Comparing the clinical efficacy and safety of second-line targeted therapy and immunotherapy in patients with mid- to advanced stages of hepatocellular carcinoma - A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: The aim of this study was to examine the efficacy and safety of second-line immunotherapy and targeted treatment in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From January 2000 to January 2023, ProQuest, PubMed, Web of Science, Scopus, Embase, and the Cochrane Library databases were searched for randomized controlled trials (RCTs) using immunotherapy or targeted therapy as second-line therapy for mid-to-advanced stages of HCC. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) are all examples of measures of success. RESULTS: This analysis included twenty Randomized Clinical Trials (RCTs) from phases II and III. Collective data revealed better OS with immunotherapy (HR = 0.79; 95% CI: 0.67, 0.93 vs. 0.85; 95% CI: 0.78, 0.92), while the targeted therapy played a more effective role in PFS (0.67; 95% CI: 0.56, 0.81). Also, the second-line immunotherapy had a lower odds ratio of AEs of grades 3-5 than the targeted therapy did (OR = 1.75; 95% CI = 0.89, 3.46). CONCLUSIONS: Overall, it appears that targeted medication and immunotherapy as a second-line treatment strategy have generally improved substantially, as well as progression-free survival for patients with mid-to-advanced HCC. Although it is difficult to judge their efficiency, the occurrences of AEs were greater in targeted therapy compared to immunotherapy.

Zoledronic acid epigenetically alleviates high-glucose-suppressed osteogenic differentiation of MC3T3-E1 cells.

OBJECTIVE: Due to the impact of excessive glucose on osteogenic differentiation, diabetic osteopathy frequently results in skeletal fragility, osteoporosis, and bone pain. Zoledronic acid, a bisphosphonate (BP) that effectively inhibits osteoclastic bone resorption is given yearly to improve bone mineral density (BMD) in patients with osteoporosis. However, the detailed molecular mechanisms remained unclear. This study investigates the possible pathways by which zoledronic acid regulates osteogenesis when blood glucose levels are high. MATERIALS AND METHODS: MC3T3-E1 cells were treated with one mM zoledronic acid or not in a standard or high glucose culture medium. A quantitative polymerase chain reaction (qPCR) assay was utilized to assess the expression of the target candidate genes, including RUNX2, MALAT1, miR-133, miR-20a, and miR-204. RESULTS: In a high-glucose condition, zoledronic acid treatment significantly lowered MALAT1 (p < 0.0001) and miR-20a (p < 0.0001) expression. Conversely, in a high-glucose condition, RUNX2, miR-133, and miR-204 expressions were found to be significantly increased in the zoledronic acid treatment group as compared to no treatment (all p < 0.0001). CONCLUSIONS: In conclusion, under a high-glucose environment, zoledronic acid can modulate the expression of the RUNX2 transcription factor through epigenetic regulation.

Fast and accurate centerline extraction algorithm for a laser stripe applied for shoe outsole inspection.

Line laser 3D reconstruction technology is widely used in industrial applications. As a key step of this technology, line laser midline extraction directly affects the accuracy of the 3D reconstructed model. In reconstructing the shoe outsole, the traditional algorithm based on the threshold method to determine the laser position may result in a large amount of information loss and miscellaneous point misjudgment owing to the irregularity of the shoe outsole surface, which critically affects the laser imaging quality. To address this problem, an algorithm based on the QQ plot inspection of the laser has been proposed. The QQ plot is a scatter plot, the abscissa is usually the quantile of the standard normal distribution, and the ordinate is the quantile of the data to be tested. If the points on the scatter plot tend to be straight lines, the data to be tested is in a normal distribution. Based on this property, the proposed algorithm aims to check whether the pixels of the image column tend to be normally distributed, rather than using traditional thresholding methods to locate the laser. The objective is to examine whether the image column pixel distribution is normal, instead of using the traditional threshold method to locate the laser. However, the calculation speed of this method is extremely low. To enhance the efficiency of testing the normality of the QQ plot, a quantile-repetition (Q-R) test method is proposed. In this approach, the degree of repetition of quantiles and the position of Q-R values are used to replace the QQ plot based evaluation of the points being on a straight line, and the exact center position is determined by the GGM. The experimental results show that the proposed algorithm can extract more effective points and fewer invalid points of the laser compared to those obtained using the traditional approach, in a rapid, stable, and accurate manner.

