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1.
Endocr J ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38910131

RESUMO

This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) by comparing liraglutide with placebo or other drugs (mainly insulin). The PubMed, Web of Science, and National Library of Medicine databases were systematically searched from their inception until December 1, 2023. A meta-analysis was performed using Stata 15.1 software. A total of 12 studies with 13 outcome measures were included. The meta-analysis results revealed that liraglutide significantly reduced body mass index (mean difference [MD] = -1.06, 95%CI: -1.41, -0.70, p < 0.001), triglycerides (MD = -0.35, 95%CI: -0.61, -0.09, p = 0.0009), visceral adipose tissue (MD = -21.06, 95%CI: -34.58, -7.55, p = 0.002), and subcutaneous adipose tissue (MD = -20.53, 95%CI: -29.15, -11.90, p < 0.001) levels in patients with T2DM and NAFLD. Of the 11 studies, 2 reported the occurrence of adverse reactions, which were primarily gastrointestinal. Compared with placebo and other drugs (e.g., insulin), liraglutide may improve glucose metabolism, lipid and liver function parameters, and visceral and subcutaneous fat in patients with T2DM and NAFLD, thus constituting an effective treatment for these patients.

2.
Plant J ; 111(1): 164-182, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35460135

RESUMO

Drought is a major environmental stress that severely affects plant growth and crop productivity. FRIGIDA (FRI) is a key regulator of flowering time and drought tolerance in model plants. However, little is known regarding its functions in woody plants, including citrus. Thus, we explored the functional role of the citrus FRI ortholog (CiFRI) under drought. Drought treatment induced CiFRI expression. CiFRI overexpression enhanced drought tolerance in transgenic Arabidopsis and citrus, while CiFRI suppression increased drought susceptibility in citrus. Moreover, transcriptomic profiling under drought conditions suggested that CiFRI overexpression altered the expression of numerous genes involved in the stress response, hormone biosynthesis, and signal transduction. Mechanistic studies revealed that citrus dehydrin likely protects CiFRI from stress-induced degradation, thereby enhancing plant drought tolerance. In addition, a citrus brassinazole-resistant (BZR) transcription factor family member (CiBZR1) directly binds to the CiFRI promoter to activate its expression under drought conditions. CiBZR1 also enhanced drought tolerance in transgenic Arabidopsis and citrus. These findings further our understanding of the molecular mechanisms underlying the CiFRI-mediated drought stress response in citrus.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Citrus , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Citrus/genética , Citrus/metabolismo , Secas , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
3.
Angew Chem Int Ed Engl ; 62(11): e202218362, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36651829

RESUMO

The enantioselective α-oxidative coupling of enals with carboxylic acids was developed via the umpolung of an NHC-bound enolate with an iodine(III) reagent. The corresponding α-acyloxyl-ß,γ-unsaturated esters were afforded in good yields, with high regio- and enantioselectivities. The key step of the reaction involves the formation of enol iodine(III) intermediate from the enolate with iodosobenzene, which changes the polarity of α-carbon of the enal from nucleophilic to electrophilic, and thus facilitates the subsequent addition of carboxylate.

4.
J Org Chem ; 87(21): 14970-14974, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36264188

RESUMO

The ε-benzylation of γ-alkenyl-γ-oxidized enals via dual photoredox and N-heterocyclic carbene catalysis has been developed, affording the corresponding ε-benzyl-α,ß-γ,δ-bisunsaturated esters in moderate to good yields with exclusive regioselectivities. The reaction is proposed via the generation of benzyl radical under photocatalysis, followed by its addition to an NHC-bound trienolate intermediate.

5.
Bioorg Med Chem Lett ; 55: 128474, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34838651

RESUMO

BU-4664L is a naturally occurring N-farnesylated dibenzodiazepinone with important biological activities. Herein, we report the synthesis and antitumor evaluation of two series of BU-4664L derivatives bearing different substituent patterns on the dibenzodiazepinone core and with diverse side chains. All of the derivatives displayed micromolar activity against the human prostate cancer PC-3 cells, while lower or no activity against the human lung H460 cells. The most active derivatives were 10a and 16c which exerted antiproliferative activity against PC-3 cells with GI50 values of 5.66 and 5.94 µM, respectively, and thus represent promising lead compounds for further development.


