Recovering from prolonged cardiac arrest induced by electric shock: A case report.

BACKGROUND: Cardiac arrest (CA) induced by electric shock is a rare occurrence, particularly in cases of prolonged CA. Currently, there is limited literature on similar incidents, and we present a relevant case report. CASE SUMMARY: A 27-year-old Asian male man, experiencing respiratory CA due to electric shock, was successfully restored to sinus rhythm after 50 min of cardiopulmonary resuscitation and 8 electrical defibrillation sessions. In the subsequent stages, the patient received multiple organ function protection measures, leading to a successful recovery and eventual discharge from the hospital. CONCLUSION: Prolonging resuscitation time can enhance the chances of survival for patients, this study provide valuable insights into the management of electric shock-induced CA.

ETS Proto-Oncogene 1-activated muskelin 1 antisense RNA drives the malignant progression of hepatocellular carcinoma by targeting miR-22-3p to upregulate ETS Proto-Oncogene 1.

Long noncoding RNA muskelin 1 antisense RNA (MKLN1-AS) acted as an oncogenic regulator in hepatocellular carcinoma (HCC). This study was performed to investigate the functional mechanism of MKLN1-AS. MKLN1-AS, microRNA-22-3p (miR-22-3p) and ETS Proto-Oncogene 1 (ETS1) levels were examined using reverse transcription-quantitative polymerase-chain reaction. Protein expression was detected by Western blot. The target relation was analyzed by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Cell proliferation ability was determined through cell counting kit-8 assay, colony formation assay and ethylenediurea assay. Angiogenesis was examined by tube formation assay. Cell migration and invasion were assessed via transwell assay. In vivo research was conducted by xenograft tumor model in nude mice. MKLN1-AS was upregulated in HCC tissues and cells. ETS1 promoted the ETS1 expression by binding to the 582-596 sites. Silence of MKLN1-AS suppressed cell growth, angiogenesis, migration, and invasion. MKLN1-AS interacted with miR-22-3p in HCC cells. The function of MKLN1-AS downregulation was relieved by miR-22-3p inhibition in HCC cells. ETS1 was validated as a target of miR-22-3p, and MKLN1-AS upregulated the ETS1 expression by sponging miR-22-3p. Overexpression of miR-22-3p retarded HCC progression by downregulating the level of ETS1. Tumor growth in vivo was also enhanced by MKLN1-AS through the regulation of miR-22-3p/ETS1 axis. These data demonstrated that ETS1-mediated MKLN1-AS contributed to the malignant phenotypes of HCC cells via depending on the miR-22-3p/ETS1 regulatory axis.

MiR-125b inhibits anaplastic thyroid cancer cell migration and invasion by targeting PIK3CD.

Emerging evidences indicate that dysregulated microRNAs are implicated in the process of tumorigenesis and progression. The miRNA-125b (miR-125b) is downregulated and identified as tumor supressor in various cancers including thyroid cancer. However, the role and mechanism of miR-125b in anaplastic thyroid cancer (ATC) migration and invasion remain unknown. In the present study, the expression levels of miR-125b were downregulated and the expression levels of phosphoinositide 3-kinase catalytic subunit delta (PIK3CD) were upregulated in ATC tissues and cell lines. Moreover, miR-125b expression was negatively related to PIK3CD expression in ATC tissues. A computational search and luciferase assay identified PIK3CD as a direct target of miR-125b in ATC and PIK3CD expression was downregulated by miR-125b in ATC cells. In terms of function, miR-125b repressed migration and invasion of ATC cells, whereas PIK3CD overexpression reversed this effect. Furthermore, we showed that exogenous miR-125b decreased the PI3K, phospho-Akt, and phospho-mTOR expression in ATC cells. In conclusion, these results indicated that miR-125b suppressed ATC cell migration and invasion by targeting PIK3CD expression, and suggested novel potential therapeutic targets for the treatment of ATC.

The expressions of NEDD9 and E-cadherin correlate with metastasis and poor prognosis in triple-negative breast cancer patients.

