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1.
Ann Surg Oncol ; 30(12): 7358-7359, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37556011

RESUMEN

BACKGROUND: Anatomical segmentectomy is a surgical procedure that completely removes a territory (or territories) of the third-order portal venous branches of a Couinaud segment (Wakabayashi et al. in J Hepatobil Pancreat Sci 29(1):82-98, 2022. https://doi.org/10.1002/jhbp.899 ). Laparoscopic segmentectomy of S8 is considered technically challenging because of the Precise dissection of the Glissonean pedicle of S8, and exposure of the middle and right hepatic veins are required (Ome et al. in J Am Coll Surg 230(3):e13-e20, 2020; Wakabayashi et al. in Ann Surg 261(4):619-29, 2015. https://doi.org/10.1097/sla.0000000000001184 ; Monden et al. in J Hepatobil Pancreat Sci 29(1):66-81, 2022. https://doi.org/10.1002/jhbp.898 ). This report describes a new approach, which can reduce unwanted damage to normal tissues and complications. METHODS: A 53-year-old man who has suffered from hepatitis B for 10 years was admitted for the treatment of two nodular tumors located in segment VIII. The surgical procedure began with the percutaneous injection of 5 mL, 0.025 mg/mL of ICG into the S8 portal branch by using an 18G PTCD needle under the guidance of laparoscopic ultrasound (Xu et al. in Surg Endosc 34(10):4683-4691, 2020. https://doi.org/10.1007/s00464-020-07691-5 ; Wang et al. in Ann Surg 274(1):97-106, 2021. https://doi.org/10.1097/sla.0000000000004718 ; Aoki et al. in J Am Coll Surg 230(3):e7-e12, 2020. https://doi.org/10.1016/j.jamcollsurg.2019.11.004 ), followed by liver transection on the cranial side of the liver, which used the ICG fluorescence images for exposing the roots of the middle and right hepatic veins and dissecting and ligating S8 portal pedicle. The excision specimen was sent for histopathological diagnosis. RESULTS: It took 200 min for the operation and 60 min for the total Pringle maneuver. The estimate of blood loss was 110 mL. The final histopathologic results of the two nodules were hepatocellular carcinoma (HCC). The patient was discharged on postoperative Day 6 with no complications. CONCLUSIONS: Laparoscopic anatomical liver resection of S8 has been demonstrated to be feasible. Under the guidance of laparoscopic ultrasonography, ICG positive staining was proven to be optimal for Anatomical segmentectomy.


Asunto(s)
Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Masculino , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Hepatectomía/métodos , Laparoscopía/métodos , Coloración y Etiquetado
2.
Future Oncol ; 19(15): 1029-1035, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37132469

RESUMEN

Advanced biliary tract cancer (BTC) has a poor prognosis, even after combined chemotherapy of gemcitabine and oxaliplatin (GEMOX). To investigate the efficacy and safety of GEMOX chemotherapy combining atezolizumab and bevacizumab in advanced BTC, the authors designed an open-label, single-arm, phase II clinical trial and will enroll patients with stage IV BTC. The participants will receive GEMOX chemotherapy combined with atezolizumab plus bevacizumab. The primary end point is objective response rate; the secondary end points are overall survival, disease control rate, progression-free survival, time to progression, duration of response and safety. The results of this trial are expected to provide novel, safe and effective treatment options for patients with advanced BTC, which could further improve their prognosis. Clinical Trial Registration: ChiCTR2100049830 (ChiCTR.org).


Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Humanos , Gemcitabina , Oxaliplatino/uso terapéutico , Cisplatino/uso terapéutico , Bevacizumab/efectos adversos , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
3.
Chaos ; 33(2): 023119, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36859226

RESUMEN

The theory of self-organized bistability (SOB) is the counterpart of self-organized criticality for systems tuning themselves to the edge of bistability of a discontinuous phase transition, rather than to the critical point of a continuous one. As far as we are concerned, there are currently few neural network models that display SOB or rather its non-conservative version, self-organized collective oscillations (SOCO). We show that by slightly modifying the firing function, a stochastic excitatory/inhibitory network model can display SOCO behaviors, thus providing some insights into how SOCO behaviors can be generated in neural network models.

