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Berberine (BBR), as a natural isoquinoline alkaloid, has demonstrated various pharmacological activities, and is widely applied in the treatment of diseases. The quantitative analysis of BBR is important for pharmacological studies and clinical applications. In this work, utilizing the specific interaction between BBR and triplex DNA, a sensitive and selective fluorescent detecting method was established with DNA-templated silver nanoclusters (DNA-AgNCs). After binding with the triplex structure in the template of DNA-AgNCs, BBR quenched the fluorescence of DNA-AgNCs and formed BBR-triplex complex with yellow-green fluorescence. The ratiometric fluorescence signal showed a linear relationship with BBR concentration in a range from 10 nM to 1000 nM, with a detection limit of 10 nM. Our method exhibited excellent sensitivity and selectivity, and was further applied in BBR detection in real samples.
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Berberina , ADN , Nanopartículas del Metal , Plata , Espectrometría de Fluorescencia , Berberina/química , Berberina/análisis , Plata/química , Nanopartículas del Metal/química , ADN/química , ADN/análisis , Espectrometría de Fluorescencia/métodos , Fluorescencia , Límite de Detección , HumanosRESUMEN
Smartphone sensors have gained considerable traction in Human Activity Recognition (HAR), drawing attention for their diverse applications. Accelerometer data monitoring holds promise in understanding students' physical activities, fostering healthier lifestyles. This technology tracks exercise routines, sedentary behavior, and overall fitness levels, potentially encouraging better habits, preempting health issues, and bolstering students' well-being. Traditionally, HAR involved analyzing signals linked to physical activities using handcrafted features. However, recent years have witnessed the integration of deep learning into HAR tasks, leveraging digital physiological signals from smartwatches and learning features automatically from raw sensory data. The Long Short-Term Memory (LSTM) network stands out as a potent algorithm for analyzing physiological signals, promising improved accuracy and scalability in automated signal analysis. In this article, we propose a feature analysis framework for recognizing student activity and monitoring health based on smartphone accelerometer data through an edge computing platform. Our objective is to boost HAR performance by accounting for the dynamic nature of human behavior. Nonetheless, the current LSTM network's presetting of hidden units and initial learning rate relies on prior knowledge, potentially leading to suboptimal states. To counter this, we employ Bidirectional LSTM (BiLSTM), enhancing sequence processing models. Furthermore, Bayesian optimization aids in fine-tuning the BiLSTM model architecture. Through fivefold cross-validation on training and testing datasets, our model showcases a classification accuracy of 97.5% on the tested dataset. Moreover, edge computing offers real-time processing, reduced latency, enhanced privacy, bandwidth efficiency, offline capabilities, energy efficiency, personalization, and scalability. Extensive experimental results validate that our proposed approach surpasses state-of-the-art methodologies in recognizing human activities and monitoring health based on smartphone accelerometer data.
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Acelerometría , Ejercicio Físico , Teléfono Inteligente , Estudiantes , Humanos , Acelerometría/métodos , Acelerometría/instrumentación , Ejercicio Físico/fisiología , Aprendizaje Profundo , Algoritmos , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentaciónRESUMEN
Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.
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Aeromonas hydrophila , Antioxidantes , Carpas , Eleutherococcus , Fermentación , Enfermedades de los Peces , Lacticaseibacillus rhamnosus , Probióticos , Animales , Lacticaseibacillus rhamnosus/metabolismo , Carpas/microbiología , Probióticos/farmacología , Probióticos/administración & dosificación , Antioxidantes/metabolismo , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/inmunología , Alimentación Animal , Inflamación/prevención & control , Citocinas/metabolismo , AcuiculturaAsunto(s)
Neoplasias de la Vaina del Nervio , Neoplasias del Sistema Nervioso Periférico , Sarcoma Sinovial , Humanos , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/cirugía , Sarcoma Sinovial/patología , Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias de la Vaina del Nervio/patología , Neoplasias del Sistema Nervioso Periférico/diagnóstico , Neoplasias del Sistema Nervioso Periférico/cirugía , Neoplasias del Sistema Nervioso Periférico/patología , Nervios Periféricos/patología , Diagnóstico Diferencial , Biomarcadores de TumorRESUMEN
It is well documented that diabetes mellitus (DM) is strongly associated with cognitive decline and structural damage to the brain. Cognitive deficits appear early in DM and continue to worsen as the disease progresses, possibly due to different underlying mechanisms. Normal iron metabolism is necessary to maintain normal physiological functions of the brain, but iron deposition is one of the causes of some neurodegenerative diseases. Increasing evidence shows that iron overload not only increases the risk of DM, but also contributes to the development of cognitive impairment. The current review highlights the role of iron overload in diabetic cognitive impairment (DCI), including the specific location and regulation mechanism of iron deposition in the diabetic brain, the factors that trigger iron deposition, and the consequences of iron deposition. Finally, we also discuss possible therapies to improve DCI and brain iron deposition.
