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BACKGROUND: Fish reproduction, development and growth are directly affected by temperature, investigating the regulatory mechanisms behind high temperature stress is helpful to construct a finer molecular network. In this study, we systematically analyzed the transcriptome and miRNA information of American shad (Alosa sapidissima) liver tissues at different cultivation temperatures of 24 â (Low), 27 â (Mid) and 30 â (High) based on a high-throughput sequencing platform. RESULTS: The results showed that there were 1594 differentially expressed genes (DEGs) and 660 differentially expressed miRNAs (DEMs) in the LowLi vs. MidLi comparison group, 473 DEGs and 84 DEMs in the MidLi vs. HighLi group, 914 DEGs and 442 DEMs in the LowLi vs. HighLi group. These included some important genes and miRNAs such as calr, hsp90b1, hsp70, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p. The DEGs were mainly enriched in the protein folding, processing and export pathways of the endoplasmic reticulum; the target genes of the DEMs were mainly enriched in the focal adhesion pathway. Furthermore, the association analysis revealed that the key genes were mainly enriched in the metabolic pathway. Interestingly, we found a significant increase in the number of genes and miRNAs involved in the regulation of heat stress during the temperature change from 24 °C to 27 °C. In addition, we examined the tissue expression characteristics of some key genes and miRNAs by qPCR, and found that calr, hsp90b1 and dre-miR-125b-2-3p were significantly highly expressed in the liver at 27 â, while novel-m0481-5p, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p had the highest expression in the heart at 30â. Finally, the quantitative expression trends of 10 randomly selected DEGs and 10 DEMs were consistent with the sequencing data, indicating the reliability of the results. CONCLUSIONS: In summary, this study provides some fundamental data for subsequent in-depth research into the molecular regulatory mechanisms of A. sapidissima response to heat stress, and for the selective breeding of high temperature tolerant varieties.
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Perfilación de la Expresión Génica , Hígado , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Animales , Hígado/metabolismo , Transcriptoma , Respuesta al Choque Térmico/genética , Redes Reguladoras de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Calor , Estrés Fisiológico/genéticaRESUMEN
Demethylcantharidin (DEM) is a widely used antitumor drug; however, its poor tumor targeting and serious organotoxicity limit its application. The aim of this study was to develop a new drug delivery system for efficient delivery of DEM. Nanoemulsion based lipid nanoparticles containing demethylcantharidin (DNLNs) were prepared by loading nanoemulsions into lipid nanoparticles. The cells proliferation, apoptosis, cycle, and uptake were investigated by Cell counting kit-8 (CCK-8), flow cytometry, and in situ fluorescence assays, respectively. Then, we established the H22 tumor-bearing mouse model to evaluate the antitumor efficacy of DNLNs and further studied its organ toxicity and distribution. DNLNs significantly inhibited the proliferation and promoted apoptosis of H22 cells, and H22 cells could take up more DNLNs. Compared with DEM, DNLNs had certain tumor-targeting properties, and the tumor inhibition rate increased by 23.24%. Moreover, DNLNs can increase white blood cell count and reduce organ toxicity. This study paves the way for nanoemulsion-based lipid nanoparticle (NLNs)-efficient DEM delivery to treat liver cancer.
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Antineoplásicos , Apoptosis , Emulsiones , Neoplasias Hepáticas , Nanopartículas , Animales , Ratones , Nanopartículas/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Línea Celular Tumoral , Emulsiones/química , Apoptosis/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Lípidos/química , Humanos , Proliferación Celular/efectos de los fármacos , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , LiposomasRESUMEN
Optical detection is an indispensable part of microfluidic systems for nutrient determination in seawater. Coupling total internal reflection capillaries with microfluidic chips is a practical alternative to increase the optical path length for high-sensitivity and a low detection limit in colorimetric assays, which has not been applied in microfluidic devices for seawater nutrients. Here, we present an online microfluidic system which integrated a total internal reflection capillary made of Teflon AF 2400 for the high-sensitivity detection of nitrite and nitrate in seawater. The off-chip capillary lengthens the optical path without changing the internal flow path of the microfluidic chip, enhancing the sensitivity, reducing the detection limit and widening the dynamic range of the system, which significantly improves the performance of the microfluidic system based on wet-chemistry. The detection limit for nitrite is 0.0150 µM using an external 20 cm capillary and 0.0936 µM using an internal 5 cm absorption cell, providing an over 6-fold improvement. Laboratory analysis of surface seawater samples collected from the South China Sea with this system and a one-month online deployment of an autonomous analyzer developed based on this system at a station revealed correlations between the nitrite and nitrate with tide, salinity and chlorophyll over slight variations and narrow ranges, demonstrating the high-sensitivity of this method.
