Elastin Shapes Small Molecule Distribution in Lymph Node Conduits.

The spatial and temporal Ag distribution determines the subsequent T cell and B cell activation at the distinct anatomical locations in the lymph node (LN). It is well known that LN conduits facilitate small Ag distribution in the LN, but the mechanism of how Ags travel along LN conduits remains poorly understood. In C57BL/6J mice, using FITC as a fluorescent tracer to study lymph distribution in the LN, we found that FITC preferentially colocalized with LN capsule-associated (LNC) conduits. Images generated using a transmission electron microscope showed that LNC conduits are composed of solid collagen fibers and are wrapped with fibroblastic cells. Superresolution images revealed that high-intensity FITC is typically colocalized with elastin fibers inside the LNC conduits. Whereas tetramethylrhodamine isothiocyanate appears to enter LNC conduits as effectively as FITC, fluorescently-labeled Alexa-555-conjugated OVA labels significantly fewer LNC conduits. Importantly, injection of Alexa-555-conjugated OVA with LPS substantially increases OVA distribution along elastin fibers in LNC conduits, indicating immune stimulation is required for effective OVA traveling along elastin in LN conduits. Finally, elastin fibers preferentially surround lymphatic vessels in the skin and likely guide fluid flow to the lymphatic vessels. Our studies demonstrate that fluid or small molecules are preferentially colocalized with elastin fibers. Although the exact mechanism of how elastin fibers regulate Ag trafficking remains to be explored, our results suggest that elastin can be a potentially new target to direct Ag distribution in the LN during vaccine design.

The long non-coding RNA H19 induces hypoxia/reoxygenation injury by up-regulating autophagy in the hepatoma carcinoma cells.

BACKGROUND: Long non-coding RNA H19 (H19) plays an important role by regulating protein expression in different tissues and organs of the body. However, whether H19 induces hypoxia/reoxygenation (h/R) injury via increase of autophagy in the hepatoma carcinoma cells is unknown. RESULTS: H19 was expressed in the hepatoma carcinoma cells (Hep G2 and HCCLM3 cells) and its expression was most in 8 h/24R. The knockdown of H19 and 3-MA (an autophagy inhibitor) protected against h/R-induced apoptosis, cell damage, the expression of cleaved caspase-3 and cleaved caspase-9, the release of cytochrome c (Cyt c). The knockdown of H19 and 3-MA also decreased the autophagic vesicles (AVs) and the expression of Beclin-1 and the ration of LC3-II/LC3-I, and increased cell viability, the expression of Bcl-2 and P62 and the phosphorylation of PI3K, Akt and mTOR. In addition, chloroquine (CQ, an inhibitor of autophagy flux) markedly decreased formation of autophagy flux (the ration of LC3-II/LC3-I). The results of the knockdown of H19 group were similar to those of the 3-MA (or CQ) group. Rapamycin (a mTOR inhibitor, an autophagy activator) further down-regulated h/R-induced decrease of the phosphorylated PI3K, Akt and mTOR. The knockdown of H19 cancelled the effect of rapamycin. The overexpression of H19 further expanded h/R-induced increase of the ration of LC3-II/LC3-I and decrease of the phosphorylated PI3K, Akt and mTOR. CONCLUSIONS: Our results suggest that the long non-coding RNA H19 induces h/R injury by up-regulation of autophagy via activation of PI3K-Akt-mTOR pathway in the hepatoma carcinoma cells.

