Lactic acid: a narrative review of a promoter of the liver cancer microenvironment.

Background and Objective: Lactic acid is a metabolite of glycolysis produced in the body, and its production is thought to be a mechanism by which cancer cells evade immune surveillance. Immune evasion and metabolic changes are well established as basic hallmarks of cancer. Although lactate has long been considered a waste product, it is now generally recognized to be a versatile small-molecule chemical that plays an important part in the tumor microenvironment (TME), with increased lactate production linked to the development of human malignancies. Metabolism in liver cancer is redirected toward glycolysis, which enhances the production of metabolic compounds used by tumor cells to produce proteins, lipids, and nucleotides, enabling them to maintain high proliferation rates and to establish the TME. Dysregulation of metabolic activity in liver cancer may impair antitumor responses owing to the immunosuppressive activity of the lactate produced by anaerobic glycolytic rates in tumor cells. This review primarily explores the link connection between lactic acid and the TME; evaluates the role of lactic acid in the occurrence, metastasis, prognosis, and treatment of liver cancer. Additionally, it investigates the associated pathways as potential targets for liver cancer treatment. Methods: Literature searches were conducted in PubMed, Web of Science, and Google Scholar, with the publication date of the most recent article included being January 2024. After eliminating duplicate articles and less relevant articles through titles and abstracts, we selected 113 articles for this review. We categorized references into two categories. One is to classify the content into lactate-related, liver cancer-related and tumor metabolism-related. The other is to classify the article types, which are divided into reviews, research articles and clinical trials. Additionally, we consulted the reference lists of the relevant articles to ensure coverage was comprehensive and unbiased. Key Content and Findings: The connection between lactic acid and the TME has recently become an area of intense research interest, and many related articles have been published in this field. The main finding of this review is to summarize the proven link between lactate and the TME and its possible impact on the TME of liver cancer. And analyzed the potential of lactate in liver cancer treatment and prognosis prediction. Conclusions: Lactate may be key to developing novel approaches in the future treatment of liver cancer. Related research on the combination of classic therapies and molecular targeted drugs may provide innovative medicines that more selectively regulate immune cell activity.

Preliminary exploration of animal models of congenital choledochal cysts.

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.

Vemurafenib induces senescence in acute myeloid leukemia and myelodysplastic syndrome by activating the HIPPO signaling pathway: implications for potential targeted therapy.

BACKGROUND: The outcome of Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remain dismal despite the development of treatment. Targeted therapy is gaining more and more attention in improving prognosis. METHODS: Expression of BRAF was analyzed by RT-qPCR in AML and MDS patients. Cells viability treated by drugs was measured by CCK-8 assay. Network pharmacology and RNA-sequence were used to analyze the mechanism of drugs and verified in vitro and xenograft tumor model. RESULTS: Here we showed that BRAF was overexpressed in AML and MDS patients, and correlated with poor prognosis. The BRAF inhibitor-Vemurafenib (VEM) could significantly induce senescence, proliferation inhibition and apoptosis in AML cells, which can be enhanced by Bortezomib (BOR). This inhibitory effect was also verified in CD34 + cells derived from AML patients. Mechanistically, we showed that VEM combined with BOR could turn on HIPPO signaling pathway, thereby inducing cellular senescence in AML cells and xenograft mouse. CONCLUSIONS: Taken together, our findings demonstrate a significant upregulation of BRAF expression in AML and MDS patients, which is associated with unfavorable clinical outcomes. We also discovered that the BRAF inhibitor Vemurafenib induces cellular senescence through activation of the HIPPO signaling pathway. Analysis of BRAF expression holds promise as a prognostic indicator and potential therapeutic target for individuals with AML and MDS.

An immune risk score predicts survival of patients with diffuse large B-cell lymphoma.

