RESUMEN
The timely identification of individuals at high risk for peptic ulcers (PUs) is vital in preventing gastrointestinal bleeding after antiplatelet therapy. This study was designed to determine PU risk factors and develop a risk assessment model for PU detection in the general Chinese population. In a prospective dataset, clinical data from individuals undergoing gastroscopic evaluation between April 2019 and May 2022 were recorded. PUs were defined as mucosal defects exceeding 5 mm confirmed via gastroscopy. Participants were categorized into development (April 2019 to April 2021) and validation (May 2021 to May 2022) sets based on chronological order. LASSO-derived logistic regression analysis was employed to create a score, which was further validated via temporal validation. A total of 902 patients were ultimately enrolled, 204 (22.6%) of whom had PUs based on endoscopic findings. In the development cohort (n = 631), seven independent risk factors emerged: male sex (OR = 2.35, P = 0.002), white blood cell (WBC) count (OR = 1.16, P = 0.010), red blood cell (RBC) count (OR = 0.49, P < 0.001), globulin level (OR = 0.92, P = 0.004), albumin level (OR = 0.94, P = 0.020), pepsinogen I (PGI) level (OR = 1.01, P < 0.001), and positive Helicobacter pylori (HP) antibody (OR = 2.50, P < 0.001). Using these factors, a nomogram (HAMPROW score [hazard ratio (HP) antibody, albumin, male, PGI, RBC, globulin, and WBC]) was developed for individual PU prediction. The ability of the HAMPROW score to predict survival was confirmed with AUCs of 0.854 (95% CI 0.816-0.891) and 0.833 (95% CI 0.771-0.895) in the development and validation sets, respectively. In conclusion, the HAMPROW score can be used to screen for PUs effectively in the general Chinese population, facilitating personalized early detection of high risk of gastrointestinal bleeding before antiplatelet therapy.
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Globulinas , Infecciones por Helicobacter , Helicobacter pylori , Úlcera Péptica , Humanos , Masculino , Úlcera Péptica Hemorrágica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Úlcera Péptica/complicaciones , Hemorragia Gastrointestinal/inducido químicamente , Albúminas/uso terapéutico , China/epidemiología , Supuración/inducido químicamente , Supuración/complicaciones , Infecciones por Helicobacter/tratamiento farmacológicoRESUMEN
BACKGROUND: Pesticide formulations based on nanotechnology can effectively improve the efficiency of pesticide utilization and reduce pesticide residues in the environment. In this study, mesoporous silica nanoparticles containing disulfide bonds were synthesized by the sol-gel method, carboxylated and adsorbed with lufenuron, and grafted with cellulose to obtain a lufenuron-loaded nano-controlled release formulation (Luf@MSNs-ss-cellulose). RESULTS: The structure and properties of Luf@MSNs-ss-cellulose were characterized. The results showed that Luf@MSNs-ss-cellulose exhibits a regular spherical shape with 12.41% pesticide loading. The highest cumulative release rate (73.46%) of this pesticide-loaded nanoparticle was observed at 7 days in the environment of glutathione and cellulase, which shows redox-enzyme dual-responsive performance. As a result of cellulose grafting, Luf@MSNs-ss-cellulose had a small contact angle and high adhesion work on corn leaves, indicating good wetting and adhesion properties. After 14 days of spraying with 20 mg L-1 formulations in the long-term control efficacy experiment, the mortality of Luf@MSNs-ss-cellulose against Ostrinia furnacalis larvae (56.67%) was significantly higher than that of commercial Luf@EW (36.67%). Luf@MSNs-ss-cellulose is safer for earthworms and L02 cells. CONCLUSION: The nano-controlled release formulation obtained in this study achieved intelligent pesticide delivery in time and space under the environmental stimulation of glutathione and cellulase, providing an effective method for the development of novel pesticide delivery systems. © 2023 Society of Chemical Industry.
