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Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/ß-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of ß-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion: The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/ß-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.
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BACKGROUND: Because spontaneous remission is common in IMN, and there are adverse effects of immunosuppressive therapy, it is important to assess the risk of progressive loss of renal function before deciding whether and when to initiate immunosuppressive therapy. Therefore, this study aimed to establish a risk prediction model to predict patient prognosis and treatment response to help clinicians evaluate patient prognosis and decide on the best treatment regimen. METHODS: From September 2019 to December 2020, a total of 232 newly diagnosed IMN patients from three hospitals in Liaoning Province were enrolled. Logistic regression analysis selected the risk factors affecting the prognosis, and a dynamic online nomogram prognostic model was constructed based on extreme gradient boost, random forest, logistic regression machine learning algorithms. Receiver operating characteristic and calibration curves and decision curve analysis were utilized to assess the performance and clinical utility of the developed model. RESULTS: A total of 130 patients were in the training cohort and 102 patients in the validation cohort. Logistic regression analysis identified four risk factors: course ≥ 6 months, UTP, D-dimer and sPLA2R-Ab. The random forest algorithm showed the best performance with the highest AUROC (0.869). The nomogram had excellent discrimination ability, calibration ability and clinical practicability in both the training cohort and the validation cohort. CONCLUSIONS: The dynamic online nomogram model can effectively assess the prognosis and treatment response of IMN patients. This will help clinicians assess the patient's prognosis more accurately, communicate with the patient in advance, and jointly select the most appropriate treatment plan.
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Glomerulonefrite Membranosa , Nomogramas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Prognóstico , Fatores de Risco , Modelos LogísticosRESUMO
PURPOSE: To develop and validate an end-to-end model for automatically predicting hematoma expansion (HE) after spontaneous intracerebral hemorrhage (sICH) using a novel deep learning framework. METHODS: This multicenter retrospective study collected cranial noncontrast computed tomography (NCCT) images of 490 patients with sICH at admission for model training (n = 236), internal testing (n = 60), and external testing (n = 194). A HE-Mind model was designed to predict HE, which consists of a densely connected U-net for segmentation process, a multi-instance learning strategy for resolving label ambiguity and a Siamese network for classification process. Two radiomics models based on support vector machine or logistic regression and two deep learning models based on residual network or Swin transformer were developed for performance comparison. Reader experiments including physician diagnosis mode and artificial intelligence mode were conducted for efficiency comparison. RESULTS: The HE-Mind model showed better performance compared to the comparative models in predicting HE, with areas under the curve of 0.849 and 0.809 in the internal and external test sets respectively. With the assistance of the HE-Mind model, the predictive accuracy and work efficiency of the emergency physician, junior radiologist, and senior radiologist were significantly improved, with accuracies of 0.768, 0.789, and 0.809 respectively, and reporting times of 7.26 s, 5.08 s, and 3.99 s respectively. CONCLUSIONS: The HE-Mind model could rapidly and automatically process the NCCT data and predict HE after sICH within three seconds, indicating its potential to assist physicians in the clinical diagnosis workflow of HE.
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Hemorragia Cerebral , Hematoma , Tomografia Computadorizada por Raios X , Humanos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Masculino , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Hematoma/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Idoso , Aprendizado Profundo , Máquina de Vetores de Suporte , Progressão da Doença , Valor Preditivo dos TestesRESUMO
OBJECTIVE: To methodically analyse the swirl sign and construct a scoring system to predict the risk of hematoma expansion (HE) after spontaneous intracerebral haemorrhage (sICH). METHODS: We analysed 231 of 683 sICH patients with swirl signs on baseline noncontrast CT (NCCT) images. The characteristics of the swirl sign were analysed, including the number, maximum diameter, shape, boundary, minimum CT value of the swirl sign, and the minimum distance from the swirl sign to the edge of the hematoma. In the development cohort, univariate and multivariate analyses were used to identify independent predictors of HE, and logistic regression analysis was used to construct the swirl sign score system. The swirl sign score system was verified in the validation cohort. RESULTS: The number and the minimum CT value of the swirl sign were independent predictors of HE. The swirl sign score system was constructed (2 points for the number of swirl signs >1 and 1 point for the minimum CT value ≤41 Hounsfield units). The area under the curve of the swirl sign score system in predicting HE was 0.773 and 0.770 in the development and validation groups, respectively. CONCLUSIONS: The swirl sign score system is an easy-to-use radiological grading scale that requires only baseline NCCT images to effectively identify subjects at high risk of HE. ADVANCES IN KNOWLEDGE: Our newly developed semiquantitative swirl sign score system greatly improves the ability of swirl sign to predict HE.
