Monitoring of the disulfide scrambled species by mixed-mode SEC-HPLC during the purification of a bispecific antibody.

Size-exclusion chromatography-high performance liquid chromatography (SEC-HPLC) is an analytical method routinely used for assessing aggregation content in protein samples. As SEC-HPLC separates analytes based on their hydrodynamic radius, it generally lacks the capability of differentiating species that are similar in size. Recently while purifying a bispecific antibody (bsAb), we noticed that SEC-HPLC can provide certain degree of resolution between the target bsAb and a disulfide scrambled form, although these two species were identical in molecular weight. In seeing the unexpected potential of SEC-HPLC at resolving species with similar size, we further tested Zenix SEC-300, a mixed-mode SEC-HPLC column from Sepax, which was reported to be capable of separating protein analytes based on other factors besides size. The Zenix column indeed provided resolution much better than the regular SEC-HPLC column. Upon further optimization, the Zenix column allowed close to baseline separation of the correctly folded and the disulfide scrambled species. The current study, as a complement to the previous reports, further demonstrates that mix-mode SEC-HPLC is capable of separating protein analytes that are close in size but are different in conformation and/or surface characteristics.

In vitro promotion of SDF-1α on the migration and proliferation of C-kit+ cardiac stem cells in neonatal mice.

The aim of this study was to explore the In Vitro effects of stromal-derived factor-1α (SDF-1α) on the migration and proliferation of c-kit+ cardiac stem cells. The lentivirus containing SDF-1α (LV-SDF-1α) was constructed. Primary myocardial fibroblasts were transfected by LV-SDF-1α, followed by primary culture of cardiac tissue cells and separation of c-kit+ cardiac stem cells with a flow cytometer, in order to investigate the effects of SDF-1α on the migration and proliferation of c-kit+ cardiac stem cells using cell co-culture, immunofluorescence and EdU tracing technologies. The results showed that myocardial fibroblasts could secrete SDF-1α after the transfection with LV-SDF-1α. High-purity c-kit+ cardiac stem cells were obtained through flow cytometry sorting and the positive rate was about 40%. The c-kit+ cardiac stem cells cultured In Vitro could be differentiated into cTnT positive cardiomyocyte-like cells. After co-culture of myocardial fibroblasts and c-kit+ cardiac stem cells transfected with lentivirus, SDF-1α might increase the migration of c-kit+ cardiac stem cells, but SDF-1α did not promote the proliferation of c-kit+ cardiac stem cells. In conclusion, the myocardial fibroblasts transfected with lentivirus can highly express SDF-1α, c-kit+ cardiac stem cells can be differentiated into cTnT positive cardiomyocyte-like cells and SDF-1α can effectively enhance the migration of c-kit+ cardiac stem cells but fails to stimulate the proliferation.

Exogenous Proline Enhances Systemic Defense against Salt Stress in Celery by Regulating Photosystem, Phenolic Compounds, and Antioxidant System.

This study aimed to explore how exogenous proline induces salinity tolerance in celery. We analyzed the effects of foliar spraying with 0.3 mM proline on celery growth, photosystem, phenolic compounds, and antioxidant system under salt stress (100 mM NaCl), using no salt stress and no proline spraying as control. The results showed that proline-treated plants exhibited a significant increase in plant biomass due to improved growth physiology, supported by gas exchange parameters, chlorophyll fluorescence, and Calvin cycle enzyme activity (Ketosasaccharide-1,5-diphosphate carboxylase and Fructose-1,6-diphosphate aldolase) results. Also, proline spraying significantly suppressed the increase in relative conductivity and malondialdehyde content caused by salt stress, suggesting a reduction in biological membrane damage. Moreover, salt stress resulted in hydrogen peroxide, superoxide anions and 4-coumaric acid accumulation in celery, and their contents were reduced after foliar spraying of proline. Furthermore, proline increased the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase) and the content of non-enzymatic antioxidants (reduced ascorbic acid, glutathione, caffeic acid, chlorogenic acid, total phenolic acids, and total flavonoids). Additionally, proline increased the activity of key enzymes (ascorbate oxidase, ascorbate peroxidase, glutathione reductase, and dehydroascorbate reductase) in the ascorbic acid-glutathione cycle, activating it to counteract salt stress. In summary, exogenous proline promoted celery growth under salt stress, enhanced photosynthesis, increased total phenolic acid and flavonoid contents, and improved antioxidant capacity, thereby improving salt tolerance in celery.

