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1.
Acta Pharmacol Sin ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907048

RESUMEN

Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous ß-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 µg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 µg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

2.
Heliyon ; 10(9): e30378, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707441

RESUMEN

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P < 0.05), and hemodynamics and SpO2 were more stable during sedation (P < 0.05). Conclusion: There was no significant difference between propofol and ciprofol in terms of euphoria experienced by patients after sedation in patients undergoing gastroscopy. Ciprofol has demonstrated addictive potential similar to that of propofol, warranting careful attention to its addictive potential during clinical application.

3.
Yi Chuan ; 46(5): 373-386, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38763772

RESUMEN

Cardioembolic stroke, characterized by severe illness, poor prognosis, and high recurrence rate, is one of the important causes of ischemic stroke. In the field of genetic research, numerous genes associated with cardioembolic stroke have been identified, and their potential in predicting disease risk and evaluating risk factors has been progressively explored. Here, we provide an overview of the latest advancements in genetics for cardioembolic stroke, including genome-wide association studies, copy number variation studies, whole-genome sequencing studies. Furthermore, we also summarize the application of genetic datasets in polygenic risk score and Mendelian randomization. The aim of this overview is to provide insights and references from multiple perspectives for future investigations on the genetic information for cardioembolic stroke.


Asunto(s)
Variaciones en el Número de Copia de ADN , Accidente Cerebrovascular Embólico , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Accidente Cerebrovascular Embólico/genética , Accidente Cerebrovascular Embólico/etiología , Factores de Riesgo
4.
Prostaglandins Other Lipid Mediat ; 172: 106832, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38460759

RESUMEN

Atherosclerosis (AS) represents a prevalent initiating factor for cardiovascular events. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an oncofetal RNA-binding protein that participates in cardiovascular diseases. This work aimed to elaborate the effects of IGF2BP3 on AS and the probable mechanism by using an oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) model. Results indicated that IGF2BP3 expression was declined in the blood of AS patients and ox-LDL-induced HUVECs. IGF2BP3 elevation alleviated ox-LDL-provoked viability loss, apoptosis, oxidative DNA damage and endothelial dysfunction in HUVECs. Moreover, IGF2BP3 bound SESN1 and stabilized SESN1 mRNA. Furthermore, SESN1 interference reversed the impacts of IGF2BP3 overexpression on the apoptosis, oxidative DNA damage and endothelial dysfunction of ox-LDL-challenged HUVECs. Additionally, the activation of Nrf2 signaling mediated by IGF2BP3 up-regulation in ox-LDL-treated HUVECs was blocked by SESN1 absence. Collectively, SESN1 stabilized by IGF2BP3 might protect against AS by activating Nrf2 signaling.


Asunto(s)
Células Endoteliales de la Vena Umbilical Humana , Lipoproteínas LDL , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , ARN Mensajero , Proteínas de Unión al ARN , Transducción de Señal , Humanos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Lipoproteínas LDL/farmacología , Lipoproteínas LDL/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Apoptosis/efectos de los fármacos , Aterosclerosis/metabolismo , Aterosclerosis/genética , Aterosclerosis/patología , Estabilidad del ARN/efectos de los fármacos , Daño del ADN , Sestrinas
5.
Eur J Anaesthesiol ; 41(4): 305-313, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38298060

