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INTRODUCTION: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. METHODS: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured bi-weekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. RESULTS: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures, and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. CONCLUSION: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.
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BACKGROUND: Digital health plays a vital role in healthcare services. Governments in many countries, including China, are increasingly advocating for the appropriate use of digital technologies to address significant health system challenges. It is crucial to incorporate digital health education into the curriculum for future nurses to adapt to the changes in the digital medical system. This study aimed to evaluate the impact of an online Digital Health and Informatics Course in China on the knowledge and comprehension of key digital health and informatics topics, self-assessment of nursing informatics competencies, and satisfaction among undergraduate nursing students. The findings of this study provide recommendations for the design and implementation of future digital health education. METHODS: This study employed a one-group, quasi-experimental mixed-methods design with pre- and post-assessments. The participants received digital health and informatics education through six three-hour online sessions in six interactive days, with online self-learning materials in between. An online quiz and focus group discussions pre- and post the course were designed to evaluate the knowledge and comprehension of key digital health and informatics topics. Also, a validated Chinese version of the Self-assessment of Nursing Informatics Competencies Scale was conducted pre- and post-course to assess self-assessment of nursing informatics competencies. Additionally, all students were invited to participate in an online survey with a performance-focused course evaluation form as well as focus group discussions to gather their feedback on the learning experience and their evaluations of the course. RESULTS: A total of 24 undergraduate nursing students were enrolled in the course. All students completed all sessions of this course, resulting in an attendance rate of 100%. Additionally, all students completed both pre- and post-assessments. In terms of the knowledge and comprehension of key digital health and informatics topics, scores of the quiz on knowledge assessment improved from the pre-test [mean pretest score: 78.33 (SD 6.005)] to the post-test [mean post-test score: 83.17 (SD 4.86)] upon completion of the course (P < 0.001). Also, students acknowledged that the course enhanced their knowledge and comprehension of informatics and digital health, the benefits of (nursing) informatics in clinical practice, and the role of health care professionals in informatics and digital health. In terms of self-assessment of nursing informatics competencies, scores on nursing informatics attitudes demonstrated significant improvement (P < 0.001). Furthermore, students reported high satisfaction with various aspects of this course, including the opportunity to explore broad horizons in informatics for future careers, engaging in group discussions, and analyzing case studies on the use of informatics and digital health in clinical practice. CONCLUSIONS: This Online Digital Health and Informatics education effectively improved undergraduate nursing students' knowledge and comprehension of the key digital health and informatics topics, nursing informatics attitudes in the self-assessment of nursing informatics competency with high levels of satisfaction. In order to ensure that future education in digital health and informatics for nursing students is in line with the technological advancements in clinical settings, it is necessary to foster collaboration between medical school training and clinical practice. This collaboration should involve the use of clinical examples to illustrate advanced digital health applications and the inclusion of practical exercises on the use of digital health technology in clinical settings.
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Currículo , Bacharelado em Enfermagem , Informática em Enfermagem , Estudantes de Enfermagem , Adulto , Humanos , Adulto Jovem , China , Saúde Digital , Educação a Distância , Avaliação Educacional , Informática em Enfermagem/educaçãoRESUMO
BACKGROUND: The goal was to analyze serums of GDM patients and healthy pregnant women using HPLC-MS and preliminarily screen differential metabolites by metabolomics. METHOD: Sixty pregnant women who underwent elective cesarean section at term in Dongguan Dalang Hospital from January 2023 to April 2023 were selected and divided into the GDM group and healthy pregnancy group. Pre-pregnancy and pregnancy examination information, such as age, BMI, OGTT results, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and other clinical data were col-lected for statistical analysis. Non-targeted metabolomics of serum from 30 GDM patients and 30 healthy pregnant women were studied by HPLC-MS, and different ions were searched. The structures of differential metabolites were identified by HMDB database. The metabolic pathways of differential metabolites were analyzed by KEGG database. RESULTS: The OGTT result, pCO2, pO2, HCO3, BE, Apgar score, and bilirubin levels in the GDM group were higher than those in the healthy pregnancy group (p < 0.05). However, there were no significant differences in age, triglyceride, total cholesterol, newborn birth weight, newborn birth blood glucose, and blood gas pH between the two groups (all p > 0.05). Using p < 0.05 as the screening standard, 55 differential metabolites were identified in serum, mainly including fatty acyl, carboxylic acids and their derivatives, steroids and their derivatives, ketoacids and their derivatives, and pyrimidine nucleosides, etc., all of which were up-regulated or down-regulated to varying degrees. The 55 metabolites were mainly involved in the metabolism of pyrimidine, pyruvate, alanine, aspartic acid, glutamic acid, and arachidonic acid, glycolysis, and biosynthesis of unsaturated fatty acids. CONCLUSIONS: The discovery of these metabolites provides a theoretical basis for an indepth understanding of GDM pathogenesis. Non-targeted metabonomics analysis of blood metabonomics research technology has shown great potential value in the early diagnosis of obstetric diseases and the study of disease mechanisms.
