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The development of tumors relies on lactate metabolic reprogramming to facilitate their unchecked growth and evade immune surveillance. This poses a significant challenge to the efficacy of antitumor immunity. To address this, a tumor-selective nano-dispatcher, PIMDQ/Syro-RNP, to enforce the immunotherapeutic effect through regulation of lactate metabolism and activation of toll-like receptors is developed. By using the tumor-targeting properties of c-RGD, the system can effectively deliver monocarboxylate transporters 4 (MCT4) inhibitor (Syro) to inhibit lactate efflux in tumor cells, leading to decreased lactate levels in the tumor microenvironment (TME) and increased accumulation within tumor cells. The reduction of lactate in TME will reduce the nutritional support for regulatory T cells (Tregs) and promote the effector function of T cells. The accumulation of lactate in tumor cells will lead to tumor death due to cellular acidosis. In addition, it will also reduce the uptake of glucose by tumor cells, reduce nutrient plunder, and further weaken the inhibition of T cell function. Furthermore, the pH-responsive release of Toll-like receptors (TLR) 7/8 agonist IMDQ within the TME activates dendritic cells (DCs) and promotes the infiltration of T cells. These findings offer a promising approach for enhancing tumor immune response through targeted metabolic interventions.
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A proportion of chronic hepatitis B virus (HBV) carriers with normal alanine transaminase (ALT) present with significant liver histological changes (SLHC). To construct a noninvasive nomogram model to identify SLHC in chronic HBV carriers with different upper limits of normal (ULNs) for ALT. The training cohort consisted of 732 chronic HBV carriers who were stratified into four sets according to different ULNs for ALT: chronic HBV carriers I, II, III, and IV. The external validation cohort comprised 277 chronic HBV carriers. Logistic regression and least absolute shrinkage and selection operator analyses were applied to develop a nomogram model to predict SLHC. A nomogram model-HBGP (based on hepatitis B surface antigen, gamma-glutamyl transpeptidase, and platelet count) demonstrated good performance in diagnosing SLHC with area under the curve (AUCs) of 0.866 (95% confidence interval [CI]: 0.839-0.892) and 0.885 (95% CI: 0.845-0.925) in the training and validation cohorts, respectively. Furthermore, HBGP displayed high diagnostic values for SLHC with AUCs of 0.866 (95% CI: 0.839-0.892), 0.868 (95% CI: 0.838-0.898), 0.865 (95% CI: 0.828-0.901), and 0.853 (95% CI: 0.798-0.908) in chronic HBV carriers I, II, III, and IV, respectively. Additionally, HBGP showed greater ability in predicting SLHC compared with the existing predictors. HBGP has shown high predictive performance for SLHC, and thus may lead to an informed decision on the initiation of antiviral treatment.
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Hepatitis B Crónica , Humanos , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/patología , Nomogramas , Virus de la Hepatitis B/genética , Cirrosis Hepática/diagnóstico , Alanina Transaminasa , ADN Viral , Antígenos e de la Hepatitis BRESUMEN
Little is known about the mediating effect of attitude toward older adults on the relationship between aging knowledge and willingness to care for older adults. We applied the theory of planned behavior (TPB) and the knowledge-attitude-behavior (KAB) model as theoretical frameworks to examine the mediation effect of attitude toward older adults. Data from 388 Chinese nursing students were analyzed. The Willingness to Care for Older People (WCOP) scale, Kogan's Attitude toward Older People scale (KAOP) and Facts on Aging Quiz (FAQ) were utilized to assess willingness, attitude and aging knowledge, respectively. Data were analyzed using SPSS 22. 0 with the PROCESS macro. Bootstrap methods were used to obtain the significance of mediating effects. The study showed that aging knowledge was significantly associated with willingness to care for older adults and that attitude toward older adults mediated the association. Bootstrapping method confirmed the significance of the indirect effect of aging knowledge through attitude, accounting for 18.9% of the total willingness variance. Overall, based on the TPB and the KAB theoretical framework, our data support the notion that improving aging knowledge and attitude may contribute to improve the willingness to aged care among nursing students.
