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1.
Artigo em Inglês | MEDLINE | ID: mdl-32197386

RESUMO

This study examined the factors related to the preference about laws to legalize same-sex relationships in participants of the first wave of a survey (Wave 1, 23 months before the same-sex marriage referendum) and the second wave of a survey (Wave 2, 1 week after the same-sex marriage referendum) in Taiwan. The data of 3286 participants in Wave 1 and 1370 participants in Wave 2 recruited through a Facebook advertisement were analyzed. Each participant completed an online questionnaire assessing their attitude toward the legal recognition of same-sex relationships, preference about laws to legalize same-sex relationships (establishing same-sex couple laws outside the Civil Code vs. changing the Civil Code to include same-sex marriage laws), belief in the importance of legalizing same-sex relationships, and perceived social attitudes toward the legal recognition of same-sex relationships. The results revealed that those who did not support legalizing same-sex relationships were more likely to prefer establishing same-sex couple laws outside the Civil Code than those who supported the legalization. The form of law preferred to legalize same-sex relationships significantly changed between Wave 1 and Wave 2. Multiple factors, including gender, age, sexual orientation, belief in the importance of legalizing same-sex relationships to human rights and the social status of sexual minorities, and perceived peers' and families' attitudes toward the legal recognition of same-sex relationships, were significantly associated with the preference of laws, although these associations varied among heterosexual and non-heterosexual participants and at various stages of the survey.

2.
N Engl J Med ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187464

RESUMO

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).

3.
Artigo em Inglês | MEDLINE | ID: mdl-32143281

RESUMO

The aim of this survey study was to examine the etiologies of attention-deficit/hyperactivity disorder (ADHD) attributed by caregivers of Taiwanese children with ADHD, particularly factors affecting such attribution. This study had 400 caregivers of children with ADHD as participants. We examined the caregiver-attributed etiologies of ADHD and factors affecting such attribution. Caregivers completed the self-report questionnaire to rate how likely they perceived various etiologies of ADHD to be; the Affiliate Stigma Scale for the level of affiliate stigma; and the short Chinese version of the Swanson, Nolan, and Pelham, Version IV Scale for child's ADHD and oppositional symptoms. Brain dysfunction (84.8%) was the most commonly attributed etiology, followed by failure of caregivers in disciplining the child (44.0%); a poor diet, such as a sugar-rich diet (40.8%); a poor living environment (38.8%); the child imitating their peers' improper behavior (37.3%); failure of school staff in disciplining the child (29.0%); the education system's overemphasis on academic performance (27.3%); and supernatural beings or divination-based reasons (3.8%). Caregivers' affiliate stigma was significantly associated with the attribution of several nonbiological etiologies other than brain dysfunction. Caregivers' education level and children's sex, hyperactivity/impulsivity, and oppositional symptoms were significantly associated with various caregiver-attributed etiologies. Therefore, to deliver more accurate knowledge about ADHD in educational programs, health professionals should consider those etiologies that are attributed by caregivers of children with ADHD.

4.
Pharmacol Res ; 155: 104755, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173585

RESUMO

Stachydrine is extracted from the leaves of Leonurus japonicus Houtt (or Motherwort, "Yi Mu Cao" in Traditional Chinese Medicine) and is the major bioactive ingredient. So far, stachydrine has demonstrated various bioactivities for the treatment of fibrosis, cardiovascular diseases, cancers, uterine diseases, brain injuries, and inflammation. The pharmacological and pharmacokinetic properties of stachydrine up to 2019 have been comprehensively searched and summarized. This review provides an updated summary of recent studies on the pharmacological activities of stachydrine. Many studies have demonstrated that stachydrine has strong anti-fibrotic properties (on various types of fibrosis) by inhibiting ECM deposition and decreasing inflammatory and oxidative stress through multiple molecular mechanisms (including TGF-ß, ERS-mediated apoptosis, MMPs/TIMPs, NF-κB, and JAK/STAT). The cardioprotective and vasoprotective activities of stachydrine are related to its inhibition of ß-MHC, excessive autophagy, SIRT1, eNOS uncoupling and TF, promotion of SERCA, and angiogenesis. In addition to its anticancer action, regulation of the uterus, neuroprotective effects, etc. the pharmacokinetic properties of stachydrine are also discussed.

