EPLIN expression in gastric cancer and impact on prognosis and chemoresistance

Epithelial protein lost in neoplasm (EPLIN) has been implicated as a suppressor of cancer progression. The current study explored EPLIN expression in clinical gastric cancer and its association with chemotherapy resistance. EPLIN transcript expression, in conjunction with patient clinicopathological information and responsiveness to neoadjuvant chemotherapy (NAC), was explored in two gastric cancer cohorts collected from the Beijing Cancer Hospital. Kaplan-Meier survival analysis was undertaken to explore EPLIN association with patient survival. Reduced EPLIN expression was associated with significant or near significant reductions of overall, disease-free, first progression or post-progression survival in the larger host cohort and Kaplan Meier plotter datasets. In the larger cohort EPLIN expression was significantly higher in the combined T1 + T2 gastric cancer group compared to the T3 + T4 group and identified to be an independent prognostic factor of disease-free survival and overall survival by multivariate analysis. In the smaller, NAC cohort, EPLIN expression was found to be significantly lower in tumour tissues than in paratumour tissues. EPLIN expression was significantly associated with responsiveness to chemotherapy which contributes to overall survival. Together, EPLIN appears to be a prognostic factor and may be associated with patient sensitivity to NAC

Characterization of Impact Ionization Coefficient of ZnO Based on a p-Si/i-ZnO/n-AZO Avalanche Photodiode

The avalanche photodiode is a highly sensitive photon detector with wide applications in optical communication and single photon detection. ZnO is a promising wide band gap material to realize a UV avalanche photodiode (APD). However, the lack of p-type doping, the strong self-compensation effect, and the scarcity of data on the ionization coefficients restrain the development and application of ZnO APD. Furthermore, ZnO APD has been seldom reported before. In this work, we employed a p-Si/i-ZnO/n-AZO structure to successfully realize electron avalanche multiplication. Based on this structure, we investigated the band structure, field profile, Current–Voltage (I-V) characteristics, and avalanche gain. To examine the influence of the width of the i-ZnO layer on the performance, we changed the i-ZnO layer thickness to 250, 500, and 750 nm. The measured breakdown voltages agree well with the corresponding threshold electric field strengths that we calculated. The agreement between the experimental data and calculated results supports our analysis. Finally, we provide data on the impact ionization coefficients of electrons for ZnO along the (001) direction, which is of great significance in designing high-performance low excess noise ZnO APD. Our work lays a foundation to realize a high-performance ZnO-based avalanche device

ALCAM, Activated leukocyte cell adhesion molecule, in clinical gastric cancer and patient's response to chemotherapies

Background/aim: Activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, has been shown to regulate cell adhesion through both homotypic and heterotypic interactions. In cancer, it might be involved in disease progression and chemotherapy drug resistance. The present study explored the clinical and prognostic significance of ALCAM in gastric cancer and its impact on patient's responses to neoadjuvant chemotherapies and cancer cells' response to chemodrugs in vitro. Materials and methods: Two independent cohorts were included to evaluate the link between ALCAM and the clinical outcomes and pathological factors of the patients. The gastric cancer cell lines HGC27 and AGS were used to generate ALCAM knockdown cell models. The cytotoxicity of chemotherapy drugs was examined using ALCAM knockdown cell models. Results: Patients with gastric cancer who had high levels of ALCAM transcripts showed a significantly shorter overall survival in both cohorts (p=0.043 and 0.006, respectively). Patients who resisted to neoadjuvant chemotherapy had marginally higher levels of ALCAM than those responded (p=0.056). Patients with low levels of ALCAM expression and resisted to neoadjuvant chemotherapy had the worst clinical outcome with a significantly shorter overall survival (p=0.004) and disease-free survival (p=0.006), whereas such results did not appear in high ALCAM expression patients. ALCAM knockdown cells were more sensitive to Cisplatin, Oxaliplatin and 5-Fluorouracil compared with their respective control cells. Conclusion: ALCAM acts as a negative prognostic indicator in patients with gastric cancer and high levels of ALCAM expression result in increased chemotherapy drug resistance. Keywords: ALCAM; CD166; drug resistance; gastric cancer; gastric cell model; neoadjuvant chemotherapy; survival

ALCAM, Activated Leukocyte Cell Adhesion Molecule, in Clinical Gastric Cancer and Patient’s Response to Chemotherapies