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Phospholipase D (PLD) lipid-signaling enzyme superfamily has been widely implicated in various human malignancies, but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma (NPC). Here, we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis. Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines, correlating with worse disease-free and overall survival in NPC patients. Functional assays further elucidate PLD1's oncogenic role, demonstrating its pivotal promotion of critical tumorigenic processes such as cell proliferation and migration in vitro, as well as tumor growth in vivo. Notably, our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression. Specifically, PLD1 enhances NF-κB activity by facilitating the phosphorylation and nuclear translocation of RELA (p65), which in turn binds to the promoter of PLD1, augmenting its expression. Moreover, RELA overexpression significantly rescues the inhibitory effects in PLD1-depleted NPC cells. Importantly, the application of the PLD1 inhibitor, VU0155069, significantly inhibits NPC tumorigenesis in a patient-derived xenograft model. Together, our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.
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Intimal hyperplasia (IH) is a common pathological feature of vascular proliferative diseases, such as atherosclerosis and restenosis after angioplasty. Urotensin II (UII) and its receptor (UTR) are widely expressed in cardiovascular tissues. However, it remains unclear whether the UII/UTR system is involved in IH. Right unilateral common carotid artery ligation was performed and maintained for 21 days to induce IH in UTR knockout (UTR-/-) and wild-type (WT) mice. Histological analysis revealed that compared with WT mice, UTR-deficient mice exhibited a decreased neointimal area, angiostenosis and intima-media ratio. Immunostaining revealed fewer smooth muscle cells (SMCs), endothelial cells and macrophages in the lesions of UTR-/- mice than in those of WT mice. Protein interaction analysis suggested that the UTR may affect cell proliferation by regulating YAP and its downstream target genes. In vitro experiments revealed that UII can promote the proliferation and migration of SMCs, and western blotting also revealed that UII increased the protein expression of RhoA, CTGF, Cyclin D1 and PCNA and downregulated p-YAP protein expression, while these effects could be partly reversed by urantide. To evaluate the translational value of UTRs in IH management, WT mice were also treated with two doses of urantide, a UTR antagonist, to confirm the benefit of UTR blockade in IH progression. A high dose of urantide (600 µg/kg/day), rather than a low dose (60 µg/kg/day), successfully improved ligation-induced IH compared with that in mice receiving vehicle. The results of the present study suggested that the UII/UTR system may regulate IH partly through the RhoA-YAP signaling pathway.
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Proteínas Adaptadoras Transductoras de Señales , Proliferación Celular , Hiperplasia , Ratones Noqueados , Receptores Acoplados a Proteínas G , Transducción de Señal , Proteínas Señalizadoras YAP , Proteína de Unión al GTP rhoA , Animales , Masculino , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Movimiento Celular , Hiperplasia/metabolismo , Hiperplasia/patología , Ligadura , Ratones Endogámicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Neointima/metabolismo , Neointima/patología , Neointima/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Proteína de Unión al GTP rhoA/metabolismo , Proteína de Unión al GTP rhoA/genética , Túnica Íntima/patología , Túnica Íntima/metabolismo , Urotensinas/metabolismo , Urotensinas/genética , Urotensinas/farmacología , Proteínas Señalizadoras YAP/metabolismoRESUMEN
Leonurine (LEO), an alkaloid isolated from Leonurus spp., has anti-oxidant, anti-inflammatory and anti-apoptotic effects and can prevent damage caused by reactive oxygen species (ROS). These properties suggest that it can improve the maturation rate of oocytes and developmental ability of embryos, which are key parameters in animal breeding. In this study, the effects of LEO on in vitro maturation and early embryonic development in sheep oocytes were evaluated. Among various doses examined (0, 10, 20 and 40 µM), a dose of 20 µM was optimal with respect to the oocyte maturation rate. Compared with estimates in the control group, GSH levels and mitochondrial membrane potential of sheep oocytes treated with 20 µM LEO were significantly higher, and 40 µM LEO would affect oocyte maturation. Additionally, ROS levels were significantly lower, expression levels of the antioxidant genes CAT and SOD1 were significantly higher, and there was no significant difference in GPX3 expression. The Bax/Bcl-2 ratio and Caspase-3 expression were significantly reduced in the 20 µM LEO group. During early embryonic development in vitro, the cleavage rate and blastocyst rate were significantly higher in the 20 µM LEO treatment group compared to other groups. GSH levels and mitochondrial membrane potential were significantly higher, while ROS levels were significantly lower, and expression levels of the antioxidant genes CAT, GPX3 and SOD1 were significantly higher in eight-cell embryos treated with 20 µM LEO than in the control group. The Bax/Bcl-2 ratio and Caspase-3 levels were significantly decreased. In summary, LEO can reduce the effect of oxidative stress, improve the oocyte maturation rate and enhance embryonic development.
