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Quinoa seeds are gluten- and cholesterol-free, contain all amino acids required by the human body, have a high protein content, provide endocrine regulation, protein supplementation, and cardiovascular protection effects. However, metabolite accumulation and transcriptional regulatory networks in quinoa seed development are not well understood. Four key stages of seed development in Dianli-3260 and Dianli-557 were thus analyzed and 849 metabolites were identified, among which sugars, amino acids, and lipids were key for developmental processes, and their accumulation showed a gradual decrease. Transcriptome analysis identified 40,345 genes, of which 20,917 were differential between the M and F phases, including 8279 and 12,638 up- and down-regulated genes, respectively. Grain development processes were mainly enriched in galactose metabolism, pentose and glucuronate interconversions, the biosynthesis of amino acids, and carbon metabolism pathways, in which raffinose, phosphoenolpyruvate, series and other metabolites are significantly enriched, gene-LOC110689372, Gene-LOC110710556 and gene-LOC110714584 are significantly expressed, and these metabolites and genes play an important role in carbohydrate metabolism, lipid and Amino acid synthesis of quinoa. This study provides a theoretical basis to expand our understanding of the molecular and metabolic development of quinoa grains.
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Chenopodium quinoa , Transcriptoma , Humanos , Chenopodium quinoa/genética , Metaboloma/genética , Sementes/genética , AminoácidosRESUMO
BACKGROUND: This cross-sectional study investigates infection prevention and control (IPC) competencies among healthcare professionals in northwest China, examining the influence of demographic factors, job titles, education, work experience, and hospital levels. METHODS: Data from 874 respondents across 47 hospitals were collected through surveys assessing 16 major IPC domains. Statistical analyses, including Mann-Whitney tests, were employed to compare competencies across variables. RESULTS: Significant differences were identified based on gender, job titles, education, work experience, and hospital levels. Females demonstrated higher IPC competencies, while senior positions exhibited superior performance. Higher educational attainment and prolonged work experience positively correlated with enhanced competencies. Variances across hospital levels underscored context-specific competencies. CONCLUSION: Demographic factors and professional variables significantly shape IPC competencies. Tailored training, considering gender differences and job roles, is crucial. Higher education and prolonged work experience positively impact proficiency. Context-specific interventions are essential for diverse hospital settings, informing strategies to enhance IPC skills and mitigate healthcare-associated infections effectively.
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Pessoal de Saúde , Humanos , Estudos Transversais , China , Feminino , Masculino , Pessoal de Saúde/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Controle de Infecções/métodos , Inquéritos e Questionários , Infecção Hospitalar/prevenção & controle , Competência Clínica/estatística & dados numéricos , HospitaisRESUMO
BACKGROUND: Quinoa is a highly nutritious and novel crop that is resistant to various abiotic stresses. However, its growth and development is restricted due to its limited utilization of soil phosphorus. Studies on the levels of phosphorus in quinoa seedlings are limited; therefore, we analyzed transcriptome data from quinoa seedlings treated with different concentrations of phosphorus. RESULTS: To identify core genes involved in responding to various phosphorus levels, the weighted gene co-expression network analysis method was applied. From the 12,085 expressed genes, an analysis of the gene co-expression network was done. dividing the expressed genes into a total of twenty-five different modules out of which two modules were strongly correlated with phosphorus levels. Subsequently we identified five core genes that correlated strongly either positively or negatively with the phosphorus levels. Gene ontology and assessments of the Kyoto Encyclopedia of Genes and Genomes have uncovered important biological processes and metabolic pathways that are involved in the phosphorus level response. CONCLUSIONS: We discovered crucial new core genes that encode proteins from various transcription factor families, such as MYB, WRKY, and ERF, which are crucial for abiotic stress resistance. This new library of candidate genes associated with the phosphorus level responses in quinoa seedlings will help in breeding varieties that are tolerant to phosphorus levels.
