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A series of novel benzimidazole derivatives were designed and synthesised based on the structures of reported oral available ALK inhibitor and HDAC inhibitor, pracinostat. In enzymatic assays, compound 3b, containing a 2-acyliminobenzimidazole moiety and hydroxamic acid side chain, could inhibit both ALK and HDAC6 (IC50 = 16 nM and 1.03 µM, respectively). Compound 3b also inhibited various ALK mutants known to be involved in crizotinib resistance, including mutant L1196M (IC50, 4.9 nM). Moreover, 3b inhibited the proliferation of several cancer cell lines, including ALK-addicted H2228 cells. To evaluate its potential for treating cancers in vivo, 3b was used in a human A549 xenograft model with BALB/c nude mice. At 20 mg/kg, 3b inhibited tumour growth by 85% yet had a negligible effect on mean body weight. These results suggest a attracting route for the further research and optimisation of dual ALK/HDAC inhibitors.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Camundongos Nus , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proliferação de Células , Inibidores de Proteínas Quinases/química , Antineoplásicos/química , Linhagem Celular TumoralRESUMO
6-hydroxydopamine (6-OHDA) is used to induce oxidative damage in neuronal cells, which can serve as an experimental model of Parkinson's disease (PD). Jujuboside A and B confer free radical scavenging effects but have never been examined for their neuroprotective effects, especially in PD; therefore, in this study, we aimed to investigate the feasibility of jujubosides as protectors of neurons against 6-OHDA and the underlying mechanisms. 6-OHDA-induced neurotoxicity in the human neuronal cell lines SH-SY5Y and SK-N-SH, was used to evaluate the protective effects of jujubosides. These findings indicated that jujuboside A and B were both capable of rescuing the 6-OHDA-induced loss of cell viability, activation of apoptosis, elevation of reactive oxygen species, and downregulation of the expression levels of superoxide dismutase, catalase, and glutathione peroxidase. In addition, jujuboside A and B can reverse a 6-OHDA-elevated Bax/Bcl-2 ratio, downregulate phosphorylated PI3K and AKT, and activate caspase-3, -7, and -9. These findings showed that jujubosides were capable of protecting both SH-SY5Y and SK-N-SH neuronal cells from 6-OHDA-induced toxicity via the rebalancing of the redox system, together with the resetting of the PI3K/AKT apoptotic signaling cascade. In conclusion, jujuboside may be a potential drug for PD prevention.
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Neuroblastoma , Fármacos Neuroprotetores , Síndromes Neurotóxicas , Apoptose , Linhagem Celular Tumoral , Humanos , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Oxidopamina/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
In Taiwan, The increase in life expectancy in Taiwan has increased the incidents of age-related problems among patients with mental illness. Therefore, the needs related to long-term care in mental health are significantly important. These needs include: (1) reducing stigmatization; (2) reducing the physical and economic burden of caregivers; (3) constructing a comprehensive, long-term care service system; and (4) developing assessment tools suitable to the long-term care of patients with mental illness. Moreover, six dilemmas in meeting long-term care needs were identified. These dilemmas include: (1) lack of a model of continuous care and of a platform for integrating hospital and community resources; (2) poor / inadequate service quality provided by certain community rehabilitation institutions; (3) the needs of patient/family centered care; (4) the persistence of stigma and misunderstanding; (5) the heavy burdens borne by family members providing long-term care; and (6) the disconnect between subsequent needs and the disability assessment system. Policy suggestions provided in this article include: (1) establish an inclusive platform for mental health long-term care information and resource integration; (2) construct long-term care centers for patients with mental health conditions; (3) train adequate manpower to provide long-term care services to these patients; and (4) promote community inclusiveness for these patients. In order to enter the era of long-term mental health care, government policy should target long-term care programs to meet the needs of patients with mental health conditions. These programs should include seamlessly integrating services into the long-term mental health care system and the care resources of community mental health, developing suitable assessment tools, establishing a multidisciplinary team of long-term care professionals to provide mental health care.
