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1.
Cancer Genomics Proteomics ; 21(3): 305-315, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38670589

RESUMEN

BACKGROUND/AIM: Glutathione peroxidases (GPXs) are crucial antioxidant enzymes, counteracting reactive oxygen species (ROS). GPX overexpression promotes proliferation and invasion in cancer cells. Glutathione peroxidase-1 (GPX1), the most abundant isoform, contributes to invasion, migration, cisplatin resistance, and proliferation in various cancers. Nuclear factor-kappa B (NF-[Formula: see text]B) participates in cell proliferation, apoptosis, and tumor progression. The inhibition of NF-[Formula: see text]B expression reduces the malignancy of esophageal squamous cell carcinoma. This study aimed to explore the GPX1 and NF-[Formula: see text]B signaling pathways and their correlation with gastric cancer cell proliferation and invasion. MATERIALS AND METHODS: Cell culture, complementary DNA microarray analysis, western blotting, reverse transcription-polymerase chain reaction, zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, GPX1 knock-down with short hairpin RNA (shRNA), standard two-chamber invasion assay, chromatin immunoprecipitation assay. RESULTS: Hepatocyte growth factor (HGF) up-regulated GPX1 expression in gastric cancer cells. The NF-[Formula: see text]B inhibitor, pyrrolidine dithiocarbamate down-regulated HGF-induced GPX1 protein levels. Furthermore, NF-[Formula: see text]B and urokinase-type plasminogen activators were down-regulated in GPX1-shRNA-treated cells. Treatment with an Akt pathway inhibitor (LY294002) led to the down-regulation of GPX1 and NF-[Formula: see text]B gastric cancer cells. GPX1 knockdown resulted in decreased HGF-mediated in vitro cell proliferation and invasion. The study identified the putative binding site of the GPX1 promoter containing the NF-[Formula: see text]B binding site, confirmed through chromatin immunoprecipitation. CONCLUSION: HGF induced GPX1 expression through the NF-[Formula: see text]B and Akt pathways, suggesting a central role in gastric cell proliferation and invasion. Hence, GPX1 emerges as a potential therapeutic target for gastric cancer.


Asunto(s)
Proliferación Celular , Glutatión Peroxidasa GPX1 , Glutatión Peroxidasa , FN-kappa B , Invasividad Neoplásica , Transducción de Señal , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , FN-kappa B/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Movimiento Celular
2.
Anticancer Res ; 44(5): 1973-1981, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38677740

RESUMEN

BACKGROUND/AIM: A role for cold-shock domain (CSD) proteins in abnormal cell proliferation has been suggested in the literature. The aim of this study was to investigate the effect of hepatocyte growth factor (HGF)-induced up-regulation of CSD protein A (CSDA) expression on vascular endothelial growth factor (VEGF) expression and its role in gastric cancer cell invasion and proliferation. MATERIALS AND METHODS: We assessed effects on two gastric cancer cell lines using reverse transcription-polymerase chain reaction, western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and CSDA knockdown with short hairpin RNA. RESULTS: Hepatocyte growth factor (HGF) elevates CSDA levels in gastric cancer cell lines. To elucidate the mechanism by which HGF prompts CSDA expression and its impact on vascular endothelial growth factor (VEGF), we applied the Mitogen Activated Protein Kinase (MAPK) inhibitor PD098059 and conducted analyses using western blot. Following the administration of PD098059, a reduction in the protein levels of HGF-stimulated VEGF was observed. Additionally, silencing of CSDA resulted in diminished levels of both VEGF and phosphorylated extracellular signal-regulated kinase (ERK). The suppression of CSDA also led to reduced HGF-induced cell proliferation and diminished invasive capabilities in vitro. Furthermore, our research pinpointed a potential activator protein-1 (AP-1) binding site within the VEGF promoter zone, validating its activity via chromatin immunoprecipitation assays. Electrophoretic mobility shift assays further disclosed that HGF-induced CSDA augmentation correlates with an increase in AP-1 binding to VEGF. CONCLUSION: CSDA is crucial for the proliferation of gastric cancer cells, and the inhibition of this protein could impede the advancement of gastric cancer.


