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1.
Curr Issues Mol Biol ; 46(5): 3794-3809, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38785504

RESUMO

The endothelial glycocalyx (EGC) is a layer of proteoglycans (associated with glycosaminoglycans) and glycoproteins, which adsorbs plasma proteins on the luminal surface of endothelial cells. Its main function is to participate in separating the circulating blood from the inner layers of the vessels and the surrounding tissues. Physiologically, the EGC stimulates mechanotransduction, the endothelial charge, thrombocyte adhesion, leukocyte tissue recruitment, and molecule extravasation. Hence, severe impairment of the EGC has been implicated in various pathological conditions, including sepsis, diabetes, chronic kidney disease, inflammatory disorders, hypernatremia, hypervolemia, atherosclerosis, and ischemia/reperfusion injury. Moreover, alterations in EGC have been associated with altered responses to therapeutic interventions in conditions such as cardiovascular diseases. Investigation into the function of the glycocalyx has expanded knowledge about vascular disorders and indicated the need to consider new approaches in the treatment of severe endothelial dysfunction. This review aims to present the current understanding of the molecular mechanisms underlying cardiovascular diseases and to elucidate the impact of heart surgery on EGC dysfunction.

2.
Small ; 20(4): e2305841, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37712105

RESUMO

Pitch-derived carbon (PC) anode features the merits of low-cost, rich edge-defect sites, and tunable crystallization degree for potassium ion batteries (PIBs). However, gaining the PC anode with both rich edge-defect sites and robust structure remains challenging. Herein, micro-sized and robust PC/expanded-graphite (EG) composites (EGC) with rich edge-defect sites are massively synthesized via melting impregnation and confined pyrolysis. The PC is in situ encapsulated in micro-sized EG skeleton with robust chemical bonds between PC and EG after thermal treatment, endowing the structural stability as micro-sized carbon-carbon composites. The confinement effect originating from EG skeleton could suppress the crystallization degree of the PC and contribute rich edge-defect sites in EGC composites. Additionally, the EG skeleton inside EGC could form continuous electronic conduction nets and establish low-tortuosity carbonaceous electrodes, facilitating rapid electron/ion migration. While applied in PIBs, the EGC anode delivers a reversible capacity that up to 338.5 mAh g-1 at 0.1 A g-1 , superior rate performance of 127.5 mAh g-1 at 5.0 A g-1 , and long-term stability with 204.8 mAh g-1 retain after 700 cycles at 1.0 A g-1 . This novel strategy highlights an interesting category of heterogeneous carbon-carbon composite materials to keep pace with the demand for the future PIBs industry.

3.
Gastric Cancer ; 27(6): 1189-1200, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39028418

RESUMO

BACKGROUND: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. METHODS: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. RESULTS: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). CONCLUSIONS: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.


Assuntos
Instabilidade de Microssatélites , Mutação , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Idoso de 80 Anos ou mais , Adulto , Seguimentos , Genômica/métodos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Receptores de LDL
4.
Ann Bot ; 130(2): 159-171, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35700109

RESUMO

BACKGROUND AND AIMS: Condensed tannins, responsible for berry and wine astringency, may have been selected during grapevine domestication. This work examines the phylogenetic distribution of condensed tannins throughout the Vitaceae phylogenetic tree. METHODS: Green berries and mature leaves of representative true-to-type members of the Vitaceae were collected before 'véraison', freeze-dried and pulverized, and condensed tannins were measured following depolymerization by nucleophilic addition of 2-mercaptoethanol to the C4 of the flavan-3-ol units in an organic acidic medium. Reaction products were separated and quantified by ultrahigh pressure liquid chromatography/diode array detection/mass spectrometry. KEY RESULTS AND CONCLUSIONS: The original ability to incorporate epigallocatechin (EGC) into grapevine condensed tannins was lost independently in both the American and Eurasian/Asian branches of the Vitaceae, with exceptional cases of reversion to the ancestral EGC phenotype. This is particularly true in the genus Vitis, where we now find two radically distinct groups differing with respect to EGC content. While Vitis species from Asia are void of EGC, 50 % of the New World Vitis harbour EGC. Interestingly, the presence of EGC is tightly coupled with the degree of leaf margin serration. Noticeably, the rare Asian EGC-forming species are phylogenetically close to Vitis vinifera, the only remnant representative of Vitis in Eurasia. Both the wild ancestral V. vinifera subsp. sylvestris as well as the domesticated V. vinifera subsp. sativa can accumulate EGC and activate galloylation biosynthesis that compete for photoassimilates and reductive power.