5.
Plant Dis ; : PDIS10192158RE, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32155113

RESUMO

Since the 2000s, production of pitahaya (Hylocereus spp.) has increased significantly in South Florida. However, very limited information is available on the main diseases affecting this crop, particularly in regard to disease epidemiology and economic impact on the commodity. In this study, we surveyed five local pitahaya orchards and documented the most prevalent diseases and their causal agents. Three genera of fungal pathogens (Neoscytalidium, Alternaria, and Colletotrichum) were the major groups associated with symptoms on pitahaya cladodes (stems) during the early growing season. Among these, N. dimidiatum was identified as the most prevalent pathogen, with an overall isolation frequency of 29.8% (range, 13.9 to 47.2%). Hence, the temporal progress of N. dimidiatum stem canker infection was monitored and the relationship between stem canker intensity (incidence and severity) and fruit canker incidence was investigated. A significant positive correlation was found between fruit canker incidence and the standardized area under the disease incidence or severity curve on cladodes, suggesting that high stem canker intensity in the early season may contribute to high fruit canker incidence and thereby impact the aesthetic and market value of fruits. In vitro assays showed that both conidial germination and mycelial growth of N. dimidiatum are positively correlated with increasing temperature, with a maximum growth area at 32°C. This finding suggests a higher risk of infection, under an environment with high temperatures, which is common in South Florida. Data obtained in this study represent baseline knowledge for the future development of integrative management programs for controlling major diseases of pitahaya in South Florida.

6.
Pathol Res Pract ; : 152853, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139259

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) TMPO antisense RNA 1 (TMPO-AS1) is reported to be oncogenic in prostate cancer and lung cancer. This study aims to investigate the expression and biological function of it in retinoblastoma (RB), and explore its regulatory role for miR-199a-5p and hypoxia-inducible factor-1α (HIF-1α). METHODS: Paired RB samples were collected, and the expression levels of TMPO-AS1, miR-199a-5p and HIF-1α were examined by quantitative real-time polymerase chain reaction (qRT-PCR); TMPO-AS1 overexpressing plasmids and TMPO-AS1 shRNA were transfected into HXO-RB44 and SO-Rb50 cell lines respectively, and then proliferation, migration and invasion of RB cells were detected by CCK-8 assay and Transwell method. qRT-PCR and western blot were used to analyze the regulatory function of TMPO-AS1 on miR-199a-5p and HIF-1α; luciferase reporter gene assay was used to determine the regulatory relationship between miR-199a-5p and TMPO-AS1. RESULTS: TMPO-AS1 was significantly up-regulated in cancerous tissues of RB samples (relatively expression: 2.97 vs 3.93, p < 0.001), negatively correlated with miR-199a-5p (r=-0.4813, p < 0.01). There was one binding site on TMPO-AS1 for miR-199a-5p. After transfection of TMPO-AS1 shRNAs into RB cells, the proliferation, migration and invasion of cancer cells was significantly inhibited, while TMPO-AS1 had opposite effects; TMPO-AS1 was also demonstrated to regulate the expression of HIF-1α on both mRNA and protein levels via negatively regulating miR-199a-5p. CONCLUSION: TMPO-AS1 is abnormally up-regulated in RB tissues, and it can modulate the proliferation and migration of RB cells. It has the potential to be the "ceRNA" to regulate HIF-1α expression by sponging miR-199a-5p.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32110955

RESUMO

This cross-sectional questionnaire survey study was designed to examine the complementary and alternative intervention strategies (CAIS) employed by caregivers for their children's attention-deficit/hyperactivity disorder (ADHD) and the associations of affiliate stigma with the employment and rated effectiveness of these strategies in Taiwan. A total of 400 caregivers of children with ADHD participated. CAIS that the caregivers employed and their effectiveness rated by the caregivers were surveyed. Associations of affiliate stigma with the application and rated effectiveness of the strategies were determined using logistic regression analysis. The results indicated that sensory integration (30.3%), exercise training (29.3%), sugar restriction (20.5%), and omega fatty acid supplementation (11.3%) were the most common CAIS that the caregivers employed. Caregivers with stronger affiliate stigma were more likely to employ sensory integration, exercise training, and omega fatty acid supplementation but also rated them as ineffective in treating their children's ADHD. Various CAIS were employed by the caregivers to manage their children's ADHD. Affiliate stigma was significantly associated with the application and rated ineffectiveness of several CAIS.

