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1.
Water Res ; 265: 122303, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39216261

RESUMEN

The Pollution source identification (PSI) is an important issue on river water quality management especially for urban receiving water. Numerical inversion method is theoretically an effective PSI technique, which employs monitored downstream pollutant breakthrough curves to identify the pollution source. In practice, it is important to know how much monitoring data should be accumulated to provide PSI results with acceptable accuracy and uncertainty. However, no literature reports on this key point and it seriously handers the numerical PSI technology to mature practical applications. To seek a monitoring guideline for PSI, we conducted extensively numerical experiments for single-point source instantaneous release taking Bayesian-MCMC method as the baseline inversion technique. The crucial time (Tc) phenomenon was found during the data accumulation process for Bayesian source inversion. After Tc, estimated source parameters subsequent sustained low error levels and uncertainty convergence. Results shown the presence of Tc impacted by the number and location of monitoring sections, while monitoring frequency and data error do not. Under different river hydrodynamic conditions, relative crucial time (Λ) is determined by the river's Peclet number, and minimum effective Λ was controlled by dispersion coefficient (Dx). Analytic spatial structure of Λ(U, Dx) was uncovered and this relationship successfully explained by the information entropy theory. Based on these findings, a novel design method of PSI emergency monitoring network for preparedness plan and a practical framework of PSI for emergency response were established. These findings fill the important knowledge gap in PSI applications and the guidelines provide valuable references for river water quality management.


Asunto(s)
Monitoreo del Ambiente , Contaminantes Químicos del Agua , Contaminación Química del Agua , Ríos , Calidad del Agua , Contaminación Química del Agua/estadística & datos numéricos , Contaminantes Químicos del Agua/análisis , Modelos Estadísticos
2.
Heliyon ; 10(7): e28775, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38617962

RESUMEN

Focusing on the situation of the low helium content in natural gas resource in China and the high cost of helium extraction, the OPEX prediction model of helium extraction that based on the Response Surface Methodology (RSM) is proposed. This method applies ASPEN-HYSYS software to simulate the helium extraction process flow for a given product composition, pressure, and temperature; Applying the Design Expert module for Response Surface Methodology(RSM) parameter design, combined with OPEX of existing projects, determine the key influencing factors and upper and lower limits of OPEX, and obtaining the corresponding OPEX for different parameter values; Applying the Box Behnken Design (BBD) principle to optimize the helium extraction process parameters of RSM, based on fitting results and parameter significance verification of second-order regression function, the OPEX prediction model is built.This method is applied to a domestic helium extraction project, and the unit helium extraction cost is between 100 and 119.52 yuan/m3, IRR is 13.37%. The result shows the project has economic benefit, and the method presents a good perspective application.

3.
ArXiv ; 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38560738

RESUMEN

In this paper we propose an algorithm for aligning three-dimensional objects when represented as density maps, motivated by applications in cryogenic electron microscopy. The algorithm is based on minimizing the 1-Wasserstein distance between the density maps after a rigid transformation. The induced loss function enjoys a more benign landscape than its Euclidean counterpart and Bayesian optimization is employed for computation. Numerical experiments show improved accuracy and efficiency over existing algorithms on the alignment of real protein molecules. In the context of aligning heterogeneous pairs, we illustrate a potential need for new distance functions.

4.
Biol Imaging ; 4: e5, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617997

RESUMEN

In this article, we propose an algorithm for aligning three-dimensional objects when represented as density maps, motivated by applications in cryogenic electron microscopy. The algorithm is based on minimizing the 1-Wasserstein distance between the density maps after a rigid transformation. The induced loss function enjoys a more benign landscape than its Euclidean counterpart and Bayesian optimization is employed for computation. Numerical experiments show improved accuracy and efficiency over existing algorithms on the alignment of real protein molecules. In the context of aligning heterogeneous pairs, we illustrate a potential need for new distance functions.

5.
Front Neurol ; 14: 1249170, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37965173

RESUMEN

In this study, we investigated the potential of electrochemical skin conductance (ESC) measurements gathered from home-based devices to detect circadian-like patterns. We analyzed data from 43,284 individuals using the Withings Body Comp or Body Scan scales, which provide ESC measurements. Our results highlighted a circadian pattern of ESC values across different age groups and countries. Our findings suggest that home-based ESC measurements could be used to evaluate circadian rhythm disorders associated with neuropathies and contribute to a better understanding of their pathophysiology. However, further controlled studies are needed to confirm these results. This study highlights the potential of digital health devices to generate new scientific and medical knowledge.

