RÉSUMÉ
Background: The observational studies investigated the impact of migraine on Alzheimer's Disease (AD). However, these findings were limited by confounding factors and reverse causation, leading to contradictory results. Methods: We utilized Univariable Mendelian Randomization (UVMR) to explore the link between migraine (13,971 cases/470,627 controls) and AD risk (Bellenguez et al., 39,106 cases/46,828 controls; FinnGen, 111,471 cases/111,471 controls). Meta-analysis was performed for comprehensive synthesis. Employing Multivariable Mendelian Randomization (MVMR), we created models incorporating migraine and 35 potential AD risk factors, examining migraine's independent impact on AD onset risk under considering these factors. Results: The meta-analysis of inverse variance weighted MR results, combining data from Bellenguez et al. (odds ratio (OR) [95% confidence interval (CI)]: 1.5717 [1.1868-2.0814], p = 0.0016) and FinnGen (OR [95% CI]: 1.2904 [0.5419-3.0730], p = 0.5646), provided evidence for a causal relationship between genetically predicted migraine and the heightened risk of AD occurrence (OR [95% CI]: 1.54 [1.18, 2.00], p < 0.01). After adjusting for Diastolic blood pressure (OR [95% CI]: 1.4120 [0.8487-2.3493], p = 0.1840) and Tumor necrosis factor alpha (OR [95% CI]: 1.2411 [0.8352-1.8443], p = 0.2852), no discernible association was detected between migraine and the risk of AD. Conclusion: This study offers compelling evidence indicating a significant correlation between genetically predicted migraine and an elevated risk of AD.
RÉSUMÉ
BACKGROUND: The number and activity of osteoblasts and osteoclasts play an important role in skeletal biology, especially in bone reconstruction. Scientific and rational regulation of osteoclast formation and activity has become a critical strategy aimed at inhibiting the loss of bone mass in the body and alleviating the occurrence of bone diseases. Currently, there are only a few reports related to hesperetin-regulated osteoclast differentiation. OBJECTIVES: To investigate the influence of hesperetin on osteoclast-like cell differentiation and formation, and determine whether the MAPK signaling pathway is involved in the differentiation process. MATERIAL AND METHODS: The RAW264.7 cells were induced and cultured in vitro to promote their differentiation into osteoclast-like cells. Tetrazolium bromide was utilized to determine the effects of different concentrations (100, 200, 400, and 600 µM) of hesperetin on the proliferation of osteoclast-like cell precursors. Osteoclast-like cell differentiation was conducted using tartrate-resistant acid phosphatase (TRAP) staining assay. The status of nuclei and actin filaments of differentiated osteoclast-like cells was observed with the use of 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) and actin-tracker green staining experiments. Changes in key proteins of the MAPK signaling pathway were detected using western blot. RESULTS: The results of TRAP staining experiments showed that the number of osteoclast-like cells decreased with the increase in hesperetin concentration. The DAPI and actin-tracker green staining demonstrated that the nuclei of differentiated osteoclast-like cells reduced in size with the increase in hesperetin concentration, and the osteoclast-like cells became smaller. Western blot for key MAPK signaling pathway proteins revealed that phospho-ERK and phospho-p38 protein levels were not significantly inhibited, but phospho-JNK protein levels were reduced. CONCLUSIONS: Hesperetin inhibits the differentiation of osteoclast-like cells. Further studies revealed that hesperetin also affects the activation level of phospho-JNK, a key signaling protein of the MAPK signaling pathway, in the induced differentiation of osteoclast-like cells.
RÉSUMÉ
The tumor microenvironment, especially the extracellular matrix (ECM), is strongly associated with tumor cell proliferation and metastasis. Numerous studies have provided evidence suggesting that fibronectin (FN) in ECM supports cancer cell escape and contributes to cell migration, resulting in distant cancer metastasis and poor outcomes in patients. In our study, it was demonstrated that FN expression was elevated in tumor tissues from highly malignant NSCLC patients, compared to those with low malignancy (p = 0.0076). Importantly, FN promoted proliferative phenotypes and strengthened tumorigenesis capabilities in NSCLC cells, including A549 and Lewis cells, leading to sustained tumor growth in vivo. Mechanistically, it was identified that FN facilitated the activation of the integrin αvß3/PI3K/AKT signaling pathway, which subsequently upregulated tumor stemness through the downstream transcription factor SOX2. Blockade of integrin αvß3 signal efficiently suppressed NSCLC proliferation and tumorigenesis both in vitro and in vivo. In conclusion, our study demonstrated that extracellular FN could facilitate NSCLC development through the integrin αvß3/PI3K/AKT/SOX2 signaling pathway. Blockade of integrin αvß3 could efficiently enhance the anticancer effects of chemotherapy, offering an innovative approach for clinical NSCLC therapy.
