RESUMO
Amylin, a member of the calcitonin family, acts via amylin receptors in the hindbrain and hypothalamus to suppress appetite. Native ligands of these receptors are peptides with short half-lives. Conjugating fatty acids to these peptides can increase their half-lives. The long-acting human amylin analog, NN1213, was generated from structure-activity efforts optimizing solubility, stability, receptor affinity, and selectivity, as well as in vivo potency and clearance. In both rats and dogs, a single dose of NN1213 reduced appetite in a dose-dependent manner and with a long duration of action. Consistent with the effect on appetite, studies in obese rats demonstrated that daily NN1213 dosing resulted in a dose-dependent reduction in body weight over a 21-day period. Magnetic resonance imaging indicated that this was primarily driven by loss of fat mass. Based on these data, NN1213 could be considered an attractive option for weight management in the clinical setting.
Assuntos
Polipeptídeo Amiloide das Ilhotas Pancreáticas , Animais , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Humanos , Cães , Ratos , Relação Estrutura-Atividade , Masculino , Obesidade/tratamento farmacológico , Peso Corporal/efeitos dos fármacos , Receptores de Polipeptídeo Amiloide de Ilhotas Pancreáticas/metabolismoRESUMO
OBJECTIVE: In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery. METHOD: A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects. RESULTS: In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P < 0.05). However, there was a higher incidence of side effects observed in the EB group (P < 0.05). CONCLUSION: The analgesic effect of PVB and EB following single-port thoracoscopic lung surgery is better than that of ICNB. PVB causes fewer side effects and complications and is safer and more effective.
Assuntos
Nervos Intercostais , Bloqueio Nervoso , Dor Pós-Operatória , Ultrassonografia de Intervenção , Humanos , Bloqueio Nervoso/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Ultrassonografia de Intervenção/métodos , Dor Pós-Operatória/prevenção & controle , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Medição da Dor , Adulto , Toracoscopia/métodos , Pulmão/cirurgiaRESUMO
Nano-sized microplastic pollution is distributed worldwide. Nano-sized microplastics can enter the blood through the digestive tract, and then transported to various tissues and organs of the body, resulting in a series of toxicological effects. In addition, nano-sized microplastics can penetrate the skin barrier. However, the toxicological effects of nano-sized microplastics on the skin are still not completely understood. Two skin cell lines were used as in vitro models to investigate the toxicological effects of nano-sized microplastics on skin cells and their potential molecular mechanisms. First, cellular behavioral research results showed that nano-sized microplastics can be internalized into skin cells in a time- and dose-dependent manner. Further experiments using western blotting, indirect immunofluorescence, and ELISA assays demonstrated that nano-sized microplastics cause an increase in skin cell inflammation levels. Additionally, our research showed that nano-sized microplastics caused skin cell senescence damage by evaluating aging-marker molecules such as p16 and p21. Subsequently, we studied the potential molecular mechanism by which nano-sized microplastics cause pathological skin injury and found that they induce mitochondrial oxidative stress, depolarize the mitochondrial membrane potential, and recruit GSDMD to the mitochondria. Subsequently, mtDNA enters the cytoplasm via GSDMD pores, which then activates the AIM2 Inflammasome. Ultimately, it causes a series of biochemical reactions such as inflammation and aging in cells. In an in vivo model, we tested the effect of nano-sized microplastics on skin regeneration and found that they acted as an inhibitor to skin regeneration and aggravated the inflammatory reaction of the skin. Overall, our results provide new evidence of the skin toxicity of nano-sized microplastics. This study provides a theoretical foundation for further research on the potential toxicological effects of nano-sized microplastics on the skin.
