Chlorogenic Acid Ameliorates Damage Induced by Fluorene-9-Bisphenol in Porcine Sertoli Cells

4,4′-(9-Fluorenylidene) diphenol (BPFL, also known as BHPF and fluorene-9-bisphenol) is a novel bisphenol A substitute that is used in the plastics industry as an organic synthesis intermediate and is a potential endocrine disruptor. However, the deleterious effects of BPFL on porcine Sertoli cells (SCs) and the possible underlying mechanisms are still unclear. Chlorogenic acid (CA) is a free radical scavenger in the cellular antioxidant system that prevents oxidative damage and apoptosis. In the present research, we found that BPFL induced impairments in porcine SCs in a dose-dependent manner and that CA protected porcine SCs against BPFL exposure-induced impairments. Cell viability, proliferation and apoptosis assay results revealed that BPFL exposure could inhibit porcine SC proliferation and induce apoptosis, while CA supplementation ameliorated the effects of BPFL. Further analysis revealed that BPFL exposure induced oxidative stress, mitochondrial membrane potential dysfunction and DNA damage accumulation. Transcriptome analysis and further real-time quantitative PCR and Western blot results showed that BPFL exposure induced endoplasmic reticulum stress and apoptosis. Supplementation with CA dramatically ameliorated these phenotypes in BPFL-exposed porcine SCs. Overall, the present research reveals the possible underlying mechanisms by which BPFL exposure induced impairments and CA supplementation protected against these impairments in porcine SCs.

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Phenyl N -tert-butylnitrone, a Free Radical Scavenger, Reduces Mechanical Allodynia in Chemotherapy-induced Neuropathic Pain in Rats

Anesthesiology ◽

10.1097/aln.0b013e3181ca31bd ◽

2010 ◽

Vol 112 (2) ◽

pp. 432-439 ◽

Cited By ~ 73

Author(s):

Hee Kee Kim ◽

Yan Ping Zhang ◽

Young Seob Gwak ◽

Salahadin Abdi

Keyword(s):

Neuropathic Pain ◽

Free Radical ◽

Mechanical Allodynia ◽

Intraperitoneal Administration ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Dependent Manner ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Dose Dependent

Background Paclitaxel is a widely used chemotherapeutic drug for breast and ovarian cancer. Unfortunately, it induces neuropathic pain, which is a dose-limiting side effect. Free radicals have been implicated in many neurodegenerative diseases. The current study tests the hypothesis that a free radical scavenger plays an important role in reducing chemotherapy-induced neuropathic pain. Methods Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on four alternate days (days 0, 2, 4, and 6) in male Sprague-Dawley rats. Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, was administered intraperitoneally as a single dose or multiple doses before or after injury. Mechanical allodynia was measured by using von Frey filaments. Results The administration of paclitaxel induced mechanical allodynia, which began to manifest on days 7-10, peaked within 2 weeks, and plateaued for at least 2 months after the first paclitaxel injection. A single injection or multiple intraperitoneal injections of PBN ameliorated paclitaxel-induced pain behaviors in a dose-dependent manner. Further, multiple administrations of PBN starting on day 7 through day 15 after the first injection of paclitaxel completely prevented the development of mechanical allodynia. However, an intraperitoneal administration of pbn for 8 days starting with the first paclitaxel injection did not prevent the development of pain behavior. Conclusions This study clearly shows that PBN alleviated mechanical allodynia induced by paclitaxel in rats. Furthermore, our data show that PBN given on days 7 through 15 after the first paclitaxel injection prevented the development of chemotherapy-induced neuropathic pain. This clearly has a clinical implication.

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Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.18:34-38 ◽

2019 ◽

Vol 18 (1) ◽

pp. 34-38

Author(s):

Chen Lei ◽

Pan Xiang ◽

Shen Yonggang ◽

Song Kai ◽

Zhong Xingguo ◽

...

Keyword(s):

Protein Kinase ◽

Guinea Pig ◽

Smooth Muscles ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Dependent Manner ◽

Underlying Mechanisms ◽

Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

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NPM1 is a Novel Therapeutic Target and Prognostic Biomarker for Ewing Sarcoma

Frontiers in Genetics ◽

10.3389/fgene.2021.771253 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yangfan Zhou ◽

Yuan Fang ◽

Junjie Zhou ◽

Yulian Liu ◽

Shusheng Wu ◽

...