RÉSUMÉ
Extensive use of renewable and clean energy is one of the promising ways to solve energy/environmental problems and promote the sustainable development of our society. As inexhaustible energy sources, the photothermal (PT) and radiative cooling (RC) energy from the sun and outer space have recently attracted tremendous interest. However, these two kinds of energy utilization have distinctly opposite spectral properties, especially in the infrared range, making it extremely difficult to integrate these two energy harvesting modes within a fixed device for continuous energy collection. Thus, in the current study, we have proposed a spectrally self-adaptive broadband absorber/emitter (SSBA/E) based on vanadium dioxide (VO2), a typical phase transition material, to achieve continuous energy harvesting via collecting solar thermal energy in PT mode during the day and obtaining cool energy in wide-band RC mode at night. Experimental results show that owing to the phase transition property of the VO2 layer, these two energy collection modes can be adaptively switched. Specifically, the VO2-based device shows a broadband infrared emissivity modulation from 0.21 to 0.75 and low critical temperatures (58.4 and 49.2 °C) during the phase transition, leading to continuous energy harvesting with high efficiency. Due to the broadband infrared emission, the RC maximum power of the SSBA/E device was estimated to be 58 W m-2. The proposed VO2 smart coatings are also applicable for many other applications such as thermal management of spacecraft, infrared camouflage, or adaptive optical devices.
RÉSUMÉ
The combination of phototherapy and chemotherapy has received extensive attention in the field of cancer therapy. Hence, graphene organic framework (GOF) with a large d-spacing was prepared by solvothermal method, and a novel nanocomposite based on bovine serum albumin (BSA) and the anticancer drug doxorubicin (DOX) was developed, which effectively achieved a photothermal-chemotherapy synergistic treatment. When the feeding ratio was 1:1.6, the DOX loading capacity was 18.51%, and the GOF-BSA/DOX nanocomposite possessed unobvious pH response characteristic, as well as the cumulative release of DOX reached 54.17% at 42°C in the acidic environment (pH = 5.0). The nanocarriers also showed excellent photothermal property and photothermal stability in vitro. In addition, under 808 nm near-infrared laser (NIR) irradiation, the GOF-BSA/DOX nanocomposites generated a large amount of heat, which significantly enhanced the synergistic antitumor effect of in vitro photothermal-chemotherapy. Furthermore, the GOF-BSA/DOX nanocomposites exhibited significantly increased cytotoxicity in the NIR compared with chemotherapy or photothermal therapy alone, suggesting that the combination of chemotherapy and photothermal therapy has excellent antitumor capacity. Therefore, porous GOF nanocarriers may have great potential in combined anti-tumour therapy.
Sujet(s)
Antinéoplasiques , Graphite , Hyperthermie provoquée , Nanoparticules , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Lignée cellulaire tumorale , Doxorubicine/pharmacologie , Doxorubicine/usage thérapeutique , Libération de médicament , Graphite/composition chimique , Nanoparticules/composition chimique , Thérapie photothermique , Sérumalbumine bovineRÉSUMÉ
Immune thrombocytopenia (ITP) is an autoimmune disease with the typical symptom of a low platelet count in blood. ITP demonstrated age and sex biases in both occurrences and prognosis, and adult ITP was mainly induced by the living environments. The current diagnosis guideline lacks the integration of molecular heterogenicity. This study recruited the largest cohort of platelet transcriptome samples. A comprehensive procedure of feature selection, feature engineering, and stacking classification was carried out to detect the ITP biomarkers using RNA sequencing (RNA-seq) transcriptomes. The 40 detected biomarkers were loaded to train the final ITP detection model, with an overall accuracy 0.974. The biomarkers suggested that ITP onset may be associated with various transcribed components, including protein-coding genes, long intergenic non-coding RNA (lincRNA) genes, and pseudogenes with apparent transcriptions. The delivered ITP detection model may also be utilized as a complementary ITP diagnosis tool. The code and the example dataset is freely available on http://www.healthinformaticslab.org/supp/resources.php.