9.
mBio ; 11(2)2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156816

RESUMO

During infection of human parvovirus B19 (B19V), one viral precursor mRNA (pre-mRNA) is transcribed by a single promoter and is alternatively spliced and alternatively polyadenylated. Here, we identified a novel cis-acting sequence (5'-GUA AAG CUA CGG GAC GGU-3'), intronic splicing enhancer 3 (ISE3), which lies 72 nucleotides upstream of the second splice acceptor (A2-2) site of the second intron that defines the exon of the mRNA encoding the 11-kDa viral nonstructural protein. RNA binding motif protein 45 (RBM45) specifically binds to ISE3 with high affinity (equilibrium dissociation constant [KD ] = 33 nM) mediated by its RNA recognition domain and 2-homo-oligomer assembly domain (RRM2-HOA). Knockdown of RBM45 expression or ectopic overexpression of RRM2-HOA in human erythroid progenitor cells (EPCs) expanded ex vivo significantly decreased the level of viral mRNA spliced at the A2-2 acceptor but not that of the mRNA spliced at A2-1 that encodes VP2. Moreover, silent mutations of ISE3 in an infectious DNA of B19V significantly reduced 11-kDa expression. Notably, RBM45 also specifically interacts in vitro with ISE2, which shares the octanucleotide (GGGACGGU) with ISE3. Taken together, our results suggest that RBM45, through binding to both ISE2 and ISE3, is an essential host factor for maturation of 11-kDa-encoding mRNA.IMPORTANCE Human parvovirus B19 (B19V) is a human pathogen that causes severe hematological disorders in immunocompromised individuals. B19V infection has a remarkable tropism with respect to human erythroid progenitor cells (EPCs) in human bone marrow and fetal liver. During B19V infection, only one viral precursor mRNA (pre-mRNA) is transcribed by a single promoter of the viral genome and is alternatively spliced and alternatively polyadenylated, a process which plays a key role in expression of viral proteins. Our studies revealed that a cellular RNA binding protein, RBM45, binds to two intron splicing enhancers and is essential for the maturation of the small nonstructural protein 11-kDa-encoding mRNA. The 11-kDa protein plays an important role not only in B19V infection-induced apoptosis but also in viral DNA replication. Thus, the identification of the RBM45 protein and its cognate binding site in B19V pre-mRNA provides a novel target for antiviral development to combat B19V infection-caused severe hematological disorders.

10.
World J Surg Oncol ; 18(1): 38, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054499

RESUMO

BACKGROUND: The development of severe esophageal stricture after endoscopic submucosal dissection (ESD) for early esophageal carcinoma is not uncommon. Dilation by Savary-Gilliard dilators or balloon dilators is the first-line treatment for such complex refractory benign stricture, but it has a high risk of treatment failure. So far, endoscopic radial incision (ERI) as a new technology for the treatment of post-ESD esophageal stricture has been rarely reported. We report a case, which we designed to assess the efficacy and safety of ERI technology for two severe strictures of the esophagus after ESD. CASE PRESENTATION: A 67-year-old man had suffered from two complex refractory benign strictures of the esophagus after ESD for early esophageal carcinoma. The patient was refractory to multiple endoscopic balloon dilation (EBD) therapy previously. Thus, the patient underwent ERI successfully and without postoperative complications such as fever, poststernal pain, bleeding, and perforation. During 3 months of follow-up after ERI, the patient had no recurrence of dysphagia. CONCLUSIONS: Refractory strictures of the esophagus after ESD are common. ERI is a safe and efficient strategy for treating such multiple refractory esophageal strictures.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32013262