Keyword(s):

Ewing Sarcoma ◽

Es Cells ◽

Differentially Expressed Gene ◽

Bioinformatic Analysis ◽

Dependent Manner ◽

Hub Gene ◽

Immune Infiltration ◽

Proliferation And Apoptosis ◽

Immune Related Genes ◽

Dose Dependent

Ewing sarcoma (ES) is a cancer that may originate from stem mesenchymal or neural crest cells and is highly prevalent in children and adolescents. In recent years, targeted therapies against immune-related genes have shown good efficacy in a variety of cancers. However, effective targets for immunotherapy in ES are yet to be developed. In our study, we first identified the immune-associated differential hub gene NPM1 by bioinformatics methods as a differentially expressed gene, and then validated it using real time-PCR and western blotting, and found that this gene is not only closely related to the immune infiltration in ES, but also can affect the proliferation and apoptosis of ES cells, and is closely related to the survival of patients. The results of our bioinformatic analysis showed that NPM1 can be a hub gene in ES and an immunotherapeutic target to reactivate immune infiltration in patients with ES. In addition, treatment with NPM1 promoted apoptosis and inhibited the proliferation of ES cells. The NPM1 inhibitor NSC348884 can induce apoptosis of ES cells in a dose-dependent manner and is expected to be a potential therapeutic agent for ES.

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Emodin promotes apoptosis of human endometrial cancer through regulating the MAPK and PI3K/ AKT pathways

Open Life Sciences ◽

10.1515/biol-2018-0058 ◽

2019 ◽

Vol 13 (1) ◽

pp. 489-496 ◽

Cited By ~ 2

Author(s):

Jun Jiang ◽

Nanyang Zhou ◽

Pian Ying ◽

Ting Zhang ◽

Ruojia Liang ◽

...

Keyword(s):

Endometrial Cancer ◽

Signaling Pathways ◽

Tumor Development ◽

Mapk Signaling ◽

Dependent Manner ◽

Western Blot Assay ◽

Anti Oxidant ◽

Underlying Mechanisms ◽

Induced Apoptosis ◽

Dose Dependent

AbstractEmodin, a major component of rhubarb, has anti-tumor effects in a variety of cancers, influencing multiple steps of tumor development through modulating several signaling pathways. The aim of this study is to examine the effect of emodin on cell apoptosis and explore the underlying mechanisms in human endometrial cancer cells. Here we report that emodin can inhibit KLE cell proliferation and induce apoptosis in a time- and dose-dependent manner. Western blot assay found that emodin was involved in MAPK and PI3K/Akt signaling pathways. Specifically, emodin significantly suppressed the phosphorylation of AKT, and enhanced the phosphorylation of MAPK pathways. Furthermore, the generation of reactive oxygen species (ROS) was up-regulated in KLE cells upon treatment with emodin, while the anti-oxidant agent N-acetyl cysteine (NAC) can inhibit emodin-induced apoptosis and promote the activation of AKT and Bcl-2. Taken together, we revealed that emodin may induce apoptosis in KLE cells through regulating the PI3K/AKT and MAPK signaling pathways, indicating the importance of emodin as an anti-tumor agent.

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Triterpenoid Saponin AG8 from Ardisia gigantifolia stapf. Induces Triple Negative Breast Cancer Cells Apoptosis through Oxidative Stress Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7963212 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Li-Hua Mu ◽

Li-Hua Wang ◽

Teng-Fei Yu ◽

Yu-Ning Wang ◽

Hong Yan ◽

...

Keyword(s):

Triple Negative ◽

Growth Factor Receptor ◽

Cell Types ◽

Ros Generation ◽

Triterpenoid Saponin ◽

Dependent Manner ◽

Breast Cancers ◽

Underlying Mechanisms ◽

Apoptotic Pathways ◽

Dose Dependent

Triple-negative breast cancers (TNBCs) are associated with poor patient survival because of the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expressions. Our previous studies have shown that the triterpenoid saponin AG8 from Ardisia gigantifolia stapf. inhibits the proliferation of MDA-MB-231 cells. In this study, the effects of AG8 were further analyzed in different TNBC cell types: MDA-MB-231, BT-549, and MDA-MB-157 cells. AG8 inhibited the viability of MDA-MB-231, BT-549, and MDA-MB-157 cells in a dose-dependent manner and showed stronger cytotoxicity to African American (AA) and mesenchymal (M) subtypes than Caucasian (CA) and mesenchymal stem-like (MSL) subtypes, respectively. AG8 impaired the uptake of MitoTracker Red CMXRos by the mitochondria of TNBC cells in a dose-dependent manner, and this was recovered by N-acetyl-l-cysteine (NAC). AG8 affected GSH, SOD, and MDA levels of TNBC cells, but different TNBC subtypes had different sensitivities to AG8 and NAC. In addition, we found that AG8 increased the Bax/Bcl-2 ratio and the levels of cytoplasmic cytochrome c and significantly decreased phosphorylation of ERK and AKT in BT549 and MDA-MB-157 cells. AG8 elicited its anticancer effects through ROS generation, ERK and AKT activation, and by triggering mitochondrial apoptotic pathways in TNBC cells. AG8 had selective cytotoxic effects against the AA and M TNBC subtypes and markedly induced MDA-MB-157 (AA subtype) cell apoptosis through pathways that were not associated with ROS, which was different from the other two subtypes. The underlying mechanisms should be further investigated.