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OBJECTIVE: To investigate the allogeneic blood transfusion (ABT) characteristics of children with acute lymphoblastic leukemia (ALL) in different risk stratification during vincristine, daunorubicin, L-asparaginase and prednisone (VDLP) induction remission. SUBJECTS AND METHODS: By referring to electronic medical records, the demographic characteristics, diagnosis, test, and treatment information including ABT were collected. According to the risk stratification of the CCCG-ALL-2015 protocol, ABTs between groups were compared, and the differences were statistically analyzed. RESULTS: One hundred sixty-three newly treated children with ALL were enrolled in this study, who received 643.5 U of red blood cells and 377.6 U of platelets (PLTs) during the VDLP. The amount of ABT in the intermediate-risk (IR) group (n=102) was significantly higher than that in the low-risk group (n=61), which were reflected in the red blood cells in the first half of VDLP (P=0.033) and the PLTs in the second half of VDLP (P<0.001). Meanwhile, the PLT counts in the IR group were significantly lower in the same period. The time node was bounded by the minimal residual disease test on the 19th day. CONCLUSIONS: Children in the IR group or with unsatisfactory induction may need more ABTs during the VDLP, and the relatively low PLT counts seem to contribute to this. The results of this study can provide a basis for patient blood management, as well as a reference for studying the long-term effects of ABT on children with ALL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transfusión Sanguínea/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Asparaginasa/administración & dosificación , Niño , Preescolar , Terapia Combinada , Daunorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Prednisona/administración & dosificación , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Vincristina/administración & dosificaciónRESUMEN
OBJECTIVE: This study aimed to investigate the most notable obesity index and its optimal cut-off point of hypertension in different age groups stratified by sexes among community residents in southern China. METHODS: In this cross-sectional study, 620 men and 631 women aged 18-59 years were enrolled. The independent-samples t-test and chi-square test were conducted to analyze continuous and categorical variables, respectively. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis assessed the association between the obesity indices and hypertension risk. RESULTS: Waist-stature ratio (WSR) and waist-hip ratio (WHR) were the most notable risk factors for hypertension in young men and women, respectively. The odds ratios (ORs) of hypertension risk increased with per standard deviation (SD) in WSR and WHR (WSR: OR = 2.877, 95% confidence interval [CI] = 1.602 to 5.167; WHR: OR = 10.683, 95%CI = 2.179 to 52.376). In the middle-aged group of both sexes, body mass index (BMI) was the most distinctive risk factor for hypertension, the ORs of hypertension risk increased with per SD in BMI (men: OR = 2.297, 95%CI = 1.683 to 3.136; women: OR = 1.810, 95%CI = 1.338 to 2.450). ROC curve analysis demonstrated WSR and PI were better indicators than other indices among young men, and WSR was the best marker among young women. However, BMI and WC were the most sensitive markers in middle-aged men and women, respectively. CONCLUSIONS: In this Chinese population, the association of obesity indices and hypertension is inconsistent in different age groups and sexes. It is important to choose appropriate indicators for specific groups of people.
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Tamaño Corporal , Hipertensión/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Estatura , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Factores de Riesgo , Factores Sexuales , Circunferencia de la Cintura , Relación Cintura-Cadera , Adulto JovenRESUMEN
BACKGROUND: Hospitalization over the last one year, an indicator of health service utilization, is an important and costly resource in older adult care. However, data on the relationship between functional status and annual hospitalization among older Chinese people are sparse, particularly for those with and without multimorbidity. In this study,we aimed to examine the association between functional status and annual hospitalization among community-dwelling older adults in Southern China, and to explore the independent contributions of socio-demographic variables, lifestyle and health-related factors and functional status to hospitalization in multimorbid and non-multimorbid groups. METHODS: This cross-sectional, community-based survey, studied 2603 older adults aged 60 years and above. Functional status was assessed by Functional Independence Measure (FIM). The outcome variable was any hospitalization over the last one year (annual hospitalization). Clustered logistic regression was used to analyze the independent contributions of FIM domains to annual hospitalization. RESULTS: Only in the multimorbid group, did the risk of annual hospitalization decrease significantly with increasing FIM score in walk domain (adjusted OR = 0.80 per SD increase, 95% CI = 0.70-0.91, P = 0.001) and its independent contribution accounted for 24.62%, more than that of socio-demographic variables (18.46%). However, among individuals without multimorbidity, there were no significant associations between FIM domains and annual hospitalization; thus, no independent contribution to the risk of hospitalization was observed. CONCLUSIONS: There exist some degree of correlation between functional status and annual hospitalization among older adults in Southern China, which might be due to the presence of multimorbidity with advanced age.
