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Gestational diabetes mellitus (GDM) is a metabolic disease with an increasing annual incidence. Our previous observational study found that pregnant women with gestational diabetes had mild cognitive decline, which may be related to methylglyoxal (MGO). This study aimed to investigate whether labor pain aggravates the increase in MGO and explored the protective effect of epidural analgesia on metabolism in pregnant women with GDM based on solid-phase microextraction gas chromatography/mass spectrometry (SPME/GC-MS). Pregnant women with GDM were divided into a natural birth group (ND group, n = 30) and epidural analgesia group (PD group, n = 30). After fasting for ≥ 10 h overnight, venous blood samples were collected pre- and post-delivery to detect MGO, interleukin-6 (IL-6), and 8-epi-prostaglandin F2 alpha (8-iso-PGF2α) by ELISA. Serum samples were analyzed for volatile organic compounds (VOCs) using SPME-GC-MS. MGO, IL-6, and 8-iso-PGF2α levels in the ND group increased significantly post-delivery (P < 0.05) and were significantly higher in this group than the levels in the PD group (P < 0.05). Compared to the PD group, VOCs in the ND group increased significantly post-delivery. Further results indicated that propionic acid may be associated with metabolic disorders in pregnant women with GDM. Epidural analgesia can effectively improve the metabolism and immune function in pregnant women with GDM.
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Analgesia Epidural , Diabetes Gestacional , Compuestos Orgánicos Volátiles , Femenino , Humanos , Embarazo , Analgesia Epidural/efectos adversos , Interleucina-6 , Óxido de Magnesio , Metabolómica , Piruvaldehído , Compuestos Orgánicos Volátiles/efectos adversosRESUMEN
The aim of the present study was to investigate the respiratory parameters that influence the exhaled breath temperature (EBT) and the feasibility of using the latter to monitor the core temperature under general endotracheal anesthesia. A total of 20 patients undergoing abdominal surgery were included in the present study. At the first stage of the experiment, the respiratory rate was adjusted, while the other respiratory parameters [tidal volume, inspiratory and expiratory time ratio (TI:TE), and positive end expiratory pressure (PEEP)] were maintained at a constant level. At the second stage, the tidal volume was adjusted, while the other respiratory parameters were maintained at a constant level. At the third stage, the TI:TE was adjusted, while the other parameters were maintained at a constant level. At the fourth stage, PEEP was adjusted, while the other parameters were maintained at a constant level. In each experiment, the EBT, the maximum temperature of exhaled air in each min, the inhaled air temperature and the nasopharyngeal temperature (T nose) were recorded every min. During the first stage of the experiment, no significant difference was noted in the EBT at different levels of respiratory rate. During the second, third and fourth stage, no significant difference was noted in the EBT at different tidal volumes, TI:TE and PEEP, respectively. The EBT was significantly correlated with the T nose. Overall, the present study demonstrated that the EBT of patients undergoing abdominal surgery under general endotracheal anesthesia was not affected by the examined respiratory parameters and that it could be considered a feasible method of monitoring core temperature.
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BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease with an increasing annual incidence rate. Our previous observational study found that pregnant women with GDM had mild cognitive decline. AIM: To analyze the changes in metabonomics in pregnant women with GDM and explore the mechanism of cognitive function decline. METHODS: Thirty GDM patients and 30 healthy pregnant women were analyzed. Solid-phase microextraction gas chromatography/mass spectrometry was used to detect organic matter in plasma and urine samples. Statistical analyses were conducted using principal component analysis and partial least squares discriminant analysis. RESULTS: Differential volatile metabolites in the serum of pregnant women with GDM included hexanal, 2-octen-1-ol, and 2-propanol. Differential volatile metabolites in the urine of these women included benzene, cyclohexanone, 1-hexanol, and phenol. Among the differential metabolites, the conversion of 2-propanol to acetone may further produce methylglyoxal. Therefore, 2-propanol may be a potential marker for serum methylglyoxal. CONCLUSION: 2-propanol may be a potential volatile marker to evaluate cognitive impairment in pregnant women with GDM.
