Safety and efficacy of Deucravacitinib for moderate to severe plaque psoriasis: A meta-analysis.

BACKGROUND: To systematically evaluate the safety and efficacy of Deucravacitinib for moderate to severe plaque psoriasis. MATERIALS AND METHODS: Randomized controlled trials (RCTs) of Deucravacitinib for moderate to severe plaque psoriasis in PubMed, Cochrane Library, Embase, and Web of Science were searched from database establishment to April 2023. Literature quality was independently evaluated by two investigators using the Cochrane risk-of-bias assessment tool, and the systematic analysis was made using StateSE15 and RevMan 5.3 software. RESULTS: Four RCTs were included, including 1751 patients with moderate to severe plaque psoriasis. Meta-analysis showed that the differences in efficacy and adverse events (AEs) between the Deucravacitinib group and placebo group were significant (p < 0.05). The patients in the Deucravacitinib group took orally 3-12 mg daily for 12 sequential weeks or 6 mg daily for 52 sequential weeks. Psoriasis Area and Severity Index (PASI) reduced by 75% (PASI 75), (PASI 90), and (PASI 100), static Physician Global Assessment (sPGA) of 0 or 1 (sPGA 0/1), Dermatology Life Quality Index of 0 or 1 (DLQI 0/1), and Psoriasis Symptoms and Signs Diary (PSSD) were significantly higher in the Deucravacitinib group compared to the placebo group, with significant differences (p < 0.05). The most frequently encountered AEs after treatment in the Deucravacitinib group was nasopharyngitis. CONCLUSION: Oral administration of Deucravacitinib is effective for moderate to severe plaque psoriasis. Attention should be paid to the occurrence of AEs, and more RCTs are required to evaluate the relationship between the dose and safety and efficacy.

Triple Surgical Technique for the Repair of Auricular Keloids: Achieving Perfect Restoration of the Ear Contour.

BACKGROUND: Ear keloids, often resulting from ear piercing or other traumas, significantly alter appearance, adversely impacting patients' quality of life and psychological well-being. Thus, developing an effective and esthetically pleasing surgical repair technique is crucial for enhancing patient quality of life. METHODS: This study introduces a novel tripartite surgical approach, which includes arcuate incision design, blind dissection for scar flap, and centrifugal keloid core serial shave excision (ABC for short). This technique is particularly suited for keloids induced by ear piercing that are inoperable for direct suturing or where direct suturing significantly alters the ear contour. RESULTS: In this study, 17 patients underwent the surgical treatment without observing special complications such as infection or necrosis. Long-term postoperative follow-up demonstrated good restoration of the ear contour, with only one case of recurrence. Patients expressed satisfaction with both the surgical process and outcomes. CONCLUSIONS: The triple surgical technique (ABC surgery method) for treating auricular keloids has demonstrated excellent repair results, significantly improving auricle shape. Despite relying on the surgeon's experience, keloid characteristics, and patient comorbidities, it provides an effective treatment option. When combined with local radiotherapy, the recurrence rate is also significantly controlled. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Selenium uptake, translocation, subcellular distribution and speciation in winter wheat in response to phosphorus application combined with three types of selenium fertilizer.

BACKGROUND: Selenium (Se) deficiency causes a series of health disorders in humans, and Se concentrations in the edible parts of crops can be improved by altering exogenous Se species. However, the uptake, transport, subcellular distribution and metabolism of selenite, selenate and SeMet (selenomethionine) under the influence of phosphorus (P) has not been well characterized. RESULTS: The results showed that increasing the P application rate enhanced photosynthesis and then increased the dry matter weight of shoots with selenite and SeMet treatment, and an appropriate amount of P combined with selenite treatment increased the dry matter weight of roots by enhancing root growth. With selenite treatment, increasing the P application rate significantly decreased the concentration and accumulation of Se in roots and shoots. P1 decreased the Se migration coefficient, which could be attributed to the inhibited distribution of Se in the root cell wall, but increased distribution of Se in the root soluble fraction, as well as the promoted proportion of SeMet and MeSeCys (Se-methyl-selenocysteine) in roots. With selenate treatment, P0.1 and P1 significantly increased the Se concentration and distribution in shoots and the Se migration coefficient, which could be attributed to the enhanced proportion of Se (IV) in roots but decreased proportion of SeMet in roots. With SeMet treatment, increasing the P application rate significantly decreased the Se concentration in shoots and roots but increased the proportion of SeCys2 (selenocystine) in roots. CONCLUSION: Compared with selenate or SeMet treatment, treatment with an appropriate amount of P combined with selenite could promote plant growth, reduce Se uptake, alter Se subcellular distribution and speciation, and affect Se bioavailability in wheat.

