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1.
J Sci Food Agric ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757804

RESUMO

BACKGROUND: Okra contains flavonoids and vitamin C as antioxidants and it contains polysaccharides as immunomodulators. Flavonoids regulate the inflammatory response in mice and may be related to gut microbiota. This study therefore aimed to investigate the impact of okra extract (OE) on inflammation in mice and to elucidate its underlying mechanism. METHOD: Forty male Kunming (KM) mice were categorized into four groups: the control (CON) group, the lipopolysaccharide stimulation (LPS) group, the 5 mg mL-1 OE intervention (LPS + OE) group, and the 5 mg mL-1 OE supplementation plus mixed antibiotics (LPS + OE + ABX) group. RESULTS: The results showed that, compared with the OE group, the expression of inflammatory signaling pathway genes was upregulated and gut barrier genes were inhibited in the OE + ABX group. The Fxr receptor was activated and the abundance of Akkermansia was increased after OE supplementation, whereas the effect was reversed in the OE + ABX group. Meanwhile, Fxr was correlated positively with Akkermansia. CONCLUSION: The OE supplementation alleviated the inflammatory response in mice under LPS stimulation, accompanied by changes in gut microbiota and bile acid receptors, whereas the addition of antibiotics caused a disturbance to the gut microbiota in the OE group, thus reducing the effect of OE in alleviating the inflammatory response. © 2024 Society of Chemical Industry.

3.
BMC Psychiatry ; 24(1): 179, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439012

RESUMO

BACKGROUND: People with schizophrenia often face challenges such as lower psychological resilience, reduced self-worth, and increased social stigma, hindering their recovery. Mindfulness-Based Cognitive Therapy (MBCT) has shown promise in boosting psychological resilience and self-esteem while diminishing stigma. However, MBCT demands professional involvement and substantial expenses, adding to the workload of professionals and the financial strain on patients. Mixed-mode Mindfulness-Based Cognitive Therapy (M-MBCT) integrates both "face-to-face" and "self-help" approaches to minimize staff effort and costs. This study aims to assess the impact of M-MBCT on the psychological resilience, self-esteem, and stigma in schizophrenia patients. METHODS: This randomized, controlled, parallel-group, assessor-blinded clinical trial enrolled 174 inpatients with schizophrenia. Participants were randomly assigned to either the experimental or control group. The experimental group underwent an 8-week M-MBCT intervention, while the control group received standard treatment. Data collection employed the Connor-Davidson Resilience Scale (CD-RISC), Internalized Stigma of Mental Illness Scale (ISMI), and Rosenberg Self-Esteem Scale (RSES) before and after the intervention. Post-intervention, significant differences in ISMI, CD-RISC, and RSES scores were observed between the experimental and control groups. RESULTS: In the experimental group, ISMI scores notably decreased, while CD-RISC and RSES scores significantly increased (P < 0.05). Multiple linear regression analysis identified age, education, and family history of mental illness as significant factors related to stigma (P < 0.05). Additionally, correlation analysis indicated a significant negative relationship between the reduction in CD-RISC scores and the reduction in ISMI scores (P < 0.05). CONCLUSION: M-MBCT effectively enhanced psychological resilience and self-esteem while diminishing stigma in individuals with schizophrenia. M-MBCT emerges as a promising treatment option for schizophrenia sufferers. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 03/06/2023 ( www.chictr.org.cn ; ChiCTR ID: ChiCTR2300069071).


Assuntos
Terapia Cognitivo-Comportamental , Atenção Plena , Testes Psicológicos , Resiliência Psicológica , Esquizofrenia , Humanos , Esquizofrenia/terapia , Estigma Social , Pacientes Internados , Autoimagem
4.
Front Immunol ; 15: 1281741, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420126

RESUMO

Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multi-system group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P<0.05) along with the improvement of clinical symptoms, regardless of the add-on of probiotics. However, the intervention did not impact the serum levels of total IgE, FS-IgE, and HDM IgE. There was no further decrease of serum FS-IgG4 level in children followed up for more than 1 year, which may be related to noncompliance with diet elimination. Multivariate regression analysis revealed that the decline of serum FS-IgG4 was an independent predictable factor for the improvement of clinical symptoms (adjusted OR:1.412,95%CI 1.017-1.96, p=0.039). The add-on of probiotics showed less efficiency in reducing the FS-IgG4 level in more patients with relief of clinical symptoms. Our results confirmed the correlation between FS-IgG4 and allergic diseases, and the decreased FS-IgG4 could be a useful predictor for the improvement of allergic symptoms. FS-IgG4-guided diet elimination is an efficient treatment for allergic diseases. Our study adds solid data to the clinical significance of FS-IgG4 in allergic diseases.