4.
Chaos ; 33(9)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37656915

RESUMEN

Up to now, it still remains an open question about the relation between the structure of brain networks and their functions. The effects of structure on the dynamics of neural networks are usually investigated via extensive numerical simulations, while analytical analysis is always very difficult and thus rare. In this work, we explored the effects of a random regular graph on the dynamics of a neural network of stochastic spiking neurons, which has a bistable region when fully connected. We showed by numerical simulations that as the number of each neuron's neighbors decreases, the bistable region shrinks and eventually seems to disappear, and a critical-like transition appears. In the meantime, we made analytical analysis that explains numerical results. We hope this would give some insights into how structure affects the dynamics of neural networks from a theoretical perspective, rather than merely by numerical simulations.


Asunto(s)
Encéfalo , Redes Neurales de la Computación , Neuronas
5.
J Bone Miner Metab ; 40(3): 478-486, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35103840

RESUMEN

INTRODUCTION: To evaluate the relationship between the gut microbial composition and intestinal cholecalciferol absorption in patients with severe osteoporosis (SOP). MATERIALS AND METHODS: Eighteen patients with primary osteoporosis (OP) and 18 with SOP were included. Their clinical data were collected and their circulating concentrations of cholecalciferol and 25(OH)D3 were measured. Fecal samples were collected and their microbial contents were analyzed using 16S rDNA sequencing. RESULTS: The age, sex, body mass index, and body mass of the participants did not differ between the groups. The prevalence of gastrointestinal symptoms in the participants with SOP was significantly higher than that in the participants with OP. There were significant differences in the 25(OH)D3 and cholecalciferol concentrations between participants with SOP or OP and there was a significant positive correlation between the concentrations of these substance. The diversity of the gut microbiota in participants with SOP was significantly higher than that in participants with OP. Firmicutes was more abundant in the SOP group and the ratio of Firmicutes/Bacteroidetes in participants with SOP was higher. Conversely, Bifidobacterium was significantly less abundant, as were the order and family it belongs to. At the species level, Bifidobacterium was the most significant difference between the two groups. CONCLUSION: Differences in the intestinal microecology, especially Bifidobacterium, are associated with differences in the absorption of cholecalciferol and in the circulating 25(OH)D3 concentration, which may influence the progression of OP to SOP.


Asunto(s)
Microbioma Gastrointestinal , Osteoporosis , Colecalciferol , Heces , Humanos , Absorción Intestinal
6.
Hepatol Res ; 52(8): 721-729, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35536197

RESUMEN

AIM: Transarterial chemoembolization (TACE) combined with a PD-1 inhibitor and TACE combined with a PD-1 inhibitor and lenvatinib have recently been reported as promising treatments to improve the prognosis of hepatocellular carcinoma (HCC) patients. This study aims to compare the efficacy of these two treatments. METHODS: A retrospective study was conducted, and patients were recruited from two centers in China. Progression-free survival (PFS) and overall survival (OS) were compared, and the objective response rate (ORR) and disease control rate (DCR) were evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Treatment-related adverse events (AEs) were analyzed to assess safety. RESULTS: The median follow-up for the entire cohort was 11.4 months. Of the 103 patients included in this study, 56 received triple therapy, and 47 received doublet therapy. PFS was significantly higher in the triple therapy group than in the doublet therapy group (mPFS 22.5 vs. 14.0 months, P < 0.001). Similar results were obtained in terms of OS (P = 0.001). The ORR and DCR were also better in the triple therapy group (64.3% vs. 38.3%, P = 0.010; 85.7% vs. 57.4%, P = 0.002). The most common AEs in the triple therapy group were decreased albumin (55.3%), decreased platelet count (51.8%) and hypertension (44.6%). CONCLUSIONS: The combination of TACE with a PD-1 inhibitor and lenvatinib in patients with BCLC stage B HCC might result in significantly improved clinical outcomes with a manageable safety profile compared with TACE with a PD-1 inhibitor.

7.
Future Oncol ; 18(30): 3367-3375, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35968836

RESUMEN

The therapeutic effect of transcatheter arterial chemoembolization (TACE) is limited for patients with hepatocellular carcinoma (HCC). Herein, we designed an open-label, single-arm phase II clinical trial to investigate the efficacy and safety of TACE combined with atezolizumab plus bevacizumab for patients with Barcelona Clinic Liver Cancer (BCLC) stage-B HCC. Patients will initially receive TACE. Atezolizumab and bevacizumab will be initiated 2-14 days after the first TACE session. TACE will be repeated on demand. The primary endpoint is the objective response rate. The secondary end points include overall survival, disease control rate, progression-free survival, time-to-progression and safety. The study results will provide evidence for establishing a novel therapeutic regimen for patients with unresectable HCC. Clinical Trial Registration: ChiCTR2100049829 (ChiCTR.org).


