Internet altruistic motivation promotes internet altruistic behavior: a moderated mediation model.

This study proposes and tests a moderated mediation model to explore the relationship between Internet altruistic motivation (IAM) and Internet altruistic behavior (IAB), as well as its underlying and conditional mechanisms. A total of 324 Chinese college students (M age = 20.31 years, SD age = 1.38; 165 females) completed a questionnaire consisting of the IAM Questionnaire, IAB Scale, Mehrabian Trait Empathy Scale and Rosenberg Self-Esteem Scale. Results indicated that IAM was positively correlated with IAB (r = 0.44, p < 0.001), and self-esteem played a partial mediating role between IAM and IAB. In addition, empathy moderated the relationship between IAM and self-esteem as well as that between IAM and IAB. Specifically, the higher the individual's empathy, the stronger the predictive effect of IAM on IAB and self-esteem. The findings can deepen understanding of how and when IAM promotes IAB.

Online violent video games and online aggressive behavior among Chinese college students: The role of anger rumination and self-control.

Online aggressive behavior (OAB) has received increasing attention in recent years, and that playing online violent video games (OVVG) is an important predictor of OAB. However, little is known of the mediating and moderating mechanisms underlying this relationship. This study aims to investigate (a) the mediating role of anger rumination in the association between OVVG and OAB and (b) the moderating role of self-control in the relationship between anger rumination and OAB. A total of 595 Chinese college students (M age = 19.59 years, SD age = 1.40) completed measurements regarding OVVG, anger rumination, self-control, and OAB. The correlation analyses showed that OVVG was significantly positively associated with anger rumination and OAB. Mediation analyses revealed anger rumination partially mediated the link between OVVG and OAB. Moderated mediation further indicated that anger rumination was not associated with OAB for individuals with high levels of self-control. However, for those with low levels of self-control, anger rumination was significantly associated with OAB. These findings suggest that the improvement of self-control and the decline of anger rumination could be a practicable way to address the issue of OAB effectively.

Exploring cancer metastasis prevention strategy: interrupting adhesion of cancer cells to vascular endothelia of potential metastatic tissues by antibody-coated nanomaterial.

BACKGROUND: Cancer metastasis caused by circulating tumor cells (CTCs) accounts for 90% cancer-related death worldwide. Blocking the circulation of CTCs in bloodstream and their hetero-adhesion to vascular endothelia of the distant metastatic organs may prevent cancer metastasis. Nanomaterial-based intervention with adhesion between CTCs and endothelia has not been reported. Driven by the novel idea that multivalent conjugation of EpCAM and Slex antibodies to dendrimer surface may enhance the capacity and specificity of the nanomaterial conjugates for capturing and down-regulating colorectal CTCs, we conjugated the dendrimer nanomaterial with the EpCAM and Slex antibodies, and examined the capacity of the dual antibody-coated nanomaterial for their roles in interrupting CTCs-related cancer metastasis. RESULTS: The antibody-coated nanomaterial was synthesized and characterized. The conjugates specifically bound and captured colon cancer cells SW620. The conjugate inhibited the cells' viability and their adhesion to fibronectin (Fn)-coated substrate or human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. In comparison with SW480 and LoVo cell lines, the activity and adhesion of SW620 to Fn-coated substrate and HUVECs were more specifically inhibited by the dual antibody conjugate because of the higher levels of EpCAM and Slex on SW620 cell surface. The hetero-adhesion between SW620 and Fn-coated substrate, or HUVECs was inhibited by about 60-70%. The dual conjugate showed the inhibition capacity more significant than its corresponding single antibody conjugates. CONCLUSIONS: The present study provides the new evidence that coating nanomaterials with more than one antibody against CTCs may effectively interfere with the interaction between SW620 and HUVECs.

CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2.

Our former report indicates that calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) is over-expressed in the SGC7901/ADR cell line. However, the potential role of CacyBP/SIP in the development of multidrug resistance (MDR) of pancreatic cancer is still uncertain. In this paper, we investigated the role of CacyBP/SIP in MDR of pancreatic cancer cells and its possible underlying mechanisms, and found that CacyBP/SIP was over-expressed in the Gemcitabine induced MDR pancreatic cancer cell PC-3/Gem compared with its parental cell PC-3. Up-regulation of CacyBP/SIP expression could enhance resistance of chemotherapy drugs on PC-3 cells and inhibit Adriamycin-induced apoptosis accompanied by decreased accumulation of intracellular Adriamycin. Furthermore, CacyBP/SIP could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene. In addition, the decrease of CacyBP/SIP expression using RNA interference or P-gp inhibitor could partially reverse CacyBP/SIP-mediated MDR. In brief, our study demonstrated that CacyBP/SIP could enhance the MDR phenotype of pancreatic cancer cells by increasing the expression of P-gp and Bcl-2, thus inhibiting apoptosis of pancreatic cancer cell.