RÉSUMÉ
Recently, nanomaterials have been well-studied in cancer therapy, but some of them often experience difficulties with degradation in vivo, which could cause severe damage to the human body. Among numerous biodegradable nanomaterials, antimonene nanosheets (AMNSs) are versatile, and possess photothermal and photodynamic properties and photoacoustic imaging (PAI) and drug loading ability. Herein, we employed a clearable multifunctional system. The small molecule photosensitizer IR820 and the gold nanoparticles (AuNPs) at small sizes of approximately 5 nm were loaded onto AMNSs coated with biodegradable chitosan (CS). This nanoplatform showed excellent photothermal and photodynamic properties, satisfactory degradability and photoacoustic imaging ability, good biocompatibility and effective NIR light triggered intracellular synergistic treatment. It also displayed good fluorescence imaging ability in the experiment of cell uptake. These suggested that this versatile nanoplatform was able to significantly enhance the therapeutic efficiency based on synergistic phototherapy, and could also be applied in fluorescence and photoacoustic dual imaging for integrating diagnosis and treatment.
Sujet(s)
Antimoine/composition chimique , Nanostructures/composition chimique , Photothérapie/méthodes , Transport biologique , Cellules HeLa , Humains , Vert indocyanine/analogues et dérivés , Vert indocyanine/composition chimique , Vert indocyanine/pharmacologie , Photosensibilisants/composition chimique , Photosensibilisants/pharmacologie , Espèces réactives de l'oxygèneRÉSUMÉ
BACKGROUND: Intranasal drip of dexmedetomidine in children with sevoflurane anesthesia can reduce anesthesia and restlessness. However, there is still some controversy. We conducted a meta-analysis to explore the effect of intranasal infusion of dexmedetomidine on the quality of recovery during the recovery period, to provide certain guidance for clinical application. METHODS: Web of Science, PubMed, Embase, and the Cochrane Library were used for literature search. Systematic reviews were based on PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analysis). RESULTS: A total of 14 articles and 1123 patients were included. The results of the meta-analysis showed that the incidence of emergence agitation [risk ratio (RR), 0.32; 95% confidence interval (CI), 0.20-0.50; P < 0.0001], satisfactory sedation at parent separation (RR, 1.41; 95% CI, 1.031-93; P = 0.034), incidence of nausea and vomiting (RR, 0.41; 95% CI, 0.21-0.78; P = 0.007), and incidence of laryngospasm (RR, 0.23; 95% CI, 0.08-0.65; P = 0.006) of the intranasal dexmedetomidine group were different compared with the control group. However, the satisfactory sedation at mask induction in the intranasal dexmedetomidine group (RR, 1.16; 95% CI, 0.87-1.54; P = 0.319), postanesthesia care unit (PACU) stay time (standardized mean deviation, 0.51; 95% CI, -0.11 to 1.12; P = 0.107), and extubation time (standardized mean deviation, 1.64; 95% CI, -1.07 to 4.35; P = 0.235) were not statistically significant compared with those of the control group. CONCLUSION: Intranasal dexmedetomidine anesthesia with sevoflurane in children can reduce the incidence of emergence agitation, provide more satisfactory sedation when the parents are separated, reduce the incidence of nausea and vomiting, and reduce the incidence of laryngospasm. In addition, the 2 µg/kg dose of dexmedetomidine may be the best dose for clinical application.
