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1.
J Surg Oncol ; 129(7): 1332-1340, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38606522

RESUMO

BACKGROUND AND OBJECTIVES: To determine early continence outcomes after three-layer vesicourethral reconstruction during robot-assisted radical prostatectomy (RARP) and the role of postoperative cystography pattern. METHODS: Between May 2015 and January 2019, a total of 170 consecutive patients with localized prostate cancer who underwent RARP, were divided into one- and three-layer groups based on the method of vesicourethral reconstruction. Continent status, preoperative, intraoperative, postoperative, clinicopathological variables, and cystography parameters were analyzed. The patients were followed up for at least 12 months. RESULTS: Of the 170 consecutive patients, 85 with one-layer vesicourethral anastomosis, and 85 with three-layer reconstruction. The continence rates immediately after catheter removal, 4, 12, and 24 weeks after RARP were 47.1%, 75.3%, 92.9%, and 98.8% in the three-layer group; compared to 15.3%, 60%, 78.8%, and 90.6% in the one-layer group, respectively. In the multivariate analysis, three-layer reconstruction was the only independent variable with a 42% risk reduction of postprostatectomy incontinence (hazard ratio (HR): 0.58, 95% confidence interval (CI) = 0.42-0.80, p = 0.001). Cystography in the three-layer group revealed less anastomotic leakage, less sharp bladder neck angle, and higher bladder neck level category. CONCLUSIONS: Three-layer anatomical reconstruction demonstrated promising early continence outcomes, and postoperative cystography revealed a specific pattern more associated with continence.


Assuntos
Cistografia , Procedimentos de Cirurgia Plástica , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Uretra , Bexiga Urinária , Incontinência Urinária , Humanos , Masculino , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Uretra/cirurgia , Uretra/diagnóstico por imagem , Bexiga Urinária/cirurgia , Bexiga Urinária/diagnóstico por imagem , Pessoa de Meia-Idade , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , Procedimentos de Cirurgia Plástica/métodos , Cistografia/métodos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Seguimentos , Estudos Retrospectivos , Recuperação de Função Fisiológica , Prognóstico
2.
Int J Mol Sci ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38279345

RESUMO

The skin of Arachis hypogaea L. (peanut or groundnut) is a rich source of polyphenols, which have been shown to exhibit a wider spectrum of noteworthy biological activities, including anticancer effects. However, the anticancer activity of peanut skin extracts against melanoma and colorectal cancer (CRC) cells remains elusive. In this study, we systematically investigated the cytotoxic, antiproliferative, pro-apoptotic, and anti-migration effects of peanut skin ethanolic extract and its fractions on melanoma and CRC cells. Cell viability results showed that the ethyl acetate fraction (AHE) of peanut skin ethanolic crude extract and one of the methanolic fractions (AHE-2) from ethyl acetate extraction exhibited the highest cytotoxicity against melanoma and CRC cells but not in nonmalignant human skin fibroblasts. AHE and AHE-2 effectively modulated the cell cycle-related proteins, including the suppression of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6), phosphorylation of Retinoblastoma (p-Rb), E2F1, Cyclin A, and activation of tumor suppressor p53, which was associated with cell cycle arrest and paralleled their antiproliferative efficacies. AHE and AHE-2 could also induce caspase-dependent apoptosis and inhibit migration activities in melanoma and CRC cells. Moreover, it is noteworthy that autophagy, manifested by microtubule-associated protein light chain 3B (LC3B) conversion and the aggregation of GFP-LC3, was detected after AHE and AHE-2 treatment and provided protective responses in cancer cells. Significantly, inhibition of autophagy enhanced AHE- and AHE-2-induced cytotoxicity and apoptosis. Together, these findings not only elucidate the anticancer potential of peanut skin extracts against melanoma and CRC cells but also provide a new insight into autophagy implicated in peanut skin extracts-induced cancer cell death.


