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In deserts, sedimentation from frequent dust activities on solar cells poses a substantial technical challenge, reducing efficiency and necessitating advanced cost-inefficient cleaning mechanisms. Herein, a novel sandfish scale-inspired self-healing fluorinated copolymer-based triboelectric layer is directly incorporated on top of the polysilicon solar cell for sustained hybrid energy harvesting. The transparent biomimetic layer, with distinctive saw-tooth microstructured morphology, exhibits ultra-low sand adhesion and high abrasion-resistant properties, inhibits sedimentation deposition on solar cells, and concurrently harvests kinetic energy from wind-driven sand particles through triboelectric nanogenerator (TENG). The film exhibits a low friction coefficient (0.149), minimal sand adhesion force (27 nN), and a small wear area (327 µm2). In addition, over 2 months, a solar cell with the sandfish scale-inspired structure demonstrates only a 16% decline in maximum power output compared to the bare solar cell, which experiences a 60% decline. Further, the sandfish scale-based TENG device's electrical output is fully restored to its original value after a 6-h self-healing cycle and maintains consistent stable outputs. These results highlight the exceptional advantages of employing biomimetic self-healing materials as robust triboelectric layers, showcasing sustained device stability and durability for prolonged use in harsh desert environments, ultimately contributing to a low cost-of-electricity generation paradigm.
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Lipid emulsions are the primary source of calories and fatty acids that are used to provide essential energy and nutrients to patients suffering from severe intestinal failure and critical illness. However, their use has been linked to adverse effects on patient outcomes, notably affecting immune defenses and inflammatory responses. ClinOleic is a lipid emulsion containing a mixture of olive oil and soybean oil (80:20). The effect of ClinOleic on the differentiation of M1 macrophages remains unclear. In this study, we isolated human monocytes and added ClinOleic to differentiation culture media to investigate whether it affects monocyte polarization into M1 macrophages and macrophage functions, such as reactive oxygen species (ROS) production and phagocytosis. ROS production was stimulated by live S. aureus and detected with L-012, a chemiluminescence emission agent. Phagocytic capacity was assayed using pHrodo™ Green S. aureus Bioparticles® Conjugate. We found that M1 cell morphology, surface markers (CD80 and CD86), and M1-associated cytokines (TNF-α and IL-6) did not significantly change upon incubation with ClinOleic during M1 polarization. However, S. aureus-triggered ROS production was significantly lower in M1 macrophages differentiated with ClinOleic than in those not treated with ClinOleic. The inhibitory effect of ClinOleic on macrophage function also appeared in the phagocytosis assay. Taken together, these findings reveal that ClinOleic has a limited impact on the M1 differentiation phenotype but obviously reduces ROS production and phagocytosis.
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With continuous population and economic growth in the 21st century, plastic pollution is a major global issue. However, the health concern of microplastics/ nanoplastics (MPs/NPs) decomposed from plastic wastes has drawn public attention only in the recent decade. This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ, which is one of the primary routes that MPs/NPs enter human bodies. The interrelated mechanisms including oxidative stress, hepatocyte energy re-distribution, cell death and autophagy, as well as immune responses and inflammation, were also featured. In addition, the disturbance of microbiome and gut-liver axis, and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease, steatohepatitis, liver fibrosis, and cirrhosis were briefly discussed. Finally, we discussed potential directions in regard to this trending topic, highlighted current challenges in research, and proposed possible solutions.
