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1.
Artigo em Inglês | MEDLINE | ID: mdl-33802858

RESUMO

To advance the understanding about social-cognitive factors related to Chinese adolescents' experience with problematic Internet use (PIU), we examined the associations between social-emotional learning (SEL) competencies (i.e., responsible decision-making, social awareness, self-management, self-awareness, and social relationship) and problematic Internet use (PIU) among 1141 11th grade high school students from Southwest China. Through comparing the latent means of PIU across students with different demographic background (i.e., gender, social-economic status, left-behind status), the study found that male students endorsed higher levels of overall PIU and more problematic time management with Internet use than female students. No latent PIU mean differences were observed across family income and students' left-behind status. Using structural equation modeling (SEM) while controlling for demographic factors, overall SEL competencies were found to have a significantly negative association with PIU. Meanwhile, all five SEL domains were also negatively associated with students' PIU. The findings imply the importance of fostering SEL competencies in preventing PIU among Chinese adolescents. The study provides important practical implications for informing school-based SEL competencies programs for PIU prevention among Chinese youths.

2.
Zygote ; : 1-8, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769243

RESUMO

This study examined the effects of zinc chloride (ZnCl2) and sodium selenite (Na2SeO3) supplementation in maturation medium on in vitro maturation (IVM) rate, oxidative biomarkers and gene expression in buffalo oocytes. Ovaries from a slaughterhouse were aspirated and good quality cumulus-oocyte complexes (COCs) with at least four layers of compact cumulus cells and evenly granulated dark ooplasm were selected. COCs were randomly allocated during IVM (22 h) to one of four treatment groups: (1) control maturation medium (basic medium), or basic medium supplemented with (2) ZnCl2 (1.5 µg/ml), (3) Na2SeO3 (5 µg/l), or (4) ZnCl2 + Na2SeO3 (1.5 µg/ml + 5 µg/l, respectively). Oocytes were denuded after 22 h of IVM in the first four replicates. Specimens were fixed and stained to evaluate the stage of nuclear maturation. The spent medium was collected for biochemical assays of total antioxidant capacity (TAC), malondialdehyde (MDA) and hydrogen peroxide concentrations. A second four replicates were used for COCs for RNA extraction. The expression levels of antioxidant (SOD1, GPX4, CAT and PRDX1), antiapoptotic (BCL2 and BCL-XL) and proapoptotic (BAX and BID) genes were measured. Supplementation with ZnCl2 and Na2SeO3 during IVM increased the ratio of oocytes reaching metaphase II at 22 h, increased TAC and decreased MDA and H2O2 concentrations in the maturation medium (P < 0.05). Moreover, beneficial effects were associated with complementary changes in expression patterns of antioxidative, antiapoptotic and proapoptotic genes, suggesting lower oxidative stress and apoptosis. Supplementation medium with zinc chloride and sodium selenite improves the maturation rate, reduces oxidative stress and increases expression levels of antioxidative and antiapoptotic genes.

3.
J Interpers Violence ; : 886260521997940, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685274

RESUMO

Existing theories and empirical studies have evidenced the association between bullying victimization and bullying perpetration. However, it is still unclear what factors mitigate or alter this risk linkage between bullying victimization and bullying perpetration to reduce bullying incidents. Guided by the social-ecological theory, this study used a longitudinal design to examine the moderating role of school climate in the association between bullying victimization and bullying perpetration at both the within-person and between-person levels among Chinese adolescents across a 1-year period. Participants included 2,997 Chinese adolescents (Mage = 14.9, 49.7% male) from 5 secondary schools. Results suggested that students who experienced high levels of bullying victimization were also involved in high levels of bullying perpetration over time (i.e., the positive within-person effect of bullying victimization on bullying perpetration). Results also showed that the between-person level of perceived school climate interacted with the within-person level of bullying victimization to predict the within-person level of bullying perpetration (i.e., cross-level effects). More specifically, the magnitude of the positive association between bullying victimization and bullying perpetration at the within-person level was mitigated among students with higher perceptions of school climate at the between-person level. Findings of the study highlighted the causal effect of bullying victimization on bullying perpetration and the buffering role of perceived school climate in the longitudinal association between bullying victimization and perpetration, which was consistent with the risk-buffering model but not the healthy context paradox hypothesis. Furthermore, the findings provided implications for bullying prevention and intervention services by using multitiered systems of support in bullying prevention efforts and highlights the need for promoting positive school climate.

