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1.
Sci Total Environ ; 806(Pt 1): 150213, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34571232

RESUMO

Tissue-nonspecific alkaline phosphatase (ALPL) and alpha-amylase (AMY) are essential in the immune and digestive systems, respectively. Microplastics (MPs) pose a risk to zooplankton which may be in a state of feeding, starvation, or subsequent refeeding. However, molecular characterization of both enzymes and the regulated mechanisms affected by nutritional statuses and MPs remain unclear in zooplankton. In the present study, four full-length genes encoding ALPL and two genes encoding AMY were cloned and characterized from an isolated marine rotifer, Brachionus rotundiformis, including alplA, alplB, alplC, alplD, amy2a, and amy2al. AMY activity and expression of amy2a and amy2al were reduced by starvation and recovered after refeeding compared with feeding. ALPL activity remained unchanged among different statuses, while alplA, alplB and alplD were down-regulated by starvation and refeeding compared with feeding. ALPL activity was not affected by exposure to 10, 100 and 1000 µg/L MPs in rotifers subjected to feeding, starvation and refeeding, whereas AMY activity was significantly enhanced by 1000 µg/L MPs in rotifers subjected to refeeding. Gene expression of the tested genes, except amy2a, was significantly responsive to MPs, especially in the feeding rotifers, depending on MPs concentrations and nutritional statuses. Two-way ANOVA confirmed that these changes were strongly associated with the interaction between MPs concentrations and nutritional statuses. The present study is the first to demonstrate a nutritional status-dependent impact of MPs on immune and digestive responses, and provides more sensitive molecular biomarkers for assessing MPs toxicity using the species as model animals.

2.
Sensors (Basel) ; 21(22)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34833840

RESUMO

Semi-active isolation systems with controllable stiffness have been widely developed in the field of seismic mitigation. Most systems with controllable stiffness perform more robustly and effectively for far-field earthquakes than for near-fault earthquakes. Consequently, a comprehensive system that provides comparable reductions in seismic responses to both near-fault and far-field excitations is required. In this regard, a new algorithm called Feed-Forward Predictive Earthquake Energy Analysis (FPEEA) is proposed to identify the ground motion characteristics of and reduce the structural responses to earthquakes. The energy distribution of the seismic velocity spectrum is considered, and the balance between the kinetic energy and potential energy is optimized to reduce the seismic energy. To demonstrate the performance of the FPEEA algorithm, a two-degree-of-freedom structure was used as the benchmark in the numerical simulation. The peak structural responses under two near-fault and far-field earthquakes of different earthquake intensities were simulated. The isolation layer displacement was suppressed most by the FPEEA, which outperformed the other three control methods. Moreover, superior control on superstructure acceleration was also supported by the FPEEA. Experimental verification was then conducted with shaking table test, and the satisfactory performance of the FPEEA on both isolation layer displacement and superstructure acceleration was demonstrated again. In summary, the proposed FPEEA has potential for practical application to unexpected near-fault and far-field earthquakes.

3.
Aquat Toxicol ; 242: 106023, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34798301

RESUMO

The present study identified that exposure to 5, 10, and 20 µg/L Cd for 48 days reduced growth, increased Cd accumulation and levels of reactive oxygen species (ROS) and lipid peroxidation, and induced ER stress and cellular apoptosis in the liver in a dose-dependent manner. However, the survival rate was not affected by Cd. The increased production of ROS might result from reduced catalase (CAT) and copper/zinc-superoxide dismutase (Cu/Zn-SOD) activities, which might trigger ER stress pathways and subsequently induce apoptotic responses, ultimately leading to growth inhibition. Transcriptomic analyses indicated that the differentially expressed genes (DEGs) involved in metabolic pathways were significantly enriched and dysregulated by Cd, suggesting that metabolic disturbances may contribute to Cd toxicity. However, there were increases in glutathione peroxidase (GPX) activity, protein levels of metallothioneins (MTs) and heat shock protein 70 (HSP70), and mRNA levels of sod1, cat, gpx, mt2, and hsp70. Furthermore, DEGs related to ribosome, protein processing in the ER, and protein export pathways were significantly enriched and up-regulated by Cd. These increases may be compensatory responses following oxidative stress, ER stress, and apoptosis to resist negative effects. Taken together, we demonstrated that environmentally relevant levels of Cd induced adaptive responses with compensatory mechanisms in fish, which may help to maintain fish survival at the cost of growth.

