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1.
Colloids Surf B Biointerfaces ; 234: 113749, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38241893

RESUMO

Exploring the natural, safe, and effective antimicrobial is one of the preferable ways to control foodborne bacteria. In this work, novel oil-in-water nanoemulsions were formulated with sophorolipids and eugenol without any co-surfactant using a self-assembling strategy. These nanoemulsions showed high stability with sizes less than 200 nm when exposure to low concentrations of salt ions, various pH values (5.0, 7.0, 10.0), storage temperature and time. The synergistic antibacterial effects against both Gram-negative Escherichia coli and Gram-positive Bacillus cereus were determined with a minimum inhibitory concentration (MIC) value of 0.5 mg/mL and 0.125 mg/mL, respectively. Further microscopy (SEM, TEM, LCSM) examination and ATP/Na+-K+-ATPase assay results showed that the morphological changes, intensive cell membrane permeability, leakage of ATP, and decreased Na+-K+-ATPase contributed to the antibacterial effects. Moreover, the bonding mechanism between nanoemulsions and cell membranes were further evaluated by FTIR and ITC using a DPPC vesicle model, which demonstrated that the nanoemulsions adsorbed on the surface of bilayer, interacted with the hydrophobic chains of DPPC membrane mainly through the hydrophobic interaction, and altered the structural integrity of the lipid bilayer. These results not only provide a facile green strategy for fabricating stable nanoemulsions, but also highlight a new perspective for stabilizing essential oils for their widely application in food industry.


Assuntos
Eugenol , Óleos Voláteis , Ácidos Oleicos , Eugenol/farmacologia , Eugenol/química , Antibacterianos/farmacologia , Antibacterianos/química , Óleos Voláteis/química , Adenosina Trifosfatases , Trifosfato de Adenosina , Emulsões/química
2.
Acta Cir Bras ; 38: e385123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38055393

RESUMO

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. METHODS: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. RESULTS: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. CONCLUSIONS: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.


Assuntos
Cistite Intersticial , Cistite , Emodina , Humanos , Camundongos , Animais , Cistite Intersticial/tratamento farmacológico , Cistite Intersticial/metabolismo , Cistite Intersticial/patologia , Emodina/farmacologia , Emodina/uso terapêutico , Cistite/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fibrose
3.
Front Nutr ; 10: 1185047, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37396130

RESUMO

Soybeans are rich in proteins and phytochemicals such as isoflavones and phenolic compounds. It is an excellent source of peptides with numerous biological functions, including anti-inflammatory, anticancer, and antidiabetic activities. Soy bioactive peptides are small building blocks of proteins that are released after fermentation or gastrointestinal digestion as well as by food processing through enzymatic hydrolysis, often in combination with novel food processing techniques (i.e., microwave, ultrasound, and high-pressure homogenization), which are associated with numerous health benefits. Various studies have reported the potential health benefits of soybean-derived functional peptides, which have made them a great substitute for many chemical-based functional elements in foods and pharmaceutical products for a healthy lifestyle. This review provides unprecedented and up-to-date insights into the role of soybean peptides in various diseases and metabolic disorders, ranging from diabetes and hypertension to neurodegenerative disorders and viral infections with mechanisms were discussed. In addition, we discuss all the known techniques, including conventional and emerging approaches, for the prediction of active soybean peptides. Finally, real-life applications of soybean peptides as functional entities in food and pharmaceutical products are discussed.

4.
BMC Surg ; 23(1): 146, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248522

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most serious complication and the main reason for morbidity and mortality after pancreaticoduodenectomy (PD). Currently, there exists no flawless pancreaticojejunal anastomosis approach. We presents a new approach called Chen's penetrating-suture technique for pancreaticojejunostomy (PPJ), which involves end-to-side pancreaticojejunostomy by suture penetrating the full-thickness of the pancreas and jejunum, and evaluates its safety and efficacy. METHODS: To assess this new approach, between May 2006 and July 2018, 193 consecutive patients who accepted the new Chen's Penetrating-Suture technique after a PD were enrolled in this study. Postoperative morbidity and mortality were evaluated. RESULTS: All cases recovered well after PD. The median operative time was 256 (range 208-352) min, with a median time of 12 (range 8-25) min for performing pancreaticojejunostomy. Postoperative morbidity was 19.7% (38/193) and mortality was zero. The POPF rate was 4.7% (9/193) for Grade A, 1.0% (2/193) for Grade B, and no Grade C cases and one urinary tract infection. CONCLUSION: PPJ is a simple, safe, and reliable technique with ideal postoperative clinical results.


