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1.
Cell ; 187(5): 1296-1311.e26, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38428397

RESUMO

Most membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use. Here, we describe GlycoSHIELD, a reductionist method that can be implemented on personal computers to graft realistic ensembles of glycan conformers onto static protein structures in minutes. Using molecular dynamics simulation, small-angle X-ray scattering, cryoelectron microscopy, and mass spectrometry, we show that this open-access toolkit provides enhanced models of glycoprotein structures. Focusing on N-cadherin, human coronavirus spike proteins, and gamma-aminobutyric acid receptors, we show that GlycoSHIELD can shed light on the impact of glycans on the conformation and activity of complex glycoproteins.


Assuntos
Glicoproteínas , Simulação de Dinâmica Molecular , Humanos , Microscopia Crioeletrônica , Glicoproteínas/química , Glicosilação , Polissacarídeos/química
2.
J Biol Chem ; 300(1): 105553, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072060

RESUMO

Proteins can spontaneously tie a variety of intricate topological knots through twisting and threading of the polypeptide chains. Recently developed artificial intelligence algorithms have predicted several new classes of topological knotted proteins, but the predictions remain to be authenticated experimentally. Here, we showed by X-ray crystallography and solution-state NMR spectroscopy that Q9PR55, an 89-residue protein from Ureaplasma urealyticum, possesses a novel 71 knotted topology that is accurately predicted by AlphaFold 2, except for the flexible N terminus. Q9PR55 is monomeric in solution, making it the smallest and most complex knotted protein known to date. In addition to its exceptional chemical stability against urea-induced unfolding, Q9PR55 is remarkably robust to resist the mechanical unfolding-coupled proteolysis by a bacterial proteasome, ClpXP. Our results suggest that the mechanical resistance against pulling-induced unfolding is determined by the complexity of the knotted topology rather than the size of the molecule.


Assuntos
Inteligência Artificial , Proteínas de Bactérias , Dobramento de Proteína , Ureaplasma urealyticum , Modelos Moleculares , Peptídeos , Proteínas de Bactérias/química , Estrutura Terciária de Proteína
3.
EMBO Rep ; 23(11): e54746, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36156348

RESUMO

Melanoma is the deadliest of skin cancers and has a high tendency to metastasize to distant organs. Calcium and metabolic signals contribute to melanoma invasiveness; however, the underlying molecular details are elusive. The MCU complex is a major route for calcium into the mitochondrial matrix but whether MCU affects melanoma pathobiology was not understood. Here, we show that MCUA expression correlates with melanoma patient survival and is decreased in BRAF kinase inhibitor-resistant melanomas. Knockdown (KD) of MCUA suppresses melanoma cell growth and stimulates migration and invasion. In melanoma xenografts, MCUA_KD reduces tumor volumes but promotes lung metastases. Proteomic analyses and protein microarrays identify pathways that link MCUA and melanoma cell phenotype and suggest a major role for redox regulation. Antioxidants enhance melanoma cell migration, while prooxidants diminish the MCUA_KD -induced invasive phenotype. Furthermore, MCUA_KD increases melanoma cell resistance to immunotherapies and ferroptosis. Collectively, we demonstrate that MCUA controls melanoma aggressive behavior and therapeutic sensitivity. Manipulations of mitochondrial calcium and redox homeostasis, in combination with current therapies, should be considered in treating advanced melanoma.


Assuntos
Cálcio , Melanoma , Humanos , Cálcio/metabolismo , Proteômica , Melanoma/genética , Melanoma/metabolismo , Oxirredução , Fenótipo , Linhagem Celular Tumoral
4.
Bioorg Med Chem ; 109: 117792, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38897139

RESUMO

Cancer has been a leading cause of death over the last few decades in western countries as well as in Taiwan. However, traditional therapies are limited by the adverse effects of chemotherapy and radiotherapy, and tumor recurrence may occur. Therefore, it is critical to develop novel therapeutic drugs. In the field of HDAC inhibitor development, apart from the hydroxamic acid moiety, 2-aminobenzamide also functions as a zinc-binding domain, which is shown in well-known HDAC inhibitors such as Entinostat and Chidamide. With recent successful experiences in synthesizing 1-(phenylsulfonyl)indole-based compounds, in this study, we further combined two features of the above chemical compounds and generated indolyl benzamides. Compounds were screened in different cancer cell lines, and enzyme activity was examined to demonstrate their potential for anti-HDAC activity. Various biological functional assays evidenced that two of these compounds could suppress cancer growth and migration capacity, through regulating epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis mechanisms. Data from 3D cancer cells and the in vivo zebrafish model suggested the potential of these compounds in cancer therapy in the future.