Asunto(s)
Proliferación Celular , Factor de Crecimiento de Hepatocito , Proteínas Inhibidoras de Proteinasas Secretoras , Neoplasias Gástricas , Factor A de Crecimiento Endotelial Vascular , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Factor de Crecimiento de Hepatocito/metabolismo , Factor de Crecimiento de Hepatocito/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Metástasis de la Neoplasia , Movimiento Celular/efectos de los fármacos , Invasividad Neoplásica
3.
Transplant Proc ; 56(3): 565-572, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38413306

RESUMEN

BACKGROUND: Normal saline is still used in patients undergoing living donor liver transplantation (LDLT) with normonatremia. We investigated whether the normal saline administered during LDLT is associated with the increased risk of acute kidney injury (AKI) compared with the balanced crystalloids. METHODS: We reviewed 1011 cases undergoing LDLT. The primary exposure variable was normal saline administered intraoperatively compared with the balanced crystalloid. To compare the risk of AKI after adjusting for potential confounders of baseline characteristics and surgical parameters, a propensity score matching analysis was performed. As a sensitivity analysis, ordinal logistic regression analysis was performed for AKI using inverse probability of treatment weighting (IPTW). RESULTS: The incidence of AKI was significantly higher in the saline group (n = 88/174, 50.6%) than in the balanced group (n = 67/174, 38.5%) after matching (P = .010). The incidence of stage 2 or 3 AKI was also significantly higher in the saline group (n = 26/174, 14.9%) than in the balanced group (n = 43/174, 24.7%) after matching (P = .022). The length of hospital stay was significantly longer in the saline group than in the balanced group after matching. Ordinal logistic regression analysis using IPTW showed that the saline group showed a significant association of saline administration with the risk of AKI (odds ratio 1.23, 95% CI 1.05-1.28, P = .013). CONCLUSION: Our propensity score analysis using propensity score matching and IPTW showed that normal saline administration during LDLT is associated with a high risk of postoperative AKI and longer hospital stays. However, our results should be interpreted carefully due to the relatively long period of data collection.


Asunto(s)
Lesión Renal Aguda , Trasplante de Hígado , Solución Salina , Humanos , Trasplante de Hígado/efectos adversos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Solución Salina/administración & dosificación , Adulto , Estudios Retrospectivos , Puntaje de Propensión , Donadores Vivos , Incidencia , Cuidados Intraoperatorios , Tiempo de Internación , Factores de Riesgo
5.
Sci Rep ; 13(1): 19947, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37968287

RESUMEN

Although pulmonary artery catheter (PAC) has been used during liver transplantation surgery, the usefulness of PAC has rarely been investigated. We evaluated whether the use of PAC is associated with better clinical outcomes compared to arterial waveform-based monitoring after liver transplantation. A total of 1565 cases undergoing liver transplantation were reviewed. We determined whether patients received PAC or not and divided our cohort into the PAC with hemodynamic monitoring using PAC and the non-PAC with arterial waveform-based monitoring using FloTrac-Vigileo. Propensity score matching was performed. Acute kidney injury (AKI), early allograft dysfunction (EAD) and 1-year all-cause mortality or graft failure were compared in the matched cohorts. Logistic regression analysis was performed in the inverse probability of treatment-weighted (IPTW) cohort for postoperative EAD and AKI, respectively. Five-year overall survival was compared between the two groups. In the matched cohort, there was no significant difference in the incidence of AKI, EAD, length of hospital or ICU stay, and 1-year all-cause mortality between the groups. In the IPTW cohort, the use of PAC was not a significant predictor for AKI or EAD (AKI: odds ratio (95% confidence interval) of 1.20 (0.47-1.56), p = 0.229; EAD: 0.99 (0.38-1.14), p = 0.323). There was no significant difference in the survival between groups after propensity score matching (Log-rank test p = 0.578). In conclusion, posttransplant clinical outcomes were not significantly different between the groups with and without PAC. Anesthetic management without the use of PAC may be possible in low-risk patients during liver transplantation. The risk should be carefully assessed by considering MELD scores, ischemic time, surgical history, previous treatment of underlying liver disease, and degree of portal and pulmonary hypertension.Registration: https://clinicaltrials.gov/ct2/show/NCT05457114 (registration date: July 15, 2022).