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Chenopodium quinoa , Plântula , Plântula/genética , Plântula/metabolismo , Chenopodium quinoa/genética , Chenopodium quinoa/metabolismo , Fósforo/metabolismo , Melhoramento Vegetal , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de PlantasRESUMO
Current studies have shown that ARNTL, an important clock gene, plays an anticancer role and is downregulated in certain types of cancer. However, the biological functions and mechanisms of ARNTL in tumors remain largely unknown. This study aimed to elucidate how ARNTL-induced autophagy impacts the biological properties of tongue squamous cell carcinoma (TSCC) cells and the mechanisms by which ARNTL expression activates autophagy. ARNTL was stably overexpressed in TSCC cells to investigate its functions in vitro and in vivo. We found that activation of autophagy induced by ARNTL decreases cell proliferation, enhances cell death, and hinders the migratory ability of TSCC cells. Moreover, ARNTL antagonizes the AKT/mTOR pathway, which potentiates autophagy induction. The manipulation of Akt activation cancels the effects of ARNTL overexpression on the biological behaviors of TSCC cells. Furthermore, after the addition of SC79, the upregulated BAX expression due to ARNTL overexpression and downregulated expressions of BCL-2 and MMP2 were remarkably rescued. In vivo tumorigenicity assays and immunohistochemistry also confirmed that ARNTL overexpression suppresses tumor development. Our study found for the first time that ARNTL inhibits the malignant behaviors of oral cancer cells by regulating autophagy in an AKT/mTOR pathway-dependent manner, which provides a novel theoretical basis for the potential future application of ARNTL to treat patients with oral cancer.
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BACKGROUND: Quinoa (Chenopodium quinoa Willd.) originates in high altitude areas, such as the Andes, and has some inherent characteristics of cold, drought, and salinity tolerance, but is sensitive to high temperature. RESULTS: To gain insight into the response mechanism of quinoa to high temperature stress, we conducted an extensive targeted metabolomic study of two cultivars, Dianli-3101 and Dianli-3051, along with a combined transcriptome analysis. A total of 794 metabolites and 54,200 genes were detected, in which the genes related to photosynthesis were found down-regulated at high temperatures, and two metabolites, lipids and flavonoids, showed the largest changes in differential accumulation. Further analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and transcription factors revealed that quinoa inhibits photosynthesis at high temperatures, and the possible strategies being used for high temperature stress management are regulation of heat stress transcription factors (HSFs) to obtain heat tolerance, and regulation of purine metabolism to enhance stress signals for rapid response to high temperature stress. The tolerant genotype could have an enhanced response through lower purine levels. The induction of the stress response could be mediated by HSF transcription factors. The results of this study may provide theoretical references for understanding the response mechanism of quinoa to high temperature stress, and for screening potential high temperature tolerant target genes and high temperature tolerant strains. CONCLUSIONS: These findings reveal the regulation of the transcription factor family HSF and the purinergic pathway in response to high temperature stress to improve quinoa varieties with high temperature tolerance.
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Chenopodium quinoa , Plântula , Plântula/genética , Chenopodium quinoa/fisiologia , Temperatura , Transcriptoma , Perfilação da Expressão Gênica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
MAIN CONCLUSION: Blue light has a greater effect on jasmonic acid and flavonoid accumulation in wheat seeds than red light; blue light reduces starch synthesis and the size of starch granules and seeds. This study sought to elucidate the effects of blue and red light on seed metabolism to provide important insights regarding the role of light quality in regulating seed growth and development. We used combined multi-omics analysis to investigate the impact of red and blue light (BL) on the induction of secondary metabolite accumulation in the hexaploid wheat Dianmai 3 after pollination. Flavonoids and alkaloids were the most differentially abundant metabolites detected under different treatments. Additionally, we used multi-omics and weighted correlation network analysis to screen multiple candidate genes associated with jasmonic acid (JA) and flavonoids. Expression regulatory networks were constructed based on RNA-sequencing data and their potential binding sites. The results revealed that BL had a greater effect on JA and flavonoid accumulation in wheat seeds than red light. Furthermore, BL reduced starch synthesis and stunted the size of starch granules and seeds. Collectively, these findings clarify the role of BL in the metabolic regulation of early seed development in wheat.
