Genistein Regulates Lipid Metabolism via Estrogen Receptor β and Its Downstream Signal Akt/mTOR in HepG2 Cells

Genistein (GEN) has been shown to significantly inhibit hepatic triglyceride accretion triggered by estrogen deficiency. The main purpose of this in vitro study was to investigate the function and molecular mechanism of estrogen receptor β (ERβ) in regulating hepatic lipid metabolism induced by GEN. Different doses of GEN or GEN with an ERβ antagonist were treated with HepG2 cells. Results showed that 25 μM GEN significantly diminished triglyceride levels. Meanwhile, GEN downregulated the levels of genes and proteins involved in lipogenesis, such as sterol-regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and stearoyl-coenzyme A desaturase 1 (SCD1), and upregulated the gene and protein levels of the regulation factors responsible for fatty acid β-oxidation, such as carnitine palmitoyltransferase 1α (CPT-1α) and peroxisome proliferator-activated receptor α (PPARα). Furthermore, 25 μM GEN reduced the levels of phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Moreover, most of these effects from GEN were reverted by pretreatment with the antagonist of ERβ. In conclusion, GEN improved hepatic lipid metabolism by activating ERβ and further modulation of Akt/mTOR signals. The results provide novel aspects of the regulatory mechanism of ERβ on hepatic lipid metabolism and might help to profoundly understand the functions of food-derived phytoestrogens in preventing and treating hepatic steatosis in postmenopausal women

Mechanism of <i>Astragalus membranaceus</i> Alleviating Acquired Hyperlipidemia Induced by High-Fat Diet through Regulating Lipid Metabolism

Astragalus membranaceus (AM) is a food and medicinal homologous plant. The current research is aimed to investigate the beneficial effects and mechanisms of AM in treating acquired hyperlipidemia. The network pharmacology and bioinformatics analysis results showed 481 AM-related targets and 474 acquired hyperlipidemia-associated targets, and 101 candidate targets were obtained through the intersection, mainly enriched in endocrine resistance, AGE-RAGE in diabetic complications and p53 signaling pathways. Quercetin, kaempferol, calycosin, formononetin and isorhamnetin were determined as the candidate active components of AM in the treatment of acquired hyperlipidemia. Moreover, key targets of AM, namely, AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), cyclin D1 (CCND1) and estrogen receptor 1 (ESR1), were screened out, which were closely related to adipogenesis, fatty acid metabolism and bile acid metabolism. The subsequent animal experiments showed that AM extract treatment improved the lipid profiles of the high-fat diet (HFD)-fed mice by reducing lipogenesis and increasing lipolysis and lipid β-oxidation, which were associated with the downregulating of AKT1 and CCND1, and the upregulating of VEGFA and ESR1 in liver and adipose tissue. Overall, AM alleviated acquired hyperlipidemia through regulating lipid metabolism, and AKT1, VEGFA, CCND1 and ESR1 might be the key targets

Sesamol promotes browning of white adipocytes to ameliorate obesity by inducing mitochondrial biogenesis and inhibition mitophagy via β3-AR/PKA signaling pathway