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Hemorragia Cerebral , Hematoma , Tomografia Computadorizada por Raios X , Humanos , Masculino , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Hematoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Medição de Risco/métodos , Idoso de 80 Anos ou mais , Valor Preditivo dos TestesRESUMO
Pseudomonas aeruginosa is one of the most common nosocomial pathogens worldwide, known for its virulence, drug resistance, and elaborate sensor-response network. The primary challenge encountered by pathogens during the initial stages of infection is the immune clearance arising from the host. The resident macrophages of barrier organs serve as the frontline defense against these pathogens. Central to our understanding is the mechanism by which bacteria modify their behavior to circumvent macrophage-mediated clearance, ensuring their persistence and colonization. To successfully evade macrophage-mediated phagocytosis, bacteria must possess an adaptive response mechanism. Two-component systems provide bacteria the agility to navigate diverse environmental challenges, translating external stimuli into cellular adaptive responses. Here, we report that the well-documented histidine kinase, LadS, coupled to a cognate two-component response regulator, PA0034, governs the expression of a vital adhesin called chaperone-usher pathway pilus cupA. The LadS/PA0034 system is susceptible to interference from the reactive oxygen species likely to be produced by macrophages and further lead to a poor adhesive phenotype with scantily cupA pilus, impairing the phagocytosis efficiency of macrophages during acute infection. This dynamic underscores the intriguing interplay: as macrophages deploy reactive oxygen species to combat bacterial invasion, the bacteria recalibrate their exterior to elude these defenses. IMPORTANCE: The notoriety of Pseudomonas aeruginosa is underscored by its virulence, drug resistance, and elaborate sensor-response network. Yet, the mechanisms by which P. aeruginosa maneuvers to escape phagocytosis during acute infections remain elusive. This study pinpoints a two-component response regulator, PA0034, coupled with the histidine kinase LadS, and responds to macrophage-derived reactive oxygen species. The macrophage-derived reactive oxygen species can impair the LadS/PA0034 system, resulting in reduced expression of cupA pilus in the exterior of P. aeruginosa. Since the cupA pilus is an important adhesin of P. aeruginosa, its deficiency reduces bacterial adhesion and changes their behavior to adopt a planktonic lifestyle, subsequently inhibiting the phagocytosis of macrophages by interfering with bacterial adhesion. Briefly, reactive oxygen species may act as environmental cues for the LadS/PA0034 system. Upon recognition, P. aeruginosa may transition to a poorly adhesive state, efficiently avoiding engulfment by macrophages.
