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Ferroptosis-mediated multimodal therapy has emerged as a promising strategy for tumor elimination, with lipid peroxide (LPO) playing a pivotal role. However, the therapeutic efficiency is limited due to insufficient intracellular levels of free fatty acids (FFA), which severely hinder the production of LPO. To address this limitation, we proposed a lipophagy strategy aimed at degrading lipid droplets (LDs) to release FFA, serving as the essential "fuel" for LPO production. In this study, the lipophagy inducer epigallocatechin gallate (EGCG) was self-assembled with reactive oxygen species (ROS)-producer phenethyl isothiocyanate (PEITC) mediated by Fe2+ to form EFP nanocapsules, which were further integrated into microneedle patches to form a "all-in-one" EFP@MNs. The metal-polyphenol network structure of EFP endow it with photothermal therapy capacity. Upon insertion into tumors, the released EFP nanocapsules were demonstrated to induce lipophagy through metabolic disturbance, thereby promoting LPO production and facilitating ferroptosis. When combined with photothermal therapy, this approach significantly remolded the tumor immune microenvironment by driving tumor-associated macrophages toward M1 phenotype and enhancing dendritic cell maturation. Encouragingly, in conjunction with αPD-L1 treatment, the proposed EFP@MNs exhibited remarkable efficacy in tumor ablation. Our study presents a versatile framework for utilizing microneedle patches to power ferroptosis-mediated multimodal therapy.
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(1) Objectives: The aim of this study was to examine the relationship between mindful parenting and children's creative tendencies and to investigate the mediating role of parent-child intimacy and connectedness to nature in the relationship between mindful parenting and children's creative tendencies. (2) Methods: In this cross-sectional study, nearly 800 mothers of children aged 3-6 were enrolled. General sociodemographic data, the Mindfulness in Parenting Questionnaire (MIPQ), the Creativity Assessment Packet (CAP), the Child-Parent Relationship Scale-Short Form (CPRS-SF), and the Connectedness to Nature Index-Parents of Preschool Children (CNI-PPC) were all included in the questionnaire survey. (3) Results: There were significant positive correlations among mindful parenting, parent-child intimacy, connectedness to nature, and children's creative tendencies. Mindful parenting had a positive predictive effect on children's creative tendencies. Parent-child intimacy played a mediating role between mindful parenting and children's creative tendencies. Connectedness to nature played a mediating role between mindful parenting and children's creative tendencies. The correlation between mindful parenting and children's creative tendencies may be impacted by the chain mediation effects of parent-child intimacy and connectedness to nature. (4) Conclusions: By promoting parent-child intimacy and connectedness to nature, and by utilizing the chain mediating effects of both, mindful parenting positively impacted children's creative tendencies.
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OBJECTIVES: This in vitro study aimed to evaluate the effect of resin infiltration combined with casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF) or bioactive glass (BAG) on the stability of enamel white spot lesions (WSLs) treatment. MATERIALS AND METHODS: Eighty-four enamel blocks were prepared from the buccal surfaces of sound human premolars. All enamel blocks were placed in a demineralisation solution for 3 days to establish the artificial enamel WSLs. Enamel blocks with WSLs were randomly divided into three groups (n = 28 each group): RI/B: one-off resin infiltration followed by twice daily BAG treatment; RI/C: one-off resin infiltration followed by twice daily CPP-ACPF treatment; RI: one-off resin infiltration treatment only (as control) and subjected to pH cycling for 7 days. Surface morphology, elemental analysis, crystal characteristics, surface roughness and microhardness of enamel surfaces were investigated by scanning electron microscopy and energy-dispersive spectrometry observation, X-ray diffraction (XRD), atomic force microscope and Vickers' hardness testing, respectively. RESULTS: Mean values of the surface roughness (mean±standard deviation (nm)) were 24.52±5.07, 27.39±5.87 and 34.36±4.55 for groups RI/B, RI/C and RI respectively (p = 0.003). The calcium to phosphate ratios were 1.32±0.16, 1.22±0.26 and 0.69±0.24 for groups RI/B, RI/C and RI respectively (p < 0.001). XRD revealed apatite formation in all three groups. The mean enamel surface microhardness (kg/mm2) of the groups were 353.93±28.49, 339.00±27.32 and 330.38±22.55 for groups RI/B, RI/C and RI respectively (p = 0.216). CONCLUSIONS: Resin infiltration combined with CPP-ACPF or BAG remineralisation appears to improve the surface properties of WSLs. CLINICAL SIGNIFICANCE: The combination of resin infiltration and CPP-ACPF/BAG remineralisation may be a potential treatment for the management of the WSLs.