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Sementes , Triticum , Triticum/genética , Triticum/metabolismo , Flavonoides/metabolismo , Amido/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Quinoa (Chenopodium quinoa Willd.) is a dicotyledonous annual amaranth herb that belongs to the family Chenopodiaceae. Quinoa can be cultivated across a wide range of climatic conditions. With regard to its cultivation, nitrogen-based fertilizers have a demonstrable effect on the growth and development of quinoa. How crops respond to the application of nitrogen affects grain quality and yield. Therefore, to explore the regulatory mechanisms that underlie the responses of quinoa seedlings to the application of nitrogen, we selected two varieties (i.e., Dianli-1299 and Dianli-71) of quinoa seedlings and analyzed them using metabolomic and transcriptomic techniques. Specifically, we studied the mechanisms underlying the responses of quinoa seedlings to varying concentrations of nitrogen by analyzing the dynamics of metabolites and genes involved in arginine biosynthesis; carbon fixation; and alanine, aspartate, and glutamate biosynthetic pathways. Overall, we found that differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) of quinoa are affected by the concentration of nitrogen. We detected 1057 metabolites, and 29,012 genes were annotated for the KEGG. We also found that 15 DEMs and 8 DEGs were key determinants of the differences observed in quinoa seedlings under different nitrogen concentrations. These contribute toward a deeper understanding of the metabolic processes of plants under different nitrogen treatments and provide a theoretical basis for improving the nitrogen use efficiency (NUE) of quinoa.
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Chenopodium quinoa , Transcriptoma , Chenopodium quinoa/metabolismo , Plântula/genética , Plântula/metabolismo , Fertilizantes , Nitrogênio/metabolismo , MetabolomaRESUMO
OBJECTIVE: To investigate the effect and regulatory mechanism of clock gene Per1 on the proliferation,apoptosis,migration,and invasion of human oral squamous carcinoma SCC15 cells. METHODS: RNA interference was used to knock down Per1 gene in human oral squamous cell carcinoma SCC15 cell line. Changes of cell proliferation and apoptosis were analyzed by flow cytometry. Transwell assay was carried out to assess cell migration and invasion. Real-time polymerase chain reaction was used to detect the mRNA expressions of Ki-67, murine double minute 2 (MDM2), c-Myc, p53, Bax, Bcl-2, metalloproteinase (MMP)2, MMP9, and vascular endothelial growth factor (VEGF). RESULTS: shRNA-mediated knockdown of Per1 promoted the proliferation, migration and invasion capacity, and inhibited cell apoptosis capacity of SCC15 cells (all P<0.05). Additionally, Per1 knockdown also increased the mRNA expressions of Ki-67, MDM2, Bcl-2, MMP2, and MMP9 and decreased the mRNA expressions of c-Myc, p53, and Bax (all P<0.05); however, the VEGF mRNA expression did not differ significantly after Per1 knockdown (P>0.05). CONCLUSIONS: Clock gene Perl can regulate important tumor-related genes downstream such as Ki-67, MDM2, c-Myc, p53, Bax, Bcl-2, MMP2, and MMP9, and the aberrant expression of Per1 can affect tumor cell proliferation,apoptosis,migration and invasion. An in-depth study of Per1 may further clarify the mechanism of tumorigenesis and tumor development and thus provides new effective molecular targets for cancer treatment.
