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Refined magnesium slag and aluminum dross are two typical hazardous solid wastes that contain significant amounts of leachable fusing agent and aluminum droplets encapsulated by dense oxidized films, respectively. This study creatively proposes a safe and green method for the joint utilization of these two wastes. The interfacial reaction behavior revealed that the dense oxidized films of the aluminum droplets were significantly broken by the erosive action of the fusing agent, providing the necessary conditions for the movement of aluminum droplets. Consequently, the aluminum droplets successfully broke free from the oxidized films and separated together with the fusing agent from the dross under the force of supergravity. The recovery ratios of metallic aluminum and fusing agent reached 98.95 % and 98.13 %, while the aluminum and fusing agent contents in the tailings were reduced to 0.82 wt% and 3.71 wt%. The study also discusses the leaching characteristic of the tailings and the scalability for industrial applications of this method in detail. This study not only achieves valuable resource recovery but also reduces the leaching risk and alleviates the land occupation and ecosystem pressure caused by industrial wastes. The tailings can be harmlessly utilized in related fields through subsequent scientific treatment.
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Aluminio , Magnesio , Aluminio/química , Magnesio/químicaRESUMEN
BACKGROUND: Psoriasis is a complex and recurrent chronic inflammatory skin disease, and the abnormal proliferation of keratinocytes plays a crucial role in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) play an indispensable role in regulating cellular functions. This research aims to explore the potential impact of lncRNA MIR181A2HG on the regulation of keratinocyte proliferation. METHODS: The expression level of MIR181A2HG and the mRNA level of KRT6, KRT16, and SOX6 were assessed using qRT-PCR. The viability and proliferation of keratinocytes were evaluated using CCK-8 and EdU assays. Cell cycle analysis was performed using flow cytometry. Dual-luciferase reporter assays were applied to test the interaction among MIR181A2HG/miR-223-3p/SOX6. Protein level was detected by Western blotting analysis. RESULTS: The findings indicated that psoriasis lesions tissue exhibited lower levels of MIR181A2HG expression compared to normal tissue. The overexpression of MIR181A2HG resulted in the inhibition of HaCaT keratinocytes proliferation. The knockdown of MIR181A2HG promoted cell proliferation. The dual-luciferase reporter assay and rescue experiments provided evidence of the interaction among MIR181A2HG, SOX6, and miR-223-3p. CONCLUSIONS: The lncRNA MIR181A2HG functions as a miR-223-3p sponge targeting SOX6 to regulate the proliferation of keratinocytes, which suggested that MIR181A2HG/miR-223-3p/SOX6 might be potential diagnostic and therapeutic targets for psoriasis.
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Proliferación Celular , Queratinocitos , MicroARNs , Psoriasis , ARN Largo no Codificante , Factores de Transcripción SOXD , Humanos , MicroARNs/metabolismo , MicroARNs/genética , Queratinocitos/metabolismo , Proliferación Celular/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción SOXD/metabolismo , Factores de Transcripción SOXD/genética , Psoriasis/genética , Psoriasis/metabolismo , Psoriasis/patología , Células HaCaTRESUMEN
Accumulating evidence indicates that microRNAs (miRNAs) have a vital effect on the pathogenesis of psoriasis. This study is conducted to investigate the potential involvement of miR-181a-5p and miR-181b-5p in the proliferation of HaCaT keratinocytes. Cell viability and proliferation were evaluated respectively in this study using the CCK-8 and the 5-ethynyl-2'-deoxyuridine (EdU) assays. The expression of Maternal Embryonic Leucine Zipper Kinase (MELK) and Keratin 16 (KRT16) mRNA and protein in tissues and cells was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The Luciferase reporter system analyzes the connection between miR-181a-5p/miR-181b-5p and MELK. The results showed that miR-181a/b-5p expression was downregulated in the psoriasis lesions and negatively regulated the proliferation of keratinocytes. MELK was directly targeted by miR-181a-5p/miR-181b-5p. In addition, HaCaT keratinocytes proliferation was inhibited by knockdown of MELK while promoted dramatically by MELK overexpression. Notably, miR-181a/b-5p mimics could attenuate the effects of MELK in keratinocytes. In conclusion, our research findings suggested miR-181a-5p and miR-181b-5p negatively regulate keratinocyte proliferation by targeting MELK, providing potential diagnostic biomarkers and therapeutic targets for psoriasis.