PURPOSE: Providing accurate prognostic models is necessary for diffuse large B-cell lymphoma, but there are still many uncertainties. So far, none of the models include immune cells. Therefore, an immune risk score was constructed to predict the survival of patients. METHODS: CIBERSORTx was chosen to estimate the proportion of 22 human immune cell subsets from public datasets and generate an immune risk score to predict patients' survival in a training cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model. RESULTS: The prognostic model had high predictive ability in the training and validation cohorts. Subjects in the training cohort with high scores had a worse prognosis compared with subjects with low scores. The same result was also found in the three validation cohorts. Multivariable analysis suggested that the immune risk score was an independent prognostic factor. The merged score, including the immune risk score and the international prognostic index (IPI) risk category, had better predictive accuracy. CONCLUSIONS: Our immune risk score promises to be a complement to current prognostic models.

Long noncoding RNA HULC regulates the NF-κB pathway and represents a promising prognostic biomarker in liver cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in a diverse array of biological processes. While lncRNAs are commonly upregulated in hepatocellular carcinoma (HCC), the specific regulatory roles they play in this oncogenic context require further study and clarification. Although HULC (lncRNA highly upregulated in liver cancer) is involved in disease pathogenesis, its precise role in this context remains unclear. METHODS: Here, we have explored the mechanistic relevance of HULC expression by assessing its expression in patient samples. The importance of this lncRNA in the onset and progression of HCC was investigated through in vitro approaches including Western blotting, quantitative PCR, Transwell assays, electron microscopy, wound healing assays, and real-time cell analysis (RTCA). Additionally, the in vivo functions of this lncRNA were assessed using an orthotopic HCC xenograft in nude mouse model system. RESULTS: HULC was identified as a lncRNA that is highly upregulated in human liver tumors. In vitro, HULC was able to promote HCC malignancy, although its excess overexpression also led robust autophagic induction, promoting the increased expression of autophagy-associated genes including LC3 and Beclin-1. At a mechanistic level, HULC was able to promote the phosphorylation of p65 and IkBkB thus enhancing autophagy by increasing LC3II levels in a manner dependent upon the NF-κB pathway. HULC downregulation was also linked to impaired orthotopic HCC tumor growth in vivo. The link between HULC and autophagy may play a role in disease progression. CONCLUSIONS: These results suggest that HULC is an oncogenic lncRNA, and may thus offer value as a prognostic biomarker and promoter of HCC development, in addition to being a potential therapeutic target in this cancer type.

[SPARC Overexpression Enhances the Sensitivity of SKM-1 Cells to Ara-C by Regulating CPBP/MLKL].

OBJECTIVE: To investigate the effect of SPARC gene overexpression on the chemotherapeutic sensitivity of AML-MDS cell line SKM-1 to Ara-C and to further explore its mechanism. METHODS: Subjects were divided into 6 groups: SKM-1 cells (Control), Negative control (LV-NC), SPARC overexpression (LV-SPARC), SKM-1 cells+30 ng/ml Ara-C (30 ng/ml Ara-C), LV-NC+30 ng/ml Ara-C and LV-SPARC+30 ng/ml Ara-C. Cell activity was detected by CCK-8 assay, cell cycle distribution and apoptosis were detected by flow cytometry, mRNA expression levels of SPARC, CPBP and MLKL were detected by RT-qPCR, and the expression levels of related protein were detected by Western blot. RESULTS: After co-treatment with SPARC overexpression and Ara-C, the cell viability decreased and apoptosis increased significantly, with obvious up-regulation of Bax and down-regulation of BCL-2 (P<0.05). Compared with the control group, the cell cycle of LV-SPARC+30 ng/ml Ara-C group was significantly arrested in S phase with obvious down-regulation of CDK2 and up-regulation of p27KIP1 (P<0.05). Compared with LV-SPARC group and 30 ng/ml Ara-C group, the mRNA and protein expression levels of CPBP and MLKL (p-MLKL) were significantly elevated in LV-SPARC+30 ng/ml Ara-C group (P<0.05). In addition, after co-treatment with SPARC overexpression and Ara-C, the protein expression level of p-AKT decreased and the protein expression level of p53 increased (P<0.05). CONCLUSION: SPARC overexpression enhanced the sensitivity of SKM-1 cells to Ara-C and promoted cell cycle arrest and apoptosis, the mechanism of which may be related to the regulation of CPBP/MLKL pathway.