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ROS-Induced GATA4 and GATA6 Downregulation Inhibits StAR Expression in LPS-Treated Porcine Granulosa-Lutein Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/5432792 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Xiaolu Qu ◽

Leyan Yan ◽

Rihong Guo ◽

Hui Li ◽

Zhendan Shi

Keyword(s):

Molecular Mechanisms ◽

Cell Model ◽

Animal Husbandry ◽

Dependent Manner ◽

Progesterone Production ◽

Progesterone Synthesis ◽

Porcine Granulosa Cell ◽

Underlying Mechanisms ◽

Dose Dependent

LPS is a major endotoxin produced by gram-negative bacteria, and exposure to it commonly occurs in animal husbandry. Previous studies have shown that LPS infection disturbs steroidogenesis, including progesterone production, and subsequently decreases animal reproductive performance. However, little information about the underlying mechanisms is available thus far. In the present study, an in vitro-luteinized porcine granulosa cell model was used to study the underlying molecular mechanisms of LPS treatment. We found that LPS significantly inhibits progesterone production and downregulates the expressions of progesterone synthesis-associated genes (StAR, CYP11A1, and 3β-HSD). Furthermore, the levels of ROS were significantly increased in an LPS dose-dependent manner. Moreover, transcriptional factors GATA4 and GATA6, but not NR5A1, were significantly downregulated. Elimination of LPS-stimulated ROS by melatonin or vitamin C could restore the expressions of GATA4, GATA6, and StAR. In parallel, StAR expression was also inhibited by the knockdown of GATA4 and GATA6. Based on these data, we conclude that LPS impairs StAR expression via the ROS-induced downregulation of GATA4 and GATA6. Collectively, these findings provide new insights into the understanding of reproductive losses in animals suffering from bacterial infection and LPS exposure.

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Hydroxyl radical induced structural changes of collagen

Spectroscopy An International Journal ◽

10.1155/2007/496174 ◽

2007 ◽

Vol 21 (2) ◽

pp. 91-103 ◽

Cited By ~ 6

Author(s):

Helan Xiao ◽

Guoping Cai ◽

Mingyao Liu

Keyword(s):

Free Radical ◽

Hydroxyl Radicals ◽

Structural Changes ◽

Type I Collagen ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Type I ◽

Dependent Manner ◽

First Time

Extracellular matrix (ECM) plays an important role in cell differentiation, growth, migration and apoptosis. Collagen is the most abundant protein familyin vivo, but its function has still not been clearly defined yet. Reactive oxygen species (ROS) have a central role in oxidative cell stress. Electron spin resonance (ESR) spectroscopy indicates that type I collagen could uniquely scavenge hydroxyl radicals in dose- and time-dependent manner; whereas BSA and gelatin (a denatured collagen) have no such an effect. However, the mechanism by which type I collagen scavenges hydroxyl radicals is different from that of GSH, a well-known free radical scavenger. Using a new method, two-dimensional FTIR correlation analysis, for the first time, we show that the order of functional group changes of type I collagen in this process is amide I earlier than amide II than amide III than –CH– thanν(C=O). The results indicates that the structure of the main chain of collagen changed first, followed by more residue groupν(C=O) exposed to hydroxyl radicals. The reaction with the carbonyl group in collagen causes the hydroxyl free radicals to be scavenged. Therefore, ECM can effectively scavenge ROS under normal physiological conditions. When the proteins of ECM were denatured in the same way as gelatin, they lost their function as a free radical scavenger. All of these results provide new insight into therapy or prevention of oxidative stress, apoptosis and ageing.

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Inhibitory Effects of Edaravone inβ-Amyloid-Induced Neurotoxicity in Rats

BioMed Research International ◽

10.1155/2014/370368 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Feng He ◽

Yan-Ping Cao ◽

Feng-Yuan Che ◽

Lian-Hong Yang ◽

Song-Hua Xiao ◽

...

