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By employing elemental selenium as the selenium source, we have realized the amidine-directed Rh(III)-catalyzed cascade C-H selenylation/[5 + 1] annulation for the direct construction of structurally novel selenadiazine, benzoselenadiazine, and benzoselenazol-3-amine frameworks with specific site selectivity and good functional group tolerance. Besides, the obtained products can serve as fundamental platforms for subsequent chemical transformations, and thus, the feasible SeNEx reaction, SeNEx/Michael addition, and simple conversion of the selenadiazine product into diverse other organoselenium molecules were demonstrated accordingly. Taken together, the developed methodology efficiently expands the chemical space of organoselenium species.
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The spatiotemporal transcription of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) are crucial events for follicular development. However, their regulatory mechanisms are unclear. DNA methylation and histone acetylation are the main epigenetic modifications, and play important roles in transcriptional expression, which regulate cell responses including cell proliferation, senescence and apoptosis. This review will discuss the dynamic epigenetic modifications of FSHR and LHCGR that occur during the process of follicular development and their response to gonadotropins. In addition, some alteration patterns that occur during these epigenetic modifications, as well as their retrospect retrotransposons, which regulate the gene expression levels of FSHR and LHCGR will be discussed.
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Epigênese Genética , Animais , Folículo Ovariano/metabolismo , Folículo Ovariano/fisiologia , Feminino , Humanos , Receptores da Gonadotropina/genética , Receptores da Gonadotropina/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismoRESUMO
Terpenoids possess significant physiological activities and are rich in essential oils. Some terpenoids have chiral centers and could form enantiomers with distinct physiological activities. Therefore, the extraction and separation of terpenoids enantiomers are very important and have attracted extensive attention in recent years. Meanwhile, the specific distribution and enantiomer excess results (the excess of one enantiomer over the other in a mixture of enantiomers) could be used as quality markers for illegitimate adulteration, origin identification, and exploring component variations and functional interrelations across different plant tissues. In this study, an overview of the progress in the extraction of terpenoids from essential oils and the separation of their enantiomers over the past two decades has been made. Extraction methods were retrieved by the resultant network visualization findings. The results showed that the predominant methods are hydrodistillation, solvent-free microwave extraction, headspace solid-phase microextraction and supercritical fluid extraction methods. GC-MS combined with chiral chromatography columns is commonly used for the separation of enantiomers, while 2D GC is found to have stronger resolution ability. Finally, some prospects for future research directions in the extraction and separation identification of essential oils are proposed.
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Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis , Terpenos , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/análise , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Estereoisomerismo , Cromatografia com Fluido Supercrítico/métodos , Microextração em Fase Sólida/métodosRESUMO
Human health and the ecological balance are both gravely threatened by heavy metal pollution brought on by global industrialization. Probiotics are thought to represent a novel class of medicinal products for reducing heavy metal toxicity. Though simultaneous poisoning of numerous heavy metals is more prevalent, the majority of current studies on probiotics in the treatment of heavy metal poisoning concentrate on a single heavy metal. Thus, a mouse damage model was created in this investigation using five heavy metals (Pb, Cd, Hg, Cr, and As), and Lactiplantibacillus plantarum CCFM8661 was utilized as an intervention therapy. The oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), antioxidant capacity (T-AOC), and malondialdehyde (MDA), were evaluated in the blood, liver, and kidney tissues of mice throughout the experiment by tracking changes in body weight. Additionally, the amounts of five heavy metals were measured in the liver and kidney tissues. The alleviation of tissue damage and the detoxifying activity of L. plantarum CCFM8661 in mice with combined heavy metal intoxication were assessed by histopathological examination of liver and kidney tissues. Results revealed that during the test period, L. plantarum CCFM8661 significantly reduced the content of MDA and the contents of Pb, Cd, Hg, Cr, and As in liver and kidney tissues, while also significantly increasing weight gain and the activities of SOD, CAT, and T-AOC in mouse blood, liver, and kidney tissues compared to the model group. Mouse liver and kidney tissue damage from combined heavy metal exposure was considerably lessened by L. plantarum CCFM8661 when compared to the model group, according to H&E staining. This study demonstrates that L. plantarum CCFM8661 may be utilized as a useful intervention for the treatment of combined heavy metal poisoning by efficiently reducing the harm that heavy metals do to the body and maintaining bodily health.