Assuntos
Proantocianidinas , Vitaceae , Vitis , Catequina/análogos & derivados , Frutas , Filogenia , Folhas de Planta , Proantocianidinas/análise , Taninos/análise , Vitis/genética
5.
Bioorg Chem ; 119: 105515, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34896919

RESUMO

Natural products are a promising and underappreciated reservoir for the preferred chemical scaffolds in the search of antidiabetic drugs. In this study twenty-one EGC-based derivatives selective to inhibit human pancreatic α-amylase (HPA), the enzyme at the top of the starch digestion pyramid, have been designed and synthesized in terms of the lead myricetin-caffeic acid conjugate 1 reported ever. We focus on methylation of caffeic acid, length of a liker, a double bond contained in the linker on the inhibition activity and selectivity of EGC-based conjugates. As a result, methylation of caffeic acid and the length of a linker affect significantly the activity and selectivity of EGC-based conjugates, but the effect of a double in caffeic acid is limited. Conjugate 2a-1 having a six-carbon-atom linker fused to EGC and caffeic acid demonstrates the most ponent inhibitory activity to HPA and its selectivity towards HPA over α-glucosidase by far superior to that construct 1. Molecular docking studies reveal that conjugate 2a-1 accommodates well to the active site of HPA with four hydrogen bonds in the form of the preorganization of two moieties EGC and caffeic acid via π-stacking interaction. Collectively, conjugating caffeic acid and EGC with an appropriate linker possibly provides a new strategy for finding the specific HPA inhibitors in the discovery of anti-diabetes mellitus drugs.


Assuntos
Ácidos Cafeicos/farmacologia , Catequina/análogos & derivados , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Ácidos Cafeicos/síntese química , Ácidos Cafeicos/química , Catequina/síntese química , Catequina/química , Catequina/farmacologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Relação Dose-Resposta a Droga , Desenho de Fármacos , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Amilases/metabolismo
6.
Clin Gastroenterol Hepatol ; 19(8): 1611-1619.e1, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32565290

RESUMO

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. METHODS: We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. RESULTS: Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. CONCLUSIONS: ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Ressecção Endoscópica de Mucosa/efeitos adversos , Mucosa Gástrica/cirurgia , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
7.
Appl Environ Microbiol ; 87(5): e0266220, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33355100

RESUMO

Currently, only 5 (SEA to SEE) out of 27 known staphylococcal enterotoxins can be analyzed using commercially available kits. Six genes (seg, sei, sem, sen, seo, and seu), encoding putative and undetectable enterotoxins, are located on the enterotoxin gene cluster (egc), which is part of the Staphylococcus aureus genomic island vSaß. These enterotoxins have been described as likely being involved in staphylococcal food-poisoning outbreaks. The aim of the present study was to determine if whole-genome data can be used for the prediction of staphylococcal egc enterotoxin production, particularly enterotoxin G (SEG) and enterotoxin I (SEI). For this purpose, whole-genome sequences of 75 Staphylococcus aureus strains from different origins (food-poisoning outbreaks, human, and animal) were investigated by applying bioinformatics methods (phylogenetic analysis using the core genome and different alignments). SEG and SEI expression was tested in vitro using a sandwich enzyme-linked immunosorbent assay method. Strains could be allocated to 14 different vSaß types, each type being associated with a single clonal complex (CC). In addition, the vSaß type and CC were associated with the origin of the strain (human or cattle derived). The amount of SEG and SEI produced also correlated with the vSaß type and the CC of a strain. The present results show promising indications that the in vitro production of SEG and SEI can be predicted based on the vSaß type or CC of a strain. IMPORTANCE Besides having infectious properties in human and animals, S. aureus can produce different enterotoxins in food. The enterotoxins can cause vomiting and diarrhea, often involving many people. Most of these outbreaks remain undiscovered, as detection methods for enterotoxins are only available for a few enterotoxins but not for the more recently discovered enterotoxins G (SEG) and I (SEI). In this study, we show promising results that in vitro production of SEG and SEI can be predicted based on the whole-genome sequencing data of a strain. In addition, these data could be used to find the source (human or cattle derived) of an outbreak strain, which is the key for a better understanding of the role SEG and SEI play in foodborne outbreaks caused by S. aureus.