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Política de Saúde , Necessidades e Demandas de Serviços de Saúde , Transtornos Mentais , Humanos , Assistência de Longa Duração/organização & administração , Transtornos Mentais/terapia , TaiwanRESUMO
BACKGROUND: Sexual health is a taboo issue in some societies. Limited assessments were conducted during nursing care in mental health services. It is unknown whether psychiatric nurses' competencies would be enhanced through short training courses. OBJECTIVE: The present study employed a quasi-experimental design to evaluate the effectiveness of an 8-hour sexual health care training for psychiatric nurses to improve sexual health knowledge, attitude, and self-efficacy in a teaching psychiatric hospital in southern Taiwan. METHOD: Volunteered psychiatric nurses were randomly assigned to the experimental or control group. The 8-hour training program contained sexual health knowledge and attitudes, case discussion, role play, and sexual identity or harassment issues. Each nurse received a pretest and a posttest in the 1-month period between August and September 2019. Descriptive and multivariate statistical analyses were used to evaluate the effects. RESULTS: Among the 75 psychiatric nurses, 43 were in the control group and 32 were in the experimental group. The two groups were not significantly different in the working year, gender, education, marriage, and other psychosocial variables. After the training, the overall performance of sexual health care knowledge, attitudes, and self-efficacy of the experimental group improved significantly than the controls. CONCLUSIONS: The sexual health care training program enhanced psychiatric nurses' confidence and generally improved their sexual knowledge and attitudes. It is suggested that sexual health care needs to be highlighted during in-job training to augment the well-being and life quality of psychiatric patients.
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Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a physiological neurotoxin reported to induce oxidative-induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. In the study, we aim at examining the feasibility of VPA as a protector for dopaminergic neurons against damage from 6-OHDA, and the intracellular mechanisms. The 6-OHDA-induced neurotoxicity to the human dopaminergic cell line SH-SY5Y was applied for examining VPA protective effects. Pretreatment with VPA was able to improve cell viability and reduce 6-OHDA-induced reactive oxygen species. Furthermore, a significant suppression of apoptotic caspases including cleaved caspase-3, caspase-7, and caspase-9 was observed. The results also revealed VPA decreased the 6-OHDA-induced Bax/Bcl2 ratio, as measured at protein level. These novel findings indicate that VPA may be capable of protecting the SH-SY5Y dopaminergic neuronal cells from 6-OHDA-induced toxicity via the deceasing of apoptotic caspases (cleaved caspase-3, caspase-7, and caspase-9) and reducing of the Bax/Bcl2 ratio. Very possibly, VPA could serve as not only a mood stabilizer but also a potential antidote for PD prevention.
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Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Ácido Valproico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dopamina/metabolismo , Humanos , Camundongos , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina/metabolismo , Oxidopamina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ácido Valproico/metabolismoRESUMO
Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cAMP synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH), but this signaling may occur through nuclear peroxisome proliferator-activated receptor-γ (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP4 receptor (EP4) expression in IPAH patients. Both IP and EP4 functionally couple with stimulatory G protein (Gs), which activates signal transduction. We investigated the effect of an EP4-specific agonist on pulmonary arterial remodeling and its regulatory mechanisms in pulmonary arterial smooth muscle cells (PASMCs). Immunoblotting evealed IP, EP4, and PPARγ expression in human pulmonary arterial hypertension (PAH) and monocrotaline (MCT)-induced PAH rat lung tissue. Isolated PASMCs from MCT-induced PAH rats (MCT-PASMCs) were treated with L-902,688, a selective EP4 agonist, to investigate the anti-vascular remodeling effect. Scant expression of IP and PPARγ but stable expression of EP4 was observed in IPAH patient lung tissues and MCT-PASMCs. L-902,688 inhibited IP-insufficient MCT-PASMC proliferation and migration by activating PPARγ in a time- and dose-dependent manner, but these effects were reversed by AH-23848 (an EP4 antagonist) and H-89 [a protein kinase A (PKA) inhibitor], highlighting the crucial role of PPARγ in the activity of this EP4 agonist. L-902,688 attenuated pulmonary arterial remodeling in hypoxic PAH mice and MCT-induced PAH rats; therefore, we conclude that the selective EP4 agonist L-902,688 reverses vascular remodeling by activating PPARγ. This study identified a novel EP4-PKA-PPARγ pathway, and we propose EP4 as a potential therapeutic target for PAH.