A Deep Spiking Neural Network Anomaly Detection Method.

Cyber-attacks on specialized industrial control systems are increasing in frequency and sophistication, which means stronger countermeasures need to be implemented, requiring the designers of the equipment in question to re-evaluate and redefine their methods for actively protecting against advanced mass cyber-attacks. The attacks in question have huge motivations, ranging from corporate espionage to political targets, but in any case, they have a substantial financial impact and severe real-world implications. It should also be said that it is challenging to defend against cyber threats because a single point of entry can be enough to destroy an entire organization or put it out of business. This paper examines threats to the digital security of vibration monitoring systems used in petroleum infrastructure protection services, such as pipelines, pumps, and tank farms, where malicious interventions can cause explosions, fires, or toxic releases, with incalculable economic and environmental consequences. Specifically, a deep spiking neural network anomaly detection method is presented, which models the spike sequences and the internal presentation mechanisms of the information to discover with very high accuracy anomalies in vibration analysis systems used in oil infrastructure protection services. This is achieved by simulating the complex structures of the human brain and the way neural information is processed and transmitted. This work uses a particularly innovative form of the Galves-Löcherbach Spiking Model (GLSM) [1], which is a spiking neural network model with intrinsic stochasticity, ideal for modeling complex spatiotemporal situations, which is enhanced with possibilities of exploiting confidence intervals by modeling optimally stochastic variable-length memory chains that have a finite state space.

CHO cathepsin B identified as the protease responsible for a target bispecific antibody fragmentation.

In a previous work we demonstrated that CHO protease caused fragmentation of an expressed bispecific antibody (bsAb) and this detrimental host cell protein (HCP) can be effectively removed through an optimized Protein A wash step. In addition, preliminary evidence suggested that the responsible protease belongs to the threonine or cysteine protease family. In the current study, this protease was further identified as cathepsin B. First, we identified several CHO proteases in the further fractionated Protein A wash using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this allowed us to select four candidate proteases. Next, by examining the cleavage pattern of each individual protease and comparing it with that observed during purification, cathepsin B was identified as the protease responsible for the observed bsAb fragmentation.

Trehalose Alleviated Salt Stress in Tomato by Regulating ROS Metabolism, Photosynthesis, Osmolyte Synthesis, and Trehalose Metabolic Pathways.

Trehalose plays a critical role in plant response to salinity but the involved regulatory mechanisms remain obscure. Here, this study explored the mechanism of exogenous trehalose-induced salt tolerance in tomato plants by the hydroponic test method. Our results indicated that 10 mM trehalose displayed remarkable plant biomass by improving growth physiology, which were supported by the results of chlorophyll fluorescence and rapid light-response curve. In the salinity environment, trehalose + NaCl treatment could greatly inhibit the decrease of malondialdehyde level, and it increases the contents of other osmotic substances, carbohydrates, K+, and K+/Na+ ratio. Meanwhile, trehalose still had similar effects after recovery from salt stress. Furthermore, trehalose pretreatment promoted trehalose metabolism; significantly increased the enzymatic activity of the trehalose metabolic pathway, including trehalose-6-phosphate synthase (TPS), trehalose-6-phosphate phosphatase (TPP), and trehalase (TRE); and upregulated the expression of SlTPS1, SlTPS5, SlTPS7, SlTPPJ, SlTPPH, and SlTRE under saline conditions. However, the transcriptional levels of SlTPS1, SlTPS5, and SlTPS7 genes and the activity of TPS enzyme were reversed after recovery. In addition, we found that hydrogen peroxide (H2O2) and superoxide anion (O2 -) were accumulated in tomato leaves because of salt stress, but these parameters were all recovered by foliar-applied trehalose, and its visualization degree was correspondingly reduced. Antioxidant enzyme activities (SOD, POD, and CAT) and related gene expression (SlCu/Zn-SOD, SlFe-SOD, SlMn-SOD, SlPOD, and SlCAT) in salt-stressed tomato leaves were also elevated by trehalose to counteract salt stress. Collectively, exogenous trehalose appeared to be the effective treatment in counteracting the negative effects of salt stress.

