•Topical application of 0.6% metformin cream alleviates the manifestation of skin damage in UVB-challenged mice.•Metformin inhibits the secretion of IL-1β and cell death in UVB-challenged ...keratinocytes.•Metformin treatment inhibits the increase in expression and nuclear translocation of C/EBPβ in UVB-challenged keratinocytes.
Excessive inflammation and cell death induced by ultraviolet (UV) cause skin photodamage. Metformin possesses anti-inflammatory and cytoprotective effects. However, whether metformin inhibits inflammation and cell death in UVB-induced acute skin damage is unclear.
To evaluate the anti-inflammatory and cytoprotective effects of metformin in vitro and in vivo. Furthermore, its potential mechanism has been explored.
Transcriptome sequencing and multiplex cytokines analysis were used to evaluate the validity of in vitro UVB-induced acute damage keratinocyte model and anti-inflammatory effects of metformin. We also determined the expression and nuclear translocation of CCAAT/enhancer-binding protein beta (C/EBPβ), an important transcriptional factor of Interleukin-1beta (IL-1β). Cell viability and cell death of keratinocytes were evaluated upon UVB irradiation in the presence or absence of metformin. 0.6% metformin cream was applied on UVB-irradiated mice to explore its pharmacological effects in vivo.
Transcriptional landscape of 50 mJ/cm2 UVB-irradiated HaCaT cells is typical of UVB-induced acute damage keratinocyte model in vitro. Metformin alleviated transcription and secretion of IL-1β, Tumor Necrosis Factor-alpha, and Fibroblast Growth Factor 2, expression and nuclear translocation of C/EBPβ in this model. Metformin also protected keratinocytes from cell death caused by UVB-induced cellular secretions, which contributed to its cytoprotective effects. Topical administration of 0.6% metformin cream alleviated UVB-induced skin damage in mice.
We proved the protective roles of metformin in UVB-challenged keratinocytes and UVB-irradiated mice, which indicated the potential value of metformin in topical therapy against skin photodamage.
Gasdermin E (GSDME)-mediated pyroptosis is induced in keratinocytes of UVB-challenged skin. The role of GSDME in UVB-caused skin damage remains unknown. To explore the role of GSDME in UVB-induced ...skin inflammation. We compared differences in skin appearance, histological features, keratinocyte death modalities, infiltration of immune cells, and levels of some inflammatory cytokines between Gsdme
mice and wild type (WT) mice after UVB exposure. We explored whether keratinocytes contribute to GSDME deficiency-caused aggravation of UVB-induced skin inflammation in GSDME knockdown keratinocyte cultured in vitro and keratinocyte-specific Gsdme conditional knockout mice. We used anti-Ly6G antibody to deplete neutrophils and explore their role in UVB-caused skin damage. Skin damage and neutrophils infiltration were aggravated in UVB-challenged Gsdme
mice, compared with UVB-challenged WT mice. Apoptosis and necroptosis, which were initiated together with GSDME-mediated pyroptosis in UVB-challenged WT mice, were not enhanced in UVB-challenged Gsdme
mice. Neutrophils activation indicators and its recruiting cytokines were increased in skin tissue of UVB-challenged Gsdme
mice. However, GSDME knockdown did not lead to the further increase of mRNA and secretion of TNF-α and IL-6 in UVB-challenged keratinocytes. Skin damage was not aggravated in UVB-challenged Gsdme cKO mice. Neutrophils depletion alleviated UVB-caused skin damage in WT mice and Gsdme
mice, and eliminated its aggravation in Gsdme
mice. This study demonstrates that GSDME plays a restrictive role in UVB-induced skin damage through inhibiting excessive recruitment and activation of neutrophils in the immune microenvironment in UVB-caused skin inflammation. However, keratinocytes might not contribute to this restrictive function.