Assuntos
Senescência Celular , Microplásticos , Mitocôndrias , Pele , Microplásticos/toxicidade , Senescência Celular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Humanos , Animais , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Camundongos , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
BACKGROUND: Patients with cognitive dysfunction may present with significantly prolonged the P2 wave latency of flash visual evoked potential. However, no studies have been reported on whether the P2 wave latency of flash visual evoked potential is prolonged in patients with subcortical arteriosclerotic encephalopathy (SAE). OBJECTIVE: To examine the relationship between flash visual evoked potential P2 wave latency (FVEP-P2 wave latency) and cognitive impairment in patients with SAE. METHODS: Overall, we recruited 38 SAE patients as the observation cohort (OC) and 34 healthy volunteers as the control cohort (CC). We measured the FVEP-P2 wave latency for both groups. The SAE patients' cognitive abilities were evaluated via mini-mental state examination (MMSE) and the association between the latency of FVEP-P2 and MMSE score was explored by Pearsons´s correlation test. RESULTS: There is no significant difference between OC (21 males and 17 females; 68.6 ± 6.7 years of age and 9.6 ± 2.8 years of education) and CC (19 males and 15 females; 65.3 ± 5.9 years of age and 10.1 ± 2.6 years of education) in gender and age composition and education level. The FVEP-P2 wave latency of the CC group was (108.80 ± 16.70) ms and the OC FVEP-P2 wave latency was (152.31 ± 20.70) ms. The OC FVEP-P2 wave latency was significantly longer than the CC (P < 0.05). In terms of MMSE scores, the MMSE scores of CC was (28.41 ± 2.34), and that of OC was (9.08 ± 4.39). Compared to the CC, the OC MMSE score was significantly lower (P < 0.05). In addition, the FVEP-P2 wave latency was inversely related to the MMSE (r = -0.4465, P < 0.05) in SAE patients. CONCLUSION: The FVEP-P2 wave latency wave latency was significantly prolonged in SAE patients and strongly associated with the degree of cognitive dysfunction.
Assuntos
Disfunção Cognitiva , Demência Vascular , Masculino , Feminino , Humanos , Potenciais Evocados Visuais , Disfunção Cognitiva/diagnóstico , Cognição , EscolaridadeRESUMO
To quantitatively evaluate the effects of drought on vegetation productivity in the Qinling-Daba Mountains, we analyzed the temporal and spatial characteristics of gross primary productivity (GPP) and drought, identified the fluctuation of negative GPP extremes under different vegetation types, and quantified the drought vulnerability and drought risk of GPP from 2001 to 2020 with MODIS GPP products and standardized precipitation evapotranspiration index (SPEI). The results showed that the annual GPP from 2001 to 2020 had an increasing trend in 98.0% of areas in the Qinling-Daba Mountains. The GPP of all vegetation types except wetlands increased significantly. SPEI decreased in 23.8% of area in the Qinling-Daba Mountains from 2001 to 2020. The number of negative GPP extremes had no significant trend, but abnormal GPP fluctuations had intensified, especially in the cultivated land. After 2011, the proportion of concurrent negative GPP extreme and drought had decreased for all vegetation types, but the spatial and temporal range of drought in these negative GPP extremes showed an expanding trend. Compared with the pattern during 2001-2010, the proportion of area with positive drought vulnerability and drought risk increased by 104.1% and 6.7% after 2011, indicating that the area with drought-induced GPP decline had expanded. Among all the vegetation types, drought caused the largest decrease of GPP in wetlands. The results revealed that drought led to an aggravation of GPP fluctuations and increased frequency of GPP extremes in the Qinling-Daba Mountains from 2001 to 2020, which resulted in GPP decline with different magnitudes in most vegetation types.
Assuntos
Secas , Ecossistema , China , Mudança ClimáticaRESUMO
The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically worldwide and, subsequently, also the risk of developing non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and cancer. Today, weight loss is the only available treatment, but administration of fibroblast growth factor 21 (FGF21) analogues have, in addition to weight loss, shown improvements on liver metabolic health but the mechanisms behind are not entirely clear. The aim of this study was to investigate the hepatic metabolic profile in response to FGF21 treatment. Diet-induced obese (DIO) mice were treated with s.c. administration of FGF21 or subjected to caloric restriction by switching from high fat diet (HFD) to chow to induce 20% weight loss and changes were compared to vehicle dosed DIO mice. Cumulative caloric intake was reduced by chow, while no differences were observed between FGF21 and vehicle dosed mice. The body weight loss in both treatment groups was associated with reduced body fat mass and hepatic triglycerides (TG), while hepatic cholesterol was slightly decreased by chow. Liver glycogen was decreased by FGF21 and increased by chow. The hepatic gene expression profiles suggest that FGF21 increased uptake of fatty acids and lipoproteins, channeled TGs toward the production of cholesterol and bile acid, reduced lipogenesis and increased hepatic glucose output. Furthermore, FGF21 appeared to reduce inflammation and regulate hepatic leptin receptor-a expression. In conclusion, FGF21 affected several metabolic pathways to reduce hepatic steatosis and improve hepatic health and markedly more genes than diet restriction (61 vs 16 out of 89 investigated genes).
