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Objective: To investigate the effects and mechanisms of long-term high-fat diet on synaptic plasticity in the visual cortex and hippocampus neurons of juvenile mice. Methods: This was an experimental study. Twenty-four 4-week-old male C57BL/6J mice were randomly divided into two groups, using a randomized numerical table, with 12 mice in each group. The ND group was fed a normal diet, while the HFD group was fed a high-fat diet. After 12 weeks of feeding, mouse body weight, body fat percentage, glucose tolerance, and blood lipid levels were recorded. Six mice from each group were randomly selected using a randomized numerical table, and long-term potentiation (LTP) in the lateral geniculate nucleus (LGN)-primary visual cortex binocular zone (V1B area) and hippocampus CA3-CA1 were recorded in vitro. Field excitatory postsynaptic potentials (fEPSPs) were measured, and the normalized fEPSP slope was calculated to evaluate changes in cortical synaptic plasticity. Subsequently, brain tissue was collected for Golgi staining to observe the development of pyramidal neurons in layers â ¡-â ¢ of the primary visual cortex and CA1 region of the hippocampus, and changes in dendritic spine morphology and quantity were compared. The remaining six mice from each group were euthanized, and brain tissue was collected for transmission electron microscopy to observe ultrastructural changes in the visual cortex V1B area and hippocampus CA1 region neurons. Independent samples t-test was used for statistical analysis. Results: After 12 weeks of feeding, the body weight of mice in the HFD group was (29.17±1.63) g, significantly lower than the ND group which was (37.99±6.87) g (t=4.33, P<0.001). The body fat percentage in the HFD group was 1.09%±0.22%, which was higher than the ND group with 0.85%±0.09% (t=2.50, P=0.032). HFD mice showed a significant increase in blood glucose level 30 minutes after glucose injection, reaching (17.80±3.94) mmol/L, compared to the ND group with (23.10±1.48) mmol/L (t=3.07, P=0.013). At 60 minutes after glucose injection, the difference in blood glucose levels between the ND group [(13.58±2.39) mmol/L] and the HFD group [(23.70±3.56) mmol/L] was statistically significant (t=5.40, P<0.001). Subsequently, both groups showed a decline in blood glucose levels, and at 120 minutes after glucose injection, the blood glucose level in the ND group decreased to (8.50±1.05) mmol/L, while the HFD group remained at a higher level of (16.03±4.17) mmol/L, showing a statistically significant difference (t=3.91, P=0.004). The serum total cholesterol levels in the ND and HFD groups were (4.08±0.35) mmol/L and (10.80±0.90) mmol/L, respectively, with the HFD group higher than the ND group (t=15.23, P<0.001). However, there was no significant difference in triglyceride levels (P>0.05). The high-density lipoprotein cholesterol level in the ND group was (2.12±0.57) mmol/L, while in the HFD group, it was (1.28±0.15) mmol/L, with the HFD group lower than the ND group (t=3.15, P=0.014). Non-high-density lipoprotein cholesterol level in the HFD group was (11.06±1.46) mmol/L, significantly higher than the ND group with (2.28±0.43) mmol/L (t=12.88, P<0.001). In the hippocampal CA3-CA1 pathway, the fEPSP slope increased by 239.1%±88.8% of baseline in the ND group, while in the HFD group, it was only 147.6%±31.6% of baseline, indicating lower LTP compared to the ND group (t=7.20, P<0.001). For the LGN-V1 pathway, the fEPSP slope increased by 204.8%±67.0% of baseline in the ND group, while in the HFD group, it was 121.1%±15.7% of baseline, showing reduced LTP compared to the ND group (t=9.11, P<0.001). Regarding the visual cortex, in the V1B area of the ND group, the number of dendritic spines per 10 µm was (1.31±1.14), while in the HFD group, it was (0.77±0.43), demonstrating a significant decrease in dendritic spine density (t=3.45, P<0.001). The proportion of mature dendritic spines in the ND group was 69.98%, while non-mature dendritic spines accounted for 30.02%. In contrast, the HFD group had 45.76% mature dendritic spines and 54.24% non-mature dendritic spines. Regarding changes in hippocampal CA1 pyramidal neurons, the cell bodies and axons were not damaged, but HFD group neurons exhibited simplified dendritic structures with reduced branching. The number of dendritic spines per 10 µm was (10.25±3.84) in the HFD group and (25.22±8.21) in the ND group, indicating significantly lower dendritic spine density in the HFD group (t=12.42, P<0.001). The proportion of mature dendritic spines in the ND group was 70.88%, while non-mature dendritic spines accounted for 29.12%. In contrast, the HFD group had 47.37% mature dendritic spines and 52.63% non-mature dendritic spines. Moreover, the ultrastructure of neurons in the visual cortex V1B area and hippocampus CA1 region of HFD mice showed evident damage, with disrupted cell structures, swollen and vacuolated mitochondria, reduced or even disappeared mitochondrial cristae, and decreased synaptic quantity with damaged structure. Conclusions: Long-term high-fat diet in juvenile mice leads to abnormal development and functional maturation of synapses in the visual cortex and hippocampal regions. Dendrites, as the foundation of synaptic structures, undergo abnormal development, which can cause alterations in synaptic plasticity of related neural circuits.