Objective. The objective is to investigate the relationship between sepsis complicated with heart failure and the expression levels of CXC chemokine ligand 8 (CXCL8) and endothelin-1 (ET-1). Methods. ...A total of 128 sepsis patients accepted by the Ganzhou People’s Hospital from March 2019 to December 2021 were collected as observation objects, and they were separated into a simple sepsis group (86 cases) and a complicated heart failure group (42 cases) according to whether they were accompanied by heart failure or not. General data such as Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) were collected; the expression levels of serum CXCL8 and ET-1 were detected by enzyme-linked immunosorbent assay (ELISA); the cardiac function parameters such as left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac output (CO), and cardiac index (CI) were measured by color Doppler ultrasound; the correlation between serum CXCL8 and ET-1 expression levels with clinical data and cardiac function parameters in patients with sepsis complicated with heart failure was analyzed by the Pearson correlation; and the influencing factors of sepsis complicated with heart failure were analyzed by the logistic regression analysis. Results. The serum CXCL8 and ET-1 expression levels, SOFA score, and APACHE II score in the complicated heart failure group were higher than those in the simple sepsis group (P<0.05), and LVEF, SV, CO, and CI in the complicated heart failure group were lower than those in the simple sepsis group (P<0.05). Serum CXCL8 was positively correlated with ET-1 in patients with sepsis complicated with heart failure (r = 0.531, P<0.05), and the two were positively correlated with SOFA score and APACHE II score (P<0.05) and were negatively correlated with LVEF, SV, CO, and CI (P<0.05). CXCL8 and ET-1 were independent risk factors for sepsis complicated with heart failure (P<0.05). Conclusion. The expression levels of serum CXCL8 and ET-1 in sepsis patients with heart failure are significantly increased, and both are risk factors for heart failure in sepsis patients.
Ankylosing spondylitis (AS) is a progressive systemic disease characterized by a chronic inflammatory response in the sacroiliac joints and spine. Long noncoding RNAs suggest significant actions in ...the progression of AS. Therefore, a specific lncRNA, highly upregulated in liver cancer (HULC), was studied here regarding its functions and related mechanisms in AS.
Measurements of miR-556-5p, HULC, and YAP1 expression were performed on AS cartilage tissues and chondrocytes. The interaction between miR-556-5p and HULC or YAP1 was verified. CCK-8, flow cytometry and enzyme-linked immunosorbent assay were used to evaluate the effects of HULC, miR-556-5p, and YAP1 on the proliferation, apoptosis, and inflammatory response of AS chondrocytes. Furthermore, the action of HULC/miR-556-5p/YAP1 was experimentally observed in AS mice.
HULC and YAP1 levels were augmented, while miR-556-5p levels were suppressed in AS cartilage tissues and chondrocytes. Downregulating HULC or upregulating miR-556-5p stimulated chondrocyte proliferation and inhibited apoptosis and inflammation in AS. miR-556-5p was a downstream factor of HULC, and YAP1 was a potential target of miR-556-5p. The improvement effect of downregulated HULC on AS chondrocytes was saved when YAP1 expression was forced. In addition, silence of HULC improved the pathological injury of spinal cartilage in AS mice by enhancing miR-556-5p-related regulation of YAP1.
HULC inhibition relieves the inflammatory response in AS by reducing miR-556-5p-mediated YAP1 expression.
Fatty liver disease (FLD) is a common liver disease, which poses a great threat to people's health, but there is still no optimal method that can be used on a large-scale screening. This research is ...based on machine learning algorithms, using electronic physical examination records in the health database as data support, to a predictive model for FLD. The model has shown good predictive ability on the test set, with its AUC reaching 0.89. Since there are a large number of electronic physical examination records in most of health database, this model might be used as a non-invasive diagnostic tool for FLD for large-scale screening.
Abstract
Keratinocyte necroptosis (with proinflammatory characteristic) is required for epidermal damage in contact hypersensitivity (CHS). In DNCB-induced CHS mice model, we observed the aggravated ...keratinocyte death and increased phosphorylation level of MLKL, RIPK3 and RIPK1. However, CHS skin lesion did not present in keratinocyte-specific
Mlkl
knockout mice. We validated that MLKL-mediated keratinocyte necroptosis is required for epidermal damage in response to immune microenvironment in CHS. Moreover, MLKL-mediated necroptosis deficiency or inhibition resulted in blocking recruitment and activation of inflammatory cells in CHS via reducing HMGB1 release in keratinocytes. This study suggests that MLKL-mediated keratinocyte necroptosis functions as a self-amplified actor in inflammatory responses and could be considered as an effective therapeutic target. It proposes an innovative prospective that inhibiting keratinocyte necroptosis can prevent the development of epidermal damage in CHS.