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Antioxidantes , Desarrollo Embrionario , Ácido Gálico/análogos & derivados , Femenino , Embarazo , Animales , Ovinos , Caspasa 3 , Antioxidantes/farmacología , Especies Reactivas de Oxígeno , Superóxido Dismutasa-1 , Proteína X Asociada a bcl-2 , OocitosRESUMEN
Mannose-binding lectin plays an essential role in bacteria or virus-triggered immune response in mammals. Previous proteomic data revealed that in Eriocheir sinensis, the mannose-binding protein was differentially expressed after Spiroplasma eriocheiris infection. However, the function of mannose-binding protein against pathogen infection in invertebrates is poorly understood. In this study, a crab mannose-binding protein (EsMBP) was characterized and enhanced the host resistance to S. eriocheiris infection. The application of recombinant C-type carbohydrate recognition domain (CTLD) of EsMBP led to increased crab survival and decreased S. eriocheiris load in hemocytes. Meanwhile, the overexpression of CTLD of EsMBP in Raw264.7 cells inhibited S. eriocheiris intracellular replication. In contrast, depletion of EsMBP by RNA interference or antibody neutralization attenuated phenoloxidase activity and hemocyte phagocytosis, rendering host more susceptible to S. eriocheiris infection. Furthermore, miR-381-5p in hemocytes suppressed EsMBP expression and negatively regulated phenoloxidase activity to exacerbate S. eriocheiris invasion of hemocytes. Taken together, our findings revealed that crab mannose-binding protein was involved in host defense against S. eriocheiris infection and targeted by miR-381-5p, providing further insights into the control of S. eriocheiris spread in crabs.
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Braquiuros , Catecol Oxidasa , Precursores Enzimáticos , Lectina de Unión a Manosa , MicroARNs , Spiroplasma , Animales , Lectina de Unión a Manosa/metabolismo , Proteómica , Monofenol Monooxigenasa/metabolismo , Fagocitosis , MicroARNs/genética , MicroARNs/metabolismo , Hemocitos/metabolismo , Mamíferos/genéticaRESUMEN
BACKGROUND: Houttuynia Cordata Thunb. (H. cordata; Saururaceae) is a medicine food homology plant that is grown in many Asian countries. Its main phytochemical constituents are volatile oils, flavonoids, polysaccharides and alkaloids. It has considerable clinical applications and health benefits. PURPOSE: This paper reviews the existing literatures and patents, summarizes the phytochemistry, pharmacological activity, safety and economic botanical applications of H. cordata, and provides a reference for systematic study of the pharmacological effects of H. cordata, improvement of quality standards and further development of its medicinal resources. METHODS: A comprehensive search of literature and patents on H. cordata and its active ingredients published before June 2023 was conducted using PubMed, Google Scholar, Web of Science, and China Knowledge Network. RESULTS: H. cordata is not only edible and medicinal but also used in various aspects of daily life such as fermented beverages, nutraceuticals, feed and cosmetics. The main phytochemical constituents of H. cordata are volatile oils, flavonoids, organic acids and alkaloids. Several in vitro and in vivo studies and clinical trials have found that H. cordata extracts possess antioxidant, anti-inflammatory, antitumor, antibacterial, hepatoprotective and renal, immunomodulatory and potent antiviral effects. The mechanisms of expression of these pharmacological effects are related to the blood-brain barrier, lipophilicity, cAMP signaling and skin permeability, including blocking the MAPK signaling pathway, inhibiting the secretion of inflammatory factors such as TNF-α and IL-1ß, and activating the AMPK pathway. CONCLUSION: This paper provides a comprehensive review of the progress of research on the traditional applications, botany, chemical composition, pharmacological effects and safety of H. cordata and discusses for the first time the economic botanical aspects, which were not explored in the previous reviews. H. cordata has a wide range of bioactive substances whose therapeutic potential has not been fully exploited, and it could provide a new non-toxic approach to many diseases. This traditional medicinal food plant should receive more attention and in-depth research in the future.