RESUMO

Substance use has become a major health problem globally for sexual minorities. However, few studies have explored multi-dimensional factors associated with smoking, drinking, and prescription drug use. We aimed to investigate the factors affecting painkiller, sedative/hypnotic, nicotine and unhealthy alcohol use among gay and bisexual men in Taiwan. We recruited 500 gay or bisexual men and assessed their experiences of using painkillers, sedatives/hypnotics, nicotine, alcohol and multi-dimensional factors with self-reported questionnaires. Multivariate logistic regression with a forward stepwise model was used to verify the factors associated with substance use. Overall, 9.4%, 5.4%, and 13.8% of the participants reported using painkillers, sedatives/hypnotics, and nicotine, respectively, and 5.6% reported unhealthy alcohol use. Victims of traditional homophobic bullying in childhood and adolescence were more likely to report nicotine use, sedative/hypnotic use, and unhealthy alcohol use in early adulthood than non-victims. Missing classes or truancy at senior high school was associated with painkiller and sedative/hypnotic use in early adulthood. Traditional homophobic bullying and missing classes or truancy in childhood and adolescence predicted substance use in early adulthood among the gay and bisexual men in this study. Timely preventions and interventions for substance use are crucial for gay and bisexual men, especially for those who experience homophobic bullying and missing classes or truancy.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32045994

RESUMO

This study examined the associations of perceived socially unfavorable attitudes toward homosexuality and same-sex marriage with suicidal ideation in non-heterosexual and heterosexual participants from first (Wave 1, 23 months prior to same-sex marriage referendums) and second (Wave 2, one week after the referendums) wave surveys in Taiwan. Data provided by 3239 participants in Wave 1 and 1337 participants in Wave 2 who were recruited through a Facebook advertisement were analyzed. Participants completed an online questionnaire assessing suicidal ideation and perceived unfavorable attitudes toward homosexuality and same-sex marriage from Taiwanese society, heterosexual friends, and family members. The results indicate that perceived unfavorable attitudes toward homosexuality from Taiwanese society, heterosexual friends, and family members were positively associated with suicidal ideation among non-heterosexual individuals in the first but not the second survey. In addition, among non-heterosexual individuals, such attitudes toward same-sex marriage in family members and in heterosexual friends were positively associated with suicidal ideation in the Wave 1 and Wave 2 surveys, respectively. Perceived unfavorable attitudes toward homosexuality and same-sex marriage in heterosexual friends were associated with suicidal ideation in heterosexual participants with a favorable attitude but not in those individuals with an unfavorable attitude toward homosexuality, in both surveys. Perceived socially unfavorable attitudes toward homosexuality and same-sex marriage were significantly associated with suicidal ideation before and after same-sex marriage referendums; however, the associations varied between non-heterosexual and heterosexual individuals.

13.
Glycobiology ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039447

RESUMO

Proinflammatory cytokines stimulate expression of ß-secretase, which increases processing of amyloid precursor protein (APP), ultimately leading to deposition of amyloid beta (Aß). The N-terminal domain of ß-cleaved APP supports Cu/NO-dependent release of heparan sulfate (HS) from the glypican-1 (Gpc-1) proteoglycan. HS is an inhibitor of ß-secretase thereby constituting a regulatory, negative feed-back loop. Here, we have investigated the effect of the proinflammatory cytokines TNF-α, IL-1ß and IL-6 on the interplay between APP processing and release of HS from Gpc-1 in neuronal cells. We have used deconvolution immunofluorescence microscopy and SDS-PAGE and a panel of monoclonal/polyclonal antibodies recognizing the released HS, the N-terminal of Aß, Aß, the C-terminal of APP and the autophagosome marker LC3 as well as the chemical lysosome marker LysoTrackerRed (LTR). We repeatedly found that N2a neuroblastoma cells and human neural stem cells grown in the presence of the cytokines developed large cytoplasmic clusters which stained positive for HS, the N-terminal of Aß, Aß, the C-terminal of APP, LC3 and LTR indicating accumulation of HS and APP/APP degradation products in enlarged autophagosomes/lysosomes. SDS-PAGE of immunoisolates obtained from TNF-α-treated N2a cells by using anti-C-terminal of APP revealed the presence of SDS-stable complexes between HS and the C-terminal fragment of ß-cleaved APP (ßCTF) migrating in the range 10-18 kDa. Clustered accumulation of ßCTF disappeared when HS release was prevented and slightly enhanced when HS release was increased. Hence, when proinflammatory cytokines induce increased processing of APP, inhibition of ß-secretase by HS is insufficient, which may lead to impaired autosomal degradation.

