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1.
Am J Clin Nutr ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476468

RESUMO

BACKGROUND: Classical risk factors, such as fasting cholesterol, blood pressure (BP), and diabetes status are used today to predict the risk of developing cardiovascular disease (CVD). However, accurate prediction remains limited, particularly in low-risk groups such as women and younger individuals. Growing evidence suggests that biomarker concentrations following consumption of a meal challenge are better and earlier predictors of disease development than biomarker concentrations. OBJECTIVE: To test the hypothesis that postprandial responses of circulating biomarkers differ between healthy subjects with and without subclinical atherosclerosis (SA) in an Asian population at low risk of coronary artery disease (CAD). METHODS: One hundred healthy Chinese subjects (46 women, 54 men) completed the study. Subjects consumed a mixed-meal test and 164 blood biomarkers were analyzed over 6 h by using a combination of chemical and NMR techniques. Models were trained using different methodologies (including logistic regression, elastic net, random forest, sparse partial least square) on a random 75% subset of the data, and their performance was evaluated on the remaining 25%. RESULTS: We found that models based on baseline clinical parameters or fasting biomarkers could not reliably predict SA. By contrast, an omics model based on magnitude and timing of postprandial biomarkers achieved high performance [receiving operating characteristic (ROC) AUC: 91%; 95% CI: 77, 100). Investigation of key features of this model enabled derivation of a considerably simpler model, solely based on postprandial BP and age, with excellent performance (AUC: 91%; 95% CI: 78, 100). CONCLUSION: We report a novel model to detect SA based on postprandial BP and age in a population of Asian subjects at low risk of CAD. The use of this model in large-scale CVD prevention programs should be explored. This trial was registered at ClinicalTrials.gov as NCT03531879.

2.
Allergol Immunopathol (Madr) ; 49(5): 87-93, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476927

RESUMO

Pneumonia is a common infectious disease with high morbidity and mortality. It is caused by a variety of pathogenic microorganisms that infect the lung parenchyma. Anti-infective drugs are one of the preferred choices for the treatment of pneumonia. Pachymic acid (PA) is a lanolin triterpene compound from Poria cocos, which has antiemetic, anti-inflamma-tory, and anticancer properties. Although PA inhibits inflammatory response in a variety of diseases, its role in pneumonia is not clear. In this study, we established that PA improved histopathological changes in the lungs of rats with pneumonia. PA inhibited the expression of inflammatory cytokines in the serum of rats having pneumonia. In addition, PA inhibited the apoptosis of cells from rat lung tissues. Mechanically, PA inhibited inflammation and cell apoptosis via NF-κB and MAPK pathways. Therefore, PA could serve as a promising drug for treating pneumonia.

3.
Cancer Cell ; 39(10): 1361-1374.e9, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34478639

RESUMO

Tumor-associated macrophages (TAMs) promote metastasis and inhibit T cells, but macrophages can be polarized to kill cancer cells. Macrophage polarization could thus be a strategy for controlling cancer. We show that macrophages from metastatic pleural effusions of breast cancer patients can be polarized to kill cancer cells with monophosphoryl lipid A (MPLA) and interferon (IFN) γ. MPLA + IFNγ injected intratumorally or intraperitoneally reduces primary tumor growth and metastasis in breast cancer mouse models, suppresses metastasis, and enhances chemotherapy response in an ovarian cancer model. Both macrophages and T cells are critical for the treatment's anti-metastatic effects. MPLA + IFNγ stimulates type I IFN signaling, reprograms CD206+ TAMs to inducible NO synthase (iNOS)+ macrophages, and activates cytotoxic T cells through macrophage-secreted interleukin-12 (IL-12) and tumor necrosis factor alpha (TNFα). MPLA and IFNγ are used individually in clinical practice and together represent a previously unexplored approach for engaging a systemic anti-tumor immune response.

4.
Eur J Endocrinol ; 185(4): 553-563, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34342595

RESUMO

Objective: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. Design: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. Results: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). Conclusion: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.


