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1.
Gastrointest Endosc ; 99(3): 387-397.e6, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37858760

RESUMO

BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Neoplasias Colorretais/patologia , Estudos Prospectivos , Estudos Retrospectivos , Estudos de Coortes , Resultado do Tratamento
2.
J Asian Nat Prod Res ; 25(10): 1012-1020, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36916389

RESUMO

Seventeen compounds were isolated and identified from the ethyl acetate part of Zanthoxylum bungeanum Maxim., including one new compound 18-acetyloxyneocryptotanshinone (1) and 16 known compounds (2-17). Their structures were elucidated by extensive spectroscopy. The absolute configuration of 1 was confirmed by electronic circular dichroism (ECD). All compounds were evaluated for the inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, of which 1 and 10 exhibited the most significant inhibitory effect, with IC50 of 17.29 and 10.27 µM, respectively.


Assuntos
Zanthoxylum , Zanthoxylum/química , Óxido Nítrico , Lipopolissacarídeos/farmacologia , Macrófagos
3.
Stroke ; 52(12): 3918-3925, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34404235

RESUMO

BACKGROUND AND PURPOSE: Researches on rare variants of NOTCH3 in the general Chinese population are lacking. This study aims to describe the spectrum of rare NOTCH3 variants by whole-exome sequencing in a Chinese community-based cohort and to investigate the association between rare NOTCH3 variants and age-related cerebral small vessel disease. METHODS: The cross-sectional study comprised 1065 participants who underwent whole-exome sequencing and brain magnetic resonance imaging. NOTCH3 variants with minor allele frequency<1% in all 4 public population databases (1000 Genomes, ESP6500siv2_ALL, GnomAD_ALL, and GnomAD_EAS) were defined as rare variants. Multivariable linear and logistic regressions were used to investigate the associations between rare NOTCH3 variants and volume of white matter hyperintensities and cerebral small vessel disease burden. Clinical and imaging characteristics of rare NOTCH3 variant carriers were summarized. RESULTS: Sixty-five rare NOTCH3 variants were identified in 147 of 1065 (13.8%) participants, including 57 missense single nucleotide polymorphisms (SNPs), 5 SNPs in splice branching sites, and 3 frameshift deletions. A significantly higher volume of white matter hyperintensities and heavier burden of cerebral small vessel disease was found in carriers of rare NOTCH3 EGFr (epidermal growth factor-like repeats)-involving variants, but not in carriers of EGFr-sparing variants. The carrying rate of rare EGFr-involving NOTCH3 variants in participants with dementia or stroke was significantly higher than those without dementia or stroke (12.4% versus 6.6%, P=0.041). Magnetic resonance imaging signs suggestive of CADASIL were found in 3.4% (5/145) rare EGFr cysteine-sparing NOTCH3 variant carriers but not in 2 cysteine-altering NOTCH3 variant carriers. CONCLUSIONS: Carriers of rare NOTCH3 variants involving the EGFr domain may be genetically predisposed to age-related cerebral small vessel disease in the general Chinese population.


Assuntos
Doenças de Pequenos Vasos Cerebrais/genética , Predisposição Genética para Doença/genética , Receptor Notch3/genética , Idoso , Povo Asiático/genética , Estudos de Coortes , Estudos Transversais , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade
4.
FASEB J ; 34(12): 16291-16306, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33078906

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most general liver disease characterized by a continuum of liver abnormalities ranging from simple fatty liver to advanced stage of nonalcoholic steatohepatitis, cirrhosis, and even hepatocellular carcinoma. The pathological drivers of NAFLD are complex and largely undefined. It is increasingly identified that the imbalance between renin-angiotensin system and ACE2/Ang-(1-7)/Mas axis, as well as mitochondrial dysfunction associated with NAFLD. However, no known empirical research has focused on exploring the effect of the regulation of mitochondrial respiration chain activity by Ang-(1-7)/Mas on the prevention of NAFLD. Here, we evaluated the interaction and relevance of hepatic Ang-(1-7)/Mas-axis challenge with glucolipid metabolism and mitochondrial condition in vivo and in vitro. In this context, we found that Mas deletion in mice contributed to the severe glucose intolerance, insulin resistance, and hepatic steatosis which accompanied by elevated levels of serum/ hepatic alanine aminotransferase, aspartate aminotransferase, and triglycerides, as well as the mitochondrial dysfunction. Whereas forced upregulation of Mas or Ang-(1-7) administration could significantly attenuate these consequences by downregulating the expression of hepatic lipogenic proteins and enzymes for gluconeogenesis. Furthermore, activation of Ang-(1-7)/Mas arm could improve the IRS-1/Akt/AMPK pathway and enhance the mitochondrial energy utilization. Considered together, it is becoming extremely hopeful to provide a new perspective for Ang-(1-7)/Mas axis for the therapeutics of NAFLD.


