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1.
World J Gastrointest Oncol ; 16(6): 2757-2768, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994162

RESUMO

BACKGROUND: Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored. AIM: To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC. METHODS: High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects' patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed. RESULTS: Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive. CONCLUSION: Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

2.
J Epidemiol ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39034108

RESUMO

BACKGROUND: This study aimed to validate self-reported medical conditions in the Taiwan Biobank (TWBB), in which participants were inquired about 30 disease conditions, by comparing them with claims records from Taiwan's National Health Insurance (NHI) claims database. METHODS: We identified 30 clinical diagnoses using ICD-CM codes from ambulatory and hospital claims within the NHI claims database, matching diseases included in the TWBB. The concordance between self-reports and claims records was evaluated using tetrachoric correlation to assess the correlation between binary variables. RESULTS: A total of 131,834 participants aged 30-70 years with data from the TWBB and NHI records were included. Concordance analysis revealed tetrachoric correlations ranged from 0.420 (chronic obstructive pulmonary disease) to 0.970 (multiple sclerosis). However, several disorders exhibited lower tetrachoric correlations. The concordance was higher among those with higher education attainment, and lower among married individuals. CONCLUSION: The concordance between self-reports in the TWBB and NHI claims records varied across clinical diagnoses, showing inconsistencies depending on participant characteristics. These findings underscore the need for further investigation, especially when these variables are crucial to research objectives. Integrating complementary databases such as clinical diagnoses, prescription records, and medical procedures can enhance accuracy through customized algorithms based on disease categories and participant characteristics and optimize sensitivity or positive predictive values to align with specific research objectives.

3.
Int J Nanomedicine ; 19: 6295-6317, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919774

RESUMO

Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These properties make MOFs valuable in biomedical applications, including biological targeting and drug delivery. They also play a critical role in tumor diagnosis and treatment, including tumor cell targeting, identification, imaging, and therapeutic methods such as drug delivery, photothermal effects, photodynamic therapy, and immunogenic cell death. The diversity of MOFs with different metal centers, organics, and surface modifications underscores their multifaceted contributions to tumor research and treatment. This review is a summary of these roles and mechanisms. The final section of this review summarizes the current state of the field and discusses prospects that may bring MOFs closer to pharmaceutical applications.


Assuntos
Estruturas Metalorgânicas , Nanocompostos , Neoplasias , Estruturas Metalorgânicas/química , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Nanocompostos/química , Nanocompostos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Animais , Fotoquimioterapia/métodos , Antineoplásicos/química , Nanomedicina/métodos
4.
Insect Sci ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728615

RESUMO

Wing dimorphism is regarded as an important phenotypic plasticity involved in the migration and reproduction of aphids. However, the signal transduction and regulatory mechanism of wing dimorphism in aphids are still unclear. Herein, the optimal environmental conditions were first explored for inducing winged offspring of green peach aphid, and the short photoperiod was the most important environmental cue to regulate wing dimorphism. Compared to 16 L:8 D photoperiod, the proportion of winged offspring increased to 90% under 8 L:16 D photoperiod. Subsequently, 5 differentially expressed microRNAs (miRNAs) in aphids treated with long and short photoperiods were identified using small RNA sequencing, and a novel miR-3040 was identified as a vital miRNA involved in photoperiod-mediated wing dimorphism. More specifically, the inhibition of miR-3040 expression could reduce the proportion of winged offspring induced by short photoperiod, whereas its activation increased the proportion of winged offspring under long photoperiod. Meanwhile, the expression level of miR-3040 in winged aphids was about 2.5 times that of wingless aphids, and the activation or inhibition of miR-3040 expression could cause wing deformity, revealing the dual-role regulator of miR-3040 in wing dimorphism and wing development. In summary, the current study identified the key environmental cue for wing dimorphism in green peach aphid, and the first to demonstrate the dual-role regulator of miR-3040 in photoperiod-mediated wing dimorphism and wing development.