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Benzamidas , Celulasas , Fluorocarburos , Nanopartículas , Plaguicidas , Preparaciones de Acción Retardada , Nanopartículas/química , Glutatión/metabolismo , Oxidación-Reducción , Celulosa , Dióxido de Silicio/química , Porosidad , Portadores de Fármacos/química , Compuestos OrgánicosRESUMEN
Background: Pancreatic cancer (PC) is a malignant cancer with poor prognosis and high mortality rate. Sine oculis homeobox homolog 1 (SIX1) participates in the development of many cancers. However, the function of SIX1 in PC is not fully understood. Methods: SIX1 expression was determined using immunohistochemistry in PC tissues and cell lines. Glucose consumption, lactate production, and ATP assays were used to detect the function of SIX1. PC cells and NK cells were cocultured to study the effect of SIX1 overexpression in PC cells on NK cell function. Chromatin immunoprecipitation (ChIP) assays were used to study the relationship between SIX1 and lactate dehydrogenase A (LDHA). A series of in vitro and in vivo assays were further applied to elucidate the important role of the SIX1/LDHA axis in metabolism and NK cell dysfunction in PC. Results: SIX1 was significantly upregulated in PC tissue; SIX1 overexpression promoted the glycolysis capacity of PANC-1 and CFPAC-1 cells and resulted in NK cell dysfunction after the NK cells had been cultured with PC cells. LDHA inhibitor partially restored the promotion of PC caused by SIX1 overexpression. According to ChIP assays, SIX1 directly binds to the LDHA promoter region. Moreover, LDHA inhibitor and lactate transporter blocker treatment promoted the function of NK cells cocultured with PC cells. In vivo experiments yielded the same results. Conclusion: The SIX1/LDHA axis promotes lactate accumulation and leads to NK cell dysfunction in PC.
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Proteínas de Homeodominio , L-Lactato Deshidrogenasa , Neoplasias Pancreáticas , Humanos , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , L-Lactato Deshidrogenasa/genética , Ácido Láctico , Neoplasias Pancreáticas/patología , Neoplasias PancreáticasRESUMEN
PURPOSE: To investigate the possible mechanism by which adhesion molecules ICAM-1 and E-selectin mediate hypertriglyceridemic pancreatitis (HTGP)-associated lung injury. METHODS: C57BL/6 mice were randomly divided into five groups: control group (Con), severe acute pancreatitis group (SAP), HTGP group (HTGP), A-205804 group (A-205804), and apocynin group (Apo). Serum biochemical markers related to pancreatitis, such as inflammatory cytokines, amylase and lipase, were measured by enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin and eosin (HE) staining was used to analyze the histopathology changes in the pancreas and lung, and myeloperoxidase (MPO) activity in lung was detected by immunohistochemistry (IHC). Molecules related to NF-κB signaling pathway and adhesion molecules were assessed by western blotting (WB), IHC and immunofluorescence staining. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in lung tissues and serum were measured with reagent kits, respectively. RESULTS: The severity of pancreatitis and lung injury in HTGP group was more severe than that in SAP group, and the expression levels of adhesion molecules ICAM-1 and E-selectin in lung tissues of HTGP mice were significantly increased. After HTGP mice were treated with adhesion molecule inhibitor A-205804, the expression of ICAM-1 and E-selectin in A-205804 group significantly decreased, and the lung injury was alleviated. The HTGP group had higher levels of oxidative stress and NF-κB pathway-related protein p-p65 expression compared with the SAP group. Apocynin treatment resulted in suppression of p-p65, ICAM-1, and E-selectin expression. CONCLUSION: In HTGP, hypertriglyceridemia may exacerbate pancreatitis-related lung injury by regulating oxidative stress and activating the NF-κB proinflammatory pathway to upregulate ICAM-1 and E-selectin levels.
