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1.
Anal Chim Acta ; 1189: 339224, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815036

RESUMO

Psoralen ultraviolet A (PUVA) therapy has thrived as a promising treatment for psoriasis. However, overdose of PUVA treatment will cause side-effects, such as melanoma formation. And these side-effects are often ignored during PUVA therapy. Hence, in situ monitoring therapeutic response of PUVA therapy is important to minimize side-effects. Aberrant expression of tyrosinase (TYR) has been proved to be associated with melanoma, indicating that TYR is a potential target for evaluation of PUVA therapy. Herein, we reported a strategy for in situ monitoring TYR activity during PUVA therapy by using a cell-array chip-based SERS platform. The cell-array chip was used to simulate cell survival environment for cell culture. Capture of single cells and living cell analysis were realized in the isolated microchambers. An enzyme-induced core-shell self-assembly substrate was used to evaluate TYR activity in living cells during PUVA therapy. The gold nanoparticle modified with a SERS reporter, 4-mercaptobenzonitrile (4-MBN), was used as the core. In the presence of oxygen and TYR, hydroxylation of l-tyrosine occurred, leading to the reduction of silver ion on the surface of gold cores. The growth of silver shells was accompanied by the increased SERS intensity of the reporter, which is related directly to TYR activity. The detection limit for TYR activity is 0.45 U/mL. Upregulation of TYR activity was successfully monitored after PUVA therapy. Notably, real-time and in situ information of therapeutic response can be obtained through monitoring PUVA therapy by using a cell-array chip-based SERS platform, which has great potential to guide the clinical application of PUVA therapy.


Assuntos
Ouro , Nanopartículas Metálicas , Terapia PUVA , Prata , Análise Espectral Raman
2.
Abdom Radiol (NY) ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825269

RESUMO

PURPOSE: Studies have found that both FibroScan (FS) and Gd-EOB-DTPA-enhanced T1 mapping magnetic resonance imaging (Gd-MRI) could assess liver fibrosis (LF) with high effectiveness. The aim of this study is to compare their accuracy in the quantitative evaluation of LF in patients with chronic hepatitis B (CHB), and to explore the diagnostic accuracy of their combination. METHODS: 160 patients with CHB were included in this study. FS and Gd-MRI were performed within 3 months before the pathological LF staging, which was classified according to the Scheuer-Ludwig scale. The liver stiffness measurement (LSM) was obtained by FS. T1 mapping images of the liver before and 20 min after enhancement were obtained by Look-Locker Gd-MRI. RESULTS: There were 45, 35, 31 and 49 patients with stage S1, S2, S3 and S4 LF, respectively. LSM increased and the reduction rate of T1 relaxation time of 20 min (rrT120min%) decreased with the severity of LF. The area under curve (AUC) of LSM, rrT120min% and LSM + rrT120min% for the diagnosis of ≥ S2 LF were 0.892, 0.811 and 0.900, respectively. The AUC for ≥ S3 LF was 0.883, 0.838 and 0.899, respectively. The AUC for S4 LF was 0.882, 0.894 and 0.928, respectively. CONCLUSION: The diagnostic accuracy of FS is better than that of Gd-MRI in the evaluation of ≥ S2 stage LF. The combination of these two methods significantly improved the diagnostic efficiency in the evaluation of S4 stage LF.

3.
Front Cardiovasc Med ; 8: 770163, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820432

RESUMO

The abnormally expressed long non-coding RNA (lncRNA) H19 has a crucial function in the development and progression of cardiovascular disease; however, its role in atherosclerosis is yet to be known. We aimed to examine the impacts of lncRNA H19 on atherogenesis as well as the involved mechanism. The outcomes from this research illustrated that the expression of lncRNA H19 was elevated in mouse blood and aorta with lipid-loaded macrophages and atherosclerosis. Adeno-associated virus (AAV)-mediated lncRNA H19 overexpression significantly increased the atherosclerotic plaque area in apoE-/- mice supplied with a Western diet. The upregulation of lncRNA H19 decreased the miR-146a-5p expression but increased the levels of ANGPTL4 in mouse blood and aorta and THP-1 cells. Furthermore, lncRNA H19 overexpression promoted lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-induced THP-1 macrophages. However, the knockdown of lncRNA H19 served as a protection against atherosclerosis in apoE-/- mice and lowered the accumulation of lipids in ox-LDL-induced THP-1 macrophages. lncRNA H19 promoted the expression of ANGPTL4 via competitively binding to miR-146a-5p, thus promoting lipid accumulation in atherosclerosis. These findings altogether demonstrated that lncRNA H19 facilitated the accumulation of lipid in macrophages and aggravated the progression of atherosclerosis through the miR-146a-5p/ANGPTL4 pathway. Targeting lncRNA H19 might be an auspicious therapeutic approach for preventing and treating atherosclerotic disease.