miR-139-5p inhibits epithelial-mesenchymal transition, migration and invasion of hepatocellular carcinoma cells by targeting ZEB1 and ZEB2.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths worldwide. miRNAs have been suggested to have important roles in HCC development. The purpose of this study was to determine the role of miR-139-5p in regulation of epithelial-mesenchymal transition (EMT) and metastasis of HCC cells. Expression levels of miR-139-5p in 49 HCC specimens with adjacent tissues and five HCC cell lines were assessed by quantitative RT-PCR. We found that miR-139-5p was down-regulated in 89.7% of the HCC tissue samples and all of the HCC cell lines. In addition, luciferase reporter assays validated direct binding of miR-139-5p to the 3' untranslated region of zinc finger E-box binding homeobox 1 (ZEB1) and ZEB2. Ectopic expression of miR-139-5p suppressed and miR-139-in promoted EMT, migration, and invasion in Hep3B and SMMC7721 cells. Furthermore, over-expression of ZEB1 and ZEB2 ablated the inhibitory effects of miR-139-5p on migration and invasion in HCC cells. Our study indicates that miR-139-5p functions as a suppressor of HCC EMT and metastasis by targeting ZEB1 and ZEB2, and it may be a therapeutic target for metastatic HCC.

microRNA-34a inhibits epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway.

BACKGROUND: Extrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon malignancies in the digestive system which is characterized by a poor prognosis. Aberrations of miRNAs have been shown involved in the progression of this disease. In this study, we evaluated the expression and effects of miR-34a on EHCC. METHODS: miR-34a expression levels were detected in EHCC tissues, adjacent non-tumor tissues, normal bile duct (NBD) specimens of patients and cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics of EHCC patients were further analyzed. Computational search, functional luciferase assay and western blot were further used to demonstrate the downstream target of miR-34a in CC cells. Immunohistochemistry was carried on to identify the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion and migration assays were further applied to confirm the anti-carcinogenic effects of miR-34a through the downstream target. RESULTS: miR-34a expression was significantly decreased in human EHCC tissues and CC cell lines when compared with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was found correlated with the migration and invasion in EHCC patients. Smad4 was over-expressed in most of the EHCC patients and was further demonstrated as one of the downstream targets of miR-34a, which was involved in the progression of EHCC. Moreover, activation of miR-34a suppressed invasion and migration through TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in vitro. CONCLUSIONS: Taken together, our results suggest that miR-34a inhibits invasion and migration by targeting Smad4 to suppress EMT through TGF- beta/Smad signaling pathway in human EHCC.

Far-lateral approach assisted by multimodal neuronavigation and electrophysiological monitoring technique for complex clival tumor.

Large clival meningiomas are a major surgical challenge with risks to life and permanent deficit. A 65-year-old man with a meningioma anterior to the medulla oblongata with brain stem compression was operated with far-lateral approach assisted by multimodal neuronavigation and neurophysiological monitoring techniques. Total resection of the tumor was achieved with no intra- or post-operative complications. This case illustrates the benefits obtained by a multimodal approach.

Clinical characteristics, treatment patterns and survival outcome of hepatocellular carcinoma patients aged 70 years or older: a single-center retrospective study from China.

BACKGROUND AND AIMS: The information about clinical presentation and outcome of elderly hepatocellular carcinoma (HCC) patients is limited. We performed this study to assess the impact of age on potential differences in clinical characteristics, treatment patterns and outcome in HCC patients. METHODS: Clinical data of 164 "elderly" (≥70 years old) and 531 "younger" (<70 years old) HCC patients treated at a Chinese tertiary university-affiliated medical center between April 2004 and April 2012 were collected and compared using various parameters. RESULTS: Compared with younger patients, the elderly patients had a higher proportion of females (32.9 % vs. 18.1 %, p < 0.001), less hepatitis B virus (HBV) infection (40.9 % vs. 76.6 %, p < 0.001), more hepatitis C virus (HCV) infection (23.8 % vs. 5.6 %, p < 0.001), less liver cirrhosis (68.3 % vs. 76.8 %, p = 0.03) and massive tumors (12.8 % vs. 21.8 %, p = 0.01). There was no significant difference between the two groups in Child-Pugh class and tumor stages. The elderly patients received less surgical resection (14.6 % vs. 29.6 %, p < 0.001) and more supportive care (48.8 % vs. 37.9 %, p = 0.01) than younger patients. The overall survival was not significantly different between the two groups (26.2 mo. vs. 28.3 mo., p = 0.75). CONCLUSION: Characteristics that distinguish elderly from younger HCC patients included more female, less HBV infection, more HCV infection, less liver cirrhosis and massive tumors. Significant differences were observed in therapeutic strategies utilized with the two groups, but the overall survival was not significantly different.

