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1.
Magn Reson Med ; 87(1): 337-348, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34355817

RESUMO

PURPOSE: To assess RF-induced heating hazards in 1.5T MR systems caused by body-loop postures. METHODS: Twelve advanced high-resolution anatomically correct human body models with different body-loop postures are created based on poseable human adult male models. Numerical simulations are performed to assess the radiofrequency (RF)-induced heating of these 12 models at 11 landmarks. A customized phantom is developed to validate the numerical simulations and quantitatively analyze factors affecting the RF-induced heating, eg, the contact area, the loop size, and the loading position. The RF-induced heating inside three differently posed phantoms is measured. RESULTS: The RF-induced heating from the body-loop postures can be up to 11 times higher than that from the original posture. The RF-induced heating increases with increasing body-loop size and decreasing contact area. The magnetic flux increases when the body-loop center and the RF coil isocenter are close to each other, leading to increased RF-induced heating. An air gap created in the body loop or generating a polarized magnetic field parallel to the body loop can reduce the heating by a factor of three at least. Experimental measurements are provided, validating the correctness of the numerical results. CONCLUSION: Safe patient posture during MR examinations is recommended with the use of insulation materials to prevent loop formation and consequently avoiding high RF-induced heating. If body loops cannot be avoided, the body loop should be placed outside the RF transmitting coil. In addition, linear polarization with magnetic fields parallel to the body loop can be used to circumvent high RF-induced heating.

2.
Elife ; 102021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34819223

RESUMO

Pathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome bcc complexes have gained interest as targets for antibiotic drug development. However, there is currently no structural information for the cytochrome bcc complex from these pathogenic mycobacteria. Here, we report the structures of Mycobacterium tuberculosis cytochrome bcc alone (2.68 Å resolution) and in complex with clinical drug candidates Q203 (2.67 Å resolution) and TB47 (2.93 Å resolution) determined by single-particle cryo-electron microscopy. M. tuberculosis cytochrome bcc forms a dimeric assembly with endogenous menaquinone/menaquinol bound at the quinone/quinol-binding pockets. We observe Q203 and TB47 bound at the quinol-binding site and stabilized by hydrogen bonds with the side chains of QcrBThr313 and QcrBGlu314, residues that are conserved across pathogenic mycobacteria. These high-resolution images provide a basis for the design of new mycobacterial cytochrome bcc inhibitors that could be developed into broad-spectrum drugs to treat mycobacterial infections.

3.
Food Funct ; 12(20): 9808-9819, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664576

RESUMO

Corni Fructus (CF) is a traditional medicine and beneficial food with multifaceted protective effects against diabetes and its complications. Since alpha-glucosidase inhibitors (GIs) are promising first-choice oral antihyperglycemic drugs for diabetes, we examined whether GIs from CF (GICF) are useful for diabetes treatment. Therefore, GICF was extracted by ultrasound-assisted enzymatic extraction (UAEE) that is optimized by a three-level, four-factor Box-Behnken design and determined by ultra-performance liquid chromatography. Compared to 36.31 mg g-1 without enzyme treatment, the GICF yield increased to 70.44 mg g-1via UAEE under optimum conditions (0.5% compound enzyme extracted in 23 min at 46 °C and pH 4.8). The activity (91.99%) of GICF was as predicted (93.28%). When GICF was used in an insulin-resistant HepG2 cell model, it significantly ameliorated the glucose metabolism in a dose-dependent manner. Our findings indicate that UAEE may be an innovative method for functional food extraction and a potential strategy for high-quality food ingredient (such as GI) production with high efficiency and productivity.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34617340