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Hipertensão Pulmonar Primária Familiar/tratamento farmacológico , Músculo Liso Vascular/efeitos dos fármacos , PPAR gama/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Pirrolidinonas/farmacologia , Receptores de Prostaglandina E Subtipo EP4/agonistas , Tetrazóis/farmacologia , Adulto , Animais , Proliferação de Células , Células Cultivadas , Hipertensão Pulmonar Primária Familiar/metabolismo , Hipertensão Pulmonar Primária Familiar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Adulto JovemRESUMO
Bipolar disorder (BD) is a severe mental illness that is characterized by chronicity, pervasive instability, and relatively high rates of recurrence and suicide. Current evidence supports that adverse circles among hereditary and genetic factors, neuroinflamation, and social rhythm constitute a crucial etiology. Pharmacological treatment is the first priority for BD patients during the acute stage. Pharmacological and psychosocial treatments should be combined during the maintenance stage in order to help patients self-manage medication, effectively control mood swings, enhance disease self-management and social functions, decrease the risks of relapse and re-hospitalization, and stabilize overall health. The present article firstly introduces the characteristics and etiological assumptions related to BD, the related evidence-based care models and their effects, and the early development of an evidence-based care model, the BalancingMySwing group, for BD patients in Taiwan. This article provides updated information to clinicians who are involved in caring for this population. Moreover, the existing data related to biological and psychosocial factors for BD in Taiwan is insufficient and developing individual-tailored psychosocial intervention is urgently needed. The authors hope that this article will elicit greater concern for this issue from policy decision-makers and healthcare providers.
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Transtorno Bipolar/terapia , Transtorno Bipolar/etiologia , Transtorno Bipolar/enfermagem , Enfermagem Baseada em Evidências , HumanosRESUMO
BACKGROUND: Public attitudes toward mental illness influence the success with which patients reenter the community. An attitude instrument suitable to the Chinese cultural setting with good reliability and validity is essential to examining public attitudes toward mental illness. Exploring the perspectives of adolescents is relevant because most mental illness occurs during adolescence. PURPOSE: This study developed and tested the psychometric quality of the Chinese-version Attitudes Toward Mental Illness (CAMI) scale among senior high school students. METHODS: The original AMI was translated into Chinese using a back and forth translation method and its content validity was examined. A cross-sectional survey of 479 senior high school students was conducted to assess the construct validity, cross validity, and internal consistency of the CAMI. RESULTS: The CAMI showed adequate content validity. The confirmatory factor analysis support: the appropriateness of CAMI's original two-factor structure of negative attitude and recovery outcomes after deleting items 9 and 11; the measurement of the negative perceptions of mentally ill patients and their risks to community; and the perceptions of recovery of mentally ill patients. The construct validity and cross validity are appropriate and the internal consistency of the total scale and two subscales are acceptable (Cronbach's α: .76, .75, .81). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The reliability and validity of the CAMI is appropriate for the sample of senior high students in this study. Future studies should target a broader range of people in order to establish the reliability and validity of the scale in different groups and to build up empirical knowledge on public attitudes toward mental illness. The application of this scale is expected to contribute to the development of anti-stigma interventions and to the creation of friendly communities for mentally ill patients.
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Atitude Frente a Saúde , Transtornos Mentais/psicologia , Estudantes/psicologia , Humanos , Reprodutibilidade dos TestesRESUMO
BACKGROUND/AIM: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL. MATERIALS AND METHODS: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair. RESULTS: The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele. CONCLUSION: Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Genótipo , Alelos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Reparo do DNA/genética , RNA Mensageiro/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Providing appropriate care to patients with dementia in acute care settings can be a challenge for healthcare professionals. A key factor is working closely with family caregivers. PURPOSE: This study aims to explore the difficulties and strategies involved in caring for patients with dementia who have been admitted to an acute care ward from the perspective of family caregivers. METHODS: Exploratory research was conducted using a qualitative data collection approach. Data were collected by means of in-depth interviews carried out with participants. Semistructured interviews were conducted with nine participants. Content analysis was performed to analyze the data. RESULTS: A number of themes and subthemes were identified based on the primary research purposes. The first theme is "vicious cycle due to multiple factors," with the following subthemes: (a) communication disturbance, (b) endless worries, (c) inadequate care skills of paid caregivers, and (d) physical and psychological exhaustion. The second theme is "do everything," with the following subthemes: (a) management of the behavioral and psychological symptoms of dementia, (b) constant accompaniment of the patient, and (c) seeking sources of support. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results may be used to help healthcare professionals better anticipate the difficulties faced by family caregivers while providing assistance to patients with dementia and understand the related strategies they use. Acute care wards should consider the specific needs of family caregivers to ensure patients with dementia receive adequate care from the relevant parties in the ecological care chain during the care process.