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Macrófagos , Fagocitose , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/metabolismo , Macrófagos/microbiologia , Macrófagos/imunologia , Camundongos , Animais , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/imunologia , Proteínas de Fímbrias/metabolismo , Proteínas de Fímbrias/genética , Regulação Bacteriana da Expressão Gênica , Fímbrias Bacterianas/metabolismo , Fímbrias Bacterianas/genética , Histidina Quinase/metabolismo , Histidina Quinase/genética , Humanos , Células RAW 264.7RESUMO
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disease resulting from the interaction of various factors such as social elements, autoimmunity, genetics, and gut microbiota. Alarmingly, recent epidemiological data points to a surging incidence of IBD, underscoring an urgent imperative: to delineate the intricate mechanisms driving its onset. Such insights are paramount, not only for enhancing our comprehension of IBD pathogenesis but also for refining diagnostic and therapeutic paradigms. Monocytes, significant immune cells derived from the bone marrow, serve as precursors to macrophages (Mφs) and dendritic cells (DCs) in the inflammatory response of IBD. Within the IBD milieu, their role is twofold. On the one hand, monocytes are instrumental in precipitating the disease's progression. On the other hand, their differentiated offsprings, namely moMφs and moDCs, are conspicuously mobilized at inflammatory foci, manifesting either pro-inflammatory or anti-inflammatory actions. The phenotypic spectrum of these effector cells, intriguingly, is modulated by variables such as host genetics and the subtleties of the prevailing inflammatory microenvironment. Notwithstanding their significance, a palpable dearth exists in the literature concerning the roles and mechanisms of monocytes in IBD pathogenesis. This review endeavors to bridge this knowledge gap. It offers an exhaustive exploration of monocytes' origin, their developmental trajectory, and their differentiation dynamics during IBD. Furthermore, it delves into the functional ramifications of monocytes and their differentiated progenies throughout IBD's course. Through this lens, we aspire to furnish novel perspectives into IBD's etiology and potential therapeutic strategies.
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Background: The relationship between early perihematomal edema (PHE) and hematoma expansion (HE) is unclear. We investigated this relationship in patients with acute spontaneous intracerebral hemorrhage (ICH), using radiomics. Methods: In this multicenter retrospective study, we analyzed 490 patients with spontaneous ICH who underwent non-contrast computed tomography within 6 h of symptom onset, with follow-up imaging at 24 h. We performed HE and PHE image segmentation, and feature extraction and selection to identify HE-associated optimal radiomics features. We calculated radiomics scores of hematoma (Radscores_HEA) and PHE (Radscores_PHE) and constructed a combined model (Radscore_HEA_PHE). Relationships of the PHE radiomics features or Radscores_PHE with clinical variables, hematoma imaging signs, Radscores_HEA, and HE were assessed by univariate, correlation, and multivariate analyses. We compared predictive performances in the training (n = 296) and validation (n = 194) cohorts. Results: Shape_VoxelVolume and Shape_MinorAxisLength of PHE were identified as optimal radiomics features associated with HE. Radscore_PHE (odds ratio = 1.039, p = 0.032) was an independent HE risk factor after adjusting for the ICH onset time, Glasgow Coma Scale score, baseline hematoma volume, hematoma shape, hematoma density, midline shift, and Radscore_HEA. The areas under the receiver operating characteristic curve of Radscore_PHE in the training and validation cohorts were 0.808 and 0.739, respectively. After incorporating Radscore_PHE, the integrated discrimination improvements of Radscore_HEA_PHE in the training and validation cohorts were 0.009 (p = 0.086) and -0.011 (p < 0.001), respectively. Conclusion: Radscore_PHE, based on Shape_VoxelVolume and Shape_MinorAxisLength of PHE, independently predicts HE, while Radscore_PHE did not add significant incremental value to Radscore_HEA.
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Corn silk is the stigma and style of corn and is rich in polysaccharides. Despite the extensive research on its polysaccharides, the hemostatic characteristics of effective parts and the related activities remain insufficiently explored. Corn silk polysaccharide (CSP) was extracted with hot water and purified using a diethylaminoethyl cellulose membrane. Then, it was separated with sephadex G-150 to obtain five fractions. These fractions were investigated for their potential in hemostasis, antioxidant, immune response, and anti-lung cancer activities. CSP-2, CSP-3, and CSP-4 significantly affected the coagulation indicators activated partial thromboplastin time (APTT) and thrombin time (TT) at 125-500 µg/mL. Corn silk flavonoids and saponins at 32.25 µg/mL significantly prolonged APTT, TT, and prothrombin time (PT). CSP-2, with potent antioxidant ability, approaches Vitamin C. At 25 µg/mL, CSPs nearly reached the phagocytosis of neutral red of lipopolysaccharides. The five fractions promoted the proliferation of RAW264.7 cells at 25-800 µg/mL and stimulated NO secretion at 25-100 µg/mL. CSP-2 also showed an 86 % inhibition rate effect on A549 at 200 µg/mL. These results indicate that CSP not only has hemostatic effects but also has immune and anti-lung cancer activities. Thus, it is a potential candidate compound with immune activity for managing bleeding in cancer.
