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The global incidence rate of kidney cancer (KC) has been steadily increasing over the past 30 years. With the aging global population, kidney cancer has become an escalating concern that necessitates vigilant surveillance. Nowadays, surgical intervention remains the optimal therapeutic approach for kidney cancer, while the availability of efficacious treatments for advanced tumors remains limited. Oncolytic viruses, an emerging form of immunotherapy, have demonstrated encouraging anti-neoplastic properties and are progressively garnering public acceptance. However, research on oncolytic viruses in kidney cancer is relatively limited. Furthermore, given the high complexity and heterogeneity of kidney cancer, it is crucial to identify an optimal oncolytic virus agent that is better suited for its treatment. The present study investigates the oncolytic activity of the Pseudorabies virus live attenuated vaccine (PRV-LAV) against KC. The findings clearly demonstrate that PRV-LAV exhibits robust oncolytic activity targeting KC cell lines. Furthermore, the therapeutic efficacy of PRV-LAV was confirmed in both a subcutaneous tumor-bearing nude mouse model and a syngeneic mouse model of KC. Combined RNA-seq analysis and flow cytometry revealed that PRV-LAV treatment substantially enhances the infiltration of a diverse range of lymphocytes, including T cells, B cells, macrophages, and NK cells. Additionally, PRV-LAV treatment enhances T cell activation and exerts antitumor effects. Importantly, the combination of PRV-LAV with anti-PD-1 antibodies, an approved drug for KC treatment, synergistically enhances the efficacy against KC. Overall, the discovery of PRV-LAV as an effective oncolytic virus holds significant importance for improving the treatment efficacy and survival rates of KC patients.
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Vacinas Anticâncer , Herpesvirus Suídeo 1 , Inibidores de Checkpoint Imunológico , Neoplasias Renais , Vírus Oncolíticos , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Herpesvirus Suídeo 1/genética , Neoplasias Renais/terapia , Vírus Oncolíticos/genética , Receptor de Morte Celular Programada 1 , Microambiente Tumoral , Vacinas Atenuadas , Vacinas Anticâncer/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
INTRODUCTION: Previous studies have confirmed that low shear stress (LSS) induces glycocalyx disruption, leading to endothelial dysfunction. However, the role of autophagy in LSS-induced glycocalyx disruption and relevant mechanism are not clear. In this study, we hypothesized that LSS may promote autophagy, disrupting the endothelium glycocalyx. METHODS: Human umbilical vein endothelial cells were subjected to physiological shear stress and LSS treatments, followed by the application of autophagy inducers and inhibitors. Additionally, cells were treated with specific matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) inhibitor. The expression of autophagic markers, glycocalyx, MMP-2, and MMP-9 was measured. RESULTS: LSS impacted the expression of endothelium autophagy markers, increasing the expression of LC3II.LC3I-1 and Beclin-1, and decreasing the levels of p62, accompanied by glycocalyx disturbance. Moreover, LSS upregulated the expression of MMP-2 and MMP-9 and downregulated the levels of syndecan-1 and heparan sulfate (HS). Additionally, expression of MMP-2 and MMP-9 was increased by an autophagy promoter but was decreased by autophagy inhibitor treatment under LSS. Autophagy and MMP-2 and MMP-9 further caused glycocalyx disruption. CONCLUSION: LSS promotes autophagy, leading to glycocalyx disruption. Autophagy increases the expression of MMP-2 and MMP-9, which are correlated with the glycocalyx destruction induced by LSS.
