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1.
Nat Plants ; 10(5): 771-784, 2024 May.
Article in English | MEDLINE | ID: mdl-38684916

ABSTRACT

The fall armyworm (FAW) poses a significant threat to global crop production. Here we showed that overexpression of jasmonate ZIM-domain (JAZ) protein GhJAZ24 confers resistance to cotton bollworm and FAW, while also causing sterility in transgenic cotton by recruiting TOPLESS and histone deacetylase 6. We identified the NGR motif of GhJAZ24 that recognizes and binds the aminopeptidase N receptor, enabling GhJAZ24 to enter cells and disrupt histone deacetylase 3, leading to cell death. To overcome plant sterility associated with GhJAZ24 overexpression, we developed iJAZ (i, induced), an approach involving damage-induced expression and a switch from intracellular to extracellular localization of GhJAZ24. iJAZ transgenic cotton maintained fertility and showed insecticidal activity against cotton bollworm and FAW. In addition, iJAZ transgenic rice, maize and tobacco plants showed insecticidal activity against their lepidopteran pests, resulting in an iJAZ-based approach for generating alternative insecticidal proteins with distinctive mechanisms of action, thus holding immense potential for future crop engineering.


Subject(s)
Crops, Agricultural , Gossypium , Moths , Plants, Genetically Modified , Animals , Crops, Agricultural/genetics , Moths/physiology , Moths/genetics , Gossypium/genetics , Gossypium/parasitology , Plant Proteins/genetics , Plant Proteins/metabolism , Oryza/genetics , Oryza/parasitology , Zea mays/genetics , Zea mays/parasitology , Nicotiana/genetics , Nicotiana/parasitology
2.
Biochem Biophys Res Commun ; 706: 149735, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38461647

ABSTRACT

Enolase-1 (Eno1) plays a critical role in regulating glucose metabolism; however, its specific impact on pancreatic islet ß-cells remains elusive. This study aimed to provide a preliminary exploration of Eno1 function in pancreatic islet ß-cells. The findings revealed that the expression of ENO1 mRNA in type 2 diabetes donors was significantly increased and positively correlated with HbA1C and negatively correlated with insulin gene expression. A high level of Eno1 in human insulin-secreting rat INS-1832/13 cells with co-localization with intracellular insulin proteins was accordingly observed. Silencing of Eno1 using siRNA or inhibiting Eno1 protein activity with an Eno1 antagonist significantly reduced insulin secretion and insulin content in ß-cells, while the proinsulin/insulin content ratio remained unchanged. This reduction in ß-cells function was accompanied by a notable decrease in intracellular ATP and mitochondrial cytochrome C levels. Overall, our findings confirm that Eno1 regulates the insulin secretion process, particularly glucose metabolism and ATP production in the ß-cells. The mechanism primarily involves its influence on insulin production, suggesting that Eno1 represents a potential target for ß-cell protection and diabetes treatment.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin-Secreting Cells , Humans , Rats , Animals , Insulin/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Insulin-Secreting Cells/metabolism , Phosphopyruvate Hydratase/genetics , Phosphopyruvate Hydratase/metabolism , Glucose/metabolism , Gene Expression , Adenosine Triphosphate/metabolism
3.
J Agric Food Chem ; 71(51): 20613-20624, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38100671

ABSTRACT

Pathogenic oomycetes infect a wide variety of organisms, including plants, animals, and humans, and cause massive economic losses in global agriculture, aquaculture, and human health. Salicylic acid (SA), an endogenous phytohormone, is regarded as an inducer of plant immunity. Here, the potato late blight pathogen Phytophthora infestans was used as a model system to uncover the inhibitory mechanisms of SA on pathogenic oomycetes. In this research, SA significantly inhibited the mycelial growth, sporulation, sporangium germination, and virulence of P. infestans. Inhibition was closely related to enhanced autophagy, suppression of translation initiation, and ribosomal biogenesis in P. infestans, as shown by multiomics analysis (transcriptomics, proteomics, and phosphorylated proteomics). Monodansylcadaverine (MDC) staining and Western blotting analysis showed that SA promoted autophagy in P. infestans by probably targeting the TOR signaling pathway. These observations suggest that SA has the potential to control late blight caused by P. infestans.


