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Dysbiosis of the gut microbiota has been implicated in hypertension, and drug-host-microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)-shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB-modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well-controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB-modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post-FMT, especially with a decreased abundance of Lactobacillus, Aggregatibacter, and Desulfovibrio. Moreover, ARB-treated microbes contributed to increased intestinal Ciart, Per1, Per2, Per3, and Cipc gene levels and decreased Nfil3 and Arntl expression were detected in response to ARB-treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB-FMT rats, including 6beta-Hydroxytestosterone and Thromboxane B2. In conclusion, ARB-modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross-talk between antihypertensive medicines and the gut microbiome.
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BACKGROUND: Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury, and finally leads to liver cirrhosis or even hepatocellular carcinoma. The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells (HSCs), which can transdifferentiate into myofibroblasts to produce an excess of the extracellular matrix (ECM). Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis. Therefore, activated hepatic stellate cells (aHSCs), the principal ECM producing cells in the injured liver, are a promising therapeutic target for the treatment of hepatic fibrosis. AIM: To explore the effect of taurine on aHSC proliferation and the mechanisms involved. METHODS: Human HSCs (LX-2) were randomly divided into five groups: Normal control group, platelet-derived growth factor-BB (PDGF-BB) (20 ng/mL) treated group, and low, medium, and high dosage of taurine (10 mmol/L, 50 mmol/L, and 100 mmol/L, respectively) with PDGF-BB (20 ng/mL) treated group. Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs. Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species (ROS), malondialdehyde, glutathione, and iron concentration. Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression of α-SMA, Collagen I, Fibronectin 1, LC3B, ATG5, Beclin 1, PTGS2, SLC7A11, and p62. RESULTS: Taurine promoted the death of aHSCs and reduced the deposition of the ECM. Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation, by decreasing autophagosome formation, downregulating LC3B and Beclin 1 protein expression, and upregulating p62 protein expression. Meanwhile, treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Furthermore, bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4, exhibiting the best average binding affinity of -20.99 kcal/mol. CONCLUSION: Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.
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Autofagia , Proliferación Celular , Ferroptosis , Células Estrelladas Hepáticas , Cirrosis Hepática , Especies Reactivas de Oxígeno , Taurina , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Humanos , Autofagia/efectos de los fármacos , Taurina/farmacología , Ferroptosis/efectos de los fármacos , Cirrosis Hepática/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Proliferación Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Becaplermina/farmacología , Becaplermina/metabolismo , Línea Celular , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patología , Supervivencia Celular/efectos de los fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Ultrasound-microwave combined extraction (UMCE), gradient ethanol precipitation, chemical characterization, and antioxidant and hypoglycemic activities of Lycium barbarum leaf polysaccharides (LLP) were systematically studied. The optimal conditions for UMCE of LLP achieved by response surface method (RSM) were as follows: microwave time of 16 min, ultrasonic time of 20 min, particle size of 100 mesh, and ratio of liquid to solid of 55:1. Three novel polysaccharide fractions (LLP30, LLP50, LLP70) with different molecular weights were obtained by gradient ethanol precipitation. Polysaccharide samples exhibited scavenging capacities against ABTS and DPPH radicals and inhibitory activities against α-glucosidase and α-amylase. Among the three fractions, LLP30 possessed relatively high antioxidant and hypoglycemic activities in vitro, which showed a potential for becoming a nutraceutical or a phytopharmaceutical for prevention and treatment of hyperglycemia or diabetes.
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Antioxidantes , Lycium , Antioxidantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/análisis , Lycium/química , Microondas , Polisacáridos/química , Hojas de la Planta/química , Etanol/análisisRESUMEN
BACKGROUND: Lumbar facet joint is an important element of spinal "three-joint complex". Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults. OBJECTIVE: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation. METHODS: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al. RESULTS: 1. The left and right transverse angle of L5S1 segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L3-L5 segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm2 in male than (18.92 ± 3.71) mm2 in female. 3. In comparison between normal and ALDH group, there was significant difference in L3-4 transverse angle (P < 0.05), L4-5 facet joint height and facet joint thickness (P < 0.05), L5S1 facet joint thickness and transverse angle (P < 0.05). CONCLUSION: When ALDH occurs in the L5S1 segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.
