IDI1 inhibits the cGAS-Sting signaling pathway in hepatocellular carcinoma.

Metabolic reprogramming is one of the prominent features that distinguishes tumor cells from normal cells. The role of metabolic abnormalities in regulating innate immunity is poorly understood. In this study, we found that IDI1 is significantly upregulated in liver cancer. IDI1 has no significant effect on the growth or invasion of liver cancer cells but significantly promotes liver cancer development in mice. Through molecular mechanism studies, we found that IDI1 interacts with the important regulator of innate immunity cGAS and recruits the E3 ligase TRIM41 to promote cGAS ubiquitination and degradation, inhibiting the cGAS-Sting signaling pathway. IDI1 inhibits the phosphorylation of TBK1 and the downstream factor IRF3 as well as the expression of CCL5 and CXCL10. In summary, this study revealed the important role of the metabolic enzyme IDI1 in the regulation of innate immunity, suggesting that it may be a potential target for liver cancer treatment.

Effect of Abdominal Compression on Total Single-Balloon Enteroscopy Rate: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether abdominal compression significantly increased the total enteroscopy rate in single-balloon enteroscopy (SBE). METHODS: Consecutive patients who underwent SBE at 2 hospitals were prospectively included between June 1, 2020, and September 30, 2021. They were randomly divided into an abdominal compression group and a non-abdominal compression group with use of sealed envelopes generated by a computer. Total enteroscopy rates were compared between the groups. RESULTS: The study included 200 patients. The total enteroscopy rates were 73% and 16% in the abdominal compression and non-abdominal compression groups, respectively (relative risk, 13.55; 95% CI, 6.79 to 27.00; P<.001). The total enteroscopy rate was higher in the 70 patients who were identified to have undergone no previous abdominal surgery or small intestinal stenosis than in the 32 patients who had undergone such procedures in the abdominal compression group (84% vs 47%; relative risk, 6.08; 95% CI, 2.36 to 15.67; P<.001). Relevant positive findings were not significantly different between the groups (58% vs 45%; P=.07). Binary logistic regression analysis found abdominal compression to be associated with a better total enteroscopy rate (odds ratio, 16.68; 95% CI, 7.92 to 35.15; P<.001), and the presence of previous abdominal surgery or small intestinal stenosis was associated with difficulty in completing the total enteroscopy procedure (odds ratio, 0.26; 95% CI, 0.12 to 0.58; P<.01). CONCLUSION: Abdominal compression significantly increased the total enteroscopy rate in SBE. Complete total enteroscopy may be challenging in patients with a history of abdominal surgery or small intestinal stenosis.

Nucleophagic Degradation of Progerin Ameliorates Defenestration in Liver Sinusoidal Endothelium Due to SIRT1-Mediated Deacetylation of Nuclear LC3.

Progerin, a permanently farnesylated prelamin A protein in cell nuclei, is potentially implicated in the defenestration of liver sinusoidal endothelial cells (LSECs) and liver fibrogenesis. Autophagy regulates the degradation of nuclear components, called nucleophagy, in response to damage. However, little is known about the role of nucleophagy in LSEC defenestration. Herein, we aim to dissect the underlying mechanism of progerin and nucleophagy in LSEC phenotype. We found an abnormal accumulation of progerin and a loss of SIRT1 in the nucleus of intrahepatic cells in human fibrotic liver tissue. In vivo, nuclear progerin abnormally accumulated in defenestrated LSECs, along with a depletion of SIRT1 and Cav-1 during liver fibrogenesis, whereas these effects were reversed by the overexpression of SIRT1 with the adenovirus vector. In vitro, H2O2 induced the excessive accumulation of progeirn, with the depletion of Lamin B1 and Cav-1 to aggravate LSEC defenestration. NAC and mito-TEMPO, classical antioxidants, inhibited NOX2- and NOX4-dependent oxidative stress to improve the depletion of Lamin B1 and Cav-1 and promoted progerin-related nucleophagy, leading to a reverse in H2O2-induced LSEC defenestration. However, rapamycin aggravated the H2O2-induced depletion of Lamin B1 and Cav-1 due to excessive autophagy, despite promoting progerin nucleophagic degradation. In addition, overexpressing SIRT1 with the adenovirus vector inhibited oxidative stress to rescue the production of Lamin B1 and Cav-1. Moreover, the SIRT1-mediated deacetylation of nuclear LC3 promoted progerin nucleophagic degradation and subsequently inhibited the degradation of Lamin B1 and Cav-1, as well as improved F-actin remodeling, contributing to maintaining LSEC fenestrae. Hence, our findings indicate a new strategy for reversing LSEC defenestration by promoting progerin clearance via the SIRT1-mediated deacetylation of nuclear LC3.