Sujet(s)
Dexmédétomidine , Anesthésie générale , Enfant , Dexmédétomidine/effets indésirables , Humains , Hypnotiques et sédatifs/effets indésirables , Agitation psychomotrice , SévofluraneRÉSUMÉ
BACKGROUND: Tumor mutation burden (TMB) and immune microenvironment are important determinants of prognosis and immunotherapeutic efficacy for cancer patients. The aim of the present study was to develop an immune signature to effectively predict prognosis and immunotherapeutic response in patients with lung squamous cell carcinoma (LUSC). METHODS: TMB and immune microenvironment characteristics were comprehensively analyzed by multi-omics data in LUSC. The immune signature was further constructed and validated in multiple independent datasets by LASSO Cox regression analysis. Next, the value of immune signature in predicting the response of immunotherapy was evaluated. Finally, the possible mechanism of immune signature was also investigated. RESULTS: A novel immune signature based on 5 genes was constructed and validated to predict the prognosis of LUSC patients. These genes were filamin-C, Rho family GTPase 1, interleukin 4-induced gene-1, transglutaminase 2, and prostaglandin I2 synthase. High-risk patients had significantly poorer survival than low-risk patients. A nomogram was also developed based on the immune signature and tumor stage, which showed good application. Furthermore, we found that the immune signature had a significant correlation with immune checkpoint, microsatellite instability, tumor infiltrating lymphocytes, cytotoxic activity scores, and T-cell-inflamed score, suggesting low-risk patients are more likely to benefit from immunotherapy. Finally, functional enrichment and pathway analyses revealed several significantly enriched immune-related biological processes and metabolic pathways. CONCLUSIONS: In the present study, we developed a novel immune signature that could predict prognosis and immunotherapeutic response in LUSC patients. The results not only help identify LUSC patients with poor survival, but also increase our understanding of the immune microenvironment and immunotherapy in LUSC.
RÉSUMÉ
Transcriptome sequencing data (6.5 Gb) of the salivary glands of the haematophagous leech Hirudo nipponia was obtained by using the BGIseq-500 platform. After identification and analysis, one transcript (Unigene5370) was annotated to hirudin HV3 from Hirudo medicinalis with an e-value of 1e-29 and was named hirudin-HN. This transcript was a new thrombin inhibitor gene belonging to the proteinase inhibitor I14 (hirudin) family. Hirudin-HN, with a 270-bp cDNA, encodes an 89-aa protein containing a 20-aa signal peptide. The mature hirudin-HN protein contains the typical structural characteristics of hirudin, e.g., three conserved disulfide bonds and the PKP and DFxxIP motifs. Proteins (Hir and M-Hir) were obtained via prokaryotic expression, and the mature hirudin-HN protein was shown to have anticoagulant activity and thrombin affinity by using the chromogenic substrate S2238 and surface plasmon resonance (SPR) interaction analysis, respectively. The N-terminal structure of the mature hirudin-HN protein was shown to be important for anticoagulant activity by comparing the activity and thrombin affinity of Hir and M-Hir. The abundances of Hirudin-HN mRNA and protein were higher in the salivary glands of starving animals than in those of feeding or fed leeches. These results provided a foundation for further study on the structure-function relationship of hirudin-HN with thrombin.
RÉSUMÉ
In recent years, increasing attention has been paid to the origin, transmission and communication of silk. However, this is still an unsolved mystery in archaeology. The identification of silk-producing species, especially silk produced by Bombyx mori (B. mori) and Antheraea pernyi (A. pernyi), is of key significance to address this challenge. In this study, two innovative methods, i.e. immunology and proteomics, were proposed and successfully established for the species identification of silks. ELISAs result demonstrated that the two prepared antibodies exhibited high sensitivity and specificity in distinguishing B. mori and A. pernyi silk. No cross-reactivity with each other was observed. Moreover, biomarkers were obtained for Bombyx and Antheraea through proteomic analysis. It was also confirmed that the biomarkers were suitable for identifying the species that produced a given silk sample. Compared with conventional methods for distinguishing silk species, immunological and proteomics techniques used in tandem can provide intact information and have the potential to provide accurate and reliable information for species identification.