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Glucemia , Dieta Alta en Grasa , Masculino , Animales , Ratones , Ratones Endogámicos C57BL , Hipocampo , Neuronas , Plasticidad Neuronal , Peso Corporal , GlucosaRESUMEN
To investigate the relationship between serum C-reactive protein (CRP) levels and work impairment in patients with ankylosing spondylitis (AS) based on real-world evidence. Outpatients with confirmed AS at Chinese PLA General Hospital were recruited consecutively by Smart-phone SpondyloArthritis Management System (SpAMS) from April 2016 to April 2018. The relationship between CRP and work productivity and activity impairment questionnaire (WPAI) were evaluated. Five hundred and fifty-one outpatients with AS in paid employment were recruited. The presenteeism, overall work impairment, and activity impairment rates increased by 1.4% (1.1%, 1.8%), 1.1% (0.5%, 1.6%), and 1.7% (1.3%, 2.1%), respectively, for every 10 mg/L increase in the CRP level (all P value<0.01). However, the CRP level was not associated with absenteeism after adjusting for covariates [0.5%(-0.4%, 1.0%),P>0.05]. There is a significant association between increased serum CRP levels at baseline and the previous 7-day work impairment in patients with AS. Higher CRP levels contribute to worse presenteeism, overall work impairment, and activity impairment rates, which suggests the necessity of monitoring CRP on treatment, and also indicates that anti-inflammatory therapy may be effective for improving work productivity.
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Espondiloartritis , Espondilitis Anquilosante , Proteína C-Reactiva , China , Empleo , Humanos , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/tratamiento farmacológico , Encuestas y CuestionariosRESUMEN
AIM: To investigate the brain magnetic resonance imaging (MRI) features of children with haemophagocytic lymphohistiocytosis (HLH) with central nervous system (CNS) involvement, and to investigate the correlation with clinical biochemical tests. MATERIAL AND METHODS: Clinical and MRI data were collected from 118 children with HLH-CNS between January 2012 and June 2019. Patients were grouped according to their MRI findings, and statistical methods were used to test for correlations between the MRI findings and biochemical variables. RESULTS: Patients were divided into three groups, including normal appearance (Group 1, 17/118), diffuse parenchymal volume loss (Group 2, 44/118), and brain parenchyma lesions (Group 3, 57/118) containing three subtypes of brain lesions and HLH-CNS complications. Comparing biochemical values among the three groups revealed a significant difference for all values (p<0.05), except for cell counts in the cerebrospinal fluid (CSF). A pairwise comparison further showed significant inter-group differences for most of the variables. Spearman's rank correlation coefficient also demonstrated that CSF cell counts (r=0.193, p=0.036), CSF microprotein content (r=0.379, p<0.001), serum aspartate aminotransferase (AST; r=0.521, p<0.001), serum lactate dehydrogenase (LDH; r=0.514, p<0.001) and activated partial thromboplastin time (APTT; r=0.326, p<0.001) correlated positively with the MRI groups, while platelet count (PLT; r=-0.633, p<0.001) and plasma fibrinogen (FIB; r=-0.258, p=0.005) correlated negatively. CONCLUSION: Classification of brain MRI findings of HLH-CNS correlates well with the results of several key biochemical tests. Brain MRI is a promising method to elucidate illness severity and clinical outcomes.