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Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is the most popular platform for untargeted metabolomics studies, but compound annotation is a challenge. In this work, we developed a new LC-HRMS data-targeted extraction method called MetEx for metabolite annotation. MetEx contains the retention time (tR), MS1, and MS2 information of 30â¯620 metabolites from freely available spectral databases, including MoNA and KEGG. The tR values of 95.4% of the compounds in our database were calculated by the GNN-RT model. The MS2 spectra of 39.4% compounds were also predicted using CFM-ID. MetEx was initially examined on a mixture of 634 standards, considering chemical coverage and accurate metabolite assignment, and later applied to human plasma (NIST SRM 1950), human urine, HepG2 cells, mouse liver tissue, and mouse feces. MetEx correctly assigned 252 out of 253 standards detected in our instruments. The platform also provided 8.0-44.2% more compounds in the biological samples compared to XCMS, MS-DIAL, and MZmine 2. MetEx is implemented and visualized in R and freely available at http://www.metaboex.cn/MetEx.
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Metabolómica , Plasma , Animales , Cromatografía Liquida/métodos , Bases de Datos Factuales , Espectrometría de Masas/métodos , Metabolómica/métodos , Metotrexato , RatonesRESUMEN
BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is associated with cognitive dysfunction in patients with type 2 diabetes. AIM: To assess a possible relationship between serum DPP4 and cognitive function in perinatal pregnant women with gestational diabetes mellitus (GDM). METHODS: The study subjects were divided into three groups: GDM group (n = 81), healthy pregnant (HP) group (n = 85), and control group (n = 51). The Montreal Cognitive Assessment (MoCA) was used to assess the cognitive status of each group. Venous blood samples were collected to measure blood lipids, glycated hemoglobin, and glucose levels. For each participant, a 3-mL blood sample was collected and centrifuged, and the serum was collected. Blood samples were stored at -80 â, and DPP4, interleukin-6 (IL-6), and 8-iso-prostaglandin F2α (8-iso-PGF2α), and brain-derived neurotrophic factor (BDNF) were detected using ELISA. RESULTS: The MoCA scores in the GDM and HP groups were significantly different from those in the control group in terms of visuospatial/executive function and attention (P < 0.05); however, the scores were not significantly different between the GDM and HP groups (P > 0.05). In terms of language, the GDM group had significantly different scores from those in the other two groups (P < 0.05). In terms of memory, a significant difference was found between the HP and control groups (P < 0.05), as well as between the GDM and HP groups. The levels of DPP4, IL-6, and 8-iso-PGF2α in the GDM group were significantly higher than those in the HP and control groups (P < 0.05); however, the differences between these levels in the HP and control groups were not significant (P > 0.05). The level of BDNF in the GDM group was significantly lower than that in the HP and control groups (P < 0.05), although the difference in this level between the HP and control groups was not significant (P > 0.05). CONCLUSION: Cognitive dysfunction in perinatal pregnant women with GDM mainly manifested as memory loss, which might be associated with elevated DPP4 levels.