Assuntos
Acetatos , Arachis , Melanoma , Humanos , Linhagem Celular Tumoral , Extratos Vegetais/farmacologia , Apoptose , Autofagia
3.
Prostate ; 82(7): 809-815, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35226371

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) is the major treatment for metastatic prostate cancer (PCa), but few studies have investigated the effects of ADT on thyroid diseases. METHODS: This population-based, nationwide cohort study utilized the Taiwan National Health Insurance Research Database (NHIRD) with 17,192 PCa patients between 1997 and 2013. We used the Cox proportional hazards models and propensity score-matched analysis to analyze the association between ADT and the development of thyroid diseases. RESULTS: A total of 17,192 newly diagnosed men with PCa were selected from the NHIRD. There were 6200 ADT users and 6200 non-ADT users after 1:1 propensity score matching. There was a significantly decreased risk of thyroid diseases among ADT users compared with non-ADT users (adjusted hazard ratio (aHR): 0.79, 95% confidence interval (CI): 0.65-0.95, p < 0.001). Further analysis showed a significantly decreased risk of thyroid diseases with increasing ADT duration (p < 0.001). CONCLUSIONS: The result showed that ADT use in men with PCa was associated with a decreased risk of thyroid disease development.


Assuntos
Neoplasias da Próstata , Doenças da Glândula Tireoide , Antagonistas de Androgênios/efeitos adversos , Androgênios , Estudos de Coortes , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/epidemiologia , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia
4.
Int J Mol Sci ; 23(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36430348

RESUMO

Cancers of the oral cavity can develop in the anatomic area extending from the lip, gum, tongue, mouth, and to the palate. Histologically, about 85-90% of oral cavity cancers are of the type squamous cells carcinomas (SCCs). The incidence of oral tongue SCC is higher in the tongue than any other anatomic area of the oral cavity. Here, we investigated the therapeutic effects and molecular mechanisms of docetaxel, which is a paclitaxel antitumor agent, on the cell growth of a human tongue SCC-derived SAS cell line. The results showed that docetaxel (10-300 nM) induced cytotoxicity and caspase-3 activity in SAS cells. Moreover, docetaxel (100 nM) promoted the expression of apoptosis-related signaling molecules, including the cleavages of caspase-3, caspase-7, and poly (ADP-ribose) polymerase (PARP). In mitochondria, docetaxel (100 nM) decreased the mitochondrial membrane potential (MMP) and Bcl-2 mRNA and protein expression and increased cytosolic cytochrome c protein expression and Bax mRNA and protein expression. In terms of mitogen-activated protein kinase (MAPK) and adenosine monophosphate-activated protein kinase (AMPK) signaling, docetaxel increased the expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-c-Jun N-terminal kinase (JNK), and p-AMPKα protein expression but not p-p38 protein expression. Moreover, the increase in caspase-3/-7 activity and Bax protein expression and decreased Bcl-2 protein expression and MMP depolarization observed in docetaxel-treated SAS cells could be reversed by treatment with either SP600125 (a JNK inhibitor), PD98059 (an MEK1/2 (mitogen-activated protein kinase kinase 1/2) inhibitor), or compound c (an AMPK inhibitor). The docetaxel-induced increases in p-JNK, p-ERK, and p-AMPKα protein expression could also be reversed by treatment with either SP600125, PD98059, or compound c. These results indicate that docetaxel induces human tongue SCC cell apoptosis via interdependent MAPK-JNK, MAPK-ERK1/2, and AMPKα signaling pathways. Our results show that docetaxel could possibly exert a potent pharmacological effect on human oral tongue SCC cell growth.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Docetaxel/farmacologia , Caspase 3/metabolismo , Proteínas Quinases Ativadas por AMP , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias da Língua/tratamento farmacológico , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2 , Células Epiteliais/metabolismo , Língua/metabolismo , RNA Mensageiro
5.
Int J Mol Sci ; 23(9)2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35563057