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Encéfalo/diagnóstico por imagen , Enfermedades del Sistema Nervioso Central/complicaciones , Enfermedades del Sistema Nervioso Central/diagnóstico por imagen , Linfohistiocitosis Hemofagocítica/complicaciones , Imagen por Resonancia Magnética/métodos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Objective: To analyze the clinical characteristics of patients with ankylosing spondylitis (AS) with inflammation bowel disease (IBD). Methods: AS patients fulfilling the 1984 modified New York diagnostic criteria were recruited in Chinese AS Prospective Imaging Cohort (CASPIC) consecutively from April 2016 to June 2017 in Chinese People's Liberation Army General Hospital by using smart management system for spondyloarthritis (SpAMS). The diagnosis of IBD was confirmed by tissue pathology via ileocolonoscopy. Demographic, clinical and biochemical data were collected. Results: In total, 893 patients with AS were recruited with the mean age 30.8 years. The majority were men (739, 82.8%). There were 64 (7.2%) patients concomitant with IBD. The mean age [(34.5±7.5) years vs. (30.5±8.8) years, P<0.001] was older and the disease duration [(10.8±6.9) years vs. (8.1±5.9) years, P=0.001] was longer in patients with IBD than patients without. Compared with patients without IBD, patients with IBD had more frequent involvement of the cervical spine [(21.9% (14/64) vs. 10.5% (87/829), P=0.006) and thoracic spine [29.7% (19/64) vs. 12.3% (102/829), P<0.001]. Uveitis [28.1% (18/64) vs. 16.4% (136/829), P=0.017] and psoriasis [7.8% (5/64) vs. 2.3% (19/829), P=0.009] were also more common in patients concomitant with IBD. In addition, patients with IBD had significantly higher scores in BASDAI (3.3±2.1 vs. 2.4±1.8, P<0.001), BASFI [2.2 (1.0,3.3) vs. 1.1(0.2,2.4), P<0.001)] and ASAS HI (7.1±4.3 vs. 5.3±3.7, P= 0.001) than patients without IBD. Conclusions: Compared with patients without IBD, AS patients concomitant with IBD have more severe disease activity and organ dysfunction. Furthermore, the uveitis and psoriasis are more frequently accompanied in AS patients with IBD.
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Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/fisiopatología , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/fisiopatología , Adulto , China , Femenino , Humanos , Masculino , Estudios Prospectivos , Psoriasis , Índice de Severidad de la Enfermedad , Espondiloartritis , UveítisRESUMEN
Objective: To investigate the efficacy of arthroscopic synovectomy on refractory knee arthritis complicated with popliteal cyst. Methods: Patients diagnosed as rheumatoid arthritis (RA) or spondyloarthritis (SpA) with refractory knee arthritis who underwent knee arthroscopic synovectomy in our hospital from 2010 to 2017 were enrolled, including 20 patients (16 RA, 4 SpA) with popliteal cyst. Clinical data, RA disease activity score (DAS28), SpA back pain score, etc, were collected to evaluate the efficacy of knee surgery. Results: Erythrocyte sedimentation rate (ESR) [58(17, 79)mm/1h vs. 19(9, 30)mm/1h, P< 0.001],C reactive protein (CRP) [3.72(0.92,8.14) mg/L vs. 0.85(0.10,3.08) mg/L,P<0.001], rheumatoid factor [64.6(20.2,193.3) vs. 20.5(10.0,58.4),P<0.001], DAS28 score(4.67±1.25 vs. 2.81±1.23,P<0.001), knee joint discomfort score [5(4,6) vs. 2(1,3),P<0.001] and the volume of knee joint effusion by ultrasound (P<0.05) in 95 RA patients were significantly decreased compared to those before operation. ESR [27(12,54)mm/1h vs. 20 (16,28) mm/1 h,P<0.001], CRP [3.27(1.06,6.95) mg/L vs. 1.41(0.34,3.03)mg/L,P<0.001],knee discomfort score [2(0,5) vs. 1(0,3),P<0.05], back pain visual analogue score (VAS) [5(4,5) vs. 2(1,3), P<0.001], and the volume of knee joint effusion by ultrasound (P<0.001) in 58 SpA patients were significantly lower than those before the operation.The rate [16.84%(16/95) vs. 6.32%(6/95),P=0.023] and grading (P=0.007) of popliteal cyst in RA were decreased after the operation. No statistically difference was observed in the rate [6.90% (4/58) vs. 5.17%(3/58), P=0.697] of popliteal cyst in patients with SpA, yet with a trend of decrease in 4 patients. Conclusion: This study provide evidence that knee arthroscopic synovectomy has a good effect for refractory knee arthritis, which can reduce disease activity, improve joint symptoms and decrease the grading of popliteal cyst.