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Proliferación Celular , Células HaCaT , Queratinocitos , MicroARNs , Proteínas Serina-Treonina Quinasas , Psoriasis , Humanos , MicroARNs/metabolismo , MicroARNs/genética , Queratinocitos/metabolismo , Proliferación Celular/genética , Psoriasis/patología , Psoriasis/genética , Psoriasis/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Queratina-16/metabolismo , Queratina-16/genética , Regulación hacia Abajo , Supervivencia Celular , Línea CelularRESUMEN
Psoriasis is a common chronic inflammatory skin disease. Abnormal proliferation of keratinocytes plays an important role in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) are involved in the regulation of a variety of cell biological processes. The purpose of this study was to investigate the potential role of lncRNA MIR181A2HG in the proliferation of human keratinocytes. qRT-PCR and Western blotting were performed to measure the expression levels of MIR181A2HG, SRSF1, KRT6, and KRT16 in tissue specimens and HaCaT keratinocytes. The effects of MIR181A2HG on HaCaT keratinocytes proliferation were evaluated using Cell Counting Kit-8 (CCK-8) assays, 5-Ethynyl-2'-deoxyuridine (EdU) incorporation, and cell-cycle assays. RNA pulldown-mass spectrometry (MS) was applied to identify the proteins interacting with MIR181A2HG. RNA pull-down-Western blotting and RNA immunoprecipitation coupled with real-time quantitative reverse transcription-PCR (RIP-qRT-PCR) assays were used to determine the interactions between MIR181A2HG and its RNA-binding proteins (RBPs). MIR181A2HG was down-regulated in psoriasis tissues. MIR181A2HG overexpression induced G0/G1 and G2/M phase cell cycle arrest and decreased the protein levels of KRT6, KRT16, Cyclin D1, CDK4, and Cyclin A2 in HaCaT keratinocytes. MIR181A2HG knockdown showed the opposite effect. By using RNA pulldown-MS, 356 proteins were identified to interact with MIR181A2HG potentially. Bioinformatics analysis showed that NOP56 and SRSF1 may be RNA binding proteins (RBPs) that may be interact with MIR181A2HG. Furthermore, by using RNA pull-down-Western blotting and RIP-qRT-PCR, SRSF1 was determined to interact with MIR181A2HG. Moreover, silencing of SRSF1 inhibited keratinocytes proliferation, which could be reversed with the knockdown of MIR181A2HG. Our findings indicated that MIR181A2HG can negatively regulate HaCaT keratinocytes proliferation by binding SRSF1, suggesting that MIR181A2HG and SRSF1 may serve as potential targets for the treatment of psoriasis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-024-00621-6.
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Among the numerous gaze-estimation methods currently available, appearance-based methods predominantly use RGB images as input and employ convolutional neural networks (CNNs) to detect facial images to regressively obtain gaze angles or gaze points. Model-based methods require high-resolution images to obtain a clear eyeball geometric model. These methods face significant challenges in outdoor environments and practical application scenarios. This paper proposes a model-based gaze-estimation algorithm using a low-resolution 3D TOF camera. This study uses infrared images instead of RGB images as input to overcome the impact of varying illumination intensity in the environment on gaze estimation. We utilized a trained YOLOv8 neural network model to detect eye landmarks in captured facial images. Combined with the depth map from a time-of-flight (TOF) camera, we calculated the 3D coordinates of the canthus points of a single eye of the subject. Based on this, we fitted a 3D geometric model of the eyeball to determine the subject's gaze angle. Experimental validation showed that our method achieved a root mean square error of 6.03° and 4.83° in the horizontal and vertical directions, respectively, for the detection of the subject's gaze angle. We also tested the proposed method in a real car driving environment, achieving stable driver gaze detection at various locations inside the car, such as the dashboard, driver mirror, and the in-vehicle screen.
