Relationship between PAH4 formation and thermal reaction products in model lipids and possible pathways of PAHs formation.

Lipids are closely related to the generation of PAHs during food thermal processing. During heating, lipids mainly triglycerides undergo hydrolysis, oxidation and decomposition. The relationship between the various products and the formation of PAHs is still unclear. This paper investigated the effect of different lipid standards on PAH4 production, and explored their thermal stability and reaction products to delve into nature of the differences in PAH4 production. Fatty acids were more prone to generate PAH4 than glycerides. The higher the degree of esterification of glycerides, the higher its thermal stability and the lower the content of PAH4 generated, implying that hydrolysis of glycerides promoted the generation of PAH4. In addition, there was a positive correlation between unsaturation in lipids and the PAH4 production. After heat treatment, hydroperoxides, unsaturated fatty alcohols and aldehydes, alkenes and aromatic substances were abundant in oleic acid and linoleic acid which produced the most PAH4. Thermal decomposition of lipid hydroperoxides was the pathway for the generation of conjugated hydrocarbon radicals, alcohols, aldehydes, and alkenes. The intramolecular cyclization and Diels-Alder reaction acted as ring-forming reactions, with consequent dehydrogenation, decarboxylation, side-chain breaks and radical reorganization, ultimately facilitating the amplification of the aromatic rings and the formation of PAHs.

The N6-methyladenosine reader protein YTHDC2 promotes gastric cancer progression via enhancing YAP mRNA translation.

N6-methyladenosine (m6A) modification is the most prevalent internal modification in eukaryotic mRNA. YTH domain containing 2 (YTHDC2), a m6A binding protein, has recently been identified as a key player in human cancer. However, its contribution to gastric cancer (GC) remains unknown. Herein, we found that YTHDC2 was significantly upregulated in human GC tissues and associated with poor prognosis. CRISPR-Cas9 mediated YTHDC2 knockout notably inhibited GC cell viability, proliferation and invasion. Transcriptome analysis coupled with mechanism experiments revealed that yes-associated protein (YAP), the well-known oncogene, is the target of YTHDC2 in GC cells. Specifically, YTHDC2 recognized m6A-modified YAP mRNA at 5`-UTR, resulting in enhancing the translation efficiency of YAP, without affecting its mRNA level. In turn, YAP/TEAD directly targeted -843∼-831 region on the promoter of YTHDC2 and activated the transcription of YTHDC2, thus forming a positive regulatory loop. Further, using the xenograft tumor model, we found that knockout of YTHDC2 markedly reduced tumor size and lung metastasis nodules in vivo. And high YTHDC2 was strongly positively correlated with high YAP in clinical GC tissues. Collectively, our data demonstrate that YTHDC2 is a novel oncogene in GC, which provides the theoretical basis for the strategy of targeting YTHDC2 for GC patients.

Circular RNA Circ-STIL Contributes to Cell Growth and Metastasis in Hepatocellular Carcinoma via Regulating miR-345-5p/AQP3 Axis.

BACKGROUND: Circular RNAs (circRNAs) are implicated in the pathogenesis and development of hepatocellular carcinoma (HCC). However, the function and latent mechanism of circ-STIL in HCC have not been elucidated. AIMS: This study was designed to explore the precise role and underlying molecular mechanism of circ-STIL in HCC advancement. METHODS: The expression levels of circ-STIL, SCL/TAL1 interrupting locus (STIL), miR-345-5p and aquaporin-3 (AQP3) were measured by quantitative real-time polymerase chain reaction or western blot. Cell proliferation was assessed by 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay. Cell apoptosis was analyzed by flow cytometry. Transwell assay was conducted to analyze cell migratory and invasive capacities. The interactions among circ-STIL, miR-345-5p and AQP3 were confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Xenograft tumor model was established to analyze the role of circ-STIL in HCC in vivo. RESULTS: Circ-STIL was upregulated in HCC tissues and cells. Circ-STIL knockdown inhibited HCC cell progression by reducing cell proliferation, migration and invasion and promoting cell apoptosis. MiR-345-5p was a direct target of circ-STIL, and AQP3 was targeted by miR-345-5p in HCC. Circ-STIL knockdown or miR-345-5p overexpression impeded cell malignant behaviors in HCC cells, and the effects could be reversed by miR-345-5p silence or AQP3 enhancement, respectively. Meanwhile, circ-STIL regulated AQP3 expression by sponging miR-345-5p. Besides, circ-STIL downregulation retarded HCC tumor growth in vivo. CONCLUSION: Circ-STIL knockdown suppressed HCC development by regulating miR-345-5p/AQP3 pathway, which might provide a promising target for HCC therapy.