Subject(s)
Phytophthora infestans , Solanum tuberosum , Humans , Salicylic Acid/pharmacology , Salicylic Acid/metabolism , Plant Diseases , Solanum tuberosum/metabolism
4.
Int J Mol Sci ; 24(17)2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37685857

ABSTRACT

Reactive oxygen species (ROS) are important regulating factors that play a dual role in plant and human cells. As the first messenger response in organisms, ROS coordinate signals in growth, development, and metabolic activity pathways. They also can act as an alarm mechanism, triggering cellular responses to harmful stimuli. However, excess ROS cause oxidative stress-related damage and oxidize organic substances, leading to cellular malfunctions. This review summarizes the current research status and mechanisms of ROS in plant and human eukaryotic cells, highlighting the differences and similarities between the two and elucidating their interactions with other reactive substances and ROS. Based on the similar regulatory and metabolic ROS pathways in the two kingdoms, this review proposes future developments that can provide opportunities to develop novel strategies for treating human diseases or creating greater agricultural value.


Subject(s)
Eukaryotic Cells , Oxidative Stress , Humans , Reactive Oxygen Species
5.
J Photochem Photobiol B ; 242: 112692, 2023 May.
Article in English | MEDLINE | ID: mdl-36958087

ABSTRACT

Ligusticum chuanxiong Hort. (Chuanxiong) is an important Chinese medicinal herb, whose rhizomes are widely used as raw materials for treating various diseases caused by blood stasis. The fresh tender stems and leaves of Chuanxiong are also consumed and have the potential as microgreens. Here, we investigated the effect of light spectra on yield and total flavonoid content of Chuanxiong microgreens by treatment with LED-based white light (WL), red light (RL), blue light (BL), and continuous darkness (DD). The results showed that WL and BL reduced biomass accumulation but significantly increased total flavonoid content compared to RL or DD treatments. Widely targeted metabolomics analysis confirmed that BL promoted the accumulation of flavones and flavonols in Chuanxiong microgreens. Further integration of transcriptomics and metabolomics analysis revealed the mechanism by which BL induces the up-regulation of transcription factors such as HY5 and MYBs, promotes the expression of key genes targeted for flavonoid biosynthesis, and ultimately leads to the accumulation of flavones and flavonols. This study suggests that blue light is a proper light spectra to improve the quality of Chuanxiong microgreens, and the research results lay a foundation for guiding the de-etiolation of Chuanxiong microgreens to obtain both yield and quality in production practice.


Subject(s)
Flavones , Ligusticum , Flavonols , Transcriptome , Flavonoids , Metabolomics
6.
Ophthalmol Ther ; 12(2): 1195-1206, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36786967

ABSTRACT

INTRODUCTION: This study aimed to investigate anterior segment parameters of eyes, with anterior chamber depth (ACD) less than 2.8 mm and axial length greater than 25.0 mm. METHODS: This cross-sectional study included 180 myopic eyes of 180 consecutive patients with axial length greater than 25.0 mm. Patients were divided into low ACD (ACD < 2.8 mm, n = 56) and normal ACD (ACD ≥ 2.8 mm, n = 124) groups. Anterior segment parameters were measured using Scheimpflug imaging and ultrasound biomicroscopy. A general linear model was used to compare parameters between the two groups, after adjusting for age and spherical equivalent. RESULTS: Compared with the normal ACD group, the low ACD group had lower values for the following parameters: corneal diameter, trabecular-anterior iris surface angle, angle-opening distance at 500 µm, anterior chamber volume, anterior chamber width, anterior vault, iris thickness at 500 µm, ciliary sulcus-to-sulcus diameter, distance between cornea and sulcus, trabecular-ciliary process distance, maximum ciliary body thickness, ciliary process length, relative anterior vault, relative distance between cornea and sulcus, and relative lens position (general linear model, p < 0.05). In contrast, central corneal thickness, iris curvature, lens thickness, lens vault, and iris-ciliary angle were greater in the low ACD group (general linear model, p < 0.05). CONCLUSION: A smaller anterior segment, as well as a thicker and more anteriorly positioned lens, may correlate with shallow ACD in eyes with long axial length.