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Massive copper slag containing heavy metals is produced in copper making and 0.5 - 8.0 wt% Cu is lost into it, deserving to be recovered. In this study, the waste coke and gypsum were employed to clean the copper slag, the lost copper was reduction-sulfurized and enriched to the matte droplets. However, the free-settling of matte droplets under normal gravity needed a higher temperature of 1350 â. On this basis, the matte droplets were efficiently separated from the cleaned slag via super-gravity at a low temperature of 1200 â within 3 min, the recovery ratio of Cu was up to 99.56%, and the grade of Cu in the matte phase and cleaned slag was 85.84 wt% and 0.08 wt%, respectively. Moreover, the migration, distribution and leaching behavior of heavy metal elements (Pb, Zn, Ni, etc.,) were performed and analyzed, and the treatment and utilization of volatilized vapors and tailings were also discussed. This study proposed a green method to clean the copper slag and simultaneously recover copper resources via reduction-sulfurizing smelting and super-gravity separation at a low temperature, providing scientific guidance and application prospects for the synergistic treatment of hot copper slag with waste coke and gypsum.
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Epigenetic biomarkers help predict the prognosis of cancer patients and evaluating the clinical outcome of immunization therapy. In this study, we present a personalized gene methylation-CpG signature to enhance the accuracy of survival prediction for individuals with hepatocellular carcinoma (HCC). Utilizing RNA sequencing and methylation datasets from GEO as well as TCGA, we conducted single sample GSEA (ssGSEA), WGCNA, as well as Cox regression. Through these analyses, we identified 175 oxidative stress and immune-related genes along with 4 CpG loci that are associated with the prognosis of HCC. Subsequently, we constructed a prognostic signature for HCC utilizing these 4 CpG sites, referred to as the HCC Prognostic Signature of Methylation-CpG sites (HPSM). Further investigation revealed an enrichment of immune-related signal pathways in the HPSM-low group, which demonstrated a positive correlation with better survival among HCC patients. Moreover, the methylation of the CpG sites in HPSM was found to be closely linked to drug sensitivity. In vitro experiments tentatively confirmed that promoter methylation regulated the expression of BMPER, one of the CpG sites within HPSM. The expression of BMPER was significantly correlated with cell death in the oxidative stress pathway, and overexpression of BMPER effectively inhibited HCC cell proliferation. Consequently, our findings suggest that HPSM is an independent predictive factor and holds promise for accurately predicting the prognosis of HCC patients.
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Benzoatos , Carcinoma Hepatocelular , Glicina/análogos & derivados , Neoplasias Hepáticas , Humanos , Pronóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Metilación , Proteínas PortadorasRESUMEN
OBJECTIVE: To summarize the product registration declaration ideas and registration technical review of the all-inside meniscal suture system, and to systematically think about of the technical review concerns of the all-inside meniscal suture system products to provide technical guidance for improving the quality of registration and application and regulatory efficiency. METHODS: Consult the public information of such products at home and abroad, and summarize the experience of registration review of such products. RESULTS: The technical review of the all-inside meniscus suture system registration mainly focuses on product basic information, pre-clinical research, clinical evaluation and product technical requirements. CONCLUSIONS: The difficulty of product registration and declaration of the all-inside meniscus suture system lies in the provision of pre-clinical research data of the product, and the applicant needs to strengthen the basic research ability, formulate scientific technical indicators and test methods to ensure the safety and effectiveness of the product, and also provide sufficient supporting data for the registration declaration.
