RESUMO
BACKGROUND: HIV prevention, diagnosis, treatment and care services might be hampered by inaccurate risk assessment. This study aimed to investigate the extent of and factors associated with the discordance between perceived risk and actual risky sexual behaviors among undergraduates in mainland China, guided by the Anderson's behavioral model. METHODS: This study involved a secondary analysis of cross-sectional data collected during the fall semester of 2018-2019 academic year. The present analysis was restricted to 8808 undergraduates with low risk perception. Those who had low perceived risk but actually engaged in risky sexual behaviors were categorized as risk discordance (RD). Univariate and multivariate Logistic regression analyses were conducted to identify factors associated with RD. RESULTS: Overall, the discordance rate between perceived and actual risk was 8.5% (95% CI: 7.9%-9.1%). Multivariate Logistic regression analysis indicated that non-heterosexual women (AOR = 0.41, 95% CI:0.27-0.60), heterosexual men (AOR = 0.45, 95% CI:0.33-0.61) and women (AOR = 0.26, 95% CI:0.19-0.35) were less likely to exhibit RD, when compared with non- heterosexual men. Furthermore, non-freshmen (AOR = 1.57, 95% CI:1.30-1.90), early initiators of sexual intercourse (AOR = 5.82, 95% CI:4.10-8.26), and those who had lower levels of HIV knowledge (AOR = 1.28, 95% CI:1.08-1.51), displayed higher levels of stigma against PLHIV (AOR = 1.50, 95% CI:1.26-1.77) and had ever been tested for HIV (AOR = 1.36, 95% CI:1.04-1.77) were more prone to reporting RD. Those with more enabling resources [i.e., displaying high levels of condom use self-efficacy (AOR = 0.70, 95% CI:0.59-0.84) and being knowledge of local testing center (AOR = 0.71, 95% CI:0.60-0.83)] were less likely to report RD. However, spending more than 2000 Yuan a month on basic needs (AOR = 2.55, 95% CI:2.07-3.14), residing in urban areas (AOR = 1.35, 95% CI:1.15-1.59) and being knowledgeable of the national AIDS policy (AOR = 1.40,95% CI:1.18-1.66) increased the chance of exhibiting RD. CONCLUSIONS: Comprehensive interventions, including targeting students with high-risk characteristics, improving the acceptability of PrEP and PEP, conducting health education, enhancing self-efficacy for using condoms and making opt-out HIV testing routine in college campus, should be taken to reduce the discordance between perceived and actual HIV risk and finally to reach the goal of Zero AIDS.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Masculino , Comportamento Sexual , Estudantes , UniversidadesRESUMO
Currently, no consensus exists regarding Sotos syndrome in the Chinese population. Here, we present a case of neonatal Sotos syndrome, followed by a retrospective analysis of five cases of neonatal Sotos syndrome, reported in China. The study subject was a twin premature infant, heavier than gestational age, with characteristic facial features, limb shaking, and hypertonia. Transient hypoglycemia, abnormal cranial magnetic resonance imaging, multiple nodules in polycystic kidneys and liver, abnormal hearing, patent ductus arteriosus, and an atrial septal defect were also noted. The subject showed overgrowth and developmental retardation at 3 months of age. Sequencing revealed a novel missense mutation, c.5000C>A, in the nuclear receptor binding the SET domain protein 1 gene, resulting in an alanine-to-glutamate substitution. The bioinformatics analysis suggested high pathogenicity at this site. This study provides insights into diagnosis of neonatal Sotos syndrome based on specific phenotypes. Subsequent treatment and follow-up should focus on developmental retardation, epilepsy, and scoliosis.