Assuntos
Antineoplásicos/farmacologia , Dibenzazepinas/farmacologia , Sesquiterpenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dibenzazepinas/síntese química , Dibenzazepinas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Sesquiterpenos/síntese química , Sesquiterpenos/química , Relação Estrutura-Atividade
6.
Immunopharmacol Immunotoxicol ; 44(5): 786-794, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35635075

RESUMO

BACKGROUND: The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD: Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS: AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1ß, and IL-6 and regulating MDA, SOD, and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1ß, and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS: AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.


Assuntos
Ácido Ascórbico , Fator de Necrose Tumoral alfa , Alanina/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Aspartato Aminotransferases , Creatinina , Citocinas/metabolismo , Glutationa Peroxidase/farmacologia , Glutationa Peroxidase/uso terapêutico , Hidrocortisona/farmacologia , Hidrocortisona/uso terapêutico , Inflamação/tratamento farmacológico , Interleucina-1beta/farmacologia , Interleucina-6 , Malondialdeído , Camundongos , NF-kappa B/metabolismo , Nitrogênio/farmacologia , Nitrogênio/uso terapêutico , Estresse Oxidativo , Espécies Reativas de Oxigênio , Superóxido Dismutase , Fator de Necrose Tumoral alfa/farmacologia , Ureia/farmacologia , Ureia/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno
7.
Prep Biochem Biotechnol ; 52(5): 590-597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34528864

RESUMO

A novel arabitol dehydrogenase (ArDH) gene was cloned from a bacterium named Aspergillus nidulans and expressed heterologously in Escherichia coli. The purified ArDH exhibited the maximal activity in pH 9.5 Tris-HCl buffer at 40 °C, showed Km and Vmax of 1.2 mg/mL and 9.1 U/mg, respectively. The ArDH was used to produce the L-xylulose and coupled with the NADH oxidase (Nox) for the regeneration of NAD+. In further optimization, a high conversion of 84.6% in 8 hours was achieved under the optimal conditions: 20 mM of xylitol, 100 µM NAD+ in pH 9.0 Tris-HCl buffer at 30 °C. The results indicated the coupling system with cofactor regeneration provides a promising approach for L-xylulose production from xylitol.


Assuntos
D-Xilulose Redutase , Xilulose , Clonagem Molecular , D-Xilulose Redutase/genética , D-Xilulose Redutase/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Complexos Multienzimáticos , NAD/metabolismo , NADH NADPH Oxirredutases , Álcoois Açúcares , Xilitol , Xilulose/química , Xilulose/metabolismo
8.
Neoplasma ; 68(3): 645-651, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33780264

RESUMO

Concurrent chemoradiotherapy (CRT) based on cisplatin is recognized as the current standard treatment for locally advanced cervical cancer. The treatment of cervical cancer has reached a plateau in the last 20 years. Previous studies have proven that the epidermal growth factor receptor is correlated with chemo- and radioresistance and treatment failure. Hence, the purpose of this study was to investigate the efficacy and safety of icotinib combined with CRT in the treatment of locally advanced cervical cancer. Eligibility criteria included patients treated in the radiotherapy department of Taizhou Central Hospital of Zhejiang Province for stage IIB to IIIB cervical cancers who had not received anti-tumor treatment before and a performance status of 0 to 2. Patients were given icotinib 125 mg three times a day for 6 weeks, which was one week before the start of radiotherapy (500 centigrays in 28 fractions) and chemotherapy (40 mg/m2 administered weekly for 3-5 cycles). There were 29 patients who completed the I+CRT treatment, and it was tolerated well. The median follow-up time was 50 months and 27 patients (93.10%) achieved complete responses. The 5-year cumulative overall survival rate and disease-free survival rate were 58.4% and 60.9%, respectively. The treatment with I+CRT is safe and effective for locally advanced cervical cancer. As far as we know, this is the first study to report the 5-year survival rate of locally advanced cervical cancer with targeted therapy combined with chemoradiotherapy.