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Diabetes Gestacional , Metabolômica , Humanos , Feminino , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/metabolismo , Gravidez , Metabolômica/métodos , Adulto , Recém-Nascido , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão/métodos , Biomarcadores/sangueRESUMO
BACKGROUND: The discovering of an osteoclast (OC) coupling active agent, capable of suppressing OC-mediated bone resorption while concurrently stimulating osteoblast (OB)-mediated bone formation, presents a promising strategy to overcome limitations associated with existing antiresorptive agents. However, there is a lack of research on active OC coupling agents. PURPOSE: This study aims to investigate the potential of Jiangu Formula (JGF) in inhibiting OCs while maintaining the OCOB coupling function. METHODS: The anti-osteoporosis efficacy of JGF was evaluated in osteoporosis models induced by ovariectomy in C57BL/6 mouse and SD rats. The effect of JGF on OCs was evaluated by detecting its capacity to inhibit OC differentiation and bone resorption in an in vitro osteoclastogenesis model induced by RANKL. The OCOB coupling activity of JGF was evaluated by measuring the secretion levels of OC-derived coupling factors, OB differentiation activity of MC3T3-E1 interfered with conditioned medium, and the effect of JGF on OC inhibition and OB differentiation in a C3H10T1/2-RAW264.7 co-culture system. The mechanism of JGF was studied by network pharmacology and validated using western blot, immunofluorescence (IF), and ELISA. Following that, the active ingredients of JGF were explored through a chemotype-assembly approach, activity evaluation, and LC-MS/MS analysis. RESULTS: JGF inhibited bone resorption in murine osteoporosis without compromising the OCOB coupling effect on bone formation. In vitro assays showed that JGF preserved the coupling effect of OC on OB differentiation by maintaining the secretion of OC-derived coupling factors. Network analysis predicted STAT3 as a key regulation point for JGF to exert anti-osteoporosis effect. Further validation assays confirmed that JGF upregulated p-STAT3(Ser727) and its regulatory factors IL-2 in RANKL-induced RAW264.7 cells. Moreover, 23 components in JGF with anti-OC activity identified by chemotype-assembly approach and verification experiments. Notably, six compounds, including ophiopogonin D, ginsenoside Re, ginsenoside Rf, ginsenoside Rg3, ginsenoside Ro, and ononin were identified as OC-coupling compounds. CONCLUSION: This study first reported JGF as an agent that suppresses bone loss without affecting bone formation. The potential coupling mechanism of JGF involves the upregulation of STAT3 by its regulators IL-2. Additionally, the chemotype-assembly approach elucidated the activity compounds present in JGF, offering a novel strategy for developing an anti-resorption agent that preserves bone formation.