Assuntos
Enterotoxinas , Doenças Transmitidas por Alimentos , Staphylococcus aureus , Animais , Técnicas de Tipagem Bacteriana , Bovinos , Enterotoxinas/genética , Doenças Transmitidas por Alimentos/epidemiologia , Humanos , Família Multigênica , Filogenia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética
8.
J Gastroenterol Hepatol ; 36(11): 3092-3101, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34089623

RESUMO

BACKGROUND AND AIM: The biological characterization of microbial environment in early gastric cancer (EGC), other than Helicobacter pylori, is limited. This study aimed to explore the microbial microenvironment in chronic gastritis (CG), fundic gland polyps (FGPs), low-grade intraepithelial neoplasia (LGIN), and EGC. METHODS: 16S-rRNA gene sequencing and bioinformatic analysis were performed on 63 individuals with 252 mucosal biopsies or endoscopic submucosal dissection margin samples from endoscopy. RESULTS: The microbiota in gastric LGIN functions analogously to EGC in terms of functional prediction. Neoplastic lesions showed a significant difference to CG or FGPs in beta diversity of the microbiota. Bacteria genera including Paracoccus, Blautia, Barnesiella, Lactobacillus, Thauera, Collinsella were significantly enriched in gastric neoplastic mucosa (LGIN and EGC) compared with non-neoplastic tissues (CG and FGPs). While Pseudomonas and Kingella were depleted in neoplastic tissues. FGPs showed a distinctive microbial network system that negatively interacted with Helicobacter. CONCLUSIONS: In terms of the mucosal microbial microenvironment, gastric LGIN and EGC showed no significant difference as early neoplastic lesions. We observed a coordinated microbial microenvironment that correlated negatively with Helicobacter.


Assuntos
Carcinoma in Situ , Mucosa Gástrica , Gastrite/microbiologia , Microbioma Gastrointestinal , Pólipos/microbiologia , Neoplasias Gástricas , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Biópsia , Carcinoma in Situ/microbiologia , Carcinoma in Situ/patologia , Doença Crônica , Endoscopia Gastrointestinal , Fundo Gástrico/microbiologia , Fundo Gástrico/patologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/patologia , Microbioma Gastrointestinal/genética , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Humanos , Pólipos/patologia , RNA Ribossômico 16S/genética , Análise de Sequência de RNA , Gastropatias/microbiologia , Gastropatias/patologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Microambiente Tumoral
9.
World J Surg Oncol ; 19(1): 285, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548086

RESUMO

OBJECTIVE: To investigate the effect of Helicobacter pylori (H. pylori) eradication on the prognosis of postoperative early gastric cancer (EGC). METHODS: This is a retrospective study based on data from 6 hospitals. We identified 429 patients with EGC who underwent curative gastrectomy from January 2010 to December 2016. All of the patients were tested for H. pylori. Patients were divided into two groups, the successful H. pylori eradication group (group A, 268 patients) and the non-H. pylori eradication group (group B, 161 patients), for calculating the disease-free survival (DFS) and overall survival (OS) of each group. RESULT: Positive node metastasis (hazard ratio (HR), 3.13; 95% confidence interval (CI), 1.84-5.32; P < 0.001), undifferentiated type (HR, 2.54; 95% CI, 1.51-4.28; P < 0.001), and non-H. pylori eradication (HR, 1.73; 95% CI, 1.08-2.77; P = 0.023) were statistically significantly independent risk factors of recurrence. Patient's age ≥60 years old (HR, 3.32; 95% CI, 2.00-5.53; P < 0.001), positive node metastasis (HR, 3.71; 95% CI, 2.25-6.12; P < 0.001), undifferentiated type (HR, 3.06; 95% CI, 1.79-5.23; P < 0.001), and non-H. pylori eradication (HR, 1.83; 95% CI, 1.11-3.02; P = 0.018) were statistically significantly independent risk factors of overall survival. CONCLUSION: H. pylori eradication treatment could prevent the recurrence of postoperative EGC to prolong the overall survival of patients with EGC.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antibacterianos/uso terapêutico , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
10.
Int J Mol Sci ; 22(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063607