Asunto(s)
Lesión Renal Aguda , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Arteria Pulmonar , Estudios Retrospectivos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Catéteres
6.
Br J Anaesth ; 131(5): 955-965, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37679285

RESUMEN

BACKGROUND: Individualised positive end-expiratory pressure (PEEP) improves respiratory mechanics. However, whether PEEP reduces postoperative pulmonary complications (PPCs) remains unclear. We investigated whether driving pressure-guided PEEP reduces PPCs after laparoscopic/robotic abdominal surgery. METHODS: This single-centre, randomised controlled trial enrolled patients at risk for PPCs undergoing laparoscopic or robotic lower abdominal surgery. The individualised group received driving pressure-guided PEEP, whereas the comparator group received 5 cm H2O fixed PEEP during surgery. Both groups received a tidal volume of 8 ml kg-1 ideal body weight. The primary outcome analysed per protocol was a composite of pulmonary complications (defined by pre-specified clinical and radiological criteria) within 7 postoperative days after surgery. RESULTS: Some 384 patients (median age: 67 yr [inter-quartile range: 61-73]; 66 [18%] female) were randomised. Mean (standard deviation) PEEP in patients randomised to individualised PEEP (n=178) was 13.6 cm H2O (2.1). Individualised PEEP resulted in lower mean driving pressures (14.7 cm H2O [2.6]), compared with 185 patients randomised to standard PEEP (18.4 cm H2O [3.2]; mean difference: -3.7 cm H2O [95% confidence interval (CI): -4.3 to -3.1 cm H2O]; P<0.001). There was no difference in the incidence of pulmonary complications between individualised (25/178 [14.0%]) vs standard PEEP (36/185 [19.5%]; risk ratio [95% CI], 0.72 [0.45-1.15]; P=0.215). Pulmonary complications as a result of desaturation were less frequent in patients randomised to individualised PEEP (8/178 [4.5%], compared with standard PEEP (30/185 [16.2%], risk ratio [95% CI], 0.28 [0.13-0.59]; P=0.001). CONCLUSIONS: Driving pressure-guided PEEP did not decrease the incidence of pulmonary complications within 7 days of laparoscopic or robotic lower abdominal surgery, although uncertainty remains given the lower than anticipated event rate for the primary outcome. CLINICAL TRIAL REGISTRATION: KCT0004888 (http://cris.nih.go.kr, registration date: April 6, 2020).


Asunto(s)
Laparoscopía , Procedimientos Quirúrgicos Robotizados , Humanos , Femenino , Anciano , Masculino , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Pulmón , Respiración con Presión Positiva/métodos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Volumen de Ventilación Pulmonar
7.
Sci Rep ; 13(1): 8643, 2023 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-37244919

RESUMEN

Early allograft dysfunction (EAD) and acute kidney injury (AKI) are common and clinically important complications after liver transplantation. Serum lactate level at the end of surgery could predict EAD and neutrophil gelatinase-associated lipocalin (NGAL) is known as a biomarker for AKI after liver transplantation. The authors investigated whether the combination of these two laboratory tests could be used as an early predictor of these two complications of EAD and AKI. We reviewed cases undergoing living donor liver transplantation (n = 353). Lactate-adjusted NGAL level, a combination of these two predictors, was calculated as the sum of each value multiplied by the odds ratio for EAD or AKI. We evaluated whether this combined predictor at the end of surgery is significantly associated with both postoperative AKI or EAD. We compared the area under the receiver operating characteristic curve (AUC) between our multivariable regression models with and without NGAL, lactate, or lactate-adjusted NGAL. NGAL, lactate and lactate-adjusted NGAL are significant predictors for EAD and AKI. The regression model for EAD or AKI including lactate-adjusted NGAL showed a greater AUC (for EAD: odds ratio [OR] 0.88, 95% confidence interval [CI] 0.84-0.91; for AKI: OR 0.89, 95% CI 0.85-0.92) compared to the AUC of the models including lactate (for EAD: OR 0.84, 95% CI 0.81-0.88; for AKI: OR 0.79, 95% CI 0.74-0.83) or NGAL alone (for EAD: OR 0.82, 95% CI 0.77-0.86; for AKI: OR 0.84, 95% CI 0.80-0.88) or the model without lactate or NGAL (for EAD: OR 0.64, 95% CI 0.58-0.69, for AKI: OR 0.75, 95% CI 0.70-0.79). In conclusion, lactate-adjusted NGAL level at the end of surgery could be a reliable combined laboratory predictor for postoperative EAD or AKI after liver transplantation with a greater discriminative ability than lactate or NGAL alone.