4.
BMC Pulm Med ; 21(1): 334, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706685

RESUMO

BACKGROUND: Despite incarcerated population being at an increased risk of tuberculosis (TB) and serving as a potential source of TB transmission for the general population, prison TB remains understudied. Given its adverse impact on progress towards TB elimination, World Health Organization (WHO) has identified prison TB research as a top priority to guide TB treatment/control interventions. METHODS: We retrospectively analyzed 921 notified TB cases that were diagnosed at Kality Federal Prison, Ethiopia during 2009-2017. To assess trends of microbiologically confirmed pulmonary TB (PTB), extra-pulmonary TB (EPTB), and TB-HIV co-infection, an ecological analysis of aggregated cases was used to report trends over time. Additionally, we used multivariable log binomial regression to identify patient characteristics associated with microbiologically confirmed PTB, EPTB, and TB-HIV co-infection. RESULTS: Microbiologically confirmed PTB proportion increased over time. Young age was identified as an important risk factor for EPTB (adjusted prevalence ratio [aPR] = 1.74, 95% CI 0.97, 3.13) while HIV coinfection was negatively associated with EPTB (aPR = 0.73, 95% CI 0.55, 0.97). While previous TB history was associated with a lower likelihood of EPTB (aPR = 0.42, 95% CI 0.25, 0.70), it was associated with an increased risk of TB-HIV coinfection (aPR = 1.37, 95% CI 1.10, 1.71). Clinically diagnosed PTB patients were more likely to have TB-HIV coinfection compared to microbiologically confirmed PTB patients (aPR = 1.32, 95% CI 1.02, 1.72). CONCLUSIONS: Increasing proportion of microbiologically confirmed PTB may suggest delayed access to treatment, severe disease and increased risk of intramural transmission. Associations with clinical/demographic factors varied for different types of TB and were not always consistent with what has been previously reported for the general population, necessitating the need to refocus prison TB control/treatment strategies based on context specific epidemiological factors.

5.
Yi Chuan ; 43(9): 910-920, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702703

RESUMO

Xanthomonas campestris pv. campestris (Xcc) is a vascular pathogen that causes black rot in host. It is an important model strain for studying the interaction between the phytopathogen and plants. In Xcc, global transcription regulator HpaR1 that belongs to the GntR family regulates many cellular processes such as the movement and synthesis of extracellular polysaccharides and extracellular enzymes, and is associated with hypersensitive response (HR) and pathogenicity. On the other hand, the global transcriptional regulator Clp regulates the secretion and synthesis of extracellular enzymes and extracellular polysaccharides, and is associated with the pathogenicity of Xanthomonas. Previous studies have shown that both HpaR1 and Clp bind to the promoter region of the glycoside hydrolase encoding gene (named ghy gene). This study investigates the molecular mechanism of the co-regulation of HpaR1 and Clp on the expression of ghy gene. Through electrophoresis mobility shift assay (EMSA), we found that both HpaR1 and Clp bind to the promoter regions of gene ghy in vitro. Both HpaR1 and Clp also bind to the promoter regions of gene ghy in vivo by chromatin immunoprecipitation (ChIP) assays. DNase I footprinting and 5'-RACE assays showed that both HpaR1 and Clp bind to the -35 region upstream of the ghy promoter. The HpaR1 binding site was located upstream of the Clp binding site. RT-qPCR and in vitro transcription assays showed that HpaR1 negatively while Clp positively regulates the transcription of gene ghy. Furthermore, HpaR1 inhibits the activation of Clp on the transcription of gene ghy in vitro. Our findings indicate that HpaR1 and Clp exhibit opposite effect on the transcription of gene ghy. It is speculated that HpaR1 may regulate the expression of gene ghy by inhibiting the activity of RNA polymerase.