4.
Sch Psychol ; 36(1): 24-33, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33646810

RESUMO

To advance cross-country understanding of parental perceptions of school climate, this study examined the psychometric properties of the Delaware School Climate Survey-Home version (DSCS-H) and also compared the parental perception of school climate among Chinese (n = 999) and American (n = 1,251) parents. Confirmatory factor analyses revealed that the DSCS-H was best supported by a second-order factor model in both samples and full measurement invariance across countries was evident. Comparison of overall school climate latent means revealed that American parents from elementary schools perceived a more positive overall school climate than did Chinese parents. Conversely, Chinese parents of students in high school perceived a more positive overall school climate than the American parents. The latent-mean difference of parental perception of the overall school climate in middle schools across the United States and China was not significantly different. Finally, the latent mean differences in school climate subfactors varied across grade levels. Implications for using the DSCS-H for assessing and understanding the perception of school climate among parents from diverse cultural and linguistic backgrounds are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

5.
Front Cell Infect Microbiol ; 11: 587150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718261

RESUMO

Vertical transmission of Toxoplasma gondii (T. gondii) infection during gestation can result in severe complications such as abortion, congenital malformation, fetal teratogenesis, etc. Immune inhibitory molecule Tim-3 was discovered to be expressed on some decidual immune cells and participates in the maintenance of maternal-fetal tolerance. Dysregulation of Tim-3 expression on decidual NK (dNK) cells was observed in several cases of pregnancy complications, whereas the role of Tim-3 on dNK cells during T. gondii infection remains unclear. In the present study, T. gondii infected Tim-3-/- pregnant mice, and anti-Tim-3 neutralizing antibody treated and infected human dNK cells were successfully established to explore the role of Tim-3 in dysfunction of dNK cells during abnormal pregnancy. Our results illustrated that Tim-3-/- pregnant mice displayed more worse pregnancy outcomes with T. gondii infection compared to infected WT pregnant mice. Also, it demonstrated that Tim-3 expression on dNK cells was significantly down-regulated following T. gondii infection. Data suggested a remarkable activation of dNK cells in Tim-3-/- mice and anti-Tim-3 neutralizing antibody treated and infected groups, with higher ratios of activating receptor NKG2D to inhibitory receptor NKG2A or KIR2DL4, IFN-γ/IL-10, and increased granule production compared with that of the infected group. Mechanism analysis proved that T. gondii-induced Tim-3 down-regulation significantly activated the phosphatidylinositol-3-kinase (PI3K)-AKT and JAK-STAT signaling pathway, by which the GranzymeB, Perforin, IFN-γ, and IL-10 production were further up-regulated. Our research demonstrated that the decrease of Tim-3 on dNK cells caused by T. gondii infection further led to dNK cells function disorder, which finally contributed to the development of abnormal pregnancy outcomes.

6.
Planta Med ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33572003

RESUMO

Radix Bupleuri is one of the most widely used herbal medicines in China for the treatment of fever, pain, and/or chronic inflammation. Quercitrin, epicatechin, and rutin, the flavonoids present in Radix Bupleuri, have been reported to display anti-inflammatory, antitumor, and antioxidant biological activities among others. Sulfation has been reported to play an important role in the metabolism of flavonoids. In this study, we aimed to systematically identify the human cytosolic sulfotransferase enzymes that are capable of catalyzing the sulfation of quercitrin, epicatechin, and rutin. Of the thirteen known human cytosolic sulfotransferases, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1C2, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward quercitrin, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A3, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward epicatechin, and six (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A2, cytosolic sulfotransferase 1A3, cytosolic sulfotransferase 1B1, cytosolic sulfotransferase 1C4, and cytosolic sulfotransferase 1E1) displayed sulfating activity toward rutin. The kinetic parameters of the cytosolic sulfotransferases that showed the strongest sulfating activities were determined. To investigate the effects of genetic polymorphisms on the sulfation of quercitrin, epicatechin, and rutin, individual panels of cytosolic sulfotransferase allozymes previously prepared were analyzed and shown to display differential sulfating activities toward each of the three flavonoids. Taken together, these results provided a biochemical basis underlying the metabolism of quercitrin, epicatechin, and rutin through sulfation in humans.