RESUMO

Ketamine-associated cystitis is characterized by suburothelial inflammation and urothelial cell death. Norketamine (NK), the main metabolite of ketamine, is abundant in urine following ketamine exposure. NK has been speculated to exert toxic effects in urothelial cells, similarly to ketamine. However, the molecular mechanisms contributing to NK-induced urothelial cytotoxicity are almost unclear. Here, we aimed to investigate the toxic effects of NK and the potential mechanisms underlying NK-induced urothelial cell injury. In this study, NK exposure significantly reduced cell viability and induced apoptosis in human urinary bladder epithelial-derived RT4 cells that NK (0.01-0.5 mM) exhibited greater cytotoxicity than ketamine (0.1-3 mM). Signals of mitochondrial dysfunction, including mitochondrial membrane potential (MMP) loss and cytosolic cytochrome c release, were found to be involved in NK-induced cell apoptosis and death. NK exposure of cells also triggered the expression of endoplasmic reticulum (ER) stress-related proteins including GRP78, CHOP, XBP-1, ATF-4 and -6, caspase-12, PERK, eIF-2α, and IRE-1. Pretreatment with 4-phenylbutyric acid (an ER stress inhibitor) markedly prevented the expression of ER stress-related proteins and apoptotic events in NK-exposed cells. Additionally, NK exposure significantly activated JNK, ERK1/2, and p38 signaling and increased intracellular calcium concentrations ([Ca2+]i). Pretreatment of cells with both PD98059 (an ERK1/2 inhibitor) and BAPTA/AM (a cell-permeable Ca2+ chelator), but not SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), effectively suppressed NK-induced mitochondrial dysfunction, ER stress-related signals, and apoptotic events. The elevation of [Ca2+]i in NK-exposed cells could be obviously inhibited by BAPTA/AM, but not PD98059. Taken together, these findings suggest that NK exposure exerts urothelial cytotoxicity via a [Ca2+]i-regulated ERK1/2 activation, which is involved in downstream mediation of the mitochondria-dependent and ER stress-triggered apoptotic pathway, consequently resulting in urothelial cell death. Our findings suggest that regulating [Ca2+]i/ERK signaling pathways may be a promising strategy for treatment of NK-induced urothelial cystitis.


Assuntos
Cistite , Ketamina , Apoptose , Estresse do Retículo Endoplasmático , Feminino , Humanos , Ketamina/análogos & derivados , Ketamina/farmacologia , Sistema de Sinalização das MAP Quinases , Masculino , Mitocôndrias/metabolismo
6.
Int J Mol Sci ; 23(5)2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35270009

RESUMO

Methylmercury (MeHg), a long-lasting organic pollutant, is known to induce cytotoxic effects in mammalian cells. Epidemiological studies have suggested that environmental exposure to MeHg is linked to the development of diabetes mellitus (DM). The exact molecular mechanism of MeHg-induced pancreatic ß-cell cytotoxicity is still unclear. Here, we found that MeHg (1-4 µM) significantly decreased insulin secretion and cell viability in pancreatic ß-cell-derived RIN-m5F cells. A concomitant elevation of mitochondrial-dependent apoptotic events was observed, including decreased mitochondrial membrane potential and increased proapoptotic (Bax, Bak, p53)/antiapoptotic (Bcl-2) mRNA ratio, cytochrome c release, annexin V-Cy3 binding, caspase-3 activity, and caspase-3/-7/-9 activation. Exposure of RIN-m5F cells to MeHg (2 µM) also induced protein expression of endoplasmic reticulum (ER) stress-related signaling molecules, including C/EBP homologous protein (CHOP), X-box binding protein (XBP-1), and caspase-12. Pretreatment with 4-phenylbutyric acid (4-PBA; an ER stress inhibitor) and specific siRNAs for CHOP and XBP-1 significantly inhibited their expression and caspase-3/-12 activation in MeHg-exposed RIN-mF cells. MeHg could also evoke c-Jun N-terminal kinase (JNK) activation and reactive oxygen species (ROS) generation. Antioxidant N-acetylcysteine (NAC; 1mM) or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox; 100 µM) markedly prevented MeH-induced ROS generation and decreased cell viability in RIN-m5F cells. Furthermore, pretreatment of cells with SP600125 (JNK inhibitor; 10 µM) or NAC (1 mM) or transfection with JNK-specific siRNA obviously attenuated the MeHg-induced JNK phosphorylation, CHOP and XBP-1 protein expression, apoptotic events, and insulin secretion dysfunction. NAC significantly inhibited MeHg-activated JNK signaling, but SP600125 could not effectively reduce MeHg-induced ROS generation. Collectively, these findings demonstrate that the induction of ROS-activated JNK signaling is a crucial mechanism underlying MeHg-induced mitochondria- and ER stress-dependent apoptosis, ultimately leading to ß-cell death.