RESUMEN

BACKGROUND: Tracheal injuries, vocal cord injuries, sore throat and hoarseness are common complications of double-lumen tube (DLT) intubation. OBJECTIVE: This study aimed to evaluate the effects of 'video double-lumen tubes' (VDLTs) on intubation complications in patients undergoing thoracic surgery. DESIGN: A randomised controlled study. SETTINGT: Xuzhou Cancer Hospital, Xuzhou, China, from January 2023 to June 2023. PATIENTS: One hundred eighty-two patients undergoing elective thoracic surgery with one-lung ventilation were randomised into two groups: 90 in the DLT group and 92 in the VDLT group. INTERVENTION: VDLT was selected for intubation in the VDLT group, and DLT was selected for intubation in the DLT group. A fibreoptic bronchoscope (FOB) was used to record tracheal and vocal cord injuries. MAIN OUTCOME MEASURES: The primary outcomes were the incidence of moderate-to-severe tracheal injury and the incidence of vocal cord injury. The secondary outcomes included the incidence and severity of postoperative 24 and 48 h sore throat and hoarseness. RESULTS: The incidence of moderate-to-severe tracheal injury was 32/90 (35.6%) in the DLT group, and 45/92 (48.9%) in the VDLT group ( P  = 0.077; relative risk 1.38, 95% CI, 0.97 to 1.95). The incidence of vocal cord injury was 31/90 (34.4%) and 34/92 (37%) in the DLT and VDLT groups, respectively ( P  = 0.449). The incidence of postoperative 24 h sore throat and hoarseness was significantly higher in the VDLT group than in the DLT group (for sore throat: P  = 0.032, relative risk 1.63, 95% CI, 1.03 to 2.57; for hoarseness: P  = 0.018, relative risk 1.48, 95% CI, 1.06 to 2.06). CONCLUSION: There was no statistically significant difference in the incidence of moderate-to-severe tracheal injury and vocal cord injury between DLTs and VDLTs. While improving the first-attempt success rate, intubation with VDLT increased the incidence of postoperative 24 h sore throat and hoarseness. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR2300067348.


Asunto(s)
Faringitis , Cirugía Torácica , Procedimientos Quirúrgicos Torácicos , Humanos , Ronquera/diagnóstico , Ronquera/epidemiología , Ronquera/etiología , Procedimientos Quirúrgicos Torácicos/efectos adversos , Broncoscopios , Faringitis/epidemiología , Faringitis/etiología
6.
Sci Rep ; 13(1): 18498, 2023 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-37898687

RESUMEN

Laryngeal squamous cell carcinoma (LSCC) is a common tumor type. High recurrence rates remain an important factor affecting the survival and quality of life of advanced LSCC patients. We aimed to build a new nomogram and a random survival forest model using machine learning to predict the risk of LSCC progress. The study included 671 patients with AJCC stages III-IV LSCC. To develop a prognostic model, Cox regression analyses were used to assess the relationship between clinic-pathologic factors and disease-free survival (DFS). RSF analysis was also used to predict the DFS of LSCC patients. The ROC curve revealed that the Cox model exhibited good sensitivity and specificity in predicting DFS in the training and validation cohorts (1 year, validation AUC = 0.679, training AUC = 0.693; 3 years, validation AUC = 0.716, training AUC = 0.655; 5 years, validation AUC = 0.717, training AUC = 0.659). Random survival forest analysis showed that N stage, clinical stage, and postoperative chemoradiotherapy were prognostically significant variables associated with survival. The random forest model exhibited better prediction ability than the Cox regression model in the training cohort; however, the two models showed similar prediction ability in the validation cohort.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Modelos de Riesgos Proporcionales , Carcinoma de Células Escamosas/patología , Calidad de Vida , Pronóstico , Aprendizaje Automático
7.
Tissue Cell ; 85: 102250, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37866150

