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1.
Pediatr Dermatol ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923547

RESUMO

An 8-year-old girl presented with white papules on the eyelid margins due to lipoid proteinosis. Microwave therapy resulted in significant reduction of the lesions. The case highlights a safe and effective treatment for eyelid lesions associated with lipoid proteinosis. In addition, we report two novel heterozygous variants in the extracellular matrix protein 1 (ECM1) gene.

2.
Plant Mol Biol ; 112(1-2): 19-31, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36929454

RESUMO

Pectin widely exists in higher plants' cell walls and intercellular space of higher plants and plays an indispensable role in plant growth and development. We identified 55 differentially expressed genes related to pectin degradation by transcriptomic analysis in the male sterile mutant, ms1. A gene encoding pectin methylesterase (GhPME21) was found to be predominantly expressed in the developing stamens of cotton but was significantly down-regulated in ms1 stamens. The tapetal layer of GhPME21 interfered lines (GhPME21i) was significantly thickened compared to that of WT at the early stage; anther compartment morphology of GhPME21i lines was abnormal, and the microspore wall was broken at the middle stage; Alexander staining showed that the pollen grains of GhPME21i lines differed greatly in volume at the late stage. The mature pollen surfaces of GhPME21i lines were deposited with discontinuous and broken sheets and prickles viewed under SEM. Fewer pollen tubes were observed to germinate in vitro in GhPME21i lines, while tiny of those in vivo were found to elongate to the ovary. The seeds harvested from GhPME21i lines as pollination donors were dry and hollow. The changes of phenotypes in GhPME21i lines at various stages illustrated that the GhPME21 gene played a vital role in the development of cotton stamens and controlled plant fertility by affecting stamen development, pollen germination, and pollen tube elongation. The findings of this study laid the groundwork for further research into the molecular mechanisms of PMEs involved in microspore formation and the creation of cotton male sterility materials.


Assuntos
Gossypium , Proteínas de Plantas , Gossypium/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismo , Pectinas , Regulação da Expressão Gênica de Plantas , Flores , Infertilidade das Plantas/genética
3.
Curr Issues Mol Biol ; 45(5): 4200-4213, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37232736

RESUMO

Histo-blood group antigens (HBGAs) comprise a family of cell-surface carbohydrates that are considered norovirus-specific binding receptors or ligands. HBGA-like molecules have also been detected in oysters as common norovirus carriers, although the pathway involved in the synthesis of these molecules in oysters has yet to be elucidated. We isolated and identified a key gene involved in the synthesis of HBGA-like molecules, FUT1, from Crassostrea gigas, named CgFUT1. Real-time quantitative polymerase chain reaction analysis showed that CgFUT1 mRNA was expressed in the mantle, gill, muscle, labellum, and hepatopancreatic tissues of C. gigas, with the hepatopancreas exhibiting the highest expression level. A recombinant CgFUT1 protein with a molecular mass of 38.0 kDa was expressed in Escherichia coli using a prokaryotic expression vector. A eukaryotic expression plasmid was constructed and transfected into Chinese hamster ovary (CHO) cells. The expression of CgFUT1 and membrane localization of type H-2 HBGA-like molecules in CHO cells were detected using Western blotting and cellular immunofluorescence, respectively. This study indicated that CgFUT1, expressed in C. gigas tissues, can synthesize type H-2 HBGA-like molecules. This finding provides a new perspective for analyzing the source and synthetic pathway of HBGA-like molecules in oysters.

4.
Theor Appl Genet ; 136(7): 163, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37368122

RESUMO

KEY MESSAGE: We demonstrated a short-cycle B. napus line, Sef1, with a highly efficient and fast transformation system, which has great potential in large-scale functional gene analysis in a controlled environment. Rapeseed (Brassica napus L.) is an essential oil crop that accounts for a considerable share of global vegetable oil production. Nonetheless, studies on functional genes of B. napus are lagging behind due to the complicated genome and long growth cycle, this is largely due to the limited availability of gene analysis and modern genome editing-based molecular breeding. In this study, we demonstrated a short-cycle semi-winter-type Brassica napus 'Sef1' with very early-flowering and dwarf phenotype, which has great potential in large-scale indoor planting. Through the construction of an F2 population of Sef1 and Zhongshuang11, bulked segregant analysis (BSA) combined with the rape Bnapus50K SNP chip assay method was used to identify the early-flowering genes in Sef1, and a mutation in BnaFT.A02 was identified as a major locus significantly affecting the flowering time in Sef1. To further investigate the mechanism of early flowering in Sef1 and discover its potential in gene function analysis, an efficient Agrobacterium-mediated transformation system was established. The average transformation efficiency with explants of hypocotyls and cotyledons was 20.37% and 12.8%, respectively, and the entire transformation process took approximately 3 months from explant preparation to seed harvest of transformed plants. This study demonstrates the great potential of Sef1 for large-scale functional gene analysis.