LncRNA 1700020I14Rik promotes AKR1B10 expression and activates Erk pathway to induce hepatocyte damage in alcoholic hepatitis.

Alcoholic hepatitis (AH), a kind of alcoholic liver disease, shows poor prognosis. Long noncoding RNAs (lncRNAs) exert critical role in liver diseases. Here, we intended to investigate the possible molecular mechanism that 1700020I14Rik-based regulation of microRNA (miR)-137/Aldo-keto reductase family 1 member B10 (AKR1B10) affecting the inflammatory response and hepatocyte damage in AH. AH-related genes and the down-stream regulatory pathway were screnned by bioinformatics. Mouse normal hepatocyte cell line AML12 was selected to construct an ethanol-induced hepatocyte injury model for in vitro mechanistic validation, while we also established an AH mouse model using the ethanol with gradually increased concentration of 2-4% (v/v) for in vivo study. Specific role of 1700020I14Rik/miR-137/AKR1B10 in AML12 cell viability, proliferation and apoptotic capacity as well as inflammation and liver damage in mice were analyzed following ectopic and depletion approaches. We found elevated AKR1B10 and 1700020I14Rik but reduced miR-137 in AH. 1700020I14Rik was able to elevated miR-137-mediated AKR1B10. In vitro cell experiments and in vivo animal experiments validated that 1700020I14Rik reduced ethanol-induced hepatocyte damage and inflammation in AH mice through regulation of miR-137-mediated AKR1B10/Erk axis. The current study underlied that 1700020I14Rik could activate AKR1B10/Erk signaling through inhibition of miR-137, thereby promoting the hepatocyte damage in AH mice.

MicroRNA-665 regulates the proliferation, apoptosis and adhesion of gastric cancer cells by binding to cadherin 3.

Numerous studies have reported that abnormal cadherin 3 (CDH3) and microRNA (miRNA/miR)-665 expression can induce the progression of gastric cancer (GC). However, the mechanism of interaction between miR-665 and CDH3 in GC requires further investigation. The present study aimed to investigate the influence of miR-665 and CDH3 in GC development. The effect of miR-665 and CDH3 on GC tissues and cell lines was examined using reverse transcription-quantitative PCR. Subsequently, CDH3 protein expression in GC cell lines was detected using western blotting. To confirm the association between miR-665 and CDH3, a dual-luciferase reporter assay system was employed. Cell proliferation and adhesion were analyzed using BrdU ELISA, MTT and cell adhesion assays. Finally, caspase-3 activity assay kit and FITC apoptosis detection kit were used for the determination of apoptosis of GC cells. The current findings confirmed the upregulation of CDH3 expression in GC cell lines and tissues. Experimental results indicated that CDH3 overexpression increased cell proliferation and adhesion, but decreased the apoptosis level of the cells. Similarly, the miR-665 inhibitor enhanced cell proliferation and adhesion, but inhibited apoptosis of GC cells. Additionally, it was observed that CDH3 was a direct target of miR-665 in GC cells and that miR-665 inhibited CDH3 expression, thereby repressing the progression of GC. In conclusion, the present study suggested that by targeting CDH3, miR-665 suppressed the progression of GC. These findings may provide a significant theoretical basis for future GC clinical therapy.

Sirtuin 1 ameliorates defenestration in hepatic sinusoidal endothelial cells during liver fibrosis via inhibiting stress-induced premature senescence.