Emotional responses of piglets under long-term exposure to negative and positive auditory stimuli.

The stress caused by sound is inevitable. The stress caused by noise and the positive effects of music can affect the endocrine of animals and their welfare. In this study, a total of 72 hybrid piglets (Large White × Duroc × Min pig) were randomly divided into 3 groups, including music (Mozart K.448, 60-70 dB), noise (recorded mechanical noise, 80-85 dB), and control (natural background sound, <40 dB) groups. S-IgA (secretory immunoglobulin A), IL-6 (interleukin-6), IL-8 (interleukin-8), and positive emotion-related behaviors were used as indicators to discuss whether noise induced stress and inflammation in piglets or whether music could have positive effects. Six hours of auditory exposure were given daily (10:00-16:00), which lasted for 56 days. Behavioral responses of the piglets were observed, and the concentrations of salivary S-IgA and serum IL-6 and IL-8 were measured. The results showed that the concentration of S-IgA increased in the noise and control groups on the 57th day (P < 0.05); S-IgA concentration in the music group was unchanged after long-term music exposure. The concentrations of IL-6 and IL-8 showed that long-term noise exposure might lead to stress and inflammation in piglets. Tail-wagging and play behaviors of the piglets in the music group were significantly greater than those in the noise and control groups, which implied that long-term music exposure improved the emotional state of the piglets in a restricted and barren environment.

Brain Perfusion Alterations on 3D Pseudocontinuous Arterial Spin-Labeling MR Imaging in Patients with Autoimmune Encephalitis: A Case Series and Literature Review.

Autoimmune encephalitis is a heterogeneous group of newly identified disorders that are being diagnosed with increasing frequency. Early recognition and treatment of autoimmune encephalitis are crucial for patients, but diagnosis remains challenging and time-consuming. In this retrospective case series, we describe the findings of conventional MR imaging and 3D pseudocontinuous arterial spin-labeling in patients with autoimmune encephalitis confirmed by antibody testing. All patients with autoimmune encephalitis showed increased CBF in the affected area, even when some of them presented with normal or slightly abnormal findings on conventional MR imaging. Additionally, serial 3D pseudocontinuous arterial spin-labeling showed perfusion reduction in 1 patient after therapy. For patients with highly suspected autoimmune encephalitis, 3D pseudocontinuous arterial spin-labeling may be added to the clinical work-up. Further studies and longitudinal data are needed to corroborate whether and to what extent 3D pseudocontinuous arterial spin-labeling improves the diagnostic work-up in patients with autoimmune encephalitis compared with conventional MR imaging.

The use of online MBSR audio in medical staff during the COVID-19 in China.

OBJECTIVE: This study aims to survey medical staff's acceptance of online Mindfulness-Based Stress Reduction (MBSR) during the Novel Coronavirus Pneumonia (NCP), and to know some information of physical and emotional response of those medical staff who worked at the forefront of COVID-19, through the playback amount of the online MBSR training. MATERIALS AND METHODS: Considering the working environment of medical staff in forefront of NCP, we designed and recorded MBSR audio album including 13 sessions, covering 24 hours of a day, then sent the album to medical staff who had been working in Wuhan, Hubei province, China. We collected the playback amount in each session on February 10th and February 24th, which were one week and three weeks after the album was finished. RESULTS: On February 10th and February 24th, there were separately 5778 and 10640 times of broadcasting. The highest broadcasting frequency session was at 5:00 am, followed by 7:00 am. The least broadcasting frequency sessions were 17:00 pm and 19:00 pm. The broadcasting amount in the 6 periods of the night (from 21:00 pm to 7:00 am) was significantly higher than those in the daytime (from 9:00 am to 19:00 pm), with a statistical difference. The tendency of the amount of playback was consistent, which was not affected by the specific content of the mindfulness exercises. CONCLUSIONS: Online MBSR exercises were well accepted by medical staff in the COVID-19. It may help them relax and reduce the risk of stress reactions. During the NCP, medical staff may have different degrees of sleep and emotional problems, which need to be paid more attention to.

Long noncoding RNA PROX1-AS1 promoted ovarian cancer cell proliferation and metastasis by suppressing KLF6.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA PROX1-AS1 promoted ovarian cancer cell proliferation and metastasis by suppressing KLF6, by L. Zhao, J.-F. Li, X.-J. Tong, published in Eur Rev Med Pharmacol Sci 2020; 24 (12): 6561-6568-DOI: 10.26355/eurrev_202006_21640-PMID: 32633343" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21640.