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Lesión Pulmonar , Pancreatitis , Animales , Ratones , Enfermedad Aguda , Selectina E , Molécula 1 de Adhesión Intercelular/metabolismo , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Pancreatitis/metabolismoRESUMEN
BACKGROUND: Developing pesticide-controlled release formulations with foliage adhesion has become the focus of current research in the field of crop protection. In this study, an excellent adhesive nanocapsule loaded with emamectin benzoate (Eb@PDA) was prepared via emulsion interfacial polymerization based on the self-polymerization ability and adhesion properties of polydopamine (PDA). RESULTS: The physicochemical properties of the Eb@PDA were characterized by scanning electron microscopy, transmission electron microscopy, particle size statistics, Fourier transform infrared spectroscopy and X-ray diffraction. The Eb@PDA presented a regular spherical shape, with an average particle size of 163.8 nm. Compared with conventional formulations, it had higher pesticide-loading content (34%) and excellent adhesion onto corn leaf. In addition, Eb@PDA showed sustained-release characteristics, facilitating the release of Eb at low pH and high temperature. Eb@PDA could effectively protect Eb against photodegradation and had a longer effective period for controlling Spodoptera frugiperda and Spodoptera exigua. Furthermore, acute toxicity tests showed that the 50% lethal concentration (LC50 ) was 80.91 and 57.91 mg kg-1 at 7 and 14 days, respectively, indicating a lower toxicity of the Eb@PDA to earthworms. The cells (L02) treated with Eb@PDA showed a higher cell viability but a lower apoptosis rate (only 5.75%), demonstrating the lower cytotoxicity of the Eb@PDA. CONCLUSION: The self-prepared Eb@PDA could be used as a formulation with the advantages of slow release, UV shielding, strong leaf adhesion, superior insecticidal properties, sustained effectiveness and biosafety. It will also facilitate the development of an efficient and safe pesticide delivery system. © 2022 Society of Chemical Industry.
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Insecticidas , Nanocápsulas , Indoles , Ivermectina/análogos & derivados , Polímeros/químicaRESUMEN
Several inflammation-related factors (IRFs) have been reported to predict organ failure of acute pancreatitis (AP) in previous clinical studies. However, there are a few shortcomings in these models. The aim of this study was to develop a new prediction model based on IRFs that could accurately identify the risk for organ failure in AP. Methods. 100 patients with their clinical information and IRF data (levels of 10 cytokines, percentages of different immune cells, and data obtained from white blood cell count) were retrospectively enrolled in this study, and 94 patients were finally selected for further analysis. Univariate and multivariate analysis were applied to evaluate the potential risk factors for the organ failure of AP. The area under the ROC curve (AUCs), sensitivity, and specificity of the relevant model were assessed to evaluate the prediction ability of IRFs. A new scoring system to predict the organ failure of AP was created based on the regression coefficient of a multivariate logistic regression model. Results. The incidence of OF in AP patients was nearly 16% (15/94) in our derivation cohort. Univariate analytic data revealed that IL6, IL8, IL10, MCP1, CD3+ CD4+ T lymphocytes, CD19+ B lymphocytes, PCT, APACHE II score, and RANSON score were potential predictors for AP organ failure, and IL6 (P = 0.038), IL8 (P = 0.043), and CD19+B lymphocytes (P = 0.045) were independent predictors according to further multivariate analysis. In addition, a preoperative scoring system (0-11 points) was constructed to predict the organ failure of AP using these three factors. The AUC of the new score system was 0.86. The optimal cut-off value of the new scoring system was 6 points. Conclusions. Our prediction model (based on IL6, IL8, and CD19+ B Lymphocyte) has satisfactory working efficiency to identify AP patients with high risk of organ failure.
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Inflamación/complicaciones , Puntuaciones en la Disfunción de Órganos , Pancreatitis/complicaciones , Adulto , Anciano , Linfocitos B/inmunología , Citocinas/análisis , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism. METHODS: SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria. RESULTS: Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2â±â30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3â±â46.8 vs. 421.7â±â48.3 pg/ml; amylase: 2102.3â±â165.3 vs. 3186.4â±â245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8â±â50.3 vs. 332.4â±â25.1 Hz; discharge amplitude: 33.4â±â5.3 vs. 20.5â±â2.9 µV). CONCLUSIONS: Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus- and α7nAChR-dependent mechanisms.