RESUMO

Angiotensin II (Ang II) regulates colon contraction, acting not only directly on smooth muscle but also indirectly, interfering with myenteric neuromodulation mediated by the activation of AT1 /AT2 receptors. In this article, we aimed to explore which mediators and cells were involved in Ang II-mediated colonic contraction in the TNBS-induced rat model of colitis. The contractile responses to Ang II were evaluated in distinct regions of the colon of control animals or animals with colitis in the absence and presence of different antagonists/inhibitors. Endogenous levels of Ang II in the colon were assessed by ELISA and the number of AT1/AT2 receptors by qPCR. Ang II caused AT1 receptor-mediated colonic contraction that was markedly decreased along the colons of TNBS-induced rats, consistent with reduced AT1 mRNA expression. However, the effect mediated by Ang II is much more intricate, involving (in addition to smooth muscle cells and nerve terminals) ICC and EGC, which communicate by releasing ACh and NO in a complex mechanism that changes colitis, unveiling new therapeutic targets.


Assuntos
Angiotensina II/genética , Colite/genética , Doenças Inflamatórias Intestinais/genética , Sistema Renina-Angiotensina/genética , Antagonistas de Receptores de Angiotensina/farmacologia , Animais , Colite/fisiopatologia , Colo/metabolismo , Colo/patologia , Sistema Nervoso Entérico/metabolismo , Sistema Nervoso Entérico/patologia , Humanos , Doenças Inflamatórias Intestinais/patologia , Células Intersticiais de Cajal/metabolismo , Células Intersticiais de Cajal/patologia , Masculino , Contração Muscular/genética , Contração Muscular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Neuroglia/metabolismo , Neuroglia/patologia , Óxido Nítrico/metabolismo , Ratos , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/genética , Transmissão Sináptica/genética
11.
Cell Physiol Biochem ; 52(3): 606-616, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30907988

RESUMO

BACKGROUND/AIMS: Aberrant expression of miR-106b is a specific symptom of many solid carcinomas. Overexpression of miR-106b has been observed in gastric cancer. The effect of miR-106b on gastric cancer has been investigated in different cell culture models. However, the effect of miR-106b on metastasis of early gastric cancer (EGC) remains unknown. METHODS: In the study, qRT-PCR, FISH, western blot, luciferase reporter assay, migration and invasion assays, flow cytometry and TUNEL staining were used to investigate the effect of miR-106b on metastasis of EGC. RESULTS: To explore the function of miR-106b in EGC, we investigated the downstream signaling of miR-106b and found that ALEX1 was a direct target of miR-106 in gastric cancer cells. Up-regulation of ALEX1 effectively rescued the cell apoptosis induced by miR-106b inhibitor and promoted the expression levels of phosphorylation of JAK1 and STAT3. Moreover, overexpression of JAK1 reduced the cell apoptosis induced by miR-106b inhibitor and decreased the expression levels of the apoptotic proteins in gastric cancer cells. Furthermore, down-regulation of miR-106b promoted apoptosis of gastric cancer cells via inhibiting JAK1/STAT3 signaling pathway in vitro and in vivo. In addition, GLPG0643, a JAK1 inhibitor, enhanced the inhibitory effect of miR-106b inhibitor on gastric cancer growth in vivo. CONCLUSION: These findings provided a potential therapeutic manner for the treatment of metastasis of EGC in clinic.


