.0001). But no significant difference existed between aranidipine and retard-released felodipine groups. Also no significant differences were found between these two antihypertensive therapy groups at the end of Weeks 4, 8 and 12 in the reduction of blood pressure, total response rate and blood pressure control rate. But 20 mg daily aranidipine was significantly superior to 10 mg daily retard-released felodipine in the control rates of SBP and DBP. Adverse events occurred at 24.22% and 29.92% in aranidipine and retard-released felodipine groups respectively (P = 0.305). CONCLUSION: Administration of aranidipine 5-20 mg/d can effectively control blood pressure and is not inferior to retard-released felodipine 5-10 mg/d. The efficacy of 20 mg/d aranidipine is superior to that of retard-released felodipine 5-10 mg/d. And the effectiveness and safety of aranidipine are similar to those of retard-released felodipine.


Assuntos
Anti-Hipertensivos/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Di-Hidropiridinas/administração & dosagem , Método Duplo-Cego , Hipertensão Essencial , Felodipino/administração & dosagem , Felodipino/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Artigo em Chinês | MEDLINE | ID: mdl-23905238

RESUMO

OBJECTIVE: To evaluate the benzene exposure level and cytopenia among the benzene exposed workers in Shanghai, China and to analyze the influential factors for the health of benzene-exposed workers. METHODS: A total of 3314 benzene-exposed workers, who were from 85 benzene-related enterprises selected by stratified random sampling based on enterprise sizes and industries, were included in the study. The time-weighted average (TWA) concentration of benzene in each workshop was measured by individual sampling and fixed point sampling, and the benzene exposure level in workshop was evaluated accordingly. The occupational health examination results and health status of benzene-exposed workers were collected. RESULTS: The median of TW A concentrations of benzene was 0.3 mg/m3. The TWA concentrations measured at 7 ( 1.4%) of the 504 sampling points were above the safety limit. Of the 7 points, 3 were from large enterprises, 2 from medium enterprises, and 2 from small enterprises; 3 were from shipbuilding industry, 1 from chemical industry, and 3 from light industry. Of the 3314 benzene-exposed workers, 451 ( 13.6%) had cytopenia, including 339 males ( 339/2548, 13.3%) and 112 females ( 112/766, 14.6% ). There were significant differences in the incidence rates of leukopenia and neutropenia among the benzene-exposed workers of different sexes and ages (P<0.05); there were significant differences in the incidence rate of cytopenia among the benzene-exposed workers of different ages and working years ( P<0.05 ); there were significant differences in the incidence of neutropenia among the benzene exposed workers of different working years ( P<0.05). CONCLUSION: Monitoring and intervention measures should be enhanced to protect the benzene-exposed workers in the large enterprises in shipbuilding industry and medium and private enterprises in chemical industry from occupational hazards.


Assuntos
Benzeno/toxicidade , Exposição Ocupacional , Pancitopenia/induzido quimicamente , Adolescente , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancitopenia/epidemiologia , Adulto Jovem
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