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Alcaloides , Houttuynia , Aceites Volátiles , Plantas Medicinales , Houttuynia/química , Extractos Vegetales/farmacología , Fitoquímicos/farmacología , Flavonoides/farmacología , EtnofarmacologíaRESUMEN
Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein-Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single-cell RNA sequencing (scRNA-seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single-cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV-encoded genes and low infiltration of tumor-associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single-cell resolution, highlighting the crucial role of malignant NK cells with EBV-encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.
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Infecciones por Virus de Epstein-Barr , Linfoma Extranodal de Células NK-T , Humanos , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/patología , Linfoma Extranodal de Células NK-T/genética , Linfoma Extranodal de Células NK-T/patología , Pronóstico , Análisis de la Célula Individual , Microambiente TumoralRESUMEN
Intimal hyperplasia (IH) is a negative vascular remodeling after arterial injury. IH occasionally occurs in elastase-induced abdominal aortic aneurysm (AAA) mouse models. This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice. A retrospective study was conducted by including 42 male elastase-induced mouse AAA models. The IH incidence, aortic diameters with or without IH, and hyperplasia lesional features of mice were analyzed. Among 42 elastase-induced AAA mouse models, 10 mice developed mild IH (24%) and severe IH was found in only 2 mice (5%). The outer diameters of the AAA segments in mice with and without IH did not show significant difference. Both mild and severe IH lesions show strong smooth muscle cell positive staining, but endothelial cells were occasionally observed in severe IH lesions. There was obvious macrophage infiltration in the IH lesions of the AAA mouse models, especially in mice with severe IH. However, only a lower numbers of T cells and B cells were found in the IH lesion. Local cell-secreted matrix metalloproteinases (MMP) 2 was highly expressed in all IH lesions, but MMP9 was only overexpressed in severe lesions. In conclusion, this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastase-induced mouse AAA model. This will help researchers better understand this model, and optimize it for use in AAA-related research.
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Background: C-reactive protein (CRP) levels are elevated in patients with abdominal aortic aneurysms (AAA). However, it has not been investigated whether CRP contributes to AAA pathogenesis. Methods: CRP deficient and wild type (WT) male mice were subjected to AAA induction via transient intra-aortic infusion of porcine pancreatic elastase. AAAs were monitored by in situ measurements of maximal infrarenal aortic external diameters immediately prior to and 14 days following elastase infusion. Key AAA pathologies were assessed by histochemical and immunohistochemical staining procedures. The influence of CRP deficiency on macrophage activation was evaluated in peritoneal macrophages in vitro. Results: CRP protein levels were higher in aneurysmal than that in non-aneurysmal aortas. Aneurysmal aortic dilation was markedly suppressed in CRP deficient (aortic diameter: 1.08 ± 0.11 mm) as compared to WT (1.21 ± 0.08 mm) mice on day 14 after elastase infusion. More medial elastin was retained in CRP deficient than in WT elastase-infused mice. Macrophage accumulation was significantly less in aneurysmal aorta from CRP deficient than that from WT mice. Matrix metalloproteinase 2 expression was also attenuated in CRP deficient as compared to WT aneurysmal aortas. CRP deficiency had no recognizable influence on medial smooth muscle loss, lymphocyte accumulation, aneurysmal angiogenesis, and matrix metalloproteinase 9 expression. In in vitro assays, mRNA levels for tumor necrosis factor α and cyclooxygenase 2 were reduced in lipopolysaccharide activated peritoneal macrophages from CRP deficient as compared to wild type mice. Conclusion: CRP deficiency suppressed experimental AAAs by attenuating aneurysmal elastin destruction, macrophage accumulation and matrix metalloproteinase 2 expression.