4.
Nat Commun ; 12(1): 6866, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824234

RESUMO

The activity of nanomaterials (NMs) in catalytically scavenging superoxide anions mimics that of superoxide dismutase (SOD). Although dozens of NMs have been demonstrated to possess such activity, the underlying principles are unclear, hindering the discovery of NMs as the novel SOD mimics. In this work, we use density functional theory calculations to study the thermodynamics and kinetics of the catalytic processes, and we develop two principles, namely, an energy level principle and an adsorption energy principle, for the activity. The first principle quantitatively describes the role of the intermediate frontier molecular orbital in transferring electrons for catalysis. The second one quantitatively describes the competition between the desired catalytic reaction and undesired side reactions. The ability of the principles to predict the SOD-like activities of metal-organic frameworks were verified by experiments. Both principles can be easily implemented in computer programs to computationally screen NMs with the intrinsic SOD-like activity.

5.
Sensors (Basel) ; 21(21)2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34770704

RESUMO

The aim of this paper is to distinguish the vehicle detection and count the class number in each classification from the inputs. We proposed the use of Fuzzy Guided Scale Choice (FGSC)-based SSD deep neural network architecture for vehicle detection and class counting with parameter optimization. The 'FGSC' blocks are integrated into the convolutional layers of the model, which emphasize essential features while ignoring less important ones that are not significant for the operation. We created the passing detection lines and class counting windows and connected them with the proposed FGSC-SSD deep neural network model. The 'FGSC' blocks in the convolution layer emphasize essential features and find out unnecessary features by using the scale choice method at the training stage and eliminate that significant speedup of the model. In addition, FGSC blocks avoided many unusable parameters in the saturation interval and improved the performance efficiency. In addition, the Fuzzy Sigmoid Function (FSF) increases the activation interval through fuzzy logic. While performing operations, the FGSC-SSD model reduces the computational complexity of convolutional layers and their parameters. As a result, the model tested Frames Per Second (FPS) on edge artificial intelligence (AI) and reached a real-time processing speed of 38.4 and an accuracy rate of more than 94%. Therefore, this work might be considered an improvement to the traffic monitoring approach by using edge AI applications.


Assuntos
Inteligência Artificial , Sulfadiazina de Prata , Algoritmos , Lógica Fuzzy , Redes Neurais de Computação
6.
Mol Ther Nucleic Acids ; 26: 1027-1034, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34786208

RESUMO

5-Methylcytosine (m5C) is an important post-transcriptional modification that has been extensively found in multiple types of RNAs. Many studies have shown that m5C plays vital roles in many biological functions, such as RNA structure stability and metabolism. Computational approaches act as an efficient way to identify m5C sites from high-throughput RNA sequence data and help interpret the functional mechanism of this important modification. This study proposed a novel species-specific computational approach, Staem5, to accurately predict RNA m5C sites in Mus musculus and Arabidopsis thaliana. Staem5 was developed by employing feature fusion tactics to leverage informatic sequence profiles, and a stacking ensemble learning framework combined five popular machine learning algorithms. Extensive benchmarking tests demonstrated that Staem5 outperformed state-of-the-art approaches in both cross-validation and independent tests. We provide the source code of Staem5, which is publicly available at https://github.com/Cxd-626/Staem5.git.

7.
Zhongguo Gu Shang ; 34(11): 1087-90, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34812030

RESUMO

Full endoscopic transforaminal lumbar interbody fusion has been used widely in the field of minimally invasive spine surgery in recent years. This paper briefly introduces the development history, technical points, indications, curative effects and complications. Authors believe that the full endoscopic transforaminal lumbar interbody fusion has the same clinical effects as traditional surgery, and can effectively reduce tissue damage and intraoperative bleeding, reduce the incidence of postoperative low back pain, shorten the time to get out of bed, and reduce the average hospitalization time. However, it is still necessary to improve the long-term follow up in order to further evaluate the effectiveness and safety of the procedure.