RESUMEN

Non-small cell lung cancer (NSCLC) is a malignant tumor with extremely high mortality. Uroplakin1B (UPK1B) promotes the occurrence and development of multiple types of cancer by enhancing the expression of c-myc and Sox4. However, whether UPK1B can modulate the development of NSCLC by regulating c-myc/Sox4 axis is unclear. In this study, UPK1B was overexpressed or knocked down in the non-small cell lung cancer cells (NSCLCs) were. Next, the proliferation and invasion of those cells were detected with the EdU staining and transwell assays. Sphere formation assays was performed to examine the stem cell characteristics of those cells. Then, we overexpressed the Sox4 in UPK1B knockdown cells and determined the proliferation and invasion of those cells. Our results showed that UPK1B promoted the proliferation, invasion and stem cell characteristics of NSCLCs. In addition, UPK1B enhanced the expression of c-myc, Sox4 and stem cell associated proteins in those cells. Overexpression of Sox4 rescued the proliferation and invasion of NSCLCs, which were suppressed by the UPK1B knockdown. In summary, our study suggested that UPK1B enhanced the invasiveness and stem cell characteristics of NSCLCs by activating c-myc/UPK1B axis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Línea Celular Tumoral , Invasividad Neoplásica/genética , Proliferación Celular/genética , Movimiento Celular/genética , Factores de Transcripción , Células Madre/patología , Regulación Neoplásica de la Expresión Génica , Uroplaquina Ib
8.
J Cardiovasc Pharmacol ; 82(6): 496-503, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37548460

RESUMEN

ABSTRACT: This study aims to investigate whether venous injection of sedative agent or regional nerve block in alliance with major anesthesia could decrease the risk of postoperative delirium occurrence in patients receiving cardiothoracic surgery. Electronic academic databases were retrieved for related publications, and statistical software was used for data pooling and analysis. Forest plot was used to show the pooled sensitivity, specificity, and diagnostic odds ratio. Combined receiver operating characteristic curve was used to show the area under the curve of complex data. Seven studies were included for analysis. The risk of occurrence of delirium still showed no difference (risk rate = 0.93, 95% CI, 0.85-1.03) between the intervention group and placebo group. Postoperative pain feeling was more alleviated in patients with prophylactic application of regional nerve block. In addition, prophylactic application of regional nerve block could decrease the risk of postoperative in-hospital stay (risk rate = 0.28, 95% CI, 0.02-0.54). Our study demonstrated that, in elderly patients or pediatric patients undergoing cardiac surgery, prophylactic application of regional nerve block failed to decrease the incidence of postoperative delirium. However, the option of regional nerve block could decrease the duration of in-hospitalization stay and alleviate the acute pain during the postoperative period after open-heart surgery.


Asunto(s)
Delirio del Despertar , Bloqueo Nervioso , Humanos , Niño , Anciano , Delirio del Despertar/etiología , Tiempo de Internación , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Bloqueo Nervioso/efectos adversos , Anestesia General
9.
Chinese Pharmacological Bulletin ; (12): 1731-1739, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013721

RESUMEN

Aim To investigate the effects of Cichorium glandulosum N-butanol extraction site (C G E) on hepatic fibrosis (H F) in SD rats and to determine the content of the main effective component matricin. Methods HPLC method was used to determine the content of matricin in CGE. The SD rats were randomly divided into control group, model group, CGE low-dose groups, medium-dose and high-dose, and curcumin group. In addition to control group rats' back subcutaneous injection (s c) normal saline, rats in the other groups were treated with body weight sc 40 % CC1

10.
Technol Cancer Res Treat ; 21: 15330338221107710, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35815926

RESUMEN

Background: Head and neck squamous cell carcinoma (HNSCC) was the seventh most common cancer worldwide in 2018. Lymphatic metastasis (LM) is closely related to HNSCC prognosis and recurrence. However, the underlying mechanism of LM remains unclear. Therefore, this study aimed to identify the key genes in the LM of HNSCC. Methods: We used The Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs) between LM and non-LM cases. A random forest model, the Search Tool for the Retrieval of Interacting Genes, Cytoscape, and cytoHubba were used to identify hub genes among DEGs, including KRT20 (Cytokeratins 20). We analyzed the survival of KRT20 in TCGA, and we overexpressed KRT20 in HNSCC cell lines to investigate its effects on migration and invasion. We also correlated the expression of KRT20 in HNSCC tissue microarrays with survival and clinicopathological features. Results: We identified 243 DEGs-143 upregulated genes and 100 downregulated genes. Further analysis revealed that KRT20 is a potential key gene associated with LM and overall survival rates among patients with HNSCC. Overexpression of KRT20 increased the migration and invasion ability of HNSCC cell lines Tu686 and FD-LSC-1. Tissue microarray studies demonstrated an overexpression of KRT20 among N1+ patients (including N1-N3 patients). Survival analysis results and the clinicopathological features of HNSCC tissue microarrays were consistent with our analysis of TCGA. Thus, a high KRT20 expression level might suggest an adverse HNSCC prognosis. Our gene set enrichment analysis showed that KRT20 participates in many metabolic pathways, including those related to tumorigenesis and cancer development. Conclusions: We propose that KRT20 may be a key gene in HNSCC with LM.