Assuntos
Brassica napus , Brassica napus/genética , Genômica , Fenótipo , Análise de Sequência com Séries de Oligonucleotídeos , Ambiente Controlado
5.
J Appl Microbiol ; 134(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37580170

RESUMO

AIMS: Vibrio parahaemolyticus is an important foodborne pathogen worldwide, which can cause gastroenteritis. This study aimed to investigate the effect of quorum sensing system LuxS/AI-2-related gene luxS on the biological characteristics and antimicrobial resistance of V. parahaemolyticus Vp2015094 from shellfish, which carried a multi-antimicrobial-resistant plasmid. METHODS AND RESULTS: The critical gene luxS related to the synthesis of AI-2 in V. parahaemolyticus Vp2015094 was knocked out by homologous recombination with suicide plasmid. The effect of luxS on the biological characteristics of V. parahaemolyticus was determined by comparing the growth, AI-2 activity, motility, biofilm formation ability, and antibiotic resistance between the wildtype strain and the luxS deletion mutant. Compared with wildtype strain, the production of AI-2, the motility and biofilm formation ability, antimicrobial resistance, and conjugation frequency of luxS deletion mutant strain were decreased. The transcriptome sequencing showed that the transcriptional levels of many genes related to motility, biofilm formation, antimicrobial resistance, and conjugation were significantly downregulated after luxS deletion. CONCLUSIONS: Quorum sensing system LuxS/AI-2-related gene luxS in V. parahaemolyticus Vp2015094 played an important role in growth characteristics, biofilm formation, antimicrobial resistance, and resistance genes' transfer.


Assuntos
Biofilmes , Vibrio parahaemolyticus , Humanos , Antibacterianos/farmacologia , Vibrio parahaemolyticus/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/farmacologia , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/farmacologia , Farmacorresistência Bacteriana , Percepção de Quorum/genética , Frutos do Mar
6.
Int J Neurosci ; 133(1): 1-12, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33499703

RESUMO

PURPOSE: Spinal cord ischemia-reperfusion (I/R) injury is an unresolved complication and its mechanisms are still not completely understood. Here, we studied the neuroprotective effects of dexmedetomidine (DEX) postconditioning against spinal cord I/R injury in rats and explored the possible mechanisms. MATERIALS AND METHODS: In the study, rats were randomly divided into five groups: sham group, I/R group, DEX0.5 group, DEX2.5 group, and DEX5 group. I/R injury was induced in experimental rats; 0.5 µg/kg, 2.5 µg/kg, 5 µg/kg DEX were intravenously injected upon reperfusion respectively. Neurological function, histological assessment, and the disruption of blood-spinal cord barrier (BSCB) were evaluated via the BBB scoring, hematoxylin and eosin staining, Evans Blue (EB) extravasation and spinal cord edema, respectively. Neutrophil infiltration was evaluated via Myeloperoxidase (MPO) activity. Microglia activation and reactive gliosis was evaluated via ionized calcium-binding adapter molecule-1(IBA-1) and glial fibrillary acidic protein (GFAP) immunofluorescence, respectively. The expression of C-X-C motif ligand 13 (CXCL13), C-X-C chemokine receptor type 5(CXCR5), caspase-3 was determined by western blotting. The expression levels of interleukin 6(IL-6), tumor necrosis factor-α(TNF-α), IL-1ß were determined by ELISA assay. RESULTS: DEX postconditioning preserved neurological assessment scores, improved histological assessment scores, attenuated BSCB leakage after spinal cord I/R injury. Neutrophil infiltration, microglia activation and reactive gliosis were also inhibited by DEX postconditioning. The expression of CXCL13, CXCR5, caspase-3, IL-6, TNF-α, IL-1ß were reduced by DEX postconditioning. CONCLUSIONS: DEX postconditioning alleviated spinal cord I/R injury, which might be mediated via inhibition of neutrophil infiltration, microglia activation, reactive gliosis and CXCL13/CXCR5 axis activation.