Assuntos
Tecido Adiposo Marrom/metabolismo , Hipertireoidismo/metabolismo , Hipertireoidismo/reabilitação , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/efeitos dos fármacos , Adulto , Idoso , Antitireóideos/farmacologia , Antitireóideos/uso terapêutico , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Carbimazol/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Fluordesoxiglucose F18 , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Doença de Graves/reabilitação , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Indução de Remissão , Singapura , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , Adulto Jovem
5.
Ecotoxicol Environ Saf ; 223: 112617, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34385058

RESUMO

PM2.5 is recently identified as a kind of material possessing severe biohazard. It can enter human body and exerts pathological effects on lung, eyes, and the central nervous system (CNS). Maternal exposure to PM2.5 can affect neural development and cause cognitive decline in offspring, with the underlying mechanisms unclear, however. The inflammasome monitors and responds to biological stressors, with HMGB1-NLRP3 inflammatory axis as an essential pathophysiological player outside the brain. The present work is to investigate its role in cognitive impairment induced by gestational exposure to PM2.5 in mice offspring. We found that HMGB1-NLRP3 pathway was activated in the hippocampus of mice offspring by gestational exposure to PM2.5 in a dose-dependent manner, with protein levels of HMGB1, NLRP3, and cleaved caspase-1 as approximately three times as high as those of control. And down-regulating HMGB1 during pregnancy could alleviate the resultant impairment on learning and working memory as well as hippocampal neurons, up-regulate the synapse related proteins of SYP and PSD-95 and correct the increased expression of 5-HT2A to comparable levels to control, as well as inhibiting the activation of microglia and decreasing the expression of HMGB1 and Iba1/HMGB1 double positive cells in the hippocampus of mice offspring. Meanwhile, protein levels of NLRP3, cleaved caspase-1, IL-1ß and IL-18, as well as TLR4, phosphorylated NF-κB, and MAPKs, were almost down-regulated to those of control. Therefore, HMGB1 intervention inhibits the NLRP3 inflammasome mediated hippocampal inflammatory response through TLR4/MAPKs/NF-κB signaling pathway, alleviating PM2.5-induced cognitive dysfunction. Further in vitro results suggest that PM2.5 can activate microglia and HMGB1-NLRP3 inflammatory axis. Pretreatment with HMGB1 inhibitor significantly reduced the phosphorylation of MAPKs and NF-κB, and inhibited the inflammatory response mediated by NLRP3 inflammasome similarly to those in vivo. These results suggest that PM2.5 exposure promotes the inflammatory response in hippocampus mediated by HMGB1-NLRP3 inflammatory axis in microglia, resulting in cognitive dysfunction in offspring, which could be alleviated by simultaneous HMGB1 suppression. These findings provide a theoretical basis for preventing cognitive impairment in offspring caused by environmental pollution during pregnancy.


Assuntos
Disfunção Cognitiva , Proteína HMGB1 , Animais , Disfunção Cognitiva/induzido quimicamente , Feminino , Proteína HMGB1/metabolismo , Hipocampo/metabolismo , Humanos , Inflamação/induzido quimicamente , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Material Particulado/toxicidade , Gravidez
6.
BMJ Open ; 11(7): e049640, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233998

RESUMO

OBJECTIVES: The primary aim of this study was to establish the normal reference ranges of the fetal left ventricular (LV) Modified Myocardial Performance Index (Mod-MPI). A secondary aim was to evaluate the agreement between manual and automatic measurements for fetal Mod-MPI. DESIGN: A prospective, multicentre, cross-sectional study. PARTICIPANTS: Normal singleton pregnancies. METHODS: The LV functions of normal singleton pregnancies were assessed in nine centres covering eight provinces in China using unified ultrasound protocols and settings and standardised measurements by pulsed Doppler at 20-24, 28-32 and 34-38 weeks of gestation. The isovolumetric relaxation time (IRT), isovolumetric contraction time, ejection time (ET) and Mod-MPI were measured both automatically and manually. RESULTS: This cross-sectional study included 2081 fetuses, and there was a linear correlation between gestational age (GA) and Mod-MPI (0.416+0.001×GA (weeks), p<0.001, r2=0.013), IRT (36.201+0.162× GA (weeks), p<0.001, r2=0.021) and ET (171.418-0.078*GA (weeks), p<0.001, r2=0.002). This finding was verified using longitudinal data in a subgroup of 610 women. The agreement between the manual and automated measurements for Mod-MPI was good. CONCLUSIONS: We constructed normal reference values of fetal LV Mod-MPI. Automatic measurement can be considered for ease of measurement in view of the good agreement between the automatic and manual values.