Background/aim: Activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, has been shown to regulate cell adhesion through both homotypic and heterotypic interactions. In cancer, it might be involved in disease progression and chemotherapy drug resistance. The present study explored the clinical and prognostic significance of ALCAM in gastric cancer and its impact on patient's responses to neoadjuvant chemotherapies and cancer cells' response to chemodrugs in vitro. Materials and methods: Two independent cohorts were included to evaluate the link between ALCAM and the clinical outcomes and pathological factors of the patients. The gastric cancer cell lines HGC27 and AGS were used to generate ALCAM knockdown cell models. The cytotoxicity of chemotherapy drugs was examined using ALCAM knockdown cell models. Results: Patients with gastric cancer who had high levels of ALCAM transcripts showed a significantly shorter overall survival in both cohorts (p=0.043 and 0.006, respectively). Patients who resisted to neoadjuvant chemotherapy had marginally higher levels of ALCAM than those responded (p=0.056). Patients with low levels of ALCAM expression and resisted to neoadjuvant chemotherapy had the worst clinical outcome with a significantly shorter overall survival (p=0.004) and disease-free survival (p=0.006), whereas such results did not appear in high ALCAM expression patients. ALCAM knockdown cells were more sensitive to Cisplatin, Oxaliplatin and 5-Fluorouracil compared with their respective control cells. Conclusion: ALCAM acts as a negative prognostic indicator in patients with gastric cancer and high levels of ALCAM expression result in increased chemotherapy drug resistance. Keywords: ALCAM; CD166; drug resistance; gastric cancer; gastric cell model; neoadjuvant chemotherapy; survival

CRISPR/Cas12a triggered SERS and naked eye dual-mode biosensor for ultrasensitive and on-site detection of nucleic acid via cascade signal amplification

Highly sensitive and on-site detection of nucleic acids has always been a critical issue in the field of analytical chemistry. Surface-enhanced Raman scattering (SERS)-based biosensing exhibits huge potential in nucleic acid detection, while the applicability is restricted in trace nucleic acid screening due to the lack of appropriate signal recognition, transducing and amplification technologies. Inspired by the specific recognition of CRISPR/Cas12a and the improved sensitivity through cascade signal amplification, we innovatively proposed a CRISPR/Cas12a triggered SERS and naked eye dual-mode biosensor for ultrasensitive and on-site detection of nucleic acid via cascade signal amplification. Upon the target DNA recognition, the activated CRISPR/Cas12a indiscriminately cleaved substrate ssDNA, leading to the failure of toehold-mediated DNA-strand displacement reaction (TSDR), and triggering hybridization chain reaction (HCR) to assemble numerous G-quadruplex/hemin DNAzyme (GQH DNAzyme) for cascade signal amplification. The generated GQH DNAzyme catalyzed the oxidation of L-cysteine to cystine, perturbing the aggregation of 4-NTP@AuNPs, resulting in significant Raman signal change. On the other hand, GQH DNAzyme catalyzed the oxidation of 2,2′-azino-di-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), leading to obvious color change to realize portable naked-eye detection. Through this strategy, target nucleic acid concentration was tactfully transformed into sensitive Raman and portable visualization signals, and the limit of detection were as low as 34.9 aM and 1 pM, respectively. Then, this biosensor was successfully applied to meat adulteration detection, which showed superb selectivity, sensitivity and applicability for on-site detection of trace nucleic acid in complicated food matrix.</p

Down-regulation of WAVE2, WASP family verprolin-homologous protein 2, in gastric cancer indicates lymph node metastasis and cell migration.

BACKGROUND: WAVE2 plays a crucial role in actin polymerisation and cell migration. We aimed to investigate the expression and cellular functions of WAVE2 in human gastric cancer (GC). MATERIALS AND METHODS: The level of WAVE2 was determined using quantitative PCR (Q-PCR) in a cohort of human gastric tissues. Expression of WAVE2, ARP2, NWASP, ROCK1 and ROCK2 was examined using RT-PCR in paired tissues. WAVE2 and ARP2 protein co-expression was examined. Anti-WAVE2 transgene ribozymes were constructed and transiently transfected into human GC cells. RESULTS: Down-regulation of WAVE2 expression in GC was significantly correlated with lymph node metastasis. WAVE2 was positively correlated with E-cadherin and negatively with TWIST. Immunohistochemically, WAVE2 and ARP2 were not co-expressed in serial mirror sections. In vitro, WAVE2 knockdown was shown to increase cell motility, whilst ROCK inhibitor treatment reduced this effect in HGC27 cells. CONCLUSION: WAVE2 is down-regulated in GC and loses its metastatic role in GC. Knockdown of WAVE2 could increase metastatic potential by promoting the growth, invasiveness, motility, adhesiveness and suppressing EMT (epithelial-mesenchymal transition) of GC cells

