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Artesunate (ART), a natural product isolated from traditional Chinese plant Artemisia annua, has not been extensively explored for its anti-melanoma properties. In our study, we found that ART inhibited melanoma cell proliferation and induced melanoma cell ferroptosis. Mechanistic study revealed that ART directly targets Ido1, thereby suppressing Hic1-mediated transcription suppression of Hmox1, resulting in melanoma cell ferroptosis. In CD8+ T cells, ART does not cause cell ferroptosis due to the low expression of Hmox1. It also targets Ido1, elevating tryptophan levels, which inhibits NFATc1-mediated PD1 transcription, consequently activating CD8+ T cells. Our study uncovered a potent and synergistic anti-melanoma efficacy arising from ART-induced melanoma cell ferroptosis and concurrently enhancing CD8+ T cell-mediated immune response both in vivo and in vitro through directly targeting Ido1. Our study provides a novel mechanistic basis for the utilization of ART as an Ido1 inhibitor and application in clinical melanoma treatment.
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Artesunato , Ferroptosis , Indolamina-Pirrol 2,3,-Dioxigenasa , Melanoma , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Ferroptosis/efectos de los fármacos , Animales , Artesunato/farmacología , Artesunato/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/patología , Ratones , Línea Celular Tumoral , Humanos , Ratones Endogámicos C57BL , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Proliferación Celular/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genéticaRESUMEN
Background: Graves' ophthalmopathy (GO) is an organ-specific autoimmune disease and is a common orbital condition that can possibly lead to blindness. Objective: Our aim was to find out how patients with GO are affected in terms of quality of life (QoL) by traditional nursing care and social support mobile care. Methods: A total of 38 patients with GO who were admitted to Beijing Chao-Yang Hospital in China between December 2018 and December 2023 underwent life evaluations before treatment, 6 weeks after treatment and 6 months after treatment. The control group comprised 27 patients and the experimental group comprised 11 patients. They were then split into 2 groups based on the European Group on Graves' Orbitopathy (EUGOGO) improvement criteria: improved and unimproved. Then, the mean value of the Graves' Ophthalmopathy-Quality of Life Inventory (GO-QOL) alterations were compared to see if there was any difference, and their post-treatment QoL was examined. Results: (1) Patients who improved in this study had a mean change in visual energy scale scores before and after treatment that was higher than the patients who did not (13.39 vs 0.00, respectively); (2) The social functioning scores on the GO-QOL scale increased by 17.05 points in the control group before and after treatment (P < .01); (3) A total of 15.4% of patients had a GO-QOL score >90 after therapy, indicating a significant impact on their lives. In the experimental group, scores on the visual power energy scale improved by 16.27 points after treatment compared with before treatment (P = .028). Conclusion: When used in conjunction with traditional treatment, social supportive mobile care improves the outcomes in patients with GO and is superior to traditional care on its own.
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Cephalosporins are currently the most widely used antibiotics in clinical practice. The main strain used for the industrial production cephalosporin C (CPC) is Acremonium chrysogenum. CPC has the advantages of possessing a broad antibacterial spectrum and strong antibacterial activity. However, the yield and titer of cephalosporins obtained from A. chrysogenum are much lower than penicillin, which is also a ß-lactam antibiotic produced by Penicillium chrysogenum. Molecular biology research into A. chrysogenum has focused on gene editing technologies, multi-omics research which has provided information on the differences between high- and low-yield strains, and metabolic engineering involving different functional genetic modifications and hierarchical network regulation to understand strain characteristics. Furthermore, optimization of the fermentation process is also reviewed as it provides the optimal environment to realize the full potential of strains. Combining rational design to control the metabolic network, high-throughput screening to improve the efficiency of obtaining high-performance strains, and real-time detection and controlling in the fermentation process will become the focus of future research in A. chrysogenum. This minireview provides a holistic and in-depth analysis of high-yield mechanisms and improves our understanding of the industrial value of A. chrysogenum. KEY POINTS: ⢠Review of the advances in A. chrysogenum characteristics improvement and process optimization ⢠Elucidate the molecular bases of the mechanisms that control cephalosporin C biosynthesis and gene expression in A. chrysogenum ⢠The future development trend of A. chrysogenum to meet industrial needs.