7.
J Adv Res ; 43: 13-26, 2023 01.
Article in English | MEDLINE | ID: mdl-36585103

ABSTRACT

INTRODUCTION: During the arms race between plants and pathogens, pathogenesis-related proteins (PR) in host plants play a crucial role in disease resistance, especially PR1. PR1 constitute a secretory peptide family, and their role in plant defense has been widely demonstrated in both hosts and in vitro. However, the mechanisms by which they control host-pathogen interactions and the nature of their targets within the pathogen remain poorly understood. OBJECTIVES: The present study was aimed to investigate the anti-oomycete activity of secretory PR1 proteins and elaborate their underlying mechanisms. METHODS: This study was conducted in the potato-Phytophthora infestans pathosystem. After being induced by the pathogen infection, the cross-kingdom translocation of secretory PR1 was demonstrated by histochemical assays and western blot, and their targets in P. infestans were identified by yeast-two-hybrid assays, bimolecular fluorescence complementation assays, and co-immunoprecipitation assay. RESULTS: The results showed that the expression of secretory PR1-encoding genes was induced during pathogen infection, and the host could deliver PR1 into P. infestans to inhibit its vegetative growth and pathogenicity. The translocated secretory PR1 targeted the subunits of the AMPK kinase complex in P. infestans, thus affecting the AMPK-driven phosphorylation of downstream target proteins, preventing ROS homeostasis, and down-regulating the expression of RxLR effectors. CONCLUSION: The results provide novel insights into the molecular function of PR1 in protecting plants against pathogen infection, and uncover a potential target for preventing pre- and post-harvest late blight.


Subject(s)
AMP-Activated Protein Kinase Kinases , Phytophthora infestans , Plants , Phytophthora infestans/genetics , Host-Pathogen Interactions , Disease Resistance/genetics
8.
Plant Dis ; 107(5): 1609-1612, 2023 May.
Article in English | MEDLINE | ID: mdl-36428256

ABSTRACT

Streptomyces angustmyceticus CQUSa03 was recently isolated from the rhizosphere soil of a potato resistant variety, which showed strong biocontrol activity against potato late blight and other fungal diseases. To elucidate the biocontrol mechanism, the whole genome of CQUSa03 was sequenced using second-generation Illumina and third-generation Nanopore sequencing technologies. The assembled genome of CQUSa03 was 8,107,672 bp, containing one chromosome and three plasmids, with an average GC content of 72.29%, 6,914 protein-coding genes, 21 rRNA, and 68 tRNA. In addition, 29 important secondary metabolite biosynthetic gene clusters were identified in the CQUSa03 genome. The related genes of ß-1,3-glucanase and chitinase, which can degrade the cell wall of fungal pathogens, were also found. CQUSa03 is predicted to have great potential in agriculture by producing a variety of antagonistic active compounds, cell wall hydrolases, and bacteriostatic peptides to control diseases. The genome sequence provided a theoretical basis for analyzing the biocontrol mechanism of S. angustmyceticus CQUSa03 and laid a foundation for the development and industrialization of biocontrol agents.