Assuntos
Neoplasias do Colo do Útero , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/uso terapêutico , Éteres de Coroa , Feminino , Humanos , Estadiamento de Neoplasias , Quinazolinas/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico
9.
Proc Natl Acad Sci U S A ; 115(9): 2210-2215, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29382762

RESUMO

Growing evidence shows that generation of reactive oxygen species (ROS) derived from antibiotic-induced metabolic perturbation contribute to antibiotic lethality. However, our knowledge of the mechanisms by which antibiotic-induced oxidative stress actually kills cells remains elusive. Here, we show that oxidation of dCTP underlies ROS-mediated antibiotic lethality via induction of DNA double-strand breaks (DSBs). Deletion of mazG-encoded 5-OH-dCTP-specific pyrophosphohydrolase potentiates antibiotic killing of stationary-phase mycobacteria, but did not affect antibiotic efficacy in exponentially growing cultures. Critically, the effect of mazG deletion on potentiating antibiotic killing is associated with antibiotic-induced ROS and accumulation of 5-OH-dCTP. Independent lines of evidence presented here indicate that the increased level of DSBs observed in the ΔmazG mutant is a dead-end event accounting for enhanced antibiotic killing. Moreover, we provided genetic evidence that 5-OH-dCTP is incorporated into genomic DNA via error-prone DNA polymerase DnaE2 and repair of 5-OH-dC lesions via the endonuclease Nth leads to the generation of lethal DSBs. This work provides a mechanistic view of ROS-mediated antibiotic lethality in stationary phase and may have broad implications not only with respect to antibiotic lethality but also to the mechanism of stress-induced mutagenesis in bacteria.


Assuntos
Antibacterianos/farmacologia , Nucleotídeos de Desoxicitosina/metabolismo , Mycobacterium smegmatis/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , DNA Bacteriano , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Deleção de Genes , Regulação Bacteriana da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Humanos , Macrófagos , Oxirredução , Pirofosfatases/genética , Pirofosfatases/metabolismo , Espécies Reativas de Oxigênio
10.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072027

RESUMO

A high-density genetic linkage map is essential for genetic and genomic studies including QTL mapping, genome assembly, and comparative genomic analysis. Here, we constructed a citrus high-density linkage map using SSR and SNP markers, which are evenly distributed across the citrus genome. The integrated linkage map contains 4163 markers with an average distance of 1.12 cM. The female and male linkage maps contain 1478 and 2976 markers with genetic lengths of 1093.90 cM and 1227.03 cM, respectively. Meanwhile, a genetic map comparison demonstrates that the linear order of common markers is highly conserved between the clementine mandarin and Poncirus trifoliata. Based on this high-density integrated citrus genetic map and two years of deciduous phenotypic data, two loci conferring leaf abscission phenotypic variation were detected on scaffold 1 (including 36 genes) and scaffold 8 (including 107 genes) using association analysis. Moreover, the expression patterns of 30 candidate genes were investigated under cold stress conditions because cold temperature is closely linked with the deciduous trait. The developed high-density genetic map will facilitate QTL mapping and genomic studies, and the localization of the leaf abscission deciduous trait will be valuable for understanding the mechanism of this deciduous trait and citrus breeding.


Assuntos
Mapeamento Cromossômico , Poncirus/genética , Locos de Características Quantitativas , Característica Quantitativa Herdável , Resposta ao Choque Frio , Biologia Computacional/métodos , Ligação Genética , Marcadores Genéticos , Humanos , Mutação INDEL , Repetições de Microssatélites , Fenótipo , Polimorfismo de Nucleotídeo Único
11.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3577-3582, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402280

RESUMO

Eucommiae Cortex is an authentic medicinal material with broad growing areas( such as Hunan and Sichuan provinces in China. It is well-known for its efficacy in tonifying liver and kidney,strengthening muscles and bones,and stabilizing fetus. It has also been proven in pharmacology to possess the functions such as lowering blood pressure and lipids. Hence,Eucommiae Cortex has attracted increasing attention. The current quality standards of Eucommiae Cortex vary in different countries or regions. The quality of Eucommiae Cortex products on the market is affected by mix-ups of non-medicinal parts and insufficient growth years. In view of these problems,this paper summarizes the current quality standards and research progress of Eucommiae Cortex in China and overseas,aiming to provide a reference for the establishment of the quality standards of Eucommiae Cortex.