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Bevacizumab/uso terapéutico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Ensayos Clínicos Fase II como Asunto , Neoplasias Hepáticas/terapia , Terapia Combinada/efectos adversos
8.
Chaos ; 32(10): 103116, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36319307

RESUMEN

A large amount of research has used the scale-free statistics of neuronal avalanches as a signature of the criticality of neural systems, which bears criticisms. For instance, the work of Touboul and Destexhe demonstrated that non-critical systems could also display such scale-free dynamics, which passed their rigorous statistical analyses. In this paper, we show that a fully connected stochastic neural network may also generate scale-free dynamics simply by jumping among many stable states.


Asunto(s)
Modelos Neurológicos , Neuronas , Potenciales de Acción/fisiología , Neuronas/fisiología , Redes Neurales de la Computación
9.
J Org Chem ; 86(16): 11220-11236, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-34288682

RESUMEN

Silverweed cinquefoil roots, as dietary supplements, foods, and medicines, are widely used in western areas of China, specifically in Tibet Autonomous Region and Gansu and Qinghai Provinces. In this paper, 10 new natural pentacyclic triterpenoid saponins (1-10), named poterinasides A-J, along with 14 known compounds (11-24) were isolated and purified from silverweed cinquefoil roots. The chemical structures of 1-10 were established by extensive analysis of 1D and 2D NMR data and mass spectrometric data. Poterinasides A (1), B (2), and G (7) with the unique position of substituents on the E ring had never been discovered in natural products before. Saponins 1-8, 14, and 22 displayed potent hepatoprotective activities, and 1-8, 10, 11, 14, 16, 19, and 22-24 showed outstanding anti-inflammatory effects. On the basis of the present results, some structure-activity relationships were summarized, in which 3α-OH, 19ß-CH3, 20α-CH3, 20ß-CH3, 21α-OH, and 30-OH groups in isolated pentacyclic triterpenoid saponins were found to strengthen the hepatoprotective and anti-inflammatory activities, respectively. Further, the following pharmacophore-based virtual screening and docking studies on special targets proteins, SIRT1 and COX-2, revealed roughly similar results with the structure-activity relationships, and this combination method was used for the first time for active natural compound screening.


Asunto(s)
Potentilla , Saponinas , Triterpenos , Antiinflamatorios/farmacología , Estructura Molecular , Raíces de Plantas , Saponinas/farmacología
10.
Clin Invest Med ; 44(3): E19-24, 2021 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-34600459

RESUMEN

PURPOSE: Incidence of contrast induced nephropathy (CIN) and related risk factors in patients with liver cancer and chronic kidney disease after trans-catheter arterial chemoembolization (TACE) is higher. The purpose of this study was to investigate the feasibility and safety of TACE therapy in such patients. METHODS: A retrospective analysis was performed on 103 patients with liver cancer and chronic kidney disease who underwent TACE treatments. TACE was performed according to Seldinger's technique of arterial embolization with minor modifications. Based on CIN diagnostic criteria, patients were divided into non-CIN (n=89) and CIN (n=14) groups. Multiple clinical parameters were assessed for the two groups after TACE. Serum creatinine levels were measured 48-72 h after TACE. RESULTS: Tumor size (>5 cm), TACE frequency, contrast agent dosage, solitary kidney, volume of iodized oil used in the TACE (ml) and urea levels were significantly higher in CIN group in comparison with the non-CIN group, while serum albumin and haemoglobin levels were significantly lower. Multivariate logistic regression analysis confirmed that the volume of iodized oil and TACE frequency were significantly positively correlated, and serum albumin level was negatively correlated in the CIN group. CONCLUSION: Volume of iodized oil, TACE frequency and low serum albumin levels were found to be independent risk factors for CIN after TACE. Thus, it is safe and feasible for hepatocellular carcinoma patients with chronic kidney disease to receive TACE treatment, but adverse events management after TACE needs to be addressed.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Insuficiencia Renal Crónica , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Medios de Contraste/efectos adversos , Humanos , Incidencia , Neoplasias Hepáticas/terapia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Factores de Riesgo
11.
BMC Med Educ ; 21(1): 194, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33823845

