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1.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(6): 1082-1087, 2023 Dec 18.
Artículo en Chino | MEDLINE | ID: mdl-38101793

RESUMEN

OBJECTIVE: To investigate the effect of gastric antrum ultrasonography in evaluating gastric emptying after oral administration of 300 mL carbohydrates two hours before cesarean section, and to analyze the risk factors of gastric emptying in pregnant women. METHODS: From August 2020 to February 2021, a total of 80 patients, aged 22-43 years, body mass index (BMI) < 35 kg/m2, gestational age≥36 weeks, falling into American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, scheduled for cesarean sections in Peking University International Hospital were recruited and divided into two groups: the intervention group (n=40)and the control group (n=40). In the intervention group, solid food was restricted after 22:00, the patients were required to take 300 mL carbohydrates two hours before cesarean section. In the control group, solid food and liquid intake were restricted after 22:00 the night before surgery. All the patients received assessment of preoperative feeling of thirst and starvation with visual analogue scale (VAS). The cross-sectional area (CSA)of gastric antrum was measured in supine position and right supine position before anesthesia, the gastric volume (GV)and the gastric volume/weight(GV/W)of the two groups was further calculated. Perlas A semi-quantitative grading assessments were performed in each patient. The blood pressure and heart rate were recorded at admission(T0), 5 minutes after anesthesia (T1), immediately after fetal delivery (T2) and at the end of the surgery (T3). The occurrence of nausea and vomiting during the operation and 24 hours after the operation were recorded. RESULTS: One case in each group was excluded because the antrum was not clearly identified during the ultrasound assessments. In the semi-sitting position, the CSA was (5.07±1.73) cm2 in the intervention group vs. (5.24±1.96) cm2 in the control group, respectively; in the right lateral decubitus position, CSA was (7.32±2.17) cm2 in the intervention group vs. (7.25±2.24) cm2 in the control group, GV was (91.74±32.34) mL vs. (90.07±31.68) mL, GV/W was (1.27±0.40) mL/kg vs. (1.22±0.41) mL/kg, respectively; all the above showed no significant difference between the two groups (P > 0.05). Perlas A semi-quantitative grading showed 0 in 20 patients (51.3%), 1 in 16 (41%), 2 in 3 (7.7%)in the intervention group and 0 in 22 (56.4%), 1 in 15 (38.5%), 2 in 2 (5.1%)in the control group, the proportion of Perlas A semi-quantitative grading showed no significant difference between the two groups (P > 0.05). For the patients with Perlas A semi-quantitative grade 2 (3 cases in the intervention group and 2 cases in the control group), metoclopramide 0.2 mg/kg was intravenously injected before anesthesia. No aspiration case was observed in this study. The intervention group was endured less thirst and hunger (P < 0.05). There was no significant difference in blood pressure and heart rate between the two groups at each time point (P > 0.05). There was no significant difference in the incidence of intraoperative hypotension between the two groups (P > 0.05). There was no significant difference in the incidence of nausea intraoperatively and postoperatively between the two groups (P > 0.05). CONCLUSION: Ultrasonography of gastric antrum can provide objective basis for evaluating gastric emptying of pregnant women perioperatively. 300 mL carbohydrates intake two hours before surgery, which does not increase GV and the risk of reflux aspiration, and is helpful in minimizing disturbance to the patient's physiological status, therefore leading to better clinical outcome.


Asunto(s)
Cesárea , Vaciamiento Gástrico , Humanos , Femenino , Embarazo , Vaciamiento Gástrico/fisiología , Estudios Prospectivos , Ultrasonografía , Carbohidratos , Náusea
2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(5): 893-898, 2023 Oct 18.
Artículo en Chino | MEDLINE | ID: mdl-37807745