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Apoptose , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Proteínas Circadianas Period/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Silenciamento de Genes , Humanos , Antígeno Ki-67/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Learning management systems (LMSs) have received substantial global attention and have undergone extensive research, with most discussions focusing on users' acceptance and continuation of LMS use in the higher education sector. However, research is scarce in terms of identifying the factors that are advantageous to K-12 students' learning and satisfaction when using LMSs for language learning. This study aims to examine the impacts of internal and contextual factors on secondary students' learning satisfaction and English achievement when using LMSs. Data were collected from 289 students through an online survey. The results of the structural equation modeling showed that satisfaction had the most significant impact on English achievement. Furthermore, both internal and contextual factors, including technology self-efficacy, interest, task value, teacher support, and technology facilitation, positively impacted learning satisfaction with LMSs. In addition, teacher support exerted the strongest impact on satisfaction, followed by interest and technology self-efficacy. However, only internal factors, such as interest and task value, were positively associated with English achievement. Neither teacher support nor technology facilitation significantly impacted English performance. Given the increasing availability of LMS usage, the findings of this study can facilitate the more effective implementation of LMSs in China and globally. The study contributes to the theory and practice of LMSs use in K-12 English education. The limitations and implications of the study were discussed as well.
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Nonverbal behaviors could play a crucial role in detecting deception, yet existing studies on deception cues have largely centered on Western populations, predominantly university students, thus neglecting the influence of cultural and sample diversity. To address this gap, our study explored deception cues within an Asian cultural setting, utilizing a mock crime paradigm. Our sample comprised Chinese participants, including both men and women with various socioeconomic status (SES) backgrounds. Our findings revealed that compared to truth tellers, liars exhibited heightened emotions and an increased cognitive load. Furthermore, liars showed a higher frequency of self-adaptors and a longer duration of gaze aversion. Our findings contribute to a more profound understanding of deception cues within Asian culture and have implications for practical fields such as criminal interrogation.
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A series of piperine derivatives were designed and successfully synthesized. The antitumor activities of these compounds against 293 T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines, were assessed through the MTT assay. Notably, compound H7 exhibited moderate activity, displaying reduced toxicity towards non-tumor 293 T cells while potently enhancing the antiproliferative effects in Hela and MDA-MB-231 cells. The IC50 values were determined to be 147.45 ± 6.05 µM, 11.86 ± 0.32 µM, and 10.50 ± 3.74 µM for the respective cell lines. In subsequent mechanistic investigations, compound H7 demonstrated a dose-dependent inhibition of clone formation, migration, and adhesion in Hela cells. At a concentration of 15 µM, its inhibitory effect on Hela cell function surpassed that of both piperine and 5-Fu. Furthermore, compound H7 exhibited promising antitumor activity in vivo, as evidenced by significant inhibition of tumor angiogenesis and reduction in tumor weight in a chicken embryo model. These findings provide a valuable scientific foundation for the development of novel and efficacious antitumor agents, particularly highlighting the potential of compound H7 as a therapeutic candidate for cervical cancer and breast cancer.
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Alcaloides , Benzodioxóis , Piperidinas , Alcamidas Poli-Insaturadas , Humanos , Piperidinas/farmacologia , Piperidinas/síntese química , Piperidinas/química , Benzodioxóis/farmacologia , Benzodioxóis/síntese química , Alcamidas Poli-Insaturadas/farmacologia , Alcamidas Poli-Insaturadas/síntese química , Alcamidas Poli-Insaturadas/química , Alcaloides/farmacologia , Alcaloides/síntese química , Alcaloides/química , Animais , Estrutura Molecular , Linhagem Celular Tumoral , Células HeLa , Embrião de Galinha , Movimento Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Desenho de Fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
Quinoa (Chenopodium quinoa wild.), a dicotyledonous plant native to the Andes, is an increasingly popular pseudograin owing to its high nutritional value, stress resistance capabilities, and gluten-free properties. In this study, we aimed to explore the dynamic changes in different varieties of quinoa at the seedling stage and their regulatory networks. Here, we found that the leaves of quinoa showed obvious coloration after 45 days, and four quinoa seedling types (red, white, yellow, and black) were subjected to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and transcriptome sequencing to identify their differentially expressed genes and metabolites. A total of 29 differential metabolites and 19 genes (14 structural and 5 regulatory genes) were identified, and consistent differences were observed in the flavonoid, phenolic acid, and alkaloid metabolites in the different quinoa types. These differential metabolites were significantly enriched in flavonoid and flavonol biosynthesis, flavonoid biosynthesis, and phenylpropanoid biosynthesis pathways. In addition, real-time fluorescence quantitative PCR (RT-qPCR) technology was used to detect the expression of four structural genes involved in the flavonoid biosynthesis pathway and four regulatory genes (interaction network). The results revealed that the structural and regulatory gene transcript levels in the flavonoid pathway were higher in the red quinoa cultivars than in the white, yellow, and black. Additionally, the differences in the leaves of these four quinoa cultivars were mainly due to differences in flavonoid, phenolic acid, and alkaloid accumulation. Our findings provide a basis for understanding the accumulation and coloration mechanisms of flavonoids, phenolic acids, and alkaloids in quinoa seedlings of different colors and also provide a theoretical basis for future investigations.
