TSC2 nonsense mutation in angiomyolipoma with epithelial cysts: a case report and literature review.

Background: Angiomyolipoma with epithelial cysts (AMLEC) is an extremely rare subtype of kidney angiomyolipoma that contains epithelial-lined cysts. The most distinctive immunohistochemical feature of AMLEC is its immunoreactivity with melanocytic markers. AMLEC also has a distinct histological structure, which aids in its pathological diagnosis. To date 27 cases of AMLEC have been reported in 11 case series. However, the molecular biology underlying the pathogenesis of AMLEC remains unexplored. Case report: A 30-year-old female was diagnosed with AMLEC and underwent partial nephrectomy. Histologically, the cross-section of cystic tissue revealed a multilocular appearance, with some cysts containing thrombus-like material, and the wall thickness was approximately 0.2 ~ 0.3 cm. Additionally, the compact subepithelial cellular stroma showed strong and diffuse nuclear labeling for estrogen receptor, progesterone receptor, and CD10, as well as HMB45 and Melan A, which are markers of melanocytic differentiation. Furthermore, using a DNA targeted sequencing panel with next-generation sequencing, we identified a nonsense mutation in TSC Complex Subunit 2 (TSC2) gene, resulting in the formation of a premature termination codon. Moreover, the mutated genes found to be enriched in the PI3K-AKT pathway. The patient in this case had a favorable postoperative follow-up at 3 months. Conclusion: To the best of our knowledge, this study represents the first analysis of genotype mutations in AMLEC, providing valuable insights for future clinical practice. These findings have significant potential in guiding the understanding and management of AMLEC, paving the way for further research and advancements in the field.

Peli1 deletion in macrophages attenuates myocardial ischemia/reperfusion injury by suppressing M1 polarization.

The polarization of macrophages to the M1 or M2 phenotype has a pivotal role in inflammatory response following myocardial ischemia/reperfusion injury. Peli1, an E3 ubiquitin ligase, is closely associated with inflammation and autoimmunity as an important regulatory protein in the Toll-like receptor signaling pathway. We aimed to explore the function of Peli1 in macrophage polarization under myocardial ischemia/reperfusion injury and elucidate the possible mechanisms. We show here that Peli1 is upregulated in peripheral blood mononuclear cells from patients with myocardial ischemia/reperfusion, which is correlated with myocardial injury and cardiac dysfunction. We also found that the proportion of M1 macrophages was reduced and myocardial infarct size was decreased, paralleling improvement of cardiac function in mice with Peli1 deletion in hematopoietic cells or macrophages. Macrophage Peli1 deletion lessened M1 polarization and reduced the migratory ability in vitro. Mechanistically, Peli1 contributed to M1 polarization by promoting K63-linked ubiquitination and nuclear translocation of IRF5. Moreover, Peli1 deficiency in macrophages reduced the apoptosis of cardiomyocytes in vivo and in vitro. Together, our study demonstrates that Peli1 deficiency in macrophages suppresses macrophage M1 polarization and alleviates myocardial ischemia/reperfusion injury by inhibiting the nuclear translocation of IRF5, which may serve as a potential intervention target for myocardial ischemia/reperfusion injury.

BCL10 correlates with bad prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma.

It has been reported that B-cell CLL-lymphoma 10 (BCL10) serves as an oncogene in cervical cancer. However, the roles of BCL10 in hepatocellular carcinoma (HCC), especially involved in immune infiltration remain not clear. This study aims to explore the relationship between BCL10 and the prognosis and clinical significance, and immune infiltration in HCC. The expression of BCL10 was analyzed between HCC samples and non-tumor samples in the multiple datasets. In addition, the prognostic values of BCL10 and its methylation in HCC were also investigated. The clinical significance of BCL10 has also been explored. Furthermore, the correlation between BCL10 and immune infiltration in HCC microenvironment was assessed. Finally, the biological behaviors of BCL10 in HCC were verified by cell function experiments. It was found that the expression levels of BCL10 were increased in HCC patients in multiple datasets. Moreover, the increased BCL10 and its reduced methylation were associated with the poor survival. BCL10 was significantly associated with immune infiltration. When BCL10 was knocked down in HCC cells, their proliferation ability was significantly inhibited, their migration was significantly decreased, their apoptosis was significantly increased, and AKT signaling pathway was inhibited. In conclusion, BCL10 is a potential prognostic and diagnostic biomarker related to immune infiltration in HCC microenvironment.