RESUMEN

OBJECTIVE: To investigate the effect of 300 mL carbohydrates intake two hours before sur-gery on the gastric volume (GV) in patients positioning in trendelenburg undergoing gynecological laparoscopic procedures by using gastric antrum sonography, and further assess the risk of reflux aspiration. METHODS: From June 2020 to February 2021, a total of 80 patients, aged 18-65 years, body mass index (BMI) 18-35 kg/m2, falling into American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, scheduled for gynecological laparoscopic procedures positioning in trendelenburg were recruited and divided into two groups: the observation group (n =40) and the control group (n=40). In the observation group, solid food was restricted after 24:00, the patients were required to take 300 mL carbohydrates two hours before surgery. In the control group, solid food and liquid intake were restricted after 24:00 the night before surgery. The cross-sectional area (CSA) of gastric antrum was measured in supine position and right lateral decubitus position before anesthesia. Primary outcome was gastric volume (GV) in each group. Secondary outcome included Perlas A semi-quantitative grading and gastric volume/weight (GV/W). All the patients received assessment of preoperative feeling of thirsty and hunger with visual analogue scale (VAS). RESULTS: Complete data were available in eighty patients. GV was (58.8±23.6) mL in the intervention group vs. (56.3±22.1) mL in the control group, GV/W was (0.97±0.39) mL/kg vs. (0.95±0.35) mL/kg, respectively; all the above showed no significant difference between the two groups (P > 0.05). Perlas A semi-quantitative grading showed 0 in 24 patients (60%), 1 in 15 patients (37.5%), 2 in 1 patient (2.5%) in the intervention group and 0 in 25 (62.5%), 1 in 13 (32.5%), 2 in 2 (5%) in the control group, the proportion of Perlas A semi-quantitative grading showed no significant difference between the two groups (P > 0.05). A total of 3 patients (1 in the intervention group and 2 in the control group) with Perlas A semi-quantitative grading 2 were treated with special intervention, no aspiration case was observed in this study. The observation group endured less thirst and hunger (P<0.05). CONCLUSION: Three hundred mL carbohydrates intake two hours before surgery along with ultrasound guided gastric content monitoring does not increase gastric volume and the risk of reflux aspiration in patients positioning in trendelenburg undergoing gynecological laparoscopic surgery, and is helpful in minimizing disturbance to the patient's physiological needs, therefore leading to better clinical outcome.


Asunto(s)
Laparoscopía , Antro Pilórico , Femenino , Humanos , Posición Supina , Estudios Prospectivos , Laparoscopía/efectos adversos , Carbohidratos
3.
J Endocrinol Invest ; 46(4): 749-761, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36224454

RESUMEN

BACKGROUND: Papillary thyroid cancer (PTC) is life-threatening due to its malignant progression. Considerable evidence demonstrates that circular RNA (circRNA) regulates PTC development. This study aims to explore the mechanism of circ_0000644 modulating PTC malignant progression. METHODS: The RNA levels of circ_0000644, microRNA-671-5p (miR-671-5p) and annexin A2 (ANXA2) were detected by quantitative real-time polymerase chain reaction. Western blot was performed to check protein expression. Cell proliferation and cell apoptosis were investigated by 5-ethynyl-29-deoxyuridine and flow cytometry. Angiogenic capacity, migration and invasion were analyzed by tube formation assay and transwell assay. The interaction between miR-671-5p and circ_0000644 or ANXA2 was identified by dual-luciferase reporter assay. Xenograft mouse model assay was performed to analyze the effect of circ_0000644 on tumor formation in vivo. RESULTS: Circ_0000644 and ANXA2 expression was significantly upregulated, while miR-671-5p was downregulated in PTC tissues and cells when compared with control groups. Circ_0000644 knockdown inhibited PTC cell proliferation, tube formation, migration, and invasion, but induced apoptosis in vitro. Moreover, circ_0000644 knockdown led to delayed tumorigenesis in vivo. In addition, circ_0000644 acted as a miR-671-5p sponge and mediated PTC cell tumor properties through miR-671-5p. ANXA2 was identified as a target gene of miR-671-5p, and its overexpression relieved miR-671-5p-induced effects in PTC cells. Furthermore, circ_0000644 depletion inhibited ANXA2 production by combining with miR-671-5p. CONCLUSION: Circ_0000644 depletion repressed PTC cell tumor properties through the miR-671-5p/ANXA2 axis.