RESUMO
Ecological stoichiometry provides a new method for understanding the characteristics, driving forces and mechanisms of C, N and P coupled cycles. However, there are few reports on the variation in ecological stoichiometry of plants during their growth. In this study, we fitted the total elemental mass of different module based on the size of Nitraria tangutorum, and derived the ecological stoichiometry models of different module and whole ramet by measuring the biomass and nutrient concentrations of the current-year stems in 2017, 2-year-old stems, more than 2-year-old stems, leaves, roots and layerings of N. tangutorum ramet. Our results showed that the derivation model could well reflect the changes in ecological stoichiometry during plant growth. The old stems and the layering had higher N:P and C:P, while leaves,current-year stems, and roots had lower N:P and C:P. The whole plant nutrient elements cumulative rate was P:N:C during the growth process. These results were consistent with the growth rate hypothesis and allometric theory, and provide evidence for nutrient reabsorption. This model could be used as an effective way to analyze the dynamic characteristics of elements in plant growth.
Assuntos
Magnoliopsida , Biomassa , Nitrogênio , Fósforo , Folhas de Planta , Raízes de Plantas , PlantasRESUMO
Semaglutide, a glucagon-like peptide 1 (GLP-1) analog, induces weight loss, lowers glucose levels, and reduces cardiovascular risk in patients with diabetes. Mechanistic preclinical studies suggest weight loss is mediated through GLP-1 receptors (GLP-1Rs) in the brain. The findings presented here show that semaglutide modulated food preference, reduced food intake, and caused weight loss without decreasing energy expenditure. Semaglutide directly accessed the brainstem, septal nucleus, and hypothalamus but did not cross the blood-brain barrier; it interacted with the brain through the circumventricular organs and several select sites adjacent to the ventricles. Semaglutide induced central c-Fos activation in 10 brain areas, including hindbrain areas directly targeted by semaglutide, and secondary areas without direct GLP-1R interaction, such as the lateral parabrachial nucleus. Automated analysis of semaglutide access, c-Fos activity, GLP-1R distribution, and brain connectivity revealed that activation may involve meal termination controlled by neurons in the lateral parabrachial nucleus. Transcriptomic analysis of microdissected brain areas from semaglutide-treated rats showed upregulation of prolactin-releasing hormone and tyrosine hydroxylase in the area postrema. We suggest semaglutide lowers body weight by direct interaction with diverse GLP-1R populations and by directly and indirectly affecting the activity of neural pathways involved in food intake, reward, and energy expenditure.
Assuntos
Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/farmacologia , Vias Neurais/efeitos dos fármacos , Animais , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/efeitos dos fármacos , Camundongos , RatosRESUMO
A Gram-stain-positive, aerobic, non-motile and coccoid-shaped bacterium, designated XNB-1T, was isolated from farmland soil in Taian, Shandong province, China. Strain XNB-1T contained iso-C15â:â0 and iso-C16â:â0 as the predominant fatty acids. The diagnostic diamino acid of the peptidoglycan was ornithine, and the interpeptide bridge was l-OrnâGly(1, 2)âd-Glu. The polar lipid profile of strain XNB-1T consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified phosphoglycolipid and three unidentified phospholipids. The predominant menaquinone of strain XNB-1T was MK-8(H4) and the DNA G+C content was 70.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XNB-1T belonged to the genus Ornithinicoccus, and shared the highest similarity with Ornithinicoccus hortensis HKI 0125T (96.0â%), followed by Ornithinicoccus halotolerans EGI 80423T (95.5â%). Genome-based analysis of average nucleotide identity of strain XNB-1T with O. hortensis HKI 0125T and O. halotolerans EGI 80423T yielded values of 73.1 and 73.3â%, respectively, while the digital DNA-DNA hybridization values were 19.5 and 19.9â%, respectively. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain XNB-1T is considered to represent a novel species of the genus Ornithinicoccus, for which the name Ornithinicoccus soli sp. nov. is proposed. The type strain is XNB-1T (=CCTCC AB 2019099T=KCTC 49259T).