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Evaluación Geriátrica , Hospitalización/estadística & datos numéricos , Multimorbilidad , Calidad de Vida , Actividades Cotidianas , Anciano , Estudios de Casos y Controles , China/epidemiología , Enfermedad Crónica/epidemiología , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
Our aim was to explore the independent attribution of Post-stroke depression (PSD) to caregiver burden of acute ischemic stroke patients. A cross-sectional survey was performed with 271 acute ischemic stroke patients in the Huai-He Hospital and First People's Hospital of Kaifeng City in China. PSD was assessed by Self-rating Depressive Scale, and caregiver burden was assessed by Zarit Caregiver Burden Interview. Clustered logistic regression was applied to identify the impact of PSD on caregiver burden. As results, female patients, normal muscle strength and PSD were associated with caregiver burden. PSD correlated with an independent influence of 17.2% on the risk of caregiver burden, The independent influence of PSD on caregiver burden was smaller than that of social-demographics of caregivers and clinical factors of stroke patients This study suggests that PSD may have a modest influence on caregiver burden.
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Isquemia Encefálica/psicología , Cuidadores/psicología , Depresión/psicología , Trastorno Depresivo/psicología , Accidente Cerebrovascular/psicología , Adaptación Psicológica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , China , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fuerza Muscular , Factores Sexuales , Accidente Cerebrovascular/etiología , Adulto JovenRESUMEN
To investigate the prevalence of fatigue, the relationship between sickness or injury within two weeks, chronic diseases and fatigue among adults aged 18-45 years. Thousand five hundred and seventy nine individuals were included in this cross-sectional study. The Chalder Fatigue Scale (CFS) was used to assess fatigue defined as CFS score ≥4. The prevalence of fatigue was 25% in this study. Our results showed that only sickness or injury within two weeks (odds ratio [OR]: 2.440) and chronic diseases (OR: 1.727) were significantly related to fatigue. Moreover, their ORs for fatigue remained the same in all models (binary logistic regression models with adjusting for demographic and health-related characteristics one by one). In conclusion, fatigue was prevalent among adults aged 18-45 years. Sickness or injury within two weeks and chronic diseases were the risk factors for fatigue independent of demographic and health-related characteristics.
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Enfermedad Crónica/psicología , Fatiga/psicología , Rol del Enfermo , Heridas y Lesiones/psicología , Adolescente , Adulto , China , Enfermedad Crónica/epidemiología , Correlación de Datos , Estudios Transversales , Fatiga/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Heridas y Lesiones/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Multimorbidity, the coexistence of two or more chronic diseases, is common in older adults. And it may lead to many adverse health outcomes, such as disability. However, data on multimorbidity and its relationship with functional independence are scarce in Asian countries. Therefore, this study aims to investigate the relationship between multimorbidity and functional status among older people in China. METHODS: Based on a cross-sectional survey, the information regarding 2705 older adults, who were of at least 60 years of age, was collected through interviews and analyzed. To assess functional status, we used the Functional Independence Measure (FIM). Exploratory factor analysis was performed to assess correlations among chronic diseases. Several logistic regression models were run in the study. RESULTS: The presence of two or more chronic conditions and the number of multimorbidity group overlaps were independent risk factors for the loss of functional independence in older adults. Hypertension and chronic pain, emerged as the most prevalent multimorbidity pair, was significantly associated with functional independence (OR = 1.64, 95% CI = 1.25-2.16), followed by the co-occurrence of hypertension and heart diseases with a lower prevalence but a higher OR compared with the former pair (OR = 1.72, 95% CI = 1.15-2.58). Of the five multimorbidity groups used for factor analysis, the bones and pain group (OR = 1.47, 95% CI = 1.23-1.77) and the cardiometabolic group (OR = 1.34, 95% CI = 1.13-1.59) were both found to be significantly correlated with lower functional independence. CONCLUSIONS: Multimorbidity was common among older people in Southern China. Studying the relationship between multimorbidity and functional status could be useful to find potential correlations among chronic diseases. Additionally, it may also be meaningful to identify multimorbidity combinations, posing an increased risk of loss of functional independence, and further improve functional status in older adults with comorbidities.