Subject(s)
Mycoses , Oomycetes , Solanum tuberosum , Biological Control Agents , Solanum tuberosum/microbiology
9.
Int J Mol Sci ; 25(1)2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38203546

ABSTRACT

Taxus, a vital source of the anticancer drug paclitaxel, grapples with a pronounced supply-demand gap. Current efforts to alleviate the paclitaxel shortage involve expanding Taxus cultivation through cutting propagation. However, traditional cutting propagation of Taxus is difficult to root and time-consuming. Obtaining the roots with high paclitaxel content will cause tree death and resource destruction, which is not conducive to the development of the Taxus industry. To address this, establishing rapid and efficient stem rooting systems emerges as a key solution for Taxus propagation, facilitating direct and continuous root utilization. In this study, Agrobacterium rhizogenes were induced in the 1-3-year-old branches of Taxus × media Rehder, which has the highest paclitaxel content. The research delves into the rooting efficiency induced by different A. rhizogenes strains, with MSU440 and C58 exhibiting superior effects. Transcriptome and metabolome analyses revealed A. rhizogenes' impact on hormone signal transduction, amino acid metabolism, zeatin synthesis, and secondary metabolite synthesis pathways in roots. LC-MS-targeted quantitative detection showed no significant difference in paclitaxel and baccatin III content between naturally formed and induced roots. These findings underpin the theoretical framework for T. media rapid propagation, contributing to the sustainable advancement of the Taxus industry.


Subject(s)
Agrobacterium , Inventions , Taxus , Taxus/genetics , Technology , Paclitaxel/pharmacology
10.
Front Neurol ; 13: 809811, 2022.
Article in English | MEDLINE | ID: mdl-35370876

ABSTRACT

Toxoplasmosis encephalopathy (TE) is a kind of encephalopathy parasitic disease caused by Toxoplasma gondii. It is the most common opportunistic for central system infection in patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus. Without early diagnosis and proper treatment, this opportunistic infection can be life-threatening. The common clinical manifestations of the disease include altered mental state, epilepsy, cranial nerve damage, paresthesia, cerebellar signs, meningitis, motor disorders, and neuropsychiatry. The most common presentation in about 75% of cases is a subacute episode of focal neurological abnormalities such as hemiplegia, personality changes, or aphasia. Imaging needs to be differentiated from multiple sclerosis, lymphoma, and metastases. We report a case of acquired immune deficiency syndrome complicated with toxoplasma encephalopathy with rapid progressive memory loss as the initial symptom and misdiagnosed as multiple sclerosis. Through the comprehensive analysis of the clinical symptoms and imaging examination of this disease, we hope to enhance the confidence of clinicians in the diagnosis of this disease.

11.
Ophthalmol Ther ; 11(3): 1187-1198, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35415777

ABSTRACT

INTRODUCTION: To evaluate the short-term safety and efficacy of the EVO implantable collamer lens (ICL) using a customized implanting orientation design based on ultrasound biomicroscope (UBM) measurement. METHODS: The prospective case series included 310 eyes of 158 patients treated with ICL. To achieve an optimal vault, an ICL of specific size was chosen and implanted in a customized orientation according to assessment of sulcus-to-sulcus (STS) diameters, distance between STS plane and crystalline lens (STSL), the morphology of ciliary sulcus (MCS), anterior chamber depth (ACD), and white-to-white (WTW). With the new design, there were 138 eyes with a non-horizontal orientation and 172 eyes with a horizontal orientation of the ICL. Refractive and ICL vault statuses were followed up for 1 day and 1 month postoperatively. RESULTS: The safety index at 1 month was 1.34 ± 0.17 for the non-horizontally implanted group and 1.33 ± 0.16 for the horizontally implanted group; the efficacy index was 1.21 ± 0.18 for the non-horizontally implanted group and 1.18 ± 0.16 for the horizontally implanted group. All eyes achieved an uncorrected distance visual acuity of 0.10 logMAR or better. No significant difference in endothelial cell density was observed between the preoperative value (2792.6 ± 247.6 cells/mm2) and value at 1 month postoperatively (2744.2 ± 243.3 cells/mm2), and no cataract or anterior subcapsular opacification was observed. Ideal vault (250-750 µm) was achieved in 84% of eyes (260/310). CONCLUSION: The customized ICL design of implanting orientation based on UBM measurement provides good safety, efficacy, and vault predictability.