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Cárie Dentária , Esmalte Dentário , Humanos , Esmalte Dentário/patologia , Fluoretos/farmacologia , Fluoretos/uso terapêutico , Fluoretos/análise , Fosfatos de Cálcio/farmacologia , Fosfatos de Cálcio/uso terapêutico , Cárie Dentária/patologiaRESUMO
The impact of maternal trait mindfulness on the development of preschoolers' social competence is receiving increasing attention from researchers. However, the mediating mechanisms that link maternal mindfulness to preschoolers' social competence are still not well understood. This study examined the mediating effect of maternal self-control and problematic social media use on the association between maternal trait mindfulness and preschoolers' social competence. We administered 407 mothers of preschoolers in China a questionnaire to assess their trait mindfulness, self-control, problematic social media use, and the degree of social competence of their children. After controlling for demographic variables, the results showed that (1) Maternal trait mindfulness was positively related to preschoolers' social competence; (2) Maternal self-control and problematic social media use independently mediated the relationship between maternal trait mindfulness and preschoolers' social competence; and (3) Maternal self-control and problematic social media use play a chain-mediating role between maternal trait mindfulness and preschoolers' social competence. These findings have enhanced our understanding of how maternal trait mindfulness influences preschoolers' social competence and holds important implications for interventions aimed at enhancing preschoolers' social competence.
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Ferroptosis is a new cell fate decision discovered in recent years. Unlike apoptosis, autophagy or pyroptosis, ferroptosis is characterized by iron-dependent lipid peroxidation and mitochondrial morphological changes. Ferroptosis is involved in a variety of physiological and pathological processes. Since its discovery, ferroptosis has been increasingly studied concerning bone-related diseases. In this review, we focus on the latest research progress and prospects, summarize the regulatory mechanisms of ferroptosis, and discuss the role of ferroptosis in the pathogenesis of bone-related diseases, such as osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), and osteosarcoma (OS), as well as its therapeutic potential.
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The diabetic wound is a prevalent and serious complication of diabetes, which easily deteriorates due to susceptibility to infection and difficulty in healing, causing a high risk of amputation and economic burden to patients. Bacterial infection, persistent excessive inflammation, and cellular and angiogenesis disorders are the main reasons for the difficulty of diabetic wound healing. In this study, glycerol monooleate (GMO) was used to prepare lyotropic liquid crystal hydrogel (LLC) containing the natural antimicrobial peptide LL37 and carbenoxolone (CBX) to achieve antibacterial, anti-inflammation, and healing promotion for the treatment of diabetic wounds. The shear-thinning properties of the LLC precursor solution allowed it to be administered in the form of a spray, which perfectly fitted the shape of the wound and transformed into a gel after absorbing wound exudate to act as a wound protective barrier. The faster release of LL37 realized rapid sterilization of wounds, controlled the source of inflammation, and accelerated wound healing. The inflammatory signaling pathway was blocked by the subsequently released CBX, and the spread of the inflammatory response was inhibited and then further weakened. In addition, CBX down-regulated connexin (Cx43) to assist LL37 to promote cell migration and proliferation better. Combined with the pro-angiogenic effect of LL37, the healing of diabetic wounds was significantly accelerated. All these advantages made LL37-CBX-LLC a promising approach for the treatment of chronic diabetic wounds.
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Cardiorespiratory function influences exercise capacity and is an important determinant of high-altitude adaptation. Some studies have investigated the characteristics of changes in cardiorespiratory fitness during high-altitude acclimatization. However, studies on changes in cardiorespiratory fitness during high-altitude de-acclimatization are still lacking and have not yet been elucidated. Furthermore, few drugs have been studied to improve cardiorespiratory function during both processes. The Shigatse CARdiorespiratory Fitness (SCARF) study is a single-center, randomized, double-blind, placebo-control clinical trial to explore the effects of ubiquinol on cardiorespiratory fitness during high-altitude acclimatization and de-acclimatization in healthy adults. Participants will be randomly assigned 1:1 to ubiquinol 200â mg daily or a placebo for 14 days before departure until the end of data collection after return in 7 days. Cardiorespiratory fitness is the primary outcome, while acute mountain sickness and high-altitude de-acclimatization symptoms are secondary endpoints. In addition, laboratory measurements, including routine blood tests and serological measurements, will be performed. To the best of our knowledge, the SCARF study will be the first to reveal the changes in the cardiorespiratory fitness characteristics during high-altitude acclimatization and de-acclimatization. Furthermore, the results of this study will contribute to exploring whether ubiquinol supplementation could be beneficial for endurance exercise capacity at different altitudes and help improve adaptation to acute hypoxia and de-acclimatization. Clinical Trial Registration: This study has been registered in the Chinese Clinical Trial Register (www.chictr.org.cn) as ChiCTR2200059900 and ChiCTR2200066328.