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Dexmedetomidina , Pancreatitis , Enfermedad Aguda , Animales , Dexmedetomidina/uso terapéutico , Inflamación/tratamiento farmacológico , Neuroinmunomodulación , Pancreatitis/tratamiento farmacológico , Ratas , Factor de Necrosis Tumoral alfaRESUMEN
Ephrin-2 (EFNB2) is expressed at abnormally high levels in some neoplasms, such as squamous cell carcinoma of the head and neck and colorectal cancer. Its overexpression is associated with the malignant progression of tumors. However, the expression of EFNB2 in pancreatic ductal adenocarcinoma (PDAC) has not been thoroughly studied. EFNB2 expression was evaluated by quantitative real-time PCR, immunohistochemistry, and western blotting. Furthermore, the association between its expression levels and the clinicopathological features of PDAC patients was explored. To determine the underlying mechanisms of EFNB2, we transfected PDAC cells with small interfering RNA and performed in vitro and in vivo experiments. EFNB2 expression levels were significantly increased in cancer tissues and were associated with PDAC clinical stage and Ki67 expression. The down-regulation of EFNB2 inhibited cell proliferation by up-regulating p53/p21-mediated G0/G1 phase blockade. Knockdown of EFNB2 decreased the migration and invasion of PDAC cells by blocking epithelial-mesenchymal transition. These results suggested that EFNB2 may participate in the development of PDAC by promoting cell proliferation, migration, and invasion. Thus, EFNB2 is a potential target for the diagnosis and treatment of PDAC.
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Adenocarcinoma/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Efrina-B2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Quinasas p21 Activadas/metabolismo , Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Movimiento Celular , Proliferación Celular , Efrina-B2/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Proteína p53 Supresora de Tumor/genética , Quinasas p21 Activadas/genéticaRESUMEN
Previous studies have reported that increased glycolytic activity enhances chemotherapy resistance in some types of malignancies. However, whether glycolysis influences the curative effect of gemcitabine (GEM) on pancreatic cancer (PC) cells remains unclear. The aim of this study was to investigate the status of glycolysis in PC and its association with tolerance to GEM. Data from The Cancer Genome Atlas (TCGA) were used to analyze the correlation between glycolysis-related gene (GRG) expression and PC progression and prognosis. 2-Deoxy-D-glucose (2-DG) was applied to assess the effect of glycolysis inhibition on PC cell death and GEM tolerance. Expression of some GRGs, such as HK1, GAPDH, PKM2, and LDHA, was significantly associated with the prognosis of PC. Furthermore, HK1, PKLR, and LDHA expression correlated positively with PC progression. Further analysis revealed that cancer cell death was markedly enhanced following glycolysis inhibition and that the sensitivity of cancer cells to GEM was notably increased in the presence of 2-DG. Our findings indicate that abnormally increased glycolytic activity promotes the development of PC and enhances drug tolerance to GEM. 2-DG combined with GEM is a potential therapy for PC.
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Desoxicitidina/análogos & derivados , Glucólisis/genética , Páncreas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Animales , Muerte Celular/genética , Línea Celular Tumoral , Desoxicitidina/farmacología , Desoxiglucosa/metabolismo , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Páncreas/metabolismo , Neoplasias Pancreáticas/patología , Pronóstico , GemcitabinaRESUMEN
Background. The incidence of hypertriglyceridemia-induced acute pancreatitis (HIAP) is increasing worldwide, and now it is the third leading cause of acute pancreatitis in the United States. But, there are only 5% of patients with severe hypertriglyceridemia (>1000 mg/dl) which might generate acute pancreatitis. In order to explore which part of the patients is easy to develop into pancreatitis, a case-control study was performed by us to consider which patient population tend to develop acute pancreatitis in patients with severe hypertriglyceridemia. To perform a retrospective case-control study, we identified severe hypertriglyceridemia patients without AP (HNAP) and with HIAP with a fasting triglyceride level of >1000 mg/dl from The First Affiliated Hospital of Nanjing Medical University during January 1, 2014, to December 31, 2016. Baseline patient characteristics, comorbidities, and risk factors were recorded and evaluated by the univariate and multivariate logistic regression analysis for HIAP and HNAP patients. A total of 124 patients with severe hypertriglyceridemia were included in this study; of which, 62 patients were in the HIAP group and 62 were in the HNAP group. Univariate logistic regression analysis showed that there was no gender difference in both groups; however, there were more younger patients in the HIAP group than in the HNAP group ( P value < 0.001), and the HIAP group had low level of high-density lipoprotein compared to the HNAP group ( P < 0.05 ). Meanwhile, the presence of pancreatitis was associated with higher level of glycemia and a history of diabetes ( P < 0.05 ). Multivariate logistic regression analysis indicated that a history of diabetes and younger age were independent risk factors for acute pancreatitis in patients with severe hypertriglyceridemia. Uncontrolled diabetes and younger age are potential risk factors in patients with severe hypertriglyceridemia to develop acute pancreatitis.