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Hemostáticos , Neoplasias Pulmonares , Humanos , Zea mays , Hemostáticos/farmacologia , Antioxidantes/farmacologia , Hemostasia , Neoplasias Pulmonares/tratamento farmacológico , Polissacarídeos/farmacologia , SedaRESUMO
This study aims to optimize the processing of Myristica fragrans Houtt. by talcum powder simmering using single-factor and orthogonal experimental methods, and the overall desirability values of dehydrodiisoeugenol and essential oils content were selected as indicators of the process. The new process reduced the total content of the three toxic components, namely myristicin, safrole and elemicin, from 1.91% to 1.16% before and after processing, indicating that the toxic components were reduced by 39%. The IC50 of the essential oils before and after processing were 1.002 ± 0.05 and 0.233 ± 0.05 mg/mL for DPPH scavenging activity and 0.132 ± 0.04 and 0.057 ± 0.05 mg/mL for ABTS scavenging activity, respectively. And the absorbance of the antioxidant activity against Ferric reducing power ranged from 0.213 to 0.709 and from 0.225 to 0.755, respectively. The minimum inhibitory concentration for Staphylococcus aureus, Bacillus pumilus and Escherichia coli were all lower after processing than before. The antioxidant activity and antibacterial activity of the essential oils after processing were better than before. The results of the survival of zebrafish embryos at different concentrations of essential oils at 0-168 h post fertilisation were higher after processing than before. These findings suggest that processing plays the role of reducing toxicity and increasing beneficial effects. They provide a scientific basis not only for the processing of M. fragrans, but also for the processing of other foods.
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Myristica , Óleos Voláteis , Animais , Antioxidantes/farmacologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Peixe-Zebra , Sementes , Óleos Voláteis/farmacologiaRESUMO
Research of lactic acid bacteria and its metabolites on biological preservatives becomes a hot topic. Lactobacillus plantarum O2, with good inhibition on Phytophthora capsici (P. capsici), was isolated from the pickle. In this study, the effects of L. plantarum O2 fermentation supernatant (FS) on pepper postharvest preservation and its induced resistance to P. capsici were studied. Results showed that weight loss rate, rot index, respiration rate, relative electrical conductivity, loss of chlorophyll content and VC of pepper in FS treatment group were decreased by 18 %, 64 %, 15 %, 26 %, 33 % and 20 % compared with blank control (BC) after 20 d storage. L* and b*-value of pepper in FS group were lower than those in the BC group. In addition, the damage-induced resistance test found that the infection rate in the FS group was reduced by 39 %, compared with CK2 after 12 d storage. Moreover, phenylalanine ammonia-lyase activity, peroxidase activity, polyphenol oxidase activity, proline content, total phenol content and flavonoid content increased by 14 %, 9 %, 30 %, 8 %, 8 % and 9 %, respectively, while malondialdehyde content decreased by 13 %. These results indicated that FS treatment showed good fresh-keeping effects on postharvest pepper. It could enhance the tolerance of pepper under stress by improving defensive enzyme activities, slowing down the damage caused by P. capsici, and inducing pepper resistance to P. capsici. Therefore, FS can be used as a microbial source bio-preservative for postharvest pepper.