Clearing the engineering characteristics of high plastic clay and its engineering application are the basis for rational use of high plastic clay to fill the embankment. In this study, a series of ...water content tests, relative density tests, liquid and plastic limit tests, the grain size analysis tests, compaction and California Bearing Ratio (CBR) tests were carried out based on high plastic clay of diseased subgrade along west-section of Hainan Beltline Freeway. The relationships between CBR and water content, coarse particle content and compaction energy were studied. The results indicated that water content, coarse particle content, and compaction energy had significant effect on CBR, and water content is the main impact factor on CBR values. The maximum CBR water content was greater than the optimal water content by 4% to 5%. The performance of CBR and dry density had obvious distinction under different consistency and compaction energy. The equilibrium water content of high plastic clay subgrade during highway running period was near the plastic limit, which is 6% to 13% higher than the optimal water content. Base on the indoor test results, the problems related to the application of high plastic clay in subgrade filling were analyzed considering the characteristics of highway engineering and climate in Hainan province. It was concluded that high plastic clay could be directly used for embankment filling when the compaction energy conducted under the maximum CBR water content.
Rotaviruses (RV) are important viral diarrheal agents in calves. Vaccination is an optimum measure to prevent bovine rotaviruses (BRV) infection. However, little research on BRV VP7 vaccine has been ...done and currently there is no BRV vaccine.
To prepare a subunit vaccine of BRV and investigate its efficacy.
Total RNA was extracted from MA104 cells infected with bovine rotavirus (BRV) strain GSB01. BRV VP7 gene was amplified using real time fluorescence quantitative PCR (qPCR). The pEASY-T3-VP7 plasmid was digested using HindⅢ and BamHI restriction endonucleases, then recombined into the prokaryotic expression vector pET32a. The pET32a-VP7 and pET32a-VP7-LTB (heat-labile enterotoxin B subunit) were transformed into BL21 (DE3) competent cells of Escherichia coli, respectively, and induced with IPTG, then analyzed using SDS-PAGE. Sixty mice were randomly divided into three groups (n=20). Group A mice was used as His-tag control and mice in group B and C were inoculated with pET32a-VP7 and pET32a-VP7-LTB, respectively. VP7 IgG antibody titers and protection efficiency of pET32a-VP7-LTB were further determined in neonatal mice challenged with GSB01 BRV strain.
SDS-PAGE analysis showed that the pET32a-VP7 was highly expressed in the BL21 (DE3) cells. PET32a-VP7 and pET32a-VP7-LTB protein could promote VP7 IgG antibody titer（8.33×103 vs. 17.26×103）in mice. Immunization protection ratios of pET32a-VP7 and pET32a-VP7-LTB proteins in the neonatal mice were 86.4% and 91.7%, respectively.
The fusion protein of pET32a-VP7-LTB had excellent immunogenicity and protected mice from BRV infection. Our findings can be used for further developing of a high-efficiency subunit vaccine of BRV.
With the rapid development of technologies such as cloud computing, big data, and the Internet of Things, the scale of data continues to grow. The recommendation system has become one of the ...important intelligent software to help users make decisions. The recommendation model based on user rating data is widely studied and applied, but the data sparsity problem and the cold start problem seriously affect the recommendation quality. In this paper, Multi-view Hybrid Recommendation Model (MHRM) based on deep learning is proposed. First, we use WLDA (an improved Latent Dirichlet Allocation method) to extract the vector representation of user review text, and then apply LSTM to contextual semantic level user review sentiment analysis. At the same time, the emotion fusion method based on user score embedding is proposed. The problems such as deviations between the user score and actual interest preference, and unbalanced distribution of the score level are solved. This paper has been tested on Amazon product data and compared with various classic recommendation algorithms, using Mean Absolute Error (MAE), hit rate and standardized discount cumulative return for performance evaluation. The experimental results show that the prediction of the MHRM proposed in this paper on the 7 recommendation data and the TopN recommendation index have been significantly improved.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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