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Effective molecular representation learning is very important for Artificial Intelligence-driven Drug Design because it affects the accuracy and efficiency of molecular property prediction and other molecular modeling relevant tasks. However, previous molecular representation learning studies often suffer from limitations, such as over-reliance on a single molecular representation, failure to fully capture both local and global information in molecular structure, and ineffective integration of multiscale features from different molecular representations. These limitations restrict the complete and accurate representation of molecular structure and properties, ultimately impacting the accuracy of predicting molecular properties. To this end, we propose a novel multi-view molecular representation learning method called MvMRL, which can incorporate feature information from multiple molecular representations and capture both local and global information from different views well, thus improving molecular property prediction. Specifically, MvMRL consists of four parts: a multiscale CNN-SE Simplified Molecular Input Line Entry System (SMILES) learning component and a multiscale Graph Neural Network encoder to extract local feature information and global feature information from the SMILES view and the molecular graph view, respectively; a Multi-Layer Perceptron network to capture complex non-linear relationship features from the molecular fingerprint view; and a dual cross-attention component to fuse feature information on the multi-views deeply for predicting molecular properties. We evaluate the performance of MvMRL on 11 benchmark datasets, and experimental results show that MvMRL outperforms state-of-the-art methods, indicating its rationality and effectiveness in molecular property prediction. The source code of MvMRL was released in https://github.com/jedison-github/MvMRL.
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Redes Neurais de Computação , Algoritmos , Aprendizado de Máquina , Modelos Moleculares , Desenho de Fármacos , Software , Estrutura Molecular , Inteligência ArtificialRESUMO
Perineuronal nets (PNNs) are important functional structures on the surface of nerve cells. Observation of PNNs usually requires dyeing or fluorescent labeling. As a network structure with a micron grid and sub-wavelength thickness but no special optical properties, quantitative phase imaging (QPI) is the only purely optical method for high-resolution imaging of PNNs. We proposed a Scattering Quantitative Interference Imaging (SQII) method which measures the geometric rather than transmission or reflection phase during the scattering process to visualize PNNs. Different from QIP methods, SQII method is sensitive to scattering and not affected by wavelength changes. Via geometric phase shifting method, we simplify the phase shift operation. The SQII method not only focuses on interference phase, but also on the interference contrast. The singularity points and phase lines of the scattering geometric phase depict the edges of the network structure and can be found at the valley area of the interference contrast parameter SINDR under different wavelengths. Our SQII method has its unique imaging properties, is very simple and easy to implement and has more worth for promotion.
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The slightest change in the extra/intracellular concentration of metal ions results in amplified effects by signaling cascades that regulate both cell fate within the tumor microenvironment and immune status, which influences the network of antitumor immunity through various pathways. Based on the fact that metal ions influence the fate of cancer cells and participate in both innate and adaptive immunity, they are widely applied in antitumor therapy as immune modulators. Moreover, nanomedicine possesses the advantage of precise delivery and responsive release, which can perfectly remedy the drawbacks of metal ions, such as low target selectivity and systematic toxicity, thus providing an ideal platform for metal ion application in cancer treatment. Emerging evidence has shown that immunotherapy applied with nanometallic materials may significantly enhance therapeutic efficacy. Here, we focus on the physiopathology of metal ions in tumorigenesis and discuss several breakthroughs regarding the use of nanometallic materials in antitumor immunotherapeutics. These findings demonstrate the prominence of metal ion-based nanomedicine in cancer therapy and prophylaxis, providing many new ideas for basic immunity research and clinical application. Consequently, we provide innovative insights into the comprehensive understanding of the application of metal ions combined with nanomedicine in cancer immunotherapy in the past few years.