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Capsicum , Lactobacillus plantarum , Phytophthora , Phytophthora/fisiologia , Fermentação , Antioxidantes , Doenças das Plantas/microbiologiaRESUMO
Acute kidney injury (AKI) is a serious disorder associated with significant morbidity and mortality. AKI and ischemia/reperfusion (hypoxia/reoxygenation, H/R) injury can be induced due to several reasons. Paeoniflorin (PF) is a traditional herbal medicine derived from Paeonia lactiflora Pall. It exerts diverse therapeutic effects, including anti-inflammatory, antioxidative, antiapoptotic, and immunomodulatory properties; thus, it is considered valuable for treating several diseases. However, the effects of PF on H/R injury-induced AKI remain unknown. In this study, we established an in vitro H/R model using COCL2 and investigated the functions and underlying mechanisms of PF on H/R injury in HK-2 cells. The cell vitality was evaluated using the cell count kit-8 assay. The DCFH-DA fluorescence probe was used to measure the levels of reactive oxygen species (ROS). Oxidative damage was detected using superoxide dismutase (SOD) and malondialdehyde (MDA) assay kits. Apoptotic relative protein and Keap1/Nrf2/HO-1 signaling were evaluated by Western blotting. Our results indicated that PF increased cell viability and SOD activity and decreased the ROS and MDA levels in HK-2 cells with H/R injury. PF inhibits apoptosis by increasing Bcl-2 and decreasing Bax. Furthermore, PF significantly upregulated the expression of HO-1 and Nrf2, but downregulated the expression of HIF-1α and Keap1. PF considerably increased Nrf2 nuclear translocation and unregulated the HO-1 expression. The Nrf2 inhibitor (ML385) could reverse the abovementioned protective effects of PF, suggesting that Nrf2 can be a critical target of PF. To conclude, we found that PF attenuates H/R injury-induced AKI by decreasing the oxidative damage via the Nrf2/HO-1 pathway and inhibiting apoptosis.
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Injúria Renal Aguda , Traumatismo por Reperfusão , Humanos , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Fator 2 Relacionado a NF-E2/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Transdução de Sinais , Estresse Oxidativo , Apoptose , Hipóxia , Superóxido Dismutase , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismoRESUMO
The aim of the present study was to elucidate the potential diagnostic value of urinary N-glycoprotein in patients with IgA nephropathy (IgAN) using mass spectrometry (MS). All procedures were performed between June 2021 and June 2023 at Guangan People's Hospital (Guangan, China). Fresh mid-morning fasting midstream urine samples were collected from a total of 30 patients with IgAN and 30 sex- and age-matched healthy volunteers. Data acquired from 6 participants are available through ProteomeXchange with the identifier PXD041151. By comparison between the IgAN group (n=3) and healthy controls (n=3) and selection criteria of P<0.05 and |log fold-change|>2, a total of 11 upregulated and 22 downregulated glycoproteins in patients with IgAN were identified. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that glycoproteins are involved in various functions, such as the regulation of cell growth, cell adhesion, cellular component organization and protein binding, as well as multiple pathways, including p53, Notch and mTOR signaling pathways. The urine levels of afamin were further measured by ELISA in a validation cohort to assess the diagnostic performance of the single indicator model. In conclusion, MS-based proteomics of urinary glycoproteins may be an alternative option for diagnosing patients with IgAN. Biomarkers of IgAN may include, but are not limited to, CCL25, PD-L1, HLA-DRB1, IL7RD and WDR82. In addition, the levels of urinary AFM indicators are of diagnostic value for IgAN.
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BACKGROUND: Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood. METHODS: A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5'-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM. RESULTS: Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iß and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages. CONCLUSION: The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.