5.
J Affect Disord ; 360: 88-96, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38821366

RESUMO

BACKGROUND: This study aimed to estimate the population-attributable fraction (PAF) of psychiatric and physical disorders for suicide among older adults, focusing on sex- and age-specific factors. METHODS: Data from Taiwan's National Health Insurance Research Data and National Death Registry included 9136 cases of suicide in individuals aged 65+, with 89,439 matched controls. Physical and psychiatric disorders were identified through diagnostic records. Conditional logistic regression assessed risk factors, and PAF was calculated using disorder prevalence and adjusted odds ratios. RESULTS: Major suicide risk factors among older adults were depressive disorders, anxiety disorders, and sleep disorders. Physical disorders like hypertension, peptic ulcers, and cancer also showed significant PAF values. The combined PAF of physical disorders equaled that of psychiatric disorders. Psychiatric disorders had a greater impact on women and the youngest-old adults, while physical disorders had a higher contribution among men, middle-old adults, and oldest-old adults. LIMITATIONS: Relying solely on claim data to identify psychiatric and physical disorders may underestimate their prevalence and associations with suicide due to unrecorded cases of individuals not seeking help and the absence of key risk factors like social isolation and family support. CONCLUSIONS: This study identifies preventable or treatable risk factors for older adult suicide, emphasizing the need to target specific psychiatric and physical disorders in suicide prevention efforts while taking into account sex- and age-specific considerations. It also underscores the importance of establishing social welfare support systems to address the unique challenges older adults face.


Assuntos
Transtornos Mentais , Suicídio , Humanos , Taiwan/epidemiologia , Masculino , Feminino , Idoso , Suicídio/estatística & dados numéricos , Fatores de Risco , Idoso de 80 Anos ou mais , Transtornos Mentais/epidemiologia , Fatores Sexuais , Prevalência , Fatores Etários , Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Neoplasias/epidemiologia , Neoplasias/psicologia , Úlcera Péptica/epidemiologia , Hipertensão/epidemiologia
6.
Alzheimers Res Ther ; 16(1): 109, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750512

RESUMO

BACKGROUND: As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD. METHODS: mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK-/-) mice. Animals' cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation. RESULTS: Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK-/- mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists. CONCLUSIONS: Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.


Assuntos
Doença de Alzheimer , Amnésia Anterógrada , Colecistocinina , Modelos Animais de Doenças , Camundongos Transgênicos , Receptor de Colecistocinina B , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Camundongos , Receptor de Colecistocinina B/genética , Receptor de Colecistocinina B/agonistas , Receptor de Colecistocinina B/deficiência , Amnésia Anterógrada/tratamento farmacológico , Colecistocinina/metabolismo , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/metabolismo , Masculino , Camundongos Knockout , Camundongos Endogâmicos C57BL , Potenciação de Longa Duração/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos
7.
J Epidemiol Community Health ; 78(8): 522-528, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38768983

RESUMO

BACKGROUND: Early retirement is highly prevalent in Taiwan. This study assesses the association between early retirement and all-cause and cause-specific mortality risks while exploring the modifying effect of sociodemographic factors. METHODS: Using Taiwan's National Health Insurance Research Database between 2009 and 2019, 1 762 621 early retirees aged 45-64 and an equal number of employed comparators were included. The date and cause of death were identified using the National Death Registry. Cox regression models were used to estimate HRs of early retirement for all-cause mortality and cause-specific mortality. To explore modifying effects, we conducted subgroup analyses based on age groups, sexes, occupation types and general health status (Charlson Comorbid Index score). RESULTS: The analysis revealed that early retirees, compared with their concurrently employed counterparts, had a higher mortality risk (adjusted HR (aHR) 1.69, 95% CI (1.67 to 1.71)). Specifically, younger individuals (aged 45-54) (aHR 2.74 (95% CI 2.68 to 2.80)), males (aHR 1.78 (95% CI 1.76 to 1.81)), those in farming or fishing occupations (aHR 2.13 (95% CI 2.06 to 2.21)) or the private sector (aHR 1.92 (95% CI 1.89 to 1.96)), and those with the poorest health conditions (aHR 1.79 (95% CI 1.76 to 1.83)) had higher mortality risks of early retirement. Regarding specific causes of death, the top three highest risks were associated with gastrointestinal disorders, followed by suicide and neurological disorders. CONCLUSIONS: This study underscores the substantial mortality risk increase linked to early retirement, emphasising the importance of policy considerations, particularly regarding vulnerable populations and specific causes of death potentially linked to unhealthy lifestyles.