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Desplazamiento del Disco Intervertebral , Articulación Cigapofisaria , Adolescente , Adulto , Estatura , Femenino , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Masculino , Tomografía Computarizada por Rayos X , Articulación Cigapofisaria/diagnóstico por imagenRESUMEN
Chronic pancreatitis (CP) is a progressive condition caused by several factors and characterised by pancreatic fibrosis and dysfunction. However, CP is difficult to diagnose at an early stage. Various advanced methods including endoscopic ultrasound based elastography and confocal laser endomicroscopy have been used to diagnose early CP, although no unified diagnostic standards have been established. In the past, the diagnosis was mainly based on imaging, and no comprehensive evaluations were performed. This review describes and compares the advantages and limitations of the traditional and latest diagnostic modalities and suggests guidelines for the standardisation of the methods used to diagnose early CP.
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Diagnóstico por Imagen de Elasticidad , Enfermedades Pancreáticas , Pancreatitis Crónica , Endosonografía , Humanos , Pancreatitis Crónica/diagnóstico por imagenRESUMEN
Endoscopic submucosal dissection (ESD) is an important method for the treatment of early esophageal cancer. However, post-procedure stenosis is one of the most common long-term complications. This meta-analysis aimed to investigate whether stent placement is effective in the stenosis prevention, and which type of stent would be more effective. A systematic and electronic search of clinical trials and observational studies conducted before March 2020 on the efficacy of stent placement in preventing esophageal stricture after ESD was performed. Search terms included "ESD," "esophageal stenosis," "esophageal stricture," and "stents." We conducted a bias risk assessment of the eligible reports and a meta-analysis of the data using Revman 5.3 software. We included two randomized controlled trials (RCTs) and a prospective cohort study involving 163 patients with esophageal mucosal defects encompassing at least three-quarters of the esophagus circumference after ESD. The meta-analysis results showed that post-ESD stenosis rates (RR, 0.37; 95% CI, 0.22-0.64; P = 0.0003) and the number of endoscopic balloon dilations (EBDs) (MD, -1.74; 95% CI, -2.46 to -1.01; P < 0.00001) were reduced in the pooled analysis of three studies, indicating that stent placement was effective for stenosis prevention, especially a polyglycolic acid (PGA) sheet combined with stent placement can prevent stenosis (RR, 0.41; 95% CI, 0.23-0.74; P = 0.003) and reduce the number of EBDs (MD, -1.65; 95% CI, -2.40 to -0.90; P < 0.0001) significantly. Stent placement can reduce the rate of esophageal stenosis after ESD, especially when stents are covered with PGA sheets. However, more high-quality, low-bias RCTs with a sufficient sample size are needed to demonstrate its effectiveness.
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Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Estenosis Esofágica , Constricción Patológica , Resección Endoscópica de la Mucosa/efectos adversos , Neoplasias Esofágicas/cirugía , Estenosis Esofágica/etiología , Estenosis Esofágica/prevención & control , Esofagoscopía , Esófago/cirugía , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , StentsRESUMEN
BACKGROUND: Endoscopic submucosal dissection to treat mucosal and submucosal lesions sometimes results in low rates of microscopically margin-negative (R0) resection. Endoscopic full-thickness resection (EFTR) has a high R0 resection rate and allows for the definitive diagnosis and treatment of selected mucosal and submucosal lesions that are not suitable for conventional resection techniques. AIM: To evaluate the efficacy and safety of EFTR using an over-the-scope clip (OTSC). METHODS: This prospective, single-center, non-randomized clinical trial was conducted at the endoscopy center of Shengjing Hospital of China Medical University. The study included patients aged 18-70 years who had gastric or colorectal submucosal tumors (SMTs) (≤ 20 mm in diameter) originating from the muscularis propria based on endoscopic ultrasound (EUS) and patients who had early-stage gastric or colorectal cancer (≤ 20 mm in diameter) based on EUS and computed tomography. All lesions were treated by EFTR combined with an OTSC for wound closure between November 2014 and October 2016. We analyzed patient demographics, lesion features, histopathological diagnoses, R0 resection (negative margins) status, adverse events, and follow-up results. RESULTS: A total of 68 patients (17 men and 51 women) with an average age of 52.0 ± 10.5 years (32-71 years) were enrolled in this study, which included 66 gastric or colorectal SMTs and 2 early-stage colorectal cancers. The mean tumor diameter was 12.6 ± 4.3 mm. The EFTR procedure was successful in all cases. The mean EFTR procedure time was 39.6 ± 38.0 min. The mean OTSC defect closure time was 5.0 ± 3.8 min, and the success rate of closure for defects was 100%. Histologically complete resection (R0) was achieved in 67 (98.5%) patients. Procedure-related adverse events were observed in 11 (16.2%) patients. The average post-procedure length of follow-up was 48.2 ± 15.7 mo. There was no recurrence during follow-up. CONCLUSION: EFTR combined with an OTSC is an effective and safe technique for the removal of select subepithelial and epithelial lesions that are not amenable to conventional endoscopic resection techniques.
