Calcium-binding protein S100P promotes tumor progression but enhances chemosensitivity in breast cancer

Background: Chemoresistance remains one of the obstacles to overcome in the treatment of breast cancer. S100 calcium-binding protein P (S100P) has been observed to be overexpressed in several cancers and has been associated with drug resistance, metastasis, and prognosis. However, the role of S100P in chemoresistance in breast cancer has not been thoroughly determined. Methods: Immunohistochemistry was used to evaluate the expression level of S100P protein in 22 pairs (pre-chemo and post-chemo) of breast cancer tissue from patients who underwent neoadjuvant chemotherapy. The influence of S100P on the biological behavior and chemosensitivity of breast cancer cells was then investigated. Results: The protein level of S100P in breast cancer tissue was significantly higher than in benign fibroadenoma (p<0.001). The S100P expression level was shown to be decreased by 46.55% after neoadjuvant chemotherapy (p=0.015). Subgroup analysis revealed that S100P reduction (57.58%) was mainly observed in the HER2+ tumors (p=0.027). Our in-vitro experiments showed that the knockdown of S100P suppressed the proliferation, adhesion, migration and invasion abilities of T47D and SK-BR-3 breast cancer cells. We further demonstrated that this knockdown increased the chemoresistance to paclitaxel and cisplatin in SK-BR-3 cells. We found that S100P exerted its function by activating NF-κB, CCND1 and Vimentin, but downregulating E-cadherin. Conclusions: S100P promotes the aggressive properties of breast cancer cells and may be considered as a promising therapeutic target. Moreover, S100P can be used to predict the therapeutic effect of chemotherapy in HER2+ breast cancer patients

The influence of cognitive ability in Chinese reading comprehension: can working memory updating change Chinese primary school students’ reading comprehension performance?

With the development of educational cognitive neuroscience, language instruction is no longer perceived as mechanical teaching and learning. Individual cognitive proficiency has been found to play a crucial role in language acquisition, particularly in the realm of reading comprehension. The primary objective of this study was to investigate two key aspects: firstly, to assess the predictive effects of the central executive (CE) on the Chinese reading comprehension scores of Chinese primary school students, and secondly, to explore the influence of CE training on the Chinese reading comprehension performance of Chinese primary school students. Chinese primary school students were recruited as participants. Experiment 1 used a Chinese N-back task, a Chinese Stroop task, and a number-pinyin conversion task to investigate the predictive effect of the CE components on Chinese reading comprehension. Experiment 2, based on the results of Experiment 1, used the Chinese character N-back training to explore the influence of updating training on Chinese reading comprehension. The findings from Experiment 1 underscored that CE had a predictive effect on Chinese reading comprehension scores. And updating had a prominent role in it. Experiment 2 revealed that the experimental group exhibited an enhancement in their updating performance following N-back training. Although the reading comprehension performance of the two groups after training did not produce significant differences in total scores, the experimental group showed maintained and higher microscopic reading comprehension scores than the control group in the more difficult post-test. In summary, this study yields two primary conclusions: (1) CE was able to predict Chinese reading comprehension scores. Updating has an important role in prediction. (2) Updating training enhances students’ updating performance and positively influences students’ Chinese microscopic reading comprehension performance

Selection of Anti-Sulfadimidine Specific ScFvs from a Hybridoma Cell by Eukaryotic Ribosome Display

BACKGROUND:Ribosome display technology has provided an alternative platform technology for the development of novel low-cost antibody based on evaluating antibiotics derived residues in food matrixes. METHODOLOGY/PRINCIPAL FINDINGS:In our current studies, the single chain variable fragments (scFvs) were selected from hybridoma cell lines against sulfadimidine (SM(2)) by using a ribosome library technology. A DNA library of scFv antibody fragments was constructed for ribosome display, and then mRNA-ribosome-antibody (MRA) complexes were produced by a rabbit reticulocyte lysate system. The synthetic sulfadimidine-ovalbumin (SM(2)-OVA) was used as an antigen to pan MRA complexes and putative scFv-encoding genes were recovered by RT-PCR in situ following each panning. After four rounds of ribosome display, the expression vector pCANTAB5E containing the selected specific scFv DNA was constructed and transformed into Escherichia coli HB2151. Three positive clones (SAS14, SAS68 and SAS71) were screened from 100 clones and had higher antibody activity and specificity to SM(2) by indirect ELISA. The three specific soluble scFvs were identified to be the same molecular weight (approximately 30 kDa) by Western-blotting analysis using anti-E tag antibodies, but they had different amino acids sequence by sequence analysis. CONCLUSIONS/SIGNIFICANCE:The selection of anti-SM(2) specific scFv by in vitro ribosome display technology will have an important significance for the development of novel immunodetection strategies for residual veterinary drugs

Comparison of Fluorescent Microspheres and Colloidal Gold as Labels in Lateral Flow Immunochromatographic Assays for the Detection of T-2 Toxin