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Rim , Fígado , Metais Pesados , Probióticos , Animais , Camundongos , Probióticos/farmacologia , Probióticos/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Lactobacillus plantarum , Superóxido Dismutase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas , Malondialdeído/metabolismo , Catalase/metabolismoRESUMO
Enhancing radiotherapy sensitivity is crucial for improving treatment outcomes in triple-negative breast cancer (TNBC) patients. In this study, we investigated the potential of targeting Elongin B (ELOB) to enhance radiotherapy efficacy in TNBC. Analysis of TNBC patient cohorts revealed a significant association between high ELOB expression and poor prognosis in patients who received radiation therapy. Mechanistically, we found that ELOB plays a pivotal role in regulating mitochondrial function via modulating mitochondrial DNA expression and activities of respiratory chain complexes. Targeting ELOB effectively modulated mitochondrial function, leading to enhanced radiosensitivity in TNBC cells. Our findings highlight the importance of ELOB as a potential therapeutic target for improving radiotherapy outcomes in TNBC. Further exploration of ELOB's role in enhancing radiotherapy efficacy may provide valuable insights for developing novel treatment strategies for TNBC patients.
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Tolerância a Radiação , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , DNA Mitocondrial/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Mitocôndrias/efeitos da radiação , Mitocôndrias/metabolismo , Prognóstico , Fatores de Transcrição/metabolismo , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
In this study, we examined the effects of various sodium alginate (ALG) concentrations (0.2%-0.8%) on the functional and physicochemical characteristics of succinylated walnut glutenin (GLU-SA). The results showed that acylation decreased the particle size and zeta potential of walnut glutenin (GLU) by 122- and 0.27-fold, respectively. In addition, the protein structure unfolded, providing conditions for glycosylation. After GLU-SA was combined with ALG, the surface hydrophobicity decreased and the net negative charge and disulfide bond content increased. The protein structure was analyzed by FTIR, Endogenous fluorescence spectroscopy, and SEM, and ALG prompted GLU-SA cross-linking to form a stable three-dimensional network structure. The results indicated that dual modification improved the functional properties of the complex, especially its potential protein gel and emulsifying properties. This research provide theoretical support and a technical reference for expanding the application of GLU in the processing of protein and oil products.
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Juglans , Juglans/química , Glicosilação , Glutens/química , Nozes/químicaRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a global metabolic disease with high prevalence in both adults and children. Importantly, NAFLD is becoming the main cause of hepatocellular carcinoma (HCC). Berberine (BBR), a naturally occurring plant component, has been demonstrated to have advantageous effects on a number of metabolic pathways as well as the ability to kill liver tumor cells by causing cell death and other routes. This permits us to speculate and make assumptions about the value of BBR in the prevention and defense against NAFLD and HCC by a global modulation of metabolic disorders. Herein, we briefly describe the etiology of NAFLD and NAFLD-related HCC, with a particular emphasis on analyzing the potential mechanisms of BBR in the treatment of NAFLD from aspects including increasing insulin sensitivity, controlling the intestinal milieu, and controlling lipid metabolism. We also elucidate the mechanism of BBR in the treatment of HCC. More significantly, we provided a list of clinical studies for BBR in NAFLD. Taking into account our conclusions and perspectives, we can make further progress in the treatment of BBR in NAFLD and NAFLD-related HCC.
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Berberina , Carcinoma Hepatocelular , Resistência à Insulina , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Criança , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/prevenção & controle , Berberina/farmacologia , Berberina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controleRESUMO
Four major studies (Checkmate577, Keynote-590, Checkmate649 and Attraction-4) of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy, represented by anti-programmed death protein (PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer, from the aspects of proof of concept, long-term survival, overall survival rate and progression-free survival. For unresectable or inoperable nonmetastatic esophageal cancer, concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines. Because its curative effect is still not ideal, it is necessary to explore radical radiotherapy and chemotherapy in the future, and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1. This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.