8.
Respir Res ; 22(1): 52, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579290

RESUMO

BACKGROUND: Chinese Yunnan Province, located in the Yunnan-Guizhou Plateau, is a famous tourist paradise where acute high-altitude illness common occurs among lowland people visitors due to non-acclimatization to the acute hypobaric hypoxia (AHH) conditions. Traditional Chinese medicine, such as Qi-Long-Tian (QLT) formula, has shown effectiveness and safety in the treatment of acute high-altitude diseases. The aim of this study was to clarify the therapeutic mechanisms of this traditional formula using a rat model in a simulated plateau environment. METHODS: Following testing, lung tissue samples were evaluated by hematoxylin-eosin staining and for biochemical characteristics. mRNA-Seq was used to compare differentially expressed genes in control rats, and in rats exposed to AHH and AHH with QLT treatment. RESULTS: Inflammation-related effectors induced following QLT treatment for AHH included MMP9 and TIMP1, and involved several phosphorylation signaling pathways implicated in AHH pathogenesis such as PI3K/AKT and MAPK signaling. CONCLUSION: This study provides insights into the major signaling pathways induced by AHH and in the protective mechanisms involved in QLT formula activity.

9.
Sci Total Environ ; 769: 144489, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33465632

RESUMO

Cyanobacterial harmful algal blooms (CyanoHABs) bring economic loss, damage aquatic ecosystems, and produce cyanobacterial toxins that threaten human health. Algicidal bacteria as pathogens can expediate the decline of CyanoHABs. In this study, a Streptomyces globisporus strain (designated G9), isolated from soil near a eutrophic pond, showed high algicidal activity against Microcystis aeruginosa. Experimental results show that G9 preyed on Microcystis through cell-to-cell contact: (1) the hyphae of G9 killed cyanobacterial cells by twining around them, while cells beyond the reach of G9 hyphae were in normal shapes; (2) No algicides were detectable in the supernatant of G9 cultures or G9-Microcystis cocultures. The algicidal ratio of G9 to M. aeruginosa reached 96.7% after 6 days. G9 selectively killed the tested cyanobacterial strains, while it had only minor impacts on the growth of tested Chlorophyceae. Differential gene expression studies show that G9 affected the expression of key genes of M. aeruginosa involved in photosynthesis, microcystin synthesis and cellular emergency responses. Further, the microcystin-LR content decreased gradually with G9 treatment. As the first reported Streptomyces sp. with algicidal (predation) activity requiring cell-to-cell contact with target prey, G9 is a good candidate for the exploration of additional cyanobacteria-bacteria interactions and the development of novel strategies to control CyanoHABs.


Assuntos
Microcystis , Streptomyces , Ecossistema , Proliferação Nociva de Algas , Humanos , Microcistinas
10.
Nat Plants ; 7(1): 73-86, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33452487

RESUMO

Symbiosis between soybean (Glycine max) and rhizobia is essential for efficient nitrogen fixation. Rhizobial effectors secreted through the type-III secretion system are key for mediating the interactions between plants and rhizobia, but the molecular mechanism remains largely unknown. Here, our genome-wide association study for nodule number identified G. max Nodule Number Locus 1 (GmNNL1), which encodes a new R protein. GmNNL1 directly interacts with the nodulation outer protein P (NopP) effector from Bradyrhizobium USDA110 to trigger immunity and inhibit nodulation through root hair infection. The insertion of a 179 bp short interspersed nuclear element (SINE)-like transposon into GmNNL1 leads to the loss of function of GmNNL1, enabling bradyrhizobia to successfully nodulate soybeans through the root hair infection route and enhancing nitrogen fixation. Our findings provide important insights into the coevolution of soybean-bradyrhizobia compatibility and offer a way to design new legume-rhizobia interactions for efficient symbiotic nitrogen fixation.