6.
Pharm Biol ; 61(1): 1082-1093, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37439220

RESUMEN

CONTEXT: Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. OBJECTIVE: This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. MATERIALS AND METHODS: Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings. RESULTS: Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1ß and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1ß, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment. DISCUSSION AND CONCLUSION: Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1ß, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.


Asunto(s)
Colitis Ulcerosa , Colitis , Masculino , Animales , Ratones , Sulfato de Dextran/toxicidad , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Transcriptoma , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico
7.
Pharm Biol ; 61(1): 337-344, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36708218

RESUMEN

CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumor cell growth in vitro and in vivo. The underlying mechanism involves the suppression of the Yes-associated protein. However, the specific role of LAF in cell cycle regulation remains unknown. OBJECTIVE: This study determined the molecular mechanism by which LAF regulates cell cycle progression. MATERIALS AND METHODS: Various colon cancer cell lines (SW480, HCT15, and HCT116) were treated with LAF (25, 50, and 75 µmol/L) for 48 h. The effects of LAF on cell proliferation and cell cycle were determined using sulforhodamine B and flow cytometry assays. Differentially expressed proteins (DEPs) were identified using quantitative proteomics. Bioinformatic analysis of DEPs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Expression levels of DEPs in the cell cycle pathway were analyzed using RT-qPCR and western blotting. RESULTS: LAF suppressed the proliferation of SW480, HCT15, and HCT116 cells (IC50 47.1, 51.4, and 32.8 µmol/L, respectively) and induced cell cycle arrest at the S phase. A total of 6331 proteins were identified and quantified, of which 127 were differentially expressed between the LAF-treated and untreated groups. GO and KEGG enrichment analyses revealed that DEPs mainly participated in the cell cycle. CDKN1C/p57 showed the most significant differential expression, with the highest fold-change (3.155-fold). Knockdown of CDKN1C/p57 attenuated the S phase cell cycle arrest and proliferation inhibition induced by LAF. CONCLUSION: LAF exerts antitumor effects via S phase arrest by activating CDKN1C/p57 in colorectal cancer cells.


Asunto(s)
Benzofuranos , Neoplasias Colorrectales , Humanos , Línea Celular Tumoral , Ciclo Celular , Benzofuranos/farmacología , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/farmacología
8.
JAMA Cardiol ; 7(12): e223859, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36515696

RESUMEN

This case report describes a diagnosis of ruptured coronary artery aneurysm after a patient presentation of chest pain and new-onset intermittent hemoptysis.


Asunto(s)
Hemoptisis , Tomografía Computarizada por Rayos X , Masculino , Humanos , Hemoptisis/etiología
9.
J Ethnopharmacol ; 294: 115353, 2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-35533911

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima is a medicinal plant, used as a raw material for cancer treatment in China. In our previous studies, 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B (MT2), the main steroid aglycone isolated from M. tenacissima, was found to significantly enhance the antitumor activity of paclitaxel (PTX) in vivo. However, it is unclear whether MT2 reverses multidrug resistance (MDR) in tumors. AIM OF THE STUDY: To determine the role and mechanism of MT2 in reversing tumor MDR. MATERIALS AND METHODS: MDR cell line HeLa/Tax was established from the human cervical carcinoma cell line HeLa by long-term exposure to subtoxic concentrations of PTX and was used to evaluate the ability of MT2 to restore chemosensitivity of cells both in vitro and in a nude mouse model. The expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) was determined using western blotting and immunohistochemistry. The substrate transport function was assessed using an MDR function assay kit. The binding modes of MT2 and P-gp were determined using the conformation-sensitive anti-P-gp antibodies. The permeability and transport properties of MT2 were analyzed in Caco-2 cell monolayers. RESULTS: Compared to parental cells, HeLa/Tax cells overexpress P-gp and MRP2 and are approximately 100-360 fold more resistant to the anticancer drugs PTX, docetaxel, and vinblastine. MT2 at 5 or 10 µmol/L significantly increased the sensitivity of HeLa/Tax to these three anticancer drugs (18-56-fold decrease in IC50 value) and suppressed the expression of P-gp and MRP2. Knockdown of P-gp with small interfering RNA partially reversed MT2-induced sensitivity to PTX in HeLa/Tax cells. Moreover, MT2 directly inhibited P-gp-mediated substrate transport while interacting with membrane P-gp in non-substrate ways. MT2 was highly permeable and could not be transported in the Caco-2 cell monolayers. In nude mice bearing HeLa/Tax xenografts, the combination treatment with MT2 and PTX exerted a synergistic inhibitory effect on the growth of tumors and the expression of P-gp and MRP2 without increasing toxicity. CONCLUSION: MT2 is a potential agent for reversing MDR. It impedes membrane drug efflux pumps by suppressing P-gp and MRP2 expression, and directly inhibiting the transport function of P-gp.