Assuntos
Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Glicolipídeos/metabolismo , Fígado/metabolismo , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fragmentos de Peptídeos/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Linhagem Celular Tumoral , Regulação para Baixo/fisiologia , Células Hep G2 , Humanos , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proto-Oncogene Mas , Transdução de Sinais/fisiologia
5.
Transpl Int ; 34(12): 2483-2493, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510581

RESUMO

The use of Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) in adoptive immunotherapy in hematopoietic stem cell transplantation (HSCT) patients with post-transplantation lymphoproliferative disorder (PTLD) has demonstrated safety and effectiveness. EBV-CTLs might also be the effective treatment of refractory PTLD of solid organ transplantation (SOT) recipients. Two independent assessors searched Pubmed, Embase, Cochrane Library, and Web of Science from their inception to November 2020. Eleven studies with 76 patients (42, 55% male) were included. We extracted the data and completed the quality assessments. Most of the studies were from Europe and the USA. Liver and kidney transplantation accounted for most of the transplant types. Thirty-five (46.1%) patients were diagnosed with monomorphic PTLD, and B lymphocyte type was the most common. All the patients received primary treatment for PTLD while it was ineffective. CTLs included autologous EBV-CTLs (15/76, 22%) and HLA-matched third-party EBV-CTLs (61/76, 78%). The response rate for EBV-CTL treatment of refractory PTLD was 66%. Of 50 patients, 36 achieved complete remission and 14 achieved partial remission. EBV-DNA level decreased in 39 patients. Adverse reactions were rare and mild. We conclude that adoptive therapy with EBV-specific CTLs is safe, well-tolerated, and effective in PTLD.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Rim , Transtornos Linfoproliferativos , Feminino , Herpesvirus Humano 4 , Humanos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Masculino , Linfócitos T Citotóxicos
6.
Molecules ; 26(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208577

RESUMO

Metal-organic frameworks (MOFs) have been rapidly developed for their broad applications in many different chemistry and materials fields. In this work, a multi-dentate building block 5-(4-(tetrazol-5-yl)phenyl)-isophthalic acid (H3L) containing tetrazole and carbolxylate moieties was employed for the synthesis of a two-dimensional (2D) lanthanide MOF [La(HL)(DMF)2(NO3)] (DMF = N,N-dimethylformamide) (1) under solvothermal condition. The fluorescent sensing application of 1 was investigated. 1 exhibits high sensitivity recognition for antibiotic nitrofurantoin (Ksv: 3.0 × 103 M-1 and detection limit: 17.0 µM) and amino acid l-tyrosine (Ksv: 1.4 × 104 M-1 and detection limit: 3.6 µM). This work provides a feasible detection platform of 2D MOFs for highly sensitive discrimination of antibiotics and amino acids.


Assuntos
Elementos da Série dos Lantanídeos/química , Nitrofurantoína/química , Tirosina/química , Antibacterianos/química , Cristalografia por Raios X/métodos , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Nitrofurantoína/metabolismo , Tirosina/metabolismo
7.
BMC Oral Health ; 21(1): 83, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622296

