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1.
Biol Imaging ; 4: e5, 2024.
Article in English | MEDLINE | ID: mdl-38617997

ABSTRACT

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.

2.
ArXiv ; 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38560738

ABSTRACT

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.

3.
Heliyon ; 10(7): e28775, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38617962

ABSTRACT

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.

4.
Front Neurol ; 14: 1249170, 2023.
Article in English | MEDLINE | ID: mdl-37965173

ABSTRACT

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.

5.
Pharm Biol ; 61(1): 1082-1093, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37439220

ABSTRACT

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.


Subject(s)
Colitis, Ulcerative , Colitis , Male , Animals , Mice , Dextran Sulfate/toxicity , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Transcriptome , Colitis/chemically induced , Colitis/drug therapy , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy
6.
Pharm Biol ; 61(1): 337-344, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36708218

ABSTRACT

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.


Subject(s)
Benzofurans , Colorectal Neoplasms , Humans , Cell Line, Tumor , Cell Cycle , Benzofurans/pharmacology , Cell Proliferation , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Cyclin-Dependent Kinase Inhibitor p57/pharmacology
7.
JAMA Cardiol ; 7(12): e223859, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36515696

ABSTRACT

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


Subject(s)
Hemoptysis , Tomography, X-Ray Computed , Male , Humans , Hemoptysis/etiology
8.
J Ethnopharmacol ; 294: 115353, 2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35533911

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Marsdenia , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Animals , Antineoplastic Agents/pharmacology , Caco-2 Cells , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Esters , Humans , Marsdenia/chemistry , Mice , Mice, Nude , Multidrug Resistance-Associated Protein 2 , Paclitaxel/pharmacology , Steroids/chemistry
9.
BMC Neurol ; 21(1): 368, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34560837

ABSTRACT

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.


Subject(s)
Cerebellar Ataxia , Positron Emission Tomography Computed Tomography , Adult , Brain/diagnostic imaging , Cerebellar Ataxia/diagnostic imaging , Child, Preschool , Female , Humans , Magnetic Resonance Imaging , Nerve Tissue Proteins , Prognosis , Receptors, Cell Surface
11.
Pharm Biol ; 59(1): 619-628, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34010589

ABSTRACT

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.


Subject(s)
4-Butyrolactone/analogs & derivatives , Antineoplastic Agents, Phytogenic/pharmacology , Benzofurans/pharmacology , Cell Cycle Proteins/antagonists & inhibitors , Cell Cycle Proteins/genetics , Protein Processing, Post-Translational/drug effects , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics , Transcription, Genetic/drug effects , 4-Butyrolactone/pharmacology , Animals , Cell Cycle Proteins/biosynthesis , Dose-Response Relationship, Drug , Female , HeLa Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Protein Processing, Post-Translational/physiology , Transcription Factors/biosynthesis , Transcription, Genetic/physiology , Xenograft Model Antitumor Assays/methods
12.
Biomed Pharmacother ; 138: 111491, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33744755

ABSTRACT

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.


Subject(s)
Cajanus , Energy Intake/drug effects , Energy Metabolism/drug effects , Lipogenesis/drug effects , Stilbenes/pharmacology , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Animals , Energy Intake/physiology , Energy Metabolism/physiology , Fatty Liver/drug therapy , Fatty Liver/metabolism , Female , Lipogenesis/physiology , Mice , Mice, Inbred C57BL , Ovariectomy/adverse effects , Ovariectomy/trends , Stilbenes/isolation & purification , Stilbenes/therapeutic use
13.
J Clin Sleep Med ; 17(6): 1217-1227, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33590821

ABSTRACT

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.


Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Polysomnography , ROC Curve , Sleep
14.
Appl Biochem Biotechnol ; 193(5): 1496-1512, 2021 May.
Article in English | MEDLINE | ID: mdl-33484444

ABSTRACT

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.


Subject(s)
Fructose/metabolism , Lactic Acid/metabolism , Lactobacillus pentosus/metabolism , Biomass , Cations , Models, Theoretical
15.
Bioresour Bioprocess ; 8(1): 27, 2021 Apr 07.
Article in English | MEDLINE | ID: mdl-38650211

ABSTRACT

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.

16.
Phytomedicine ; 78: 153290, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32777485

ABSTRACT

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.


