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Background: The present study aimed to explore the biological role and underlying mechanism of the long non‐coding RNA actin filament‐associated protein 1‐antisense RNA1 (lncRNA AFAP1‐AS1) in the progression of tongue squamous cell carcinoma (TSCC). Methods: A quantitative reverse transcriptase‐PCR (RT‐qPCR) was conducted to assess relative levels of the miR‐133a‐5p, lncRNAs AFAP1‐AS1 and zinc finger family member 2 (ZIC2) in TSCC cell lines and specimens, whereas ZIC2 protein levels were measured using western blotting. After modifying the levels of expression of lncRNA AFP1‐AS1, miR‐133a‐5p and ZIC2 using lentivirus or plasmid transfection, we examined AKT/epithelial–mesenchymal transition signaling pathway alterations, in vivo carcinogenesis of TSCC in nude mice and in vitro malignant phenotypes. A dual‐luciferase reporter assay was conducted to confirm the targeting relationship between ZIC2 and miR‐133a‐5p, as well as between miR‐133a‐5p and lncRNA AFAP1‐AS1. Based on The Cancer Genome Atlas (TCGA) database, we additionally validated AFP1‐AS1. The potential biological pathway for AFP1‐AS1 was investigated using gene set enrichment analysis (GSEA). We also evaluated the clinical diagnostic capacities of AFP1‐AS1 and clustered the most potential biomarkers with the Mfuzz expression pattern. Finally, we also made relevant drug predictions for AFP1‐AS1. Results: In TSCC cell lines and specimens, lncRNA AFAP1‐AS1 was upregulated. ZIC2 was upregulated in TSCC cells as a result of lncRNA AFAP1‐AS1 overexpression, which also promoted TSCC cell migration, invasion, viability, and proliferation. Via the microRNA sponge effect, it was found that lncRNA AFAP1‐AS1 could upregulate ZIC2 by competitively inhibiting miR‐133a‐5p. Interestingly, knockdown of ZIC2 reversed the biological roles of lncRNA AFAP1‐AS1 with respect to inducing malignant phenotypes in TSCC cells. In addition, in vivo overexpression of lncRNA AFAP1‐AS1 triggered subcutaneous tumor growth in nude mice implanted with TSCC cells and upregulated ZIC2 in the tumors. The TCGA database findings revealed that AFAP1‐AS1 was significantly upregulated in TSCC specimens and had good clinical diagnostic value. The results of GSEA showed that peroxisome proliferator‐activated receptor signaling pathway was significantly correlated with low expression of AFP1‐AS1. Finally, the results of drug prediction indicated that the group with high AFAP1‐AS1 expression was more sensitive to docetaxel, AZD4547, AZD7762 and nilotinib. Conclusions: The upregulation of lncRNA AFAP1‐AS1, which increases TSCC cell viability, migration, proliferation and invasion via the AFAP1‐AS1/miR‐133a‐5p/ZIC2 axis, aids in the progression of TSCC. [ABSTRACT FROM AUTHOR]

Autoimmunity is reported involving in reproductive failures, and antinuclear antibody (ANA) positivity has been regarded as a typical feature of autoimmunity. Published studies on the association of ANA with reproductive failures including infertility are controversial. The aim of this meta‐analysis was to analyse whether the presence of ANA positivity increases the risk of infertility in women. We searched the PubMed and Embase databases for relevant literature without any restrictions prior to April 28, 2021. All analyses were performed using the RevMan 5.3 software. Twelve studies with 2734 participants, including 1482 patients with infertility, met the inclusion and exclusion criteria. The total positivity rate of ANA was 23.8% (353/1482) in all infertile patients and 8.5% (107/1252) in the control group. Infertile females had a significantly higher ANA positivity rate than the control group (odds ratio [OR] = 2.90, 95% confidence interval [CI]: 1.72–4.87, I2 = 65%, P <.0001). Several subgroup analyses were performed to reduce the heterogeneity. ANA positivity was associated with female infertility in studies either performed by indirect immunofluorescence (OR = 2.26, 95% CI:1.67–3.06, P <.00001) or by ELISA (OR = 10.76, 95% CI:1.82–63.64, P <.00001). ANA was significantly associated with increased risk of women infertility either after the definite exclusion of individuals with autoimmune diseases (AID) or without exclusion [(OR = 1.99, 95% CI:1.29–3.06, P =.002), (OR = 2.76, 95% CI:1.56–4.88, P =.0005), respectively]. This meta‐analysis provides a comprehensive overview of the prevalence of antinuclear antibodies (ANA) in infertile women and suggests that ANA positivity increases the risk of infertility. [ABSTRACT FROM AUTHOR]