Asunto(s)
Anexina A2 , MicroARNs , Neoplasias de la Tiroides , Humanos , Animales , Ratones , Cáncer Papilar Tiroideo/genética , Anexina A2/genética , Carcinogénesis , Proliferación Celular , Modelos Animales de Enfermedad , Neoplasias de la Tiroides/genética , MicroARNs/genética , Línea Celular Tumoral
4.
J Intensive Care ; 9(1): 71, 2021 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-34838150

RESUMEN

BACKGROUND: In patient requiring vasopressors, the radial artery pressure may underestimate the true central aortic pressure leading to unnecessary interventions. When using a femoral and a radial arterial line, this femoral-to-radial arterial pressure gradient (FR-APG) can be detected. Our main objective was to assess the accuracy of non-invasive blood pressure (NIBP) measures; specifically, measuring the gradient between the NIBP obtained at the brachial artery and the radial artery pressure and calculating the non-invasive brachial-to-radial arterial pressure gradient (NIBR-APG) to detect an FR-APG. The secondary objective was to assess the prevalence of the FR-APG in a targeted sample of critically ill patients. METHODS: Adult patients in an intensive care unit requiring vasopressors and instrumented with a femoral and a radial artery line were selected. We recorded invasive radial and femoral arterial pressure, and brachial NIBP. Measurements were repeated each hour for 2 h. A significant FR-APG (our reference standard) was defined by either a mean arterial pressure (MAP) difference of more than 10 mmHg or a systolic arterial pressure (SAP) difference of more than 25 mmHg. The diagnostic accuracy of the NIBR-APG (our index test) to detect a significant FR-APG was estimated and the prevalence of an FR-APG was measured and correlated with the NIBR-APG. RESULTS: Eighty-one patients aged 68 [IQR 58-75] years and an SAPS2 score of 35 (SD 7) were included from which 228 measurements were obtained. A significant FR-APG occurred in 15 patients with a prevalence of 18.5% [95%CI 10.8-28.7%]. Diabetes was significantly associated with a significant FR-APG. The use of a 11 mmHg difference in MAP between the NIBP at the brachial artery and the MAP of the radial artery led to a specificity of 92% [67; 100], a sensitivity of 100% [95%CI 83; 100] and an AUC ROC of 0.93 [95%CI 0.81-0.99] to detect a significant FR-APG. SAP and MAP FR-APG correlated with SAP (r2 = 0.36; p < 0.001) and MAP (r2 = 0.34; p < 0.001) NIBR-APG. CONCLUSION: NIBR-APG assessment can be used to detect a significant FR-APG which occur in one in every five critically ill patients requiring vasoactive agents.

5.
Am J Emerg Med ; 50: 442-448, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34492589

RESUMEN

OBJECTIVE: To evaluate effectiveness of combinational use of dexmedetomidine and ketamine (DEX-KET) for pediatric procedural sedation or premedication. METHODS: Relevant studies were identified after a literature search in electronic databases and study selection was based on precise eligibility criteria. Meta-analyses of mean differences were performed to examine differences in sedation onset and recovery times between DEX-KET and comparators. Changes from baseline in heart rate (HR), respiratory rate, oxygen saturation, and mean arterial pressure (MAP), were pooled. Meta-analyses of proportions were performed to estimate incidence of adverse events. RESULTS: 15 studies (1087 patients) were included. Onset of sedation was significantly shorter in DEX-KET than in DEX group. HR declined in DEX-KET group from start (-3.5 beats per minute (BPM) [95% CI: -5.1, -1.9]) through midpoint (-7.2 BPM [95% CI: -12.1, -2.3]) and at end of sedation (-8.7 BPM [95% CI: -13.1, -4.4]). Decrease in HR after DEX administration at start was -11.6 BPM [95% CI: -16.0, -7.1] and remained consistent afterward. There was no change in MAP during DEX-KET sedation. However, after DEX administration, MAP decreased by -6.9 [95% CI: -10.4, -3.3] at start, -7.8 [95% CI: -11.4, -4.2] at middle, and by -6.6 [95% CI: -14.4, 1.1] at end of sedation. Incidence of hypotension was 3% [95% CI: 0, 9] in DEX-KET, 7% [95% CI: 2, 14] in DEX, and 0% [95% CI: 0, 2] in KET groups. Incidence of bradycardia was 2% [95% CI: 0, 6] with DEX-KET and 12% [95% CI: 5, 20] with DEX. Incidence of oxygen desaturation was 3% [95% CI: 0, 8] in DEX-KET, 2% [95% CI: 0, 6] in DEX, 12% [95% CI: 5, 20] in KET, and 13% [95% CI: 6, 21] in PROP-KET groups. MIDA-KET sedation had 13% [95% CI: 4, 25] incidence of tachycardia. CONCLUSIONS: DEX-KET for pediatric sedation results in better sedation outcomes than DEX or KET by shortening onset of sedation and recovery while maintaining hemodynamic and respiratory stability with low incidence of adverse events. DEX sedation was associated with higher incidence of bradycardia. Higher incidence of oxygen desaturation was observed with KET and PROP-KET whereas MIDA-KET was associated with higher incidence of tachycardia.


