RESUMEN
BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Hepatectomía , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Anciano , Curva ROC , Estudios Retrospectivos , Estimación de Kaplan-Meier , Adulto , Factores de RiesgoRESUMEN
BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.
Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Hepatectomía , Neoplasias Hepáticas , Microondas , Vena Porta , Ablación por Radiofrecuencia , Humanos , Hepatectomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Quimioembolización Terapéutica/métodos , Ablación por Radiofrecuencia/métodos , Microondas/uso terapéutico , Estudios Retrospectivos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirugía , Anciano , Adulto , Hígado/cirugía , Hígado/irrigación sanguínea , Embolización Terapéutica/métodos , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Tasa de Supervivencia , China/epidemiología , Terapia CombinadaRESUMEN
BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.
Asunto(s)
Laparoscopía , Hepatopatías , Complicaciones Posoperatorias , Impresión Tridimensional , Humanos , Femenino , Masculino , Persona de Mediana Edad , Laparoscopía/métodos , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Hepatopatías/cirugía , Anciano , Enfermedades de las Vías Biliares/prevención & control , Enfermedades de las Vías Biliares/cirugía , Enfermedades de las Vías Biliares/etiología , Hepatectomía/métodos , Hepatectomía/efectos adversos , Adulto , Estudios Retrospectivos , Estudios de CohortesRESUMEN
BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Laparoscopía , Neoplasias Hepáticas , Complicaciones Posoperatorias , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados , Humanos , Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Masculino , Laparoscopía/efectos adversos , Femenino , Procedimientos Quirúrgicos Robotizados/efectos adversos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Bases de Datos Factuales , Tiempo de Internación , Factores de Riesgo , Factores de Tiempo , Medición de Riesgo , AdultoRESUMEN
BACKGROUND: Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS: From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS: Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS: In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Síndrome Metabólico , Humanos , Hepatitis B Crónica/complicaciones , Carcinoma Hepatocelular/cirugía , Síndrome Metabólico/complicaciones , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/cirugíaRESUMEN
BACKGROUND: Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy. METHODS: Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR. RESULTS: 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P < 0.05). In multivariate COX regression analysis, PDWLR was demonstrated as an independent risk factor for OS (HR: 1.549, P = 0.041) and RFS (HR: 1.655, P = 0.005). Moreover, PDWLR demonstrated a superior capacity for predicting prognosis compared to other indicators. CONCLUSION: Preoperative PDWLR has a potential value in predicting the prognosis of HCC patients following hepatectomy, which may help in clinical decision-making for individual treatment.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Pronóstico , Hepatectomía/efectos adversos , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Linfocitos/patologíaRESUMEN
PURPOSE: Positive lymph node (LN) is a key prognostic factor in radically resected gallbladder cancer (GBCA). However, only a few underwent an adequate lymphadenectomy, and the number and extent of lymph node dissection (LND) have not been standardized. This study aims to develop an en bloc and standardized surgical procedure of LND for GBCA under laparoscopy. METHODS: Data of patients with GBCA underwent laparoscopic radical resection using a standardized and en bloc technique for LND were collected. Perioperative and long-term outcomes were retrospectively analyzed. RESULTS: A total of 39 patients underwent laparoscopic radical resection using standardized and en bloc technique for LND except one case (open conversion rate: 2.6%). Patients with stage T1b had significantly lower LNs involved rate than patients with stage T3 (P = 0.04), whereas median LN count in stage T1b was significantly higher than that in stage T2 (P = 0.04), which was significantly higher than that in stage T3 (P = 0.02). Lymphadenectomy with ≥ 6 LNs accounted for 87.5% in stage T1b, up to 93.3% in T2 and 81.3% in T3, respectively. All the patients in stage T1b were alive without recurrence at this writing. The 2-year recurrence-free survival rate was 80% for T2 and 25% for T3, and the 3-year overall survival rate was 73.3% for T2 and 37.5% for T3. CONCLUSION: The standardized and en bloc LND permits complete and radical removal of lymph stations for patients with GBCA. This technique is safe and feasible with low complication rates and good prognosis. Further studies are required to explore its value and long-term outcomes compared to conventional approaches.
Asunto(s)
Neoplasias de la Vesícula Biliar , Laparoscopía , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patologíaRESUMEN
PURPOSE: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. METHODS: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). RESULT: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80-1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88-1.70, P = 0.238). CONCLUSION: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection.