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Nefropatias , Obstrução Ureteral , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fosfatidilinositol 3-Quinases , Ratos Sprague-Dawley , Nefropatias/tratamento farmacológico , Fibrose , Piridonas/farmacologia , Piridonas/uso terapêutico , Obstrução Ureteral/complicações , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/metabolismo , Autofagia , Mitocôndrias/metabolismoRESUMO
BACKGROUND: The leading cause of end-stage renal disease is diabetic nephropathy (DN). A key factor in DN is immune cell infiltration (ICI). It has been shown that immune-related genes play a significant role in inflammation and immune cell recruitment. However, neither the underlying mechanisms nor immune-related biomarkers have been identified in DNs. Using bioinformatics, this study investigated biomarkers associated with immunity in DN. METHODS: Using bioinformatic methods, this study aimed to identify biomarkers and immune infiltration associated with DN. Gene expression profiles (GSE30528, GSE47183, and GSE104948) were selected from the Gene Expression Omnibus database. First, we identified 23 differentially expressed immune-related genes and 7 signature genes, LYZ, CCL5, ALB, IGF1, CXCL2, NR4A2, and RBP4. Subsequently, protein-protein interaction networks were created, and functional enrichment analysis and genome enrichment analysis were performed using the gene ontology and Kyoto Encyclopedia of Genes and Genome databases. In the R software, the ConsensusClusterPlus package identified 2 different immune modes (cluster A and cluster B) following the consistent clustering method. The infiltration of immune cells between the 2 clusters was analyzed by applying the CIBERSORT method. And preliminarily verified the characteristic genes through in vitro experiments. RESULTS: In this study, the samples of diabetes nephropathy were classified based on immune related genes, and the Hub genes LYZ, CCL5, ALB, IGF1, CXCL2, NR4A2 and RBP4 related to immune infiltration of diabetes nephropathy were obtained through the analysis of gene expression differences between different subtypes. CONCLUSIONS: This study was based on bioinformatics technology to analyze the biomarkers of immune related genes in diabetes nephropathy. To analyze the pathogenesis of diabetes nephropathy at the RNA level, and ultimately provide guidance for disease diagnosis, treatment, and prognosis.
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Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/genética , Biomarcadores , Análise por Conglomerados , Biologia Computacional , Bases de Dados Factuais , Proteínas Plasmáticas de Ligação ao RetinolRESUMO
Parasitic diseases pose a significant threat to global public health, particularly in developing countries. Host genetic factors play a crucial role in determining susceptibility and resistance to infection. Recent advances in molecular and biological technologies have enabled significant breakthroughs in understanding the impact of host genes on parasite adaptation. In this comprehensive review, we analyze the host genetic factors that influence parasite adaptation, including hormones, nitric oxide, immune cells, cytokine gene polymorphisms, parasite-specific receptors, and metabolites. We also establish an interactive network to better illustrate the complex relationship between host genetic factors and parasite-host adaptation. Additionally, we discuss future directions and collaborative research priorities in the parasite-host adaptation field, including investigating the impact of host genes on the microbiome, developing more sophisticated models, identifying and characterizing parasite-specific receptors, utilizing patient-derived sera as diagnostic and therapeutic tools, and developing novel treatments and management strategies targeting specific host genetic factors. This review highlights the need for a comprehensive and systematic approach to investigating the underlying mechanisms of parasite-host adaptation, which requires interdisciplinary collaborations among biologists, geneticists, immunologists, and clinicians. By deepening our understanding of the complex interactions between host genetics and parasite adaptation, we can develop more effective and targeted interventions to prevent and treat parasitic diseases. Overall, this review provides a valuable resource for researchers and clinicians working in the parasitology field and offers insights into the future directions of this critical research area.