Assuntos
Antineoplásicos , Apoptose , Ciclo Celular , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal , Inibidores de Histona Desacetilases , Peixe-Zebra , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/síntese química , Humanos , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Histona Desacetilases/metabolismo
5.
Mol Ther ; 31(11): 3322-3336, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37689971

RESUMO

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.


Assuntos
Anticorpos Monoclonais , Anticorpos Amplamente Neutralizantes , COVID-19 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/genética , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais , COVID-19/terapia , Dependovirus/genética , RNA Viral , SARS-CoV-2/genética , Anticorpos Amplamente Neutralizantes/farmacologia , Anticorpos Amplamente Neutralizantes/uso terapêutico
6.
J Stroke Cerebrovasc Dis ; 33(8): 107826, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908612

RESUMO

BACKGROUND AND PURPOSE: Post-stroke cognitive impairment (PSCI) is highly prevalent in modern society. However, there is limited study implying an accurate and explainable machine learning model to predict PSCI. The aim of this study is to develop and validate a web-based artificial intelligence (AI) tool for predicting PSCI. METHODS: The retrospective cohort study design was conducted to develop and validate a web-based prediction model. Adults who experienced a stroke between January 1, 2004, and September 30, 2017, were enrolled, and patients with PSCI were followed up from the stroke index date until their last follow-up. The model's performance metrics, including accuracy, area under the curve (AUC), recall, precision, and F1 score, were compared. RESULTS: A total of 3209 stroke patients were included in the study. The model demonstrated an accuracy of 0.8793, AUC of 0.9200, recall of 0.6332, precision of 0.9664, and F1 score of 0.7651. In the external validation phase, the accuracy improved to 0.9039, AUC to 0.9094, recall to 0.7457, precision to 0.9168, and F1 score to 0.8224. The final model can be accessed at https://psci-calculator.my.id/. CONCLUSION: Our results are able to produce a user-friendly interface that is useful for health practitioners to perform early prediction on PSCI. These findings also suggest that the provided AI model is reliable and can serve as a roadmap for future studies using AI models in a clinical setting.

7.
Cancer Sci ; 114(10): 4063-4072, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37489252

RESUMO

The study used clinical data to develop a prediction model for breast cancer survival. Breast cancer prognostic factors were explored using machine learning techniques. We conducted a retrospective study using data from the Taipei Medical University Clinical Research Database, which contains electronic medical records from three affiliated hospitals in Taiwan. The study included female patients aged over 20 years who were diagnosed with primary breast cancer and had medical records in hospitals between January 1, 2009 and December 31, 2020. The data were divided into training and external testing datasets. Nine different machine learning algorithms were applied to develop the models. The performances of the algorithms were measured using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1-score. A total of 3914 patients were included in the study. The highest AUC of 0.95 was observed with the artificial neural network model (accuracy, 0.90; sensitivity, 0.71; specificity, 0.73; PPV, 0.28; NPV, 0.94; and F1-score, 0.37). Other models showed relatively high AUC, ranging from 0.75 to 0.83. According to the optimal model results, cancer stage, tumor size, diagnosis age, surgery, and body mass index were the most critical factors for predicting breast cancer survival. The study successfully established accurate 5-year survival predictive models for breast cancer. Furthermore, the study found key factors that could affect breast cancer survival in Taiwanese women. Its results might be used as a reference for the clinical practice of breast cancer treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Adulto , Estudos Retrospectivos , Aprendizado de Máquina , Valor Preditivo dos Testes , Curva ROC
8.
Cancer ; 129(24): 3928-3937, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37867369