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Recently, p-nitrophenol (PNP), a common organic environmental pollutant, has been reported to be degraded by biochar. Although the degradation mechanism of PNP by biochar has been explored, the role of biochar-derived dissolved organic matter (BDOM) in PNP degradation remains unclear. Two BDOM samples were prepared in this study, and their PNP degradation performance was analyzed. BDOM5 (prepared at 500 °C) exhibited higher PNP degradation ratio than BDOM7 (prepared at 700 °C). The extent of PNP degradation per unit of BDOM5 and BDOM7 reached 9.54 and 4.19 mg/mg, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis showed that both oxidative and reductive processes contributed to the PNP degradation by BDOM. Compared with BDOM7, the higher PNP removal of BDOM5 was due to the higher electron exchange capacity. Furthermore, hydroxyl radicals (OH) played a critical role in the oxidative degradation process of PNP by BDOM. This study sheds light on the phenomenon of PNP degradation by BDOM and these results may be useful for accurately assessing the environmental impact of biochar application.
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Matéria Orgânica Dissolvida , Poluentes Ambientais , Nitrofenóis , Carvão Vegetal/químicaRESUMO
Quinoa is of great interest because it is cold- and drought-resistant; however, little research has been performed on quinoa under high relative humidity (RH) stress. In this study, quinoa seedlings of a highly HR-resistant variety ("Dianli-439") and a sensitive variety ("Dianli-969") were subjected to morphological and physiological measurements and metabolome and transcriptome analyses to investigate their response to high RH stress. In total, 1060 metabolites were detected, and lipids and flavonoids were the most abundant, with 173 and 167 metabolites, respectively. In total, 13,095 differentially expressed genes were identified, and the results showed that abscisic acid, auxin, and jasmonic-acid-related genes involved in plant hormone signaling may be involved in the response of quinoa seedlings to high RH stress. The analysis of the transcription factors revealed that the AP2/ERF family may also play an important role in the response to high RH stress. We identified the possible regulatory mechanisms of the hormone signaling pathways under high RH stress. Our findings can provide a basis for the selection and identification of highly resistant quinoa varieties and the screening of the metabolite-synthesis- and gene-regulation-related mechanisms in quinoa in response to RH stress.