OBJECTIVE: Premature senescence is related to progerin and involves in endothelial dysfunction and liver diseases. Activating sirtuin 1 (SIRT1) ameliorates liver fibrosis. However, the mechanisms of premature senescence in defenestration of hepatic sinusoidal endothelial cells (HSECs) and how SIRT1 affects HSECs fenestrae remain elusive. METHODS: We employed the CCl4 -induced liver fibrogenesis rat models and cultured primary HSECs in vitro, administered with the SIRT1-adenovirus vector, the activator of SIRT1 and knockdown NOX2. We measured the activity of senescence-associated ß-galactosidase (SA-ß-gal) in HSECs. Meanwhile, the protein expression of SIRT1, NOX2, progerin, Lamin A/C, Ac p53 K381 and total p53 was detected by Western blot, co-immunoprecipitation and immunofluorescence. RESULTS: In vivo, premature senescence was triggered by oxidative stress during CCl4 -induced HSECs defenestration and liver fibrogenesis, whereas overexpressing SIRT1 with adenovirus vector lessened premature senescence to relieve CCl4 -induced HSECs defenestration and liver fibrosis. In vitro, HSECs fenestrae disappeared, with emerging progerin-associated premature senescence; these effects were aggravated by H2 O2 . Nevertheless, knockdown of NOX2, activation of SIRT1 with resveratrol and SIRT1-adenovirus vector inhibited progerin-associated premature senescence to maintain fenestrae through deacetylating p53. Furthermore, more Ac p53 K381 and progerin co-localized with the abnormal accumulation of actin filament (F-actin) in the nuclear envelope of H2 O2 -treated HSECs; in contrast, these effects were rescued by overexpressing SIRT1. CONCLUSION: SIRT1-mediated deacetylation maintains HSECs fenestrae and attenuates liver fibrogenesis through inhibiting oxidative stress-induced premature senescence.

hsa_circ_0006916 promotes hepatocellular carcinoma progression by activating the miR-337-3p/STAT3 axis.

BACKGROUND: Circular RNAs (circRNAs) are thought to be involved in the development of various malignancies. The expression and function of hsa_circ_0006916, a newly identified circRNA, in hepatocellular carcinoma remain unclear. METHODS: Quantitative RT-PCR was used to detect hsa_circ_0006916 in hepatocellular carcinoma. In vitro function assays were conducted to explore growth and invasion of hepatocellular carcinoma cells. Next, the mechanism of hsa_circ_0006916 function in hepatocellular carcinoma was determined by luciferase reporter and RIP assays. RESULTS: Hsa_circ_0006916 was substantially overexpressed in hepatocellular carcinoma tissues and cells. High levels of hsa_circ_0006916 in hepatocellular carcinoma patients were associated with advanced clinical characteristics. Down-regulation of hsa_circ_0006916 decreased the growth and invasion of hepatocellular carcinoma cells in vitro. The results suggested that hsa_circ_0006916 acted as a sponge of miR-337-3p and had an important functional use in the regulation of STAT3 levels in hepatocellular carcinoma cells. Moreover, miR-337-3p inhibition or STAT3 overexpression abolished the effect of hsa_circ_0006916 suppression on the progression of hepatocellular carcinoma cells. CONCLUSIONS: Our data suggest a novel hsa_circ_0006916/miR-337-3p/STAT3 axis in hepatocellular carcinoma, and provide a new target for treatment.

Silencing circSLAMF6 represses cell glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in gastric cancer under hypoxia.

BACKGROUND: Gastric cancer (GC) is a malignant tumor of the digestive tract. Hypoxia plays an important role in the development of cancer, including GC. The present study aimed to investigate the role of circular RNA SLAMF6 (circSLAMF6) in the progression of GC under hypoxia. METHODS: The expression of circSLAMF6, microRNA-204-5p (miR-204-5p) and myosin heavy chain 9 (MYH9) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). GC cells were maintained under hypoxia (1% O2) for experiments in vitro. Glucose consumption and lactate production were determined by a Glucose Assay Kit and a Lactate Assay Kit, respectively. Levels of all protein were detected by Western blot. Cell migration and invasion were examined by Transwell assay. The interaction between miR-204-5p and circSLAMF6 or MYH9 was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Murine xenograft model was established to explore the role of circSLAMF6 in vivo. RESULTS: CircSLAMF6 expression was increased in GC cells under hypoxia. Hypoxia promoted glycolysis, migration, and invasion in GC cells, which were reversed by circSLAMF6 knockdown. CircSLAMF6 was validated as a miR-204-5p sponge, and MYH9 was a target of miR-204-5p. Functionally, miR-204-5p inhibitor weakened the inhibition of circSLAMF6 knockdown on GC cell progression under hypoxia. Besides, MYH9 depletion suppressed glycolysis, migration, and invasion in GC cells under hypoxia. Importantly, circSLAMF6 deficiency inhibited tumor growth in vivo by regulating the miR-204-5p/MYH9 axis. CONCLUSION: CircSLAMF6 was involved in glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in GC cells under hypoxia.