Research on drug resistance mechanism of trastuzumab caused by activation of the PI3K/Akt signaling pathway.

AIM OF THE STUDY: To discuss the activation of the signal transduction pathway of phosphatidylinositol 3'-kinase/serine-threonine kinase (PI3K/Akt), one of the important targets of drug resistance of trastuzumab, which provides a theoretical basis for the targeted therapy of drug resistance of trastuzumab in breast cancer. MATERIAL AND METHODS: Establish the drug-resistance sub-strain BT-HerR of trastuzumab for the continuous treatment of human breast cancer cell strain BT474, conduct Her-2 phenotype analysis on the drug-resistance cell strain BT-HerR with the FISH method, detect the proliferation inhibition in vitro of trastuzumab to BT474 and BT-HerR cells with the MTT method, detect the apoptosis variation after interference of trastuzumab with a flow cytometer and detect p-Akt and apoptosis-related protein expression with Western blot after PI3K/Akt inhibitor LY294002 interferes with the cells. RESULTS: The gene expression of drug-resistance cell strain BT-HerR Her-2 is strongly positive; 72 hours after interference of trastuzumab, the proliferation in vitro of the BT474 and BT-HerR cells is inhibited, which is strengthened with the increase of concentration, showing a significant difference (p < 0.01); after treatment of trastuzumab, comparison of the cell apoptosis rate of BT474 and BT-HerR shows a significant difference (p < 0.01); trastuzumab can only inhibit the Akt protein phosphorylation of BT474, while LY294002 can inhibit the BT-HerR and BT474 Akt protein phosphorylation simultaneously. CONCLUSIONS: Akt protein phosphorylation of trastuzumab drug-resistance cells is activated; LY294002, a PI3K/Akt inhibitor, can obviously inhibit Akt protein phosphorylation of trastuzumab drug-resistance cells and there is a clear association between the PI3K/Akt signal transduction pathway and trastuzumab resistance.

2D-2D heterostructure of ionic liquid-exfoliated MoS2/MXene as lithium polysulfide barrier for Li-S batteries.

Suppressing the dissolution and shuttling of lithium polysulfides (LiPSs) in electrolytes in lithium-sulfur batteries (LSBs) is the focus of researchers. Herein, functional liquid phase exfoliated MoS2 and MXene (IL-MoS2/MX) interlayer is proposed as the separator of LSBs. The unique alternating intercalation structure of the IL-MoS2/MX interlayer provides a channel for ion transport while achieving uniform Li+ deposition on the anode side. Moreover, IL-MoS2 achieves physical and chemical anchoring to LiPSs and lowers the energy barrier for battery reactions. As a result, the separator in the coin cell delivers an initial capacity of 764.4 mAh·g-1 at 1C and high retention of 58.7 % after 700 cycles, with a decay only 0.059 % per cycle. Simultaneously, the excellent stability is also verified under varying current densities. Beyond that, ionic conductivity and lithium-ion migration number are adopted to confirm unique ion transport channels and uniform deposition of lithium. X-ray photoelectron spectroscopy, S8 and Li2S decomposition and nucleation energy barrier analysis are performed to verify the adsorption and catalytic conversion mechanisms. The convenient preparation and excellent performance of IL-MoS2/MX provide a design strategy for functionalized interlayers for LSBs, and the possibility for commercialization.

A Novel Magnetorheological Fluid with High-Temperature Resistance.

