scholarly journals CYP450s-Activity Relations of Celastrol to Interact with Triptolide Reveal the Reasons of Hepatotoxicity of Tripterygium wilfordii

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2162 ◽  
Author(s):  
Chunhuan Jin ◽  
Zijun Wu ◽  
Lili Wang ◽  
Yoshikatsu Kanai ◽  
Xin He
Keyword(s):  
Mitochondrial Membrane ◽  
Detection Method ◽  
Enzyme Inhibitor ◽  
Rat Hepatocytes ◽  
Toxic Effects ◽  
Tripterygium Wilfordii ◽  
Primary Rat Hepatocytes ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
Potential Hepatotoxicity

Celastrol and triptolide, as the two main bio-activity ingredients in Tripterygium wilfordii, have wide anticancer pharmacological potency, as well as anti-inflammatory and immunosuppression effects. However, they have potential hepatotoxicity and underlying mechanisms of them-induced toxicity mediated by hepatic CYP450s have not been well delineated. In the present study, we accessed the toxic effects and possible mechanism of celastrol and triptolide on primary rat hepatocytes. Models of subdued/enhanced activity of CYP450 enzymes in primary rat hepatocytes were also constructed to evaluate the relationship between the two ingredients and CYP450s. LC-MS/MS was used to establish a detection method of the amount of triptolide in rat hepatocytes. As the results, cell viability, biochemical index, and mitochondrial membrane potential indicated that celastrol and triptolide had toxic potencies on hepatocytes. Moreover, the toxic effects were enhanced when the compounds combined with 1-aminobenzotriazole (enzyme inhibitor) while they were mitigated when combined with phenobarbital (an enzyme inducer). Meanwhile, celastrol could affect the amount of triptolide in the cell. We therefore put forward that increase of triptolide in the cell might be one of the main causes of hepatotoxicity caused by Tripterygium wilfordii.

scholarly journals Hepatitis B Virus HBx Protein Localizes to Mitochondria in Primary Rat Hepatocytes and Modulates Mitochondrial Membrane Potential

2008 ◽  
Vol 82 (14) ◽  
pp. 6798-6811 ◽  
Author(s):  
Amy J. Clippinger ◽  
Michael J. Bouchard
Keyword(s):  
Membrane Potential ◽  
Hepatitis B Virus ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Rat Hepatocytes ◽  
Mitochondrial Localization ◽  
Primary Rat Hepatocytes ◽  
B Virus

ABSTRACT Over 350 million people are chronically infected with hepatitis B virus (HBV), and a significant number of chronically infected individuals develop primary liver cancer. HBV encodes seven viral proteins, including the nonstructural X (HBx) protein. The results of studies with immortalized or transformed cells and with HBx-transgenic mice demonstrated that HBx can interact with mitochondria. However, no studies with normal hepatocytes have characterized the precise mitochondrial localization of HBx or the effect of HBx on mitochondrial physiology. We have used cultured primary rat hepatocytes as a model system to characterize the mitochondrial localization of HBx and the effect of HBx expression on mitochondrial physiology. We now show that a fraction of HBx colocalizes with density-gradient-purified mitochondria and associates with the outer mitochondrial membrane. We also demonstrate that HBx regulates mitochondrial membrane potential in hepatocytes and that this function of HBx varies depending on the status of NF-κB activity. In primary rat hepatocytes, HBx activation of NF-κB prevented mitochondrial membrane depolarization; however, when NF-κB activity was inhibited, HBx induced membrane depolarization through modulation of the mitochondrial permeability transition pore. Collectively, these results define potential pathways through which HBx may act in order to modulate mitochondrial physiology, thereby altering many cellular activities and ultimately contributing to the development of HBV-associated liver cancer.

Mechanistic Approach for Toxic Effects of Bupropion in Primary Rat Hepatocytes

Drug Research ◽  
2017 ◽  
Vol 67 (04) ◽  
pp. 217-222 ◽  
Author(s):  
Elham Ahmadian ◽  
Hossein Babaei ◽  
Alireza Mohajjel Nayebi ◽  
Aziz Eftekhari ◽  
Mohammad Ali Eghbal
Keyword(s):  
Rat Hepatocytes ◽  
Toxic Effects ◽  
Primary Rat Hepatocytes ◽  
Mechanistic Approach

Characterization of Microcystin-Induced Dualistic Toxic Effects on Primary Rat Hepatocytes

2017 ◽  
Vol 36 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Yi Shuai ◽  
Dan Lou ◽  
Jianxun Yin ◽  
Xiaolan Qian ◽  
Yanqin Wang ◽  
...  
Keyword(s):  
Rat Hepatocytes ◽  
Toxic Effects ◽  
Primary Rat Hepatocytes

Management of Platelets in a Persian Girl with the Tetralogy_Pantalogy of Fallot (Tof_Pof): A Case Report Study

2020 ◽  
Author(s):  
Bahram Alamdary Badlou
Keyword(s):  
Case Report ◽  
Ventricular Septal Defect ◽  
Atrial Septal Defect ◽  
Sleep Disorders ◽  
Social Life ◽  
Rare Case ◽  
Septal Defect ◽  
Old Persian ◽  
Underlying Mechanisms ◽  
The Relationship

We report a rare case of unrepaired Tetralogy_Pantalogy of Fallot (TOF_POF) in a 20 years old Persian girl Mrs Zeynab S., who presented with cyanotic finger tops appearance, ongoing chronic thrombolytic destruction processes, and remarkable thrombocytopenia [1,2], heart ventricular septal defect (VSD), and might atrial septal defect (ASD), anxiety, sleep disorders, nightmares, and limited social life. Additionally, the relationship between underlying mechanisms, possible treatments of the thrombocytopenia, erythrocytosis, and unrepaired cardiovascular leakages remains unknown.