Insulin-like growth factor-1 attenuates oxidative stress-induced hepatocyte premature senescence in liver fibrogenesis via regulating nuclear p53-progerin interaction.

Stress-induced premature senescence (SIPS), a state of cell growth arrest due to various stimuli, is implicated in the pathogeneses of hepatic fibrogenesis. Progerin, a permanently farnesylated mutant lamin A protein, likely leads to premature senescence to influent liver diseases. The previous reports showed that activation of insulin-like growth factor-1 (IGF-1) signaling could enhance cell longevity and attenuate liver fibrosis. However, the underlying mechanisms about hepatocyte premature senility in liver fibrosis, and how IGF-1 regulates cell premature aging and fibrogenesis, remain poorly understood. In the present study, we found the augment of hepatocyte oxidation and premature aging, along with the decrease of plasm IGF-1 level in patients with liver fibrosis and CCl4-induced liver injury rat models. Nevertheless, IGF-1 gene transfer to CCl4 rats to overexpress intrahepatic IGF-1 relieved hepatocyte oxidative stress and premature senescence, which was likely mediated by the p53/progerin pathway, to improve hepatic steatosis and fibrogenesis. In vitro, H2O2 caused abnormal accumulation of progerin in nuclear and activation of nuclear p53-progerin interaction to trigger primary rat hepatocyte premature senescence through the p21-independent pathway; while these effects were rescued by prolonged exogenous IGF-1 or the IGF-1 adenovirus vector. Furthermore, the IGF-1 adenovirus vector, transfected to H2O2-treated hepatocytes, reversed oxidative stress-induced premature senescence via enhancing cytoplasmic AKT1-p53 interaction and subsequently inhibiting nuclear p53-progerin interaction. Consequently, our data illuminate a novel role of IGF-1 in regulating stress-induced hepatocyte premature senescence in liver fibrosis: prolonged IGF-1 relieves oxidative stress-initiated hepatocyte premature senescence via inhibition of nuclear p53-progerin interaction to ameliorate hepatic steatosis and fibrogenesis.

Dual role of twist1 in cancer-associated fibroblasts and tumor cells promoted epithelial-mesenchymal transition of esophageal cancer.

Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression. However, the role and mechanism underlying CAFs in esophageal cancer (EC) remain unclear. In this study, primary CAFs and normal esophageal fibroblasts (NOFs) were isolated and characterized by immunofluorescence, qRT-PCR and western blot. Clinical significance of twist1 in CAFs were evaluated by immunohistochemistry assay. Conditioned medium (CM) was collected from CAFs to evaluate the influence on epithelial-mesenchymal transition (EMT) of EC cells. EC cells were mixed with CAFs and subcutaneously injected into nude mice to assess the in vivo tumor growth. As the result, twist1 was overexpressed in CAFs compared with NOFs and exhibited adverse prognostic significance. In CAFs, twist1 promoted the expression and secretion of CXCL12. In EC cells, activated CXCL12/CXCR4 signaling promoted the EMT process through ERK/AKT - twist1 - MMP1/E-cadherin pathway. In addition, knockdown of twist1 in CAFs also suppressed in vivo tumor growth. In conclusion, our results revealed a dual role of twist1 in CAFs and EC cells to promote the EMT process.

FoxC1 promotes epithelial-mesenchymal transition through PBX1 dependent transactivation of ZEB2 in esophageal cancer.

Esophageal cancer (EC) was one of the most lethal malignancies worldwide with intricate mechanisms. Here we reported that Forkhead box C1 (FoxC1), a member of the forkhead family transcription factors, was up-regulated in EC tissues and cell lines in comparison with controls. FoxC1 levels were negatively correlated with tumor stage, lymph node metastasis and survival status of EC patients. Knockdown of FoxC1 inhibited the proliferation, colony formation and epithelial-mesenchymal transition (EMT) of EC cells, while overexpression of FoxC1 promoted these biological behaviors. Mechanically, serial deletion and chromatin immunoprecipitation assays showed that ZEB2, a well-reported transcriptional suppressor of E-cadherin, was a direct transcriptional target of FoxC1. Moreover, FoxC1 was recruited to the ZEB2 promoter by its interaction with the pioneer transcription factor pre-B-cell leukemia homeobox 1 (PBX1). Importantly, significant correlation between levels of FoxC1 and ZEB2 was observed in EC tissues and the two proteins could be used as prognostic biomarkers together. Hence, our results revealed a critical role of FoxC1 in the EMT process of EC and uncovered a novel mechanism for the regulation of ZEB2-E-cadherin axis in EC.

Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB.

In the present study, the effects and molecular mechanisms of thymoquinone (TQ) on colon cancer cells were investigated. Cell viability was determined using a Cell Counting Kit-8 assay, and the results revealed that treatment with TQ significantly decreased cell viability in COLO205 and HCT116 cells in a dose-dependent manner. TQ treatment additionally sensitized COLO205 and HCT116 cells to cisplatin therapy in a concentration-dependent manner. To investigate the molecular mechanisms of TQ action, western blot analysis was used to determine the levels of phosphorylated p65 and nuclear factor-κB (NF-κB)-regulated gene products vascular endothelial growth factor (VEGF), c-Myc and B-cell lymphoma 2 (Bcl-2). The results indicated that TQ treatment significantly decreased the level of phosphorylated p65 in the nucleus, which indicated the inhibition of NF-κB activation by TQ treatment. Treatment with TQ also decreased the expression levels of VEGF, c-Myc and Bcl-2. In addition, the inhibition of NF-κB activation with a specific inhibitor, pyrrolidine dithiocarbamate, potentiated the induction of cell death and caused a chemosensitization effect of TQ in colon cancer cells. Overall, the results of the present study suggested that TQ induced cell death and chemosensitized colon cancer cells by inhibiting NF-κB signaling.

Tanshinone IIA enhances chemosensitivity of colon cancer cells by suppressing nuclear factor-κB.

The aim of the present study was to investigate the effect and molecular mechanism of tanshinone IIA (TSA) on colon cancer cells. Cell viability was determined using Cell Counting kit-8 assay and the results demonstrated that TSA treatment significantly decreased the cell viability of HCT1116 and COLO205 cells in a dose-dependent manner. TSA treatment also sensitized HCT1116 and COLO205 cells to fluorouracil therapy in a concentration-dependent manner. Western blotting was performed in order to investigate the molecular mechanisms of TSA action and determine the level of phosporylated p65 and nuclear factor-κB (NF-κB)-regulated genes, including vascular endothelial growth factor (VEGF), c-Myc, cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2). The results revealed that TSA treatment greatly decreased the level of phosphorylated p65 in the nucleus, which indicated the inhibition of NF-κB activation by TSA treatment. TSA also decreased the expression levels of VEGF, c-Myc, COX-2 and Bcl-2. Furthermore, the inhibition of NF-κB activation with the specific inhibitor, pyrrolidine dithiocarbamate, increased the induction of cell death and chemosensitization effect of TSA in colon cancer cells. In conclusion, these results suggest that TSA induces cell death and chemosensitizes colon cancer cells through the suppression of NF-κB signaling.

A preliminary study of plasma cyclase-associated protein 2 as a novel biomarker for early stage and alpha-fetoprotein negative hepatocellular carcinoma patients.

BACKGROUND AND OBJECTIVE: Cyclase-associated protein 2 (CAP2) has recently been suggested to be a candidate biomarker for hepatocellular carcinoma (HCC). We aim to investigate the application of CAP2 as a novel biomarker for HCC patients especially for those at early stage and are AFP-negative. METHODS: The CAP2 and AFP plasma levels were analyzed by enzyme-linked-immunosorbent assay in 86 HCC, 59 cirrhotic patients, and 30 normal individuals. Their correlation with HCC tumor behavior, disease stages, diagnostic sensitivity, specificity and accuracy were analyzed. RESULTS: The results showed that both CAP2 and AFP plasma levels in HCC patients were significantly elevated when compared to cirrhosis and controls. CAP2 levels correlate well with HCC patient's histological grade, clinical stage and tumor size, but not with patient's age, gender, hepatitis B virus infection status and plasma AFP level. CAP2 had better sensitivity as compared to AFP (82.6% vs 59.3%) for general HCC, and early stage of HCC patients (78.6% vs 40.4%). In addition, CAP2 is able to complement AFP to predict 82.9% of HCC in AFP-negative patients. CONCLUSION: We suggest that CAP2 is a novel biomarker for HCC patient, this may be especially useful for detection of early stage HCC and when plasma AFP level is negative.