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Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Metais/uso terapêutico , Imunoterapia/métodos , Transdução de Sinais , Íons , Nanomedicina/métodos , Microambiente TumoralRESUMO
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterised by recurrent subcortical ischemic events, migraine with aura, dementia and mood disturbance. Strokes are typically lacunar infarcts; however, bilateral multiple subcortical lacunar infarcts have been described only sporadically. METHOD: We described four CADASIL patients who presented with acute bilateral multiple subcortical infarcts as the first manifestation. We also briefly summarised the case reports detailing the bilateral multiple infarcts in CADASIL. RESULTS: Patient 1 and patient 2 were family members, and they presented with cognitive impairment. Patient 3 and patient 4 presented with slurred speech and hemiparesis. Patients 1, 3 and 4 developed hemodynamic fluctuations before the occurrence of ischemic stroke. Laboratory tests revealed elevated fibrinogen levels in patients 3 and 4. The brain magnetic resonance imaging showed acute bilateral multiple subcortical infarcts on the periventricular white matter in all the patients. CONCLUSION: CADASIL, with a poor brain hemodynamic reserve, is vulnerable to hemodynamic alterations (e.g. blood pressure fluctuation, dehydration, blood loss and anaemia) and intolerable to ischemia and hypoxia of the brain. Furthermore, blood hypercoagulation may contribute to acute multiple bilateral infarctions in CADASIL. Therefore, it is necessary to avert these predispositions in CADASIL patients in their daily life.
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CADASIL , Leucoencefalopatias , Transtornos de Enxaqueca , Acidente Vascular Cerebral Lacunar , Humanos , CADASIL/complicações , CADASIL/diagnóstico por imagem , CADASIL/patologia , Acidente Vascular Cerebral Lacunar/patologia , Receptor Notch3/genética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Transtornos de Enxaqueca/patologia , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/etiologia , Leucoencefalopatias/patologia , Imageamento por Ressonância MagnéticaRESUMO
Spin superconductor (SSC) is an exciton condensate state where the spin-triplet exciton superfluidity is charge neutral while spin 2(â/2). In analogy to the Majorana zero mode (MZM) in topological superconductors, the interplay between SSC and band topology will also give rise to a specific kind of topological bound state obeying non-Abelian braiding statistics. Remarkably, the non-Abelian geometric phase here originates from the Aharonov-Casher effect of the "half-charge" other than the Aharonov-Bohm effect. Such topological bound state of SSC is bound with the vortex of electric flux gradient and can be experimentally more distinct than the MZM for being electrically charged. This theoretical proposal provides a new avenue investigating the non-Abelian braiding physics without the assistance of MZM and charge superconductor.
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We numerically demonstrate that the topological corner states residing in the corners of higher-order topological insulator possess non-Abelian braiding properties. Such topological corner states are Dirac fermionic modes other than Majorana zero modes. We claim that Dirac fermionic modes protected by nontrivial topology also support non-Abelian braiding. An analytical description on such non-Abelian braiding is conducted based on the vortex-induced Dirac-type fermionic modes. Finally, the braiding operators for Dirac fermionic modes, especially their explicit matrix forms, are analytically derived and compared with the case of Majorana zero modes.
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OBJECTIVE: To determine serum vascular endothelial growth factor B (VEGF-B) levels in polycystic ovary syndrome, their association with insulin resistance and ß-cell dysfunction, and the effect of metformin on serum VEGF-B levels. DESIGN: A cross-sectional, interventional study. PATIENTS: We recruited 103 women with polycystic ovary syndrome and 96 age-matched healthy controls. Serum VEGF-B levels were determined in all participants, and 44 polycystic ovary syndrome patients randomly received metformin. MEASUREMENTS: We measured VEGF-B levels in healthy controls and women with polycystic ovary syndrome before and after metformin treatment. RESULTS: Women with polycystic ovary syndrome had higher serum VEGF-B levels, which decreased with metformin treatment. In the lean and overweight/obese groups, patients with polycystic ovary syndrome had higher plasma VEGF-B levels than did healthy controls (P < 0·05). VEGF-B levels were correlated with body mass index, body fat percentage, M values, homeostasis model assessment of insulin resistance and ß-cell function indices. A multiple linear regression analysis showed that VEGF-B level was associated with M values after adjusting for age, body mass index, serum sex hormones and serum lipids in women with polycystic ovary syndrome. CONCLUSIONS: Serum VEGF-B is significantly higher in women with polycystic ovary syndrome and is closely and positively related to insulin resistance. Metformin treatment reduces VEGF-B levels and ameliorates insulin resistance.