Sodium caprylate wash during Protein A chromatography as an effective means for removing protease(s) responsible for target antibody fragmentation.

For recombinant proteins produced in Chinese hamster ovary (CHO) cells, fragmentation is a common phenomenon that results in generation of product-related low-molecular-weight (LMW) species. Recently while purifying a bispecific antibody (bsAb), we observed that the target protein experienced cleavage at a couple of potential sites, leading to truncated products. Further studies suggest that the cleavage can likely be attributed to residual CHO cell protease activity. In order to maximally remove potential protease(s) that contribute fragmentation, we optimized Protein A chromatography by adding sodium caprylate (SC) to the wash buffer. Upon optimization, fragmentation of Protein A eluate happened to a much lesser degree as compared to that of eluate from unoptimized process, and the increased sample stability is in accordance with significantly reduced host cell protein (HCP) level. Taken together, the data suggest that SC wash during Protein A chromatography is an effective means for removing HCPs including endogenous protease(s) that are responsible for target antibody fragmentation.

Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis.

Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin-eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.

Prognostic and clinicopathological significance of miR-638 in cancer patients: A meta-analysis.

INTRODUCTION: MiR-638 is believed to be involved in human cancers. However, the prognostic value of miR-638 in human carcinomas is controversial and inconclusive. Therefore, we conducted this meta-analysis to investigate the association between miR-638 expression and clinical outcomes in the patients with various cancers. METHODS: We searched Pubmed, Embase, Wanfang, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2020 to identify relevant studies. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to correlate expression of miR-638 with prognosis and clinicopathological features. RESULTS: A total of 18 studies involving 1886 patients were included in the meta-analysis. The results revealed that low miR-638 expression was significantly correlated with poor overall survival (OS) (HR = 2.09, 95% CI: 1.46-2.98, P < .001), but not with disease-free survival (DFS) (HR = 1.71, 95% CI: 0.31-9.56, P = .540). Subgroup analysis found that low miR-638 expression was associated with worse OS in patients with digestive system cancer (HR = 2.47, 95% CI: 1.85-3.30, P < .001), the reported directly from articles group (HR = 2.12, 95% CI: 1.34-3.33, P < .001), survival curves group (HR = 2.02, 95% CI: 1.07-3.80, P = .029), in studies with sample size ≥100 (HR = 2.12, 95% CI: 1.34-3.35, P = .001), and in studies with sample size <100 (HR = 2.02, 95%CI: 1.09-3.75, P = .025). Moreover, cancer patients with low miR-638 expression were prone to tumor size (OR = 1.47, 95% CI: 1.03-2.09, P = .035), earlier lymph node metastasis (present vs absent, OR = 2.26, 95% CI: 1.63-3.14, P < .001), earlier distant metastasis (present vs absent, OR = 2.60, 95% CI: 1.45-4.67, P < .001), TNM stage (III-IV vs I-II, OR = 2.01, 95% CI: 1.35-2.99, P = .001), and portal vein invasion (present vs absent, OR = 4.39, 95% CI:2.23-8.64, P < .001), but not associated with age, gender, tumor differentiation, and vascular invasion. CONCLUSIONS: MiR-638 may serve as a promising indicator in the prediction of prognosis and clinicopathological features in patients with different kinds of cancers.

Quality Assessment and Antioxidant Activities of the Blossoms of Inula Nervosa Wall.

BACKGROUND: Currently, although Inula nervosa Wall is substantially investigated, little is understood about blossoms of Inula nervosa Wall (BINW). OBJECTIVE: In this work, we systematically investigated the antioxidant activity of the extract from BINW by various standard assays including 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical ability, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) di-ammonium salt radical cation (ABTS), and ferric reducing antioxidant potential (FRAP). METHODS: Chemical compounds were tentatively identified through an UHPLC-QTOF-MS system. Furthermore, the contents of nine compounds were detected with UHPLC method coupled with photodiode array (PDA) detector. By carefully analyzing the quantitative data via clusters analysis and principal component analysis (PCA). RESULTS: Forty-six compounds were tentatively identified, and our results showed that nine compound samples in 21 batches of BINW collected from different areas could be differentiated and analyzed by a heatmap visualization. In addition, the contents of nine compounds (flavonoids, phenolic acids) exhibited a total of higher amounts and better antioxidant activities from Yunnan than those from the other three origins. CONCLUSIONS: Our study not only developed a powerful platform to explain the difference between traditional Chinese medicines species that are closely related through the chemometric and chemical profiling, but also presented a useful method to establish quality criteria of BINW with multiple origins. HIGHLIGHTS: To characterize the BINW in detail, we not only performed DPPH, FRAP, and ABTS assays to investigate its antioxidant activity, but also established UHPLC-QTOF-MS/MS- and UHPLC-PDA-based methods to comprehensively identify and qualitatively analyze its components.