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Microplásticos , Enfermedad del Hígado Graso no Alcohólico , Humanos , Microplásticos/efectos adversos , Plásticos , Cirrosis HepáticaRESUMEN
Secondary hyperparathyroidism (SHPT) is a common complication of end-stage kidney disease (ESKD). Hungry bone syndrome (HBS) occurs frequently in patients on maintenance dialysis receiving parathyroidectomy for refractory SHPT. However, there is scanty study investigating the clinical risk factors that predict postoperative HBS, and its outcome in peritoneal dialysis (PD) patients. We conducted a single-center retrospective study to analyze 66 PD patients who had undergone parathyroidectomy for secondary hyperparathyroidism at Chang Gung Memorial Hospital between 2009 and 2019. The patients were stratified into two groups based on the presence (n=47) or absence (n=19) of HBS after parathyroidectomy. Subtotal parathyroidectomy was the most common surgery performed (74.2%), followed by total parathyroidectomy with autoimplantation (25.8%). Pathological examination of all surgical specimens revealed parathyroid hyperplasia (100%). Patients with HBS had lower levels of postoperative nadir corrected calcium, higher alkaline phosphate (ALP), and higher potassium levels compared with patients without HBS (all P<0.05). A multivariate logistic regression model confirmed that lower preoperative serum calcium level (OR 0.354, 95% CI 0.133-0.940, P=0.037), higher ALP (OR 1.026, 95% CI 1.008-1.044, P=0.004), and higher potassium level (OR 6.894, 95% CI 1.806-26.317, P=0.005) were associated with HBS after parathyroidectomy. Patients were followed for 58.2±30.8 months after the surgery. There was no significant difference between HBS and non-HBS groups in persistence (P=0.496) or recurrence (P=1.000) of hyperparathyroidism. The overall mortality rate was 10.6% with no significant difference found between both groups (P=0.099). We concluded that HBS is a common complication (71.2%) of parathyroidectomy for SHPT and should be managed appropriately.
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The high incidence of hepatocellular carcinoma (HCC) recurrence negatively impacts outcomes of patients treated with curative intent despite advances in surgical techniques and other locoregional liver-targeting therapies. Over the past few decades, the emergence of transcriptome analysis tools, including real-time quantitative reverse transcription PCR, microarrays, and RNA sequencing, has not only largely contributed to our knowledge about the pathogenesis of recurrent HCC but also led to the development of outcome prediction models based on differentially expressed gene signatures. In recent years, the single-cell RNA sequencing technique has revolutionized our ability to study the complicated crosstalk between cancer cells and the immune environment, which may benefit further investigations on the role of different immune cells in HCC recurrence and the identification of potential therapeutic targets. In the present article, we summarized the major findings yielded with these transcriptome methods within the framework of a causal model consisting of three domains: primary cancer cells; carcinogenic stimuli; and tumor microenvironment. We provided a comprehensive review of the insights that transcriptome analyses have provided into diagnostics, surveillance, and treatment of HCC recurrence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Medicina de Precisión , Perfilación de la Expresión Génica , Transcriptoma , Microambiente TumoralRESUMEN
Gestational diabetes mellitus (GDM) is characterized by glucose intolerance in pregnant women without a previous diagnosis of diabetes. While the etiology of GDM remains elusive, the close association of GDM with increased maternal adiposity and advanced gestational age implicates insulin resistance as a culpable factor for the pathogenesis of GDM. Pregnancy is accompanied by the physiological induction of insulin resistance in the mother secondary to maternal weight gain. This effect serves to spare blood glucose for the fetus. To overcome insulin resistance, maternal ß-cells are conditioned to release more insulin into the blood. Such an adaptive response, termed ß-cell compensation, is essential for maintaining normal maternal metabolism. ß-cell compensation culminates in the expansion of ß-cell mass and augmentation of ß-cell function, accounting for increased insulin synthesis and secretion. As a result, a vast majority of mothers are protected from developing GDM during pregnancy. In at-risk pregnant women, ß-cells fail to compensate for maternal insulin resistance, contributing to insulin insufficiency and GDM. However, gestational ß-cell compensation ensues in early pregnancy, prior to the establishment of insulin resistance in late pregnancy. How ß-cells compensate for pregnancy and what causes ß-cell failure in GDM are subjects of investigation. In this mini-review, we will provide clinical and preclinical evidence that ß-cell compensation is pivotal for overriding maternal insulin resistance to protect against GDM. We will highlight key molecules whose functions are critical for integrating gestational hormones to ß-cell compensation for pregnancy. We will provide mechanistic insights into ß-cell decompensation in the etiology of GDM.