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Metformina/uso terapêutico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Fator B de Crescimento do Endotélio Vascular/sangue , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Modelos Lineares , Lipídeos/sangue , Obesidade/sangue , Sobrepeso/sangue , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Women with polycystic ovary syndrome (PCOS) mostly have profound insulin resistance (IR) and ß-cell dysfunction. Although thioredoxin-interacting protein (TXNIP) is a major regulator in IR and insulin secretion, no data on the plasma TXNIP level in patients with PCOS are available. This study aimed to determine the plasma TXNIP level and discuss the relationship between TXNIP and ß-cell dysfunction/IR in patients with PCOS. PATIENTS: Eighty-three women with PCOS and 52 controls. MEASUREMENTS: Insulin sensitivity was expressed by M value obtained from euglycaemic-hyperinsulinaemic clamp. Homoeostatic model assessment for ß-cell function (HOMA-ß), â³Ins30/â³Glu30 and AUCins/glu were considered as the indices of fasting state, early-phase and total insulin secretion during oral glucose tolerance test, respectively. To evaluate ß-cell function adjusted for insulin sensitivity, disposition index (DI) was used: basal DI (DI0), early-phase DI (DI30) and total DI (DI120). Plasma TXNIP levels were measured by enzyme-linked immunosorbent assay. DESIGN: Case-control study. RESULTS: Patients with PCOS had higher serum TXNIP, whereas lower M value, DI0, DI30 and DI120 than controls (P < 0·05); their TXNIP correlated positively with weight, waist-to-hip ratio (WHR), body mass index (BMI), Ins0, Ins120 and HOMA-ß and correlated negatively with M value and DI120 (P < 0·05). Multiple stepwise regression analysis indicated that TXNIP remained associated with M value in PCOS subjects, after adjusting weight, BMI, WHR, HOMA-ß, Ins0, Ins120 and DI120. However, no relationship between TXNIP and impaired ß-cell function was found. CONCLUSION: Serum TXNIP is elevated in women with PCOS and may be a contributing factor for IR.
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Proteínas de Transporte/sangue , Resistência à Insulina/fisiologia , Síndrome do Ovário Policístico/sangue , Adulto , Feminino , Humanos , Insulina/metabolismo , Secreção de Insulina , Tiorredoxinas/metabolismoRESUMO
In the regime of Fresnel diffraction, a novel algorithm is proposed for aperture design for getting expected diffraction patterns. Experiments have verified the feasibility of this method. It may be used in beam transition, optics communication, information encryption, and other related fields.
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Due to the immunosuppressive tumor microenvironment (TME) and potential systemic toxicity, chemotherapy often fails to elicit satisfactory anti-tumor responses, so how to activate anti-tumor immunity to improve the therapeutic efficacy remains a challenging problem. Photothermal therapy (PTT) serves as a promising approach to activate anti-tumor immunity by inducing the release of tumor neoantigens in situ. In this study, we designed tetrasulfide bonded mesoporous silicon nanoparticles (MSNs) loaded with the traditional drug doxorubicin (DOX) inside and modified their outer layer with polydopamine (DOX/MSN-4S@PDA) for comprehensive anti-tumor studies in vivo and in vitro. The MSN core contains GSH-sensitive tetrasulfide bonds that enhance DOX release while generating hydrogen sulfide (H2S) to improve the therapeutic efficacy of DOX. The polydopamine (PDA) coating confers acid sensitivity and mild photothermal properties upon exposure to near-infrared (NIR) light, while the addition of hyaluronic acid (HA) to the outermost layer enables targeted delivery to CD44-expressing tumor cells, thereby enhancing drug accumulation at the tumor site and reducing toxic side effects. Our studies demonstrate that DOX/MSN@PDA-HA can reverse the immunosuppressive tumor microenvironment in vivo, inducing potent immunogenic cell death (ICD) of tumor cells and improving anti-tumor efficacy. In addition, DOX/MSN@PDA-HA significantly suppresses tumor metastasis to the lung and liver. In summary, DOX/MSN@PDA-HA exhibits controlled drug release, excellent biocompatibility, and remarkable tumor inhibition capabilities through synergistic chemical/photothermal combined therapy.