Assuntos
Pancreaticoduodenectomia , Pancreaticojejunostomia , Humanos , Pancreaticojejunostomia/métodos , Pancreaticoduodenectomia/métodos , Anastomose Cirúrgica/métodos , Pâncreas/cirurgia , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/etiologia , Técnicas de Sutura/efeitos adversos
5.
Acta cir. bras ; 38: e385123, 2023. graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1527601

RESUMO

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.


Assuntos
Animais , Camundongos , Fibrose , Emodina , Cistite Intersticial , Inflamação
6.
Biomolecules ; 12(11)2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36358972

RESUMO

The antioxidant activity of protein-derived peptides was one of the first to be revealed among the more than 50 known peptide bioactivities to date. The exploitation value associated with food-derived antioxidant peptides is mainly attributed to their natural properties and effectiveness as food preservatives and in disease prevention, management, and treatment. An increasing number of antioxidant active peptides have been identified from a variety of renewable sources, including terrestrial and aquatic organisms and their processing by-products. This has important implications for alleviating population pressure, avoiding environmental problems, and promoting a sustainable shift in consumption. To identify such opportunities, we conducted a systematic literature review of recent research advances in food-derived antioxidant peptides, with particular reference to their biological effects, mechanisms, digestive stability, and bioaccessibility. In this review, 515 potentially relevant papers were identified from a preliminary search of the academic databases PubMed, Google Scholar, and Scopus. After removing non-thematic articles, articles without full text, and other quality-related factors, 52 review articles and 122 full research papers remained for analysis and reference. The findings highlighted chemical and biological evidence for a wide range of edible species as a source of precursor proteins for antioxidant-active peptides. Food-derived antioxidant peptides reduce the production of reactive oxygen species, besides activating endogenous antioxidant defense systems in cellular and animal models. The intestinal absorption and metabolism of such peptides were elucidated by using cellular models. Protein hydrolysates (peptides) are promising ingredients with enhanced nutritional, functional, and organoleptic properties of foods, not only as a natural alternative to synthetic antioxidants.


Assuntos
Antioxidantes , Peptídeos , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Disponibilidade Biológica , Peptídeos/química , Hidrolisados de Proteína , Manipulação de Alimentos , Aditivos Alimentares
7.
J Mol Neurosci ; 72(5): 1108-1115, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35258801

RESUMO

Opioid addiction is a complicated and highly heritable brain disease. Dysfunction in dopaminergic signaling is involved in the pathogenesis of addictive disorders. Encoding a dopamine synthetase, the tyrosine hydroxylase (TH) gene has long been an interesting candidate in genetic association studies for opioid addiction. However, the mechanisms underlying associations of risk gene variants and opioid addiction remain unknown. In the present study, we first analyzed the association between TH gene variants and susceptibility and traits of heroin addiction in 801 patients with heroin addiction and 930 healthy controls. Methylation levels in the promoter region of the TH gene were detected and compared between the heroin addiction and healthy control groups. To reveal the potential mechanism of the association of TH gene variants and heroin addiction, correlations between the risk TH single nucleotide polymorphism (SNPs) for heroin addiction and the methylation and expression levels of the TH gene were examined. Our results demonstrated that SNP rs6356 was associated with susceptibility to heroin addiction. CpG TH_15 was hypermethylated in the heroin addiction group compared with the healthy control group. Notably, SNP rs6356 was correlated in an allele-specific manner with expression of the TH gene in the hippocampus and nucleus accumbens but not with methylation levels of CpG TH_15. Our findings suggest that the eQTL rs6356 was associated with susceptibility to heroin addiction by potentially affecting the expression of the TH gene in brain regions in the mesocorticolimbic dopamine system, including the hippocampus and nucleus accumbens.