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Exotic phenomena due to the interplay of different quantum orders have been observed and the study of these phenomena has emerged as a new frontier in condensed matter research, especially in the two-dimensional limit. Here, we report the coexistence of charge density waves (CDWs), superconductivity, and nontrivial topology in monolayer 1H-MSe2 (M = Nb, Ta) triggered by momentum-dependent electron-phonon coupling through electron doping. At a critical electron doping concentration, new 2 × 2 CDW phases emerge with nontrivial topology, Dirac cones, and van Hove singularities. Interestingly, these 2 × 2 CDW phases are also superconducting. Our findings not only reveal a route towards realizing nontrivial electronic characters by CDW engineering, but also provide an exciting platform to modulate different quantum states at the confluence of CDWs, superconductivity, nontrivial topology, and electron-phonon coupling.
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Myeloid-derived suppressor cells (MDSCs) are a group of heterogenous immature myeloid cells with potent immune suppressive properties that not only constrain anti-tumor immune activation and functions, promote tumor progression, but also contribute to treatment resistance and tumor relapse. Targeting MDSCs may be a promising new cancer treatment method, but there is still a problem of low treatment efficiency. Combined application with radiotherapy may be a potential method to solve this problem. Drug delivery systems (DDSs) provide more efficient targeted drug delivery capability and can reduce the toxicity and side effects of drugs. Recent advance in DDSs targeting development, recruitment, differentiation, and elimination of MDSCs have shown promising effect in reversing immune inhibition and in overcoming radiotherapy resistance. In this review, we systematically summarized DDSs applied to target MDSCs for the first time, and classified and discussed it according to its different mechanisms of action. In addition, this paper also reviewed the biological characteristics of MDSCs and their role in the initiation, progression, and metastasis of cancer. Moreover, this review also summarizes the role of DDSs targeting MDSCs in radiosensitization. Finally, the future development of DDSs targeting MDSCs is also prospected.
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Células Supressoras Mieloides , Diferenciação Celular , Sistemas de Liberação de MedicamentosRESUMO
BACKGROUND: Cardiorespiratory fitness plays an important role in coping with hypoxic stress at high altitudes. However, the association of cardiorespiratory fitness with the development of acute mountain sickness (AMS) has not yet been evaluated. Wearable technology devices provide a feasible assessment of cardiorespiratory fitness, which is quantifiable as maximum oxygen consumption (VO2max) and may contribute to AMS prediction. OBJECTIVE: We aimed to determine the validity of VO2max estimated by the smartwatch test (SWT), which can be self-administered, in order to overcome the limitations of clinical VO2max measurements. We also aimed to evaluate the performance of a VO2max-SWT-based model in predicting susceptibility to AMS. METHODS: Both SWT and cardiopulmonary exercise test (CPET) were performed for VO2max measurements in 46 healthy participants at low altitude (300 m) and in 41 of them at high altitude (3900 m). The characteristics of the red blood cells and hemoglobin levels in all the participants were analyzed by routine blood examination before the exercise tests. The Bland-Altman method was used for bias and precision assessment. Multivariate logistic regression was performed to analyze the correlation between AMS and the candidate variables. A receiver operating characteristic curve was used to evaluate the efficacy of VO2max in predicting AMS. RESULTS: VO2max decreased after acute high altitude exposure, as measured by CPET (25.20 [SD 6.46] vs 30.17 [SD 5.01] at low altitude; P<.001) and SWT (26.17 [SD 6.71] vs 31.28 [SD 5.17] at low altitude; P<.001). Both at low and high altitudes, VO2max was slightly overestimated by SWT but had considerable accuracy as the mean absolute percentage error (<7%) and mean absolute error (<2 mL·kg-1·min-1), with a relatively small bias compared with VO2max-CPET. Twenty of the 46 participants developed AMS at 3900 m, and their VO2max was significantly lower than that of those without AMS (CPET: 27.80 [SD 4.55] vs 32.00 [SD 4.64], respectively; P=.004; SWT: 28.00 [IQR 25.25-32.00] vs 32.00 [IQR 30.00-37.00], respectively; P=.001). VO2max-CPET, VO2max-SWT, and red blood cell distribution width-coefficient of variation (RDW-CV) were found to be independent predictors of AMS. To increase the prediction accuracy, we used combination models. The combination of VO2max-SWT and RDW-CV showed the largest area under the curve for all parameters and models, which increased the area under the curve from 0.785 for VO2max-SWT alone to 0.839. CONCLUSIONS: Our study demonstrates that the smartwatch device can be a feasible approach for estimating VO2max. In both low and high altitudes, VO2max-SWT showed a systematic bias toward a calibration point, slightly overestimating the proper VO2max when investigated in healthy participants. The SWT-based VO2max at low altitude is an effective indicator of AMS and helps to better identify susceptible individuals following acute high-altitude exposure, particularly by combining the RDW-CV at low altitude. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200059900; https://www.chictr.org.cn/showproj.html?proj=170253.