RESUMO

BACKGROUND: Although diabetes is a poor prognostic factor for colorectal cancer (CRC), whether diabetes severity provides an additional predictive value for CRC prognosis remains unclear. The study aimed to investigate the prognostic differences after curative CRC resection among patients with different diabetic severities. METHODS: This population-based retrospective cohort study analyzed data registered between 2007 and 2015 in the Cancer Registry Database, which is linked to the National Health Insurance Research Database and National Death Registry. Patients with CRC who underwent curative radical resection for stage I-III disease were evaluated, with their diabetic status subdivided into no diabetes, diabetes without complication, and diabetes with complications. Cox regressions were applied to determine the association between diabetes severity and CRC survival, including overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS). RESULTS: A total of 59,202 patients with CRC were included. Compared with the no diabetes group, the diabetes without complication group has insignificantly worse OS (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09), DFS (HR, 1.08; 95% CI, 1.04-1.12), and CSS (HR, 0.98; 95% CI, 0.93-1.03), whereas those with complicated diabetes had a significantly higher risk of poor survival (OS: HR, 1.85; 95% CI, 1.78-1.92; DFS: HR, 1.75; 95% CI, 1.69-1.82; CSS: HR, 1.41; 95% CI, 1.33-1.49). Patients with CRC and diabetes also had a higher risk of recurrence than did those without diabetes. Sex and TNM staging were important effect modifiers. CONCLUSIONS: Among patients with CRC who undergo curative resection, the severity of the diabetes is inversely correlated with long-term outcomes, especially in women and patients in the earlier stages of CRC. PLAIN LANGUAGE SUMMARY: The prognostic impact of diabetes severity in colorectal cancer (CRC) is yet to be clarified. In this cohort study of 59,202 patients with CRC, compared with patients with CRC and without diabetes, those with uncomplicated diabetes had an insignificantly worse CRC survival, whereas those with complicated diabetes had a significantly higher risk of poor survival. Multidisciplinary medical care to prevent progression into diabetes with complications is needed to improve survival among patients with CRC and diabetes.


Assuntos
Neoplasias Colorretais , Diabetes Mellitus , Humanos , Feminino , Estudos de Coortes , Estudos Retrospectivos , Taiwan/epidemiologia , Prognóstico , Estadiamento de Neoplasias , Diabetes Mellitus/epidemiologia , Intervalo Livre de Doença , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia
9.
BMC Med ; 21(1): 249, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37424030

RESUMO

BACKGROUND: This study aimed to determine whether primary parathyroid cancer patients were associated with increased metabolic and cardiovascular comorbidities in comparison to the general population. METHODS: We used the National Taiwan Cancer Registry Database to construct a cohort of patients with parathyroid cancer from January 1, 2004, to December 31, 2019. We compared the incidence of hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, coronary heart disease, and heart failure with the general population matched based on a propensity score in a one-to-five fashion. RESULTS: A total of 72 parathyroid cancer patients and 360 matched general population (mean age: 55 years; 59% women) were included, with different exclusive numbers for each metabolic and cardiovascular comorbidity cohort. The number of cases based on a total of 2347.7 person-years of observation included 53 deaths, 29 hypertension, 9 diabetes, 13 hyperlipidemia, 10 atrial fibrillation, 18 coronary artery disease, and 13 heart failure. According to multivariate analysis, parathyroid cancer remained significantly associated with diabetes [hazard ratio (HR): 9.28; 95% confidence interval (CI): 1.72-50.07], hyperlipidemia (HR: 5.86; 95% CI: 1.61-21.31), and heart failure (HR: 4.46; 95% CI: 1.18-16.84). Sub-distribution of competing mortality events and subgroup analysis showed robust evidence of metabolic and cardiovascular comorbidities. This national cohort study demonstrated that adult parathyroid cancer patients had a significantly higher incidence of diabetes mellitus, hyperlipidemia, and heart failure than the general population. CONCLUSIONS: An increased risk of metabolic and cardiac comorbidities among parathyroid cancer patients required great caution.


Assuntos
Fibrilação Atrial , Doença da Artéria Coronariana , Insuficiência Cardíaca , Hiperlipidemias , Hipertensão , Neoplasias das Paratireoides , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos de Coortes , Fibrilação Atrial/epidemiologia , Taiwan/epidemiologia , Neoplasias das Paratireoides/epidemiologia , Comorbidade , Hipertensão/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Insuficiência Cardíaca/epidemiologia , Hiperlipidemias/epidemiologia , Incidência , Fatores de Risco , Estudos Retrospectivos
10.
BMC Womens Health ; 23(1): 606, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964288