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Diabetes Gestacional , Resistencia a la Insulina , Células Secretoras de Insulina , Femenino , Humanos , Embarazo , Glucemia/metabolismo , Diabetes Gestacional/patología , Prueba de Tolerancia a la Glucosa , Insulina , Células Secretoras de Insulina/fisiologíaRESUMEN
Antibody-mediated rejection (ABMR) is the major cause of chronic allograft dysfunction and loss in kidney transplantation. The immunological mechanisms of ABMR that have been featured in the latest studies indicate a highly complex interplay between various immune and nonimmune cell types. Clinical diagnostic standards have long been criticized for being arbitrary and the lack of accuracy. Transcriptomic approaches, including microarray and RNA sequencing of allograft biopsies, enable the identification of differential gene expression and the continuous improvement of diagnostics. Given that conventional bulk transcriptomic approaches only reflect the average gene expression but not the status at the single-cell level, thereby ignoring the heterogeneity of the transcriptome across individual cells, single-cell RNA sequencing is rising as a powerful tool to provide a high-resolution transcriptome map of immune cells, which allows the elucidation of the pathogenesis and may facilitate the development of novel strategies for clinical treatment of ABMR.
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Trasplante de Riñón , Trasplante de Riñón/efectos adversos , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Transcriptoma , Anticuerpos/genética , Trasplante Homólogo , RiñónRESUMEN
In patients of oral cavity or oropharyngeal cancers, resection of the tumor and reconstruction of the defect may reduce the framework, add a bulky flap, alter the tissue flexibility, and contribute to postoperative obstructive sleep apnea (OSA). Postoperative OSA and the potential consequences may decrease the survival rate and reduce patients' quality of life. It is unclear whether the surgery is associated with postoperative OSA. Here, we compared the polysomnographies (PSGs) before and after the surgery in 15 patients of oral cavity or oropharyngeal cancers (out of 68 patients of head and neck cancers) without a chemo- or radio-therapy. Each patient received the second PSG before the start of any indicated adjuvant therapy to prevent its interference. There were 14 men and 1 woman, with a mean age and a standard deviation (SD, same in the following) of 56.2 ± 12.8 years. There were 6 tongue cancers, 5 buccal cancers, 2 tonsil cancer, 1 lower gum cancer, and 1 trigone cancer. The results show that the surgery changed sleep parameters insignificantly in apnea-hypopnea index (AHI), mean oxyhemoglobin saturation of pulse oximetry (SpO2), minimum SpO2, mean desaturation, and desaturation index but increased mean heart rate in the patients with free flaps. These results hint that the effect of surgery on developing OSA was small in this sample, with a longer plate or a larger framework for a bulkier free flap. It needs future studies with a large sample size to generalize this first observation.
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Neoplasias de la Boca/fisiopatología , Neoplasias de la Boca/cirugía , Neoplasias Orofaríngeas/fisiopatología , Neoplasias Orofaríngeas/cirugía , Sueño/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oximetría , Saturación de Oxígeno , OxihemoglobinasRESUMEN
The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Fallo Renal Crónico , Neoplasias Hepáticas , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , PronósticoRESUMEN
ABSTRACT: Malnutrition is common among patients who have oral cavity squamous cell carcinoma (OSCC), but its effect on the incidence of postoperative complications remains uncertain. Validated nutrition and complication assessment tools were used to evaluate the effects of nutrition on the likelihood of postoperative complications after curative surgery for OSCC.A retrospective study that spanned January 2014 to December 2018 enrolled 70 patients who received curative surgery for OSCC. Nutritional status before surgery was evaluated with the scored Patient-Generated Subjective Global Assessment (PG-SGA), and patients were classified as either well-nourished (rating A) or malnourished (ratings B and C). Complications 30 days after the operation were graded using Clavien-Dindo classification. The perioperative clinicopathological characteristics of the groups were compared, and risk factors for postoperative complications were identified through logistic regression.A total of 44 (62.8%) patients formed the malnourished group, and they tended to be older (Pâ=â.03), weigh less (Pâ=â.001), have lower Body Mass Index (Pâ=â.003), higher PG-SGA scores (Pâ<â.001), higher neutrophil-to-lymphocyte ratio (Pâ=â.034), more postoperative complications (Pâ<â.001), and longer hospital stays (Pâ=â.021). Major complications (Clavien-Dindo classification ≥ IIIa) were experienced by 18.5% (nâ=â13) of patients and were more common in the malnourished group (Pâ=â.007). Multivariate logistic regression demonstrated that PG-SGA score ≥4 was an independent risk factor for postoperative complications (hazard ratioâ=â4.929, Pâ=â.008).Malnutrition defined using the PG-SGA is an independent risk factor for postoperative complications of curative surgery in patients with OSCC. More prospective studies are warranted to confirm our findings.
