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1.
Exp Ther Med ; 22(6): 1480, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34765021

RESUMO

Fluorescence in situ hybridization (FISH) serves as an ancillary tool for assessing chromosomal abnormalities and is important in differential diagnoses and treatment decisions. In clinical practice, pathologists encounter unsatisfactory formalin-fixed paraffin-embedded (FFPE) sections exhibiting weak fluorescence signals, mostly due to inappropriate tissue processing or preservation, leading to interpretation difficulties. For the present study, FFPE samples for which conventional FISH failed were collected. Instead of a pretreatment step using a commercial kit, heat-induced antigen retrieval (HIAR) was introduced using either citrate buffer or Tris-EDTA buffer, while the subsequent experimental workflow remained unchanged. After HIAR-assisted FISH, the hybridization efficiency and signal intensity were markedly enhanced and no difference in signal adequacy was observed when comparing the effect of the two AR solutions. The present study demonstrated that HIAR is a reliable tool for FISH, particularly for poor-quality FFPE sections yielding weak or no fluorescence signals in the conventional analysis.

2.
Biomed Pharmacother ; 143: 112200, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649342

RESUMO

The pathology of cerebrovascular disorders takes an important role in traumatic brain injury (TBI) by increasing intracranial pressure. Fibroblast growth factor 20 (FGF20) is a brain-derived neurotrophic factor, that has been shown to play an important role in the survival of dopaminergic neurons and the treatment of Parkinson's disease (PD). However, little is known about the role of FGF20 in the treatment of TBI and its underlying mechanism. The purpose of this study was to evaluate the protective effect of recombinant human FGF20 (rhFGF20) on protecting cerebral blood vessels after TBI. In this study, we indicated that rhFGF20 could reduce brain edema, Evans blue penetration and upregulated the expression of blood-brain barrier (BBB)-related tight junction (TJ) proteins, exerting a protective effect on the BBB in vivo after TBI. In the TBI repair phase, rhFGF20 promoted angiogenesis, neurological and cognitive function recovery. In tumor necrosis factor-α (TNF-α)-induced human brain microvascular endothelial cells (hCMEC/D3), an in vitro BBB disruption model, rhFGF20 reversed the impairment in cell migration and tube formation induced by TNF-α. Moreover, in both the TBI mouse model and the in vitro model, rhFGF20 increased the expression of ß-catenin and GSK3ß, which are the two key regulators in the Wnt/ß-catenin signaling pathway. In addition, the Wnt/ß-catenin inhibitor IWR-1-endo significantly reversed the effects of rhFGF20. These results indicate that rhFGF20 may prevent vascular repair and angiogenesis through the Wnt/ß-catenin pathway.

3.
Syst Rev ; 10(1): 277, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34702347

RESUMO

BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by HIV in China. Globally, younger MSM are at higher risk for incident HIV infections, but there has been substantial variation in the estimates of age-stratified HIV incidence among MSM in mainland China, potentially due to regional differences in the nature of the epidemic. Given the need for quality epidemiological data to meet the global goal of ending new HIV infections by 2030, this systematic review and meta-analysis aims to determine age-stratified HIV incidence in mainland China, including consideration by geographic region and time. METHODS: This review will include longitudinal studies, cross-sectional surveys, and surveillance reports among MSM in mainland China that have reported HIV incidence. We will search studies and reports published from January 1, 2003, to April 30, 2020, in both English and Chinese language literature databases. For each study considered, two reviewers will independently screen, determine eligibility, and extract relevant data, with discrepancies resolved by consensus of a third reviewer. The methodological quality of included studies will be assessed by the Quality Assessment Tool for Systematic Reviews of Observational Studies Score (QATSO). We will develop age-stratified estimates of HIV incidence with geographic variations and temporal trends. Heterogeneity will be examined using statistical techniques appropriate to the dataset. For subgroup analyses, we will conduct mixed-effects meta-analysis models. DISCUSSION: This review will contribute to a better understanding of the HIV epidemic among MSM in mainland China by providing age-stratified estimates of HIV incidence with a portrayal of geographic and temporal variations. Findings will reflect epidemic dynamics, informing local and national intervention programs and policies for HIV prevention, and providing estimation data to inform future research among MSM in China. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID 154834.