Aim: Psilocin is an active metabolite form of psilocybin and exerts psychoactive effects. Recent studies suggest that psilocin may have regulatory effects on abuse drugs, but the mechanisms remain unclear. In this study, we want to explore the effects of psilocin on methamphetamine (METH)‐induced alterations of behavior in mice and its molecular mechanisms. Methods: Acute METH administration model and conditioned place preference (CPP) model were used to investigate the effects of psilocin on METH‐induced alterations of behavior. Western blot was used to detect the expression of proteins. Results: In the acute 2 mg/kg METH administration model, 1 mg/kg psilocin counteracted METH‐induced elevation of activity. In the 1 mg/kg METH‐induced CPP model, 1 mg/kg psilocin inhibited CPP formation during the acquisition phase. However, psilocin did not impact METH extinction and relapse. Molecular results showed that the regulatory effect of psilocin on METH was underscored by altered expression of dopamine 2 receptor (D2R) and phosphorylated extra‐cellular signal‐regulated kinase (p‐ERK) in the prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA). Trifluoperazine (TFP)‐2HCl is a D2R inhibitor, and SCH772984 is a selective extra‐cellular signal‐regulated kinase (ERK) inhibitor that effectively inhibits ERK1/2 phosphorylation. The results indicated that 2 mg/kg TFP‐2HCl and 10 mg/kg SCH772984 blocked METH‐induced hyperactivity and acquisition of METH‐induced CPP. Conclusion: Psilocin has regulatory effects on METH‐induced alterations of behavior in mice via D2R‐mediated signal regulation of ERK phosphorylation. [ABSTRACT FROM AUTHOR]

Background. The mortality rate of breast cancer (BC) ranks first among female tumors worldwide and presents a trend of younger age, which poses a great threat to women's health and life. Neoadjuvant chemotherapy (NAC) for breast cancer is defined as the first step of treatment for breast cancer patients without distant metastasis before planned surgical treatment or local treatment with surgery and radiotherapy. According to the current NCCN guidelines, patients with different molecular types of BC should receive neoadjuvant chemotherapy (NAC), which can not only achieve tumor downstaging, increase the chance of surgery, and improve the breast-conserving rate. In addition, it can identify new genetic pathways and drugs related to cancer, improve patient survival rate, and make new progress in breast cancer management. Objective. To explore the role of the nomogram established by the combination of ultrasound parameters and clinical indicators in the degree of pathological remission of breast cancer. Methods. A total of 147 breast cancer patients who received neoadjuvant chemotherapy and elective surgery in the Department of Ultrasound, Nantong Cancer Hospital, from May 2014 to August 2021 were retrospectively included. Postoperative pathological remission was divided into two groups according to Miller–Payne classification: no significant remission group (NMHR group, n = 93) and significant remission group (MHR group, n = 54). Clinical characteristics of patients were recorded and collected. The multivariate logistic regression model was used to screen the information features related to the MHR group, and then, a nomogram model was constructed; ROC curve area, consistency index (C-index, CI), calibration curve, and H-L test were used to evaluate the model. And the decision curve is used to compare the net income of the single model and composite model. Results. Among 147 breast cancer patients, 54 (36.7%) had pathological remission. Multivariate logistic regression showed that ER, reduction/disappearance of strong echo halo, Adler classification after NAC, PR + CR, and morphological changes were independent risk factors for pathological remission (P < 0.05). Based on these factors, the nomogram was constructed and verified. The area under the curve (AUC) and CI were 0.966, the sensitivity and specificity were 96.15% and 92.31%, and the positive predictive value (PPV) and negative predictive value (NPV) were 87.72% and 97.15%, respectively. The mean absolute error of the agreement between the predicted value and the real value is 0.026, and the predicted risk is close to the actual risk. In the range of HRT of about 0.0∼0.9, the net benefit of the composite evaluation model is higher than that of the single model. H-L test results showed that χ2 = 8.430, P = 0.393 > 0.05. Conclusion. The nomogram model established by combining the changes of ultrasound parameters and clinical indicators is a practical and convenient prediction model, which has a certain value in predicting the degree of pathological remission after neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Fibroblast‐like synoviocytes (FLS) are the