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Desnutrición , Estado Nutricional , Procedimientos Quirúrgicos Orales/efectos adversos , Complicaciones Posoperatorias , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Masculino , Desnutrición/diagnóstico , Desnutrición/epidemiología , Desnutrición/etiología , Persona de Mediana Edad , Neoplasias de la Boca/complicaciones , Neoplasias de la Boca/patología , Neoplasias de la Boca/cirugía , Evaluación Nutricional , Procedimientos Quirúrgicos Orales/métodos , Complicaciones Posoperatorias/clasificación , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Medición de Riesgo , Factores de RiesgoRESUMEN
Autophagy is a potential target for the treatment of triple negative breast cancer (TNBC). Because of a lack of targeted therapies for TNBC, it is vital to find optimal agents that avoid chemoresistance and metastasis. Flavopereirine has anti-proliferation ability in cancer cells, but whether it regulates autophagy in breast cancer cells remains unclear. A Premo™ Tandem Autophagy Sensor Kit was used to image the stage at which flavopereirine affects autophagy by confocal microscopy. A plasmid that constitutively expresses p-AKT and siRNA targeting p38 mitogen-activated protein kinase (MAPK) was used to confirm the related signaling pathways by Western blot. We found that flavopereirine induced microtubule-associated protein 1 light chain 3 (LC3)-II accumulation in a dose- and time-dependent manner in MDA-MB-231 cells. Confocal florescent images showed that flavopereirine blocked autophagosome fusion with lysosomes. Western blotting showed that flavopereirine directly suppressed p-AKT levels and mammalian target of rapamycin (mTOR) translation. Recovery of AKT phosphorylation decreased the level of p-p38 MAPK and LC3-II, but not mTOR. Moreover, flavopereirine-induced LC3-II accumulation was partially reduced in MDA-MB-231 cells that were transfected with p38 MAPK siRNA. Overall, flavopereirine blocked autophagy via LC3-II accumulation in autophagosomes, which was mediated by the AKT/p38 MAPK signaling pathway.
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Autofagia/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Carbolinas/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Femenino , HumanosRESUMEN
BACKGROUND: Allograft kidney transplantation has become a treatment of choice for patients with end-stage renal disease (ESRD), and post-transplant diabetes mellitus (PTDM) has been associated with impaired patient and graft survival. Taiwan has the highest incidence and prevalence rates of ESRD with many recipients and candidates of kidney transplantation. However, information about the epidemiologic features of PTDM in Taiwan is incomplete. Therefore, we aimed to investigate the prevalence and incidence of PTDM with subsequent patient and graft outcomes. METHODS: Using the Taiwan National Health Insurance Research Database (NHIRD), 3663 kidney recipients between 1997 and 2011 were enrolled. We calculated the cumulative incidences of diabetes mellitus (DM) after transplantation. Cox proportional hazards model with competing risk analysis was used to calculate the hazard ratio (HR) and 95% confidence intervals (CI) between three targeted groups (DM, PTDM, non-DM). The outcomes of primary interest were the occurrence of graft failure excluding death with functioning graft, all-cause mortality, death with functioning graft and major adverse cardiovascular events (MACE) including myocardial infarction (MI), cerebrovascular accident (CVA) and congestive heart failure (CHF). Subgroup analysis for graft failure excluding death with functioning graft, MACE and all-cause mortality was performed, and interaction between PTDM and recipient age was examined. RESULTS: Of 3663 kidney transplant recipients, 531 (14%) had pre-existing DM and 631 (17%) developed PTDM. Compared with non-DM group, the PTDM and DM groups exhibited higher risk of graft failure excluding death with functioning graft (PTDM: HR 1.65, 95% CI 1.47-1.85; DM: HR 1.33, 95% CI 1.18-1.50), MACE (PTDM: HR 1.51, 95% CI 1.31-1.74; DM: HR 1.64, 95% CI 1.41-1.9), all-cause mortality (PTDM: HR 1.79, 95% CI 1.59-2.01; DM: HR 2.03, 95% CI 1.81-2.18), and death with functioning graft (PTDM: HR 1.94, 95% CI 1.71-2.20; DM: HR 1.94, 95% CI 1.71-2.21). Both PTDM and DM groups had increased cardiovascular disease-related mortality (PTDM: HR 2.14, 95% CI 1.43-3.20, p < 0.001; DM: HR 1.89, 95% CI 1.25-2.86, p = 0.002), cancer-related mortality (PTDM: HR 1.56, 95% CI 1.18-2.07, p = 0.002; DM: HR 1.89, 95% CI 1.25-2.86, p = 0.027), and infection-related mortality (PTDM: HR 1.47, 95% CI 1.14-1.90, p = 0.003; DM: HR 2.25, 95% CI 1.77-2.84, p < 0.001) compared with non-DM group. The subgroup analyses showed that the add-on risks of MACE and mortality from PTDM were mainly observed in patients who were younger and those without associated comorbidities including atrial fibrillation, cirrhosis, CHF, and MI. Age significantly modified the association between PTDM and MACE (pinteraction < 0.01) with higher risk in recipients with PTDM aged younger than 55 years (adjusted HR 1.64, 95% CI 1.40-1.92, p < 0.001). A trend (pinteraction = 0.06) of age-modifying effect on the association between PTDM and all-cause mortality was also noted with higher risk in recipients with PTDM aged younger than 55 years. CONCLUSIONS: In the present population-based study, the incidence of PTDM peaked within the first year after kidney transplantation. PTDM negatively impacted graft and patient outcomes. The magnitude of cardiovascular and survival disadvantages from PTDM were more pronounced in recipients aged less than 55 years. Further trials to improve prediction of PTDM and to prevent PTDM are warranted.
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Objective: Mucus provides a protective barrier separating sensitive epithelial surfaces from the outside world. The mouse colonic mucus is organized as a bacteria-free inner layer and a bacteria-colonized outer layer. Antibiotic treatments are known to disturb gut microbiota, but their effect on the mucosal barrier is rarely discussed. The aim was to evaluate and visualize the impact of antibiotics on the colonic mucus and the microbial community. Materials and Methods: Two sets of experiments were conducted. In the antibiotic experiment, mice orally ingested both streptomycin and bacitracin for 7 days. In the recovery experiment, mice were allowed to recover for 7 days without antibiotics after having received the 7-day antibiotic treatment. Mouse colons were isolated and divided into proximal, middle, and distal parts. Specimens were examined under a transmission electron microscope to identify morphological changes. The gut microbial community was evaluated by analyzing 16S rDNA sequences isolated from the different parts of the mouse colon. Results: The antibiotic-treated mice were physiologically normal. However, a significantly increased inner mucus layer in the proximal and middle colon and a dramatic decrease in bacterial numbers in the outer mucus layers were observed. The 16S rDNA compositions showed a similarity in the dominant taxa among different colon sections. While control mice had a diverse microbiota, antibiotic treatments effectively eliminated most of the bacteria, such that the community was dominated by only one genus (Turicibacter or Staphylococcus). Furthermore, following antibiotic withdrawal in treated mice, the thickness of the inner mucus layer returned to control levels, and the microbial community regained a more complex structure, dominated by Firmicutes, Bacteroidetes, and Proteobacteria. Conclusions: Our results indicated that antibiotic treatments not only disturbed the microbiota but also altered the structure of the mucus layer. After the withdrawal of antibiotics, the mucus layer was quickly regenerated within days, probably in response to microbial growth. The recolonization by gut inhabitants with diverse ecological roles, such as mucin-degraders and fermenters indicate that the gut ecosystem is functionally sound and highly resilient.