Assuntos
Síndrome de Sotos , Histona Metiltransferases/genética , Histona-Lisina N-Metiltransferase/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Mutação de Sentido Incorreto/genética , Proteínas Nucleares/química , Proteínas Nucleares/genética , Estudos Retrospectivos , Síndrome de Sotos/genéticaRESUMO
ZNFX1 anti-sense RNA 1 (ZFAS1) has been indicated in the tumorigenesis of various human cancers. However, the role of ZFAS1 in prostate cancer (PCa) progression and the underlying mechanisms remain incompletely understood. In the present study, we discovered that ZFAS1 is upregulated in PCa and that ZFAS1 overexpression predicted poor clinical outcomes. ZFAS1 overexpression notably promoted the proliferation, invasion, and epithelial-mesenchymal transition of PCa cells. Furthermore, we not only discovered that miR-27a/15a/16 are targeted by ZFAS1, which binds to their miRNA-response elements, but also revealed their tumor suppressor roles in PCa. We also identified that the Hippo pathway transducer YAP1, as well as its cooperator, TEAD1, are common downstream targets of miR-27a/15a/16. In addition, H3K9 demethylase KDM3A was found to be another target gene of miR-27a. Importantly, YAP1, TEAD1, and KDM3A all act as strong c-Myc inducers in an androgen-independent manner. Taken together, we suggest a regulatory network in which ZFAS1 is capable of enhancing c-Myc expression by inducing the expression of YAP1, TEAD1, and KDM3A through crosstalk with their upstream miRNAs, thereby globally promoting prostate cancer tumorigenesis.
Assuntos
Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-myc/genética , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Redes Reguladoras de Genes , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genéticaRESUMO
It is now widely recognized that carcinoma-associated fibroblasts which are believed to be myofibroblasts, promote the transformation of prostate epithelial cells to cancer cells, enhance their proliferation and invasiveness, and induce the acquisition of resistance to cancer therapy and immune evasiveness. Prostate-associated gene 4 (PAGE4) is an intrinsically disordered protein that is remarkably prostate-specific. PAGE4 is also a stress-response protein that functions as a transcriptional regulator and is upregulated in early-stage prostate cancer (PCa) and its precursor lesions. However, PAGE4 is downregulated in high-grade PCa and metastatic disease. Here, we show that PAGE4 is highly expressed in the stromal cells surrounding the cancer-adjacent "normal" glands and low-grade PCa lesions but not in lesions proximal to high-grade PCa. Overexpression of PAGE4 in a stromal cell line inhibits the migration and invasion of PCa epithelial cells in multiple coculture systems. PAGE4 overexpression also inhibits the downregulation of E-cadherin in PCa epithelial cells when cocultured with stromal cells. Furthermore, signaling via tumor necrosis factor-α and transforming growth factor-ß pathways is decreased in the stromal cells overexpressing PAGE4 suggesting that PAGE4 appears to play a protective role against disease progression by perturbing interactions between epithelial cells and stromal cells in PCa. Taken together, these findings support previous observations that upregulation of PAGE4 in PCa correlates with a better prognosis and highlight PAGE4 as a novel therapeutic target for early-stage "low-risk" disease.
Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Células Epiteliais/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/patologia , Células Estromais/patologia , Antígenos de Neoplasias/genética , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Células Epiteliais/metabolismo , Humanos , Masculino , Invasividade Neoplásica , Fosforilação , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Células Estromais/metabolismo , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Bone metastasis is the most happened metastatic event in prostate cancer (PCa) and needs a large effort in treatment. When PCa metastasizes to the bone, the new microenvironment can induce the epigenome reprogramming and stemness remodeling of cancer cells, thereby increasing the adaptability of cancer cells to the bone microenvironment, and this even leads to the occurrence of secondary tumor metastasis. Our group has previously found that RNA binding motif 3 (RBM3) affects the stem cell-like properties of PCa by interfering with alternative splicing of CD44. However, whether RBM3, as a stress-response protein, can resist microenvironmental remodeling of PCa particularly in bone metastasis remains unknown. By co-culturing PCa cells with osteoblasts to mimic PCa bone metastases, we found that RBM3 upregulates the N6-methyladenosine (m6A) methylation on the mRNA of catenin beta 1 (CTNNB1) in a manner dependent on methyltransferase 3 (METTL3), an N6-adenosine-methyltransferase complex catalytic subunit. Consequently, this modification results in a decreased stability of CTNNB1 mRNA and a followed inactivation of Wnt signaling, which ultimately inhibits the stemness remodeling of PCa cells by osteoblasts. Thus, the present study may extend our understanding of the inhibitory role of RBM3 on particularly bone metastasis of PCa.