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Doença da Altitude , Humanos , Doença Aguda , Altitude , Doença da Altitude/diagnóstico , Teste de Esforço , Consumo de OxigênioRESUMO
Evodol is one of the furanoids isolated from the fruits of Evodia rutaecarpa that has been widely prescribed for the treatment of gastrointestinal diseases in China. The aim of this study was to investigate the inhibitory effect of evodol on CYP3A.A 30-min preincubation of evodol with human liver microsomes raised an obvious left IC50 shift, 3.9-fold for midazolam 1'-hydroxylation and 3.2-fold for testosterone 6ß-hydroxylation. Evodol inactivated CYP3A in a time-, concentration- and NADPH-dependent manner, with KI and kinact of 5.1 µM and 0.028 min-1 for midazolam 1'-hydroxylation and 3.0 µM and 0.022 min-1 for testosterone 6ß-hydroxylation.Co-incubation of ketoconazole attenuated the inactivation while the inclusion of glutathione (GSH) and catalase/superoxide dismutase displayed no such protection.cis-Butene-1, 4-dial (BDA) intermediate derived from evodol were trapped by glutathione and N-acetyl-lysine in microsomes and characterised by HR-MS spectra. The BDA intermediate was believed to play a key role in CYP3A inactivation. CYP3A4 and 2C9 were the primary enzymes contributing to the bioactivation of evodol.To sum up, for the first time evodol was characterised as a mechanism-based inactivator of CYP3A.
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Citocromo P-450 CYP3A , Midazolam , Humanos , Midazolam/farmacologia , Microssomos Hepáticos , Cetoconazol/farmacologia , TestosteronaRESUMO
Myeloid-derived suppressor cells (MDSCs), which originated from hematopoietic stem cells, are heterogeneous population of cells that have different differentiation patterns and widely presented in tumor microenvironment. For tumor research, myeloid suppressor cells have received extensive attention since their discovery due to their specific immunosuppressive properties, and the mechanisms of immunosuppression and therapeutic approaches for MDSCs have been investigated in a variety of different types of malignancies. To improve the efficacy of treatment for head and neck squamous cell carcinoma (HNSCC), a disease with a high occurrence, immunotherapy has gradually emerged in after traditional surgery and subsequent radiotherapy and chemotherapy, and has made some progress. In this review, we introduced the mechanisms on the development, differentiation, and elimination of MDSCs and provided a detailed overview of the mechanisms behind the immunosuppressive properties of MDSCs. We summarized the recent researches on MDSCs in HNSCC, especially for targeting-MDSCs therapy and combination with other types of therapy such as immune checkpoint blockade (ICB). Furthermore, we looked at drug delivery patterns and collected the current diverse drug delivery systems for the improvement that contributed to therapy against MDSCs in HNSCC. Most importantly, we made possible outlooks for the future research priorities, which provide a basis for further study on the clinical significance and therapeutic value of MDSCs in HNSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Células Supressoras Mieloides , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Células Mieloides/metabolismo , Células Mieloides/patologia , Microambiente TumoralRESUMO
Hypobaric hypoxia (HH) is the primary challenge at highland. Prolonged HH exposure impairs right cardiac function. Mitochondria-associated membrane (MAM) plays a principal role in regulating mitochondrial function under hypoxia, but the mechanism was unclear. In this study, proteomics analysis identified that PACS2, a key protein in MAM, and mitophagy were downregulated in HH. Metabolomics analysis indicated suppression of glucose and fatty acids aerobic oxidation in HH conditions. Cardiomyocyte Pacs2 deficiency disrupted MAM formation and endoplasmic reticulum (ER)-mitochondria calcium flux, further inhibiting mitophagy and energy metabolism in HH. Pacs2 overexpression reversed these effects. Cardiac-specific knockout of Pacs2 exacerbated mitophagy inhibition, cardiomyocyte injury, and right cardiac dysfunction induced by HH. Conditional knock-in of Pacs2 recovered HH-induced right cardiac impairment. Thus, PACS2 is essential for protecting cardiomyocytes through ER-mitochondria calcium flux, mitophagy, and mitochondrial energy metabolism. Our work provides insight into the mechanism of HH-induced cardiomyocyte injury and potential targets for maintaining the right cardiac function at the highland.