main cell component in the inflamed joints of patients with rheumatoid arthritis (RA). FLS intimately interact with infiltrating T cells. Fibroblasts have potent inhibitory effects on T cells, leading to the resolution of inflammation and immune tolerance. However, this "regulatory" phenotype is defect in RA, and FLS in RA instead act as "proinflammatory" phenotype mediating inflammation perpetuation. Signals that orchestrate fibroblast heterogeneity remain unclear. Here, it is demonstrated that different cytokines can induce distinct phenotypes of FLS. Interferon‐gamma (IFN‐γ) is pivotal in inducing the regulatory phenotype of FLS (which is termed FLSreg) characterized by high expressions of several inhibitory molecules. Rapamycin enhances the effect of IFN‐γ on FLS. Based on the characteristics of FLSreg, a novel biomimetic therapeutic strategy for RA is designed by coating cell membrane derived from FLSreg induced by IFN‐γ and rapamycin on nanoparticles, which is called FIRN. FIRN show good efficacy, stability, and inflammatory joint targeting ability in an RA mouse model. The findings clarify how fibroblast phenotypes are modulated in the inflammatory microenvironment and provide insights into novel therapeutic designs for autoimmune diseases based on regulatory fibroblasts. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), which is among the most globally prevalent cancers, is strongly associated with liver cirrhosis. Using a bioinformatics approach, we have identified and investigated the hub genes responsible for the progression of cirrhosis into HCC. We analyzed the Gene Expression Omnibus (GEO) microarray datasets, GSE25097 and GSE17549, to identify differentially expressed genes (DEGs) in these two conditions and also performed protein-protein interaction (PPI) network analysis. STRING database and Cytoscape software were used to analyze the modules and locate hub genes following which the connections between hub genes and the transition from cirrhosis to HCC, progression of HCC, and prognosis of HCC were investigated. We used the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to detect the molecular mechanisms underlying the action of the primary hub genes. In all, 239 DEGs were obtained, with 94 of them showing evidence of upregulation and 145 showing evidence of downregulation in HCC tissues as compared to cirrhotic liver tissues. We identified six hub genes, namely, BUB1B, NUSAP1, TTK, HMMR, CCNA2, and KIF2C, which were upregulated and had a high diagnostic value for HCC. Besides, these six hub genes were positively related to immune cell infiltration. Since these genes may play a direct role in the progression of cirrhosis to HCC, they can be considered as potential novel molecular indicators for the onset and development of HCC. [ABSTRACT FROM AUTHOR]

Purpose: To investigate meibomian gland (MG) alteration in patients with systemic lupus erythematosus (SLE). Methods: This study included 23 SLE patients evaluated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and 21 healthy controls (HCs). All the subjects were evaluated with Ocular Surface Disease Index (OSDI) questionnaire, and the eyes were performed examinations of tear meniscus height (TMH), non-invasive keratographic tear film break-up time (NIKBUT), Schirmer I Test, MG eyelid score, meibography score, and in vivo confocal microscopy (IVCM) on the meibomian gland. Results: There was no significant difference between the SLE patients and the HCs in the TMH, NIKBUT, and Schirmer I Test. However, the SLE patients had higher MG eyelid scores and meibography scores on both upper eyelid and lower eyelid than the HCs. Through meibography observation, 34.8% of the SLE patients presented MG deficiency in Grade 3, whereas that of all the HCs were less than Grade 3. The SLE patients were found to have significant MG atrophy and vascular enrichment around the meibomian glands (MGs). The SLE patients were also found to have excessive inflammatory cell infiltration around the MGs, especially the typical lymph node-like foci of inflammatory cell infiltration. Conclusions: MG alteration can be found in the SLE patients. Examinations of the MGs can help diagnose or infer ocular diseases at an early stage of SLE. [ABSTRACT FROM AUTHOR]

