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1.
Cancer Sci ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888067

RESUMO

The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE-induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)-mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1-dehydro-6-gingerdione and 8-shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer.

2.
Cell Oncol (Dordr) ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888847

RESUMO

PURPOSE: This study investigates the role and effectiveness of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in oral cancer, focusing on the clinical relevance of EGFR and myeloid cell leukemia-1 (Mcl-1) in head and neck cancers (HNCs). It aims to explore the molecular mechanism of afatinib, a TKI, in treating human oral cancer. METHODS: We conducted an in silico analysis using databases like The Cancer Genome Atlas, Gene Expression Omnibus, and Clinical Proteomic Tumor Analysis Consortium, along with immunohistochemistry staining, to study EGFR and Mcl-1 expression in HNCs. For investigating afatinib's anticancer properties, we performed various in vitro and in vivo analyses, including trypan blue exclusion assay, Western blotting, 4'-6-diamidino-2-phenylindole staining, flow cytometry, quantitative real-time PCR, Mitochondrial membrane potential assay, overexpression vector construction, transient transfection, and a tumor xenograft model. RESULTS: Higher expression levels of EGFR and Mcl-1 were observed in HNC patient tissues compared to normal tissues, with their co-expression significantly linked to poor prognosis. There was a strong correlation between EGFR and Mcl-1 expressions in oral cancer patients. Afatinib treatment induced apoptosis and suppressed Mcl-1 in oral cancer cell lines without the EGFR T790M mutation. The mechanism of afatinib-induced apoptosis involved the EGFR/mTOR/Mcl-1 axis, as shown by the effects of mTOR activator MHY1485 and inhibitor rapamycin. Afatinib also increased Bim expression, mitochondrial membrane permeabilization, and cytochrome c release. It significantly lowered tumor volume without affecting body, liver, and kidney weights. CONCLUSION: Afatinib, targeting the EGFR/mTOR/Mcl-1 axis, shows promise as a therapeutic strategy for oral cancer, especially in patients with high EGFR and Mcl-1 expressions.

3.
Sleep Med ; 121: 69-76, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38936046

RESUMO

BACKGROUND: Shift work disrupts circadian rhythms and alters sleep patterns, resulting in various health problems. To quantitatively assess the impact of shift work on brain health, we evaluated the brain age index (BAI) derived from sleep electroencephalography (EEG) results in night-shift workers and compared it with that in daytime workers. METHODS: We studied 45 female night shift nurses (mean age: 28.2 ± 3.3 years) and 44 female daytime workers (30.5 ± 4.7 years). Sleep EEG data were analyzed to calculate BAI. The BAI of night shift workers who were asleep during the daytime with those of daytime workers who were asleep at night were statistically compared to explore associations between BAI, duration of shift work, and sleep quality. RESULTS: Night-shift workers exhibited significantly higher BAI (2.14 ± 6.04 vs. 0 ± 5.35), suggesting accelerated brain aging and altered sleep architecture, including reduced delta and sigma wave frequency activity during non-rapid eye movement sleep than daytime workers. Furthermore, poor deep sleep quality, indicated by a higher percentage of N1, lower percentage of N3, and higher arousal index, was associated with increased BAI among shift workers. Additionally, a longer duration of night-shift work was correlated with increased BAI, particularly in older shift workers. CONCLUSION: Night-shift work, especially over extended periods, may be associated with accelerated brain aging, as indicated by higher BAI and alterations in sleep architecture. Interventions are necessary to mitigate the health impacts of shift work. Further research on the long-term effects and potential strategies for sleep improvement and mitigating brain aging in shift workers is warranted.

4.
Front Neurosci ; 18: 1306070, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601092

RESUMO

Introduction: Night-shift workers often face various health issues stemming from circadian rhythm shift and the consequent poor sleep quality. We aimed to study nurses working night shifts, evaluate the electroencephalogram (EEG) pattern of daytime sleep, and explore possible pattern changes due to ambient light exposure (30 lux) compared to dim conditions (<5 lux) during daytime sleep. Moethods: The study involved 31 participants who worked night shifts and 24 healthy adults who had never worked night shifts. The sleep macro and microstructures were analyzed, and electrophysiological activity was compared (1) between nighttime sleep and daytime sleep with dim light and (2) between daytime sleep with dim and 30 lux light conditions. Results: The daytime sleep group showed lower slow or delta wave power during non-rapid eye movement (NREM) sleep than the nighttime sleep group. During daytime sleep, lower sigma wave power in N2 sleep was observed under light exposure compared to no light exposure. Moreover, during daytime sleep, lower slow wave power in N3 sleep in the last cycle was observed under light exposure compared to no light exposure. Discussion: Our study demonstrated that night shift work and subsequent circadian misalignment strongly affect sleep quality and decrease slow and delta wave activities in NREM sleep. We also observed that light exposure during daytime sleep could additionally decrease N2 sleep spindle activity and N3 waves in the last sleep cycle.