RESUMEN

BACKGROUND: We combined anatomy with imaging, transformed the 2D information of various imaging techniques into 3D information, and form the assessment system of real medical imaging cases in order to make up for the deficiencies in the current teaching of the medical imaging technology students. METHODS: A total of 460 medical imaging students were selected and randomly divided into two groups. The research group received the teaching of the fusion of the original CT and MR data 3D model and the original image combined with 3D anatomical image. CT and MRI data are imported through load DICOM of 3D slicer. Different tissues and organs are segmented by threshold and watershed algorithm of segment editor module. Models are exported through export / import models and label maps in segmentation. Save the NHDR file of the original data and Obj file of the corresponding model through save the NHDR and corresponding Obj files are loaded into probe 1.0 software. The software can give different colors to the three-dimensional models of different organs or tissues to display the stereo models and related data, and display the hook edges of organ models on coronal, sagittal and axial images. At the same time, annotation can be established in the corresponding anatomical position. Finally, it can be saved as a single file of Hwl, and the teaching can be opened at any time through the program of probe 1.0. Statistical analysis Academic self-efficacy scale and Self-directed learning ability scale was adopted by self-directed learning evaluation scale between two groups. RESULTS: Compare the theoretical scores and case analysis scores of the two groups. The scores of the study and control groups were significantly higher than those of the control group. Before the experiment, no significant difference was detected in the self-efficacy of learning ability and learning behavior between the two groups, while after the experiment, these differences between the two groups were statistically significan. Moreover, the learning ability self-efficacy and learning behavior of the two groups of students after the experiment was significantly higher than that before the experiment. The self-efficacy of the learning behavior of the control group was higher after the experiment than that before the experiment, albeit the difference was not statistically significant. CONCLUSIONS: The modern, information-based and humanized experimental teaching mode will be constantly improved under the support of PACS system in order to optimize the medical imaging teaching activities for the development of modern medical education.


Asunto(s)
Imagenología Tridimensional , Estudiantes de Medicina , Humanos , Aprendizaje , Imagen por Resonancia Magnética , Enseñanza , Tecnología
12.
BMC Cancer ; 20(1): 208, 2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32164623

RESUMEN

BACKGROUND: Inflammation-related parameters have been revealed to have prognostic value in multiple caners. However, the significance of some inflammation-related parameters, including the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and prognostic nutritional index (PNI), remains controversial in T1-2 rectal cancer (RC). METHODS: Clinical data of 154 T1-2 RC patients were retrospectively reviewed. The cut-off values for NLR, PLR, LMR, and PNI were determined by receiver operating characteristic curves. The relationships of these parameters with postoperative morbidities and prognosis were statistically analysed. RESULTS: The optimal cut-off values for preoperative NLR, PLR, LMR and PNI were 2.8, 140.0, 3.9, and 47.1, respectively. Significant but heterogeneous associations were found between NLR, PLR, LMR and PNI and clinicopathological factors. In addition, high NLR, high PLR, and low PNI were correlated with an increased postoperative morbidity rate. Patients with high NLR/PLR or low LMR/PNI had lower OS and DFS rates. On multivariate analysis, only high NLR was identified as an independent risk factor for poor DFS. CONCLUSIONS: NLR, PLR, and PNI are valuable factors for predicting postoperative complications in T1-2 RC patients. A preoperative NLR of more than 2.8 is an independent prognostic factor for poor DFS in T1-2 RC patients.


Asunto(s)
Monocitos/metabolismo , Neutrófilos/metabolismo , Neoplasias del Recto/sangre , Neoplasias del Recto/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Recuento de Plaquetas , Pronóstico , Curva ROC , Neoplasias del Recto/mortalidad , Estudios Retrospectivos
13.
Biomed Chromatogr ; 34(12): e4903, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32428305

