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Cancer‐associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer‐associated MSCs (LC‐MSCs) and hepatocellular ... carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC‐MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC‐MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC‐MSCs compared with liver normal MSCs (LN‐MSCs) from adjacent cancer‐free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC‐MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)‐155 in HCC cells was significantly up‐regulated by coculture with LC‐MSCs and by S100A4 ectopic overexpression. The invasion‐promoting effects of S100A4 were significantly attenuated by a miR‐155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR‐155 expression in HCC cells. We demonstrate that S100A4 secreted from LC‐MSCs promotes the expression of miR‐155, which mediates the down‐regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. Conclusion: S100A4 secreted from LC‐MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013) more

The high incidence rate of hepatocellular carcinoma (HCC) is mainly the result of frequent metastasis and tumor recurrence. Unfortunately, the underlying molecular mechanisms driving HCC metastasis ... are still not fully understood. It has been demonstrated that tumor stroma cells contribute to primary tumor growth and metastasis. Within the HCC environment, activated hepatic stellate cells (HSCs) can release a number of molecules and enhance cancer cell proliferation and invasiveness in a paracrine manner. Here, for the first time, we demonstrate that epimorphin (EPM; also called syntaxin‐2), an extracellular protein, is strongly elevated in activated HSCs within tumor stroma. We show that knockdown of EPM expression in HSCs substantially abolishes their effects on cancer cell invasion and metastasis. Ectopic expression of EPM in HCC cancer cells enhances their invasiveness; we demonstrate that the cells expressing EPM have markedly increased metastasis potential. Furthermore, EPM‐mediated invasion and metastasis of cancer cells is found to require up‐regulation of matrix metalloproteinase‐9 (MMP‐9) through the activation of focal adhesion kinase (FAK)/extracellular signal‐regulated kinase (ERK) axis. Conclusion: Our results show that EPM, secreted by activated HSCs within HCC stroma, promotes invasion and metastasis of cancer cells by activating MMP‐9 expression through the FAK‐ERK pathway. (HEPATOLOGY 2011;) more

Human mesenchymal stem cells (MSCs) have therapeutic potential because of their ability to self-renew and differentiate into multiple tissues. However, senescence often occurs in MSCs when they are ... cultured in vitro and the molecular mechanisms underlying this effect remain unclear. In this study, we found that NAD-dependent protein deacetylase SIRT1 is differentially expressed in both human bone marrow-derived MSCs (B-MSCs) and adipose tissue-derived MSCs after increasing passages of cell culture. Using lentiviral shRNA we demonstrated that selective knockdown of SIRT1 in human MSCs at early passage slows down cell growth and accelerates cellular senescence. Conversely, overexpression of SIRT1 delays senescence in B-MSCs that have undergone prolonged in vitro culturing and the cells do not lose adipogenic and osteogenic potential. In addition, we found that the delayed accumulation of the protein p16 is involved in the effect of SIRT1. However, resveratrol, which has been used as an activator of SIRT1 deacetylase activity, only transiently promotes proliferation of B-MSCs. Our findings will help us understand the role of SIRT1 in the aging of normal diploid cells and may contribute to the prevention of human MSCs senescence thus benefiting MSCs-based tissue engineering and therapies. more

Aspirin can efficiently inhibit liver cancer growth, but the mechanism is poorly understood. In this study, we report that aspirin modulates glucose uptake through downregulating glucose transporter ... 1 (GLUT1), leading to the inhibition of hepatoma cell proliferation. Our data showed that aspirin significantly decreased the levels of reactive oxygen species (ROS) and glucose consumption in hepatoma cells. Interestingly, we identified that GLUT1 and HIF1α could be decreased by aspirin. Mechanically, we demonstrated that the -1008/-780 region was the regulatory element of transcriptional factor NF-κB in GLUT1 promoter by luciferase report gene assays. PDTC, an inhibitor of NF-κB, could suppress the expression of GLUT1 in HepG2 and H7402 cells, followed by affecting the levels of ROS and glucose consumption. CoCl -activated HIF1α expression could slightly rescue the GLUT1 expression inhibited by aspirin or PDTC, suggesting that aspirin depressed GLUT1 through targeting NF-κB or NF-κB/HIF1α signaling. Moreover, we found that GLUT1 was highly expressed in clinical HCC tissues relating to their paired adjacent normal tissues. Importantly, we observed that high level of GLUT1 was significantly correlated with the poor relapse-free survival of HCC patients by analysis of public data. Functionally, overexpression of GLUT1 blocked the PDTC-induced or aspirin-induced inhibition of glucose metabolism in HepG2 cells. Conversely, aspirin failed to work when GLUT1 was stably knocked down in the cells. Administration of aspirin could depress the growth of hepatoma cells through controlling GLUT1 in vitro and in vivo. Thus, our finding provides new insights into the mechanism by which aspirin depresses liver cancer. more