5.
Arch Oral Biol ; 162: 105940, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479277

RESUMO

OBJECTIVE: Pseudolaric acid B (PAB) is a novel diterpenoid derived from the traditional Chinese medicinal herb Cortex pseudolaricis that exerts anticancer, anti-inflammatory, and immunomodulatory properties. While the anticancer potential of PAB has been studied, its effects on metastasis have not been well-studied. This study aims to determine the inhibitory effects of PAB on HSC-3 human tongue squamous cell carcinoma (TSCC) cell line. DESIGN: Cell viability and soft agar colony formation assays were conducted to assess cellular proliferation and in vitro tumorigenic capacity of TSCC cells, respectively. Additionally, wound healing, transwell migration, and invasion assays were conducted to monitor the aggressive behavior of TSCC cells. Furthermore, Western blotting analysis was conducted to reveal the signaling pathways involved in the modulation of epithelial-mesenchymal transition (EMT). RESULTS: The migratory and invasive capacities of HSC-3 cells were suppressed by PAB irrespective of their proliferation states. PAB's effects on EMT involved upregulation of E-cadherin expression and downregulation of Twist; these were concomitantly accompanied by downregulated phosphorylation of epidermal growth factor receptor (EGFR). CONCLUSIONS: PAB suppresses human TSCC in vitro by regulating Twist/E-cadherin through the EGFR signaling pathway. PAB may have potential as a candidate antimetastatic drug for TSCC treatment.


Assuntos
Carcinoma de Células Escamosas , Diterpenos , Neoplasias da Língua , Humanos , Neoplasias da Língua/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Diterpenos/farmacologia , Proliferação de Células , Língua/patologia , Receptores ErbB/metabolismo , Caderinas/metabolismo , Movimento Celular , Regulação Neoplásica da Expressão Gênica
6.
Oncol Rep ; 51(2)2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38099422

RESUMO

Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare form of head and neck cancer that is notorious for its poor prognosis and low overall survival rate. This highlights the need for new therapeutic options for this malignancy. The objective of the present study was to examine the ability of caffeic acid phenethyl ester (CAPE), which is an active compound found in propolis, to combat HSCC tumor growth. CAPE exerted its tumor­suppressive activity in HSCC cell lines through the induction of apoptosis. Mechanistically, the CAPE­mediated apoptotic process was attributed to the perturbation of the mitochondrial membrane potential and the activation of caspase­9. CAPE also modulated survivin and X­linked inhibitor of apoptosis, which are potent members of the inhibitors of apoptosis protein family, either through transcriptional or post­translational regulation, leading to HSCC cell line death. Therefore, the findings of the present study suggested that CAPE is an effective treatment alternative for HSCC via the stimulation of mitochondria­dependent apoptosis.


Assuntos
Neoplasias de Cabeça e Pescoço , Álcool Feniletílico , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Linhagem Celular Tumoral , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Apoptose , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico
7.
Asian Pac J Cancer Prev ; 24(11): 3837-3844, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38019241