RESUMEN

We present a simple and robust LC-MS/MS assay for the simultaneous quantitation of an antibody cocktail of trastuzumab and pertuzumab in monkey serum. The LC-MS/MS method saved costs, decreased the analysis time, and reduced quantitative times relative to the traditional ligand-binding assays. The serum samples were digested with trypsin at 50°C for 60 min after methanol precipitation, ammonium bicarbonate denaturation, dithiothreitol reduction, and iodoacetamide alkylation. The tryptic peptides were chromatographically separated using a C18 column (2.1 × 50 mm, 2.6 µm) with mobile phases of 0.1% formic acid in water and acetonitrile. The other monoclonal antibody, infliximab, was used as internal standards to minimize the variability during sample processing and detection. A unique peptide for each monoclonal antibody was simultaneously quantified using LC-MS/MS in the multiple reaction monitoring mode. Calibration curves were linear from 2.0 to 400 µg/mL. The intra- and inter-assay precision (%CV) was within 8.9 and 7.4% (except 10.4 and 15.1% for lower limit of quantitation), respectively, and the accuracy (%Dev) was within ±13.1%. The other validation parameters were evaluated, and all results met the acceptance criteria of the international guiding principles. Finally, the method was successfully applied to a pharmacokinetics study after a single-dose intravenous drip administration to cynomolgus monkeys.


Asunto(s)
Anticuerpos Monoclonales Humanizados/sangre , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Trastuzumab/sangre , Animales , Anticuerpos Monoclonales Humanizados/farmacocinética , Femenino , Modelos Lineales , Macaca fascicularis , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Trastuzumab/farmacocinética
14.
Ren Fail ; 41(1): 698-703, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31352865

RESUMEN

Background: Several studies have shown that non-renal factors such as corticosteroids may increase plasma cystatin C levels without affecting kidney function. However, the mechanisms underlying this are unclear. We hypothesized that corticosteroids may increase cystatin C levels in the plasma by promoting its production in tissues. In the present study, we aimed to test our hypothesis in rats by investigating the effect of corticosteroids on cystatin C production in tissues and the glomerular filtration rate (GFR), as measured by the gold standard method (i.e., inulin clearance). Results: Dexamethasone treatment was associated with much higher concentrations of cystatin C in all organ tissue homogenates tested. Dexamethasone increased plasma cystatin C levels in rats, without any decrease in renal inulin clearance. The impact of dexamethasone on plasma and organ tissue cystatin C levels was abolished by RU486, indicating the effect was glucocorticoid receptor-mediated. Conclusions: Our study provides direct evidence that corticosteroids may increase cystatin C levels in the plasma by promoting its production, without any decrease in GFR.


Asunto(s)
Corticoesteroides/farmacología , Cistatina C/sangre , Dexametasona/farmacología , Animales , Tasa de Filtración Glomerular/efectos de los fármacos , Inulina/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley
15.
Hepatology ; 65(1): 134-151, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27774607

RESUMEN

Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma. Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. We demonstrate an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas. In the subset of hepatocellular carcinoma patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting in impairment of respiratory metabolism, which sequentially led to depletion of α-ketoglutarate, stabilization of hypoxia inducible factor-α, and expression of target genes such as EPO. Cell lines and patient-derived xenograft models were used to demonstrate that EPO promoted cancer stem cell self-renewal and expansion in an autocrine/paracrine manner through enhanced Janus kinase/signal transducer and activator of transcription signaling both in vitro and in vivo. Furthermore, to explore the therapeutic targeting of EPO-induced tumor changes, we found that blocking EPO signaling with soluble EPO receptor extracellular domain Fc fusion protein could inhibit tumor growth both in vitro and in vivo. CONCLUSION: These findings suggest clinical and therapeutic implications for erythrocytosis in hepatocellular carcinoma. There is an underlying link between mitochondrial function and hypoxia inducible factor alpha signaling, revealing a mechanism of erythrocytosis in a subset of hepatocellular carcinoma patients who may benefit from treatment involving EPO signaling interference. (Hepatology 2017;65:134-151).


Asunto(s)
Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/genética , ADN Mitocondrial/genética , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/genética , Mutación , Síndromes Paraneoplásicos/etiología , Policitemia/etiología , Carcinoma Hepatocelular/fisiopatología , Hipoxia de la Célula , Femenino , Humanos , Neoplasias Hepáticas/fisiopatología , Masculino , Enfermedades Mitocondriales/genética , Policitemia/fisiopatología , Pronóstico
16.
Mediators Inflamm ; 2018: 5823823, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29706799

RESUMEN

Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words "pyro" and "ptosis" in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis.