Asunto(s)
Lesión Renal Aguda , Trasplante de Hígado , Humanos , Lipocalina 2 , Trasplante de Hígado/efectos adversos , Proteínas Proto-Oncogénicas , Lipocalinas , Proteínas de Fase Aguda , Donadores Vivos , Biomarcadores , Ácido Láctico , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Aloinjertos , Valor Predictivo de las Pruebas
8.
Sci Rep ; 12(1): 20606, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36446941

RESUMEN

Thoracic epidural analgesia (TEA) and transversus abdominis plane (TAP) block are used for pain control after abdominal surgery. Although there have been several meta-analyses comparing these two techniques, the conclusion was limited by a small number of studies and heterogeneity among studies. Our meta-analysis used the Medline, EMBASE, and Cochrane central library databases from their inception through September 2022. Randomized controlled trials (RCTs) comparing TEA and TAP block were included. The pre-specified primary outcome was the pain score at rest at 12 h postoperatively. Twenty-two RCTs involving 1975 patients were included. Pooled analyses showed the pain score at rest at 12 h postoperatively was significantly different between groups favoring TEA group (Mean difference [MD] 0.58, 95% confidence interval CI - 0.01, 1.15, P = 0.04, I2 = 94%). TEA group significantly reduced the pain score at 48 h at rest (MD 0.59, 95% CI 0.15, 1.03, P = 0.009, I2 = 86%) and at 48 h at movement (MD 0.53, 95% CI 0.07, 0.99, P = 0.03, I2 = 76%). However, there was no significant difference at other time points. Time to ambulation was shorter in TAP block but the incidence of hypotension at 24 h and 72 h was significantly lower in TAP block compared to TEA. Trial sequential analysis showed that the required information size has not yet been reached. Our meta-analysis demonstrated there was no significant or clinically meaningful difference in the postoperative pain scores between TEA and TAP block group. Given the insufficient information size revealed by TSA, the high risk of bias of our included studies, and the significant heterogeneity of our meta-analysis results, our results should be interpreted carefully but it is not likely that the addition of further studies could prove any clinically meaningful difference in pain score between these two techniques.


Asunto(s)
Analgesia Epidural , Anestesia Epidural , Bloqueo Nervioso , Humanos , Analgesia Controlada por el Paciente , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología
9.
Life (Basel) ; 12(7)2022 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-35888049

RESUMEN

Many chronic stroke patients suffer from worsened hand function, and functional recovery of the hand does not occur well after six months of stroke. Therefore, predicting final hand function after stroke through acute phase imaging would be an important issue in counseling with the patients or their family. Thus, we investigated the remaining white matter integrity in the corticospinal tract (CST) and cortico-ponto-cerebellar tract (CPCT) at the acute stage of stroke and chronic hand function after stroke, and present the cut-off value of fiber number (FN) and fractional anisotropy (FA) of CST and CPCT at the acute stage for predicting final hand function after the recovery period. This retrospective case-control study included 18 stroke patients who were classified into two groups: poor hand function with stroke (n = 11) and good hand function with stroke (n = 7). DTI was done within two months ± 15 days after onset, and the Jebson's Hand Function test was conducted 6-12 months after onset. The investigation of white matter was focused on the values of FN and FA for CST and CPCT, which were measured separately. The normalized (affected/non-affected) FA and FN values in the CPCT in the good hand function group were higher than those in the poor hand function group. The normalized FN and FA values in the CST were not significantly different between the poor hand function group and the good hand function group. The normalized cut-off value that distinguished the good hand function group from the poor hand function group was 0.8889 for FA in the CPCT. The integrity of the CPCT in the acute stage was associated with hand function in the chronic stage after a stroke. Ultimately, the integrity of the CPCT in the early stage after onset can be used to predict chronic hand function. Based on these results, cerebellar afferent fiber measurements may be a useful addition to predict hand function and plan specific rehabilitation strategies in stroke patients.