Autoimmune or infectious diseases often instigate the undesirable damages to tissues or organs to trigger immune-related diseases, which involve plenty of immune cells, pathogens and autoantibodies. Nanomedicine has a great potential in modulating immune system. Particularly, biomimetic nanomodulators can be designed for prevention, diagnosis and therapy to achieve a better targeted immunotherapy. With the development of materials science and bioengineering, a wide range of membrane-coated nanomodulators are available. Herein, we summarize recent advancements of bioinspired membrane-coated nanoplatform for systemic protection against immune-related diseases including autoimmune and infectious diseases. We also rethink the challenges or limitations in the progress of the therapeutic nanoplatform, and discuss the further application of the nanomodulators in the view of translational medicine for combating immune-related diseases. Biomimetic nanomodulators can be designed for prevention, diagnosis and therapy to achieve a better targeted immunotherapy in autoimmune and infectious diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective. To study the expression of programmed cell death ligand-1 (PD-L1) and breast cancer susceptibility gene 1 (BRCA1) in triple-negative breast cancer (TNBC) patients and analyze their relationship with clinicopathological characteristics. Methods. 76 TNBC tissues were collected as the research object, while 60 adjacent tissues were used as controls. All patients underwent surgical treatment, and the expression of PD-L1 and BRCA1 in cancer tissues and adjacent tissues was detected by immunohistochemistry. At the same time, the relationship between PD-L1, BRCA1, and clinicopathological characteristics of patients with TNBC (including patient age, menopausal status, tumor size, lymph node metastasis, histological grade, Ki-67 expression, and p53 expression) were analyzed by univariate and logistic multivariate analysis. Results. The positive expression rate of PD-L1 in the TNBC group was 64.47%, which was higher than the control group by 41.67%. The positive expression rate of BRCA1 was 27.63%, which was lower than the control group by 48.33%. PD-L1 expression has no significant relationship with age, menopausal status, and p53 expression in TNBC patients. TNBC patients with tumors ≥2 cm, histological grade III, lymph node metastasis, and Ki-67 expression ≥20% had higher PD-L1 positive expression rates. The tumor size, Ki-67 expression, and PD-L1 expression of TNBC patients have independent effects. The expression of BRCA1 has no significant relationship with menopausal status, tumor size, Ki-67 expression, etc. TNBC patients with age <45 years, histological grade I or II, no lymph node metastasis, and high p53 expression positive rate had higher BRCA1 positive expression rate. The age of TNBC patients, p53 expression, and BRCA1 expression have independent effects. Conclusion. In TNBC cancer tissues, there is a high expression of PD-L1 and low expression of BRAC1. The tumor size, Ki-67 expression, and PD-L1 expression of TNBC patients have independent effects. The age of TNBC patients, p53 expression, and BRCA1 expression have independent effects. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α (TNF-α) inhibitors are the main types of biological conventional synthetic disease-modifying antirheumatic drugs and have efficacy in treating ankylosing spondylitis (AS) which is not sensitive for nonsteroidal anti-inflammatory drug. However, the impact of TNF-α inhibitors on immune cells in patients with AS is still clearly undefined, and the impact of immune cells on treatment response is also largely elusive. This study is aimed at evaluating the longitudinal changes of circulating immune cells after anti-TNF-α therapy and their associations with treatment response in AS patients. Thirty-five AS patients receiving the treatment of anti-TNF-α therapy were included into this prospective observational study. The frequencies of immune cells including Th1, Th2, Th17, regulatory T cell (Treg), T follicular helper cell (Tfh), and regulatory B cell (Breg) in the peripheral blood were measured by flow cytometry at baseline and 4 time points after therapy. The difference in the circulating immune cells between responders and nonresponders was compared. This study suggested that anti-TNF-α therapy could significantly reduce circulating proinflammatory immune cells such as Th17 and Tfh, but significantly increased the percentages of circulating Treg and Breg. Moreover, circulating Breg may be a promising predictor of response to anti-TNF-α therapy in AS patients. [ABSTRACT FROM AUTHOR]