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Meniscos Tibiales , Lesiones de Menisco Tibial , Humanos , Meniscos Tibiales/cirugía , Técnicas de Sutura , Lesiones de Menisco Tibial/cirugía , Suturas , Artroscopía/métodosRESUMEN
OBJECTIVE: To study the mechanical properties related to the typical functional failure modes of non-absorbable suture anchor in clinical use, and to support product design, development and verification. METHODS: By retrieving the database of relevant adverse events, the typical functional failure modes of non-absorbable suture anchor were summarized, and the influencing factors of functional failure were further analyzed by studying the mechanical properties related to functional failure. The publicly available test data was retrieved for verification and provided reference for the researchers. RESULTS: The typical functional failure modes of non-absorbable suture anchor include anchor failure, suture failure, fix loosening, inserter failure, which are related to the mechanical properties of products, such as screw-in torque and break torque of screw-in anchors, insertion force of knock-in anchors, suture strength, pull-out force before and after system fatigue test and elongation of sutures after fatigue test. CONCLUSIONS: Enterprises should pay attention to improving the mechanical performance level of products through material, structural design and the suture weaving process to ensure the safety and effectiveness of products.
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Anclas para Sutura , Técnicas de Sutura , Suturas , Implantes Absorbibles , Fenómenos Biomecánicos , Ensayo de MaterialesRESUMEN
Bone is the main site of metastasis from prostate cancer; therefore, it is important to investigate the microRNAs (miRNAs) and mRNA associated with bone metastases from prostate cancer. Since an appropriate mechanical environment is important in the growth of bone, in the present study, the miRNA, mRNA, and long non-coding RNA (lncRNA) profiles of mechanically strained osteoblasts treated with conditioned medium (CM) from PC-3 prostate cancer cells were studied. MC3T3-E1 osteoblastic cells were treated with the CM of PC-3 prostate cancer cells and were simultaneously stimulated with a mechanical tensile strain of 2,500 µÎµ at 0.5 Hz; the osteoblastic differentiation of the MC3T3-E1 cells was then assessed. In addition, the differential expression levels of mRNA, miRNA and lncRNA in MC3T3-E1 cells treated with the CM of PC-3 cells were screened, and some of the miRNAs and mRNAs were verified by reverse transcription-quantitative PCR (RT-qPCR). The signal molecules and signaling pathways associated with osteogenic differentiation were predicted by bioinformatics analysis. The CM of PC-3 prostate cancer cells suppressed osteoblastic differentiation of MC3T3-E1 cells. A total of seven upregulated miRNAs and 12 downregulated miRNAs were selected by sequencing and further verified using RT-qPCR, and related differentially expressed genes (11 upregulated and 12 downregulated genes) were also selected by sequencing and further verified using RT-qPCR; subsequently, according to the enrichment of differentially expressed genes in signaling pathways, nine signaling pathways involved in osteogenic differentiation were screened out. Furthermore, a functional mRNA-miRNA-lncRNA regulatory network was constructed. The differentially expressed miRNAs, mRNAs and lncRNAs may provide a novel signature in bone metastases of prostate cancer. Notably, some of the signaling pathways and related genes may be associated with pathological osteogenic differentiation caused by bone metastasis of prostate cancer.
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The 'plainification of materials' has been conceptualized to promote the sustainable development of materials. This perspective, for the first time in the field of biomaterials, proposes and defines 'plain metallic biomaterials (PMBs)' with demonstrated research and application case studies of pure titanium with high strength and toughness, and biodegradable, fine-grained and high-purity magnesium. Then, after discussing the features, benefits and opportunities of PMBs, the challenges are analyzed from both technical and regulatory aspects. Regulatory perspectives on PMB-based medical devices are also provided for the benefit of future research, development and commercialization.