RESUMO

PURPOSE: The longitudinal influence of parental leisure-time physical activity (LTPA) on their offspring's LTPA is poorly understood. This study examined the longitudinal associations between parental LTPA and offspring's LTPA at two-time intervals. METHOD: Child (offspring) participants (N = 3596) were enrolled from the Cardiovascular Risk in Young Finns Study in 1980. Their LTPA was self-rated through nine phases from baseline to 2018 and categorized by year into youth (1980-1986) and adult (1992-2018) LTPA. Parental LTPA was assessed with a single self-reported question at three phases from 1980 to 1986. Latent growth curve modeling stratified by gender was fitted to estimate the potential pathways between parental LTPA and offspring's youth and adult LTPA. RESULTS: Higher initial levels of paternal and maternal LTPA were independently associated with greater initial levels of youth and adult LTPA of offspring in both genders, respectively, except maternal LTPA, which did not associate with male offspring's adult LTPA. The initial levels of paternal LTPA were directly related to changes in male offspring's youth LTPA after adjusting for age, residential place, paternal education and occupation, having siblings, and offspring's body mass index. CONCLUSION: Our study demonstrates that the initial levels of parental LTPA are directly linked to the initial levels of offspring's LTPA during youth and adulthood, while changes in parental LTPA are unrelated to changes in offspring's youth and adult LTPA for either gender over time. These results imply that higher initial levels of LTPA in parents may serve as a predictor of offspring's LTPA across life stages.

5.
J Biomed Nanotechnol ; 17(8): 1525-1534, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544530

RESUMO

The development of science and technology has deepened people's understanding of cancer, changing the management of malignant tumors in the medical field. Given the common precancerous characteristics of colorectal cancer (CRC), researchers studied early CRC screening. The complexity of traditional diagnostics forced medical staff to speed up CRC innovation early screening methods. Here, we prepared nano-colloidal gold raw materials with different particle sizes (15 and 30 nm) and observed the morphological characteristics and properties of the materials. Simultaneously, the nanocolloidal gold double antibody sandwich kit was designed through the optimum pH value and protein content screening experiment. The results of clinical enteroscopy confirmed the important guiding significance of the equipment in early CRC screening.


Assuntos
Neoplasias Colorretais , Sangue Oculto , Cromatografia de Afinidade , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Coloide de Ouro , Humanos
6.
BMC Anesthesiol ; 21(1): 231, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34560835

RESUMO

BACKGROUND: To investigate the effects of different plasma target concentrations of remifentanil on the minimum alveolar concentration (MAC) for blocking adrenergic response (BAR) of sevoflurane in children with laparoscopic herniorrhaphy. METHODS: Seventy-five children with 3-7 years old scheduled for laparoscopic herniorrhaphy were randomly divided into group R0, group R1, and group R2 according to different remifentanil plasma target concentration (0, 1, and 2 ngml-1), respectively. The MACBAR of sevoflurane was determined by the up-and-down and sequential method in each group. The concentrations of epinephrine and noradrenaline were also determined at corresponding time points. RESULTS: A total of 52 child patients were used among the anticipated 75 patients. In groups R0, R1, and R2, the MACBAR of sevoflurane was (3.29 ± 0.17) %, (2.12 ± 0.10) % and (1.29 ± 0.11) %, respectively, and a significant difference was found among the three groups (P<0.05). The changes of epinephrine and noradrenaline concentrations in each group before and after insufflation of carbon dioxide pneumoperitoneum showed no significant differences. CONCLUSION: Remifentanil by target-controlled infusion can effectively reduce the MACBAR of sevoflurane during laparoscopic surgery in children. At a similar effect of MACBAR, both the changes of epinephrine and noradrenaline concentrations are not affected by the infusion of different remifentanil target concentrations. TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn ( ChiCTR1800019393 , 8, Nov, 2018).

7.
J Clin Pharm Ther ; 46(6): 1776-1783, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34514614

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus,and liver dysfunction will significantly reduce the MACBAR (minimum alveolar concentration for blocking adrenergic response) of sevoflurane. However, the effects of different remifentanil concentrations on the MACBAR of sevoflurane in patients with liver dysfunction are unclear. The aim of this study was to observe the effects of different remifentanil concentrations by intravenous target-controlled infusion on the MACBAR of sevoflurane in patients with grade B liver dysfunction under carbon dioxide pneumoperitoneum stimulus. METHODS: Seventy-five patients with grade B liver dysfunction undergoing elective laparoscopic surgery were selected, and randomly divided into three groups with remifentanil plasma target concentrations of 0 (group R0 ), 1 (group R1 ) and 2 (group R2 ) ng/ml. Anaesthesia was induced by intravenous injection of propofol 2-3 mg/kg, remifentanil 2 µg/kg and cisatracurium 0.15 mg/kg. All groups were inhaled different concentrations of sevoflurane. The determination of sevoflurane MACBAR in each group was used a method of sequential-allocation technique, and venous blood samples were taken before and after the creation of carbon dioxide pneumoperitoneum to determine plasma adrenaline and noradrenaline concentrations. RESULTS AND DISCUSSIONS: The MACBAR of sevoflurane in groups R0 , R1 and R2 was 4.83%, 3.00% and 2.10%, respectively. The MACBAR of sevoflurane was significantly difference among the three groups. When a similar effect of MACBAR had achieved in each group, no significant differences were found in the changes of plasma adrenaline and noradrenaline concentrations before and after the creation of pneumoperitoneum. What is new and conclusion Target-controlled infusion of different concentrations of remifentanil can reduce sevoflurane MACBAR during pneumoperitoneum stimulation in patients with liver dysfunction in some degree. However, the changes of plasma adrenaline and noradrenaline concentrations are consistent in the three groups when patient's stress response was inhibited at the same degree.