Asunto(s)
Neoplasias de Cabeza y Cuello , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Humanos , Queratina-20/genética , Metástasis Linfática , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética
11.
Thorac Cardiovasc Surg ; 70(5): 439-444, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34521135

RESUMEN

OBJECTIVES: Thoracic surgery often causes postoperative delirium (POD) in geriatric patients. This study aimed to explore the effect of ultrasound-guided continuous thoracic paravertebral block (UG-TPVB) on POD in geriatric patients undergoing pulmonary resection. METHODS: Total 128 patients who underwent pulmonary resection were randomly allocated to either the conventional patient-controlled analgesia (PCA) group or the UG-TPVB group (n = 64 per group). The consumption of opioid agents (propofol and remifentanil), postoperative hospital stay, postoperative pulmonary atelectasis, postoperative nausea/vomiting, and postoperative itchiness were recorded. The diagnosis of delirium was dependent on the Nursing Delirium Screening Scale. The postoperative pain was assessed by visual analogue scale (VAS) score. The serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α were used to evaluate the postoperative neuroinflammation. RESULTS: The consumption of propofol and remifentanil, postoperative hospital stay, postoperative pulmonary atelectasis, postoperative nausea/vomiting, and postoperative itchiness in the UG-TPVB group were lower than that in the PCA group. Compared with the PCA group, the prevalence of POD was decreased in the UG-TPVB group. In addition, use of UG-TPVB not only reduced postoperative pain (VAS score) but also decreased postoperative neuroinflammation compared with PCA in geriatric patients undergoing pulmonary resection. CONCLUSIONS: This study determined the benefits of UG-TPVB over PCA, providing an effectiveness approach to alleviate POD in geriatric patients undergoing pulmonary resection.


Asunto(s)
Delirio , Propofol , Atelectasia Pulmonar , Anciano , Delirio/diagnóstico , Delirio/etiología , Delirio/prevención & control , Humanos , Náusea , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Propofol/efectos adversos , Remifentanilo , Resultado del Tratamiento , Vómitos
12.
Acta Pharmacol Sin ; 42(12): 2094-2105, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33686245

RESUMEN

Aristolochic acid I (AAI) is a well-known nephrotoxic carcinogen, which is currently reported to be also associated with hepatocellular carcinoma (HCC). Whether AAI is a direct hepatocarcinogen remains controversial. In this study we investigated the association between AAI exposure and HCC in adult rats using a sensitive rat liver bioassay with several cofactors. Formation of glutathione S-transferase placental form-positive (GST-P+) foci was used as the marker for preneoplastic lesions/clonal expansion. We first conducted a medium-term (8 weeks) study to investigate whether AAI had any tumor-initiating or -promoting activity. Then a long-term (52 weeks) study was conducted to determine whether AAI can directly induce HCC. We showed that oral administration of single dose of AAI (20, 50, or 100 mg/kg) in combination with partial hepatectomy (PH) to stimulate liver proliferation did not induce typical GST-P+ foci in liver. In the 8-week study, only high dose of AAI (10 mg · kg-1 · d-1, 5 days a week for 6 weeks) in combination with PH significantly increased the number and area of GST-P+ foci initiated by diethylnitrosamine (DEN) in liver. Similarly, only high dose of AAI (10 mg· kg-1· d-1, 5 days a week for 52 weeks) in combination with PH significantly increased the number and area of hepatic GST-P+ foci in the 52-week study. No any nodules or HCC were observed in liver of any AAI-treated groups. In contrast, long-term administration of AAI (0.1, 1, 10 mg· kg-1· d-1) time- and dose-dependently caused death due to the occurrence of cancers in the forestomach, intestine, and/or kidney. Besides, AAI-DNA adducts accumulated in the forestomach, kidney, and liver in a time- and dose-dependent manner. Taken together, AAI promotes clonal expansion only in the high-dose group but did not induce any nodules or HCC in liver of adult rats till their deaths caused by cancers developed in the forestomach, intestine, and/or kidney. Findings from our animal studies will pave the way for further large-scale epidemiological investigation of the associations between AA and HCC.