Assuntos
Proteínas do Domínio Armadillo/metabolismo , MicroRNAs/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias Gástricas/patologia , Animais , Antagomirs/metabolismo , Apoptose , Proteínas do Domínio Armadillo/química , Proteínas do Domínio Armadillo/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Humanos , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Metástase Neoplásica , Proteínas Oncogênicas/química , Proteínas Oncogênicas/genética , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Regulação para Cima
12.
J Pediatr ; 206: 113-118, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30573213

RESUMO

OBJECTIVES: To assess the impact of participation in an educational presentation on electrocardiogram (ECG) interpretation in children on pediatric practitioners' ability to accurately interpret ECGs. STUDY DESIGN: Pediatric healthcare providers at a pediatric clinic with >65 000 visits/year were eligible to participate. A 1-hour ECG educational module that provided a systematic approach to ECG interpretation was presented to 8 providers who consented (6 pediatricians, 2 pediatric nurse practitioners). A test on 11 ECGs (normal, normal-variant, and abnormal ECGs) was given before and 2 weeks after the educational module. Outcomes included correct interpretation of each ECG as normal or abnormal and correct identification of specific ECG findings. Data analysis was descriptive and included χ2 and Student t test. RESULTS: Mean score (SD) for correct interpretation of ECGs as normal or abnormal improved from 35% (48%) (95% CI 25.0-45.4) to 77% (42%) (95% CI 68.3-86.2) after the ECG educational module (P < .001). Mean (SD) pretest score for correct identification in the normal ECG category improved from 45% (50%) (95% CI 28.9-61.1) to 68% (47%) (95% CI 52.3-82.7) (P= .003). In the abnormal ECG category, correct identification improved from 31% (47%) (95% CI 17.6-44.9) to 83% (5%) (95% CI 72.4-94.3) after the module (P < .001). CONCLUSIONS: Education of pediatric practitioners on ECG interpretation significantly improves their ability to distinguish normal from abnormal and to identify specific abnormalities. Limitations included small sample size and short-term follow-up.


Assuntos
Cardiologia/métodos , Cardiologia/normas , Eletrocardiografia , Pediatria , Arritmias Cardíacas/diagnóstico , Criança , Competência Clínica , Morte Súbita Cardíaca/prevenção & controle , Estudos de Viabilidade , Feminino , Humanos , Capacitação em Serviço , Masculino , Variações Dependentes do Observador , Profissionais de Enfermagem Pediátrica , Estudos Prospectivos , Reprodutibilidade dos Testes
13.
Pharmacol Res ; 146: 104283, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31129178

RESUMO

Natural products have represented attractive alternatives for disease prevention and treatment over the course of human history and have contributed to the development of modern drugs. These natural products possess beneficial efficacies as well as adverse efffects, which vary largely among individuals because of genetic variations in their pharmacokinetics and pharmacodynamics. As with other synthetic chemical drugs, the dosing of natural products can be optimized to improve efficacy and reduce toxicity according to the pharmacogenetic properties. With the emergence and development of pharmacogenomics, it is possible to discover and identify the targets/mechanisms of pharmacological effects and therapeutic responses of natural products effectively and efficiently on the whole genome level. This review covers the effects of genetic variations in drug metabolizing enzymes, drug transporters, and direct and indirect interactions with the pharmacological targets/pathways on the individual response to natural products, and provides suggestions on dosing regimen adjustments of natural products based on their pharmacokinetic and pharmacogenetic paratmeters. Finally, we provide our viewpoints on the importance and necessity of pharmacogenetic and pharmacogenomic research of natural products in natural medicine's rational development and clinical application of precision medicine.


Assuntos
Produtos Biológicos/farmacologia , Produtos Biológicos/farmacocinética , Transporte Biológico , Humanos , Farmacogenética
14.
Biosci Biotechnol Biochem ; 82(2): 200-206, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29327676

RESUMO

The functions of food have three categories: nutrition, palatability, and bioregulation. As the onset of lifestyle-related diseases has increased, many people have shown interest in functional foods that are beneficial to bioregulation. We believe that functional foods should be highly palatable for increased acceptance from consumers. In order to design functional foods with a high palatability, we have investigated about the palatability, especially in relation to the taste of food. In this review, we discuss (1) the identification of taste receptors that respond to functional food components; (2) an analysis of the peripheral taste transduction system; and (3) the investigation of the relationship between physiological functions and taste signals.