8.
J Craniofac Surg ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34456284

RESUMO

OBJECTIVES: To investigate whether and how the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) sponges microRNA-96 (miR-96) to achieve the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). METHODS: Protein levels were detected by Western blot. Mineralized bone matrix formation was studied by alizarin red staining. Metastasis-associated lung adenocarcinoma transcript 1, miR-96, and osteogenesis-related Messenger RNA expression was assessed by Quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The interactions between miR-96 and osterix (Osx), MALAT1, and miR-96 were determined by luciferase reporter assay. RESULTS: The expression of MALAT1 was upregulated whereas that of miR-96 was downregulated in osteogenic hBMSCs. In addition, the expression of MALAT1 significantly decreased whereas that of miR-96 increased in the hBMSCs of osteoporosis (OP) patients. qRT-PCR and alizarin red staining assays showed that MALAT1 silencing or miR-96 overexpression inhibits hBMSC osteogenic differentiation and vice versa. Overexpression of miR-96 reversed the promotive effect of MALAT1 on the osteogenic differentiation of hBMSCs. Dual luciferase report assay verified that miR-96 is a regulatory target of MALAT1 and that Osx is a gene target of miR-96. CONCLUSIONS: Taken together, the results demonstrate that MALAT1 promotes the osteogenic differentiation of hBMSCs by regulating the miR-96/Osx axis. Our study provides novel mechanistic insights into the critical role of lncRNA MALAT1 as a microRNA sponge in OP patients and sheds new light on lncRNA-directed diagnostics and therapeutics in OP.

9.
EBioMedicine ; 70: 103537, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34391093

RESUMO

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common intractable epilepsy in adults, and elucidation of the underlying pathological mechanisms is needed. Voltage-gated chloride channels (ClC) play diverse physiological roles in neurons. However, less is known regarding their functions in the epilepogenesis of TLE. METHODS: ClC-mediated current and the spontaneous inhibitory synaptic currents (sIPSC) in hippocampal neurons of epileptic lesions were investigated by electrophysiological recording. The EEG data were analyzed by Z-scored wavelet and Fourier transformations. The expression of ClC-3, a member of ClC gene family, was detected by immunostaining and western blot. FINDINGS: ClC-mediated current was increased in the hippocampal neurons of chronic TLE mice. Application of chloride channel blockers, NPPB (5-Nitro-2- [3-phenylpropylamino] benzoic acid) and DIDS (4,4'-Diisothiocyanato-2,2'-stilbenedisulfonic acid disodium salt) reduced ClC-mediated current and increased inhibitory synaptic transmission in TLE mice. NPPB and DIDS reduced the seizure frequency and the average absolute power of ictal high-frequency oscillations (HFOs, 80-500 Hz) in TLE mice. In addition, both drugs induced outwardly rectified currents, which might be tonic inhibitory currents in the hippocampal neurons of TLE patients. Furthermore, the expression of ClC-3 was increased in the hippocampus of TLE mice and patients and positively correlated with both the absolute power and number of ictal HFOs per seizure in the sclerotic hippocampus. INTERPRETATION: These data suggest that ClC participate in the epilepogenetic process of TLE and the inhibition of ClC may have anti-epileptic effect. FUNDING: This work was supported by National Natural Science Foundation of China (No. 81601143, No. 81771217).