CXCL11 negatively regulated by MED19 favours antitumour immune infiltration in breast cancer.

BACKGROUND: Through microarray results, we found that the C-X-C motif chemokine ligand 11 (CXCL11) was negatively regulated by mediator complex subunit 19 (MED19), a protumour factor. However, the biological role and potential mechanism of CXCL11 need to be explored in breast cancer (BRCA). METHODS: The BRCA dataset was obtained from the Cancer Genome Atlas (TCGA) dataset. Our microarray data and the BRCA dataset of TCGA were analysed and visualized using the R software package. The mRNA and protein levels were measured by qRT-PCR and western blotting. RESULTS: Inhibition of MED19 in MDA-MB-231 cells caused CXCL11 upregulation. The relative positive regulation of cytokine pathways was enriched after MED19 knockdown. High CXCL11 was determined to be positively correlated with immune response activation, increased antitumour immune cell infiltration, immune checkpoint molecule expression, and enhanced sensitivity to immunotherapy and chemotherapy. Collectively, CXCL11 promoted antitumour immunity and was regulated by MED19 in BRCA. Clarifying the prognostic value and underlying mechanism of CXCL11 in BRCA could provide a theoretical basis to find new diagnostic and therapeutic targets.

LINC00536 Promotes Breast Cancer Progression by Regulating ROCK1 via Sponging of miR-214-5p.

Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play a significant role in regulating gene expression and participating in the progression of various malignancies. In our study, by analyzing data from The Cancer Genome Atlas (TCGA), LINC00536 was found to be highly expressed in breast cancer (BC) tissues, but its function and clinical significance in BC are still unknown. Therefore, we aimed to explore the role and molecular mechanism of LINC00536 in BC. We collected human BC tissue specimens and validated that LINC00536 was overexpressed in BC tissues. Increased LINC00536 expression was associated with advanced TNM stage, larger tumor diameter, lymph node metastasis and poor prognosis in patients with BC. Univariate and multivariate Cox regression analyses showed that high LINC00536 expression was an independent prognostic risk factor for overall survival in BC patients. Furthermore, quantitative reverse transcription PCR (qRT-PCR) showed that LINC00536 was upregulated in BC cell lines. Then, we confirmed that LINC00536 silencing-inhibited BC cell proliferation, migration, and invasion and led to cell cycle arrest in vitro. Animal experiments showed that knockdown of LINC00536 expression suppressed tumorigenesis in vivo. Mechanistically, LINC00536 serves as a ceRNA for miR-214-5p, increasing the expression of ROCK1, which acts as a tumor promoter in BC. Rescue assays revealed that miR-214-5p inhibition or ROCK1 overexpression could neutralize the suppressive effects of LINC00536 knockdown on cell proliferation, migration and invasion. Our data indicated that LINC00536 accelerates BC progression by regulating the miR-214-5p/ROCK1 pathway, which might provide a new perspective to investigate the development process of BC.

The monocyte to lymphocyte ratio not only at baseline but also at relapse predicts poor outcomes in patients with hepatocellular carcinoma receiving locoregional therapy.