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Doxorrubicina , Indóis , Nanopartículas , Terapia Fototérmica , Polímeros , Silício , Silício/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Animais , Camundongos , Indóis/química , Indóis/farmacologia , Indóis/administração & dosagem , Porosidade , Nanopartículas/química , Nanopartículas/administração & dosagem , Polímeros/química , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Humanos , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Feminino , Terapia Combinada , Camundongos Endogâmicos BALB CRESUMO
PR39 is an antimicrobial peptide (AMP) with a variety of biological functions, including antimicrobial, wound healing, leukocyte chemotaxis, angiogenesis, and immunomodulation; however, its therapeutic efficacy in colitis (IBD) has rarely been reported. For this reason, the present study aimed to investigate the therapeutic effect of PR39 on IBD and its underlying mechanisms. In this experiment, a mouse model of ulcerative colitis (UC) was induced with 3 % dextran sulfate (DSS) and administered by rectal injection of PR39. The results of the study showed that 5 mg/kg of PR39 was able to ameliorate the clinical manifestations of DSS-induced UC mice by improving the clinical symptoms, colonic tissue damage, up-regulating the expression of tight junction proteins, and alleviating the systemic inflammation in mice in various ways. The mechanism of action may involve inhibition of the phosphorylation level of proteins related to the NF-κB/MAPK signaling pathway and modulation of the relative abundance of potentially pathogenic (Bacteroides, Pseudoflavonifractor, Barnesiella, and Oscillibacter) and potentially beneficial bacteria (Candidatus_Saccharibacteria, Desulfovibrio, Saccharibacteria) in the intestinal flora. The results enriched the biological functions of PR-39 and also suggested that PR-39 may be able to be used as a novel drug for the treatment of IBD.
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Colite Ulcerativa , Colite , Camundongos , Animais , Suínos , NF-kappa B/metabolismo , Peptídeos Antimicrobianos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Transdução de Sinais , Colo/patologia , Inflamação/metabolismo , Modelos Animais de Doenças , Sulfato de Dextrana/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that cannot be completely cured by current treatments. C. nudiflora Hook has antibacterial, anti-inflammatory, and hemostatic biological functions; however, the therapeutic role of C. nudiflora Hook or its extracts in IBD remains poorly understood. In this study, we extracted and purified three fractions of C. nudiflora Hook polysaccharides by hydroalcohol precipitation method, which were named as CNLP-1, CNLP-2 and CNLP-3, respectively. CNLP-2, the main component of the polysaccharides of C. nudiflora Hook is an pyranose type acidic polysaccharide composed of Fuc, Rha, Ara, Gal, Glc, Xyl, Man, Gal-UA and Glc-UA, with an Mn of 15.624 kDa; Mw of 31.375 kDa. CNLP-2 was found to have a smooth lamellar structure as observed by scanning electron microscopy. To investigate the effect of CNLP-2 (abbreviated to CNLP) on dextran sodium sulfate (DSS)-induced UC mice and its mechanism of action, we treated DSS-induced UC mice by administering CNLP at a dose of 100 mg/kg every other day. The results of the study showed that CNLP alleviated the clinical symptoms such as body weight (BW) loss, pathological damage, and systemic inflammation. The mechanism may be through the regulation of intestinal flora and its metabolism, which in turn affects the expression of NF-κB/MAPK pathway-related proteins through the metabolites of intestinal flora to further alleviate inflammation and ultimately improve the intestinal barrier function in UC mice. In conclusion, CNLP has great potential for the treatment of IBD.