Assuntos
Xanthomonas campestris , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Glicosídeo Hidrolases/genética , Glicosídeos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Xanthomonas campestris/genética , Xanthomonas campestris/metabolismo
6.
Nat Prod Res ; : 1-10, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34694166

RESUMO

Three new biflavonoids, umcephabiovins C - E (1 - 3), along with fourteen known compounds were isolated from the twigs and leaves of Cephalotaxus oliveri. Their structures and configurations were elucidated by UV, IR, NMR, ECD, and HR-ESI-MS spectra. Compounds 1 - 3 exhibited significant α-glucosidase inhibitory activity with IC50 values of 7.05 ± 2.66, 24.45 ± 4.73, and 1.84 ± 1.14 µM, respectively. Compound 11 showed moderate cytotoxicity against the BaF3/T315I cell line.

7.
Molecules ; 26(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34641483

RESUMO

A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones G‒P (1-10), along with four known ones (11-14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 µM.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34694263

RESUMO

OBJECTIVE: To evaluate neurodevelopmental status among children with inherited cholestatic liver diseases with native liver and variables predictive of impairment. METHODS: Participants with Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and alpha 1 antitrypsin deficiency (A1AT) enrolled in a longitudinal, multicenter study and completed the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV. Full Scale IQ (FSIQ) was analyzed continuously and categorically (≥100, 85-99, 70-84, < 70). Univariate linear regression was performed to study association between FSIQ and risk factors, stratified by disease. RESULTS: 215 completed testing (ALGS n = 70, PFIC n = 43, A1AT n = 102); median age was 7.6 years (3.0-16.9). Mean FSIQ in ALGS was lower than A1AT (94 vs. 101, p = 0.01). Frequency of FSIQ< 85 (>1 SD below average) was highest in ALGS (29%) versus 18.6% in PFIC and 12.8% in A1AT, and was greater than expected in ALGS based on normal distribution (29% vs. 15.9%, p = 0.003). ALGS scored significantly lower than test norms in almost all Wechsler composites; A1AT scored lower on Working Memory and Processing Speed; PFIC was not different from test norms. Total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education were significantly associated with FSIQ. CONCLUSIONS: Patients with ALGS are at increased risk of lower FSIQ, whereas our data suggest A1AT and PFIC are not. A1AT and ALGS appear vulnerable to working memory and processing speed deficits suggestive of attention/executive function impairment. Malnutrition, liver disease severity, and sociodemographic factors appear related to FSIQ deficits, potentially identifying targets for early interventions.

9.
Oncogenesis ; 10(10): 67, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642309

RESUMO

Transient receptor potential canonical (TRPC) channels are the most prominent nonselective cation channels involved in various diseases. However, the function, clinical significance, and molecular mechanism of TRPCs in colorectal cancer (CRC) progression remain unclear. In this study, we identified that TRPC1 was the major variant gene of the TRPC family in CRC patients. TRPC1 was upregulated in CRC tissues compared with adjacent normal tissues and high expression of TRPC1 was associated with more aggressive tumor progression and poor overall survival. TRPC1 knockdown inhibited cell proliferation, cell-cycle progression, invasion, and migration in vitro, as well as tumor growth in vivo; whereas TRPC1 overexpression promoted colorectal tumor growth and metastasis in vitro and in vivo. In addition, colorectal tumorigenesis was significantly attenuated in Trpc1-/- mice. Mechanistically, TRPC1 could enhance the interaction between calmodulin (CaM) and the PI3K p85 subunit by directly binding to CaM, which further activated the PI3K/AKT and its downstream signaling molecules implicated in cell cycle progression and epithelial-mesenchymal transition. Silencing of CaM attenuated the oncogenic effects of TRPC1. Taken together, these results provide evidence that TRPC1 plays a pivotal oncogenic role in colorectal tumorigenesis and tumor progression by activating CaM-mediated PI3K/AKT signaling axis. Targeting TRPC1 represents a novel and specific approach for CRC treatment.