RESUMO

BACKGROUND: Optimum Glide Path (OGP) is a new reciprocating motion aiming to perform efficient glide path preparation in constricted canals. The aim of this study was to investigate and compare manual and OGP movement in terms of canal transportation and centering ability in glide path preparation of constricted canals. METHODS: Thirty constricted mesial root canals of mandibular molars, with initial apical size no larger than ISO#8, were selected and negotiated with #6-#8 K-files under the microscope. Canals were randomly divided into two experimental groups: Group 1 (MAN, n = 15): Glide path was established by using #10-#15 stainless steel K-files manually; Group 2 (OGP, n = 15): #10-#15 Mechanical Glide Path super-files were used with OGP motion (OGP 90°, 300 rpm). Each instrument was used to prepare only 2 canals (as in one mesial root). Canals were scanned before and after glide path preparation with micro-computed tomography (micro-CT) to evaluate root canal transportation and centering ratio at 1, 3 and 5 mm levels from the root apex. File distortions and separations were recorded. Paired t-test was used to statistically evaluate the data (P < .05). RESULTS: Group 2 showed a significantly lower transportation value than group 1 at 1-mm and 3-mm levels (P < .05), however the difference at 5-mm level was not significant. There was no significant difference regarding the centering ratio between the groups. Six #10 K-files were severely distorted in group 1, while no file separation or distortion was found in group 2. CONCLUSIONS: OGP motion performed significantly less canal transportation (apical 3 mm) and file distortion during glide path establishment in constricted canals comparing to manual motion, while the centering ability between the two was similar. CLINICAL RELEVANCE: OGP reciprocating motion provides a safer and efficient clinical approach compared to traditional manual motion in glide path establishment with small files in constricted canals.


Assuntos
Cavidade Pulpar , Preparo de Canal Radicular , Cavidade Pulpar/diagnóstico por imagem , Desenho de Equipamento , Humanos , Dente Molar/diagnóstico por imagem , Dente Molar/cirurgia , Raiz Dentária , Microtomografia por Raio-X
8.
Epidemiol Infect ; 148: e127, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32054550

RESUMO

Transmission of varicella occurs frequently in schools and households. We investigated the characteristics of varicella cases derived from within-household transmission and the modes of varicella transmission between school and household settings in Shanghai, China, from 2009 to 2018. Within-household transmission occurred in 278 households, of which 134 transmission events were between children. Sixty-one household varicella transmission events may be attributed to isolation procedures for infected students during school outbreaks, and 7.6% of school outbreaks were caused by schoolchildren cases derived from within-household transmission. The frequency of 'school-household-school' transmission adds an additional layer of complexity to the control of school varicella outbreaks. Administration of varicella vaccine as post-exposure prophylaxis after exposure is considered to be an effective measure to control varicella spread within households and schools.


Assuntos
Varicela/epidemiologia , Varicela/transmissão , Surtos de Doenças , Instituições Acadêmicas , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Características da Família , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
9.
J Cell Physiol ; 234(9): 15647-15653, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30740678

RESUMO

Long noncoding RNAs (lncRNAs) are involved in multiple nervous system diseases, including neuropathic pain. Previous studies have demonstrated that lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a diagnostic biomarker in many diseases. Nevertheless, the function of MALAT1 in neuropathic pain progression is still unclear. Here, we established a chronic constriction injury (CCI) rat model. We found that MALAT1 was remarkably upregulated in CCI rats. In addition, neuropathic pain behaviors such as mechanical and thermal hyperalgesia were reduced by the inhibition of MALAT1. Meanwhile, the loss of MALAT1 was able to depress the neuroinflammation process via the inhibition of COX-2, interleukin-1ß, and interleukin-6. A previous study has indicated that miR-206 upregulation can restrain the CCI-induced neuropathic pain. Furthermore, we exhibited that miR-206 was significantly downregulated and silence of MALAT1 restrained its expression in CCI rats. For another, ZEB2 was a target of miR-206 and it was shown that ZEB2 was elevated in CCI rats in a time-dependent manner. Overexpression of miR-206 obviously suppressed ZEB2 levels in rat microglial cells. Subsequently, it was demonstrated that upregulation of miR-206 rescued the neuropathic pain triggered by ZEB2 overexpression in vivo through neuroinflammation inhibition. Overall, we indicated that suppression of MALAT1 ameliorated neuropathic pain progression via miR-206/ZEB2 axis.