Prognostic and clinicopathological significance of MicroRNA-153 in human cancers: A meta-analysis.

BACKGROUND: Several studies have explored the prognostic value of MicroRNA-153 (miR-153) in various cancers, but obtained inconsistent results. Thus, we conducted a meta-analysis to assess the prognostic significance of miR-153 for patients with cancer. METHODS: Eligible studies were identified by searching the online databases Pubmed, Embase, Web of Science, Medline,and the China National Knowledge Infrastructure (CNKI) up to March 2020. Hazard ratios (HRs) with 95% CIs and were calculated to clarify the correlation between miR-153 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between miR-153 with clinicopathological characteristics of cancer patients. RESULTS: In total, 933 patients from 11 articles were enrolled in our meta-analysis. The results revealed that low miR-153 expression was significantly correlated with poor overall survival (OS) (HR = 2.45, 95% CI = 1.66-3.63, P < .001), but not with disease-free survival (DFS) (HR = 1.67, 95% CI = 0.45-6.19, P = .442). Subgroup analysis found that low miR-153 expression was associated with worse OS in the reported directly from articles group (HR = 2.67, 95% CI: 1.32-5.37, P = .006), survival curves group (HR = 2.10, 95% CI: 1.56-2.84, P < .001), digestive system tumor (HR = 2.76, 95% CI: 1.73-4.41, P < .001), and breast cancer (HR = 4.01, 95% CI: 1.46-11.04, P = .007).Moreover, cancer patients with low miR-153 expression were prone to poor tumor differentiation(poor vs well+moderate, OR = 2.41, 95% CI = 1.52-3.82, P < .001), earlier lymph node metastasis (present vs absent, OR = 2.19, 95% CI = 1.12-4.25, P = .021) and earlier distant metastasis (present vs absent,OR = 8.24, 95% CI = 2.93-23.21, P < .001), but not associated with age,gender and TNM stage. CONCLUSIONS: This meta-analysis indicated that low miR-153 expression is associated with poor prognosis. miR-153 may serve as an effective predictive biomarker for tumor prognosis, especially for digestive system tumor and breast cancer.

Macroscopic macroporous titanosilicate constructed of a micro-mesoporous ultrathin nanofilm.

A novel micro-mesoporous nanofilm-constructed macroscopic macroporous titanosilicate (MNCMM-TiSi) has been successfully prepared by a templating approach. The resultant materials exhibit greatly improved TOFs in bulky alkene epoxidation compared to the conventional TS-1 zeolite and Ti-MCM-41.

Nrf2 activation mediates tumor-specific hepatic stellate cells-induced DIgR2 expression in dendritic cells.

Our previous studies discovered that tumor-specific hepatic stellate cells (tHSCs) induced dendritic cell-derived immunoglobulin receptor 2 (DIgR2) expression in bone marrow-derived dendritic cells (mDCs), inhibiting splenic T cell activation. The current study aims to explore the underlying mechanism of DIgR2 expression by focusing on Nrf2 (nuclear-factor-E2-related factor 2) signaling. We show that tHSCs co-culture induced significant Nrf2 signaling activation in mDCs. The latter was evidenced by Nrf2-Keap1 disassociation, Nrf2 protein stabilization, accumulation and nuclear translocation. Expression of Nrf2-dependent genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), were detected in tHSCs-co-cultured mDCs. Importantly tHSCs-induced DIgR2 expression was blocked by Nrf2 shRNA or knockout (KO, by CRISPR/Cas9 method). Conversely, forced activation of Nrf2, by Keap1 shRNA or the Nrf2 activators (3H-1,2-dithiole-3-thione and MIND4-17), induced significant DIgR2 expression. tHSCs stimulation induced reactive oxygen species (ROS) production in mDCs. Conversely, ROS scavengers inhibited tHSCs-induced ROS production, Nrf2 activation and DIgR2 expression in mDCs. Significantly, tHSCs inhibited production of multiple cytokines (CD80, CD86 and IL-12) in mDCs, reversed by Nrf2 depletion. Moreover, Nrf2 shRNA or KO attenuated splenic T cell inhibition by tHSCs-stimulated mDCs. Together, we conclude that Nrf2 activation mediates tHSCs-induced DIgR2 expression in mDCs.