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Glicocálix , Metaloproteinase 2 da Matriz , Humanos , Glicocálix/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Autofagia , Estresse MecânicoRESUMO
OBJECTIVE: Protein kinase C (PKC) has been implicated in the increased contraction of human airway smooth muscle cells (HASMCs) in asthma. Using the three-dimensional collagen gel contraction system, the study aimed to determine the effects of LY333531, a specific inhibitor of the PKC-ß isoform, on the contraction of tumor necrosis factor (TNF)-α-sensitized HASMCs. METHODS: Cultured HASMCs were divided into five groups: the control group received no treatment, and the cells in the TNF-α group were sensitized with 10 ng/mL TNF-α for 48 h, while TNF-α was administered to sensitize HASMCs in the presence of 0.1, 0.2, and 0.5 µM LY333531 for 48 h in the 0.1LY, 0.2LY, and 0.5LY groups, respectively. Following this, HASMCs contraction was stimulated with 1 mM acetylcholine (ACh) for up to 24 h in each group and assessed using a three-dimensional collagen gel contraction assay. Furthermore, western blot and immunofluorescence analysis were performed. RESULTS: The collagen gel contraction assay revealed that TNF-α increased the protein expression of phosphorylated PKC-ß2, CPI-17, and MLC while exacerbating ACh-induced HASMCs contraction. LY333531 significantly attenuated HASMCs contraction and downregulated the protein expression of both p-CPI-17 and p-MLC. CONCLUSIONS: At least in part by regulating CPI-17 and MLC phosphorylation, LY333531 attenuates augmented contraction of TNF-α-sensitized HASMCs in a collagen gel contraction system.
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Miócitos de Músculo Liso , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Contração Muscular/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Proteína Quinase C/metabolismo , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C beta/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
The investigation of deep-sea microorganisms holds immense significance and value in advancing the fields of life sciences, biotechnology, and environmental conservation. However, the current lack of specialized underwater objectives specifically designed for in situ studies of deep-sea microorganisms hampers progress in this area. To address this limitation, we present the design of a multi-band Raman tweezer objective tailored for deep-sea environments. The objective is integrated into a high-pressure chamber capable of withstanding depths up to 1.5â km, enabling in situ microscopic imaging, optical tweezer capture, and Raman detection of deep-sea microorganisms. Through meticulous structural optimization, meticulous material selection, and thorough mechanical analysis of the underwater optical window, the objective exhibits remarkable attributes such as multi-band functionality, extended working distance, and high numerical aperture. Our design yields image quality near the diffraction limit, successfully achieving flat-field and apochromatic performance in each respective wavelength bands. Moreover, the tolerance analysis demonstrates that the full-field root mean square (RMS) wave aberration approaches λ/14, effectively meeting the demands of manufacturing and practical applications. This objective lens constitutes a vital tool for the in situ exploration of deep-sea microorganisms.
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Pinças Ópticas , Microbiologia da Água , Organismos Aquáticos , Água do MarRESUMO
In recent years, many studies on photocatalysis focused on improving efficiency. However, the cycle performance is also an important index for industrialization. Here, an Ag2O/TiO2 heterostructure photocatalyst is prepared for continuous photodegradation of methylene blue (MB) under visible light, and the samples after the first and fifth round reactions are recycled to study the microstructure evolution of the photocatalyst. The results show that the performance is obviously improved in the second round and remains stable in the following reaction round. Due to the charge transfer, Ag2O/TiO2 gradually changes to Ag2O@Ag-TiO2-x during the photocatalytic reaction. The resulting localized surface plasmon resonance effect and the change of the interface structure greatly increase the number of carriers and prolong the lifetime of carriers. Such variations of microstructures and photoelectric properties of the samples due to the charge transfer and redox reaction on the surface of the photocatalyst dominate the cycle performance.