RESUMO

BACKGROUND: Sarcopenia is a chronic disease marked by gradual muscle system and functional decline. Prior research indicates its prevalence in those under 60 varies from 8 to 36%. There is limited evidence on the effectiveness of non-pharmacological interventions for sarcopenia prevention in menopausal women aged 40-60. This study examines the influence of such interventions for sarcopenia prevention on these women. METHODS: PubMed, EMBASE, Medline, Cochrane Library, CINAHL, PEDro, and Airiti Library were searched from inception until May 5, 2023. Randomized controlled trials that examined exercise, vitamin D and protein supplementation effects on muscle mass, strength, and physical function. Quality assessment used the Cochrane risk of bias tool, and analysis employed Comprehensive Meta-Analysis version 2.0. RESULTS: A total of 27 randomized controlled trials, involving 1,989 participants were identified. Meta-analysis results showed exercise improved lean body mass (SMD = 0.232, 95% CI: 0.097, 0.366), handgrip strength (SMD = 0.901, 95% CI: 0.362, 1.441), knee extension strength (SMD = 0.698, 95% CI: 0.384, 1.013). Resistance training had a small effect on lean body mass, longer exercise duration (> 12 weeks) and higher frequency (60-90 min, 3 sessions/week) showed small to moderate effects on lean body mass. Vitamin D supplementation improved handgrip strength (SMD = 0.303, 95% CI: 0.130, 0.476), but not knee extension strength. There was insufficient data to assess the impact of protein supplementation on muscle strength. CONCLUSIONS: Exercise effectively improves muscle mass, and strength in menopausal women. Resistance training with 3 sessions per week, lasting 20-90 min for at least 6 weeks, is most effective. Vitamin D supplementation enhances small muscle group strength. Further trials are needed to assess the effects of vitamin D and protein supplementation on sarcopenia prevention. REGISTRATION NUMBER: This review was registered on PROSPERO CRD42022329273.


Assuntos
Sarcopenia , Humanos , Feminino , Sarcopenia/prevenção & controle , Força da Mão , Ensaios Clínicos Controlados Aleatórios como Assunto , Força Muscular , Vitamina D/uso terapêutico , Menopausa
11.
BMC Ophthalmol ; 23(1): 15, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627584

RESUMO

BACKGROUND: This study attempted to illustrate the demographic of inpatient eye careservice from 1997 to 2011 in Taiwan, and also the ophthalmic disease landscape and utilization change over time. These insights might apply to resource allocation planning and trainees' better understandings of ophthalmic inpatient practice. METHODS: This study utilized Taiwan's National Health Insurance Research Database (NHIRD). Admission records of eye service that occurred since 1997 and until 2011 were included. Records were separated into operative and non-operative. The records were further divided according to their time: a group of early time before 2006 and a late one after 2006. RESULTS: Patients' mean age were 56 and 44 years for operative and non-operative records. The sex ratio (male to female) was 1.3, and the average of admission duration was 4 days. The average spending was around 1000 United State Dollars per admission and a gradually upgoing trend was also noted. The number of inpatient eye services decreased over time, from 3,248 to 2,174 in the studied period. Cases admitted for operation primarily underwent cataract surgery, vitrectomy, and scleral buckling during the studied period. Trabeculectomy emerged as another major indication of admission during the later time. Cases admitted for non-operative management were primarily corneal ulcer, glaucoma, and infection, including orbital cellulitis and lid abscess. Corneal ulcers made up a major proportion of admission records in the non-operative group during both periods. CONCLUSIONS: This study described the demographics of inpatient eye service in Taiwan. Ophthalmologist, especially trainees, and officials could make better policies according to the presented results in this study.


Assuntos
Úlcera da Córnea , Glaucoma , Oftalmologia , Humanos , Masculino , Feminino , Taiwan/epidemiologia , Pacientes Internados , Hospitalização
12.
Nucleic Acids Res ; 49(W1): W336-W345, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34048582

RESUMO

With the continuing rise of lipidomic studies, there is an urgent need for a useful and comprehensive tool to facilitate lipidomic data analysis. The most important features making lipids different from general metabolites are their various characteristics, including their lipid classes, double bonds, chain lengths, etc. Based on these characteristics, lipid species can be classified into different categories and, more interestingly, exert specific biological functions in a group. In an effort to simplify lipidomic analysis workflows and enhance the exploration of lipid characteristics, we have developed a highly flexible and user-friendly web server called LipidSig. It consists of five sections, namely, Profiling, Differential Expression, Correlation, Network and Machine Learning, and evaluates lipid effects on cellular or disease phenotypes. One of the specialties of LipidSig is the conversion between lipid species and characteristics according to a user-defined characteristics table. This function allows for efficient data mining for both individual lipids and subgroups of characteristics. To expand the server's practical utility, we also provide analyses focusing on fatty acid properties and multiple characteristics. In summary, LipidSig is expected to help users identify significant lipid-related features and to advance the field of lipid biology. The LipidSig webserver is freely available at http://chenglab.cmu.edu.tw/lipidsig.