RESUMO

OBJECTIVE: This study aimed to evaluate the correlation between maximal standardized uptake value (SUVmax) of primary colon cancer and serum neutrophil-to-lymphocyte ratio (NLR), and to assess the prognostic value of SUVmax and serum NLR in stage I and II colon cancer patients. METHODS: In this retrospective study a total of 128 patients with pathologically confirmed stage I and II colon cancer diagnosed between January 2014 and December 2017 were included. All patients underwent F-18 Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and differential white blood cell (WBC) counts before surgery. The correlations between SUVmax and NLR were assessed. The prognostic value of SUVmax and NLR for predicting recurrence-free survival (RFS) was investigated. RESULTS: The mean NLR was 2.2 ± 1.2, and the mean SUVmax of primary tumor was 15.2 ± 7.9. There was significant correlation between NLR and SUVmax (rho=0.2, p=0.02). Mean follow-up period was 59.8 ± 19.2 months and 12 patients experienced a recurrence. In univariable analysis, NLR (p=0.0084, HR=5.0223, 95% CI=1.5117-16.6853), C-reactive protein (CRP) (p=0.021, HR=4.1115, 95% CI=1.2380-13.6551), carbohydrate antigen 19-9 (CA19-9) (p=0.0134, HR=4.2683, 95% CI=1.3519-13.4766), and Kirsten ras sarcoma viral oncogene (KRAS) mutation (p=0.0338, HR=3.4703, 95% CI=1.0998-10.9499) were significant prognostic factors for the recurrence. In multivariable analysis, NLR (p=0.0256, HR=4.1155, 95% CI=1.1887-14.2490) and CA19-9 (p=0.0257, HR=4.139, 95% CI=1.1880-14.4200) were independent prognostic factors for the recurrence. CONCLUSIONS: Significant correlation was observed between SUVmax of primary colon cancer and serum NLR. Furthermore, in the multivariable analysis conducted on early colon cancer cases, NLR and CA19-9 were found to be independently associated with RFS. This suggested that NLR could be used as a supplementary tool for identifying patients at high risk of recurrence in early colon cancer. However, SUVmax was not associated with prognosis, suggesting that it cannot be used for predicting prognosis in early colon cancer.


Assuntos
Neoplasias do Colo , Neutrófilos , Humanos , Prognóstico , Antígeno CA-19-9 , Estudos Retrospectivos , Linfócitos
8.
Longit Life Course Stud ; 14(4): 566-591, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37874210

RESUMO

This study explored how middle-aged workers' career trajectory patterns were associated with their financial security later in life. Grounded by a life course perspective, we approached their career trajectories by considering a 'human agency within structure' framework. We explored sequences of employment status, starting with their lifetime main job to subsequent jobs after contractual retirement, using data from 1,010 middle-aged adults in Seoul, South Korea. The sequence analysis identified six career trajectory patterns. Stable career patterns included the Permanent to permanent trajectory as well as the Permanent to self-employment trajectory and these were most common among males with higher education degrees, higher earnings and better career alignment. Unstable career patterns such as the Temporary to temporary trajectory, the Permanent to temporary trajectory or the Churning trajectory were most common among those who were female, had lower levels of education lower earnings or had retired involuntarily. Further results showed that unstable career patterns were associated with lower levels of monthly earnings and total assets post-contractual retirement. Individuals with unstable career patterns were also less likely to be financially prepared for retirement. We suggest individualising education programmes for retirement preparation based on various career trajectories and demographic attributes to aid middle-aged adults in preparing for financial security later in life.


Assuntos
Renda , Aposentadoria , Masculino , Pessoa de Meia-Idade , Humanos , Adulto , Feminino , Emprego , República da Coreia , Escolaridade
9.
Cell Biochem Funct ; 41(8): 1319-1329, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37792550

RESUMO

Genipin, a natural compound derived from the fruit of Gardenia jasminoides Ellis, was reported to have activity against various cancer types. In this study, we determined the underlying mechanism for genipin-induced cell death in human oral squamous cell carcinoma (OSCC). The growth-inhibitory effects of genipin in human OSCC cells was examined by the Cell Counting Kit-8 and soft agar assays. The effects of genipin on apoptosis were assessed by nuclear morphological changes by 4',6-diamidino-2-phenylindole staining, measurement of the sub-G1 population, and Annexin V-fluorescein isothiocyanate/propidium iodide double staining. The underlying mechanism of genipin activity was analyzed by western blot analysis, subcellular fractionation of the nucleus and cytoplasm, immunocytochemistry, and quantitative real-time polymerase chain reaction. Genipin inhibited the growth of OSCC cells and induced apoptosis, which was mediated by a caspase-dependent pathway. Genipin reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and its nuclear localization. Furthermore, inhibition of p-STAT3Tyr705 levels following genipin treatment was required for the reduction of survivin and myeloid cell leukemia-1 (Mcl-1) expression, leading to apoptotic cell death. The genipin-mediated reduction in survivin and Mcl-1 expression was caused by transcriptional and/or posttranslational regulatory mechanisms. The results provide insight into the regulatory mechanism by which genipin induces apoptotic cell death through the abrogation of nuclear STAT3 phosphorylation and suggest that genipin may represent a potential therapeutic option for the treatment of human OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Survivina/metabolismo , Survivina/farmacologia , Survivina/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Neoplasias Bucais/patologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células
10.
Cell Oncol (Dordr) ; 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37787967