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Callicarpa , Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Masculino , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Inflamação/patologia , Polissacarídeos/farmacologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Colo , Colite/patologia , Camundongos Endogâmicos C57BLRESUMO
Ulcerative colitis (UC) is a kind of inflammatory bowel disease (IBD) that often recurs and is difficult to cure, and no drugs with few side effects are available to treat this disease. LfcinB is a small molecular peptide obtained by the hydrolysis of bovine lactoferrin in the digestive tract of animals. It has strong antibacterial and anti-inflammatory activities. However, direct evidence that LfcinB improves the condition of colitis in mice is rarely reported. In this study, UC was induced in mice by adding 2.5% dextran sulfate (DSS) to drinking water and LfcinB was orally administered. The results showed that oral administration of LfcinB improved colonic tissue damage and inflammatory cell infiltration, increased the expression of tight junction proteins, and down-regulated the phosphorylation of proteins related to the NF-κB/MAPK inflammatory signalling pathway in mice. It also significantly suppressed the relative abundance of potentially pathogenic bacteria (Bacteroides, Barnesiella and Escherichia) in the intestinal flora. In conclusion, oral administration of LfcinB significantly alleviated DSS-induced UC. This may be related to the regulation of inflammatory signalling pathways and gut microbial composition by LfcinB.
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Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Microbiota , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Administração Oral , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
During the process of flower opening, most petals move downward in the direction of the pedicel (i.e., epinastic movement). In most Delphinium flowers, however, their two lateral petals display a very peculiar movement, the mirrored helical rotation, which requires the twist of the petal stalk. However, in some lineages, their lateral petals also exhibit asymmetric bending that increases the degree of mirrored helical rotation, facilitating the formation of a 3D final shape. Notably, petal asymmetric bending is a novel trait that has not been noticed yet, so its morphological nature, developmental process, and molecular mechanisms remain largely unknown. Here, by using D. anthriscifolium as a model, we determined that petal asymmetric bending was caused by the localized expansion of cell width, accompanied by the specialized array of cell wall nano-structure, on the adaxial epidermis. Digital gene analyses, gene expression, and functional studies revealed that a class I homeodomain-leucine zipper family transcription factor gene, DeanLATE MERISTEM IDENTITY1 (DeanLMI1), contributes to petal asymmetric bending; knockdown of it led to the formation of explanate 2D petals. Specifically, DeanLMI1 promotes cell expansion in width and influences the arrangement of cell wall nano-structure on the localized adaxial epidermis. These results not only provide a comprehensive portrait of petal asymmetric bending for the first time but also shed some new insights into the mechanisms of flower opening and helical movement in plants.
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Delphinium , Ranunculaceae , Ranunculaceae/metabolismo , Delphinium/metabolismo , Fatores de Transcrição/metabolismo , Flores/anatomia & histologia , Regulação da Expressão Gênica de PlantasRESUMO
F-box only protein 38 (FBXO38) is a member of the F-box family that mediates the ubiquitination and proteasome degradation of programmed death 1 (PD-1), and thus has important effects on T cell-related immunity. While its powerful role in adaptive immunity has attracted much attention, its regulatory roles in innate immune pathways remain unknown. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an important innate immune pathway that regulates type I interferons. STING protein is the core component of this pathway. In this study, we identified that FBXO38 deficiency enhanced tumor proliferation and reduced tumor CD8+ T cells infiltration. Loss of FBXO38 resulted in reduced STING protein levels in vitro and in vivo, further leading to preventing cGAS-STING pathway activation, and decreased downstream product IFNA1 and CCL5. The mechanism of reduced STING protein was associated with lysosome-mediated degradation rather than proteasomal function. Our results demonstrate a critical role for FBXO38 in the cGAS-STING pathway.