Assuntos
Dependência de Heroína , Dopamina , Expressão Gênica , Dependência de Heroína/genética , Hipocampo/metabolismo , Humanos , Núcleo Accumbens/metabolismo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Tirosina 3-Mono-Oxigenase/genética
8.
Psychopharmacology (Berl) ; 238(12): 3511-3518, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34476566

RESUMO

RATIONALE: Opioid use disorder is a complicated brain disease with high heritability. The underlying mechanisms of the genetic underpinnings in the susceptibility and treatment response of opioid use disorder remain elusive. OBJECTIVES: To reveal the potential associations of genotypes and gene methylations of dopaminergic system genes, as well as roles of them in opioid use disorder. In the present study, we detected the DNA methylation in the promoter regions of five representative dopaminergic system genes (DRD1, DRD2, SLC6A3, TH, and COMT) between 120 patients with heroin use disorder in methadone maintenance treatment (MMT) program and 111 healthy controls. The associations of 25 SNPs in the above genes and methylation of 237 CpG sites, known as methylation quantitative trait loci (mQTLs), were determined. Then, the correlations of the above mQTLs and traits of heroin use disorder were analyzed in a sample set of 801 patients with heroin use disorder and 930 healthy controls. RESULTS: Our results demonstrated that several mQTLs in the DRD1 and DRD2 genes were identified both in the heroin use disorder and healthy control groups. Interestingly, rs4867798-CpG_174872884 and rs5326-CpG_174872884 in the DRD1 gene were the unique SNP-CpG pairs in the patients with heroin use disorder. Furthermore, mQTL rs5326 was associated with the susceptibility and effective dosage of MMT for heroin use disorder, and demonstrated allele-specific correlation with the expression of the DRD1 gene in the human caudate. CONCLUSIONS: Our findings suggest that some mQTLs may be associated with traits of opioid use disorder by implicating the DNA methylation and gene expression.


Assuntos
Dependência de Heroína , Locos de Características Quantitativas , Metilação de DNA , Proteínas da Membrana Plasmática de Transporte de Dopamina , Heroína , Dependência de Heroína/tratamento farmacológico , Dependência de Heroína/genética , Humanos , Metadona/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética
9.
Transl Androl Urol ; 10(8): 3465-3475, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532271

RESUMO

BACKGROUND: Holmium lasers have been used to treat bladder stones and achieve good therapeutic effects, but its efficacy remains to be explored. METHODS: The PubMed, Embase, Medline, Ovid, Springer, and Web of Sciences databases were searched from their establishment to December 31, 2020. Studies of randomized control trials (RCTs) examining the treatment of vesical calculi by holmium laser lithotripsy were identified. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was used to assess risk bias, and Rev Man5.3 was used to conduct the meta-analysis. RESULTS: A total of 10 studies, comprising 1,642 subjects, were included. The meta-analysis results showed that the surgery time and the hospitalization time of patients treated with holmium laser lithotripsy decreased, and the calculus removal rate increased. The experimental group had a lower incidence of adverse reactions, such as postoperative urinary tract infection, mucosal damage, vesical perforation, residual calculi, hematuria, and abdominal pain than the control group; however, no notable difference was observed in relation to surgery time, hospital stay, the calculus removal rate, mucosal damage, bladder perforation, hematuria, and abdominal pain between the 2 groups. DISCUSSION: Holmium laser lithotripsy significantly reduced the hospitalization time of patients treated with holmium laser lithotripsy and elevated the removal rate.

10.
Materials (Basel) ; 14(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34300822

RESUMO

The self-lubricating effect of the porous oil-containing cage is realized by storing and releasing lubricants through its internal micro-scale pore structure. The internal flow and heat transfer process in the micron-submicron pore structure is crucial to the self-lubricating mechanism of the porous oil-containing cage. To this end, a new modeling method of porous cage was proposed based on random seeds theory, and the local two-dimensional models of porous cage with different micro-scale pore structure were established. The multiphysics coupling simulation analysis of lubricating oil inside the porous cage with the effect of centrifugal force and thermal expansion was carried out based on the COMSOL Multiphysics platform. In order to characterize the micro-scale pore structure, new structural parameter indicators, such as relative surface perimeter, effective porosity, tortuosity and fluid properties related to the internal flow process, were all extracted from the above models. Combing with the Hagen-Poiseuille equation, a flow resistance model of oil flow inside the porous oil-containing cage was obtained. Finally, comparison of simulation results and analytical solutions of the micro-scale resistance model was carried out to verify the correctness of the micro-scale resistance model. The work provides a new direction for the study of the lubrication mechanism of the porous oil-containing cage.