Keyword(s):

Learning And Memory ◽

Rat Model ◽

Basal Forebrain ◽

Neuroprotective Effect ◽

Memory Performance ◽

Cholinergic Neurons ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Dependent Manner ◽

Induced Voltage

Amyloid protein can damage nerve cells through a variety of biological mechanisms including oxidative stress, alterations in calcium homeostasis, and proapoptosis. Edaravone, a potent free radical scavenger possessing antioxidant effects, has been proved neuroprotective effect in stroke patients. The current study aimed to investigate the effects of EDA in an Aβ-induced rat model of AD, by studying Aβ1–40-induced voltage-gated calcium channel currents in hippocampal CA1 pyramidal neurons, learning and memory behavioral tests, the number of surviving cholinergic neurons in the basal forebrain, and the acetylcholine level in the hippocampus in this rat model of AD. The results showed that the Aβ1–40-induced increase ofICacan be inhibited by EDA in a dose-dependent manner. Treatment with EDA significantly improved Aβ1–40-induced learning and memory performance. Choline acetyltransferase positive cells in basal forebrain and acetylcholine content in the hippocampus were increased by the administration of EDA as compared with the non-EDA treated Aβ1–40group. These results demonstrate that EDA can inhibit the neurotoxic effect of Aβtoxicity. Collectively, these findings suggest that EDA may serve as a potential complemental treatment strategy for AD.

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Sargachromenol fromSargassum micracanthumInhibits the Lipopolysaccharide-Induced Production of Inflammatory Mediators in RAW 264.7 Macrophages

The Scientific World JOURNAL ◽

10.1155/2013/712303 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Eun-Jin Yang ◽

Young Min Ham ◽

Kyong-Wol Yang ◽

Nam Ho Lee ◽

Chang-Gu Hyun

Keyword(s):

Screening Program ◽

Prostaglandin E ◽

Raw 264.7 ◽

Dependent Manner ◽

Raw 264.7 Macrophages ◽

Macrophage Cells ◽

Raw 264.7 Macrophage Cells ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Dose Dependent

During our ongoing screening program designed to determine the anti-inflammatory potential of natural compounds, we isolated sargachromenol fromSargassum micracanthum. In the present study, we investigated the anti-inflammatory effects of sargachromenol on lipopolysaccharide (LPS)-induced inflammation in murine RAW 264.7 macrophage cells and the underlying mechanisms. Sargachromenol significantly inhibited the LPS-induced production of nitric oxide (NO) and prostaglandin E2(PGE2) in a dose-dependent manner. It also significantly inhibited the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner in LPS-stimulated macrophage cells. Further analyses showed that sargachromenol decreased the cytoplasmic loss of inhibitorκBα(IκBα) protein. These results suggest that sargachromenol may exert its anti-inflammatory effects on LPS-stimulated macrophage cells by inhibiting the activation of the NF-κB signaling pathway. In conclusion, to our knowledge, this is the first study to show that sargachromenol isolated fromS. micracanthumhas an effective anti-inflammatory activity. Therefore, sargachromenol might be useful for cosmetic, food, or medical applications requiring anti-inflammatory properties.

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Activation of the TCA Cycle to Provide Immune Protection in Zebrafish Immunized by High Magnesium-Prepared Vibrio alginolyticus Vaccine

Frontiers in Immunology ◽

10.3389/fimmu.2021.739591 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jun Yang ◽

Xiao-li Yang ◽

Yu-bin Su ◽

Xuan-xian Peng ◽

Hui Li

Keyword(s):

Tca Cycle ◽

Dependent Manner ◽

High Concentration ◽

Immune Genes ◽

Bacterial Diseases ◽

The Tca Cycle ◽

Aquaculture Industry ◽

Innate Immune Genes ◽

Underlying Mechanisms ◽

Dose Dependent

Vaccines are safe and efficient in controlling bacterial diseases in the aquaculture industry and are in line with green farming. The present study develops a previously unreported approach to prepare a live-attenuated V. alginolyticus vaccine by culturing bacteria in a high concentration of magnesium to attenuate bacterial virulence. Furthermore, metabolomes of zebrafish immunized with the live-attenuated vaccines were compared with those of survival and dying zebrafish infected by V. alginolyticus. The enhanced TCA cycle and increased fumarate were identified as the most key metabolic pathways and the crucial biomarker of vaccine-mediated and survival fish, respectively. Exogenous fumarate promoted expression of il1β, il8, il21, nf-κb, and lysozyme in a dose-dependent manner. Among the five innate immune genes, the elevated il1β, il8, and lysozyme are overlapped in the vaccine-immunized zebrafish and the survival from the infection. These findings highlight a way in development of vaccines and exploration of the underlying mechanisms.

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