Assuntos
Dexmedetomidina , Traumatismo por Reperfusão , Isquemia do Cordão Espinal , Ratos , Animais , Dexmedetomidina/farmacologia , Caspase 3/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Infiltração de Neutrófilos , Microglia/metabolismo , Gliose/metabolismo , Medula Espinal/metabolismo , Isquemia do Cordão Espinal/tratamento farmacológico , Isquemia do Cordão Espinal/patologia , Traumatismo por Reperfusão/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 48(18): 5102-5112, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802852

RESUMO

In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Revisões Sistemáticas como Assunto , Resultado do Tratamento , Síndrome , Publicações , Medicamentos de Ervas Chinesas/uso terapêutico
8.
J Sci Food Agric ; 102(4): 1674-1683, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34453344

RESUMO

BACKGROUND: The substitution or mislabeling of toothfish is an issue of significant concern for seafood authorities; it also reduces the effectiveness of marine conservation and management programs for its over-exploitation and illegal trafficking, boosting the need for identification methods. RESULTS: Two species-specific real-time polymerase chain reaction (PCR) assays for the identification of Patagonian toothfish (Dissostichus eleginoides) and Antarctic toothfish (Dissostichus mawsoni) and a genus-specific real-time PCR assay for Dissostichus spp. identification were developed based on fragments of the 16S rRNA and COI (cytochrome c oxidase subunit I) genes. These methods were confirmed to be rapid, simple, and sensitive (absolute sensitivity of 0.0002 ng µL-1 and relative sensitivity of 0.1 g kg-1 with good specificity). These methods can be applied to processed and commercial fish products. CONCLUSIONS: These approaches can be beneficial for protecting both consumers and producers from economic fraud and might also help protect toothfish from over-exploitation as well as combat illegal, unreported, and unregulated (IUU) fisheries. © 2021 Society of Chemical Industry.


Assuntos
Pesqueiros , Alimentos Marinhos , Animais , Regiões Antárticas , RNA Ribossômico 16S , Reação em Cadeia da Polimerase em Tempo Real
9.
BMC Microbiol ; 21(1): 140, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952201

RESUMO

BACKGROUND: Group B Streptococcus (GBS) infection is the leading cause of septicemia, meningitis, and pneumonia in neonates. Aberrant gut colonization in early life may predispose children to various diseases in adulthood. However, the associations between gut microbial changes and GBS colonization is still unclear. RESULTS: The composition and diversity of meconium microbiota in GBS group were similar to that of healthy controls. However, we identified several specific taxa that were differentially abundant between the two groups (linear discriminant analysis (LDA) effect size (LEfSe): p < 0.05, LDA > 2.0). Particularly, the relative abundance of Lactobacillus paracasei was significantly reduced, indicating a role in GBS colonization. CONCLUSIONS: Our study presented a series of bacterial species colonized by GBS, thus providing novel evidence in support of initial intestinal microbiota dysbiosis in the neonates with mother's GBS colonization.


Assuntos
Biodiversidade , Microbioma Gastrointestinal/fisiologia , Mecônio/microbiologia , Infecções Estreptocócicas/microbiologia , Feminino , Humanos , Recém-Nascido , Streptococcus/fisiologia
10.
Exp Eye Res ; 206: 108529, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33676964

RESUMO

Retinoblastoma (RB) is an intraocular malignancy that occurs in children. Circular RNAs (circRNAs) have been confirmed to play an essential role in tumorigenesis and development. This study aimed to ascertain the role and potential mechanism of hsa_circ_0099198 in RB. The levels of circ_0099198, microRNA-1287 (miR-1287) and low-density lipoprotein receptor-related protein 6 (LRP6) were determined by real-time quantitative polymerase chain reaction and Western blot. Cell proliferation was assessed by colony formation assay. Cell cycle arrest and apoptosis were evaluated by flow cytometry. Cell migration and invasion were tested using transwell assay. The activity of caspase-3/caspase-9 was examined with commercial kits. The interaction among circ_0099198, miR-1287 and LRP6 were verified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay or RNA pull-down assay. Xenograft experiment was used to assess tumor growth in vivo. circ_0099198 and LRP6 levels were increased, while miR-1287 level was reduced in RB cells. circ_0099198 silencing suppressed proliferation and metastasis and expedited cell cycle arrest and apoptosis in Y79 and So-RB50 cells. In addition, depletion of circ_0099198 inhibited RB cell progression via regulating miR-1287/LRP6 axis. Moreover, knockdown of circ_0099198 blocked the growth of xenograft tumors. circ_0099198 contributed to RB progression by sponging miR-1287 and up-regulating LRP6, which provided novel biomarkers for RB therapy.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , MicroRNAs/genética , Retinoblastoma/genética , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/biossíntese , MicroRNAs/biossíntese , Neoplasias da Retina/genética , Retinoblastoma/metabolismo , Retinoblastoma/patologia , Regulação para Cima
11.
Mol Cell Biochem ; 476(1): 69-80, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32844346