Assuntos
Fusão Vertebral , Endoscopia , Humanos , Vértebras Lombares/cirurgia , Região Lombossacral , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos , Resultado do Tratamento
8.
J Hazard Mater ; 424(Pt C): 127589, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34740155

RESUMO

Knowledge on the interaction between microplastics (MPs) and zinc oxide nanoparticles (ZnO NPs) is limited. Here, we investigated effects of embryo-larvae exposure to 500 µg/L polystyrene MPs (5 µm), 1200 µg/L ZnO NPs (< 100 nm), 500 µg/L dissolved Zn2+ from ZnSO4, and the mixtures of MPs and ZnO NPs or ZnSO4 on exposed F0 larvae and unexposed F1 larvae. Consequently, ZnO particles adhered to MPs surfaces rather than Zn2+, and increased Zn transport into larvae. Growth inhibition, oxidative stress, apoptosis, and disturbance of growth hormone and insulin-like growth factor (GH/IGF) axis were induced by MPs and ZnO NPs alone, which were further aggravated by their co-exposure in F0 larvae. MPs + ZnO increased apoptotic cells in the gill and esophagus compared with MPs and ZnO NPs alone. Reduced growth and antioxidant capacity and down-regulated GH/IGF axis were merely observed in F1 larvae from F0 parents exposed to MPs + ZnO. Contrary to ZnO NPs, dissolved Zn2+ reversed MPs toxicity, suggesting the protective role of Zn2+ may be not enough to ameliorate thfie negative effects of ZnO particles. To summarize, we found that particles rather than released Zn2+ from ZnO nanoparticles amplified MPs toxicity in early stages of exposed zebrafish and their unexposed offspring.

9.
J Dent ; 115: 103882, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34742831

RESUMO

OBJECTIVE: To evaluate the influence of crown coverage of surgical guides on the accuracy of static computer-assisted implant surgeries (sCAISs) in different partially edentulous situations. METHODS: Acrylic models with five types of partially edentulous situations were fabricated in this study. In coDiagnostiX software (Dental Wings, Montreal, Canada), surgical templates were designed and fabricated with reduced crown coverage (RCC), standard crown coverage (SCC) and extended crown coverage (ECC). Then, fully guided implant placement into the acrylic models was performed by dental surgeons with more than 10 years of experience. In total, 120 models and 120 guides were manufactured, and 168 bone-level Straumann replica implants (4.1 × 10 mm, Institut Straumann AG, Basel, Switzerland) were inserted. Postoperative implant positions were scanned (Trios 3, 3 shape, Copenhagen, Denmark) and compared with the preplanned virtual positions via coDiagnostiX (Dental Wings, Montreal, Canada). The angular, coronal and apical deviations were measured and analyzed to evaluate the accuracy of implant insertion. Statistical analysis was performed using one-way ANOVA and Tukey's test. RESULTS: For single tooth missing situations, the RCC group was similar to the SCC group and ECC group in anterior sites. In premolar or molar sites, the SCC and ECC groups had no statistically significant difference (p > .05), while the RCC group had more coronal and apical deviation (p < .05). For multiple teeth missing situations, there was no difference among the RCC, SCC and ECC groups (p > .05). No difference was found among the five edentulous situations with different CCs (p > .05). CONCLUSION: The CC of templates can significantly affect the accuracy of guided surgeries when implants are inserted in a single gap at posterior sites. Templates with CC extended to the undercut line may be an optimal choice for static guided surgeries. CLINICAL SIGNIFICANCE: The accuracy of static guided implant surgery can be influenced by the CC of templates, and proper CC with the guide covering extending to the undercut line may contribute to improved accuracy. CC should be taken into consideration when designing surgical templates.