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Reabsorção Óssea , Diferenciação Celular , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos C57BL , Osteoblastos , Osteoclastos , Osteoporose , Ratos Sprague-Dawley , Animais , Osteoclastos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Osteoporose/tratamento farmacológico , Osteoblastos/efeitos dos fármacos , Feminino , Células RAW 264.7 , Diferenciação Celular/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Ovariectomia , Ligante RANK , Ratos , Osteogênese/efeitos dos fármacos , Modelos Animais de Doenças , Fator de Transcrição STAT3/metabolismoRESUMO
BACKGROUND: Extractive methods for machine reading comprehension (MRC) tasks have achieved comparable or better accuracy than human performance on benchmark data sets. However, such models are not as successful when adapted to complex domains such as health care. One of the main reasons is that the context that the MRC model needs to process when operating in a complex domain can be much larger compared with an average open-domain context. This causes the MRC model to make less accurate and slower predictions. A potential solution to this problem is to reduce the input context of the MRC model by extracting only the necessary parts from the original context. OBJECTIVE: This study aims to develop a method for extracting useful contexts from long articles as an additional component to the question answering task, enabling the MRC model to work more efficiently and accurately. METHODS: Existing approaches to context extraction in MRC are based on sentence selection strategies, in which the models are trained to find the sentences containing the answer. We found that using only the sentences containing the answer was insufficient for the MRC model to predict correctly. We conducted a series of empirical studies and observed a strong relationship between the usefulness of the context and the confidence score output of the MRC model. Our investigation showed that a precise input context can boost the prediction correctness of the MRC and greatly reduce inference time. We proposed a method to estimate the utility of each sentence in a context in answering the question and then extract a new, shorter context according to these estimations. We generated a data set to train 2 models for estimating sentence utility, based on which we selected more precise contexts that improved the MRC model's performance. RESULTS: We demonstrated our approach on the Question Answering Data Set for COVID-19 and Biomedical Semantic Indexing and Question Answering data sets and showed that the approach benefits the downstream MRC model. First, the method substantially reduced the inference time of the entire question answering system by 6 to 7 times. Second, our approach helped the MRC model predict the answer more correctly compared with using the original context (F1-score increased from 0.724 to 0.744 for the Question Answering Data Set for COVID-19 and from 0.651 to 0.704 for the Biomedical Semantic Indexing and Question Answering). We also found a potential problem where extractive transformer MRC models predict poorly despite being given a more precise context in some cases. CONCLUSIONS: The proposed context extraction method allows the MRC model to achieve improved prediction correctness and a significantly reduced MRC inference time. This approach works technically with any MRC model and has potential in tasks involving processing long texts.
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Due to low immobilized ligand density, limited binding capacity, and severe interference from serum proteins, developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge. In this study, mimotope peptide modified pompon mum-like biomimetic magnetic microparticles (MMPs, 3.8 µm) that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time. Benefit from the numerous ligand binding sites (Ni2+) on the pompon mum-like MMPs, these novel materials achieved ≥10 times higher peptide ligand densities (>2300 mg/g) and antibody binding capacities (1380 mg/g) compared to previous reported biomaterials. Leveraging the high specificity of the mimotope peptide, rituximab can be precisely recognized and enriched from cell culture media or serum samples. We also established an LCâMS/MS method using the MMPs for tracking rituximab biotransformation in patient serum. Intriguingly, deamidation of Asn55 and Asn33, as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab, which could potentially influence antibody function and require careful monitoring. Overall, these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies, offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.
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ABSTRACT: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. CVD and kidney disease are closely related, with kidney injury increasing CVD mortality. The pathogenesis of cardiovascular and renal diseases involves complex and diverse interactions between multiple extracellular and intracellular signaling molecules, among which transient receptor potential vanilloid 1 (TRPV1)/transient receptor potential ankyrin 1 (TRPA1) channels have received increasing attention. TRPV1 belongs to the vanilloid receptor subtype family of transient receptor potential ion channels, and TRPA1 belongs to the transient receptor potential channel superfamily. TRPV1/TRPA1 are jointly involved in the management of cardiovascular and renal diseases and play important roles in regulating vascular tension, promoting angiogenesis, antifibrosis, anti-inflammation, and antioxidation. The mechanism of TRPV1/TRPA1 is mainly related to regulation of intracellular calcium influx and release of nitric oxide and calcitonin gene-related peptide. Therefore, this study takes the TRPV1/TRPA1 channel as the research object, analyzes and summarizes the process and mechanism of TRPV1/TRPA1 affecting cardiovascular and renal diseases, and lays a foundation for the treatment of cardiorenal diseases.