Sujet(s)
Bombyx/immunologie , Bombyx/métabolisme , Papillons de nuit/immunologie , Papillons de nuit/métabolisme , Protéomique , Soie/analyse , Soie/classification , Animaux , Anticorps/immunologie , Spécificité des anticorps/immunologie , Marqueurs biologiques , Réactions croisées/immunologie , Bases de données génétiques , Test ELISA , Protéines d'insecte , Phénotype , Protéome , Protéomique/méthodes , Soie/composition chimique , Soie/ultrastructure , Spécificité d'espèce , Analyse spectraleRÉSUMÉ
The novel antimicrobial gene Hirudomacin (Hmc), with a 249-bp cDNA, encodes a mature protein of 61 amino acids and a 22-amino acid signal peptide. Hmc exhibits the highest similarity, at 90.1%, with macin family members found in the salivary gland of the leech Hirudo nipponica Whitman. A mature Hmc protein concentration of 219⯵g/mL was detected using the Bradford method. The mature Hmc protein is 6862.82â¯Da and contains 8 cysteine residues. Antimicrobial assays showed a minimum bactericidal concentration and 50% lethal dose of 1.56⯵g/mL and 0.78⯵g/mL, respectively, for Staphylococcus aureus and 0.39⯵g/mL and 0.195⯵g/mL, respectively, for Bacillus subtilis. Transmission electron microscopy revealed membrane integrity disruption in S. aureus and B. subtilis, which resulted in bacterial lysis. The level of Hmc mRNA in the salivary gland during three blood meal stages indicated a remarkable trend of increase (Pâ¯<â¯.05), and western blotting demonstrated that among the three blood meal stages, expression of the mature Hmc protein was highest in both the salivary gland and intestine at the fed stage (Pâ¯<â¯.05). Immunofluorescence further showed the mature Hmc protein to be localized outside the cell nucleus, with the signal intensity in the salivary gland peaking at the fed stage (Pâ¯<â¯.05). In conclusion, the mature Hmc protein exhibits broad-spectrum antimicrobial effects against gram-positive and gram-negative bacteria, and a blood meal upregulates Hmc gene and protein expression in H. nipponica.
Sujet(s)
Aliment pour animaux , Antibactériens/métabolisme , Sang , Régulation de l'expression des gènes , Sangsues/génétique , Protéines/génétique , Animaux , Antibactériens/pharmacologie , Bacillus subtilis/effets des médicaments et des substances chimiques , Clonage moléculaire , Protéines/pharmacologie , ARN messager/génétique , ARN messager/métabolisme , Staphylococcus aureus/effets des médicaments et des substances chimiquesRÉSUMÉ
Species identification is of key significance for exploring the origin and transmission of ancient silks. In this study, two novel methods, i.e. western blot (WB) and proteomics analyses, were proposed and established to identify the differences between silks from Bombyx mori (B. mori) and two other distinctive species (Eri silkworm and Chestnut silkworm). Three diagnostic antibodies, a polyclonal anti-silk fibroin (anti-SF) antibody (pAb), a polyclonal anti-SF-specific peptide antibody (pAsb), and a monoclonal anti-SF antibody (mAb) were designed and prepared to distinguish silk species using the antibody-based WB technique. Proteomics analysis by liquid chromatography-tandem mass spectrometry was performed to further identify silk species at the protein level. WB results indicated that the three antibodies showed high specificity and affinity and could discern B. mori silk from Eri and Chestnut silks. Biomarkers for each SF were obtained using proteomics analysis, and they have the potential to serve as standards for identifying silk species. Thus, combining WB and proteomics analyses with conventional methods can provide more accurate silk information and may be suitable for identifying other proteinaceous materials in archaeological field.
Sujet(s)
Bombyx/métabolisme , Protéomique , Soie/métabolisme , Séquence d'acides aminés , Animaux , Technique de Western , Bombyx/classification , Soie/composition chimique , Spécificité d'espèceRÉSUMÉ
BACKGROUND/AIMS: Immunosuppression frequently occurs during the development of sepsis and is closely associated with poor outcome. Characteristics of immunosuppressive CD4+ T lymphocytes in sepsis have been reported to include dramatic cell loss and inactivation. p53 acts as a pivotal transcription factor in regulating cell proliferation and apoptosis, which control tumorigenesis. However, few studies have investigated the universal role of p53 in immune cells, especially in the development of sepsis. METHODS: A mouse model of sepsis was produced by cecal ligation and puncture (CLP), and isolated splenic CD4+ T cells or Jurkat cells were exposed to lipopolysaccharide (LPS) stimulation in vitro. We used genetic knockout (p53-/-) mice or the specific inhibitor pifithrin-α (PFT) to investigate the regulatory mechanisms of p53. Cell proliferation ability was assessed using a Cell Counting Kit-8 assay, and apoptotic cells were stained with annexin V/propidium iodide and then analyzed using a FACScan flow cytometer. Protein and mRNA expression levels were measured by western blotting and real-time PCR, and cytokine levels in culture supernatants were determined by enzyme-linked immunosorbent assay. RESULTS: Splenic CD4+ T lymphocytes from CLP mice expressed gradually elevated p53 mRNA and protein levels, which resulted in extracellular regulated protein kinase 1/2 inactivation and expression of apoptotic molecules. Specific inhibition of p53 by PFT or genetic knockout (p53-/-) maintained CD4+ T lymphocyte homeostasis, as indicated by protection from cell loss and restoration of immune function. A medium dose of PFT improved the survival rate of mice, while mortality rate showed only a slight improvement in p53-/- mice compared with wild-type mice. The in vitro responses to LPS were consistent with these results, and upregulation of p53 clearly affected the proliferation, apoptosis, and immune dysfunction of CD4+ T lymphocytes. In addition, we confirmed the regulatory effect of p53 in Jurkat cells, and inhibition of p53 by either inhibition or short hairpin RNA transduction markedly protected cells from LPS stimulation. CONCLUSION: Elevation of p53 in T lymphocytes during sepsis or endotoxin challenge might be responsible for inhibiting cell proliferation and enhancing both apoptosis and immune dysfunction of T cells.