Assuntos
Metiltransferases , Neoplasias da Próstata , Masculino , Humanos , RNA Mensageiro/genética , Metiltransferases/metabolismo , Neoplasias da Próstata/patologia , Adenosina/metabolismo , Microambiente Tumoral , Proteínas de Ligação a RNA/metabolismo , beta Catenina/metabolismoRESUMO
Recent experimental studies demonstrated playing violent video games induced denying humanness to other people and suggested that other-dehumanization might account for the effect of violent video games on aggressive behavior. However, whether long-term violent video game exposure (VVGE) correlates with other-dehumanization has not been confirmed and the role of self-dehumanization in this effect is still controversial. Thus, this study attempted to provide correlational evidence and examined direct and indirect associations of VVGE and aggressive behavior through self- or other-dehumanization in 612 adolescents. We revealed other-dehumanization was linked with VVGE and it mediated the relationship between VVGE and aggressive behavior. In addition, we did not observe the predictive effect of VVGE for self-dehumanization. Our study suggested the short-term effect of playing a violent video game on other-dehumanization, observed in previous experimental investigations, could be extended to the long-term effect of VVGE. Perceiving others as less human, but not the players themselves, accounted for the effect of VVGE on aggressive behavior.
Assuntos
Exposição à Violência , Jogos de Vídeo , Adolescente , Agressão , Desumanização , Humanos , ViolênciaRESUMO
Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is a natural herbal drug that has been widely used to treat many diseases. The antitumor effects of G. pentaphyllum were first described in the illustrated catalog of plants. Gypenosides are the major active components of G. pentaphyllum, and they have been widely reported to possess antitumor effects in prostate cancer, gastric cancer, hepatocellular carcinoma, colon cancer, lung cancer, and breast cancer. However, research on the use of gypenoside in the treatment of bladder cancer has not been conducted. In this study, we explored the potential molecular mechanisms of gypenosides in the treatment of bladder cancer using network pharmacology and experimental validation. First, we used a network pharmacology-based method to identify both the effective components of gypenosides and the molecular mechanism underlying their antibladder cancer effects. The results were further confirmed by molecular docking, CCK8 and colony formation assays, and cell cycle and cell apoptosis analyses. Additionally, a mouse xenograft model of bladder cancer was used to investigate the antitumor effect of gypenosides in vivo. We identified 10 bioactive ingredients and 163 gene targets of gypenosides. Network exploration suggested that VEGFA, STAT3, and PI3KCA may be candidate agents for the antibladder cancer effect of gypenosides. In addition, analysis of the Kyoto Encyclopedia of Genes and Genomes pathway revealed that the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway may play a crucial role in the mechanism of action of gypenosides against bladder cancer. Molecular docking revealed that gypenosides combine well with PI3K, AKT, and mTOR. As expected, gypenosides displayed apoptosis-inducing properties in bladder cancer cells by inactivating the PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, gypenosides significantly (P < 0.05) inhibited the growth of bladder cancer cells in vivo. Mechanistically, gypenosides induced the apoptosis of bladder cancer cells via inactivation of the PI3K/AKT/mTOR signaling pathway.
Assuntos
Fosfatidilinositol 3-Quinase , Neoplasias da Bexiga Urinária , Animais , Apoptose , Proliferação de Células , Gynostemma , Humanos , Masculino , Mamíferos , Camundongos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
Renal cell carcinoma (RCC) has the highest mortality rate of all urological malignancies. Clear cell renal cell carcinoma (ccRCC) accounts for approximately 80% of all RCC cases and is often accompanied by the accumulation of lipid droplets. Growing evidence indicates that ccRCC is a metabolism-related disease. Gypenosides are commonly used for the clinical treatment of hyperlipidemia, and their antitumor activity has also been recognized. However, the potential inhibitory effects and mechanisms of action of gypenoside L (Gyp L) and gypenoside LI (Gyp LI) in ccRCC remain unclear. In this study, we confirmed that Gyp L and Gyp LI significantly inhibited proliferation and induced apoptosis in ccRCC cells in vitro. We performed network pharmacology and RNA-seq, and verified the results by Western blotting, RT-qPCR, and immunofluorescence experiments. Our results demonstrated that Gyp L and Gyp LI upregulate the expression of COX2 and downregulate the expression levels of cPLA2 and CYP1A1, resulting in reduced arachidonic acid and apoptosis. Gyp L and Gyp LI upregulated the protein levels of DUSP1, p-JUN, and p-JNK, and downregulated p-MEK1/2, p-ERK, and p-P38 levels. Moreover, gypenosides significantly inhibited tumor growth in vivo, and gypenosides significantly reduced cPLA2 and CYP1A1 expression. Furthermore, we performed absolute quantification of arachidonic acid (AA) content in ccRCC cells and tumor tissues by HPLC-MS, and found that the arachidonic acid content was significantly reduced after Gyp L, Gyp LI, and gypenoside intervention. In conclusion, our data suggest that Gyp L, Gyp LI, and gypenosides decrease the content of arachidonic acid in ccRCC cells and tumor tissues, but do not have cytotoxic effects on nude mice. Thus, Gyp L, Gyp LI, and total gypenosides extracted from Gynostemma pentaphyllum exhibited antitumor activities against ccRCC.