Mesenchymal stem cells (MSCs) play a critical role in promoting cancer progression. However, it is not clear whether MSCs are located in breast cancer tissues and correlated with tumor proliferation. ... The aim of this study was to investigate the presence of MSCs in breast cancer tissues and evaluate their interactions with cancer cells. We successfully isolated and identified MSCs from primary breast cancer tissues. Breast cancer-associated MSCs (BC-MSCs) showed homogenous immunophenotype, and possessed tri-lineage differentiation potential (osteoblast, adipocyte, and chondrocyte). When co-transplanted with cancer cells in a xenograft model in vivo, BC-MSCs significantly increased the volume and weight of tumors. We observed that BC-MSCs stimulated mammosphere formation in the transwell co-culture system in vitro. This effect was significantly suppressed by the EGF receptor inhibitor. We verified that BC-MSCs could secrete EGF and activate cancer cell’s EGF receptors. Furthermore, our data showed that EGF derived from BC-MSCs could promote mammosphere formation via the PI3K/Akt signaling pathway. Our results confirmed the presence of MSC in primary breast cancer tissues, and they could provide a favorable microenvironment for tumor cell growth in vivo , partially enhance mammosphere formation via the EGF/EGFR/Akt pathway. more

Purpose： The intraorbital wooden foreign body is often misdiagnosed or missed on computed tomog- raphy （CT） scan, due to the invisible or unclear images. The residual foreign bodies often occur ... during surgical removal. The clinical manifestations, imaging features and treatment of intraorbital wooden foreign bodies were discussed in this study. Method： We retrospectively analyzed 14 cases of intraorbital wooden foreign bodies managed at our hospital between January 2007 and May 2015. All patients underwent orbital CT examination before surgery, and surgery was performed under general anesthesia with orbital wound debridement and suture, as well as exploration and removal of wooden foreign bodies. Results： At first, 11 cases underwent removal of foreign bodies, including 1 case with incomplete removal and then receiving a secondary surgery. Foreign bodies were not found in three cases with preoperative misdiagnosis and orbital MRI found residual foreign bodies in the orbit. Operations were performed via primary wound approach in eight cases, conjunctival approach in two cases, and anterior orbitotomy in four cases. Postoperatively, one case was complicated with eye injuries, three cases with ocular muscle injuries, eight cases with visual loss, and eight cases with orbital abscess. The length of foreign bodies ranged from 1.8 cm to 11.0 cm. The maximum of four foreign bodies were removed at the same time. Conclusion： Because the imaging of orbital wooden foreign bodies is complex and varied, MRI should be combined when they are invisible on CT scan. At the same time injuries trajectory and clinical manifestations of patients should be taken into account. Surgical exploration should be extensive and thorough, and foreign bodies and orbital abscess must be cleared. more

Objective The purpose of this study was to screen target miRNA related to RB and explore the expression levels of target miRNA in RB and its potential value of diagnosis. Methods The Affymetrix ... GeneChip miRNA 4.0 Array was used to screen the differential miRNAs in the plasma of 5 RB patients before and after intravenous chemotherapy, and the most significant down-regulated miRNA was selected for target miRNA. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is used to verify the expression levels of plasma target miRNA in 30 RB patients. Then, qRT-PCR was performed to further verify the expression of target miRNA in plasma of RB patients and RB tumor tissues. Finally, receiver-operating-characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the diagnostic power of plasma target miRNA. Results The miRNA Array obtain 8 core miRNAs, 1 up-regulated and 7 down-regulated, of which miR-6089 was the most significantly down-regulated. Plasma miR-6089 levels were significantly up-regulated in RB patients. Besides, in RB tumor tissues, miR-6089 levels were also obviously up-regulated. After intravenous chemotherapy, the expression of plasma miR-6089 was significantly decreased. Furthermore, ROC curve analysis showed that miR-6089 in the plasma had a good sensitivity and specificity for distinguishing RB from the healthy control group. Conclusions MiR-6089 may be considered as a novel potential diagnostic biomarker for RB. Trial registration number ChiCTR2000040154; date of registration: 2020/11/22; retrospectively registered. more