10.
Chin J Integr Med ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581940

RESUMO

OBJECTIVE: To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons. METHODS: The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway. RESULTS: MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01). CONCLUSION: TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.

11.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3123-3132, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467704

RESUMO

The chemical constituents from the leaves of Ilex guayusa were investigated. Sixteen triterpenoids were isolated from the 95% ethanol extract of dried leaves of I. guayusa by silica gel, Sephadex LH-20, and ODS column chromatographies and semi-prepa-rative HPLC. Those triterpenoids were identified by NMR, HR-MS, and literature analysis: 3ß-hydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13ß-olide(1), 3ß-hydroxy-24-nor-4(23),12-oleanadien-28-methyl ester(2), oleanolic acid(3), 3ß,28-dihydroxy-12-oleanene(4), 2α,3ß-dihydroxy-11α,12α-epoxy-24-'nor-olean-4(23)-ene-28,13ß-olide(5), ursolic acid(6), 3ß,23-dihydroxy ursolic acid(7), 3ß,28-dihydroxy-12-ursene(8), 3ß-28-nor-urs-12-ene-3,17-diol(9), 3ß-hydroxyurs-11-ene-28,13ß-olide(10), 13ß,28-epoxy-3ß-hydroxy-11-ursene(11), 3ß-hydroxy-28,28-dimethoxy-12-ursene(12), 3ß-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid(13), 3ß-hydroxy-24-nor-urs-4(23),12-dien-28-methyl ester(14), 2α,3ß-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13ß-olide(15) and 2α,3ß-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23),20(30)-dien-28,13ß-olide(16). Compounds 1-2 were new compounds, and compounds 4-5, 7 and 9-16 were isolated from I. guayusa for the first time.


Assuntos
Medicamentos de Ervas Chinesas , Ilex guayusa , Ácido Oleanólico , Triterpenos , Estrutura Molecular , Folhas de Planta
13.
World J Clin Cases ; 9(24): 7053-7061, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34540960

RESUMO

BACKGROUND: Fracture risk assessment in children with benign bone lesions of long bones remains poorly investigated. AIM: To investigate the risk factors for pathological fracture in children with benign bone lesions and to propose a modified scoring system for quantitative analysis of the pathologic fracture risk. METHODS: We retrospectively reviewed 96 pediatric patients with benign bone lesions. We compared radiographic and clinical features between 40 patients who had fractures through a benign bone lesion and 56 who had no fracture. Information including histological diagnosis, anatomical site, radiographic appearance, severity of pain, and lesion size was recorded for the patients. A modified scoring system was proposed to predict the risk of fracture. RESULTS: The univariate comparisons showed a significant difference between the fracture and non-fracture groups in terms of lesion type, pain, lesion-to-bone width, and axial cortical involvement of the patients (P < 0.05). Lesion type, pain, lesion-to-bone width, and axial cortical involvement were independently correlated with an increased risk of fracture. The mean score of the fracture group was 7.89, whereas the mean score of the non-fracture group was 6.01. The optimum cut-off value of the score to predict pathological fracture was 7. The scoring system had a sensitivity of 70% and a specificity of 80% for detecting patients with fractures. The Youden index was 0.5, which was the maximum value. The area under the receiver operator characteristic was 0.814. CONCLUSION: Lesion type, pain, lesion-to-bone width, and axial cortical involvement are risk factors for pathological fracture. The modified scoring system can provide evidence for clinical decision-making in children with benign bone lesions. A bone lesion with a total score > 7 indicates a high risk of a pathologic fracture and is an indication for prophylactic internal fixation.

14.
ACS Sens ; 6(10): 3800-3807, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550676

RESUMO

In recent years, the performance research of perovskite materials is not only concentrated in the field of solar cells or optics, but the field of gas sensing has gradually entered the public view. However, the detection of nitric oxide (NO) by lead-free halide perovskites has not yet been reported. Herein, we use Cs2PtI6 to realize the first example of a halide perovskite applied to NO sensing. Due to favoring Pt-N binding, the material has some excellent properties such as a NO detection limit as low as 100 parts-per-billion (ppb), ultrahigh selectivity to NO, and can work at room temperature for more than 2 months. In situ sum frequency generation (SFG) spectra and crystal orbital Hamilton population (COHP) analysis reveal that the strong bonding interaction between Pt 5s and N 2s ensure the high adsorption energy, and Pt 5d electron back donation to N 2px, N 2pz antibonding causes the conductive change of the sensors. In addition, its flexible wearable technology shows the application potential of the device and promotes the further development of perovskite materials.