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BACKGROUND: The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue. METHODS: We analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan-Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene-drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results. RESULTS: Compared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05). CONCLUSIONS: The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.
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Biologia Computacional , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Estimativa de Kaplan-Meier , Neoplasias de Cabeça e Pescoço/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Microambiente TumoralRESUMO
This study aimed to examine the associations between parental mindfulness and preschool child behavior problems and to investigate the mediating role of marital satisfaction and coparenting in the relationship between mindfulness and preschool child behavior problems. This was a cross-sectional study in which general sociodemographic data were obtained from 3448 parents of children in grades junior to senior of kindergarten who were assessed using instruments such as the Mindful Attention Awareness Scale (MAAS), the Strengths and Difficulties Questionnaire (SDQ), the ENRICH Marital Satisfaction Scale (TEMSS), and the Parents' Perceptions of the Coparenting Relationship Questionnaire (PPCR). (1) Mindfulness, preschool child behavior problems, marital satisfaction, and coparenting were significantly correlated with each other, where mindfulness was positively correlated with marital satisfaction and coparenting and significantly negatively correlated with preschool child behavior problems. (2) Mindfulness negatively predicted preschool children's problem behaviors. (3) Marital satisfaction independently mediated the relationship between mindfulness and preschool child behavior problems. (4) Coparenting also independently mediated the relationship between mindfulness and preschool child behavior problems. (5) Marital satisfaction and coparenting play a chain-mediating role between mindfulness and preschool children's problem behaviors. Mindfulness predicted preschool child behavior problems, with marital satisfaction and coparenting as mediators.
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Atenção Plena , Comportamento Problema , Humanos , Pré-Escolar , Criança , Estudos Transversais , Poder Familiar , Atenção , Comportamento InfantilRESUMO
Objective: To examine the relationship between miRNA-3679 and hepatocellular carcinoma (HCC) cell lines, and to verify the downstream target genes of miRNA-3679. Methods: PCR was used to determine the expression of miRNA-3679 in liver cancer cell lines, and databases, including ENCORI, miRDB and TargetScan, were used to predict the downstream target genes of miRNA-3679. qPCR of the normal control group (or NC group), miR-3679 inhibitor group and transfection negative control group (or inhibitor NC group) was done to determine the transfection efficiency of the target gene, thereby identifying zinc-binding alcohol dehydrogenase domain containing 2 (ZADH2) as the target gene. Western blot was used to determine the ZADH2 protein expression after miRNA-3679 inhibitor transfection. 5-Ethynyl-2'-deoxyuridine (EdU) staining was done to determine the effect of transfection of miRNA-3679 inhibitor and simultaneous transfection of miRNA-3679 and ZADH2 inhibitors on cell proliferation. Clone formation assay was done to determine the ability of cell clone formation. Flow cytometry was done to examine cell apoptosis. Results: The expression level of miRNA-3679 in HCC cell lines was higher than that in normal human liver cell lines (P<0.05). Through screening conducted with the databases, six genes, including GLUD1, B3GAT1, SLC46A3, MAP2K3, ATF5, and ZADH2, were found to be down-regulated in HCC. qPCR showed that ZADH2 expression increased significantly after transfection with miRNA-3679 inhibitor (P<0.01) and luciferase activity increased after transfection with miR-3679 inhibitor (P<0.01). Western blot results showed that ZADH2 protein expression of the miR-3679 inhibitor group was higher than that of the NC group (P<0.01). EdU analysis showed that the number of positive cells in the miRNA-3679 inhibitor group was lower than that in the NC group and the Inhibitor NC group (P<0.05). The clone count of the miR-3679 inhibitor+si-ZADH2 group was significantly higher than that of the miR-3679 inhibitor group (P<0.01). Flow cytometry showed that the number of apoptotic cells of the miR-3679 inhibitor+si-ZADH2 group was significantly lower than that of the miR-3679 inhibitor group (P<0.01). Conclusion: miRNA-3679 is significantly highly expressed in HCC cells and miRNA-3679 can directly interact with ZADH2 gene and affect its expression. Moreover, miRNA-3679 promotes the proliferation of HCC cells and inhibits their apoptosis by suppressing ZADH2.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Antígenos de Superfície , Apoptose , Carcinoma Hepatocelular/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Zinco/metabolismoRESUMO