Assuntos
Causas de Morte , Mortalidade , Aposentadoria , Humanos , Masculino , Taiwan/epidemiologia , Feminino , Pessoa de Meia-Idade , Mortalidade/tendências , Fatores de Risco , Fatores Etários
8.
Int J Epidemiol ; 53(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38553032

RESUMO

BACKGROUND: Studying the causes of death among deceased spouses and surviving partners may provide insights into the underlying mechanisms of the association between widowhood and mortality. This study investigated the mortality risk of widowhood in Taiwan, examined the association of the cause of death between widowed individuals and their deceased spouses and explored potential modifying effects by age, gender and duration after widowhood. METHODS: This matched cohort study utilized Taiwan's National Health Insurance claims database and National Death Registry. In total, 204 010 widowed men and 596 136 widowed women were identified with a mean follow-up period of 6.9 and 7.9 years, respectively, and 816 040 comparison men and 2 384 544 comparison women were selected. RESULTS: Widowhood was associated with an increased mortality risk, with widowed men having a 1.32 increased risk and widowed women having a 1.27 increased risk. Age at spousal death and duration modified the associations after widowhood. The widowed individuals are more likely to die by the same cause as the deceased spouse if they died by suicide, accident, endocrine, gastrointestinal disorders or infection. CONCLUSIONS: The study suggests that healthcare policies and interventions should be developed to improve widowed individuals' health and overall welfare.


Assuntos
Suicídio , Viuvez , Masculino , Humanos , Feminino , Estudos de Coortes , Taiwan/epidemiologia
9.
J Craniofac Surg ; 35(4): 1261-1263, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38349356

RESUMO

OBJECTIVE: Depressed scarring is a common complication after incisional upper blepharoplasty and frequently contributes to patient dissatisfaction. Correcting this deformity presents a significant challenge for oculoplastic surgeons. This study aims to investigate the clinical effectiveness of employing the turnover orbicularis-septum composite flap technique in correcting depressed scars after double eyelid surgery. METHODS: This is a retrospective study of 118 patients who underwent revision blepharoplasty with depressed scar from November 2020 to February 2023. During the revision procedure, the adhesions of the original scar were meticulously dissected, and the residual orbital fat was thoroughly released. The orbicularis-septum composite flap was then inverted downward and smoothly laid over the depressed scar area to address the tissue deficit. After surgery, patient satisfaction was evaluated by assessing the improvement of the depressed scars and the shape of the double eyelid folds. RESULTS: Follow-up assessments were conducted over a period of 6 to 24 months postoperatively. The results were judged as fully satisfied in 78 cases (66.1%), basically satisfied in 32 cases (27.1%), and unsatisfied in 8 cases (6.8%). Among the unsatisfied patients, 5 patients complained of eyelid fold shallow or disappear, and 3 patients complained of asymmetry. All patients exhibited varying degrees of improvement in the depressed scars. CONCLUSIONS: The turnover orbicularis-septum composite flap technique provides an effective approach for the treatment of depressed scars with a high satisfaction rate.


Assuntos
Blefaroplastia , Cicatriz , Satisfação do Paciente , Retalhos Cirúrgicos , Humanos , Blefaroplastia/métodos , Feminino , Cicatriz/cirurgia , Cicatriz/etiologia , Estudos Retrospectivos , Masculino , Adulto , Pessoa de Meia-Idade , Reoperação , Complicações Pós-Operatórias/cirurgia , Pálpebras/cirurgia , Idoso , Resultado do Tratamento
10.
Kidney Med ; 6(2): 100768, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38304580

RESUMO

Rationale & Objective: We aimed to study the comparative effectiveness of percutaneous coronary intervention with drug-eluting stent and coronary artery bypass grafting in patients receiving dialysis. Study Design: This was a retrospective observational cohort study. Setting & Participants: This population-based study identified patients receiving dialysis hospitalized for coronary revascularization between January 1, 2009 and December 31, 2015, in the Taiwan National Health Insurance Research Database. Exposures: Patients received percutaneous coronary intervention with drug-eluting stent versus coronary artery bypass grafting. Outcomes: The study outcomes were all-cause mortality, in-hospital mortality, and repeat revascularization. Analytical Approach: Propensity scores were used to match patients. Cox proportional hazards models and logistic regression models were constructed to examine associations between revascularization strategies and mortality. Interval Cox models were fitted to estimate time-varying hazards during different periods. Results: A total of 1,840 propensity score-matched patients receiving dialysis were analyzed. Coronary artery bypass grafting was associated with higher in-hospital mortality (coronary artery bypass grafting vs percutaneous coronary intervention with drug-eluting stent; crude mortality rate 12.5% vs 3.3%; adjusted OR, 5.22; 95% CI, 3.42-7.97; P < 0.001) and longer hospitalization duration (median [IQR], 20 [14-30] days vs 3 [2-8] days; P < 0.001). After discharge, repeat revascularization, acute coronary syndrome, and repeat hospitalization all occurred more frequently in the percutaneous coronary intervention with drug-eluting stent group. Importantly, with a median follow-up of 2.8 years, coronary artery bypass grafting was significantly associated with a higher risk of all-cause overall mortality (adjusted HR, 1.19; 95% CI, 1.05-1.35; P = 0.006) in the multivariable Cox proportional hazard model. Sensitivity and subgroup analyses yielded consistent results. Limitations: This was an observational study with mainly Asian ethnicity. Conclusions: Percutaneous coronary intervention with drug-eluting stent may be associated with better survival than coronary artery bypass grafting in patients receiving dialysis. Future studies are warranted to confirm this finding.