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BACKGROUND: Breast cancer remains one of the most dreadful female malignancies globally, in which cancer stem cells (CSCs) play crucial functions. Circular RNAs have drawn great attention in cancer research area and propofol is a widely applied intravenous anesthetic agent. METHODS: In the current study, we explored the function of circular RNA nucleolar and coiled-body phosphoprotein 1 (circNOLC1) in CSCs of breast cancer and the inhibitory impact of propofol on circNOLC1. RESULTS: The expression of circNOLC1 was induced in breast cancer tissues compared with the non-tumor tissues. The silencing of circNOLC1 was able to repress the viability of breast cancer cells. Meanwhile, the numbers of colony formation were suppressed by circNOLC1 knockdown in breast cancer cells. The inhibition of circNOLC1 reduced the invasion and migration ability of breast cancer cells. The mRNA and protein levels of E-cadherin were enhanced but Vimentin levels were reduced by the silencing of circNOLC1. The repression of circNOLC1 decreased the side population (SP) ratio in breast cancer cells. Meanwhile, the sphere formation ability of breast cancer cells was attenuated by the silencing of circNOLC1. The levels of ATP-binding cassette (ABC) superfamily G member 2 (ABCG2), c-Myc, B cell-specific Moloney murine leukemia virus integration site 1 (Bmi1), and SRY-box transcription factor 2 (Sox2) were repressed by the depletion of circNOLC1 in the cells. Regarding to the mechanism, circNOLC1 functioned as a competing endogenous RNAs (ceRNAs) for microRNA-365a-3p (miR-365a-3p) and the inhibition of miR-365a-3p rescued circNOLC1 depletion-repressed proliferation and cancer stem cell activity of breast cancer. MiR-365a-3p targeted signal transducer and activator of transcription 3 (STAT3) in breast cancer cells and circNOLC1 enhanced STAT3 expression by sponging miR-365a-3p. The overexpression of STAT3 could reverse miR-365a-3p or circNOLC1 depletion-inhibited proliferation and cancer stem cell properties of breast cancer. Interestingly, the expression of circNOLC1 and STAT3 was repressed by the treatment of propofol. The enrichment of STAT3 on circNOLC1 promoter was inhibited by propofol. The expression of circNOLC1 was suppressed by the silencing of STAT3 in the cells. The inhibition of circNOLC1 expression by propofol was rescued under the co-treatment of STAT3 overexpression. The overexpression of circNOLC1 rescued propofol-attenuated proliferation and cancer stem cell functions in vitro and in vivo. CONCLUSIONS: Thus, we concluded that circNOLC1 contributes to CSCs properties and progression of breast cancer by targeting miR-365a-3p /STAT3 axis and propofol inhibited circNOLC1 by repressing STAT3 in a feedback mechanism.
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MicroARNs , Neoplasias , Propofol , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Ratones , MicroARNs/genética , Células Madre Neoplásicas/metabolismo , Propofol/farmacología , ARN Circular , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
Purpose: To explore whether pregnant women with gestational diabetes mellitus (GDM) had cognitive impairment and assess cognitive function in normal pregnant women. Methods: A total of 75 consecutive women diagnosed with GDM (GDM group), 70 normal pregnant women (NP group) without diabetes and matched for age, and 51 female volunteers (CG group) with the similar age level, normal blood glucose, and nonpregnancy were included in the study. For the assessment of cognitive functions, Montreal Cognitive Assessment (MoCA) was performed. Venous blood samples were collected to measure blood glucose, glycated hemoglobin (HbA1c), methylglyoxal (MGO), beta amyloid (Aß), and tau protein. Results: The score of MoCA of GDM was lowest, and the score of the NP group was lower than volunteers (P < 0.05). The incidence of cognitive dysfunction increased significantly in the GDM group with statistical significance (P < 0.05). The levels of tau and MGO in the GDM group were significantly less than those in the NP and CG groups, and Aß in the GDM group was significantly more than that in the NP and CG groups (P < 0.05), but the differences between NP and CG groups were not statistically significant (P < 0.05). Conclusion: The pregnant women with GDM showed a significant decline in cognitive function, and the normal pregnant women also showed a decline in cognitive function which is very light.
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Disfunción Cognitiva , Diabetes Gestacional , Adulto , Glucemia , Disfunción Cognitiva/epidemiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Embarazo , Mujeres EmbarazadasRESUMEN
BACKGROUND: Central nervous system (CNS) infectious diseases are common diseases in emergency rooms and neurology departments. CNS pathogen identification methods are time consuming and expensive and have low sensitivity and poor specificity. Some studies have shown that bacteria and viruses can produce specific volatile organic compounds (VOCs). The aim of this study is to find potential biomarkers by VOC analysis of cerebrospinal fluid (CSF) in patients with bacterial and viral meningitis/encephalitis (ME). METHODS: CSF samples from 16 patients with bacterial ME and 42 patients with viral ME were collected, and solid-phase microextraction combined with gas chromatography-mass spectrometry was used to analyze the metabolites in the CSF. RESULTS: There are 2 substances (ethylene oxide and phenol) that were found to be different between the 2 groups. Ethylene oxide was significantly greater in the group of bacterial ME patients than in the viral ME group of patients (p < 0.05). In addition, phenol was remarkably increased in the group of ME patients compared with the bacterial ME patients (p < 0.05). CONCLUSIONS: Ethylene oxide and phenol may be potential biomarkers to distinguish bacterial ME and viral ME. VOC analysis of CSF may be used as a supporting tool for clinical diagnosis.