Assuntos
Ecocardiografia Doppler , Ultrassonografia Pré-Natal , China , Estudos Transversais , Feminino , Coração Fetal/diagnóstico por imagem , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos , Valores de Referência
7.
J Exp Bot ; 72(18): 6510-6523, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34165534

RESUMO

Phosphate (Pi)-starved crops utilize phospholipids as a source for internal Pi supply by replacing non-phosphorus glycolipids. In rice, sulfoquinovosyl diacylglycerol synthase 1 (OsSQD1) functions as a key enzyme in the first step to catalyze sulfoquinovosyldiacylglycerol (SQDG) formation. Here we study differential expression of OsSQD1 in response to Pi, nitrogen, potassium, and iron-deficiencies in rice. Electrophoretic mobility shift assay suggested that OsSQD1 is regulated by OsPHR2 (Phosphate Starvation Response2), a MYB (v-myb avian myeloblastosis viral oncogene homolog) domain-containing transcription factor. The concentrations of different lipid species in ossqd1 knockout mutant demonstrated that OsSQD1 silencing increased the phospholipid content and altered fatty acid composition under Pi-deficiency. Moreover, OsSQD1 silencing reduces glycolipid accumulation under Pi-deficiency, and triggered the saturation of fatty acids in phospholipids and glycolipids treated with different Pi regimes. Relative amounts of transcripts related to phospholipid degradation and glycolipid synthesis were assessed to explore the mechanism by which OsSQD1 exerts an effect on lipid homeostasis under P-deficiency. Furthermore, OsSQD1 silencing inhibited photosynthesis, especially under Pi-deficient conditions, by down-regulating glycolipids in rice shoots. Taken together, our study reveals that OsSQD1 plays a key role in lipid homeostasis, especially glycolipid accumulation under Pi-deficiency, which results in the inhibition of photosynthesis.

8.
Sci Rep ; 11(1): 11468, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075125

RESUMO

Cadmium (Cd) is highly toxic to living organisms and the contamination of Cd in paddy soil in China has received much attention. In the present study, by conducting pot experiment, the influence of S fertilizer (S0) on rice growth, iron plaque formation, Cd accumulation in rice plants and bacterial community in rice rhizosphere soil was investigated. The biomass of rice plants was significantly increased by S0 addition (19.5-73.6%). The addition of S0 increased the formation of iron plaque by 24.3-45.8%, meanwhile the amount of Cd sequestered on iron plaque increased. In soil treated with 5 mg/kg Cd, addition of 0.2 g/kg S0 decreased the diffusive gradients in thin films (DGT) extractable Cd by 60.0%. The application of S0 significantly decreased the concentration of Cd in rice grain by 12.1% (0.1 g/kg) and 36.6% (0.2 g/kg) respectively. The addition of S0 significantly increased the ratio of Acidobacteria, Bacteroidetes in rice rhizosphere soil. Meanwhile, the ratio of Planctomycetes and Chloroflexi decreased. The results indicated that promoting Fe- and S-reducing and residue decomposition bacterial in the rhizosphere by S0 may be one biological reason for reducing Cd risk in the soil-rice system.

9.
Psychosom Med ; 83(7): 707-714, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34117157

RESUMO

OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.

10.
Pharmacol Res ; 169: 105659, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33971268

RESUMO

The rising prevalence of obesity and being overweight is a worldwide health concern. Food reward dysregulation is the basic factor for the development of obesity. Dopamine (DA) neurons in the ventral tegmental area (VTA) play a vital role in food reward. Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor that can be activated by saturated fatty acids. Here, we show that the deletion of TLR4 specifically in DA neurons increases body weight, increases food intake, and decreases food reward. Conditional deletion of TLR4 also decreased the activity of DA neurons while suppressing the expression of tyrosine hydroxylase (TH) in the VTA, which regulates the concentration of DA in the nucleus accumbens (NAc) to affect food reward. Meanwhile, AAV-Cre-GFP mediated VTA-specific TLR4-deficient mice recapitulates food reward of DAT-TLR4-KO mice. Food reward could be rescued by re-expressing TLR4 in VTA DA neurons. Moreover, effects of intra-VTA infusion of lauric acid (a saturated fatty acid with 12 carbon) on food reward were abolished in mice lacking TLR4 in DA neurons. Our study demonstrates the critical role of TLR4 signaling in regulating the activity of VTA DA neurons and the normal function of the mesolimbic DA system that may contribute to food reward.