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Objective: Systemic lupus erythematosus (SLE) displays the characteristics of abnormal activity of the immune system, contributing to diverse clinical symptoms. Herein, this study was conducted for discovering novel immune cell-relevant therapeutic targets. Methods: The abundance of diverse immune cells was estimated in PBMCs of SLE and healthy controls from the GSE50772 dataset with CIBERSORT approach. Immune cell-relevant co-expression modules were screened with WGCNA and relevant characteristic genes were determined with LASSO algorithm. Inflammatory chemokines were measured in serum of twenty SLE patients and twenty controls through ELISA. Bone marrow mesenchymal stem cells (BMSCs) were isolated and TK1 expression was measured in BMSCs through RT-qPCR and western blotting. TK1-overexpressed and TK-1-silenced BMSCs of SLE were conducted and apoptosis and cell cycle were measured with flow cytometry. Apoptosis-, cell cycle- and senescence-relevant proteins were tested with western blotting. Results: We determined three co-expression modules strongly linked to immune cells. Five characteristic genes (CXCL1, CXCL2, CXCL8, CXCR1 and TK1) were screened and ROC curves proved the excellent diagnostic performance of this LASSO model. Inflammatory chemokines presented widespread up-regulations in serum of Systemic lupus erythematosus patients, demonstrating the activation of inflammatory response. TK1 expression was remarkably elevated in SLE BMSCs than controls. TK1 overexpression enhanced IL-1ß expression, apoptosis, cell cycle arrest, and senescent phenotypes of SLE BMSCs and the opposite results were proved in TK1-silenced SLE BMSCs. Conclusion: Collectively, our findings demonstrate that silencing TK1 alleviates inflammation, growth arrest and senescence in BMSCs of SLE, which highlights TK1 as a promising therapeutic target against SLE.
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As an important regulator involved in cell activity, microRNAs (miRNAs) are important in the process of exercise influencing bone metabolism. The present study aimed to detect and select differentially expressed miRNAs in the bone tissues of mice trained on a treadmill, predict the target genes of these differentially expressed miRNAs and lay a foundation for exploring the effect of treadmill training on bone metabolism through miRNAs. In this experiment, after the mice were trained on a treadmill for 8 weeks, the mechanical properties of mouse femur bone were assessed, and the alkaline phosphatase (ALP) activity and osteocalcin (OCN) protein levels of the bone were assayed. miRNA microarray and reverse transcription-quantitative (RT-q)PCR were performed to select and validate differentially expressed miRNAs in the bone, and the target genes of these miRNAs were predicted with bioinformatics methods. In addition, the differentially expressed miRNAs in the bone tissues were compared with those in mechanically strained osteocytes in vitro. Treadmill training improved the mechanical properties of the femur bones of mice, and elevated the ALP activity and OCN protein level in the bone. In addition, 122 differentially expressed miRNAs were detected in the bone, of which nine were validated via RT-qPCR. Among the target genes of these differentially expressed miRNAs, certain candidates were involved in bone metabolism. A total of eight miRNAs were differentially expressed in both bone tissue and osteocytes, exhibiting the same expression trends, and various target genes of these eight miRNAs were also involved in bone metabolism. Treadmill training resulted in altered miRNA expression profiles in the bones of mice (mainly in osteocytes) and the differentially expressed miRNAs may serve important roles in regulating bone metabolism and osteogenic differentiation.
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Cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg) and arsenic (As) are potent toxicants to human health via dietary intake. It is imperative to establish accurate soil thresholds based on soil-plant transfer models and food safety standards for safe agricultural production. This study takes rice genotypes and soil properties into account to derive soil thresholds for five heavy metal(loid)s using the bioconcentration factors (BCF) and species sensitivity distribution (SSD) based on the food safety standard. The BCF generated from two paddy soils was calculated to investigate the sensitivity of heavy metal accumulation in nine rice cultivars in a greenhouse pot experiment. Then, empirical soil-plant transfer models were developed from a middle-sensitivity rice cultivar (Denong 2000, one selected from nine rice) grown in nineteen paddy soils with various soil properties under a proper exogenously metal(loid)s concentration gradient. After normalization, hazardous concentrations from the fifth percentile (HC5) were calculated from the SSD curves, and the derived soil thresholds were obtained from HC5 prediction models that based on the combination of pH and organic carbon (OC) or cation exchange capacity (CEC). The soil Cd threshold derived based on pH and organic carbon (pH < 7.5, OC ≥ 20 g kg-1) was 1.3-fold of those only considering pH, whereas the Pb threshold (pH > 6, CEC ≥ 20 cmolc kg-1) was 3.1 times lower than the current threshold. The derived thresholds for five elements were validated to be reliable through literature data and field experiments. The results suggested that deriving soil heavy metal(loid)s threshold using SSD method and local food safety standards is feasible and also applicable to other crops as well as other regions with potential health risks of toxic elements contamination in agricultural production.