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Doenças Cardiovasculares , Nefropatias , Transdução de Sinais , Canal de Cátion TRPA1 , Canais de Cátion TRPV , Humanos , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPV/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia , Animais , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Sinalização do Cálcio/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Fármacos Cardiovasculares/farmacologiaRESUMO
To in-depth explore the action mechanism of C-reactive protein (CRP) and precisely study its signaling pathways, it is essential to acquire high-purity CRP while preserving its intact structure and functionality. In this study, we propose and fabricate a high-density 2-methacryloyloxyethyl phosphorylcholine (MPC)-modified membrane roll column (MPC-MRC) using a surface-initiated atom transfer radical polymerization (SI-ATRP) approach, which can overcome these limitations (long incubation time and low adsorption capacity) of conventional enrichment materials. The MPC-MRC incorporates a high-density 2-hydroxyethyl methacrylate polymer brush to prevent non-specific protein adsorption and multiple MPC polymer brush layers for high-performance enrichment of CRP in the company of calcium ions. Furthermore, the MPC-MRC exhibits high permeability, hydrophilicity, and mechanical strength. Compared to previous technologies, this novel material demonstrates significantly higher CRP binding capacity (310.3 mg/g), shorter processing time (only 15 min), and lower cost (only 12 USD/column). Notably, the MPC-MRC enables fast and effective purification of CRP from both human and rat serum, exhibiting good selectivity, recovery (> 91.3 %), and purity (> 95.2 %). Thus, this proposed purification approach based on MPC-MRC holds great potential for target protein enrichment from complex samples, as well as facilitating in-depth studies of its biological functions.
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Biomimética , Proteína C-Reativa , Animais , Humanos , Ratos , Proteína C-Reativa/química , Metacrilatos/química , Polímeros/química , Fosforilcolina/química , Propriedades de Superfície , AdsorçãoRESUMO
The accurate and rapid detection of specific antibodies in blood is very important for efficient diagnosis and precise treatment. Conventional methods often suffer from time-consuming operations and/or a narrow detection range. In this work, for the rapid determination of bevacizumab in plasma, a series of chimeric hairpin DNA aptamer-based probes were designed by the modification, labeling and theoretical computation of an original aptamer. Then, the dissociation constant of the modified hairpin DNA to bevacizumab was measured and screened using microscale thermophoresis. The best chimeric hairpin DNA aptamer-based probe was then selected, and a one-step platform for the rapid determination of bevacizumab was constructed. This strategy has the advantages of being simple, fast and label-free. Because of the design and screening of the hairpin DNA, as well as the optimization of the concentration and electrochemical parameters, a low detection limit of 0.37 pM (0.054 ng mL-1) with a wide linear range (1 pM-1 µM) was obtained. Finally, the rationally constructed biosensor was successfully applied to the determination of bevacizumab in spiked samples, and it showed good accuracy and precision. This method is expected to truly realize accurate and rapid detection of bevacizumab and provides a new idea for the precise treatment of diseases.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Bevacizumab , Técnicas Biossensoriais/métodos , DNA , Sondas de DNA/genética , Limite de Detecção , Técnicas EletroquímicasRESUMO
Introduction: Metabolic reprogramming potentiates host protection against antibiotic-sensitive or -resistant bacteria. However, it remains unclear whether a single reprogramming metabolite is effective enough to combat both antibiotic-sensitive and -resistant bacteria. This knowledge is key for implementing an antibiotic-free approach. Methods: The reprogramming metabolome approach was adopted to characterize the metabolic state of zebrafish infected with tetracycline-sensitive and -resistant Edwardsiella tarda and to identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite. Results: Aspartate was identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite. Exogenous aspartate protects zebrafish against infection caused by tetracycline-sensitive and -resistant E. tarda. Mechanistically, exogenous aspartate promotes nitric oxide (NO) biosynthesis. NO is a well-documented factor of promoting innate immunity against bacteria, but whether it can play a role in eliminating both tetracycline-sensitive and -resistant E. tarda is unknown. Thus, in this study, aspartate was replaced with sodium nitroprusside to provide NO, which led to similar aspartate-induced protection against tetracycline-sensitive and -resistant E. tarda. Discussion: These findings support the conclusion that aspartate plays an important protective role through NO against both types of E. tarda. Importantly, we found that tetracycline-sensitive and -resistant E. tarda are sensitive to NO. Therefore, aspartate is an effective reprogramming metabolite that allows implementation of an antibiotic-free approach against bacterial pathogens.