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Artritis/cirugía , Artroscopía/efectos adversos , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Quiste Poplíteo/cirugía , Sinovectomía/efectos adversos , Artritis/complicaciones , Artritis/patología , Artroscopía/métodos , Humanos , Articulación de la Rodilla/patología , Quiste Poplíteo/patología , Sinovectomía/métodos , Resultado del TratamientoRESUMEN
Objective: The aim of this study was to set up a large, longitudinal and prospective database to compare the clinical manifestations in human leucocyte antigen (HLA)-B(27) positive and negative patients with ankylosing spondylitis(AS) based on real-world evidence in Chinese population. Methods: A total of 897 outpatients with confirmed AS were recruited consecutively by smart management system for spondyloarthritis (SMSP) from April 13, 2016 to June 6, 2017 in Chinese PLA General Hospital from 30 provinces and autonomous regions. 801 patients with HLA-B(27) data were included in the analysis. Demographic and clinical parameters including Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), ankylosing spondylitis disease activity score (ASDAS), arthritis, enthesitis, Bath ankylosing spondylitis metrology index (BASMI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were compared between HLA-B(27) positive and negative groups. Results: A total of 801 patients were included in the analysis with an average age of (30.7±8.8) years. There were 659 males and 142 females and HLA-B(27) was present in 88.0%(705/801). Males were significantly more in HLA-B(27) positive patients [83.3%(587/705) vs. 75.0%(72/96); P=0.047].The average age at disease onset was (22.3±7.6)years in HLA-B(27) positive patients and (24.4±8.7) years in HLA-B(2)7 negative ones (P=0.028).There was significant difference in diagnose delay between two groups [14.3(2.5,43.6)months in HLA-B(27) positive patients vs. 20.3(5.0,67.4) months in HLA-B(27) negative ones, P=0.041]. Anterior uveitis was found to be significantly more common in HLA-B(27) positive patients [18.9% (133/705)vs.7.3%(7/96),P=0.005], and knee involvement less common in HLA-B(27) positive patients [4.0%(27/682) vs.10.0%(9/90), P=0.010], conversely. CRP[6.5(3.0, 16.4)mg/L vs. 3.5(1.6, 12.3)mg/L] and ESR[11.0(4.0, 24.0)mm/1h vs. 7.0(3.0, 16.0)mm/1h] were significantly higher in HLA-B(27) positive patients(P=0.005,0.013, respectively).But no differences in BASDAI,ASDAS,BASFI and BASMI were obtained between two groups. Conclusions: HLA-B(27) positive patients had a higher proportion of males, a younger age of onset and a greater risk for occurrence of anterior uveitis, suggesting a poorer prognosis.
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Proteína C-Reactiva/metabolismo , Antígeno HLA-B27/genética , Espondilitis Anquilosante/genética , Adulto , Sedimentación Sanguínea , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/sangre , Encuestas y CuestionariosRESUMEN
Objective: To explore postoperative delirium (POD)risk factors for geriatric patients who suffered hip fracture under the care of orthogeriatric unit mode. Methods: Patients aged 65 years or older, who were admitted to the orthogeriatric unit in Beijing Jishuitan Hospital from April to October 2017 for hip fracture surgery, were eligible for this prospective cohort study. After univariable analysis, significant risk factors associated with POD were further evaluated with multivariable analysis, to establish independent risk factors associated with POD. Results: A total of 203 patients with an average age of 80(65-96)years were enrolled in the study. The overall incidence of POD was 9.4%(19/203)in which hyperactive and hypoactive type accounting for 84.2%(16/19)and 15.8%(3/19), respectively. Significant difference was found between POD and non-POD groups in patients' age (P=0.003), albumin(P=0.006), TSH(P=0.018), PaCO(2) level(P=0.003), visual analogue scale (VAS )both at rest (P=0.013)and movement(P=0.010) on post-operative day 1.The further Logistic stepwise regression analysis showed that significant differences existed between groups in age(P=0.027), albumin(P=0.003), PaCO(2)(P=0.014)and VAS at rest(P=0.002). Conclusion: The independent risk factors of POD in geriatric patients undergoing hip fracture under the orthogeriatric unit mode include patients' age, pre-operative albumin as well as PaCO(2) level and post-operative VAS at rest.