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Context: Kidney renal clear-cell carcinoma (KIRC) is a malignant tumor. At an early stage, KIRC patients may experience only mild fever and fatigue or even no symptoms, and these early nonspecific indications can delay treatment. Neurotransmitters and their receptors may be very useful in determining tumorigenesis and predicting metastasis. Objective: The study intended to investigate the predictive value of neurotransmitter receptor-related genes (NRRGs) using public KIRC data, by determining the biological processes that implicate the prognostic NRRGs and establishing a predictive NR-related risk model, to provide an empirical basis for identifying and treating KIRC patients. Design: The research team performed a genetic case-control study. Setting: The study took place at Research Center of Health, Big Data Mining and Applications, Wannan Medical College, Wuhu, China. Methods: The research team: (1) obtained the transcriptome data related to KIRC from the Cancer Genome Atlas (TCGA) and ArrayExpress databases; (2) developed the differentially expressed NRRGs (DENRRGs) by identifying the NRRGs that intersected with DEGs in KIRC and normal samples; (3) carried out functional enrichment analyses of the DENRRGs; (4) screened the characteristic genes of the DENRRGs using machine learning; (5) created a predictive model using multivariate Cox analyses of the distinctive genes; (6) obtained independent prognostic factors for KIRC patients and established a nomograph model; (7) investigated the sensitivity of KIRC patients to therapeutic agents to examine the variations in immunological features between high-risk and low-risk individuals. Results: Differential analysis found that 115 NRRGs intersected with 5275 DEGs to provide 52 DENRRGs. Functional enrichment showed that DENRRGs were mainly involved in signal transduction in the nervous system. The machine learning on the 52 DENRRGs filtered out nine characteristic genes. Subsequently, the research team found eight prognostic biomarkers-histamine receptor H2 (HRH2), gamma-aminobutyric acid (GABA) receptor subunit epsilon (GABRE), cholinergic receptor nicotinic delta subunit (CHRND), glutamate receptor ionotropic subunit 2D (GRIN2D), glutamate metabotropic receptor 4 (GRM4), glycine receptor alpha 3 (GLRA3), cholinergic receptor nicotinic beta 4 subunit (CHRNB4), and cholinergic receptor muscarinic-1 (CHRM1)-and established a predictive model. Furthermore, the team precisely predicted the KIRC patients' prognoses using a nomogram that combined their ages, risk scores, and M stages. The infiltration levels of 21 immune cells also significantly differed between the high-risk and low-risk groups, with neutrophils having a significant positive correlation with GABRE and HRH2 and a significant negative correlation with CHRNB4 and GRM4. Finally, the 50% inhibitory concentration (IC50) values for various drugs, such as 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR), 8-hydroxy-7-(6-sulfonaphthalen-2-yl)diazenyl-quinoline-5-sulfonic acid (NSC-87877), Sunitinib, c-Jun N-terminal kinase (JNK) inhibitor VIII, and tanespimyci (X17.AAG) were significantly lower for high-risk group. Conclusions: By studying the relevance of biomarkers to the immunological microenvironment of KIRC, the current research team was able to propose a new predictive model for KIRC based on NRRGs, to offer a novel viewpoint for investigating KIRC. The study's results suggest new avenues for research into the pathophysiology and therapy of KIRC. Determining the precise molecular processes by which predictive biomarkers regulate KIRC requires further evidence and analysis.