BACKGROUND: Monocyte to lymphocyte ratio (MLR) represents a pro-inflammatory immune microenvironment. The aim of this study was to elucidate the effect of MLR and subsequent MLR when relapse occurred (R-MLR) on prognosis for hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) combined with ablation. METHODS: A prospective analysis was conducted on 606 patients with HCC who were treated with TACE combined with local ablation in Beijing You'an Hospital affiliated to Capital Medical University from January 1, 2012 to December 31, 2016. MLR or R-MLR were stratified according to the optimal cut-off values. The cumulative recurrence-free survival (RFS), overall survival (OS) , and recurrence-death survival (RDS) rates were calculated by Kaplan-Meier method. The Cox proportion hazard model and logistic regression analysis was conducted to screen for independent predictive factors for indicating early relapse and long-term prognosis. RESULTS: High MLR was significantly associated with relapse, early recurrence, and overall survival. After a median follow-up of 59.4 months, The cumulative 1-, 3-, 5-year RFS rates of low MLR were 74.6%, 43.8%, and 34.0%; while 66.1%, 32.2%, and 22.6% for high group (P < 0.001). There were also significant differences in corresponding OS rates of the two groups (P = 0.003). The cumulative 1-, 3-, 5-year OS rates of low R-MLR were 99.5%, 87.2%, 75.5%; while 98.3%, 78.3%, 61.7% for high group (P < 0.001). There were also significant differences in corresponding RDS rates in the two groups (P = 0.008). 436 patients were divided into four groups on the base of cut-off values of MLR and R-MLR (low-low, low-high, high-low, and high-high). The low-low group has shown better outcomes including the cumulative 1-, 3-, 5-year OS, and RDS rates(P < 0.001). CONCLUSIONS: High MLR was related to unfavorable outcome. Subsequent change of MLR between baseline and HCC relapse could indicate poor long-term survival after relapse.

Effects of Tai Chi Exercise on Balance Function in Stroke Patients: An Overview of Systematic Review.

Background: Tai chi (TC) has received increased attention in stroke rehabilitation, yet services are greatly underutilized. An increasing number of systematic reviews and meta-analyses (SRs/MAs) have begun to investigate the effects of TC on balance function in stroke patients. The aim of this current study was to systematically collate, appraise, and synthesize the results of these SRs/MAs using a systematic overview. Methods: Eight databases were searched: PubMed, Cochrane Library, Embase, Web of Science, CNKI, SinoMed, Chongqing VIP, and Wanfang Data. SRs/MAs of TC on balance function in stroke patients were included. Literature selection, data extraction, and assessment of the review quality were performed by two independent reviewers. Methodological quality was assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), reporting quality by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and evidence quality by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: Nine SRs/MAs were included in this study. For methodological quality, what resulted in unsatisfactory methodological quality was noncompliance with critical item 4 (using a comprehensive literature search strategy) and critical item 7 (providing the list of excluded research literature). For reporting quality, what resulted in unsatisfactory reporting quality was inadequate reporting of Q1 (protocol and registration), Q8 (search), Q15 (risk of bias across studies), Q16 (additional analyses), Q22 (risk of bias across studies), Q23 (additional analysis), and Q27 (funding). For GRADE, the evidence quality was high in 0, moderate in 3, low in 11, and very low in 6. Risk of bias was the most common factor leading to downgrading of evidence, followed by inconsistency, imprecision, publication bias, and indirectness. Conclusions: TC may have beneficial effects on balance function in stroke survivors; however, this finding is limited by the generally low methodology, reporting quality, and evidence quality for published SRs/MAs.

YOLO-SASE: An Improved YOLO Algorithm for the Small Targets Detection in Complex Backgrounds.

To improve the detection ability of infrared small targets in complex backgrounds, an improved detection algorithm YOLO-SASE is proposed in this paper. The algorithm is based on the YOLO detection framework and SRGAN network, taking super-resolution reconstructed images as input, combined with the SASE module, SPP module, and multi-level receptive field structure while adjusting the number of detection output layers through exploring feature weight to improve feature utilization efficiency. Compared with the original model, the accuracy and recall rate of the algorithm proposed in this paper were improved by 2% and 3%, respectively, in the experiment, and the stability of the results was significantly improved in the training process.

EYA2 suppresses the progression of hepatocellular carcinoma via SOCS3-mediated blockade of JAK/STAT signaling.