Assuntos
Lipidômica/métodos , Software , Animais , Biomarcadores , Mineração de Dados , Ácidos Graxos/química , Ferroptose , Internet , Metabolismo dos Lipídeos , Lipídeos/química , Aprendizado de Máquina , Camundongos , Neoplasias/metabolismo
13.
BMC Med Educ ; 23(1): 400, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268926

RESUMO

BACKGROUND: Physicians' values about what constitute their professional identities are integral in understanding how they ascribe meaning to their practice. However, there is no general consensus on the conceptualization and measurement of physicians' professional identities. This study developed and validated a values-based scale for measuring physicians' professional identities. METHODS: A hybrid research method was used to gather both qualitative and quantitative data. We employed literature review, semi-structured interview, Q-sorting exercise to examine the conceptualization of emergency physicians' professional identities and to initially develop a 40-item scale. A panel of five experts assessed the scale's content validity. Using 150 emergency physicians as our sample, we conducted Confirmatory Factor Analyses (CFA) to test the fit of our hypothesised four-factor model based on our preliminary findings. RESULTS: Initial CFA suggested revisions to the model. Following theoretical assumptions and modification indices, the model was revised and adjusted to a four-factor 20 item Emergency Physicians Professional Identities Value Scale (EPPIVS) with acceptable fit statistics χ2 = 389.38, df = 164, Normed χ2 = 2.374, GFI = 0.788, CFI = 0.862, RMSEA = 0.096. The Cronbach's alpha, McDonald's Omega reliability and composite reliability of the subscales ranged from α: 0.748 to 0.868, Omega: 0.759 to 0.868 and CR: 0.748 to 0.851, respectively. CONCLUSION: The results indicate that the EPPIVS is a valid and reliable scale for measuring physicians' professional identities. Further research on the sensitivity of this instrument to important changes over career progression in emergency medicine is warranted.


Assuntos
Formação de Conceito , Médicos , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Psicometria
14.
Int J Mol Sci ; 24(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36835224

RESUMO

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan's Health and Welfare Data Science Center (2000-2016) and linked with Taiwan Cancer Registry (1979-2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85-0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20-39 years (aOR: 0.70, 95% CI: 0.58-0.85), 40-64 years (aOR: 0.77, 95% CI: 0.74-0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.91), and overall (aOR: 0.81, 95% CI: 0.79-0.84). Ovarian cancer risk was significantly lower in the groups aged 40-64 years (aOR: 0.76, 95% CI: 0.69-0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75-092), and overall (aOR: 0.79, 95% CI: 0.74-0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20-39 years (aOR: 2.54, 95% CI: 1.79-3.61), 40-64 years (aOR: 1.08, 95% CI: 1.02-1.14), and overall (aOR: 1.06, 95% CI: 1.01-1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40-64 years (aOR: 0.88, 95% CI: 0.84-0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.90), and overall (aOR: 0.88, 95% CI: 0.85-0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86-0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality.


Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Neoplasias do Endométrio , Hipertensão , Neoplasias Ovarianas , Sistema Renina-Angiotensina , Feminino , Humanos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Casos e Controles , Neoplasias do Endométrio/epidemiologia , Hipertensão/tratamento farmacológico , Neoplasias Ovarianas/epidemiologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco
15.
Molecules ; 28(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37298827