14.
Int J Mol Sci ; 22(21)2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34768793

ABSTRACT

Botany-derived antimicrobial peptides (BAMPs), a class of small, cysteine-rich peptides produced in plants, are an important component of the plant immune system. Both in vivo and in vitro experiments have demonstrated their powerful antimicrobial activity. Besides in plants, BAMPs have cross-kingdom applications in human health, with toxic and/or inhibitory effects against a variety of tumor cells and viruses. With their diverse molecular structures, broad-spectrum antimicrobial activity, multiple mechanisms of action, and low cytotoxicity, BAMPs provide ideal backbones for drug design, and are potential candidates for plant protection and disease treatment. Lots of original research has elucidated the properties and antimicrobial mechanisms of BAMPs, and characterized their surface receptors and in vivo targets in pathogens. In this paper, we review and introduce five kinds of representative BAMPs belonging to the pathogenesis-related protein family, dissect their antifungal, antiviral, and anticancer mechanisms, and forecast their prospects in agriculture and global human health. Through the deeper understanding of BAMPs, we provide novel insights for their applications in broad-spectrum and durable plant disease prevention and control, and an outlook on the use of BAMPs in anticancer and antiviral drug design.


Subject(s)
Antimicrobial Peptides/genetics , Antimicrobial Peptides/metabolism , Antimicrobial Peptides/pharmacology , Agriculture , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antiviral Agents/pharmacology , Drug Design/methods , Humans , Plant Immunity/drug effects , Plants/drug effects , Viruses/drug effects
15.
Mol Plant Pathol ; 22(10): 1239-1255, 2021 10.
Article in English | MEDLINE | ID: mdl-34288333

ABSTRACT

Fusarium oxysporum is the causal agent of the devastating Fusarium wilt by invading and colonizing the vascular system in various plants, resulting in substantial economic losses worldwide. Target of rapamycin (TOR) is a central regulator that controls intracellular metabolism, cell growth, and stress responses in eukaryotes, but little is known about TOR signalling in F. oxysporum. In this study, we identified conserved FoTOR signalling pathway components including FoTORC1 and FoTORC2. Pharmacological assays showed that F. oxysporum is hypersensitive to rapamycin in the presence of FoFKBP12 while the deletion mutant strain ΔFofkbp12 is insensitive to rapamycin. Transcriptomic data indicated that FoTOR signalling controls multiple metabolic processes including ribosome biogenesis and cell wall-degrading enzymes (CWDEs). Genetic analysis revealed that FoTOR1 interacting protein 4 (FoTIP4) acts as a new component of FoTOR signalling to regulate hyphal growth and pathogenicity of F. oxysporum. Importantly, transcript levels of genes associated with ribosome biogenesis and CWDEs were dramatically downregulated in the ΔFotip4 mutant strain. Electrophoretic mobility shift assays showed that FoTIP4 can bind to the promoters of ribosome biogenesis- and CWDE-related genes to positively regulate the expression of these genes. These results suggest that FoTOR signalling plays central roles in regulating hyphal growth and pathogenicity of F. oxysporum and provide new insights into FoTOR1 as a target for controlling and preventing Fusarium wilt in plants.