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The study aimed to explore tumor suppressor mechanism of ARNTL from the perspective of autophagy in oral cancer. Human oral squamous carcinoma HN6 cells stably overexpressing ARNTL were established, cell viability and apoptosis were detected by CCK-8 and TUNEL assays, and intracellular autophagosomes were observed under electron microscopy. Western Blot detected expressions of Beclin1, LC3 II/I, ATG-12, P62, BAX and BCL-2. Bafilomycin A1 was used to detect autophagic flux, and Western Blot was used to detect changes of LC3II and P62 proteins. Autophinib was added to cells with ARNTL overexpression for recovery experiments, and cell proliferation and apoptosis were detected by flow cytometry. In vivo tumorigenesis experiment was used to evaluate the in vivo anti-tumor efficacy of ARNTL, and Western blot simultaneously detected ARNTL, LC3 II/I, Beclin1, P62 and ATG-12 expressions. ARNTL overexpression promoted apoptosis and autophagy and inhibited cell viability. In ARNTL-overexpressing cells, expressions of Beclin1, LC3 II/I, and BAX were significantly up-regulated, while P62 and BCL-2 expressions were decreased, and ATG-12 expression wasn't significantly changed. When the autophagy inhibitor Autophinib was used, expressions of elevated BAX and decreased BCL-2 were reversed effectively, as were decreased cell proliferation index and increased apoptosis index. An in vivo tumorigenesis assay also showed ARNTL overexpression inhibited tumor growth, and autophagy-related protein expressions were consistent with the in vitro data. The research demonstrated for the first time that ARNTL induced apoptosis and inhibited cell proliferation dependent on autophagy in oral cancer, which provides theoretical basis for potential therapeutic targets.
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Relógios Circadianos , Neoplasias Bucais , Fatores de Transcrição ARNTL/farmacologia , Apoptose , Autofagia , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Carcinogênese , Linhagem Celular Tumoral , Humanos , Neoplasias Bucais/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sincalida/farmacologia , Proteína X Associada a bcl-2RESUMO
Quinoa, a cool-weather high-altitude crop, is susceptible to low-temperature stress throughout its reproductive phase. Herein, we performed broadly targeted metabolic profiling of quinoa seedlings to explore the metabolites' dynamics in response to low-temperature stress and transcriptome analysis to determine the underlying genetic mechanisms. Two variants, namely, Dian Quinoa 2324 and Dian Quinoa 281, were exposed to temperatures of -2, 5, and 22 °C. A total of 794 metabolites were detected; 52,845 genes, including 6628 novel genes, were annotated using UPLC-MS/MS analysis and the Illumina HiSeq system. Combined with morphological indicators to resolve the mechanism underlying quinoa seedling response to low-temperature stress, the molecular mechanisms of quinoa changed considerably based on temperature exposure. Soluble sugars heavily accumulated in plants with cold damage and changes in regulatory networks under freeze damage, such as the upregulation of α-linolenic acid metabolism and a reduction in energy substrates, may explain the spatial patterns of biosynthesis and accumulation of these metabolites. Genes that are actively expressed during cold responses, as revealed by co-expression analyses, may be involved in the regulation thereof. These results provide insights into the metabolic factors in quinoa under low-temperature stress and provide a reference for the screening of quinoa varieties resistant to low temperature.
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Chenopodium quinoa , Chenopodium quinoa/genética , Cromatografia Líquida , Regulação da Expressão Gênica de Plantas , Plântula/genética , Espectrometria de Massas em Tandem , Temperatura , TranscriptomaRESUMO
A series of injectable and biocompatible delivery DOX-loaded supramolecular hydrogels were fabricated by using presynthesized DOX-2N-ß-CD, Pluronic F-127 and α-CD through host-guest interactions and cooperative multivalent hydrogen bonding interactions. The compositions and morphologies of these hydrogels were confirmed by PXRD and SEM measurements. Moreover, the Rheological measurements of these hydrogels were studied and the studies found that they showed a unique thixotropic behavior, indicting a fast self-healing property after the continuous oscillatory shear stress. Using α-CD as a capping agent, slow and sustained DOX release was observed at different pH values after 72 h. The amount of DOX released at pH 7.4 was determined to be 49.0% for hydrogel 1, whereas the releasing amount of the DOX was increased to 66.3% for hydrogel 1 during the same period at pH 5.5 (P < 0.05), indicating a higher release rate of the drug under more acidic conditions. Taking hydrogel 1 as a representative material, the toxicities of DOX and hydrogel 1 on ovarian cancer cells (SKOV-3) at different exposure durations were examined. The results revealed that hydrogel 1 was less cytotoxic than free DOX to SKOV-3 cells (P < 0.05), suggesting sustained release by these hydrogels in the presence of ovarian cancer cells. It is anticipated that this exploration can provide a new strategy for preparing drug delivery systems.