Background: Obesity is defined as an imbalance between energy intake and expenditure, and it is a serious risk factor of non-communicable diseases. Recently many studies have shown that promoting browning of white adipose tissue (WAT) to increase energy consumption has a great therapeutic potential for obesity. Sesamol, a lignan from sesame oil, had shown potential beneficial functions on obesity treatment. Objective: In this study, we used C57BL/6J mice and 3T3-L1 adipocytes to investigate the effects and the fundamental mechanisms of sesamol in enhancing the browning of white adipocytes to ameliorate obesity. Methods: Sixteen-week-old C57BL/6J male mice were fed high-fat diet (HFD) for 8 weeks to establish the obesity models. Half of the obese mice were administered with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage for another 8 weeks. Triacylglycerol (TG) and total cholesterol assay kits were used to quantify serum TG and total cholesterol (TC). Oil red O staining was used to detect lipid droplet in vitro. Mito-Tracker Green was used to detect the mitochondrial content. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the levels of beige-specific genes. Immunoblotting was used to detect the proteins involved in beige adipocytes formation. Results: Sesamol decreased the content of body fat and suppressed lipid accumulation in HFD-induced obese mice. In addition, sesamol significantly upregulated uncoupling protein-1 (UCP1) protein in adipose tissue. Further research found that sesamol also significantly activated the browning program in mature 3T3-L1 adipocytes, manifested by the increase in beige-specific genes and proteins. Moreover, sesamol greatly increased mitochondrial biogenesis, as proved by the upregulated protein levels of mitochondrial biogenesis, and the inhibition of the proteins associated with mitophagy. Furthermore, β3-adrenergic receptor (β3-AR), protein kinase A-C (PKA-C) and Phospho-protein kinase A (p-PKA) substrate were elevated by sesamol, and these effects were abolished by the pretreatment of antagonists β3-AR. Conclusion: Sesamol promoted browning of white adipocytes by inducing mitochondrial biogenesis and inhibiting mitophagy through the β3-AR/PKA pathway. This preclinical data promised the potential to consider sesamol as a metabolic modulator of HFD-induced obesity

Cell-Membrane Biomimetic Indocyanine Green Liposomes for Phototheranostics of Echinococcosis

Echinococcosis is an important zoonotic infectious disease that seriously affects human health. Conventional diagnosis of echinococcosis relies on the application of large-scale imaging equipment, which is difficult to promote in remote areas. Meanwhile, surgery and chemotherapy for echinococcosis can cause serious trauma and side effects. Thus, the development of simple and effective treatment strategies is of great significance for the diagnosis and treatment of echinococcosis. Herein, we designed a phototheranostic system utilizing neutrophil-membrane-camouflaged indocyanine green liposomes (Lipo-ICG) for active targeting the near-infrared fluorescence diagnosis and photothermal therapy of echinococcosis. The biomimetic Lipo-ICG exhibits a remarkable photo-to-heat converting performance and desirable active-targeting features by the inflammatory chemotaxis of the neutrophil membrane. In-vitro and in-vivo studies reveal that biomimetic Lipo-ICG with high biocompatibility can achieve in-vivo near-infrared fluorescence imaging and phototherapy of echinococcosis in mouse models. Our research is the first to apply bionanomaterials to the phototherapy of echinococcosis, which provides a new standard for the convenient and noninvasive detection and treatment of zoonotic diseases

One Dimensional Convolutional Neural Networks for Seizure Onset Detection Using Long-term Scalp and Intracranial EEG

Epileptic seizure detection using scalp electroencephalogram (sEEG) and intracranial electroencephalogram (iEEG) has attracted widespread attention in recent two decades. The accurate and rapid detection of seizures not only reflects the efficiency of the algorithm, but also greatly reduces the burden of manual detection during long-term electroencephalogram (EEG) recording. In this work, a stacked one-dimensional convolutional neural network (1D-CNN) model combined with a random selection and data augmentation (RS-DA) strategy is proposed for seizure onset detection. Firstly, we segmented the long-term EEG signals using 2-sec sliding windows. Then, the 2-sec interictal and ictal segments were classified by the stacked 1D-CNN model. During model training, a RS-DA strategy was applied to solve the problem of sample imbalance, and the patient-specific model was trained with event-based K-fold (K is the number of seizures per patient) cross validation for detecting all seizures of each patient. Finally, we evaluated the performances of the proposed approach in the two levels: the segment-based level and the event-based level. The proposed method was tested on two long-term EEG datasets: the CHB-MIT sEEG dataset and the SWEC-ETHZ iEEG dataset. For the CHB-MIT sEEG dataset, we achieved 88.14 sensitivity, 99.62 specificity and 99.54 accuracy in the segment-based level. From the perspective of the event-based level, 99.31 sensitivity, 0.2/h false detection rate (FDR) and mean 8.1-sec latency were achieved. For the SWEC-ETHZ iEEG dataset, in the segment-based level, 90.09 sensitivity, 99.81 specificity and 99.73 accuracy were obtained. In the event-based level, 97.52 sensitivity, 0.07/h FDR and mean 13.2-sec latency were attained. From these results, we can see that our method can effectively use both sEEG and iEEG data to detect epileptic seizures, and this may provide a reference for the clinical application of seizure onset detection.peerReviewe