Nowadays, the application of a UAV swarm is becoming more and more widespread in the military field, and more and more attention is paid to the security of mission resource allocation. However, the relay node forwarding in the wireless transmission process brings greater risks to data leakage, and the computing power and energy of the UAV consumption is limited, so a lighter solution is required. This paper proposes a mechanism for the safe allocation of UAV swarm mission resources based on random labels. Each task has a random label to solve the problem of database security and wireless transmission security in the process of UAV task assignment. Furthermore, a lightweight stream cipher encryption scheme is illustrated to ensure the security of the UAV database. The irreversible hash function SHA-256 and the lightweight foam structure hash function SPONGENT-128 are used to generate random labels and then allocate task resources. In the case of energy consumption, it reduces the possibility of the enemy successfully obtaining private data. The simulation results show that the scheme has good performance in terms of security and has better performance than existing methods in terms of throughput and delay, without increasing too much energy consumption. [ABSTRACT FROM AUTHOR]

Background. Multiple studies have reported the significance of the systemic immune-inflammation index (SII) in the prognosis of colorectal cancer (CRC), but no consensus has yet been reached. The purpose of this study was to systematically assess the prognostic value of SII in patients with CRC. Materials and Methods. We performed a systematic literature search in PubMed, Embase, and the Cochrane Library for eligible studies. The correlation between pretreatment SII and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) in CRC patients was evaluated by combining the hazard ratio (HR) and 95% confidence interval (CI). Results. Twelve studies involving 3919 patients were included. Comprehensive analysis results showed that high SII indicated poor OS in CRC patients (HR = 1.777 , 95% CI: 1.328-2.376). Compared with patients with low SII values, patients with high SII had lower PFS (HR = 1.658 , 95% CI: 1.189-2.311). Subgroup analysis further verified the above results. Conclusions. SII may be a noninvasive and powerful tool for predicting survival outcomes in CRC patients. However, more well-designed studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Immunologic mechanisms have been proposed as part of the pathogenesis mechanisms involved in recurrent pregnancy loss (RPL). Presence of positive antinuclear antibodies (ANA) is regarded as a typical feature of autoimmunity. Many studies had tried to clarify the association of ANA with RPL, but the conclusions were controversial. The aim of this meta-analysis was to assess whether ANA was positively associated with increased RPL risk. We searched PubMed and Embase databases for relevant literatures on the association between ANA positivity and RPL. The odds ratios (OR) with 95% confidence intervals (95%CI) were pooled using meta-analysis, and either fixed-effect or random-effect model was used based on heterogeneity across the included studies. Twenty-one studies with 5038 participants (including 2683 RPL patients and 2355 controls) met the inclusion criteria were included. The total positive rate of ANA was 22.0% (591/2683) in RPL group, and 8.3% (196/2355) in the control group. RPL patients had a significantly higher ANA positive rate than controls (OR = 2.97, 95%CI 1.91-4.64, P<0.00001; I² = 75%), and a significant association between positive ANA and unexplained RPL was also observed (OR = 3.27, 95%CI 2.01-5.31, P<0.00001; I² = 70%). ANA positivity was also significantly associated with increased risk of RPL in women without defined autoimmune diseases (OR = 2.23, 95%CI 1.40-3.55, P=0.0007). Subgroup analysis demonstrated low titers of ANA (1:40≤ANA≤1: 80) were not associated with RPL (OR = 2.44, 95%CI 0.42-14.06, P=0.32), while higher ANA titer (≥1:160) had a significant association with RPL (OR = 45.89, 95%CI 8.44-249.45, P<0.00001). A higher rate of homogenous pattern in RPL patients was observed (OR = 4.89, 95%CI 2.20-10.87, P<0.001), and no significant difference in speckled pattern or nucleolar pattern was found. This study demonstrated that ANA positivity was positively associated with increased RPL risk. ANA positivity is an important risk factor for RPL which needed to be screened among women with RPL. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptors (FGFRs) are frequently altered in a variety of human cancer cells and are overexpressed in hepatocellular carcinoma (HCC). Several literatures have proven that they are efficacious for HCC therapy, however, the underlying mechanism remains unclear. Here, we found FGFR4 was overexpressed in HCC cell lines HepG2 and Hep3B and we used PD173074, an FGFR4 inhibitor, to explore the role of FGFR4 and its underlying mechanism in these cell lines. The results showed that PD173074 significantly arrested HepG2 and Hep3B cells in G1 phase and inhibited cell proliferation. Furthermore, Western blot analysis revealed that PD173074 decreased the levels of P-FRS2α, P-ERK, CDK2, cyclin E and NF-κB (p65) in the nucleus while it increased the levels of ubiquitin and CUL3, an E3 ubiquitin ligase which involves in cyclin E degradation. Meanwhile, the data from RT-qPCR showed that PD173074 also decreased miR-141 level. In conclusion, these results suggest that FGFR4 is involved in HCC by ERK/CUL3/cyclin E signaling pathway, and the finding may provide a potential theoretical basis for treatment by targeting FGFR4 in HCC. [ABSTRACT FROM AUTHOR]