14.
Adv Healthc Mater ; 9(5): e1901469, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31994326

RESUMO

Bone healing is a dynamic process regulated by biochemical signals such as chemokines and growth factors, and biophysical signals such as topographical and mechanical features of extracellular matrix or mechanical stimuli. Hereby, a mechanically tough and bioactive hydrogel based on autologous injectable platelet-rich fibrin (iPRF) modified with gelatin nanoparticles (GNPs) is developed. This composite hydrogel demonstrates a double network (DN) mechanism, wherein covalent network of fibrin serves to maintain material integrity, and self-assembled colloidal network of GNPs dissipates force upon loading. A rabbit sinus augmentation model is used to investigate the bioactivity and osteogenesis capacity of the DN hydrogels. The DN hydrogels adapt to the local environmental complexity of bone defects, i.e., accommodate the irregular shape of the defects and withstand the pressure formed in the maxillary sinus during animal's respiration process. The DN hydrogel is also demonstrated to absorb and prolong the release of the bioactive growth factors stemming from iPRF, which could have contributed to the early angiogenesis and osteogenesis observed inside the sinus. This adaptable and bioactive DN hydrogel can achieve enhanced bone regeneration in treating complex bone defects by maintaining long-term bone mass and withstanding the functional mechanical stimuli.

15.
Medicine (Baltimore) ; 99(4): e18838, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977880

RESUMO

Human serotonin receptor 4 (HTR4) encodes a 5-HT4 receptor involved in learning, memory, depression, anxiety, and feeding behavior. The aim of this study was to investigate the association between the deoxyribonucleic acid (DNA) methylation of HTR4 promoter and autism spectrum disorder (ASD), a disease characterized by communication disorder and repetitive or restrictive behavior.Peripheral blood DNA was obtained from 61 ASD children and 66 healthy children, and the DNA methylation of HTR4 promoter was assessed by quantitative methylation-specific polymerase chain reaction. We used percentage of methylated reference (PMR) to represent DNA methylation level.Due to significant age differences between ASD cases and controls (3 [2, 5] years and 6 [5, 6] years, P = 3.34E-10), we used binary logistic regression analysis for adjustment. Our results showed that the DNA methylation levels of HTR4 promoter were significantly lower in children with ASD than in healthy children (median PMR: 66.23% vs 94.31%,P = .028, age-adjusted P = .034). In addition, the DNA methylation of HTR4 promoter was inversely associated with age in male ASD cases (total cases: r = -0.283, P = .027; male cases: r = -0.431, P = .002; female cases: r = -0.108, P = .752). Dual-luciferase reporter gene assay showed that the reporter gene expression in the strain with recombinant pGL3-promoter-HTR4 plasmid was significantly higher than that in the strain with pGL3-promoter plasmid (fold change = 2.01, P = .0065), indicating that the HTR4 promoter fragment may contain transcription factors to upregulate promoter activity.Our study suggested that hypomethylation of the HTR4 promoter is a potential biomarker for predicting the risk of male ASD.


Assuntos
Transtorno do Espectro Autista/genética , Receptores 5-HT4 de Serotonina/genética , Biomarcadores/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Metilação de DNA , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Fatores Sexuais
16.
Artigo em Inglês | MEDLINE | ID: mdl-31963190

RESUMO

This cross-sectional questionnaire study examined factors related to affiliate stigma among caregivers of children with attention-deficit/hyperactivity disorder (ADHD) and the association of affiliate stigma with caregivers' unfavorable attitude toward ADHD and moderators. The affiliate stigma of 400 caregivers of children with ADHD was assessed using the Affiliate Stigma Scale. Caregivers' and children's factors related to affiliate stigma were examined using multiple regression analysis. Associations of affiliate stigma with caregivers' unfavorable attitudes toward children's diagnoses, pharmacotherapy, behavioral therapy, and biological explanations of the etiologies of ADHD were examined using logistic regression analysis. Female caregivers and those caring for girls with ADHD had higher levels of affiliate stigma than did male caregivers and those caring for boys. Higher education levels in caregivers and more severe inattention symptoms in children were associated with higher levels of affiliate stigma. A higher level of affiliate stigma was also significantly associated with unfavorable attitudes toward children's diagnoses, pharmacotherapy and behavioral therapy, and etiological explanations for ADHD. Multiple factors of caregivers and children were related to affiliate stigma in caregivers of children with ADHD. Affiliate stigma is significantly associated with caregivers' unfavorable attitude toward ADHD.

