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Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the "on medication" state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.
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Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Humanos , Atrofia de Múltiples Sistemas/diagnóstico por imagen , Atrofia de Múltiples Sistemas/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/fisiopatología , Anciano , Imagen por Resonancia Magnética/métodos , Corteza Motora/diagnóstico por imagen , Corteza Motora/fisiopatología , Electromiografía , Neuroimagen/métodosRESUMEN
We investigated the effectiveness of online Sensate Focus exercises, delivered online as a series of 11 animation videos, in improving participants' sexual functioning and enhancing intimacy, relationship and sexual satisfaction. We studied 35 Chinese heterosexual couples, assessed them at pretest, post-test, and a three-month follow-up. Compared to the waitlist control group, the experimental group showed improvement in orgasm in women, and this was maintained at follow-up. Also, for those with a lower function at pretest, the intervention was possibly effective in improving erectile function among men, as well as overall sexual function and pain among women. These improvements were maintained at follow-up as well. Findings from the current study suggest that online Sensate Focus intervention has potential in treating sexual dysfunction of Chinese heterosexual couples. It may also serve as the first part of a stepped care approach or be integrated with other medication or cognitive behavioral therapy treatment.
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Heterosexualidad , Humanos , Femenino , Masculino , Adulto , Heterosexualidad/psicología , China , Parejas Sexuales/psicología , Disfunciones Sexuales Psicológicas/terapia , Disfunciones Sexuales Psicológicas/psicología , Disfunciones Sexuales Fisiológicas/terapia , Disfunciones Sexuales Fisiológicas/psicología , Orgasmo , Conducta Sexual/psicología , Satisfacción Personal , Persona de Mediana Edad , Relaciones Interpersonales , Terapia de Parejas/métodos , Pueblos del Este de AsiaRESUMEN
PURPOSE: Random item effects item response theory (IRT) models have received much attention for more than a decade. However, more research is needed on random item effects IRT models for polytomous data. Additionally, to improve the utility of this new class of IRT models, the scoring issue must be addressed. METHODS: We proposed a new random item effects generalized partial credit model (GPCM), which considers both random person and random item and category-specific effects. In addition, we introduced a multiple imputation (MI)-based scoring procedure that applies to various random item effects IRT models. To evaluate the proposed model and scoring procedure, we analyzed data from a Quality of Life (QoL) scale for the Chronically Mentally III and conducted a preliminary simulation study. RESULTS: In the empirical data analysis, we found that patient scores generated based on the proposed model and scoring procedure were almost identical to those obtained through the conventional GPCM and scoring method. However, the standard errors (SEs) associated with the scores were slightly larger when the proposed approach was utilized. In the simulation study, we observed adequate recovery of the model parameters and patient scores. CONCLUSION: The proposed model and MI-based scoring procedure contribute to the literature. The proposed model substantially reduces the number of free parameters in comparison to a conventional GPCM, which can be desired when sample sizes are small, e.g., special populations. In addition, the MI-based scoring procedure addresses the scoring issue and can be easily extended for scoring with other random item effects IRT models.
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Calidad de Vida , Proyectos de Investigación , Humanos , Calidad de Vida/psicología , Tamaño de la Muestra , Simulación por Computador , Encuestas y CuestionariosRESUMEN
Student evaluation of teaching (SET) questionnaires are ubiquitously applied in higher education institutions in North America for both formative and summative purposes. Data collected from SET questionnaires are usually item-level data with cross-classified structure, which are characterized by multivariate categorical outcomes (i.e., multiple Likert-type items in the questionnaires) and cross-classified structure (i.e., non-nested students and instructors). Recently, a new approach, namely the cross-classified IRT model, was proposed for appropriately handling SET data. To inform researchers in higher education, in this article, the cross-classified IRT model, along with three existing approaches applied in SET studies, including the cross-classified random effects model (CCREM), the multilevel item response theory (MLIRT) model, and a two-step integrated strategy, was reviewed. The strengths and weaknesses of each of the four approaches were also discussed. Additionally, the new and existing approaches were compared through an empirical data analysis and a preliminary simulation study. This article concluded by providing general suggestions to researchers for analyzing SET data and discussing limitations and future research directions.