Ti3AlC2 MXene nanosheets as a novel corrosion inhibitor for carbon steel in 0.5 M sulfuric acid solution.

Herein we report that Ti3AlC2 MXene nanosheets were identified as a highly effective cathodic protection corrosion inhibitor for carbon steel in hydrochloric acid solution. Ti3AlC2 Mxene nanosheets form a stable inhibition layer on metal surfaces due to their high adsorption capacity and act as a barrier or protective film to prevent attacks from corrosive substances and thus lead to an extended metal service life.

The association between common genetic variant of microRNA-499 and cancer susceptibility: a meta-analysis.

Published data on the association between microRNA-499 (miR-499) rs3746444 T>C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of this relationship, a comprehensive meta-analysis was performed on nine published studies, with a total sample of 4,794 cases and 5,971 controls. Overall, no significant association was found between miR-499 polymorphism and cancer risk after all studies were pooled into the meta-analysis. However, in the subgroup analysis by ethnicity, significant association with an increased risk was found in Asian (CC vs. TT: OR = 1.439, 95 % CI = 1.118-1.852, P = 0.005, p-heterogeneity = 0.116). Moreover, in the the subgroup analysis by cancer type, this SNP was associated with an increased risk of breast cancer in the recessive model (OR = 1.077, 95 % CI = 1.008-1.151, P = 0.028, p-heterogeneity = 0.125). Our findings support the view that miR-499 rs3746444 T>C polymorphism is associated with breast cancer and the C allele can increase cancer susceptibility in Asian.

The effect of a modified perioperative management model on the mental state, quality of life, and self-care ability score of patients after radical prostatectomy: A retrospective study.

To explore the effects of an improved perioperative management model on the mental state, quality of life, and self-care ability scores of patients after radical prostatectomy. Overall, 96 postoperative prostate cancer patients admitted to our hospital between November 2019 and May 2021 were retrospectively analyzed and classified into an observation group and a control group with 48 patients each, according to the management model they received. The patients in the control group received routine care and were discharged. The observation group implemented an improved perioperative management model than the control group. Differences in mental state, quality of life, and self-care ability scores between the 2 groups were compared. After nursing, the self-rating anxiety scale and self-rating depression scale scores of the 2 groups were significantly lower than those before nursing, and the observation group's self-rating anxiety scale and self-rating depression scale scores were significantly lower than those of the control group (P < .05). Regarding emotion, cognition, and society, the observation group's quality of life scores was significantly higher than those of the control group. In contrast, overall health was significantly lower than that of the control group (P < .05). After nursing, the observation group's self-care skills, self-responsibility, health knowledge, and self-concept scores were significantly better than those of the control group (P < .05). The improved prostate cancer perioperative management model helps improve patients' unhealthy mental state, quality of life, self-care ability, and provides guidelines for the clinical care of patients after prostate cancer surgery.

Construction and validation of a predictive model for the risk of three-month-postoperative malnutrition in patients with gastric cancer: a retrospective case-control study.