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Complicaciones de la Diabetes/etiología , Diabetes Mellitus/patología , Hipertrigliceridemia/etiología , Pancreatitis/etiología , Estudios de Casos y Controles , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Ayuno/fisiología , Femenino , Humanos , Hipertrigliceridemia/metabolismo , Incidencia , Masculino , Persona de Mediana Edad , Pancreatitis/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Triglicéridos/metabolismoRESUMEN
BACKGROUND: The efficacy of some therapeutic methods (open surgical debridement (OSD), conservative treatment (CST) and minimally invasive drainage (MID)) for severe acute pancreatitis (SAP) and moderately severe acute pancreatitis (MSAP) has been widely evaluated. However, the results remained controversial. We performed this study to illuminate whether any difference in incidence exists on patients with SAP/MSAP treated with OSD and MID. METHODS: Eligible articles were collected base of a comprehensive review of PUBMED, EMBASE, COCHRANE, CKNI and WANGFANG for published randomized controlled trials. Two steps of meta-analysis were performed, routine pair-wise meta-analysis and network meta-analysis. RESULTS: Thirteen studies were included in this study. Participants were classed as 5 groups, CST, early MID (EMID), late MID (LMID), early OSD (EOSD) and late OSD (LOSD). And MID contains endoscopic drainage (ESD), percutaneous catheter drainage (PCD) and minimally invasive surgery (MIS). Compared with CST, MID could decrease both mortality and multiple organ dysfunction syndrome (MODS) rate but OSD couldn't. Both EMID and MID can significantly decrease the mortality and MODS rate compared to CST. PCD might be most likely to have a benefit compared to CST. CONCLUSION: Existing evidence for the use of MID in SAP/MSAP is reliable and it can be used as early treatment. OSD, if necessary, should be avoided or delayed as long as possible.
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Desbridamiento , Drenaje/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Pancreatitis/cirugía , Tratamiento Conservador , Desbridamiento/efectos adversos , Drenaje/efectos adversos , Endoscopía/efectos adversos , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/prevención & control , Metaanálisis en Red , Pancreatitis/complicaciones , Pancreatitis/mortalidad , Complicaciones Posoperatorias , Índice de Severidad de la EnfermedadRESUMEN
Severe acute pancreatitis (SAP) is an acute abdominal disease that can develop locally to the multiple organs. It is characterized by pancreatic tissue self-digestion, and the rapid release of inflammatory cytokines, which play a dominant role in local or even systemic inflammation. In this study, we investigate the protective effect of T-614 against SAP induced by cerulein plus LPS in mice. Biochemical markers associated with pancreatitis in serum such as inflammatory cytokines, amylase and lipase activities were measured. Related proteins of NLRP3 inflammasome and NF-κB signaling pathway were evaluated by western blotting. Hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) were used to evaluate changes of inflammation in pancreatic tissue. T-614 significantly alleviated the elevation markers of pancreatitis and suppresses the pancreatic tissue damage, including histopathological and molecular manifestations. In conclusion, T-614 plays a protective role in experimental SAP mice model via anti-inflammatory effects.