Assuntos
Alimento Funcional , Percepção Gustatória/efeitos dos fármacos , Animais , Alimento Funcional/análise , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Biosci Biotechnol Biochem ; 82(4): 636-646, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29191128

RESUMO

Inhibition of excessive fructose intake in the small intestine could alleviate fructose-induced diseases such as hypertension and non-alcoholic fatty liver disease. We examined the effect of phytochemicals on fructose uptake using human intestinal epithelial-like Caco-2 cells which express the fructose transporter, GLUT5. Among 35 phytochemicals tested, five, including nobiletin and epicatechin gallate (ECg), markedly inhibited fructose uptake. Nobiletin and ECg also inhibited the uptake of glucose but not of L-leucine or Gly-Sar, suggesting an inhibitory effect specific to monosaccharide transporters. Kinetic analysis further suggested that this reduction in fructose uptake was associated with a decrease in the apparent number of cell-surface GLUT5 molecules, and not with a change in the affinity of GLUT5 for fructose. Lastly, nobiletin and ECg suppressed the permeation of fructose across Caco-2 cell monolayers. These findings suggest that nobiletin and ECg are good candidates for preventing diseases caused by excessive fructose intake.


Assuntos
Catequina/análogos & derivados , Flavonas/farmacologia , Frutose/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Células CACO-2 , Catequina/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Transportador de Glucose Tipo 5/metabolismo , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Cinética , Compostos Fitoquímicos/farmacologia
16.
Molecules ; 23(4)2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29690635

RESUMO

Green tea is consumed as a beverage worldwide and has beneficial effects, such as a lower risk of cardiovascular disease and cancer. A quantitative analysis of the beneficial components in plasma is important for understanding the potential health benefits of green tea. Four catechins­epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), epigallocatechin (EGC), and epicatechin (EC)­which account for the majority of the components of green tea, were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In this study, a validated method was optimized to obtain the blood concentrations after the one-time ingestion of 630 mg green tea extract with digoxin and then after the ingestion of 630 mg green tea repeatedly for 15 days. The calibration curve, including the LLOQ, was constructed over 1⁻500 ng/mL for EGCG, ECG, and EGC and 0.1⁻50 ng/mL for EC. The method for inter- and intra-validation was applied, acceptable for both accuracy and precision. We successfully developed an appropriate UPLC-MS/MS method for human plasma with good reproducibility and sensitivity. Thus, this method could be applied for future preclinical and clinical studies on EGCG, ECG, EGC, and EC.


Assuntos
Catequina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Chá/química , Catequina/análogos & derivados , Humanos , Reprodutibilidade dos Testes
17.
Toxicol Appl Pharmacol ; 329: 112-120, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28532672

RESUMO

In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1ß signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1ß signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea.


Assuntos
Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Catequina/análogos & derivados , Fibroblastos/efeitos dos fármacos , Interleucina-1beta/farmacologia , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Chá/química , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antirreumáticos/química , Antirreumáticos/isolamento & purificação , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Domínio Catalítico , Catequina/química , Catequina/isolamento & purificação , Catequina/farmacologia , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Fibroblastos/imunologia , Fibroblastos/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/química , MAP Quinase Quinase Quinases/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Fosforilação , Fitoterapia , Plantas Medicinais , Ligação Proteica , Inibidores de Proteínas Quinases/isolamento & purificação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Foodborne Pathog Dis ; 13(11): 592-601, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27792397