Long noncoding RNA PROX1-AS1 promoted ovarian cancer cell proliferation and metastasis by suppressing KLF6.

OBJECTIVE: Recently, the role of long noncoding RNAs (lncRNAs) in tumor progression has attracted much attention worldwide. Numerous studies have identified lncRNA PROX1-AS1 as an oncogene in cancers. Therefore, the aim of this research was to explore the function of PROX1-AS1 in the development of ovarian cancer. PATIENTS AND METHODS: PROX1-AS1 expression in both ovarian cancer patients and normal subjects was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Subsequently, PROX1-AS1 shRNA was constructed and transfected in vitro. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, colony formation assay, transwell assay, and Matrigel assay were utilized to detect the function of PROX1-AS1 in ovarian cancer. In addition, the potential mechanism was explored using qRT-PCR and Western blot assay. RESULTS: PROX1-AS1 was highly expressed in ovarian carcinoma samples and cell lines (p<0.05). The proliferation, migration, and invasion of ovarian cells were significantly inhibited after PROX1-AS1 was downregulated in vitro (p<0.05). Besides, the mRNA and protein expressions of KLF6 were significantly promoted after PROX1-AS1 knockdown in ovarian cancer cells (p<0.05). Further functional assays showed that KLF6 expression was negatively correlated with PROX1-AS1 expression in ovarian cancer samples. CONCLUSIONS: PROX1-AS1 enhances the metastasis and proliferation of ovarian cancer cells via suppressing KLF6. Our findings suggest that PROX1-AS1 may be applied as a novel target for therapy of ovarian cancer.

Long non-coding RNA PICART1 inhibits cell proliferation by regulating the PI3K/AKT and MAPK/ERK signaling pathways in gastric cancer.

OBJECTIVE: Gastric cancer (GC) is one of the most frequent malignancies and the second leading cause of cancer-related death in the world. The aim of this work was to illustrate the functional role of long non-coding RNA (lnRNA)-PICART1 (p53-inducible cancer-associated RNA transcript 1) in GC, thereby providing novel insights into biomarkers and therapeutic strategies in GC. PATIENTS AND METHODS: The relative expression level of lncRNA-PICART1 was evaluated by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay and colony formation assay were used to determine the ability of cell proliferation. Flow cytometric analysis was performed to detect cell cycle and cell apoptosis. The protein expressions of ERK, p-ERK, AKT and p-AKT were detected by Western blotting. Furthermore, the transfected cells were used to perform tumor xenograft formation assay. RESULTS: LncRNA-PICART1 was lowly expressed in both GC tissues and cell lines. CCK-8 assay, colony formation assay and flow cytometric analysis validated that up-regulated lncRNA-PICART1 significantly suppressed cell proliferation, whereas promoted cell apoptosis. Besides, the over-expression of lncRNA-PICART1 remarkably inhibited the PI3K/AKT and ERK/MAPK signaling pathways. Tumor xenograft formation assay indicated that lncRNA-PICART1 overexpression significantly inhibited tumor formation. CONCLUSIONS: Our research illustrated that lncRNA-PICART1 functioned as a tumor suppressor in GC. The regulation of the PI3K/AKT and ERK/MAPK signaling pathways might be the underlying mechanism of the tumor suppressor role of lncRNA-PICART1. In addition, our study might bring novel insights into biomarkers and therapeutic strategies for GC.

Depth dependant element analysis of PbMg1/3Nb2/3O3 using muonic x-rays.

The relaxor PbMg1/3Nb2/3O3 (PMN) has received attention due to its potential applications as a piezoelectric when doped with PbTiO3 (PT). Previous results have found that there are two phases existing in the system, one linked to the near-surface regions of the sample, the other in the bulk. However, the exact origin of these two phases is unclear. In this paper, depth dependant analysis results from negative muon implantation experiments are presented. It is shown that the Pb content is constant throughout all depths probed in the sample, but the Mg and Nb content changes in the near-surface region below 100 µm. At an implantation depth of 60 µm, it is found that there is a 25% increase in Mg content, with a simultaneous 5% decrease in Nb content in order to maintain charge neutrality. These results show that the previously observed skin effects in PMN are due to a change in concentration and unit cell.

Alteration of endothelial nitric oxide synthase expression in acute pulmonary embolism: a study from bench to bioinformatics.