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis.

AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis. METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period. RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 10(9)/L vs 63.3 ± 15.7 × 10(9)/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation. CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.

Plasma minichromosome maintenance complex component 6 is a novel biomarker for hepatocellular carcinoma patients.

AIM: This study aimed to investigate the presence of plasma minichromosome maintenance complex component 6 (MCM6) mRNA and protein levels in hepatocellular carcinoma (HCC) patients and evaluate their diagnostic value for HCC. METHODS: Blood samples were collected from 61 HCC and 29 cirrhotic patients, and 30 healthy individuals. Circulating RNA was extracted from plasma of all samples. The mRNA for MCM6 were amplified and quantified by real-time polymerase chain reaction. Plasma MCM6 and α-fetoprotein (AFP) protein levels were measured by enzyme-linked immunosorbent assay. RESULTS: In HCC patients, MCM6 mRNA and protein levels were significantly increased over the cirrhotic and healthy controls. The levels of MCM6 mRNA and protein in the plasma of HCC patients correlated to vascular invasion (P < 0.01). Higher MCM6 protein levels also correlated with tumor stage progression and lymph node metastasis. The MCM6 protein has sensitivity of 67.2% and specificity of 89.8% in differentiating total HCC from non-HCC individuals. In the AFP negative HCC group, MCM6 mRNA and protein could both detect 76.9% of HCC patients; combining the two of them increased the detection rate to 84.6%. In small HCC patients, MCM6 mRNA and protein could detect 64.3% and 71.4% of patients, respectively; combining AFP, MCM6 mRNA and MCM6 protein could detect 85.7% of small HCC patients. CONCLUSION: Our results suggest that MCM6 mRNA and protein levels in plasma can be promising independent biomarkers for HCC, especially in AFP negative and small HCC patients.

Plasma CD24 as a novel useful biomarker in differentiating hepatocellular carcinoma patients from normal individuals.

BACKGROUND/AIMS: CD24 is reported to be up-regulated in the tissues of HCC patients when compared with normal liver tissues. We aim to determine whether CD24 protein is also overexpressed in the plasma of HCC patients, and its diagnostic value for HCC. METHODOLOGY: Plasma levels of CD24 protein and AFP were measured by enzyme linked immunosorbent assay (ELISA) in the plasma of 90 patients with hepatocellular carcinoma and 30 healthy controls. The sensitivity and specificity were calculated and the relationship between the expression of CD24 and clinical pathological parameters was analyzed. RESULTS: Both plasma CD24 protein and AFP levels in HCC patients were higher than those in healthy controls (p<0.05). There was no correlation between plasma levels of AFP and CD24 in 90 patients with HCC (r=-0.084, p=0.430). The best cut-off value of CD24 was 3.31ng/mL, which yielded a sensitivity and specificity of 83.3% and 93.3%, respectively, for screening HCC; and plasma CD24 level was not associated with gender, age, hepatitis infection status, tumor size and histological differentiation and TNM stage (p>0.05). CONCLUSIONS: Plasma CD24 protein might serve as a novel tumor marker in differentiating HCC patients from normal individuals as well as monitor HCC status in AFP negative HCC patients.

Therapeutic effects of plasma exchange for the treatment of 39 patients with acute fatty liver of pregnancy.

AIM: Analysis of the efficacy and timing of plasma exchange (PE) in the treatment of acute fatty liver of pregnancy (AFLP). METHODS: The clinical data of 39 cases of AFLP treated with PE from September 2004 to March 2011 include symptoms, physical signs, adverse effects, and all relevant laboratory test results before and after PE. RESULTS: (1) Adverse reactions during PE were generally mild and tolerable, and no patients discontinued treatment due to adverse events; symptoms, physical signs, and liver and kidney functions improved significantly after PE (P<0.05); (2) of the 39 cases treated, 37 were cured, 2 died, with a cure rate of 94.87%; (3) of the 37 cases cured, the sooner a patient received PE the faster the recovery and the fewer number of PEs needed for a complete recovery (P<0.01). CONCLUSION: Treatment of AFLP by PE is safe and effective, and timely application of PE in the early phase of the disease can effectively halt and reverse the progression of AFLP.