Asunto(s)
Sedación Consciente , Dexmedetomidina/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Ketamina/administración & dosificación , Premedicación , Niño , Combinación de Medicamentos , Humanos
6.
Neurobiol Learn Mem ; 171: 107204, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32145405

RESUMEN

Sleep plays a crucial role in memory consolidation. However, the influence of sleep on emotional memory consolidation in older adults, especially in the context of associative memory, which is more cognitively demanding than item memory, remains elusive. For this study we recruited young and older adults, and randomly assigned them into the sleep or wake condition. They were administrated a visual-spatial associative memory task, which required them to remember a picture and its location. We measured memory performance for positive, neutral, and negative stimuli before and after a 12-h interval of being awake or asleep. An accuracy analysis indicated a beneficial effect of sleep on location memory regardless of age and valence. In addition, in a more fine-grained analysis, the drift rate from diffusion modeling showed that sleep facilitated the consolidation of negative stimuli in young adults, while this emotion bias shifted to positive stimuli in older adults. Moreover, negative correlations were observed between the change of memory performance and sleep characteristics in older adults, indicating that more sleep results in fewer negative memories. Our results provide a relatively weak support for an age-related emotional bias in the context of associative memory, manifested in the absence of an age-by-valence interaction in accuracy, whilst a modeling parameter in consideration of both accuracy and response time yielded evidence consistent with the predictions of the socioemotional selectivity theory.


Asunto(s)
Aprendizaje por Asociación/fisiología , Consolidación de la Memoria/fisiología , Memoria/fisiología , Sueño/fisiología , Vigilia/fisiología , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Adulto Joven
7.
Gene ; 680: 99-104, 2019 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-30099021

RESUMEN

Copy number variation (CNV) related to complex traits, such as disease and quantitative phenotype, is considered an important and wealthy source of genetic and phenotypic diversity. It suggests that the copy number variation of function gene maybe leads to the phenotypic changes. Kupple like factor 3 (KLF3) gene is a vital transcription factor associated with the growth and development of muscle and adipose tissue. It has been mapped in a CNV region by animal genome re-sequencing. In this study, we detected the distribution diversity of KLF3 gene copy numbers in six Chinese cattle breeds (QC, NY, XN, PN, QDM and JX) and associated the phenotypic traits with it. Then, we analyzed the KLF3 gene transcription expression level in different tissues of Jiaxian (JX) cattle. Furthermore, we detected mRNA expression level of muscle and fat tissues of Jiaxian cattle (JX), Angus × Jiaxian (AJ). The results showed that the copy number in CNV loss was more frequent in QC than others. And we revealed a positive effect of KLF3 CNV on growth traits, such as body mass and heart girth (P < 0.05). In a word, we ascertained the significance between CNVs of KLF3 gene and growth traits in different cattle breeds, and our data indicates that the CNVs of KLF3 gene may as a marker for the future molecular breeding of Chinese beef cattle.


Asunto(s)
Tejido Adiposo/crecimiento & desarrollo , Variaciones en el Número de Copia de ADN , Estudios de Asociación Genética/métodos , Factores de Transcripción de Tipo Kruppel/genética , Músculo Esquelético/crecimiento & desarrollo , Animales , Peso Corporal , Bovinos , Mapeo Cromosómico , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Fenotipo , Carácter Cuantitativo Heredable , Análisis de Secuencia de ADN
8.
Anim Biotechnol ; 28(2): 104-111, 2017 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-27532432