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Neoplasias , Transdução de Sinais , Humanos , Linfócitos T CD8-Positivos/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Lisossomos/metabolismo , Imunidade InataRESUMO
Callicarpa nudiflora Hook (C. nudiflora) is an anti-inflammatory, antimicrobial, antioxidant, and hemostatic ethnomedicine. To date, little has been reported regarding the activity of C. nudiflora against ulcerative colitis (UC). In this study, we investigated the effect of a flavonoid extract of C. nudiflora on Dextran Sulfate Sodium (DSS)-induced ulcerative colitis in mice. Mice in the treatment group (CNLF+DSS group) and drug-only (CNLF group) groups were administered 400 mg/kg of flavonoid extract of C. nudiflora leaf (CNLF), and drinking water containing 2.5 % DSS was given to the model and treatment groups. The symptoms of colitis were detected, relevant indicators were verified, intestinal barrier function was assessed, and the contents of the cecum were analyzed for intestinal microorganisms. The results showed that CNLF significantly alleviated the clinical symptoms and histological morphology of colitis in mice, inhibited the increase in pro-inflammatory factors (TNF-α, IL-6, IL-1ß, and IFN-γ), and increased the level of IL-10. The expression of NF-κB and MAPK inflammatory signal pathway-related proteins (p-p65, p-p38, p-ERK, p-JNK) was regulated. The expression of tight junction proteins (ZO-1, OCLDN, and CLDN1) was increased, while the content of D-LA, DAO, and LPS was decreased. In addition, 16S rRNA sequencing showed that CNLF restored the gut microbial composition, and increased the relative abundance of Prevotellaceae, Intestinimonas butyriciproducens, and Barnesiella_intestinihominis. In conclusion, CNLF alleviated colitis by suppressing inflammation levels, improving intestinal barrier integrity, and modulating the intestinal microbiota, and therefore has promising future applications in the treatment of UC.
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Callicarpa , Sulfato de Dextrana , Flavonoides , Extratos Vegetais , Animais , Extratos Vegetais/farmacologia , Flavonoides/farmacologia , Masculino , Camundongos , Callicarpa/química , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Folhas de Planta/química , NF-kappa B/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Pleurocidin is an antimicrobial peptide derived from the mucous membranes of the skin or intestinal secretions of Pseudopleuronectes americanus that has antimicrobial and immunomodulatory activities. Ulcerative colitis is recognized as a widespread human disease that may be influenced by environmental and genetic factors. Evidence emphasizes the critical role of the gut microbiota in UC. Synthetic Pleurocidin was analyzed by a combination of liquid chromatography and mass spectrometry. Pleurocidin pharmacological effects were evaluated by DAI score, colon histological score, cytokine levels, and tight junction protein expression in mice. The preliminary molecular mechanism was explored by the levels of key proteins in the NF-κB and MAPK inflammatory signaling pathways in colon tissues. The main analytical methods such as immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blot were used. We then used 16S rRNA gene sequences to characterize the gut microbiota. Firstly, our study demonstrated that rectal injection of Pleurocidin at 5 mg/kg body weight alleviated clinical symptoms and colonic histopathological changes in UC mice caused by DSS. Secondly, Pleurocidin altered the abnormal levels of inflammatory and immune-related cytokines in serum, modulated the significant down-regulation of tight junction proteins, and inhibited the expression of NF-κB and MAPK inflammatory signaling pathway-related proteins. Finally, Pleurocidin can regulate gut microbiota, increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. In conclusion, Pleurocidin alleviates UC symptoms in mice, and its effects on the gut microbiome may be potential pathways. It is providing a promising therapeutic option for UC.