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Infecções por Enterobacteriaceae , Doenças dos Peixes , Animais , Peixe-Zebra , Edwardsiella tarda , Óxido Nítrico , Ácido Aspártico/farmacologia , Antibacterianos/farmacologia , Bactérias , TetraciclinasRESUMO
Medical time series are sequential data collected over time that measures health-related signals, such as electroencephalography (EEG), electrocardiography (ECG), and intensive care unit (ICU) readings. Analyzing medical time series and identifying the latent patterns and trends that lead to uncovering highly valuable insights for enhancing diagnosis, treatment, risk assessment, and disease progression. However, data mining in medical time series is heavily limited by the sample annotation which is time-consuming and labor-intensive, and expert-depending. To mitigate this challenge, the emerging self-supervised contrastive learning, which has shown great success since 2020, is a promising solution. Contrastive learning aims to learn representative embeddings by contrasting positive and negative samples without the requirement for explicit labels. Here, we conducted a systematic review of how contrastive learning alleviates the label scarcity in medical time series based on PRISMA standards. We searched the studies in five scientific databases (IEEE, ACM, Scopus, Google Scholar, and PubMed) and retrieved 1908 papers based on the inclusion criteria. After applying excluding criteria, and screening at title, abstract, and full text levels, we carefully reviewed 43 papers in this area. Specifically, this paper outlines the pipeline of contrastive learning, including pre-training, fine-tuning, and testing. We provide a comprehensive summary of the various augmentations applied to medical time series data, the architectures of pre-training encoders, the types of fine-tuning classifiers and clusters, and the popular contrastive loss functions. Moreover, we present an overview of the different data types used in medical time series, highlight the medical applications of interest, and provide a comprehensive table of 51 public datasets that have been utilized in this field. In addition, this paper will provide a discussion on the promising future scopes such as providing guidance for effective augmentation design, developing a unified framework for analyzing hierarchical time series, and investigating methods for processing multimodal data. Despite being in its early stages, self-supervised contrastive learning has shown great potential in overcoming the need for expert-created annotations in the research of medical time series.
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Aprendizagem , Fatores de Tempo , Mineração de Dados , Bases de Dados FactuaisRESUMO
BACKGROUND: Hypertensive nephropathy (HN) is one kind of kidney disorders caused by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In recent years, nephropathy accompanied by hypertension is becoming one of the main causes for kidney replacement therapy, but few effective treatments have been reported for HN treatment. Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear. METHODS: To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying mechanisms of AC extracts treatment in the HN rat model. RESULTS: AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFß1 and NF-кB in HN rats. CONCLUSION: The finding of the article demonstrated that AC extracts had the better therapeutic effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.
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Hipertensão Renal , Hipertensão , Ratos , Animais , Hipertensão Renal/complicações , Hipertensão Renal/patologia , Hipertensão/tratamento farmacológico , Ratos Endogâmicos SHR , Colesterol , Rim , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Aim: Diabetic nephropathy (DN) is the primary cause of end-stage renal disease worldwide. Although etiology for DN is complex and still needs to be fully understood, lipid metabolism disorder is found to play a role in it. Previously, we found Yishen Huashi (YSHS) granule could inhibit diabetic damage and reduce level of microalbuminuria (mALB) in DN animals. To explore its role and mechanism in lipid metabolism under DN settings, this study was designed. Materials and methods: DN rats were induced by streptozotocin (STZ), HepG2 and CaCO2 cells were applied for in vitro study. Hematoxylin-Eosin (HE), periodic acid-Schiff (PAS) staining, and Transmission Electron Microscopy (TEM) were applied for histological observation; 16s Sequencing was used for intestinal microbiota composition analysis; western blotting (WB) and immunofluorescence were carried out for molecular biological study, and enzyme-linked immunosorbent assay (ELISA) was used for lipid determination. Results: YSHS administration significantly reduced levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL-C), while increased level of high-density lipoprotein (HDL-C); meanwhile, histological changes and steatosis of the liver was ameliorated, integrity of the intestinal barrier was enhanced, and dysbacteriosis within intestinal lumen was ameliorated. Mechanism study found that YSHS modulated mitophagy within hepatocytes and inhibited mTOR/AMPK/PI3K/AKT signaling pathway. Conclusion: In conclusion, we found in the present study that YSHS administration could ameliorate lipid metabolism disorder in DN animals, and its modulation on intestinal-liver axis played a significant role in it.