RESUMEN

DNA methylation is essential for the regulation of gene expression and important roles in muscle development. To assess the extent of epigenetic modifications and gene expression on the differentially methylated region (DMR) in ZBED6, we simultaneously examined DNA methylation and expression in six tissues from two different developmental stages (fetal bovine and adult bovine). The DNA methylation pattern was compared using bisulfite sequencing polymerase chain reaction (BSP) and combined bisulfite restriction analysis (COBRA). The result of quantitative real-time PCR (qPCR) analysis showed that ZBED6 has a broad tissue distribution and is highly expressed in adult bovine (P < 0.05 or P < 0.01). The DNA methylation level was significantly different in liver, lung and spleen between the two cattle groups (P < 0.05 or P < 0.01). The adult bovine group exhibited a significantly higher mRNA level and lower DNA methylation level than the fetal bovine group in liver, lung, and spleen. No significant association was detected between DNA methylation level and muscle, heart, and kidney at two different stages. In this study, the statistical analyses indicated that DNA methylation patterns are associated with mRNA level in some tissues, these results may be a useful parameter to investigate muscle developmental in cattle and as a model for studies in other species, potentially contributing to an improvement of growth performance selection in beef cattle breeding program.


Asunto(s)
Envejecimiento/genética , Bovinos/embriología , Bovinos/fisiología , Islas de CpG/genética , Metilación de ADN , ARN Mensajero/genética , Proteínas Represoras/genética , Envejecimiento/metabolismo , Animales , Regulación del Desarrollo de la Expresión Génica/fisiología , Especificidad de Órganos/genética , ARN Mensajero/metabolismo , Proteínas Represoras/metabolismo , Estadística como Asunto , Distribución Tisular
12.
Int Immunopharmacol ; 23(1): 77-84, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25179784

RESUMEN

Ginsenoside Rg1 is one of the major active components of ginseng, which has been shown to regulate the immune response of hosts. However, the mechanism underlying the immunomodulatory effect of Rg1 is incompletely understood. In this study, we aimed to explore whether and how Rg1 regulates the innate immune response in macrophages. The results showed that Rg1 treatment significantly increased tumor necrosis factor (TNF)-α but decreased interleukin-6 (IL-6) protein expression in both lipopolysaccharide (LPS)-activated RAW 264.7 cells and mouse peritoneal macrophages. However, Rg1 reduced the mRNA levels of both cytokines in LPS-activated macrophages, which might be a consequence of decreased activation of IκB and nuclear factor-κB (NF-κB). Importantly, Rg1 treatment further promoted LPS-induced activation of the Akt/mechanistic target of rapamycin (mTOR) pathway, which is critical for controlling protein translation. The elevated Akt/mTOR signaling was likely responsible for increased production of TNF-α protein at the translational level, as suppression of this pathway by LY294002, an inhibitor of the upstream phosphatidylinositol 3-kinase (PI3K), abrogated such an enhancement of TNF-α protein expression even though its mRNA levels were conversely increased. These findings highlight a novel mechanism for Rg1 to regulate the innate immune response in macrophages through differentially modulating the NF-κB and PI3K/Akt/mTOR pathways.


Asunto(s)
Ginsenósidos/farmacología , Inmunidad Innata/efectos de los fármacos , Inmunomodulación , Macrófagos Peritoneales/efectos de los fármacos , Animales , Línea Celular , Cromonas/farmacología , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/metabolismo , Macrófagos Peritoneales/inmunología , Ratones , Ratones Endogámicos C57BL , Morfolinas/farmacología , FN-kappa B/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
13.
Int J Clin Exp Pathol ; 7(7): 3865-75, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25120763