Assuntos
Compostos de Cálcio , Óxido Nítrico , Óxidos , Titânio
15.
Environ Res ; 204(Pt B): 112035, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509483

RESUMO

Activated carbon is commonly used to remove dioxins from flue gas via adsorption. Improving the targeted adsorption capacity of activated carbon for dioxins can reduce the consumption of adsorbents and help achieve emission standards for target pollutants. Here, commercial coal-based activated carbon was used as a raw material and modified by urea impregnation along with treatment at high temperature under a nitrogen atmosphere. It was found that modification with urea effectively improved the pore structure of activated carbon while incorporating a certain amount of nitrogen. The best modification effect was achieved at a modification temperature of 600 °C, an impregnation ratio of urea to activated carbon of 1:1, and with high-temperature treatment for 2 h. The mesopore volume of the modified activated carbon (AC600) reached 0.38 cm3/g, accounting for 57.58% of the total pore volume. With an impregnation ratio of urea to activated carbon of 1:1, high-temperature treatment for 2 h, and a modification temperature of 800 °C, a certain amount of nitrogen was introduced into the carbon rings to form a modified activated carbon (AC800) rich in pyridine and pyrrole groups (atomic percentage = 4.84%). The activated carbon modified by urea and the unmodified activated carbon were subsequently selected for dioxin adsorption experiments using a dioxin generation and adsorption system. AC600 showed the highest adsorption efficiency for dioxins, reaching 97.65%, based on toxicity equivalents. Although AC800 has poor pore properties, it has more pyridine and pyrrole groups than AC600. Consequently, the efficiency of AC800 at adsorbing low-concentration dioxins reached 85.24% based on toxicity equivalents. Overall, this study describes two mechanisms for effectively modifying activated carbon with urea based on (1) optimizing the pore structure of activated carbon and (2) incorporating nitrogen.

16.
Cell Prolif ; 54(11): e13133, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34585448

RESUMO

OBJECTIVES: Maternal factors that are enriched in oocytes have attracted great interest as possible key factors in somatic cell reprogramming. We found that surfeit locus protein 4 (Surf4), a maternal factor, can facilitate the generation of induced pluripotent stem cells (iPSCs) previously, but the mechanism remains elusive. MATERIALS AND METHODS: In this study, we investigated the function and mechanism of Surf4 in somatic cell reprogramming using a secondary reprogramming system. Alkaline phosphatase (AP) staining, qPCR and immunofluorescence (IF) staining of expression of related markers were used to evaluate efficiency of iPSCs derived from mouse embryonic fibroblasts. Embryoid body and teratoma formation assays were performed to evaluate the differentiation ability of the iPSC lines. RNA-seq, qPCR and western blot analysis were applied to validate the downstream targets of Surf4. RESULTS: Surf4 can significantly facilitate the generation of iPSCs in a proliferation-independent manner. When co-expressed with Oct4, Sox2, Klf4 and c-Myc (OSKM), Surf4 can activate the response to endoplasmic reticulum (ER) stress at the early stage of reprogramming. We further demonstrated that Hspa5, a major ER chaperone, and the active spliced form of Xbp1 (sXbp1), a major mediator of ER stress, can mimic the effects of Surf4 on somatic cell reprogramming. Concordantly, blocking the unfolded protein response compromises the effect of Surf4 on reprogramming. CONCLUSIONS: Surf4 promotes somatic cell reprogramming by activating the response to ER stress.