Assuntos
Actinobacteria/classificação , Fazendas , Filogenia , Microbiologia do Solo , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
A Gram-stain-positive, strictly aerobic, non-motile, non-spore-forming and rod-shaped bacterium, designated as strain G-1T, was isolated from farmland soil sampled in in Fuyang, Anhui Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain G-1T was closely related to Cumulibacter manganitolerans 2-36T (97.7â% similarity). Strain G-1T contained iso-C16â:â0, C17â:â1ω6c, iso-C15â:â0 and iso-C14â:â0 as the predominant fatty acids. The polar lipids of strain G-1T were diphosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified lipid and two unidentified glycolipids. The predominant respiratory quinone of strain G-1T was MK-9(H4). The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid. The G+C content of the genomic DNA based on genome calculations was 64.2 mol%. Average nucleotide identity and the digital DNA-DNA hybridization values for the draft genomes between strain G-1T and strain 2-36T were 75.7 and 20.2 %, respectively. On the basis of phenotypic and phylogenetic data, strain G-1T is considered to represent a novel species of the genus Cumulibacter, for which the name Cumulibacter soli sp. nov. is proposed. The type strain is G-1T (=CCTCC AB2019021T=KCTC 49258T).
Assuntos
Actinobacteria/classificação , Fazendas , Filogenia , Microbiologia do Solo , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
Lung adenocarcinoma (LUAD) is one of the leading causes of cancer death globally. This study aims to investigate the underlying mechanisms implicated with LUAD and identify the key biomarkers. LUAD-associated gene expression dataset (GSE10072) was obtained from GEO database. Based on the GEO2R tool, we screened the differentially expressed genes (DEGs) between the patients with LUAD and normal individuals. Subsequently, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to find out the enriched pathways of these DEGs. Meanwhile, a protein-protein interaction (PPI) network was also employed to construct to visualize the interactions of these DEGs. Finally, the survival analysis of the top5 up-regulated and top5 down-regulated genes were conducted via GEPIA, aiming to figure out their potential effects on LUAD. In our study, a total of 856 DEGs were captured, including 559 up-regulated genes and 297 down-regulated genes. Among these DEGs, the top5 up-regulated genes were AGER, SFTPC, FABP4, CYP4B1 and WIF1 while the top5 down-regulated genes were GREM1, SPINK1, MMP1, COL11A1 and SPP1. GO analysis disclosed that these DEGs were mainly enriched in DNA synthesis, cell adhesion, signal transduction and cell apoptosis. KEGG analysis unveiled that the enriched pathway included pathways in cancer, PI3K/Akt signaling pathway, MAPK signaling pathway and cell cycle. Survival analysis showed that the expression level of ZG16 may correlate with the prognosis of LUAD patients. Furthermore, according to the connectivity degree of these DEGs, we selected the top15 hub genes, namely IL6, MMP9, EDN1, FOS, CDK1, CDH1, BIRC5, VWF, UBE2C, CDKN3, CDKN2A, CD34, AURKA, CCNB2 and EGR1, which were expected to be promising therapeutic target in LUAD. In conclusion, our study disclosed potential biomarkers and candidate targets in LUAD, which could be helpful to the diagnosis and treatment of LUAD.
Assuntos
Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/metabolismo , Apoptose , Adesão Celular , Ciclo Celular , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transdução de Sinais , Resultado do TratamentoRESUMO
Objective: Lung cancer is a deadly disease with the highest 5-year survival rate. Lung adenocarcinoma is the main subtype of non-small cell lung cancer (NSCLC). Correct staging is critical as the basis of treatment. So, the identification of genes associated with pathologic stages of lung adenocarcinoma is helpful in understanding the pathological mechanism and designing targeted therapeutic drugs. Methods: Random forest was suitable for high-dimensional data to identify variables associated with the outcome. The variable importance-based selection method was used to rank the candidate genes associated with pathologic stages of lung adenocarcinoma. Univariate regression was used to analyze the relationship between gene expression and prognosis. The protein-protein interaction network was used to show the interactions among the identified genes. The identified genes functional enrichment analysis was performed by GSEA software. Results: Twelve genes significantly associated with pathologic stages of lung adenocarcinoma were identified by random forest analysis. Eight of these genes were found to play roles in survival of patients with lung adenocarcinoma. Among the 12 genes, 4 genes such as CENPH, SRSF5, PITX2 and NSG1 interacted with each other. And these genes were mainly enriched in p53 signaling pathway, cell cycle signaling pathway, JAK STAT signaling pathway and DNA replication signaling pathway. Conclusion: The identified genes may drive the changes among pathologic stages of lung adenocarcinoma and will be helpful in understanding the molecular changes underlying the pathologic stages.