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Extracellular vesicles (EVs) derived from human adipose mesenchymal stem cells (hADSCs) may exert a therapeutic benefit in alleviating sepsis-induced organ dysfunction by delivering cargos that include RNAs and proteins to target cells. The current study aims to explore the protective effect of miR-150-5p delivered by hADSC-EVs on sepsis-induced acute lung injury (ALI). We noted low expression of miR-150-5p in plasma and bronchoalveolar lavage fluid samples from patients with sepsis-induced ALI. The hADSC-EVs were isolated and subsequently cocultured with macrophages. It was established that hADSC-EVs transferred miR-150-5p to macrophages, where miR-150-5p targeted HMGA2 to inhibit its expression and, consequently, inactivated the MAPK pathway. This effect contributed to the promotion of M2 polarization of macrophages and the inhibition of proinflammatory cytokines. Further, mice were made septic by cecal ligation and puncture in vivo and treated with hADSC-EVs to elucidate the effect of hADSC-EVs on sepsis-induced ALI. The in vivo experimental results confirmed a suppressive role of hADSC-EVs in sepsis-induced ALI. Our findings suggest that hADSC-EV-mediated transfer of miR-150-5p may be a novel mechanism underlying the paracrine effects of hADSC-EVs on the M2 polarization of macrophages in sepsis-induced ALI.
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Lesão Pulmonar Aguda , Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Sepse , Humanos , Animais , Camundongos , Sepse/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/terapia , MicroRNAs/genéticaRESUMO
Introduction: Low-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development. However, the significance of the pathway and family genes in LGG are poorly understood. Methods: We conducted gene expression profiling analysis using the TCGA dataset to investigate the gene set associated with the Notch signaling pathway. we have proposed a metric called "NotchScore" that quantifies the strength of the Notch signaling pathway and enables us to assess its significance in predicting prognosis and immune response in LGG. We downregulated JAG1 in low-grade gliomas to assess its influence on the proliferation and migration of these tumors. Ultimately, we determined the impact of the transcription factor VDR on the transcription of PDL1 through chip-seq data analysis. Results: Our findings indicate that tumors with a higher NotchScore, exhibit poorer prognosis, potentially due to their ability to evade the anti-tumor effects of immune cells by expressing immune checkpoints. Among the genes involved in the Notch signaling pathway, JAG1 has emerged as the most representative in terms of capturing the characteristics of both NotchScore and Notch pathways. The experimental results demonstrate that silencing JAG1 yielded a significant decrease in tumor cell proliferation in LGG cell lines. Our study revealed mechanisms by which tumors evade the immune system through the modulation of PDL1 transcription levels via the PI3K-Akt signaling pathway. Additionally, JAG1 potentially influences PDL1 in LGG by regulating the PI3K-Akt signaling pathway and the expression of the transcription factor VDR. Discussion: These findings contribute to our understanding of immune evasion by tumors in LGG. The insights gained from this research may have implications for the development of therapeutic interventions for LGG.
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Glioma , Fosfatidilinositol 3-Quinases , Humanos , Proteínas Proto-Oncogênicas c-akt , Recidiva Local de Neoplasia , Glioma/genética , Prognóstico , Imunidade , Fatores de Transcrição , Proteína Jagged-1/genéticaRESUMO
Past studies have revealed that relationship conflict has negative effects on individual performance. To avoid the losses caused by such conflicts, individuals often choose to avoid interacting with coworkers instead of confronting the issues. However, our present study sheds light on the dark side of this avoidance strategy: it may diminish an individual's creativity. Our study aimed to examine the appropriate response for knowledge employees when faced with relationship conflict. The results indicate that relationship conflict triggers a sequential response, which significantly hampers the creativity of knowledge employees. Specifically, coworker ostracism and knowledge hoarding play serial mediating roles in the impact of relationship conflict on the creativity of knowledge employees. Furthermore, the level of emotional intelligence determines the ability of knowledge employees to effectively manage the negative consequences of relationship conflict. The results provide theoretical and practical insights that help to better explain the impact of relationship conflict on creativity.