17.
Cochrane Database Syst Rev ; 1: CD003437, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31989584

RESUMO

BACKGROUND: Depression is an important morbidity associated with stroke that impacts on recovery yet often undetected or inadequately treated. This is an update and expansion of a Cochrane Review first published in 2004 and updated in 2008. OBJECTIVES: Primary objective • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce the prevalence of diagnosable depression after stroke Secondary objectives • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce levels of depressive symptoms, improve physical and neurological function and health-related quality of life, and reduce dependency after stroke • To assess the safety of and adherence to such treatments SEARCH METHODS: We searched the Specialised Registers of Cochrane Stroke and Cochrane Depression Anxiety and Neurosis (last searched August 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), in the Cochrane Library, MEDLINE (1966 to August 2018), Embase (1980 to August 2018), the Cumulative Index to Nursing and Alllied Health Literature (CINAHL) (1982 to August 2018), PsycINFO (1967 to August 2018), and Web of Science (2002 to August 2018). We also searched reference lists, clinical trial registers (World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) to August 2018; ClinicalTrials.gov to August 2018), and conference proceedings, and we contacted study authors. SELECTION CRITERIA: Randomised controlled trials comparing (1) pharmacological interventions with placebo; (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care; (3) one of various forms of psychological therapy with usual care and/or attention control; (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and usual care and/or attention control; (5) non-invasive brain stimulation and pharmacological intervention with pharmacological intervention and sham stimulation or usual care; (6) pharmacological intervention and one of various forms of psychological therapy with placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation with placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and (9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy, with the intention of treating depression after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic and certainty of the evidence according to GRADE. MAIN RESULTS: We included 49 trials (56 comparisons) with 3342 participants. Data were available for: (1) pharmacological interventions with placebo (with 20 pharmacological comparisons); (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care (with eight non-invasive brain stimulation comparisons); (3) one of various forms of psychological therapy with usual care and/or attention control (with 16 psychological therapy comparisons); (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and usual care and/or attention control (with two comparisons); and (5) non-invasive brain stimulation and pharmacological intervention with pharmacological intervention and sham stimulation or usual care (with 10 comparisons). We found no trials for the following comparisons: (6) pharmacological intervention and various forms of psychological therapy interventions versus placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation versus placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and (9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy. Treatment effects observed: very low-certainty evidence from eight trials suggests that pharmacological interventions decreased the number of people meeting study criteria for depression (RR 0.70, 95% CI 0.55 to 0.88; 1025 participants) at end of treatment, and very low-certainty evidence from six trials suggests that pharmacological interventions decreased the number of people with less than 50% reduction in depression scale scores at end of treatment (RR 0.47, 95% CI 0.32 to 0.69; 511 participants) compared to placebo. No trials of non-invasive brain stimulation reported on meeting study criteria for depression at end of treatment. Only one trial of non-invasive brain stimulation reported on the outcome <50% reduction in depression scale scores; thus, we were unable to perform a meta-analysis for this outcome. Very low-certainty evidence from six trials suggests that psychological therapy decreased the number of people meeting the study criteria for depression at end of treatment (RR 0.77, 95% CI 0.62 to 0.95; 521 participants) compared to usual care/attention control. No trials of combination therapies reported on the number of people meeting the study criteria for depression at end of treatment. Only one trial of combination (non-invasive brain stimulation and pharmacological intervention) therapy reported <50% reduction in depression scale scores at end of treatment. Thus, we were unable to perform a meta-analysis for this outcome. Five trials reported adverse events related to the central nervous system (CNS) and noted significant harm in the pharmacological interventions group (RR 1.55, 95% CI 1.12 to 2.15; 488 participants; very low-certainty evidence). Four trials found significant gastrointestinal adverse events in the pharmacological interventions group (RR 1.62, 95% CI 1.19 to 2.19; 473 participants; very low-certainty evidence) compared to the placebo group. No significant deaths or adverse events were found in the psychological therapy group compared to the usual care/attention control group. Non-invasive brain stimulation interventions and combination therapies resulted in no deaths. AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that pharmacological or psychological therapies can reduce the prevalence of depression. This very low-certainty evidence suggests that pharmacological therapy, psychological therapy, non-invasive brain stimulation, and combined interventions can reduce depressive symptoms. Pharmacological intervention was associated with adverse events related to the CNS and the gastrointestinal tract. More research is required before recommendations can be made about the routine use of such treatments.