Anti-PADI4 antibody suppresses breast cancer by repressing the citrullinated fibronectin in the tumor microenvironment.

BACKGROUND: PADI4, an enzyme catalyzing arginine residues to citrulline residues, is highly expressed in malignant tumors. This study prepared a monoclonal anti-human PADI4 antibody and investigated the therapeutic effect of the antibody on breast tumors and the functional mechanism. METHODS: After treatment with PADI4 antibody, the changes in tumor-bearing mice were examined by PET-CT, pathological assays, biochemical tests, routine blood tests, cytokine assays and metabolic assays. We used PADI4 recombinant protein to catalyze fibronectin (Fn) and then used citrullinated fibronectin (Cit-Fn) to culture MDA-MB-231 cells. We also treated Cit-Fn cultured cells with PADI4 antibody. The cultured cells were examined using cell proliferation, apoptosis, colony formation, migration and glycolic ATP production. Citrullination in the tumor tissues and peripheral blood was measured using Western blotting and ELISA, respectively. RESULTS: Following PADI4 antibody treatment, tumor growth was significantly suppressed, and the number of apoptotic cells in tumor tissues was increased. The citrullination level in peripheral blood and tumor tissues was decreased, EMT-related gene expression in tumors was also decreased, and the spontaneous movement of tumor-bearing mice was increased following treatment. Following antibody treatment, the serum concentrations of IL-10, IL-12p70, IL-23, ALT and AST were significantly decreased. MDA-MB-231 cells treated with Cit-Fn showed increased cell proliferation, cell migration, colony formation and glycolytic ATP production and decreased apoptosis. The growth and migration of MDA-MB-231 cells were reduced following PADI4 antibody treatment, and PADI4 antibody inhibited the citrullination of fibronectin in vitro. CONCLUSIONS: The PADI4 antibody had a therapeutic effect on breast tumors by inhibiting the citrullination of fibronectin to change the tumor tissue microenvironment. PADI4 antibody is a potential means for tumor treatment.

BDNF-overexpressing MSCs delivered by hydrogel in acute ischemic stroke treatment.

Background: Ischemic stroke treatment is a challenge worldwide. The efficacy and safety of mesenchymal stem cells (MSCs) for stroke have been confirmed. However, poor survival of MSCs in the ischemic environment limits the therapy efficacy. Changes in MSC status in the ischemic environment after transplantation is difficult to monitor. This study aimed to deliver brain-derived neurotrophic factor (BDNF)-overexpressing MSCs by hydrogel (H-B-MSCs) to promote recovery after ischemic stroke. Methods: MSCs were transfected with lentivirus carrying luc2 and BDNF cassette. The properties of hydrogel were tested after synthesis with thiolated gelatin (Gel-SH), thiolated hyaluronic acid (HA-SH), and polyethylene glycol diacrylate (PEGDA). Oxygen-glucose deprivation (OGD) test was carried out to confirm the protective effects of hydrogel in the ischemic environment. Three days after stroke induction, H-B-MSCs, hydrogel carrying MSCs (H-MSCs), or phosphate-buffered saline (PBS) was injected into the brains of mice, respectively. Bioluminescence imaging (BLI) was performed at 3, 7, 14, and 21 days post-cell-transplantation to monitor the dynamic status of MSCs. In the meantime, histology, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), western blot, and behavior tests were carried out at different time points. Results: Hydrogel with good biocompatibility was synthesized. Lentivirus transfection significantly increased the expression of BDNF. BDNF-MSCs could be tracked by BLI in vitro. In vitro OGD/reperfusion (OGD/R) test results suggested that MSCs carried by hydrogel could survive longer in an environment with low oxygen and glucose. H-B-MSCs significantly improved functional recovery after ischemic stroke. Furthermore, H-B-MSCs treatment promoted neurogenesis, white matter recovery, and angiogenesis after ischemic stroke. MSC dynamics could be monitored in vivo with BLI. Conclusions: We effectively established a robust MSC delivery system with hydrogel. Prolonged survival of transplanted BDNF-MSCs with a hydrogel delivery system could promote the recovery of ischemic stroke via the continuous release of BDNF.