Assuntos
Estresse do Retículo Endoplasmático , Compostos de Metilmercúrio , Animais , Apoptose , Caspase 3/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases , Mamíferos/metabolismo , Compostos de Metilmercúrio/farmacologia , Mitocôndrias/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
7.
Prostate ; 81(3): 194-201, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33393676

RESUMO

BACKGROUND: To evaluate the possible major adverse cardiovascular events (MACE) associated with second-line hormonal therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We performed a population-based real-world cohort study of 4962 prostate cancer patients between 2014 and 2017 utilizing the Chang Gung Research Database of Taiwan. The second-line hormonal therapies included enzalutamide and abiraterone acetate. The outcomes of interest were MACE, including acute coronary syndrome (ACS), ischemic stroke (IS), and heart failure (HF) events that resulted in hospitalization. Cox proportional-hazards models with inverse probability of treatment weighting (IPTW) with propensity scores were used. RESULTS: After IPTW, 288 patients were prescribed second-line hormonal therapy and 1575 received first-line androgen-deprivation therapy (ADT). Of all patients diagnosed with MACE, the event rates were 2.92% in the second-line hormonal group and 2.22% in the first-line ADT group. The mean follow-up period was 9.52 months for the second-line hormonal group. Patients who received second-line hormonal therapy exhibited a significantly increased risk for MACE (hazard ratio [HR]: 3.15; 95% confidence interval [CI]: 2.03-4.89), ACS (HR: 4.94; 95% CI: 2.36-10.33), and HF (HR: 2.83; 95% CI: 1.53-5.25), compared with the first-line ADT group, but a similar risk for IS was observed in both groups (HR: 1.70; 95% CI: 0.95-3.04). CONCLUSIONS: The real-world evidence study revealed increased risks for MACE in mCRPC patients receiving second-line hormonal therapy.


Assuntos
Doenças Cardiovasculares/epidemiologia , Metástase Neoplásica/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona/efeitos adversos , Acetato de Abiraterona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Fatores de Risco , Inibidores da Síntese de Esteroides , Taiwan/epidemiologia , Resultado do Tratamento
8.
Oncology ; 98(3): 146-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31794969

RESUMO

OBJECTIVES: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC. METHODS: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis. RESULTS: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84-5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11-3.65, p = 0.02) were independent prognostic factors. CONCLUSION: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Urológicas/tratamento farmacológico , Urotélio/efeitos dos fármacos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma/mortalidade , Carcinoma/secundário , Cisplatino/efeitos adversos , Progressão da Doença , Feminino , Humanos , Masculino , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Urotélio/patologia
9.
Epidemiol Infect ; 147: e138, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30869041

RESUMO

Cellulitis is a common infection of the skin and soft tissue. Susceptibility to cellulitis is related to microorganism virulence, the host immunity status and environmental factors. This retrospective study from 2001 to 2013 investigated relationships between the monthly incidence rate of cellulitis and meteorological factors using data from the Taiwanese Health Insurance Dataset and the Taiwanese Central Weather Bureau. Meteorological data included temperature, hours of sunshine, relative humidity, total rainfall and total number of rainy days. In otal, 195 841 patients were diagnosed with cellulitis and the incidence rate was strongly correlated with temperature (γS = 0.84, P < 0.001), total sunshine hours (γS = 0.65, P < 0.001) and total rainfall (γS = 0.53, P < 0.001). The incidence rate of cellulitis increased by 3.47/100 000 cases for every 1° elevation in environmental temperature. Our results may assist clinicians in educating the public of the increased risk of cellulitis during warm seasons and possible predisposing environmental factors for infection.


Assuntos
Celulite (Flegmão)/epidemiologia , Conceitos Meteorológicos , Humanos , Incidência , Estudos Retrospectivos , Taiwan/epidemiologia
10.
Biomacromolecules ; 19(2): 544-554, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29334612