RESUMO

Oxidative degradation of 2,4-dinitrotoluenes in aqueous solution was executed using persulfate combined with semiconductors motivated by ultrasound (probe type, 20 kHz). Batch-mode experiments were performed to elucidate the effects of diverse operation variables on the sono-catalytic performance, including the ultrasonic power intensity, dosage of persulfate anions, and semiconductors. Owing to pronounced scavenging behaviors caused by benzene, ethanol, and methanol, the chief oxidants were presumed to be sulfate radicals which originated from persulfate anions, motivated via either the ultrasound or sono-catalysis of semiconductors. With regard to semiconductors, the increment of 2,4-dinitrotoluene removal efficiency was inversely proportional to the band gap energy of semiconductors. Based on the outcomes indicated in a gas chromatograph-mass spectrometer, it was sensibly postulated that the preliminary step for 2,4-dinitrotoluene removal was denitrated into o-mononitrotoluene or p-mononitrotoluene, followed by decarboxylation to nitrobenzene. Subsequently, nitrobenzene was decomposed to hydroxycyclohexadienyl radicals and converted into 2-nitrophenol, 3-nitrophenol, and 4-nitrophenol individually. Nitrophenol compounds with the cleavage of nitro groups synthesized phenol, which was sequentially transformed into hydroquinone and p-benzoquinone.


Assuntos
Dinitrobenzenos , Poluentes Químicos da Água , Águas Residuárias , Oxirredução , Nitrobenzenos , Poluentes Químicos da Água/análise , Semicondutores
16.
Molecules ; 28(9)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37175152

RESUMO

Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.


Assuntos
Sulfatos de Condroitina , Versicanas , Ratos , Animais , Versicanas/genética , Sulfatos de Condroitina/farmacologia , Ratos Wistar , Axônios/metabolismo , Regeneração Nervosa , RNA Interferente Pequeno/farmacologia
17.
Nurs Ethics ; 30(1): 133-144, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36200369

RESUMO

BACKGROUND: Ethical dilemmas that arise in the clinical setting often require the collaboration of multiple disciplines to be resolved. However, medical and nursing curricula do not prioritize communication among disciplines regarding this issue. A common teaching strategy, problem-based learning, could be used to enhance communication among disciplines. Therefore, a university in southern Taiwan developed an interprofessional ethics education program based on problem-based learning strategies. This study described tutors' experience teaching in this program. AIM: To explore the phenomenon of teaching and learning in interprofessional ethics education for medical and nursing students from the perspectives of tutors. DESIGN: Phenomenological qualitative research. METHODS: Medical and nursing students completed a 6-week interprofessional ethics education program moderated by either physician or nurse tutors. At the conclusion of the ethics education program, all 14 tutors were invited to participate in focus group interviews. Among them, six tutors (three nursing tutors and three physician tutors) participated in additional individual interviews. All of the contents from the focus group interviews and individual interviews were recorded and transcribed. Using the phenomenological approach, the phenomenon of teaching and learning in interprofessional ethics education were generated. ETHICAL CONSIDERATION: The study was approved by the Institutional Review Board. FINDINGS: Three themes emerged from the tutors' teaching perspectives, including the instructor's motivation to teach, the use of narrative case scenarios, and the emphasis on improving interprofessional ethics communication. DISCUSSION: Problem-based learning creates an interprofessional communication platform in interprofessional ethics education. The phenomenon of value convergence between tutors and students, between different students' professions, and between different students' professional maturities is observed. CONCLUSION: Problem-based learning is an effective teaching strategy for creating a communication platform for interprofessional ethics education. Ethic curriculum should emphasize motivating instructor, use narrative case scenarios, and focus on interprofessional communication.


Assuntos
Aprendizagem , Estudantes de Medicina , Humanos , Aprendizagem Baseada em Problemas , Currículo , Motivação , Pesquisa Qualitativa , Ensino
18.
Hu Li Za Zhi ; 70(4): 95-102, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37469324

RESUMO

Taiwan has been an aging society since 2018. As a result, long-term care, end-of-life autonomy, and hospice care have received increasing attention. The government of Taiwan promotes home-based healthcare through the National Health Insurance System to enable the efficient utilization of medical resources and reduce overall medical costs. Taiwan's community hospice and palliative care network is expected to serve as the main care model supplementing partial hospitalization and institutional care. In this article, we review the history of and policies related to hospice and palliative care in Taiwan using a literature review and examining Pingtung County as a case study. The implementation of home-based palliative care is also outlined and policy revisions are proposed. The results are intended to provide a reference for healthcare authorities and medical institutions to promote community hospice and palliative care policies. The integrated care model can enhance the capacity of community-based palliative care, support patients receiving palliative care and their family members and caregivers, and ensure physical and psychological comfort for patients. This model contributes to the realization of older adults' preference for dying at home, which is especially pronounced in cultures where traditional Chinese ideas are deeply rooted.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Humanos , Idoso , Cuidados Paliativos/psicologia , Taiwan , Hospitais de Ensino
19.
BMC Cancer ; 22(1): 1198, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411401