10.
Biochem Biophys Res Commun ; 508(2): 556-562, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30509498

RESUMO

Regulatory Factor X-box binding transcriptional factor 6 (Rfx6) plays an important role in the differentiation and development of pancreas in mammals. However, the direct target genes of Rfx6 to regulate this process were largely unknown. The present study aimed to investigate the function of Rfx6 on regulating pancreatic differentiation and development in a physiologically-relevant context. We performed the chromatin immunoprecipitation followed by the next generation sequencing analysis (ChIP-seq) using whole pancreatic tissue harvested from C57/BL6 adult mice to find target genes of Rfx6. We captured 4146 unique peaks in the genome region of the adult murine pancreas. Among all these binding peaks, a majority were located in intron or intergenic regions. We further annotated all peaks to their nearest gene, and over 1000 genes were captured as Rfx6-binding genes in the pancreas. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis found that Rfx6-binding genes to be associated with the pancreas developmental process. A portion of selected ChIP-seq targets related with pancreas differentiation including Pdx1, Neurod1, Hnf1a, Nkx6-1, St18 and Shox2 were selected and validated as true targets by independent qPCR experiments. In addition, Rfx6 can directly bind to upstream of MiR-145, MiR-195, and possibly other non-protein-coding functional RNAs to control adult mouse pancreatic differentiation. Interestingly, our study revealed that Rfx6 played an important role in insulin translation by binding to the Eif2ak1, Upf1, and Eif5. Our data provide direct target genes of Rfx6 during pancreas development and point to Rfx6 as a potential therapeutic target for improving insulin protein content.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Insulina/biossíntese , Pâncreas/crescimento & desenvolvimento , Fatores de Transcrição de Fator Regulador X/genética , Animais , Diferenciação Celular , Regulação da Expressão Gênica , Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Organogênese , Pâncreas/química , Ligação Proteica , Fatores de Transcrição de Fator Regulador X/metabolismo
11.
BMC Infect Dis ; 19(1): 592, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286917

RESUMO

BACKGROUND: Norovirus (NoV) is recognized as a leading cause of acute gastroenteritis (AGE) outbreaks in settings globally. Studies have shown that employees played an important role in the transmission mode during some NoV outbreaks. This study aimed to investigate the prevalence of NoV infection and duration of NoV shedding among employees during NoV outbreaks, as well as factors affecting shedding duration. METHODS: Specimens and epidemiological data were collected from employees who were suspected of being involved in the transmission or with AGE symptoms during NoV outbreaks in Xuhui District, Shanghai, from 2015 to 2017. Specimens were detected using real-time RT-PCR to determine whether or not employees had become infected with NoV. Specimens were collected every 3-7 days from NoV-infected employees until specimens became negative for NoV. RESULTS: A total of 421 employees were sampled from 49 NoV outbreaks, and nearly 90% of them (377/421) were asymptomatic. Symptomatic employees showed significantly higher prevalence of NoV infection than asymptomatic ones (70.5% vs. 17.0%, P < 0.01). The average duration of NoV shedding was 6.9 days (95% confidence interval: 6.1-7.7 days) among 88 NoV-infected individuals, and was significantly longer in symptomatic individuals than in asymptomatic ones (9.8 days vs. 5.6 days, P < 0.01). In Cox proportional-hazards model, after adjusting age and gender, symptoms was the only factor associated with duration of NoV shedding. CONCLUSIONS: Compared with asymptomatic employees, symptomatic employees had higher prevalence of NoV infection and longer durations of NoV shedding. Since NoV shedding duration among NoV-infected employees tends to be longer than their isolation time during outbreaks, reinforcement of hygiene practices among these employees is especially necessary to reduce the risk of virus secondary transmissions after their return to work.