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BACKGROUND: Umbilical artery serum-derived exosomes (UEs) serve as messengers for maternal-fetal information exchange and cellular regulation. Intravenous remifentanil could be considered as an effective adjunct to epidural anesthesia in providing a favorable analgesia effect for cesarean section (C-section), but its effects on UEs are currently unknown. METHODS: From 01/12/2021 to 30/06/2022, eligible parturients scheduled for repeated C-section at the First Affiliated Hospital of Wenzhou Medical University were randomized to receive either an intravenous bolus (0.15 µg/kg) followed by a continuous infusion (0.075 µg/kg/min) of remifentanil or normal saline throughout the procedure. The primary outcome was the number of UEs. Secondary outcomes included the size and protein amount of UEs, the vital signs, visceral pain score, sedation score, maternal satisfaction score, Apgar score, the incidence of neonatal asphyxia, umbilical arterial pH, and the presence of complications. RESULTS: Nanoparticle tracking analysis indicated similar size of UEs between the two groups, but the number and protein amount of UEs were increased in the remifentanil group compared to the control group (P < 0.05). In parturients receiving remifentanil, visceral pain scores were decreased, which was accompanied by the increased scores of maternal satisfaction with the anesthetic method (P < 0.05). Other maternal and neonatal outcomes were comparable between the two groups (P > 0.05). CONCLUSION: The intravenous administration of remifentanil increased the number of UEs in parturients undergoing repeated C-section under epidural anesthesia, with improved birth experience and minimal neonatal complications.
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Anestesia Epidural , Exossomos , Dor Visceral , Recém-Nascido , Gravidez , Humanos , Feminino , Remifentanil , Analgésicos Opioides/uso terapêutico , Piperidinas , Cesárea , Artérias Umbilicais , Dor Visceral/tratamento farmacológico , Anestesia Epidural/métodos , Infusões IntravenosasRESUMO
INTRODUCTION: Double-filtration plasmapheresis (DFPP) has been utilized for immunomodulation in kidney transplantation. Anticoagulation is important to maintain circuit patency during DFPP. We aimed to compare the efficacy and safety of regional citrate anticoagulation (RCA) with systemic heparin anticoagulation during DFPP in kidney transplant recipients. METHODS: A retrospective cohort study was conducted to compare the efficacy and safety of RCA (RCA-DFPP) to systemic heparin anticoagulation (Hep-DFPP) for DFPP among kidney transplant recipients in a single tertiary center. RESULTS: A total of 112 sessions of DFPP were performed for 23 subjects, of which 62 sessions were RCA-DFPP and 50 sessions were Hep-DFPP. There were 13 sessions (11.6%) of premature circuit clotting, 10 sessions (16.1%) for RCA-DFPP and 3 sessions (6.0%) for Hep-DFPP (P = .10). All premature circuit clotting episodes occurred in subjects who underwent DFPP through a vascular catheter. Premature circuit clotting was associated with the use of a vascular catheter (odds ratio [OR] 14.2, 95% confidence interval [CI] 2.7-73.7; P < .01) and high postfilter ionized calcium (OR 12.7, 95% CI 1.4-112.5; P < .01). There was no major bleeding event. Hep-DFPP was associated with higher occurrence of hypocalcemia (OR 1.1, 95% CI 1.0-1.2; P < .01) and metabolic acidosis (OR 1.4, 95% CI 1.2-2.0; P = .04), while hypomagnesemia was more common for RCA-DFPP (OR 2.9, 95% CI 1.1-7.4; P = .03). CONCLUSION: Amongst kidney transplant patients who receive DFPP therapy, RCA-DFPP may be comparable to Hep-DFPP for the maintenance of circuit patency. Functioning vascular access is vital in avoiding premature clotting of the circuit. Close monitoring of electrolyte imbalances and coagulopathy related to DFPP is recommended.