11.
Biomater Sci ; 9(5): 1855-1871, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33464244

RESUMO

The satisfactory efficient tumor treatment and complete tumor ablation using a mono-therapeutic approach are limited owing to the tumor complexity, diversity, heterogeneity and the multiple pathways involved in tumor pathogenesis. Herein, novel, intelligent and tumor microenvironment (TME)-responsive biotin/R8 peptide co-modified nanocarriers (BRNC) loading paclitaxel (PTX)/glucose oxidase (GOx) were constructed. GOx could catalyze the oxidation of intracellular glucose to gluconic acid and poisonous H2O2 to cause the deterioration of the tumor survival microenvironment, simultaneously achieving starvation and oxidation therapy. The acidic amplification during the GOx-mediated oxidation progress could in turn accelerate the cleavage of the acid-degradable hydrazone bond, promoting the deep penetration of nanocarriers into tumors. Even better, the aforementioned two aspects further increased the tumors' sensitivity to chemotherapeutic agents. Both in vitro and in vivo investigations indicated that the co-administration of GOx-BRNC and PTX-BRNC can remarkably improve the therapeutic efficacy and reduce side effects through the high-specific tumor targeting multimodal synergistic starvation/oxidation/chemotherapy, which would be a promising strategy for the next generation cancer therapy.

12.
Biomed Res Int ; 2021: 5847153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33511202

RESUMO

Background: As the skin is the largest organ of the human body, it is aging inevitably and produces cosmetic and psychological problems, and even disease. Therefore, the molecular mechanisms related to the prevention of skin aging need to be further explored. Methods: Aging models were constructed by D-galactose. Mice were administrated with polygoni multiflori radix preparat (PMRP), PMRP and 3-methyladenine, or PMRP and rapamycin intragastrically. The apparent and viscera index of aged rats was measured. Then, the physicochemical property, antioxidant ability, histological structure, mitochondrial membrane potential, ATP and ROS levels, and mitophagy of aged skins were determined. Finally, the expression of PINK1, Parkin, P62, and LC3II/I; apoptosis-related proteins; and the percentage of apoptotic cells were measured. Results: PMRP relieved skin aging with reducing of thymus index, improvement of pathological damage and histological structure, increase of the expression area of fibrous tissue, the ratio of type I to type III collagen, and antioxidant ability of aged skins. Importantly, PMRP also improved mitochondrial dysfunction with an increase in the content of mitochondrial membrane potential and ATP and a decrease of ROS levels. Moreover, mitophagy was enhanced with the treatment of PMRP when observed using electron microscopy, and the expression of PINK1, Parkin, and LC3I/II was increased with PMRP treatment but P62 expression was decreased. Meanwhile, PMRP alleviated apoptosis with a decrease of apoptotic cell and the expression of Cleaved-cas3, Bax, Cyt-c, AIF, and Smac as well as an increase of Bcl-2 expression. Conclusion: The results demonstrated that the polygoni multiflori radix preparata may delay skin aging by inducing mitophagy.

13.
Inflammation ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33398543

RESUMO

Tadalafil (TAD) is primarily a treatment drug for erectile dysfunction. Studies have shown that TAD has a therapeutic effect on prostatitis, but the specific mechanism has not been reported. LPS induced RWPE-1 cells to form a model of chronic nonbacterial prostatitis (CNP). Cell activity was measured by MTT assay. Apoptosis was detected by TUNEL assay. Western blot was used to detect the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, and cleaved caspase3. ELISA was used to detect the expression of inflammatory cytokines TNF-α, IL-6, and IL-8. GSH, catalase (CAT), and malondialdehyde (MDA) kits were used to detect the expression of oxidative stress-related indicators GSH, CAT, and MDA. Western blot was used to detect the expression of proteins related to Akt/Nrf2 signaling pathway. After different concentrations of TAD were given, the survival rate of LPS-induced RWPE-1 cells decreased, apoptosis increased, and inflammation and oxidative stress decreased. This process is accompanied by the activation of the Akt/Nrf2 signaling pathway. The addition of AKT inhibitor (HY-10249A) reversed the inhibitory effect of TAD on LPS-induced inflammatory response and oxidative stress of RWPE-1 cell. TAD alleviated LPS-induced inflammation and oxidative stress of RWPE-1 cell by regulating the Akt/Nrf2 signaling pathway.