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INTRODUCTION: This study aimed to investigate the role of miR-214 in the bidirectional regulation of p53 and PTEN and its influence on myocardial fibrosis and cardiac mesenchymal transformation in mice with viral myocarditis (VMC). METHODS: The study established a VMC model in BALB/c mice by injecting them with the CVB3 virus intraperitoneally. Techniques such as ELISA, H&E staining, Masson staining, immunohistochemical staining, RT-qPCR, western blot, and dual-luciferase reporter gene assay were used to detect the expression levels of relevant factors in tissues and cells. Isolation and culture of cardiac fibroblasts (CFs) were also conducted. RESULTS: The study found that miR-214 bidirectional regulation of p53 and PTEN promotes myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. The expression levels of collagen-related peptides, inflammatory-related factors, miR-214, mesenchymal transformation-related factors, and fibrosis-related factors were significantly increased, while the expression levels of p53, PTEN, and epithelial/endothelial cell phenotype marker factors were significantly decreased. Downregulation of miR-214 or upregulation of p53 and PTEN expression inhibited inflammatory cell and fibroblast infiltration in VMC mouse myocardial tissue. It reduced the proliferation ability while increasing the apoptosis of cardiac fibroblasts. CONCLUSION: miR-214 plays a significant role in the bidirectional inhibition of p53 and PTEN, which leads to myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. Downregulation of miR-214 or upregulation of p53 and PTEN expression may provide potential therapeutic targets for treating VMC-induced cardiac fibrosis and mesenchymal transformation.
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Cardiomiopatias , MicroRNAs , Miocardite , Animais , Camundongos , Cardiomiopatias/genética , Proliferação de Células , Fibrose , MicroRNAs/genética , MicroRNAs/metabolismo , Miocardite/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
Electrochemical biosensors represent a class of sensors that employ biological materials as sensitive elements, electrodes as conversion elements, and potential or current as detection signals. The integration of CRISPR/Cas systems into electrochemical biosensors holds immense potential, offering enhanced versatility, heightened sensitivity and specificity, reduced recovery time, and the ability to capture and identify analytes at low concentrations. In this review, we provided a succinct summary of the fundamental principles underlying electrochemical biosensors and CRISPR/Cas systems, and new progress of electrochemical biosensors based on CRISPR/Cas systems in virus, bacteria, and cancer detections. Besides, we discussed its pros and cons, present gaps, potential problem-solvers, and future prospects. To sum up, CRISPR/Cas mediated electrochemical biosensors will surely benefit us a lot in the detection of cells and microorganisms, and of course in other promising fields.
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Técnicas Biossensoriais , Vírus , Sistemas CRISPR-Cas/genética , Técnicas Eletroquímicas , Bactérias/genética , Vírus/genéticaRESUMO
Monocyte-derived exosomes (Exos) have been implicated in inflammation-related autoimmune/inflammatory diseases via transferring bioactive cargoes to recipient cells. The purpose of this study was to investigate the possible effect of monocyte-derived Exos on the initiation and the development of acute lung injury (ALI) by delivering long non-coding RNA XIST. Key factors and regulatory mechanisms in ALI were predicted by bioinformatics methods. BALB/c mice were treated with lipopolysaccharide (LPS) to establish an ALI in vivo model and then injected with Exos isolated from monocytes transduced with sh-XIST to evaluate the effect of monocyte-derived exosomal XIST on ALI. HBE1 cells were co-cultured with Exos isolated from monocytes transduced with sh-XIST for further exploration of its effect. Luciferase reporter, RIP and RNA pull-down assays were performed to verify the interaction between miR-448-5p and XIST, miR-448-5p and HMGB2. miR-448-5p was significantly poorly expressed while XIST and HMGB2 were highly expressed in the LPS-induced mouse model of ALI. Monocyte-derived Exos transferred XIST into HBE1 cells where XIST competitively inhibited miR-448-5p and reduced the binding of miR-448-5p to HMGB2, thus upregulating the expression of HMGB2. Furthermore, in vivo data revealed that XIST delivered by monocyte-derived Exos downregulated miR-448-5p expression and up-regulated HMGB2 expression, ultimately contributing to ALI in mice. Overall, our results indicate that XIST delivered by monocyte-derived Exos aggravates ALI via regulating the miR-448-5p/HMGB2 signaling axis.
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Lesão Pulmonar Aguda , MicroRNAs , RNA Longo não Codificante , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína HMGB2/genética , Monócitos/metabolismo , Lipopolissacarídeos/efeitos adversos , Fatores de Transcrição , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/terapia , RNA Longo não Codificante/genéticaRESUMO
This study pays attention to within-person fluctuations in meaningful work and its antecedents and consequences. Considering self- and other-oriented dimensions as crucial pathways to meaningful work, effects of daily perceived autonomy support and prosocial impact on one's meaningful work were examined. A daily diary study was conducted in which 86 nurses from varied hospitals reported their work experiences for 10 consecutive workdays (860 occasions). Results of multilevel modeling showed that both day-level perceived autonomy support and prosocial impact were positively related to day-level meaningful work, which served as the mediator between them and work engagement. Prosocial orientation strengthened the positive relationship between day-level perceived prosocial impact and day-level meaningful work. However, autonomy orientation negatively moderated the effect of day-level perceived autonomy support on day-level meaningful work, suggesting the necessity to distinguish between assisted and asserted autonomy orientation. Our findings illustrate the transient and dynamic nature of meaningful work and provide empirical evidences linking suggested managerial practices to employees' meaningful work.