4.
AIDS Care ; : 1-10, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34369230

RESUMO

Young Black men who have sex with men (YBMSM) bear a disproportionate burden of HIV, and HIV pre-exposure prophylaxis (PrEP) uptake has been slow. Decisions regarding PrEP initiation change in different life contexts over time. Our YBMSM cohort study found about 1/3 of those who initially declined PrEP subsequently changed and initiated PrEP care. This study explores the process of their PrEP decision changes. The study interviewed participants who initially voiced strong and clear reservations about PrEP, but subsequently started PrEP 1-14 months later. In "review/renew" follow-up interviews, participants reviewed their past statements from a time they declined PrEP, and renew their understanding regarding perspective and behavioral change. Analyzing the data with a positive deviance framework, we found that shifting the decisional balance in favor of PrEP initiation only required change in some areas. There were not consistent factors that prevented or facilitated PrEP uptake. Instead, YBMSM initiated PrEP while maintaining an array of substantial reservations. PrEP initiation discussions should be viewed by health practitioners as a longitudinal process, and routine PrEP offers should be made over time. To optimally facilitate PrEP use among YBMSM, the diverse benefits of PrEP should be emphasized rather than focusing on allaying all concerns.

5.
J Med Internet Res ; 23(6): e24303, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061035

RESUMO

BACKGROUND: Social network-based strategies can expand HIV/syphilis self-tests among men who have sex with men (MSM). Sexual health influencers are individuals who are particularly capable of spreading information about HIV and other sexually transmitted infections (STIs) within their social networks. However, it remains unknown whether a sexual health influencer can encourage their peers to self-test for HIV/syphilis. OBJECTIVE: The aims of this study were to examine the impact of MSM sexual health influencers on improving HIV/syphilis self-test uptake within their social networks compared to that of nonsexual health influencers. METHODS: In Zhuhai, China, men 16 years or older, born biologically male, who reported ever having had sex with a man, and applying for HIV/syphilis self-tests were enrolled online as indexes and encouraged to distribute self-tests to individuals (alters) in their social network. Indexes scoring >3 on a sexual health influencer scale were considered to be sexual health influencers (Cronbach α=.87). The primary outcome was the mean number of alters encouraged to test per index for sexual health influencers compared with the number encouraged by noninfluencers. RESULTS: Participants included 371 indexes and 278 alters. Among indexes, 77 (20.8%) were sexual health influencers and 294 (79.2%) were noninfluencers. On average, each sexual health influencer successfully encouraged 1.66 alters to self-test compared to 0.51 alters encouraged by each noninfluencer (adjusted rate ratio 2.07, 95% CI 1.59-2.69). More sexual health influencers disclosed their sexual orientation (80.5% vs 67.3%, P=.02) and were community-based organization volunteers (18.2% vs 2.7%, P<.001) than noninfluencers. More alters of sexual health influencers came from a rural area (45.5% vs 23.8%, P<.001), had below-college education (57.7% vs 37.1%, P<.001), and had multiple casual male sexual partners in the past 6 months (25.2% vs 11.9%, P<.001). CONCLUSIONS: Being a sexual health influencer was associated with encouraging more alters with less testing access to self-test for HIV/syphilis. Sexual health influencers can be engaged as seeds to expand HIV/syphilis testing coverage.