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Enfermedades Transmisibles , Meningitis Bacterianas , Virus , Compuestos Orgánicos Volátiles , Bacterias , Sistema Nervioso Central , Humanos , Proyectos PilotoRESUMEN
In order to study anesthetic pharmacokinetics and adequately adjust the anaesthesia depth of patients, real-time measurement of the intraoperative exhaled propofol concentration is of significant importance for anaesthetists. Although a series of analytical techniques and methods have been developed for the detection of exhaled propofol, differential mobility spectrometry (DMS) with the advantages of a much smaller instrument, faster response time and cheaper cost shows great potential for the point of care in the operating room. In this paper, a planar DMS was constructed for real-time continuous measurement of trace propofol in exhaled air. The effects of DMS parameters, such as the radio frequency voltage, the drift gas flow rate and the sampling flow rate of exhaled air on the propofol measurement under high humidity conditions were carefully investigated and discussed. Under the optimum experimental conditions, the limit of detection (LOD) for propofol was achieved in ppbv with a linear range of 0.5 to 25 ppbv, both of which meet clinical requirements. Finally, the planar DMS was performed on a patient undergoing thyroidectomy surgery to real-time monitor the intraoperative exhaled propofol, which demonstrated the capability of DMS for sensitive and breath-by-breath continuous measurement of intraoperative trace exhaled propofol.
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Propofol , Pruebas Respiratorias , Espiración , Humanos , Monitoreo Fisiológico , Análisis EspectralRESUMEN
We aimed to investigate the role and mechanism of sevoflurane (SEV) preconditioning in liver ischemia-reperfusion (I/R) injury. In vivo, rats were randomly divided into Sham group, I/R rat model group, I/R + SEV group and SEV group. In vitro, hypoxia-reoxygenation (H/R) cell model were established. Hematoxylin-Eosin (H&E) and TUNEL assay were used to evaluate the degree of tissue damage and detect apoptosis in rats, respectively. HO-1, nuclear Nrf2 and cytosolic Nrf2 expressions were detected by immunohistochemical staining, Western blot analysis and quantitative real-time PCR (qRT-PCR), respectively. Contents of Lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS) were determined by corresponding kits. Inflammatory factor levels, cell viability, apoptosis were detected by enzyme-linked immunosorbent assay (ELISA), MTT assay, and flow cytometry, respectively.In the I/R group, liver damage was severe, apoptosis-positive cells were increased, HO-1 and nuclear Nrf2 expressions were increased, and cytosolic Nrf2 expression was decreased. After SEV pretreatment, the degree of liver injury and apoptosis in rats were significantly reduced, HO-1 and nuclear Nrf2 expressions were increased significantly, and cytosolic Nrf2 expression was decreased. 4% SEV had the best mitigating effect on H/R-induced liver cell damage, as evidenced by reduced contents of LDH and MDA, decreased inflammatory factors, a lowered apoptosis rate, inhibited ROS production, effectively promoted Nrf2 nucleation, and activated Nrf/HO-1 pathway. ML385 pretreatment significantly inhibited the effect of SEV on hepatocytes.Sevoflurane protects the liver from ischemia-reperfusion injury by regulating the Nrf2/HO-1 pathway.