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BACKGROUNDS: Hypertensive nephropathy (HN) is a kind of renal disease caused by essential hypertension that eventually worsens into end-stage renal disease (ESRD). HN could damage the renal tubules, induce kidney damage and renal failure, and increase the risk of stroke, heart disease or death, but there are few ideal drugs for HN treatment. METHODS: In this study, we explored the therapeutic effect of bajijiasu (a compound from Morinda officinalis how and a common traditional Chinese medicine for tonifying the kidney) on the HN rat model. Biochemical analysis, HE staining, and PAS staining were used to assess the effects of bajijiasu on HN rat model. Western blotting was used to analyze the potential mechanisms. RESULTS: The results of HE staining and PAS staining showed that bajijiasu could alleviate the pathological changes in HN rat models; biochemical analysis found that the concentration of Malondialdehyde (MDA), total protein (TP), albumin (ALB), microalbuminuria (MALB), blood urea nitrogen (BUN), creatinine (Cr), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) were significantly decreased compared with the model group after bajijiasu treatment; and bajijiasu could regulate the expression of TNF-α, IL-6, MDA, SOD1 and AGEs in HN rats; the result of western blotting demonstrated that bajijiasu could down-regulate the expression of TGFß1, NOX4, JNK, p- JNK and up-regulate the expression PPARγ and SOD 1 in HN rats. CONCLUSION: Those results demonstrated that bajijiasu could alleviate the pathological changes and physiological and biochemical symptoms of HN rat models by regulating the expression of TGFß1, PPARγ, JNK, p-JNK, NOX4 and SOD1 but could not lower the blood pressure of HN rats. Those pieces of evidence may provide a new therapeutic method for HN treatment.
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Hipertensão Renal , PPAR gama , Ratos , Animais , Superóxido Dismutase-1 , Rim/patologia , Hipertensão Renal/tratamento farmacológico , Hipertensão Renal/patologiaRESUMO
Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes and the primary cause of end-stage renal disease. At present, renin-angiotensin-aldosterone system (RAAS) blockers have been applied as first-class drugs to restrain development of DN; however, its long-term effect is limited. Recent evidence has shown definite effects of Chinese medicine on DN. Yishen Huashi (YSHS) granule is a traditional Chinese Medicine prescription that has been used in the clinic to treat DN, but its mechanism is not understood. Methods: In the present study, both in vitro and in vivo studies were carried out. The DN model was induced by STZ in Wistar rats, and GEnC and HPC cell lines were applied in the in vitro study. Quality of YSHS was evaluated by LC-MS/MS. A metabolomic study of urine was carried out by LC-MS; influence of YSHS on composition of DN was analyzed by network pharmacology. Mechanism of the YSHS on DN was analyzed by Q-PCR, Western Blot, and multi-immunological methods. Results: We found YSHS administration significantly reduced levels of HbA1c and mALB. Histopathological analysis found that YSHS preserved integrity of glomerular filtration barrier by preserving viability of glomerular endothelial cells and podocytes, inhibiting glomerular fibrosis, reducing oxidative stress damage, and enhancing cross-talk among glomerular endothelial cells and podocytes. Network pharmacology, differential metabolite analysis, as well as intracellular pathway experimental study demonstrated that the PI3K/AKT/mTOR signaling pathway played a pivotal role in it. Conclusion: Our present findings supplied new understanding toward the mechanism of YSHS on inhibiting DN.