Effects of bundled nursing combined with peer support on psychological state and self-efficacy of patients with cervical cancer undergoing chemotherapy.

OBJECTIVE: This study analyzed the effects of bundled nursing combined with peer support on psychological state and self-efficacy of cervical cancer patients undergoing chemotherapy. METHODS: A total of 86 patients with cervical cancer undergoing chemotherapy who were hospitalized from July 2019 to July 2020 were enrolled as study subjects. According to the method of a random number table, the selected patients were divided into a control group and an observation group and each group contained 43 patients. The control group was treated with bundled nursing care, while the observation group underwent combining treatment of both bundled nursing as well as education supported by peers. The changes of psychological state, self-efficacy and health-related quality of life of patients before and after nursing intervention were compared. RESULTS: The scores of depression and anxiety in two groups were remarkably decreased after intervention compared with prior-treatment, and the range of decrease in the observation group was critically greater than that in control group (P<0.05). The self-efficacy scores of the two groups were substantially increased after nursing care, and the increase of the score in the observation group was critically higher than that in control group (P<0.05). In addition, the health-related quality of life scores of the two groups increased remarkably after nursing, and the extent of increase in the observation group was notably greater than that in control group (P<0.05). The degree of serum tumor markers CA125, CEA, CA199 and SCC-A in the observation group after intervention were notably lower than those in the control group (P<0.05). CONCLUSION: The combinative practice of bundled nursing care and the supported education of peers can effectively improve the psychological status of cervical cancer patients with chemotherapy, and improve their self-efficacy and quality of life, which are all worthy of clinical promotion.

Effect of 5A nursing mode combined with fine nursing management on perioperative self-efficacy and living quality of hysteromyoma.

OBJECTIVE: In this study, we investigated the effects of 5A nursing mode combined with fine nursing management on perioperative self-efficacy and living quality of hysteromyoma. METHODS: 116 hysteromyoma patients admitted to our hospital during August 2018 to August 2020 were enrolled as the research objects, and divided into control group and observation group by random-number-table method. Each group contained 58 cases. The control-group patients were treated with conventional basic nursing, while the observation-group patients received combined treatment of 5A nursing mode and fine nursing management. Subsequently, the changes of self-efficacy, living quality of the two groups of patients before and after interventions, and the occurrence of postoperative complications in both groups were recorded and compared. RESULTS: The self-efficacy scores of both groups after intervention were markedly higher than those before intervention (P < 0.05), and the score of the observation-group after intervention was obviously higher than that of control-group (P < 0.05). The scores of the quality of life of the two groups after intervention were remarkably higher than those before intervention (P < 0.05), and the score of observation group after intervention was substantially higher than that of control group (P < 0.05). In addition, the incidence of complications in observation group was notably lower than that in control group, and the difference was statistically significant (10.34%, 29.31%, χ2 = 6.5619, P = 0.0104). CONCLUSION: The combined treatment of 5A nursing mode and fine nursing management has showed good nursing concept and standard nursing methods. It can effectively improve the self-efficacy and quality of life in hysteromyoma patients during perioperative period.

Chemotherapeutic effect of calcidiol derivative B3CD in a neuroblastoma xenograft model.