A new highly specific and sensitive monoclonal antibody (MAb) to T-2 toxin (T-2) was produced, providing an IC50 value of 1.02 ng/mL and negligible cross-reactivity (CR) to other related mycotoxins. Based on the new MAb, a lateral-flow immunochromatographic assay (LFIA) using colloidal gold (CG) and fluorescent microspheres (FMs) as labels was proposed for T-2. Under the optimized conditions, in rapid qualitative assay, the cut-off values of the CG-LFIA were 400 μg/kg in rice and 50 μg/L in fresh milk, and the cut-off values of the FMs-LFIA were 100 μg/kg in both rice and chicken feed. For the quantitative assay with the FMs-LFIA, the limit of detection (LOD) were 0.23 μg/kg and 0.41 μg/kg in rice and chicken feed, respectively, and the average recoveries ranged from 80.2% to 100.8% with the coefficient of variation (CV) below 10.8%. In addition, we found that the CG-LFIA could tolerate the matrix effect of fresh milk better than the FMs-LFIA, while the FMs-LFIA could tolerate the matrix effect of chicken feed better than CG-LFIA under the same experimental conditions. These results provide a certain reference for the selection of appropriate labels to establish a rapid LFIA in various biological samples

Effect of Carotid Artery Morphological Variations on Cognitive Function

Background. Carotid artery morphological variations (CAMV) are common variations on medical imaging; the effects of CAMV on cognition were still unknown. This study is aimed at investigating whether carotid artery morphological variations (CAMV) cause cognitive impairment. Methods. Hospitalized patients from March 2017 to October 2017 who underwent digital subtract angiography (DSA) were divided into non-CAMV group, T-type group, K-type group, and C-type group according to their carotid artery morphology. Cognitive function in each group was evaluated with the Mini-Mental State Scale (MMSE), the Montreal Cognitive Assessment (MoCA), the Verbal Fluency Test (VFT), and the Digital Span Test (DST). Results. A total of 96 patients were included in the study (32 in non-CAMV group, 34 in T-type group, 30 in K-type group, and none in C-group). The positive rate of MMSE in the non-CAMV group, the T-type group, and the K-type group was 15.6%, 14.7%, and 20.0%, respectively, with no statistical difference in the three groups (p=0.836). The positive rate of MoCA in the K-type group was significantly higher than that in the non-CAMV and the T-type groups (p<0.001), but there was no significant difference between the non-CAMV group and the T-type group (p=0.826). The VFT, DST forward score, and backward score in the K-type group were significantly lower than those in the non-CAMV and the T-type groups (p<0.001). Conclusions. K-type CAMV may cause cognitive impairment, and MoCA is superior to MMSE in identifying mild cognitive impairment caused by CAMV

Synthesis of haptens and production of antibodies to bisphenol A

Three immunizing haptens of bisphenol A (BPA), including two new haptens, were used to produce highly sensitive and specific polyclonal antibodies. The spacer arms of haptens for coupling to the protein carrier were located at different positions in BPA, and different length spacer arms were tested. Highly sensitive polyclonal antibodies were obtained and characterized using indirect competitive enzyme-linked immunosorbent assay (icELISA). Under optimized conditions, the half maximal inhibitory concentration (IC50) value of the best polyclonal antibody was 2.1 mg&#183;L&#8722;1, based on coating heterogeneous antigens, and this optimal polyclonal antibody was highly sensitive toward BPA and displayed negligible cross-reactivity with bisphenol B and bisphenol E. A sensitive icELISA method utilizing the polyclonal antibody was developed for the determination of BPA in milk. In spiked samples (5, 10 and 20 mg&#183;L&#8722;1), the recovery ranged from 80% to 102% with a coefficient of variation (CV) value below 15.8%. The limit of detection of icELISA was 1.95 mg&#183;L&#8722;1. These results indicate that the icELISA method is suitable for the detection of BPA in milk

Development of a Highly Sensitive and Specific ic-ELISA and Lateral Flow Immunoassay for Diacetoxyscirpenol

To monitor the contamination of a type A trichothecene, diacetoxyscirpenol (DAS), one monoclonal antibody (mAb) 8A9 with high affinity and specificity was prepared in the present study. The mAb 8A9 showed a 50% inhibition concentration (IC50) of 0.31 &mu;g/L, which is of the highest affinity reported to date. An indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and lateral flow immunoassay (LFIA) based on mAb 8A9 were developed and exhibited limits of detection as low as 0.65 &mu;g/kg and 100 &mu;g/kg in rice samples, respectively. The molecular recognition mechanism of mAb 8A9 to DAS was explored by molecular docking. The results showed that the hydrophobic amino acids of mAb 8A9 interacted with DAS by forming hydrogen bonds and a pi-sigma bond, which lead to a highly specific recognition of DAS. In summary, we produced one mAb, developed ELISA and LFIA for DAS detection in rice with significantly sensitivity, specificity, accuracy, and precision