Assuntos
Hipersensibilidade , Imunoglobulina G , Criança , Animais , Humanos , Alérgenos , Imunoglobulina E , Dieta , Pyroglyphidae , Dermatophagoides pteronyssinus , Leite
5.
J Colloid Interface Sci ; 660: 961-973, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38281477

RESUMO

High-performance photocatalysts for catalytic reduction of CO2 are largely impeded by inefficient charge separation and surface activity. Reasonable design and efficient collaboration of multiple active sites are important for attaining high reactivity and product selectivity. Herein, Cu-Cu2O and Ag nanoparticles are confined as dual sites for assisting CO2 photoreduction to CH4 on TiO2. The introduction of Cu-Cu2O leads to an all-solid-state Z-scheme heterostructure on the TiO2 surface, which achieves efficient electron transfer to Cu2O and adsorption and activation of CO2. The confined nanometallic Ag further enhances the carrier's separation efficiency, promoting the conversion of activated CO2 molecules to •COOH and further conversion to CH4. Particularly, this strategy is highlighted on the TiO2 system for a photocatalytic reduction reaction of CO2 and H2O with a CH4 generation rate of 62.5 µmol∙g-1∙h-1 and an impressive selectivity of 97.49 %. This work provides new insights into developing robust catalysts through the artful design of synergistic catalytic sites for efficient photocatalytic CO2 conversion.

7.
BMC Psychiatry ; 23(1): 740, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821875

RESUMO

BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide reliable pharmacotherapeutic evidence for in the clinical treatment of schizophrenia. METHODS: We systematically searched the PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases for head-to-head randomized controlled trials that compared blonanserin with risperidone for the treatment of schizophrenia. We extracted the following data: author, year, country, diagnostic criteria, sample size, course of treatment, dosage and outcomes. Our main endpoint was the changes in the Positive and Negative Syndrome Scale (PANSS) total scores. Meta-analysis of the included data was conducted by RevMan 5.3 software. We used the GRADE criteria to evaluate the certainty of the evidence. RESULTS: A total of 411 studies were initially; 8 trials were eligible and were included in our analysis (N = 1386 participants). Regarding efficacy, there was no difference in changes in the PANSS total scores between the two groups (P > 0.05). In terms of safety, compared to risperidone, the incidence of serum prolactin increases and weight gain in the blonanserin group was lower (P<0.05), but the incidence of extrapyramidal symptoms (EPS) was higher (P<0.05). CONCLUSION: The efficacy of blonanserin is similar to that of risperidone, but it is unclear whether blonanserin is more effective than risperidone at improving cognitive and social function. More high-quality studies are needed to verify the efficacy and safety of blonanserin in the future.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Int J Mol Sci ; 24(9)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37175590

RESUMO

Many essential cellular functions are carried out by multi-protein complexes that can be characterized by their protein-protein interactions. The interactions between protein subunits are critically dependent on the strengths of their interactions and their cellular abundances, both of which span orders of magnitude. Despite many efforts devoted to the global discovery of protein complexes by integrating large-scale protein abundance and interaction features, there is still room for improvement. Here, we integrated >7000 quantitative proteomic samples with three published affinity purification/co-fractionation mass spectrometry datasets into a deep learning framework to predict protein-protein interactions (PPIs), followed by the identification of protein complexes using a two-stage clustering strategy. Our deep-learning-technique-based classifier significantly outperformed recently published machine learning prediction models and in the process captured 5010 complexes containing over 9000 unique proteins. The vast majority of proteins in our predicted complexes exhibited low or no tissue specificity, which is an indication that the observed complexes tend to be ubiquitously expressed throughout all cell types and tissues. Interestingly, our combined approach increased the model sensitivity for low abundant proteins, which amongst other things allowed us to detect the interaction of MCM10, which connects to the replicative helicase complex via the MCM6 protein. The integration of protein abundances and their interaction features using a deep learning approach provided a comprehensive map of protein-protein interactions and a unique perspective on possible novel protein complexes.