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Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Adolescente , Adulto , Anciano , China , Resección Endoscópica de la Mucosa/efectos adversos , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Abscess formation is one of the complications after radical resection of rectal cancer; cases with delayed postoperative anastomotic abscess are rare. Here, we report a rare case of postoperative anastomotic abscess with a submucosal neoplasm appearing after rectal surgery. Ultimately, the patient was diagnosed and treated by endoscopic fenestration. In addition, we review the literature on the appearance of an abscess as a complication after rectal cancer surgery. CASE SUMMARY: A 57-year-old man with a history of rectal malignancy resection complained of a smooth protuberance near the anastomotic stoma. Endoscopic ultrasonography revealed a hypoechoic structure originating from the muscularis propria, and a submucosal tumor was suspected. The patient was subsequently referred to our hospital and underwent pelvic contrast-enhanced computed tomography, which revealed no thickening or strengthening of the anastomotic wall. In order to clarify the origin of the lesion and obtain the pathology, endoscopic fenestration was performed. After endoscopic procedure, a definitive diagnosis of delayed anastomotic submucosal abscess was established. The patient achieved good recovery and prognosis after the complete clearance of abscess. CONCLUSION: Endoscopic fenestration may be safe and effective for the diagnosis/treatment of delayed intestinal smooth protuberance after rectal cancer surgery.
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BACKGROUND: People with achalasia typically have a thick lower esophageal muscularis propria (LEMP), and peroral endoscopic myotomy (POEM) has been effective in treating most patients. LEMP thickness may be associated with the outcomes and prognosis after POEM. However, more evidence is needed regarding the relationship between LEMP thickness and patient prognosis after POEM. AIM: To assess the association between LEMP thickness, measured using endoscopic ultrasound (EUS), and long-term prognosis, especially relapse, after POEM for achalasia. METHODS: All medical records, including EUS data, of patients who underwent POEM to treat achalasia at Shengjing Hospital of China Medical University from January 2012 to September 2018 were retrospectively reviewed. LEMP thickness was measured by EUS, and a thickness of ≥ 3 mm was defined as thickened. The severity of patient symptoms was evaluated using the Eckardt score. Relapse was defined as a 3-point rise in the Eckardt score after a period of clinical remission. The relationship between patient characteristics, muscle thickness, and recurrence was analyzed. RESULTS: Eighty-two patients (32 males and 50 females, aged 17-78 years) and 85 POEM procedures were included. In total, 76.8% (63/82 patients) of patients had a thickened muscularis propria. Older age and longer disease course were associated with muscularis propria thickening (P < 0.05). The mean postoperative follow-up time was 35.4 ± 17.2 mo (range, 8-87.5 mo) in 60 patients. Five patients with Eckardt scores > 3 refused further management after their symptoms were relieved. The relapse rate was 12.73% (7/55 cases). Five patients, four of whom had muscularis propria thickening, had disease recurrence within 12 mo after the procedure. Achalasia relapsed in one patient who had a thickened muscularis propria after 24 mo and in another patient who did not have a thickened muscularis propria after 30 mo. Patients with recurrence were typically younger and had a shorter disease course (P < 0.05). The relapse rate in patients with a non-thickened muscularis propria tended to be higher (18.2%, 2/11 patients) than that in patients with a thickened muscularis propria (11.4%, 5/44 patients), although no significant difference was found. Age (hazard ratio = 0.92; 95% confidence interval: 0.865-0.979; P < 0.05) and being male (hazard ratio = 7.173; 95% confidence interval: 1.277-40.286; P < 0.05) were identified as risk factors for symptomatic recurrence by multivariable analysis using the Cox model. CONCLUSION: Patients with a thickened muscularis are typically older and have a longer disease course. Younger age and the male sex are associated with increased recurrence. Patients with a thin muscularis propria may be prone to relapse, although further validation is needed.