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Estudiantes , Enseñanza , Humanos , Estudiantes/estadística & datos numéricos , Enseñanza/estadística & datos numéricos , Encuestas y Cuestionarios , Modelos Estadísticos , Interpretación Estadística de Datos , Evaluación Educacional/métodos , Evaluación Educacional/estadística & datos numéricos , Simulación por Computador/estadística & datos numéricosRESUMEN
BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC), which has a complex pathogenesis and poor prognosis, is one of the most common malignancies worldwide. Hepatitis virus B infection is the most common cause of HCC in Asian patients. Autophagy is the process of digestion and degradation, and studies have shown that autophagy-associated effects are closely related to the development of HCC. In this study, we aimed to construct a prognostic model based on autophagy-related genes (ARGs) for the Asian HCC population to provide new ideas for the clinical management of HCC in the Asian population. METHODS: The clinical information and transcriptome data of Asian patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and 206 ARGs were downloaded from the human autophagy database (HADB). We performed differential and Cox regression analyses to construct a risk score model. The accuracy of the model was validated by using the Kaplan-Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox independent prognostic analyses. The results Thirteen ARGs that were significantly associated with prognosis were finally identified by univariate and multivariate Cox regression analyses. The K-M survival curves showed that the survival rate of the low-risk group was significantly higher than that of the high-risk group (p < 0.001), and the multi-indicator ROC curves further demonstrated the predictive ability of the model (AUC = 0.877). CONCLUSION: The risk score model based on ARGs was effective in predicting the prognosis of Asian patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Asiático , Autofagia/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , PronósticoRESUMEN
BACKGROUND: As highly-conserved types of lipid flippases among fungi, P4-ATPases play a significant role in various cellular processes. Cdc50 acts as the regulatory subunit of flippases, forming heterodimers with Drs2 to translocate aminophospholipids. Cdc50 homologs have been reported to be implicated in protein trafficking, drug susceptibility, and virulence in Saccharomyces cerevisiae, Candida albicans and Cryptococcus neoformans. It is likely that Cdc50 has an extensive influence on fungal cellular processes. The present study aimed to determine the function of Cdc50 in Candida glabrata by constructing a Δcdc50 null mutant and its complemented strain. RESULTS: In Candida glabrata, the loss of Cdc50 led to difficulty in yeast budding, probably caused by actin depolarization. The Δcdc50 mutant also showed hypersensitivity to azoles, caspofungin, and cell wall stressors. Further experiments indicated hyperactivation of the cell wall integrity pathway in the Δcdc50 mutant, which elevated the major cell wall contents. An increase in exposure of ß-(1,3)-glucan and chitin on the cell surface was also observed through flow cytometry. Interestingly, we observed a decrease in the phagocytosis rate when the Δcdc50 mutant was co-incubated with THP-1 macrophages. The Δcdc50 mutant also exhibited weakened virulence in nematode survival tests. CONCLUSION: The results suggested that the lipid flippase subunit Cdc50 is implicated in yeast budding and cell wall integrity in C. glabrata, and thus have a broad influence on drug susceptibility and virulence. This work highlights the importance of lipid flippase, and offers potential targets for new drug research.
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Adenosina Trifosfatasas , Saccharomyces cerevisiae , Adenosina Trifosfatasas/metabolismo , Saccharomyces cerevisiae/metabolismo , Candida glabrata/genética , Candida glabrata/metabolismo , Caspofungina , Pared Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMEN
BACKGROUND: The breast-conserving surgery and reconstruction rate in China is relatively low when compared with those in Western countries. Moreover, predictors of surgical choices for women with breast cancer in China have not yet been explored. This study aims to explore differences in the surgical choices of women with different demographic and clinical characteristics and the predictors that influence surgical choices of women with early-stage breast cancer. METHODS: This retrospective study included women with early-stage (0-II) breast cancer who underwent surgeries at one of two Xiamen University-affiliated hospitals between 2009 and 2017. Using medical records, eleven variables were collected: the woman's age, year of diagnosis, hospital, marital status, payment method, cancer stage, presence of positive axillary lymph node, histology, neoadjuvant chemotherapy, radiotherapy, and the type(s) of surgery they chose. Binary logistic regression was used to analyse predictors of surgical choice. RESULTS: A total of 1,787 cases were included in this study. Of the total number of women with breast cancer, 61.3% underwent mastectomy without breast reconstruction, 26.4% underwent mastectomy with breast reconstruction, and the remaining 12.2% chose breast-conserving surgery. Women with different demographic and clinical characteristics underwent different types of surgery. Cancer stage, neoadjuvant chemotherapy, radiotherapy, and the choice of hospital were found to be predictors of breast-conserving surgery. Meanwhile, age, year of diagnosis, payment method, neoadjuvant chemotherapy, and the choice of hospital were found to be predictors of reconstruction after mastectomy in women with early-stage breast cancer. CONCLUSIONS: In China, surgical choices for women with breast cancer have diversified. Healthcare workers should understand the surgical preferences of women of different ages. For early detection of breast cancer, knowledge of breast self-examination and breast cancer screening should be provided. Adequate information about the safety of reconstruction and advocacy for medical insurance coverage of reconstruction should be offer. Breast surgeons need specialised training and standardising protocols towards different types of breast surgery. These actions will help women make better, well-informed decisions about their breast surgeries.