Assuntos
Infecções por HIV , Saúde Sexual , Minorias Sexuais e de Gênero , Sífilis , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Parceiros Sexuais , Inquéritos e Questionários , Sífilis/diagnóstico , Sífilis/epidemiologia
6.
Psychopharmacology (Berl) ; 238(9): 2543-2553, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34046717

RESUMO

BACKGROUND: Olanzapine (OLZ) is one of the most effective atypical antipsychotics but is associated with severe metabolic side effects, in which the gut microbiota plays an important role. Akkermansia muciniphila (A. muciniphila; Akk), a Gram-negative anaerobic bacterium in the intestine, can potentially improve metabolic syndrome. OBJECTIVE: This study investigated the effect and underlying mechanisms of an A. muciniphila subtype (A. muciniphilasub; Akksub) on OLZ-induced metabolic dysfunction in lean and obese mice. METHODS: C57BL/6 female mice were fed a high-fat diet to induce obesity or normal chow for 8 weeks before OLZ treatment for 16 weeks. During the treatment period, mice in each group were orally administrated A. muciniphilasub. Weight gain, glucose and lipid metabolism, and inflammation were evaluated. RESULTS: A. muciniphilasub decreased OLZ-related weight gain only at week 16 in lean mice and significantly alleviated OLZ-induced hyperglycemia irrespective of diet. This was accompanied by reduced levels of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK)-key enzymes in hepatic gluconeogenesis-and OLZ-associated insulin resistance. Moreover, OLZ-induced increases in serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were improved by A. muciniphilasub in both obese and lean mice. OLZ did not increase serum lipid levels or hepatic fat accumulation. CONCLUSIONS: A. muciniphilasub improves OLZ-related hyperglycemia via regulation of G6Pase and PEPCK levels and insulin resistance. Moreover, A. muciniphilasub alleviates systemic inflammation caused by OLZ. A. muciniphilasub is a promising probiotic treatment for OLZ-induced metabolic dysfunction.


Assuntos
Antipsicóticos , Síndrome Metabólica/tratamento farmacológico , Probióticos , Akkermansia , Animais , Composição de Bases , Feminino , Glucose , Homeostase , Síndrome Metabólica/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Olanzapina , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA
7.
Front Pharmacol ; 12: 671131, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967812

RESUMO

Stroke is the leading cause of death worldwide, and its treatment remains a challenge. Complex pathological processes are involved in stroke, which causes a reduction in the supply of oxygen and energy to the brain that triggers subsequent cascade events, such as oxidative stress, inflammatory responses and apoptosis, resulting in brain injury. Stroke is a devastating disease for which there are few treatments, but physical rehabilitation can help improve stroke recovery. Although there are very few treatments for stroke patients, the discovery of fibroblast growth factors (FGFs) in mammals has led to the finding that FGFs can effectively treat stroke in animal models. As presented in this review, FGFs play essential roles by functioning as homeostatic factors and controlling cells and hormones involved in metabolism. They could be used as effective therapeutic agents for stroke. In this review, we will discuss the pharmacological actions of FGFs on multiple targets, including their ability to directly promote neuron survival, enhance angiogenesis, protect against blood-brain barrier (BBB) disruption, and regulate microglial modulation, in the treatment of ischemic stroke and their theoretical mechanisms and actions, as well as the therapeutic potential and limitations of FGFs for the clinical treatment of stroke.