RESUMEN

Unclassified renal cell carcinoma (URCC) is a rare variant of RCC, accounting for only 3-5% of all cases. Studies on the molecular genetics of URCC are limited, and hence, we report on 2 cases of URCC analyzed using comparative genome hybridization (CGH) and the genome-wide human exon GeneChip technique to identify the genomic alterations of URCC. Both URCC patients (mean age, 72 years) presented at an advanced stage and died within 30 months post-surgery. Histologically, the URCCs were composed of undifferentiated, multinucleated, giant cells with eosinophilic cytoplasm. Immunostaining revealed that both URCC cases had strong p53 protein expression and partial expression of cluster of differentiation-10 and cytokeratin. The CGH profiles showed chromosomal imbalances in both URCC cases: gains were observed in chromosomes 1p11-12, 1q12-13, 2q20-23, 3q22-23, 8p12, and 16q11-15, whereas losses were detected on chromosomes 1q22-23, 3p12-22, 5p30-ter, 6p, 11q, 16q18-22, 17p12-14, and 20p. Compared with 18 normal renal tissues, 40 mutated genes were detected in the URCC tissues, including 32 missense and 8 silent mutations. Functional enrichment analysis revealed that the missense mutation genes were involved in 11 different biological processes and pathways, including cell cycle regulation, lipid localization and transport, neuropeptide signaling, organic ether metabolism, and ATP-binding cassette transporter signaling. Our findings indicate that URCC may be a highly aggressive cancer, and the genetic alterations identified herein may provide clues regarding the tumorigenesis of URCC and serve as a basis for the development of targeted therapies against URCC in the future.


Asunto(s)
Carcinoma de Células Renales/genética , Genoma Humano , Neoplasias Renales/genética , Anciano , Carcinoma de Células Renales/patología , Hibridación Genómica Comparativa , Análisis Mutacional de ADN , Exones/genética , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/patología , Masculino , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos
14.
PLoS One ; 9(4): e93547, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24691407

RESUMEN

Cucurbitacin B (CuB), a potent antineoplastic agent of cucurbitacin triterpenoids, induces rapid disruption of actin cytoskeleton and aberrant cell cycle inhibiting carcinogenesis. However, the underlying molecular mechanism of such anticancer effects remains incompletely understood. In this study, we showed that CuB treatment rapidly induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation (i.e. activation) at the Ser157 residue and generated VASP clumps which were co-localized with amorphous actin aggregates prior to the formation of highly-ordered cofilin-actin rods in melanoma cells. Knockdown of VASP or inhibition of VASP activation using PKA-specific inhibitor H89 suppressed CuB-induced VASP activation, actin aggregation and cofilin-actin rod formation. The VASP activation was mediated by cAMP-independent PKA activation as CuB decreased the levels of cAMP while MDL12330A, an inhibitor of adenylyl cyclase, had weak effect on VASP activation. Knockdown of either Gα13 or RhoA not only suppressed VASP activation, but also ameliorated CuB-induced actin aggregation and abrogated cofilin-actin rod formation. Collectively, our studies highlighted that the CuB-induced actin aggregation and cofilin-actin rod formation was mediated via the Gα13/RhoA/PKA/VASP pathway.


Asunto(s)
Carcinogénesis/efectos de los fármacos , Moléculas de Adhesión Celular/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas de Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Citoesqueleto de Actina/efectos de los fármacos , Citoesqueleto de Actina/metabolismo , Factores Despolimerizantes de la Actina/genética , Factores Despolimerizantes de la Actina/metabolismo , Animales , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/genética , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Humanos , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/genética , Melanoma Experimental/patología , Ratones , Proteínas de Microfilamentos/antagonistas & inhibidores , Proteínas de Microfilamentos/genética , Fosfoproteínas/antagonistas & inhibidores , Fosfoproteínas/genética , Agregado de Proteínas/efectos de los fármacos , Triterpenos/administración & dosificación , Proteínas de Unión al GTP rho/genética , Proteína de Unión al GTP rhoA
15.
PLoS One ; 9(2): e89751, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24587010

RESUMEN

Cucurbitacin IIb (CuIIb) is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A)-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1) and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+) T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65), it blocked the nuclear translocation of NF-κB (p65). In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.