RESUMO

Retinoblastoma (RB) is an intraocular malignancy that mainly occurs in infants and young children under 5 years of age. Circular RNA hsa_circ_0000034 (circ_0000034) was reported to be upregulated in RB tissues. Nevertheless, the function and mechanism of circ_0000034 in RB are unclear. Expression of circ_0000034, microRNA-361-3p (miR-361-3p), and a disintegrin and metalloproteinase 19 (ADAM19) was examined via quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, migration, invasion, and apoptosis were determined though Cell Counting Kit-8 (CCK-8), transwell, or flow cytometry assays. Caspase-3 activity was detected using a caspase-3 activity assay kit. Some protein levels were examined using Western blot analysis. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or RNA pull-down assay were performed to verify the relationship between circ_0000034 or ADAM19 and miR-361-3p. The function of circ_0000034 in vivo was confirmed via animal experiment. We verified that circ_0000034 expression was elevated in RB tissues and cells. Circ_0000034 silencing reduced RB growth in vivo, repressed viability, migration, invasion, and EMT, and induced apoptosis of RB cells in vitro. Circ_0000034 acted as a sponge for miR-361-3p, which targeted ADAM19 in RB cells. Furthermore, the inhibition of miR-361-3p restored circ_0000034 knockdown-mediated impacts on viability, migration, invasion, apoptosis, and EMT of RB cells. Moreover, ADAM19 overexpression abolished the influence of miR-361-3p mimic on viability, migration, invasion, apoptosis, and EMT of RB cells. Circ_0000034 expedited RB progression through upregulating ADAM19 via sponging miR-361-3p, which indicated that circ_0000034 might a target for RB therapy.


Assuntos
Proteínas ADAM/metabolismo , MicroRNAs/metabolismo , RNA Circular/genética , Neoplasias da Retina/genética , Retinoblastoma/genética , Proteínas ADAM/genética , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Pré-Escolar , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Lactente , Recém-Nascido , MicroRNAs/genética , Invasividade Neoplásica , RNA/metabolismo , Neoplasias da Retina/metabolismo , Retinoblastoma/metabolismo , Regulação para Cima
12.
Appl Microbiol Biotechnol ; 105(13): 5461-5470, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34241646

RESUMO

Foodborne pathogens have caused many public health incidents and heavy economic burden. Endolysins have been proven to have efficient bactericidal activity against pathogens with low incidence of resistance. In this study, the recombinant endolysin LysSP1 encoded by Salmonella Typhimurium lytic bacteriophage SLMP1 was obtained by prokaryotic expression, and its characteristics were analyzed. Ethylenediaminetetraacetic acid (EDTA) can be used as the outer membrane permeabilizer to increase the bactericidal activity of LysSP1. Under the synergism of 5 mmol/L EDTA, LysSP1 exhibited a strong bactericidal activity against Salmonella Typhimurium ATCC14028. LysSP1 was stable at 4°C for 7 days and at -20°C for 180 days. LysSP1 remained the optimal activity at 40°C and was efficiently active at alkaline condition (pH 8.0-10.0). Divalent metal ions could not enhance the bactericidal activity of LysSP1 and even caused the significant reduction of bactericidal activity. LysSP1 not only could lyse Salmonella, but also could lyse other Gram-negative strains and Gram-positive strains. These results indicated that LysSP1 is a broad-spectrum endolysin and has potential as an antimicrobial agent against Salmonella and other foodborne pathogens. KEY POINTS: • Recombinant endolysin LysSP1 can be prepared by prokaryotic expression. • LysSP1 has stable nature and strong bactericidal activity on Salmonella Typhimurium with EDTA. • LysSP1 has a broad range of hosts including Gram-negative bacteria and Gram-positive bacteria.