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Cromonas/uso terapéutico , Inflamasomas/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pancreatitis/tratamiento farmacológico , Pancreatitis/metabolismo , Transducción de Señal , Sulfonamidas/uso terapéutico , Enfermedad Aguda , Amilasas/sangre , Animales , Cromonas/farmacología , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Lipasa/sangre , Masculino , Ratones Endogámicos C57BL , Infiltración Neutrófila/efectos de los fármacos , Páncreas/efectos de los fármacos , Páncreas/patología , Pancreatitis/sangre , Pancreatitis/patología , Transducción de Señal/efectos de los fármacos , Sulfonamidas/farmacologíaRESUMEN
Single nucleotide polymorphisms (SNPs) within the interleukins (IL) gene may affect the risk of acute pancreatitis. Many epidemiological studies have reported an association between the IL gene and acute pancreatitis risk, but the results remain inconsistent. Given the controversial available data, we carried out a meta-analysis to systematically evaluate and clarify the association between IL gene polymorphisms and AP. A systematic search of studies for this association was obtained from the PubMed, EMBASE, Web of Science and Chinese National Knowledge Infrastructure (CNKI) databases until June 1, 2017. We also searched the references of the included studies to identify additional studies. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to pool the effect size. Stata12.0 was used for whole statistical analysis. Fifteen studies that contained 3371 AP cases and 3506 controls were included in final combination. Overall, a significant association was found between the IL-8-251 T/A (rs4073) polymorphism, the IL-10-1082 A/G (rs1800896) polymorphism and the AP risk in four genetic models (homozygote model, recessive model, dominant model, allele model). Meanwhile, individuals with IL-1ß+3954 C/T (rs1143634, (homozygote model, recessive model)), IL-1ß -511 C/T (rs16944, (dominant model)) and IL-6-634C/G (rs1800796, (allele model)) polymorphism were associated with an increased risk of AP. No evidence of an association was found between IL and 10-592 C/A (rs1800872) and IL-10-819 C/T (rs1800871) polymorphism and AP risk.
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Predisposición Genética a la Enfermedad/genética , Interleucinas/genética , Pancreatitis/genética , Polimorfismo de Nucleótido Simple/genética , Alelos , Humanos , Oportunidad Relativa , Factores de RiesgoRESUMEN
Severe acute pancreatitis (SAP) is a medical emergency that is often associated with multiple organ failure and high mortality. Although an SAP diagnosis requires prompt treatment, therapeutic options remain limited. SRT1720 is a newly formulatedSIRT1 activator that exerts multiple pharmacological activities with beneficial health effects. However, its potential as an SAP treatment has not been explored. The current study assessed the effect of SRT1720 on a rat model of sodium taurocholate-induced SAP and explored the underlying mechanism. SAP was induced in rats by retrograde injection of a 3.5% sodium taurocholate solution (1 ml/kg) in the biliopancreatic duct. SRT1720 (5 mg/kg) was administered intraperitoneally after sodium taurocholate exposure. Serum samples were analysed for inflammatory cytokine levels and select enzymatic activities using the enzyme-linked immunosorbent assay and commercial enzyme activity assay kits, respectively; protein expression levels were evaluated by western blotting; mRNA levels of biomarkers were determined by quantitative real-time PCR; histopathological changes were analysed by haematoxylin and eosin staining and immunohistochemistry.SRT1720 treatment significantly reduced serum amylase, lipase, pancreatic histological scores, proinflammatory cytokine (TNF-α and IL-6) levels, and expression of NF-κB and p65 in sodium taurocholate-induced SAP rats. Importantly, the treatment stimulated SIRT1 and IκBα levels in pancreatic tissue. Our data suggest that SRT1720 protects rats from sodium taurocholate-induced SAP by suppressing the NF-κB signalling pathway.