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Aneurisma de la Aorta Abdominal , Metaloproteinasa 2 de la Matriz , Humanos , Masculino , Animales , Ratones , Porcinos , Proteína C-Reactiva/genética , Elastina , Aneurisma de la Aorta Abdominal/inducido químicamente , Aorta AbdominalRESUMEN
Dysregulation of serine/arginine splicing factors (SRSFs) and abnormal alternative splicing (AS) have been widely implicated in various cancers but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts an oncogenic function in NPC progression. Transcriptome analysis reveals 1,934 SRSF3-regulated AS events in genes related to cell cycle and mRNA metabolism. Among these events, we verify the generation of a long isoform of AMOTL1 (AMOTL1-L) through a direct bond of the SRSF3 RRM domain with the exon 12 of AMOTL1 to promote exon inclusion. Functional studies also reveal that AMOTL1-L promotes the proliferation and migration of NPC cells, while AMOTL1-S does not. Furthermore, overexpression of AMOTL1-L, but not -S, significantly rescues the inhibitory effects of SRSF3 knockdown. Additionally, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than the cell membrane, leading to a more robust interaction with YAP1 to promote nucleus translocation. Our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could serve as promising prognostic biomarkers and therapeutic targets for NPC.
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Neoplasias Nasofaríngeas , Empalme del ARN , Humanos , Carcinoma Nasofaríngeo/genética , Transformación Celular Neoplásica/genética , Empalme Alternativo/genética , Neoplasias Nasofaríngeas/genética , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , AngiomotinasRESUMEN
Aim: Signal transducer and activator of transcription (STAT) signaling is critical for the pathogenesis of abdominal aortic aneurysms (AAAs). Though protein inhibitor of activated STAT3 (PIAS3) negatively modulates STAT3 activity, but its role in AAA disease remains undefined. Method: AAAs were induced in PIAS3 deficient (PIAS3-/-) and wild type (PIAS3+/+) male mice via transient intra-aortic elastase infusion. AAAs were assessed by in situ measurements of infrarenal aortic external diameters prior to (day 0) and 14 days after elastase infusion. Characteristic aneurysmal pathologies were evaluated by histopathology. Results: Fourteen days following elastase infusion, aneurysmal aortic diameter was reduced by an approximately 50% in PIAS3-/- as compared to PIAS3+/+ mice. On histological analyses, PIAS3-/- mice showed less medial elastin degradation (media score: 2.5) and smooth muscle cell loss (media score: 3.0) than those in PIAS3+/+ mice (media score: 4 for both elastin and SMC destruction). Aortic wall leukocyte accumulation including macrophages, CD4+ T cells, CD8+ T cells and B cells as well as mural neovessel formation were significantly reduced in PIAS3-/- as compared to PIAS3+/+ mice. Additionally, PIAS3 deficiency also downregulated the expression levels of matrix metalloproteinases 2 and 9 by 61% and 70%, respectively, in aneurysmal lesion. Conclusion: PIAS3 deficiency ameliorated experimental AAAs in conjunction with reduced medial elastin degradation and smooth muscle cell depletion, mural leukocyte accumulation and angiogenesis.
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Accumulated evidence shows that elevated urotensin II (UII) levels are associated with cardiovascular diseases. However, the role of UII in the initiation, progression, and regression of atherosclerosis remains to be verified. Different stages of atherosclerosis were induced in rabbits by a 0.3% high cholesterol diet (HCD) feeding, and either UII (5.4 µg/kg/h) or saline was chronically infused via osmotic mini-pumps. UII promoted atherosclerotic fatty streak formation in ovariectomized female rabbits (34% increase in gross lesion and 93% increase in microscopic lesion), and in male rabbits (39% increase in gross lesion). UII infusion significantly increased the plaque size of the carotid and subclavian arteries (69% increase over the control). In addition, UII infusion significantly enhanced the development of coronary lesions by increasing plaque size and lumen stenosis. Histopathological analysis revealed that aortic lesions in the UII group were characterized by increasing lesional macrophages, lipid deposition, and intra-plaque neovessel formation. UII infusion also significantly delayed the regression of atherosclerosis in rabbits by increasing the intra-plaque macrophage ratio. Furthermore, UII treatment led to a significant increase in NOX2 and HIF-1α/VEGF-A expression accompanied by increased reactive oxygen species levels in cultured macrophages. Tubule formation assays showed that UII exerted a pro-angiogenic effect in cultured endothelial cell lines and this effect was partly inhibited by urantide, a UII receptor antagonist. These findings suggest that UII can accelerate aortic and coronary plaque formation and enhance aortic plaque vulnerability, but delay the regression of atherosclerosis. The role of UII on angiogenesis in the lesion may be involved in complex plaque development.