Assuntos
Medicamentos de Ervas Chinesas , Eucommiaceae , China , Humanos , Padrões de Referência
12.
BMC Genomics ; 21(1): 233, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171259

RESUMO

BACKGROUND: Iron (Fe) deficiency is a common problem in citrus production. As the second largest superfamily of transcription factors (TFs), the basic/helix-loop-helix (bHLH) proteins have been shown to participate in the regulation of Fe homeostasis and a series of other biological and developmental processes in plants. However, this family of members in citrus and their functions in citrus Fe deficiency are still largely unknown. RESULTS: In this study, we identified a total of 128 CgbHLHs from pummelo (Citrus grandis) genome that were classified into 18 subfamilies by phylogenetic comparison with Arabidopsis thaliana bHLH proteins. All of these CgbHLHs were randomly distributed on nine known (125 genes) and one unknown (3 genes) chromosomes, and 12 and 47 of them were identified to be tandem and segmental duplicated genes, respectively. Sequence analysis showed detailed characteristics of their intron-exon structures, bHLH domain and conserved motifs. Gene ontology (GO) analysis suggested that most of CgbHLHs were annotated to the nucleus, DNA-binding transcription factor activity, response to abiotic stimulus, reproduction, post-embryonic development, flower development and photosynthesis. In addition, 27 CgbHLH proteins were predicted to have direct or indirect protein-protein interactions. Based on GO annotation, RNA sequencing data in public database and qRT-PCR results, several of CgbHLHs were identified as the key candidates that respond to iron deficiency. CONCLUSIONS: In total, 128 CgbHLH proteins were identified from pummelo, and their detailed sequence and structure characteristics and putative functions were analyzed. This study provides comprehensive information for further functional elucidation of CgbHLH genes in citrus.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Citrus/crescimento & desenvolvimento , Deficiências de Ferro , Mapeamento Cromossômico , Citrus/genética , Citrus/metabolismo , Duplicação Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteínas de Plantas/genética , Análise de Sequência de DNA , Análise de Sequência de RNA
13.
Int J Mol Sci ; 21(8)2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32295035

RESUMO

Autophagy is a highly conserved intracellular degradation pathway that breaks down damaged macromolecules and/or organelles. It is involved in plant development and senescence, as well as in biotic and abiotic stresses. However, the autophagy process and related genes are largely unknown in citrus. In this study, we identified 35 autophagy-related genes (CsATGs-autophagy-related genes (ATGs) of Citrus sinensis, Cs) in a genome-wide manner from sweet orange (Citrus sinensis). Bioinformatic analysis showed that these CsATGs were highly similar to Arabidopsis ATGs in both sequence and phylogeny. All the CsATGs were randomly distributed on nine known (28 genes) and one unknown (7 genes) chromosomes. Ten CsATGs were predicted to be segmental duplications. Expression patterns suggested that most of the CsATG were significantly up- or down-regulated in response to drought; cold; heat; salt; mannitol; and excess manganese, copper, and cadmium stresses. In addition, two ATG18 members, CsATG18a and CsATG18b, were cloned from sweet orange and ectopically expressed in Arabidopsis. The CsATG18a and CsATG18b transgenic plants showed enhanced tolerance to osmotic stress, salt, as well as drought (CsATG18a) or cold (CsATG18b), compared to wild-type plants. These results highlight the essential roles of CsATG genes in abiotic stresses.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Autofagia/genética , Citrus sinensis/genética , Genes de Plantas , Adaptação Biológica , Arabidopsis/genética , Citrus sinensis/classificação , Códon de Iniciação , Secas , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Genômica/métodos , Filogenia , Tolerância ao Sal , Estresse Fisiológico
14.
J Pept Sci ; 25(9): e3201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31309656