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Acremonium , Acremonium/genética , Acremonium/metabolismo , Antibacterianos/metabolismo , Cefalosporinas , Fermentación , PenicilinasRESUMEN
A mineral assessment study for dairy buffaloes, Nili-Ravi breed, was carried out seasonally at silvopasture farm at Sargodha, Pakistan. Sampling for soil, forage, and buffalo serum was done seasonally for a period of 1 year for mineral (P, Mg, Na, K, Ca) evaluation. In the study, experiments on forages showed significant differences in mean concentrations of Mg and P with changing seasons, whereas the values for Ca, Mg, Na, and K did not vary significantly. Three groups of buffaloes were checked for mineral concentration in blood serum, viz., calves, lactating and non-lactating. Ca mean concentration varied significantly for non-lactating buffaloes and calves between two seasons. Na mean level showed a significant difference for two sampling seasons among calves and lactating buffaloes. Mean level for Mg only differed significantly in serum of non-lactating buffaloes between the two seasons. Mean levels for Ca and P in soil and forage remained higher than the optimal level, whereas soil Na was below the critical level. K concentrations in soil and blood serum were above the critical level, while Mg levels remained below the optimal range in soil, forage, and blood serum. K concentration in forage remained below the optimal level. All buffalo categories displayed lower levels of Ca and P in serum. Na concentration in forage and serum exceeded the critical level. Furthermore, Ca yielded significant and positive correlation between soil and serum level, whereas K had significant but negative correlation for soil-forage and forage-serum. Overall, it was determined that P deficiency existed among buffaloes, which could be improved via supplementation. Similarly, K deficiency and Mg deficiency were exhibited for forage and soil respectively which could be countered through addition of fertilizers rich for these minerals. In brief, the mineral utilization of buffaloes is affected by reduced availability of essential nutrients and may result in lower productivity. It is suggested to add mineral supplementation in addition to natural diet of buffaloes to enhance the productivity of these animals.
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Alimentación Animal/análisis , Búfalos/sangre , Minerales/análisis , Suelo/química , Animales , Análisis Químico de la Sangre , Dieta/veterinaria , Femenino , PakistánRESUMEN
Proliferation and metastasis are significantly malignant characteristics of human lung cancer, but the underlying molecular mechanisms are poorly understood. Chromobox 4 (CBX4), a member of the Polycomb group (PcG) family of epigenetic regulatory factors, enhances cellular proliferation and promotes cancer cell migration. However, the effect of CBX4 in the progression of lung cancer is not fully understood. We found that CBX4 is highly expressed in lung tumours compared with adjacent normal tissues. Overexpression of CBX4 significantly promotes cell proliferation and migration in human lung cancer cell lines. The knockdown of CBX4 obviously suppresses the cell growth and migration of human lung cancer cells in vitro. Also, the proliferation and metastasis in vivo are blocked by CBX4 knockdown. Furthermore, CBX4 knockdown effectively arrests cell cycle at the G0/G1 phase through suppressing the expression of CDK2 and Cyclin E and decreases the formation of filopodia through suppressing MMP2, MMP9 and CXCR4. Additionally, CBX4 promotes proliferation and metastasis via regulating the expression of BMI-1 which is a significant regulator of proliferation and migration in lung cancer cells. Taken together, these data suggest that CBX4 is not only a novel prognostic marker but also may be a potential therapeutic target in lung cancer.
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Biomarcadores de Tumor/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Ligasas/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/patología , Complejo Represivo Polycomb 1/metabolismo , Proteínas del Grupo Polycomb/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Femenino , Humanos , Ligasas/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Complejo Represivo Polycomb 1/genética , Proteínas del Grupo Polycomb/genética , Pronóstico , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
IR-783 is a kind of heptamethine cyanine dye that exhibits imaging, cancer targeting and anticancer properties. A previous study reported that its imaging and targeting properties were related to mitochondria. However, the molecular mechanism behind the anticancer activity of IR-783 has not been well demonstrated. In this study, we showed that IR-783 inhibits cell viability and induces mitochondrial apoptosis in human breast cancer cells. Exposure of MDA-MB-231 cells to IR-783 resulted in the loss of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) depletion, mitochondrial permeability transition pore (mPTP) opening and cytochrome c (Cyto C) release. Furthermore, we found that IR-783 induced dynamin-related protein 1 (Drp1) translocation from the cytosol to the mitochondria, increased the expression of mitochondrial fission proteins mitochondrial fission factor (MFF) and fission-1 (Fis1), and decreased the expression of mitochondrial fusion proteins mitofusin1 (Mfn1) and optic atrophy 1 (OPA1). Moreover, knockdown of Drp1 markedly blocked IR-783-mediated mitochondrial fission, loss of MMP, ATP depletion, mPTP opening and apoptosis. Our in vivo study confirmed that IR-783 markedly inhibited tumour growth and induced apoptosis in an MDA-MB-231 xenograft model in association with the mitochondrial translocation of Drp1. Taken together, these findings suggest that IR-783 induces apoptosis in human breast cancer cells by increasing Drp1-mediated mitochondrial fission. Our study uncovered the molecular mechanism of the anti-breast cancer effects of IR-783 and provided novel perspectives for the application of IR-783 in the treatment of breast cancer.
