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1.
Food Chem Toxicol ; 192: 114934, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151877

RESUMEN

Quercetin has been shown to mitigate the cytotoxic effects of heavy metals. While copper is an essential trace element for bodily functions, excessive intake has been linked to impaired female reproductive function. Transcriptome analysis was employed to identify genes that are differentially expressed in response to high copper and were validated through qRT-PCR and western blotting. ATP content and Tunel were used to identify the damage of mitochondrial and cell apoptosis. PPI analysis revealed that MKI67, TOPII, ASPM, CASP3, PLK1, and TTK are central proteins within the network. Additionally, exposure to elevated levels of copper resulted in the dysregulation of 86 genes associated with mitochondria. Conversely, treatment with quercetin (QUE) in combination with high copper led to the normalization of 42 mitochondria-related genes previously affected by high copper levels. Furthermore, CuSO4 decreases ATP content and induces cell apoptosis, which can be reversed by QUE. Results suggest that elevated copper levels could lead to oxidative stress and apoptosis by inducing mitochondrial damage, while QUE has the potential to mitigate these effects, ultimately safeguarding granulosa cells and halting the progression of cell death. This study provides novel insights into the molecular pathways involved in female reproductive toxicity caused by excessive copper exposure.


Asunto(s)
Apoptosis , Cobre , Perfilación de la Expresión Génica , Quercetina , Femenino , Quercetina/farmacología , Cobre/toxicidad , Animales , Apoptosis/efectos de los fármacos , Reproducción/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Transcriptoma/efectos de los fármacos , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Estrés Oxidativo/efectos de los fármacos
2.
Domest Anim Endocrinol ; 90: 106881, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39213807

RESUMEN

Copper is a vital micronutrient necessary for the maintenance of physiological functions. However, excessive amounts can lead to organ damage. Porcine ovarian granulosa cells are damaged by a high concentration of CuSO4, which can reduce the reproductive capacity of sows. Quercetin has shown remarkable efficacy in mitigating the harmful effects of heavy metals. Therefore, the aim of this study was to investigate the effects of a high concentration of CuSO4 on autophagy and apoptosis in porcine ovarian granulosa cells and to explore whether quercetin can counteract these toxic effect. Cell morphology, and the mRNA expression levels of autophagy-related genes (LC3-Ⅰ, ATG5, ATG7, ATG12, Beclin1, mTOR, LC3-Ⅱ and P62) were significantly changed upon treatment with 200 and 400 µM CuSO4. Treatment with 200 µM CuSO4 increased expression of P62 protein (P<0.05), promoted LC3-Ⅰ to LC3-Ⅱ conversion (P<0.05), and reduced PINK1 protein expression and the ATP content (P<0.05). In addition, expression of Caspase3 protein was increased and TUNEL staining indicated that the number of apoptotic cells was increased. However, co-treatment with 10 µM quercetin significantly decreased expression of P62 and conversion of LC3-Ⅰ to LC3-Ⅱ. Furthermore, flow cytometric analysis revealed that addition of 10 µM quercetin significantly reduced apoptosis induced by a high concentration of CuSO4. In summary, the results indicate that a high concentration of CuSO4 can trigger mitochondrial and autophagy dysfunction, activate mitochondrial apoptosis pathway, and exert cytotoxic effects. Quercetin can mitigate autophagy dysfunction, enhance autophagic processes, and alleviate apoptosis.

4.
Animals (Basel) ; 13(17)2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37685009

RESUMEN

CuSO4 is the most commonly used feed additive in pig production at present, but long-term ingestion of excessive copper would lead to chronic copper toxicity. High copper could reduce the reproductive efficiency of sows and seriously affect the development of the pig industry. Quercetin (QUE), a powerful antioxidant, reduces toxicity of a number of heavy metals. Porcine granulosa cells (pGCs) are crucial to the fate of follicle development. The present study found that high concentrations of CuSO4 induced ROS production, which resulted in decreased mRNA expression of antioxidant-related genes GPX4, CAT, and SOD2 and increased mRNA expression of SOD1, TRX, and HO-1. The protein expression of antioxidant enzymes SOD2 and HO-1 decreased. Moreover, the concentration of MDA increased, the activity of CAT decreased, and the content of GSH decreased. After high copper treatment, the mitochondrial membrane potential (MMP) was decreased and the morphological structure was changed. However, the combined treatment with Quercetin (QUE) reversed these changes, and the level of cellular oxidative stress decreased. Therefore, we conclude that high copper has oxidative toxicity to pGCs, and QUE could remove the ROS induced by high copper, protect mitochondria from oxidative stress damage, and improve the function of pGCs.