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Hemo Oxigenasa (Desciclizante)/metabolismo , Hemo-Oxigenasa 1/metabolismo , Hepatocitos/efectos de los fármacos , Hepatopatías/prevención & control , Hígado/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Daño por Reperfusión/prevención & control , Sevoflurano/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Hemo Oxigenasa (Desciclizante)/genética , Hemo-Oxigenasa 1/genética , Hepatocitos/enzimología , Hepatocitos/patología , Mediadores de Inflamación/metabolismo , Hígado/enzimología , Hígado/patología , Hepatopatías/enzimología , Hepatopatías/patología , Masculino , Proteínas de la Membrana/genética , Ratones , Estrés Oxidativo/efectos de los fármacos , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Transducción de SeñalRESUMEN
Humidity as a major issue affects the quantitative performance of ion mobility spectrometry (IMS) in field applications. According to the kinetic equations of ion-molecular reaction, the intensity ratio of the product ion peak (PIP) over the reactant ion peak (RIP) is proposed as a quantitative factor to correct real-time humidity variation. By coupling this method with a unidirectional anisole-assisted photoionization IMS, direct breath-by-breath measurement of intraoperative propofol was achieved for the first time, which provided more clinical information for studying the anesthetics pharmacokinetics. Although the signal intensities of the RIP and the propofol PIP both declined along with the increase of humidity, the intensity ratio of Propofol/(RIP + Propofol) kept almost constant in a wide relative humidity range of 0%-98%, enabling direct quantitation of exhaled propofol with varying humidity. Furthermore, interfering ion peaks resulted from the high concentration humidity and anesthetics in single exhalation were eliminated during the balanced anesthesia as the exhaled sample was diluted by the unidirectional gas flow scheme. As a demonstration, breath-by-breath variation profiles of propofol were obtained via monitoring end-tidal propofol concentration of intraoperative anesthetized patients (n = 7). The analyses were quantitative, corrected for humidity in real-time, without measuring the humidity content of each breath sample during operation, which show potential for the quantitative analysis of other high humidity samples.
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Propofol , Anisoles , Pruebas Respiratorias , Espiración , Humanos , Humedad , Espectrometría de Movilidad Iónica , Propofol/análisisRESUMEN
BACKGROUND: Gastric cancer is a common malignancy with poor prognosis, in which ferroptosis plays a crucial function in its development. Propofol is a widely used anesthetic and has antitumor potential in gastric cancer. However, the effect of propofol on ferroptosis during gastric cancer progression remains unreported. AIM: To explore the function of propofol in the regulation of ferroptosis and malignant phenotypes of gastric cancer cells. METHODS: MTT assays, colony formation assays, Transwell assays, wound healing assay, analysis of apoptosis, ferroptosis measurement, luciferase reporter gene assay, and quantitative reverse transcription polymerase chain reaction were used in this study. RESULTS: Our data showed that propofol was able to inhibit proliferation and induce apoptosis of gastric cancer cells. Meanwhile, propofol markedly repressed the invasion and migration of gastric cancer cells. Importantly, propofol enhanced the erastin-induced inhibition of growth of gastric cancer cells. Consistently, propofol increased the levels of reactive oxygen species, iron, and Fe2+ in gastric cancer cells. Moreover, propofol suppressed signal transducer and activator of transcription (STAT)3 expression by upregulating miR-125b-5p and propofol induced ferroptosis by targeting STAT3 in gastric cancer cells. The miR-125b-5p inhibitor or STAT3 overexpression reversed propofol-attenuated malignant phenotypes of gastric cancer cells. CONCLUSION: Propofol induced ferroptosis and inhibited malignant phenotypes of gastric cancer cells by regulating the miR-125b-5p/STAT3 axis. Propofol may serve as a potential therapeutic candidate for gastric cancer.