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Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Adolescente , Adulto , Anciano , China/epidemiología , Acalasia del Esófago/diagnóstico por imagen , Acalasia del Esófago/cirugía , Esfínter Esofágico Inferior/diagnóstico por imagen , Esfínter Esofágico Inferior/cirugía , Esofagoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miotomía/efectos adversos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Background Impaired right ventricular ( RV ) function indicates RV involvement in patients with hypertrophic cardiomyopathy ( HCM ). We aimed to assess RV function at rest and during exercise in HCM patients and to examine the association between impaired RV mechanics and exercise capacity. Methods and Results A total of 76 HCM patients (48 without and 28 with RV hypertrophy) and 30 age- and sex-matched controls were prospectively recruited. RV function was evaluated at rest and during semisupine bicycle exercise by conventional echocardiography and 2-dimensional speckle-tracking imaging. Exercise capacity was measured by metabolic equivalents. RV functional reserve was calculated as the difference of functional parameters between peak exercise and rest. Compared with controls, HCM patients had significantly higher RV free wall thickness, lower RV global longitudinal strain and RV free wall longitudinal strain at rest and during exercise, and reduced RV systolic functional reserve. Compared with those with HCM without RV hypertrophy, patients with HCM with RV hypertrophy had lower metabolic equivalents. Among HCM patients, an effective correlation was seen between exercise capacity and peak exercise RV global longitudinal strain and peak exercise RV free wall longitudinal strain. A binary logistic regression model revealed several independent predictors of exercise intolerance in HCM patients, but receiver operating characteristic curve analysis indicated exercise RV global longitudinal strain had the highest area under the curve for the prediction of exercise intolerance in HCM patients. Conclusions HCM patients have RV dysfunction and reduced contractile reserve. Exercise RV global longitudinal strain correlates with exercise capacity and can independently predict exercise intolerance. In addition, patients with HCM with RV hypertrophy exhibit more reduced exercise capacity, suggesting more severe disease and poorer prognosis.
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Cardiomiopatía Hipertrófica/fisiopatología , Tolerancia al Ejercicio , Hipertrofia Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/fisiopatología , Función Ventricular Derecha , Adulto , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Estudios de Casos y Controles , Ecocardiografía Doppler de Pulso , Ecocardiografía de Estrés , Prueba de Esfuerzo , Femenino , Humanos , Hipertrofia Ventricular Derecha/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Disfunción Ventricular Derecha/diagnóstico por imagenRESUMEN
The present study investigated the changes of biventricular mechanics at rest and during exercise and examined the association between exercise capacity and biventricular mechanics and functional reserve in nonobstructive hypertrophic cardiomyopathy (NHCM) patients. A total of 50 NHCM patients and 25 controls were consecutively recruited for this study. Using echocardiography and two-dimensional speckle-tracking imaging, an experienced echocardiographer determined the following indices: RV free wall longitudinal strain (RVFWLS), LV global longitudinal strain (LVGLS), strain rate (SR), and functional reserve of strain values. We also investigated the relationships between biventricular mechanics and exercise capacity using metabolic equivalents (METs). NHCM patients had lower RVFWLS, LVGLS, systolic SR, early diastolic SR, and systolic and diastolic reserve during exercise compared to controls. An association of biventricular mechanics (LVGLS, RVFWLS) with exercise capacity at rest and during exercise was established. Multivariable logistic regression revealed that RVFWLS and LVE/e' during exercise (RVFWLS-exe, E/e'-exe) were independent predictors of exercise intolerance. Receiver operating characteristic curve analysis indicated that LVE/e'-exe had a higher area under the curve for predicting exercise intolerance in NHCM patients. In hierarchical analysis, RVFWLS-exe provided an incremental predictive value of exercise intolerance over LVGLS during exercise (LVGLS-exe) and LVE/e'-exe. LVE/e'-exe also changed incrementally compared to LVGLS-exe and RVFWLS-exe. NHCM patients have decreased biventricular mechanics at rest and during exercise and impaired biventricular functional reserve, and biventricular mechanics are associated with functional capacity. We propose that simultaneous evaluation of biventricular function should provide incremental predictive value for exercise intolerance.