Assuntos
Infecções por Caliciviridae , Surtos de Doenças/estatística & dados numéricos , Gastroenterite , Norovirus/genética , Adulto , Canal Anal/virologia , Infecções Assintomáticas/epidemiologia , Infecções por Caliciviridae/diagnóstico , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , China/epidemiologia , Feminino , Gastroenterite/diagnóstico , Gastroenterite/epidemiologia , Gastroenterite/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/análise , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real
12.
Lipids Health Dis ; 18(1): 207, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775868

RESUMO

OBJECTIVE: Endoplasmic reticulum (ER) stress and mitochondrial function affected intramuscular fat accumulation. However, there is no clear evident on the effect of the regulation of ER stress and mitochondrial function by Angiotensin-converting enzyme 2 (ACE2) on the prevention of intramuscular fat metabolism. We investigated the effects of ACE2 on ER stress and mitochondrial function in skeletal muscle lipid metabolism. METHODS: The triglyceride (TG) content in skeletal muscle of ACE2 knockout mice and Ad-ACE2-treated db/db mice were detected by assay kits. Meanwhile, the expression of lipogenic genes (ACCα, SREBP-1c, LXRα, CPT-1α, PGC-1α and PPARα), ER stress and mitochondrial function related genes (GRP78, eIF2α, ATF4, BCL-2, and SDH6) were analyzed by RT-PCR. Lipid metabolism, ER stress and mitochondrial function related genes were analyzed by RT-PCR in ACE2-overexpression C2C12 cell. Moreover, the IKKß/NFκB/IRS-1 pathway was determined using lysate sample from skeletal muscle of ACE2 knockout mice. RESULTS: ACE2 deficiency in vivo is associated with increased lipid accumulation in skeletal muscle. The ACE2 knockout mice displayed an elevated level of ER stress and mitochondrial dysfunctions in skeletal muscle. In contrast, activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced TG content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice. Additionally, ACE2 improved skeletal muscle lipid metabolism and ER stress genes in the C2C12 cells. Mechanistically, endogenous ACE2 improved lipid metabolism through the IKKß/NFκB/IRS-1 pathway in skeletal muscle. CONCLUSIONS: ACE2 was first reported to play a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function. This study may provide a strategy for treating insulin resistance in skeletal muscle.


Assuntos
Estresse do Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Metabolismo dos Lipídeos/genética , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Peptidil Dipeptidase A/genética , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Chaperona BiP do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Peptidil Dipeptidase A/deficiência , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo , Triglicerídeos/metabolismo
13.
Inorg Chem ; 57(11): 6218-6221, 2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29775051

RESUMO

A CuI-MOF was found to be a highly selective visual sensor for recognizing C2H2. Gas chromatography studies indicated that it can be used to effectively remove minor amounts of C2H2 from C2H4/C2H2 mixtures (98:2) and produce highly pure C2H4 (nearly 100%).

14.
Phytother Res ; 31(8): 1119-1127, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28504367

RESUMO

The autophagy-lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Autofagia/efeitos dos fármacos , Produtos Biológicos/farmacologia , Lisossomos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Neurônios Dopaminérgicos/patologia , Humanos
15.
Int J Mol Sci ; 18(2)2017 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-28134846

RESUMO

Hippocampal neurogenesis plays a critical role in the formation of new neurons during learning and memory development. Attenuation of neurogenesis in the brain is one of the primary causes of dementia in Alzheimer's disease (AD), and, conversely, modulating the process of hippocampal neurogenesis benefit patients with AD. Traditional Chinese medicine (TCM), particularly herbal medicine, has been in use for thousands of years in Asia and many regions of the world for the treatment of cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the role of neurotrophic factors, signal transducing factors, epigenetic modulators and neurotransmitters in neurogenesis, and we also discuss the functions of several Chinese herbs and their active molecules in activating multiple pathways involved in neurogenesis. TCM herbs target pathways such as Notch, Wnt, Sonic Hedgehog and receptor tyrosine kinase pathway, leading to activation of a signaling cascade that ultimately enhances the transcription of several important genes necessary for neurogenesis. Given these pathway activating effects, the use of TCM herbs could be an effective therapeutic strategy for the treatment of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Neurogênese , Animais , Humanos , Medicina Tradicional Chinesa , Transdução de Sinais
16.
Biomed Environ Sci ; 29(11): 818-824, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27998388