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Ácido Cítrico , Heparina , Humanos , Heparina/uso terapêutico , Ácido Cítrico/uso terapêutico , Anticoagulantes/uso terapêutico , Estudos Retrospectivos , Citratos , PlasmafereseRESUMO
Sterol O-acyltransferase 1 (SOAT1) is a key enzyme in lipid metabolism, which mediates cholesterol esterification metabolism and is closely associated with many cancers. However, the role of SOAT1 in lung cancer invasion remains unclear. We found that SOAT1 expression was positively correlated with lung cancer invasion. Downregulation of SOAT1 inhibited invasion, mitochondrial fragmentation, AKT phosphorylation, and phospho-Drp (Ser616) in lung cancer cells and promoted intracellular free cholesterol accumulation. Mechanistically, the AKT phosphorylation inhibitor MK-2206 alleviated both SOAT1 overexpression and high expression-induced mitochondrial fragmentation and lung cancer cell invasion. Furthermore, intracellular free cholesterol accumulation reduced AKT phosphorylation, SREBP1 mRNA expression, cell invasion, and mitochondrial fragmentation in lung cancer cells with high SOAT1 expression. In summary, our findings suggest that SOAT1 promotes lung cancer invasion by activating the PI3K/AKT signaling pathway by downregulating intracellular free cholesterol levels, thereby affecting the regulation of mitochondrial fragmentation.
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Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-akt , Colesterol/metabolismo , Humanos , Pulmão/metabolismo , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases , Esterol O-AciltransferaseRESUMO
With reference to the production process documented in Chinese Pharmacopoeia, this paper prepared the calibrator samples of Xiaochaihu Granules from multiple batches and established a method for fingerprint analysis and content determination that could be used to evaluate Xiaochaihu Granules available in market. Multiple batches of Chinese herbal pieces contained in Xiaochaihu Granules were collected for preparing the calibrator samples according to the process in Chinese Pharmacopoeia. Following the establishment of fingerprints for calibrator samples by UHPLC, the method for determining the contents of saikosaponin B2, saikosaponin B1, baicalin, wogonoside, baicalein, liquiritin, glycyrrhizin G2 and glycyrrhizic acid in Xiaochaihu Granules was established. The experimental results showed that the fingerprints of calibrator samples had 26 common peaks, covering the chemical compounds of main herbs Bupleuri Radix, Scutellariae Radix, Changii Radix, Glycyrrhizae Radix et Rhizoma, and Rhizoma Zingiberis Recens. The similarity of fingerprints for 47 batches of Xiaochaihu Granules from 31 companies with the calibrator sample fingerprint ranged from 0.74 to 0.99, indicating good applicability of the established fingerprint. The contents of main components baicalin, saikosaponin B2, and glycyrrhizic acid in Xiaochaihu Granules were within the ranges of 22.917-49.108 mg per bag(RSD 19%), 0.28-2.19 mg per bag(RSD 62%), and 0.897-6.541 mg per bag(RSD 41%), respectively. The quality difference in saikosaponin B2, and glycyrrhizic acid among different manufacturers was significant. The fingerprint analysis and content determination method for calibrator samples of Xiaochaihu Granules prepared according to the production process in Chinese Pharmacopoeia has been proved suitable for evaluating the quality of Xiaochaihu Granules from different manufacturers. Saikosaponin B2, glycyrrhizic acid, and liquiritin should be added as content control indicators for Xiaochaihu Granules, aiming to further improve the product quality.
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Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Ácido Glicirrízico/análise , Rizoma/química , Scutellaria baicalensisRESUMO
Seasonal influenza is an acute respiratory infection causing around 500 000 global deaths annually. There is an unmet medical need to develop more effective antiviral drugs and vaccines against influenza infection. A rapid, accurate, high-throughput titration assay for influenza virus particles or neutralizing antibodies would be extremely useful in these research fields. However, commonly used methods such as tissue culture infective dose and plaque-forming units (PFU) for virus particle quantification, and the plaque reduction neutralization test (PRNT) for antibody determination are time-consuming, laborious, and have limited accuracy. In this study, we developed an efficient assay based on the enzyme-linked immunospot (ELISPOT) technique for the influenza virus and neutralizing antibody titration. Two broad-spectrum antibodies recognizing the nucleoproteins of influenza A and B viruses were used in the assay to broadly and highly sensitively detect influenza virus-infected cells at 16 hours postinfection. An optimized cell culture medium with no tosyl phenylalanyl chloromethyl ketone trypsin and high dose oseltamivir acid was used to improve quantitation accuracy. This ELISPOT assay displayed a good correlation (R2 = 0.9851) with the PFU assay when used to titrate 30 influenza virus isolates. The assay was also applied to measure influenza-neutralizing antibodies in 40 human sera samples, showing a good correlation (R2 = 0.9965) with the PRNT assay. This ELISPOT titration assay is a rapid, accurate, high-throughput assay for quantification of influenza virus and neutralizing antibodies, and provides a powerful tool for research into and development of drugs and vaccines against influenza.