Subject(s)
Cajanus/chemistry , Non-alcoholic Fatty Liver Disease/prevention & control , Obesity/prevention & control , Stilbenes/pharmacology , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Animals , Anti-Obesity Agents/pharmacology , Apolipoprotein B-100/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Body Weight/drug effects , Diet , Female , Gene Expression Regulation/drug effects , Lipogenesis/drug effects , Lipogenesis/genetics , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/etiology , Obesity/etiology , Ovariectomy/adverse effects , Postmenopause , Stilbenes/therapeutic use , Triglycerides/metabolism
17.
J Med Internet Res ; 22(6): e19787, 2020 06 19.
Article in English | MEDLINE | ID: mdl-32501803

ABSTRACT

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.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Data Aggregation , Data Analysis , Fitness Trackers , Locomotion , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Social Isolation , Adult , Betacoronavirus , COVID-19 , Coronavirus Infections/transmission , Europe , Female , France , Humans , Male , Middle Aged , Pneumonia, Viral/transmission , SARS-CoV-2 , Spain
18.
Artif Cells Nanomed Biotechnol ; 48(1): 800-809, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32432484

ABSTRACT

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.


Subject(s)
Apoptosis/drug effects , Metal Nanoparticles , Pseudomonas aeruginosa/metabolism , Reactive Oxygen Species/metabolism , Silver/metabolism , Silver/pharmacology , Thyroid Neoplasms/pathology , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Intracellular Space/drug effects , Intracellular Space/metabolism , Lipid Peroxidation/drug effects , Membrane Potential, Mitochondrial/drug effects , Silver/chemistry
19.
Medicine (Baltimore) ; 98(36): e16887, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31490372

ABSTRACT

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.


Subject(s)
Neurosyphilis/diagnosis , Anti-Bacterial Agents/therapeutic use , Brain/diagnostic imaging , Brain/pathology , Diagnosis, Differential , HIV Seronegativity , Humans , Magnetic Resonance Imaging , Male , Neurosyphilis/diagnostic imaging , Neurosyphilis/drug therapy , Penicillin G/therapeutic use , Spinal Cord/diagnostic imaging , Spinal Cord/pathology , Young Adult
20.
J Cell Biochem ; 120(8): 13275-13288, 2019 08.
Article in English | MEDLINE | ID: mdl-30891825

ABSTRACT

Although it has been reported that arctigenin (ARG) can reduce the body weight and inhibit adipogenic differentiation by activating AMP-activated protein kinase (AMPK), the exact signals responsible for the ARG-mediated antiobesity mechanism through AMPK are not well understood. In this study, we investigated the potential improvement of AGR on lipid metabolism using a high-fat diet (HFD)-induced hyperlipidemia rats and 3T3-L1 mature adipocytes. The levels of AMPK and its downstream factors were examined by Western blot analysis and real-time fluorescent quantitative polymerase chain reaction. We observed that ARG lowered the HFD-induced body weight and the levels of serum lipid. Moreover, ARG clearly alleviated fat deposition in the liver and reduced epididymal fat accumulation. ARG also suppressed lipogenesis and lipolysis but promoted fatty acid ß-oxidation in adipocytes. Most importantly, ARG increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and upregulated the messenger RNA levels of downstream genes related to fatty acid ß-oxidation, such as carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 but downregulated the expression of peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1c) and their targets, including lipogenesis-related genes such as CCAAT/enhancer-binding protein α, lipoprotein lipase, adipocyte protein 2, and fatty acid synthase (FAS), as well as lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase. The activity of FAS was also decreased by ARG. We conclude that AMPK activation is important for the pharmacological effects of ARG. ARG may improve lipid metabolism by regulating the AMPK-ACC and AMPK-PPARγ/SREBP1c signaling pathways.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Furans/pharmacology , Lignans/pharmacology , Lipid Metabolism/drug effects , 3T3-L1 Cells , Acetyl-CoA Carboxylase/metabolism , Adipocytes/drug effects , Adipocytes/metabolism , Animals , Cell Survival/drug effects , Fatty Acid Synthase, Type I/metabolism , Lipoprotein Lipase/metabolism , Male , Mice , PPAR gamma/metabolism , Rats , Sterol Regulatory Element Binding Protein 1/metabolism
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