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Delirio , Fracturas de Cadera , Anciano , Anciano de 80 o más Años , Delirio/complicaciones , Fracturas de Cadera/complicaciones , Hospitalización , Humanos , Complicaciones Posoperatorias , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To investigate the value of (18)F fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F FDG-PET-CT) in the diagnosis and the evaluation of disease activity and remission of dermatomyositis(DM). METHODS: DM patients who were admitted to the Department of Rheumatology, the People's Liberation Army General Hospital (PLAGH) and underwent (18)F FDG-PET-CT examination were retrospectively reviewed from January 2012 to May 2015.Gender and age matched healthy controls (HC) were also enrolled.The standardized uptake value (SUV) of proximal limb girdle muscles in both groups were recorded and compared, so as between patients with DM or subclinical DM.The correlation between myodynamia of proximal limb girdle muscle, creatine kinase(CK), CK-MB, serum ferritin and SUV of each muscle group were analyzed. RESULTS: There were 58 patients with DM and 29 controls consecutively recruited in the study.The SUV of upper arms (1.814±0.830) g/ml, shoulders (2.134±0.797) g/ml and hips (1.883±0.683) g/ml in patients with classic DM were significantly higher than those with subclinical DM [(0.938±0.218) g/ml, (1.152±0.315) g/ml, (0.945±0.249) g/ml; P<0.05]. SUV of muscles in newly diagnosed patients was (1.051±0.031) g/ml, which was higher than that in subclinical patients.But the difference was not statistically significant (P>0.05). The average SUV of evaluated muscles in DM group (2.033±0.858) g/ml was significantly higher than that in controls (1.076±0.167) g/ml (P<0.001). Receiver operating characteristic(ROC) analysis revealed the area under the curve(AUC) of abnormal SUV detected by (18)F FDG-PET-CT for diagnosing DM was 0.953.The myodynamia of upper arms and SUV was negatively correlated (rs=-0.440, P=0.031). However, the level of serum creatine kinase and SUV was positively correlated (rs=0.500, P=0.013). The average SUV of patients whose time to remission was less than 3 months (1.746±0.466) g/ml was obviously less than that of patients with 3 to 6 months to obtain remission (2.815±0.848) g/ml (P=0.015). CONCLUSIONS: The SUV of proximal limb girdle muscles detected by (18)F FDG-PET-CT has a positive diagnostic value for DM.Moreover, the SUV in upper arms is correlated with the muscle strength and the level of creatine kinase, which reflect disease activity. (18)F FDG-PET-CT might be an alternative method to evaluate the response of treatment.
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Dermatomiositis/diagnóstico por imagen , Fluorodesoxiglucosa F18/farmacocinética , Músculos/metabolismo , Radiofármacos/farmacocinética , Humanos , Imagen Multimodal , Fuerza Muscular , Músculos/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate the clinical value of Short Form-36 (SF-36) questionnaire and the most commonly used clinical measures in a prospective cohort study of ankylosing spondylitis (AS) patients. METHODS: A total of 517 AS patients were collected from the Department of Rheumatology, Chinese PLA General Hospital from August 2013 to September 2015. The Quality of Life (QoL) was assessed by SF-36 questionnaire and compared with the general population. The correlations between QoL and clinical measures of AS, including the Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI) et al, were analyzed. RESULTS: BASDAI and BASFI were significantly correlated with SF-36 scores (r>0.3, P<0.01). Logistic multiple regression analysis showed that BASDAI, BASFI, BASMI and education had close correlation with the baseline global QoL, physical and mental health. Among these clinical measures, BASDAI variation showed the most important influence on the change of global QoL, physical health and mental health (OR=0.235, 0.209, 0.125; P<0.01). CONCLUSIONS: SF-36 can objectively reflect the QoL of patients with AS. Clinical measures such as BASDAI and BASFI show great application value in this prospective cohort study of AS patients.