10.
Med Sci Sports Exerc ; 53(8): 1615-1623, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261992

RESUMO

PURPOSE: This study aimed to investigate the tracking and changes of steps per day in adults and their determinants over 13 yr. METHODS: A total of 2195 subjects (1236 women) 30-45 yr of age were randomly recruited from the ongoing Cardiovascular Risk in Young Finns Study in 2007 and were followed up in 2020. Steps per day, including both total and aerobic steps per day, were monitored for seven consecutive days with a pedometer in 2007-2008 and 2011-2012 and with an accelerometer in 2018-2020. Tracking was analyzed using Spearman's correlation. Stability and changes of steps per day over time in both low-active and high-active groups (based on median values) were described by percentage agreements, kappa statistics, and logistic regression. Associations of sex, age, and body mass index with the initial number and changes in steps per day were analyzed using linear growth curve modeling. RESULTS: Tracking correlations of total steps per day at 4-, 9-, and 13-yr intervals were 0.45-0.66, 0.33-0.70, and 0.29-0.60, while corresponding correlations for aerobic steps per day were 0.28-0.55, 0.23-0.52, and 0.08-0.55, respectively. Percentage agreements were higher than 54%, and kappa statistics ranged from slight to fair over time. Compared with the low-active group, the high-active group at baseline had a higher probability of being active later in adulthood. Female sex and higher age were associated directly with the initial number of steps per day and inversely with changes in the number of steps per day. Body mass index was inversely associated with the initial number of steps per day and changes in the number of total steps per day. CONCLUSION: The 13-yr tracking of steps per day in adulthood was found to be low to moderately high. Daily ambulatory activity is essential to maintaining an active lifestyle throughout adulthood. Changes in the amount of adult steps per day vary by sex, age, and BMI.


Assuntos
Caminhada , Actigrafia , Índice de Massa Corporal , Feminino , Finlândia , Monitores de Aptidão Física , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
11.
Methods Mol Biol ; 2358: 137-144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270051

RESUMO

Plants absorb water and nutrients from soil through roots and transmit these resources through the xylem to the shoot. Roots therefore participate in information and material transduction as well as signal communication with the shoot. The importance of reversible protein phosphorylation in the regulation of plant growth and development has been amply demonstrated through decades of research. Here, we present a simple mass spectrometry-based shotgun phosphoproteomics protocol for Arabidopsis root tissue. Through this method, we can profile the Arabidopsis root phosphoproteome and construct signal networks of key proteins to better understand their roles in plant growth and development.

12.
Methods Mol Biol ; 2358: 229-237, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270059

RESUMO

Phosphorylation of a substrate by protein kinases leads to the activation or inactivation of numerous signaling pathways and metabolic processes. The assessment of kinase activity by using a specific or generic substrate plays a crucial role in characterization of kinase specificity and activity. Here we describe a protocol using either a synthetic peptide as a specific substrate or using myelin basic protein (MBP) as a generic substrate for the kinase activity assay. The kinase of interest is fused with a GFP (green fluorescent protein) tag and can be purified by GFP magnetic beads. Kinase-GFP complexes are then incubated with ATP, substrate, and coordinated reaction reagent for the kinase reaction. The assay is then quantified through mass spectrometry or enzymatic luminescence.

13.
J Food Sci ; 86(8): 3720-3729, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34309034

RESUMO

Sodium saccharin is a common artificial sweetener. However, due to its possible carcinogenic effects and causing metabolic disorders, many countries have strictly regulated its use in food. In the study, we prepared a specific monoclonal antibody (mAb 2H11) using the new hapten (6-carboxylsaccharin) and developed a direct competitive enzyme-linked immunosorbent assay (dcELISA) for the screening of sodium saccharin residue in food. The half-maximum inhibition concentration (IC50 ) and working range (IC20 -IC80 , the concentrations causing 20% and 80% inhibition by sodium saccharin) were 32.5 and 6.47 to 164 ng/mL, which was 6.5 times more sensitive than the previously reported immunoassay. The average recoveries of sodium saccharin in spiked food samples detected by dcELISA ranged from 82.1% to 117%. Among 70 food samples bought in the physical stores and online, sodium saccharin residues were only detected in four samples purchased online (one canned pineapple, two winter jujube, and one kimchi). The content measured by dcELISA agreed well with those determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The developed dcELISA was proved to be a sensitive and accurate method for determining sodium saccharin in food. PRACTICAL APPLICATION: Quantitation of sodium saccharin residue in food is very necessary and important for consumers and regulatory agencies.