Asunto(s)
Piroptosis/fisiología , Sepsis/patología , Animales , Humanos , Lipopolisacáridos/metabolismo , Insuficiencia Multiorgánica/metabolismo , Insuficiencia Multiorgánica/patología , Proteínas de Neoplasias/metabolismo , Sepsis/metabolismo
17.
Cell Physiol Biochem ; 44(1): 255-266, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29190611

RESUMEN

BACKGROUND/AIMS: The tripartite motif containing (TRIM) family plays crucial roles in tumor development and progression. However, little is known about the function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). METHODS: The expression levels of TRIM11 were examined by real-time PCR, Western blot and Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by lentivirus infection, and functional assays, such as MTT, colony formation assay, migration and invasion assays and a xenograft tumor model were used to investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on p53 signaling and its downstream molecules. RESULTS: We found that TRIM11 mRNA and protein levels were significantly increased in HCC tissues as compared with normal tissues; increased levels correlated with poor patient survival. By loss- and gain-of-function investigations, knockdown of TRIM11 suppressed cell proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover, TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. CONCLUSIONS: These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating p53 both in vitro and in vivo. Our data provide new insights into the pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic target for HCC treatment.


Asunto(s)
Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Regulación hacia Arriba , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Movimiento Celular , Proliferación Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación hacia Abajo , Transición Epitelial-Mesenquimal , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Trasplante Heterólogo , Proteínas de Motivos Tripartitos/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/genética , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores
18.
Mediators Inflamm ; 2017: 4024672, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28210072

RESUMEN

Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo-/- mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25- T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo-/- mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-ß (TGF-ßm+), and the secretion of inhibitory cytokines [including TGF-ß and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo-/- septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression.


Asunto(s)
Ácido Ascórbico/uso terapéutico , Insuficiencia Multiorgánica/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Animales , Linfocitos T CD4-Positivos/metabolismo , Antígeno CTLA-4/metabolismo , Factores de Transcripción Forkhead/metabolismo , Terapia de Inmunosupresión , Interleucina-10/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , L-Gulonolactona Oxidasa/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Insuficiencia Multiorgánica/inmunología , Insuficiencia Multiorgánica/metabolismo , Sepsis/inmunología , Sepsis/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
19.
Clin Lab ; 62(1-2): 203-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27012051

RESUMEN

BACKGROUND: Human cystatin C is a single non-glycosylated polypeptide chain consisting of 120 amino acid residues. Its concentration in the circulation is mainly determined by glomerular filtration rate. However, non-renal factors, i.e., drugs, may dramatically affect its levels in the circulation. The aim of this study was to evaluate the effect of corticosteroid treatment on serum cystatin C concentration in patients with symptomatic heart failure. METHODS: Fifty-six symptomatic heart failure patients were treated with prednisone. Concentrations of serum cystatin C and serum creatinine were recorded at baseline, and after about 2 weeks of treatment. Twenty-four hour urinary creatinine was also measured to directly calculate glomerular filtration rate. RESULTS: Prednisone treatment significantly increased serum cystatin C concentration from 1.24 +/- 0.40 mg/L at baseline to 1.61 +/- 0.80 mg/L at the end of study (p < 0.05). However, the elevation in serum cystatin C concentration was not associated with renal function impairment. Prednisone not only significantly decreased serum creatinine concentrations from 89.66 +/- 28.63 pmol/L at baseline to 76.55 +/- 20.80 micromol/L after prednisone treatment (p < 0.05), but also significantly increased fractional excretion of sodium and urine flow rate. The data also showed there was a slight and but nonstatistically significant increase in glomerular filtration rate in such patients after prednisone treatment. CONCLUSIONS: Important non-renal factors, such as corticosteroids, can influence cystatin C concentration. Thus, it needs to be considered when interpreting cystatin C values in patients with heart failure receiving corticosteroid therapy.


Asunto(s)
Corticoesteroides/uso terapéutico , Cistatina C/sangre , Insuficiencia Cardíaca/tratamiento farmacológico , Riñón/efectos de los fármacos , Prednisona/uso terapéutico , Adulto , Anciano , Biomarcadores/sangre , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Natriuresis/efectos de los fármacos , Sodio/sangre , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Urodinámica/efectos de los fármacos
20.
Can J Physiol Pharmacol ; 94(7): 797-800, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27144905

RESUMEN

Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.


Asunto(s)
Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/orina , Tasa de Depuración Metabólica/efectos de los fármacos , Prednisona/uso terapéutico , Ácido Úrico/sangre , Ácido Úrico/orina , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Masculino , Tasa de Depuración Metabólica/fisiología , Persona de Mediana Edad , Prednisona/farmacología
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