scholarly journals Conditional regard, stress, and dyadic adjustment in primiparous couples: A dyadic analysis perspective

2021 ◽  
pp. 026540752199356
Author(s):  
Alexandra Cournoyer ◽  
Julie C. Laurin ◽  
Marie-Ève Daspe ◽  
Sophie Laniel ◽  
Anne-Sophie Huppé
Keyword(s):  
Transition To Parenthood ◽  
Psychological Needs ◽  
Basic Psychological Needs ◽  
Dyadic Adjustment ◽  
Dyadic Analysis ◽  
Mediation Model ◽  
Online Questionnaire ◽  
Mediating Role ◽  
Underlying Mechanisms ◽  
The Relationship

Many couples transitioning into parenthood are at risk for dyadic adjustment declines. It is therefore important to explore key, theory-driven deterrents of enduring relationships during this period, as well as potential underlying mechanisms. This study examined the relationship between perceived conditional negative regard (i.e. a behavior that thwarts basic psychological needs; T1), stress (T1), and dyadic adjustment (T2) during the transition to parenthood. Primiparous couples ( N = 144) were recruited to fill out an online questionnaire when their babies were 6-months (T1) and 12-months (T2). Path analysis with an Actor-Partner Interdependence Mediation Model was conducted. Results show that for each partner (actor effects), stress (T1) mediated the link between perceived conditional negative regard (T1), and later dyadic adjustment (T2). For the partner effects, while stress (T1) did not play a mediating role between these variables, other partner effects were found. Each primiparous parent’s perceived conditional negative regard (T1) was associated with the other parent’s later dyadic adjustment (T2). However, when examining longitudinal changes in stress and dyadic adjustment over time (T2, controlling for respective T1), no significant associations were found. Overall, the findings shed light on the dyadic associations of conditional negative regard, and the mechanisms through which it is negatively tied with dyadic adjustment during the transition to parenthood.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

Mother Phubbing and Adolescent Cyberbullying: The Mediating Role of Perceived Mother Acceptance and the Moderating Role of Emotional Stability

2020 ◽  
pp. 088626052098390
Author(s):  
Jiahui Qu ◽  
Li Lei ◽  
Xingchao Wang ◽  
Xiaochun Xie ◽  
Pengcheng Wang
Keyword(s):  
High School Students ◽  
Positive Association ◽  
Emotional Stability ◽  
School Students ◽  
Mediation Analyses ◽  
Mediating Role ◽  
Indirect Path ◽  
Underlying Mechanisms ◽  
The Relationship

Previous studies have found some risk factors of cyberbullying. However, little is known about how mother phubbing may influence adolescent cyberbullying, and the mediating and moderating mechanisms underlying this relationship. “Phubbing,” which is a portmanteau of “phone” and “subbing,” refers to snubbing other people and focus on smartphones in social interactions. This study examined whether mother phubbing, which refers to being phubbed by one’s mother, would be positively related to adolescent cyberbullying, whether perceived mother acceptance would mediate the relationship between mother phubbing and adolescent cyberbullying, and whether emotional stability would moderate the pathways between mother phubbing and adolescent cyberbullying. The sample consisted of 4,213 Chinese senior high school students (mean age 16.41 years, SD = 0.77, 53% were female). Participants completed measurements regarding mother phubbing, cyberbullying, perceived mother acceptance, and emotional stability. The results indicated that mother phubbing was positively related to cyberbullying, which was mediated by perceived mother acceptance. Further, moderated mediation analyses showed that emotional stability moderated the direct path between mother phubbing and cyberbullying and the indirect path between mother phubbing and perceived mother acceptance. This study highlighted the harmful impact of mother phubbing on adolescents by showing a positive association between mother phubbing and adolescent cyberbullying, as well as the underlying mechanisms between mother phubbing and adolescent cyberbullying.

scholarly journals Correspondence Learning for Deep Multi-Modal Recognition and Fraud Detection

Electronics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 800
Author(s):  
Jongchan Park ◽  
Min-Hyun Kim ◽  
Dong-Geol Choi
Keyword(s):  
Deep Learning ◽  
Simple Technique ◽  
Detection Method ◽  
Fraud Detection ◽  
Complementary Information ◽  
Multiple Modalities ◽  
Vending Machines ◽  
Emotion Intensity ◽  
The Relationship ◽  
Extract Information

Deep learning-based methods have achieved good performance in various recognition benchmarks mostly by utilizing single modalities. As different modalities contain complementary information to each other, multi-modal based methods are proposed to implicitly utilize them. In this paper, we propose a simple technique, called correspondence learning (CL), which explicitly learns the relationship among multiple modalities. The multiple modalities in the data samples are randomly mixed among different samples. If the modalities are from the same sample (not mixed), then they have positive correspondence, and vice versa. CL is an auxiliary task for the model to predict the correspondence among modalities. The model is expected to extract information from each modality to check correspondence and achieve better representations in multi-modal recognition tasks. In this work, we first validate the proposed method in various multi-modal benchmarks including CMU Multimodal Opinion-Level Sentiment Intensity (CMU-MOSI) and CMU Multimodal Opinion Sentiment and Emotion Intensity (CMU-MOSEI) sentiment analysis datasets. In addition, we propose a fraud detection method using the learned correspondence among modalities. To validate this additional usage, we collect a multi-modal dataset for fraud detection using real-world samples for reverse vending machines.

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