19.
J Virol ; 94(2)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31666379

RESUMO

Human bocavirus 1 (HBoV1), which belongs to the genus Bocaparvovirus of the Parvoviridae family, causes acute respiratory tract infections in young children. In vitro, HBoV1 infects polarized primary human airway epithelium (HAE) cultured at an air-liquid interface (HAE-ALI). HBoV1 encodes a small nonstructural protein, nuclear protein 1 (NP1), that plays an essential role in the maturation of capsid protein (VP)-encoding mRNAs and viral DNA replication. In this study, we determined the broad interactome of NP1 using the proximity-dependent biotin identification (BioID) assay combined with mass spectrometry (MS). We confirmed that two host mRNA processing factors, DEAH-box helicase 15 (DHX15) and cleavage and polyadenylation specificity factor 6 (CPSF6; also known as CFIm68), a subunit of the cleavage factor Im complex (CFIm), interact with HBoV1 NP1 independently of any DNA or mRNAs. Knockdown of CPSF6 significantly decreased the expression of capsid protein but not that of DHX15. We further demonstrated that NP1 directly interacts with CPSF6 in vitro and colocalizes within the virus replication centers. Importantly, we revealed a novel role of CPSF6 in the nuclear import of NP1, in addition to the critical role of CPSF6 in NP1-facilitated maturation of VP-encoding mRNAs. Thus, our study suggests that CPSF6 interacts with NP1 to escort NP1 imported into the nucleus for its function in the modulation of viral mRNA processing and viral DNA replication.IMPORTANCE Human bocavirus 1 (HBoV1) is one of the significant pathogens causing acute respiratory tract infections in young children worldwide. HBoV1 encodes a small nonstructural protein (NP1) that plays an important role in the maturation of viral mRNAs encoding capsid proteins as well as in viral DNA replication. Here, we identified a critical host factor, CPSF6, that directly interacts with NP1, mediates the nuclear import of NP1, and plays a role in the maturation of capsid protein-encoding mRNAs in the nucleus. The identification of the direct interaction between viral NP1 and host CPSF6 provides new insights into the mechanism by which a viral small nonstructural protein facilitates the multiple regulation of viral gene expression and replication and reveals a novel target for potent antiviral drug development.

20.
Biosci Biotechnol Biochem ; 84(4): 695-702, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31809639

RESUMO

Emerging evidence has shown that microRNAs are important regulators in osteoarthritis (OA). Here, we investigated the function role of miR-455-3p in the pathogenesis of OA and the underlying molecular mechanisms. We first established the in vitro OA model using IL-1ß treated human chondrocyte cell line CHON-001. Using quantitative real time PCR, we observed the expression of miR-455-3p expression was up-regulated in the OA cartilage tissues and IL-1ß-treated chondrocytes. A series of function assays, including CCK-8 assay, flow cytometry, and ELISA assay showed that miR-455-3p contributed to IL-1ß-induced apoptosis and inflammation. Moreover, COL2A1 was confirmed as a target of miR-455-3p by luciferase reporter assay. Furthermore, COL2A1 knockdown reversed the effects of miR-455-3p inhibition, and aggravated the effects of miR-455-3p overexpression on IL-1ß-induced OA-like phenomenon. Taken together, these results revealed that miR-455-3p/COL2A1 axis might provide a novel molecular target for the treatment of OA.

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