Assuntos
Aprendizado Profundo , Proteômica/métodos , Subunidades Proteicas , Aprendizado de Máquina , Espectrometria de Massas
9.
Neural Netw ; 163: 10-27, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37011517

RESUMO

Image dehazing is a challenging task in computer vision. Currently, most dehazing methods adopt the U-Net architecture that directly fuses the decoding layer with the corresponding scale encoding layer. These methods ignore the effective utilization of different encoding layer information and existing feature information dilute problems, resulting in suboptimal edge details and overall scene aspects of dehazed image restoration. In addition, Squeeze and Excitation (SE) channel attention is widely used in dehazing network. However, the two fully-connected layers of dimensionality reduction operation in SE will negatively affect the weight prediction of feature channels, thus reducing the performance of the dehazing network. To solve the above problems, we propose a Multi-level Feature Interaction and Non-local Information Enhanced Channel Attention (MFINEA) dehazing model. Specifically, a multi-level feature interaction module is proposed to enable the decoding layer to fuse shallow and deep feature information extracted from different encoding layers for better recovery of edge details and the overall scene. Furthermore, an efficient non-local information enhanced channel attention module is proposed to mine more effective feature channel information for the weight assignment of the feature maps. The experimental results on several challenging benchmark datasets show that our MFINEA outperforms the state-of-the-art dehazing methods.


Assuntos
Benchmarking , Processamento de Imagem Assistida por Computador
10.
Mol Ecol ; 32(13): 3686-3701, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36965005

RESUMO

The extremely high species diversity of soil bacterial community has fascinated and puzzled community ecologists. Although theory predicts that fluctuations in environments can facilitate diversity maintenance, the effects of fluctuating temperature on species diversity have rarely been investigated in species-rich microbial communities. Here, we examined whether fluctuating temperature had positive effects on species diversity relative to constant temperatures in soil bacterial communities, and investigated the effects of fluctuating temperature on bacterial performances (changes in relative abundance). We performed a temperature manipulation experiment with soils collected from temperate and subtropical zones, where the soils were subjected to constant high, low or fluctuating temperatures. We found that fluctuating temperatures showed significant positive effects on species diversity. The time-averaged effect of fluctuating temperatures (i.e., averaging out the differences between species in their environment-dependent performances) appeared to delay species loss in both the temperate and the subtropical communities. In addition, we found that the performances of temperature-responsive species at fluctuating temperatures significantly deviated from their time-weighted average performances at constant high and low temperatures, which was defined as fluctuation-dependent effects in our study. Intriguingly, fluctuation-dependent effects beyond time-averaged effect led to an opposite trend: differences in temperature-responsive species' performances decreased in the temperate communities, but increased in the subtropical communities. Our findings provide new insights into diversity maintenance in soil bacterial communities, and imply that the effects of fluctuating temperature on species diversity in soil bacterial community might vary across latitude.


Assuntos
Microbiota , Solo , Temperatura , Bactérias/genética , Microbiota/genética , Microbiologia do Solo
11.
Front Immunol ; 13: 1084879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36591252

RESUMO

Kimura disease (KD) is a rare and benign chronic inflammatory disease of unknown cause. It is characterized by subcutaneous granuloma of soft tissues in the head and neck region, increased eosinophil count, and elevated serum IgE. Currently, no definitive treatments are recommended. A 57-year-old Chinese man was diagnosed with KD after 7 years of slow subcutaneous masses growth. The patient underwent treatment of oral glucocorticoids for 1 year, but the masses recurred as the dosage was tapered down. Subsequent anti-IgE therapy of omalizumab administered subcutaneously at 450 mg/day at a 4-week interval did not show improvement. The size of masses and serum IgE and circulating eosinophils did not decrease significantly after 19 cycles of continuous treatment. Ultimately, switched strategy of dupilumab was applied at an initial dose of 600 mg, followed by 300 mg every 2 weeks for 4 months. This treatment demonstrated dramatical effects with reduced masses in each area and fast dropdown of eosinophil counts, while the high level of serum IgE remained without changes. Recently, different biologics including anti-IgE, anti-IL-5, and anti-IL-4/IL-13 have been applied to treat KD with satisfied results and help to explore the pathogenesis of this rare disease. To our knowledge, this is the first report that demonstrates the effects of two different biologics in the same patient and reveals the impressive clinical efficacy of dupilumab to treat KD independent of IgE. Therefore, further investigation of the underlying mechanism and the development of diagnosis and treatment of KD is valuable.