12.
Chin Med J (Engl) ; 134(9): 1070-1078, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33883411

RESUMO

BACKGROUND: Fetal weight is an important parameter to ensure maternal and child safety. The purpose of this study was to use three-dimensional (3D) limb volume ultrasound combined with fetal abdominal circumference (AC) measurement to establish a model to predict fetal weight and evaluate its efficiency. METHODS: A total of 211 participants with single pregnancy (28-42 weeks) were selected between September 2017 and December 2018 in the Beijing Obstetrics and Gynecology Hospital of Capital Medical University. The upper arm (AVol)/thigh volume (TVol) of fetuses was measured by the 3D limb volume technique. Fetal AC was measured by two-dimensional ultrasound. Nine cases were excluded due to incomplete information or the interval between examination and delivery >7 days. The enrolled 202 participants were divided into a model group (134 cases, 70%) and a verification group (68 cases, 30%) by mechanical sampling method. The linear relationship between limb volume and fetal weight was evaluated using Pearson Chi-squared test. The prediction model formula was established by multivariate regression with data from the model group. Accuracy of the model formula was evaluated with verification group data and compared with traditional formulas (Hadlock, Lee2009, and INTERGROWTH-21st) by paired t-test and residual analysis. Receiver operating characteristic curves were generated to predict macrosomia. RESULTS: AC, AVol, and TVol were linearly related to fetal weight. Pearson correlation coefficient was 0.866, 0.862, and 0.910, respectively. The prediction model based on AVol/TVol and AC was established as follows: Y = -481.965 + 12.194TVol + 15.358AVol + 67.998AC, R2adj = 0.868. The scatter plot showed that when birth weight fluctuated by 5% (i.e., 95% to 105%), the difference between the predicted fetal weight by the model and the actual weight was small. A paired t-test showed that there was no significant difference between the predicted fetal weight and the actual birth weight (t = -1.015, P = 0.314). Moreover, the residual analysis showed that the model formula's prediction efficiency was better than the traditional formulas with a mean residual of 35,360.170. The combined model of AVol/TVol and AC was superior to the Lee2009 and INTERGROWTH-21st formulas in the diagnosis of macrosomia. Its predictive sensitivity and specificity were 87.5% and 91.7%, respectively. CONCLUSION: Fetal weight prediction model established by semi-automatic 3D limb volume combined with AC is of high accuracy, sensitivity, and specificity. The prediction model formula shows higher predictive efficiency, especially for the diagnosis of macrosomia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03002246; https://clinicaltrials.gov/ct2/show/NCT03002246?recrs=e&cond=fetal&draw=8&rank=67.


Assuntos
Peso Fetal , Coxa da Perna , Peso ao Nascer , Criança , Feminino , Macrossomia Fetal , Humanos , Gravidez , Estudos Prospectivos , Coxa da Perna/diagnóstico por imagem , Ultrassonografia Pré-Natal
13.
J Nanosci Nanotechnol ; 21(10): 5275-5281, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875118

RESUMO

Waste toner powders are considered as hazardous materials to human and living things, and should be properly recycled by many effective ways due to their fine particle sizes and complex components. In this paper, waste toner powders were used as raw materials to successfully synthesize three dimensions (3D) graphene oxide (GO) hydrogel by means of a one-pot chemical transformation based on the improved Hummers' method. The obtained 3D GO hydrogel has porous structure and abundant oxygen-containing functional groups because of the inherent 3D solid structure of waste toner powder and the strong oxidation process of the improved Hummers' method. Interestingly, the as-prepared 3D GO hydrogel with excellent adsorptive property could quickly remove Pb(II) ions (100 mg/L, removal efficiency of 96% and removal capacity of 144 mg/g) and methylene blue (50 mg/L, removal efficiency of 97% and removal capacity of 48 mg/g) from water, respectively. The preparation process of 3D GO hydrogel was simple and easy to operate, and the output can be moderately mass produced, thus it would provide a new and effective disposal way for the recycling and reusing of waste toner.