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Enfermedad Crónica/clasificación , Enfermedad Crónica/epidemiología , Comorbilidad/tendencias , Personas con Discapacidad/estadística & datos numéricos , Distribución por Edad , Anciano , Pueblo Asiatico , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Enfermedades Metabólicas/epidemiología , Persona de Mediana Edad , Morbilidad/tendencias , Neoplasias/epidemiología , Prevalencia , Calidad de Vida , Factores de RiesgoRESUMEN
BACKGROUND: Previous studies have confirmed that low serum albumin levels in acute ischemic stroke patients increased the risk for poor outcome and death, demonstrating the neuroprotective role of albumin. However, there are few studies investigating the relationship between albumin levels and recurrence of stroke. The aim of this study was to evaluate the effect of serum albumin level on the risk of recurrence in patients with acute ischemic stroke. METHODS: Seven hundred fifty-three consecutive patients with acute first-ever ischemic stroke were recruited in this study. Recurrent outcome was measured 1 year after stroke through home interviews (n = 692). RESULTS: Patients with recurrence had significantly lower serum albumin level than those without recurrence (37.07 ± 4.21 vs 38.91 ± 3.25). The multiple logistic regression adjustment for confounding factors showed that the association remained significant for patients in the second albumin quartile, the third quartile, and the fourth quartile compared with patients in the first quartile (adjusted odds ratio [aOR] = 0.543, 95% confidence interval [CI]: 0.307-0.959, P= .036; aOR = 0.449, 95% CI: 0.249-0.812, P= .008; and aOR = 0.290, 95% CI: 0.148-0.570, P < .001). CONCLUSION: Lower serum albumin level increases the risk of recurrence in patients with acute ischemic stroke, suggesting that serum albumin level might be used as an indicator for stroke recurrence.
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Isquemia Encefálica/metabolismo , Hipoalbuminemia/metabolismo , Obesidad/metabolismo , Sobrepeso/metabolismo , Albúmina Sérica/metabolismo , Accidente Cerebrovascular/metabolismo , Delgadez/metabolismo , Anciano , Isquemia Encefálica/complicaciones , Isquemia Encefálica/epidemiología , China/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hipoalbuminemia/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/epidemiología , Oportunidad Relativa , Sobrepeso/epidemiología , Pronóstico , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Delgadez/epidemiologíaRESUMEN
Objective: We investigated the clinical characteristics, fall outcomes, and related factors of falls in patients who were hospitalized in the rehabilitation department, and explored strategies to reduce the incidence of falls and prevent falls in patients. Methods: Data from 60 patients who fell in the rehabilitation department between 2016 and 2021 were analyzed for clinical characteristics, associated factors, incidence of falls, injuries, and patient demographics. Under the random stratified sampling method, 60 patients who did not fall during the same period were selected as the control group, and relevant data was collected. Measurement data were compared using an independent sample t-test. Enumeration data were compared using chi-squared (χ2) test was employed to compare these data between the two groups. Non-parametric data were analyzed using the Mann-Whitney U-test. Factors potentially influencing falls were scrutinized through both univariate and binary logistic regression analyses. Results: The median annual incidence of falls among patients who were hospitalized in the rehabilitation department was 0.04%, while the overall fall injury rate was 60%. Falls were most prevalent within 30 days of hospitalization (71.67%). The most common fall-related condition was craniocerebral disease (83.33%). The incidents of falls location of fall were mainly reported in nearby areas of rehabilitation ward (70%). Most accidents occurred between 7:00 a.m.-12:00 p.m. and 3:01 p.m.-6:00 p.m. (63.33%), and dyskinesia was the most common cause of falls (71.67%). There were 39 patients (65.00%) with Barthel Index (BI) scores ranging between 40-60. Conclusion: Patients in the rehabilitation department had a greater incidence of falls and fall injuries. Within 30 days of admission, patients with moderately dependent craniocerebral disorders and dyskinesia frequently experienced falls during typical daytime shifts in areas characterized by endemic conditions.