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Mastectomía/métodos , Estudios Retrospectivos , Mastectomía Segmentaria , China/epidemiologíaRESUMEN
Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations. By population-based omics analysis, we revealed that rare functional variants across in the leptin and peroxisome proliferator-activated receptors (PPARs) gene sets were imbalanced with rare functional variants across the APs-induced Mets and Non-Mets cohort. Besides, we discovered that APs-induced Mets are hypermethylated in ABCG1 (chr21:43642166-43642366, adjusted P < 0.05) than Non-Mets, and hypermethylation of this area was associated with higher TC (total cholesterol) and TG (triglycerides) levels in HepG2 cells. Candidate genes from omics studies were furtherly screened in C. elegans and 17 gene have been verified to associated with olanzapine (OLA) induced fat deposit. Among them, several genes were expressed differentially in Mets cohort and APs-induced in vitro/in vivo models compared to controls, demonstrating the validity of omics study. Overexpression one of the most significant gene, PTPN11, exhibited compromised glucose responses and insulin resistance. Pharmacologic inhibition of PTPN11 protected HepG2 cell from APs-induced insulin resistance. These findings provide important insights into our understanding of the mechanism of the APs-induced Mets.
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Antipsicóticos , Leptina , Síndrome Metabólico , Receptores Activados del Proliferador del Peroxisoma , Animales , Humanos , Antipsicóticos/efectos adversos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Caenorhabditis elegans , Resistencia a la Insulina/genética , Leptina/genética , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/complicaciones , Síndrome Metabólico/genética , Multiómica , Receptores Activados del Proliferador del Peroxisoma/genéticaRESUMEN
Unlike other death forms, such as autophagy, necrosis, and apoptosis, ferroptosis is a novel type of programmed cell death with iron-dependent properties. Esteroxygenase affects the content of unsaturated fatty acids and promotes lipid peroxidation. In addition, GSH can cause the reduction of GPX4, which can cause ferroptosis. P53 and its signaling pathways also regulate ferroptosis. Recent studies have confirmed that ferroptosis also promotes the death of RGC. The progressive loss of RGC is one of the pathological features of glaucoma, indicating that ferroptosis may be related to the onset of glaucoma. Down-regulation of GPX4 leads to the loss of nerve cells, which suggests that ferroptosis may also be related to diseases related to optic nerve damage. At present, ferroptosis has been extensively researched and advanced in systemic diseases, such as cardiovascular diseases, gastrointestinal tumors such as stomach, liver, and pancreas, and brain diseases. This review focuses on the research progress of ferroptosis in ophthalmic diseases, especially glaucoma and optic nerve damage.
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Ferroptosis , Glaucoma , Humanos , Apoptosis , Peroxidación de Lípido , Nervio ÓpticoRESUMEN
We investigated the prevalence of problematic masturbation using different criteria. We also investigated if masturbation-related distress was associated with sexual abuse history, family attitudes towards sexuality during childhood, and depression and anxiety symptoms. Here, 12,271 Finnish men and women completed a survey reporting masturbation frequency, desired masturbation frequency, sexual distress, childhood sexual abuse, sex-positive family background, as well as depression and anxiety symptoms. Among both sexes, those whose masturbation frequency did not match with desired frequency experienced more sexual distress. Different conceptualizations of problematic masturbation resulted in different proportions of individuals categorized as having it (i.e., 8.3% of men and 2.7% of women experienced self-perceived problematic masturbation, that is masturbating more than they desired and experiencing sexual distress; 2% of men and 0.6% of women masturbated more frequently than average and meanwhile experienced self-perceived problematic masturbation; 6.3% of men and 2.1% of women masturbated less frequently than average but still experienced self-perceived problematic masturbation). Moreover, among both sexes, self-perceived problematic masturbation was positively associated with childhood sexual abuse, depression, and anxiety, while negatively associated with a sex-positive family background. Our results point to the complexity of defining problematic masturbation. Causes of sexual distress related to masturbation need to be carefully examined case by case to choose an appropriate clinical approach.