9.
Hepatology ; 74(2): 835-846, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33462854

RESUMO

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is a prototypical organ-specific autoimmune disease that is mediated by autoreactive T-cell attack and destruction of cholangiocytes. Despite the clear role of autoimmunity in PBC, immune-directed therapies have failed to halt PBC, including biologic therapies effective in other autoimmune diseases. MicroRNA (miRNA) dysregulation is implicated in the pathogenesis (PBC). In the dominant-negative TGF-ß receptor type II (dnTGFßRII) mouse model of PBC, autoreactive CD8 T cells play a major pathogenic role and demonstrate a striking pattern of miRNA down-regulation. Enoxacin is a small molecule fluoroquinolone that enhances miRNA biogenesis, partly by stabilizing the interaction of transactivation response RNA-binding protein with Argonaute (Ago) 2. APPROACH AND RESULTS: We hypothesized that correcting aberrant T-cell miRNA expression with enoxacin in dnTGFßRII mice could modulate autoreactive T-cell function and prevent PBC. Here, we show that liver-infiltrating dnTGFßRII CD8 T cells have significantly decreased levels of the miRNA biogenesis molecules prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and Ago2 along with significantly increased levels of granzyme B and perforin. Enoxacin treatment significantly up-regulated miRNAs in dnTGFßRII CD8 T cells and effectively treated autoimmune cholangitis in dnTGFßRII mice. Enoxacin treatment directly altered T cells both ex vivo and in vitro, resulting in altered memory subset numbers, decreased proliferation, and decreased interferon-γ production. Enoxacin significantly decreased CD8 T-cell expression of the transcription factor, Runx3, and significantly decreased perforin expression at both the mRNA and protein levels. CONCLUSIONS: Enoxacin increases miRNA expression in dnTGFßRII CD8 T cells, reduces CD8 T-cell pathogenicity, and effectively halted progression of autoimmune biliary disease. Targeting the miRNA pathway is a therapeutic approach to autoimmunity that corrects pathological miRNA abnormalities in autoreactive T cells.

10.
HIV Med ; 22(6): 467-477, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33511687

RESUMO

OBJECTIVES: An intervention developed through participatory crowdsourcing methods increased HIV self-testing among men who have sex with men [MSM; relative risk (RR) = 1.89]. We estimated the long-term impact of this intervention on HIV transmission among MSM in four cities (Guangzhou, Shenzhen, Jinan and Qingdao). METHODS: A mathematical model of HIV transmission, testing and treatment among MSM in China was parameterized using city-level demographic and sexual behaviour data and calibrated to HIV prevalence, diagnosis and antiretroviral therapy (ART) coverage data. The model was used to project the HIV infections averted over 20 years (2016-2036) from the intervention to increase self-testing, compared with current testing rates. RESULTS: Running the intervention once would avert < 2.2% infections over 20 years. Repeating the intervention (RR = 1.89) annually would avert 6.4-10.7% of new infections, while further increases in the self-testing rate (hypothetical RR = 3) would avert 11.7-20.7% of new infections. CONCLUSIONS: Repeated annual interventions would give a three- to seven-fold increase in long-term impact compared with a one-off intervention. Other interventions will be needed to more effectively reduce the HIV burden in this population.

11.
Clin Infect Dis ; 73(7): e2251-e2257, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32588883

RESUMO

BACKGROUND: Social media and secondary distribution (distributing self-testing kits by indexes through their networks) both show strong promise to improve human immunodeficiency virus (HIV) self-testing uptake. We assessed an implementation program in Zhuhai, China, which focused on the secondary distribution of HIV/syphilis self-test kits among men who have sex with men (MSM) via social media. METHODS: Men aged ≥16 years, born biologically male, and ever had sex with another man were recruited as indexes. Banner ads on a social media platform invited the participants to apply for up to 5 self-test kits every 3 months. Index men paid a deposit of US$15/kit refundable upon submitting a photograph of a completed test result via an online submission system. They were informed that they could distribute the kits to others (referred to as "alters"). RESULTS: A total of 371 unique index men applied for 1150 kits (mean age, 28.7 [standard deviation, 6.9] years), of which 1141 test results were returned (99%). Among them, 1099 were valid test results; 810 (74%) were from 331 unique index men, and 289 tests (26%) were from 281 unique alters. Compared to index men, a higher proportion of alters were naive HIV testers (40% vs 21%; P < .001). The total HIV self-test reactivity rate was 3%, with alters having a significantly higher rate than indexes (5% vs 2%; P = .008). A total of 21 people (3%) had a reactive syphilis test result. CONCLUSIONS: Integrating social media with the secondary distribution of self-test kits may hold promise to increase HIV/syphilis testing coverage and case identification among MSM.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Mídias Sociais , Sífilis , Adulto , China/epidemiologia , HIV , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Programas de Rastreamento , Autoteste , Sífilis/diagnóstico , Sífilis/epidemiologia
12.
Haematologica ; 106(5): 1381-1389, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32273477