Asunto(s)
Ácidos Aristolóquicos/toxicidad , Carcinógenos/toxicidad , Carcinoma Hepatocelular/etiología , Hepatocitos/metabolismo , Neoplasias Hepáticas/etiología , Mutágenos/toxicidad , Animales , Carcinogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Aductos de ADN/efectos de los fármacos , Gutatión-S-Transferasa pi/metabolismo , Neoplasias Intestinales/inducido químicamente , Intestinos/patología , Riñón/patología , Neoplasias Renales/inducido químicamente , Hígado/metabolismo , Hígado/patología , Masculino , Ratas Sprague-Dawley , Estómago/patología , Neoplasias Gástricas/inducido químicamente
13.
Medicine (Baltimore) ; 99(17): e19896, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32332664

RESUMEN

BACKGROUND: Delirium is a common postoperative complication in older patients undergoing thoracic surgery and presages poor outcomes. Postoperative pain is an important factor in the progression of delirium. The purpose of this study was to test whether continuous thoracic paravertebral block (PVB), a more effective approach for analgesia, could decrease the incidence of delirium in elderly patients undergoing esophagectomy. METHODS: A total of 180 geriatric patients undergoing esophagectomy were randomly divided into 2 groups and treated with PVB or patient-controlled analgesia (PCA). Perioperative plasma CRP, IL-1ß, IL-6, and TNF-α levels were detected in all patients. Pain intensity was measured by a numerical rating scale. Delirium was assessed using the confusion assessment method. RESULTS: The incidence of postoperative delirium was significantly lower in the PVB group than in the PCA group. Patients in the PVB group had lower plasma CRP, IL-1ß, IL-6, and TNF-α levels and less pain when coughing after surgery. CONCLUSIONS: Ultrasound-guided continuous thoracic paravertebral block improved analgesia, reduced the inflammatory reaction and decreased the occurrence of delirium after surgery.


Asunto(s)
Delirio/prevención & control , Esofagectomía/normas , Bloqueo Nervioso/métodos , Ultrasonografía/normas , Anciano , Anciano de 80 o más Años , Analgesia Controlada por el Paciente/métodos , Analgesia Controlada por el Paciente/normas , Delirio/tratamiento farmacológico , Esofagectomía/métodos , Femenino , Geriatría/métodos , Humanos , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/normas , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Ultrasonografía/métodos , Ultrasonografía/estadística & datos numéricos
14.
Acta Pharmacol Sin ; 41(3): 348-357, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31506573