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PURPOSE: To assess the predictive value of liver stiffness measurement (LSM) and three bleeding risk scoring systems for esophagogastric varices bleeding (EGVB) in patients with hepatitis B cirrhosis during hospitalization. METHODS: In this study, 210 patients who had hepatitis B cirrhosis were selected as the subjects. They were categorized into two groups based on whether EGVB occurred during hospitalization: a bleeding group (70 cases) and a non-bleeding group (140 cases). Logistic regression was used to analyze the factors related to the occurrence of EGVB, and the diagnostic performance was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: Significant differences were observed between the two groups in systolic blood pressure, platelet count, albumin, urea nitrogen, LSM, pre-endoscopic Rockall score (PRS), Glasgow-Blatchford score (GBS), and AIMS65 score (P < 0.05). The correlation analysis showed that LSM had significant positive relationship with PRS, GBS and AIMS65 score. Logistic regression analysis revealed that LSM and GBS score were independent risk factors for EGVB occurrence during hospitalization. ROC curve analysis showed that the combined prediction model of LSM and GBS score had the best prediction performance for EGVB occurrence, with an ROC curve area of 0.811, which was significantly better than the three risk scoring systems (P < 0.05), but similar to the predicted value of LSM (P = 0.335). CONCLUSIONS: The combination of LSM and GBS score can significantly improve the predictive efficacy of EGVB occurrence in patients with hepatitis B cirrhosis during hospitalization, which has important clinical significance for patients' prognosis.
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Várices Esofágicas y Gástricas , Hepatitis B , Várices , Humanos , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/epidemiología , Várices Esofágicas y Gástricas/complicaciones , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/etiología , Medición de Riesgo , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Pronóstico , Factores de Riesgo , Curva ROC , Várices/complicaciones , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: A previous comparative tissue proteomics study by the authors of the current study led to the identification of caldesmon (CaD) as one of the proteins associated with cervical metastasis of oral cavity squamous cell carcinoma (OSCC). In the current investigation, the authors focused on the potential functions of CaD in patients with OSCC. METHODS: CaD expression was examined in tissue samples from 155 patients using immunohistochemical analysis. The expression of CaD variants was determined by Western blot analysis and reverse transcriptase-polymerase chain reaction. In addition, the specific effects of CaD gene overexpression and silence were determined in OSCC cell lines. RESULTS: CaD expression was found to be significantly higher in tumor cells from metastatic lymph nodes compared with primary tumor cells, and was nearly absent in normal oral epithelia. Higher CaD expression was found to be correlated with positive N classification, poor differentiation, perineural invasion, and tumor depth (P = .001, P = .029, P = .001, and P = .031, respectively). In survival analyses, OSCC patients with higher CaD expression were found to have poorer prognosis with regard to disease-specific survival and disease-free survival (P = .003 and P = .014, respectively). Multivariate analyses further indicated that higher CaD expression was an independent predictor of disease-specific survival (P = .043). Serum CaD levels were found to be significantly higher in patients with OSCC, but this finding was not associated with clinicopathological manifestations. Data obtained from in vitro suppression, rescue, and overexpression of CaD in OEC-M1 cells indicated that CaD promotes migration and invasive processes in OSCC cells. CONCLUSIONS: The findings of the current study collectively suggest that the low-molecular-weight CaD expression in OSCC tumors is associated with tumor metastasis and patient survival.