RESUMO

Mantle cell lymphoma (MCL) with MYC rearrangement (MYC-R) is rare and little is known about the importance of MYC extra copies (EC) in the absence of MYC-R in MCL patients. This study includes 88 MCL patients with MYC tested by fluorescence in situ hybridization and/or conventional cytogenetics, including 27 with MYC-R, 21 with MYC-EC, and 40 with normal (NL) MYC. MCL patients with MYC-R more often had blastoid/pleomorphic morphology; a higher frequency of CD10, MYC, and simultaneous MYC and BCL2 expression; a higher level of MYC; and a higher Ki67 proliferation rate (p<0.05) than those without MYC-R. Although patients with MYC-R more frequently received aggressive chemotherapy (p=0.001), their overall survival (OS) was significantly shorter than those without MYC-R. Compared with patients with MYC/BCL2 double hit lymphoma (DHL), patients with MYC-R MCL had a similar OS but more commonly had bone marrow involvement, stage 4 disease, and a different immunophenotype. MCL patients with MYC-EC showed an OS intermediate between those with MYC-R and MYC-NL, either all or only blastoid/pleomorphic MCL patients included. Multivariate analysis showed that MYC-R, but not MYC-EC, had an independent and negative impact on OS. In conclusion, MYC-R but not MYC-EC showed a higher MYC expression and is an adverse prognostic factor for MCL patients. Although the OS of MCL patients with MYC-R is similar to that of MYC/BCL2 DHL patients, these groups have different clinicopathologic features supporting the retention of MCL with MYC-R in the category of MCL, as recommended in the revised World Health Organization classification.


Assuntos
Linfoma de Células B , Linfoma Difuso de Grandes Células B , Linfoma de Célula do Manto , Adulto , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Linfoma de Células B/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética
13.
Viruses ; 12(10)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007975

RESUMO

Grapevine leafroll-associated virus 1 (GLRaV-1) is a major pathogen associated with grapevine leafroll disease. However, the molecular mechanisms underlying GLRaV-1 interactions with plant cells are unclear. Using Agrobacterium infiltration-mediated RNA-silencing assays, we demonstrated that GLRaV-1 p24 protein (p24G1) acts as an RNA-silencing suppressor (RSS), inhibiting local and systemic RNA silencing. Electrophoretic mobility shift assays showed that p24G1 binds double-stranded 21-nucleotide small interfering RNA (siRNA), and that siRNA binding is required but not sufficient for its RSS activity. p24G1 localizes in the nucleus and can self-interact through its amino acid 10 to 210 region. Dimerization is needed for p24G1 interaction with importin α1 before moving to the nucleus, but is not required for its siRNA binding and RSS activity. Expression of p24G1 from a binary pGD vector or potato virus X-based vector elicited a strong hypersensitive response in Nicotiana species, indicating that p24G1 may be a factor in pathogenesis. Furthermore, p24G1 function in pathogenesis required its RSS activity, dimerization and nuclear localization. In addition, the region of amino acids 122-139 played a crucial role in the nuclear import, siRNA binding, silencing suppression and pathogenic activity of p24G1. These results contribute to our understanding of the molecular mechanisms underlying GLRaV-1 infection.