RESUMO

Biocompatible bacterial cellulose pellicle (BCP) is a candidate for biomedical material such as wound dressing. However, due to lack of antibacterial activity, to grant BCP with the property is crucial for its biomedical application. In the present study, BCP was modified by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation using TEMPO/NaClO/NaBr system at pH 10 to form TEMPO-oxidized BCP (TOBCP) with anionic C6 carboxylate groups. The TOBCP was subsequently ion-exchanged in AgNO3 solution and silver nanoparticles (AgNP) with diameter of ∼16.5 nm were in situ synthesized on TOBC nanofiber surfaces by thermal reduction without using a reducing agent. Field emission scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectra, Fourier transform infrared spectroscopy, and thermogravimetric analysis were carried out to confirm morphology and structure of the pellicles with AgNP. The AgNP continuously released Ag+ with a rate of 12.2%/day at 37 °C in 3 days. The TOBCP/AgNP exhibited high biocompatibility according to the result of in vitro cytotoxicity test (cell viability >95% after 48 h of incubation) and showed significant antibacterial activities of 100% and 99.2% against E. coli and S. aureus, respectively. Hence, the highly biocompatible and highly antibacterial TOBCP/AgNP prepared in the present study is a promising candidate for wound dressing.


Assuntos
Antibacterianos , Celulose , Óxidos N-Cíclicos/química , Escherichia coli/crescimento & desenvolvimento , Nanopartículas Metálicas/química , Prata , Staphylococcus aureus/crescimento & desenvolvimento , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Celulose/química , Celulose/farmacologia , Camundongos , Células NIH 3T3 , Oxirredução , Prata/química , Prata/farmacologia
11.
BMC Pregnancy Childbirth ; 18(1): 79, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587654

RESUMO

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections in pregnant women due to anatomic and physiologic changes in the female urinary tract during pregnancy, and antepartum UTIs can cause adverse pregnancy outcomes that may induce mental stress. There have only been a few studies, however, investigating antepartum UTIs and mental stress. As such, the present study was conducted in order to investigate the association between antepartum UTIs and postpartum depression (PPD). METHODS: We used data from the 2000-2013 National Health Insurance Research Database (NHIRD) of Taiwan. Data regarding a total of 55,087 singleton pregnancies was utilized, including data regarding 406 women who were newly diagnosed with PPD in the first 6 months postpartum. The associations between PPD and antepartum UTIs or other risk factors were examined by multiple logistic regression analysis. RESULTS: The logistic regression analysis results indicated that PPD was associated with antepartum UTIs (adjusted odds ratio [aOR] 1.27; 95% confidence interval [CI] (1.07-1.65). Furthermore, the risk of PPD was higher in women with an upper antepartum UTI (aOR 2.97 (1.31, 6.77) than in those with a lower antepartum UTI (aOR 1.21 (1.02, 1.58)). CONCLUSIONS: Antepartum UTIs, particularly upper antepartum UTIs, are significantly associated with PPD. This information may encourage physicians to pay greater attention to the mental health of women who have suffered upper UTIs during their pregnancies.


Assuntos
Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/etiologia , Complicações Infecciosas na Gravidez/psicologia , Infecções Urinárias/psicologia , Adulto , Bases de Dados Factuais , Feminino , Humanos , Seguro Saúde/estatística & dados numéricos , Modelos Logísticos , Razão de Chances , Gravidez , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
12.
Rheumatol Int ; 37(7): 1125-1134, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28421357

RESUMO

Scabies is a commonly occurring infectious immune-mediated inflammatory skin disease. Immune-mediated inflammatory processes are also observed in autoimmune diseases. There have been very few previous studies; however, that have investigated the possible association between scabies and autoimmune diseases. To address this research gap, we conducted a nationwide population-based cohort study that included a total of 4481 scabies patients and 16,559 control subjects matched by gender, age, insured region, urbanization and income. We tracked both cohorts for a 7-year period to identify the incidence of autoimmune diseases in both groups during that follow-up period. Relatedly, a Cox regression analysis was performed to calculate and compare the hazard ratio (HR) for autoimmune diseases of both groups. An overall increased risk for 19 autoimmune diseases was observed in the scabies patients, with an adjusted HR (aHR) of 1.14 (95% CI 1.04-1.25). Compared with the control group, the scabies patients exhibited increased risks of hypersensitivity vasculitis (aHR 5.44, 95% CI 1.64-18.07), dermatomyositis (aHR 4.91, 95% CI 1.80-13.38), polyarteritis nodosa (aHR 2.89, 95% CI 1.46-5.73), systemic lupus erythematosus (aHR 2.73, 95% CI 1.33-5.64), psoriasis (aHR 2.31, 95% CI 1.85-2.88), myasthenia gravis (aHR 2.01, 95% CI 1.31-3.12), type 1 diabetes mellitus (aHR 1.93, 95% CI 1.53-2.44), pernicious anemia (aHR 1.92, 95% CI 1.42-2.61), and rheumatoid arthritis (aHR 1.43, 95% CI 1.12-1.83). In conclusion, the associations between scabies and a variety of autoimmune diseases may exist. Further studies are needed to clarify the shared etiologies and relationships between scabies and autoimmune diseases.