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Proteínas de Unión a Calmodulina/biosíntesis , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de la Boca/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Unión a Calmodulina/genética , Proteínas de Unión a Calmodulina/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Técnicas de Cultivo de Célula , Movimiento Celular/fisiología , Supervivencia sin Enfermedad , Femenino , Silenciador del Gen , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Adulto JovenRESUMEN
BACKGROUND: XinJiErKang (XJEK), a Chinese herbal formula, is identified as an effective preparation to treat coronary heart disease and myocarditis. The aim of the study is to investigate the anti-hypertensive effects of XJEK by oral administration and also to find out whether the drug has any role in oxidative stress and vascular endothelial function. METHODS: Clipping of the renal artery resulted in gradual elevation of the systolic blood pressure (SBP) which reached a plateau after 4 weeks of surgery. Treatment of hypertensive rats (20 mmHg higher than basic systolic blood pressure) with XJEK (6, 12, 24 g/kg/day) and fosinopril (15 mg/kg/day) respectively by intragastric administration started 4 weeks after surgery and continued for 4 weeks. The sham-operated (Sh-Op) controls received drinking water. BP was monitored weekly using tail-cuff apparatus. At the end of 8 wk, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate of rise of left ventricular pressure (±dp/dtmax) were examined (PowerLab 8/30, AD Instruments, Australia). The myocardial hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes were investigated by hematoxylin and eosin (HE) and Van Gieson (VG) stain. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) content in serum, contents of hydroxyproline (Hyp) in the ventricular tissue were assayed by xanthin oxidase method, thiobarbituric acid (TBA) method, Griess method and alkaline hydrolysis method, respectively. Angiotensin II (Ang II) content in serum was detected by radioimmunoasssay method. RESULTS: XJEK therapy potently improved cardiac function, inhibited myocardial hypertrophy, improved cardiac pathology change, decreased the myocardial cross-section area (CSA), collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA), reduced the content of Hyp in the left ventricular tissue, inhibited the decrease of SOD activity and increase of MDA, Ang II content in serum. Moreover, treatment with XJEK improved endothelial dysfunction (ED) manifested by promoting endothelial-dependent vasodilation of thoracic aortic rings and enhancing the NO activity in serum. CONCLUSIONS: These findings suggest that administration of XJEK possess protective effects against 2K1C induced hypertension and cardiac remodeling in rats, preserve NO activity and endothelial function.
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Medicamentos Herbarios Chinos/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Corazón/efectos de los fármacos , Hipertensión/patología , Miocardio , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Angiotensina II/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Aorta Torácica , Australia , Presión Sanguínea , Medicamentos Herbarios Chinos/farmacología , Hipertensión/sangre , Hipertensión/metabolismo , Magnoliopsida , Masculino , Malondialdehído/sangre , Medicina Tradicional China , Miocardio/metabolismo , Miocardio/patología , Óxido Nítrico/sangre , Ratas , Superóxido Dismutasa/metabolismo , Vasodilatación/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacosRESUMEN
Growing experimental and clinical data highlights the important roles of increased reactive oxygen species production in cardiovascular remodeling (CR). Oligomeric grape seed proanthocyanidins (GSPs) have been shown to be potent antioxidants and free radical scavengers. Mice were treated with DOCA-salt to induce CR and were given distilled water or oligomeric GSPs for 4 weeks. The heart weight (HW) index and kidney weight (KW) index were expressed as heart weight/body weight (HW/BW) and kidney weight/body weight (KW/BW); the histological changes were investigated by hematoxylin and eosin and Van Gieson staining.The endothelial-dependent vasodilation function induced by acetylcholine was investigated in isolated thoracic aorta ring. Colorimetric analysis was used to assay superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and nitric oxide (NO) content in serum and hydroxyproline content in cardiac tissue. Administration of GSPs markedly alleviated the elevation of HW/BW ratio, KW/BW ratio and cross-sectional area of cardiomyocytes, decreased collagen deposition in heart and attenuated histopathology injury, and improves endothelial-dependent aorta ring relaxation in vitro accompany by increasing of NO content in serum. Meanwhile, treatment with GSPs significantly ameliorated oxidative stress via increasing SOD activities and decreasing MDA formation. These findings suggest that administration of GSPs has the potential to attenuate DOCA-salt induced CR and KH and preserve NO activity and endothelial function, which mechanism may contribute to its antioxidant characteristic, at least in part.