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Breast cancer, which is the most frequently diagnosed cancer, is quite heterogeneous. For breast cancer subtypes lacking targeted therapies, it is vitally essential to find novel agents that prevent chemoresistance and metastatic relapse. Flavopereirine is a ß-carboline alkaloid that has antiplasmodial activity, and its antiproliferative effect in different cancers remains unclear. The effect of flavopereirine on cell cycle arrest and apoptosis signaling in breast cancer cells was analyzed by flow cytometry. An inhibitor and siRNA were used to confirm the related signaling pathways by Western blot analysis. We found that flavopereirine caused G0/G1 phase arrest in MCF-7â¯cells and S phase arrest in MDA-MB-231â¯cells. MDA-MB-231â¯cells were more sensitive to flavopereirine-induced apoptosis. Furthermore, we found that flavopereirine-induced apoptosis was partially reduced in MDA-MB-231â¯cells treated with an extracellular regulated kinase (ERK) inhibitor and p38 mitogen-activated protein kinase (MAPK) siRNA. Moreover, p38 siRNA treatment simultaneously reduced phosphorylated ERK expression levels. Conversely, the recovered phosphorylation of AKT decreased the levels of p-ERK and p-p38 MAPK. Overall, flavopereirine induces cell cycle arrest and the AKT/p38 MAPK/ERK signaling pathway, which contribute to flavopereirine-induced apoptosis in MDA-MB-231â¯cells.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Carbolinas/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Células MCF-7 , Mitocondrias/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Neutrophil extracellular traps (NETs) are net-like chromatin fibers that can trap and kill microorganisms. Although several anti-inflammatory effects of intravenous anesthetics have been reported, it has not been investigated whether intravenous anesthetics influence NET formation. AIMS: To compare the effects of four intravenous anesthetics (propofol, thiamylal sodium, midazolam, and ketamine) on phorbol myristate acetate (PMA)-induced NET formation and analyze the associated signaling pathways. MATERIALS AND METHODS: PMA-stimulated NETs formed in the absence or presence of intravenous anesthetics were stained with SYTOX Green and then quantified. Inhibitors were applied to investigate the related mechanism, which was confirmed by western blotting, and ROS were detected. KEY FINDINGS: The neutrophils incubated with propofol showed the lowest degree of NET formation compared with those incubated with the other intravenous anesthetics. Propofol significantly reduced the level of myeloperoxidase (MPO)-derived HOCl but not that of superoxide. Aminopyrine, an MPO inhibitor, markedly decreased the number of PMA-induced NETs, indicating the involvement of HOCl in the inhibitory effect of propofol on NET formation. According to western blotting results, the level of p-ERK was reduced by propofol during PMA-induced NET formation. The ERK inhibitor PD98059 decreased NET formation but did not inhibit PMA-induced HOCl generation, and aminopyrine did not reduce ERK phosphorylation. SIGNIFICANCE: Through this study, we define a new anti-inflammatory effect of intravenous anesthetics. Of the four intravenous anesthetics tested, propofol was the most potent inhibitor of NET formation. Moreover, propofol resulted in a decrease in PMA-induced NET formation by two independent mechanisms: inhibition of HOCl and p-ERK.
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Trampas Extracelulares/efectos de los fármacos , Propofol/farmacología , Anestésicos Intravenosos/metabolismo , Anestésicos Intravenosos/farmacología , Cromatina/efectos de los fármacos , Voluntarios Sanos , Humanos , Ácido Hipocloroso/metabolismo , Ketamina/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Midazolam/farmacología , Neutrófilos/fisiología , Propofol/metabolismo , Especies Reactivas de Oxígeno , Transducción de Señal , Acetato de Tetradecanoilforbol/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Tiamilal/farmacologíaRESUMEN
Anesthetics have immunomodulatory effects, but the use of different assay systems has contributed to inconsistent results in the literature. IL-1ß and reactive oxygen species (ROS) secreted by phagocytes are important factors that protect against Staphylococcus aureus infection. In this study, the effects of four intravenous anesthetics (propofol, thiamylal sodium, midazolam, and ketamine) on IL-1ß secretion, ROS, and bacterial survival in S. aureus-infected RAW264.7 cells were evaluated. S. aureus-infected RAW264.7 cells with or without intravenous anesthetic treatment were established as the experimental model. Cell supernatants were subjected to ELISAs to measure secreted IL-1ß. Cell pellets were subjected to qPCR and western blot analyses to analyze IL-1ß mRNA and protein levels. Luminol chemiluminescence assays were used to detect ROS, and bacterial survival was determined by counting the colony forming units at the beginning and end of the infection. Compared with the levels after treatment with the other intravenous anesthetics, secreted IL-1ß levels were lowest in the supernatant of S. aureus-infected RAW264.7 cell cultures after propofol treatment, but propofol did not decrease IL-1ß mRNA or protein expression. However, thiamylal sodium and midazolam decreased IL-1ß mRNA and protein expression in a dose-dependent manner. Additionally, propofol substantially decreased S. aureus-stimulated ROS and phagocytosis. Bacterial survival was strongly increased by propofol treatment. Of the four intravenous anesthetics, propofol was the most potent inhibitor of IL-1ß secretion and ROS level in S. aureus-infected RAW264.7 cells; moreover, propofol resulted in an increase in bacterial survival by inhibiting ROS and phagocytosis.