RESUMO

PURPOSE: Neuropilin-2 (NRP2) is a multifunctional single-pass transmembrane receptor that binds to two disparate ligands, namely, vascular endothelial growth factors (VEGFs) and semaphorins (SEMAs). It is reportedly involved in neuronal and vascular development. In this study, we uncovered the exact functional role of NRP2 and its molecular mechanism during aggressive behaviors and lymph node (LN) metastasis in human head and neck cancer (HNC) and identified algal methanol extract as a potential novel NRP2 inhibitor. METHODS: In silico analyses and immunohistochemistry were used to investigate the relationship between NRP2 expression and the prognosis of HNC patients. The functional role of NRP2 on the proliferation, migration, invasion, and cancer stem cell (CSC) properties of HNC cells was examined by MTS, soft agar, clonogenic, transwell migration and invasion assays, and sphere formation assays. Signaling explorer antibody array, western blot, and qPCR were performed toward the investigation of a molecular mechanism that is related to NRP2. RESULTS: NRP2 was highly expressed in HNC and positively correlated with LN metastasis and advanced tumor stage and size in patients. Using loss- or gain-of-function approaches, we found that NRP2 promoted the proliferative, migratory, and invasive capacities of human HNC cells. Furthermore, NRP2 regulated Sox2 expression to exhibit aggressiveness and CSC properties of human HNC cells. We demonstrated that p90 ribosomal S6 kinase 1 (RSK1) elevates the aggressiveness and CSC properties of human HNC cells, possibly by mediating NRP2 and Sox2. Zeb1 was necessary for executing the NRP2/RSK1/Sox2 signaling pathway during the induction of epithelial-to-mesenchymal transition (EMT) and aggressive behaviors of human HNC cells. Moreover, the methanol extract of Codium fragile (MECF) repressed NRP2 expression, inhibiting the RSK1/Sox2/Zeb1 axis, which contributed to the reduction of aggressive behaviors of human HNC cells. CONCLUSIONS: These findings suggest that NRP2 is a critical determinant in provoking EMT and aggressive behaviors in human HNC through the RSK1/Sox2/Zeb1 axis, and MECF may have the potential to be a novel NRP2 inhibitor for treating metastasis in HNC patients.

11.
Int J Mol Med ; 52(5)2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37711052

RESUMO

Podophyllotoxin (PPT), which is derived from the podophyllum plant, exhibits marked cytotoxic effects against cancer cells; however, the precise molecular mechanism underlying its activity against human oral squamous cell carcinoma (OSCC) has not been elucidated. In the present study, the mechanism by which PPT induced cytotoxicity in two OSCC cell lines, HSC3 and HSC4, was determined. The effects of PPT on cytotoxicity in HSC3 and HSC4 cells were analyzed using Annexin V/PI double staining, Sub­G1 analysis, soft agar assays, western blotting, and quantitative PCR. The changes in the mitochondrial membrane potential were assessed using a JC­1 assay and cytosolic and mitochondrial fractionation. A myeloid cell leukemia­1 (Mcl­1) overexpression cell lines were also established to study the role of Mcl­1 on apoptosis. The results showed that PPT inhibited the growth of the two human OSCC cell lines and induced apoptosis, which was accompanied by mitochondrial membrane depolarization. Compared with the control, PPT reduced the expression of Mcl­1 in both cell lines through a proteasome­dependent protein degradation process. Overall, these results suggested that targeting of Mcl­1 protein by PPT induced apoptosis, providing a foundation for further pre­clinical and clinical study of its value in the management of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Leucemia , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Podofilotoxina/farmacologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Neoplasias Bucais/tratamento farmacológico , Células Mieloides
12.
J Med Internet Res ; 25: e46520, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37733411