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Carcinoma , Receptores de Neurotransmisores , Humanos , Pronóstico , Estudios de Casos y Controles , Biomarcadores , Receptores Colinérgicos , Riñón , Microambiente Tumoral , Receptor Muscarínico M1RESUMEN
Neuroinflammation plays a crucial role in the occurrence and development of cognitive impairment in type 2 diabetes mellitus (T2DM), but the specific injury mechanism is not fully understood. Astrocyte polarization has attracted new attention and has been shown to be directly and indirectly involved in neuroinflammation. Liraglutide has been shown to have beneficial effects on neurons and astrocytes. However, the specific protection mechanism still needs to be clarified. In this study, we assessed the levels of neuroinflammation and A1/A2-responsive astrocytes in the hippocampus of db/db mice and examined their relationships with iron overload and oxidative stress. First, in db/db mice, liraglutide alleviated the disturbance of glucose and lipid metabolism, increased the postsynaptic density, regulated the expression of NeuN and BDNF, and partially restored impaired cognitive function. Second, liraglutide upregulated the expression of S100A10 and downregulated the expression of GFAP and C3, and decreased the secretion of IL-1ß, IL-18, and TNF-α, which may confirm that it regulates the proliferation of reactive astrocytes and A1/A2 phenotypes polarize and attenuate neuroinflammation. In addition, liraglutide reduced iron deposition in the hippocampus by reducing the expression of TfR1 and DMT1 and increasing the expression of FPN1; at the same time, liraglutide by up-regulating the levels of SOD, GSH, and SOD2 expression, as well as downregulation of MDA levels and NOX2 and NOX4 expression to reduce oxidative stress and lipid peroxidation. The above may attenuate A1 astrocyte activation. This study preliminarily explored the effect of liraglutide on the activation of different astrocyte phenotypes and neuroinflammation in the hippocampus of a T2DM model and further revealed its intervention effect on cognitive impairment in diabetes. Focusing on the pathological consequences of astrocytes may have important implications for the treatment of diabetic cognitive impairment.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. METHODS: A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. RESULTS: Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01ï¼P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. CONCLUSION: EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.
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Terapia por Acupuntura , Electroacupuntura , Urticaria , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Mastocitos , Proteína 1 Similar al Receptor de Interleucina-1 , Histamina , Azul de Evans , Interleucina-33/genética , Solución Salina , Urticaria/genética , Urticaria/terapia , Inmunoglobulina E , Puntos de Acupuntura , Receptores de Interleucina-1RESUMEN
Allergic diseases such as allergic rhinitis (AR), allergic asthma (AAS), atopic dermatitis (AD), food allergy (FA), and eczema are systemic diseases caused by an impaired immune system. Accompanied by high recurrence rates, the steadily rising incidence rates of these diseases are attracting increasing attention. The pathogenesis of allergic diseases is complex and involves many factors, including maternal-fetal environment, living environment, genetics, epigenetics, and the body's immune status. The pathogenesis of allergic diseases exhibits a marked heterogeneity, with phenotype and endotype defining visible features and associated molecular mechanisms, respectively. With the rapid development of immunology, molecular biology, and biotechnology, many new biological drugs have been designed for the treatment of allergic diseases, including anti-immunoglobulin E (IgE), anti-interleukin (IL)-5, and anti-thymic stromal lymphopoietin (TSLP)/IL-4, to control symptoms. For doctors and scientists, it is becoming more and more important to understand the influencing factors, pathogenesis, and treatment progress of allergic diseases. This review aimed to assess the epidemiology, pathogenesis, and therapeutic interventions of allergic diseases, including AR, AAS, AD, and FA. We hope to help doctors and scientists understand allergic diseases systematically.
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Asma , Hipersensibilidad , Humanos , Hipersensibilidad/epidemiología , Hipersensibilidad/genética , Hipersensibilidad/terapia , Citocinas , Asma/epidemiología , Asma/genética , Asma/terapia , Linfopoyetina del Estroma TímicoRESUMEN
Stroke, one of the leading causes of disability and death worldwide, is a severe neurological disease that threatens human life. Protopanaxatriol (PPT), panaxatriol-type saponin aglycone, is a rare saponin that exists in Panax ginseng and Panax Noto-ginseng. In this study, we established an oxygen-glucose deprivation (OGD)-PC12 cell model and middle cerebral artery occlusion/reperfusion (MCAO/R) model to evaluate the neuroprotective effects of PPT in vitro and in vivo. In addition, metabolomics analysis was performed on rat plasma and brain tissue samples to find relevant biomarkers and metabolic pathways. The results showed that PPT could significantly regulate the levels of LDH, MDA, SOD, TNF-α and IL-6 factors in OGD-PC12 cells in vitro. PPT can reduce the neurological deficit score and infarct volume of brain tissue in rats, restore the integrity of the blood-brain barrier, reduce pathological damage, and regulate TNF-α, IL-1ß, IL-6, MDA, and SOD factors. In addition, the results of metabolomics found that PPT can regulate 19 biomarkers involving five metabolic pathways, including amino acid metabolism, arachidonic acid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. Thus, it could be inferred that PPT might serve as a novel natural agent for MCAO/R treatment.