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Cuidadores , Demência , Humanos , Cuidadores/psicologia , Demência/psicologia , Pessoal de Saúde , Hospitais , Assistência ao Paciente , Pesquisa Qualitativa , Família/psicologiaRESUMO
BACKGROUND/AIM: Interleukin 8 (IL-8) is highly expressed in refractory acute lymphocytic leukemia (ALL) cells. This study aimed to investigate the contribution of IL-8 polymorphisms to the risk of childhood ALL. MATERIALS AND METHODS: The genotypes of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were determined in 266 childhood ALL cases and 266 controls using the PCR-RFLP method. Additionally, we assessed whether the interactions of these genotypes with age and sex contributed to childhood ALL risk. RESULTS: The distributions of genotypic and allelic frequencies of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were not significantly different between childhood ALL cases and controls (all p>0.05). However, carriers of the variant AA genotype at IL-8 rs4073 had a significantly higher risk of childhood ALL among those aged ≤3.5 years and among girls (OR=2.39 and 3.32, 95%CI=1.21-4.73 and 1.51-7.30, p=0.0182 and 0.0042, respectively). In the stratification analysis, IL-8 rs4073 AT and AA genotypes were associated with higher childhood ALL risk classification and shorter survival time (OR=2.21 and 4.13, 95%CI=1.29-3.78 and 1.87-9.10, p=0.0054 and 0.0002, respectively). There was no positive association for rs2227306, rs2227543, or rs1126647 (all p>0.05). CONCLUSION: The A allele of IL-8 rs4073 can serve as a diagnostic predictor for childhood ALL, but only in girls and patients younger than or equal to 3.5 years old. More importantly, it can serve as a prognostic marker for high-risk classification and shorter survival time. Further validation studies can help extend the use of this prognostic predictor in clinical practice.
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Interleucina-8 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Feminino , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Interleucina-8/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , PrognósticoRESUMO
BACKGROUND/AIM: Acute lymphoblastic leukemia (ALL) is frequent among children. Few studies have researched the relationship between maternally expressed gene 3 (MEG3) and cancer risk. We hypothesized long non-coding RNA MEG3 polymorphisms might influence the risk of childhood ALL. MATERIALS AND METHODS: In a total of 266 patients with childhood ALL and 266 healthy controls, genotypes of MEG3 rs7158663, rs3087918, rs11160608 and rs4081134 single nucleotide polymorphisms were investigated for their associations with childhood ALL. RESULTS: MEG3 rs7158663 AG and AA genotypes were significantly associated with ALL [odds ratio=1.61 (95% confidence interval=1.12-2.31) and 2.21 (1.16-4.22), respectively]. The A allele also exhibited a statistical association with higher risk of ALL (p=0.0015). There was no positive association as for rs3087918, rs11160608 or rs4081134. Interestingly, a significant interaction between MEG3 rs7158663 and age (≥3.5 years) and gender (male) was found. CONCLUSION: MEG3 rs7158663 AG/AA genotypes were associated with higher susceptibility to childhood ALL. These novel findings should be validated in larger populations and different ethnicities.
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Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Leucemia/genética , RNA Longo não Codificante/genética , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Humanos , Leucemia/epidemiologia , Masculino , Polimorfismo de Nucleotídeo Único , Medição de Risco/métodosRESUMO
BACKGROUND/AIM: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk. MATERIALS AND METHODS: In 266 childhood ALL cases and 266 healthy controls, the CDKN1B rs34330 and 2066827 polymorphisms were genotyped, and the association of CDKN1B genotypes with childhood ALL risk were analyzed. RESULTS: The genotypes of CDKN1B rs34330 and 2066827 were similarly distributed between the control and case groups (p for trend=0.8718 and 0.4030, respectively). The allelic frequency also exhibited no statistical difference (p=1.0000 and 0.6666, respectively). There was no significant interaction between CDKN1B genotypes and age or sex. CONCLUSION: CDKN1B genotypes were not found to be minor contributors to childhood ALL susceptibility in Taiwan.