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Interleucina-1beta/metabolismo , Viabilidad Microbiana/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Propofol/farmacología , Infecciones Estafilocócicas/metabolismo , Staphylococcus aureus/metabolismo , Animales , Ratones , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
In this study, natural organic matter (NOM) in source water, as well as the treated water after coagulation with or without potassium permanganate (KMnO4) preoxidation, was characterized by using high performance size exclusion chromatography with organic carbon detector (HPSEC-OCD) and fluorescence excitation emission matrices (F-EEMs) with parallel factor (PARAFAC) analysis. Bulk parameters, such as dissolved organic carbon (DOC) and ultraviolet light absorbance at 254 nm (UV254), were also analyzed. The results show that KMnO4 preoxidation caused the breakdown of high molecular weight (MW) organics into low MW organics. All organics, whether those that existed in the source water or those generated by KMnO4 preoxidation, could be partly removed by coagulation. Combining the derived organic fractions obtained from HPSEC-OCD with peak-fitting and from F-EEMs with PARAFAC on the same sample, humic substances have been specified as the main organic composition. Further, the predictive models for trihalomethanes formation potential (THMFP) and haloacetic acids formation potential (HAAFP) based on organic fractions from HPSEC-OCD have higher accuracy than those based on the components from PARAFAC modeling. These models provide useful tools to specify the organic fractions from HPSEC-OCD and F-EEMs that constitute active precursors towards trihalomethanes (THMs) or haloacetic acids (HAAs) formation in water. Further, by knowing the major organic precursors, it would facilitate choosing the appropriate water treatment process for disinfection by-products (DBPs) control.
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Agua Potable/química , Monitoreo del Ambiente/métodos , Sustancias Húmicas/análisis , Compuestos Orgánicos/análisis , Trihalometanos/química , Contaminantes Químicos del Agua/química , Agua Potable/análisis , Compuestos Orgánicos/química , Taiwán , Trihalometanos/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
PURPOSE: Mangled lower extremity with Mangled extremity severity score (MESS) more than 7 are considered unsalvageable. We are looking for a factor helps us predicting the salvage potential in the patient with MESS score between 7 and 9. MATERIALS AND METHODS: We reviewed the patients with lower extremities open fracture type IIIB or IIIC and received salvaged procedure or amputation in CGMH between 2002/01 and 2010/09. The patients are subgroup according to their MESS score. ISS score, Gustilo open fracture classification were compared between patient with successful salvage and patient with delay amputation. Logistic regression and stepwise modeling were used to determine the effect of each covariate. RESULTS: 242 patients were enrolled in the study. 33 patients had primary amputation, 160 patients had successfully salvaged limbs and 49 patients received delay amputation. Among patients with MESS score less than 7, 116 patients had successful salvage limbs and 7 patients received delay amputation. Among patient with MESS between 7 and 9, 44 patients discharged with salvaged limbs and 39 patients were failed to salvage their limbs. Successful salvaged patients in this group had significant lower ISS score in compare to delay amputated patients. Patients with ISS score more than 18 in this group has higher delay amputated rate (P value=0.01). CONCLUSION: Systemic injury severity score can help us tell potentially salvaged patient from potentially amputated patient. In patients with MESS score between 7 and 9 concurrently have ISS score less then 17 are potentially salvageable. Level of Evidence & Study Type: Level 3 Retrospective cohort study/prognostic study.