Assuntos
Fagos de Salmonella , Antibacterianos , Endopeptidases/genética , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Fagos de Salmonella/genética
13.
Ecotoxicol Environ Saf ; 214: 112081, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33677383

RESUMO

Perfluorooctanoic acid (PFOA), a persistent environmental contaminant, resists environmental degradation and bioaccumulates in food chains. Lots of literatures have proved that PFOA exposure could disrupt detoxifying function in a variety of organisms, however, it still remained poorly known about this in mollusk. Here, we examined physiological, transcriptomic, and metabolomic responses to PFOA in Mytilus edulis, a model organism frequently used in studies of aquatic pollution. We aimed to characterize PFOA-induced stress responses and detoxification mechanisms. PFOA exposure significantly altered antioxidant enzyme activity levels and the abundances of lipid peroxidation products. In addition, transcriptomic analysis indicated that several genes associated with oxidative stress and detoxication were differentially expressed after PFOA exposure. In combination, transcriptomic and metabolomic analyses showed that PFOA exposure disturbed several metabolic processes in M. edulis, including the lipid metabolism, amino acid metabolism, and carbohydrate metabolism etc. Molecular examination and enzymes assay of PFOA-exposed M. edulis after a 7-day depuration period still did not recover to control levels. The Pathway enrichment analysis proved that several pathways related to detoxification, such as c-Jun N-terminal kinase (JNK) and p38-dependent mitogen-activated protein kinase (MAPK) pathway, Peroxisome proliferator-activated receptor γ (PPARγ) pathway etc, were obviously affected. The present work verifies firstly PFOA disruption to molluscan detoxification and identifies the key pathways to understand the molecular mechanisms thereof. This study provides new insights into the detoxication disruption invoked in response to PFOA exposure in M. edulis.


Assuntos
Caprilatos/toxicidade , Fluorocarbonos/toxicidade , Mytilus edulis/fisiologia , Animais , Antioxidantes/metabolismo , Metabolismo dos Lipídeos , Metabolômica , Mytilus edulis/metabolismo , Estresse Oxidativo , PPAR gama/metabolismo , Transcriptoma
14.
J Sci Food Agric ; 101(5): 1792-1799, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32892369

RESUMO

BACKGROUND: Oilfish (Ruvettus pretiosus) and escolar (Lepidocybium flavobrunneum) are often used to adulterate high-value aquatic products, causing serious economic losses to consumers, and even keriorrhea in severe cases. It was difficult to identify them by morphological features for these two fish were processed into steak or fillet. The purpose of this study, therefore, is to develop an accurate and efficient method for detecting the oilfish- and escolar-derived components. RESULTS: By comparing the mitochondrial 16S ribosomal RNA gene sequences of oilfish, escolar, and 16 varieties susceptible to adulteration, specific primers/probes were designed, and a duplex real-time polymerase chain reaction (PCR) method was established to detect oilfish- and escolar-derived components. The specificity and sensitivity of the method were analyzed, and the method was used to analyze 70 commercial samples to evalutate its applicability to actual samples in the market. The method developed was highly specific, without any cross-reaction on the other 16 species, with a limit of detection (LOD) for DNA of 0.0002 ng µL-1 for R. pretiosus and 0.002 ng µL-1 for L. flavobrunneum. In addition, the LOD for mixed muscle tissues was 0.1 g kg-1 . Oilfish- and escolar-derived components were detected in 12 of the 70 commercial samples, a result that is consistent with the classic DNA barcoding test results. CONCLUSION: The duplex real-time PCR method developed can be used to detect oilfish and escolar specifically, sensitively and accurately; it provides a good technical support for the identification of authentic aquatic products. © 2020 Society of Chemical Industry.


Assuntos
Produtos Pesqueiros/análise , Perciformes/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Animais , Primers do DNA/genética , Análise Discriminante , Proteínas de Peixes/genética , Contaminação de Alimentos/análise , Limite de Detecção , Perciformes/classificação
15.
Neurochem Res ; 45(2): 331-344, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865521