Assuntos
Produtos Biológicos , Doença de Kimura , Masculino , Humanos , Pessoa de Meia-Idade , Doença de Kimura/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Omalizumab/uso terapêutico , Imunossupressores , Produtos Biológicos/uso terapêutico
12.
J Proteome Res ; 20(9): 4381-4392, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34343000

RESUMO

Acquired resistance to MAPK inhibitors limits the clinical efficacy in melanoma treatment. We and others have recently shown that BRAF inhibitor (BRAFi)-resistant melanoma cells can develop a dependency on the therapeutic drugs to which they have acquired resistance, creating a vulnerability for these cells that can potentially be exploited in cancer treatment. In drug-addicted melanoma cells, it was shown that this induction of cell death was preceded by a specific ERK2-dependent phenotype switch; however, the underlying molecular mechanisms are largely lacking. To increase the molecular understanding of this drug dependency, we applied a mass spectrometry-based proteomic approach on BRAFi-resistant BRAFMUT 451Lu cells, in which ERK1, ERK2, and JUNB were silenced separately using CRISPR-Cas9. Inactivation of ERK2 and, to a lesser extent, JUNB prevents drug addiction in these melanoma cells, while, conversely, knockout of ERK1 fails to reverse this phenotype, showing a response similar to that of control cells. Our analysis reveals that ERK2 and JUNB share comparable proteome responses dominated by reactivation of cell division. Importantly, we find that EMT activation in drug-addicted melanoma cells upon drug withdrawal is affected by silencing ERK2 but not ERK1. Moreover, transcription factor (regulator) enrichment shows that PIR acts as an effector of ERK2 and phosphoproteome analysis reveals that silencing of ERK2 but not ERK1 leads to amplification of GSK3 kinase activity. Our results depict possible mechanisms of drug addiction in melanoma, which may provide a guide for therapeutic strategies in drug-resistant melanoma.


Assuntos
Melanoma , Preparações Farmacêuticas , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Quinase 3 da Glicogênio Sintase , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Inibidores de Proteínas Quinases/farmacologia , Proteômica , Proteínas Proto-Oncogênicas B-raf/genética
13.
Front Plant Sci ; 12: 638796, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025690

RESUMO

Phenotypic plasticity affords invasive plant species the ability to colonize a wide range of habitats, but physiological plasticity of their stems is seldom recognized. Investigation of the stem plasticity of invasive plant species could lead to a better understanding of their invasiveness. We performed pot experiments involving defoliation treatments and isolated culture experiments to determine whether the invasive species Mikania micrantha exhibits greater plasticity in the stems than do three non-invasive species that co-occur in southern China and then explored the mechanism underlying the modification of its stem photosynthesis. Our results showed that the stems of M. micrantha exhibited higher plasticity in terms of either net or gross photosynthetic rate in response to the defoliation treatment. These effects were positively related to an increased stem elongation rate. The enhancement of stem photosynthesis in M. micrantha resulted from the comprehensive action involving increases in the Chl a/b ratio, D1 protein and stomatal aperture, changes in chloroplast morphology and a decrease in anthocyanins. Increased plasticity of stem photosynthesis may improve the survival of M. micrantha under harsh conditions and allow it to rapidly recover from defoliation injuries. Our results highlight that phenotypic plasticity promotes the invasion success of alien plant invaders.

14.
Org Chem Front ; 7(22): 3608-3615, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33184589

RESUMO

Two formal syntheses and one total synthesis of fostriecin (1) have been achieved, as well as, the synthesis of its related congener dihydro-dephospho-fostriecin. All the routes use the Sharpless dihydroxylation to set the absolute stereochemistry at C-8/9 positions and a Leighton allylation to set the C-5 position of the natural product. In the formal syntheses a Noyori transfer hydrogenation of an ynone was used to set the C-11 position while the total synthesis employed a combination of asymmetric dihydroxylation and Pd-π-allyl reduction to set the C-11 position. Finally in the total synthesis, a trans-hydroboration of the C-12/13 alkyne was used in combination with a Suzuki cross coupling to establish the Z,Z,E-triene of fostriecin (1).