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Isquemia Encefálica , Fármacos Neuroprotectores , Daño por Reperfusión , Saponinas , Ratas , Humanos , Animales , Isquemia Encefálica/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Factor de Necrosis Tumoral alfa , Interleucina-6 , Infarto de la Arteria Cerebral Media/patología , Glucosa , Daño por Reperfusión/metabolismo , Saponinas/farmacología , Saponinas/uso terapéutico , Superóxido DismutasaRESUMEN
Combined central and peripheral demyelination (CCPD) is an extremely rare disease characterized by inflammatory demyelination in both the central and peripheral nervous systems. Herein, we reported case of a 14-year-old teenager who initially presented with the symptoms of acute myelitis (AM). Subsequently, the patient developed symptoms consistent with Guillain-Barré syndrome (GBS), which was supported by nerve conduction studies (NCV) and cerebrospinal fluid (CSF) analysis. Throughout the course of the disease, the patient experienced abdominal pain and abnormal liver function. After a comprehensive evaluation, we determined that the abnormal liver function was a result of hepatitis E virus (HEV) infection, which may have acted as a trigger for GBS. The patient was treated with corticosteroids, intravenous immunoglobulin and Rituximab, resulting in symptom relief and clinical improvement after therapy and follow-up. This case highlights the potential responsiveness and reversibility of CCPD. Given the heterogeneous nature of CCPD, there is currently no standardized diagnostic criteria or clear consensus on its treatment. Therefore, we recommend a thorough assessment of all possibilities and the development of consolidated management guidelines based on available data for this disorder.
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Ulcerative colitis (UC) is a chronic, nonspecific inflammation of the bowel that mainly affects the mucosa and submucosa of the rectum and colon. Ginsenosides are the main active ingredients in ginseng and show many therapeutic effects in anti-inflammatory diseases, cancer, and nervous system regulation. Protopanaxatriol saponin (PTS) is an important part of saponins, and there is no research on its pharmacological effects on colitis. In this study, a model of ulcerative colitis in mice was induced by having mice freely drink 3.5% dextran sodium sulfate (DSS) solution, and UPLC-Q-TOF-MS-based metabolomics methods were applied to explore the therapeutic effect and protective mechanism of PTS for treating UC. The results showed that PTS could significantly prevent colon shortening and pathological damage and alleviate abnormal changes in UC mouse physiological and biochemical parameters. Moreover, PTS intervention regulated proinflammatory cytokines such as TNF-α, IL-6, and IL-1 in serum, and MPO and NO in colon. Interestingly, PTS could significantly inhibit UC mouse metabolic dysfunction by reversing abnormal changes in 29 metabolites and regulating eleven metabolic pathways. PTS has potential application in the treatment of UC and could alleviate UC in mice by affecting riboflavin metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, retinol metabolism, and steroid hormone biosynthesis and by regulating pentose and glucuronate conversion, linoleic acid metabolism, phenylalanine metabolism, ether lipid metabolism, sphingolipid metabolism, and tyrosine metabolism, which points at a direction for further research and for the development of PTS as a novel natural agent.
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Colitis Ulcerosa , Colitis , Saponinas , Ratones , Animales , Sulfato de Dextran/efectos adversos , Saponinas/metabolismo , Modelos Animales de Enfermedad , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colon/metabolismo , Colitis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Ratones Endogámicos C57BLRESUMEN
Immunoglobulin G antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) associated disease is a rare, demyelinated disease in the central nerve system (CNS) predominately involving optic nerve, spinal cord, and brain leading to optic neuritis (ON), transverse myelitis (TM), encephalitis. The phenotype of MOG-IgG-associated encephalitis is similar to acute disseminated encephalomyelitis (ADEM) presenting with seizures, abnormal behavioral and psychological symptoms, and cognitive impairment. A few brain biopsies show multiple sclerosis (MS) pattern histopathology with T cells, macrophages, and complement activation. To date, how MOG-IgG is produced is unknown. Herein, we report a case of a 32-year-old male with MOG-IgG-associated encephalitis presenting MOG-IgG in cerebrospinal fluid (CSF) but seronegative, as well as Epstein-Barr virus (EBV) infection and Alzheimer's pathologic change in CSF (Aß42 = 317 pg/ml, T-Tau = 538 pg/ml, p-Tau =10.09 pg/ml). With a combination treatment of administering intravenous immunoglobulin (0.4 mg/kg/d, 5 days) with a low dose of methylprednisolone (80 mg/d, 5 days) and rituximab (100 mg/week, 3 weeks), the patient recovered significantly after 3 months follow-up. This case provides us with new thoughts into the production of MOG-IgG and the possible pathologic mechanism of MOG-IgG-associated disease (MOG-AD) and simultaneously further confirms the interaction between EBV and changes of CSF biomarkers of Alzheimer's disease (AD).