BACKGROUND: Somatic mutations are involved in hepatocellular carcinoma (HCC) progression, but the genetic mechanism associated to hepatocarcinogenesis remains poorly understood. We report that Eyes absent homolog 2 (EYA2) suppresses the HCC progression, while EYA2(A510E) mutation identified by exome sequencing attenuates the tumor-inhibiting effect of EYA2. METHODS: Whole-exome sequencing was performed on six pairs of human HCC primary tumors and matched adjacent tissues. Focusing on EYA2, expression level of EYA2 in human HCC samples was evaluated by quantitative real-time PCR, western blot and immunohistochemistry. Loss- and gain-of-function studies, hepatocyte-specific deletion of EYA2 (Eya2-/-) in mice and RNA sequencing analysis were used to explore the functional effect and mechanism of EYA2 on HCC cell growth and metastasis. EYA2 methylation status was evaluated using Sequenom MassARRAY and publicly available data analysis. RESULTS: A new somatic mutation p.Ala510Glu of EYA2 was identified in HCC tissues. The expression of EYA2 was down-regulated in HCC and associated with tumor size (P = 0.001), Barcelona Clinic Liver Cancer stage (P = 0.016) and tumor differentiation (P = 0.048). High level of EYA2 was correlated with a favorable prognosis in HCC patients (P = 0.003). Results from loss-of-function and gain-of-function experiments suggested that knockdown of EYA2 enhanced, while overexpression of EYA2 attenuated, the proliferation, clone formation, invasion, and migration of HCC cells in vitro. Delivery of EYA2 gene had a therapeutic effect on inhibition of orthotopic liver tumor in nude mice. However, EYA2(A510E) mutation led to protein degradation by unfolded protein response, thus weakening the inhibitory function of EYA2. Hepatocyte-specific deletion of EYA2 in mice dramatically promoted diethylnitrosamine-induced HCC development. EYA2 was also down-regulated in HCC by aberrant CpG methylation. Mechanically, EYA2 combined with DACH1 to transcriptionally regulate SOCS3 expression, thus suppressing the progression of HCC via SOCS3-mediated blockade of the JAK/STAT signaling pathway. CONCLUSIONS: In our study, we identified and validated EYA2 as a tumor suppressor gene in HCC, providing a new insight into HCC pathogenesis.

Let-7 mediated airway remodelling in chronic obstructive pulmonary disease via the regulation of IL-6.

BACKGROUND: Myofibroblast differentiation and extracellular matrix (ECM) deposition are observed in chronic obstructive pulmonary disease (COPD). However, the mechanisms of regulation of myofibroblast differentiation remain unclear. MATERIALS AND METHODS: We detected let-7 levels in peripheral lung tissues, serum and primary bronchial epithelial cells of COPD patients and cigarette smoke (CS)-exposed mice. IL-6 mRNA was explored in lung tissues of COPD patients and CS-exposed mice. IL-6 protein was detected in cell supernatant from primary epithelial cells by ELISA. We confirmed the regulatory effect of let-7 on IL-6 by luciferase reporter assay. Western blotting assay was used to determine the expression of α-SMA, E-cadherin and collagen I. In vitro, cell study was performed to demonstrate the role of let-7 in myofibroblast differentiation and ECM deposition. RESULTS: Low expression of let-7 was observed in COPD patients, CS-exposed mice and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased IL-6 was found in COPD patients, CS-exposed mice and CSE-treated HBE cells. Let-7 targets and silences IL-6 protein coding genes through binding to 3' untranslated region (UTR) of IL-6. Normal or CSE-treated HBE cells were co-cultured with human embryonic lung fibroblasts (MRC-5 cells). Reduction of let-7 in HBE cells caused myofibroblast differentiation and ECM deposition, while increase of let-7 mimics decreased myofibroblast differentiation phenotype and ECM deposition. CONCLUSION: We demonstrate that CS reduced let-7 expression in COPD and, further, identify let-7 as a regulator of myofibroblast differentiation through the regulation of IL-6, which has potential value for diagnosis and treatment of COPD.

LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK signalling pathway.

Long non-coding RNAs (lncRNAs) are regarded as important functional regulators of various biological processes and are also known to be involved in the occurrence and development of human cancers, including breast cancer (BC). In our present study, the RNA expression profiling data for a large cohort of human BC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the differentially expressed lncRNAs were screened out. We found that the expression of ST8SIA6-AS1 was elevated in BC tumour tissues compared with the adjacent normal tissues in the samples from the TCGA and GEO datasets, as well as in 138 BC tissue samples obtained by us. The high expression of ST8SIA6-AS1 was associated with estrogen receptor-negative, progesterone receptor-negative, advanced tumour-node-metastasis stage and worse survival in BC patients. In vitro functional studies revealed that high expression of ST8SIA6-AS1 promoted proliferation, invasion and migration of BC cell lines. The results of the in vivo studies indicated that upregulation of ST8SIA6-AS1 promoted xenograft tumour growth of BC. Mechanistically, ST8SIA6-AS1 regulated AKT1 and p38 mitogen-activated protein kinase (MAPK) gene expression by affecting their mRNA and protein levels, respectively, and it also affected the phosphorylation of AKT1 protein. Rescue experiments indicated that ST8SIA6-AS1 promoted BC cell proliferation, invasion and migration in a p38 MAPK signalling-mediated manner. Together, our data suggest that ST8SIA6-AS1 plays an important role in the occurrence and development of BC and may therefore serve as a promising therapeutic target.