10.
Am J Ophthalmol ; 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34818515

RESUMO

PURPOSE: To evaluate the diagnostic yield of congenital ectopia lentis (EL) in a Chinese cohort by combining panel-based next-generation sequencing with clinical findings DESIGN: A cohort study. METHODS: In total, 175 patients with congenital EL and their available family members (n = 338) were enrolled. All congenital EL patients underwent genetic testing. Genotype-phenotype analyses were conducted to assess the biometric and structural ocular manifestations of congenital EL. RESULTS: In total, 175 patients with congenital EL and 338 of their relatives were included in this study. In these patients, 92.57% (162/175) of disease-related variants were detected in FBN1 (83.43%), CPAMD8 (1.71%), COL4A5 (0.57%), ADAMTSL4 (3.43%), LTBP2 (1.71%), and CBS (2.29%). Based on genetic and clinical findings, the primary diagnostic rate was increased to 40.57% from 19.43% with the exception of the 91 diagnoses of potential MFS, with a new diagnostic strategy for congenital ectopia lentis thus having been developed. Within this group of patients harboring FBN1 mutations, 16.44% (19/141) probands were diagnosed with ectopia lentis syndrome (ELS) and 2.13% (3/141) were diagnosed with Marfan syndrome (MFS). CONCLUSIONS: The results of this cohort study expand the genomic landscape associated with congenital EL in Chinese cohorts. FBN1 mutations represent the most common cause of congenital EL in this population, and we have developed a new diagnostic strategy for congenital EL subtypes via the use of a well-designed panel-based next-Generation Sequencing (NGS) which can be used to efficiently and precisely diagnose patients with congenital EL in a cost-effective manner.

11.
J Bioinform Comput Biol ; : 2150029, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34806952

RESUMO

O-glycosylation is a protein posttranslational modification important in regulating almost all cells. It is related to a large number of physiological and pathological phenomena. Recognizing O-glycosylation sites is the key to further investigating the molecular mechanism of protein posttranslational modification. This study aimed to collect a reliable dataset on Homo sapiens and develop an O-glycosylation predictor for Homo sapiens, named Captor, through multiple features. A random undersampling method and a synthetic minority oversampling technique were employed to deal with imbalanced data. In addition, the Kruskal-Wallis (K-W) test was adopted to optimize feature vectors and improve the performance of the model. A support vector machine, due to its optimal performance, was used to train and optimize the final prediction model after a comprehensive comparison of various classifiers in traditional machine learning methods and deep learning. On the independent test set, Captor outperformed the existing O-glycosylation tool, suggesting that Captor could provide more instructive guidance for further experimental research on O-glycosylation. The source code and datasets are available at https://github.com/YanZhu06/Captor/.

12.
J Am Chem Soc ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807592

RESUMO

Homogeneous and heterogeneous catalyzed reactions can seldom operate synergistically under the same conditions. Here we communicate the use of a single rhodium precursor that acts in both the homogeneous and heterogeneous phases for the asymmetric full saturation of vinylarenes that, to date, constitute an unmet bottleneck in the field. A simple asymmetric hydrogenation of a styrenic olefin, enabled by a ligand accelerated effect, accounted for the facial selectivity in the consecutive arene hydrogenation. Tuning the ratio between the phosphine ligand and the rhodium precursor controlled the formation of homogeneous and heterogeneous catalytic species that operate without interference from each other. The system is flexible in terms of both the chiral ligand and the nature of the external olefin. We anticipate that our findings will promote the development of asymmetric arene hydrogenations.

13.
Front Endocrinol (Lausanne) ; 12: 705827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690924

RESUMO

The prevalence of obesity has become a threatening global public health issue. The consequence of obesity is abnormal energy metabolism. Unlike white adipose tissue (WAT), brown adipose tissue (BAT) has a unique role in nonshivering thermogenesis. Lipids and glucose are consumed to maintain energy and metabolic homeostasis in BAT. Recently, accumulating evidence has indicated that exposure to excess maternal energy intake affects energy metabolism in offspring throughout their life. However, whether excess intrauterine energy intake influences BAT metabolism in adulthood is not clear. In this study, mouse dams were exposed to excess energy intake by feeding a high-fat diet (HFD) before and during pregnancy and lactation. The histology of BAT was assessed by hematoxylin and eosin staining. The genome-wide methylation profile of BAT was determined by a DNA methylation array, and specific site DNA methylation was quantitatively analyzed by methylated DNA immunoprecipitation (MeDIP) qPCR. We found that intrauterine exposure to a high-energy diet resulted in blood lipid panel disorders and impaired the BAT structure. Higher methylation levels of genes involved in thermogenesis and fatty acid oxidation (FAO) in BAT, such as Acaa2, Acsl1, and Cox7a1, were found in 16-week-old offspring from mothers fed with HFD. Furthermore, the expression of Acaa2, Acsl1, and Cox7a1 was down-regulated by intrauterine exposure to excess energy intake. In summary, our results reveal that excess maternal energy leads to a long-term disorder of BAT in offspring that involves the activation of DNA methylation of BAT-specific genes involved in fatty acid oxidation and thermogenesis.