5.
Chem Commun (Camb) ; 59(77): 11516-11519, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37691476

RESUMEN

A triazine pyridinium derivative (TAZpy) was encapsulated into the cavity of a cucurbit[7]uril and further assembled with sulfonatocalix[4]-arene, hyaluronic acid and commercial dyes, which not only achieved fluorescence cascade enhancement and an effective FRET process based on macrocyclic confinement, but was also applied in two-photon NIR targeted cell imaging.


Asunto(s)
Transferencia Resonante de Energía de Fluorescencia , Gastrópodos , Animales , Diagnóstico por Imagen , Colorantes , Triazinas
6.
Chem Sci ; 14(31): 8401-8407, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37564418

RESUMEN

Herein, a triphenylamine derivative (TP-3PY) possessing 4-(4-bromophenyl)pyridine (PY) as an electron-accepting group and tris[p-(4-pyridylvinyl)phenyl]amine (TPA) with large two-photon absorption cross-sections as an electron-donating group was obtained, and showed intense absorption in the visible light region (λmax = 509 nm) and weak near-infrared (NIR) fluorescence emission at 750 nm. After complexation with cucurbit[8]uril (CB[8]), TP-3PY showed bright NIR fluorescence emission at 727 nm and phosphorescence emission at 800 nm. When the supramolecular assembly (TP-3PY⊂CB[8]) further interacted with dodecyl-modified sulfonatocalix[4]arene (SC4AD), the fluorescence and phosphorescence emissions were further enhanced at 710 and 734 nm, respectively. However, only the fluorescence emission of TP-3PY was enhanced in the presence of cucurbit[7]uril (CB[7]) and SC4AD. More interestingly, the photoluminescence of TP-3PY⊂CB[8]@SC4AD and TP-3PY⊂CB[7]@SC4AD assemblies could be excited by both visible (510 nm) and NIR light (930 nm). Finally, these ternary supramolecular assemblies with bright NIR light emission were applied to lysosome imaging of tumor cells and real-time biological imaging of mice.

7.
Int J Mol Sci ; 23(18)2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36142569

RESUMEN

In mammals, female fertility is determined by the outcome of follicular development (ovulation or atresia). The TGF-ß/SMAD signaling pathway is an important regulator of this outcome. However, the molecular mechanism by which the TGF-ß/SMAD signaling pathway regulates porcine follicular atresia has not been fully elucidated. Microrchidia family CW-type zinc finger 2 (MORC2) is anovel epigenetic regulatory protein widely expressed in plants, nematodes, and mammals. Our previous studies showed that MORC2 is a potential downstream target gene of the TGF-ß/SMAD signaling pathway. However, the role of MORC2 in porcine follicular atresia is unknown. To investigate this, qRT-PCR, western blotting, and TdT-mediated dUTP nick-end labeling were performed. Additionally, the luciferase activity assay was conductedto confirm that the TGF-ß/SMAD signaling pathway regulates MORC2. Our results demonstrate that MORC2 is animportant anti-apoptotic molecule that prevents porcine follicular atresia via a pathway involving mitochondrial apoptosis, not DNA repair. Notably, this studyrevealsthat the TGF-ß/SMAD signaling pathway inhibits porcine granulosa cell apoptosis by up-regulating MORC2. The transcription factor SMAD4 regulated the expression of MORC2 by binding to its promoter. Our results will help to reveal the mechanism underlying porcine follicular atresia and improve the reproductive efficiency of sows.