Retracted Article: A Study on the Impact of Anxiety on the Perception of Communication Engineering Teachers about Self-Efficacy

This article has been retracted by the iJET editorial team: The article on this page has been associated with fraudulent publication practices after its publication in iJET. The work could be linked to a criminal paper mill selling authorships and articles for publication in several online journals to paying customers. The iJET editorial team was initially informed about the paper mill’s fraudulent activities by Dr. Perron (University of Michigan) and his team on 08/03/2021. The investigation results were published on RetractionWatch under https://retractionwatch.com/author/perronetal/ on 12/20/2021. Based on the evidence provided by Dr. Perron and his team, the iJET editorial team considerably questions the paper’s scientific integrity and legitimacy as part of the scientific body. Finally, iJET decided to retract the paper. Neither iJET, Online-Journals.org, nor IAOE stands in any contact with the paper mill’s fraudulent activities. We condemn such procedures and dissociate ourselves from any person or entity, which is knowingly or unknowingly part of it

Experimental Evaluation of the Transport Mechanisms of PoIFN-α in Caco-2 Cells

For the development of an efficient intestinal delivery system for Porcine interferon-α (PoIFN-α), the understanding of transport mechanisms of which in the intestinal cell is essential. In this study, we investigated the absorption mechanisms of PoIFN-α in intestine cells. Caco-2 cells and fluorescein isothiocyanate-labeled (FITC)-PoIFN-α were used to explore the whole transport process, including endocytosis, intracellular trafficking, exocytosis, and transcytosis. Via various techniques, the transport pathways of PoIFN-α in Caco-2 cells and the mechanisms were clarified. Firstly, the endocytosis of PoIFN-α by Caco-2 cells was time, concentration and temperature dependence. And the lipid raft/caveolae endocytosis was the most likely endocytic pathway for PoIFN-α. Secondly, both Golgi apparatus and lysosome were involved in the intracellular trafficking of PoIFN-α. Thirdly, the treatment of indomethacin resulted in a significant decrease of exocytosis of PoIFN-α, indicating the participation of cyclooxygenase. Finally, to evaluate the efficiency of PoIFN-α transport, the transepithelial electrical resistance (TEER) value was measured to investigate the tight junctional integrity of the cell monolayers. The fluorescence microscope results revealed that the transport of PoIFN-α across the Caco-2 cell monolayers was restricted. In conclusion, this study depicts a probable picture of PoIFN-α transport in Caco-2 cells characterized by non-specificity, partial energy-dependency and low transcytosis

Changes of the postcentral cortex in irritable bowel syndrome patients

The postcentral cortex (poCC) is commonly found to respond to visceral stimulation, but researchers usually pay less attention to this role of the poCC in the patients with functional gastrointestinal disorders, because it is a primary receptor for general bodily feeling of touch, such as temperature and pain. The current study focuses on the changes around the poCC in irritable bowel syndrome (IBS) patients based on the resting-state functional magnetic resonance imaging, aiming to investigate whether the poCC-centric brain metrics may be directly related to visceral perception. In the study, we calculated the regional homogeneity, seed-based correlation (SBC) and nodal centralities of the poCC to explore the changes in the regional activity and information flow around the poCC in IBS patients. Moreover, we examined the performance of the poCC-centric features in classifying the IBS group and healthy group in comparison to those features unrelated to the poCC. The results found that central alterations around the poCC in IBS patients were associated with the level of visceral pain, and exhibited a better discriminative power than those around the whole brain and the insula when classifying the IBS group and healthy group. In conclusion, the preliminary investigation provided fundamental advances in understanding the roles of the poCC in the pathphysiology of the IBS