RESUMO

Targeted delivery of antitumor drugs is especially important for tumor therapy. Cell-penetrating peptides (CPPs) have been shown to be very effective drug carriers for tumor therapy. However, most CPPs lack tumor cell specificity. Here, we identified a highly efficient CPP, CAT, from the newly identified buffalo-derived cathelicidin family, which exhibits a preferential binding capacity for multiple tumor cell lines and delivers carried drug molecules into cells. CAT showed an approximately threefold to sixfold higher translocation efficiency than some reported cell-penetrating antimicrobial peptides, including the well-known classical CPP TAT. Moreover, the delivery efficiency of CAT was greater in a variety of tested tumor cells than in normal cells, especially for the human hepatoma cell line SMMC-7721, for which delivery was 7 times more efficient than the normal human embryonic lung cell line MRC-5, according to fluorescent labeling experiment results. CAT was conjugated to the Momordica charantia-derived type-I ribosome-inactivating protein MAP 30, and the cytotoxicity of the MAP 30-CAT fusion protein in the tumor cell line SMMC-7721 was significantly enhanced compared with that of the unconjugated MAP 30. The IC50 value of MAP 30-CAT was approximately 83 times lower than the IC50 value of the original MAP 30. Interestingly, the IC50 value of MAP 30 alone for MRC-5 was approximately twofold higher than the value for SMMC-7721, showing a small difference. However, when MAP 30 was conjugated to CAT, the difference in IC50 values between the two cell lines was significantly increased by 38-fold. The results of the flow cytometric detection of apoptosis revealed that the increase in cytotoxicity after CAT conjugation was mainly caused by the increased induction of apoptosis by the fusion protein. These results suggest that CAT, as a novel tumor-homing CPP, has great potential in drug delivery applications in vivo and will be beneficial to the development of tumor therapeutics.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Antineoplásicos/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Búfalos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Portadores de Fármacos/isolamento & purificação , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Relação Estrutura-Atividade , Catelicidinas
15.
BMC Med Educ ; 19(1): 182, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159796

RESUMO

BACKGROUND: Maladjustment and emotional distress are extremely prevalent among first-year medical students in college and are associated with numerous negative consequences for medical freshmen, their families and universities. The current research aimed to detect the efficacy of a well-being therapy in promoting adaptation to college life and alleviating emotional distress among medical freshmen. METHODS: One hundred one participants who met the inclusion criteria were enrolled in a single-blind randomized controlled trial. Well-being therapy was given to the intervention group weekly for 5 weeks (WBT, n = 50). At the same time, students in the placebo control condition (CC, n = 51) were required to record early memory for 5 weeks and at weekly meetings it would be shared voluntarily. Psychological well-being, adaptation, anxiety and depression were recorded at pretest, posttest, and at three-month follow-up. Data from 87 first-year students with complete follow-ups (WBT, n = 39; CC, n = 48) were analyzed over three time periods. RESULTS: Compared with the control group, students undergoing the 5-week well-being therapy reported larger improvements in psychological well-being and adaptation, and greater alleviation in symptoms of anxiety and depression from pretest to posttest to follow-up. CONCLUSIONS: Well-being intervention may provide first-year medical students with skills to efficiently manage maladjustment and emotional distress. It seems that medical freshmen would benefit a lot when such an intervention programme could be incorporated into the general medical education. TRIAL REGISTRATION NUMBER: ChiCTR-ROC-17012636. Registered 11 September 2017 (Retrospectively registered) at Chinese Clinical Trial Registry.


Assuntos
Adaptação Psicológica , Angústia Psicológica , Psicoterapia/métodos , Estudantes de Medicina/psicologia , Feminino , Humanos , Masculino , Estresse Psicológico/prevenção & controle , Adulto Jovem
16.
Clin Endocrinol (Oxf) ; 88(6): 928-935, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29504633