Assuntos
Contaminação de Alimentos , Sacarina , Cromatografia Líquida , Ensaio de Imunoadsorção Enzimática , Contaminação de Alimentos/análise , Sódio , Espectrometria de Massas em Tandem
14.
Sensors (Basel) ; 21(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070009

RESUMO

Traditional two-dimensional radar images can only reflect the target azimuth and slant range and thus suffer problems of geometric deformation and overlapping. The unique three-dimensional (3D) imaging capability of ground-based real-aperture radar can more accurately and directly achieve correlation between the radar image and the slope monitoring scenarios, thus providing reliable information for the early warning and forecasting of landslides and collapse disasters. The latest method of selecting a slope target from a high-resolution range profile includes two indexes: maximum amplitude and coherence, which will affect the accuracy of displacement measurement when there is an interference target. We present a three-dimensional slope imaging method based on smoothness constraints. On the basis of the latest method, the objective fact of the practically smooth and continuous distribution of slope surfaces is considered. This method can be used for image interpretation on strongly scattered targets within the slope. The independently developed ground-based real-aperture slope radar system was deployed in the Heidaigou Open-Pit Coal Mine in Inner Mongolia to carry out 3D slope imaging experiments. The effectiveness of this method in slope monitoring and imaging was confirmed by comparing the surface roughness and the spatial positions of the targets with the high-density point cloud data in the projective plane obtained during the same time period. We used RMSE function and roughness as two measures. It shows that the method presented in this paper is more suitable for actual three-dimensional slope imaging.

15.
Sci Rep ; 11(1): 10763, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031435

RESUMO

Research on drugs against SARS-CoV-2 (cause of COVID-19) has been one of the major world concerns at present. There have been abundant research data and findings in this field. The interference of drugs on gene expression in cell lines, drug-target, protein-virus receptor networks, and immune cell infiltration of the host may provide useful information for anti-SARS-CoV-2 drug research. To simplify the complex bioinformatics analysis and facilitate the evaluation of the latest research data, we developed OmiczViz ( http://medcode.link/omicsviz ), a web tool that has integrated drug-cell line interference data, virus-host protein-protein interactions, and drug-target interactions. To demonstrate the usages of OmiczViz, we analyzed the gene expression data from cell lines treated with chloroquine and ruxolitinib, the drug-target protein networks of 48 anti-coronavirus drugs and drugs bound with ACE2, and the profiles of immune cell infiltration between different COVID-19 patient groups. Our research shows that chloroquine had a regulatory role of the immune response in renal cell line but not in lung cell line. The anti-coronavirus drug-target network analysis suggested that antihistamine of promethaziney and dietary supplement of Zinc might be beneficial when used jointly with antiviral drugs. The immune infiltration analysis indicated that both the COVID-19 patients admitted to the ICU and the elderly with infection showed immune exhaustion status, yet with different molecular mechanisms. The interactive graphic interface of OmiczViz also makes it easier to analyze newly discovered and user-uploaded data, leading to an in-depth understanding of existing findings and an expansion of existing knowledge of SARS-CoV-2. Collectively, OmicsViz is web program that promotes the research on medical agents against SARS-CoV-2 and supports the evaluation of the latest research findings.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Interface Usuário-Computador , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Cloroquina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Internet , Ligação Proteica , Pirazóis/farmacologia , Índice de Gravidade de Doença
16.
J Clin Endocrinol Metab ; 106(9): 2574-2591, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34050765

RESUMO

BACKGROUND: Age at natural menopause (ANM) is an important index for women's health. Either early or late ANM is associated with a series of adverse outcomes later in life. Despite being an inheritable trait, its genetic determinant has not yet been fully understood. METHODS: Aiming to better characterize the genetic architecture of ANM, we conducted genome-wide association study (GWAS) meta-analyses in European-specific as well as trans-ancestry samples by using GWAS summary statistics from the following 3 large studies: the Reproductive Genetics Consortium (ReproGen; N = 69 626), the UK Biobank cohort (UKBB; N = 111 593) and the BioBank Japan Project (BBJ; N = 43 861), followed by a series of bioinformatical assessments and functional annotations. RESULTS: By integrating the summary statistics from the 3 GWAS of up to 225 200 participants, this largest meta-analysis identified 49 novel loci and 3 secondary signals that were associated with ANM at the genome-wide significance level (P < 5 × 10-8). No population specificity or heterogeneity was observed at most of the associated loci. Functional annotations prioritized 90 candidate genes at the newly identified loci. Among the 26 traits that were genetically correlated with ANM, hormone replacement therapy (HRT) exerted a causal relationship, implying a causal pattern by which HRT was determined by ANM. CONCLUSION: Our findings improved our understanding of the etiology of female menopause, as well as shed light on potential new therapies for abnormal menopause.