Network Pharmacology and Experimental Validation Reveal the Effects of Chidamide Combined With Aspirin on Acute Myeloid Leukemia-Myelodysplastic Syndrome Cells Through PI3K/AKT Pathway.

Chidamide (CDM), a novel histone deacetylase inhibitor, is currently used for patients with peripheral T-cell lymphoma. Aspirin (ASA), an anti-inflammatory drug, has been shown to exert anticancer activity. Herein, we investigated the effect of CDM combined with ASA on myelodysplastic syndromes-derived acute myeloid leukemia (AML-MDS) cells and explored the underlying mechanism. The putative targets of CDM and ASA were predicted by network pharmacology approach. GO functional and KEGG pathway enrichment analyses were performed by DAVID. Furthermore, experimental validation was conducted by Cell Counting Kit-8 assay, Flow cytometry and Western blotting. Network pharmacology analysis revealed 36 AML-MDS-related overlapping genes that were targets of CDM and ASA, while 10 hub genes were identified by the plug-in cytoHubba in Cytoscape. Pathway enrichment analysis indicated CDM and ASA significantly affected PI3K/AKT signaling pathway. Functional experiments demonstrated that the combination of CDM and ASA had a remarkable synergistic anti-proliferative effect by blocking the cell cycle in G0/G1 phase and inducing apoptosis. Mechanistically, the combination treatment significantly down-regulated the phosphorylation levels of PI3K and AKT. In addition, insulin-like growth factor 1 (IGF-1), an activator of PI3K/AKT pathway, reversed the effects of the combination treatment. Our findings suggested that CDM combined with ASA exerted a synergetic inhibitory effect on cell growth by inactivating PI3K/AKT pathway, which might pave the way for effective treatments of AML-MDS.

Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation.

BACKGROUND: Chidamide, a novel benzamide-type histone deacetylase (HDAC) inhibitor, exerts antitumor effects on several types of cancer. However, the role of Chidamide in chronic myeloid leukemia (CML) remains elusive. Therefore, the present study aimed to investigate the effects of Chidamide on CML cell proliferation and explore its underlying mechanism. METHODS: Cell proliferation was assessed by CCK-8 assay, cell cycle distribution and apoptosis were detected by flow cytometry and the expression of related proteins was evaluated by western blot analysis. The potential mechanisms were systematically explored by the network-based pharmacological methods, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. RESULTS: The results revealed that Chidamide inhibited the proliferation of K562 cells in a dose- and time-dependent manner. In addition, Chidamide blocked cells in the G0/G1 phase via downregulating cyclin-dependent kinase 4, and induced apoptosis via upregulating Bax and downregulating of Bcl-2. Additionally, using network- based pharmacological methods, we found that PI3K/AKT signaling pathway is involved and significantly related to cell proliferation in CML. Intriguingly, cell treatment with Chidamide suppressed the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway via decreasing the levels of phosphorylated (p)-PI3K and p-AKT. Moreover, insulin-like growth factor 1 (IGF-1), a PI3K/AKT activator, reversed the inhibitory effects of Chidamide on K562 cell proliferation. CONCLUSION: The study demonstrated that Chidamide may inhibit the proliferation of K562 cells by promoting cell cycle arrest and apoptosis via suppressing the PI3K/AKT pathway, suggesting that Chidamide could be a promising approach to the treatment of CML.