RESUMEN

Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy. Superoxide dismutase (SOD) is a potential therapy for mucositis but efficient product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion. Multi-modified Stable Anti-Oxidant Enzymes® (MS-AOE®) is a new recombinant SOD with better resistance to pepsin and trypsin. We referred it as MS-SOD to distinguish from other SODs. In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms. An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU (50 mg/kg every day, ip). MS-SOD (800 IU/10 g, ig) was given once daily for 9 days. 5-FU caused severe mucositis with intestinal morphological damage, bodyweight loss and diarrhea; MS-SOD significantly decreased the severity. 5-FU markedly increased reactive oxygen species (ROS) and inflammatory cytokines in the intestine which were ameliorated by MS-SOD. Furthermore, MS-SOD modified intestinal microbes, particularly reduced Verrucomicrobia, compared with the 5-FU group. In Caco2 cells, MS-SOD (250-1000 U/mL) dose-dependently decreased tBHP-induced ROS generation. In RAW264.7 cells, MS-SOD (500 U/mL) had no effect on LPS-induced inflammatory cytokines, but inhibited iNOS expression. These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury, thus play an indirect role in anti-inflammatory and barrier protein protection. In conclusion, MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation, and influencing microbes. MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic.


Asunto(s)
Fluorouracilo/efectos adversos , Mucosa Intestinal/metabolismo , Superóxido Dismutasa/metabolismo , Administración Oral , Animales , Fluorouracilo/administración & dosificación , Fluorouracilo/metabolismo , Inyecciones Intraperitoneales , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/metabolismo , Superóxido Dismutasa/administración & dosificación
15.
Acta Pharmacol Sin ; 39(12): 1865-1873, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30061734

RESUMEN

Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18ß-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect. According to the results, 18b-GA markedly attenuated ANIT-induced liver injury as indicated the hepatic plasma chemistry index and histopathology examination. In addition, the expression levels of nuclear factors, including Sirt1, FXR and Nrf2, and their target efflux transporters in the liver, which mainly mediate bile acid homeostasis in hepatocytes, significantly increased. Furthermore, we first revealed that 18b-GA treatment significantly activated FXR, and which can be significantly reduced by EX-527 (a potent and selective Sirt1 inhibitor), indicating that 18b-GA activates FXR through Sirt1. Taken together, 18b-GA confers hepatoprotection against ANIT-induced cholestasis by activating FXR through Sirt1, which promotes gene expression of the efflux transporter, and consequently attenuates dysregulation of bile acid homeostasis in hepatocyte compartments.


Asunto(s)
Colestasis/prevención & control , Ácido Glicirretínico/análogos & derivados , Sustancias Protectoras/uso terapéutico , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo , 1-Naftilisotiocianato , Animales , Colestasis/inducido químicamente , Ácido Glicirretínico/uso terapéutico , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Ratas Sprague-Dawley
16.
Front Neurol ; 9: 633, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30131758

RESUMEN

Objective: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor celecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the effects of celecoxib on POCD in geriatric patients. Methods: A total of 178 geriatric patients undergoing total knee arthroplasty were randomly divided into two groups and treated with celecoxib (group C) or placebo (group P). The levels of perioperative plasma COX-2, IL-1ß, IL-6, TNF-α, neuron-specific enolase, and S100ß were detected in all patients. The pain intensity was measured by numerical rating scale (NRS). A battery of 9 neuropsychological tests was performed pre-operatively and 1 week, and 3 months postoperatively. Patients, whose postoperative performance declined by ≧1 standard deviation as compared to each preoperative test score on ≧2 tests, were classified as POCD. Results: A significant decrease in POCD incidence was found in group C as compared to group P on postoperative day 7 (12.3% vs. 34.1%; p < 0.05). POCD incidence did not differ between the two groups at the 3-month follow-up (8.8 vs. 9.7%). NRS scores at days 3 and 4 post-surgery were significantly lower in group C (p < 0.05). Patients in group C showed lower level of plasma COX-2, IL-1ß, IL-6, TNF-α, and S100ß as compared to group P postoperatively (p < 0.05). Conclusion: These results demonstrated that celecoxib can decrease early POCD incidence after total knee arthroplasty in geriatric patients, which might be mediated by suppressing inflammation and acute postoperative pain caused by surgical trauma. Registration: Chinese Clinical Trial Register, ChiCTR-IOR-16008168.