Assuntos
Closteroviridae/genética , Necrose/metabolismo , Interferência de RNA/fisiologia , Tabaco/virologia , Agrobacterium/genética , Closteroviridae/patogenicidade , Necrose/virologia , Doenças das Plantas/virologia , Folhas de Planta/metabolismo , Folhas de Planta/virologia , Potexvirus/genética , RNA Interferente Pequeno/metabolismo
14.
BMC Infect Dis ; 20(1): 732, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028241

RESUMO

BACKGROUND: Adolescent sexual debut and non-consensual sex have been linked to higher sexual risk and STI infection in adulthood among men who have sex with men (MSM) in high-income countries. This study aimed to examine adolescent and non-consensual anal sexual debut among Chinese MSM and to evaluate factors associated with adolescent sexual debut and non-consensual anal sex. METHODS: A cross-sectional study was conducted recently among Chinese men assigned male sex at birth, ≥18 years old, and who had ever engaged in anal sex with a man. Participants answered questions regarding socio-demographics, condomless sex, age at anal sexual debut with a man, and whether the first anal sex was consensual. Factors associated with an adolescent sexual debut (< 18 years old) and non-consensual sex at sexual debut were evaluated. We defined adolescent sexual debut as having anal sex with another man at 17 years old or younger, and the participants were asked whether their first male-to-male anal sex was non-consensual. RESULTS: Overall, 2031 eligible men completed the survey. The mean age of sexual debut was 20.7 (SD = 4.3) years old. 17.6% (358/2031) of men reported adolescent sexual debut, and 5.0% (101/2031) reported a non-consensual sexual debut. The adolescent sexual debut was associated with having more male sexual partners (adjusted OR 1.10, 95% CI 1.06-1.15) and condomless anal sex in the last three months (AOR = 1.71, 95% CI 1.34-2.18). MSM whose sexual debut was non-consensual were more likely to have condomless anal sex (AOR = 1.76, 95% CI 1.17-2.66), and to have reported an adolescent sexual debut (AOR = 2.72, 95% CI 1.75-4.21). CONCLUSIONS: Many Chinese MSM reported adolescent sexual debut and non-consensual sex, both of which are associated with sexual risk behaviors and drive STI transmission. These findings highlight the need for designing tailored interventions for MSM who experienced adolescent sexual debut and non-consensual sex at debut.


Assuntos
Homossexualidade Masculina/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Adolescente , Adulto , China , Preservativos , Estudos Transversais , Infecções por HIV/patologia , Humanos , Masculino , Razão de Chances , Assunção de Riscos , Inquéritos e Questionários , Adulto Jovem
15.
Ann Surg Treat Res ; 99(2): 118-126, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32802817

RESUMO

Purpose: This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. Methods: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. Results: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients' age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. Conclusion: The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

16.
BMC Cancer ; 20(1): 816, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854650

RESUMO

BACKGROUND: Recently, copy number alteration (CNA) of 9p24.1 were demonstrated in 10% of diffuse large b-cell lymphoma (DLBCL), with gene expression and mutation profiles that were similar to those of primary mediastinal large B-cell lymphoma (PMBCL). However, their CNA-based profile and clinical impact still remain unclear. METHODS: Multiplex ligation-dependent probe amplification were employed to investigate the prevalence of JAK2/PD-L2 amplification in DLBCL and their CNA-based pattern of driver genes. The clinical outcome and characteristics were also analyzed. RESULTS: Using unsupervised hierarchical clustering, a small group of DLBCL (10.5%, 8/76) was clustered together with PMBCL as Cluster_2, demonstrating amplification of JAK2 (100%,8/8) and PD-L2 (75.0%,6/8). This subgroups of DLBCL demonstrated significant higher expression of PD-L1 than those with MYD88 L265P mutation(p = 0.024). And they exhibited dismal OS and PFS as compared with DLBCL_others(p = 0.003 and 0.001, respectively), which is similar to DLBCL with MYD88 L265P mutation. CONCLUSIONS: DLBCL with amplification of JAK2/PD-L2 exhibits CNA pattern that is similar to PMBCL, and demonstrates unfavorable clinical outcome that resembles those with MYD88 L265P mutation. It is essential to identify this subgroup of DLBCL who may acquire more benefits from the JAK2 and PD-L1 signaling inhibition.