Asunto(s)
Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Puntaje de Propensión , Estudios Retrospectivos , Laparoscopía/efectos adversos , Tiempo de InternaciónRESUMEN
BACKGROUND: The Eastern Staging System, which was specially developed for patients undergoing surgical resection for hepatocellular carcinoma (HCC), has been proposed for more than ten years. To prospectively validate the predictive accuracy of the Eastern staging on long-term survival after HCC resection. METHODS: Patients who underwent hepatectomy for HCC from 2011 to 2020 at 10 Chinese hospitals were identified from a prospectively collected database. The survival predictive accuracy was evaluated and compared between the Eastern Staging with six other staging systems, including the JIS, BCLC, Okuda, CLIP, 8th AJCC TNM, and HKLC staging. RESULTS: Among 2365 patients, the 1-, 3-, and 5-year overall survival rates were 84.2%, 64.5%, and 52.6%, respectively. Among these seven staging systems, the Eastern staging was associated with the best monotonicity of gradients (linear trend χ2: 408.5) and homogeneity (likelihood ratio χ2: 447.3), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.776, 0.787, and 0.768, respectively). In addition, the Eastern staging was the most informative staging system in predicting survival (Akaike information criterion: 2982.33). CONCLUSION: Using a large multicenter prospectively collected database, the Eastern Staging was found to show the best predictive accuracy on long-term overall survival in patients with resectable HCC than the other 6 commonly-used staging systems.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Estadificación de Neoplasias , China , Hepatectomía/efectos adversos , PronósticoRESUMEN
BACKGROUND: Assessment of quality in the perioperative period is critical to ensure good patient care. Textbook outcomes (TO) have been proposed to combine several parameters into a single defined quality metric. The association of preoperative body mass index (BMI) with incidences of achieving or not achieving TO (non-TO) among patients undergoing hepatectomy for hepatocellular carcinoma (HCC) was characterized. METHODS: Patients who underwent curative-intent hepatectomy for HCC between 2015 and 2018 were identified from a multicenter database. These patients were divided into three groups based on preoperative BMI: low-BMI (≤ 18.4 kg/m2), normal-BMI (18.5-24.9 kg/m2), and high-BMI (≥ 25.0 kg/m2). The incidences of non-TO among these three groups were compared. Multivariate analyses were performed to identify whether there was any independent association between preoperative BMI and non-TO. RESULTS: Among 1206 patients, 100 (8.3%), 660 (54.7%), and 446 (37.0%) were in the low-BMI, normal-BMI, and high-BMI groups, respectively. The incidence of non-TO was 65.6% in the whole cohort. The incidence of non-TO was significantly higher among patients in the low- and high-BMI cohorts versus the normal-BMI cohort (75.0% and 74.7% versus 58.0%, both P < 0.01). After adjustment of other confounding factors on multivariate analysis, low-BMI and high-BMI were independently associated with higher incidences of non-TO compared with normal-BMI (OR: 1.98 and 2.27, both P < 0.05). CONCLUSIONS: Two out of three patients did not achieve TO after hepatectomy for HCC. Both preoperative low-BMI and high-BMI were independently associated with lower odds to achieve optimal TO following HCC resection.
RESUMEN
Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer-related death worldwide. However, the clinical diagnosis and treatment modalities are still relatively limited, which urgently require the development of new effective technologies. Recently, nanotechnology has gained extensive attention in HCC surveillance, imaging and pathological diagnosis, and therapeutic strategies. Typically, nanomedicines have been focused on early HCC diagnosis and precise treatment of advanced HCC, which has developed and improved a variety of new technologies and agents for future clinical practice. Furthermore, strategies of facilitating drug release and delivery in current treatment processes such as ablation, systematic therapy, transcatheter arterial chemoembolization, molecular targeted therapy, and immune-modulating therapy have also been studied widely. This review summarizes the recent advances in this area according to current clinical HCC guidelines: 1) Nanoparticle-based HCC surveillance; 2) Nanotechnology for HCC diagnosis; 3) Therapeutic advances for HCC Management; 4) Limitations of applications in nanotechnology for HCC; 5) Conclusions and perspectives. Although there are still many limitations and difficulties to overcome, the investigations of nanomedicines are believed to show potential applications in clinical practice.
Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Terapia Molecular Dirigida , NanotecnologíaRESUMEN
Surgical resection is the only potentially curative treatment for patients with resectable perihilar cholangiocarcinoma (PHC). There is still no consensus on the value of lymphadenectomy despite evidence indicating lymph node (LN) status is an important prognostic indicator for postoperative long-term survival. We sought to perform a meta-analysis to summarize the current evidence on the value of lymphadenectomy among patients undergoing surgery for PHC. The PubMed (OvidSP), Embase and Cochrane Library were systematically searched for studies published before July 2020 that reported on lymphadenectomy at the time of surgery for PHC after curative surgery. 7748 patients from 28 studies were included in the meta-analysis. No survival benefit was identified with increased number of LN resected (all P > 0.05). Meanwhile, overall LN status was an important prognostic factor. Patients with lymph node metastasis had a pooled estimate hazard ratio of death that was over two-fold higher than patients without lymph node metastasis (HR 2.07, 95% CI 1.65-2.59, P < 0.001). The examination of 5 LNs on histology was associated with better staging of lymph node status and stratification of patients into positive or negative LN groups. While the extent of LN dissection was not associated with a survival benefit, examination of more than 5 LNs better staged patients into positive or negative LN groups with a lower risk of nodal understaging.
RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a recognized sequalae of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. This study aimed to identify long-term survival and prognostic factors after curative resection for HCC among patients with chronic HCV infection. METHODS: From a Chinese multicenter database, the data of consecutive patients with HCV infection undergoing curative liver resection for initial HCC between 2006 and 2015 were retrospectively reviewed. Postoperative 30-day mortality and morbidity, long-term overall survival (OS) and recurrence-free survival (RFS) were evaluated. RESULTS: Among 382 HCC patients with HCV infection, 68 (18%) had concurrent HBV infection and 110 (29%) had portal hypertension. Postoperative 30-day morbidity and mortality rates were 45% and 2.9%, respectively. The 5-year OS and RFS rates were 45% and 34%, respectively. Multivariable Cox-regression analyses identified that concurrent HBV infection, presence of portal hypertension, largest tumor size > 5 cm, and macrovascular and microvascular invasion were independently associated with worse OS and RFS, while postoperative regular anti-HCV therapy was independently associated with better OS. CONCLUSION: Long-term prognosis after HCC resection among patients with HCV infection was worse in those with concurrent HBV infection and concomitant portal hypertension. Postoperative regular anti-HCV therapy was associated with better OS.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirugía , China/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Humanos , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia , Pronóstico , Estudios RetrospectivosRESUMEN
Elevated iron deposition has been reported in Parkinson's disease (PD). However, the route of iron uptake leading to high deposition in the substantia nigra is unresolved. Here, we show a mechanism in enhanced Fe2+ uptake via S-nitrosylation of divalent metal transporter 1 (DMT1). While DMT1 could be S-nitrosylated by exogenous nitric oxide donors, in human PD brains, endogenously S-nitrosylated DMT1 was detected in postmortem substantia nigra. Patch-clamp electrophysiological recordings and iron uptake assays confirmed increased Mn2+ or Fe2+ uptake through S-nitrosylated DMT1. We identified two major S-nitrosylation sites, C23 and C540, by mass spectrometry, and DMT1 C23A or C540A substitutions abolished nitric oxide (NO)-mediated DMT1 current increase. To evaluate in vivo significance, lipopolysaccharide (LPS) was stereotaxically injected into the substantia nigra of female and male mice to induce inflammation and production of NO. The intranigral LPS injection resulted in corresponding increase in Fe2+ deposition, JNK activation, dopaminergic neuronal loss and deficit in motoric activity, and these were rescued by the NO synthase inhibitor l-NAME or by the DMT1-selective blocker ebselen. Lentiviral knockdown of DMT1 abolished LPS-induced dopaminergic neuron loss.SIGNIFICANCE STATEMENT Neuroinflammation and high cytoplasmic Fe2+ levels have been implicated in the initiation and progression of neurodegenerative diseases. Here, we report the unexpected enhancement of the functional activity of transmembrane divalent metal transporter 1 (DMT1) by S-nitrosylation. We demonstrated that S-nitrosylation increased DMT1-mediated Fe2+ uptake, and two cysteines were identified by mass spectrometry to be the sites for S-nitrosylation and for enhanced iron uptake. One conceptual advance is that while DMT1 activity could be increased by external acidification because the gating of the DMT1 transporter is proton motive, we discovered that DMT1 activity could also be enhanced by S-nitrosylation. Significantly, lipopolysaccharide-induced nitric oxide (NO)-mediated neuronal death in the substantia nigra could be ameliorated by using l-NAME, a NO synthase inhibitor, or by ebselen, a DMT1-selective blocker.
Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Neuronas Dopaminérgicas/metabolismo , Hierro/metabolismo , Locomoción , Óxido Nítrico/química , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismo , Animales , Proteínas de Transporte de Catión/química , Femenino , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Lipopolisacáridos/administración & dosificación , Masculino , Ratones TransgénicosRESUMEN
Using a single test to comprehensively evaluate multiple cardiac biomarkers for early diagnosis and prevention of acute myocardial infarction (AMI) has faced enormous challenges. Here, we have developed paper-based fluorogenic immunodevices for multiplexed detection of three cardiac biomarkers, namely, human heart-type fatty acid binding protein (FABP), cardiac troponin I (cTnI), and myoglobin, simultaneously. The detection is based on a strategy using zinc oxide nanowires (ZnO NWs) to enhance fluorescence signals (â¼5-fold compared to that on pure paper). The immunodevices showed high sensitivity and selectivity for FABP, cTnI, and myoglobin with detection limits of 1.36 ng/mL, 1.00 ng/mL, and 2.38 ng/mL, respectively. Additionally, the paper-based immunoassay was rapid (â¼5 min to complete the test) and portable (using a homemade chamber with a smartphone and an ultraviolet lamp). The developed devices integrated with ZnO NWs enable quantitative, sensitive, and simultaneous detection of multiple cardiac biomarkers in point-of-care settings, which provides a useful approach for monitoring AMI diseases and may be extended to other medical diagnostics and environmental assessments.
Asunto(s)
Proteína 3 de Unión a Ácidos Grasos/sangre , Inmunoensayo/métodos , Mioglobina/sangre , Nanocables/química , Papel , Troponina I/sangre , Biomarcadores/sangre , Humanos , Inmunoensayo/instrumentación , Límite de Detección , Miocardio/química , Óxido de Zinc/químicaRESUMEN
Monoamine oxidases (MAOs) are the enzymes that catalyze the oxidation of monoamines, such as dopamine, norepinephrine, and serotonin, which serve as key neurotransmitters in the central nervous system (CNS). MAOs play important roles in maintaining the homeostasis of monoamines, and the aberrant expression or activation of MAOs underlies the pathogenesis of monoamine neurotransmitter disorders, including neuropsychiatric and neurodegenerative diseases. Clearly, detecting and inhibiting the activities of MAOs is of great value for the diagnosis and therapeutics of these diseases. Accordingly, many specific detection probes and inhibitors have been developed and substantially contributed to basic and clinical studies of these diseases. In this review, progress in the detecting and inhibiting of MAOs and their applications in mechanism exploration and treatment of neurotransmitter-related disorders is summarized. Notably, how the detection probes and inhibitors of MAOs were developed has been specifically addressed. It is hoped that this review will benefit the design of more effective and sensitive probes and inhibitors for MAOs, and eventually the treatment of monoamine neurotransmitter disorders.
Asunto(s)
Enfermedades del Sistema Nervioso Central , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa , Animales , Monoaminas Biogénicas/metabolismo , Células Cultivadas , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Humanos , Monoaminooxidasa/química , Monoaminooxidasa/fisiologíaRESUMEN
Vortex beam generators are promising to improve the transmission data rate and enlarge the communication capacity due to the fact that they inherently carry the orbital angular momentum (OAM). However, current available devices are limited because of high profiles and low efficiencies, especially for the transmissive case. Here, we propose a new strategy to design an ultrathin (0.07λ0) transmissive Pancharatnam-Berry (PB) metasurface with nearly unit transmittance. The carefully optimized metasurface integrates an anisotropic crossbar structure with positive permittivity and a holey metallic ring resonator with negative permittivity based on certain criterions placed on both sides of a dielectric substrate, which realize an exact π phase difference due to the control of permittivities at both polarizations. As a proof of concept, a microwave vortex beam generator is designed, fabricated and experimentally characterized. Both measured far-field and near-field characterizations are in excellent agreement with numerical simulations, indicating that our transmissive PB meta-device (operating at 10.6 GHz) exhibits a maximum experimental efficiency of 87%. Our findings can motivate the realizations of high-performance transmissive PB meta-devices with a very low profile or operation at other frequency domains.
RESUMEN
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.