LncRNA ST8SIA6-AS1 promotes hepatocellular carcinoma progression by regulating MAGEA3 and DCAF4L2 expression.

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. In this study, we aimed to explore the role and mechanism of lncRNA ST8SIA6-AS1 in HCC. We found that ST8SIA6-AS1 was upregulated in HCC tissues and associated with poorer overall survival of HCC patients from TCGA. Moreover, ST8SIA6-AS1 was highly expressed in HCC in-house tissues and cells, and ST8SIA6-AS1 upregulation was related to aggressive tumor phenotypes and the poor overall survival of HCC patients. Downregulation of ST8SIA6-AS1 suppressed HCC cell proliferation, migration and invasion in vitro and restrained HCC tumorigenesis in vivo. In terms of mechanism, ST8SIA6-AS1 regulated melanoma-associated antigen (MAGE)-A3 (MAGEA3) and DDB1-and Cul4-associated factor 4-like 2 (DCAF4L2) expression, and rescue experiments verified that ST8SIA6-AS1 played a protumorigenic role in HCC via the regulation of MAGEA3 and DCAF4L2. ST8SIA6-AS1 partly directly bound to miR-129-5p and functioned as a competing endogenous RNA (ceRNA), subsequently facilitating the expression of the miR-129-5p target gene DCAF4L2 to play its role in HCC. In summary, our results identified ST8SIA6-AS1 as an oncogenic lncRNA predicting poor clinical outcomes of patients with HCC. These findings suggest that ST8SIA6-AS1 is a potential therapeutic target for HCC.

Impact of the systematic use of the volume-viscosity swallow test in patients with acute ischaemic stroke: a retrospective study.

BACKGROUND: Dysphagia is common after stroke. Patients with dysphagia have a higher risk of stroke-associated pneumonia (SAP) and poor outcomes. Early detection of dysphagia is necessary to identify and manage patients at high risk of aspiration. The aim of the study was to assess the impact of the systematic administration of the volume-viscosity swallow test (V-VST) in patients with acute ischaemic stroke. METHODS: This was a retrospective observational study that enrolled patients with acute ischaemic stroke in two consecutive time periods: pre-V-VST, when the 30-mL water-swallowing test (WST) was systematically administered, and V-VST, when all patients underwent the WST and the V-VST test was systematically administered if the patient failed the WST. RESULTS: Two hundred and 42 patients were enrolled. The mean age of the participants was 68.8 ± 10.88 years, 61.2% were male, and the median National Institutes of Health Stroke Scale score was 3 (IQR, 1-6). A total of 147 patients were enrolled during the pre-V-VST period and 95 were enrolled during the V-VST period. There was a significant difference in the occurrence of SAP (21.8% vs. 10.5%, p = 0.024) and the rate of nasogastric tube feeding (25.9% vs. 14.7%, p = 0.040) between the two groups, and no differences were found in the length of hospital stay (p = 0.277) or the total cost of hospitalization (p = 0.846). CONCLUSIONS: The V-VST was a better clinical screening tool, and it can also provide detailed suggestions regarding dietary modifications to prevent aspiration and SAP.

Clinical outcomes of percutaneous thermal ablation for pulmonary metastases from hepatocellular carcinoma: a retrospective study.