Asunto(s)
Atresia Folicular , Células de la Granulosa , Animales , Femenino , Atresia Folicular/genética , Células de la Granulosa/metabolismo , Luciferasas/metabolismo , Mamíferos/metabolismo , Transducción de Señal , Porcinos , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo
8.
Environ Sci Pollut Res Int ; 29(53): 80532-80548, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35718849

RESUMEN

The rational allocation of chemical fertilizer resources is of strategic importance in mitigating agricultural source pollution and achieving agricultural green development. The spatiotemporal correlation of chemical fertilizer supply/demand and its determinants remains unclear. In this study, based on the inter-provincial chemical fertilizer supply/demand panel data of China from 1994 to 2018, an improved gravity model was employed to determine provincial chemical fertilizer supply/demand correlations. Finally, the chemical fertilizer supply/demand evolution and its driving factors were analyzed using social network analysis and a quadratic assignment procedure. The results indicated that (1) the intensity of the spatial relationship of inter-provincial chemical fertilizer supply/demand increased in a fluctuating fashion, but there was still room for improvement. The network structure presented good stability, and the spillover effect exhibited multiple superposition characteristics; (2) the spatial correlation network of inter-provincial chemical fertilizer supply/demand presented a "core-periphery" distribution pattern of the supply, demand, and balance areas. The division of blocks in the network changed in time and space, and some provinces changed their roles and positions in the network during development; (3) chemical fertilizer-related policies (e.g., Exemption Agricultural Tax, Notice on the resumption of value added tax policy on fertilizers, and Rural Revitalization Strategy) have played a positive role in the formation and development of the interprovincial spatial correlation network of chemical fertilizer supply/demand in China; (4) natural conditions and socioeconomic factors interact to promote the formation of the spatial correlation network of chemical fertilizer supply/demand. The differences in the scale of the rural labor force, the scale of agricultural mechanization, the agricultural planting structure, the populations, and urbanization levels all had a significant impact on it. The identification of the spatial characteristics of chemical fertilizer supply/demand correlation networks offers a new perspective on taking various measures to realize the cross-regional coordination of chemical fertilizer resources, strengthen the protection and utilization of agricultural resources, and promote green agricultural development.


Asunto(s)
Agricultura , Fertilizantes , Urbanización , Contaminación Ambiental , China
9.
Med Sci Monit ; 28: e934102, 2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-35075100

RESUMEN

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Coronavirus/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , SARS-CoV-2/efectos de los fármacos , Alcaloides/química , Alcaloides/farmacología , Caspasa 3/efectos de los fármacos , Caspasa 3/genética , Coronavirus/metabolismo , Infecciones por Coronavirus/tratamiento farmacológico , Ciclooxigenasa 2/efectos de los fármacos , Ciclooxigenasa 2/genética , Bases de Datos Farmacéuticas , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Flavanonas/química , Flavanonas/farmacología , Humanos , Indoles/química , Indoles/farmacología , Interleucina-6/genética , Lignina/química , Lignina/farmacología , Luteolina/química , Luteolina/farmacología , Proteína Quinasa 14 Activada por Mitógenos/efectos de los fármacos , Proteína Quinasa 14 Activada por Mitógenos/genética , Proteína Quinasa 8 Activada por Mitógenos/efectos de los fármacos , Proteína Quinasa 8 Activada por Mitógenos/genética , Simulación del Acoplamiento Molecular , Subunidad p50 de NF-kappa B/efectos de los fármacos , Subunidad p50 de NF-kappa B/genética , Naftoles/química , Naftoles/farmacología , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/genética , Mapas de Interacción de Proteínas , Quercetina/química , Quercetina/farmacología , SARS-CoV-2/metabolismo , Transducción de Señal , Sitoesteroles/química , Sitoesteroles/farmacología , Transcriptoma/efectos de los fármacos , Transcriptoma/genética
10.
Comput Biol Chem ; 86: 107258, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32304977