Sujet(s)
Lymphocytes T CD4+/métabolisme , Sepsie/anatomopathologie , Protéine p53 suppresseur de tumeur/métabolisme , Animaux , Apoptose/effets des médicaments et des substances chimiques , Benzothiazoles/pharmacologie , Benzothiazoles/usage thérapeutique , Lymphocytes T CD4+/cytologie , Lymphocytes T CD4+/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine , Humains , Cellules Jurkat , Lipopolysaccharides/pharmacologie , Mâle , Souris , Souris de lignée C57BL , Souris knockout , Mitogen-Activated Protein Kinase 1/métabolisme , Mitogen-Activated Protein Kinase 3/métabolisme , Interférence par ARN , Petit ARN interférent/métabolisme , Sepsie/traitement médicamenteux , Sepsie/mortalité , Taux de survie , Toluène/analogues et dérivés , Toluène/pharmacologie , Toluène/usage thérapeutique , Protéine p53 suppresseur de tumeur/antagonistes et inhibiteurs , Protéine p53 suppresseur de tumeur/génétique , Régulation positive/effets des médicaments et des substances chimiquesRÉSUMÉ
Psoralen could inhibit the proliferation of human breast cancer cells, however, the molecular mechanism was unclear. We evaluated the anti-proliferative effects of psoralen by MTT, plate colony formation assay and cell cycle analysis in MCF-7 and MDA-MB-231 cells. The effects of psoralen on activation of Wnt/ß-catenin and the related target genes were examined by quantitative real-time PCR, western blotting and cell immunofluorescence. The tumor growth was conducted in BALB/c nude mice and the pathological changes of heart, liver and kidney were also observed. Our results demonstrate that psoralen significantly inhibited cell proliferation by inducing G0/G1 phase arrest in MCF-7 cells and G2/M phase arrest in MDA-MB-231 cells. The expression of Fra-1 was reduced and Axin2 was promoted both in MCF-7 and MDA-MB-231 cells after psoralen treatment. The cytoplasmic accumulation and nuclear translocation of ß-catenin were significantly reduced by psoralen. Psoralen increased the levels of phospho-(Y142) ß-catenin, while decreased the expression of total ß-catenin and its downstream target Fra-1 in vitro and vivo. Moreover, psoralen didn't cause any significant toxicity at the effective concentration. Overall, our results might provide theoretical basis for clinical application of psoralen in breast cancer.