Assuntos
Loci Gênicos , Estudo de Associação Genômica Ampla , Menopausa/genética , Fatores Etários , Terapia de Reposição de Estrogênios , Feminino , Humanos , Desequilíbrio de Ligação , Menopausa/etnologia , Polimorfismo de Nucleotídeo Único , Transdução de Sinais
17.
Theranostics ; 11(12): 6074-6089, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897900

RESUMO

Epilepsy is a highly prevalent and drug-refractory neurological disorder characterized by spontaneous recurrent seizures. Estrogen is identified to be proconvulsant and lowers the seizure threshold of female epilepsy. Estrogen receptor ß (ERß) has been proposed to mediate neuroprotection in epilepsy, although the underlying mechanism remains unknown. Rationale: In this study, we investigated the role of ERß in the epileptogenesis of female temporal lobe epilepsy (TLE). Methods: Immunohistochemistry, immunofluorescence, western blots, Golgi staining, 1H MRS and whole-cell patch-clamp were used to evaluate ERß expression, pathological changes, and synaptic excitation /inhibition (E/I) balance in female TLE patients and ovariectomized (OVX) chronic epileptic mice. Electroencephalogram (EEG) recordings were recorded to evaluate the epileptic susceptibility in OVX WT and ERß-/- mice. And high-throughput RNA-sequence was performed to identify differential expression genes (DEGs) which can elucidate the potential mechanism of ERß regulating the seizure susceptibility. Results: ERß expression was decreased in the brains of female TLE patients and OVX chronic epileptic mice. ERß deletion enhanced seizure susceptibility and exacerbated the imbalance of synaptic E/I in hippocampal CA1 area of OVX epileptic mice. In line with these observations, RNA-sequence data further identified glutamine ligase (GLUL) as the target of ERß involved in regulating synaptic E/I in CA1. Furthermore, ERß agonist WAY-200070 markedly suppressed epileptic phenotypes and normalized GLUL expression in CA1 region of kainic acid (KA) induced OVX chronic epileptic model. Conclusions: Our data provide novel insight into the pathogenesis of female TLE, and indicate ERß provides a new therapeutic strategy for female TLE patients.


Assuntos
Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Receptor beta de Estrogênio/metabolismo , Sinapses/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Humanos , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Convulsões/metabolismo , Convulsões/patologia
18.
Proc Natl Acad Sci U S A ; 118(15)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33876763

RESUMO

Complex II, also known as succinate dehydrogenase (SQR) or fumarate reductase (QFR), is an enzyme involved in both the Krebs cycle and oxidative phosphorylation. Mycobacterial Sdh1 has recently been identified as a new class of respiratory complex II (type F) but with an unknown electron transfer mechanism. Here, using cryoelectron microscopy, we have determined the structure of Mycobacterium smegmatis Sdh1 in the presence and absence of the substrate, ubiquinone-1, at 2.53-Å and 2.88-Å resolution, respectively. Sdh1 comprises three subunits, two that are water soluble, SdhA and SdhB, and one that is membrane spanning, SdhC. Within these subunits we identified a quinone-binding site and a rarely observed Rieske-type [2Fe-2S] cluster, the latter being embedded in the transmembrane region. A mutant, where two His ligands of the Rieske-type [2Fe-2S] were changed to alanine, abolished the quinone reduction activity of the Sdh1. Our structures allow the proposal of an electron transfer pathway that connects the substrate-binding and quinone-binding sites. Given the unique features of Sdh1 and its essential role in Mycobacteria, these structures will facilitate antituberculosis drug discovery efforts that specifically target this complex.