Assuntos
Adenocarcinoma de Pulmão/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Estadiamento de Neoplasias , Adenocarcinoma de Pulmão/patologia , Idoso , Ciclo Celular , Biologia Computacional , Reações Falso-Positivas , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Análise de Regressão , Transdução de Sinais , Software , Resultado do TratamentoRESUMO
Pancreatic beta cells (ß-cells) differentiate during fetal life, but only postnatally acquire the capacity for glucose-stimulated insulin secretion (GSIS). How this happens is not clear. In exploring what molecular mechanisms drive the maturation of ß-cell function, we found that the control of cellular signaling in ß-cells fundamentally switched from the nutrient sensor target of rapamycin (mTORC1) to the energy sensor 5'-adenosine monophosphate-activated protein kinase (AMPK), and that this was critical for functional maturation. Moreover, AMPK was activated by the dietary transition taking place during weaning, and this in turn inhibited mTORC1 activity to drive the adult ß-cell phenotype. While forcing constitutive mTORC1 signaling in adult ß-cells relegated them to a functionally immature phenotype with characteristic transcriptional and metabolic profiles, engineering the switch from mTORC1 to AMPK signaling was sufficient to promote ß-cell mitochondrial biogenesis, a shift to oxidative metabolism, and functional maturation. We also found that type 2 diabetes, a condition marked by both mitochondrial degeneration and dysregulated GSIS, was associated with a remarkable reversion of the normal AMPK-dependent adult ß-cell signature to a more neonatal one characterized by mTORC1 activation. Manipulating the way in which cellular nutrient signaling pathways regulate ß-cell metabolism may thus offer new targets to improve ß-cell function in diabetes.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Transdução de Sinais , Proteínas Quinases Ativadas por AMP/genética , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Secreção de Insulina/genética , Células Secretoras de Insulina/patologia , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Camundongos KnockoutRESUMO
BACKGROUND: Metabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent models employ high fat, high cholesterol, high fructose, methionine/choline deficient diets or combinations of these to induce NAFLD/NASH. The FATZO mice spontaneously develop the above metabolic disorders and type 2 diabetes (T2D) when fed with a normal chow diet. The aim of the present study was to determine if FATZO mice fed a high fat and fructose diet would exacerbate the progression of NAFLD/NASH. METHODS: Male FATZO mice at the age of 8 weeks were fed with high fat Western diet (D12079B) supplemented with 5% fructose in the drinking water (WDF) for the duration of 20 weeks. The body weight, whole body fat content, serum lipid profiles and liver function markers were examined monthly along with the assessment of liver histology for the development of NASH. In addition, the effects of obeticholic acid (OCA, 30 mg/kg, QD) on improvement of NASH progression in the model were evaluated. RESULTS: Compared to normal control diet (CD), FATZO mice fed with WDF were heavier with higher body fat measured by qNMR, hypercholesterolemia and had progressive elevations in AST (~ 6 fold), ALT (~ 6 fold), liver over body weight (~ 2 fold) and liver triglyceride (TG) content (1.4-2.9 fold). Histological examination displayed evidence of NAFLD/NASH, including hepatic steatosis, lobular inflammation, ballooning and fibrosis in FATZO mice fed WDF. Treatment with OCA for 15 weeks in FATZO mice on WDF significantly alleviated hypercholesterolemia and elevation of AST/ALT, reduced liver weight and liver TG contents, attenuated hepatic ballooning, but did not affect body weight and blood TG levels. CONCLUSION: WDF fed FATZO mice represent a new model for the study of progressive NAFLD/NASH with concurrent metabolic dysregulation.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Frutose/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Edulcorantes/efeitos adversos , Animais , Progressão da Doença , Fígado/patologia , Fígado/fisiopatologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologiaRESUMO
A brain-computer interface (BCI) is a communication approach that permits cerebral activity to control computers or external devices. Brain electrical activity recorded with electroencephalography (EEG) is most commonly used for BCI. Noise-assisted multivariate empirical mode decomposition (NA-MEMD) is a data-driven time-frequency analysis method that can be applied to nonlinear and nonstationary EEG signals for BCI data processing. However, because white Gaussian noise occupies a broad range of frequencies, some redundant components are introduced. To solve this leakage problem, in this study, we propose using a sinusoidal assisted signal that occupies the same frequency ranges as the original signals to improve MEMD performance. To verify the effectiveness of the proposed sinusoidal signal assisted MEMD (SA-MEMD) method, we compared the decomposition performances of MEMD, NA-MEMD, and the proposed SA-MEMD using synthetic signals and a real-world BCI dataset. The spectral decomposition results indicate that the proposed SA-MEMD can avoid the generation of redundant components and over decomposition, thus, substantially reduce the mode mixing and misalignment that occurs in MEMD and NA-MEMD. Moreover, using SA-MEMD as a signal preprocessing method instead of MEMD or NA-MEMD can significantly improve BCI classification accuracy and reduce calculation time, which indicates that SA-MEMD is a powerful spectral decomposition method for BCI.
Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia/métodos , Processamento de Sinais Assistido por Computador , Adulto , Algoritmos , Encéfalo/fisiologia , Feminino , Humanos , Imaginação/fisiologia , Análise MultivariadaRESUMO
A Gram-stain-negative, aerobic, non-motile, non-spore-forming and rod-shaped bacterium, designated YHM-9T, was isolated from soil in Yangquan, Shanxi Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YHM-9T belonged to the genus Pedobacter and shared the highest similarity (97.4â%) to the type strain Pedobacter lignilitoris W-WS13T. Strain YHM-9T exhibited low DNA-DNA relatedness with P. lignilitoris W-WS13T (21.7±1.3â%). The DNA G+C content was 38.9 mol%. The major fatty acids were iso-C15â:â0, summed feature 3 (C16â:â1ω7c and/or C16â:â1ω6c) and iso-C17â:â0 3-OH. The respiratory quinone was MK-7, the major polyamine was sym-homospermidine and the major polar lipids were phosphatidylethanolamine. Based on the morphological, physiological, biochemical and chemotaxonomic characteristics, strain YHM-9T was recognized as a representative of a novel species within the genus Pedobacter, for which the name Pedobacteragrisoli sp. nov. is proposed. The type strain is YHM-9T (=JCM 32093T=CCTCC AB 2017125T).
Assuntos
Fazendas , Pedobacter/classificação , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Pedobacter/genética , Pedobacter/isolamento & purificação , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Espermidina/análogos & derivados , Espermidina/química , Vitamina K 2/químicaRESUMO
OBJECTIVE: To investigate the neuroprotective effects of transforming growth factor beta 1(TGF-ß1) on the expression and secretion of cytokines induced by Aß1-42 in hippocampal neurons and microglial co-cultures. METHODS: Hippocampal neurons and microglia obtained from SD rat were co-cultured. TGF-ß1 was applied on day 5 after the neurons and microglia co-cultures were incubated at the concentrations of 5 or 20 ng/ml, Aß1-42 was added 1 h following TGF-ß1 application at a concentration of 5 µmol/L. They were incubated for 72 h and then assessed for further studies. Western blot analyses were employed to examine the expression of inducible nitric oxide synthase (iNOS); Real-time PCR and ELISA were used to detect the mRNA expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and insulin-like growth factor-1 (IGF-1). RESULTS: In the hippocampal neuron-microglia co-cultures, Aß1-42 induced upregulation of iNOS, TNF-α and IL-1ß, downregulation of IGF-1. TGF-ß1 pretreatment ameliorated the pro-inflammatory effects caused by Aß1-42. CONCLUSIONS: TGF-ß1 significantly inhibits the increase in inflammatory cytokines and the decrease in neurotrophic factor which are caused by Aß1-42-induced microglia activation.