Purpose: To determine the effectiveness of ablation for pulmonary metastases (PM) from hepatocellular carcinoma (HCC).Methods: Between 2010 and 2017, the study analyzed 39 patients who had a median age of 59 years. Primary HCC was under control and the number of PM was less than 5 (median: 2), with a maximum diameter of ≤60 mm (median: 15 mm). The primary endpoints were overall survival (OS) and local tumor progression-free survival (LTPFS). Secondary endpoints included technique success (TS), complication and tumor response. TS referred to PM treated using the treatment protocol. Multivariate analysis using the Cox proportional hazard model was conducted on the potential risk factors (univariate: p < 0.5) to determine the independent factors (multivariate: p < 0.05).Results: The TS rate was 100%. Major complications included pneumothorax (n = 3) requiring chest tube placement and pleural effusion requiring drainage (n = 2). Complete ablation was achieved in 32/38 patients (valid percent: 84.2%) at 1 month after ablation. The 1-, 3- and 5-year OS rates were 79.8, 58 and 30.9%, respectively. The 1-, 3- and 5-year LTPFS rates were 60.7, 34.2 and 22.8%, respectively. The extent (unilateral vs. bilateral) of PM (hazard ratio (HR): 0.197, 95% confidence interval (CI): 0.043-0.890, p = 0.035) and the number (≤2 vs. >2) of PM (HR: 0.555, 95% CI: 0.311-0.991, p = 0.047) were found to be the independent risk factors for predicting OS.Conclusion: Percutaneous thermal ablation is a safe and effective treatment for PM from HCC.

A prognostic nomogram for colorectal cancer liver metastases after percutaneous thermal ablation.

PURPOSE: To assess the efficacy of percutaneous thermal ablation in treating colorectal cancer liver metastases (CRCLM), and to propose a prognostic nomogram for overall survival (OS). MATERIALS AND METHODS: Seventy-one patients with CRCLM undergoing thermal ablation at our institute from 2009 to 2013 were identified and analysed to formulate a prognostic nomogram. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the nomogram. The nomogram was compared with two current prognostic nomograms for patients with CRCLM who had undergone hepatectomy (Kattan) and selective internal radiation therapy (Fendler). Predictive validity was assessed in the validation cohort of 25 patients who had undergone thermal ablation from 2014 to 2016. RESULTS: The median OS in the primary cohort was 26.4 months, whereas the 1-, 3- and 5-year OS rates were 72.2%, 37.2% and 17%, respectively. The median progression-free survival was 4.2 months. After univariate and multivariate analysis, a prognostic nomogram was formulated based on four predictors, including the number of tumours, maximum diameter of the tumour, CA19-9 level and ablation margin. The C-index of the nomogram was 0.815. Based on the patients of this study, the C-index was significantly higher than that of the Fendler nomogram (C-index, 0.698) and Kattan nomogram (C-index, 0.514, p < 0.001). Predictive accuracy of the proposed nomogram was also satisfactory in the validation cohort, with a C-index of 0.884. CONCLUSIONS: Thermal ablation was an effective therapy for CRCLM. Moreover, the nomogram was effective and simple for CRCLM patients undergoing thermal ablation.

A Transparent Antipeep Piezoelectric Nanogenerator to Harvest Tapping Energy on Screen.

Aligning PbZr(0.52)Ti(0.48)O3 (PZT) nanowires in polydimethylsiloxane introduces dielectrophoresis, improving the electromechanical properties of nanogenerators, and the light transmittance of composite films. A novel transparent and antipeep piezoelectric nanogenerator is developed that can be used for harvesting the energy from the light tapping of a finger on a cell phone, with an output current of 0.8 nA.

A Huaier polysaccharide inhibits hepatocellular carcinoma growth and metastasis.

This study was carried out to evaluate the effects of a Huaier polysaccharide (TP-1) on the tumor growth and immune function in hepatocellular carcinoma (HCC) H22-based mouse in vivo. Results showed that TP-1 was capable of repressing transplanted H22 solid hepatic tumor cell growth in vivo, prolonging the live time of mice bearing ascetic H22 tumors, and repressing the pulmonary metastasis of H22-bearing mice. Moreover, the relative weight of immune organ (spleen and thymus) and lymphocyte proliferation were improved after TP-1 treatment. Furthermore, the treatment with TP-1 could promote immune-stimulating serum cytokines, such as IL-2 and IFN-γ, but inhibit immune-suppressing serum cytokines IL-10 secretion in H22-bearing mice. Besides, the percentage of CD4+ T cells and NK cells was increased, whereas the number of CD8+ T cells decreased in tumor-bearing mice following TP-1 administration. In addition, this compound displayed little toxic effects to major organ of tumor-bearing mice at the therapeutic dose, such as the liver and kidney. This experimental finding suggested that TP-1 exhibited prominent antitumor activities in vivo via enhancement of host immune system function in H22 tumor-bearing mice. This product could be developed individually as a safe and potent biological response modifier for HCC therapy.