A magnetorheological fluid (MR fluid) is mainly composed of soft magnetic particles, surfactants, and the base carrier fluid. Among these, soft magnetic particles and the base carrier fluid influence the MR fluid significantly in a high-temperature environment. Therefore, a study was carried out to investigate the changes in the properties of soft magnetic particles and base carrier fluids in high-temperature environments. On this basis, a novel magnetorheological fluid with high-temperature resistance was prepared, and the novel magnetorheological fluid had excellent sedimentation stability, of which the sedimentation rate was only 4.42% after heat treatment at 150 °C followed by one-week placement. At 30 °C, the shear yield stress of the novel fluid was 9.47 kPa under the magnetic field of 817 mT: higher than the general magnetorheological fluid with the same mass fraction. Moreover, its shear yield stress was less affected by the high-temperature environment, reducing by only 4.03% from 10 °C to 70 °C. The novel MR fluid can be applied to a high-temperature environment, effectively expanding the application range of MR fluid.

Real-world treatment patterns and survival for locally advanced esophageal squamous cell carcinoma.

The "real world" treatment mode and clinical efficacy of locally advanced esophageal squamous cell carcinoma (LAESCC) are unclear. Meanwhile, the role of immunotherapy in the clinical practice is also puzzling. We conducted the research to investigate the statue of "real world" LAESCC. The clinical data of patients with locally advanced esophageal squamous cell carcinoma which met the criteria from January 2010 to December 2019 have been retrospectively analyzed, and the distribution of clinical treatment patterns has been analyzed. They cover such aspects as dfferences in survival time and further analysis of the differences in overall survival (OS) and progression-free survival (PFS) between patients who received immunotherapy and those who did not receive immunotherapy. What is more, Cox risk regression model has also been used to evaluate the risk factors affecting the prognosis of LAESCC. The cases of a total of 5328 newly diagnosed patients with esophageal cancer were collected, and a total of 363 patients were included in the study, with a median age of (46.2 ± 7.8) years old; 84 (23.1%) and 279 (76.9%) patients received 1L and ≥ 2L, respectively; Concurrent chemoradiotherapy (74.1%) and paclitaxel combined with platinum-based chemotherapy (14.3%) were the main first-line treatment options; fluorouracil combined with cisplatin regimen-based chemotherapy (63.8%) was the main treatment option for ≥ 2L, of which 69 patients (25.3%) received immunization treatment; OS of patients with 1 line of therapy and ≥ 2L were (22.4 ± 7.2) months and (38.7 ± 8.5) months, respectively, and the comparison between groups was statistically significant (P < .05); among 69 patients with ≥ 2L who received immunotherapy, PFS and The OS was (14.6 ± 6.9) and (45.3 ± 9.7) respectively, and the comparison between the groups was statistically significant (all P < .05). Cox multivariate analysis has shown that clinical stage, immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are the main factors affecting OS. and immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are independent factors affecting PFS. Concurrent chemoradiotherapy is currently one of the standard treatments for LAESCC, and most patients are still willing to receive second-line or above treatments. Adding immunotherapy to standard treatment modalities may further optimize clinical treatment modalities and improve patient outcomes.

Comparative efficacy and safety for second-line treatment with ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma progressed on sorafenib treatment: A network meta-analysis.

BACKGROUND: The present network meta-analysis was conducted to perform an indirect comparison among ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma (HCC) progressed on sorafenib treatment. METHODS: A systematic review through Medline, Embase, and Cochrane library was developed, with eligible randomized clinical trials been included. Hazard ratios (HRs) including progression-free survival (PFS), overall survival (OS), odds ratios of disease control rate (DCR), objective response rate (ORR), and adverse events were compared indirectly with network meta-analysis using random model in software STATA version 13.0. RESULTS: A total of 4 randomized clinical trials including 2137 patients met the eligibility criteria and enrolled. Indirect comparisons showed that there was no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among agents of regorafenib, cabozantinib, and ramucirumab in advanced HCC patients with elevated α-fetoprotein (AFP) (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib was the only agent associated with significant superiority in OS, compared with placebo (hazard ratio 0.67, 95% CI, 0.50-0.90). CONCLUSIONS: The present network meta-analysis revealed that there might be no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among regorafenib, cabozantinib, or ramucirumab in advanced HCC patients with elevated AFP (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib might be associated with significant superiority in OS, compared to placebo, which need further investigation in clinical practice.

Biomimetic superelastic sodium alginate-based sponges with porous sandwich-like architectures.