Subject(s)
Fusarium , Plant Diseases , Sirolimus/pharmacology , Virulence
16.
Int J Mol Sci ; 22(9)2021 May 06.
Article in English | MEDLINE | ID: mdl-34066497

ABSTRACT

Autophagy is an intracellular process in all eukaryotes which is responsible for the degradation of cytoplasmic constituents, recycling of organelles, and recycling of proteins. It is an important cellular process responsible for the effective virulence of several pathogenic plant fungal strains, having critical impacts on important crop plants including potatoes. However, the detailed physiological mechanisms of autophagy involved in the infection biology of soil-borne pathogens in the potato crop needs to be investigated further. In this study, the autophagy-related gene, FoATG12, in potato dry rot fungus Fusarium oxysporum was investigated by means of target gene replacement and overexpression. The deletion mutant ∆FoATG12 showed reduction in conidial formation and exhibited impaired aerial hyphae. The FoATG12 affected the expression of genes involved in pathogenicity and vegetative growth, as well as on morphology features of the colony under stressors. It was found that the disease symptoms were delayed upon being inoculated by the deletion mutant of FoATG12 compared to the wild-type (WT) and overexpression (OE), while the deletion mutant showed the disease symptoms on tomato plants. The results confirmed the significant role of the autophagy-related ATG12 gene in the production of aerial hyphae and the effective virulence of F. oxysporum in the potato crop. The current findings provid an enhanced gene-level understanding of the autophagy-related virulence of F. oxysporum, which could be helpful in pathogen control research and could have vital impacts on the potato crop.


Subject(s)
Autophagy-Related Protein 12/genetics , Autophagy/genetics , Fungal Proteins/genetics , Fusarium/cytology , Fusarium/genetics , Genes, Fungal , Plant Diseases/microbiology , Solanum tuberosum/microbiology , Autophagy-Related Protein 12/metabolism , Fungal Proteins/metabolism , Fusarium/pathogenicity , Gene Expression Regulation, Fungal , Hyphae/growth & development , Mutation/genetics , Phenotype , Plant Diseases/genetics , Spores, Fungal/growth & development , Stress, Physiological/genetics
17.
Phytopathology ; 111(11): 2067-2079, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33787286

ABSTRACT

Reactive oxygen species (ROSs) are critical for the growth, development, proliferation, and pathogenicity of microbial pathogens; however, excessive levels of ROSs are toxic. Little is known about the signaling cascades in response to ROS stress in oomycetes such as Phytophthora infestans, the causal agent of potato late blight. Here, P. infestans was used as a model system to investigate the mechanism underlying the response to ROS stress in oomycete pathogens. Results showed severe defects in sporangium germination, mycelium growth, appressorium formation, and virulence of P. infestans in response to H2O2 stress. Importantly, these phenotypes mimic those of P. infestans treated with rapamycin, the inhibitor of target of rapamycin (TOR, 1-phosphatidylinositol-3-kinase). Strong synergism occurred when P. infestans was treated with a combination of H2O2 and rapamycin, suggesting that a crosstalk exists between ROS stress and the TOR signaling pathway. Comprehensive analysis of transcriptome, proteome, and phosphorylation omics showed that H2O2 stress significantly induced the operation of the TOR-mediated autophagy pathway. Monodansylcadaverine staining showed that in the presence of H2O2 and rapamycin, the autophagosome level increased in a dosage-dependent manner. Furthermore, transgenic potatoes containing double-stranded RNA of TOR in P. infestans (PiTOR) displayed high resistance to P. infestans. Therefore, TOR is involved in the ROS response and is a potential target for control of oomycete diseases, because host-mediated silencing of PiTOR increases potato resistance to late blight.


Subject(s)
Phytophthora infestans , Solanum tuberosum , Hydrogen Peroxide , Plant Diseases , Reactive Oxygen Species
18.
Front Cell Infect Microbiol ; 11: 786348, 2021.
Article in English | MEDLINE | ID: mdl-35047417

ABSTRACT

Viruses typically hijack the cellular machinery of their hosts for successful infection and replication, while the hosts protect themselves against viral invasion through a variety of defense responses, including autophagy, an evolutionarily ancient catabolic pathway conserved from plants to animals. Double-membrane vesicles called autophagosomes transport trapped viral cargo to lysosomes or vacuoles for degradation. However, during an ongoing evolutionary arms race, viruses have acquired a strong ability to disrupt or even exploit the autophagy machinery of their hosts for successful invasion. In this review, we analyze the universal role of autophagy in antiviral defenses in animals and plants and summarize how viruses evade host immune responses by disrupting and manipulating host autophagy. The review provides novel insights into the role of autophagy in virus-host interactions and offers potential targets for the prevention and control of viral infection in both plants and animals.