Assuntos
Variações do Número de Cópias de DNA , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Janus Quinase 2/genética , Linfoma Difuso de Grandes Células B/genética , Neoplasias do Mediastino/genética , Fator 88 de Diferenciação Mieloide/genética , Proteína 2 Ligante de Morte Celular Programada 1/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Feminino , Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Adulto Jovem
17.
BMC Complement Med Ther ; 20(1): 236, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711521

RESUMO

BACKGROUND: Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human ß-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. METHODS: The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. RESULTS: Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris, Actinidia arguta, Robinia pseudoacacia, and Amygdalus persica. One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC50 from 292.0 to 673.9 µg mL- 1. Fourteen samples presented potent inhibitory activity against human BACE1 with EC50 from 236.0 to 881.1 µg mL- 1. All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC50 from 2.7 to 14.4 mg mL- 1, 0.9 to 12.7 mg mL- 1, 5.0 to > 25 mg mL- 1, 2.7 to 17.7 mg mL- 1, and 2.4 to 8.7 mg mL- 1, respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. CONCLUSION: Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production.


Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Pólen , Acetilcolinesterase/metabolismo , Animais , Apiterapia , Abelhas , Linhagem Celular Tumoral , Humanos , República da Coreia
18.
J Biol Chem ; 295(31): 10726-10740, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32532820

RESUMO

Mediator complex subunit 16 (MED16) is a component of the mediator complex and functions as a coactivator in transcriptional events at almost all RNA polymerase II-dependent genes. In this study, we report that the expression of MED16 is markedly decreased in papillary thyroid cancer (PTC) tumors compared with normal thyroid tissues. In vitro, MED16 overexpression in PTC cells significantly inhibited cell migration, enhanced sodium/iodide symporter expression and iodine uptake, and decreased resistance to radioactive 131I (RAI). Conversely, PTC cells in which MED16 had been further knocked down (MED16KD) exhibited enhanced cell migration, epithelial-mesenchymal transition, and RAI resistance, accompanied by decreased sodium/iodide symporter levels. Moreover, cell signaling through transforming growth factor ß (TGF-ß) was highly activated after the MED16 knockdown. Similar results were obtained in MED12KD PTC cells, and a co-immunoprecipitation experiment verified interactions between MED16 and MED12 and between MED16 and TGF-ßR2. Of note, the application of LY2157299, a potent inhibitor of TGF-ß signaling, significantly attenuated MED16KD-induced RAI resistance both in vitro and in vivo In conclusion, our findings indicate that MED16 reduction in PTC contributes to tumor progression and RAI resistance via the activation of the TGF-ß pathway.


Assuntos
Radioisótopos do Iodo/farmacologia , Complexo Mediador/metabolismo , Proteínas de Neoplasias/metabolismo , Tolerância a Radiação , Transdução de Sinais , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Complexo Mediador/genética , Camundongos , Camundongos Nus , Proteínas de Neoplasias/genética , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia
19.
Lancet Infect Dis ; 20(8): 976-982, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32530426

