Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells.

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.

Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice.

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.

Combination of structural MRI, functional MRI and brain PET-CT provide more diagnostic and prognostic value in patients of cerebellar ataxia associated with anti-Tr/DNER: a case report.

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.

Lappaol F, an anticancer agent, inhibits YAP via transcriptional and post-translational regulation.

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.

Wearable Activity Trackers for Monitoring Adherence to Home Confinement During the COVID-19 Pandemic Worldwide: Data Aggregation and Analysis.

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.

Arctigenin improves lipid metabolism by regulating AMP-activated protein kinase and downstream signaling pathways.

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.

Alignment of Density Maps in Wasserstein Distance.

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.

Alignment of density maps in Wasserstein distance.

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.

Prediction model and its application of helium extraction OPEX based on response surface methodology.

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.

Circadian-like patterns in electrochemical skin conductance measured from home-based devices: a retrospective study.

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.

An ester derivative of tenacigenin B from Marsdenia tenacissima (Roxb.) Wight et Arn reversed paclitaxel-induced MDR in vitro and in vivo by inhibiting both P-gp and MRP2.

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.

[Isolation and characterization of promoter of ADS from Artemisia annua].

OBJECTIVE: To try to find the ways to enhance the expression of ADS gene encoding amorpha-4,11-diene synthase, a key enzyme in artemisinin biosynthesis pathway catalyzing the formation of amorpha-4,11-diene from farnesyl diphosphate, and accelerate the artemisinin synthesis, the promoter of ADS was isolated and characterized. METHOD: 5' untranslated regions of ADS were isolated from Artemisia annua with PCR. For functional characterization, the isolated fragment was fused with GUS reporter gene and introduced into Nicotiana tabacum by Agrobacterium-mediated transformation. The GUS expression regulated by 5' untranslated regions of ADS in transgenic N. tabacum under the normal or stressed conditions were detected by histochemical staining and quantitative spectrophotometry assay. RESULT: The 2 448 bp DNA fragment upstream of ADS coding sequence was isolated from A. annua and introduced into N. tabacum. Histochemical staining showed that the isolated fragment conferred stable GUS expression in transgenic plants. The quantitative results showed that the GUS activity in transgenic tobacco plants treated by low-temperature (4 degrees C) and ultraviolet irradiation were 1. 6 and 2.2 folds higher than that in the controls. CONCLUSION: It was suggested that the isolated fragment had promoter activity and maybe responsive to adverse environmental stresses.

Validation of the Withings Sleep Analyzer, an under-the-mattress device for the detection of moderate-severe sleep apnea syndrome.

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.

Optimization of Initial Cation Concentrations for L-Lactic Acid Production from Fructose by Lactobacillus pentosus Cells.

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.

Cajanolactone A, a stilbenoid from Cajanus cajan, inhibits energy intake and lipid synthesis/storage, and promotes energy expenditure in ovariectomized mice.

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.

L-Lactic acid production from fructose by chitosan film-coated sodium alginate-polyvinyl alcohol immobilized Lactobacillus pentosus cells and its kinetic analysis.

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.

Senescent leaves of Artemisia annua are one of the most active organs for overexpression of artemisinin biosynthesis responsible genes upon burst of singlet oxygen.

To dissect and penetrate complexicity regarding the tissue-specific and environment-induced expression modes of cytosolic and plastidial terpene biosynthetic genes in A. annua, corresponding mRNAs relevant to terpene biosynthesis were quantitatively compared among distinctive organs and during different growth stages. Although all examined mRNAs gradually elevate from June to August in tested organs, a putative artemisinin biosynthesis responsible DBR2 mRNA represents the most abundant transcript anyplace and anytime. Apart from others, senescent leaves endow global activation of artemisinin biosynthetic genes and ultimately lead to enhanced artemisinin production. Direct measurement of (1)O (2) burst from senescent leaves strongly supports an involvement of (1)O (2) in conversion from precursor(s) to artemisinin. In the context of environmental stresses, physical and chemical stress signals that include those invoking (1)O (2) burst were evaluated as if inducing artemisinin biosynthetic genes. The quantitative data have reiterated a common pattern of modulating artemisinin production in A. annua by triggering (1)O (2) burst during senescence and under chilling acclimatization. In conclusion, a missing link concatenating senescence-coupled (1)O (2) generation to (1)O (2)-induced upregulation of artemisinin biosynthetic genes has been re-established, which would provide a fertile base for future endeavors pursuing further enhancements of artemisinin production.

Pseudomonas aeruginosa synthesized silver nanoparticles inhibit cell proliferation and induce ROS mediated apoptosis in thyroid cancer cell line (TPC1).

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.

Cajanolactone A, a stilbenoid from cajanus cajan, prevents ovariectomy-induced obesity and liver steatosis in mice fed a regular diet.

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.