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Microbiota , Parasitos , Humanos , Animais , Parasitos/genética , Adaptação ao Hospedeiro , Citocinas , Óxido NítricoRESUMO
Introduction: Xiaoai Jiedu recipe (XJR), a classical prescription of traditional Chinese medicine (TCM), has been clinically proven to be effective in ameliorating colorectal cancer (CRC). However, its exact mechanism of action is still elusive, limiting its clinical application and promotion to a certain extent. This study aims to evaluate the effect of XJR on CRC and further illustrate mechanism underlying its action. Methods: We investigated the anti-tumor efficacy of XJR in vitro and vivo experiments. An integrated 16S rRNA gene sequencing and UPLC-MS based metabolomics approach were performed to explore possible mechanism of XJR anti-CRC on the gut microbiota and serum metabolic profiles. The correlation between altered gut microbiota and disturbed serum metabolites was investigated using Pearson's correlation analysis. Results: XJR effectively displayed anti-CRC effect both in vitro and in vivo. The abundance of aggressive bacteria such as Bacteroidetes, Bacteroides, and Prevotellaceae decreased, while the levels of beneficial bacteria increased (Firmicutes, Roseburia, and Actinobacteria). Metabolomics analysis identified 12 potential metabolic pathways and 50 serum metabolites with different abundances possibly affected by XJR. Correlation analysis showed that the relative abundance of aggressive bacteria was positively correlated with the levels of Arachidonic acid, Adrenic acid, 15(S)-HpETE, DL-Arginine, and Lysopc 18:2, which was different from the beneficial bacteria. Discussion: The regulation of gut microbiota and related metabolites may be potential breakthrough point to elucidate the mechanism of XJR in the treatment of the CRC. The strategy employed would provide theoretical basis for clinical application of TCM.
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Premature ovarian insufficiency (POI) has become one of the greatest health threats to the reproduction of women during their fertile age. Lycium barbarum polysaccharides (LBPs) are known for anti-aging and reproductive protective functions. Here, we investigated the protective effect of LBP on POI mice and revealed its possible mechanism by a combination of 16S rRNA sequencing and metabolomics analysis. In the current study, female C57BL/6J mice treated with D-galactose were used as a model to investigate the reversal effect of LBP on the degenerative ovarian function. The ameliorative effect of LBP on POI was evaluated from the estrous cycle, ovarian reserve, serum sex hormone levels, and fertility testing. Additionally, 16S rRNA gene sequencing and untargeted metabolomics were integrated to analyze the effects of LBP on the gut microbiota and fecal metabolic profile in the POI mice. The results showed that LBP administration significantly increased the total number of follicles and the number of follicles at different developmental stages in the POI mice. In addition, LBP was effective in reducing the serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), regularizing the disordered estrous cycle, and increasing the number of offspring of the POI mice. The results from 16S rRNA sequencing showed that LBP had beneficial effects on the composition and structure of the gut microbiota in the POI mice. In a metabolomics study, a total of 23 metabolites were finally identified as potential biomarkers of POI, and multiple pathways were regulated after the treatment of LBP, especially the arginine biosynthesis, glycerophospholipid metabolism and steroid hormone biosynthesis pathways. Pearson's correlation analysis showed that the regulation effect of LBP on metabolites was closely related to Faecalibaculum, Bilophila and Anaerofustis in the gut microbiota. In summary, the results demonstrated that LBP could improve the ovarian reserve and provides evidence both on the gut microbiota and metabolism, which provide beneficial support for the applications of LBP in female ovarian function degeneration.
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Microbioma Gastrointestinal , Lycium , Insuficiência Ovariana Primária , Humanos , Camundongos , Feminino , Animais , Galactose/farmacologia , RNA Ribossômico 16S/genética , Camundongos Endogâmicos C57BL , Insuficiência Ovariana Primária/tratamento farmacológico , Metaboloma , Lycium/químicaRESUMO
To investigate the differences between Korean Ganoderma lucidum spore powder (KP), broken-spo-roderm KP (BSKP), Chinese traditional G. lucidum spore powder (CP), and broken-sporoderm CP (BSCP), they were identified by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), second derivative infrared spectroscopy (SD-IR), dual-index sequence analysis (DISA) and X-ray diffraction (XRD). SEM showed that there were no significant differences in microstructure between the two kinds of spore powders. FT-IR spectra showed that the four spore powders appeared with characteristic peaks of 3400, 3006, 2925, 1745, 1535, 1454, 1249, 1074, 1049, and 896 cm-1, respectively, they were contained the characteristic peaks of total triterpenes, polysaccharides and fatty acids. DISA showed that the same species of spore powders, the overall similarity of before and broken the sporoderm was high with minor differences and there were no differences between the different kinds of spore powders. Similarity analysis showed that the four spore powders were in high agreement and were no differences. The polysaccharide, total triterpene, spore oil and protein content of the four spore powders were determined separately. The results showed that the active ingredients content of the batch of KP were lower than that of CP, that of BSKP were lower than that of BSCP, while the active ingredients content of both broken-sporoderm spore powders were higher than that of before broken-sporoderm. It is inferred that the structure of the main chemical and component of KP is the same as that of CP. This study provides a reference for the future development and application of G. lucidum.