The role of host microbes in the pathogenesis of several diseases has been established, and altered microbiomes have been related to diseases. However, the variability of the urinary microbiome in individuals with gout has not been evaluated to date. Therefore, we conducted the present prospective study to characterize the urinary microbiome and its potential relation to gout. Urine samples from 30 patients with gout and 30 healthy controls were analyzed by Illumina MiSeq sequencing of the 16S rRNA hypervariable regions, and the microbiomes were compared according to alpha-diversity indices, complexity (beta diversity) with principal component analysis, and composition with linear discriminant analysis effect size. The most significantly different taxa at the phylum and genus levels were identified, and their potential as biomarkers for discriminating gout patients was assessed based on receiver operating characteristic (ROC) curve analysis. Compared with the healthy controls, there was a dramatic decrease in microbial richness and diversity in the urine of gout patients. The phylum Firmicutes and its derivatives (Lactobacillus_iners, Family_XI, and Finegoldia), the phylum Actinobacteria and its derivatives (unidentified_Actinobacteria, Corynebacteriales, Corynebacteriale, Corynebacterium_1, and Corynebacterium_tuberculostearicum), and the genera Prevotella and Corynebacterium_1 were significantly enriched in the urine of gout patients. ROC analysis indicated that the top five altered microbial genera could be reliable markers for distinguishing gout patients from healthy individuals. These findings demonstrate that there are specific alterations in the microbial diversity of gout patients. Thus, further studies on the causal relationship between gout and the urinary microbiome will offer new prospects for diagnosing, preventing, and treating gout. [ABSTRACT FROM AUTHOR]

Improving the seismic time–frequency resolution is a crucial step for identifying thin reservoirs. In this paper, we propose a new high‐precision time–frequency analysis algorithm, synchroextracting generalized S‐transform, which exhibits superior performance at characterizing reservoirs and detecting hydrocarbons. This method first calculates time–frequency spectra using generalized S‐transform; then, it squeezes all but the most smeared time–frequency coefficients into the instantaneous frequency trajectory and finally obtains highly accurate and energy‐concentrated time–frequency spectra. We precisely deduce the mathematical formula of the synchroextracting generalized S‐transform. Synthetic signal examples testify that this method can correctly decompose a signal and provide a better time–frequency representation. The results of a synthetic seismic signal and real seismic data demonstrate that this method can identify some reservoirs with thincknesses smaller than a quarter wavelength and can be successfully applied for hydrocarbon detection. In addition, examples of synthetic signals with different levels of Gaussian white noise show that this method can achieve better results under noisy conditions. Hence, the synchroextracting generalized S‐transform has great application prospects and merits in seismic signal processing and interpretation. [ABSTRACT FROM AUTHOR]

Abstract Psoriasis (PSO) is a chronic inflammatory skin disease characterized with skin lesions and abnormal keratinocyte proliferation. The immune dysregulation is involved in the pathogenesis of PSO. However, the detail of immune regulation in PSO is still not very clear. Gαq, the alpha subunit of the Gq protein, played important role in the immune regulation. In this study, we aimed to investigate whether Gαq was involved in the pathogenesis of PSO. We detected the Gαq expression level and analyzed its relationship with test parameters of PSO patients. Furthermore, we used imiquimod to induce PSO mouse model in Gnaq -/- bone marrow (BM) chimeric mice. The inflammatory cytokines and its correlation with Gαq expression were analyzed both in PSO patients