Asunto(s)
Amputación Quirúrgica/estadística & datos numéricos , Toma de Decisiones Clínicas , Fracturas Abiertas/cirugía , Traumatismos de la Pierna/cirugía , Recuperación del Miembro/estadística & datos numéricos , Traumatismos de los Nervios Periféricos/cirugía , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Fracturas Abiertas/fisiopatología , Humanos , Traumatismos de la Pierna/fisiopatología , Masculino , Persona de Mediana Edad , Traumatismos de los Nervios Periféricos/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Traumatismos de los Tejidos Blandos/fisiopatología , Índices de Gravedad del Trauma , Adulto JovenRESUMEN
BACKGROUND: Computerized acoustic voice measurement is essential for the diagnosis of vocal pathologies. Previous studies showed that ambient noises have significant influences on the accuracy of voice quality assessment. OBJECTIVE: This paper presents a voice quality assessment system that can accurately measure qualities of voice signals, even though the input voice data are contaminated by low-frequency noises. METHODS: The ambient noises in our living rooms and laboratories are collected and the frequencies of these noises are analyzed. Based on the analysis, a filter is designed to reduce noise level of the input voice signal. Then, improved numerical algorithms are employed to extract voice parameters from the voice signal to reveal the health of the voice signal. RESULTS: Compared with MDVP and Praat, the proposed method outperforms these two widely used programs in measuring fundamental frequency and harmonic-to-noise ratio, and its performance is comparable to these two famous programs in computing jitter and shimmer. CONCLUSIONS: The proposed voice quality assessment method is resistant to low-frequency noises and it can measure human voice quality in environments filled with noises from air-conditioners, ceiling fans and cooling fans of computers.
Asunto(s)
Algoritmos , Enfermedades de la Laringe/diagnóstico , Ruido , Procesamiento de Señales Asistido por Computador , Calidad de la Voz , Humanos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Mutant Ras plays multiple functions in tumorigenesis including tumor formation and metastasis. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a metastasis inhibitor gene, suppresses matrix metalloproteinase (MMP) activity in the metastatic cascade. Clarifying the relationship between Ras and RECK and understanding the underlying molecular mechanism may lead to the development of better treatment for Ras-related tumors. METHODS: Suppression subtractive hybridization PCR (SSH PCR) was conducted to identify Ha-ras (val12) up-regulated genes in bladder cancer cells. Stable cell lines of human breast cancer (MCF-7-ras) and mouse NIH3T3 fibroblasts (7-4) harboring the inducible Ha-ras (val12) oncogene, which could be induced by isopropylthio-ß-D-galactoside (IPTG), were used to clarify the relationship between Ras and the up-regulated genes. Chromatin immunoprecipitation (ChIP) assay, DNA affinity precipitation assay (DAPA) and RECK reporter gene assay were utilized to confirm the complex formation and binding with promoters. RESULTS: Retinoblastoma binding protein-7 (RbAp46) was identified and confirmed as a Ha-ras (val12) up-regulated gene. RbAp46 could bind with histone deacetylase (HDAC1) and Sp1, followed by binding to RECK promoter at the Sp1 site resulting in repression of RECK expression. High expression of Ras protein accompanied with high RbAp46 and low RECK expression were detected in 75% (3/4) of the clinical bladder cancer tumor tissues compared to the adjacent normal parts. Ras induced RbAp46 expression increases invasion of the bladder cancer T24 cells and MMP-9 activity was increased, which was confirmed by specific lentiviral shRNAs inhibitors against Ras and RbAp46. Similarly, knockdown of RbAp46 expression in the stable NIH3T3 cells "7-4" by shRNA decreased Ras-related lung metastasis using a xenograft nude mice model. CONCLUSIONS: We confirmed that RbAp46 is a Ha-ras (val12) up-regulated gene and binds with HDAC1 and Sp1. Furthermore, RbAp46 binds to the RECK promoter at the Sp1 site via recruitment by Sp1. RECK is subsequently activated, leading to increased MMP9 activity, which may lead to increased metastasis in vivo. Our findings of Ras upregulation of RbAp46 may lead to revealing a novel mechanism of Ras-related tumor cell metastasis.