Although coronary artery bypass grafting offers better long-term survival in the general population than percutaneous coronary intervention with drug-eluting stent, patients receiving dialysis may be too frail to tolerate the increased perioperative mortality risk of coronary artery bypass grafting. In this retrospective study in a national cohort of patients receiving dialysis from Taiwan, percutaneous coronary intervention with drug-eluting stent is associated with lower in-hospital mortality and better long-term survival when compared with coronary artery bypass grafting. Subsequent acute coronary syndrome, repeat revascularization, and rehospitalization were noted more frequently in the percutaneous coronary intervention with drug-eluting stent group. These findings may suggest percutaneous coronary intervention with drug-eluting stent as a safe revascularization strategy for patients receiving dialysis.

11.
Am J Physiol Endocrinol Metab ; 326(5): E547-E554, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38363735

RESUMO

Type 2 diabetes (T2D) prevalence in adults at a younger age has increased but the disease status may go unnoticed. This study aimed to determine whether the onset age and subsequent diabetic complications can be attributed to the polygenic architecture of T2D in the Taiwan Han population. A total of 9,627 cases with T2D and 85,606 controls from the Taiwan Biobank were enrolled. Three diabetic polygenic risk scores (PRSs), PRS_EAS and PRS_EUR, and a trans-ancestry PRS (PRS_META), calculated using summary statistic from East Asian and European populations. The onset age was identified by linking to the National Taiwan Insurance Research Database, and the incidence of different diabetic complications during follow-up was recorded. PRS_META (7.4%) explained a higher variation for T2D status. And the higher percentile of PRS is also correlated with higher percentage of T2D family history and prediabetes status. More, the PRS was negatively associated with onset age (ß = -0.91 yr), and this was more evident among males (ß = -1.11 vs. -0.76 for males and females, respectively). The hazard ratio of diabetic retinopathy (DR) and diabetic foot were significantly associated with PRS_EAS and PRS_META, respectively. However, the PRS was not associated with other diabetic complications, including diabetic nephropathy, cardiovascular disease, and hypertension. Our findings indicated that diabetic PRS which combined susceptibility variants from cross-population could be used as a tool for early screening of T2D, especially for high-risk populations, such as individuals with high genetic risk, and may be associated with the risk of complications in subjects with T2D. NEW & NOTEWORTHY Our findings indicated that diabetic polygenic risk score (PRS) which combined susceptibility variants from Asian and European population affect the onset age of type 2 diabetes (T2D) and could be used as a tool for early screening of T2D, especially for individuals with high genetic risk, and may be associated with the risk of diabetic complications among people in Taiwan.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Masculino , Adulto , Feminino , Humanos , Diabetes Mellitus Tipo 2/genética , Estratificação de Risco Genético , Taiwan , Predisposição Genética para Doença , Idade de Início , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , Fatores de Risco
12.
Insect Mol Biol ; 33(3): 218-227, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38319237