TRAIL promotes hepatocellular carcinoma apoptosis and inhibits proliferation and migration via interacting with IER3.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce substantial cytotoxicity in tumor cells but rarely exert cytotoxic activity on non-transformed cells. In the present study, we therefore evaluated interactions between TRAIL and IER3 via co-immunoprecipitation and immunofluorescence analyses, leading us to determine that these two proteins were able to drive the apoptotic death of hepatocellular carcinoma (HCC) cells and to disrupt their proliferative and migratory abilities both in vitro and in vivo. From a mechanistic perspective, we determined that TRAIL and IER3 were capable of inhibiting Wnt/ß-catenin signaling. Together, these results indicate that TRAIL can control the pathogenesis of HCC at least in part via interacting with IER3 to inhibit Wnt/ß-catenin signaling, thus indicating that this TRAIL/IER3/ß-catenin axis may be a viable therapeutic target in HCC patients.

MiR-148b-3p Regulates the Expression of DTYMK to Drive Hepatocellular Carcinoma Cell Proliferation and Metastasis.

Deoxythymidilate kinase (DTYMK) has been identified as a putative oncogene associated with the incidence of hepatocellular carcinoma (HCC), but the mechanisms whereby it regulates this cancer type remain uncertain. The present study was therefore designed to explore the role of DTYMK in HCC and to evaluate the underlying molecular mechanisms. MiRNAs associated with DTYMK expression levels in HCC were identified through analyses of both clinical samples and publically available gene expression datasets. We then assessed the putative functions of DTYMK and miR-148b-3p in this oncogenic context through studies of HCC cells and a murine xenograft model system. Correlation analyses and in vitro experiments led us to confirm DTYMK as a target of miR-148b-3p. In addition, we assessed dTTP levels associated with the DTYMK pathway in HCC cells to understand the functional implications of our experimental findings. We found that HCC tissues and cells exhibited marked DTYMK upregulation and miR-148b-3p downregulation, with the expression levels of DTYMK and miR-148b-3p being negatively correlated with one another. The impact of overexpressing DTYMK in tumor cells was partially reversed upon cellular transfection with miR-148b-3p mimics, providing conclusive evidence that DTMYK is a target of this miRNA. Importantly, DTYMK-related dTTP levels were also impacted by miR-148b-3p mimic transfection. DTYMK is a key regulator of HCC progression, and its expression is suppressed by miR-148b-3p, suggesting that this miR-148b-3p/DTYMK regulatory axis may be amenable to therapeutic targeting in patients with HCC.

Racial/Ethnic Disparities on the Risk of Second Malignant Neoplasm Among Hodgkin Lymphoma Survivors.

BACKGROUND: Hodgkin lymphoma survivors are at risk for second malignant neoplasm (SMN). How race/ethnicity affects the risk remains unclear. METHODS: This retrospective cohort study included 22,415 patients diagnosed with primary Hodgkin lymphoma from January 1992 to December 2015 in 13 Surveillance, Epidemiology, and End Results-based registries and divided patients into four groups: non-Hispanic whites, non-Hispanic blacks, Hispanics, and Asian/others. Taking non-Hispanic whites as a reference, both the proportional subdistribution hazard (PSH) and the cause-specific hazard (CSH) methods were used to calculate the SMN hazard ratio for other racial/ethnic groups with and without considering the competing mortality risk. RESULTS: 1,778 patients developed SMN with a median follow-up of 11.63 years. In the adjusted PSH model, Hispanic, Asian/others, and non-Hispanic black patients had 26% (PSH, 0.74; 95% CI, 0.63-0.87), 20% (PSH, 0.80; 95% CI, 0.64-1.01), and 12% (PSH, 0.88; 95% CI, 0.75-1.03) decreased overall SMN hazard, respectively. Moreover, the PSH method revealed the racial/ethnic difference in the SMN risk in the skin, the respiratory system, and the endocrine system. These hazards were slightly higher and different with the use of the CSH approach. In addition to the aforementioned overall SMN and subtypes, adjusted CSH analysis also revealed the racial/ethnic disparities in the risk of subsequent female breast cancer, digestive cancer, and non-Hodgkin lymphoma. CONCLUSIONS: The subtype and SMN risk among Hodgkin lymphoma survivors varied by race/ethnicity. The use of CSH and PSH provides a dynamic view of racial/ethnic effects on SMN risk in Hodgkin lymphoma survivors.