RESUMO

BACKGROUND: Sleep disorders, such as obstructive sleep apnea (OSA), comorbid insomnia and sleep apnea (COMISA), and insomnia are common and can have serious health consequences. However, accurately diagnosing these conditions can be challenging as a result of the underrecognition of these diseases, the time-intensive nature of sleep monitoring necessary for a proper diagnosis, and patients' hesitancy to undergo demanding and costly overnight polysomnography tests. OBJECTIVE: We aim to develop a machine learning algorithm that can accurately predict the risk of OSA, COMISA, and insomnia with a simple set of questions, without the need for a polysomnography test. METHODS: We applied extreme gradient boosting to the data from 2 medical centers (n=4257 from Samsung Medical Center and n=365 from Ewha Womans University Medical Center Seoul Hospital). Features were selected based on feature importance calculated by the Shapley additive explanations (SHAP) method. We applied extreme gradient boosting using selected features to develop a simple questionnaire predicting sleep disorders (SLEEPS). The accuracy of the algorithm was evaluated using the area under the receiver operating characteristics curve. RESULTS: In total, 9 features were selected to construct SLEEPS. SLEEPS showed high accuracy, with an area under the receiver operating characteristics curve of greater than 0.897 for all 3 sleep disorders, and consistent performance across both sets of data. We found that the distinction between COMISA and OSA was critical for accurate prediction. A publicly accessible website was created based on the algorithm that provides predictions for the risk of the 3 sleep disorders and shows how the risk changes with changes in weight or age. CONCLUSIONS: SLEEPS has the potential to improve the diagnosis and treatment of sleep disorders by providing more accessibility and convenience. The creation of a publicly accessible website based on the algorithm provides a user-friendly tool for assessing the risk of OSA, COMISA, and insomnia.


Assuntos
Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Feminino , Humanos , Apneia Obstrutiva do Sono/diagnóstico , Aprendizado de Máquina , Transtornos do Sono-Vigília/diagnóstico , Fatores de Risco
13.
Sleep ; 46(9)2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37422720

RESUMO

The prevalence of artificial light exposure has enabled us to be active any time of the day or night, leading to the need for high alertness outside of traditional daytime hours. To address this need, we developed a personalized sleep intervention framework that analyzes real-world sleep-wake patterns obtained from wearable devices to maximize alertness during specific target periods. Our framework utilizes a mathematical model that tracks the dynamic sleep pressure and circadian rhythm based on the user's sleep history. In this way, the model accurately predicts real-time alertness, even for shift workers with complex sleep and work schedules (N = 71, t = 13~21 days). This allowed us to discover a new sleep-wake pattern called the adaptive circadian split sleep, which incorporates a main sleep period and a late nap to enable high alertness during both work and non-work periods of shift workers. We further developed a mobile application that integrates this framework to recommend practical, personalized sleep schedules for individual users to maximize their alertness during a targeted activity time based on their desired sleep onset and available sleep duration. This can reduce the risk of errors for those who require high alertness during nontraditional activity times and improve the health and quality of life for those leading shift work-like lifestyles.


Assuntos
Vigília , Dispositivos Eletrônicos Vestíveis , Humanos , Qualidade de Vida , Tolerância ao Trabalho Programado , Sono , Ritmo Circadiano , Modelos Teóricos
15.
J Korean Acad Nurs ; 53(1): 39-54, 2023 Feb.
Artigo em Coreano | MEDLINE | ID: mdl-36898684

RESUMO

PURPOSE: This study aimed to investigate the nationwide intention to delegate clinical practice of medical specialists in accordance with the enactment of the scope of practice for advanced practice nurses (APNs). METHODS: Data were collected from October to December 2021 using Google Surveys. In total, 147 medical specialists from 12 provinces responded to the survey. The survey questionnaire was categorized into four legislative draft duties, according to the scope of practice (a total of 41 tasks): Twenty-nine tasks on treatments, injects, etc., performed under the guidance of a physician and other activities necessary for medical treatment (treatment domain); two tasks on collaboration and coordination; six tasks on education, counseling, and quality improvement; four regarding other necessary tasks. Participants were asked whether they were willing to delegate the tasks to APN. RESULTS: The intention to delegate tasks to APN was higher for non-invasive tasks such as blood sampling (97.3%) or simple dressing (96.6%). Invasive tasks such as endotracheal tube insertion (10.2%), sampling: bone marrow biopsy & aspiration (23.8%) showed low intention to delegate in the treatment domain. Participants who were older, male, and had more work careers with APN, showed a higher intention to delegate tasks. CONCLUSION: To prevent confusion in the clinical setting, a clear agreement on the scope of APN practice as APN delegated by physicians should be established. Based on this study, legal practices that APN can perform legally should be established.