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Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , ELISPOT/métodos , Ensaios de Triagem em Larga Escala/métodos , Influenza Humana/diagnóstico , Orthomyxoviridae/imunologia , Anticorpos Monoclonais/imunologia , Meios de Cultura/química , ELISPOT/normas , Ensaios de Triagem em Larga Escala/normas , Humanos , Influenza Humana/imunologia , Testes de Neutralização/métodos , Testes de Neutralização/normas , Orthomyxoviridae/química , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Vascular air embolism (VAE) is a rare but important complication that has not been paid enough attention to in the medical process such as surgery and anesthesia. CASE PRESENTATION: We report for the first time that a 54-year-old male patient with central lung cancer developed severe complications of CAE after right pneumonectomy. After targeted first-aid measures such as assisted breathing, mannitol dehydration and antibiotic treatment, the patient gradually improved. The patient became conscious at discharge after 25 days of treatment but left limb was left with nerve injury symptoms. CONCLUSION: We analyzed the possible causes of CAE in this case, and the findings from this report would be highly useful as a reference to clinicians.
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Carcinoma de Células Escamosas/cirurgia , Infarto Cerebral/diagnóstico por imagem , Embolia Aérea/diagnóstico , Embolia Intracraniana/diagnóstico , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Complicações Pós-Operatórias/diagnóstico , Angiografia Cerebral , Infarto Cerebral/etiologia , Infarto Cerebral/terapia , Angiografia por Tomografia Computadorizada , Diuréticos Osmóticos/uso terapêutico , Embolia Aérea/complicações , Embolia Aérea/fisiopatologia , Embolia Aérea/terapia , Humanos , Embolia Intracraniana/complicações , Embolia Intracraniana/fisiopatologia , Embolia Intracraniana/terapia , Masculino , Manitol/uso terapêutico , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Respiração ArtificialRESUMO
To analyze the effect of traditional Chinese medicine Paishi decoction combined with laparoscopic ureterectomy and lithotripsy in the treatment of complex kidney stones. Totally 100 patients with complicated kidney stones admitted to our hospital from January 2019 to January 2021 were selected and randomly divided into a control group and an experimental group, with 50 cases in each group. The control group was treated with laparoscopic ureterectomy for stone removal, the experimental group was treated with traditional Chinese medicine Paishi decoction combined with laparoscopic ureterectomy for stone removal. The therapeutic effects of the two groups were compared. The total effective rate of treatment in the control group was 76% and that of the experimental group was 96%. The stone clearing time, time to pain resolution and time to hematuria disappearance time in the experimental group were significantly shorter as compared with the control group. After treatment, the levels of serum creatinine and blood urea nitrogen in the experimental group were significantly lower than those in the control group. Traditional Chinese medicine Paishi decoction combined with laparoscopic ureterectomy and lithotripsy for treatment of complex kidney stones ameliorates the treatment efficacy, shortens the time of stone removal, mitigates the clinical symptoms of patients, and helps restore renal function, which is worthy of clinical promotion and application.