RESUMO

Zeugodacus cucurbitae Coquillett (Diptera: Tephritidae) is an agriculturally and economically important pest worldwide that has developed resistance to ß-cypermethrin. Glutathione S-transferases (GSTs) have been reported to be involved in the detoxification of insecticides in insects. We have found that both ZcGSTd6 and ZcGSTd10 were up-regulated by ß-cypermethrin induction in our previous study, so we aimed to explore their potential relationship with ß-cypermethrin tolerance in this study. The heterologous expression of ZcGSTd6 and ZcGSTd10 in Escherichia coli showed significantly high activities against 1-chloro-2,4-dinitrobenzene (CDNB). The kinetic parameters of ZcGSTd6 and ZcGSTd10 were determined by Lineweaver-Burk. The Vmax and Km of ZcGSTd6 were 0.50 µmol/min·mg and 0.3 mM, respectively. The Vmax and Km of ZcGSTd10 were 1.82 µmol/min·mg and 0.53 mM. The 3D modelling and molecular docking results revealed that ß-cypermethrin exhibited a stronger bounding to the active site SER-9 of ZcGSTd10. The sensitivity to ß-cypermethrin was significantly increased by 18.73% and 27.21%, respectively, after the knockdown of ZcGSTd6 and ZcGSTd10 by using RNA interference. In addition, the inhibition of CDNB at 50% (IC50) and the inhibition constants (Ki) of ß-cypermethrin against ZcGSTd10 were determined as 0.41 and 0.33 mM, respectively. The Ki and IC50 of ß-cypermethrin against ZcSGTd6 were not analysed. These results suggested that ZcGSTd10 could be an essential regulator involved in the tolerance of Z. cucurbitae to ß-cypermethrin.


Assuntos
Glutationa Transferase , Proteínas de Insetos , Resistência a Inseticidas , Inseticidas , Tephritidae , Animais , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Resistência a Inseticidas/genética , Simulação de Acoplamento Molecular , Piretrinas/farmacologia , Interferência de RNA , Tephritidae/genética , Tephritidae/enzimologia , Tephritidae/efeitos dos fármacos , Tephritidae/metabolismo
13.
Int J Epidemiol ; 53(1)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38199793

RESUMO

BACKGROUND: Whether paternal age associated with offspring's epilepsy risk is a cause of de novo mutation as men age, or just an association due to confounding factors, is still unclear. METHODS: We performed a population-based, multi-generation and sibling comparison study in Taiwan, which included 2 751 232 singletons born in 2001-17 who were followed until 2020. Of these, 819 371/826 087 with information on paternal/maternal grandparents were selected for multi-generation analyses and 1 748 382 with sibling(s) were selected for sibling comparison. Cox proportional hazard regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the total cohort, there was an increased risk of epilepsy in individuals with advanced paternal age, e.g. the HR for paternal age ≥50 was1.36 (95% CI: 1.15-1.61) compared with paternal age 25-29, and fathers older than mothers, e.g. the HR for parental age difference ≥15 years was 1.29 (95% CI: 1.16-1.43). When accounting for parental age difference, the association between paternal age and epilepsy in offspring was attenuated (HR for paternal age ≥50 was 1.11, 95% CI: 0.93-1.34). Multi-generation analyses did not support the association of advanced grand-paternal age at childbirth of the parent with offspring's risk of epilepsy. Sibling comparison analyses did not support the association of older paternal age with increased risk of epilepsy (HR was 0.96 for per year increase in paternal age, 95% CI: 0.96-0.97). CONCLUSIONS: These results do not support the hypothesis that advanced paternal age is associated with epilepsy in offspring. Instead, familial factors may explain the observed paternal age association with the offspring's risk of epilepsy.


Assuntos
Epilepsia , Idade Paterna , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Adolescente , Pai , Fatores de Risco , Causalidade , Epilepsia/etiologia , Epilepsia/genética
14.
Am J Nephrol ; 55(1): 86-105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37734331