Assuntos
Intenção , Médicos , Humanos , Masculino , Âmbito da Prática , Inquéritos e Questionários
16.
Asian Nurs Res (Korean Soc Nurs Sci) ; 17(1): 15-22, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36592887

RESUMO

PURPOSE: This study aimed to identify the early sedation depth in the first 48 hours of mechanical ventilation and its relationship to clinical outcomes to promote the transition to light sedation. METHODS: This retrospective single-center cohort study was conducted in two medical intensive care units (MICUs) at a general tertiary hospital, using a standardized sedation protocol. To investigate the early sedation depth, the Sedation Index was used, which can indicate changes over the first 48 hours. Patients were divided into three groups based on tertiles of Sedation Index. The primary outcome was mortality at 30, 90, and 180 days. The secondary outcomes included length of stay in the ICU and ventilator-free days. Kaplan-Meier analysis and multivariable Cox regression were conducted to compare factors influencing mortality. RESULTS: This study included 394 patients. The deepest sedation group showed more severe illness, delirium, and deeper sedation at admission (p < .001). The survival curve decreased as sedation increased, even within the light sedation levels. In the deepest sedation group, 30-day mortality (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.33-3.34), 90-day mortality (HR 2.00, 95% CI 1.31-3.06), and 180-day mortality (HR 1.77, 95% CI 1.17-2.67) increased. The length of stay in the ICU and ventilator-free days did not show statistical differences. CONCLUSIONS: These results indicate that early deep sedation is a modifiable factor that can potentially affect mortality. The protocol for inducing the transition into light sedation must comply with recommendations to improve clinical outcomes.


Assuntos
Unidades de Terapia Intensiva , Respiração Artificial , Humanos , Estudos Retrospectivos , Estudos de Coortes , Respiração Artificial/métodos , Hospitais , Tempo de Internação
17.
Cell Oncol (Dordr) ; 46(2): 267-282, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36441378

RESUMO

PURPOSE: PD-L1 is an immune checkpoint protein that allows cells to evade T-cell-mediated immune responses. Herein, we uncover a tumor-intrinsic mechanism of PD-L1 that is responsible for the progression and aggressiveness of HNC and reveal that the extracts of a brown alga can target the tumor-intrinsic signaling pathway of PD-L1. METHODS: The biological functions of PD-L1 in the proliferation and aggressiveness of HNC cells in vitro were examined by metabolic activity, clonogenic, tumorigenicity, wound healing, migration, and invasion assays. The clinical importance of PD-L1 in the prognosis of patients with HNC was analyzed by immunohistochemistry. The relationship between PD-L1 and EMT was confirmed via western blotting, qPCR, and immunocytochemistry. RESULTS: Through our in silico approach, we found that PD-L1 was upregulated in HNC and was correlated with an unfavorable clinical outcome in patients with HNC. PD-L1 was crucial for promoting tumor growth, both in vitro and in vivo. High expression of PD-L1 was closely correlated with LN metastasis in OSCC. PD-L1 facilitated the cytoskeletal reorganization and aggressiveness of HNC cells. Moreover, PD-L1 enhanced the EMT of HNC cells by regulating the Snail/vimentin axis. Consistently, MEIO suppressed the PD-L1/Snail/vimentin axis, thereby inhibiting the aggressiveness of HNC cells. Inhibition of PD-L1 induced by PD-L1 silencing or MEIO treatment caused Snail degradation through a GSK3ß-dependent mechanism. The tumor-intrinsic function of PD-L1 could be attributed to the regulation of the GSK3ß/Snail/vimentin axis. CONCLUSION: The discovery of MEIO targeting the tumor-intrinsic function of PD-L1 may prove particularly valuable for the development of novel and effective anticancer drug candidates for HNCs overexpressing PD-L1.