RESUMO

BACKGROUND: WHO recommends that men who have sex with men (MSM) receive gonorrhoea and chlamydia testing, but many evidence-based preventive services are unaffordable. The pay-it-forward strategy offers an individual a gift (eg, a test for sexually transmitted diseases) and then asks whether they would like to give a gift (eg, a future test) to another person. This study examined the effectiveness of a pay-it-forward programme to increase gonorrhoea and chlamydia testing among MSM in China. METHODS: We did a randomised controlled superiority trial at three HIV testing sites run by MSM community-based organisations in Guangzhou and Beijing, China. We included MSM aged 16 years or older who were seeking HIV testing and met indications for gonorrhoea and chlamydia testing. Restricted randomisation was done using computer-generated permuted blocks. 30 groups were randomised into three arms (1:1:1): a pay-it-forward arm in which men were offered free gonorrhoea and chlamydia testing and then asked whether they would like to donate for testing of prospective participants, a pay-what-you-want arm in which men were offered free testing and given the option to pay any desired amount for the test, and a standard-of-care arm in which testing was offered at ¥150 (US$22). There was no masking to arm assignment. The primary outcome was gonorrhoea and chlamydia test uptake ascertained by administrative records. We used generalised estimating equations to estimate intervention effects with one-sided 95% CIs and a prespecified superiority margin of 20%. The trial is registered with ClinicalTrials.gov, NCT03741725. FINDINGS: Between Dec 8, 2018, and Jan 19, 2019, 301 men were recruited and included in the analysis. 101 were randomly assigned to the pay-it-forward group, 100 to the pay-what-you-want group, and 100 to the standard-of-care group. Test uptake for gonorrhoea and chlamydia was 56% (57 of 101 participants) in the pay-it-forward arm, 46% (46 of 100 participants) in the pay-what-you-want arm, and 18% (18 of 100 participants) in the standard-of-care arm. The estimated difference in test uptake between the pay-it-forward and standard-of-care group was 38·4% (95% CI lower bound 28·4%). Among men in the pay-it-forward arm, 54 of 57 (95%) chose to donate to support testing for others. INTERPRETATION: The pay-it-forward strategy can increase gonorrhoea and chlamydia testing uptake among Chinese MSM and could be a useful tool for scaling up preventive services that carry a mandatory fee. FUNDING: US National Institute of Health; Special Programme for Research and Training in Tropical Diseases, sponsored by UNICEF, UNDP, World Bank, and WHO; the National Key Research and Development Program of China; Doris Duke Charitable Foundation; and Social Entrepreneurship to Spur Health.


Assuntos
Infecções por Chlamydia/epidemiologia , Gonorreia/epidemiologia , Homossexualidade Masculina , Reembolso de Seguro de Saúde , Doenças Sexualmente Transmissíveis/epidemiologia , Adulto , China/epidemiologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Testes Diagnósticos de Rotina , Gonorreia/diagnóstico , Gonorreia/microbiologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doenças Sexualmente Transmissíveis/diagnóstico , Doenças Sexualmente Transmissíveis/microbiologia , Fatores Socioeconômicos , Adulto Jovem
20.
Int J Behav Med ; 27(5): 602-608, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32415590

RESUMO

BACKGROUND: In China, men who have sex with men (MSM) shoulder a disproportionate HIV burden. Early initiation and adherence to HIV antiretroviral therapy (ART) will be critical to reversing the HIV epidemic in China, but ART usage remains suboptimal among MSM diagnosed with HIV. One understudied but potentially important factor underpinning suboptimal ART usage is personal belief in supernatural explanatory models of health and illness (supernatural explanatory models). This study examines associations between beliefs in supernatural explanatory models and ART usage among MSM in China. METHOD: In 2017, an online survey was distributed nationwide throughout China by gay community-based organizations. Eligible study participants were self-identified MSM between 16 and 30 years old who had tested positive for HIV and who had seen a doctor in the last 2 years. Beliefs in supernatural explanatory models were measured using a three-item scale developed specifically for the Chinese population (range, 3-15). RESULTS: Of 73 participants, the majority were currently using ART (83.6%) and 42.5% expressed some endorsement of belief in supernatural explanatory models. However, among 21 participants with the strongest belief in supernatural explanatory models, prevalence of current ART usage was 61.9%. Stronger belief in supernatural explanatory models was significantly associated with lower likelihood of current ART usage (adjusted odds ratio = 0.52; 95% confidence interval = 0.13-0.75). CONCLUSION: Belief in supernatural explanatory models may be a powerful predictor of ART usage among MSM living with HIV in China. Further studies are needed to corroborate these findings and elucidate mechanisms of association.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Adolescente , Adulto , Antirretrovirais/uso terapêutico , China/epidemiologia , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Adulto Jovem
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