RESUMO

BACKGROUND: The associations with cancer and cardiovascular diseases (CVD) had inconsistent results. The study aimed to investigate the risk of cardiovascular diseases (CVD) between populations with and without cancer. METHODS: Patients with common cancers in Taiwan were enrolled in the study between 2007 and 2018 using the Taiwan Cancer Registry. We focused on colorectal cancer, women's breast cancer, lung cancer, liver cancer, oral cancer, prostate cancer, and thyroid cancers. The study endpoint was fatal and non-fatal CVD, which was defined as ischemic heart disease and ischemic stroke according to the National Health Insurance Research Database. We compared the risk of CVD between patients with cancer and age- and sex-matched (1:1 ratio) participants who did not have cancer or CVD. Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression analysis. To evaluate the chronological trend, we estimated the HRs and 95% CI yearly since the diagnosis. RESULTS: Among the 552,485 cancer patients (mean age, 60.6 years; women, 47.7%) during the median follow-up period of 4.1 years, 32,634 cases of fatal and non-fatal CVD were identified. Compared with that noted in the non-cancer population, the overall fully adjusted HR with 95% CI was 1.28 (1.25, 1.30) in the cancer population. The CVD risk was the highest in the first year, the adjusted HR with 95% CI was 2.31 (2.23, 2.40), and this risk decreased yearly. CONCLUSIONS: Patients with cancer had a significantly higher risk of fatal or non-fatal CVD. The risk was the highest in the first year since diagnosis and decreased yearly.


Assuntos
Doenças Cardiovasculares , Neoplasias Hepáticas , Neoplasias da Glândula Tireoide , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Doenças Cardiovasculares/epidemiologia , Taiwan/epidemiologia
20.
Int J Clin Pract ; 2022: 4736231, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263233

RESUMO

Background: Physical activity (PA) is a basic and initiative conservative management for people with knee osteoarthritis (KOA). This study aimed to explore the potential indicators of PA levels in people with KOA. Methods: We designed a cross-sectional study where people with KOA were consecutively approached by the Orthopedic Outpatient Department in a hospital in southern Taiwan. People older than 50 years that could communicate and consent to the present study were enrolled. As a dependent variable, the Chinese version of the Physical Activity Scale for the Elderly (PASE-C) was used to assess the participant's PA levels. Considering differences in sex, a PASE-C score cut-off point of 140 for men and 120 for women was used. Participants were then divided into "active" and "inactive" groups. We measured independent variables consisting of the demographic and clinical characteristics, such as comorbidities measured by the Charlson Comorbidity Index (CCI), depression status measured by the Geriatric Depression Scale-5, body mass index, KOA history (<5, 5-<10, and ≥10 years), knee pain (unilateral or bilateral), the severity of symptoms measured by the Western Ontario and McMaster Universities Osteoarthritis Index, and 6-meter preferred walking speed. Multiple logistic regression was performed to identify significant relationships between PA among people with KOA. Results: We analyzed a total of 188 people with KOA (56 men and 132 women) with a mean age of 69.4 ± 7.9 (range: 51 to 90 years). Approximately 72.9% (n = 137) were categorized as "inactive PA," while 27.1% (n = 51) of participants were categorized as "active PA" (male: 32.1%; female: 25.0%). Multiple logistic regression showed a positive association of 6-meter preferred walking speed with active PA (OR: 7.08; 95% CI:1.14-44.13), whereas advanced age and comorbidity (CCI≥1 vs. CCI<1) were negatively associated with active PA with an OR (95% CI) score of 0.91 (0.86-0.97) and 0.37 (0.15-0.87), respectively. Conclusions: People with KOA require appropriate lifestyle management to increase PA. Walking speed may be an effective factor for predicting PA among people with KOA. Healthcare providers treating KOA patients should be aware of their PA levels, especially those at risk.


Assuntos
Osteoartrite do Joelho , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/complicações , Estudos Transversais , Modelos Logísticos , Taiwan/epidemiologia , Exercício Físico
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