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Cardiomiopatía Hipertrófica/fisiopatología , Tolerancia al Ejercicio , Contracción Miocárdica , Función Ventricular Izquierda , Función Ventricular Derecha , Adulto , Fenómenos Biomecánicos , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Estudios de Casos y Controles , Ecocardiografía Doppler de Pulso , Ecocardiografía de Estrés/métodos , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
Pulmonary arterial hypertension (PAH) is more prevalent in females. Paradoxically, female patients have better right ventricular (RV) function and higher survival rates than males. However, the effects of 17ß-estradiol (E2) on RV function in PAH has not been studied. Twenty-four male rats were exposed to monocrotaline (MCT) to induce experimental PAH, while treated with E2 or vehicle respectively. Together with eight control rats, thirty-two rats were examined by echocardiography 4 weeks after drug administration. Echocardiographic measurement of RV function included: tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), RV fractional area change (RVFAC) and tricuspid annular systolic velocity (s'). RV free wall longitudinal strain (RVLSFW) and RV longitudinal shortening fraction (RVLSF) were also used to quantify RV function. RV morphology was determined by echocardiographic and histological analysis. TAPSE, RVFAC and s' were reduced, and RIMP was elevated in the MCT-treated group and vehicle-treated group, when compared with control group (P < 0.01). TAPSE, RVFAC and s' in the E2 group were higher, while RIMP was lower than those in the MCT-treated group and vehicle-treated group (P < 0.01). Myocardial functional parameters (RVLSFW and RVLSF) were also higher in the E2 group. Enhanced serum E2 levels were closely correlated with the improvement in RV functional parameters and enhancement of serum BNP levels (P < 0.01 for all groups). RV function decreased significantly in male rats with MCT-induced PAH, while E2 exhibited a protective effect on RV function, suggesting that E2 is a critical modulator of sex differences in PAH.
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Ecocardiografía , Estradiol/farmacología , Ventrículos Cardíacos/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertrofia Ventricular Derecha/prevención & control , Disfunción Ventricular Derecha/prevención & control , Función Ventricular Derecha/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Biomarcadores/sangre , Modelos Animales de Enfermedad , Estradiol/sangre , Fibrosis , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Hemodinámica/efectos de los fármacos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Hipertrofia Ventricular Derecha/sangre , Hipertrofia Ventricular Derecha/diagnóstico por imagen , Hipertrofia Ventricular Derecha/fisiopatología , Masculino , Monocrotalina , Péptido Natriurético Encefálico/sangre , Ratas Sprague-Dawley , Factores de Tiempo , Disfunción Ventricular Derecha/sangre , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/fisiopatologíaRESUMEN
Fusobacterium nucleatum (Fn) is an important tumour-associated bacterium in colorectal cancer (CRC). The antioxidant protein alkyl hydroperoxide reductase subunit C (AhpC) can induce strong antibacterial immune response during various pathogen infections. Our study aimed to evaluate the efficacy of Fn-AhpC as a candidate vaccine. In this work, by western blot analysis, we showed that Fn-AhpC recombinant protein could be recognized specifically by antibodies present in the sera of CRC patients; using the mouse Fn-infection model, we observed that systemic prophylactic immunization with AhpC/alum conferred significant protection against infection in 77.3% of mice. In addition, we measured the anti-AhpC antibody level in the sera of CRC patients and found that there was no obvious increase of anti-AhpC antibodies in the early-stage CRC group. Furthermore, we treated Fn with the sera from both immunized mice and CRC patients and found that sera with high anti-AhpC antibodies titre could inhibit Fn growth. In conclusion, our findings support the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fn in the intestinal tract, which could provide a practical strategy for the prevention of CRC associated with Fn infection.