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Metales Pesados/normas , Oryza/crecimiento & desarrollo , Contaminantes del Suelo/normas , Suelo/normas , Arsénico/análisis , Arsénico/normas , Cadmio/análisis , Cadmio/normas , Cromo/análisis , Cromo/normas , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/normas , Inocuidad de los Alimentos , Humanos , Plomo/análisis , Plomo/normas , Mercurio/análisis , Mercurio/normas , Metales Pesados/análisis , Oryza/química , Oryza/genética , Suelo/química , Contaminantes del Suelo/análisisRESUMEN
BACKGROUND: Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyperproliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. METHODS: HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. RESULTS: Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. CONCLUSIONS: Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.
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Adyuvantes Inmunológicos , Antiinflamatorios , Imiquimod , Inflamación , Psoriasis , Umbeliferonas , Adyuvantes Inmunológicos/efectos adversos , Animales , Antiinflamatorios/farmacología , Proliferación Celular , Humanos , Imiquimod/efectos adversos , Inflamación/tratamiento farmacológico , Queratinocitos , Ratones , Ratones Endogámicos BALB C , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Conejos , Umbeliferonas/farmacologíaRESUMEN
BACKGROUND: Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the population worldwide. Hyperproliferative keratinocytes were thought to be an amplifier of inflammatory response, thereby sustaining persistence of psoriasis lesions. Agents with the ability to inhibit keratinocyte proliferation or induce apoptosis are potentially useful for psoriasis treatment. 18ß-Glycyrrhetinic acid (GA), an active metabolite of glycyrrhizin, exhibits diverse pharmacological activities, including anti-inflammatory, anti-bacteria and anti-proliferation. The current study aims to evaluate the effects of GA on the proliferation and apoptosis of human HaCaT keratinocytes in vitro and investigate the effects of GA on the skin lesions of imiquimod (IMQ)-induced psoriasis-like mouse model in vivo. METHODS: Cell viability was assayed by CCK-8. Flow cytometry was performed to measure apoptosis and reactive oxygen species (ROS), with Annexin V-FITC/PI detection kit and DCFH-DA probe respectively. Caspase 9/3 activities were measured using caspase activity assay kits. The protein levels of Akt and p-Akt were determined using Western blotting. IMQ was applied to induce psoriasis-like skin lesions in mice. The histological change in mouse skin lesions was detected using hematoxylin and eosin (H&E) staining. The severity of skin lesions was scored based on Psoriasis Area Severity Index (PASI). RT-PCR was employed to examine the relative expression of TNF-α, IL-22 and IL-17A in mouse skin lesions. RESULTS: GA decreased HaCaT keratinocytes viability and induced cell apoptosis in a dose-dependent manner. In the presence of GA, intracellular ROS levels were significantly elevated. NAC, a ROS inhibitor, attenuated GA-mediated HaCaT keratinocytes growth inhibition and apoptosis. In addition, GA treatment remarkably decreased p-Akt protein level, which could be restored partially when cells were co-treated with GA and NAC. LY294002 (a PI3K inhibitor) treatment significantly enhanced GA-mediated cytotoxicity. Moreover, GA ameliorated IMQ-induced psoriasis-like skin lesions in mice. CONCLUSIONS: GA inhibits proliferation and induces apoptosis in HaCaT keratinocytes through ROS-mediated inhibition of PI3K-Akt signaling pathway, and ameliorates IMQ-induced psoriasis-like skin lesions in mice.