11.
BMC Plant Biol ; 21(1): 287, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167489

RESUMO

BACKGROUND: Phosphoenolpyruvate carboxylase (PEPC) plays an important role in the primary metabolism of higher plants. Several studies have revealed the critical importance of PEPC in the interaction of carbon and nitrogen metabolism. However, the function mechanism of PEPC in nitrogen metabolism is unclear and needs further investigation. RESULTS: This study indicates that transgenic rice expressing the sugarcane C4-PEPC gene displayed shorter primary roots and fewer crown roots at the seedling stage. However, total nitrogen content was significantly higher in transgenic rice than in wild type (WT) plants. Proteomic analysis revealed that there were more differentially expressed proteins (DEPs) responding to nitrogen changes in transgenic rice. In particular, the most enriched pathway "glutathione (GSH) metabolism", which mainly contains GSH S-transferase (GST), was identified in transgenic rice. The expression of endogenous PEPC, GST and several genes involved in the TCA cycle, glycolysis and nitrogen assimilation changed in transgenic rice. Correspondingly, the activity of enzymes including GST, citrate synthase, 6-phosphofructokinase, pyruvate kinase and ferredoxin-dependent glutamate synthase significantly changed. In addition, the levels of organic acids in the TCA cycle and carbohydrates including sucrose, starch and soluble sugar altered in transgenic rice under different nitrogen source concentrations. GSH that the substrate of GST and its components including glutamic acid, cysteine and glycine accumulated in transgenic rice. Moreover, the levels of phytohormones including indoleacetic acid (IAA), zeatin (ZT) and isopentenyladenosine (2ip) were lower in the roots of transgenic rice under total nutrients. Taken together, the phenotype, physiological and biochemical characteristics of transgenic rice expressing C4-PEPC were different from WT under different nitrogen levels. CONCLUSIONS: Our results revealed the possibility that PEPC affects nitrogen metabolism through regulating GST, which provide a new direction and concepts for the further study of the PEPC functional mechanism in nitrogen metabolism.


Assuntos
Glutationa Transferase/metabolismo , Nitrogênio/metabolismo , Oryza/enzimologia , Fosfoenolpiruvato Carboxilase/metabolismo , Saccharum/enzimologia , Carbono/metabolismo , Oryza/genética , Oryza/metabolismo , Fosfoenolpiruvato Carboxilase/genética , Plantas Geneticamente Modificadas , Proteômica , Saccharum/genética , Transcriptoma
12.
J Mol Neurosci ; 71(9): 1752-1760, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34173192

RESUMO

To study the potential role of brain-derived neurotrophic factor (BDNF) methylation in heroin addiction, we first detected the methylation level of seven CpG islands that included 106 CpG sites in the promoter regions of BDNF from 120 people addicted to heroin and 113 controls. Methylation quantitative trait locus (mQTL) analysis was then employed to determine the association between the single-nucleotide polymorphism rs6265, a well-known locus shown to be correlated with heroin addiction, and the methylation levels of these CpG sites. Finally, we used the JASPAR database to predict whether transcription factors could bind to these CpG sites. We found that the methylation levels of CpG islands 6 and 7 and the methylation levels of BDNF_45 and BDNF_80 were significantly higher in the heroin addiction group than in the control group. We also found that rs6265 was an mQTL and was associated with the methylation level of BDNF_58. Using the JASPAR database, we found that ALX homeobox 3 (ALX3), achaete-scute family bHLH transcription factor 1 (ASCL1) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) could bind to CpG island 6, and ALX3 could bind to CpG island 7. In summary, we showed that increased DNA methylation in the promoter regions of the BDNF gene was associated with heroin addiction in Han Chinese.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Metilação de DNA , Dependência de Heroína/genética , Adulto , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ilhas de CpG , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas
13.
BMC Med Genet ; 21(1): 157, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736537

RESUMO

BACKGROUND: Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence. METHODS: A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions. RESULTS: We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence. CONCLUSIONS: Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.