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Background: Promoting cholesterol reverse transport (RCT) has been proven to be a promising hyperlipidemia therapy since it is more effective for the treatment of atherosclerosis (AS) caused by hyperlipidemia. Liver X receptor (LXR) agonists can accelerate RCT, but most of them trigger undesirable liver steatosis due to the activation of liver LXRα. Aim: We aim to figure out whether isochlorogenic acid C (ICAC) facilitates RCT without causing hepatic steatosis. Methods: In vitro study, we established foam macrophages and macrophages with loaded NBD-cholesterol models to investigate the competence of RCT promoting ICAC. RT-qPCR and Western blot were used to verify ICAC's regulation of RCT and NF-κB inflammatory pathways. In this in vivo study, male 6-week-old C57BL/6 mice were fed a high-fat diet (HFD) to investigate ICAC's anti-hyperlipidemic effect and its functions in regulating RCT. The anti-hyperlipidemic effect of ICAC was evaluated by blood and liver lipid levels, liver hematoxylin, oil red o staining, and liver coefficient. Finally, mRNA levels of genes involved in RCT and inflammation pathways in the liver and intestine were detected by RT-qPCR. Results: ICAC prevented macrophages from foaming by up-regulating the LXRα mediated RCT pathway and down-regulating expression of the cholesterol absorption genes LDLR and CD36, as well as suppressing iNOS, COX2, and IL-1ß inflammatory factors. In HFD-fed mice, ICAC significantly lowered the lipid level both in the serum and the liver. Mechanistic studies showed that ICAC strengthened the RCT pathway in the liver and intestine but didn't affect liver LXRα. Furthermore, ICAC impeded both adipogenesis and the inflammatory response in the liver. Conclusion: ICAC accelerated RCT without affecting liver LXRα, thus resulting in a lipid-lowering effect without increasing liver adipogenesis. Our results indicated that ICAC could be a new RCT promoter for hyperlipidemia treatment without causing liver steatosis.
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BACKGROUND: Systemic steroid therapies for Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have been challenged because of their limited benefits. Whether additional tumor necrosis factor (TNF) α inhibition provides an optimized approach remains unexplored. OBJECTIVE: To investigate the efficacy of TNF-α inhibition combined with a steroid to treat SJS/TEN and to identify potential biomarkers. METHODS: Twenty-five patients with SJS/TEN were recruited and divided into 2 groups: 10 patients received methylprednisolone and 15 patients received etanercept plus methylprednisolone. Serum levels of granzyme B, perforin, interferon-γ, interleukin (IL) 6, IL-15, IL-18, macrophage inflammatory protein 1α, macrophage inflammatory protein 1ß, and TNF-α were measured by multiplex cytokine analysis kits during the acute and resolution phases. RESULTS: Compared with the steroid monotherapy, the combination therapy significantly shortened the course of the initial steroid treatment and the duration of the acute stage, hospitalization stay, and skin re-epithelialization. Although both therapies significantly reduced IL-15 levels; the combination therapy also decreased IL-6 and IL-18 levels. While the level of IL-15 was positively correlated with skin re-epithelialization time in both groups, the level of IL-6 served as an additional marker for the course of the disease in the combination therapy group. LIMITATIONS: The cohort size is relatively small. CONCLUSION: Additional TNF-α inhibition to steroid treatment appeared to improve outcomes for SJS/TEN.