RESUMEN

BACKGROUND: Thyroid carcinoma (THCA) is one of the most frequent endocrine cancers and has increasing morbidity. Annexin A2 (ANXA2) has been found to be highly expressed in various cancers; however, its expression level and potential mechanism in THCA remain unknown. This study investigated the clinicopathological value and primary molecular machinery of ANXA2 in THCA. MATERIAL AND METHODS: Public RNA-sequencing and microarray data were obtained and analyzed with ANXA2 expression in THCA and corresponding non-cancerous thyroid tissue. A Pearson correlation coefficient calculation was used for the acquisition of ANXA2 coexpressed genes, while edgR, limma, and Robust Rank Aggregation were employed for differentially expressed gene (DEG) in THCA. The probable mechanism of ANXA2 in THCA was predicted by gene ontology and pathway enrichment. A dual-luciferase reporter assay was employed to confirm the targeting relationships between ANXA2 and its predicted microRNA (miRNA). RESULTS: Expression of ANXA2 was significantly upregulated in THCA tissues with a summarized standardized mean difference of 1.09 (P < 0.0001) based on 992 THCA cases and 589 cases of normal thyroid tissue. Expression of ANXA2 was related to pathologic stage. Subsequently, 1442 genes were obtained when overlapping 4542 ANXA2 coexpressed genes with 2248 DEGs in THCA; these genes were mostly enriched in pathways of extracellular matrix-receptor interaction, cell adhesion molecules, and complement and coagulation cascades. MiR-23b-3p was confirmed to target ANXA2 by dual-luciferase reporter assay. CONCLUSIONS: Upregulated expression of ANXA2 may promote the malignant biological behavior of THCA by affecting the involving pathways or being targeted by miR-23b-3p.


Asunto(s)
Anexina A2/genética , Neoplasias de la Tiroides/genética , Ontología de Genes , Humanos , MicroARNs , Análisis de Secuencia de ARN , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Neoplasias de la Tiroides/patología , Regulación hacia Arriba
11.
World J Clin Cases ; 7(21): 3671-3682, 2019 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-31750352

RESUMEN

BACKGROUND: Primitive neuroectodermal tumors are rare, highly malignant small round cell tumors belonging to the Ewing sarcoma family. The purpose of this article is to present clinical manifestation, histology, treatment, and prognosis of two primitive neuroectodermal tumors (PNETs) in extremely rare anatomic locations, the abdominal wall and vulva. CASE SUMMARY: Case 1 was a 66-month-old girl with lesions on the abdominal wall; tumor size was about 3.4 cm × 6.1 cm × 2 cm. The patient underwent radical resection of the tumor. After the operation, an alternating vincristine, doxorubicin, and cyclophosphamide/ifosfamide and etoposide (IE) regimen was given for eight cycles, and the patient survived for 66 mo without progression. Case 2 was a 40-month-old girl, with a vulvar lesion; tumor size was about 3.3 cm × 5 cm × 2.5 cm. The tumor was partially resected by surgery. The family left treatment after two cycles of vincristine, pirarubicin, and cyclophosphamide/IE chemotherapy, and the patient died at home six months after surgery. CONCLUSION: PNET is a rare, fast-growing, highly malignant tumor that requires histologic and molecular analyses for exact diagnosis, and multimodal treatment is required to achieve a good prognosis.

12.
Plant Physiol Biochem ; 87: 124-32, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25579659

RESUMEN

This study investigated the effects of grafting on the carbohydrate status and the enzymes of carbohydrate metabolism in self-grafted and grafted cucumber seedlings using the salt-tolerant pumpkin rootstock 'Qingzhen 1' (Cucurbita maxima × Cucurbita moschata) under 80 mM Ca(NO3)2 stress for 6 d. The growth of self-grafted seedlings was significantly inhibited after the treatment of Ca(NO3)2 stress, whereas the inhibition of growth was alleviated in pumpkin rootstock-grafted seedlings. Ca(NO3)2 stress increased the contents of the total soluble sugar, sucrose and fructose, but decreased the starch content in rootstock-grafted leaves. However, compared with self-grafted plants, rootstock-grafted seedlings were observed with a higher content of sucrose and total soluble sugar (TSS) under salt stress. Rootstock-grafted seedlings exhibited higher activities of acid invertase (AI), neutral invertase (NI) and phosphate sucrose synthase (SPS) of sucrose metabolism in leaves than that of self-grafted seedlings under salinity. Moreover, the activities of fructokinase (FK), hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) of glycolysis were maintained at a higher level in leaves of rootstock-grafted seedlings after Ca(NO3)2 stress. Additionally, rootstock-grafting decrease the high percentage enhancement of key enzymes gene expression in glycolysis in the scion leaves of cucumber seedlings induced by salt stress. These results suggest that the rootstock-grafting improved salt tolerance, which might play a role in elevated sucrose metabolism and a glycolytic pathway regulated by the pumpkin rootstock.


Asunto(s)
Compuestos de Calcio/farmacología , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Cucurbita/química , Nitratos/farmacología , Raíces de Plantas/química , Plantones/metabolismo , Estrés Fisiológico/efectos de los fármacos
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