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The lack of a standardized reliable and valid instrument makes it difficult to measure attitudes toward lesbian women and gay men (ATLG) consistently and thus poses a challenge to compare and contrast intervention measures. This study aimed to validate Herek's ATLG scale among undergraduates in mainland China and identify factors associated with negative attitudes toward LG. A total of 6,036 eligible undergraduates conveniently drawn from 30 provinces across mainland China were randomly split in half. Item analysis was first used to select unrelated or redundant items for deletion. Exploratory factor analysis (EFA) were then conducted on the first half of the sample (n = 3,001), followed by confirmatory factor analysis (CFA) and reliability analysis in the second half (n = 3035). Logistic regression analyses were finally carried out to identify their determinants. Six items were removed from the item analysis. EFA supported the existence of two factors (ATL and ATG). CFA results indicated that the two-factor model fit the data better than the one-factor model. Logistic regression analyses indicated that being female, majoring in non-health-related disciplines, attributing homosexuality to uncontrollable causes, non-adherence to traditional gender norms and exposure to homosexual content were significantly associated with less negative attitudes toward both L and G. Urban students were marginally less likely to express negative attitudes toward L but not G, while non-heterosexuals and those who had prior personal contact with homosexuals exhibited less negative attitudes toward G but not L. However, grade showed no significant associations with either ATL or ATG. The retained 14-item version of Herek's ATLG scale has been proven to be a reliable and valid tool. Furthermore, ATL and ATG were determined by different factors and thus would be treated separately. In order to reduce negative attitudes toward LG among undergraduates in mainland China, a comprehensive intervention plan such as conducting comprehensive sex education and pushing the process of legalizing same-sex marriage should be designed, implemented and evaluated.
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Renal cell carcinoma (RCC) is the most common type of kidney cancer. By analysing The Cancer Genome Atlas (TCGA) database, 16 genes were identified to be consistently highly expressed in RCC tissues compared with the matched paratumour tissues. Using a highthroughput cell viability screening method, it was found that downregulation of only two genes significantly inhibited the viability of 786O cells. Among the two genes, pleckstrin homology domain containing O1 (PLEKHO1) has never been studied in RCC, to the best of our knowledge, and its expression level was shown to be associated with the prognosis of patients with RCC in TCGA dataset. The upregulation of PLEKHO1 in RCC was first confirmed in 30 paired tumour and paratumour tissues. Then, the effect of PLEKHO1 on cell proliferation and apoptosis was assessed in vitro. Additionally, xenograft tumour models were established to investigate the function of PLEKHO1 in vivo. The results showed that PLEKHO1 knockdown significantly inhibited cell viability and facilitated apoptosis in vitro and impaired tumour formation in vivo. Thus, PLEKHO1 is likely to be associated with the viability of RCC cells in vitro and in vivo. Further gene expression microarray and coexpression analyses showed that PLEKHO1 may be involved in the serine/threonineprotein kinase hippo and JNK signalling pathways. Together, the results of the present study suggest that PLEKHO1 may contribute to the development of RCC, and therefore, further study is needed to explore its potential as a therapeutic target.