Asunto(s)
Antineoplásicos , Marsdenia , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Antineoplásicos/farmacología , Células CACO-2 , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Ésteres , Humanos , Marsdenia/química , Ratones , Ratones Desnudos , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Paclitaxel/farmacología , Esteroides/química
10.
BMC Neurol ; 21(1): 368, 2021 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-34560837

RESUMEN

BACKGROUND: Brain magnetic resonance imaging (MRI) rarely reveals structural changes in patients with suspected anti-Tr/DNER encephalitis and thus provides very limited information. Here, we combined structural MRI, functional MRI, and positron emission tomography-computed tomography (PET-CT) findings to characterize this rare disorder in a patient. CASE PRESENTATION: A 43-year-old woman presented with progressive cerebellar ataxia, memory impairment, anxiety, and depression. Anti-Tr antibodies were detected in both her serum (1:10) and cerebrospinal fluid (1:10). A diagnosis of anti-Tr-positive autoimmune cerebellar ataxia was established. The patient's symptoms were worse, but her brain MRI was normal. Meanwhile, voxel-based morphometry analysis showed bilateral reduced cerebellar volume, especially in the posterior lobe and uvula of the cerebellum and the middle of the left temporal lobe compared with 6 sex- and age-matched healthy subjects (6 females, 43 ± 2 years; p < 0.05). Using seed-based functional connectivity analysis, decreased connectivity between the posterior cingulate cortex/precuneus and left frontal lobe compared to the control group (p < 0.05) was detected. PET-CT revealed bilateral hypometabolism in the cerebellum and relative hypermetabolism in the cerebellar vermis and bilateral frontal lobe, but no malignant changes. CONCLUSIONS: A combination of structural MRI, functional MRI, and brain PET-CT has higher diagnostic and prognostic value than conventional MRI in patients with suspected anti-Tr/DNER encephalitis.


Asunto(s)
Ataxia Cerebelosa , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Encéfalo/diagnóstico por imagen , Ataxia Cerebelosa/diagnóstico por imagen , Preescolar , Femenino , Humanos , Imagen por Resonancia Magnética , Proteínas del Tejido Nervioso , Pronóstico , Receptores de Superficie Celular
12.
Pharm Biol ; 59(1): 619-628, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34010589

RESUMEN

CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumour cell growth by inducing cell cycle arrest. However, its underlying anticancer mechanism remains unclear. OBJECTIVE: The effects of LAF on the Hippo-Yes-associated protein (YAP) signalling pathway, which plays an important role in cancer progression, were explored in this study. MATERIALS AND METHODS: Cervical (HeLa), colorectal (SW480), breast (MDA-MB-231) and prostate (PC3) cancer cell lines were treated with LAF at different concentrations and different durations. BALB/c nude mice bearing colon xenografts were intravenously injected with vehicle, LAF (10 or 20 mg/kg) or paclitaxel (10 mg/kg) for 15 days. The expression and nuclear localisation of YAP were analysed using transcriptome sequencing, quantitative PCR, western blotting and immunofluorescence. RESULTS: LAF suppressed the proliferation of HeLa, MDA-MB-231, SW480 and PC3 cells (IC50 values of 41.5, 26.0, 45.3 and 42.9 µmol/L, respectively, at 72 h), and this was accompanied by significant downregulation in the expression of YAP and its downstream target genes at both the mRNA and protein levels. The expression of 14-3-3σ, a protein that causes YAP cytoplasmic retention and degradation, was remarkably increased, resulting in a decrease in YAP nuclear localisation. Knockdown of 14-3-3σ with small interfering RNA partially blocked LAF-induced YAP inhibition and anti-proliferation effects. In colon xenografts, treatment with LAF led to reduced YAP expression, increased tumour cell apoptosis and tumour growth inhibition. CONCLUSION: LAF was shown to be an inhibitor of YAP. It exerts anticancer activity by inhibiting YAP at the transcriptional and post-translational levels.