10.
J Infect Chemother ; 28(10): 1415-1418, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35810104

RESUMEN

Cytomegalovirus (CMV) is a major infectious agent causing severe complications in allogeneic hematopoietic cell transplantation (HCT) recipients, thereby warranting the need for aggressive preemptive or targeted antiviral therapy. However, prolonged or repeated use of antiviral agents, such as ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), can result in drug-resistant CMV infection, posing challenges to successful outcomes. Here, we report a case of a patient with acute myeloid leukemia and drug-resistant CMV infection who presented with persistent CMV DNAemia, colitis, pneumonia, and encephalitis. An intra-host diversity of UL97 and UL54 mutations were detected through the genotypic resistance testing conducted on two blood samples (D+199 and D+224) and a cerebrospinal fluid (CSF) specimen (D+260) collected from the patient. UL97 L595W/L595F and L595W mutations were detected in the blood and CSF samples, respectively, that conferred GCV resistance. UL54 F412L mutation detected in all three samples conferred GCV/CDV resistance. However, the V787L mutation of UL54, conferring GCV/FOS resistance, was observed only in the D+224 blood sample. Despite combination therapy with FOS and high dose GCV and adjunctive therapy with leflunomide, the patient died from CMV infection and multiple organ failure on D+279. Further data on resistant mutations and intra-host diversity of CMV should be accumulated to elucidate the antiviral resistance and related outcomes.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Antivirales/farmacología , Antivirales/uso terapéutico , Cidofovir/uso terapéutico , Citomegalovirus/genética , Infecciones por Citomegalovirus/tratamiento farmacológico , Farmacorresistencia Viral/genética , Foscarnet/uso terapéutico , Ganciclovir/farmacología , Ganciclovir/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Mutación , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/uso terapéutico
11.
Am J Transl Res ; 14(3): 1507-1517, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35422931

RESUMEN

OBJECTIVE: Human cervical cancer oncogene (HCCR)-1, previously identified in cervical cancer and its cell lines, has been reported to play an important role in tumor progression in several cancers as a suppressor of apoptosis. However, the role of HCCR-1 in the tumorigenesis of stomach cancer has not been identified. This study examined the role of HCCR-1 as a suppressor of apoptosis during tumorigenesis in gastric cancer, along with its possible regulatory pathway. METHODS: We employed several techniques including western blotting, semiquantitative reverse transcription polymerase chain reaction, diphenyltetrazolium bromide assay, chromatin immunoprecipitation assay, fluorescence-activated cell sorting, and HCCR-1 knockdown with short hairpin RNA to elucidate the role of HCCR-1. RESULTS: We observed that hepatocyte growth factor (HGF) upregulated HCCR-1 expression. In addition, the expression levels of ß-catenin, T cell factor-1 (TCF1), and B-cell lymphoma 2 (bcl2) were increased, whereas that of tumor protein 53 (p53) was decreased following HGF treatment. HCCR-1 knockdown in NUGC-3 and MKN-28 cells decreased the expression of TCF1 and phosphorylated ß-catenin and increased the binding activity on the binding site of the HCCR-1 promoter. This identifies the possible involvement of the Wnt/ß-catenin pathway in HGF-induced HCCR-1 regulation. We also confirmed the role of HCCR-1 in HGF-induced anti-apoptotic activity. p53 protein expression was increased, whereas that of bcl2 was decreased with HGF treatment in HCCR-1 knockdown cells, while the apoptotic activity was increased. CONCLUSION: Our study suggests the anti-apoptotic activity of HGF-induced HCCR-1 expression and that HGF may regulate HCCR-1 via TCF1/ß-catenin in stomach cancer.

12.
Support Care Cancer ; 30(7): 6103-6112, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35420330

RESUMEN

PURPOSE: This study aimed to investigate the clinical efficacy of tapentadol extended-release (ER) on pain control and the quality of life (QoL) of patients with moderate to severe chronic cancer pain in clinical practice in Korea. METHODS: In this prospective, open-label, multicenter trial, patients with sustained cancer pain as well as chronic pain, who were or were not using other analgesics were enrolled. Thirteen centers recorded a total of 752 patients during the 6-month observation period, based on the tapentadol ER dose and tolerability, prior and concomitant analgesic treatment, pain intensity, type of pain, adverse effects, and clinical global impression change (CGI-C). Of those 752 patients, 688 were enrolled, and 650 completed the study for efficacy and adverse drug reactions; among them, 349 were cancer patients. RESULTS: Tapentadol ER significantly reduced the mean pain intensity including neuropathic pain during the observation period by 2.9 points (from a mean 7 ± 0.87 to 4.1 ± 2.02). Furthermore, QoL was observed to be significantly improved based on the CGI-C, an objective measure. CONCLUSION: This study showed that tapentadol ER was effective for treating patients with moderate to severe cancer pain and neuropathic pain, and therefore it significantly improved the patients' QoL.