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Rapid and quantitative determination of blood propofol concentration is important for anesthesiologists to accurately control intraoperative propofol dose, timely monitor physiological statuses of patients and greatly improve the safety of surgery. Herein, a dopant-assisted negative photoionization ion mobility spectrometer with the optimized ionization region structure and the three-way inlet design was developed, increasing the generation ratio of the reactant ions O2-, and improving the ionization efficiency of propofol molecules. Besides, the addition of methanol-anisole solution during injection promoted the neutral desorption of propofol in blood, further improving the detection sensitivity by an order of magnitude, eliminating any sample pretreatment and effectively reducing the single analysis time to less than 1 min compared to the previous article. The dual calibration quantitative method, i.e. the method of calibrating the O2- concentration and the sample concentration changes during the entire process of detecting propofol through the integral value of M·O2- and the maximum signal intensity of O2-, successfully achieved accurate quantification of blood propofol. And the linear calibration curve of propofol was obtained with the range of 0.1-15 ng µL-1 and with the limit of detection of 0.03 ng µL-1, which was fulfilled to conduct propofol determination throughout the perioperative period. Finally, this method was applied to clinically measure the blood propofol concentration in patients newly regained consciousness with concentrations ranging from 0.2 ng µL-1 to 3 ng µL-1, and it turned out that the older patient had the lower propofol concentration in blood.
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Propofol , Calibración , Humanos , Iones , Periodo Perioperatorio , SolventesRESUMEN
BACKGROUND: It has proved that there is an association between cancer and volatile organic compounds (VOCs) of exhaled breath. This study targets on verifying the existence of specific VOCs in breathing in breast cancer patients, especially those with ductal carcinoma in situ (DCIS). METHODS: There were a total of 203 participants included in the final analysis, which included 71 (35.0%) patients with histologically confirmed breast cancer (including 13 with DCIS, 31 with lymph node metastasis-negative status, and 27 with lymph node metastasis-positive status), 78 (38.4%) healthy volunteers, and 54 (26.6%) patients with histologically confirmed gastric cancer. Gas chromatography-mass spectrometry and solid-phase microextraction were used to analyze the breath samples for the presence of VOCs. RESULTS: There were significant differences in the volatile organic metabolites between the DCIS, lymph node metastasis-negative breast cancer, and lymph node metastasis-positive breast cancer groups compared with the healthy controls as well as between the breast cancer and gastric cancer patients. An overlapping set of seven VOCs, including (S)-1,2-propanediol, cyclopentanone, ethylene carbonate, 3-methoxy-1,2-propanediol, 3-methylpyridine, phenol, and tetramethylsilane, was significantly different between the breast cancer patients and healthy individuals as well as between the breast cancer and gastric cancer patients. The combination of these seven compounds was considered as a biomarker for breast cancer. The sensitivity for predicting DCIS by this set of seven compounds was determined to be 80.77%, and the specificity was determined to be 100%. CONCLUSIONS: This set of seven breast cancer-specific VOCs can be regarded as one particular expiratory marker for DCIS and will help to establish new screening methods for early breast cancer.
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Neoplasias de la Mama/diagnóstico , Pruebas Respiratorias/métodos , Carcinoma Intraductal no Infiltrante/diagnóstico , Detección Precoz del Cáncer/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Compuestos Orgánicos Volátiles/análisisRESUMEN
Because of the greatly different physicochemical properties of metabolites, comprehensive metabolite profiling analysis has always been a challenging task. Reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) have been used to the analysis of nonpolar metabolites and polar metabolites, respectively. In this work, an alternate HILIC/RPLC-mass spectrometry (MS) approach was developed for the comprehensive and high-throughput analysis of polar and nonpolar metabolites. HILIC and RPLC are respectively performed on two ultra-high performance LC (UHPLC) systems, and coupled to one mass spectrometer to acquire the data. When HILIC gradient elution is running RPLC is in a washing and equilibration state, and vice versa. As a result, the total analysis time was reduced by about one third to 25.4 min. Two hundred and eight representative standards including at least twelve types of commonly met metabolites, SRM 1950 plasma, serum, urine and liver tissue samples were used to test the established alternate HILIC/RPLC-MS method. The results demonstrated that the method possessed high metabolite coverage. The developed method was validated to have good linearity and repeatability. As an example of application, 61 significantly changed metabolites in the colon cancer tissues were defined by this established method.