Assuntos
Dopamina/biossíntese , Dopamina/metabolismo , Estudos de Associação Genética , Predisposição Genética para Doença , Dependência de Heroína/genética , Adulto , Euforia , Feminino , Interação Gene-Ambiente , Heroína/efeitos adversos , Dependência de Heroína/fisiopatologia , Humanos , Masculino , Memória , Metadona/efeitos adversos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética
14.
Cytogenet Genome Res ; 160(2): 63-71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092754

RESUMO

DCC netrin 1 receptor (DCC) affects the structure and function of the dopamine circuitry, which in turn affects the susceptibility to developing addiction. In a previous study, we found that single nucleotide polymorphism (SNP) rs12607853 in the 3' untranslated region (3'-UTR) of DCC was significantly associated with heroin addiction. In the current study, we first used bioinformatics prediction to identify the DCC rs12607853 C allele as a potential hsa-miR-422a and hsa-miR-378c target site. We then used vector construction and dual-luciferase reporter assays to investigate the targeting relationship of DCC rs12607853 with hsa-miR-422a and hsa-miR-378c. The dual-luciferase reporter gene assay confirmed that the C allele of rs12607853 in combination with hsa-miR-422a led to repressed dual-luciferase gene expression. Moreover, gene expression assays disclosed that hsa-miR-422a inhibited DCC expression at both the mRNA and protein levels. We also found that morphine inhibited the expression of hsa-miR-422a but increased the expression of DCC mRNA, and this change in the expression of hsa-miR-422a could not be reversed by naloxone, which suggested that the role of DCC in opioid addiction might be regulated by hsa-miR-422a. In summary, this study improves our understanding of the role of hsa-miR-422a and identifies the genetic basis of rs12607853, which might contribute to the discovery of new biomarkers or therapeutic targets for opioid addiction.


Assuntos
Receptor DCC/genética , Receptor DCC/metabolismo , Regulação para Baixo , Dependência de Heroína/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Biologia Computacional/métodos , Regulação para Baixo/efeitos dos fármacos , Células HEK293 , Humanos , Morfina/farmacologia , Naloxona/farmacologia , Polimorfismo de Nucleotídeo Único
15.
Neurosci Lett ; 717: 134704, 2020 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-31866536

RESUMO

INTRODUCTION: Heroin addiction is a chronic complex brain disease that contains multiple phenotypes, which vary widely among addicts and may be affected by genetic factors. A total of 801 unrelated heroin addicts were recruited and divided into different subgroups according to eight phenotypes of heroin addiction. Polymorphisms in GAD1 (rs3762555, rs3762556, rs3791878, rs3749034, rs11532313 and rs769395) and GAD2 (rs2839669, rs2839670 and rs2236418) were genotyped using the SNaPshot assay. Associations between genetic variants and the eight phenotypes were mainly assessed by binary logistic regression. RESULTS: We found that the frequencies of G allele of GAD1 rs3749034 and rs3762555 were associated with daily dose of methadone use and memory change after heroin addiction. The C allele frequency of GAD1 rs3762556 was associated with lower daily dose of methadone use. In GAD1, SNPs rs3762556, rs3762555, rs3791878 and rs3749034 had strong linkage, and the frequency of the C-G-C-A haplotype was higher in the lower dose of methadone group. Patients with the TT genotype of rs11542313 were maintained on lower dose of methadone than patients with the CC genotype. The G alleles of rs3762555 and rs3749034 were lower, while the T allele of rs11542313 was higher, in the memory decreased group. The results of association analyses of GAD2 with phenotypes of heroin addiction showed no significant differences. CONCLUSION: GAD1 polymorphisms were associated with phenotypes of heroin addiction, especially the daily dose of methadone use and memory change in the Han Chinese population. These results may provide individualized guidance for the treatment of heroin addiction.