Assuntos
Reprogramação Celular/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Fibroblastos/metabolismo , Proteínas de Membrana/metabolismo , Animais , Diferenciação Celular/fisiologia , Corpos Embrioides/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Camundongos , Fatores de Transcrição/metabolismo
17.
Nat Prod Res ; : 1-7, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507510

RESUMO

Bixasteroid (1), one new steroid together with five known compounds (2-6), were isolated from the ethyl acetate fraction of ethanol extract of Bixa orellana fruits. All of these known compounds were isolated from the plant for the first time. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configuration of compound 1 was determined by X-ray crystallographic data analysis as well as by the quantum chemical ECD calculations. All the isolated compounds were tested for their anti-inflammatory activities. Compounds 1 and 2 showed inhibiting NO release activities in LPS-induced RAW 264.7 macrophages with the IC50 values of 4.72 ± 0.28 and 5.48 ± 1.48 µM, respectively.

18.
Stat Med ; 40(26): 5947-5960, 2021 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542193

RESUMO

In medical and social science research, reliability of testing methods measured through inter- and intraobserver agreement is critical in disease diagnosis. Often comparison of agreement across multiple testing methods is sought in situations where testing is carried out on the same experimental units rendering the outcomes to be correlated. In this article, we first developed a Bayesian method for comparing dependent agreement measures under a grouped data setting. Simulation studies showed that the proposed methodology outperforms the competing methods in terms of power, while maintaining a decent type I error rate. We further developed a Bayesian joint model for comparing dependent agreement measures adjusting for subject and rater-level heterogeneity. Simulation studies indicate that our model outperforms a competing method that is used in this context. The developed methodology was implemented on a key measure on a dichotomous rating scale from a study with six raters evaluating three classification methods for chest radiographs for pneumoconiosis developed by the International Labor Office.


Assuntos
Teorema de Bayes , Simulação por Computador , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes
19.
ACS Chem Neurosci ; 12(19): 3650-3661, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34541857

RESUMO

Impaired differentiation of newborn neurons or abnormalities at the synapses resulted from stress maladaptation could be the key etiology of depression. Recent studies have shown that mTOR, a crucial factor for neuronal differentiation and synapse development, acts as a common factor that mediates the rapid antidepression effects of several new-class antidepressants. In this study, the antidepressant-like activity of securinine, an alkaloid that has central nervous system stimulation ability, was investigated. Both securinine and its enantiomer virosecurinine exhibited potent in vitro activity on neuronal differentiation and synapse development in Neuro-2a cells and cultured hippocampal neurons, and this activity was dependent on the activation of the AKT-mTOR-S6K pathway. Interestingly, only securinine but not virosecurinine showed mTOR stimulation and antidepressant-like activity in mice. Importantly, a single dose of securinine was capable of alleviating the behavioral deficits induced by both acute and chronic stress models within 30 min of administration, suggesting that securinine has rapid onset of action. Moreover, neither a single dose nor a 3 week treatment of securinine had adverse effects on exploratory locomotion of mice. Together, this study identifies that securinine is a potent agent in promoting neuronal differentiation and synapse formation and shows rapid antidepressant-like activity, without inducing abnormal locomotion, via mTOR activation.


Assuntos
Compostos Heterocíclicos de Anel em Ponte , Serina-Treonina Quinases TOR , Animais , Antidepressivos/farmacologia , Azepinas , Diferenciação Celular , Compostos Heterocíclicos de Anel em Ponte/farmacologia , Lactonas , Camundongos , Piperidinas
20.
Sensors (Basel) ; 21(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34450775

RESUMO

Three-dimensional imaging for multi-node interferometric synthetic aperture radar (InSAR) or multi-task imaging sensors has become the prevailing trend in the field of aerial remote sensing, which requires multi-node motion information to carry out the motion compensation. A distributed position and orientation system (DPOS) can provide multi-node motion information for InSAR by transfer alignment technology. However, due to wing deformation, the relative spatial relationship between the nodes will change, which will lead to lower accuracy of the transfer alignment. As a result, the flexible baseline between the nodes affects the interferometric phase error compensation and further deteriorates the imaging quality. This paper proposes a flexible baseline measuring system based on optics, which achieves non-connect measurement and overcomes the problem that it is difficult to build an accurate wing deformation model. An accuracy test was conducted in the laboratory, and results showed that the measurement accuracy of the baseline under static and dynamic conditions was less than 0.3 mm and 0.67 mm, respectively.

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