Asunto(s)
Dolor en Cáncer , Dolor Crónico , Neoplasias , Neuralgia , Analgésicos/uso terapéutico , Analgésicos Opioides/uso terapéutico , Dolor en Cáncer/inducido químicamente , Dolor en Cáncer/etiología , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/etiología , Preparaciones de Acción Retardada/uso terapéutico , Humanos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Fenoles/uso terapéutico , Estudios Prospectivos , Calidad de Vida , Tapentadol/uso terapéutico , Resultado del Tratamiento
13.
Nat Commun ; 13(1): 497, 2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-35079017

RESUMEN

Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Although ectopic expression in model organisms suggests that morphogen gradients form through diffusion, little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis due to the combined difficulties of measuring endogenous morphogen levels and observing development in utero. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells, during specification of germ layers. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a paradigm for tissue patterning by an activator-inhibitor pair.


Asunto(s)
Blastocisto/metabolismo , Gástrula/metabolismo , Gastrulación/genética , Células Madre Embrionarias Humanas/metabolismo , Proteína Nodal/genética , Blastocisto/citología , Línea Celular , Difusión , Técnica del Anticuerpo Fluorescente/métodos , Gástrula/citología , Regulación del Desarrollo de la Expresión Génica , Técnicas de Inactivación de Genes , Células Madre Embrionarias Humanas/citología , Humanos , Hibridación Fluorescente in Situ/métodos , Factores de Determinación Derecha-Izquierda/genética , Factores de Determinación Derecha-Izquierda/metabolismo , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos , Proteína Nodal/metabolismo
14.
Anticancer Res ; 42(1): 519-530, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34969762

RESUMEN

BACKGROUND/AIM: The 14-3-3 protein family has a variety of functions in cellular responses in different organisms, including cell-cycle regulation, apoptosis, and malignant transformation. 14-3-3 Sigma protein (14-3-3σ) induces G2 arrest, which enables repair of damaged DNA. The purpose of this study was to identify the role of 14-3-3σ up-regulation by hepatocyte growth factor (HGF) in cancer cell proliferation and invasion in gastric cancer. MATERIALS AND METHODS: In this study, cell culture, western blotting, real-time polymerase chain reaction, zymography, 14-3-3σ knock-down using short hairpin RNA (shRNA), electrophoresis mobility-shift assay, chromatin immunoprecipitation assay and standard two-chamber invasion assay were applied. RESULTS: Firstly, we confirmed that the expression of 14-3-3σ in gastric cancer cells was up-regulated by HGF. To identify how HGF-induced 14-3-3σ expression affects matrix metalloproteinase-1 (MMP1) expression, the cells were treated with the mitogen-activated protein kinase kinase inhibitor PD098059 and analyzed using western blotting. The HGF-mediated expression of MMP1 protein decreased in the presence of PD098059. The role of 14-3-3σ in MMP1 expression was determined through 14-3-3σ knockdown using shRNA. 14-3-3σ-shRNA cells showed reduced levels of MMP1, phosphorylated extracellular signal-regulated kinase, and pp38. HGF-mediated cell proliferation and in vitro invasion were reduced in 14-3-3σ knockdown cells. Serum 14-3-3σ levels were also significantly reduced following gastrectomy in patients with stage II or stage III gastric cancer (p<0.05). CONCLUSION: These results suggest that 14-3-3σ plays an important role in cell proliferation and metastasis in gastric cancer, and 14-3-3σ may be a novel target for detection and prevention of progression of gastric cancer. In addition, the serum 14-3-3σ level is associated with treatment status in patients with locally advanced gastric cancer.


Asunto(s)
Proteínas 14-3-3/genética , Exorribonucleasas/genética , Factor de Crecimiento de Hepatocito/genética , Metaloproteinasa 1 de la Matriz/genética , Neoplasias Gástricas/genética , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Transducción de Señal , Neoplasias Gástricas/patología
15.
Brain Neurorehabil ; 14(3): e26, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36741223

RESUMEN

The direct-acting oral anticoagulants (DOACs) would be the standard treatment for the prevention of stroke and thromboembolism in nonvalvular atrial fibrillation patients. The adverse effects of greatest concern are bleeding especially major bleeding. We present a case of a patient with a history of nonvalvular atrial fibrillation and pacemaker, who developed severe anemia after massive hemoptysis while taking DOAC; however, he has continued taking DOAC. Through this case, we have summarized the current management of major bleeding associated with anticoagulation and discuss the optimal regimen for restarting of anticoagulation therapy.