Assuntos
Doenças Autoimunes/epidemiologia , Escabiose/epidemiologia , Adulto , Idoso , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Autoimunidade , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Escabiose/diagnóstico , Escabiose/imunologia , Taiwan/epidemiologia , Fatores de Tempo , Adulto Jovem
13.
Int J Mol Sci ; 18(1)2017 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-28098816

RESUMO

BACKGROUND: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers. RESULTS: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line. Therefore, we believe that these three genes increase the tolerance of MCF7 to mitoxantrone (MX). The data showed that the high expression of COX6C made MCF-7/MX have more stable on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) expression than normal MCF7 cells under hypoxic conditions. The accumulation of MX was greater in the ATP-depleted treatment MCF7/MX cells than in normal MCF7/MX cells. Furthermore, E2 increased the tolerance of MCF7 cells to MX through inducing the expression of ABCG2. However, E2 could not increase the expression of ABCG2 after the inhibition of estrogen receptor α (ERα) in MCF7 cells. According to the above data, under the E2 treatment, MDA-MB231, which lacks ER, had a higher sensitivity to MX than MCF7 cells. CONCLUSIONS: E2 induced the expression of ABCG2 through ERα and the over-expressed ABCG2 made MCF7 more tolerant to MX. Moreover, the over-expressed ATP synthase and COX6c affected mitochondrial genes and function causing the over-expressed ABCG2 cells pumped out MX in a concentration gradient from the cell matrix. Finally lead to chemoresistance.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Estrogênios/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/metabolismo , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Genes Mitocondriais , Humanos , Células MCF-7 , Modelos Biológicos , Análise de Sequência com Séries de Oligonucleotídeos , Espécies Reativas de Oxigênio/metabolismo
14.
Can J Infect Dis Med Microbiol ; 2017: 1506857, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28316630

RESUMO

Background. Epididymo-orchitis is a common infectious disease among men, especially men aged 20 to 39 years. The aim of this study was to analyze possible associations of various meteorological indicators on the incidence of epididymo-orchitis in Taiwan. Methods and Materials. This nationwide population-based study collected data on cases of epididymo-orchitis that were newly diagnosed from 2001 to 2013 in Taiwan. Monthly meteorological indicators, including average temperatures, humidity, rainfall, total rain days, and sunshine hours, were collected from the Central Weather Bureau of Taiwan. Data for a total of 7,233 patients with epididymo-orchitis were collected for this study. Results. The monthly incidence of epididymo-orchitis was positively correlated with temperature, rainfall, and sunshine hours. The average monthly temperature had a linear correlation with the incidence of epididymo-orchitis (ß = 0.11). The monthly average temperature is significantly related, with a positive linear correlation, to the incidence of epididymo-orchitis in Taiwan. Conclusion. This finding may constitute useful information in terms of helping physicians to distinguish between patients with epididymo-orchitis and testicular torsion in hot or cold weather.