OBJECTIVE: This study sought to explore endothelial nitric oxide synthase (eNOS) expression in acute pulmonary thromboembolism (APE). MATERIALS AND METHODS: eNOS expression in lung tissue and bone marrow-derived endothelial progenitor cells (BM-EPCs) from APE mouse models was assessed by immunohistochemistry and real-time PCR. A gene expression profile meta-analysis was performed on human venous thromboembolism (VTE) whole blood samples recorded in the Gene Expression Omnibus (GEO) repository. Significantly expressed genes were determined from the microarray data by unsupervised clustering and supervised classification. Selected sample data with significantly expressed genes were further analyzed by principal component analysis (PCA), followed by Bayesian probit regression. Key discriminate genes were further grouped and annotated using functional annotations and gene enrichments using the online Database for Annotation, Visualization and Integrated Discovery (DAVID) software (v. 6.7). RESULTS: While eNOS expression was significantly higher, serum nitric oxide levels were significantly lower in APE mice (20.42 ± 2.15 µM) compared to controls (53.50 ± 5.69 µM, p<0.001). eNOS mRNA and protein levels were significantly upregulated in BM-EPCs from APE mice. GEO repository data reported 3,397 upregulated and 4,173 downregulated genes (including eNOS) in VTE patients. In this regression analysis, the significant principal component PC1 and PC2 (p<0.05) were useful in distinguishing the VTE classification. The coefficient value of eNOS was -0.47707 in PC1 and -0.08429 in PC2, which did have some proportions on these significantly discriminated components but did not contribute significantly to the VTE classification. Functional enrichment in terms of acetylation and phosphoproteins were high. CONCLUSIONS: Our findings, therefore, suggest that expression of eNOS is significantly altered in APE and may be a potential peripheral blood biomarker. Modulation of eNOS expression may be used for APE treatment.

Hypoxia-induced miR-17-5p ameliorates the viability reduction of astrocytes via targeting p21.

OBJECTIVE: Glial scars are widely seen as a mechanical barrier to central nervous system regeneration. Up to now, several studies have addressed and clarified how different lesion microenvironment properties affect astrogliosis. In particular, hypoxia induces the astrocyte astrogliosis, and thus promotes the formation of glial scars. However, little is known about the mechanism underlining such process. In the present study, we investigated the regulation by the miR-17-5p on the hypoxia-induced viability via targeting p21. MATERIALS AND METHODS: We examined the expression of miR-15a, miR-16, miR-17-5p, hypoxia inducible factor-1α (HIF-1α) and p21 in the astrocytes under hypoxia, with quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) methods. Then investigated the regulatory role of miR-17-5p on the level of HIF-1α and p21, with qRT-PCR, WB and luciferase reporting assay, and examined the activity of astrocytes under normoxia or hypoxia. RESULTS: Results demonstrated that miR-15a, miR-16, miR-17-5p were significantly upregulated, while HIF-1α and p21 were markedly downregulated in the hypoxia-treated astrocytes. And the transfection with miR-17-5p mimics significantly downregulated the expression of HIF-1α and p21 in such cells. And the luciferase reporter assay confirmed the targeting inhibiting of p21 by miR-17-5p in astrocytes. Moreover, the viability of astrocytes was significantly upregulated by the miR-17-5p mimics transfection under the hypoxia condition. CONCLUSIONS: Our novel data suggest that the upregulated miR-17-5p contributes to the proliferation of astrocytes, in response to hypoxia, implying the potential role of miR-17-5p in the formation of glial scars.

The role of human epididymis protein 4 in the diagnosis of epithelial ovarian cancer

Purpose: Epithelial ovarian cancer is one of the most lethal female genital tract cancers. Early diagnosis of EOC would benefit the patients a lot. Human epididymis protein 4 (HE4) has been regarded as a new powerful biomarker in diagnosis of EOC; we hope to obtain system knowledge of HE4 and understand the role of HE4 in diagnosis of epithelial ovarian cancer (EOC). Methods: We searched Pubmed, Embase, Medline, and Chinese National Knowledge Infrastructure (CNKI) for articles that included HE4's origin, characteristics, detection methods, clinical efficacy alone or combined with CA125, the risk of malignancy index, and the risk of ovarian malignancy algorithm. The diagnostic performance for the EOC and the role in the recurrence and procession in EOC were also discussed. Results: We got 83 most related articles and found that there were significantly difference existing among the studies, such as the clinical characteristics of patients, the methodology for measuring HE4, the different cut-offs for HE4 and so on. Conclusion: HE4 is a promising biomarker for the early diagnosis of EOC. However, each lab should establish its own reference internal of HE4 (AU)

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The role of human epididymis protein 4 in the diagnosis of epithelial ovarian cancer.