IL-2 Modulates TAMs Derived Exosomal MiRNAs to Ameliorate Hepatocellular Carcinoma Development and Progression.

Background. Interleukin-2 (IL-2) is proved to play an irreplaceable role in antitumor regulation in numerous experimental and clinical trials. Tumor-associated macrophages (TAMs) are able to release exosomes to promote the development and progression of hepatocellular carcinoma (HCC) as essential component of microenvironment. In this study, our intention is to explore the effects of the exosomes from TAMs with IL-2 treatment on HCC development. TAMs were collected and cultured from HCC tissues. The exosomes from the TAMs treated with IL-2 (ExoIL2-TAM) or not (ExoTAM) were identified and used to treat HCC cells in vivo and in vitro. The proliferation, apoptosis, and metastasis of HCC cells were measured. The changes of miRNAs in exosomes were explored to clarify the possible mechanisms. Both decrease of cell proliferation and metastasis and increase of apoptosis were observed with ExoIL2-TAM treatment compared with ExoTAM in vivo and in vitro. miR-375 was obviously augmented in ExoIL2-TAM and HCC cells treated with ExoIL2-TAM. Taken together, IL-2 may modulate exosomal miRNAs from TAMs to ameliorate hepatocellular carcinoma development. This study provides a new perspective to explain the mechanism by which IL-2 inhibits hepatocellular carcinoma and implies the potential clinical value of exosomal miRNAs released by TAMs.

Risk and protection strategies of Amolops wuyiensis intestine against gastrointestinal nematode (Cosmocercoides wuyiensis n. sp.) infection.

Anuran amphibians are susceptible to infection by intestinal nematodes, but the damage and response mechanisms that occur in their intestines after infection are only partially understood. In this study, the intestinal disruption and response mechanisms in Amolops wuyiensis frogs infected with Cosmocercoides wuyiensis n. sp. were revealed through analysis of the intestinal histopathology, digestive enzyme activity, transcriptome and intestinal microbiota. Tissue section analysis showed histological damage and inflammation in the infected intestine, and the digestive enzyme activity indicated a decrease in digestion and absorption of some nutrients. We found that infection led to differences in the intestinal microbiota composition, including lower diversity and symbiotic relationships. The greater relative abundance of the genera Burkholderia and Rhodococcus may enhance intestinal immunity to resist pathogenic infections. A comparison of the transcriptomes of infected and uninfected intestines revealed 1055 differentially expressed genes. GO enrichment and KEGG pathways analyses suggested that the guts of infected C. wuyiensis n. sp. show enhanced complement activation, cell adhesion molecule function, NOD-like receptor signalling pathway activity and other innate immunity responses. Among the adaptive immune responses, the intestinal immune network for IgA production was significantly enriched, and the expression of IL-17D and transforming growth factor beta-1 genes were upregulated in the infected intestine. These results imply that C. wuyiensis n. sp. infection of A. wuyiensis intestine may trigger innate and adaptive immune responses, which reduce the post-infection burden. Furthermore, the intestine of A. wuyiensis may also respond to C. wuyiensis n. sp. infection by increasing metallocarboxypeptidase activity and accelerating smooth muscle contraction.

Early genetic diagnosis of clarithromycin resistance in Helicobacter pylori.