Assuntos
Proteínas de Bactérias/química , Complexo III da Cadeia de Transporte de Elétrons/química , Flavoproteínas/química , Mycobacterium tuberculosis/enzimologia , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Microscopia Crioeletrônica , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Flavoproteínas/metabolismo , Simulação de Dinâmica Molecular , Ligação Proteica , Ubiquinona/química , Ubiquinona/metabolismo
19.
Foods ; 10(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33809821

RESUMO

Saponins have been extensively used in the food and pharmaceutical industries because of their potent bioactive and pharmacological functions including hypolipidemic, anti-inflammatory, expectorant, antiulcer and androgenic properties. A lot of saponins-containing foods are recommended as nutritional supplements for diabetic patients. As a medicine and food homologous material, Corni Fructus (CF) contains various active ingredients and has the effect of treating diabetes. However, whether and how CF saponins attenuate diabetes is still largely unknown. Here, we isolated total saponins from CF (TSCF) using ultrasonic microwave-assisted extraction combined with response surface methodology. The extract was further purified by a nonpolar copolymer styrene type macroporous resin (HPD-300), with the yield of TSCF elevated to 13.96 mg/g compared to 10.87 mg/g obtained via unassisted extraction. When used to treat high-fat diet and streptozotocin-induced diabetic mice, TSCF significantly improved the glucose and lipid metabolisms of T2DM mice. Additionally, TSCF clearly ameliorated inflammation and oxidative stress as well as pancreas and liver damages in the diabetic mice. Mechanistically, TSCF potently regulated insulin receptor (INSR)-, glucose transporter 4 (GLUT4)-, phosphatidylinositol 3-kinase (PI3K)-, and protein kinase B (PKB/AKT)-associated signaling pathways. Thus, our data collectively demonstrated that TSCF could be a promising functional food ingredient for diabetes improvement.

20.
BMC Public Health ; 21(1): 533, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740917

RESUMO

BACKGROUND: Evidence on whether leisure-time physical activity (LTPA) facilitates individuals' adoption of multiple healthy behaviors remains scarce. This study investigated the associations of diverse longitudinal LTPA trajectories from childhood to adulthood with diet, screen time, smoking, binge drinking, sleep difficulties, and sleep duration in adulthood. METHODS: Data were drawn from the Cardiovascular Risk in Young Finns Study. Participants were aged 9-18 years (N = 3553; 51% females) in 1980 and 33-49 years at the latest follow-up in 2011. The LTPA trajectories were identified using a latent profile analysis. Differences in self-reported health-related behaviors across the LTPA trajectories were studied separately for women and men by using the Bolck-Croon-Hagenaars approach. Models were adjusted for age, body mass index, education level, marital status, total energy intake and previous corresponding behaviors. RESULTS: Persistently active, persistently low-active, decreasingly and increasingly active trajectories were identified in both genders and an additional inactive trajectory for women. After adjusting the models with the above-mentioned covariates, the inactive women had an unhealthier diet than the women in the other trajectories (p <  0.01; effect size (ES) > 0.50). The low-active men followed an unhealthier diet than the persistently and increasingly active men (p <  0.01; ES > 0.50). Compared to their inactive and low-active peers, smoking frequency was lower in the increasingly active women and men (p <  0.01; ES > 0.20) and persistently active men (p <  0.05; ES > 0.20). The increasingly active men reported lower screen time than the low-active (p <  0.001; ES > 0.50) and persistently active (p <  0.05; ES > 0.20) men. The increasingly and persistently active women reported fewer sleep difficulties than the inactive (p <  0.001; ES > 0.80) and low-active (p <  0.05; ES > 0.50 and > 0.80, respectively) women. Sleep duration and binge drinking were not associated with the LTPA trajectories in either gender, nor were sleep difficulties in men and screen time in women. CONCLUSIONS: Not only persistently higher LTPA but also an increasing tendency to engage in LTPA after childhood/adolescence were associated with healthier diet and lower smoking frequency in both genders, having less sleep difficulties in women and lower screen time in increasingly active men. Inactivity and low activity were associated with the accumulation of several unhealthy behaviors in adulthood. Associations were stronger in women.


Assuntos
Doenças Cardiovasculares , Adolescente , Adulto , Doenças Cardiovasculares/epidemiologia , Criança , Exercício Físico , Feminino , Finlândia , Comportamentos Relacionados com a Saúde , Fatores de Risco de Doenças Cardíacas , Humanos , Atividades de Lazer , Masculino , Fatores de Risco , Adulto Jovem
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