Assuntos
Frequência do Gene/genética , Glutamato Descarboxilase/genética , Dependência de Heroína/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
16.
J Affect Disord ; 235: 96-104, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29655081

RESUMO

BACKGROUND: Alcohol abuse and anxiety disorders often occur concurrently, but their underlying cellular mechanisms remain unclear. Neuroadaptation within the medial prefrontal cortex (mPFC) have been implicated in the molecular mechanisms underlying alcohol drinking behavior and withdrawal. METHODS: A chronic alcohol exposure rat model (35 consecutive days of 10% alcohol intake and 48 h of withdrawal) was established, then, wortmannin (0.5 µg/side) was injected bilaterally into the mPFC. The elevated plus maze (EPM) and open field test (OFT) were used to assess anxiety-like behavior. Western blot assays were used to assess protein levels. RESULTS: We found that anxiety-like behavior peaked approximately 6 h after alcohol withdrawal. However, wortmannin greatly decreased alcohol intake and attenuated anxiety-like behavior in the alcohol exposure rats. Moreover, the PI3K-AKT-GSK3ß signaling pathway was activated after alcohol withdrawal, and phosphorylation of the downstream cAMP response element-binding protein (CREB) was increased. Wortmannin uniformly reversed PI3K-AKT-GSK3ß-CREB pathway phosphorylation. LIMITATIONS: The downstream GSK3ß activity was not intervened and a single dose level of wortmannin was used. CONCLUSION: Our results suggest that activating the PI3K-AKT-GSK3ß-CREB pathway in the mPFC is an important contributor to the molecular mechanisms underlying alcohol withdrawal. PI3K signaling pathway inhibitors are thus potential candidates for treating alcohol abuse.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Ansiedade/metabolismo , Transdução de Sinais/fisiologia , Síndrome de Abstinência a Substâncias/metabolismo , Consumo de Bebidas Alcoólicas/metabolismo , Animais , Ansiedade/induzido quimicamente , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Córtex Pré-Frontal/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Síndrome de Abstinência a Substâncias/psicologia
17.
Brain Res ; 1688: 54-64, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29550268

RESUMO

Ankyrin repeat and kinase domain containing 1 (ANKK1) and dopamine receptor D2 (DRD2) gene polymorphisms have long been considered to contribute to susceptibility to heroin dependence. Despite their adjacent locations, few studies have elucidated the role of the potential interaction between ANKK1 and DRD2 in heroin dependence. In the present study, we performed a systematic analysis of the association between 39 single nucleotide polymorphisms (SNPs) in these two genes and heroin dependence in 593 Chinese subjects. According to our results, polymorphisms of four unreported loci were associated with heroin dependence, among which rs11214598 of ANKK1 were still significant after multiple testing. We also conducted a meta-analysis of the association between a widely studied variant, rs1800497, and heroin dependence as a representative example and obtained a consistent outcome with our results. Notably, a 35.8 kilobases (kb) haplotype spanning ANKK1 and DRD2 was found to be a strong protective factor for heroin dependence. Gene-gene interaction analysis suggested that interactions exist within the ANKK1-DRD2 haplotype block between rs11214598 and rs1800497 in ANKK1 and rs2245805 and rs1079597 in DRD2. Our study highlights the importance of considering haplotypes spanning adjacent genes and the cooperation and interaction of proximal variants or genes in genetic association studies.


Assuntos
Dependência de Heroína/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de Dopamina D2/genética , Adulto , Povo Asiático , China , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
18.
Food Chem ; 243: 249-257, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29146335

RESUMO

Four peptide fractions PF1 (>5;kDa), PF2 (3-5;kDa), PF3 (1-3;kDa), PF4 (<1;kDa) were isolated from soybean hydrolysate using the ultrafiltration method. Then, d-xylose and l-cysteine were reacted with specific peptide solution at 120;°C for 2;h, and the molecular weight distribution (MWD), pH, colour, browning intensity, DPPH radical-scavenging activity, free amino acids and sensory characteristics of corresponding Maillard reaction products (MRPF1, MRPF2, MRPF3 and MRPF4) were evaluated, respectively. Peptides with low molecular weight showed higher contribution to the changes of pH, colour and browning intensity during Maillard reaction. The DPPH radical-scavenging activity of PF4 was significantly improved after Maillard reaction. Aroma volatiles and PLSR analysis suggested MRPF3 had the best sensory characteristics with higher contents of umami amino acids and lower of bitter amino acids, therefore it could be deduced that the umami and meaty characteristics were correlated with the peptides of 1-3;kDa.