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Cromatografía de Fase Inversa/métodos , Espectrometría de Masas/métodos , Metaboloma/fisiología , Metabolómica/métodos , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Neoplasias del Colon/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Límite de Detección , Modelos Lineales , Hígado/metabolismo , Ratones , Reproducibilidad de los ResultadosRESUMEN
Unclarified molecular mechanism and lack of practical diagnosis biomarkers hinder the effective treatment of non-small-cell lung cancer. Herein, we performed liquid chromatography-mass spectrometry-based nontargeted metabolomics analysis in 131 patients with their lung tissue pairs to study the metabolic characteristics and disordered metabolic pathways in lung tumor. A total of 339 metabolites were identified in metabolic profiling. Also, 241 differential metabolites were found between lung carcinoma tissues (LCTs) and paired distal noncancerous tissues; amino acids, purine metabolites, fatty acids, phospholipids, and most of lysophospholipids significantly increased in LCTs, while 3-phosphoglyceric acid, phosphoenolpyruvate, 6-phosphogluconate, and citrate decreased. Additionally, pathway enrichment analysis revealed that energy, purine, amino acid, lipid, and glutathione metabolism are markedly disturbed in lung cancer (LCa). Using binary logistic regression, we further defined candidate biomarkers for different subtypes of lung tumor. Xanthine and PC 35:2 were selected as combinational biomarkers for distinguishing benign from malignant lung tumors with a 0.886 area under curve (AUC) value, and creatine, myoinositol and LPE 16:0 were defined as combinational biomarkers for discriminating adenocarcinoma from squamous cell lung carcinoma with a 0.934 AUC value. Overall, metabolic characterization and pathway disturbance demonstrated apparent metabolic reprogramming in LCa. The defined candidate metabolite marker panels are useful for subtyping of lung tumors to assist clinical diagnosis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Biomarcadores , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Cromatografía Liquida , Humanos , Neoplasias Pulmonares/diagnóstico , Espectrometría de Masas , Redes y Vías Metabólicas , MetabolómicaRESUMEN
Online measuring end-tidal propofol concentration during balanced anesthesia is important for anesthetists to learn the patient's anesthesia depth as exhaled propofol concentration is well related to blood propofol concentration. In previous work, exhaled propofol was detected using acetone assisted negative photoionization ion mobility spectrometer, however, the existence of high concentration sevoflurane interfered the response of propofol. In this work, an anisole assisted photoionization ion mobility spectrometer operated in positive mode was developed to sensitively and selectively measure the end-tidal propofol by eliminating the interferences of exhaled humidity and sevoflurane during balanced anesthesia. Anisole molecular ion is stable enough not to go under proton transfer reaction with water presents in the exhaled breath. Hence, the exhaled humidity related peaks were eliminated and only one propofol product ion peak (K0 = 1.50 cm2 V-1 s-1) was observed. The relative standard deviation (RSD) ranging from 0.64%-0.91% showed good repeatability and the quantitative range was 0.2-40 ppbv with a response time of 4 s. Finally, the performance of the proposed method was demonstrated by monitoring end-tidal propofol of balanced anesthetized patients during gastric cancer surgery.
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Anestésicos Intravenosos/análisis , Anisoles/análisis , Pruebas Respiratorias/métodos , Monitoreo de Drogas/métodos , Espectrometría de Movilidad Iónica/métodos , Propofol/análisis , Neoplasias Gástricas/cirugía , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/farmacocinética , Anestesia Balanceada/métodos , Pruebas Respiratorias/instrumentación , Espiración , Femenino , Humanos , Persona de Mediana Edad , Sistemas en Línea , Propofol/administración & dosificación , Propofol/farmacocinética , Distribución TisularRESUMEN
The concentration of propofol in blood is an important indicator for anesthesiologists to monitor and regulate the anesthesia depth of patients during surgery. Herein, a negative photoionization ion mobility spectrometry with acetone as the dopant was developed for rapid and direct determination of intraoperative blood propofol concentration in the operating theatre. High concentration of acetone molecules in the carrier gas was used not only to enhance neutral desorption and release free propofol molecules from the whole blood, but also to increase the intensity of reactant O2- and reduce the amount of non-reactive CO3- ions simultaneously, which allowed to measure trace propofol in less than 2â¯min without any tedious pretreatment. Under optimized conditions, a linear calibration curve of propofol was obtained with the range of 0.5-20â¯ng⯵L-1 and with a limit of detection of 0.14â¯ng⯵L-1, which met the clinical requirements and correlated well with standard HPLC methods. Finally, the method was applied to detect intraoperative blood propofol concentration in nearly 100 surgical patients, demonstrating its excellent detection capability and facilitating the study of propofol pharmacokinetics.