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Síndrome de Stevens-Johnson , Humanos , Interleucina-15 , Interleucina-18 , Interleucina-6 , Proteínas Inflamatórias de Macrófagos , Metilprednisolona/uso terapêutico , Esteroides , Síndrome de Stevens-Johnson/etiologia , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: To firstly examine the relationship between serum brain-derived neurotrophic factor (BDNF) levels and antidepressant response to ketamine as an anaesthesia in electroconvulsive therapy (ECT) in Chinese patients with treatment-refractory depression (TRD). METHODS: Thirty patients with TRD were enrolled and underwent eight ECT sessions with ketamine anaesthesia (0.8 mg/kg) alone. Depression severity, response and remission were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17). Enzyme-linked immunosorbent assay (ELISA) was applied to examine serum BDNF levels in patients with TRD at baseline and after the second, fourth and eighth ECT sessions. Baseline serum samples were also collected for 30 healthy controls. RESULTS: No significant differences were observed in serum BDNF levels between patients with TRD and healthy controls at baseline (p > 0.05). The remission rate was 76.7% (23/30) after the last ECT treatment, although all patients with TRD obtained antidepressant response criteria. Serum BDNF levels were not altered compared to baseline, even between remitters and nonremitters (all p > 0.05), despite the significant reduction in HAMD-17 and Brief Psychiatric Rating Scale (BPRS) scores after ECT with ketamine anaesthesia (all p < 0.05). The antidepressant effects of ECT with ketamine anaesthesia were not correlated with changes in serum BDNF levels (all p > 0.05). CONCLUSION: This preliminary study indicated that serum BDNF levels do not appear to be a reliable biomarker to determine the antidepressant effects of ketamine as an anaesthesia in ECT for patients with TRD. Further studies with larger sample sizes are warranted to confirm these findings.
RESUMO
BACKGROUND: Complications involving internal organs are usually present in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, pancreatic complications are rarely reported and studied. OBJECTIVE: To summarize clinical characteristics of SJS/TEN-associated acute pancreatic injuries and to investigate underlying inflammatory mechanisms. METHODS: Clinical records of 124 inpatients with SJS/TEN were reviewed. Serum levels of tumor necrosis factor α, interleukin (IL) 6, IL-18, IL-15, IL-12p70, and soluble CD56 were determined in 18 healthy donors and 17 patients with SJS/TEN, including 3 with acute pancreatic injuries. RESULTS: Acute pancreatic injury was diagnosed in 7.3% of patients (9/124) in the SJS/TEN cohort. Elevation of serum transaminase level and hypoalbuminemia occurred more frequently in patients with acute pancreatic injuries compared with those without pancreatic symptoms (P = .004 and <.001, respectively). Although acute pancreatic injury did not alter mortality rate of SJS/TEN, it was associated with longer hospitalization stays (P = .008). Within the serum cytokines whose levels were elevated in SJS/TEN, only IL-18 was found to be selectively increased in patients with acute pancreatic injuries compared with those without them (P = .03). LIMITATIONS: Cohort was small. CONCLUSION: Acute pancreatic injury is a gastrointestinal complication of SJS/TEN in which hepatotoxicity is more likely to occur. Overexpression of IL-18 might be involved in this unique entity.
Assuntos
Interleucina-18/sangue , Pancreatite/imunologia , Síndrome de Stevens-Johnson/complicações , Adolescente , Adulto , Idoso , Antígeno CD56/sangue , Antígeno CD56/imunologia , Criança , Feminino , Humanos , Interleucina-12/sangue , Interleucina-12/imunologia , Interleucina-15/sangue , Interleucina-15/imunologia , Interleucina-18/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Estudos Retrospectivos , Síndrome de Stevens-Johnson/sangue , Síndrome de Stevens-Johnson/imunologia , Síndrome de Stevens-Johnson/mortalidade , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
Family socioeconomic status (SES) differences in early childhood development (ECD) are well documented, as are the neighborhood effects in early development outcomes. However, little is known about whether the SES gradient in ECD outcomes varies across geographic contexts by county-level variables in contemporary China. This study examines the effects of county-level socioeconomic background on inequalities in the developmental outcomes of young Chinese children. Individual-level child development data based on four early development milestones-taking a first step, first sentences, counting 10 objects, fully independent toileting-were combined with family- and county-level socioeconomic data from the China Family Panel Studies (CFPS). Using a hierarchical linear model (HLM) to examine how the broader socioeconomic context plays a role in the attainment of developmental milestones at expected times as young children grow and develop, we have found significant cross-level interaction effects between family SES and county-level variables in relation to developmental milestone attainment. The family SES gradient in the achievement of children's developmental milestones is steeper for those in the under-developed regions than their counterparts in the more developed regions. Our findings suggest that low-SES children who are living in socioeconomically deprived regions suffer from a double disadvantage in terms of early development outcomes. Further research would be needed to contextualize the observed interactions and better explain the underlying mechanisms.