Design and fabrication of structurally optimized three-dimensional porous materials are highly desirable for engineering applications. Herein, through a facile bidirectional freezing technique, we prepared superelastic biomass sponges in air and underwater, which possess biomimetic porous sandwich-like architectures with lamellar layers interconnected by porous microstructures, similar to the structure of rice stems. This distinctive architecture was obtained by incorporating Typha orientalis fibers (TOFs) and graphene oxide (GO) nanosheets into sodium alginate (SA) matrix, in which SA flakes and GO nanosheets were intimately grown along TOFs. The porous sandwich-like microstructure allows stress to be distributed throughout the lamellar to avoid stress concentration and endows SA/TOFs/GO sponge with excellent mechanical compressibility and recoverability. Especially, underwater superelasticity and superoleophobicity of the sponge facilitates removal of water-miscible contaminants or oil/water separation with high efficiency. This novel strategy for the design biomimetic architecture of superelastic biomass sponge can promote its application for protecting environment.

Publisher Correction: Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles.

There are disease-causing biohazards in the blood that cannot be treated with modern medicines. Here we show that an intelligently designed safe biomaterial can precisely identify, tow and dump a targeted biohazard from the blood into the small intestine. Positively charged mesoporous silica nanoparticles (MSNs) functionalized with EGFR-targeting aptamers (MSN-AP) specifically recognize and bind blood-borne negatively charged oncogenic exosomes (A-Exo), and tow A-Exo across hepatobiliary layers and Oddi's sphincter into the small intestine. MSN-AP specifically distinguish and bind A-Exo from interfering exosomes in cell culture and rat and patient blood to form MSN-AP and A-Exo conjugates (MSN-Exo) that transverse hepatocytes, cholangiocytes, and endothelial monolayers via endocytosis and exocytosis mechanisms, although Kupffer cells have been shown to engulf some MSN-Exo. Blood MSN-AP significantly decreased circulating A-Exo levels, sequentially increased intestinal A-Exo and attenuated A-Exo-induced lung metastasis in mice. This study opens an innovative avenue to relocate blood-borne life-threatening biohazards to the intestine.

[Gemcitabine combined with capecitabine in the treatment for 41 patients with relapsed or metastatic biliary tract carcinoma].

OBJECTIVE: To investigate the efficacy of the combination of gemcitabine with capecitabine in the chemotherapy for patients with relapsed or metastatic biliary tract carcinoma. METHODS: Forty-one patients with unresectable relapsed or metastatic carcinoma of the biliary tract were treated from March 2000 to December 2004. The regimen consisted of intravenous administration of gemcitabine plus oral intake of capecitabine every 3 weeks for more than 2 cycles. The parameters including tumor response, clinical benefit rate,survival and safety were observed. RESULTS: Thirty-six patients were valuable and 5 patients were excluded from this series due to various reasons. Eleven patients (30.1%) had a partial response and another 11 patients (30.1%) experieced stable disease with a clinical benefit rates of 61.1%. The median overall survival time and time to progression were 10 months and 6 months, respectively. The one-year survival rate was 40.0%. The adverse events including nausea, diarrhea and hand-foot syndrome, fatigue, neutropenia, thrombocytopenia were frequently observed, which were usually in grade I or II, rarely in grade III and none in grade IV (NCI-CTC). CONCLUSION: Our results show that the regimen of gemcitabine combined with capecitabine is effective and well tolerated in patients with unresectable relapsed or metastatic carcinoma of the biliary tract.

Fecal fusobacterium nucleatum for detecting colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis was to evaluate the efficacy of fecal Fusobacterium nucleatum ( Fn) for detecting colorectal cancer. It is the first systematic review and meta-analysis to focus exclusively on fecal Fn for colorectal cancer. MATERIALS AND METHODS: Comprehensive searches of several databases before January 2018 were conducted. Fecal Fn for detecting colorectal cancer was evaluated via pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve. Heterogeneity was explored using meta-regression and subgroup analyses. The publication bias and the overall quality of evidence were also analyzed. RESULTS: Our analysis included six papers containing seven case-control studies in the systematic review and meta-analysis. Overall sensitivity and specificity were 0.68 (95% confidence interval (CI) 0.64, 0.72) and 0.78 (95% CI 0.75, 0.81), respectively. The positive likelihood ratio and negative likelihood ratio in detecting colorectal cancer were 2.87 (95% CI 1.62, 5.10) and 0.40 (95% CI 0.30, 0.54) respectively. The diagnostic odds ratio (OR) was 8.75 (95% CI 4.86, 15.78) and the area under the curve was 0.80. A subgroup analysis showed that in Asia, the colorectal cancer sample size ⩾50 had higher specificity (specificity 0.85, 95% CI 0.80, 0.88). No publication bias existed. The GRADEpro showed a moderate level of the available evidence. CONCLUSIONS: Compared to other examinations, the fecal Fn test seems a good choice for detecting colorectal cancer. It also has better diagnostic performance in Asians. However, more clinical trials with large sample sizes and strict randomization are needed to further verify the evidence.