15.
Appl Microbiol Biotechnol ; 100(6): 2629-39, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26572522

RESUMO

In this study, taro waste (TW) was utilized for Lactobacillus acidophilus BCRC 14079 cultivation and the anti-tumor and immune-modulatory properties of heat-killed cells (HKCs), cytoplasmic fraction (CF), and exopolysaccharide (EPS) were evaluated. The optimum liquefaction enzyme dosage, temperature, and time determined by Box-Behnken design response surface methodology (BBD-RSM) were 9 mL/L of α-amylase, 79.2 °C, and 5 h of reaction, respectively. The optimum temperature and reaction time for saccharification were determined as 60 °C and 3 h. The optimum medium, CGMY1 medium, constitutes of TW hydrolysate containing 37 g/L of glucose, 25 g/L of corn gluten meal (CGM), and 1 g/L of yeast extract (YE). Results of MTT assay showed that HKCs and EPS from CGM medium exhibited the highest anti-proliferative in HT-29 (IC50 of HKCs, 467.25 µg/mL; EPS, 716.10 µg/mL) and in Caco-2 cells (IC50 of EPS, 741.60 µg/mL). Luciferase-based NF-ΚB and COX-2 systems indicated HKCs from CGM medium stimulated the highest expression of luciferin in both systems. The luciferase activities by using 100 and 500 µg/mL of HKCs from CGM were 24.30- and 45.83-fold in NF-ΚB system and 11.54- and 4.93-fold in COX-2 system higher than the control. In conclusion, this study demonstrated the potential of TW medium for L. acidophilus cultivation and the production of non-viable probiotics with enhanced biological activities.


Assuntos
Antineoplásicos/farmacologia , Colocasia/metabolismo , Fatores Imunológicos/metabolismo , Resíduos Industriais , Lactobacillus acidophilus/crescimento & desenvolvimento , Lactobacillus acidophilus/metabolismo , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Meios de Cultura/química , Células HT29 , Humanos , Concentração Inibidora 50 , Temperatura
16.
BMC Complement Altern Med ; 15: 65, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25885960

RESUMO

BACKGROUND: Breast cancer-related mortality increases annually. The efficacy of current breast cancer treatments is limited, and they have numerous side effects and permit high recurrence. Patients with estrogen receptor (ER)-negative or triple-negative breast cancer are particularly difficult to treat. Treatment for this type of cancer is lacking, and its prognosis is poor, necessitating the search for alternative treatments. METHODS: This study screened Chinese herb Hibiscus syriacus extracts and identified a novel anti-cancer drug for patients with ER-negative breast cancer. The inhibitory effects on cell viability and migration were evaluated for each compound, and the molecular regulatory effects were evaluated on both mRNA and protein levels. RESULT: We found several triterpenoids including betulin (K02) and its derivatives (K03, K04, and K06) from H. syriacus inhibited human triple-negative breast cancer cell viability and migration but revealed smaller cytotoxic effects on normal mammalian epithelial cells. Betulin and its derivatives induced apoptosis by activating apoptosis-related genes. In addition, they activated p21 expression, which induced cell cycle arrest in breast cancer cells. Betulin (K02) and betulinic acid (K06) had stronger inhibitory effects on cell viability and migration than K03 and K04. CONCLUSIONS: H. syriacus extracts might inhibit breast cancer cell viability and induce apoptosis by activating p53 family regulated pathways and inhibiting AKT activation. H. syriacus extracts may provide important insight into the development of novel alternative therapies for breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Hibiscus , Fitoterapia , Triterpenos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Triterpenos Pentacíclicos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Triterpenos/uso terapêutico , Ácido Betulínico
17.
Curr Res Toxicol ; 6: 100155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379848

RESUMO

Paraquat (PQ), a toxic and nonselective bipyridyl herbicide, is one of the most extensively used pesticides in agricultural countries. In addition to pneumotoxicity, the liver is an important target organ for PQ poisoning in humans. However, the mechanism of PQ in hepatotoxicity remains unclear. In this study, we found that exposure of rat hepatic H4IIE cells to PQ (0.1-2 mM) induced significant cytotoxicity and apoptosis, which was accompanied by mitochondria-dependent apoptotic signals, including loss of mitochondrial membrane potential (MMP), cytosolic cytochrome c release, and changes in the Bcl-2/Bax mRNA ratio. Moreover, PQ (0.5 mM) exposure markedly induced JNK and ERK1/2 activation, but not p38-MAPK. Blockade of JNK and ERK1/2 signaling by pretreatment with the specific pharmacological inhibitors SP600125 and PD98059, respectively, effectively prevented PQ-induced cytotoxicity, mitochondrial dysfunction, and apoptotic events. Additionally, PQ exposure stimulated significant oxidative stress-related signals, including reactive oxygen species (ROS) generation and intracellular glutathione (GSH) depletion, which could be reversed by the antioxidant N-Acetylcysteine (NAC). Buffering the oxidative stress response with NAC also effectively abrogated PQ-induced hepatotoxicity, MMP loss, apoptosis, and phosphorylation of JNK and ERK1/2 protein, however, the JNK or ERK inhibitors did not suppress ROS generation in PQ-treated cells. Collectively, these results demonstrate that PQ exposure induces hepatic cell toxicity and death via an oxidative stress-dependent JNK/ERK activation-mediated downstream mitochondria-regulated apoptotic pathway.