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Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , FN-kappa B/metabolismo , Pancreatitis/tratamiento farmacológico , Pancreatitis/metabolismo , Transducción de Señal , Enfermedad Aguda , Animales , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Interleucina-6/sangre , Masculino , Páncreas/efectos de los fármacos , Páncreas/patología , Pancreatitis/sangre , Pancreatitis/inducido químicamente , Ratas Sprague-Dawley , Sirtuina 1/metabolismo , Ácido Taurocólico , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVES: Thymidine kinase 1 (TK1) is one of the salvage enzymes engaged in the synthesis of DNA. Although a pro-carcinogenetic role of TK1 has been reported in various types of cancers, its role in pancreatic ductal adenocarcinoma (PDAC) is still unknown. The study is aimed to elaborate the function of TK1 in PDAC and the potential mechanisms in the following study. MATERIALS AND METHODS: TK1 expression was analysed by immunohistochemistry, real-time PCR and Western blot, and its relationship with clinicopathological characteristics of PDAC patients was further investigated. To verify the function of TK1 and potential mechanism, TK1 siRNA was used to transfect PDAC cells and performed a series of assays in cell and animal models. RESULTS: The level of TK1 expression was higher in cancerous tissues compared with matched adjacent tissues. TK1 overexpression was associated with progression of PDAC and poor prognosis. Knockdown of TK1 could suppress cell proliferation via inducing S phase arrest mediated by upregulation of P21. Further mechanism investigation suggested that transcription factor E2F-1 could directly regulate the TK1 and promote tumour proliferation. CONCLUSIONS: The results suggested that TK1 might be involved in the development and progression of PDAC by regulating cell proliferation and show that TK1 may work as a promising therapeutic target in patients with PDAC.
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Carcinoma Ductal Pancreático/enzimología , Proliferación Celular , Neoplasias Pancreáticas/enzimología , Timidina Quinasa/genética , Anciano , Animales , Apoptosis , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Movimiento Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Progresión de la Enfermedad , Factor de Transcripción E2F1/metabolismo , Femenino , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Trasplante de Neoplasias , Neoplasias Pancreáticas/patología , Interferencia de ARN , ARN Interferente Pequeño/genética , Transducción de Señal , Timidina Quinasa/metabolismoRESUMEN
OBJECTIVE: Lymphocytes are one of the main effector cells in the inflammatory response of acute pancreatitis (AP). The purpose of the study was to evaluate whether peripheral blood lymphocyte (PBL) subsets at admission change during AP based on clinical outcomes and to explore whether these changes vary by aetiology of AP. Hence, we performed a prospective study to find a predictor in lymphocyte subsets that might allow easier, earlier, and more accurate prediction of clinical outcomes. METHODS: Patients with AP were enrolled from December 2017 to June 2018 at the First Affiliated Hospital of Nanjing Medical University. Age, sex, clinical and biochemical parameters, and aetiology of AP were obtained at admission. PBL counts were assessed within 24 hours after admission. Clinical outcomes were observed as endpoints. The areas under the curve (AUCs) of different predictors were calculated using the receiver operating characteristic (ROC) curve. RESULTS: Overall, 133 patients were included. Patients (n=24) with organ failure (OF) had significantly lower CD4+ T lymphocyte levels than those (n=109) with No OF (NOF) (39.60 (33.94-46.13) vs. 32.41 (26.51-38.00), P=0.004). The OF group exhibited significantly higher CD19+ B lymphocytes than the NOF group (16.07 (10.67-21.06) vs. 23.78 (17.84-29.45), P=0.001). Of the AP cases, 68.8% were caused by gallstones; 10.1% were attributed to alcohol; 16.5% were due to hyperlipidaemia; and 4.6% had other causes. Across all aetiologies, a lower CD4+ T lymphocyte level was significantly related to OF (P<0.05). However, CD19+ B lymphocytes were significant only in gallstone pancreatitis (P<0.05). The ROC curve results showed that the AUC values of CD4+T lymphocytes, CD19+ B lymphocytes, and combined CD4+T lymphocytes and CD19+ B lymphocytes were similar to those of traditional scoring systems, such as APACHEII and Ranson. CONCLUSIONS: CD4+ T and CD19+ B lymphocytes during the early phase of AP can predict OF.