RESUMO

Autophagy is crucial for cell survival, development, division, and homeostasis. The mammalian target of rapamycin (mTOR), which is the foremost negative controller of autophagy, plays a key role in many endogenous processes. The present study investigated whether rapamycin can ameliorate surgery-induced cognitive deficits by inhibiting mTOR and activating autophagy in the hippocampus. Both adult and aged C57BL/6J mice received an intraperitoneal injection of rapamycin (10 mg/kg/day) for 5 days per week for one and a half months. Mice were then subjected to partial hepatectomy under general anesthesia. Behavioral performance was assessed on postoperative days 3, 7, and 14. Hippocampal autophagy-related (Atg)-5, phosphorylated mTOR, and phosphorylated p70S6K were examined at each time point. Brain derived neurotrophic factor (BDNF), synaptophysin, and tau hyperphosphorylation (T396) in the hippocampus were also examined. Surgical trauma and anesthesia exacerbated spatial learning and memory impairment in aged mice on postoperative days 3 and 7. Following partial hepatectomy, the levels of phosphorylated mTOR, phosphorylated 70S6K, and phosphorylated tau were all increased in the hippocampus. A corresponding decline in BDNF and synaptophysin were observed. Rapamycin treatment restored autophagy function, attenuated phosphorylation of tau protein, and increased BDNF and synaptophysin expression in the hippocampus of surgical mice. Furthermore, surgery and anesthesia induced spatial learning and memory impairments were also reversed by rapamycin treatment. Autophagy impairments and mTOR hyperactivation were detected along with surgery-induced behavioral deficits. Inhibiting the mTOR signaling pathway with rapamycin successfully ameliorated surgery-related cognitive impairments by sustaining autophagic degradation, inhibiting tau hyperphosphorylation, and increasing synaptophysin and BDNF expression.


Assuntos
Autofagia/fisiologia , Hepatectomia/efeitos adversos , Fármacos Neuroprotetores/uso terapêutico , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Fatores Etários , Animais , Hipocampo/metabolismo , Fígado/cirurgia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , Complicações Cognitivas Pós-Operatórias/etiologia , Sevoflurano/efeitos adversos , Regulação para Cima
16.
Cell Physiol Biochem ; 46(4): 1398-1411, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29689568

RESUMO

BACKGROUND/AIMS: TREM2 plays a crucial role in modulating microglial function through interaction with DAP12, the adapter for TREM2. Emerging evidence has demonstrated that TREM2 could suppress neuroinflammatory responses by repression of microglia-mediated cytokine production. This study investigated the potential role of TREM2 in surgery-induced cognitive deficits and neuroinflammatory responses in wild-type (WT) and APPswe/PS1dE9 mice. METHODS: Adult APPswe/PS1dE9 transgenic male mice (a classic transgenic model of Alzheimer's disease, 3 months old) and their age-matched WT mice received intracerebral lentiviral particles encoding the mouse TREM2 gene and then were subjected to partial hepatectomy at 1 month after the lentiviral particle injection. The behavioral changes were evaluated with an open-field test and Morris water maze test on postoperative days 3, 7, and 14. Hippocampal TREM2, DAP12, and interleukin (IL)-1ß were measured at each time point. Ionized calcium-binding adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, synaptophysin, tau hyperphosphorylation (T396), and glycogen synthase kinase-3ß (GSK-3ß) were also examined in the hippocampus. RESULTS: Surgical trauma induced an exacerbated cognitive impairment and enhanced hippocampal IL-1ß expression in the transgenic mice on postoperative days 3 and 7. A corresponding decline in the levels of TREM2 was also found on postoperative days 3, 7, and 14. Overexpression of TREM2 downregulated the levels of IL-1ß, ameliorated T396 expression, inhibited the activity of GSK-3ß, and improved sickness behavior. Increased Arg1 expression and a high level of synaptophysin were also observed in the transgenic mice following TREM2 overexpression. CONCLUSION: The downregulation of TREM2 exacerbated surgery-induced cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Overexpression of TREM2 potentially attenuated these effects by decreasing the associated production of proinflammatory cytokines, inhibiting tau hyperphosphorylation, and enhancing synaptophysin expression.