BACKGROUND: The drug resistance rate of clinical Helicobacter pylori (H. pylori) isolates has increased. However, the mechanism of drug resistance remains unclear. In this study, drug-resistant H. pylori strains were isolated from different areas and different populations of Chinese for genomic analysis. AIM: To investigate drug-resistant genes in H. pylori and find the genes for the early diagnosis of clarithromycin resistance. METHODS: Three drug-resistant H. pylori strains were isolated from patients with gastritis in Bama County, China. Minimal inhibitory concentrations of clarithromycin, metronidazole, and levofloxacin were determined and complete genome sequencing was performed with annotation. Hp1181 and hp1184 genes were found in these strains and then detected by reverse transcription polymerase chain reaction. The relationships between hp1181 or hp1184 and clarithromycin resistance were ascertained with gene mutant and drug-resistant strains. The homology of the strains with hp26695 was assessed through complete genome detection and identification. Differences in genome sequences, gene quantity, and gene characteristics were detected amongst the three strains. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains, which was the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains was assessed. RESULTS: The strains showing a high degree of homology with hp26695, hp1181, and hp1184 genes were found in these strains; the expression of the genes hp1184 and hp1181 was associated with clarithromycin resistance. CONCLUSION: Hp1181 and hp1184 mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the potential target genes for the diagnosis, prevention, and treatment of clarithromycin resistance.

[Chrysin inhibited epithelial-mesenchymal transition of type â ¡ alveolar epithelial cell by regulating NF-κB/Twist 1 signaling pathway].

This study aimed to assess whether chrysin(ChR) can inhibit epithelial-mesenchymal transition(EMT) of type Ⅱ alveolar epithelial cell and produce anti-pulmonary fibrosis effect by regulating the NF-κB/Twist 1 signaling pathway. Sixty rats were randomly divided into the control group, the bleomycin(BLC) group, BLC+ChR(50 mg·kg~(-1)) group and BLC+ChR(100 mg·kg~(-1)) group, with 15 rats in each group. The pulmonary fibrosis model was induced by intratracheal injection of BLC(7 500 U·kg~(-1)). Rats were orally administered with different doses of ChR after BLC injection for 28 days. The cells were divided into control group, TGF-ß1 group(5 ng·mL~(-1)), and TGF-ß1+ChR(1, 10, 100 µmol·L~(-1)) groups. The type Ⅱ alveolar epithelial cells were treated with TGF-ß1 for 24 h, and then treated with TGF-ß1 for 48 h in the presence or absence of different doses of ChR(1, 10 and 100 µmol·L~(-1)). The morphological changes and collagen deposition in lung tissues were analyzed by HE staining, Masson staining and immunohistochemistry. The mRNA and protein expression levels of collagen Ⅰ, E-cadherin, zonula occludens-1(ZO-1), vimentin, alpha smooth muscle actin(α-SMA), inhibitor of nuclear factor kappa B alpha(IκBα), nuclear factor-kappa B p65(NF-κB p65), phospho-NF-κB p65(p-p65) and Twist 1 in lung tissues and cells were detected by qPCR and Western blot, respectively. The animal experiment results showed that as compared with the BLC group, after administration of ChR for 28 days, bleomycin-induced pulmonary fibrosis in rats was significantly relieved, collagen Ⅰ expression in lung tissues was significantly reduced(P<0.05 or P<0.01), and EMT of alveolar epithelial cells was obviously inhibited [the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], concomitantly with significantly reduced IκBα and p65 phosphorylation level in cytoplasm and decreased NF-κB p65 and Twist 1 expression in nucleus(P<0.05 or P<0.01). The cell experiment results showed that different doses of ChR(1, 10 and 100 µmol·L~(-1)) significantly reduced TGF-ß1-induced collagen Ⅰ expression(P<0.05 or P<0.01), significantly inhibited EMT of type Ⅱ alveolar epithelial cells[the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], and inhibited IκBα and p65 phosphorylation in cytoplasm and down-regulated NF-κB p65 and Twist 1 expression in nucleus induced by TGF-ß1(P<0.05 or P<0.01). The results suggest that ChR can reverse EMT of type Ⅱ alveolar epithelial cell and alleviate pulmonary fibrosis in rats, and its mechanism may be associated with reducing IκBα phosphorylation and inhibiting NF-κB p65 phosphorylation and nuclear transfer, thus down-regulating Twist 1 expression.

Molecular characterization, expression analysis of myostatin gene and its negative regulation by miR-29b-3p in Chinese concave-eared frogs (Odorrana tormota).