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Maternal separation (MS) is a type of early-life stress that has been linked to neuropsychiatric disorders, especially depression. Increasing evidence indicates that the adenosine triphosphate (ATP) level in the prefrontal cortex (PFC) is involved in the pathophysiology of depression. To investigate the potential relationship between ATP in PFC and antidepressant effects of electroacupuncture (EA) treatment, we assessed genes involved in ATP biosynthesis as well as the extracellular ATP levels in a rat model exposed to neonatal MS. Our results demonstrated that reduced expression of ABCG2 (an ATP-binding cassette protein) and ATP levels in the PFC of depressive-like rats exposed to MS can be attenuated by EA stimulus at the Baihui (GV20) and Yintang (GV29) acupoints. Moreover, the antidepressant effect of EA treatment was blocked by administration of suramin, a broad purinergic P2 receptor antagonist. Together, these results suggested that electroacupuncture may be able to modulate extracellular ATP levels in the PFC of depressive-like MS rats, potentially contributing to its antidepressant effects.
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Eletroacupuntura , Ratos , Animais , Ratos Sprague-Dawley , Eletroacupuntura/métodos , Privação Materna , Córtex Pré-Frontal , Antidepressivos/farmacologiaRESUMO
ORANGE (OR) plays essential roles in regulating carotenoid homeostasis and enhancing the ability of plants to adapt to environmental stress. However, OR proteins have been functionally characterized in only a few plant species, and little is known about the role of potato OR (StOR). In this study, we characterized the StOR gene in potato (Solanum tuberosum L. cv. Atlantic). StOR is predominantly localized to the chloroplast, and its transcripts are tissue-specifically expressed and significantly induced in response to abiotic stress. Compared with wild type, overexpression of StOR increased ß-carotene levels up to 4.8-fold, whereas overexpression of StORHis with a conserved arginine to histidine substitution promoted ß-carotene accumulation up to 17.6-fold in Arabidopsis thaliana calli. Neither StOR nor StORHis overexpression dramatically affected the transcript levels of carotenoid biosynthetic genes. Furthermore, overexpression of either StOR or StORHis increased abiotic stress tolerance in Arabidopsis, which was associated with higher photosynthetic capacity and antioxidative activity. Taken together, these results indicate that StOR could be exploited as a potential new genetic tool for the improvement of crop nutritional quality and environmental stress tolerance.
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Arabidopsis , Solanum tuberosum , Arabidopsis/genética , Arabidopsis/metabolismo , beta Caroteno , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Carotenoides/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genéticaRESUMO
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis and drug-resistance. Disheveled3 (DVL3) is involved in malignant behaviors of cancer. However, the role and potential mechanism of DVL3 remain elusive in EMT and CSLCs of colorectal cancer (CRC). METHODS: UALCAN and PrognoScan databases were employed to evaluate DVL3 expression in CRC tissues and its correlation with CRC prognosis, respectively. Transwell, sphere formation and CCK8 assay were used to assess metastasis, stemness and drug sensitivity of CRC cells, respectively. Western blotting and dual luciferase assay were performed to analyze the protein expression and Wnt/ß-catenin activation, respectively. Lentiviral transfection was used to construct the stable cell lines. Animal studies were performed to analyze the effect of silencing DVL3 on tumorigenicity and metastasis of CRC cells in vivo. RESULTS: DVL3 was overexpressed in CRC tissues and several CRC cell lines. DVL3 expression was also higher in CRC tissues with lymph node metastasis than tumor tissues without metastasis, and correlated with poor prognosis of CRC patients. DVL3 positively regulated the abilities of migration, invasion and EMT-like molecular changes in CRC cells. Moreover, DVL3 promoted CSLCs properties and multidrug resistance. We further identified that Wnt/ß-catenin was crucial for DVL3-mediated EMT, stemness and SOX2 expression, while silencing SOX2 inhibited DVL3-mediated EMT and stemness. Furthermore, c-Myc, a direct target gene of Wnt/ß-catenin, was required for SOX2 expression and strengthened EMT and stemness via SOX2 in CRC cells. Finally, knockdown of DVL3 suppressed tumorigenicity and lung metastasis of CRC cells in nude mice. CONCLUSION: DVL3 promoted EMT and CSLCs properties of CRC via Wnt/ß-catenin/c-Myc/SOX2 axis, providing a new strategy for successful CRC treatment.