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Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Carbocianinas/farmacología , GTP Fosfohidrolasas/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Asociadas a Microtúbulos/genética , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas Mitocondriales/genética , Adenosina Trifosfato/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citocromos c/genética , Citocromos c/metabolismo , Dinaminas , Femenino , GTP Fosfohidrolasas/antagonistas & inhibidores , GTP Fosfohidrolasas/metabolismo , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Desnudos , Proteínas Asociadas a Microtúbulos/antagonistas & inhibidores , Proteínas Asociadas a Microtúbulos/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Dinámicas Mitocondriales/genética , Proteínas de Transporte de Membrana Mitocondrial/genética , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Proteínas Mitocondriales/antagonistas & inhibidores , Proteínas Mitocondriales/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The basic helix-loop-helix (bHLH) transcription factors (TFs) form a huge superfamily and play crucial roles in many essential developmental, genetic, and physiological-biochemical processes of eukaryotes. In total, 109 putative bHLH TFs were identified and categorized successfully in the genomic databases of cattle, Bos Taurus, after removing redundant sequences and merging genetic isoforms. Through phylogenetic analyses, 105 proteins among these bHLH TFs were classified into 44 families with 46, 25, 14, 3, 13, and 4 members in the high-order groups A, B, C, D, E, and F, respectively. The remaining 4 bHLH proteins were sorted out as 'orphans.' Next, these 109 putative bHLH proteins identified were further characterized as significantly enriched in 524 significant Gene Ontology (GO) annotations (corrected P value ≤ 0.05) and 21 significantly enriched pathways (corrected P value ≤ 0.05) that had been mapped by the web server KOBAS 2.0. Furthermore, 95 bHLH proteins were further screened and analyzed together with two uncharacterized proteins in the STRING online database to reconstruct the protein-protein interaction network of cattle bHLH TFs. Ultimately, 89 bHLH proteins were fully mapped in a network with 67 biological process, 13 molecular functions, 5 KEGG pathways, 12 PFAM protein domains, and 25 INTERPRO classified protein domains and features. These results provide much useful information and a good reference for further functional investigations and updated researches on cattle bHLH TFs.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/aislamiento & purificación , Genoma/genética , Secuencia de Aminoácidos/genética , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/clasificación , Bovinos , Anotación de Secuencia Molecular , FilogeniaRESUMEN
The basic helix-loop-helix (bHLH) transcription factors are one of the largest families of gene regulatory proteins and play crucial roles in genetic, developmental and physiological processes in eukaryotes. Here, we conducted a survey of the Sus scrofa genome and identified 109 putative bHLH transcription factor members belonging to super-groups A, B, C, D, E, and F, respectively, while four members were orphan genes. We identified 6 most significantly enriched KEGG pathways and 116 most significant GO annotation categories. Further comprehensive surveys in human genome and other 12 medical databases identified 72 significantly enriched biological pathways with these 113 pig bHLH transcription factors. From the functional protein association network analysis 93 hub proteins were identified and 55 hub proteins created a tight network or a functional module within their protein families. Especially, there were 20 hub proteins found highly connected in the functional interaction network. The present study deepens our understanding and provided insights into the evolution and functional aspects of animal bHLH proteins and should serve as a solid foundation for further for analyses of specific bHLH transcription factors in the pig and other mammals.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Genoma/genética , Familia de Multigenes , Sus scrofa/genética , Secuencia de Aminoácidos , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/clasificación , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Sitios de Unión/genética , Evolución Molecular , Ontología de Genes , Humanos , Datos de Secuencia Molecular , Filogenia , Unión Proteica , Mapas de Interacción de Proteínas , Homología de Secuencia de Aminoácido , Transducción de Señal/genética , Sus scrofa/metabolismoRESUMEN
Recent advances in cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), have revolutionized the clinical outcome of many cancer patients. Despite the fact that impressive progress has been made in recent decades, the response rate remains unsatisfactory, and many patients do not benefit from ICIs. Herein, we summarized advanced studies and the latest insights on immune inhibitory factors in the tumor microenvironment. Our in-depth discussion and updated landscape of tumor immunosuppressive microenvironment may provide new strategies for reversing tumor immune evasion, enhancing the efficacy of ICIs therapy, and ultimately achieving a better clinical outcome.