Assuntos
Antioxidantes/farmacologia , Produtos Finais de Glicação Avançada , Glycine max/química , Proteínas de Plantas/química , Paladar , Aminoácidos/análise , Antioxidantes/química , Cor , Nariz Eletrônico , Sequestradores de Radicais Livres/farmacologia , Concentração de Íons de Hidrogênio , Hidrólise , Análise dos Mínimos Quadrados , Reação de Maillard , Peso Molecular , Peptídeos/química , Xilose/química
19.
Adv Mater ; 30(2)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29178432

RESUMO

A series of zirconium polyphenolate-decorated-(metallo)porphyrin metal-organic frameworks (MOFs), ZrPP-n (n = 1, 2), featuring infinite ZrIV -oxo chains linked via polyphenolate groups on four peripheries of eclipse-arranged porphyrin macrocycles, are successfully constructed through a top-down process from simulation to synthesis. These are the unusual examples of Zr-MOFs (or MOFs in general) based on phenolic porphyrins, instead of commonly known carboxylate-based types. Representative ZrPP-1 not only exhibits strong acid resistance (pH = 1, HCl) but also remains intact even when immersed in saturated NaOH solution (≈20 m), an exceptionally large range of pH resistance among MOFs. The metallation at the porphyrin core gives rise to materials with enhanced sorption and catalytic properties. In particular, ZrPP-1-Co, with precise and uniform distribution of active centers, exhibits not only high CO2 trapping capability (≈90 cm3 g-1 at 1 atm, 273 K, among the highest in Zr-MOFs) but also high photocatalytic activity for reduction of CO2 into CO (≈14 mmol g-1 h-1 ) and high selectivity over CH4 (>96.4%) without any cocatalyst under visible-light irradiation (λ > 420 nm). Given the strong chemical resistance under extreme alkali conditions, these catalysts can be recycled without appreciable loss of activity. The possible mechanism for photocatalytic reduction of CO2 -to-CO over ZrPP-1-Co is also proposed.

20.
Oncotarget ; 8(14): 23110-23119, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28416745

RESUMO

Recently, lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, regulates post-translational modifications and has great promise as new targets for cancer and other diseases. Moreover, the ability of LSD1 to induce the differentiation of stem cells has attracted great attention in biological fields. In this study, we designed LSD1 peptide inhibitor based on its substrate H3 peptide. Through introducing a disulfide bond to stabilize the native peptide into alpha helical structure, we get a peptide with higher cell permeability and stability compared to its parent form. Using gold nanorods (AuNRs) as delivery systems to deliver stable peptide into human MSCs, the delivery efficiency has been enhanced significantly by flow cytometry and cell fluorescent imaging. The intracellular delivery of stable peptide by AuNRs-PEI-based nanocarriers could inhibit the activation of LSD1, which together with hepatocyte growth factor (HGF) exhibits obviously synergistic effect to induce human MSCs differentiation. Furthermore, the hepatic marker genes AFP (alpha fetal protein) and ck19 are up-regulated by AuNRs-stable peptide (AuNRs- SP- PEI) with HGF. In conclusion, our study is the first time to use stable H3 peptide to inhibit LSD1 activation, which has been further delivered by AuNRs as nanocarriers into human MSCs.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Ouro , Histona Desmetilases/antagonistas & inibidores , Histonas/administração & dosagem , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanotubos , Células Cultivadas , Portadores de Fármacos/química , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Histona Desmetilases/metabolismo , Histonas/química , Histonas/farmacologia , Humanos , Células-Tronco Mesenquimais/fisiologia , Nanotubos/química , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacologia
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