16.
Can J Anaesth ; 67(7): 810-816, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32314262

RESUMEN

BACKGROUND: Patients with symptomatic gallbladder diseases exhibit delayed gastric emptying. We evaluated the residual gastric content in fasted patients scheduled for elective laparoscopic cholecystectomy because of symptomatic gallbladder disease using ultrasonography. METHODS: This prospective observational single-cohort study was approved by the Institutional Review Board, and written informed consent was obtained from all included patients. Before anesthesia induction, the gastric antrum was examined by ultrasound. Once the presence of solid content was excluded, the patients were classified using a three-point grading system (grade 0: no fluid; grade 1: fluid in the right lateral decubitus position; grade 2: fluid in both the supine and right lateral decubitus positions), and the fluid volume was measured. A stomach was considered empty if it had no contents or ≤ 1.5 mL·kg-1 of fluid, and was considered full if solid content or > 1.5 mL·kg-1 of fluid was detected. RESULTS: Among 138 patients, 18 patients (13%) presented with a full stomach, 12 (9%) of whom had solid content, and six (4%) of whom had >1.5 mL·kg-1 of fluid in their stomach. Among the remaining 120 patients with an empty stomach, 65 patients presented with a grade 0 antrum, and 55 patients with a grade 1 or 2 antrum with ≤ 1.5 mL·kg-1 of fluid. CONCLUSION: The gastric ultrasound assessment revealed that 13% of patients scheduled for elective cholecystectomy because of symptomatic gallbladder disease had a full stomach despite following the fasting guidelines. This was higher than the reported incidence of a full stomach among the general surgical population. Further studies are required to delineate the clinical implications of our findings. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03259841); registered 4 August, 2017.


RéSUMé: CONTEXTE: Les patients atteints de maladies vésiculaires symptomatiques souffrent de retard de la vidange gastrique. Nous avons évalué par échographie le contenu gastrique résiduel chez des patients à jeun devant subir une cholécystectomie non urgente par laparoscopie en raison de maladie vésiculaire symptomatique. MéTHODE: Cette étude prospective observationnelle sur une cohorte unique a été approuvée par le Comité d'éthique indépendant et le consentement éclairé écrit a été obtenu de tous les patients inclus. Avant l'induction de l'anesthésie, l'antre gastrique a été examiné par échographie. Une fois la présence de solides exclue, les patients ont été catégorisés selon un système de notation de 3 grades (0 : aucun liquide; 1 : liquides détectés en position de décubitus latéral droit; 2 : liquides détectés en décubitus dorsal et en décubitus latéral droit), et le volume liquidien a été mesuré. Un estomac était considéré comme vide s'il n'avait aucun contenu solide et ≤ 1,5 mL·kg−1 de liquides, et considéré comme plein si du contenu solide ou > 1,5 mL·kg−1 de liquides était détecté. RéSULTATS: Parmi 138 patients, 18 (13 %) se sont présentés avec un estomac plein, parmi lesquels 12 (9 %) avaient du contenu solide, et six (4 %) avaient > 1,5 mL·kg−1 de liquides dans l'estomac. Parmi les 120 patients restants avec un estomac vide, 65 présentaient un antre gastrique de grade 0 et 55 présentaient un antre de grade 1 ou 2 avec ≤ 1,5 mL·kg−1 de liquides. CONCLUSION: L'évaluation gastrique par échographie a révélé que 13 % des patients devant subir une cholécystectomie non urgente en raison de maladie vésiculaire symptomatique avaient un estomac plein tout en ayant respecté les directives de jeûne. Ce chiffre était plus élevé que l'incidence rapportée d'estomac plein parmi la population chirurgicale générale. Des études supplémentaires sont nécessaires pour déterminer les implications cliniques de nos résultats. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03259841); enregistrée le 4 août 2017.