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Masturbación , Conducta Sexual , Masculino , Femenino , Humanos , Sexualidad , Encuestas y Cuestionarios , ActitudRESUMEN
Helicobacter pylori is closely linked to many gastric diseases such as gastric ulcers and duodenal ulcers. Therefore, biosensing H. pylori has attracted wide attention from both scientists and clinicians. Here, we proposed an electrochemiluminescence (ECL)-based platform that could sensitively detect H. pylori DNA. In this platform, a novel target-cycling synchronized rolling circle amplification was used for signal amplification. Silver nanoclusters (Ag NCs) were synthesized on the circle DNA products, embedding them with the ability to catalyze the electrochemical reduction of K2 S2 O8 , in turn resulting in rapid consumption of the ECL co-reactant near the working electrode, and leading to a decrease in the ECL emission intensity. In addition to its excellent stability and selectivity, the proposed strategy had a low detection limit of 10 pM, an indication that it can be beneficially applied to test biosamples. Furthermore, a biosensing chip was designed to improve the throughput and shed new light on large-scale clinical biosensing applications.
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Técnicas Biosensibles , Helicobacter pylori , Nanopartículas del Metal , Helicobacter pylori/genética , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , ADN/genética , Límite de DetecciónRESUMEN
Nanoscale phenomena such as surface hydration and the molecular layering of liquids under strong nanoscale confinement play a critical role in liquid-mediated surface adhesion that is not accounted for by available models, which assume a uniform liquid density with or without considering surface forces and associated disjoining pressure effects. This work introduces an alternative theoretical description that via the potential of mean force (PMF) considers the strong spatial variation of the liquid number density under nanoscale confinement. This alternative description based on the PMF predicts a dual effect of surface hydration by producing: (i) strong spatial oscillations of the local liquid density and pressure and, more importantly, (ii) a configuration-dependent liquid-solid surface energy under nanoscale confinement. Theoretical analysis and molecular dynamics simulations for the case of an axisymmetric water bridge with nanoscale heights show that the latter hydration effect is critical for the accurate prediction of the surface energy and adhesion forces when a small volume of liquid is nanoscopically confined by two surfaces approaching contact.
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BACKGROUND: Accurate prediction of survival is crucial for both physicians and women with breast cancer to enable clinical decision making on appropriate treatments. The currently available survival prediction tools were developed based on demographic and clinical data obtained from specific populations and may underestimate or overestimate the survival of women with breast cancer in China. OBJECTIVE: This study aims to develop and validate a prognostic app to predict the overall survival of women with breast cancer in China. METHODS: Nine-year (January 2009-December 2017) clinical data of women with breast cancer who received surgery and adjuvant therapy from 2 hospitals in Xiamen were collected and matched against the death data from the Xiamen Center of Disease Control and Prevention. All samples were randomly divided (7:3 ratio) into a training set for model construction and a test set for model external validation. Multivariable Cox regression analysis was used to construct a survival prediction model. The model performance was evaluated by receiver operating characteristic (ROC) curve and Brier score. Finally, by running the survival prediction model in the app background thread, the prognostic app, called iCanPredict, was developed for women with breast cancer in China. RESULTS: A total of 1592 samples were included for data analysis. The training set comprised 1114 individuals and the test set comprised 478 individuals. Age at diagnosis, clinical stage, molecular classification, operative type, axillary lymph node dissection, chemotherapy, and endocrine therapy were incorporated into the model, where age at diagnosis (hazard ratio [HR] 1.031, 95% CI 1.011-1.051; P=.002), clinical stage (HR 3.044, 95% CI 2.347-3.928; P<.001), and endocrine therapy (HR 0.592, 95% CI 0.384-0.914; P=.02) significantly influenced the survival of women with breast cancer. The operative type (P=.81) and the other 4 variables (molecular classification [P=.91], breast reconstruction [P=.36], axillary lymph node dissection [P=.32], and chemotherapy [P=.84]) were not significant. The ROC curve of the training set showed that the model exhibited good discrimination for predicting 1- (area under the curve [AUC] 0.802, 95% CI 0.713-0.892), 5- (AUC 0.813, 95% CI 0.760-0.865), and 10-year (AUC 0.740, 95% CI 0.672-0.808) overall survival. The Brier scores at 1, 5, and 10 years after diagnosis were 0.005, 0.055, and 0.103 in the training set, respectively, and were less than 0.25, indicating good predictive ability. The test set externally validated model discrimination and calibration. In the iCanPredict app, when physicians or women input women's clinical information and their choice of surgery and adjuvant therapy, the corresponding 10-year survival prediction will be presented. CONCLUSIONS: This survival prediction model provided good model discrimination and calibration. iCanPredict is the first tool of its kind in China to provide survival predictions to women with breast cancer. iCanPredict will increase women's awareness of the similar survival rate of different surgeries and the importance of adherence to endocrine therapy, ultimately helping women to make informed decisions regarding treatment for breast cancer.