Background: This study analyzed both the influencing factors of malnutrition in patients with gastric cancer and established a multi-dimensional risk model to predict postoperative malnutrition three months after surgery. Methods: The clinical data of gastric cancer patients hospitalized for the first time and receiving laparoscopic surgery in the general surgery department of our hospital were retrospectively analyzed through the hospital information system and divided into a training set and a validation set in the ratio of 7:3. Nutritional status was assessed using the Patient Generated Subjective Global Assessment scale and follow-up records three months after surgery. Patients were divided into a non-malnutrition group and a malnutrition group, and a risk prediction model was established and displayed in the form of a nomogram. Results: A total of 344 patients were included, with 242 in the training and 102 in the validation set. Tumor node metastasis stage (TNM Stage, P=0.020), cardiac function grading (CFG, P=0.013), prealbumin (PAB, P<0.001), neutrophil-to-lymphocyte ratio (NLR, P=0.027), and enteral nutrition within 48 hours post-operation (EN 48 h post-op, P=0.025) were independent risk factors. We established a prediction model with the above variables and displayed it via a nomogram, then verified its effectiveness through internal and external verification. This revealed a C-index of 0.84 (95% CI: 0.79-0.89), and the area under curve (AUC) areas of 0.840 (training set) and 0.854 (validation set), which was better than the nutritional risk screening 2002 (NRS2002) scale. The calibration curve brier scores were 0.159 and 0.195, and the Hosmer-Lemeshow test chi-square values were 14.070 and 1.989 (P>0.05). The decision curve analysis (DCA) of the training set model indicated the clinical applicability was good and within the threshold probability range of 10%-85%, which was also better than NRS2002. Conclusions: A clinical prediction model including multi-dimensional variables was established based on independent risk factors of malnutrition three months after gastrectomy in patients with gastric cancer. The model yields greater prediction accuracy of the risk of three-month-postoperative malnutrition in patients with gastric cancer, helps screen high-risk patients, formulates targeted nutritional prescriptions early, and improves the overall prognosis of patients.

Prevalence and risk factors for colonisation and infection with carbapenem-resistant Enterobacterales in intensive care units: A prospective multicentre study.

OBJECTIVES: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit. RESEARCH METHODOLOGY/DESIGN: A prospective and multicentre study. SETTING: This study was conducted in 24 intensive care units in Anhui, China. MAIN OUTCOME MEASURES: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay. RESULTS: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition. CONCLUSION: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales. IMPLICATIONS FOR CLINICAL PRACTICE: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units.

Polysaccharide-K (PSK) increases p21(WAF/Cip1) and promotes apoptosis in pancreatic cancer cells.

BACKGROUND: Polysaccharide-K (PSK, Krestin(®)) is a natural remedy and one of the most commonly used medicinal mushroom extracts. It has been used as oral adjuvant treatment in cancer therapy in Japan and other Asian countries for more than 40 years. PSK is thought to be an immune modulator, however, its antitumor actions remain undefined. The aim of the present study was to investigate underlying mechanisms by which PSK exerts its antitumor effects on malignant epithelial cells. METHODS: Antitumor activities of PSK were evaluated on multiple human pancreatic adenocarcinoma cells in vitro. Cell viability, apoptotic pathways, cytokine expression and involvement of TLR2 and TLR4 were monitored by MTT, flow cytometry, Western blotting and protein arrays. RESULTS: We demonstrate that PSK acts as a growth inhibitor for pancreatic cancer cells, known otherwise to be highly resistant to conventional chemotherapies. Pancreatic cancer cells can be protected against PSK-mediated growth inhibition by neutralizing antibodies against TLR2 and TLR4. The antiproliferative actions were associated with upregulated cell cycle regulatory p21(WAF/Cip1) and pro-apoptotic protein Bax levels, resulting in cell cycle arrest and induction of apoptosis. In addition, a significant growth inhibition and additive effect was observed with PSK and gemcitabine administered as combined treatment. CONCLUSION: While previous studies have emphasized the potential importance of PSK in immune activation, the present results uncover additional mechanisms on epithelial cells that may contribute to the antitumor effects provided by PSK as suggested by clinical observations.

[Retracted] MicroRNA­466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data shown in Figs. 2C, 4C and 5C, and the cell invasion assay data shown in Figs. 2D and E, 4D and E and 5D and E were strikingly similar to data appearing in different form in other articles by different authors. In addition, the authors independently contacted the Editorial Office to request that this paper be retracted owing to the fact that they had not obtained approval from the Ethics Committee of The Second Affiliated Hospital of Harbin Medical University to use the tissue samples, even though they had written that this study was approved by the Ethics Committee, and written informed consent had been provided by all patients enrolled in the research. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, and the authors' own admission of serious problems concerning the ethical nature of the study, the Editor has decided that this paper should be retracted from the Journal. The authors have agreed to the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 40: 3890­3898, 2018; DOI: 10.3892/or.2018.6763].