Assuntos
Agaricales , Reishi , Triterpenos , China , Polissacarídeos/análise , Pós , Reishi/química , República da Coreia , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , Esporos Fúngicos/química , Triterpenos/químicaRESUMO
The polysaccharides from Sea buckthorn leaves (SBLPs) were extracted by hot water and purified by DEAE cellulose, then separated into six polysaccharides (SBLP-S) by DEAE-52 column. Six separated polysaccharides were characterized by Ultraviolet Spectroscopy, Infrared Spectrum, High Performance Liquid Chromatographic and Congo red analysis. The antioxidant activity and immunological activity were investigated in vitro. The results revealed that the monosaccharide composition of SBLP-S-1, SBLP-S-2, SBLP-S-3, SBLP-S-5 and SBLP-S-6 contained Man, GlcN, Rib, Rha, GluA, GalA, Glu, Gal, Xyl, Ara and Fuc, among them, rare glucosamine was found. And SBLP-S-4 contained all above components except GlcN and GluA. FT-IR showed that SBLP-S were sulfated polysaccharide containing uronic acid. Molecular weights of SBLP-S were 338.659, 401.305, 599.849, 393.904, 626.895 and 176.862 kDa. The Congo-red test indicated that SBLP-S-2, SBLP-S-4, SBLP-S-5, and SBLP-S-6 had triple helix conformation. Crude polysaccharides had the strong scavenging activities on DPPH radicals, ABTS radicals and hydroxyl radicals. The six polysaccharides had the activity of immune stimulation on RAW264.7 cell. SBLP-S-2 promoted the phagocytosis best and SBLP-S-6 promoted the NO production best. The results suggested that SBLPs could be used as potential antioxidants and immunomodulatory agents in pharmaceutical and functional food fields.
Assuntos
Antioxidantes , Hippophae , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Estrutura Molecular , Polissacarídeos/farmacologia , Polissacarídeos/química , Folhas de Planta/químicaRESUMO
Colorectal cancer (CRC) is one of highly prevalent cancer. Immunotherapy with immune checkpoint inhibitors (ICIs) has dramatically changed the landscape of treatment for many advanced cancers, but CRC still exhibits suboptimal response to immunotherapy. The gut microbiota can affect both anti-tumor and pro-tumor immune responses, and further modulate the efficacy of cancer immunotherapy, particularly in the context of therapy with ICIs. Therefore, a deeper understanding of how the gut microbiota modulates immune responses is crucial to improve the outcomes of CRC patients receiving immunotherapy and to overcome resistance in nonresponders. The present review aims to describe the relationship between the gut microbiota, CRC, and antitumor immune responses, with a particular focus on key studies and recent findings on the effect of the gut microbiota on the antitumor immune activity. We also discuss the potential mechanisms by which the gut microbiota influences host antitumor immune responses as well as the prospective role of intestinal flora in CRC treatment. Furthermore, the therapeutic potential and limitations of different modulation strategies for the gut microbiota are also discussed. These insights may facilitate to better comprehend the interplay between the gut microbiota and the antitumor immune responses of CRC patients and provide new research pathways to enhance immunotherapy efficacy and expand the patient population that could be benefited by immunotherapy.