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Espondilitis Anquilosante/diagnóstico , Encuestas y Cuestionarios , Humanos , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la EnfermedadRESUMEN
AIMS: To improve the yield and productivity of docosahexaenoic acid (DHA) by Schizochytrium sp. in terms of the analysis of microbial physiology. METHODS AND RESULTS: A two-stage oxygen supply control strategy, aimed at achieving high concentration and high productivity of DHA, was proposed. At the first 40 h, K(L) a was controlled at 150·1 h(-1) to obtain high µ for cell growth, subsequently K(L) a was controlled at 88·5 h(-1) to maintain high q(p) for high DHA accumulation. Finally, the maximum lipid, DHA content and DHA productivity reached 46·6, 17·7 g l(-1) and 111 mg l(-1) h(-1), which were 43·83%, 63·88% and 32·14% over the best results controlled by constant K(L) a. CONCLUSIONS: This paper described a two-stage oxygen supply control strategy based on the kinetic analysis for efficient DHA fermentation by Schizochytrium sp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed the advantage of two-stage control strategy in terms of microbial physiology. As K(L) a is a scaling-up parameter, the idea developed in this paper could be scaled-up to industrial process and applied to other industrial biotechnological processes to achieve both high product concentration and high productivity.
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Ácidos Docosahexaenoicos/biosíntesis , Microbiología Industrial/métodos , Oxígeno/metabolismo , Estramenopilos/metabolismo , Fermentación , CinéticaRESUMEN
PURPOSE: We aimed to evaluate the association of early versus late initiation of Continuous renal replacement therapy (CRRT) with mortality in patients with fluid overload. METHODS: This was a retrospective cohort study of patients with fluid overload (FO) treated with CRRT due to severe acute kidney injury (AKI) between January 2015 and December 2017 in a mixed medical intensive care unit of a teaching hospital in Beijing, China. Patients were divided into early (≤15 h) and late (>15 h) groups based on the median time from ICU admission to CRRT initiation. The primary outcome was all-cause mortality at day 60. Multivariable Cox model analysis was used for analysis. RESULTS: The study patients were male predominant (84/150) with a mean age of 64.8 ± 16.7 years. The median FO value before CRRT initiation was 10.1% [6.2-16.1%]. The 60-day mortality rates in the early vs the late CRRT groups were 53.9% and 73%, respectively. On multivariable Cox modelling, the late initiation of CRRT was independently associated with an increased risk of death at 60 days (HR 1.75, 95% CI 1.11-2.74, p = 0.015). CONCLUSIONS: Early initiation of CRRT was independently associated with survival benefits in severe AKI patients with fluid overload.