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Medicamentos de Ervas Chinesas , Cálculos Renais , Laparoscopia , Procedimentos Cirúrgicos Urológicos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Terapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/terapia , Laparoscopia/efeitos adversos , Litotripsia , Distribuição Aleatória , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos/efeitos adversosRESUMO
PURPOSE: Current guidelines favor 4F-PCC over plasma for reversal of warfarin. Uncertainty remains on the hemostatic effectiveness and thrombotic risk of 4F-PCC for direct-acting oral anticoagulants (DOACs), particularly in patients with intracranial hemorrhage (ICH). This study sought to evaluate the effectiveness and safety of a lower dose protocol of 25 units/kg 4F-PCC for the management of DOAC-associated ICH in a real-world setting. MATERIALS AND METHODS: This was a retrospective study of adult patients who received at least one dose of 4F-PCC from March 2014 to December 2015 for DOAC-associated ICH. The primary outcome was hemostatic effectiveness within 24 hours. The secondary outcome was thromboembolic events within 14 days. RESULTS: Twenty-two patients received 4F-PCC for DOAC-associated ICH and were included in the analysis. Hemostasis was evaluable in 19 patients with post-4F-PCC imaging available and occurred in 18/19 (94.7%) patients. Thromboembolism occurred in 2 out of 22 patients (9.1%). CONCLUSIONS: The use of a lower dose protocol of 25 units/kg of 4F-PCC resulted in high rates of hemostasis in patients with DOAC-associated ICH. Two patients developed thrombotic events within 14 days of 4F-PCC administration.
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Anticoagulantes , Fatores de Coagulação Sanguínea , Anticoagulantes/efeitos adversos , Humanos , Hemorragias Intracranianas/induzido quimicamente , Estudos Retrospectivos , VarfarinaRESUMO
BACKGROUND: This study was designed to examine whether severe aortic regurgitation will affect the pharmacodynamics (PD) and pharmacokinetics (PK) of cisatracurium during anesthetic induction. METHODS: A total of 32 patients were divided into two groups: the AR group (n = 16) and the control group (n = 16). Arterial blood samples were drawn before and at 1, 2, 4, 6, 8, 10, 16 and 20 min after intravenous injection of 0.15 mg/kg cisatracurium. TOF tests were applied to determine the onset time of maximal muscle relaxation. The concentration of cisatracurium in plasma was determined by high-performance liquid chromatography. RESULTS: The onset time to maximal neuromuscular block was prolonged from 2.07 ± 0.08 min to 4.03 ± 0.14 min, which indicated that the PD responses to cisatracurium were significantly delayed in the AR group (P < 0.05) compared to the control group. A conventional two-compartment PK model showed a higher plasma concentration of cisatracurium among the AR group with markedly reduced intercompartment transfer rate (K12 = 0.19 ± 0.02 and K21 = 0.11 ± 0.01 in the AR group vs. K12=0.26 ± 0.01 and K21 = 0.19 ± 0.01 in the control group, P < 0.01) compared to the control group. CONCLUSION: Backward blood flow during diastole in severe AR impaired distribution of cisatracurium from the central compartment to the peripheral compartment, which accounted for the lagged PD responses. Findings in this study underlie the importance of muscular blockade monitoring among patients with severe aortic regurgitation during anesthetic induction. REGISTRATION: Name of the registry: Abnormal Cisatracurium Pharmacodynamics and Pharmacokinetics among Patients with Severe Aortic Regurgitation during Anesthetic Induction. TRIAL REGISTRATION NUMBER: ChiCTR1800019654. Date of registration: November 20th 2018.