Assuntos
Grafite , Poluentes Químicos da Água , Adsorção , Humanos , Hidrogéis , Águas Residuárias , Poluentes Químicos da Água/análise
14.
Sensors (Basel) ; 21(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806481

RESUMO

Data missing is a common problem in wireless sensor networks. Currently, to ensure the performance of data processing, making imputation for the missing data is the most common method before getting into sensor data analysis. In this paper, the temporal and spatial nearest neighbor values-based missing data imputation (TSNN), a new imputation based on the temporal and spatial nearest neighbor values has been presented. First, four nearest neighbor values have been defined from the perspective of space and time dimensions as well as the geometrical and data distances, which are the bases of the algorithm that help to exploit the correlations among sensor data on the nodes with the regression tool. Next, the algorithm has been elaborated as well as two parameters, the best number of neighbors and spatial-temporal coefficient. Finally, the algorithm has been tested on an indoor and an outdoor wireless sensor network, and the result shows that TSNN is able to improve the accuracy of imputation and increase the number of cases that can be imputed effectively.

15.
Adv Colloid Interface Sci ; 291: 102403, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33780858

RESUMO

Traditional froth flotation is the primary method for the separation and upgrading of fine mineral particles. However, it is still difficult for micro-fine and low-quality minerals to effectively separate. It is generally believed that bubble miniaturization is of great significance to improve flotation efficiency. Due to their unique physical and chemical properties, the application of nanobubbles (NBs) in ore flotation and other fields has been widely investigated as an important means to solve the problems of fine particle separation. Therefore, a fundamental understanding of the effect of NBs on flotation is a prerequisite to adapt it for the treatment of fine and low-quality minerals for separation. In this paper, recent advances in the field of nanobubble (NB) formation, preparation and stability are reviewed. In particular, we highlight the latest progress in the role of NBs on particles flotation and focus in particular on the particle-particle and particle-bubble interaction. A discussion of the current knowledge gap and future directions is provided.

16.
FASEB J ; 35(4): e21444, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33749901

RESUMO

Skeletal muscle is the largest organ of the body, the development of skeletal muscle is very important for the health of the animal body. Prolyl hydroxylases (PHDs) are the classical regulator of the hypoxia inducible factor (HIF) signal pathway, many researchers found that PHDs are involved in the muscle fiber type transformation, muscle regeneration, and myocyte differentiation. However, whether PHDs can impact the protein turnover of skeletal muscle is poorly understood. In this study, we constructed denervated muscle atrophy mouse model and found PHD3 was highly expressed in the atrophic muscles and there was a significant correlation between the expression level of PHD3 and skeletal muscle weight which was distinct from PHD1 and PHD2. Then, the similar results were getting from the different weight muscles of normal mice. To further verify the relationship between PHD3 and skeletal muscle protein turnover, we established a PHD3 interference model by injecting PHD3 sgRNA virus into tibialis anterior muscle (TA) muscle of MCK-Cre-cas9 mice and transfecting PHD3 shRNA lentivirus into primary satellite cells. It was found that the Knock-out of PHD3 in vivo led to a significant increase in muscle weight and muscle fiber area (P < .05). Besides, the activity of protein synthesis signal pathway increased significantly, while the protein degradation pathway was inhibited evidently (P < .05). In vitro, the results of 5-ethynyl-2'-deoxyuridine (EdU) and tetramethylrhodamine ethyl ester (TMRE) fluorescence detection showed that PHD3 interference could lead to a decrease in cell proliferation and an increase of cell apoptosis. After the differentiation of satellite cells, the production of puromycin in the interference group was higher than that in the control group, and the content of 3-methylhistidine in the interference group was lower than that in the control group (P < .05) which is consistent with the change of protein turnover signal pathway in the cell. Mechanistically, there is an interaction between PHD3, NF-κB, and IKBα which was detected by immunoprecipitation. With the interfering of PHD3, the expression of the inflammatory signal pathway also significantly decreased (P < .05). These results suggest that PHD3 may affect protein turnover in muscle tissue by mediating inflammatory signal pathway. Finally, we knocked out PHD3 in denervated muscle atrophy mice and LPS-induced myotubes atrophy model. Then, we found that the decrease of PHD3 protein level could alleviate the muscle weight and muscle fiber reduction induced by denervation in mice. Meanwhile, the protein level of the inflammatory signal pathway and the content of 3-methylhistidine in denervated atrophic muscle were also significantly reduced (P < .05). In vitro, PHD3 knock-out could alleviate the decrease of myotube diameter induced by LPS, and the expression of protein synthesis pathway was also significantly increased (P < .05). On the contrary, the expression level of protein degradation and inflammatory signal pathway was significantly decreased (P < .05). Through these series of studies, we found that the increased expression of PHD3 in denervated muscle might be an important regulator in inducing muscle atrophy, and this process is likely to be mediated by the inflammatory NF-κB signal pathway.