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Aterosclerosis , Hipercolesterolemia , Placa Aterosclerótica , Urotensinas , Animales , Conejos , Masculino , Femenino , Placa Aterosclerótica/metabolismo , Aterosclerosis/metabolismo , Urotensinas/metabolismo , Urotensinas/farmacología , Macrófagos/metabolismo , Aorta/metabolismo , Hipercolesterolemia/metabolismoRESUMEN
BACKGROUND: Plant growth regulators are chemicals that regulate plant growth and development, which can regulate hormonal balance and affect plant growth, thereby increasing crop yield and improving crop quality. Our studies have revealed a new compound, GZU001, which could be used as a plant growth regulator. This compound has been observed to affect root elongation in maize significantly. However, the exact mechanism of this phenomenon is still being investigated. RESULTS: Metabolomics and proteomics were used in unison in this study to explore the response pathway and regulation mechanism of GZU001 in promoting maize root elongation. From the appearance, we can see that both roots and plants of maize treated with GZU001 are significantly improved. Maize root metabolism revealed 101 differentially abundant proteins and 79 differentially expressed metabolites. The current study identified altered proteins and metabolites associated with physiological and biochemical processes. GZU001 treatment has been demonstrated to promote primary metabolism, essential for carbohydrates, amino acids, energy, and secondary metabolism. The result suggests that the stimulation of primary metabolism is beneficial for the growth and development of maize and plays a significant role in sustaining metabolism and growth. CONCLUSIONS: This study recorded the changes of related proteins and metabolites in maize roots after GZU001 treatment and provided evidence for this compound's action mode and mechanism in plants.
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Proteómica , Zea mays , Zea mays/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Metabolómica , Raíces de Plantas/metabolismoRESUMEN
Convenient, ultrasensitive, and accurate detection of rare variants is essential for early cancer diagnosis and precision medicine, however, despite years of efforts, tools that have all these qualities remain elusive. Here, we developed a one-step CRISPR/Cas12a-based digital diagnostic platform for accurately quantifying mutant alleles, referred to as the CRISPR ASsoaciated Mutation Allele Rapid Test (CASMART). The platform accurately quantifies the variant allele frequency of EGFR L858R within 1 h at 42 °C and can detect mutant targets as low as 0.3 copies/µL (0.498 aM) in mock multiplex cfDNA samples. We further investigated the applicability of CASMART using human genomic samples with confirmed EGFR L858R mutations previously measured variant allele frequency by next-generation sequencing. Comparison across platforms revealed equivalent detection performance (Pearson's correlation coefficient, R2 = 0.9208) and high quantification accuracy for mutation allele frequency (intraclass correlation coefficient = 0.959). Our one-step approach enables easy and accurate variant allele frequency measurement of rare mutant alleles without PCR instrumentation, while the assay time was reduced by approximately half compared to the digital PCR with the shortest turnaround. The CASMART is an alternative to conventional single nucleotide polymorphism detection methods with great potential as a next-generation biosensor for rapidly quantifying the variant allele fraction, especially in resource-limited settings.
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Técnicas Biosensibles , Sistemas CRISPR-Cas , Humanos , Alelos , Sistemas CRISPR-Cas/genética , Mutación , Receptores ErbB/genéticaRESUMEN
AIMS: This study aimed to evaluate the roles and molecular targets of miRNA-141-3p in the cisplatin sensitivity of osteosarcoma. BACKGROUND: Osteosarcoma is one of the most common-type bone tumors, occurring mainly in children and adolescents. Cancer cells display dysregulated cellular metabolism, such as the abnormally elevated glutamine metabolism. OBJECTIVE: Non-coding RNA miRNA-141-3p has been reported to act as a tumor suppressor in osteosarcoma. Currently, the precise molecular mechanisms for the miR- 141-3p-mediated chemosensitivity through regulating glutamine metabolism remain unclear. METHODS: We collected thirty paired OS tumors and their adjacent normal tissues. The osteosarcoma cell lines [Saos-2] and normal osteoblast cells, hFOB1.19, were used for in vitro experiments. RT-qPCR and Western blot were applied for gene expression detections. Targets of miR-141-3p were predicted from starBase. The MTT and flow cytometric assays were performed to determine cell growth and apoptosis rates. The cellular glutamine metabolism was monitored by glutamine uptake assay and the glutaminase [GLS] activity assay. RESULTS: We reported that miR-141-3p were significantly downregulated in osteosarcoma tissues and cells. Overexpression of miR-141-3p suppressed OS cell growth and sensitized OS cells to cisplatin. In addition, glutamine metabolism was significantly increased in osteosarcoma. We characterized that GLS played oncogenic roles in osteosarcoma and validated GLS was a direct target of miR-141-3p in OS cells. Rescue experiments consistently demonstrated that miR-141-3p-promoted cisplatin sensitivity was achieved by targeting GLS directly. CONCLUSION: Overall, our findings revealed new molecular mechanisms of the miR-141- 3p-modulated cisplatin sensitization through targeting the GLS-glutamine metabolism pathway. This study will contribute to developing new therapeutic approaches for the treatments of chemoresistant osteosarcoma.