The role of phosphatidylinositol 3-kinase signaling pathways in pancreatic cancer.

BACKGROUND: Pancreatic cancer is a highly malignant cancer and the fourth leading cause of cancer-related death. It is characterized by a rapid disease progression, a highly invasive tumor phenotype, and frequently resistance to chemotherapy. Despite significant advances in diagnosis, staging, and surgical management of the disease during the past decade, prognosis of pancreatic cancer is still dismal. METHODS AND RESULTS: The phosphatidylinositol 3-kinase (PI3K) signaling pathways regulate cellular growth, metabolism, survival, and motility in pancreatic cancer. Pancreatic cancer is associated with a high degree of genetic alterations that can result in aberrant activation of the PI3K signaling pathway. Elucidating the role of the PI3K signaling pathway in pancreatic cancer may thus be both meaningful and necessary. CONCLUSION: Improved knowledge of the PI3K signaling pathway in pancreatic cancer would furthermore be helpful in understanding mechanisms of tumor initiation and progression, and in identifying appropriate targeted anticancer treatment in pancreatic cancer. and IAP.

ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer.

The infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein-protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

Cyclin B1 acts as a tumor microenvironment-related cancer promoter and prognostic biomarker in hepatocellular carcinoma.

OBJECTIVES: The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. METHODS: The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein-protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. RESULTS: The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. CONCLUSIONS: The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.

A secretory function of human insulin-producing cells in vivo.

BACKGROUND: Mesenchymal stem cells derived from human umbilical cord blood (UCB-MSCs) have good research and application prospects in the treatment of diabetes. We once induced UCB-MSCs to differentiate into insulin-producing cells (IPCs) in vitro, but we did not know the functions of these cells in vivo. The aim of this study was to assess the functional effects of IPCs on insulin secretion and their role in the treatment of diabetes in vivo. METHODS: UCB-MSCs were induced to IPCs by an inducing protocol with extracellular matrix gel. BALB/C nude mice were made hyperglycemic by intraperitoneal injection of streptozotocin. The diabetic mice were transplanted with 1X10(7) IPCs under the renal capsule or with phosphate-buffered saline as a control. After transplantation, the grafts were analyzed by immunocytochemistry for the expression of human insulin; the serum human insulin levels were measured; and blood glucose and body weight status were monitored. RESULTS: Immunofluorescence showed that numerous IPCs under the kidney capsule were insulin-positive. On day 14 after transplantation, the serum human insulin level of the treatment group (n=9) averaged 0.44+/-0.12 mU/L, which was higher than that of the control group (n=9) that did not express insulin (t=10.842, P<0.05). The diabetic mice remained hyperglycemic and kept losing body weight after IPC transplantation, and there was no significant difference in the control group. CONCLUSION: IPCs differentiated from UCB-MSCs generate human insulin in diabetic mice, but more research is needed to make further use of them to regulate hyperglycemia and body weight in vivo.

miR­92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in gastric carcinoma cells.

MicroRNAs (miRNAs) are a class of short noncoding RNAs that negatively regulate gene expression and act as oncogenes or tumor suppressors. Numerous miRNAs have been reported be associated with the occurrence and development of gastric carcinoma (GC). For instance, miR­92a has been observed to be overexpressed in GC; however, the precise mechanisms underlying the role of miR­92a in GC and its role in clinical therapy require further investigation. In the present study, it was reported that miR­92a expression was significantly upregulated in GC tissues compared with in adjacent tissues. Additionally, suppression of miR­92a significantly reduced SGC7901 cell viability as demonstrated by a Cell Counting Kit­8 and colony formation assays. Suppression of miR­92a inhibited SGC7901 cell proliferation as determined by Ki­67 immunofluorescence staining, and the expression levels of proliferating cell nuclear antigen, cyclin dependent kinase (CDK)4 and CDK6, and increased that of p53. In addition, we reported that suppression of miR­92a induced apoptosis in SGC7901 cells. Furthermore, bioinformatics analysis identified that ING2 as a potential target of miR­92a. Downregulation of miR­92a significantly increased ING2 expression at the mRNA and protein levels. A dual­luciferase reporter assay validated a direct binding site of miR­92a on ING2. In addition, SGC7901 cells with suppression of miR­92a were more sensitive to doxorubicin treatment. Knockdown of miR­92a reduced the half­maximal inhibitory concentration of doxorubicin from 147.6 nM to 82.1 nM in SGC7901 cells. Knockdown of miR­92a also reduced SGC7901 cell survival under doxorubicin stimulation. Furthermore, SGC7901 cells with suppression of miR­92a harbored a greater number of DNA damage foci upon doxorubicin treatment compared with in control cells. The findings of the present study revealed that miR­92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in GC cells, which suggests a potential therapeutic strategy for the treatment of GC.

Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells.

BACKGROUND: Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes. However, this therapy is not widely used because of the severe shortage of transplantable donor islets. This study investigated whether mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) could be transdifferentiated into insulin producing cells in vitro and the role of extracellular matrix (ECM) gel in this procedure. METHODS: Human UCB samples were collected and MSCs were isolated. MSCs specific marker proteins were analyzed by a flow cytometer. The capacities of osteoblast and adipocyte to differentiate were tested. Differentiation into islet like cell was induced by a 15-day protocol with or without ECM gel. Pancreatic characteristics were evaluated with immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Insulin content and release in response to glucose stimulation were detected with chemiluminescent immunoassay system. RESULTS: Sixteen MSCs were isolated from 42 term human UCB units (38%). Human UCB-MSCs expressed MSCs specific markers and could be induced in vitro into osteoblast and adipocyte. Islet like cell clusters appeared about 9 days after pancreatic differentiation in the inducing system with ECM gel. The insulin positive cells accounted for (25.2 +/- 3.4)% of the induced cells. The induced cells expressed islet related genes and hormones, but were not very responsive to glucose challenge. When MSCs were induced without ECM gel, clusters formation and secretion of functional islet proteins could not be observed. CONCLUSIONS: Human UCB-MSCs can differentiate into islet like cells in vitro and ECM gel plays an important role in pancreatic endocrine cell maturation and formation of three dimensional structures.

MicroRNA­466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin.

Numerous microRNAs (miRNAs) have been demonstrated to be downregulated or upregulated in hepatocellular carcinoma (HCC) and play important roles in its occurrence and development. Therefore, the investigation of miRNAs and their functions implicated in the genesis and development of HCC may provide key clues for the identification of effective therapeutic approaches for patients with this disease. The aims of the present study were to detect miRNA­466 (miR­466) expression in HCC tissues and cell lines and to determine its effects on HCC cell proliferation, apoptosis and metastasis, as well as to explore the mechanisms underlying the tumor­suppressing roles of miR­466 in HCC. In the present study, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was performed to detect miR­466 expression in HCC tissues and cell lines. The effects of miR­466 upregulation on HCC cell proliferation, apoptosis, migration and invasion were determined using Cell Counting Kit­8 assay, flow cytometry analysis and Transwell chamber assay, respectively. The potential target gene of miR­466 was predicted using bioinformatic analysis, which was further confirmed by luciferase reporter assay, RT­qPCR and western blot analysis. It was found that miR­466 was obviously decreased in HCC tissues and cell lines. The results of functional experiments revealed that restoration of miR­466 expression suppressed the proliferation, induced apoptosis, and reduced the metastasis of HCC cells. In addition, metadherin (MTDH) was identified as a direct target of miR­466 in HCC cells. Furthermore, MTDH was upregulated in HCC tissues, which was inversely correlated with the miR­466 level. Moreover, inhibition of MTDH displayed similar tumor­suppressing roles as miR­466 upregulation in HCC cells. In addition, MTDH reintroduction restored the tumor­suppressor activity of miR­466 overexpression in HCC cells. These findings suggest that miR­466 is a potential therapeutic tool for HCC therapy.