14.
Molecules ; 26(19)2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34641574

RESUMO

Wuliangye baijiu is one of the most famous baijiu in China, with a rich, harmonic aroma profile highly appreciated by consumers. Thousands of volatiles have been identified for the unique aroma profile. Among them, fatty acid esters have been identified as the main contributors to the aroma profile. In addition, many non-ester minor compounds, many of which are more polar than the esters, have been identified to contribute to the characteristic aroma unique to Wuliangye baijiu. The analysis of these minor compounds has been challenging due to the dominance of esters in the sample. Thus, it is desirable to fractionate the aroma extract into subgroups based on functional group or polarity to simplify the analysis. This study attempts a new approach to achieve simultaneous volatile extraction and fractionation using tandem LiChrolut EN and silica gel solid-phase extraction (SPE) columns. A baijiu sample (10 mL, diluted in 40 mL of water) was first passed through the LiChrolut EN (1.0 g) column. The loaded LiChrolut EN column was then dried with air and coupled with a silica gel (5.0 g) SPE column with anhydrous Na2SO4 (10.0 g) in between. The volatile compounds were eluted from the LiChrolut EN column and simultaneously fractionated on the silica gel column based on polarity. The simultaneous extraction and fractionation technique enabled the fractionations of all fatty acid esters into less polar fractions. Fatty acids, alcohols, pyrazines, furans, phenols, hydroxy esters, and other polar compounds were collected in more polar fractions. This technique was used to study the volatile compounds in Wuliangye, Moutai, and Fengjiu baijiu. In addition to fatty acid esters, many minor polar compounds, including 2,6-dimethylpyrazine, 2-ethyl-6-methylpyrazine, 2-ethyl-3,5-dimethylpyrazine, p-cresol, and 2-acetylpyrrole, were unequivocally identified in the samples. The procedure is fast and straightforward, with low solvent consumption.

15.
Yi Chuan ; 43(9): 890-900, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702701

RESUMO

Based on reports in the literature and search results on the circBase database, 8 circular transcripts of the mouse growth hormone receptor (GHR) gene were identified. In order to confirm the existence of the circular transcripts of the GHR gene (circGHRs) and to explore their expression patterns, the Kunming mouse (Mus musculus) was used as a research animal. This study detected the existence of circGHRs by RT-PCR amplification and sequencing, one of which was selected as circGHR for detailed analysis. The circular structure of circGHR was confirmed by RNase R treatment and reverse transcription. The spatiotemporal expression of circGHR and GHR mRNA was analyzed by qRT-PCR. The results showed that the full length of mouse circGHR was 820 nt, which was formed by circularization of exons 2-8 of the transcript of the GHR gene. RNase R tolerance analysis shows that mouse circGHR has the general characteristics of circular molecules and is not easily degraded by RNase R. Compared with oligo-d(T)18 primers, random primers have higher reverse transcription efficiency for circGHR, which further shows that circGHR is a poly(A)-free cyclic structure molecule. Tissue expression profile results show that circGHR is highly expressed in the liver and kidney of 1 week-old and 7-week old Kunming mice, but is low in pectoral muscles and leg muscles. The time-series expression profile of circGHR does not show any significant difference between the liver and pectoral muscle tissue. The circGHR expression in the leg muscle was low before 5 weeks of age but increased after 7 weeks of age. This study confirmed the existence of a circular transcript circGHR of the mouse GHR gene, and initially revealed the expression pattern of circGHR. The results of the study laid a foundation for in-depth developmental studies on the biological functions of the mouse circGHR and its mechanism of action regarding the growth and development of mice.