and mice. The results showed that the Gαq expression in PSO patients was much lower and negatively correlated with PSO Area and Severity Index (PASI), CRP, cholesterol and low-density lipoprotein. In PSO mice models, the skin lesion and keratinocyte proliferation were much more serious in Gnaq -/- BM chimeric mice. Also, the proportions of Th17 cells in Gnaq -/- BM chimeric mice were much higher than WT mice. Furthermore, the IL-17A and TNF-α in Gnaq -/- chimeric mice were also higher. Moreover, IL-17A and TNF-α in PSO patients were negatively associated with the Gαq expression. Our results indicated that Gαq was involved in the pathogenesis of PSO, and its regulation on Th17 cell differentiation and cytokine production might contribute to part of the mechanism of immune dysfunction of PSO. Highlights • Gαq expression was much lower in PBMC of psoriasis patients and negatively correlated with disease activity. • Gαq expression was negatively correlated with the CRP, cholesterol and low-density lipoprotein in psoriasis patients. • Imuquimod induced much serious psoriasis like inflammation in Gnaq knock out bone marrow chimeric mice. • The proportions of Th17 cells in Gnaq -/- chimeric were much higher than WT chimeric mice when treating with imiquimod. • The IL-17A and TNF-α were negatively related with the Gαq expression in PSO patients and in Gnaq -/- chimeric mice. [ABSTRACT FROM AUTHOR]

Aims: Tumor endothelial cells (TECs) have been investigated using human tumor xenografts in mice models. In order to provide pure human TECs for the updating of clinical anti‐angiogenic cancer therapy, in the present study we established a protocol of purification of TECs derived from clinical hepatocellular carcinoma (HCC) and revealed the TEC features by in vitro and in vivo assays. Methods: We isolated TECs from fresh surgical resections of HCC by magnetic‐activated cell sorting and purified by flow cytometry sorting upon CD31 expression, referred to as ECDHCCs. Next, we identified cultured ECDHCCs by morphology, phenotype, genotype, and functional assays. Results: The ECDHCCs appeared as Weibel–Palade bodies under electron microscopy. They expressed endothelial markers, such as CD31, CD105, and vascular endothelial growth factor receptor 2, and expressed the genes that are associated with pro‐angiogenesis, especially vascular endothelial growth factor, epiregulin, and programmed cell death 10. Functionally, ECDHCCs were capable of tube formation, wound healing, and Transwell migration in vitro. These in vitro behaviors were validated by in vivo Matrigel plug assay in mice. Finally, comparison of ECDHCC with the Hep‐G2 liver cancer cell line showed there was no similarity of phenotype or function between these two types of cells. Conclusions: Tumor endothelial cells derived from human HCC can be isolated and purified from clinical samples by flow cytometer. They have the endothelial phenotype and morphologic features and are capable of tube formation and migration. This study provides a useful model for researchers to study tumor angiogenesis and screening of candidate targets. [ABSTRACT FROM AUTHOR]

Tumor endothelial cells (TECs) have been isolated from solid tumors by using immunological magnetic beads and magnetic active cell sorting, and lead to a more precise way to investigate tumor angiogenesis as well as screening of vascular targeting drugs. However, the question of which endothelial marker is a stable molecular signature in TECs and can be used for the isolation of TECs from tumor tissues remains unclear. In this study, we investigated the endothelial markers CD105 and CD31 in the tumor vessels from 90 patients with hepatocellular carcinoma (HCC) by tissue microarray, in addition to their expression in TECs isolated from fresh tissues resected from 11 patients with HCC by flow cytometry and confocal microscopy. The results revealed that among 90 cases of TMA, all tumor vessels were CD31 positive whereas 39 cases (43.3%) had little or no CD105 expression in tumors and their vessels but not peritumoral tissue spots, and that among these 39, 29 cases (74.4%) were poor-differentiated HCC. These findings were further verified by flow cytometry and confocal analysis of TECs isolated from HCC. Overall, the results suggested that CD105 may not be expressed in TECs derived from poor-differentiated HCC cases. In addition, combined with previous studies in which CD105 is not only expressed in TECs, but also in tumor cells, the results indicated a high risk of contamination with CD105+ tumor cells. Thus, there is a limitation to the use CD105 as an endothelial marker for the isolation of TECs. [ABSTRACT FROM AUTHOR]