Surgical treatment of multiple magnet ingestion in children: A single-center study.

BACKGROUND: Since 2017, the number of magnet ingestion cases has increased year over year in our hospital. Almost all of the ingested magnetic foreign bodies were magnetic beads, and most of the patients experienced intestinal perforations, causing substantial damage. AIM: To summarize our experience with surgical treatment of multiple magnet ingestion in children. METHODS: The data for general surgeries were collected from January 2010 to April 2020, and the clinical characteristics, treatment methods, and outcomes were summarized and analyzed. Several typical cases were selected and discussed. RESULTS: Fifty-six cases of ingested magnetic foreign bodies were collected, of which 47 were magnetic beads. The average patient age was 4.7 ± 3.0 years old. The number of ingested magnetic foreign bodies ranged from 2 to 73. There were 26 cases with symptoms at the time of admission, including two cases of shock. Thirteen patients were discharged successfully following conservative treatment and 43 were treated by surgery. Laparotomy was the main method of operation. Laparoscopy was used in four cases, of which three were converted to open surgery, and one was treated successfully using surgery through the navel. Postoperative complications occurred in seven cases, incision infections were observed in six, and adhesive ileus was observed in one. CONCLUSION: Clinicians need to summarize their experiences with treating magnetic foreign body ingestions in detail and carry out clinical research to reduce the damage to children.

Dermatopontin inhibits WNT signaling pathway via CXXC finger protein 4 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of tumor associated deaths globally. Annually, the prevalence of HCC is increasing and the lack of early prognostic indicators manifests a dismal prognosis for HCC patients. A deep understanding of the molecular events that promote HCC progression are required for the design of new diagnostics and therapeutics. Dermatopontin (DPT) is an extracellular matrix protein that regulates the metastatic phenotypes of many cancers. However, the effects of DPT on HCC cell growth remain undefined. In this study, we demonstrate that the exogenous expression of DPT inhibits HCC cell growth both in vitro and in vivo. Furthermore, we show that DPT regulates CXXC4, which in turn targets c-Myc, EZH2, SOX2 and ß-catenin, through its ability to impact Wnt signaling pathway. These data suggest that DPT regulates CXXC4, c-Myc, EZH2, SOX2 and ß-catenin, through Wnt signaling to repress HCC proliferation. This highlights DPT as promising target for future HCC diagnostics and therapeutic targets.

TUG1 long non-coding RNA enlists the USF1 transcription factor to overexpress ROMO1 leading to hepatocellular carcinoma growth and metastasis.

Hepatocellular carcinoma (HCC) is a prevalent and highly aggressive cancer. Long non-coding RNAs (lncRNAs) are recognized as potential molecular targets for HCC and are currently under increased research focus. Here, we investigate the regulatory processes underlying the axis of the lncRNA taurine upregulated gene 1 (TUG1), Upstream Transcription Factor 1 (USF1), and reactive oxygen species modulator 1 (ROMO1) in the propagation and metastasis of HCC cells. Distribution of lncRNA TUG1 was found to be prominent in HCC cell cytoplasm and nuclei. LncRNA TUG1 conscripted the USF1 transcription factor to enhance the promoter function of ROMO1. Enlisting the USF1 transcription factor to increase ROMO1 expression following upregulation of TUG1 lncRNA enhanced HCC Huh7 cell proliferation, motility, and metastasis. Rapid tumor proliferation in nude mice provided in vivo verification. The importance of the lncRNA TUG1/USF1/ROMO1 complex as a target for HCC therapy is a key result of this investigation which is exemplified by its role in regulating the proliferation, motility, and metastasis of HCC cells.

Nursing research on a first aid model of double personnel for major burn patients.