Genotoxicity evaluation of sodium dehydroacetate

Objective To study the genotoxicity of sodium dehydroacetate (Na-DHA). Methods Five strains of Salmonella Typhimurium (TA97a, TA98, TA100, TA102 and TA1535) were used with the presence and absence of S9 in bacterial reverse mutation test. Bacteria were treated with Na-DHA at the dose levels of 1 667, 556, 185, 62, 21 μg/plate. Both negative and positive controls were set. The number of revertant colonies per plate were counted. Kunming mice used for micronucleus test were treated with Na-DHA at 549.0, 275.0 and 137.0 mg/kg BW by gavage twice a day with a 24 h interval. The femurs of mice were removed at 6 h after the second gavage. The numbers of red blood cell (RBC), polychromatic erythrocytes (PCE) and micronucleus (MN) were observed. The PCE/RBC and MN/PCE (the incidence of micronucleus) were calculated. Chinese hamster ovary (CHO) cells were treated with Na-DHA (2 000, 1 000, 500 μg/ml) in the presence and absence of S9 for 6 or 24 h. Three hundred well-spread metaphases per group were scored, following the incidence of chromosomal aberration recorded. Results No significant difference in the number of mutant colonies of TA97a, TA98, TA100, TA102 and TA1535 between the treated groups and the negative control group (P>0.05). The incidence of micronucleus in each dose group was not significantly different from that in the negative control group (P>0.05). No significant difference in the incidence of CHO cell chromosome aberration between the dose group and the negative control group (P>0.05). The mutant colony number, the incidence of micronucleus and the incidence of chromosome aberration in the three tests were significantly lower than that in the positive control groups, with statistically significant differences (P<0.01). Conclusion No genotoxicity of Na-DHA was found in vivo nor in vitro

Protective effects of various ratios of DHA/EPA supplementation on high-fat diet-induced liver damage in mice

Abstract Background A sedentary lifestyle and poor diet are risk factors for the progression of non-alcoholic fatty liver disease. However, the pathogenesis of hepatic lipid accumulation is not completely understood. Therefore, the present study explored the effects of dietary supplementation of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on a high-fat diet-induced lipid metabolism disorder and the concurrent liver damage. Methods Using high-fat diet-fed C57BL/6 J mice as the animal model, diets of various ratios of DHA/EPA (2:1, 1:1, and 1:2) with an n-6/n-3 ratio of 4:1 were prepared using fish and algae oils enriched in DHA and/or EPA and sunflower seed oils to a small extent instead of the high-fat diet. Results Significantly decreased hepatic lipid deposition, body weight, serum lipid profile, inflammatory reactions, lipid peroxidation, and expression of adipogenesis-related proteins and inflammatory factors were observed for mice that were on a diet supplemented with DHA/EPA compared to those in the high-fat control group. The DHA/EPA 1:2 group showed lower serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol levels, lower SREBP-1C, FAS, and ACC-1 relative mRNA expression, and higher Fra1 mRNA expression, with higher relative mRNA expression of enzymes such as AMPK, PPARα, and HSL observed in the DHA/EPA 1:1 group. Lower liver TC and TG levels and higher superoxide dismutase levels were found in the DHA/EPA 2:1 group. Nonetheless, no other notable effects were observed on the biomarkers mentioned above in the groups treated with DHA/EPA compared with the DHA group. Conclusions The results showed that supplementation with a lower DHA/EPA ratio seems to be more effective at alleviating high-fat diet-induced liver damage in mice, and a DHA/EPA ratio of 1:2 mitigated inflammatory risk factors. These effects of n-3 polyunsaturated fatty acids (PUFA) on lipid metabolism may be linked to the upregulation of Fra1 and attenuated activity of c-Jun and c-Fos, thus ultimately reducing the severity of the lipid metabolism disorder and liver damage to some extent