Sujet(s)
Tumeurs du sein/anatomopathologie , Points de contrôle du cycle cellulaire/effets des médicaments et des substances chimiques , Psoralène/pharmacologie , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Photosensibilisants/pharmacologie , Voie de signalisation Wnt/effets des médicaments et des substances chimiques , bêta-Caténine/métabolisme , Animaux , Apoptose/effets des médicaments et des substances chimiques , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/métabolisme , Prolifération cellulaire/effets des médicaments et des substances chimiques , Femelle , Humains , Souris , Souris de lignée BALB C , Souris nude , Cellules cancéreuses en culture , Tests d'activité antitumorale sur modèle de xénogreffe , bêta-Caténine/génétiqueRÉSUMÉ
The identification of ancient wool is of great importance in archaeology. Despite lots of meaningful information can be achieved by conventional detection methods, that is, light and electron microscopy, spectroscopy, and chromatography, the efficacy is likely to be limited in the detection of ancient samples with contamination or severe degradation. In this work, an immunoassay was proposed and performed for the identification of ancient wool. First, a specific antibody, which has the benefits of low cost, easy operation, and extensive applicability, was developed directly through immunizing rabbits with complete antigen (keratin). Then, an enzyme-linked immunosorbent assay (ELISA) and a colloidal gold-labelled immunochromatographic strip (ICS) were developed to qualitatively identify the corresponding protein in ancient wool samples unearthed from Kazakhstan and China. The anti-keratin antibody exhibited high sensitivity and specificity for the identification of modern and ancient wool. The limit of detection (LOD) of the ELISA method was 10 ng/mL, and no cross-reactions with other interfering antigens have been noted. It is concluded that the immunoassays are reliable methods for the identification of ancient wool.
RÉSUMÉ
BACKGROUND: Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. METHOD: In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo). Exosomes were characterized by morphology, exosomal markers and size distribution. The ability of ADR/exo to transfer multidrug resistance was assessed by MTT and real-time quantitative PCR. The different formation and secretion of exosomes were detected by immunofluorescence and transmission electron microscopy. Then we performed comparative transcriptomic analysis using RNA-Seq technology and real-time quantitative PCR to better understand the gene expression regulation in exosmes formation and release after psoralen treatment. RESULTS: Our data showed that exosomes derived from MCF-7/ADR cells were able to promote active sequestration of drugs and could induce a drug resistance phenotype by transferring drug-resistance-related gene MDR-1 and P-glycoprotein protein. Psoralen could reduce the formation and secretion of exosomes to overcome drug resistance. There were 21 differentially expressed genes. Gene ontology (GO) pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most significantly expressed genes were linked to PPAR and P53 signaling pathways which were related to exosomes formation, secretion and cargo sorting. CONCLUSIONS: Psoralen can affect the exosomes and induce the reduction of resistance transmission via exosomes might through PPAR and P53 signaling pathways, which might provide a novel strategy for breast cancer resistance to chemotherapy in the future.
Sujet(s)
Tumeurs du sein/génétique , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Exosomes/effets des médicaments et des substances chimiques , Psoralène/pharmacologie , Sous-famille B de transporteurs à cassette liant l'ATP/génétique , Sous-famille B de transporteurs à cassette liant l'ATP/métabolisme , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/métabolisme , Lignée cellulaire tumorale , Exosomes/métabolisme , Femelle , Analyse de profil d'expression de gènes , Réseaux de régulation génique , Humains , Cellules MCF-7 , Récepteurs activés par les proliférateurs de peroxysomes/génétique , Analyse de séquence d'ARN , Protéine p53 suppresseur de tumeur/génétiqueRÉSUMÉ
BACKGROUND: Epilepsy is one of the most common serious neurological disorders. The present study aimed to investigate the influence of occupational status on the quality of life of Chinese adult patients with epilepsy. METHODS: This study surveyed 819 subjects clinically diagnosed with epilepsy for more than 1 year in 11 hospitals in Beijing; 586 were employed (71.55%). All subjects completed the case report form with inquiries on demographic data, social factors, and illness. The patients' quality of life was assessed using the quality of life in patients with epilepsy-31 items (QOLIE-31) questionnaire. RESULTS: The QOLIE-31 score in the employed group was significantly higher than that in the unemployed group. Furthermore, the scores in all the sections (overall quality of life, energy/fatigue, emotional well-being, seizure worry, cognition, social function, and medication effects) of the employed group were higher than those of the unemployed group. Both the employed and unemployed groups achieved the highest difference in social function. The QOLIE-31 score of students was higher than those of farmers and workers. Both the students and workers scored higher in the quality of life compared with the adult peasants living with epilepsy. The students and farmers showed significant differences in QOLIE-31 score, cognition, emotional well-being, overall quality of life, energy/fatigue, and social function. In contrast, no significant difference was noted in seizure worry and medication effects across the three different kinds of occupation. CONCLUSION: Occupational status might affect the quality of life of Chinese adult patients with epilepsy, and social function is the most important contributing factor.