RESUMO

This cross-sectional study aimed to examine the association between selenium levels and diabetes in an older population with life-long natural exposure to selenium in rural China. A total of 1856 subjects aged 65 years or older from four Chinese rural counties with different environmental selenium levels were evaluated. Analysis of covariance models and logistic regression models were used to examine the relationship between nail selenium levels and serum glucose, serum insulin, insulin resistance [using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)], and the risk of diabetes. The mean nail selenium level was 0.461 µg/g and the prevalence rate of diabetes was 8.3% in this population. The mean nail selenium level was significantly higher in the group with diabetes than in the group without diabetes (P<0.0001). The adjusted odds ratios for diabetes were 2.65 (95% CI: 1.48 to 4.73), 2.47 (95% CI: 1.37 to 4.45), and 3.30 (95% CI: 1.85 to 5.88) from the second selenium quartile to the fourth quartile, respectively, compared with the first quartile group. The mean serum glucose and HOMA-IR in the higher selenium quartile groups were significantly higher than those of the lowest quartile group. However, no significant differences in insulin were observed among the four quartile groups. A long-term, higher level of exposure to selenium may be associated with a higher risk of diabetes. Future studies are needed to elucidate the association between selenium and insulin resistance.


Assuntos
Diabetes Mellitus/metabolismo , Unhas/metabolismo , Selênio/metabolismo , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Humanos , Masculino , População Rural
17.
Artigo em Inglês | MEDLINE | ID: mdl-29620799

RESUMO

We reported a 16-year-old boy who developed Henoch-Schönlein purpura (HSP) 15 days after receiving a seasonal influenza vaccine. His symptoms improved temporally with treatment but he developed HSP nephritis (HSPN) that relapsed multiple times over the following three years. This case of Henoch-Schönlein purpura may have been due to the seasonal influenza vaccine. The mechanism for this association is unclear. Practitioners should be aware of this possible complication.


Assuntos
Vasculite por IgA/etiologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Vacinação/efeitos adversos , Adolescente , Humanos , Masculino , Nefrite/etiologia
19.
Environ Pollut ; 342: 123090, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38072026

RESUMO

Perfluorooctanoic acid (PFOA) is a widely used industrial compound that has been found to induce intestinal toxicity. However, the underlying mechanisms have not been fully clarified and effective interventions are rarely developed. Inulin, a prebiotic, has been used as a supplement in human daily life as well as in gastrointestinal diseases and metabolic disorders. In this study, male mice were exposed to PFOA with or without inulin supplementation to investigate the enterotoxicity and potential intervention effects of inulin. Mice were administered PFOA at 1 mg/kg/day, PFOA with inulin at 5 g/kg/day, or Milli-Q water for 12 weeks. Histopathological analysis showed that PFOA caused colon shortening, goblet cell reduction, and inflammatory cell infiltration. The expression of the tight junction proteins ZO-1, occludin and claudin5 significantly decreased, indicating impaired barrier function. According to the RNA-sequencing analysis, PFOA exposure resulted in 917 differentially expressed genes, involving 39 significant pathways, such as TNF signaling and cell cycle pathways. In addition, the protein expression of TNF-α, IRG-47, cyclinB1, and cyclinB2 increased, while Gadd45γ, Lzip, and Jam2 decreased, suggesting the involvement of the TNF signaling pathway, cell cycle, and cell adhesion molecules in PFOA-associated intestinal injury. Inulin intervention alleviated PFOA-induced enterotoxicity by activating the PI3K/AKT/mTOR signaling pathway and increasing the protein expression of Wnt1, ß-catenin, PI3K, Akt3, and p62, while suppressing MAP LC3ß, TNF-α, and CyclinE expression. These findings suggested that PFOA-induced intestinal injury, including inflammation and tight junction disruption, was mitigated by inulin through modifying the PI3K/AKT/mTOR signaling pathways. Our study provides valuable insights into the enterotoxic effects of PFOA and highlights the potential therapeutic role of inulin.


Assuntos
Caprilatos , Fluorocarbonos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Humanos , Masculino , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inulina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
20.
Ultrason Sonochem ; 106: 106883, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703594

RESUMO

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.


Assuntos
Antioxidantes , Fenômenos Químicos , Ficus , Pectinas , Ondas Ultrassônicas , Pectinas/química , Pectinas/isolamento & purificação , Ficus/química , Antioxidantes/química , Temperatura , Tamanho da Partícula , Concentração de Íons de Hidrogênio
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