The molecular characteristics, expression patterns and functions of the amphibian myostatin (MSTN) gene are unknown. Here, we isolated a full-length Odorrana tormota MSTN cDNA sequence of 1701 bp (Ot-MSTN), containing a putative N-terminal signal peptide, a TGF-ß propeptide domain and an active peptide. Ot-MSTN was expressed in 9 selected tissues examined, and the highest level of expression was in thigh muscle, followed by brain and female gonadal tissue. The expression of Ot-MSTN in multiple O. tormota tissues supported that the activities of MSTN may be not limited to skeletal muscle. Ot-MSTN expression was decreased from stage 31 to stage 40, while the growth rate was increased. The expression of Ot-MSTN in adult male frogs increased with age, indicating that adult male frogs may inhibit the continued hypertrophy of thigh muscle fibers and decrease the growth rate of thigh muscle to ensure muscles do not grow too large. Luciferase reporter assays showed that miR-29b-3p directly targeted the 3'-UTR of Ot-MSTN. miR-29b-3p expression in the thigh muscle of 2 yrs. females who grew faster was significantly lower than that of the slow-growing 2 yrs. male individuals, which showed an opposite trend with Ot-MSTN expression. In addition，miR-29b-3p expression reversed trends of Ot-MSTN expression at different developmental stages in thigh muscle. Therefore, these data indicate that miR-29-3p may negatively regulate the expression of MSTN and regulate thigh muscle growth and development in O. tormota.

Malignant glomus tumor of the thyroid gland: a case report.

OBJECTIVE: Primary malignant glomus tumors of the thyroid gland are a rare occurrence. METHODS: A 68-year-old man found a mass on the right side of his neck in October 2017. An X-ray examination on 9 January 2018 showed multiple round reinforced masses in both sides of the lung. Computed tomography imaging of the neck showed a low-density mass on the right side of the thyroid gland. RESULTS: The immunohistochemistry results were positive for smooth muscle actin, calponin, collagen IV, and Ki-67 60%. The patient received chemotherapy starting on 17 January 2018, 8 February 2018, and 11 March 2018. The chemotherapy drugs included ifosfamide, epirubicin, and cisplatin. However, the patient subsequently developed multiple organ failure and died in April 2018, approximately 6 months after the initial discovery of the mass in his neck. CONCLUSIONS: Primary malignant glomus tumors of the thyroid gland are rare, and examination of their pathology and immunohistochemistry is vital for making an accurate final diagnosis. This case also indicates that primary malignant glomus tumors of the thyroid gland may have a poor prognosis, despite chemotherapy.

Upregulated forkhead-box A3 elevates the expression of forkhead-box A1 and forkhead-box A2 to promote metastasis in esophageal cancer.

Esophageal cancer (EC) is one of the most lethal cancers currently known. Members of the forkhead-box A (FOXA) family, including FOXA1 and FOXA2, have been reported to regulate EC progression. However, the role of FOXA3, which is another FOXA member, has not yet been investigated. In the present study, public dataset analyses and immunohistochemistry of 96 samples from patients with EC were performed to determine the potential roles of FOXA3 in EC. The results revealed that FOXA3 was significantly upregulated in EC tumor tissues and Barrett's esophagus tissues. In addition, FOXA3 upregulation was positively associated with tumor invasion, distant metastasis, tumor-node-metastasis stage and shorter overall survival in patients with EC, and multivariate analysis identified FOXA3 as an independent prognostic marker. In vitro experiments demonstrated that the migratory and invasive abilities of EC109 and EC9706 cell lines were inhibited following FOXA3 knockdown. Notably, FOXA3 expression levels were positively correlated with FOXA1 and FOXA2 expression levels according to The Cancer Genome Atlas dataset analysis. Furthermore, FOXA3 knockdown decreased the expression levels of FOXA1 and FOXA2 in EC109 and EC9706 cell lines. Conversely, FOXA1 or FOXA2 overexpression compensated for the effects of FOXA3 knockdown on the migratory and invasive capacities of EC cells. In conclusion, the present study demonstrated that FOXA3 upregulation in EC cells promoted metastasis through regulation of other FOXA members.