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Proteínas Bacterianas/inmunología , Vacunas Bacterianas/inmunología , Neoplasias Colorrectales/microbiología , Infecciones por Fusobacterium/inmunología , Intestinos/microbiología , Peroxirredoxinas/inmunología , Animales , Anticuerpos Antibacterianos/inmunología , Carga Bacteriana , Proteínas Bacterianas/genética , Femenino , Fusobacterium/inmunología , Fusobacterium/patogenicidad , Infecciones por Fusobacterium/terapia , Humanos , Ratones , Ratones Endogámicos BALB C , Peroxirredoxinas/genéticaRESUMEN
tRNA-derived small RNAs (tDRs) are a group of small, non-coding RNAs derived from transfer RNAs (tRNAs). They can be classified as tRNA halves and tRNA-derived small RNA fragments (tRFs). Accumulating experimental evidence suggests their functional roles in cells and in various biological processes. Advances in next-generation sequencing (NGS) techniques allow a large amount of small RNA deep-sequencing data to be generated. To investigate tDRs from these data, software to identify tDRs and databases to retrieve or manage tDR data have been devised. In this review, we summarized the tools and databases for tDR identification and collection, with the aim of helping researchers choose the best tools for their analysis and inspiring the invention or improvement of tools in the field.
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To test the applicability of lichens in the biomonitoring of atmospheric elemental deposition in a typical steppe zone of Inner Mongolia, China, six foliose lichens (Physcia aipolia, PA; P. tribacia, PT; Xanthoria elegans, XE; X. mandschurica, XM; Xanthoparmelia camtschadalis, XPC; and Xp. tinctina, XPT) were sampled from the Xilin River Basin, Xilinhot, Inner Mongolia, China. Twenty-five elements (Al, Ba, Cd, Ce, Cr, Cs, Cu, Fe, K, La, Mn, Mo, Na, Ni, P, Pb, Sb, Sc, Sm, Tb, Th, Ti, Tl, V and Zn) in the lichens were analysed using inductively coupled plasma mass spectrometry (ICP-MS). The results show that Cd, Pb and Zn were mainly atmospheric in origin, whereas the other elements were predominantly of crustal origin. Compared with other studies, our data were higher in crustal element concentrations and lower in atmospheric element concentrations, matching with the frequent, severe dust storms and road traffic in the area. The elemental concentrations in lichens are both species- and element-specific, highlighting the importance of species selection for biomonitoring air pollution using lichens. We recommend PT, XE, XM and XPT for monitoring atmospheric deposition of crustal elements; XPC and XPT for Cd and Pb; PA for Cd and Zn; and PT for Cd.
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Contaminantes Atmosféricos/aislamiento & purificación , Contaminación del Aire/análisis , Polvo/análisis , Líquenes/química , Oligoelementos/aislamiento & purificación , China , Ecosistema , Monitoreo del Ambiente , Humanos , Espectrofotometría AtómicaRESUMEN
Lichens are one of the best materials for air quality biomonitoring, and they have been widely used in atmospheric element deposition monitoring in many regions. Inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) are two efficient techniques widely used in quantifying and quantifying plant elements. However, elemental levels in lichens from some regions in China are much higher than in other plants, and their variation is highly dependent on space, time, species and elements. Although atmospheric pollution monitoring is urgently needed in China in recent decades, little studies have been performed on biomonitoring in the country. Therefore, the methodological studies on the determination of lichen elements in China are needed to accelerate future biomonitoring studies with lichens. Two techniques such as ICP-MS and ICP-AES were used to determine elements in four reference materials, as GBW10014 (cabbage), GBW10015 (spinach), GBW10052 (green tea) and IAEA-336 (lichen), with an attempt to reveal the effects of different digestions, sampling size, spectral lines, isotopes and internal standard elements on measured results. ICP-AES after dry ashing-alkali fusion digestion and ICP-MS after microwave digestion were optimized for lichen element determination. In the optimized techniques, good linear relationship (r>0.999 0), low detection limit, high analytic accuracy and precision were obtained. The optimized techniques were applied to lichen samples collected from Taihang Mountains of China and Ardley Island of Antarctica. The results show that all lichen samples from Taihang Mountains were much higher in elemental concentration with the contribution of atmospheric deposition higher than those from Antarctica. These results suggest the applicability of the techniques in determining lichen elements, and provide evidences and technique supports for air pollution biomonitoring in China.