Assuntos
Carcinoma de Células Renais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Renais/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Feminino , Técnicas de Silenciamento de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Via de Sinalização Hippo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Regulação para CimaRESUMO
Renal cell carcinoma (RCC), which is one of the most diagnosed urological malignancies worldwide, is usually associated with abnormality in both genetic and cellular processes. In the present study, through analyzing The Cancer Genome Atlas (TCGA) dataset, we screened out ERCC6L as a candidate gene that is potentially related to the development of RCC based on its increased expression in ccRCC tissues compared with normal kidney tissues as well as its possible relevance to cancer prognosis. Evidence indicates that ERCC6L is an indispensable component of mammalian cell mitosis, while it fails to disclose the role of ERCC6L in tumorigenesis. By using RT-PCR, it was confirmed that the mRNA expression of ERCC6L was upregulated in RCC tissues as compared to normal controls in 28 pared samples. In addition, the immunohistochemistry study in a tissue microarray (TMA) containing 150 ccRCC samples showed that the staining score of ERCC6L was positively correlated with the Fuhrman grade of cancers. Next, when the expression of ERCC6L was lowered by specific shRNA, the cell viability was significantly inhibited in 786-O and Caki-1 cells, while the apoptosis was induced accordingly. At the same time, RCC cells those were transfected with shRNA targeting to ERCC6L grew significantly slower than parental cells in immunodeficient mice. These results consistently suggest that ERCC6L may play a role in regulating the cell viability of RCC both in vitro and in vivo. Further, gene expression microarray analysis followed by the validating western blot after knocking down ERCC6L expression in 786-O cells highlighted the involvement of MAPK signaling pathway in regulation of ERCC6L on cellular process of RCC. In conclusion, the present study suggests a likely promoting role of ERCC6L on the development of RCC. Thus, further study to explore the potential utility of ERCC6L as a novel therapeutic target of RCC is clearly needed.
Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , DNA Helicases/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Sistema de Sinalização das MAP Quinases , Animais , Apoptose/genética , Biomarcadores , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , DNA Helicases/metabolismo , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Imuno-Histoquímica , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Camundongos , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in male worldwide. Oxidative stress has been recognized as one of the driving signals pathologically linked to PCa progression. Nevertheless, the association of oxidative stress with PCa progression remains unclear. METHODS: Western blot, q-RT-PCR and bioinformatics analyses were used to examine PAGE4 expression. Comet assay and Annexin V/ PI dual staining assay were performed to investigate DNA damage and cell death under oxidative stress. Mouse xenograft model of PCa cells was established to verify the role of PAGE4 in vivo. Transcriptomic analysis was performed to investigate the underlying mechanism for the function of PAGE4 under oxidative stress. Western blot assay was conducted to determine the status of MAPK pathway. Immunohistochemistry was used to identify protein expression of PAGE4 in tumor tissues. RESULTS: In this study, we found that PAGE4 expression was increased in PCa cells under oxidative stress condition. PAGE4 overexpression protected PCa cells from oxidative stress-inducing cell death by reducing DNA damage. PAGE4 overexpression promoted PCa cells growth in vivo. Mechanistically, PAGE4 promoted the survival of prostate cancer cells through regulating MAPK pathway which reflected in decreasing the phosphorylation of MAP2K4, JNK and c-JUN but increasing phosphorylation of ERK1/2. CONCLUSION: Our findings indicate that PAGE4 protects PCa cells from DNA damage and apoptosis under oxidative stress by modulating MAPK signalling pathway. PAGE4 expression may serve as a prognostic biomarker for clinical applications.
Assuntos
Antígenos de Neoplasias/genética , Sistema de Sinalização das MAP Quinases , Estresse Oxidativo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Animais , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Expressão Gênica , Xenoenxertos , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Modelos Biológicos , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
RNAbinding motif 3 (RBM3) is a coldshock protein that has been previously shown to attenuate cancer stem celllike features in prostate cancer (PCa) cells. However, the mechanism underlying RBM3 regulation in PCa cells is largely unknown. The present study investigated the impact of RBM3 expression on the whole transcriptome of PCa cells using highthroughput RNA sequencing (RNAseq). Differentially expressed genes (DEGs) that were identified through RNAseq were applied to Gene Ontology (GO), pathway analysis, pathwayaction networks and proteinprotein interaction network analysis. GO and pathway ananlyses showed that RBM3 expression was associated with several metabolism pathways. Combining GO analysis and pathway analysis, certain DEGs, including phospholipase A2 group IIA (PLA2G2A), PLA2G2F, PLA2G4C, endothelin 1, cytochrome P450 family 2 subfamily B member 6, G protein subunit γ5, nitric oxide synthase 3 and CD38 molecule, were shown to be closely associated with RBM3 regulation in PCa cells. Furthermore, the changes in expression of selected genes upon RBM3knockdown in RNAseq were confirmed by separate reverse transcriptionquantitativepolymerase chain reaction, validating the results of RNAseq. Thus, the present study provides a series of valuable reference genes and pathways for the future study of the pathogenic role of RBM3 in the development of PCa.