This study explored the effect of a first aid model employing two nurses on the efficient rescue operation time and the efficient resuscitation time for major burn patients. A two-nurse model of first aid was designed for major burn patients. The model includes a division of labor between the first aid nurses and the re-organization of emergency carts. The clinical effectiveness of the process was examined in a retrospective chart review of 156 cases of major burn patients, experiencing shock and low blood volume, who were admitted to the intensive care unit of the department of burn surgery between November 2009 and June 2013. Of the 156 major burn cases, 87 patients who received first aid using the double personnel model were assigned to the test group and the 69 patients who received first aid using the standard first aid model were assigned to the control group. The efficient rescue operation time and the efficient resuscitation time for the patients were compared between the two groups. Student's t tests were used to the compare the mean difference between the groups. Statistically significant differences between the two groups were found on both measures (P's < 0.05), with the test group having lower times than the control group. The efficient rescue operation time was 14.90 ± 3.31 min in the test group and 30.42 ± 5.65 min in the control group. The efficient resuscitation time was 7.4 ± 3.2 h in the test group and 9.5 ± 2.7 h in the control group. A two-nurse first aid model based on scientifically validated procedures and a reasonable division of labor can shorten the efficient rescue operation time and the efficient resuscitation time for major burn patients. Given these findings, the model appears to be worthy of clinical application.

ER stress and ASK1-JNK activation contribute to oridonin-induced apoptosis and growth inhibition in cultured human hepatoblastoma HuH-6 cells.

Oridonin, the main active component of Rabdosia rubescens, has antitumor activities in experimental and clinical settings. The aims of the current study were to explore the anticancer abilities of oridonin in hepatoblastoma (HB) HuH-6 cells and to investigate the underlying mechanisms. We found that oridonin inhibited HuH-6 cell in vitro growth in a dose- and time-dependent manner. Further, oridonin induced HuH-6 cell apoptosis and G2/M cell cycle arrest. Upon studying the mechanism, we found that oridonin treatment caused endoplasmic reticulum (ER) stress activation. Meanwhile, ER stress inhibitor salubrinal- or inositol-requiring enzyme 1 (IRE-1) shRNA silencing inhibited oridonin's anti-HuH-6 effects, while ER stress inducers thapsigargin (Tg) and tunicamycin (Tm) mimicked oridonin's actions on HuH-6 cells. Oridonin also activated apoptosis signal regulating kinase 1 (ASK1)-c-Jun N-terminal kinase 1 (JNK1) signaling in cultured HuH-6 cells, which was inhibited by IRE-1 silencing. Importantly, the JNK inhibitors suppressed oridonin-induced growth inhibition and apoptosis in HuH-6 cells. In conclusion, our results suggest that oridonin induces growth inhibition and apoptosis in cultured HuH-6 cells involving ER stress and ASK1/JNK signaling pathways, which enhances our understanding of the molecular mechanisms of oridonin in HB management.

Identification of polycyclic aromatic hydrocarbons (PAHs) in soil by constant energy synchronous fluorescence detection.

In this paper, a novel method of constant energy synchronous fluorescence (CESF) was proposed to the simultaneous determination of different polycyclic aromatic hydrocarbons (PAHs) in a mixture of 16 components. When different appropriate intervals of the constant energy (Deltanu=1400 or 4800cm(-1)) were chosen during constant energy synchronous scanning, 13 PAHs could be identified and quantified by the corresponding synchronous spectra. Results show that their linear relations are fine and the limits of detection (LODs) were between 0.2 and 7.6ngml(-1). Then the application of CESF method proposed in the analysis of the real soil samples under the optimum conditions indicated that 11 PAHs could be identified and the total concentration of PAHs in a real soil sample is 5.1microg g(-1), most of PAHs in the soil samples had three or four rings. Recoveries of these PAHs were from 70.9 to 121.4% in most cases. This CESF method is a simple, rapid, sensitive method with high resolution and also suitable to analyze the complex mixtures of PAHs in other environmental samples.