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Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Desequilibrio Hidroelectrolítico , Lesión Renal Aguda/terapia , Anciano , Anciano de 80 o más Años , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Terapia de Reemplazo Renal , Estudios RetrospectivosRESUMEN
OBJECTIVE: Acute liver injury (ALI) leads to inflammatory response and tissue damage. Inflammatory activation of infiltrative macrophages plays a critical role in liver histology destruction and dysfunction. Hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), one of the polyphenols extracted from extra virgin olive oil, currently acts as a treatment for neuroinflammatory responses, but its effect on ALI is elusive. The present study aims to examine the mechanism of HT in macrophages inflammation and evaluate treatment effect of HT on ALI. MATERIALS AND METHODS: In vitro, the expressions of type M1/M2 macrophages biomarkers (CD11c/CD206) and cytokines (TNF-α, IL-1ß, IL-6, IL-10, IL-4) following lipopolysaccharide (LPS) stimulation and HT administration were detected using immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). Mechanically, HT was used to treat cells and phosphorylation level of extracellular-signal-regulated kinase 1/2 (ERK1/2) protein in cells was analyzed using Western blotting. In murine acute liver injury, inflammatory cytokines and liver injury degree were exhibited by qRT-PCR, IHC and HE staining. Furthermore, hepatic function was exhibited via hepatic metabolic enzymes (ALT/AST) and total bilirubin (TBil) in serum. RESULTS: It was demonstrated that HT treatment attenuated M1 macrophages and increased M2 macrophages after LPS stimulation. Furthermore, the pro-inflammatory cytokine level was descended, while an-inflammatory cytokine was increased via HT suppressing ERK pathway in macrophages. In vivo, HT reduced inflammatory level and mitigated hepatic histological injury, thus ameliorating liver function after acute liver injury. CONCLUSIONS: HT exerts a hepatoprotective and anti-inflammation effect on acute liver injury, which restrains inflammation by inhibiting ERK pathway and regulating macrophages polarization. Moreover, HT prevents liver tissues from inflammatory injury. Therefore, HT serves as a potential implication to treat ALI through modulating inflammation of macrophages.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Lipopolisacáridos/antagonistas & inhibidores , Alcohol Feniletílico/análogos & derivados , Animales , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Alcohol Feniletílico/farmacología , Células RAW 264.7RESUMEN
Objective: To explore the effect of combination regimen of interferon alpha-1b, interleukin-2 and thalidomide (ITI regimen) on minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) who were in hematologic remission but MRD-positive. Methods: Eighteen patients (17 from Tumor Hospital of Zhengzhou University and 1 from the First People's Hospital of Pingdingshan City) with AML admitted from July 2016 to June 2018, who were in hematologic remission but MRD-positive were treated with different doses of ITI regimen, and the MRD levels were monitored. Results: Among 18 patients who received a conventional dose of ITI regimen for 1 to 2 months, 7 patients had undetectable MRD, 3 had significant decrease in MRD levels, 3 had elevated MRD level and had hematologic recurrence. Three patients with elevated MRD level received a higher dose of ITI regimen, 2 of them turned to MRD negative and the other 1 patient had decreased MRD level. The total response rate was 72.2%, and the response rate in patients with MRD > 1.0% was 57.1% (4/7) , and that of patients with MRD < 1.0% was 81.8% (9/11) , respectively. Conclusion: The ITI regimen can reduce the MRD level of patient with AML who are in hematologic remission but MRD-positive. The therapeutic effect could be improved by a higher dose administration of ITI regimen, and therapeutic effect may be negatively correlated with MRD level before treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda , Citometría de Flujo , Humanos , Interferón-alfa , Interleucina-2 , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasia Residual , Pronóstico , Inducción de Remisión , TalidomidaRESUMEN
OBJECTIVE: LncRNA LINC00473 was reported to be upregulated in human cancers. Whereas, the role of LINC00473 in head and neck squamous cell carcinoma (HNSCC) and radiotherapy remains elusive. PATIENTS AND METHODS: Gene array analysis was performed to detect lncRNA LINC00473. Then, the expression of LINC00473 in HNSCC 78 pairs of tissues and cell lines was measured by qRT-PCR assay. To explore the detailed functions of LINC00473 on cell proliferation, MTT and colony formation assays were conducted. We also investigated the influence of LINC00473 expression on radioresistance of HNSCC cells. Western blot assay was used to confirm the relationship between LINC00473 and Wnt/ß-catenin signaling pathway. Furthermore, the effects of x-ray treatment on LINC00473 expression and Wnt/ß-catenin signaling pathway were detected by Western blot assay. RESULTS: LncRNA LINC00473 was upregulated in HNSCC tissues and cell lines. Functional assays showed that LINC00473 acted as oncogene to promote cell proliferation and inhibit apoptosis. In addition, downregulation of LINC00473 enhanced the sensitivity of radiotherapy for HNSCC cells. Furthermore, Western blot assays demonstrated that Wnt/ß-catenin signaling pathway was inhibited by LINC00473 knockdown. Notably, Western blot assay revealed that x-ray treatment suppressed the activity of Wnt/ß-catenin signaling pathway after LINC00473 knockdown. CONCLUSIONS: These data suggested that the upregulation of lncRNA LINC00473 promotes the radioresistance of HNSCC cells through activating Wnt/ß-catenin signaling pathway.