Asunto(s)
4-Butirolactona/análogos & derivados , Antineoplásicos Fitogénicos/farmacología , Benzofuranos/farmacología , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Transcripción Genética/efectos de los fármacos , 4-Butirolactona/farmacología , Animales , Proteínas de Ciclo Celular/biosíntesis , Relación Dosis-Respuesta a Droga , Femenino , Células HeLa , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Procesamiento Proteico-Postraduccional/fisiología , Factores de Transcripción/biosíntesis , Transcripción Genética/fisiología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
13.
Biomed Pharmacother ; 138: 111491, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33744755

RESUMEN

BACKGROUND: We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated. METHODS: Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed. FINDINGS: In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX, ORXR2, pMCH and Gal) in the hypothalami, of lipogenic genes (CD36, SREBP-1c, ChREBP, PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides. INTERPRETATION: CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA.


Asunto(s)
Cajanus , Ingestión de Energía/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Estilbenos/farmacología , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Animales , Ingestión de Energía/fisiología , Metabolismo Energético/fisiología , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Femenino , Lipogénesis/fisiología , Ratones , Ratones Endogámicos C57BL , Ovariectomía/efectos adversos , Ovariectomía/tendencias , Estilbenos/aislamiento & purificación , Estilbenos/uso terapéutico
14.
J Clin Sleep Med ; 17(6): 1217-1227, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33590821

RESUMEN

STUDY OBJECTIVES: To assess the diagnostic performance of a nonintrusive device placed under the mattress to detect sleep apnea syndrome. METHODS: One hundred eighteen patients suspected to have obstructive sleep apnea syndrome completed a night at a sleep clinic with a simultaneous polysomnography (PSG) and recording with the Withings Sleep Analyzers. PSG nights were scored twice: first as simple polygraphy, then as PSG. RESULTS: Average (standard deviation) apnea-hypopnea index from PSG was 31.2 events/h (25.0) and 32.8 events/h (29.9) according to the Withings Sleep Analyzers. The mean absolute error was 9.5 events/h. The sensitivity, specificity, and area under the receiver operating characteristic curve at thresholds of apnea-hypopnea index ≥ 15 events/h were, respectively, sensitivity (Se)15 = 88.0%, specificity (Sp)15 = 88.6%, and area under the receiver operating characteristic curve (AUROC) 15 = 0.926. At the threshold of apnea-hypopnea index ≥ 30 events/h, results included Se30 = 86.0%, Sp30 = 91.2%, AUROC30 = 0.954. The average total sleep time from PSG and the Withings Sleep Analyzers was 366.6 (61.2) and 392.4 (67.2) minutes, sleep efficiency was 82.5% (11.6) and 82.6% (11.6), and wake after sleep onset was 62.7 (48.0) and 45.2 (37.3) minutes, respectively. CONCLUSIONS: Withings Sleep Analyzers accurately detect moderate-severe sleep apnea syndrome in patients suspected of sleep apnea syndrome. This simple and automated approach could be of great clinical value given the high prevalence of sleep apnea syndrome in the general population. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Validation of Withings Sleep for the Detection of Sleep Apnea Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT04234828; Identifier: NCT04234828.


Asunto(s)
Síndromes de la Apnea del Sueño , Apnea Obstructiva del Sueño , Humanos , Polisomnografía , Curva ROC , Sueño
15.
Appl Biochem Biotechnol ; 193(5): 1496-1512, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33484444

RESUMEN

In this study, Box-Behnken design was applied to optimize the initial concentrations of 4 cations for L-lactic acid production from fructose by homologous batch fermentation of Lactobacillus pentosus cells. The optimum initial cation concentrations were obtained as 6.542 mM Mg2+, 3.765 mM Mn2+, 2.397 mM Cu2+, and 3.912 mM Fe2+, respectively. The highest L-lactic acid yield and productivity were obtained as 0.935 ± 0.005 g/g fructose and 1.363 ± 0.021 g/(L × h), respectively, with a maximum biomass concentration of 7.97 ± 0.17 g/L. The effectiveness of the optimization by Box-Behnken design was confirmed based on the small errors between predicted results and experimental results shown as 0.3%, - 0.2%, and - 1.2%, respectively. The quadratic models with high accuracy and reliability can be applied to mathematically forecasted the fermentation performance. After the optimization, the lactic acid yield and productivity were significantly improved by 3.7% and 21.0%, respectively.