PURPOSE: Epithelial ovarian cancer is one of the most lethal female genital tract cancers. Early diagnosis of EOC would benefit the patients a lot. Human epididymis protein 4 (HE4) has been regarded as a new powerful biomarker in diagnosis of EOC; we hope to obtain system knowledge of HE4 and understand the role of HE4 in diagnosis of epithelial ovarian cancer (EOC). METHODS: We searched Pubmed, Embase, Medline, and Chinese National Knowledge Infrastructure (CNKI) for articles that included HE4's origin, characteristics, detection methods, clinical efficacy alone or combined with CA125, the risk of malignancy index, and the risk of ovarian malignancy algorithm. The diagnostic performance for the EOC and the role in the recurrence and procession in EOC were also discussed. RESULTS: We got 83 most related articles and found that there were significantly difference existing among the studies, such as the clinical characteristics of patients, the methodology for measuring HE4, the different cut-offs for HE4 and so on. CONCLUSION: HE4 is a promising biomarker for the early diagnosis of EOC. However, each lab should establish its own reference internal of HE4.

Redistribution of body composition in patients with Graves' disease after iodine-131 treatment.

OBJECTIVE: The objective of this study was to investigate body composition redistribution at 3 months after radioactive iodine therapy (RAI). METHODS: Eighty patients with Graves' disease (GD) for RAI and 18 volunteers were recruited. All patients underwent thyroid status test and dual-energy x-ray absorptiometry at baseline and 3 months after RAI. According to the second thyroid status test, patients were divided into the following groups: A, with aggravated hyperthyroidism; B-1, with improved hyperthyroidism; B-2, with euthyroidism; and B-3, with hypothyroidism. RESULTS: Total lean mass (LM) but fat mass (FM) and bone mineral content (BMC) of whole GD patients after RAI recovered to be not different with controls. Compared with baseline, in group A, FM in the left leg increased, and LM in left arm, right arm, trunk and total LM decreased (P<0.05). In B-2, FM in the head increased, and LM in the head, right arm, trunk and total LM increased (P<0.05). In B-3, FM in the right leg and total body fat percentage decreased, but FM in the head, android-to-gynoid fat ratio and body mass index increased (P<0.05); LM of all sites, weight and total mass increased (P<0.05); BMC in lumbar spine and left leg, and total BMC decreased (P<0.05). Body composition of unmentioned sites was retained after RAI in each group (P>0.05). CONCLUSIONS: Replenishment of LM gets priority rather than FM and BMC during the first 3 months after RAI, and the increase in LM starts from the upper body; head is the regional site in which FM recovery occurs first.

Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.

Elevated plasma sphingomyelin (d18:1/22:0) is closely related to hepatic steatosis in patients with chronic hepatitis C virus infection.

Hepatic steatosis affects disease progression in patients with chronic hepatitis C virus (HCV) infection. We investigated the plasma sphingolipid profile in patients with chronic hepatitis C (CHC) and whether there was an association between HCV-related steatosis and plasma sphingolipids. We used high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze plasma sphingolipids in 120 interferon-naïve, non-diabetic, and non-obese CHC patients. Hepatic steatosis was defined as ≥5 % hepatocytes with fat based on histopathological analysis. Blood biochemical indicators and HCV load and genotype were also determined. Thirty-six (30.0 %) of 120 patients presented with hepatic steatosis Grades 1-3. Forty-four plasma sphingolipids were detected. Plasma sphingomyelin (SM) (d18:1/22:0) and ceramide (Cer) (d18:1/24:0)-1-P correlated with steatosis grade (r = 0.22, p = 0.015; r = -0.23, p = 0.012, respectively). SM (d18:1/22:0) [odds ratio (OR) = 1.12] and Cer (d18:1/24:0)-1-P (OR = 0.88) were independent factors for the presence of hepatic steatosis in CHC patients. The area under the curve (AUC) of SM (d18:1/22:0) and Cer (d18:1/24:0)-1-P was 0.637 and 0.638, respectively, to identify the presence of steatosis. Further analysis for genotype 2 CHC showed that only SM (d18:1/22:0) was independently linked to steatosis (OR = 1.21). The AUC of SM (d18:1/22:0) to identify hepatic steatosis in genotype 2 CHC was 0.726. Its sensitivity and negative predictive value reached 0.813 and 0.886, respectively. This study suggested that altered plasma SM (d18:1/22:0) was closely related to hepatic steatosis in chronic HCV infection, especially with genotype 2. Experimental studies are needed to determine further the underlying mechanisms responsible for these associations.