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Líquenes , Contaminación del Aire , Regiones Antárticas , China , Monitoreo del Ambiente , Contaminación Ambiental , Isótopos , Espectrometría de Masas , MicroondasRESUMEN
BACKGROUND: Echocardiography is widely used to evaluate right ventricular (RV) function. However, the value of echocardiographic parameters to assess RV function in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. In this study, we analyzed the correlations between echocardiographic parameters and the RV ejection fraction (RVEF) as measured by cardiac magnetic resonance (CMR) imaging to systematically elucidate the role of echocardiographic parameters in the assessment of RV function in patients with CTEPH. METHODS: Echocardiography was used to measure the tissue Doppler-derived tricuspid lateral annular systolic velocity (S'), fractional area change (FAC), myocardial performance index (MPI), and tricuspid annular plane systolic excursion (TAPSE). CMR was used to measure the RV end-diastolic volume (RVEDV) and end-systolic volume (RVESV), and the RVEF was calculated. RESULTS: A significant positive correlation was found between S' and RVEF (r=0.689, P<0.0001) and between FAC and RVEF (r=0.423, P=0.022), a significant negative correlation was found between MPI and RVEF (r=-0.387, P=0.048), and no correlation was found between TAPSE and RVEF (r=0.451, P=0.22). CONCLUSION: Echocardiography can be routinely used in the clinical setting to measure S', FAC, and MPI for the evaluation of right heart function in patients with CTEPH.
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Ecocardiografía/métodos , Hipertensión Pulmonar/diagnóstico , Imagen por Resonancia Magnética/métodos , Disfunción Ventricular Derecha/diagnóstico por imagen , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , TromboemboliaRESUMEN
OBJECTIVE: To explore the clinical efficacy and mechanism of acupuncture and tapping therapy in the treatment of type 2 diabetes of yin deficiency pattern combined with stasis in the patients. METHODS: One hundred and twelve patients were treated with acupuncture, followed by tapping method. The reinforcing method with lifting, thrusting and rotating needle technique was used at Taixi (KI 3), Shenmen (HT 7), Taibai (SP 3), Taiyuan (LU 9), Sanyinjiao (SP 6) and Zusanli (ST 36); and the even-needling technique was used at Taichong (LR 3), Hegu (LI 4), Xuehai (SP 10) and Fenglong (ST 40). The needles were remained for 30 min. After needle removal, the tapping method with plum-blossom needle was applied to Geshu (BL 17), Yishu (EX-B 3), Ganshu (BL 18), Shenshu (BL 23) and Pishu (BL 20), once every two days. The treatment of 3 months was required. The changes were observed before and after treatment in the relevant indices of fat-islet axis such as fasting plasma glucose (FPG), fasting leptin (FLP), fasting insulin (FINS), insulin sensitivity index (ISI), insulin resistance (Homa IR), insulin secretion index (Homa-beta) and the indices of obesity and blood lipids in the patients. RESULTS: After treatment, the total effective rate was 84.8% (95/112), in which the efficacy on the stasis predominated syndrome was better than that of yin deficiency predominated syndrome [92.9% (52/56) vs 76.8% (43/56), P < 0.05]. Before treatment, FPG, FLP, FINS, Homa-IR, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), body mass, body mass index (BMI), fat percentage (F%) and obesity degree in the patients were higher obviously than those in the normal group (all P < 0.01); high-density lipoprotein cholesterol (HDL-C) and ISI were lower than those in the normal group (both P < 0.01). After treatment, FPG, FLP, FINS, Homa-IR, TC, TG, LDL-C, body mass, BMI, F% and obesity degree were all reduced obviously as compared with those before treatment (all P < 0.01). ISI and HDL-C were increased apparently (both P < 0.01). The efficacy on mild obesity was superior to that on moderate and severe obesity, and the efficacy in the young patients was better than that in the elderly, the efficacy in the males was better than that in the females, but the differences were not significant (all P > 0.05). The efficacy in the cases with 10 years duration of sickness was superior to those with over 10 years duration of sickness (P < 0. 01). CONCLUSION: Acupuncture and tapping therapy achieves the significant efficacy on type 2 diabetes of yin deficiency pattern combined with stasis and its effect mechanism is related to the positive regulation of glucose, lipid metabolism and fat-islet axis.