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Circadian rhythms are generated via variations in the expression of clock genes that are organized into a complex transcriptional-translational autoregulatory network and regulate the diverse physiological and behavioral activities that are required to adapt to periodic environmental changes. Aberrant clock gene expression is associated with a heightened risk of diseases that affect all aspects of human health, including cancers. Within the past several years, a number of studies have indicated that clock genes contribute to carcinogenesis by altering the expression of clock-controlled and tumor-related genes downstream of many cellular pathways. This review comprehensively summarizes how clock genes affect the development of tumors and their prognosis. In addition, the review provides a full description of the current state of oral cancer research that aims to optimize cancer diagnosis and treatment modalities.
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BACKGROUND: Accumulating evidence suggests that the abnormal expression of the circadian clock gene PER1 is closely related to the development and progression of cancer. However, the exact molecular mechanism by which the abnormal expression of PER1 induces carcinogenesis is unclear. This study was conducted to investigate the alterations in downstream cell cycle genes, cell cycle distribution, cell proliferation, apoptosis, and in vivo tumorigenicity in SCC15 oral squamous cell carcinoma cells after PER1 downregulation. MATERIALS AND METHODS: A stable SCC15 cell line was established to constitutively express shRNA targeting PER1. Quantitative real-time polymerase chain reaction (PCR) and Western blot analyses were conducted to estimate PER1 mRNA and protein expression. The expression of PER1, P53, CyclinD1, CyclinE, CyclinA2, CyclinB1, cyclin-dependent kinase (CDK) 1, CDK2, CDK4, CDK6, P16, P21, WEE1, and CDC25 mRNA was detected by quantitative real-time PCR. Cell cycle distribution, cell proliferation, and apoptosis were determined by flow cytometry. The in vivo tumorigenicity of SCC15 cells was evaluated in female BALB/c nu/nu mice. RESULTS: PER1 downregulation resulted in significantly increased mRNA expression levels of CyclinD1, CyclinE, CyclinB1, CDK1, and WEE1 (P<0.05), and significantly decreased mRNA expression levels of P53, CyclinA2, P16, P21, and CDC25 (P<0.05) compared to control cells. Additionally, PER1 downregulation led to significantly fewer cells in S phase (P<0.05), but significantly more cells in G2/M phase (P<0.05) compared to the control group. After PER1 downregulation, the cell proliferation index was significantly higher (P<0.05), and the apoptotic index was significantly lower (P<0.05). The in vivo tumorigenicity of SCC15 cells was significantly enhanced by PER1 downregulation (P<0.05). CONCLUSION: PER1 is an important tumor suppressor gene which acts by regulating the Cyclin-CDK-cyclin-dependent kinase inhibitor regulatory network. An in-depth characterization of this gene may further illuminate the molecular mechanisms responsible for the development and progression of cancer, thus providing novel molecular targets for cancer treatment.
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Abnormal expression of the clock gene PER1 is highly correlated with carcinogenesis and the development of malignant tumors. Here, we designed short hairpin RNAs (shRNAs) to effectively knock down PER1 in SCC15 human oral squamous cell carcinoma cells. shRNA-mediated PER1 knockdown promoted SCC15 cell growth, proliferation, apoptosis resistance, migration and invasion in vitro. PER1 knockdown also increased the cells' expression of KI-67, MDM2, BCL-2, MMP2 and MMP9 mRNA, and decreased expression of C-MYC, p53, BAX and TIMP-2. In BALB/c nu/nu nude mice subcutaneously injected with SCC15 cells, PER1 knockdown in the cells enhanced tumor development, leading to increased tumor weights and volumes. These results suggest that PER1 is an important tumor suppressor gene and may be a useful molecular target for the treatment of cancer.