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Colite Ulcerativa , Colite , Proteínas de Peixes , Linguado , Humanos , Animais , Camundongos , NF-kappa B , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , RNA Ribossômico 16S , Citocinas , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , ColoRESUMO
Abaecin is a natural antimicrobial peptide (AMP) rich in proline from bees. It is an important part of the innate humoral immunity of bees and has broad-spectrum antibacterial ability. This study aimed to determine the effect of Abaecin on dextran sulfate sodium (DSS) -induced ulcerative colitis (UC) in mice and to explore its related mechanisms. Twenty-four mice with similar body weight were randomly divided into 4 groups. 2.5% DSS was added to drinking water to induce colitis in mice. Abaecin and PBS were administered rectally on the third, fifth, and seventh days of the experimental period. The results showed that Abaecin significantly alleviated histological damage and intestinal mucosal barrier damage caused by colitis in mice, reduced the concentration of pro-inflammatory cytokines IL-1ß, IL-6, TNF-α, IFN-γ, and the phosphorylation of NF-κB / MAPK inflammatory signaling pathway proteins, and improved the composition of intestinal microorganisms. These findings suggest that Abaecin may have potential prospects for the treatment of UC.
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Colite Ulcerativa , Colite , Animais , Camundongos , Peptídeos Antimicrobianos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Transdução de Sinais , NF-kappa B/metabolismo , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Colo/metabolismo , Modelos Animais de DoençasRESUMO
DNA adducts are a major cause of DNA mutation and DNA mutation-related diseases, but the simultaneous identification of multiple DNA adducts has been a challenge for a decade. An adductome approach using consecutive liquid chromatography and double mass spectrometry after micrococcal nuclease treatment has paved the way to demonstrations of numerous DNA adducts in a single experiment and is expected to contribute to the comprehensive understanding of overall environmental and endogenous exposures to possible mutagens in individuals. In this report, we applied an adductome approach to gastric mucosa samples taken at the time of a gastrectomy for gastric cancer in Lujiang, China, and in Hamamatsu, Japan. Seven lipid peroxidation-related DNA adducts [1,N6-etheno-2'-deoxyadenosine, butanone-etheno-2'-deoxycytidine (BεdC), butanone-etheno-2'-deoxy-5-methylcytidine, butanone-etheno-2'-deoxyadenosine (BεdA), heptanone-etheno-2'-deoxycytidine, heptanone-etheno-2'-deoxyadenosine (HεdA) and heptanone-etheno- 2'-deoxyguanosine] were identified in a total of 22 gastric mucosa samples. The levels of these adducts ranged from 0 to 30,000 per 10(9) bases. Although the presence of Helicobacter pylori DNA in the mucosa was not related to these adducts level, the levels of BεdC, BεdA and HεdA were higher in the Japanese gastric mucosa samples. The profiles of these 7 adduct levels among the 21 cases were capable of discriminating between the possible origins (China or Japan) of the gastric mucosa samples. Our report is the first demonstration of lipid peroxidation-related DNA adducts in the human stomach, and these observations warrant further investigation in the context of the significance of DNA adducts in human gastric carcinogenesis.
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Adutos de DNA , Mucosa Gástrica/metabolismo , Peroxidação de Lipídeos , Idoso , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
RGB color is a basic visual feature. Here we use machine learning and visual evoked potential (VEP) of electroencephalogram (EEG) data to investigate the decoding features of the time courses and space location that extract it, and whether they depend on a common brain cortex channel. We show that RGB color information can be decoded from EEG data and, with the task-irrelevant paradigm, features can be decoded across fast changes in VEP stimuli. These results are consistent with the theory of both event-related potential (ERP) and P300 mechanisms. The latency on time course is shorter and more temporally precise for RGB color stimuli than P300, a result that does not depend on a task-relevant paradigm, suggesting that RGB color is an updating signal that separates visual events. Meanwhile, distribution features are evident for the brain cortex of EEG signal, providing a space correlate of RGB color in classification accuracy and channel location. Finally, space decoding of RGB color depends on the channel classification accuracy and location obtained through training and testing EEG data. The result is consistent with channel power value distribution discharged by both VEP and electrophysiological stimuli mechanisms.