Asunto(s)
Fructosa/metabolismo , Ácido Láctico/metabolismo , Lactobacillus pentosus/metabolismo , Biomasa , Cationes , Modelos Teóricos
16.
Bioresour Bioprocess ; 8(1): 27, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38650211

RESUMEN

Under the optimal conditions of immobilization and fermentation, the highest LA yield of 0.966 ± 0.006 g/g fructose and production rate of 2.426 ± 0.018 g/(L × h) with an error of -0.5% and -0.2% to the predicted results were obtained from batch fermentation by the CS film-coated SA-PVA immobilized L. pentosus cells. The LA yield and production rate of these immobilized cells were 2.7% and 10.1% higher than that of normal SA-PVA immobilized cells respectively, and they were 5.7% and 48.4% higher than that of free cells, respectively. The effect of temperature on different types of immobilized cells and free cells was significantly different, but the effect of pH on different types of cells was not much different. The kinetic models could effectively describe the different fermentation performances of three types of cells. The immobilized cells have excellent reusability to conduct 9 runs of repeated batch fermentation.

17.
Phytomedicine ; 78: 153290, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32777485

RESUMEN

BACKGROUND: Visceral obesity and fatty liver are prevalent in postmenopausal women. The stilbene-rich extract of Cajanus cajan (L.) Millsp. has been reported to prevent ovariectomy-induced and diet-induced weight gain in animal models, and stilbenoids from C. cajan are thought to have the potential to prevent postmenopausal obesity and fatty liver. PURPOSE: Cajanolactone A (CLA) is the main stilbenoid from C. cajan with osteoblastogenic promoting activity. This study investigated the potential of CLA to prevent postmenopausal obesity and fatty liver. Underlying mechanisms were also investigated. METHOD: Ovariectomized C57BL/6 mice fed a regular diet were used as mimics of postmenopausal women and given 10, 20, or 40 mg/kg/d of CLA, 0.1 mg/kg/d of estradiol valerate (EV, positive control), or vehicle (OVX) orally for 16 weeks. Mice of the same age subjected to a sham operation were used as control (Sham). Body weights were recorded every 2 weeks for 16 weeks. Body compositions were analyzed via micro-CT. Serum levels of lipids, adipocytokines and aminotransferases were measured using the relevant kits. mRNA levels of genes of interest were detected by RT-qPCR. Proteomic study of perigonadal white adipose tissue (pWAT) was performed using tandem-mass-tags-based proteomic technology combined with Parallel-Reaction-Monitoring (PRM) validation. RESULTS: CLA showed potential equivalent to that of EV to prevent ovariectomy-induced overweight, obesity, dyslipidemia, liver steatosis and liver dysfunction, but did not prevent uterine atrophy. In the liver, CLA significantly inhibited ovariectomy-induced upregulation in expression of lipogenic genes SREBP-1c and ChREBP, and stimulated the mRNA expression of apolipoprotein B gene ApoB. In pWAT, CLA reversed, or partially reversed ovariectomy-induced downregulation in the expression of a number of metabolism- and mitochondrial-function-related proteins, including Ndufa3, Pcx, Pdhb, Acly, Acaca, Aldh2, Aacs and Echs1. In addition, ovariectomy-inhibited mRNA expression of Pdhb, Aacs, Acsm5, Echs1, and Aldh2 genes in pWAT was also reversed. CONCLUSION: CLA was demonstrated to be a potential non-estrogen-like drug candidate for prevention of postmenopausal obesity and fatty liver. The underlying mechanism might involve the inhibition of lipogenesis and promotion of triglycerides output in the liver, and the promotion of metabolism and mitochondrial functions of visceral white adipose tissue.


Asunto(s)
Cajanus/química , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/prevención & control , Estilbenos/farmacología , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Animales , Fármacos Antiobesidad/farmacología , Apolipoproteína B-100/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Peso Corporal/efectos de los fármacos , Dieta , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/etiología , Ovariectomía/efectos adversos , Posmenopausia , Estilbenos/uso terapéutico , Triglicéridos/metabolismo
18.
J Med Internet Res ; 22(6): e19787, 2020 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-32501803