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Espectrometría de Movilidad Iónica , Propofol/sangre , Humanos , Espectrometría de Movilidad Iónica/instrumentación , Procesos FotoquímicosRESUMEN
As the number of elderly patients increases, some patients with heart problems may also need surgery. The purpose of this study was to investigate whether dexmedetomidine (DEX), a common used anesthetic, was beneficial to the patients with heart problems. Myocardial cells induced by doxorubicin (DOX) was to simulate the myocardium injury in vitro. H9c2 cells were treated with DOX, DEX/DOX, Compound C and Compound C/DEX/DOX, respectively. The expression of p-AMPK, AMPK, p-GSK3ß, GSK3ß, Bcl2, Bax, Cleaved caspase3, Caspase3, TXNIP, NLRP3, ASC, Cleaved caspase-1 and Caspase-1 were analyzed by Western blot. CCK-8 assay and flow cytometry analysis were used to detect the cell viability and cell apoptosis. The levels of TNF-α, IL-1ß and IL-18 were detected by ELISA assay and the levels of NO, ROS, LDH, SOD, MDA and taurine were detected by corresponding assay kits. As a result, DEX promoted the cell viability and inhibited the inflammation, oxidative stress and apoptosis. In addition, DEX suppressed the expression of taurine, TXNIP, NLRP3, ASC and cleaved caspase-1 and activated the expression of p-AMPK and p-GSK3ß. However, those above changes could be reversed by Compound C. In conclusion, this study indicated that DEX could reduce the inflammation and apoptosis of DOX-induced myocardial cells through activating the AMPK-GSK3ß signaling pathway. Because of the above effects of DEX, it may be beneficial for surgical patients with heart problems.
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Apoptosis/efectos de los fármacos , Dexmedetomidina/farmacología , Doxorrubicina/efectos adversos , Inflamación/patología , Miocitos Cardíacos/patología , Adenilato Quinasa/metabolismo , Animales , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Taurina/metabolismoRESUMEN
BACKGROUND: Volatile organic compound (VOC) analysis provides an elegant approach for colorectal cancer screening. An organic compound with a high vapor pressure or volatility can be detected in the headspace of cancer cells or blood samples. Therefore, analyzing VOCs in the blood of rats inoculated with colorectal cancer tissue and in SW480 medium from cultured colorectal cancer cells may provide accurate results. METHODS: After collecting venous blood from rats inoculated with cancer cells at different times, the cancer tissue was removed from the inoculated rats, and the medium was harvested from the cancer cells and cultured in the presence or absence of a chemotherapy drug of intestinal epithelial cells. We used solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) to analyze the headspace of the blood and media to evaluate the VOC profiles. Statistical analysis was conducted using principal component analysis (PCA) and orthogonal partial least-squares analysis (OP-LSDA). RESULTS: The in vivo and in vitro analyses of the colorectal cancer samples revealed a variety of compounds, such as cyclohexanone, 1-hexanol, 2-ethyl-, butylated hydroxytoluene, cyclotrisiloxane, hexamethyl-, pentanoic acid, 2,2,4-trimethyl-3-hydroxy-isobutyl ester and acetone. Butylated hydroxytoluene is unique with regard to its presence during tumor growth and resection; it is also present during tumor cell growth and necrosis. Acetone showed unique trends in the in vivo experimental group. CONCLUSIONS: By analyzing VOC fingerprints related to colorectal cancer (CRC), we found that butylated hydroxytoluene and acetone have unique signatures that may provide the basis for clinical diagnosis and disease assessment.