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Ácido Glicirretínico/análogos & derivados , Psoriasis/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Citocinas/genética , Femenino , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/uso terapéutico , Humanos , Imiquimod , Queratinocitos/efectos de los fármacos , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Psoriasis/inducido químicamente , Psoriasis/metabolismo , Psoriasis/patología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patologíaRESUMEN
BACKGROUND: Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyper-proliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. METHODS: HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. RESULTS: Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. CONCLUSIONS: Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.
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Humanos , Animales , Ratones , Conejos , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Umbeliferonas/farmacología , Adyuvantes Inmunológicos/efectos adversos , Imiquimod/efectos adversos , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Queratinocitos , Proliferación Celular , Ratones Endogámicos BALB CRESUMEN
Class III medical devices are defined as those which are implanted inside the human body and applied to maintain normal life and retain original tissue or organic functions. Because these devices are associated with high risk, their effectiveness and safety should be strictly monitored and clinically investigated. The aim of clinical investigation of these medical devices is to ensure the acceptability of their effectiveness and safety levels. On designing the clinical trial, the investigator should determine the indices to assess the effectiveness and safety of medical devices, select reasonable data-analyzing methods, and pay attention to several other issues. Although some guidelines on specific class III medical devices have illustrated those aspects in detail, there is still no comprehensive report that details all those principles and methodologies. This article aims to summarize the common features among the instruction principles and provide technological support for the clinical study of class III medical devices.
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Ensayos Clínicos como Asunto , Seguridad de Equipos , Equipos y Suministros/normas , Proyectos de Investigación , China , HumanosRESUMEN
BACKGROUD: The red spider mite Tetranychus urticae is known as a worldwide pest in cassava production which can caused serious economic losses. Because no threshold levels are established for T. urticae in cassava cropping, many growers in China are applying excessive chemical applications per cassava cropping period. This is not only expensive, but also results in lower yields because of severe leaf damage and development of resistance. This study aims to develop an immediate threshold level for T. urticae control which could be determined in the laboratory and fit the field application requirements. RESULTS: The mite density of 25 mites/leaf was the threshold which caused significant decrease of photosynthetic pigment contents and protective enzyme activities in cassava leaves in the laboratory. Moreover, 25 mites/leaf was also the threshold density which resulted in significantly lower leaf damage and higher yield levels compared with a higher level of mites/leaf where calendar sprays were used. CONCLUSION: The mite density threshold that brought about significant physiological and biochemical changes in the laboratory basically coincided with the threshold that resulted in significant yield loss in the field. It is therefore concluded that the optimum threshold acaricide spray for T. urticae on cassava is 25 mites/leaf. © 2019 Society of Chemical Industry.
Asunto(s)
Acaricidas , Manihot , Tetranychidae , Control de Ácaros y Garrapatas , Animales , China , Manihot/crecimiento & desarrollo , Densidad de Población , Tetranychidae/fisiologíaRESUMEN
A green method was proposed for respectively recovering rare earths (REEs) under super-gravity from rare-earth tailings which are massively stockpiled in the Bayan Obo tailings dams. Firstly, the REEs (Ce, La, Pr, Nd) were discovered to be precipitated as the rare earth oxyfluoride, rare earth ferrate and britholite phases respectively at various temperature ranges of 1773-1673 K, 1673-1473 K and 1473-1373 K. However, the Re-rich phases were intimately intertwined with each other in the normal-gravity. Consequently, respective recovery of REEs (Ce, La, Pr, Nd) at their corresponding precipitation temperatures was conducted under the super-gravity. 98.38% of (Ce) were firstly enriched into the rare earth oxyfluoride and separated from the tailings as driven by the super-gravity, 97.70% of (La) were enriched into the rare earth ferrate and separated subsequently, and the residual REEs were precipitated further into britholite. Accordingly, high-purity of rare earth oxyfluoride, rare earth ferrate and britholite phases were attained respectively, achieving the green and efficient recovery of REEs (Ce, La, Pr, Nd) from the tailings with no additives, no hazardous wastes and no secondary pollution.