RESUMEN

BACKGROUND: In the context of home confinement during the coronavirus disease (COVID-19) pandemic, objective, real-time data are needed to assess populations' adherence to home confinement to adapt policies and control measures accordingly. OBJECTIVE: The aim of this study was to determine whether wearable activity trackers could provide information regarding users' adherence to home confinement policies because of their capacity for seamless and continuous monitoring of individuals' natural activity patterns regardless of their location. METHODS: We analyzed big data from individuals using activity trackers (Withings) that count the wearer's average daily number of steps in a number of representative nations that adopted different modalities of restriction of citizens' activities. RESULTS: Data on the number of steps per day from over 740,000 individuals around the world were analyzed. We demonstrate the physical activity patterns in several representative countries with total, partial, or no home confinement. The decrease in steps per day in regions with strict total home confinement ranged from 25% to 54%. Partial lockdown (characterized by social distancing measures such as school closures, bar and restaurant closures, and cancellation of public meetings but without strict home confinement) does not appear to have a significant impact on people's activity compared to the pre-pandemic period. The absolute level of physical activity under total home confinement in European countries is around twofold that in China. In some countries, such as France and Spain, physical activity started to gradually decrease even before official commitment to lockdown as a result of initial less stringent restriction orders or self-quarantine. However, physical activity began to increase again in the last 2 weeks, suggesting a decrease in compliance with confinement orders. CONCLUSIONS: Aggregate analysis of activity tracker data with the potential for daily updates can provide information regarding adherence to home confinement policies.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Agregación de Datos , Análisis de Datos , Monitores de Ejercicio , Locomoción , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Aislamiento Social , Adulto , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/transmisión , Europa (Continente) , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Neumonía Viral/transmisión , SARS-CoV-2 , España
19.
Artif Cells Nanomed Biotechnol ; 48(1): 800-809, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32432484

RESUMEN

We used cell-free culture filtrate of Pseudomonas aeruginosa as a reducing mediator of AgNO3 to silvernanoparticles (AgNPs) and possibly used as a potential anticancer agent against thyroid cancer cells (TPC1). The bio-generation of AgNPs was firmly established by taking a UV spectrum at 380-500 nm wavelength. The Fourier transform spectrum analysis reveals the association of alcohol, phenol and aromatic functional groups with P. aeruginosa synthesized AgNPs (Ps-AgNPs). By observing under transmission electron microscopy (TEM), the size and structure of the Ps-AgNPs were characterized as the size was 30-70 nm and spherical in shape. The concentration-dependent cytotoxicity of Ps-AgNPs on TPC1 cells was observed and IC50 value was calculated. The alteration of oxidative and antioxidant biomarkers in Ps-AgNPs treated cells were observed. The induced apoptosis was determined by staining the Ps-AgNPs treated cells with DCFH-DA, Rh-123 dye, Acridine Orange (AO) and ethidium bromide (EtBr). Increased level of intracellular reactive oxygen species (ROS) generation and decreased level of mitochondrial membrane potential was observed in Ps-AgNPs treated TPC1 cells. Moreover, the apoptotic morphological changes were explored, which indicates increased apoptosis by inducing cell membrane damage in Ps-AgNPs treated cells. This biogenic approach will enable an effective and significant improvement in nano-oncotherapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Nanopartículas del Metal , Pseudomonas aeruginosa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Plata/metabolismo , Plata/farmacología , Neoplasias de la Tiroides/patología , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Plata/química
20.
Medicine (Baltimore) ; 98(36): e16887, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31490372

RESUMEN

RATIONALE: Multiple syphilitic gummas involving both the brain and spinal cord are quite rare. Central nervous system (CNS) syphilitic gummas are commonly misdiagnosed as CNS tumors, and clinical suspicion and diagnosis of a syphilitic gumma by physicians are vital to avoiding unnecessary surgeries. Our case emphasizes the importance of routine serologic syphilis tests and standard therapy with penicillin in patients with a CNS mass. PATIENT CONCERNS: A 22-year-old previously healthy man presented with a 9-day history of progressive right lower limb weakness. DIAGNOSIS: The diagnosis of gummatous neurosyphilis was based on positive serological, cerebrospinal fluid tests for syphilis and magnetic resonance imaging (MRI) findings, which revealed the presence of multiple dural-based enhancing masses with marked edema. INTERVENTIONS: Therapy consisting of intravenous penicillin G at 24 million units daily divided into 6 doses were given for a total of 21 days, along with 3 weekly intramuscular injections of benzathine penicillin G (2.4 million units) to ensure that the syphilitic lesions in the CNS were adequately treated. OUTCOMES: Complete resolution of the lesions was observed on MRI over a 3-month period. LESSONS: The importance of routine serologic syphilis tests and standard therapy with penicillin in patients with central CNS mass lesions is noted to avoiding unnecessary surgeries.


Asunto(s)
Neurosífilis/diagnóstico , Antibacterianos/uso terapéutico , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Diagnóstico Diferencial , Seronegatividad para VIH , Humanos , Imagen por Resonancia Magnética , Masculino , Neurosífilis/diagnóstico por imagen , Neurosífilis/tratamiento farmacológico , Penicilina G/uso terapéutico , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología , Adulto Joven
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