RESUMO

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) have been associated with adverse health outcomes for both mothers and children. Previous studies examining associations of maternal thyroid autoantibodies with HDP indicate conflicting results. The objective of this study was to examine associations of maternal thyroid autoantibody positivity in the first and the second trimesters with the risk of HDP. DESIGN, PARTICIPANTS AND MEASUREMENTS: In the Ma'anshan Birth Cohort study, a population-based prospective study in China, a total of 3474 pregnant women were enrolled between May 2013 and September 2014. Thyroid autoantibodies, including antithyroperoxidase autoantibody (TPOAb) and antithyroglobulin autoantibody (TgAb), as well as thyroid function tests, were measured in both the first and the second trimesters in 2893 pregnant women. Multivariate logistic regression analyses were conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for the associations between thyroid autoantibodies and HDP. RESULTS: Multivariate logistic regression analyses showed that TPOAb positivity in the first trimester was associated with a 1.80 (95% CI = 1.17-2.78) increased odds of HDP after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.93, 95% CI = 1.17-3.18). In addition, TgAb positivity in the first trimester was associated with a higher risk of HDP (OR = 1.78, 95% CI = 1.16-2.73) after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.89, 95% CI = 1.15-3.11). These associations were also seen among euthyroid women. Women with positive TPOAb in the second trimester seemed to have a higher risk of gestational hypertension (OR = 1.87, 95% CI = 1.02-3.43) after adjustment for confounders. However, among euthyroid women, TPOAb positivity in the second trimester was not associated with HDP. The TgAb status in the second trimester was not associated with HDP. CONCLUSIONS: Our results show that TPOAb positivity and TgAb positivity in the first trimester are associated with an increased risk of HDP. These data demonstrate that these associations are even seen among euthyroid women.


Assuntos
Hipertensão Induzida pela Gravidez/imunologia , Glândula Tireoide/imunologia , Adulto , Estudos de Coortes , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Adulto Jovem
17.
Environ Res ; 160: 239-246, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29028488

RESUMO

OBJECTIVE: There is concern over the potential placental effects of prenatal phthalate exposure, and the potential adverse effects of prenatal phthalate exposure require further study; however, few data are available in humans. We investigated the associations between phthalate exposure in each trimester and both placental size and shape at birth. METHODS: We measured the urinary concentrations of phthalate metabolites among 2725 pregnant women in the Ma'anshan Birth Cohort. Before collecting urine samples from each of the three trimesters, the pregnant women were interviewed via questionnaires. Placental information was obtained from hospital records. We estimated the sex-specific associations between urinary phthalate concentrations in each trimester and both placental size and shape at birth using adjusted multiple regression. A linear mixed model was used for the repeated measures analysis with subject-specific random intercepts and slopes for gestational age at sample collection to test the effect of phthalate levels on placental size and shape and to estimate the effect sizes. RESULTS: Overall, placental breadth increased by 0.148cm (95% CI: 0.078, 0.218) with each 1 ln-concentration increase in MBP in the first trimester. The difference between placental length and breadth (length-breadth) decreased by 0.086cm (95% CI: -0.159, -0.012) and 0.149cm (95% CI: -0.221, -0.076) with each 1 ln-concentration increase in MMP and MBP, respectively, in the first trimester. In the second trimester, placental thickness increased by 0.017cm (95% CI: 0.006, 0.027), 0.020cm (95% CI: 0.004, 0.036), 0.028cm (95% CI: 0.007, 0.048), and 0.035cm (95% CI: 0.018, 0.053) with each 1 ln-concentration increase in MMP, MBP, MEOHP, and MEHHP, respectively. In the third trimester, placental thickness increased by 0.037cm (95% CI: 0.019, 0.056) and 0.019cm (95% CI: 0, 0.037) with each 1 ln-concentration increase in MBP and MEHP, respectively. Multiple linear regression for each offspring sex indicated that prenatal phthalate exposure increased placental thickness in both the first and second trimesters in males, whereas the corresponding relationship was close to null in females. Linear mixed models (LMMs) yielded similar results. CONCLUSION: Our results suggest the presence of associations between prenatal phthalate exposure and placental size and shape. Exposure to certain phthalates may cause the placenta to become thicker and more circular. Associations appeared stronger for the subsample representing male offspring than those for the subsample representing female offspring. Given the few studies on this topic, additional research is warranted.