RESUMO

INTRODUCTION: Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer. Studies have revealed that DEHP exposure can cause kidney damage. Green tea is among the most popular beverages in China. Green tea polyphenols (GTPs) have been proven to have therapeutic effects on organ damage induced by heavy metal exposure. However, few studies have reported on GTP-relieving DEHP-induced kidney damage. METHODS: C57BL/6J male mice aged 6-8 weeks were treated with distilled water (control group), 1,500 mg/kg/d DEHP + corn oil (model group), 1,500 mg/kg/d DEHP + corn oil + 70 mg/kg GTP (treatment group), corn oil (oil group), and 70 mg/kg GTP (GTP group) by gavage for 8 weeks, respectively. The renal function of mice and renal tissue histopathology of each group were evaluated. The renal tissues of mice in the model, treatment, and control groups were analyzed using high-throughput sequencing. We calculated the differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) using the limma R package, the CIBERSORT algorithm was used to predict immune infiltration, the starBase database was used to screen the miRNA-mRNA regulatory axis, and immunohistochemical analyses were performed to verify protein expression. RESULTS: GTP alleviated the deterioration of renal function, renal inflammation and fibrosis, and mitochondrial and endoplasmic reticulum lesions induced by DEHP in mice. Differential immune infiltrations of plasma, dendritic, T, and B cells were noted between the model and treatment groups. We found that three differentially expressed miRNAs (mmu-miR-383-5p, mmu-miR-152-3p, and mmu-miR-144-3p), three differentially expressed mRNAs (Ddit4, Dusp1, and Snx18), and three differentially expressed proteins (Ddit4, Dusp1, and Snx18) played crucial roles in the miRNA-mRNA-protein regulatory axes when GTPs mitigate DEHP-induced kidney damage in mice. CONCLUSION: GTP can alleviate DEHP-induced kidney damage and regulate immune cell infiltration. We screened four important miRNA-mRNA-protein regulatory axes of GTP, mitigating DEHP-induced kidney damage in mice.


Assuntos
Dietilexilftalato , MicroRNAs , Ácidos Ftálicos , Animais , Camundongos , Masculino , Dietilexilftalato/toxicidade , Óleo de Milho/farmacologia , Camundongos Endogâmicos C57BL , Antioxidantes , Rim , MicroRNAs/genética , MicroRNAs/farmacologia , RNA Mensageiro , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Guanosina Trifosfato/farmacologia
15.
Cell Genom ; 3(12): 100436, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38116116

RESUMO

Genome-wide association studies (GWASs) have identified tens of thousands of genetic loci associated with human complex traits. However, the majority of GWASs were conducted in individuals of European ancestries. Failure to capture global genetic diversity has limited genomic discovery and has impeded equitable delivery of genomic knowledge to diverse populations. Here we report findings from 102,900 individuals across 36 human quantitative traits in the Taiwan Biobank (TWB), a major biobank effort that broadens the population diversity of genetic studies in East Asia. We identified 968 novel genetic loci, pinpointed novel causal variants through statistical fine-mapping, compared the genetic architecture across TWB, Biobank Japan, and UK Biobank, and evaluated the utility of cross-phenotype, cross-population polygenic risk scores in disease risk prediction. These results demonstrated the potential to advance discovery through diversifying GWAS populations and provided insights into the common genetic basis of human complex traits in East Asia.

16.
BMC Public Health ; 23(1): 2346, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012695

RESUMO

BACKGROUND: Most studies have focused on the risk factors, treatment, and care of affective psychosis, and several have reported a relationship between ambient air quality and this psychosis. Although an association has been reported between psychosis and genes, studies mainly explored the associations between one type of psychosis and one gene; few have identified genes related to affective psychosis. This study investigates the genetic and environmental factors of affective psychosis. METHODS: In this retrospective longitudinal study, 27 604 participants aged 30-70 were selected from Taiwan Biobank. The participants' propensity scores were calculated based on their demographic information, and propensity score matching was performed to divide the participants into an experimental (i.e., affective psychosis) and control group at a 1:5 ratio. Plink was used to analyze the major and minor types of gene expression related to affective psychosis, and PM2.5 exposure was incorporated into the analyses. RESULTS: According to the generalized estimating equation analysis results, 8 single nucleotide polymorphisms (SNPs) belonging to the ANK3, BDNF, CACNA1C, and GRID1 genotypes were significantly correlated with depressive disorder (P < .001), with the majority belonging to the ANK3 and CACNA1C. A total of 5 SNPs belonging to the CACNA1C, GRID1, and SIRT1 genotypes were significantly correlated with bipolar disorder (P < .001), with the majority belonging to the CACNA1C. No significant correlation was identified between ambient air pollution and affective psychosis. CONCLUSIONS: CACNA1C and GRID1 are common SNP genotypes for depressive disorder and bipolar disorder and should be considered associated with affective psychosis.