BACKGROUND: Neural precursor cell expressed, developmentally downregulated 9 (NEDD9), a member of Crk-associated substrate family, is involved in cancer cell adhesion, migration, invasion, and epithelial-mesenchymal transition. E-cadherin is a key event in the cellular invasion during the epithelial-mesenchymal transition mechanism. The aim of this study was to evaluate the association among NEDD9 expression, E-cadherin expression, and survival in triple-negative breast cancer (TNBC) patients. METHODS: NEDD9 and E-cadherin expressions were analyzed by immunohistochemistry in 106 TNBC patients and 120 non-TNBC patients. And the association of clinicopathological factors with survival was analyzed using Kaplan-Meier analysis and Cox regression in TNBC patients. RESULTS: The results revealed that the rate of increased expression of NEDD9 and reduced expression of E-cadherin was significantly higher in TNBC group than that in non-TNBC group (P<0.001, both). Comparison of features between TNBC and non-TNBC groups showed that histological type (P=0.026) and lymph node metastasis (P=0.001) were significantly different. Correlation analysis showed that positive NEDD9 expression and negative E-cadherin expression were significantly correlated with lymph node metastasis and tumor-node-metastasis stage (P<0.05). In addition, the enhanced NEDD9 expression was significantly associated with a reduced 5-year survival for TNBC patients (overall survival [OS]: P=0.013; disease-free survival [DFS]: P=0.021). Negative E-cadherin expression showed a significantly worse 5-year OS and DFS (OS: P=0.011; DFS: P=0.012). Multivariate analysis showed that lymph node metastasis (OS: P=0.006; DFS: P=0.004), tumor-node-metastasis stage (OS: P=0.012; DFS: P=0.001), NEDD9 (OS: P=0.046; DFS: P=0.022), and E-cadherin (OS: P=0.022; DFS: P=0.025) independently predicted a poor prognosis of OS and DFS. Moreover, patients with NEDD9-positive/E-cadherin-negative expression had a significantly worse outcome than other groups (OS: P=0.004; DFS: P=0.001). CONCLUSION: Our finding demonstrated the potential value of NEDD9 and E-cadherin expression levels as prognostic molecular markers and a target for new therapies for TNBC patients.

RUNX3 plays an important role in As2O3­induced apoptosis and allows cells to overcome MSC­mediated drug resistance.

The interaction between bone marrow stromal cells and leukemia cells is critical for the persistence and progression of leukemia, and this interaction may account for residual disease. However, the link between leukemia cells and their environment is still poorly understood. In our study, runt­related transcription factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and involved in mesenchymal stem cell (MSC)­mediated protection of leukemia cells from As2O3­induced apoptosis. We observed induction of RUNX3 expression and the translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells. In K562 chronic myeloid leukemia cells, downregulation of endogenous RUNX3 compromised As2O3­induced growth inhibition, cell cycle arrest, and apoptosis. In the presence of MSC, As2O3­induced expression of RUNX3 was reduced significantly and this reduction was modulated by CXCL12/CXCR4 signaling. Furthermore, overexpression of RUNX3 restored, at least in part, the sensitivity of leukemic cells to As2O3. We conclude that RUNX3 plays an important role in As2O3­induced cellular responses and allows cells to overcome MSC­mediated drug resistance. Therefore, RUNX3 is a promising target for therapeutic approaches to overcome MSC­mediated drug resistance.

Improved antitumor activity of epirubicin-loaded CXCR4-targeted polymeric nanoparticles in liver cancers.

A liver-targeted drug delivery system (CX-EPNP) composed of PLGA/TPGS was prepared and characterized. The surface of nanoparticle was conjugated with LFC131 peptide to increase the specific interaction of carrier with CXCR4 overexpressing liver cancers to enhance the Epirubicin (EPI) delivery to tumors. The particles were nanosized with size than 150 nm and portrayed a sustained release kinetics suggesting its suitability for cancer targeting. The in vitro cell uptake results showed that the introduction of LFC131 to the nanoparticles could increase significantly the affinity to human hepatic carcinoma cells (HepG2) with approximately a 3-fold improvement in cellular uptake than non-targeted one. A specific receptor-mediated uptake was observed by confocal laser scanning microscopy. In addition, CX-EPNP showed remarkable cytotoxicity towards HepG2 cells, and could effectively inhibit tumor growth. The more significant EPI accumulation from CX-EPNP in the cancer cells gave rise to the enhanced EPI cytotoxicity and cell apoptosis. The CX-EPNP distributed mostly in the xenograft tumor after intravenous administration to mice and adequately remained in the blood for at least 24h. It seemed that CX-EPNP upon intravenous injection avoided rapid recognition by Kupffer cells and adequately remained in the blood. These findings suggest that CX-EPNP could effectively inhibit the growth of liver tumors in situ and could potentially reduce the systemic side effects. However, extensive investigation is still needed to assess the possible applications of the CX-EPNP in humans.

MicroRNA-26a inhibits proliferation by targeting high mobility group AT-hook 1 in breast cancer.

OBJECTIVES: To investigate the crucial role of miR-26a in breast cancer and to validate whether miR-26a could regulate proliferation of breast cancer cells by targeting high mobility group AT-hook 1 (HMGA1). METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the expression levels of miR-26a in breast cancer and adjacent non-cancerous breast tissues. MTT, cell migration and invasion assay were carried out to characterize the miR-26a function. Finally, to validate the target gene of miR-26a, luciferase reporter assay was employed, followed by RT-PCR and Western blot confirmation. RESULTS: Compared with normal tissues, a significant down-regulation of miR-26a expression was observed in breast cancer tissues (P=0.002). miR-26a suppresses MDA-MB-231 and Mcf-7 breast cancer cell lines proliferation and motility. The luciferase activity was significantly decreased after co-transfection with psiCHECK-2/HMGA1 3'-UTR and miR-26a mimics in comparison with control cells, and qRT-PCR and Western blotting analysis found that HMGA1 expression at the mRNA and protein levels decreased in the miR-26a mimic-treatment group relative to NC. MTT assay showed that down regulation of HMGA1 by siRNA could significantly enhance the tumor-suppressive effect of miR-26a (P < 0.05). CONCLUSIONS: The results of the present study indicate that miR-26a may be associated with human breast carcinogenesis, which inhibits tumor cell proliferation by targeting HMGA1.