Asunto(s)
Colecistectomía Laparoscópica , Ayuno , Humanos , Estudios Prospectivos , Antro Pilórico/diagnóstico por imagen , Ultrasonografía
17.
Microbiol Resour Announc ; 8(28)2019 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-31296687

RESUMEN

Here, we report the complete genome sequence of Kocuria indica CE7, isolated from human skin. This strain possesses a 2,809-kbp chromosome and a 32-kbp plasmid with 2,507 coding sequences. In particular, the genome contains multiple genes potentially involved in adaptations in pH homeostasis and salt tolerance.

18.
Nat Commun ; 10(1): 851, 2019 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-30787285

RESUMEN

The manipulation of the transition states of a chemical process is essential to achieve the desired selectivity. In particular, transition states of chemical reactions can be significantly modified in a confined environment. We report a catalytic reaction with remarkable amplification of stereochemical information in a confined water cage. Surprisingly, this amplification is significantly dependent on droplet size. This water-induced chirality amplification stems from the hydrophobic hydration effects, which ensures high proximity of the catalyst and substrates presumably at the transition state, leading to higher enantioselectivity. Flow and batch reactors were evaluated to confirm the generality of this water-induced chirality amplification. Our observation on efficient chiral induction in confined water cages might lead to an understanding of the chirality amplification in the prebiotic era, which is a key feature for the chemical evolution of homochirality.

19.
Acta Anaesthesiol Scand ; 62(10): 1374-1382, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29992550

RESUMEN

BACKGROUND: The objective of this retrospective study was to determine the risk factors for acute kidney injury (AKI), including albumin, in children who underwent cardiac surgery. In addition, we evaluated the association between preoperative serum albumin level and postoperative AKI in these patients. METHODS: This retrospective study included 505 pediatric patients who underwent congenital cardiac surgery. Preoperative and perioperative risk factors for AKI, including serum albumin level, were assessed. AKI incidence within 7 postoperative days was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression analysis was performed to evaluate the association between possible risk factors and postoperative AKI. RESULTS: Of 505 pediatric patients, 185 (36.6%) developed postoperative AKI. The preoperative serum albumin level was associated with postoperative AKI (odds ratio [OR] 0.506, 95% confidence interval [CI] 0.325-0.788; P = 0.003). Other independent factors associated with AKI were age <12 months (OR 1.911, 95% CI 1.166-3.132; P = 0.007), preoperative pulmonary hypertension (OR 1.853, 95% CI 1.182-2.907; P = 0.01), and cardiopulmonary bypass (CPB) duration (OR 1.006, 95% CI 1.003-1.009; P = 0.002). Patients with AKI had higher incidence of postoperative complications, longer mechanical ventilation times, and more prolonged intensive care unit and hospital stays than patients without AKI. CONCLUSIONS: Preoperative serum albumin level, age <12 months, preoperative pulmonary hypertension, and CPB duration were associated with risk for postoperative AKI in children who underwent congenital cardiac surgery.


Asunto(s)
Lesión Renal Aguda/etiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Posoperatorias/etiología , Factores de Edad , Puente Cardiopulmonar/efectos adversos , Preescolar , Femenino , Humanos , Hipertensión Pulmonar/complicaciones , Lactante , Modelos Logísticos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica/análisis
20.
J Phys Ther Sci ; 30(1): 73-76, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29410570

RESUMEN

[Purpose] This study aimed to examine the effects of a client-centered leisure activity program on satisfaction, upper limb function, self-esteem, and depression in elderly residents of a long-term care facility. [Subjects and Methods] This study included 12 elderly subjects, aged 65 or older, residing in a nursing home. The subjects were divided into an experimental and a control group. Subjects in the control group received leisure activities already provided by the facility. The experimental group participated in a client-centered leisure activity program. The subjects conducted individual activities three times per week, 30 minutes per session. The group activity was conducted three times per week for eight weeks. Each subject's performance of and satisfaction with the leisure activity programs, upper limb function, self-esteem, and depression were measured before and after the intervention. [Results] After participating in a program, significant improvements were seen in both the Canadian Occupational Performance Measure and upper limb function in the experimental group. Also after the intervention, the subjects' self-esteem significantly increased and their depression significantly decreased. [Conclusion] A client-centered leisure activity program motivates elderly people residing in a long-term care facility and induces their voluntary participation. Such customized programs are therefore effective for enhancing physical and psychological functioning in this population.

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