Assuntos
Denervação , Músculo Esquelético/inervação , Atrofia Muscular/metabolismo , NF-kappa B/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Animais , Regulação da Expressão Gênica , Hipertrofia , Inflamação/genética , Inflamação/metabolismo , Metilistidinas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/patologia , NF-kappa B/genética , Pró-Colágeno-Prolina Dioxigenase/genética , Puromicina , Células Satélites de Músculo Esquelético/fisiologia , Transdução de Sinais
17.
Food Funct ; 12(6): 2580-2590, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33629672

RESUMO

Origanum vulgare L. (O. vulgare) is an important medicine food homology in diabetes. The present study aimed to assess the hypoglycemic effect of the leaf extract of O. vulgare in HepG2 and HepG2-GFP-CYP2E1 (E47) cells, and disclose its potential active components by the HPLC-ESI-QTOF-MS method. Firstly, we evaluated the anti-diabetic capacity of the leaf extract of O. vulgare through inhibition of α-glucosidase activity, promotion of glucose uptake, inhibition of glycosylation and relieving of oxidative stress. Secondly, the promoter activity, the mRNA and protein expression of PEPCK and SREBP-1c, and the expression of CPY2E1 and GLUT2 in the O. vulgare mediated anti-diabetic capacity were analyzed in HepG2 and E47 cells. Finally, HPLC-ESI-QTOF-MS analysis was performed to identify the herb's main components under 280 nm irradiation. In vitro assays demonstrated that the extract inhibited α-glucosidase activity, promoted glucose uptake, inhibited glycosylation and relieved oxidative stress, which suggested that O. vulgare leaf extract has a strong hypoglycemic capacity. Moreover, mechanistic analysis also showed that the extract decreased the promoter activity and the mRNA and protein expression of PEPCK and SREBP-1c. In addition, the extract inhibited the expression of CPY2E1 and enhanced the expression of GLUT2. Moreover, the UV chromatogram at 280 nm showed six main peaks, identified as amburoside A (or 4-(3',4'-dihydroxybenzoyloxymethyl) phenyl O-ß-d-glucopyranoside), luteolin 7-O-glucuronide, apigenin 7-O-glucuronide, rosmarinic acid, lithospermic acid and a novel compound, demethylbenzolignanoid, based on accurate MS data. This work supported the ethnopharmacological usage of O. vulgare as an antidiabetic herbal medicine or dietary supplement and identified its main phenolic compounds.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Hipoglicemiantes , Origanum/química , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/farmacologia , Glucose/análise , Glucose/metabolismo , Produtos Finais de Glicação Avançada/análise , Produtos Finais de Glicação Avançada/metabolismo , Inibidores de Glicosídeo Hidrolases/análise , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Células Hep G2 , Humanos , Hipoglicemiantes/análise , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , alfa-Glucosidases/metabolismo
18.
Int J Oral Sci ; 13(1): 5, 2021 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-33550328