17.
Medicine (Baltimore) ; 95(32): e4440, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27512858

RESUMEN

Anesthesia followed by placement in the prone position takes time and may result in complications. This study aimed to evaluate the feasibility of awake nasotracheal fiberoptic intubation and self-positioning followed by anesthesia induction in prone-positioned patients under general anesthesia.Sixty-two patients (ASA physical status I-II) scheduled for awake nasotracheal fiberoptic intubation and prone self-positioning before surgery under general anesthesia were selected. Patient preparation began with detailed preoperative counseling regarding the procedure. Premedication with sedative and antisialagogue was followed by airway anesthesia with topical lidocaine; then, awake nasotracheal fiberoptic intubation was carried out. The patients then positioned themselves comfortably before induction of general anesthesia. The changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), incidence of coughing or gagging, and rate pressure product (RPP) were assessed. Statistical analysis was performed with repeated-measures one-way analysis of variance.Fifty-eight of the 62 patients completed prone self-positioning smoothly. Compared with values before intubation, SBP, DBP, HR, and RPP were slightly increased after intubation, although the difference was not statistically significant (P > 0.05). One patient had moderate coughing and 1 patient had gagging during prone self-positioning, which were tolerable.These findings indicated that awake nasotracheal fiberoptic intubation and self-positioning followed by induction of anesthesia is safe and feasible alternative to routine prone positioning after induction of general anesthesia.


Asunto(s)
Anestesia General/métodos , Intubación Gastrointestinal/métodos , Posicionamiento del Paciente , Anciano , Presión Sanguínea , Estado de Conciencia , Tos/etiología , Estudios de Factibilidad , Femenino , Atragantamiento , Frecuencia Cardíaca , Humanos , Masculino , Fibras Ópticas , Proyectos Piloto , Posición Prona
18.
Oncotarget ; 5(21): 10571-83, 2014 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-25301735

RESUMEN

SOX10 was identified as a methylated gene in our previous cancer methylome study. Here we further analyzed its epigenetic inactivation, biological functions and related cell signaling in digestive cancers (colorectal, gastric and esophageal cancers) in detail. SOX10 expression was decreased in multiple digestive cancer cell lines as well as primary tumors due to its promoter methylation. Pharmacologic or genetic demethylation reversed SOX10 silencing. Ectopic expression of SOX10 in SOX10-deficient cancer cells inhibits their proliferation, tumorigenicity, and metastatic potentials in vitro and in vivo. SOX10 also suppressed the epithelial to mesenchymal transition (EMT) and stemness properties of digestive tumor cells. Mechanistically, SOX10 competes with TCF4 to bind ß-catenin and transrepresses its downstream target genes via its own DNA-binding property. SOX10 mutations that disrupt the SOX10-ß-catenin interaction partially prevented tumor suppression. SOX10is thus a commonly inactivated tumor suppressor that antagonizes Wnt/ß-catenin signaling in cancer cells from different digestive tissues.


Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/prevención & control , Neoplasias Hepáticas/prevención & control , Factores de Transcripción SOXE/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animales , Apoptosis , Western Blotting , Adhesión Celular , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal , Técnica del Anticuerpo Fluorescente , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Masculino , Melanoma/metabolismo , Melanoma/patología , Melanoma/prevención & control , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción SOXE/genética , Transducción de Señal , Análisis de Matrices Tisulares , Células Tumorales Cultivadas , Proteínas Wnt/genética , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/genética
19.
World J Gastroenterol ; 20(29): 10166-73, 2014 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-25110445