MicroRNA-21 attenuates BDE-209-induced lipid accumulation in THP-1 macrophages by downregulating Toll-like receptor 4 expression.

Growing evidence demonstrates a possible response of specific microRNA (miRNA) to environmental pollutant stimuli in multiple biological processes. We previously reported that a persistent organic pollutant, decabromodiphenyl ether (BDE-209), can enhance Toll-like receptor 4 (TLR4)-dependent lipid uptake in THP-1 macrophages; whether miRNAs are involved in this process remains unclear. In the present study, we investigated the levels of several miRNAs related to TLR4 signaling, including miRs-9, -21, -27b, -125b, -132, -146a, -147, -155, and -let-7e, in THP-1 macrophages after stimulation by BDE-209 and oxidized low-density lipoprotein. The results showed that the levels of miR-21 were significantly suppressed by BDE-209 at concentrations of 6.25, 12.5 and 25 µM, in a dose-dependent manner; whereas there was no significant changes for the other miRNAs investigated. Moreover, the suppression of miR-21 was accompanied by an upregulated TLR4 expression, at both mRNA and protein levels. Further analysis showed that the up-regulated TLR4 induced by BDE-209 was inhibited in macrophages transfected with miR-21 mimic; meanwhile opposite results were exhibited when an anti-miR-21 inhibitor was transfected to the macrophages. Additionally, transfection with miR-21 mimic effectively attenuated BDE-209-induced lipid accumulation in macrophages. Together, these data illustrate that miR-21 inhibits BDE-209-triggered lipid accumulation in macrophages through down-regulating TLR4 expression.

Decarbromodiphenyl ether (BDE-209) promotes monocyte-endothelial adhesion in cultured human aortic endothelial cells through upregulating intercellular adhesion molecule-1.

There is growing evidence that exposure to persistent organic pollutants (POPs) is statistically associated with incidence of cardiovascular disease (CVD) or its risk factors. Decarbromodiphenyl ether (BDE-209) is a new POP which exists extensively in human tissues, but its potential effects on CVD have so far received less focus. The adhesion of circulating monocytes to endothelial cells is one of the critical underlying steps in the initiation and development of CVD. In the present study, we investigated the effect of BDE-209 on the adhesion of THP-1 monocytes to human aortic endothelial cells (HAECs) and identified the molecular mechanisms involved. Our results showed that 6.25, 12.5 and 25 µM of BDE-209 exposures caused significant increases in monocyte-endothelial cell adhesion, in a dose-dependent manner. Mechanistically, BDE-209 exposure increased the expression of intercellular adhesion molecule-1 (ICAM-1). Moreover, the up-regulation of ICAM-1 was accompanied by a decrease in the expression of microRNA-141 (miR-141). Furthermore, the up-regulation of ICAM-1 and the increased adhesion induced by BDE-209 could be reversed by miR-141 supplement. Taken together, our results show that BDE-209 potentiates monocyte-endothelial cell interaction via miR-141/ICAM-1 pathway in HAECs.

Decabromodiphenyl ether (BDE-209) enhances foam cell formation in human macrophages via augmenting Toll-like receptor 4-dependent lipid uptake.

Growing epidemiological evidence is substantiating an association between exposure to persistent organic pollutants (POPs) and incidence of atherosclerosis. Decabromodiphenyl ether (BDE-209) is a new POP which presents extensively in human populations; whether this contaminant is potentially arteriosclerotic remains unclear. In this study, we investigated the effects of BDE-209 on macrophage-derived foam cell formation, a hallmark of early atherosclerosis, using THP-1-derived macrophages incubated with oxidized low-density lipoprotein (oxLDL) as a foam cell model. The results showed that 6.25, 12.5 and 25.0 µM of BDE-209 significantly enhanced lipid accumulation inside the foam cells, in a dose-dependent manner. Further mechanism assays suggested that BDE-209 significantly increased the expression of Toll-like receptor 4 (TLR4), a signal transducing integral membrane protein mediating lipid uptake in macrophages, at both the mRNA and protein levels. In contrast, there was no significant changes for several key regulators involving in lipid efflux, lipogenesis, and lipid oxidation in macrophages. Furthermore, the augmented lipid accumulation was almost completely abrogated by treatment with an anti-TLR4 antibody. Together, these data illustrate that BDE-209 enhances oxLDL-induced macrophage foam cell formation via augmenting TLR4-dependent lipid uptake in the cells.