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Neoplasias de la Mama , Aplicaciones Móviles , Área Bajo la Curva , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To assess nurses' perceived competence in pressure injury (PI) care and explore the association between perceived competence and nurses' backgrounds, knowledge, attitudes, and self-efficacy in PI care. METHODS: This study used a descriptive correlational design. During January and February 2021, the authors sent an online questionnaire to 117 nurses caring for patients with or at risk of PI at a tertiary level hospital in Kunming, Yunnan Province, China, to collect information regarding demographics, knowledge, attitude, self-efficacy, and perceived competence in PI care. Univariate and multiple regressions were performed to assess the associations. RESULTS: A total of 111 completed questionnaires were obtained, a response rate of 94.9%. Nurses reported inadequate knowledge and relatively low self-efficacy in PI care. However, they had positive attitudes and acceptable levels of perceived competence in PI care. According to a univariate analysis, being a wound specialist, having read PI-related articles or practice guideline within the past year, and having knowledge and self-efficacy in PI care were associated with nurses' perceived competence. CONCLUSIONS: Pressure injury-related knowledge, attitude, and self-efficacy are independently associated with nurses' perception of their competency in PI care.
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Enfermeras y Enfermeros , Personal de Enfermería en Hospital , Úlcera por Presión , Humanos , Actitud del Personal de Salud , China , Competencia Clínica , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Centros de Atención TerciariaRESUMEN
In this Letter, we experimentally demonstrate liquid crystal-based moiré lenses with a wide and tunable focal length by direct-writing photoalignment. Our moiré lenses, which consist of two cascaded diffractive optical elements, have a large range of refractive power between $\pm 0.85\;{{\rm m}^{- 1}}$ at 532 nm and a mutual rotation between $\pm 90^\circ$ with high diffraction efficiency ($\gt\!{75}\%$). Based on the as-designed moiré lenses, we propose high-dynamic-resolution optical edge detection without any axial shift or substitution of components. The minimum edge width is 13.2 µm and can be adjusted within 100 µm by mutual rotation of this device, which has great potential to be used in adaptive and compact optical systems.
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In this Letter, we employ photo-aligned liquid crystals to record a flat lens pattern through a simple exposure method to produce a large focal length Pancharatnam-Berry (PB) lens with a film thickness of 2µm without using expensive equipment. This PB lens with a focal length of 240.6 m (at 532 nm) can transmit up to 97% across visible wavelengths and maintain high diffraction efficiency (>90%). An improved two-dimensional optical edge detection design based on this lens is proposed. We experimentally demonstrate the integrity and high efficiency of edge information that may play an important role in the application of image processing and high-contrast microscopy.
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Some studies have shown that gut microbiota along with its metabolites is closely associated with diabetic mellitus (DM). In this study we explored the relationship between gut microbiota and kidney injuries of early diabetic nephropathy (DN) and its underlying mechanisms. Male SD rats were intraperitoneally injected with streptozotocin to induce DM. DM rats were orally administered compound broad-spectrum antibiotics for 8 weeks. After the rats were sacrificed, their blood, urine, feces, and renal tissues were harvested for analyses. We found that compared with the control rats, DM rats had abnormal intestinal microflora, increased plasma acetate levels, increased proteinuria, thickened glomerular basement membrane, and podocyte foot process effacement in the kidneys. Furthermore, the protein levels of angiotensin II, angiotensin-converting enzyme, and angiotensin II type 1 receptor in the kidneys of DM rats were significantly increased. Administration of broad-spectrum antibiotics in DM rats not only completely killed most intestinal microflora, but also significantly lowered the plasma acetate levels, inhibited intrarenal RAS activation, and attenuated kidney damage. Finally, we showed that plasma acetate levels were positively correlated with intrarenal angiotensin II protein expression (r = 0.969, P < 0.001). In conclusion, excessive acetate produced by disturbed gut microbiota might be involved in the kidney injuries of early DN through activating intrarenal RAS.