Bromoacetoxy-calcidiol (B3CD), a pro-apoptotic and cytotoxic agent in neuroblastoma (NB) cell lines, displayed therapeutic potential in vivo as an anticancer drug in a NB xenograft mouse model. Tumors of all animals treated intraperitoneally with B3CD went into regression within 10-30 days of treatment, while tumors in control animals grew aggressively. The response mechanisms of NB cells to B3CD in vitro were studied and included differential targeting of cell cycle key regulators p21 and cyclin D1 on the transcriptional and expression level leading to arrest in G0/G1 phase. In contrast to the effect in ovarian cancer cells, B3CD-induced cell death in SMS-KCNR NB cells was only marginally mediated by the p38 MAPK signaling pathway. Signaling induced by exogenous recombinant EGF leads to a partial restoration of the negative effects of B3CD on SMS-KCNR cell proliferation and survival. Upon combinational treatment of SMS-KCNR cells with B3CD and recombinant EGF, the EGF receptor (EGF-R) was highly activated. We suggest future studies to include analysis of the effects of B3CD in combination therapy with pharmacological inhibitors of cell cycle regulators or with EGF-R-targeting inhibitors, -toxins or -antibodies in vitro and their translation into in vivo models of tumor development.

Anti-proliferative and pro-apoptotic properties of 3-bromoacetoxy calcidiol in high-risk neuroblastoma.

The cytotoxic, anti-proliferative and apoptotic effects of 3-Bromoacetoxy Calcidiol (B3CD), a derivative of vitamin D3 precursor calcidiol, on human neuroblastoma (NB) cells were examined. NB, predominantly a tumor of early childhood, is the most common extracranial solid tumor. Despite aggressive treatments, survival for advanced stages remains low and novel treatment strategies are needed. B3CD-induced apoptosis in various neuroblastic cells via caspases-3 and -9 activation. B3CD upregulated mitochondrial pro-apoptotic Bax and anti-apoptotic Bcl-2 expression, caused cytochrome c release, downregulated N-Myc expression and activated pro-survival marker Akt. Accordingly, B3CD treatment dose dependently reduced the viability of NB cells with IC50 values between 1 and 3 microm. The cytotoxicity of B3CD was significantly higher than for the calcemic parent-compound vitamin D3 (IC50 between 10 and 30 microm). Further studies revealed that B3CD treatment inhibits the proliferation of NB cells at low concentrations (IC50 between 30 and 100 nm). Cell cycle analysis showed a dramatic increase in the apoptotic sub-diploidal population along with a cell cycle block. In summary, the present study shows that B3CD is toxic to NB cells via suppression of cell proliferation and cell viability by caspase activation and regulation of survival signals. These results suggest that B3CD could be developed as a treatment for NB.

Effect of indole ethyl isothiocyanates on proliferation, apoptosis, and MAPK signaling in neuroblastoma cell lines.

Several indole ethyl isothiocyanate (IEITC) analogs were designed, synthesized, and screened to evaluate their cytotoxicity against neuroblastoma (NB) cells in-vitro. In NB, predominantly a tumor of early childhood, survival remains low despite aggressive treatments. Therefore, novel treatment strategies are greatly needed. The objective of the present study was to study the therapeutic potential of IEITC by analyzing the cytotoxic, anti-proliferative, and apoptotic effects on NB cell lines. 7-Methyl-indole-3-ethyl isothiocyanate (7Me-IEITC) proved to be cytotoxic to various NB cell lines (SMS-KCNR, SK-N-SH, SH-SY5Y, and IMR-32) with an IC(50) at 2.5-5.0 microM, while primary control cells (lung fibroblasts) were not affected. 7Me-IEITC led to the activation of apoptotic markers caspase-3, -8, and -9, caused activation of pro-apoptotic p38 MAPK and SAP/JNK, and down-regulated pro-survival factor AKT in SMS-KCNR cells. Moreover, 7Me-IEITC displayed anti-proliferative effects (IC(50) at 600 nM) and caused an arrest in cell cycle progression. This wide effect of 7Me-IEITC on NB cell signaling and survival suggests that it could be developed as a therapeutic agent against neuroblastoma.