Asunto(s)
Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/radioterapia , ARN Largo no Codificante/metabolismo , Tolerancia a Radiación , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Vía de Señalización Wnt/efectos de la radiación , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/patología , Humanos , ARN Largo no Codificante/genética , Tolerancia a Radiación/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Vía de Señalización Wnt/genéticaRESUMEN
Meisoindigo, a second generation derivative of indirubin, is an effective chemotherapeutic agent with very low toxicity used in the treatment of chronic myeloid leukemia. To determine the nature of this activity, the effect of a nontoxic concentration (0.72 micrograms/mL) of this compound on ML-1 human myeloblastic leukemic cells was examined. At such a concentration, differentiation induction was found to be the most pronounced drug effect. During the 3-day drug incubation period, the viable cell number remained essentially constant, with approximately 48% of the cells demonstrating a mature phenotype with increased acid phosphatase activity and nitroblue tetrazolium dye reduction. As observed with other DNA-specific agents, induction of ML-1 differentiation by meisoindigo was accompanied by the down-regulation of c-myb gene expression. These data suggest that induction of leukemic cell differentiation associated with decreased c-myb expression may be one of the mechanisms of the antitumor action of meisoindigo.
Asunto(s)
Antineoplásicos/farmacología , Regulación hacia Abajo/efectos de los fármacos , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Leucemia Mieloide/tratamiento farmacológico , Proteínas Proto-Oncogénicas/genética , Transactivadores/genética , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Humanos , Indoles/farmacología , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas c-myb , Transactivadores/biosíntesis , Células Tumorales CultivadasRESUMEN
Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. Experiments have shown the improved absorption of meisoindigo, compared to indirubin to be one of the major reasons for the enhancement of antitumor activity. Studies on the mechanism of meisoindigo action indicate that it strongly inhibits DNA biosynthesis in tumor cells. Strong inhibition of the drug on assembly of microtubule protein was also obtained. By means of FCM technique the effects of meisoindigo on mouse leukemia L1210 cell cycle were examined. Experimental results showed that under the action of meisoindigo the S phase cells accumulated and the traverse of the cells in G2 + M phase to G1 phase may also be blocked to some extent.
Asunto(s)
Antineoplásicos/farmacología , Animales , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Indoles/farmacocinética , Indoles/farmacología , RatasRESUMEN
This paper describes the cytotoxicity of ranunculin (RAN) and its mechanism of action. The IC50 of RAN against the KB and Bel7402 cells in colony test were found to be 0.21 and 0.35 mumol/L respectively. RAN inhibited the incorporation of 3H-labeled precursors into DNA and RNA of L1210 cells. RAN (15 mumol/L) markedly decreased DNA synthesis catalyzed by DNA polymerase I and promoted the generation of superoxide anions in DMSO/KO2 system. In the meantime, SOD and CAT were shown to partly revoke the inhibitory effects of RAN upon the incorporation of 3H-TdR into DNA. No direct reaction between RAN and DNA template was observed and no effect of RAN on DNA TOPO II or RNA polymerase was found. Our results suggest that the cytotoxicity of RAN in vitro may be due to inhibition of DNA polymerase and increase of oxygen free radicals.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Furanos/farmacología , Metilglicósidos/farmacología , Animales , Bovinos , División Celular/efectos de los fármacos , ADN/biosíntesis , ADN de Neoplasias/biosíntesis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Radicales Libres , Humanos , Leucemia L1210/patología , Neoplasias Hepáticas/patología , Oxígeno/metabolismo , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Ranunculin (RAN) was shown to be an antimutagenic agent selectively against mitomycin C (MMC) or methyl methane sulfanate (MMS) treated Salmonella typhimminum TA100/TA102. It decreased the formation of micronucleus of MMC induced polychromatic erythrocytes (PEC) from 46 +/- 9.2% to 20 +/- 6% in mice. The inhibition of RAN on the incorporation of 3H-TdR into DNA disappeared after incubation with rat liver microsomes and cytoplasm since RAN was found to be metabolized by rat liver microsomes in vitro, resulting in a new absorbance peak at 258 nm, determined by RP-HPLC. The data show that RAN may have both antimutagen and antitumor activity, but the latter action may disappear by metabolic transformation.