Sujet(s)
Emploi , Épilepsie/épidémiologie , Qualité de vie , Adolescent , Adulte , Sujet âgé , Asiatiques , Femelle , Humains , Mâle , Adulte d'âge moyen , Enquêtes et questionnaires , Jeune adulteRÉSUMÉ
The resistance of cancer to chemotherapeutic agents is a major obstacle during chemotherapy. Clinical multidrug resistance (MDR) is commonly mediated by membrane drug efflux pumps, including ATPbinding cassette subfamily B member 1, also termed P-glycoprotein (P-gp). P-gp is a membrane transporter encoded by the MDR1 gene. The current study aimed to investigate the impact of psoralen on the expression and function of Pgp. The 10% inhibitory concentration (IC10) of psoralen, and its capacity to reduce MDR in adriamycin (ADR)resistant MCF7/ADR cells were determined using MTT assay. The ability of psoralen to modulate the transport activity of Pgp in MCF7/ADR cells was evaluated by measuring the accumulation and efflux of rhodamine 123 (Rh 123) and adriamycin with flow cytometry. The present study evaluated the mRNA level of MDR1 in MCF7 and MCF7/ADR cells treated with psoralen using reverse transcription-quantitative polymerase chain reaction. The protein expression level of Pgp was examined by western blot analysis. The current study demonstrated that the IC10 of psoralen in MCF7/ADR cells was 8 µg/ml. At 8 µg/ml, psoralen reduced MDR and the sensitivity of the MCF7/ADR cells to ADR compared with untreated cells. Additionally, psoralen significantly increased the intracellular accumulation of ADR and Rh 123. However, the IC10 of psoralen did not affect the protein expression levels of Pgp or mRNA levels of MDR1 (P>0.05). Psoralen reduces MDR by inhibiting the efflux function of Pgp, which may be important for increasing the efficiency of chemotherapy and improving the clinical protocols aiming to reverse P-gp-mediated MDR.
Sujet(s)
Antibiotiques antinéoplasiques/pharmacologie , Tumeurs du sein/traitement médicamenteux , Réactifs réticulants/pharmacologie , Doxorubicine/pharmacologie , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Psoralène/pharmacologie , Sous-famille B de transporteurs à cassette liant l'ATP/génétique , Sous-famille B de transporteurs à cassette liant l'ATP/métabolisme , Antibiotiques antinéoplasiques/pharmacocinétique , Transport biologique/effets des médicaments et des substances chimiques , Tumeurs du sein/génétique , Tumeurs du sein/métabolisme , Prolifération cellulaire/effets des médicaments et des substances chimiques , Doxorubicine/pharmacocinétique , Multirésistance aux médicaments/effets des médicaments et des substances chimiques , Femelle , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Humains , Cellules MCF-7 , ARN messager/génétique , Rhodamine 123/pharmacocinétiqueRÉSUMÉ
OBJECTIVE AND DESIGN: This prospective experimental study aims to investigate whether matrilin-2 is released from burn injury and induces post-burn inflammatory responses as an endogenous danger signal. SUBJECTS: Fifteen burn patients, 15 volunteers, 12 matrilin-2-deficient mice, 36 C57BL/6 mice and raw 264.7 cells. METHODS: Matrilin-2 levels were detected by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction. The inflammatory cytokines production in Matn2 deficient mice and wide type mice were detected by ELISA. Macrophages were activated by recombinant mouse MATN2 with or without adding anti-Toll-like receptor (TLR) 4 antibody. Student's t test and one-way analysis of variance were used for statistical analysis. RESULTS: The matrilin-2 levels in serum of burned patients were drastically elevated as compared to those of healthy controls. The matrilin-2 levels in burned mice were significantly increased than those of non-burned controls, whereas the matrilin-2 mRNA expression was not significantly changed after burn. In addition, Matn2 deficient mice showed remarkably less inflammatory cytokines production and less neutrophil infiltration in lung. Exogenous MATN2 induced potent expression of proinflammatory cytokines production in macrophages, which was inhibited by anti-TLR4 antibody. CONCLUSION: Matrilin-2 induces post-burn inflammatory responses as an endogenous danger signal, partly through a TLR4-mediated mechanism.