Asunto(s)
Inmunidad Adaptativa/efectos de los fármacos , Antiinflamatorios/farmacología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cucurbitacinas/farmacología , Linfocitos/efectos de los fármacos , Análisis de Varianza , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Western Blotting , Concanavalina A/metabolismo , Citoesqueleto/efectos de los fármacos , Cartilla de ADN/genética , Citometría de Flujo , Lectinas Tipo C/metabolismo , Ganglios Linfáticos/citología , Ratones , Microscopía Fluorescente , Reacción en Cadena en Tiempo Real de la Polimerasa
16.
Biochem Biophys Res Commun ; 441(4): 970-5, 2013 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-24220335

RESUMEN

Autophagy is a conserved mechanism for controlling the degradation of misfolded proteins and damaged organelles in eukaryotes and can be induced by nutrient withdrawal, including serum starvation. Although differential acetylation of autophagy-related proteins has been reported to be involved in autophagic flux, the regulation of acetylated microtubule-associated protein 1 light chain 3 (LC3) is incompletely understood. In this study, we found that the acetylation levels of phosphotidylethanolamine (PE)-conjugated LC3B (LC3B-II), which is a critical component of double-membrane autophagosome, were profoundly decreased in HeLa cells upon autophagy induction by serum starvation. Pretreatment with lysosomal inhibitor chloroquine did not attenuate such deacetylation. Under normal culture medium, we observed increased levels of acetylated LC3B-II in cells treated with tubacin, a specific inhibitor of histone deacetylase 6 (HDAC6). However, tubacin only partially suppressed serum-starvation-induced LC3B-II deacetylation, suggesting that HDAC6 is not the only deacetylase acting on LC3B-II during serum-starvation-induced autophagy. Interestingly, tubacin-induced increase in LC3B-II acetylation was associated with p62/SQSTM1 accumulation upon serum starvation. HDAC6 knockdown did not influence autophagosome formation but resulted in impaired degradation of p62/SQSTM1 during serum starvation. Collectively, our data indicated that LC3B-II deacetylation, which was partly mediated by HDAC6, is involved in autophagic degradation during serum starvation.


Asunto(s)
Autofagia/fisiología , Histona Desacetilasas/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Acetilación , Anilidas/farmacología , Autofagia/efectos de los fármacos , Medio de Cultivo Libre de Suero/farmacología , Técnicas de Silenciamiento del Gen , Células HeLa , Histona Desacetilasa 6 , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/genética , Humanos , Ácidos Hidroxámicos/farmacología , Lisosomas/fisiología , Fusión de Membrana , Proteolisis
17.
Chin Med J (Engl) ; 126(20): 3851-5, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24157144

RESUMEN

BACKGROUND: Multimodal cocktail periarticular injection (MCPI) with a large volume of low concentration local anesthetics, adrenaline, and anti-inflammatory agents such as non-steroidal anti-inflammatory drug or steroids have shown good pain control and improvement in range of motion after surgery. This study compares the efficacy of pain control after total knee arthroplasty, using multimodal cocktail periarticular injection with steroid or without steroid. METHODS: This is a prospective, double-blinded, randomized and control study. Seventy-two patients with osteoarthritis that met clinical criteria for total knee arthroplasty were recruited into the study, and were randomized to receive either multimodal cocktail periarticular injection with steroid or without steroid. Pain was assessed by visual analogue scale (VAS) at preoperative and postoperative at rest, and during activity. The range of motion was recorded preoperatively and postoperatively. The amount of daily and cumulative morphine consumption were measured by patient-controlled analgesia in the first 72 hours postoperatively. The duration of celecoxib usage was also recorded at the last follow-up. RESULTS: There were no differences between the non-steroid and steroid groups with regard to VAS at rest and during activity, or range of motion, at any postoperative observation time. The postoperative Knee Society Knee Score in the steroid group improved significantly as compared with that in non-steroid group at the one-month (84.1±13.1 and 65.9±12.1; P < 0.0045), three-month follow-up (90.2±16.3 and 72.5±16.6; P < 0.0027), but after postoperative six-month the Knee Society Knee Score showed no significant difference between the groups. There was no significant difference in consumption of the morphine about daily or total consumption within 72 hours between the two groups. The duration of celecoxib usage in patients in the steroid group was significantly shorter than that in the non-steroid group ((7.2±0.7) compared with (10.5±1.9) weeks; P = 0.012). CONCLUSION: The patients who received the steroid injection had faster rehabilitation and less non-steroidal antiinflammatory drugs consumption.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Anciano , Celecoxib , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Femenino , Humanos , Inyecciones Intraarticulares , Masculino , Dimensión del Dolor , Pirazoles/administración & dosificación , Pirazoles/uso terapéutico , Esteroides/administración & dosificación , Esteroides/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico
18.
Food Chem Toxicol ; 60: 424-30, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23939040