BACKGROUND: LINC00473 is a promising long non-coding RNA. There is increasing evidence that SNHG7 is abnormally expressed in various tumors and is associated with cancer prognosis. However, identification of the effect of long non-coding RNA LINC00473 in tumors remains necessary. METHODS: Up to August 15, 2021, we searched electronic databases, including PubMed, Cochrane Library, EMBASE, Medline, and Web of Science. The results were evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: There weres 13 included literature totaling cancer patients involved in this meta-analysis. The aggregated results revealed that high expression of LINC00473 was significantly associated with unfavorable overall survival (HRâ =â 1.66, 95% CI: 1.48-1.86, Pâ <â .00001), disease-free survival (HRâ =â 1.59, 95% CI: 1.09-2.32, Pâ =â .02) in a variety of cancers. Additionally, increased LINC00473 expression was also correlated with tumor node metastasis stage ((III/IV vs I/II) ORâ =â 4.67, 95% CIâ =â 3.11-7.02, Pâ <â .00001), differentiation ((poor/moderately vs well) ORâ =â 3.25, 95% CIâ =â 1.41-7.50, Pâ =â .006), tumor size ((larger vs smaller) ORâ =â 2.49, 95% CIâ =â 1.26-4.91, Pâ =â .03), and lymph node metastasis ((positive vs negative) ORâ =â 3.10, 95% CIâ =â 2.13-4.51, Pâ =â .008) in patients with cancers. Besides, the Gene Expression Profiling Interactive Analysis dataset evaluated that LINC00473 was upregulated in a variety of tumors and predicted worse prognosis. CONCLUSION: Our results of this meta-analysis demonstrated that high LINC00473 expression may become a potential target for predicting prognosis of human cancers.
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Neoplasias , RNA Longo não Codificante , Humanos , Prognóstico , RNA Longo não Codificante/genética , Neoplasias/patologia , Intervalo Livre de Doença , Metástase Linfática , Intervalo Livre de Progressão , Biomarcadores Tumorais/genéticaRESUMO
Chemical compositions, antioxidants, and anti-aging activities of Cortex Moutan (CM), from different collection periods and different producing areas, were measured and compared in order to obtain excellent CM extracts. The bioactivities of CM extracts were examined by an in vitro antioxidant method and a UVB irradiated human dermal fibroblast (HDF) model. Phytochemical properties were obtained from ultra-fast liquid chromatography quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF-MS) prior to the multivariate statistical analysis. As for the results, the extracts of Heze CM (HZCM) and Luoyang CM (LYCM) collected in June had better in vitro antioxidant activities, significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA), compared to other CM extracts. HZCM and LYCM extracts could upregulate the relative expression of SOD and GSH-Px mRNA. The extract of HZCM collected in June could significantly repress the production of matrix metalloproteinase 1 (MMP-1) and improve the production of procollagen type I (PCOL)-I in UVB irradiated HDF. In total, 50 compounds, including 17 monoterpenoids, 19 flavonoids, 13 phenols, and 1 amino acid were identified or tentatively identified in the CM extracts. Gallic acid, p-hydroxybenzoic acid, oxypaeoniflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloyl glucose, and paeonol were predominant compounds in the CM extracts. Taken together, CM collected from April to September had better antioxidant and anti-aging effects for external usage.
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Antioxidantes/farmacologia , Paeonia/química , Compostos Fitoquímicos/farmacologia , Linhagem Celular , Cromatografia Líquida de Alta Pressão/métodos , Glutationa Peroxidase/metabolismo , Humanos , Malondialdeído/metabolismo , Espectrometria de Massas/métodos , Paeonia/metabolismo , Fenóis/química , Compostos Fitoquímicos/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estações do Ano , Superóxido Dismutase/metabolismoRESUMO
It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).
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Angina Estável/tratamento farmacológico , Fármacos Cardiovasculares/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Adolescente , Adulto , Idoso , Angina Estável/genética , Angina Estável/patologia , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
[This corrects the article DOI: 10.3389/fpsyg.2020.01430.].