Assuntos
Hipocampo , Microglia , Animais , Células Cultivadas , Técnicas de Cocultura , Citocinas , Neurônios , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfaRESUMO
Alzheimer's disease (AD), the most common chronic neurodegenerative disease, is pathologically characterized by the formation of neurofibrillary tangles because of hyperphosphorylation of tau protein and extracellular deposits of amyloid-ß (Aß) protein termed senile plaques. Recent studies indicate that neuronal apoptosis caused by chronic neuroinflammation is one of the important pathogenesis of AD. Transforming growth factor (TGF)-ß1 is a pleiotropic cytokine with immunosuppressive and anti-inflammatory properties. However, it is poorly known whether the anti-inflammatory property of TGF-ß1 is involved in a neuroprotection in AD. Here, an AD cell model of hippocampal neurons induced by Aß1-42 was used to show an anti-inflammatory and neuroprotective effect of TGF-ß1 through its receptor transforming growth factor-ß receptor type I (TßR-I). As expected, Aß1-42-induced an upregulation in neuronal expression of amyloid precursor protein (APP), tumor necrosis factor-α, cyclooxygenase-2, Bax, cleaved caspase-3, and cleaved caspase-9, and a downregulation in the expression of Bcl-2, as well as an increase in the number of NeuN/terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) double-positive cells. TGF-ß1 pretreatment reduced the Aß1-42-induced effects of upregulating APP, tumor necrosis factor-α, Bax, cleaved caspase-3 and cleaved caspase-9, and downregulating Bcl-2, in addition to increasing NeuNTUNEL cell number. TßR-I expression in hippocampal neurons was downregulated by Aß1-42 exposure, but upregulated by TGF-ß1 pretreatment. Silencing of the TßR-I gene in the neurons abolished the anti-inflammatory and antiapoptotic effects of TGF-ß1 in the Aß1-42-induced AD cell model. These findings suggest that TGF-ß1 protects neurons against Aß1-42-induced neuronal inflammation and apoptosis by activation of TßR-I.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Hipocampo/metabolismo , Neurônios/metabolismo , Neuroproteção/fisiologia , Fragmentos de Peptídeos/toxicidade , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/metabolismo , Animais , Apoptose/fisiologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Células Cultivadas , Regulação da Expressão Gênica , Hipocampo/patologia , Inflamação/metabolismo , Inflamação/patologia , Neurônios/patologia , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/metabolismo , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I , Fator de Crescimento Transformador beta1/administração & dosagem , Fator de Crescimento Transformador beta1/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Cavities are important in clinical diagnosis of pulmonary tuberculosis (TB) infected by Mycobacterium tuberculosis. Although microRNAs (miRNAs) play a vital role in the regulation of inflammation, the relation between plasma miRNA and pulmonary tuberculosis with cavity remains unknown. In this study, plasma samples were derived from 89 cavitary pulmonary tuberculosis (CP-TB) patients, 89 non-cavitary pulmonary tuberculosis (NCP-TB) patients and 95 healthy controls. Groups were matched for age and gender. In the screening phase, Illumina high-throughput sequencing technology was employed to analyze miRNA profiles in plasma samples pooled from CP-TB patients, NCP-TB patients and healthy controls. During the training and verification phases, quantitative RT-PCR (qRT-PCR) was conducted to verify the differential expression of selected miRNAs among groups. Illumina high-throughput sequencing identified 29 differentially expressed plasma miRNAs in TB patients when compared to healthy controls. Furthermore, qRT-PCR analysis validated miR-769-5p, miR-320a and miR-22-3p as miRNAs that were differently present between TB patients and healthy controls. ROC curve analysis revealed that the potential of these 3 miRNAs to distinguish TB patients from healthy controls was high, with the area under the ROC curve (AUC) ranged from 0.692 to 0.970. Moreover, miR-320a levels were decreased in drug-resistant TB patients than pan-susceptible TB patients (AUC = 0.882). In conclusion, we identified miR-769-5p, miR-320a and miR-22-3p as potential blood-based biomarkers for TB. In addition, miR-320a may represent a biomarker for drug-resistant TB.