HDAC5 promotes cell proliferation in human hepatocellular carcinoma by up-regulating Six1 expression.

OBJECTIVES: Histone deacetylases (HDACs) plays important roles in the regulation of genes expression and contribute to the growth of cancer cells. The present study aimed to investigate the function of HDAC5 in human hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The expression of HDAC5 in human hepatocellular carcinoma tissues and cells was detected. MTT assay was used to measure the proliferation of HCC cell lines. siRNA technology was employed to down-regulate the protein expression of HDAC5 and Six1. RESULTS: Western blot showed that the HDAC5 expression was increased in human HCC tissues. The mRNA and protein levels of HDAC5 were up-regulated in human HCC cell lines. MTT assay showed that over-expression of HDAC5 promoted cell proliferation in human HCC cell lines. Down-regulation of HDAC5 caused a significantly inhibition of liver cancer cells proliferation. Furthermore, we found that HDAC5 promoted the Six1 expression both at the mRNA and protein levels in HCC cell lines. CONCLUSIONS: The current study demonstrated for the first time that HDAC5 promoted HCC cell proliferation through up-regulation of Six1 expression and might provide novel therapeutic targets in the treatment of HCC.

Glycogen synthase kinase-3 reduces acetylcholine level in striatum via disturbing cellular distribution of choline acetyltransferase in cholinergic interneurons in rats.

Cholinergic interneurons, which provide the main source of acetylcholine (ACh) in the striatum, control the striatal local circuits and deeply involve in the pathogenesis of neurodegenerative diseases. Glycogen synthase kinase-3 (GSK-3) is a crucial kinase with diverse fundamental functions and accepted that deregulation of GSK-3 activity also plays important roles in diverse neurodegenerative diseases. However, up to now, there is no direct proof indicating whether GSK-3 activation is responsible for cholinergic dysfunction. In the present study, with combined intracerebroventricular injection of Wortmannin and GF-109203X, we activated GSK-3 and demonstrated the increased phosphorylation level of microtubule-associated protein tau and neurofilaments (NFs) in the rat striatum. The activated GSK-3 consequently decreased ACh level in the striatum as a result of the reduction of choline acetyltransferase (ChAT) activity. The alteration of ChAT activity was due to impaired ChAT distribution rather than its expression. Furthermore, we proved that cellular ChAT distribution was dependent on low phosphorylation level of NFs. Nevertheless, the cholinergic dysfunction in the striatum failed to induce significant neuronal number reduction. In summary, our data demonstrates the link between GSK-3 activation and cholinergic dysfunction in the striatum and provided beneficial evidence for the pathogenesis study of relevant neurodegenerative diseases.

The plasma level of soluble receptor for advanced glycation end products is decreased in patients with systemic lupus erythematosus.

In recent years, the role of high mobility group box-1 (HMGB1) protein and its receptors in autoimmune diseases has received increasing attention. It has been documented that HMGB1 is associated with disease activity in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine the potential role of receptor for advanced glycation end products (RAGE), one receptor for HMGB1, in the pathogenesis of SLE. Plasma levels of soluble RAGE (sRAGE) from 105 patients with clinical diagnosis of SLE and 43 healthy controls were determined by ELISA. Associations between sRAGE levels and clinical, laboratory characteristics were assessed. The data showed that plasma levels of sRAGE in patients with SLE were significantly lower than those in healthy controls (HC) (P = 0.003). Plasma sRAGE in patients receiving short-period treatment showed an immediate decrease compared with the untreated patients (P = 0.023). In contrast, plasma sRAGE in patients receiving long-period treatment were significantly increased compared to those with short-period treatment (P = 0.000) and comparable with those in HC (P = 0.305). The significant decreased levels of sRAGE in patients with SLE suggest the potential association of RAGE signalling and SLE clinical pathology, whereas, long-period antilupus treatment may counteract the decreased sRAGE levels in patients with SLE.