RESUMO

The enterotoxin gene cluster (egc) has been proposed to contribute to the Staphylococcus aureus colonization, which highlights the need to evaluate genetic diversity and virulence gene profiles of the egc-positive population. Here, a total of 43 egc-positive isolates (16.2%) were identified from 266 S. aureus isolates that were obtained from various food and clinical specimens in Shanghai. Seven different egc profiles were found based on the polymerase chain reaction (PCR) result for egc genes. Then, these 43 egc-positive isolates were further typed by multilocus sequence typing, pulsed-field gel electrophoresis (PFGE), multiple-locus variable-number tandem-repeat analysis (MLVA), and accessory gene regulatory (agr) typing. It showed that the 43 egc-positive isolates displayed 17 sequence types, 28 PFGE patterns, 29 MLVA types, and 4 agr types, respectively. Among them, the dominant clonal lineage was CC5-agr II (48.84%). Thirty toxin and 20 adhesion-associated genes were detected by PCR in egc-positive isolates. Notably, invasive toxin genes showed a high prevalence, such as 76.7% for Panton-Valentine leukocidin encoding genes, 27.9% for sec, and 23.3% for tsst-1. Most of the examined adhesion-associated genes were found to be conserved (76.7-100%), whereas the fnbB gene was only found in 8 (18.6%) isolates. In addition, 33 toxin gene profiles and 13 adhesion gene profiles were identified, respectively. Our results imply that isolates belonging to the same clonal lineage harbored similar adhesion gene profiles but diverse toxin gene profiles. Overall, the high prevalence of invasive virulence genes increases the potential risk of egc-positive isolates in S. aureus infection.


Assuntos
Enterotoxinas/metabolismo , Microbiologia de Alimentos , Regulação Bacteriana da Expressão Gênica , Família Multigênica , Intoxicação Alimentar Estafilocócica/microbiologia , Staphylococcus aureus/metabolismo , Fatores de Virulência/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , China , Eletroforese em Gel de Campo Pulsado , Enterotoxinas/genética , Exotoxinas/genética , Exotoxinas/metabolismo , Perfilação da Expressão Gênica , Humanos , Leucocidinas/genética , Leucocidinas/metabolismo , Tipagem Molecular/métodos , Tipagem de Sequências Multilocus , Filogenia , Polimorfismo Genético , Intoxicação Alimentar Estafilocócica/fisiopatologia , Staphylococcus aureus/classificação , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , Sequências de Repetição em Tandem , Transativadores/genética , Transativadores/metabolismo , Fatores de Virulência/genética , Vômito/etiologia
19.
Pak J Med Sci ; 31(6): 1437-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26870111

RESUMO

OBJECTIVE: To detect the clinicopathological factors associated with lymph node metastases in early gastric cancer. METHODS: We retrospectively evaluated the distribution of metastatic nodes in 198 patients with early gastric cancer treated in our hospital between May 2008 and January 2015, the clinicopathological factors including age, gender, tumor location, tumor size, macroscopic type, depth of invasion, histological type and venous invasion were studied, and the relationship between various parameters and lymph node metastases was analyzed. RESULTS: In this study, one hundred and ninety-eight patients with early gastric cancer were included, and lymph node metastasis was detected in 28 patients. Univariate analysis revealed a close relationship between tumor size, depth of invasion, histological type, venous invasion, local ulceration and lymph node metastases. Multivariate analysis revealed that the five factors were independent risk factors for lymph node metastases. CONCLUSION: The clinicopathological parameters including tumor size, depth of invasion, local ulceration, histological type and venous invasion are closely correlated with lymph node metastases, should be paid high attention in early gastric cancer patients.

20.
Clin Gastroenterol Hepatol ; 12(1): 120-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23954641

RESUMO

Gastrointestinal cancers are among the commonest cancers worldwide. Treatment of these cancers at an early stage will result in a significantly better prognosis. Endoscopic submucosal dissection (ESD) is a new method of endoscopic resection that can achieve higher rates of en bloc resection for early gastrointestinal neoplasia. Three retrospective case-control studies showed that ESD achieved significantly higher en bloc resection with lower recurrence rates than endoscopic mucosal resection for treatment of early gastric cancers. Most of the reports on clinical outcomes of ESD were from countries with a high incidence of gastric cancers, including Japan and Korea. The development of ESD has been slow for countries outside Japan and Korea because ESD requires a high level of endoscopic skills, and the dissection was performed single-handedly without assistance. A newly developed robotic endoscopic platform will enhance the performance of ESD through the use of 2 robotic arms: one arm for retraction of the mucosa and the other arm for dissection.


Assuntos
Endoscopia/métodos , Neoplasias Gástricas/cirurgia , Humanos , Japão , Coreia (Geográfico) , Robótica/métodos , Resultado do Tratamento
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