Subject(s)
Virus Diseases , Viruses , Animals , Autophagosomes , Autophagy , Host-Pathogen Interactions , Immunity, Innate , Virus Replication
19.
J Hazard Mater ; 398: 122869, 2020 11 05.
Article in English | MEDLINE | ID: mdl-33027880

ABSTRACT

Evidence has shown that the activation of AhR (aryl hydrocarbon receptor) can promote cancer cell metastasis. However, limited studies have been carried out on mixed exposure to endocrine-disrupting chemicals (EDCs), especially in human breast cancer. Therefore, using MCF7 human breast cancer cells, we investigated the effects of coexposure to MEHP (mono 2-ethylhexyl phthalate) and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on cell migration and invasion, as well as the roles of AhR and the MMP/slug pathway. Our data suggest that MEHP or TCDD can induce migration and invasion in MCF7 cells, and the promotion is partly AhR dependent. We also observed that MEHP antagonized TCDD to reduce AhR-mediated CYP1A1 expression. Subsequently, we revealed that MEHP recruited AhR to dioxin response element (DRE) sequences and decreased TCDD-induced AhR-DRE binding in CYP1A1 genes. Overall, MEHP is a potential AHR agonist, capable of decreasing TCDD-induced AhR-DRE binding in CYP1A1 genes. The antagonizing effect of coexposure led to the inhibition of the epithelial-mesenchymal transition (EMT) in MCF7 cells. Our study provides new evidence for the potential mechanisms involved in EDCs exposure and their interactions in EMT.


Subject(s)
Breast Neoplasms , Polychlorinated Dibenzodioxins , Breast Neoplasms/genetics , Cytochrome P-450 CYP1A1/genetics , Diethylhexyl Phthalate/analogs & derivatives , Humans , MCF-7 Cells , Polychlorinated Dibenzodioxins/toxicity , Receptors, Aryl Hydrocarbon/genetics
20.
Article in English | MEDLINE | ID: mdl-32714426

ABSTRACT

Icaritin (ICT) is the main component in the traditional Chinese herb Epimedium, and it has been shown to have anti-Alzheimer's disease (AD) effects, but its neuroprotective effects and the pharmacological mechanisms are unclear. In the present study, senescence-accelerated mouse prone 8 (SAMP8) mice were randomly divided into a model group and an ICT-treated group. Learning and memory abilities were detected by the Morris water maze assay, and the expression of amyloid beta protein (Aß) and ß-site APP cleavage enzyme 1 (BACE1) was determined by Western blotting and polymerase chain reaction (PCR). Histological changes in CA1 and CA3 were detected by hematoxylin-eosin staining (H&E staining), and the immunohistochemical analysis was used to detect the expression and localization of Bax and Bcl-2. The results showed that compared with the SAMP8 mice, the ICT-treated SAMP8 mice showed improvements in spatial learning and memory retention. In addition, the number of necrotic cells and the morphological changes in CA1 and CA3 areas were significantly alleviated in the group of ICT-treated SAMP8 mice, and the expression of BACE1, Aß 1-42 levels, and the Bax/Bcl-2 ratio in the hippocampus was obviously decreased in the ICT-treated group compared with the control group. The results demonstrated that ICT reduced BACE-1 levels, the contents of Aß 1-42, and the Bax/Bcl-2 ratio, suggesting that ICT might have potential therapeutic benefits by delaying or modifying the progression of AD.

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