A Huaier polysaccharide reduced metastasis of human hepatocellular carcinoma SMMC-7721 cells via modulating AUF-1 signaling pathway.

TP-1 is a polysaccharide from one famous fungus Huaier. Treatment with TP-1 significantly inhibited the cell growth, adhesion, migration, and motility of SMMC-7721 cells in a dose-dependent manner. Real-time quantitative RT-PCR revealed a dose-dependent decrease in RNA-binding factor 1 (AUF-1) and astrocyte elevated gene-1 (AEG-1) messenger RNA (mRNA) levels in TP-1-treated SMMC-7721 cells, which is consistent with their protein expression detected by Western blotting. On the contrary, microRNA-122 (miR-122) expression increased in SMMC-7721 cells following TP-1 treatment. Moreover, TP-1 treatment at three doses apparently increased epithelial marker E-cadherin protein expression but decreased the mesenchymal marker N-cadherin protein level. In addition, the hematoxylin-eosin (H & E) staining showed that the TP-1 significantly inhibited the lung metastasis of liver cancer in mice orthotopic implanted with SMMC-7721 tumor tissue. Taken together, these findings proved the inhibitory effect of TP-1 on the growth and metastasis of SMMC-7721 cells, and TP-1 might be offered for future application as a powerful chemopreventive agent against hepatocellular carcinoma (HCC) metastasis.

Histological correlation of diffusional kurtosis and white matter modeling metrics in cuprizone-induced corpus callosum demyelination.

The cuprizone mouse model is well established for studying the processes of both demyelination and remyelination in the corpus callosum, and it has been utilized together with diffusion tensor imaging (DTI) to investigate myelin and axonal pathology. Although some underlying morphological mechanisms contributing to the changes in diffusion tensor (DT) metrics have been identified, the understanding of specific associations between histology and diffusion measures remains limited. Diffusional kurtosis imaging (DKI) is an extension of DTI that provides metrics of diffusional non-Gaussianity, for which an associated white matter modeling (WMM) method has been developed. The main goal of the present study was to quantitatively assess the relationships between diffusion measures and histological measures in the mouse model of cuprizone-induced corpus callosum demyelination. The diffusional kurtosis (DK) and WMM metrics were found to provide additional information that enhances the sensitivity to detect the morphological heterogeneity in the chronic phase of the disease process in the rostral segment of the corpus callosum. Specifically, in the rostral segment, axonal water fraction (d = 2.6; p < 0.0001), radial kurtosis (d = 2.0; p = 0.001) and mean kurtosis (d = 1.5; p = 0.005) showed the most sensitivity between groups with respect to yielding statistically significant p values and high Cohen's d values. These results demonstrate the ability of DK and WMM metrics to detect white mater changes and inflammatory processes associated with cuprizone-induced demyelination. They also validate, in part, the application of these new WMM metrics for studying neurological diseases, as well as helping to elucidate their biophysical meaning.

Astrocyte elevated gene-1 is a novel biomarker of epithelial-mesenchymal transition and progression of hepatocellular carcinoma in two China regions.

Astrocyte elevated gene-1 (AEG-1) is involved in important biological processes including cell invasion, metastasis, and carcinogenesis. However, its clinical significance has remained largely unknown in hepatocellular carcinoma. Here, specimens from 144 patients with hepatocellular carcinomas in Beijing and Heilongjiang regions were investigated by immunohistochemical staining for AEG-1, vimentin, and E-cadherin expressions. A clinicopathological study revealed that AEG-1 expression level in tumor cells was significantly correlated with TNM stage (P = 0.001) and Edmonson grade (P < 0.0001). In addition, AEG-1, vimentin, and E-cadherin (epithelial-mesenchymal transition (EMT) biomarker) expressions were correlated with each other. These findings suggest that AEG-1 may be an epithelial-mesenchymal transition-associated biomarker in human hepatocellular carcinoma and play important roles in the progression of hepatocellular carcinoma. In addition, the AEG-1 gene is a potential target for elimination of hepatocellular carcinoma in the future.