14.
Plant Mol Biol ; 105(4-5): 405-417, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387175

RESUMO

KEY MESSAGE: We reported that DGS1 plays a positive role in regulating grain size in rice and was regulated by OsBZR1. Grain size is an important agronomic trait that contributes to grain yield. However, the underlying molecular mechanisms that determine final grain size are still largely unknown. We isolated a rice mutant showing reduced grain size in a 60Co-irradiated variety Nanjing 35 population. We named the mutant decreased grain size1 (dgs1). Map-based cloning and subsequent transgenic CRISPR and complementation assays indicated that a mutation had occurred in LOC_Os03g49900 and that the DGS1 allele regulated grain size. DGS1 encodes a protein with a 7-transmembrane domain and C3HC4 type RING domain. It was widely expressed, especially in young tissues. DGS1 is a membrane-located protein. OsBZR1 (BRASSINAZOLE-RESISTANT1), a core transcription activator of BR signaling, also plays a positive role in grain size. We provided preliminary evidence that OsBZR1 can bind to the DGS1 promoter to activate expression of DGS1.


Assuntos
Grão Comestível/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Membrana/genética , Oryza/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Sequência de Bases , Grão Comestível/metabolismo , Grão Comestível/ultraestrutura , Proteínas de Membrana/metabolismo , Microscopia Eletrônica de Varredura , Mutação , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Interferência de RNA , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Fatores de Transcrição/metabolismo
15.
Epigenomics ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290106

RESUMO

Aims: Given the reversibility of methylation, biomarkers with discriminating ability are of great interest for targeted therapeutic sites. Materials & methods: Methylation array data of 461 lung adenocarcinoma (LUAD) patients comprising of 458 tumor and 32 LUAD paracancerous samples were compared using partial least squares discrimination analysis and receiver operating characteristics analysis. Results: A six-DNA methylation signature (corresponding to five genes) was found to significantly discriminate normal and LUAD samples. Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment of methylation sites in the Wnt pathway in LUAD compared with controls. Conclusion: This six-DNA methylation signature demonstrated potential as a novel biomarker for diagnosis and therapeutic targets. Further, inhibition of Wnt signaling pathway may be an important step in LUAD progression.

16.
Stem Cell Res Ther ; 11(1): 519, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261658

RESUMO

BACKGROUND: Human umbilical cord mesenchymal stem cells (HUC-MSCs) present in the umbilical cord tissue are self-renewing and multipotent. They can renew themselves continuously and, under certain conditions, differentiate into one or more cell types constituting human tissues and organs. HUC-MSCs differentiate, among others, into osteoblasts, chondrocytes, and adipocytes and have the ability to secrete cytokines. The possibility of noninvasive harvesting and low immunogenicity of HUC-MSCs give them a unique advantage in clinical applications. In recent years, HUC-MSCs have been widely used in clinical practice, and some progress has been made in their use for therapeutic purposes. MAIN BODY: This article describes two aspects of the clinical therapeutic effects of HUC-MSCs. On the one hand, it explains the benefits and mechanisms of HUC-MSC treatment in various diseases. On the other hand, it summarizes the results of basic research on HUC-MSCs related to clinical applications. The first part of this review highlights several functions of HUC-MSCs that are critical for their therapeutic properties: differentiation into terminal cells, immune regulation, paracrine effects, anti-inflammatory effects, anti-fibrotic effects, and regulating non-coding RNA. These characteristics of HUC-MSCs are discussed in the context of diabetes and its complications, liver disease, systemic lupus erythematosus, arthritis, brain injury and cerebrovascular diseases, heart diseases, spinal cord injury, respiratory diseases, viral infections, and other diseases. The second part emphasizes the need to establish an HUC-MSC cell bank, discusses tumorigenicity of HUC-MSCs and the characteristics of different in vitro generations of these cells in the treatment of diseases, and provides technical and theoretical support for the clinical applications of HUC-MSCs. CONCLUSION: HUC-MSCs can treat a variety of diseases clinically and have achieved good therapeutic effects, and the development of HUC-MSC assistive technology has laid the foundation for its clinical application.