Assuntos
Bancos de Espécimes Biológicos , Predisposição Genética para Doença , Humanos , Estudos Retrospectivos , Estudos Longitudinais , Taiwan/epidemiologia , Canais de Cálcio Tipo L/genética , Transtornos do Humor , Polimorfismo de Nucleotídeo Único , Material Particulado/efeitos adversos , Estudo de Associação Genômica Ampla
17.
J Inflamm Res ; 16: 4461-4470, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842189

RESUMO

The activation of the cGAS-STING pathway is associated with many sterile inflammatory and inflammatory conditions, including acute kidney injury. As a cytoplasmic DNA sensor, sensitization of the cGAS-STING pathway can ignite the innate immune response in vivo and trigger a series of biological effects. In recent years, there is increasing evidence showing that the cGAS-STING pathway plays a vital role in acute kidney injury, a non-inflammatory disease induced by activation of innate immune cells, and closely related to intracellular reactive oxygen species, mitochondrial DNA, and the cGAS-STING pathway. This review provides a prospect of the cGAS-STING pathway and its relationship to acute kidney injury.

19.
Psychiatry Res ; 328: 115461, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37729717

RESUMO

Previous studies found that an NMDA receptor (NMDAR) enhancer, sodium benzoate, improved cognitive function of patients with early-phase Alzheimer's disease (AD). Transcranial direct current stimulation (tDCS) induces NMDAR-dependent synaptic plasticity and strengthens cognitive function of AD patients. This study aimed to evaluate efficacy and safety of tDCS plus benzoate in early-phase dementia. In this 24-week randomized, double-blind, placebo-controlled trial, 97 patients with early-phase AD received 10-session tDCS during the first 2 weeks. They then took benzoate or placebo for 24 weeks. We assessed the patients using Alzheimer's disease assessment scale - cognitive subscale (ADAS-cog), Clinician's Interview-Based Impression of Change plus Caregiver Input, Mini Mental Status Examination, Alzheimer's disease Cooperative Study scale for ADL in MCI, and a battery of additional cognitive tests. Forty-seven patients received sodium benzoate, and the other 50 placebo. The two treatment groups didn't differ significantly in ADAS-cog or other measures. Addition of benzoate to tDCS didn't get extra benefit or side effect in this study. For more thoroughly studying the potential of combining tDCS with benzoate in the AD treatment, future research should use other study designs, such as longer-term benzoate treatment, adding benzoate in the middle of tDCS trial sessions, or administering benzoate then tDCS.


Assuntos
Doença de Alzheimer , Estimulação Transcraniana por Corrente Contínua , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Benzoato de Sódio/farmacologia , Benzoato de Sódio/uso terapêutico , Cognição , Método Duplo-Cego
20.
Cancer Med ; 12(19): 19968-19977, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37706606

RESUMO

BACKGROUND: The co-occurrence of depression and diabetes mellitus has been linked to an increased risk of developing cancer. This study aimed to investigate whether depression further amplifies the risk of cancer among individuals with diabetes. METHODS: This population-based matched cohort study utilized Taiwan's National Health Insurance claims database. A total of 85,489 newly diagnosed diabetic patients with depressive disorders were selected, along with 427,445 comparison subjects. The matching process involved age, sex, and the calendar year of diabetes onset. The average follow-up duration for the two cohorts was 6.4 and 6.5 years, respectively. The primary outcome of interest was the occurrence of overall cancer or cancer at specific anatomical sites. RESULTS: The adjusted hazard ratios for overall cancer incidence were 1.08 (95% CI, 1.05-1.11). For site-specific cancers, depression exhibited significant associations with oropharyngeal, esophageal, liver, gynecological, prostate, kidney, and hematologic malignancies among patients with diabetes. Notably, a severity-response relationship was observed, indicating that patients with recurrent episodes of major depressive disorders exhibited a higher incidence of cancer compared to those diagnosed with dysthymia or depressive disorder not otherwise specified. Furthermore, the strength of the association between depression and cancer risk was more pronounced among younger patients with diabetes as opposed to older adults. However, no significant relationship was observed between adherence to antidepressant treatment and cancer risk. CONCLUSIONS: The findings of this study indicate a significant association between depression and an elevated risk of cancer among individuals diagnosed with diabetes. Future investigations should replicate our findings, explore the effects of pharmacological and non-pharmacological treatments on cancer risk, and identify the underlying mechanisms.


Assuntos
Transtorno Depressivo Maior , Diabetes Mellitus , Neoplasias , Masculino , Humanos , Idoso , Estudos de Coortes , Depressão/complicações , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Incidência , Neoplasias/epidemiologia , Fatores de Risco , Taiwan/epidemiologia
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