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Mr.Vc is a database of curated Vibrio cholerae transcriptome data and annotated information. The main objective is to facilitate the accessibility and reusability of the rapidly growing Vibrio cholerae omics data and relevant annotation. To achieve these goals, we performed manual curation on the transcriptome data and organized the datasets in an experiment-centric manner. We collected unknown operons annotated through text-mining analysis that would provide more clues about how Vibrio cholerae modulates gene regulation. Meanwhile, to understand the relationship between genes or experiments, we performed gene co-expression analysis and experiment-experiment correlation analysis. In additional, functional module named "Interactions" which dedicates to collecting experimentally validated interactions about Vibrio cholerae from public databases, MEDLINE documents and literature in life science journals. To date, Mr.Vc v2, which is significantly increased from the previous version, contains 107 microarray experiments, 106 RNA-seq experiments, and 3 Tn-seq projects, covering 56,839 entries of DEGs (Differentially Expressed Genes) from transcriptomes and 7,463 related genes from Tn-seq, respectively. and a total of 270,129 gene co-expression entries and 11,990 entries of experiment-experiment correlation was obtained, in total 1,316 entries of interactions were collected, including 496 protein-chemical signaling molecule interactions, 472 protein-protein interactions, 306 TF (Transcription Factor)-gene interactions and 42 Vibrio cholerae-virus interactions, most of which obtained from 402 literature through text-mining analysis. To make the information easier to access, Mr.Vc v2 is equipped with a search widget, enabling users to query what they are interested in. Mr.Vc v2 is freely available at http://mrvcv2.biownmc.info.
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The number of patients with allergic asthma is rising yearly, and hormonal drugs, such as dexamethasone, have unique advantages and certain limitations. In the treatment of allergic diseases especially allergic asthma, increasing the percentage or the function of immunosuppressive cells, such as Treg cells, may achieve a good effect. On the basis of good clinical results, we found that Guominkang (GMK) especially high-concentration GMK can achieve a similar effect with dexamethasone in controlling the symptoms of allergic asthma and inhibiting inflammation of allergic asthma. In our study, GMK can inhibit the recruitment of inflammatory cells, decrease mucus production, and reduce airway resistance. Besides, GMK can reconstruct the cellular immune balance of Th1/2 and Treg/Th17 cells. Metabolome results show that DL-glutamine, L-pyroglutamic acid, prostaglandin b1, prostaglandin e2, and 3,4-dihydroxyhydrocinnamic acid are the metabolic biomarkers and are associated with Th1/2 and Treg/Th17 cell balance. GMK can also change the gut microbiota in the allergic asthma mouse model. The genus_Muriculum, genus_(Clostridium) GCA900066575, genus_klebsiella, genus_Desulfovibrio, genus_Rikenellaceae RC9 gut group, family_Chitinophagaceae, family_Nocardioidaceae, and genus_Corynebacterium are gut microbiota biomarkers treated by GMK. Among these biomarkers, genus_Muriculum is the gut microbiota biomarker associated with Th1/2 and Treg/Th17 cell balance. Interestingly, we first found that DL-glutamine, L-pyroglutamic acid, prostaglandin b1, prostaglandin e2, and 3,4-dihydroxyhydrocinnamic acid are all associated with genus_Muriculum. GMK will be a new strategy for the treatment of eosinophilic asthma, and biomarkers will also be a new research direction.
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In this study, deep learning and triplet loss function methods are used for finger vein verification research, and the model is trained and validated between different kinds of datasets including FV-USM, HKPU, and SDUMLA-HMT datasets. This work gives the accuracy and other evaluation indexes of finger vein verification calculated for different training-validation set combinations and gives the corresponding ROC curves and AUC values. The accuracy of the best result has reached 98%, and all the ROC AUC values are above 0.98, indicating that the obtained model can identify the finger veins well. Since the experiments are cross-validated between different kinds of datasets, the model has good adaptability and applicability. From the experimental results, it is also found that the model trained on the dataset that is more difficult to be distinguished will be a better and more robust model.