15.
Inflamm Res ; 69(5): 509-521, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32179955

RESUMO

BACKGROUND: Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with an abnormal immune response. Accumulating evidence has demonstrated that aquaporin 1 (AQP1) prevents kidney tissue injury in LPS-induced AKI by mediating immune response. However, the underlying mechanisms remain obscure. Macrophages as immune cells with multiple phenotypes are important mediators in tissue homeostasis and host defense. We propose that macrophage polarization is implicated in AQP1-mediated immune response. METHODS: Herein we established sepsis-induced AKI model rats through intraperitoneal injection of LPS into Wistar rats to reveal immune mechanism of damage. We also used LPS-induced mouse RAW264.7 cells to elucidate the molecular mechanism of macropage polarization. RESULTS: Histopathology showed that renal tubular epithelial cells in the model group were swollen, inflammatory exudation was obvious and the inflammatory factors, interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were increased. Western blotting showed PI3K was upregulated in the model group. Serum creatinine and urea nitrogen increased after LPS injection. Renal AQP1 mRNA is downregulated and serum AQP1 protein increased first and then decreased in LPS-induced AKI rats. M2 macrophage markers (Arg-1, CD206) were increased in repair stage. In addition, treatment of murine macrophages (RAW264.7) with AQP1 siRNA resulted in decreased PI3K activation and M2 polarization, but increased IL-6 and TNF-α. Moreover, inhibiting PI3K with wortmannin imitated the results of AQP1 silencing. CONCLUSIONS: Macrophage M2 polarization is likely the cellular mechanism underlying the anti-AKI property of AQP1, and PI3K activation is involved in the AQP1-induced M2 phenotype switch.


Assuntos
Injúria Renal Aguda/imunologia , Aquaporina 1/imunologia , Macrófagos/imunologia , Fosfatidilinositol 3-Quinases/imunologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Animais , Aquaporina 1/sangue , Aquaporina 1/genética , Interleucina-6/imunologia , Rim/patologia , Lipopolissacarídeos , Masculino , Camundongos , Óxido Nítrico Sintase Tipo II/imunologia , Células RAW 264.7 , Ratos Wistar , Fator de Necrose Tumoral alfa/imunologia
16.
Org Lett ; 21(20): 8334-8338, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31584287

RESUMO

A formal synthesis of fostriecin (1) and a total synthesis of its related congener dihydro-dephospho-fostriecin 2 have been achieved. The route relies upon the use of the Sharpless dihydroxylation to set the absolute stereochemistry at C-8/9 and Noyori transfer hydrogenation and Leighton allylation to set the C-11 and C-5 relative stereochemistry, respectively. Finally, the divergent functionalization of a C-12/13 alkyne was used to establish the Z,E-dienyne of dehydro-dephospho-fostriecin 2 and the Z,Z,E-triene of fostriecin (1).


Assuntos
Polienos/síntese química , Pironas/síntese química , Estrutura Molecular , Polienos/química , Pironas/química , Estereoisomerismo
17.
Inflamm Res ; 68(12): 1035-1047, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31529146

RESUMO

OBJECTIVE: This study was designed to investigate the role of AQP1 in the development of LPS-induced AKI and its potential regulatory mechanisms in the inflammatory responses of macrophages. METHODS: Male Wistar rats were injected intraperitoneally with LPS, and biochemical and histological renal damage was assessed. The levels of inflammatory mediators, macrophage markers and AQP1 in blood and kidney tissues were assessed by ELISA. RTPCR was used to assess changes in the relative levels of AQP1 mRNA induced by LPS. Western blot and immunofluorescence analyses were performed to assay the activation of the p38 MAPK and NF-κB pathways, respectively. The same detection methods were used in vitro to determine the regulatory mechanisms underlying AQP1 function. RESULTS: AQP1 mRNA levels were dramatically decreased in AKI rats following the increased expression of inflammatory factors. In vitro experiments demonstrated that silencing the AQP1 gene increased inflammatory mediator secretion, altered the classical activation of macrophages, greatly enhanced the phosphorylation of p38 and accelerated the translocation of NF-κB. Furthermore, these results were blocked by doramapimod, a p38 inhibitor. Therefore, these effects were mediated by the increased phosphorylation of p38 MAPK. CONCLUSION: Our results suggest that altered AQP1 expression may be associated with the development of inflammation in AKI. AQP1 plays a protective role in modulating acute renal injury and can attenuate macrophage-mediated inflammatory responses by downregulating p38 MAPK activity in LPS-induced RAW264.7 cells. The pharmacological targeting of AQP1-mediated p38 MAPK signalling may provide a novel treatment approach for AKI.