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Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias , Escape del Tumor , Microambiente Tumoral , Microambiente Tumoral/inmunología , Humanos , Neoplasias/inmunología , Neoplasias/terapia , Animales , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodosRESUMEN
Durian contains rich flavor components that undergo complex changes during drying. In this study, durian was subjected to integrated freeze-drying (IFD), conventional freeze-drying (CFD), and hot air drying (AD). Compared with the fresh samples, those dried by IFD, CFD, and AD lost 11, 9, and 7 original volatile compounds, respectively, and generated 7, 6, and 8 new volatile compounds, respectively, and showed a rapid and then slow decreasing trend in the total content during drying. However, the types of amino acids and soluble sugars remained unchanged during each of the drying methods. Furthermore, volatile compounds showed a significant negative correlation with the majority of amino acids and a significant positive correlation with soluble sugars. The IFD samples had the highest content of volatile compounds, amino acids, and soluble sugars. Therefore, IFD is recommended as a preferable drying method for durian.
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This study aimed to investigate the effects of edible gum addition on moisture changes in freeze-dried restructured strawberry blocks (FRSB), which involved five groups: the control, 1.2% guar gum, 1.2% gelatin, 1.2% pectin, and the composite group with 0.5% guar gum, 0.5% gelatin, and 0.45% pectin. The results indicated that the drying rates of the five groups of FRSB presented similar early acceleration and later deceleration trends. Moisture content in FRSB was linearly predicted by peak area of low field nuclear magnetic resonance with R2 higher than 0.90 for all the five groups. The FRSB samples in the gelatin and composition groups formed a denser porous structure and had a lower hygroscopicity after four days of storage. This study provides a theoretical basis for controlling the processing of FRSB.
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Fragaria , Liofilización , Galactanos , Gelatina , Mananos , Pectinas , Gomas de Plantas , Agua , Galactanos/química , Gomas de Plantas/química , Mananos/química , Gelatina/química , Pectinas/química , Fragaria/química , Agua/química , Frutas/químicaRESUMEN
Although immune checkpoint therapy has significantly improved the prognosis of patients with melanoma, urgent attention still needs to be paid to the low patient response rates and the challenges of precisely identifying patients before treatment. Therefore, it is crucial to investigate novel immunosuppressive mechanisms and targets in the tumor microenvironment in order to reverse tumor immune escape. In this study, we found that the cell cycle checkpoint Aurora kinase B (AURKB) suppressed the anti-tumor immune response, and its inhibitor, Tozasertib, effectively activated T lymphocyte cytokine release in vitro and anti-tumor immunity in vivo. Tozasertib significantly inhibited melanoma xenograft tumor growth by decreasing the number of inhibitory CD4+ Treg cells in the tumors, which, in turn, activated CD8+ T cells. Single-cell analysis revealed that AURKB suppressed anti-tumor immunity by increasing MIF-CD74/CXCR4 signaling between tumor cells and lymphocytes. Our study suggests that AURKB is a newly identified anti-tumor immunity suppressor, whose inhibitors may be developed as novel anti-tumor immunity drugs and may have synergistic anti-melanoma effects with immune checkpoint therapies.