Assuntos
Disfunção Cognitiva/prevenção & controle , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Arginase/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Masculino , Aprendizagem em Labirinto , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Neurocirurgia , Receptores Imunológicos/genética , Sinaptofisina/metabolismo , Regulação para Cima , Proteínas tau/metabolismo
17.
Cell Mol Neurobiol ; 38(6): 1293-1303, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29948551

RESUMO

Ischemia-reperfusion (I/R)-induced spinal cord injury can cause apoptotic damage and subsequently act as a blood-spinal cord barrier damage. MicroRNAs (miRNAs) contributed to the process of I/R injury by regulating their target mRNAs. miR-199a-5p is involved in brain and heart I/R injury; however, its function in the spinal cord is not yet completely clarified. In this study, we investigated the role of miR-199a-5p on spinal cord I/R via the endothelin-converting enzyme 1, especially the apoptosis pathway. In the current study, the rat spinal cord I/R injury model was established, and the Basso Beattie Bresnahan scoring, Evans blue staining, HE staining, and TUNEL assay were used to assess the I/R-induced spinal cord injury. The differentially expressed miRNAs were screened using microarray. miR-199a-5p was selected by unsupervised hierarchical clustering analysis. The dual-luciferase reporter assay was used for detecting the regulatory effects of miR-199a-5p on ECE1. In addition, neuron expression was detected by immunostaining assay, while the expressions of p-ERK, ERK, p-JNK, JNK, caspase-9, Bcl-2, and ECE1 were evaluated by Western blot. The results indicated the successful establishment of the I/R-induced spinal cord injury model; the I/R induced the damage to the lower limb motor. Furthermore, 18 differentially expressed miRNAs were detected in the I/R group compared to the sham group, and miR-199a-5p protected the rat spinal cord injury after I/R. Moreover, miR-199a-5p negatively regulated ECE1, and silencing the ECE1 gene also protected the rat spinal cord injury after I/R. miR-199a-5p or silencing of ECE1 also regulated the expressions of caspase-9, Bcl-2, p-JNK, p-ERK, and ECE1 in rat spinal cord injury after I/R. Therefore, we demonstrated that miR-199a-5p might protect the spinal cord against I/R-induced injury by negatively regulating the ECE1, which could aid in developing new therapeutic strategies for I/R-induced spinal cord injury.


Assuntos
Regulação para Baixo , Enzimas Conversoras de Endotelina/metabolismo , MicroRNAs/genética , Traumatismo por Reperfusão/genética , Regulação para Cima , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Neurônios/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Ativação Transcricional/genética
18.
J BUON ; 23(3): 758-762, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30003748

RESUMO

PURPOSE: To investigate the role and significance of neoadjuvant chemotherapy in advanced ovarian cancer. METHODS: 128 patients clinically diagnosed with stage IIC-IV advanced epithelial ovarian cancer (EOC) were randomized into neoadjuvant chemotherapy (NACT) combined with interval cytoreductive surgery (ICS) group (n=66) and primary cytoreductive surgery (PCS) group (n=62). Chemotherapy in the PCS group was administered after cytoreductive surgery. RESULTS: Age, body mass index, clinical symptoms, clinical staging, histopathological grading and histopathological type had no differences between PCS and ICS groups (p>0.05). In NACT-ICS group, the mean operation time was shorter, the bleeding was less, the rate of optimal debulking surgery was higher and the total effective rate of clinical remission was higher, compared with those in PCS group (p<0.05). No significant differences were found in the survival rate, progression-free survival (PFS) and overall survival (OS) between the two groups. CONCLUSIONS: In comparison to PCS, NACT-ICS can improve the intraoperative conditions, increase the cytoreductive rate, reduce the bleeding of operation, reduce the operation time and increase the clinical remission rate, but it has no impact on PFS and OS.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias/métodos , Neoplasias Ovarianas/patologia , Taxa de Sobrevida
20.
J Nanosci Nanotechnol ; 17(1): 507-16, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29625521

RESUMO

The mesoporous manganese dioxide with high specific surface area was obtained through a one-pot prepare procedure at ambient temperature under acidic conditions. And the graphene/mesoporous manganese dioxide composite was synthesized by a simple hydrothermal approach. As a comparison, silver nanowires also as a conductor was added to the mesoporous manganese dioxide. Both of the graphene and silver nanowires can increase the capacitance of the mesoporous manganese dioxide-based composite electrode materials. Compared with the graphene/mesoporous manganese dioxide composite, the silver nanowires/mesoporous manganese dioxide mixture has a better electrochemical performance, the specific capacitance and energy density is almost 2.2 times larger than that of the composites. The morphology and detail structure were investigated by the Scanning electron microscopy, X-ray diffraction, Raman spectra, Fourier transform infrared spectrometry and Nitrogen adsorption­desorption isotherms. The electrochemical performance was assessed by the cyclic voltammograms, galvanostatic charge/discharge and electrochemical impedance spectroscopy.

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