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Aorta/efectos de los fármacos , Extracto de Semillas de Uva/farmacología , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Estrés Oxidativo , Proantocianidinas/farmacología , Animales , Peso Corporal , Desoxicorticosterona , Riñón/patología , Masculino , Malondialdehído/metabolismo , Ratones , Miocardio/patología , Óxido Nítrico/sangre , Tamaño de los Órganos , Superóxido Dismutasa/metabolismo , Remodelación Ventricular , Vitis/químicaRESUMEN
Poly (ADP-ribose) polymerase 1 (PARP1) is a key DNA damage sensor that is recruited to damaged sites after DNA strand breaks to initiate DNA repair. This is achieved by catalyzing attachment of ADP-ribose moieties, which are donated from NAD+, on the amino acid residues of itself or other acceptor proteins. PARP inhibitors (PARPi) that inhibit PARP catalytic activity and induce PARP trapping are commonly used for treating BRCA1/2-deficient breast and ovarian cancers through synergistic lethality. Unfortunately, resistance to PARPi frequently occurs. In this review, we present the novel substrates and regulators of the PARP1-catalyzed poly (ADP-ribosyl)ation (PARylatison) that have been identified in the last 3 years. The overall aim is the presentation of protein interactions of potential therapeutic intervention for overcoming the resistance to PARPi.
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The present study was conducted to evaluate the effects of Clostridium butyricum (CB) and fructooligosaccharide (FOS) singly or combined, on performance, egg quality, amino acid digestibility, jejunal morphology, immune function and antioxidant capacity in peak-phase laying hens. A total of 288 Hy-Line Brown laying hens (30 weeks of age) were randomly assigned to 4 dietary groups that included basal diet, basal diet +0.02% of CB (zlc-17: 1 × 109 CFU/g) (PRO), basal diet +0.6% FOS (PRE), and basal diet +0.02% CB + 0.6% FOS (SYN) for 12 weeks. Each treatment had 6 replicates with 12 birds each. The results demonstrated that probiotics (PRO), prebiotics (PRE) and synbiotics (SYN) (p ≤ 0.05), respectively, exerted a positive effect on the performance and physiological response of the birds. There were significant increases in egg production rate, egg weight, egg mass, daily feed intake and reduced number of damaged eggs. and zero mortality rate due to dietary PRO, PRE and SYN (p ≤ 0.05) respectively. Also, feed conversion was improved by PRO (p ≤ 0.05). In addition, egg quality assessment showed that; eggshell quality was increased by PRO (p ≤ 0.05) and albumen indices (Haugh unit, thick albumen content, and albumen height) were enhanced by PRO, PRE and SYN (p ≤ 0.05). Further analysis showed that PRO, PRE and SYN (p ≤ 0.05), reduced heterophil to lymphocyte ratio, increased antioxidant enzymes and immunoglobulin concentration. Although spleen index was higher for PRO (p ≤ 0.05) group. The significant increase in villi height, villi width, villi height to crypt depth ratio and reduced crypt depth were obvious for PRO, PRE, and SYN (p ≤ 0.05). Furthermore, improved nutrient absorption and retention evidenced by increased digestibility of crude protein and amino acids, were notable for PRO, PRE, and SYN (p ≤ 0.05) group. Collectively, our findings revealed that dietary CB and FOS alone, or combined, enhanced productive performance, egg quality, amino acid digestibility, jejunal morphology, and physiological response in peak-phase laying hens. Our results would provide direction on nutritional strategies for gut enhancers and better physiological response of peak laying hens.