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Aprendizaje Profundo , Humanos , Curva ROC , Venas/diagnóstico por imagenRESUMEN
Gastric ulcer (GU) is a peptic disease with high morbidity and mortality rates affecting approximately 4% of the population throughout the world. Current therapies for GU are limited by the high relapse incidence and side effects. Therefore, novel effective antiulcer drugs are urgently needed. Ginsenosides have shown good anti-GU effects, and the major intestinal bacterial metabolite of ginsenosides, protopanaxatriol (PPT), is believed to be the active component. In this study, we evaluated the anti-GU effect of PPT in rats in an acetic acid-induced GU model. High (H-PPT) and medium (M-PPT) doses of PPT (20.0 and 10.0 mg/mg/day) significantly reduced the ulcer area and the ET-1, IL-6, EGF, SOD, MDA and TNF-α levels in serum were regulated by PPT in a dose-dependent manner. We also investigated the mechanisms of anti-GU activity of PPT based on metabolomics coupled with network pharmacology strategy. The result was that 16 biomarkers, 3 targets and 3 metabolomic pathways were identified as playing a vital role in the treatment of GU with PPT and were further validated by molecular docking. In this study, we have demonstrated that the integrated analysis of metabolomics and network pharmacology is an effective strategy for deciphering the complicated mechanisms of natural compounds.
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Ginsenósidos , Úlcera Gástrica , Ratas , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Ácido Acético/toxicidad , Ginsenósidos/uso terapéutico , Factor de Necrosis Tumoral alfa , Simulación del Acoplamiento Molecular , Interleucina-6/efectos adversos , Factor de Crecimiento Epidérmico/efectos adversos , Farmacología en Red , Metabolómica , Biomarcadores , Superóxido DismutasaRESUMEN
BACKGROUND: Autoimmune encephalitis (AE) with neuronal surface antibodies (NSAbs) presents pathogenesis mediated by B cell-secreting antibodies. Rituximab is a second-line choice for the treatment for AE with NSAbs, which can cause B cell depletion via targeting CD20. However, the optimal protocol and dosage of rituximab combined with first-line therapy for NSAbs-associated AE remains unclear so far. In this study, we explored the efficacy and safety of low-dose rituximab combined with first-line treatment for NSAbs-associated AE. METHODS: Fifty-nine AE patients with NSAbs were enrolled, and retrospectively divided into common first-line therapy (41 patients) and combined low-dose rituximab (100 mg induction weekly with 3 circles, followed by 100 mg reinfusion every 6 months) with first-line therapy (18 patients). Outcome measures included changes in the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) score (primary endpoint), changes in the modified Rankin Scale (mRS), the Mini-mental State Examination (MMSE), the patient and caregiver Neuropsychiatric Inventory (NPI) score at each visit (baseline, discharge, 6 months, 12 months and last follow-up) between two groups (secondary endpoint), as well as oral prednisone dosage, relapse and adverse effects during follow-up. RESULTS: Compared with traditional first-line therapy group, for primary outcome, CASE scores at last follow-up were significantly improved in combined rituximab group, as well as markedly improving changes of CASE scores between baseline and each visit. While changes of mRS, MMSE and NPI scores, as secondary endpoint, were all markedly accelerating improvement between baseline and each visit, as well as both oral prednisone dosage and relapse were also greatly reduced during follow-up. Meanwhile, longitudinal analysis in combination of rituximab cohort also revealed persistently marked amelioration in a series of scales from baseline even more than 1 year. Moreover, analysis in rituximab subgroup showed no difference in any clinical outcomes between combination with single first-line and with repeated first-line treatment (≥ 2 times), while compared to delayed combination with rituximab (> 3 months), early initiation of combination (≤ 3 months) might achieve better improvements in CASE and MMSE assessment even 1 year later. No rituximab-correlated serious adverse events have been reported in our patients. CONCLUSIONS: Our simplified regimen of combined low-dose rituximab firstly showed significantly accelerating short-term recovery and long-term improvement for AE with NSAbs, in parallel with markedly reduced prednisone dosage and clinical relapses. Moreover, opportunity of protocol showed earlier initiation (≤ 3 months) with better long-term improvement.