18.
Toxicol In Vitro ; 86: 105483, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36252918

RESUMO

Chlorpyrifos (CPF) is one of the most abundant and widely used organophosphate pesticides for agricultural, industrial, and household purposes in the world. Epidemiological studies have reported that CPF can induce neurotoxic impairments in mammalian, which is linked to an important risk factor for development of neurodegenerative diseases (NDs). However, limited information is available on CPF-induced neurotoxicity, with the underlying exact mechanism remains unclear. In this study, CPF exposure (10-400 µM) significantly reduced Neuro-2a cell viability and induced apoptotic events, including the increase in caspase-3 activity, apoptotic cell population, and cleavage of caspase-3/-7 and PARP. Exposure of Neuro-2a cells to CPF also triggered CHOP activation. Transfection with CHOP-specific siRNA markedly suppressed the expression of CHOP, and attenuated cytotoxicity and apoptotic events in CPF-exposed Neuro-2a cells. Furthermore, CPF exposure obviously evoked the phosphorylation of Akt as well as ROS generation in a time-dependent manner. Pretreatment with LY294002 (an Akt inhibitor) effectively attenuated the CPF-induced Akt phosphorylation, CHOP activation, and apoptotic events, but not that ROS production. Of note, buffering the ROS generation with antioxidant N-acetylcysteine effectively prevented the CPF-induced ROS generation, CHOP activation, and apoptotic events, but not that the Akt phosphorylation. Collectively, these findings indicate that CPF exposure exerts neuronal cytotoxicity via the independent pathways of ROS generation and Akt activation downstream-regulated CHOP-triggered apoptosis, ultimately leading to neuronal cell death.


Assuntos
Clorpirifos , Animais , Clorpirifos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Caspase 3/metabolismo , Estresse Oxidativo , Morte Celular , Apoptose , Mamíferos/metabolismo
19.
Cancers (Basel) ; 15(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36980748

RESUMO

BACKGROUND: Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. METHODS: We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan-Meier analyses for survival curves. RESULTS: The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan-Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. CONCLUSIONS: Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.

20.
BMC Cardiovasc Disord ; 12: 6, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22333273

RESUMO

BACKGROUND: Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms have been associated with acute coronary syndrome (ACS); however, several controversial results have also been found in different studied populations. This hospital-based, emergency room, case-control study in Taiwan retrospectively investigated 111 ACS patients, and 195 non-coronary subjects as a control group, to study the effects of ACE I/D polymorphism in the most urgent ACS patients. ACE I/D polymorphisms were determined by polymerase chain reaction-based assays and their associations with ACS risk, severity, and sudden cardiac death were determined. RESULTS: The ACE DD genotype was associated with ACS incidence. The DD genotype was associated with a significant 4-fold higher risk of ACS in multivariate analysis (odds ratio (OR) = 4.295; 95% confidence interval (CI): 1.436-12.851, p = 0.009), and a 3.35-fold higher risk of acute myocardial infarction. DD genotype carriers also had more than 3-fold higher risks of stenosis in all the three coronary arteries, left anterior descending artery infarction, and anterior wall infarction. In addition, the DD genotype was also associated with a higher risk of sudden cardiac death (OR = 6.484, 95% CI: 1.036-40.598, p = 0.046). CONCLUSIONS: This study demonstrated that the ACE DD genotype is an independent risk factor for ACS, and in particular, for acute myocardial infarction. In addition, the ACE DD genotype is also associated with greater ACS severity and a higher risk of sudden cardiac death. ACE genotyping is recommended for patients with a history of ACS, and more intensive preventive care is suggested for patients with the DD genotype.


Assuntos
Síndrome Coronariana Aguda/genética , Morte Súbita Cardíaca/epidemiologia , Genótipo , Infarto do Miocárdio/genética , Peptidil Dipeptidase A/genética , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Morte Súbita Cardíaca/etiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Polimorfismo Genético , Fatores de Risco , Taiwan
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