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Neoplasias Colorretais , Proteínas Desgrenhadas , Transição Epitelial-Mesenquimal , Via de Sinalização Wnt , beta Catenina , Animais , Camundongos , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Humanos , Proteínas Desgrenhadas/genética , Células-Tronco NeoplásicasRESUMO
Background: Immune checkpoint inhibitors (ICIs) play an important role in the treatment of esophageal cancer (EC). However, their efficacy is variable, and there are still no effective and convenient biomarkers to identify and assess their efficacy. In recent years, programmed cell death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and other commonly used biomarkers still cannot meet clinical needs. PNI is easy to obtain and its predictive value for the prognosis of immunotherapy has been confirmed in many cancer species, but the relationship between PNI and the efficacy of immunotherapy for esophageal cancer is still unclear. Therefore, this study aims to explore the predictive value of PNI in advanced esophageal cancer treated with ICIs. Methods: The clinicopathological features of 78 patients with advanced EC who received immunotherapy in the 900th Hospital of the Joint Logistics Team from September 2018 to May 2022 were retrospectively analyzed. The laboratory test results within 10 days prior to the start of ICI treatment were recorded, including absolute lymphocyte count and albumin (ALB) level. Meanwhile, the effects of pre-treatment prognostic nutritional index (PNI) and body mass index (BMI) on the overall survival (OS) and progression-free survival (PFS) in patients with advanced EC were analyzed. Results: The median age of the enrolled patients was 58 years, and 38 patients (48.7%) received second-or-later-line therapy. The median progression-free survival (mPFS) and median overall survival (mOS) were 7.4 months and 13 months, respectively. The mPFS and mOS were 8.8 months and 15 months, respectively, in the high baseline PNI subgroup, which were significantly higher than those in the low baseline PNI subgroup (4.7 and 8.2 months, respectively; both P<0.05). Multivariate regression analysis showed that low baseline PNI was an independent predictor of poor PFS [hazard studio (HR) =0.35, 95% CI: 0.14-0.85, P=0.020) and poor OS (HR =0.41, 95% CI: 0.17-0.99, P=0.047) and treatment line was an independent predictor of PFS. Baseline BMI was not significantly associated with prognosis. Conclusions: PNI is a simple and effective biomarker for predicting the prognosis of immunotherapy in patients with advanced EC, although further prospective studies are warranted.
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Melatonin, a pleiotropic regulatory molecule, is involved in the defense against heavy metal stress. Here, we used a combined transcriptomic and physiological approach to investigate the underlying mechanism of melatonin in mitigating chromium (Cr) toxicity in Zea mays L. Maize plants were treated with either melatonin (10, 25, 50 and 100 µM) or water and exposed to 100 µM K2Cr2O7 for seven days. We showed that melatonin treatment significantly decreased the Cr content in leaves. However, the Cr content in the roots was not affected by melatonin. Analyses of RNA sequencing, enzyme activities, and metabolite contents showed that melatonin affected cell wall polysaccharide biosynthesis, glutathione (GSH) metabolism, and redox homeostasis. During Cr stress, melatonin treatment increased cell wall polysaccharide contents, thereby retaining more Cr in the cell wall. Meanwhile, melatonin improved the GSH and phytochelatin contents to chelate Cr, and the chelated complexes were then transported to the vacuoles for sequestration. Furthermore, melatonin mitigated Cr-induced oxidative stress by enhancing the capacity of enzymatic and non-enzymatic antioxidants. Moreover, melatonin biosynthesis-defective mutants exhibited decreased Cr stress resistance, which was related to lower pectin, hemicellulose 1, and hemicellulose 2 than wild-type plants. These results suggest that melatonin alleviates Cr toxicity in maize by promoting Cr sequestration, re-establishing redox homeostasis, and inhibiting Cr transport from the root to the shoot.