RESUMO

Considering the adverse effects of nonimpacted third molars (N-M3s) on the periodontal health of adjacent second molars (M2s), the removal of N-M3s may be beneficial to the periodontal health of their neighbors. This study aimed to investigate the clinical, immunological, and microbiological changes of the periodontal condition around M2s following removal of neighboring N-M3s across a 6-month period. Subjects with at least one quadrant containing an intact first molar (M1), M2, and N-M3 were screened and those who met the inclusion criteria and decided to receive N-M3 extraction were recruited in the following investigation. M2 periodontal condition was interrogated before M3 extraction (baseline) and at 3 and 6 months postoperatively. Improvements in clinical periodontal indexes of M2s in response to their adjacent N-M3 removal, along with changes in inflammatory biomarkers among gingival crevicular fluid (GCF) and the composition of subgingival plaque collected from the distal sites of the M2s of the targeted quadrant were parallelly analyzed. Complete data of 26 tooth extraction patients across the follow-up period were successfully obtained and subsequently applied for statistical analysis. Compared to the baseline, the periodontal condition of M2s was significantly changed 6 months after N-M3 removal; specifically, the probing depth of M2s significantly reduced (P < 0.001), the matrix metalloproteinase (MMP)-8 concentration involved in GCF significantly decreased (P = 0.025), and the abundance of the pathogenic genera unidentified Prevotellaceae and Streptococcus significantly decreased (P < 0.001 and P = 0.009, respectively). We concluded that N-M3 removal was associated with superior clinical indexes, decreased GCF inflammatory biomarkers, and reduced pathogenic microbiome distribution within the subgingival plaque. Although the retention or removal of N-M3s continues to be controversial, our findings provide additional evidence that medical decisions should be made as early as possible or at least before the neighboring teeth are irretrievably damaged.


Assuntos
Dente Serotino , Doenças Periodontais , Humanos , Dente Molar/cirurgia , Dente Serotino/cirurgia , Índice Periodontal , Extração Dentária
19.
J Int Med Res ; 49(1): 300060520986369, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33445988

RESUMO

OBJECTIVE: This study aimed to investigate the protective effects of naringin on myocardial deformation and oxidative responses in rats with sepsis-induced myocardial dysfunction (SIMD). METHODS: Global and segmental layer-specific longitudinal strain (LS) was assessed by speckle tracking echocardiography. Serum levels of creatine kinase, lactate dehydrogenase, superoxide dismutase, and malondialdehyde were measured. The activity of cleaved caspase-3 was determined by immunohistochemistry. Protein expression levels of Kelch-like ECH-related protein 1 (Keap1), nuclear erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were measured by western blotting. RESULTS: Naringin inhibited the lipopolysaccharide-induced decrease in global and layer-specific LS of the left ventricle. Naringin also increased superoxide dismutase expression and decreased malondialdehyde, creatine kinase, lactate dehydrogenase, and cleaved caspase-3 expression in rats with SIMD. Furthermore, naringin increased Nrf2 and HO-1 protein expression levels, and decreased Keap1 protein expression levels in rats with SIMD. CONCLUSION: Layer-specific LS analysis of myocardial function by speckle tracking echocardiography can reflect early changes in myocardial systolic function. Naringin may possess a protective effect through moderating lipopolysaccharide-induced myocardial oxidative stress via the Keap1/Nrf2/HO-1 pathway in rats with SIMD.


Assuntos
Fator 2 Relacionado a NF-E2 , Sepse , Animais , Flavanonas , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ratos , Sepse/tratamento farmacológico , Transdução de Sinais
20.
Brain Imaging Behav ; 15(2): 630-642, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32314199

RESUMO

Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID); neuroimaging studies have shown brain functional abnormalities in thalamo-cortical regions in patients with FGID. However, association between FCon and topological characteristics of brain networks remains largely unknown. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory approach to investigate functional brain topological organization in 42 patients with FCon and 41 healthy controls (HC) from perspectives of global, regional and modular levels. Results showed patients with FCon had a significantly lower normalized clustering coefficient and small-worldness, implying decreased brain functional connectivity. Regions showed altered nodal degree and efficiency mainly located in the thalamus, rostral anterior cingulate cortex (rACC), and supplementary motor area (SMA), which are involved in somatic/sensory, emotional processing and motor-control. For the modular analysis, thalamus, rACC and SMA had an aberrant within-module nodal degree and nodal efficiency, and thalamus-related network exhibited abnormal interaction with the limbic network (amygdala and hippocampal gyrus). Nodal degree in the thalamus was negatively correlated with difficulty of defecation, and nodal degree in the rACC was negatively correlated with sensation of incomplete evacuation. These findings indicated that FCon was associated with abnormalities in the thalamo-cortical network.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Constipação Intestinal/diagnóstico por imagem , Humanos , Neuroimagem , Tálamo/diagnóstico por imagem
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