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Background and Aims: To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT). Methods: We grouped 439 CHB patients using different ULNs for ALT: cohort I, ≤40 U/L (439 subjects); cohort II, ≤35/25 U/L (males/females; 330 subjects); and cohort III, ≤30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (≤40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression. Results: Fibrosis-adjusted LSM values significantly increased with increasing inflammation. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A≥2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A≥2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, external, and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3, and no significant differences in AUCs among the four groups. LSM and globulin independently predicted A≥2. The AUC of an LSM-globulin model for A≥2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM. Conclusions: LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.
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OBJECTIVE: To investigate the effects of Xinjierkang on two kidney one clip -induced hypertension and target organ injury in rats. METHODS: Two kidney one clip-induced hypertension rats model was established. Rats were divided into control group, model group, Xinjierkang group, and fosinopril group. At the end of 8th w, the hemodynamics indexes were recorded. The cardiac hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes of heart, aorta and kidney were investigated by HE and/or Van Gieson stain. RESULTS: Compared with control group, the heart systolic and diastolic function were impaired, the heart weight index, cardiomyocytes cross section area (CSA), cardiac collagen deposition, vascular remodeling index and glomerulus area were increased markedly in model group rats. Administration of Xinjierkang and fosinopril markedly ameliorated hemodynamic indexes, inhibited the elevation of HW/BW ratio, CSA of cardiomyocytes, vascular remodeling index and glomerulus hypertrophy, decreased collagen deposition in heart. CONCLUSION: Xinjierkang has protective effects against two kidney one clip-induced hemodynamic impairment, cardiovascular remodeling and glomerulus hypertrophy in rats.
Asunto(s)
Antihipertensivos/farmacología , Medicamentos Herbarios Chinos/farmacología , Hipertensión Renal/tratamiento farmacológico , Glomérulos Renales/patología , Miocardio/patología , Remodelación Ventricular/efectos de los fármacos , Animales , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Combinación de Medicamentos , Medicamentos Herbarios Chinos/uso terapéutico , Fosinopril/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión Renal/complicaciones , Hipertensión Renal/patología , Glomérulos Renales/efectos de los fármacos , Masculino , Plantas Medicinales/química , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Arteria Renal/cirugía , Función Ventricular Izquierda/efectos de los fármacos , Presión Ventricular/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the effects of Xinji' erkang (XJEK), a compound Chinese herbal medicine, on isoproterenol-induced ventricular remodeling in mice. METHODS: Isoproterenol was given subcutaneously (1 mg/kg, twice per day for 7 d) to induce ventricular remodeling in mice. Mice were divided into normal control group, model group, XJEK low-, medium- and high- dose groups, XJEK water layer group, XJEK n-butanol layer group and metoprolol group. All drugs were given by intragastric administration. At the end of the 7th day, the hearts of the rats were weighted, and myocardial hypertrophy index was expressed as heart weight/body weight (HW/BW). The histological changes were observed by hemotoxylin-eosin and Van Gieson staining. Colorimetric method was used to determine the content of hydroxyproline in heart, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum. RESULTS: Compared with the isoproterenol injection only, XJEK potently inhibited cardiomyocyte hypertrophy and the increase of hydroxyproline content in heart (P<0.01), improved cardiac pathology change, inhibited the decrease of SOD activity and the increase of MDA content in serum (P<0.01). XJEK water layer also inhibited the increase of cardiomyocyte hypertrophy (P<0.01) while XJEK n-butanol layer inhibited cardiomyocyte hypertrophy and fibrosis (P<0.01). CONCLUSION: XJEK possesses protective effects against isoproterenol-induced ventricular remodeling in mice, which may be related to its actions in reducing the oxidative stress and improving the antioxidant activity of the body. XJEK water layer and XJEK n-butanol layer attenuated ventricular remodeling without significant oxidative stress state changing, which indicates that a non-antioxidative stress mechanism may exist.