RESUMEN

AIM: To assess the clinical significance of pouch size in total gastrectomy for gastric malignancies. METHODS: We manually searched the English-language literature in PubMed, Cochrane Library, Web of Science and BIOSIS Previews up to October 31, 2013. Only randomized control trials comparing small pouch with large pouch in gastric reconstruction after total gastrectomy were eligible for inclusion. Two reviewers independently carried out the literature search, study selection, data extraction and quality assessment of included publications. Standard mean difference (SMD) or relative risk (RR) and corresponding 95%CI were calculated as summary measures of effects. RESULTS: Five RCTs published between 1996 and 2011 comparing small pouch formation with large pouch formation after total gastrectomy were included. Eating capacity per meal in patients with a small pouch was significantly higher than that in patients with a large pouch (SMD = 0.85, 95%CI: 0.25-1.44, I(2) = 0, P = 0.792), and the operative time spent in the small pouch group was significantly longer than that in the large pouch group [SMD = -3.87, 95%CI: -7.68-(-0.09), I (2) = 95.6%, P = 0]. There were no significant differences in body weight at 3 mo (SMD = 1.45, 95%CI: -4.24-7.15, I(2) = 97.7%, P = 0) or 12 mo (SMD = -1.34, 95%CI: -3.67-0.99, I(2) = 94.2%, P = 0) after gastrectomy, and no significant improvement of post-gastrectomy symptoms (heartburn, RR = 0.39, 95%CI: 0.12-1.29, I(2) = 0, P = 0.386; dysphagia, RR = 0.86, 95%CI: 0.58-1.27, I(2) = 0, P = 0.435; and vomiting, RR = 0.5, 95%CI: 0.15-1.62, I(2) = 0, P = 0.981) between the two groups. CONCLUSION: Small pouch can significantly improve the eating capacity per meal after surgery, and may improve the post-gastrectomy symptoms, including heartburn, dysphagia and vomiting.


Asunto(s)
Gastrectomía , Procedimientos de Cirugía Plástica , Neoplasias Gástricas/cirugía , Estructuras Creadas Quirúrgicamente , Ingestión de Alimentos , Conducta Alimentaria , Gastrectomía/efectos adversos , Humanos , Complicaciones Posoperatorias/etiología , Procedimientos de Cirugía Plástica/efectos adversos , Neoplasias Gástricas/patología , Estructuras Creadas Quirúrgicamente/efectos adversos , Resultado del Tratamiento
20.
Artículo en Chino | MEDLINE | ID: mdl-23687821

RESUMEN

OBJECTIVE: To explore the sustainable development control strategies on soil-transmitted parasitic diseases appropriate to current epidemic characteristics so as to effectively reduce the epidemic level and harm to people in Shandong Province. METHODS: This project was led by the Shandong Medical Department, governed and instructed by the Shandong Institute of Parasitic Diseases, concretely implemented by the centers for disease control and prevention in counties or cities. All the work was carried out according to the Control Programming of National Key Parasitic Diseases, and with the combination of routine and key control strategies according to the actual situation. RESULTS: The average infection rate of soil-transmitted parasitic diseases in Shandong Province was 18.26% in 2003. During the 2007 to 2009 period, 3,115,194 people from 74 counties in 9 cities received anthelmintic medicine. The numbers receiving health education were 39 866 923 in county, 34,730,663 in city, 3,2000 in province, respectively. The coverage rate of non-hazardous sanitary latrines was 58.05%. In 2009, 6,581 people were surveyed from 7 counties or cities and the infection rate of soil-transmitted parasitic diseases was 7.61%. During three years, 30 provincial training classes were held and 2,130 people attended, 52 municipal classes were held and 3110 people attended, and 403 county classes were held and 12,789 people attended. In the whole province, the infection rate of soil-transmitted parasitic diseases reduced to 7.10% in 2009, with the reduction rate of 61.12%, reaching the national objective. CONCLUSIONS: The comprehensive control model for soil-transmitted parasitic diseases is very successful in Shandong Province.


Asunto(s)
Control de Enfermedades Transmisibles/métodos , Enfermedades Parasitarias/prevención & control , Enfermedades Parasitarias/transmisión , Suelo/parasitología , Animales , China/epidemiología , Control de Enfermedades Transmisibles/estadística & datos numéricos , Humanos , Enfermedades Parasitarias/epidemiología
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