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Acetatos/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Nefropatías Diabéticas/fisiopatología , Disbiosis/fisiopatología , Microbioma Gastrointestinal/fisiología , Sistema Renina-Angiotensina/fisiología , Acetatos/sangre , Animales , Antibacterianos/farmacología , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/patología , Microbioma Gastrointestinal/efectos de los fármacos , Riñón/patología , Masculino , Ratas Sprague-DawleyRESUMEN
Background: Nephrotoxicity, especially acute kidney injury (AKI), is the main dose-limiting toxicity of cisplatin. Although recent studies showed that curcumin prevented cisplatin-induced AKI effectively, further studies to understand the mechanism are required.Methods: We established an AKI mouse model. Male C57BL/6 mice were assigned to three groups: saline group (control), cisplatin group (CP), and curcumin + cisplatin group (CP + Cur). The CP group received a single intraperitoneal (i.p.) injection of cisplatin, while the control group received saline. The CP + Cur group received i.p. curcumin three days before cisplatin injection and curcumin administered for another three days until the day before euthanization. Renal injury was assessed by serological and histological analysis. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the phosphatase and tensin homolog (PTEN), and microRNA (miR)-181a expression in the renal tissues. Bioinformatics prediction and western blotting methods validated the targets of miR-181a in vitro.Results: Curcumin treatment alleviated cisplatin-induced nephrotoxicity as validated by the blood urea nitrogen (BUN) values, and histological analysis of kidneys. At the molecular level, curcumin treatment decreased miR-181a expression level, which was induced by cisplatin and restored the in vivo expression of PTEN, which was suppressed by cisplatin. We verified the direct regulation of PTEN by miR-181a in cultured human embryonic kidney 293T cells.Conclusions: We showed the involvement of miR-181a/PTEN axis in the renoprotective effect of curcumin against cisplatin-induced AKI, and provide new evidence on the ability of curcumin to alleviate cisplatin-induced nephrotoxicity.
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Lesión Renal Aguda/prevención & control , Antiinflamatorios no Esteroideos/farmacología , Curcumina/farmacología , MicroARNs/metabolismo , Fosfohidrolasa PTEN/metabolismo , Lesión Renal Aguda/inducido químicamente , Animales , Apoptosis/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Cisplatino/toxicidad , Regulación de la Expresión Génica , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
The reaction of thiols and anhydrides to form ring opened thioester/acids is shown to be highly reversible and it is accordingly employed in the fabrication of covalent adaptable networks (CANs) that possess tunable dynamic covalent chemistry. Maleic, succinic, and phthalic anhydride derivatives were used as bifunctional reactants in systems with varied stoichiometries, catalyst, and loadings. Dynamic characteristics such as temperature-dependent stress relaxation, direct reprocessing and recycling abilities of a range of thiol-anhydride elastomers, glasses, composites and photopolymers are discussed. Depending on the catalyst strength, 100 % of externally imposed stresses were relaxed in the order of minutes to 2â hours at mild temperatures (80-120 °C). Pristine properties of the original materials were recovered following up to five cycles of a hot-press reprocessing technique (1â h/100 °C).
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BACKGROUND: Overfeeding reduces laying performance in broiler breeder hens, which is associated with obesity, hepatic steatosis and systemic inflammation. To unravel the underlying mechanisms governing the effect of feeding regimes on energy metabolism and egg production, a transcriptomics approach was carried out for screening differentially expressed genes (DEGs) in ovary, liver and adipose tissues of broiler chickens under ad libitum and restricted feeding. RESULTS: It showed that 289, 388 and 204 DEGs were identified in the adipose, liver and ovary, respectively. These DEGs were significantly enriched in phagosome pathway, lipid transport, activity and nutrient reservoir activity in ovary; steroid hormone biosynthesis and metabolism of xenobiotics by cytochrome P450 pathways in adipose tissue; and the metabolic pathways, peroxisome proliferator-activated receptor (PPAR) and Jak-STAT signaling pathway in liver. Estrogen receptor 1, identified as one of important hubs by constructing PPI network, was up-regulated in ad libitum group, which would make more apolipoproteins be transferred to ovary. CONCLUSIONS: High expression of VTGs, APOB, CYBB and CTSS in ovary would induce excess lipid deposit, oxidative stress and potential damage to ovulation. Our results contribute to understanding effects of feeding regimes on metabolic regulation during egg production of broiler breeder hens and also provide new evidence of metabolic regulation from integrated multi-tissue processes.