RESUMEN

Piperine, an alkaloid from black and long peppers (Piper nigrum Linn & Piper longum Linn), has been reported to exhibit antitumor activities in vitro and in vivo. To further understand the antitumor mechanism of piperine, we investigated the growth inhibitory effects of piperine on human prostate cancer DU145, PC-3 and LNCaP cells. Piperine treatment resulted in a dose-dependent inhibition of the proliferation of these cell lines. Cell cycle arrest at G0/G1 was induced and cyclin D1 and cyclin A were downregulated upon piperine treatment. Notably, the level of p21(Cip1) and p27(Kip1) was increased dose-dependently by piperine treatment in both LNCaP and DU145 but not in PC-3 cells, in line with more robust cell cycle arrest in the former two cell lines than the latter one. Although piperine induced low levels of apoptosis, it promoted autophagy as evidenced by the increased level of LC3B-II and the formation of LC3B puncta in LNCaP and PC-3 cells. The piperine-induced autophagic flux was further confirmed by assaying LC3-II accumulation and LC3B puncta formation in the presence of chloroquine, a well-known autophagy inhibitor. Taken together, these results indicated that piperine exhibited anti-proliferative effect in human prostate cancer cells by inducing cell cycle arrest and autophagy.


Asunto(s)
Alcaloides/toxicidad , Autofagia/efectos de los fármacos , Benzodioxoles/toxicidad , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Piperidinas/toxicidad , Alcamidas Poliinsaturadas/toxicidad , Neoplasias de la Próstata/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ciclina A1/genética , Ciclina A1/metabolismo , 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 , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Fase G1/efectos de los fármacos , Humanos , Masculino , Neoplasias de la Próstata/metabolismo , Regulación hacia Arriba
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(5): 599-602, 2012 May.
Artículo en Chino | MEDLINE | ID: mdl-22679716

RESUMEN

OBJECTIVE: To study the effects of tuina on the mechanical properties of skeletal muscles of four limbs in patients with chronic fatigue syndrome (CFS). METHODS: Thirty CFS patients were recruited as the test group, while another 30 healthy volunteers were recruited as the healthy control group. Patients in the test group received tuina therapy, 30 min each time, once every other day, for totally 10 times. Isokinetic testing technology was used to compare peak torque (PT), total watt (TW), average power (AP), and flexor/extensor (F/E) ratio in the elbow and knee muscles of CFS patients before and after treatment. The Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale was used to evaluate the fatigue degree before and after treatment, and compared with the healthy control group. RESULTS: After treatment the FACIT fatigue scale score decreased significantly in the test group when compared with before treatment (27.5 +/- 9.1 vs 42.5 +/- 11.2), showing statistical difference (P < 0.05). The pre-treatment PT, TW, AP, and F/E ratio in the skeletal muscle were all lower in the test group than in the healthy control group. Compared with before treatment in the test group, patients' elbow 60 degrees/s angular velocity values during exercise extensor PT and TW, knee 60 degrees/s and 180 degrees/s angular velocity values during exercise flexor PT and TW increased significantly; elbow extensor and knee extensor, flexor AP was significantly elevated; knee in 180 degrees/s angular velocity of movement F/E ratio significantly increased, and all the differences were statistically significant (P < 0.05). The improvement of the fatigue degree in CFS patients and elbow in 60 degrees/s angular velocity values under the flexor and extensor TW, and flexor AP value of the degree of improvement were negatively correlated (r = -0.282, -0.482, -0.285, P < 0.05, P < 0.01). Meanwhile, the muscles with the knee in 180 degrees/s angular velocity was negatively correlated with the F/E ratio of the degree of improvement (r = -0. 330, P < 0.05). CONCLUSIONS: CFS patients have lowered mechanical properties of four limbs. Tuina therapy can improve the biomechanical properties of limb skeletal muscle and reduce the overall degree of fatigue in patients. The changes of limb skeletal muscle and mechanical properties can provide objective reference for the clinical diagnosis and assessment of CFS.


Asunto(s)
Síndrome de Fatiga Crónica/fisiopatología , Síndrome de Fatiga Crónica/terapia , Medicina Tradicional China , Músculo Esquelético/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad
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