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Inibidor de Quinase Dependente de Ciclina p27 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Inibidor de Quinase Dependente de Ciclina p27/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , TaiwanRESUMO
BACKGROUND/AIM: Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). CONCLUSION: IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.
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Interleucina-18 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , TaiwanRESUMO
BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome that predominantly affects women. Its pathophysiology remains unclear but connective tissue disorders (CTD) and other vasculopathies have been observed in many SCAD patients. A genetic component for SCAD is increasingly appreciated, although few genes have been robustly implicated. We sought to clarify the genetic cause of SCAD using targeted and genome-wide methods in a cohort of sporadic cases to identify both common and rare disease-associated variants. METHODS: A cohort of 91 unrelated sporadic SCAD cases was investigated for rare, deleterious variants in genes associated with either SCAD or CTD, while new candidate genes were sought using rare variant collapsing analysis and identification of novel loss-of-function variants in genes intolerant to such variation. Finally, 2 SCAD polygenic risk scores were applied to assess the contribution of common variants. RESULTS: We identified 10 cases with at least one rare, likely disease-causing variant in CTD-associated genes, although only one had a CTD phenotype. No genes were significantly associated with SCAD from genome-wide collapsing analysis, however, enrichment for TGF (transforming growth factor)-ß signaling pathway genes was found with analysis of 24 genes harboring novel loss-of-function variants. Both polygenic risk scores demonstrated that sporadic SCAD cases have a significantly elevated genetic SCAD risk compared with controls. CONCLUSIONS: SCAD shares some genetic overlap with CTD, even in the absence of any major CTD phenotype. Consistent with a complex genetic architecture, SCAD patients also have a higher burden of common variants than controls.
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Síndrome Coronariana Aguda , Anomalias dos Vasos Coronários , Doenças Vasculares , Anomalias dos Vasos Coronários/genética , Feminino , Humanos , Doenças Vasculares/congênito , Doenças Vasculares/genéticaRESUMO
The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08-2.14, p = 0.0429) and 1.94 (95%CI, 1.15-3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.
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BACKGROUND/AIM: This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. RESULTS: There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls. CONCLUSION: CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.
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Ciclina D1/genética , Predisposição Genética para Doença/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Alelos , Criança , Pré-Escolar , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Green lacewings (Neuroptera: Chrysopidae) are important beneficial insects that can be raised on artificial diets for culturing experimental lines. An encapsulation method for embedding a core material within a sealed shell to prevent evaporation and biological contamination is crucial for providing food to these predatory insects. RESULTS: This study presents a new encapsulation process to mass produce a core-shell microcapsule diet for rearing Mallada basalis (Walker) (Neuroptera: Chrysopidae). This new process provided consistent quality control and effectiveness of the microcapsule diet (742.1 ± 11.3 µm in diameter and 44.2 ± 1.9 µm in shell thickness). Furthermore, significant differences were measured in larval development (24.0 ± 0.3 vs. 20.1 ± 0.6 days) and fecundity (465 ± 65.05 vs. 678 ± 54.91 eggs) on comparing the development of M. basalis larvae fed the old and new diets. Survival rates increased in both single- and group-rearing tests for adults fed the new diet during the larval stages. Neither diet affected predation rates for M. basalis larvae preying on nymphs of Aphis gossypii Glover (Hemiptera: Aphididae) and Bemisia argentifolli Bellows and Perring (Hemiptera: Aleyrodidae). CONCLUSION: Compared with the old process, the new encapsulation process requires reduced effort during preparation, and reduces the weight, cost and space occupied by the equipment. The results of this study suggest that this new spherical microcapsule artificial diet is suitable for group-rearing of M. basalis and may be appropriate for mass-rearing of other types of carnivorous insects. © 2019 Society of Chemical Industry.
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Insetos , Animais , Cápsulas , Dieta , Larva , Controle Biológico de VetoresRESUMO
BACKGROUND/AIM: The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. CONCLUSION: The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.
Assuntos
Povo Asiático/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Idade de Início , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , TaiwanRESUMO
BACKGROUND/AIM: Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). CONCLUSION: MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.