Circular RNA hsa_circ_0000567 can be used as a promising diagnostic biomarker for human colorectal cancer.

BACKGROUND: Recent studies have revealed that circular RNAs are involved in the biological process of some kinds of human cancers. However, little is known about their diagnostic values and functions in colorectal cancer (CRC). METHODS: The expression levels of hsa_circ_0000567 in 102 paired CRC tissues and adjacent noncancerous tissues, 5 CRC cell lines, and a normal colorectal epithelial cell line were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations between hsa_circ_0000567 expression levels and the clinicopathological factors of patients with CRC were analyzed. Furthermore, the loss-of-function assay was performed to investigate the functions of hsa_circ_0000567 in vitro. Finally, a receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0000567. RESULTS: Hsa_circ_0000567 expression was significantly downregulated in CRC tissues and CRC cell lines. In addition, the decreased hsa_circ_0000567 expression in CRC was negatively correlated with tumor size (P = .011), lymph metastasis (P = .003), distal metastasis (P < .0001), and tumor-node-metastasis (TNM) stage (P = .003) in CRC. Moreover, knockdown of hsa_circ_0000567 promoted CRC cells proliferation and migration in vitro. Importantly, the area under the ROC curve (AUC) was 0.8653, which indicates hsa_circ_0000567 can serve as a diagnostic biomarker. CONCLUSION: Hsa_circ_0000567 may be a novel suppressor and a potential diagnosis biomarker in CRC.

Inhibition of NF-κB pathway in fibroblast-like synoviocytes by α-mangostin implicated in protective effects on joints in rats suffering from adjuvant-induced arthritis.

α-Mangostin (MG) is a bioactive compound isolated from mangosteen. This study was aimed to investigate effects of MG on adjuvant-induced arthritis (AA) in rats and decipher the underlying mechanisms. Clinical severity of AA was evaluated by paw oedema, arthritis score, and hematological parameters. Digital radiography (DR) and histological examinations were employed to assess joints destructions. Immune functions were evaluated by T cell subsets distribution. Effects on NF-κB pathway were investigated by immunohistochemical, western-blot and immunofluorescence methods both in vivo and vitro. It was found MG possessed superior anti-inflammatory effects in vivo, suggested by attenuated paw swelling, reduced inflammatory cells infiltration and decreased the secretion of TNF-α and IL-1ß in serum. Meanwhile MG inhibited fibrous hyperplasia, synovial angiogenesis, cartilage and bone degradation in AA rats. Although MG exerted little effects on CD4+ population, it greatly decreased IFN-γ positive cells and promoted expression of FOXP3 in immune organs, indicating restoration of Th1/Treg cells ratio and recovery of immune homeostasis in vivo. Inhibition of NF-κB induced by MG was indicated by reduced the expression of p-p65 and VEGF in synovium. In vitro experiments found MG at 10 µg/ml significantly suppressed the expression and phosphorylation of key proteins implicated in NF-κB pathway and inhibited nucleus translocation of p65. These changes led to increased apoptosis and proliferation inhibition of HFLS-RA cells. The results demonstrated regulation of immune functions was deeply involved in the therapeutic actions of MG on AA, and it's inhibition on NF-κB in fibroblast-like synoviocytes was associated to the protective effects on joints.

HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma.