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Cisplatino , MicroARNs , Niño , Humanos , Adolescente , Cisplatino/farmacología , Glutamina , MicroARNs/genéticaRESUMEN
Sea buckthorn (Hippophae rhamnoides L.), an ancient miraculous plant, is of great interest because of its tenacity, richness in nutritional active substances, and biological activity. Sea buckthorn is a deciduous shrub or tree of the genus Hippophae in the family Elaeagnaceae. It is a pioneer tree species for soil improvement, wind and sand control, and soil and water conservation. Sea buckthorn contains many nutritional active components, such as vitamins, carotenoids, polyphenols, fatty acids, and phytosterols. Moreover, sea buckthorn has many health benefits, such as antioxidant, anticancer, anti-hyperlipidemic, anti-obesity, anti-inflammatory, antimicrobial, antiviral, dermatological, neuroprotective, and hepatoprotective activities. Sea buckthorn not only has great medicinal and therapeutic potential, but also is a promising economic plant. The potential of sea buckthorn in the human food industry has attracted the research interest of researchers and producers. The present review mainly summarizes the phytochemistry, nutrients, health benefits, and food applications of sea buckthorn. Overall, sea buckthorn is a dietary source of bioactive ingredients with the potential to be developed into functional foods or dietary supplements for the prevention and treatment of certain chronic diseases, which deserves further research.
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Sesame (Sesamum indicum L.), of the Pedaliaceae family, is one of the first oil crops used in humans. It is widely grown and has a mellow flavor and high nutritional value, making it very popular in the diet. Sesame seeds are rich in protein and lipids and have many health benefits. A number of in vitro and in vivo studies and clinical trials have found sesame seeds to be rich in lignan-like active ingredients. They have antioxidant, cholesterol reduction, blood lipid regulation, liver and kidney protection, cardiovascular system protection, anti-inflammatory, anti-tumor, and other effects, which have great benefits to human health. In addition, the aqueous extract of sesame has been shown to be safe for animals. As an important medicinal and edible homologous food, sesame is used in various aspects of daily life such as food, feed, and cosmetics. The health food applications of sesame are increasing. This paper reviews the progress of research on the nutritional value, chemical composition, pharmacological effects, and processing uses of sesame to support the further development of more functionalities of sesame.
Asunto(s)
Lignanos , Sesamum , Animales , Antiinflamatorios/análisis , Antioxidantes/análisis , Humanos , Lignanos/farmacología , Lípidos/análisis , Valor Nutritivo , Fitoquímicos/análisis , Semillas/química , Sesamum/químicaRESUMEN
A total of eleven new dimeric chromanones, paecilins F-P (2-12), were isolated from the endophytic fungus Xylaria curta E10, along with four known analogs (1, 13-15). Their structures and absolute configurations were determined by extensive experimental spectroscopic methods, single-crystal X-ray diffraction, and equivalent circulating density (ECD) calculations. In addition, the structure of paecilin A, which was reported to be a symmetric C8-C8' dimeric pattern, was revised by analysis of the nuclear magnetic resonance (NMR) data, and single-crystal X-ray diffraction. Compound 1 showed antifungal activity against the human pathogenic fungus Candida albicans with a minimum inhibitory concentration of 16 µg/mL, and Compounds 8 and 10 showed antibacterial activity against the gram-negative bacterium Escherichia coli with the same minimum inhibitory concentration of 16 µg/mL.