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Antineoplásicos , Melanoma , Humanos , Melanoma/patología , Linfocitos T Reguladores , Linfocitos T CD8-positivos , Antineoplásicos/uso terapéutico , Microambiente TumoralRESUMEN
BACKGROUND: Mild traumatic brain injury (mTBI) is characterized as brain microstructural damage, which may cause a wide range of brain functional disturbances and emotional problems. Brain network analysis based on machine learning is an important means of neuroimaging research. Obtaining the most discriminating functional connection is of great significance to analyze the pathological mechanism of mTBI. METHODS: To better obtain the most discriminating features of functional connection networks, this study proposes a hierarchical feature selection pipeline (HFSP) composed of Variance Filtering (VF), Lasso, and Principal Component Analysis (PCA). Ablation experiments indicate that each module plays a positive role in classification, validating the robustness and reliability of the HFSP. Furthermore, the HFSP is compared with recursive feature elimination (RFE), elastic net (EN), and locally linear embedding (LLE), verifying its superiority. In addition, this study also utilizes random forest (RF), SVM, Bayesian, linear discriminant analysis (LDA), and logistic regression (LR) as classifiers to evaluate the generalizability of HFSP. RESULTS: The results show that the indexes obtained from RF are the highest, with accuracy = 89.74%, precision = 91.26%, recall = 89.74%, and F1 score = 89.42%. The HFSP selects 25 pairs of the most discriminating functional connections, mainly distributed in the frontal lobe, occipital lobe, and cerebellum. Nine brain regions show the largest node degree. LIMITATIONS: The number of samples is small. This study only includes acute mTBI. CONCLUSIONS: The HFSP is a useful tool for extracting discriminating functional connections and may contribute to the diagnostic processes.
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Conmoción Encefálica , Lesiones Encefálicas , Humanos , Conmoción Encefálica/diagnóstico por imagen , Conmoción Encefálica/patología , Teorema de Bayes , Reproducibilidad de los Resultados , Encéfalo , Aprendizaje AutomáticoRESUMEN
The main approach for analyzing resting-state functional magnetic resonance imaging (rs-fMRI) is the low-order functional connectivity network (LoFCN) based on the correlation between two brain regions. Based on LoFCN, researchers recently proposed the topographical high-order FCN (tHoFCN) and the associated high-order FCN (aHoFCN) to explore the high-order interactions among brain regions. In this work, we designed a Deep Self-Attention (DSA) framework called mTBI-DSANet to diagnose mild traumatic brain injury (mTBI) using multi-level FCNs, including LoFCN, tHoFCN, and aHoFCN. The multilayer perceptron and self-attention mechanism in mTBI-DSANet were designed to capture important features for the mTBI diagnosis. We evaluated the mTBI-DSANet's performance on the real rs-fMRI dataset, which was collected by Third Xiangya Hospital of Central South University from April 2014 to February 2021. We compared the performance of mTBI-DSANet with distinct FCNs and their combinations under 10-fold cross-validation. Based on the LoFCN+aHoFCN combination, the average performance of mTBI-DSANet achieved the best accuracy of 0.834, which is significantly better than peer methods. The experiments demonstrated the potential of the mTBI-DSANet in assisting mTBI diagnosis.
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Conmoción Encefálica , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodosRESUMEN
BACKGROUND: Cancer is the world's leading cause of death and a key hindrance to extending life expectancy. Celastrol, a bioactive compound derived from Tripterygium wilfordii, has been shown to have excellent antitumor activity, but its poor solubility and severe organ toxicity side effects have hampered its clinical application. METHODS: In this study, a self-assembled nanodrug (PLC-NP) was designed to deliver celastrol to tumor sites while efficiently reducing its side effects by conjugating celastrol with the bioactive material LMWH and P-selectin targeting peptide (PSN). Extensive in vitro and in vivo experiments were performed to investigate both therapeutic efficacy and adverse effects. Furthermore, the specific mechanism of the antitumor activity has also been explored. FINDING: The PLC-NP nanodrugs were spherical in shape, with a mean particle size of 115.83 ± 6.93 nm. PLC-NP was sufficiently stable during blood circulation, with a selective target to P-selectin-highly expressed tumor cells, followed by releasing the containing celastrol under acidic environment and high levels of esterase in tumor cells. Both in vitro and in vivo results confirmed that celastrol's antitumor and anti-metastatic abilities were not attenuated and were actually strengthened after being formed into nanodrugs. More importantly, the organ toxicities of the modified celastrol nanodrug were dramatically reduced. Mechanistic study indicated that the inactivation of PI3K/Akt/mTOR signaling pathway and ROS-mediated mitochondrial dysfunction play critical roles in celastrol-mediated autophagy and apoptosis. INTERPRETATION: Our findings could offer a potential strategy for the translation of toxic compounds into clinical therapeutic nanomedicine. FUNDING: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Nanopartículas , Neoplasias , Triterpenos , Humanos , Triterpenos/farmacología , Selectina-P , Fosfatidilinositol 3-Quinasas/metabolismo , Heparina de Bajo-Peso-Molecular/farmacología , Neoplasias/tratamiento farmacológico , Nanopartículas/uso terapéutico , ApoptosisRESUMEN