Assuntos
Injúria Renal Aguda/imunologia , Aquaporina 1/imunologia , Macrófagos/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Aquaporina 1/sangue , Aquaporina 1/genética , Citocinas/sangue , Rim/patologia , Lipopolissacarídeos , Masculino , Camundongos , NF-kappa B/imunologia , Células RAW 264.7 , Ratos Wistar
18.
Commun Biol ; 2: 325, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508500

RESUMO

Extracellular vesicles (EVs) are a potential source of disease-associated biomarkers for diagnosis. In breast cancer, comprehensive analyses of EVs could yield robust and reliable subtype-specific biomarkers that are still critically needed to improve diagnostic routines and clinical outcome. Here, we show that proteome profiles of EVs secreted by different breast cancer cell lines are highly indicative of their respective molecular subtypes, even more so than the proteome changes within the cancer cells. Moreover, we detected molecular evidence for subtype-specific biological processes and molecular pathways, hyperphosphorylated receptors and kinases in connection with the disease, and compiled a set of protein signatures that closely reflect the associated clinical pathophysiology. These unique features revealed in our work, replicated in clinical material, collectively demonstrate the potential of secreted EVs to differentiate between breast cancer subtypes and show the prospect of their use as non-invasive liquid biopsies for diagnosis and management of breast cancer patients.


Assuntos
Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Vesículas Extracelulares/metabolismo , Proteômica/métodos , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/ultraestrutura , Bovinos , Linhagem Celular Tumoral , Vesículas Extracelulares/ultraestrutura , Feminino , Humanos , Proteínas de Neoplasias/metabolismo , Fosfoproteínas/metabolismo , Análise de Componente Principal , Proteoma/metabolismo
19.
Cell Mol Biol Lett ; 23: 38, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30140293

RESUMO

BACKGROUND: Inflammation is an important pathogenic component of endotoxemia-induced acute kidney injury (AKI), finally resulting in renal failure. Diacerein is an interleukin-1ß (IL-1ß) inhibitor used for osteoarthritis treatment by exerting anti-inflammatory effects. This study aims to investigate the effects of diacerein on endotoxemia-induced AKI. METHODS: Male C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/kg) for 24 h prior to diacerein treatment (15 mg/kg/day) for another 48 h. Mice were examined by histological, molecular and biochemical approaches. RESULTS: LPS administration showed a time-dependent increase of IL-1ß expression and secretion in kidney tissues. Diacerein treatment normalized urine volume and osmolarity, reduced blood urea nitrogen (BUN), fractional excretion of sodium (FENa), serum creatinine and osmolarity, and protected renal function in an endotoxemic AKI mice model. In the histopathologic study, diacerein also improved renal tubular damage such as necrosis of the tubular segment. Moreover, diacerein inhibited LPS-induced increase of inflammatory cytokines, such as IL-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1 and nitric oxide synthase 2. In addition, LPS administration markedly decreased aquaporin 1 (AQP1), AQP2, AQP3, Na,K-ATPase α1, apical type 3 Na/H exchanger and Na-K-2Cl cotransporter expression in the kidney, which was reversed by diacerein treatment. We also found that diacerein or IL-1ß inhibition prevented the secretion of inflammatory cytokines and the decrease of AQP and sodium transporter expression induced by LPS in HK-2 cells. CONCLUSION: Our study demonstrates for the first time that diacerein improves renal function efficiently in endotoxemic AKI mice by suppressing inflammation and altering tubular water and sodium handing. These results suggest that diacerein may be a novel therapeutic agent for the treatment of endotoxemic AKI.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antraquinonas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Injúria Renal Aguda/complicações , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Animais , Citocinas/imunologia , Endotoxemia/complicações , Endotoxemia/tratamento farmacológico , Endotoxemia/imunologia , Endotoxemia/patologia , Inflamação/complicações , Inflamação/imunologia , Inflamação/patologia , Rim/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL
20.
J Enzyme Inhib Med Chem ; 31(6): 1443-50, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26888050

RESUMO

Drug target interactions (DTIs) are crucial in pharmacology and drug discovery. Presently, experimental determination of compound-protein interactions remains challenging because of funding investment and difficulties of purifying proteins. In this study, we proposed two in silico models based on support vector machine (SVM) and random forest (RF), using 1589 molecular descriptors and 1080 protein descriptors in 9948 ligand-protein pairs to predict DTIs that were quantified by Ki values. The cross-validation coefficient of determination of 0.6079 for SVM and 0.6267 for RF were obtained, respectively. In addition, the two-dimensional (2D) autocorrelation, topological charge indices and three-dimensional (3D)-MoRSE descriptors of compounds, the autocorrelation descriptors and the amphiphilic pseudo-amino acid composition of protein are found most important for Ki predictions. These models provide a new opportunity for the prediction of ligand-receptor interactions that will facilitate the target discovery and toxicity evaluation in drug development.


Assuntos
Prednisolona/análogos & derivados , Ligantes , Prednisolona/metabolismo , Ligação Proteica , Máquina de Vetores de Suporte
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