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Insuficiência da Valva Aórtica/fisiopatologia , Atracúrio/análogos & derivados , Bloqueadores Neuromusculares/farmacologia , Insuficiência da Valva Aórtica/sangue , Atracúrio/sangue , Atracúrio/farmacocinética , Atracúrio/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueadores Neuromusculares/sangue , Bloqueadores Neuromusculares/farmacocinéticaRESUMO
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac surgery that influences the clinical outcomes and quality of life of patients. This study aimed to evaluate the effects of Shenmai injection (SMI) on POCD of patients who underwent cardiac valve replacement under cardiopulmonary bypass (CPB). METHODS: This prospective, randomized, controlled trial was conducted from September 2014 to January 2017. Eighty-eight patients receiving cardiac valve replacement under CPB were randomized into the control (C) or the SMI (S) group. SMI (0.6 mL/kg) was administered intravenously from the time of anesthesia induction to the beginning of CPB. Cognitive function was assessed at 3 days before surgery and 3 days, 7 days, and 1 month after surgery using the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) score. The serum levels of neuroglobin (Ngb), hypoxia-inducible factor-1α (HIF-1α), and neuron-specific enolase (NSE) were measured at 30 min after induction (T0), immediately after the endonasal temperature rewarmed to 36 °C (T1), and 1 h (T2), 6 h (T3), 24 h (T4), 48 h (T5), and 72 h (T6) after CPB. RESULTS: Compared with the baseline values at T0, the serum Ngb levels in group C were significantly decreased at T1-2 and then increased at T3-6, while the levels in group S were decreased at T1-2 and increased at T4-6, compared to group C (p < 0.05). The serum HIF-1α levels at T1-4 and the serum NSE levels at T1-6 were significantly increased in both groups (p < 0.05). The serum levels of Ngb at T3, HIF-1α at T1-3, and NSE at T3-4,6 were lower in group S, compared to group C (p < 0.01). The MoCA-BJ scores were decreased at 3 and 7 days after surgery in both groups, and the MoCA-BJ scores in group S were higher than those in group C at 3 and 7 days after surgery (p < 0.01). CONCLUSION: Cognitive function is impaired postoperatively in patients who have undergone cardiac valve replacement under CPB. In addition, treatment with the traditional Chinese medicine SMI decreases the serum levels of Ngb, HIF-1α, and NSE as well as attenuates cognitive dysfunction. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov as ChiCTR-TRC-14004373 on March 11, 2014.
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Ponte Cardiopulmonar/efeitos adversos , Disfunção Cognitiva/prevenção & controle , Medicamentos de Ervas Chinesas/administração & dosagem , Implante de Prótese de Valva Cardíaca/métodos , Administração Intravenosa , Idoso , Ponte Cardiopulmonar/métodos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Masculino , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/metabolismo , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Qualidade de Vida , Fatores de TempoRESUMO
In this study, we investigated arsenic uptake and enzymatic activities in rice seedlings after the addition of nanoparticles. Hydroponic experiments were conducted to investigate the effects of different nanomaterials (high-quality graphene oxide, multilayer graphene oxide, 20â¯nm hydroxyapatite (HA20), 40â¯nm hydroxyapatite (HA40), nano-Fe3O4 (nFe3O4) and nano-zerovalent iron [nFe]) on the biomass, arsenic uptake, and enzyme activities in seedlings of the rice cultivars T705 and X24. Compared with the control, the addition of different nanomaterials increased seedling growth, with X24 rice growing better than T705 rice. Nanomaterials effectively reduced arsenic uptake in T705 rice seedlings under low and high arsenic concentrations; however, they were only effective at lower arsenic concentrations in X24 seedlings. nFe3O4 and nFe performed better than other nanomaterials in preventing arsenic from being transported to the aboveground parts of the rice seedlings. Different nanomaterials obviously influenced enzyme activities in the T705 seedlings at low arsenic concentrations (≤ 0.8â¯mgâ¯L-1). High-quality and multilayer graphene oxide decreased enzyme activities in the aboveground parts of the T705 seedlings, whereas, HA20 and HA40 increased the enzyme activities. nFe3O4 and nFe also reduced the effect of antioxidants in the aboveground parts of the T705 seedlings. Nanomaterials effectively reduced the arsenic uptake of T705 and X24 rice seedlings at low arsenic concentrations.