Cu2-xSe nanoparticles (Cu2-xSe NPs) as a new therapeutic drug platform is widely used in disease treatment due to their strong near-infrared optical absorption. In recent years, with their continuous expansion of applications in different fields, their own biological effects have received increasing attention. However, little is known about the effect of Cu2-xSe NPs on cancer cell. In this research, we found that Cu2-xSe NPs inhibited proliferation of HepG2 cells (IC50: 15.91µM) and SMMC-7721 cells (IC50: 43.15µM) and they mainly induced cell cycle arrest at the G2/M phase. Moreover, Cu2-xSe NPs inhibited HepG2 and SMMC-7721 cell migration and lamellopodia formation. Further studies indicated that Cu2-xSe NPs impaired mitochondrial respiration by inhibiting electron transport chain complex activity, thus reducing adenosine triphosphate levels. The insufficient energy supply subsequently impaired actin cytoskeleton assembly, ultimately inhibiting HepG2 and SMMC-7721 cell proliferation and migration. These findings suggest that Cu2-xSe NPs may have potentially antitumor activity, which might provide new insights of NPs into specific cancer treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/uso terapéutico , Células Hep G2 , Proliferación CelularRESUMEN
Src homolog and collagen homolog binding protein 1 (SHCBP1) binds to the SH2 domain of SHC-transforming protein 1 (SHC1) and is involved in midbody organization and cytokinesis completion. SHCBP1 has been reported to be a cancer driver gene, promoting cancer progression. However, the functional role and underlying mechanism of SHCBP1 in regulating lung adenocarcinoma (LUAD) cell proliferation and migration are incompletely understood. Here, we discovered that SHCBP1 is overexpressed in LUAD tissues and is associated with a poor prognosis. SHCBP1 knockdown inhibited LUAD cell proliferation and migration by arresting the cell cycle and preventing epithelial-mesenchymal transition (EMT) via decreasing cyclin-dependent kinase 1 (CDK1) expression. Mechanistically, CDK1 overexpression reversed SHCBP1 knockdown-induced inhibition of proliferation and migration, confirming CDK1 as a key downstream target of SHCBP1. In addition, we proposed that rucaparib may be a small-molecule inhibitor of SHCBP1 and validated both in vitro and in vivo that rucaparib inhibits cell proliferation and migration via suppression of the SHCBP1/CDK1 pathway in LUAD. Our study elucidates a newly identified role of SHCBP1 in promoting cell proliferation and migration in LUAD, and suggests rucaparib as a potential inhibitor for LUAD treatment.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Proteína Quinasa CDC2/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Proliferación Celular , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Movimiento Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteínas Adaptadoras de la Señalización ShcRESUMEN
Xenopus is an important model animal for biomedicine researches. In order to probe into the classification and function of the basic helix-loop-helix (bHLH) transcription factor family, we conducted a genome-wide survey and identified 70 bHLH transcription factors using the Xenopus tropicalis genome project data in the study. Among these transcription factors, 69 bHLH transcription factors were classified into 6 large groups composed of 34 sub-families and the remaining one was classified as 'orphan'. Results of Gene Ontology (GO) enrichment statistics showed 51 frequent GO annotation categories. Statistical analysis of the GO annotations showed that these 70 bHLH proteins tended to be frequently related to transcription regulator activity, regulation of transcription, DNA binding, regulation of RNA metabolic process, DNA-dependent regulation of transcription, transcription, and transcription factor activity, indicating that they were expected to be the most common GO categories of transcriptional factors. Moreover, a number of bHLH genes were revealed to play important regulation roles in special development and physiological processes, such as muscle tissue and organ (striated muscle, skeletal muscle, eye muscle, and pharyngeal muscle) differentiation and development, e.g., digestive system development, pharynx development and sensory organ development, regulation of nucleobase, nucleoside and nucleotide and nucleic acid metabolic process, regulation of biosynthetic process, DNA binding, and protein heterodimerization activity, etc. There were also some important signaling pathways in the significant GO categories. We made the evolutionary analysis of Hes transcription factor family as well. This preliminary result lays a solid foundation for further re-searches on X. tropicalis.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Evolución Molecular , Proteínas de Xenopus/genética , Xenopus/genética , Secuencia de Aminoácidos , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/química , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Datos de Secuencia Molecular , Filogenia , Alineación de Secuencia , Xenopus/clasificación , Xenopus/metabolismo , Proteínas de Xenopus/química , Proteínas de Xenopus/metabolismoRESUMEN