Assuntos
Fígado , Receptores da Somatotropina , Animais , Clonagem Molecular , Primers do DNA , Éxons , Camundongos , RNA Mensageiro , Receptores da Somatotropina/genética
16.
FASEB J ; 35(11): e22003, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34706105

RESUMO

Maternal overnutrition during pregnancy and lactation is an important risk factor for the later development of metabolic disease, especially diabetes, among mothers and their offspring. As a fructan-type plant polysaccharide, inulin has prebiotic functions and is widely used as a natural antidiabetic supplement. However, to date, the mechanism of maternal inulin treatment in the livers of offspring has not been addressed, especially with respect to long noncoding RNAs (lncRNAs). In this study, female C57BL6/J mice were fed either a high-fat diet (HFD) with or without inulin supplementation or a standard rodent diet (SD) during gestation and lactation. After the offspring were weaned, they were fed a SD for 5 weeks. At 8 weeks of age, the glucose metabolism indexes of the offspring were assessed, and their livers were collected to assay lncRNA and mRNA profiles to investigate the effects of early maternal inulin intervention on offspring. Our results indicate that male offspring from HFD-fed dams displayed glucose intolerance and an insulin resistance phenotype at 8 weeks of age. Early maternal inulin intervention improved glucose metabolism in male offspring of mothers fed a HFD during gestation and lactation. The lncRNA and mRNA profile data revealed that compared with the offspring from HFD dams, offspring from the early inulin intervention dams had 99 differentially expressed hepatic lncRNAs and 529 differentially expressed mRNAs. The differentially expressed lncRNA-mRNA coexpression analysis demonstrated that early maternal inulin intervention may change hepatic lncRNA expression in offspring; there lncRNAs are involved in metabolic pathways and the AMP-activated protein kinase signaling pathway. Importantly, the early maternal inulin intervention alleviated glucose metabolism by inhibiting the lncRNA Serpina4-ps1/let-7b-5p/Ppargc1a as a competing endogenous RNA in male offspring.


Assuntos
Hipoglicemiantes , Inulina , Fígado , Hipernutrição/tratamento farmacológico , Fenômenos Fisiológicos da Nutrição Pré-Natal/efeitos dos fármacos , RNA Longo não Codificante/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Hepatócitos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Inulina/administração & dosagem , Inulina/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Cultura Primária de Células
17.
Front Nutr ; 8: 657848, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485357

RESUMO

Substantial evidence indicated that maternal malnutrition could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes in adulthood. It is increasingly apparent that the brain, especially the hypothalamus, plays a critical role in glucose homeostasis. However, little information is known about the mechanisms linking maternal protein restriction combined with post-weaning high-fat (HF) feeding with altered expression of brain neurotransmitters, and investigations into the epigenetic modifications of hypothalamus in offspring have not been fully elucidated. Our objective was to explore the effects of maternal protein restriction combined with post-weaning HF feeding on glucose metabolism and hypothalamic POMC methylation in male offspring mice. C57/BL6 mice were fed on either low-protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the male offspring were randomly weaned to either NC or high-fat (HF) diet until 32 weeks of age. Gene expressions and DNA methylation of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in male offspring. The results showed that birth weights and body weights at weaning were both significantly lower in male offspring mice of the dams fed with a LP diet. Maternal protein restriction combined with post-weaning high-fat feeding, predisposes higher body weight, persistent glucose intolerance (from weaning to 32 weeks of age), hyperinsulinemia, and hyperleptinemia in male offspring mice. POMC and MC4R expressions were significantly increased in offspring mice fed with maternal LP and postnatal high-fat diet (P < 0.05). Furthermore, maternal protein restriction combined with post-weaning high-fat feeding induced hypomethylation of POMC promoter in the hypothalamus (P < 0.05) and POMC-specific methylation (%) was negatively correlated with the glucose response to a glucose load in male offspring mice (r = -0.42, P = 0.039). In conclusion, maternal LP diet combined with post-weaning high-fat feeding predisposed the male offspring to impaired glucose metabolism and hypothalamic POMC hypomethylation. These findings can advance our thinking about hypothalamic POMC gene methylation between maternal LP diet combined with post-weaning high-fat feeding and metabolic health in offspring.