Assuntos
Antígeno B7-H1 , Neoplasias de Cabeça e Pescoço , Humanos , Vimentina/metabolismo , Antígeno B7-H1/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral
18.
Asian Pac J Cancer Prev ; 23(10): 3501-3506, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36308376

RESUMO

OBJECTIVE: This study aimed to evaluate the correlation of the maximum standardized uptake value (SUVmax) with the Kirsten ras sarcoma viral oncogene (KRAS) mutation and microsatellite instability (MSI) status in colon cancer. METHODS: This retrospective study included 195 patients with colon cancer who underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) before surgery between January 2014 and December 2017. All patients underwent KRAS mutation and MSI analyses using surgical specimens of the primary tumor. The associations of SUVmax with KRAS mutation and MSI were analyzed. RESULTS: The SUVmax differed significantly between the microsatellite stable (MSS) and MSI groups (14.5 ± 7.0 vs. 19.1 ± 10.9; P = 0.0249), and between the KRAS wild-type and KRAS mutation groups (14.1 ± 7.6 vs. 17.5 ± 7.9; P = 0.0017). CONCLUSIONS: SUVmax obtained using 18F-FDG PET/CT showed significant differences in relation to KRAS mutation and MSI status. 18F-FDG PET/CT could be used as a supplemental modality for assessing KRAS mutations and MSI status in colon cancer.


Assuntos
Neoplasias do Colo , Fluordesoxiglucose F18 , Humanos , Instabilidade de Microssatélites , Proteínas Proto-Oncogênicas p21(ras)/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/genética , Mutação/genética , Compostos Radiofarmacêuticos
19.
Cancer Cell Int ; 22(1): 182, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524332

RESUMO

BACKGROUND: B cell lymphoma-2 (Bcl-2) family members play important roles in cell survival as well as cell death. The role of myeloid cell leukemia-1 (Mcl-1), an important member of the Bcl-2 family, is well established in hematopoietic malignancies. However, the association between Mcl-1 and oral cavity, cancers is not clearly defined. METHODS: A scoping review was conducted until June 30, 2021, using four major databases, PubMed, Scopus, Web of Science, and Embase. Medical subject headings keywords for Mcl-1, along with its other identifiers, and head and neck cancers (only oral cavity tumors) were used to evaluate the expression, function, molecular association, and therapeutic approach of Mcl-1 in oral cavity cancers and precancers. FINDINGS: Mcl-1 expression was associated with the progression of oral cavity cancers. The molecular mechanism and pathways of Mcl-1 in oral cavity cancers established via experimental results have been highlighted in this review. Moreover, the various synthetic and naturally derived therapeutic agents targeting Mcl-1 have been documented. NOVELTY/IMPROVEMENT: Based on our present review, Mcl-1 appears to be an effective anticancer target that can be used in the therapeutic management of oral cancers.

20.
PLoS One ; 17(4): e0267441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35476719

RESUMO

OBJECTIVES: Many patients with obstructive sleep apnea syndrome (OSAS) have nocturia. However, the predictive index of nocturia in patients with OSAS is currently not well known. We aimed to investigate the prevalence of nocturia in patients with OSAS and determine the factors that could predict nocturia in these patients. METHODS: In this retrospective cross-sectional study, we enrolled 1,264 untreated patients with OSAS (Apnea-Hypopnea Index, AHI ≥5/h on polysomnography [PSG]) from January 2017 to January 2020. Participants completed the Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth Sleepiness Scale. Participants were divided by sex and then subdivided into nocturia and non-nocturia groups according to the following question, "Do you go to the bathroom two times or more during your sleep?" Participants' characteristics and underlying disease were investigated, and all information, including PSG data, was compared between the two groups using the t-test or chi-square test. RESULTS: Overall, 35.2% (337/958) of male participants with OSAS and 59.8% (183/306) of female participants with OSAS had nocturia. The nocturia group was older; scored higher on the BDI-II, PSQI, and ISI; and had more underlying disease in both sexes. There was no difference in the AHI between the two groups among both sexes, but the hypoxia-related PSG parameters and sleep quality parameters, such as higher 90% oxygen desaturation index (90% ODI), lesser N3 sleep, and higher wakefulness after sleep onset, were worse among male participants with OSAS in the nocturia group than in the non-nocturia group. In multivariate logistic analysis, 90% ODI was an independent risk factor associated with nocturia in male participants with OSAS. CONCLUSIONS: Considerable number of patients with OSAS had nocturia and poor sleep quality. Nocturia should be evaluated in male OSAS patients with severe hypoxia observed during sleep.


Assuntos
Noctúria , Apneia Obstrutiva do Sono , Estudos Transversais , Feminino , Humanos , Hipóxia/complicações , Masculino , Noctúria/complicações , Noctúria/epidemiologia , Prevalência , Estudos Retrospectivos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia
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