The SOCS3 proteins played important roles in regulating the energy metabolism processes. They are crucial intracellular inhibitors related to animal obesity, immunity and inflammation. This makes SOCS3 genes very important in animal genetics and breeding. The research was conducted to investigate and explore the recent advance in the present studies on SOCS3 in animal energy and lipid metabolism processes. All the references were carefully retrieved from the PubMed database by searching key words "suppressor of cytokine signaling (SOCS)", "SOCS3", "animal carbohydrate metabolism", "animal lipid metabolism", "animal energy metabolism", "insulin resistance", "leptin", "obesity", "SOCS*" and "AMPK". All the related references retrieved were initially screened and fully reviewed for manual inspection. This effort intends to get a quick understanding and make insights into the mechanisms of Suppressor of Cytokine Signaling 3 (SOCS3) and their molecular interactions with the other cellular proteins. In this review, it was found that SOCS3 proteins could regulate cytokine receptors' signal transduction mainly through the JAK/STAT and GH/IGF-I and mTOR-STAT3-SOCS3 signaling pathways, whereas the genetic mutations or knockouts of SOCS3 genes had significant effects on animal energy metabolism. The review summarized all the relevant research reports on SOCS3 in the animal carbohydrate and lipid metabolism processes, which can provide practical reference for the genetic breeding of high-quality domestic animal breeds. It is also of great significance to further research on the genetic regulation mechanism of SOCS3 genes affecting energy metabolism and the well development of the animal breeding system.
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Metabolismo de los Lípidos , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas , Animales , Carbohidratos , Citocinas/genética , Citocinas/metabolismo , Metabolismo de los Lípidos/genética , Obesidad/metabolismo , Transducción de Señal/fisiología , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/metabolismoRESUMEN
Global warming and world-wide climate change caused by increasing carbon emissions have attracted a widespread public attention, while anthropogenic activities account for most of these problems generated in the social economy. In order to comprehensively measure the levels of carbon emissions and carbon sinks in Anhui Province, the study adopted some specific carbon accounting methods to analyze and explore datasets from the following suggested five carbon emission sources of energy consumption, food consumption, cultivated land, ruminants and waste, and three carbon sink sources of forest, grassland and crops to compile the carbon emission inventory in Anhui Province. Based on the compiled carbon emission inventory, carbon emissions and carbon sink capacity were calculated from 2000 to 2019 in Anhui Province, China. Combined with ridge regression and scenario analysis, the STIRPAT model was used to evaluate and predict the regional carbon emission from 2020 to 2040 to explore the provincial low-carbon development pathways, and carbon emissions of various industrial sectors were systematically compared and analyzed. Results showed that carbon emissions increased rapidly from 2000 to 2019 and regional energy consumption was the primary source of carbon emissions in Anhui Province. There were significant differences found in the increasing carbon emissions among various industries. The consumption proportion of coal in the provincial energy consumption continued to decline, while the consumption of oil and electricity proceeded to increase. Furthermore, there were significant differences among different urban and rural energy structures, and the carbon emissions from waste incineration were increasing. Additionally, there is an inverted "U"-shape curve of correlation between carbon emission and economic development in line with the environmental Kuznets curve, whereas it indicated a "positive U"-shaped curve of correlation between carbon emission and urbanization rate. The local government should strengthen environmental governance, actively promote industrial transformation, and increase the proportion of clean energy in the energy production and consumption structures in Anhui Province. These also suggested a great potential of emission reduction with carbon sink in Anhui Province.