Assuntos
Exposição Materna/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Placenta/efeitos dos fármacos , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Ácidos Ftálicos/urina , Placenta/patologia , Gravidez , Adulto Jovem
18.
J Reprod Dev ; 63(3): 289-294, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28331165

RESUMO

During pregnancy, CD8+ T cells are important regulators in the balance of fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are well-recognized negative co-stimulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that CD8+ T cells co-expressing Tim-3 and PD-1 were down-regulated in the deciduae of female mice in abortion-prone matings compared with normal pregnant mice. In addition to their reduced numbers, the Tim-3+PD-1+CD8+ T cells produced lower levels of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, as well as a higher level of the pro-inflammatory cytokine interferon (IFN)-γ, relative to those from normal pregnancy. Furthermore, normal pregnant CBA/J females challenged with Tim-3- and/or PD-1-blocking antibodies were more susceptible to fetal resorption. These findings indicate that Tim-3 and PD-1 pathways play critical roles in regulating CD8+ T cell function and maintaining normal pregnancy.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Perda do Embrião , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Prenhez/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Animais , Feminino , Tolerância Imunológica , Interferon gama/metabolismo , Masculino , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Gravidez
19.
J Nutr ; 146(3): 509-15, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26817714

RESUMO

BACKGROUND: Evidence exists that maternal zinc status during pregnancy is linked to adverse pregnancy outcomes including abortion, fetal growth restriction, and neural tube defects. However, it remains unclear whether maternal serum zinc concentration (SZC) during pregnancy is associated with risk of preterm birth. OBJECTIVE: This study was designed to investigate the association between maternal SZC during pregnancy and risk of preterm birth. METHODS: For this substudy of the China-Anhui Birth Cohort Study, 3081 maternal-singleton pairs with detailed birth records and available serum samples were identified. The maternal SZC was determined with flame atomic absorption spectroscopy. A total of 169 preterm births were identified. In this study, the women were divided into tertiles on the basis of their SZC: low (<76.7 µg/dL), medium (76.7-99.6 µg/dL), and high (≥99.7 µg/dL). The ORs for preterm birth were estimated by using multiple logistic regression models. RESULTS: The median SZC was 87.3 µg/dL (range: 11.1-211 µg/dL). Incidences of preterm birth were 7.3% and 6.0% among subjects with low and medium SZCs, respectively, which were significantly higher than 3.1% among subjects with a high SZC [ORs (95% CIs) for low and medium SZCs: 2.45 (1.60, 3.74), P < 0.001, and 2.00 (1.29, 3.09), P < 0.01, respectively]. After adjustment for prepregnancy body mass index, maternal age, time of serum collection, gravidity, parity, and monthly income, adjusted ORs were 2.41 (95% CI: 1.57, 3.70; P < 0.001) and 1.97 (95% CI: 1.27, 3.05; P < 0.01) among subjects with low and medium maternal SZCs. CONCLUSIONS: Maternal serum zinc concentration during pregnancy is inversely associated with risk of preterm birth in the Chinese population, and the results are driven by maternal SZC in the first trimester.


Assuntos
Povo Asiático , Nascimento Prematuro/sangue , Nascimento Prematuro/epidemiologia , Zinco/sangue , Adulto , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Modelos Logísticos , Estado Nutricional , Gravidez , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
20.
Small ; 11(38): 5151-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26192395

RESUMO

Despite the great advantages of microporous carbons for applications in gas phase separation, liquid phase enrichment, and energy storage devices, direct experiment data and theoretical calculations on the relevance of properties and structures are quite limited. Herein, two model carbon materials are designed and synthesized, i.e., microporous carbon nanosheets (MCN) and microporous carbon spheres (MCS). They both have nearly same composition, surface chemistry, and specific surface area, known morphology, but distinguishable diffusion paths. Based on these two types of materials, a reliable relationship between the morphology with different diffusion paths and adsorption kinetics in both gas phase and liquid phase environments is established. When used for CO2 capture, MCN shows a high saturated CO2 capacity of 8.52 µmol m(-2) and 18.4 mmol cm(-3) at 273 K and ambient pressure, and its calculated first-order rate constant is ≈7.4 times higher than that of MCS. Moreover, MCN shows a quick and high uptake of Cr (VI) and a higher-rate performance for supercapacitors than MCS does. These results strongly confirm that MCN exhibits improved kinetics in gas phase separation, liquid phase enrichment, and energy storage devices due to its shorter diffusion paths and larger exposed geometrical area resulting from the nanosheet structure.

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