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Arsênio/toxicidade , Nanopartículas , Oryza/efeitos dos fármacos , Poluentes do Solo/toxicidade , Antioxidantes/metabolismo , Arsênio/metabolismo , Hidroponia , Oryza/enzimologia , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Plântula/efeitos dos fármacos , Plântula/enzimologia , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Poluentes do Solo/metabolismoRESUMO
OBJECTIVE: To investigate the expressions of sphingosine 1-phosphate (S1P) and S1P G-protein-coupled receptor 1 (S1PR1) in pulmonary ischemia reperfusion injury (PIRI) tissues and explore their relationship. METHODS: The model of PIRI was established in vivo male C57BL/6 mice (n=8). The left pulmonary hilum was occluded for 30 min with a microvascular clamp through a left thoracotomy. Reperfusion began with removal of the clamp. Normal group (n=8) and sham group (n=8) were set as control. The hematoxylin and eosin (HE) staining of ultrastructural changes and wet-to-dry mass ratio in lung tissues were measured for judging the succeed model. The mRNA expressions of sphingosine kinase 1 (SphK1) and S1PR1 were determined by real-time PCR, and ELISA was used to detect the concentrations of S1P and S1PR1 in the lung tissues. RESULTS: The mRNA expressions of SphK1, S1PR1 and the concentrations of S1P and S1PR1 and wet-to-dry mass ratio of the lung tissues in ischemia-reperfusion mice were higher than those normal mice and sham operation mice (P<0.05). CONCLUSIONS: The increased expressions of S1P and S1PR1 in lung tissues after PIRI suggest that the S1P/S1PR1 signal pathway is involved in the pathophysiological process of PIRI, and may be a potential therapeutic target for it.
RESUMO
BACKGROUND: Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid mediator involved in modulating inflammatory process. We investigated the effects of FTY720, a structural analogue of S1P after phosphorylation, on lung injury induced by hindlimb ischemia reperfusion (IR) in rats. METHODS: Fifty Sprague-Dawley rats were divided into groups SM, IR, F3, F5, and F10. Group SM received sham operation, and bilateral hindlimb IR was established in group IR. The rats in groups F3, F5, and F10 were pretreated with 3, 5, and 10 mg/kg/d FTY720 for 7 days before IR. S1P lyase (S1PL), sphingosine kinase (SphK) 1, and SphK2 mRNA expressions, wet/dry weight (W/D), and polymorphonuclear/alveolus (P/A) in lung tissues were detected, and the lung injury score was evaluated. RESULTS: W/D, P/A, and mRNA expressions of S1PL, SphK1, and SphK2 were higher in group IR than in group SM, while these were decreased in both groups F5 and F10 as compared to IR (p < 0.05). The lung tissue presented severe lesions in group IR, which were attenuated in groups F5 and F10 with lower lung injury scores than in group IR (p < 0.05). CONCLUSIONS: FTY720 pretreatment could attenuate lung injury induced by hindlimb IR by modulating S1P metabolism and decreasing pulmonary neutrophil infiltration.
Assuntos
Cloridrato de Fingolimode/uso terapêutico , Membro Posterior/patologia , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Traumatismo por Reperfusão/complicações , Animais , Gasometria , Imunossupressores/uso terapêutico , Masculino , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Sprague-DawleyRESUMO
The aim of this study was to develop a cost-effective method for As removal from aqueous systems. To this end, pristine biochar (BC) was impregnated with Fe-Mn oxides and a comparative analysis was conducted on the adsorption capacities of BC, Fe-Mn binary oxide (FMO), and Fe/Mn modified biochar (FMBC). The ferromanganese oxides increased the specific surface areas of BC. FMBC presented greater adsorption of As (Qmax = 8.25mgg-1) than FMO and BC. Energy dispersive spectrometer analysis and electron microscope scanning revealed numerous pores of FMBC with the existence of Fe-Mn oxide using. Distinguished binding energy shifting of the As3d, Fe2p, O1s, and Mn2p3/2 regions after As sorption were found, indicating that Mn(III) oxidation and interaction of oxygen-containing function groups in the FMBC promoted the conversion of As(III) to As(V). Furthermore, chemisorption was found to be the main mechanism for As sorption on FMBC. Thus, the results suggest that FMBC could be used as an inexpensive and highly efficient adsorbent for As removal from water environment.