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Terapia por Acupuntura , Diabetes Mellitus Tipo 2/terapia , Deficiencia Yin/terapia , Puntos de Acupuntura , Adulto , Anciano , Glucemia/metabolismo , Colesterol/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Insulina/metabolismo , Leptina/metabolismo , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Triglicéridos/metabolismo , Deficiencia Yin/metabolismoRESUMEN
Interferon gamma (IFN-γ) is a potent proinflammatory cytokine which plays a pivotal role in the antiviral, antiproliferative, and antitumor activities. A T-to-A transition at the position +874 of human IFN-γ gene (IFNG) has been reported to influence the secretion of IFN-γ and affect cancer susceptibility. However, results from published studies on the association between IFNG +874 T/A polymorphism and cancer risk are inconclusive or even controversial. In order to derive a more precise estimation of the association, a meta-analysis of 38 eligible studies including 5,630 cases and 6,096 controls was conducted with odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI). Overall, no significant association was detected in allelic model (A allele vs. T allele-OR = 0.96, 95 % CI, 0.86-1.08), homozygote comparison (AA vs. TT-OR = 0.97, 95 % CI, 0.79-1.21), heterozygote comparison (AT vs. TT-OR = 1.03, 95 % CI, 0.87-1.23), dominant model (AA + AT vs. TT-OR = 1.00, 95 % CI, 0.87-1.15), nor recessive model (AA vs. AT + TT-OR = 0.93, 95 % CI, 0.78-1.12). Further subgroup analyses based on ethnicity, cancer types, and Hardy-Weinberg equilibrium status failed to demonstrate any significant relationship except in African population under recessive model (AA vs. AT + TT-OR = 0.68, 95 % CI, 0.47-0.97). In conclusion, the current meta-analysis suggested that IFNG +874 T/A polymorphism may not contribute to cancer susceptibility, and further well-designed studies with large sample size are warranted to validate our conclusion.
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Predisposición Genética a la Enfermedad , Interferón gamma/genética , Neoplasias/genética , Alelos , Estudios de Asociación Genética , Humanos , Factores de RiesgoRESUMEN
AIM: YCP, a novel (1,4)-alpha-D-glucan, was isolated from the mycelium of the marine filamentous fungus Phoma herbarum YS4108. In this work, we investigated a YCP-binding cellular receptor expressed by macrophages and the intracellular signal transduction pathways involved in YCP-induced macrophage activation. METHODS: Fluorescence-labeled YCP (fl-YCP) was prepared using the CDAP-activation method. Fluorescence confocal laser microscopy and fluorescence-activated cell sorting (FACS) were used to analyze the effect of fl-YCP on macrophages. To characterize the properties of the YCP receptor, carbohydrates and antibodies were used to inhibit the binding of fl-YCP to macrophages. Moreover, we investigated the role of membrane receptors Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), Toll-like receptor 6 (TLR6) and complement receptor 3 (CR3). We also examined the role of the p38 kinase pathway in mediating nitric oxide (NO) production. RESULTS: YCP had an in vitro stimulatory effect on the release of NO in macrophage, and fl-YCP can bind directly to receptors on the surface of macrophages in a time- and dose-dependent manner. Competition studies show that LPS, laminarin, anti-TLR4 antibody and anti-CD11b (CR3) antibody could inhibit fl-YCP binding to macrophages. Conversely, mannose, anti-TLR2 and anti-TLR6 antibody could not. Treatment of RAW264.7 cells with YCP resulted in significant activation of p38 in a time-dependent manner. The specific p38 inhibitor SB203580 abrogated YCP-induced NO generation. Treatment of RAW264.7 cells with anti-TLR4 antibody and anti-CR3 antibody significantly reduced YCP-induced NO production and p38 activation. CONCLUSION: We have demonstrated that YCP-induced NO production occurs through the TLR4 and CR3 membrane receptors in a p38 kinase-dependent manner in macrophages.Acta Pharmacologica Sinica (2009) 30: 1008-1014; doi: 10.1038/aps.2009.93.