17.
J Food Biochem ; : e13565, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219537

RESUMO

Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. This study was mainly aimed at investigating the effects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in serum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyze LDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42 mg/g DW) and isoquercitrin (4.60 mg/g DW) were the main constituents of ACE using HPLC analysis. Furthermore, ACE reduced the levels of TC, TG, LDL-C, and MDA, and increased HDL levels and elevated SOD activity both in serum and liver in hyperlipidemic SD rats (p < .05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and the lipid and foam cells of the aortic arch of the rats in ACE group were markedly ameliorated. WB results showed that ACE promoted the degradation of HMGCR and increased LDLR expression in liver (p < .05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR. PRACTICAL APPLICATIONS: Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, during atherosclerosis development, hyperlipidemia is an important risk factor. To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the side effects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statin lipid-lowering agent.

18.
PeerJ ; 8: e10397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240680

RESUMO

Purpose: Yes associated protein 1 (YAP1), which is a standout amongst the most essential effectors of the Hippo pathway, assumes a vital part in a few kinds of cancer. However, whether YAP1 is an oncogene in CRC (colorectal cancer) remains controversial, and the association between the subcellular localization of YAP1 and clinical implications in CRC remains unknown. Patients and methods: In this study, we investigated the subcellular localization of YAP1 in CRC cells by immunohistochemistry and then associate these findings with clinical information in a large CRC cohort with 919 CRC patients. Results: The results show that CRC tissues has a significant higher expression of cytoplasmic YAP1 compared to adjacent normal tissues (all P < 0.001). Cytoplasmic YAP1 expression was significantly associated with the number of lymph nodes removed and differentiation grade (all P < 0.001). Furthermore, after correcting confounding variables, for example, TNM stage and differentiation grade, the multivariate Cox analysis confirmed cytoplasmic YAP1-high subgroup had a significant shorter DFS (HR = 3.255; 95% CI [2.290-4.627]; P < 0.001) and DSS (HR = 4.049; 95% CI [2.400-6.830]; P < 0.001) than cytoplasmic YAP1-low subgroup. High cytoplasmic YAP1 expression is associated with a worse survival in stage III CRC patients who received chemotherapy. Conclusion: Cytoplasmic YAP1 could be could be utilized as a prognosis factor in CRC patients, and may be an indicator of whether certain patients population could benefit from postoperative chemotherapy.

19.
Bioorg Med Chem ; : 115852, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33189509

RESUMO

Glioma is one of the most common primary intracranial tumor, but the current treatments of glioma are far from satisfying. As the major treatment option for malignant glioma, chemotherapy has its own disadvantages, including low chemotherapeutic agents delivery across blood-brain barrier (BBB) and lack of specificity. Therefore, new approach permitting glioma targeting ability that can allow an efficient therapeutic delivery into the glioma regions is urgently required. Ligand-mediated liposomes have shown great potential for improving the efficiency of glioma treatment. In our study, the multi-targeting liposomes based on glucose and biotin were constructed for the first time. We synthesized two ligands (Glu3-Chol, Bio2-Chol), prepared three types of modified liposomes (Glu3-Lip, Bio2-Lip and Bio2 + Glu3-Lip) and evaluated the glioma-targeting ability of these liposomes which were using paclitaxel (PTX) as the model drug in vitro. Besides, the uptake mechanism of Bio2 + Glu3-Lip was investigated. PTX-loaded Bio2 + Glu3-Lip (PTX-Bio2 + Glu3-Lip) exhibited satisfactory targeting effect in Bend.3 and C6 cells in vitro, in which the cellular uptake of Bio2 + Glu3-Lip were 4.04- and 3.49-fold more than that of the uncoated liposomes (Lip). The results suggested the multi-targeting liposomes (Bio2 + Glu3-Lip) is a promising formulation for glioma, which was almost consistent with the results of in vivo imaging. In summary, we have designed and fabricated an effective delivery system to treat glioma.

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