In vivo inhibition of circulating tumor cells by two apoptosis-promoting circular aptamers with enhanced specificity.

Circulating tumor cells (CTCs) are known as the root cause of cancer metastasis that accounts for 90% of cancer death. Owing to the rarity of blood CTCs and their microenvironmental complexity, the existing biotechnology could not precisely capture and apoptosize CTCs in vivo for cancer metastasis prevention. Here, we designed two double strand circular aptamers aimed to simultaneously target MUC1 and HER2 surface biomarkers on mesenchymal cancer cells. The circular aptamers are composed of a capture arm for binding and seizing CTCs and a circular body for resisting degradation by exonucleases. We conjugated the two circular aptamers onto dendrimer PAMAM G4.5 (dcAp1-G-dcAp2), and the conjugate entity showed both significantly-enhanced biostability in serum for days compared with their linear counterparts and capture specificity in RBC (1:108) compared with their single circular aptamers. dcAp1-G-dcAp2 apoptosized the targeted cells and inhibited their bioenergetic activities significantly by lowing △Ψm, ATP and lactate productions while increasing ROS production. dcAp1-G-dcAp2 captured CTCs in mice in vivo and in patient blood. This study lays the foundation for developing multiple biostable circular aptamers and conjugating them together to precisely capture and apoptosize mesenchymal CTCs in vivo.

Predictive SNPs for radiation-induced damage in lung cancer patients with radiotherapy: a potential strategy to individualize treatment.

In the treatment of lung cancer, radiotherapy has become one of the most important therapies, despite its sometimes unpredictable side effects. As such, identifying lung cancer patients who are at high risk of developing severe radiation-induced damage (mainly radiation pneumonitis and radiation-induced esophageal toxicity) and applying effect intervention or monitoring techniques are important. Although human diversity to a certain amount is explained by clinical and dosimetric factors, the presence of specific genetic determinants also influences the occurrence of radiation-induced damage. Here we summarize the data on mechanisms of radiation pneumonitis and radiation-induced esophageal toxicity supporting the involvement of variances of genes in the evolution of radiation-induced damage. Furthermore, the available evidence from current clinical studies of genetic polymorphisms for the prediction of radiation pneumonitis and radiation-induced esophageal toxicity is discussed. Eventually, this may help to truly individualize radiotherapy, using a personal genetic profile of the most relevant genes for each lung cancer patient.

Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil.

Recent scientific advances have increased our understanding of the cancer metastatic complexities and provided further impetus for new combination therapies to prevent cancer metastasis. Here, we demonstrated that a combination (HAMPT) of aspirin, lysine, mifepristone and doxycycline can effectively and safely prevent cancer metastasis. The pharmaceutically-formulated HAMPT inhibited adhesion of cancer cells to either endothelial cells or extracellular matrix via down-regulating cell adhesion molecules ICAM-1 and α4-integrin. HAMPT inhibited the cloak effect by activated platelets on cancer cells, thereby interfering adhesion and invasion of cancer cells to the underlying stroma. At the effective concentration, HAMPT induced cancer cells into dormancy with minor inhibition on cell viability. Four-day pretreatment followed by 30-day oral administration of HAMPT (33.5-134 mg/kg) to the mice inoculated with cancer cells produced significant inhibition on cancer metastasis dose-dependently without marked side effects. Fifty-day rat toxicity study with HAMPT at doses (335-1340 mg/kg) 20-fold higher than its therapeutic dose produced no significant toxicity. Interestingly, the acute toxic death could not be reached at the maximum administrable dose (5 g/kg). This proof-of-concept study provides the first conceptual evidence that cancer metastasis can be controlled by using affordable old drugs to restrain circulating tumor cells from gemmating on the metastatic soil without the need for cytotoxicity.

Systems pharmacology of mifepristone (RU486) reveals its 47 hub targets and network: comprehensive analysis and pharmacological focus on FAK-Src-Paxillin complex.