Background: Aspirin, with its pleiotropic effects such as anti-inflammatory and anti-platelet aggregation, has been widely used for anti-inflammatory, analgesic, and cardiovascular diseases. However, ... the association between the use of aspirin before the intensive care unit (ICU) and clinical outcomes in critically ill patients with acute kidney injury (AKI) is unknown. Methods: Patients with AKI in this retrospective observational study were selected from the Marketplace for Medical Information in Intensive Care IV (MIMIC-IV). The association between aspirin intervention and 30-day mortality was assessed using Cox proportional hazards model. Logistic regression models were used to assess the association of aspirin intervention with the risks of intracranial hemorrhage, gastrointestinal bleeding and blood transfusion. The propensity score matching (PSM) method was adopted to balance the baseline variables. Sensitivity analysis was performed to validate the results by multiple interpolations for the missing data. Results: The study included 4237 pre-ICU aspirin users and 9745 non-users. In multivariate models, we found a decreased risk of mortality in those who received aspirin before ICU compared to those who did not (30-day:hazard ratio HR, 0.70; 95% CI, 0.62–0.79; p < 0.001; 90-day:HR, 0.70; 95% CI, 0.63–0.77, p < 0.001; 180-day:HR, 0.72; 95%CI,0.65–0.79, p < 0.001). This benefit was consistent in the post-PSM analyses, sensitivity analyses, and subgroup analyses. Moreover, aspirin intervention was associated with a reduced risk of intracranial hemorrhage and gastrointestinal bleeding (HR, 0.16; 95% CI, 0.10–0.25; p < 0.001; HR, 0.59; 95% CI, 0.38–0.88, p = 0.012) after being adjusted by relating covariates, whereas with a increased risk of blood transfusion (HR, 1.28; 95% CI, 1.16–1.46; p < 0.001). Conclusion: Patients with AKI treated with aspirin before ICU admission might have reduced 30-day, 90-day and 180-day mortality without increasing the risk of intracranial hemorrhage (ICH) or gastrointestinal bleeding, but may increase the risk of transfusion. more

SPINDLIN1, a new member of the SPIN/SSTY gene family, was first identified as a gene highly expressed in ovarian cancer cells. We have previously shown that it is involved in the process of spindle ... organization and chromosomal stability and plays a role in the development of cancer. Nevertheless, the mechanisms underlying its oncogenic role are still largely unknown. Here, we first showed that expression of SPINDLIN1 is upregulated in clinical tumors. Ectopic expression of SPINDLIN1 promoted cancer cell proliferation and activated WNT/T-cell factor (TCF)-4 signaling. The Ser84 and Ser99 amino acids within SPINDLIN1 were further identified as the key functional sites in WNT/TCF-4 signaling activation. Mutation of these two sites of SPINDLIN1 abolished its effects on promoting WNT/TCF-4 signaling and cancer cell proliferation. We further found that Aurora-A could interact with and phosphorylate SPINDLIN1 at its key functional sites, Ser84 and Ser99, suggesting that phosphorylation of SPINDLIN1 is involved in its oncogenic function. Collectively, these results suggest that SPINDLIN1, which may be a novel substrate of the Aurora-A kinase, promotes cancer cell growth through WNT/TCF-4 signaling activation. more

目的:了解先天性泪囊炎行泪道探通术的临床疗效.方法:选取2011-01/2016-12于我院就诊的先天性泪囊炎患儿322例361眼作为研究对象,患儿均行泪道探通术.术后1wk,1、3mo复诊观察疗效.结果:先天性泪囊炎患儿322例361眼治愈率为99.2％(358眼),3眼鼻泪管为板块样骨性阻塞;1眼发生皮下水肿,11眼泪小点出血,其他无明显并发症发生;8～18月龄患儿一次性探通成功率85.0％(204/240),显著高于>18月龄患儿一次性探通率60.2％(71/118),差异有统计学意义(χ2=27.387,P<0.05);泪道多处阻塞或粘连一次性探通率4.4％(3/68)显著低于泪道下端膜性阻塞探通率94.1％(273/290),差异有统计学意义(χ2=251.134,P<0.05).结论:泪道探通术治疗先天性泪囊炎疗效显著,有效解除患儿泪囊炎症状,其手术操作简单,安全可靠,但其治疗疗效与泪道阻塞性质有密切关系.