18.
Arch Med Sci ; 17(5): 1378-1387, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522267

RESUMO

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether vildagliptin protected endothelial function in diabetic rats and explored the involved mechanism. Material and methods: Experimental diabetic rats were obtained by feeding a high-fat diet and administering an intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups: controls (CON), diabetes (DM), diabetes + low dose of vildagliptin (Lvil, 10 mg/kg/day), and diabetes + high dose of vildagliptin (Hvil, 20 mg/kg/day). The metabolic parameters, endothelial function, and whole miRNA expression were measured. Results: After a 12-week treatment, vildagliptin-treated rats showed a significant reduction in blood glucose and blood lipid levels. Moreover, vildagliptin recovered aortic endothelial function in diabetic rats. We identified 31 miRNAs that were differentially expressed in the Hvil group compared with the diabetic group. Importantly, through miRNA target biological function and pathway analysis, we found that vildagliptin activated miR-190-5p to inhibit Ccl2 expression and inhibited miR-134-5p and miR-375-3p to increase Bdnf and Pdk1 expression in the aorta. Conclusions: Our present study indicates that vildagliptin can recover endothelial function in diabetic rats. Anti-inflammatory and anti-apoptosis mechanisms and endothelial moderation may be the intervention targets of vildagliptin to protect the cardiovascular system through miRNA regulation.

19.
Open Forum Infect Dis ; 8(9): ofab463, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34584902

RESUMO

The drivers of low-level viremia (LLV) between 20 and 200 copies/mL remain unclear. In 1042 person-visits from 497 persons with HIV on tenofovir disoproxil fumarate-containing antiretroviral therapy (ART), the association between LLV and cumulative antiretroviral adherence (quantified using tenofovir diphosphate [TFV-DP] in dried blood spots) was assessed. Lower TFV-DP levels were associated with higher odds of LLV. As TFV-DP (fmol/punch) categories decreased from >1650 to 800-1650; 800-1650 to <800; and >1650 to <800, the adjusted odds ratios for LLV vs HIV VL <20 copies/mL were 2.0 (95% CI, 1.2-3.1), 2.4 (95% CI, 1.1-5.0), and 4.6 (95% CI, 2.2-9.9), respectively. This suggests that adherence could impact LLV.

20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(9): 775-780, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34533123

RESUMO

Objective To investigate the effect of necrostatin-1 on locomotor recovery after spinal cord injury (SCI) in mice, and to explore the role of apoptosis and M1 type-microglia/macrophage-mediated pro-inflammation in the protective effect. Methods Male C57BL/6 mice were randomly divided into four groups: control group, necrostatin-1 group, SCI model group, necrostatin-1-treated group after SCI, with 20 mice in each. For SCI model group, mice were anesthetized with 10 g/L pentobarbital sodium with a dose of 8 mL/kg. After skin disinfection, T8 laminectomy was performed under operating microscope, and the T8 spinal cord was clearly revealed. The injury model was established with a device designed by our own with the parameter at 0.2 mm-width for 20 seconds. Manual urination was performed once a day. For necrostatin-1-treated group after SCI, 7.8 mg/kg of necrostatin-1 was intravenously administrated at the 1, 2, and 3 days after SCI. For necrostatin-1 group, necrostatin-1 was intravenously injected for three days. Basso Mouse Scale(BMS) score and standardized rump-height index were used to evaluate locomotor function at 1-, 3-, 5-, 7-, 10- and 14-day after injury. To observe cell apoptosis in injured cord, TUNEL staining was performed at 1-, 3-, 7-, and 14-day after injury. Western blot and immunohistochemical staining were performed to detect the expression of inducible nitric oxide synthase (iNOS), a classical marker of M1 type microglia/macrophage. Real time quantitative PCR was used to detect mRNA levels of TNF-α, interleukin-1ß (IL-1ß), IL-18, IL-4, IL-5, and IL-10. Results Necrostatin-1 significantly promoted the locomotor recovery in mice after SCI, reduced cell apoptosis around the SCI area; decreased the protein expression of M1 type microglia/macrophage marker iNOS and the number of iNOS-positive microglia/macrophage, and down-regulated the transcription levels of pro-inflammatory cytokines TNF-α, IL-18, and IL-1ß, while promoting the transcription of anti-inflammatory cytokines IL-4, IL-5, and IL-10. Conclusion Necrostatin-1 significantly promotes locomotor function recovery after SCI in mice by reducing the number of apoptotic cells and inhibiting M1 microglia/macrophages-mediated pro-inflammatory factors.


Assuntos
Microglia , Traumatismos da Medula Espinal , Animais , Apoptose , Imidazóis , Indóis , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Recuperação de Função Fisiológica , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico
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