Genetic variations of CAV1 gene contribute to HCC risk: a case-control study.

Hepatocellular carcinoma (HCC) is the sixth common cancer and the third common cause of cancer mortality worldwide. However, the exact molecular mechanism of HCC remains uncertain. Caveolin-1 (CAV1) is the main protein in the caveolin family and plays an important role in tumorigenesis signaling. However, the contribution of CAV1 genetic variants to HCC is still unknown. The purpose of this study was to evaluate the association between the tagSNPs of the CAV1 gene and HCC risk. In this case-control study, we enrolled 1,000 HCC patients and 1,000 cancer-free controls, which were frequency-matched by age, gender, and HBV infection status. We found that CAV1 rs729949 was statistically associated with increased risk of HCC (odds ratio (OR) = 1.28; 95% confidence interval (CI), 1.11-1.48; P = 8.53 × 10(-4)), even after Bonferroni correction (P = 5.97 × 10(-3)); the expression levels of CAV1 in cancer tissues were significantly lower than those in adjacent normal tissues (P = 0.012). We also detected a significant association for CAV1 rs3807989 under the log-additive model (OR = 0.85; 95% CI, 0.74-0.98; P = 0.026). Significant associations were also detected for CAV1 rs6466583 (GG vs AA: OR = 2.53; 95% CI, 1.24-5.17; P = 0.011) and CAV1 rs3807986 (AG vs AA: OR = 3.16; 95% CI, 1.68-5.91; P = 3.36 × 10(-4)) among genotype comparisons. These findings indicated that genetic variants n CAV1 might contribute to HCC susceptibility.

HGF/c-Met signaling mediated mesenchymal stem cell-induced liver recovery in intestinal ischemia reperfusion model.

PURPOSE: Liver injury triggered by intestinal ischemia-reperfusion (IIR) usually presage multiorgan dysfunction and death in patients. Recent studies suggest mesenchymal stem cells (MSCs) possess a protective potential against organ damage. Since relative evidence is insufficient and the mechanism is not well understood, we investigated the effect of hepatocyte growth factor c-Met signaling (HGF/c-Met) on recruitment of MSCs and subsequent protection against liver injury triggered by IIR in a rat model. METHODS: IIR models were built as rats were subjected to 75 min of superior mesenteric artery occlusion and subsequent 4 h reperfusion. Either of pure MSCs and MSCs pretreated with HGF or SU11274 (c-Met inhibitor) were injected into rat models. Biochemical and pathologic alterations of liver in IIR model were measured to evaluate the therapeutic effect of MSCs and drug treatment. Concurrently, the effect of HGF and SU11274 on c-Met and phosphorylated Met expression in MSCs and MSCs migration were assessed in in vitro experiment. RESULTS: IIR-induced liver injury was manifested by significant increase in serum ALT, AST and HGF levels as well as pathological change. MSCs with highly c-Met expression ameliorated the increase of serum transaminase levels and hepatic histopathological change, while SU11274 weaken these effects. HGF upregulated c-Met and phosphorylated Met expression in MSCs and enhanced its liver protection effect. Transwell assays demonstrated HGF promoted MSCs migration, which was blocked by SU11274. CONCLUSIONS: HGF/c-Met signaling pathway plays an essential role in the homing of MSCs towards injured liver triggered by intestinal ischemia-reperfusion, and then mediates MSC-induced liver repair.

Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injuries via inactivation of the MEK/ERK signaling pathway in rats.

BACKGROUND: Primary graft dysfunction or nonfunction after liver transplantation, which is usually caused by ischemia/reperfusion injury (IRI), is a serious clinical problem. Although bone marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy for IRI in several organs, the mechanism(s) by which MSCs offer protection is unclear. METHODS: In the present study, we injected MSCs systemically via the tail vein in the rat model of 70% hepatic IRI and measured the biochemical and pathologic alterations to evaluate the therapeutic effect of MSC transplantation. Concurrently, H(2)O(2) was used in vitro to mimic oxidative injury and to induce apoptosis in the human normal liver cell line LO2 to evaluate the protective effects of mesenchymal stem cell conditioned medium (MSC-CM) on LO2 cells. RESULTS: The systemic infusion of MSCs led to a significant prevention of liver enzyme release and an improvement in the histology of the acutely injured liver. In vitro assays demonstrated that MSC-CM promoted hepatocyte proliferation and had a direct inhibitory effect on hepatocyte apoptosis induced by H(2)O(2). In addition, we demonstrated that the prevention of MEK/ERK pathway activation played a pivotal role in the protection. CONCLUSIONS: These data suggest that MSC may represent a potential therapeutic strategy to alleviate hepatic ischemia/reperfusion injuries after liver transplantation via inactivation of the MEK/ERK signaling pathway.