Despite increasing evidence of the involvement of histone deacetylase (HDAC)10 in cancer tumorigenesis, the potential role of HDAC10 in colon cancer remains unclear. Oncomine database analysis revealed that HDAC10 mRNA was significantly upregulated in colon cancer. In an independent cohort, consistent with mRNA expression levels, constitutively high HDAC10 expression was observed in the cytoplasm and nucleus compared with in adjacent normal tissues (cytoplasm, 93.12±12.98 vs. 31.65±26.50%; nucleus, 84.16±19.23 vs. 68.64±19.00%). Cytoplasmic HDAC expression correlated with gender (r=0.265; P<0.05), lymph node metastasis (N stage; r=0.256; P<0.05) and distant metastasis (M stage; r=0.331; P<0.05) in paracarcinoma tissues. Cytoplasmic HDAC10 expression in tumors was not associated with the four DNA mismatch repair genes examined, but was negatively correlated with mutL homolog 1 (MLH1) (r=-0.244; P<0.05), mutS homolog (MSH)2 (r=-0.410; P<0.01) and MSH6 (r=-0.240; P<0.05) in paracarcinoma tissues. Similarly, nuclear HDAC10 expression was negatively correlated with MLH1 expression (r=-0.288; P<0.05). The findings of the current study suggest that HDAC10 expression is associated with good prognosis in colon cancer tissues and poor prognosis in paracarcinoma tissues with a potential involvement in DNA mismatch repair.

Heparanase Contributes To Trans-Endothelial Migration of Hepatocellular Carcinoma Cells.

The overall outcome of patients with hepatocellular carcinoma (HCC) is still very poor due to its high metastasis and recurrence rate. During metastasis, trans-endothelial migration (TEM) of HCC cells is a key step. Heparanase (HPSE) is an endo-beta-glucuronidase and exerts prometastatic properties for normal and tumor-derived cells. However, it is remains unclear that HPSE contributes to TEM of HCC cells. In this study, human umbilical vein endothelial cells-C (HUVEC-C) was used to simulate vascular endothelial cells (VECs), and the HCCLM3 cells with high HPSE expression were chosen and used for in vitro TEM assay and in vivo experiment. As results, we found that HCCLM3 cells showed higher TEM rate compared with other HCC cells. Downregulation or inhibition of HPSE activity resulted in suppression of TEM of HCC cells both in vitro and in vivo. Our findings suggest that HPSE contributes to TEM of HCC cells, which may be a new biological function of HPSE.

Agkistrodon acutus-purified protein C activator protects human umbilical vein endothelial cells against H2O2-induced apoptosis.

CONTEXT: Recent studies show that the Agkistrodon acutus (Viperidae) (syn. Deinagkistrodon acutus) protein C activator (PCA) treats acute myocardial infarction and ischaemia-reperfusion animal models effectively, while the underlying mechanism remains unknown. OBJECTIVE: To study the effect of PCA on the injury of human umbilical vein endothelial cells (HUVECs) induced by H2O2 and the underlying mechanism. MATERIALS AND METHODS: Primary cultured HUVECs were pretreated with PCA (20, 40 and 80 µg/mL) for 1 h, then HUVEC apoptosis was induced by 300 µmol/mL H2O2. Apoptosis was analyzed by AnnexinV-FITC/PI, and reactive oxygen species (ROS) level was tested by flow cytometry. Colorimetric methods were used to detect the levels of NO and IL-1. In addition, real-time PCR and western blot analyses were used to detect the expression of eNOS and phospho-p38/MAPK. RESULTS: Morphological changes were induced by H2O2 in HUVECs. The cell survival rate was increased by 43.9, 64.0 and 80.6% in each PCA pretreated group (20, 40 and 80 µg/mL) compared to the model group. In each PCA pretreated group, oxidative stress level was also decreased to 54.7, 42.7 and 25.1%. Moreover, the level of IL-1 was decreased to 83.3, 62.2 and 30.7%. The level of NO was increased by 155.9, 232.4 and 317.6%. Apoptosis rate was decreased to 59.0, 47.7 and 32.7%. Phospho-p38 expression was downregulated, but eNOS expression was upregulated. DISCUSSION AND CONCLUSION: The results suggest that PCA can effectively protect the endothelial cells from injury induced by H2O2, which may be associated with antioxidation, upregulation of eNOS and downregulation of p38-MAPK.