Mifepristone (RU486), a synthetic steroid compound used as an abortifacient drug, has received considerable attention to its anticancer activity recently. To explore the possibility of using mifepristone as a cancer metastasis chemopreventive, we performed a systems pharmacology analysis of mifepristone-related molecules in the present study. Data were collected by using Natural Language Processing (NLP) and 513 mifepristone-related genes were dug out and classified functionally using a gene ontology (GO) hierarchy, followed by KEGG pathway enrichment analysis. Potential signal pathways and targets involved in cancer were obtained by integrative network analysis. Total thirty-three proteins were involved in focal adhesion-the key signaling pathway associated with cancer metastasis. Molecular and cellular assays further demonstrated that mifepristone had the ability to prevent breast cancer cells from migration and interfere with their adhesion to endothelial cells. Moreover, mifepristone inhibited the expression of focal adhesion kinase (FAK), paxillin, and the formation of FAK/Src/Paxillin complex, which are correlated with cell adhesion and migration. This study set a good example to identify chemotherapeutic potential seamlessly from systems pharmacology to cellular pharmacology, and the revealed hub genes may be the promising targets for cancer metastasis chemoprevention.

[Effects of Erk signal transduction on the cell cycle of rat hepatic stellate cells stimulated by acetaldehyde].

OBJECTIVE: To investigate the effect of PD98059 on the proliferation and cell cycle of rat hepatic stellate cells (HSCs) stimulated by acetaldehyde and explore its mechanism. METHODS: Rat HSCs stimulated by acetaldehyde were incubated with different concentrations of PD98059. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle was analysed by flow cytometry. The mRNA of cyclin D1 and CDK4 were examined by RT-PCR. RESULTS: 20, 50, 100 micromol/L PD98059 could significantly inhibit the proliferation of HSCs stimulated by acetaldehyde in a does-dependent manner (0.109+/-0.020, 0.081+/-0.010 and 0.056+/-0.020 vs 0.146+/-0.030, F=31.385, P<0.05) and provoke G0/G1 phase arrest of HSCs stimulated by acetaldehyde in a does-dependent manner (61.9%+/-6.3%, 64.1%+/-3.3% and 70.9%+/-4.8% vs 55.2%+/-4.4%, F=16.402, P<0.05). 50, 100 micromol/L PD98059 could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<0.05) and CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406, P<0.05). CONCLUSION: The Erk signal transduction pathway plays an important role in regulating the proliferation and cell cycle of rat hepatic stellate cells stimulated by acetaldehyde, which may be partly related to its regulative effect on the expression of cyclin D1 gene and CDK4 gene

Influence of UGT1A1 gene methylation level in colorectal cancer cells on the sensitivity of the chemotherapy drug CPT-11.

OBJECTIVE: To study the influence of the methylation level of UGT1A1 gene related to CPT-11 metabolic enzymes in colorectal cancer cells on the sensitivity of chemotherapy drugs. METHODS: Test the changes in sensitivity of seven colorectal cancer cell strains that have been/not been subject to DAC treatment to CPT-11, analyze its correlation with CES2, UGT1A1 and GUSB mRNA expression according to IC50; screen the effective interference sequence of UGT1A1 siRNA, test the changes in cytotoxicity of CPT-11 after UGT1A1 siRNA is transfected, select RK0 cells and make them transfected with the chemosynthetic UGT1A1 siRNA after their UGT1A1 expression is restored with or without demethylation treatment. RESULTS: The sensitivity of different colorectal cancer cell strains to CPT-11 showed difference (P<0.05), UGT1A1 expression in colorectal cell lines had a negative correlation with the IC50 (r=0.790648, P<0.05), the interference efficiency of the screened UGT1A1 siRNA was up to 78%. The IC50 value of siRNA decreased by nearly one time after transfected with HT-29 (P<0.01); which of methylated RK0 cells of UGT1A1 gene increased instead after the demethylation treatment. However, the IC50 value of the demethylation treatment group increased compared with the non-demethylation treatment group after UGT1A1 siRNA was transfected. CONCLUSIONS: The cytotoxicity of CPT-11 to colorectal cancer cells has a negative correlation with UGT1A1 expression, and positive correlation with CES2 and GUSB. The specific silencing UGT1A1 gene of siRNA could significantly increase the sensitivity of CPT-11 to the chemotherapy of colorectal cancer cells. UGT1A1 methylation was an important factor affecting the chemosensitivity of CPT-11.