Prognostic value of high stanniocalcin 2 expression in solid cancers: A meta-analysis.

BACKGROUND: Several studies have explored the prognostic value of stanniocalcin 2 (STC2) in various cancers, but obtained inconsistent results. Therefore, this meta-analysis was performed to determine the prognostic and clinicopathologic significance of STC2 in various cancers. METHODS: Eligible studies were identified by searching the online databases PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure up to March 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) and were calculated to clarify the correlation between STC2 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between STC2 with clinicopathologic characteristics of patients with cancer. RESULTS: A total of 16 eligible studies with 4074 patients with cancer were included in our meta-analysis. The results showed that high STC2 expression can predict poor overall survival (OS) for cancer (HR = 1.48, 95% CI: 1.15-1.90, P = .002). Subgroup analysis found that high STC2 expression was associated with worse OS in Asian (HR = 1.85, 95% CI: 1.35-2.55), the reported directly from articles group (HR = 1.39, 95% CI: 1.05-1.84), survival curves group (HR = 1.93, 95% CI: 1.36-2.74), and gastric cancer (HR = 1.43, 95% CI: 1.04-1.95). Furthermore, high STC2 expression was significantly related to advanced T stage (OR = 1.83, 95% CI: 1.17-2.86, P = .008), lymph node metastasis (OR = 2.29, 95% CI: 1.51-3.45, P < .001), lymphatic invasion (OR = 2.15, 95% CI: 1.53-3.02, P < .001), venous invasion (OR = 1.97, 95% CI: 1.30-2.99, P = .001), and more advanced clinical stage (OR = 2.36, 95% CI: 1.74-3.19, P < .001) CONCLUSION:: Elevated expression of STC2 suggested a poor prognosis in patients with cancer and may serve as a new tumor marker to monitor cancer development and progression.

Prognostic and clinicopathological significance of S100A14 expression in cancer patients: A meta-analysis.

BACKGROUND: The prognostic significance of S100A14 for survival of cancer patients remains controversial. Therefore, we conducted this meta-analysis to explore the association between S100A14 expression and cancer prognosis. METHOD: Eligible studies were identified by searching the online databases Pubmed and EMBASE up to August 2018. Odds ratios (ORs) with 95% confidence intervals (CIs) severed as the summarized statistics for clinicopathological assessments and hazard ratios (HRs) with 95% CIs were calculated to clarify the correlation between S100A14 expression and prognosis of different cancers. RESULTS: A total of 11 studies with 1651 cancer patients were enrolled. The results indicated that S100A14 expression was not significantly associated with overall survival (OS) in total various cancers (HR = 1.54, 95% CI:0.89-2.67, P = .121). Further subgroup analysis stratified by tumor type showed that elevated S100A14 expression was associated with poor OS in breast cancer (HR = 3.66, 95% CI: 1.75-7.62, P < .001) and in ovarian cancer patients (HR = 3.78, 95%CI: 1.63-8.73, P = .002). Interestingly, high S100A14 expression was correlated with poor tumor differentiation (OR = 2.51, 95% CI: 1.52-4.13, P < .001). However, there were no significant correlations between S100A14 expression and other clinicopathologic characteristics. Begg funnel plot and Egger test showed that no publication bias was detected. CONCLUSIONS: Our meta-analysis suggests that S100A14 overexpression might be a predictive biomarker for poor prognosis in patients with breast cancer and ovarian cancer. Large-scale studies are required to confirm these results.

The Effect of Zhongyong Thinking on Remote Association Thinking: An EEG Study.

The Doctrine of the Mean (zhongyong) introduced by Confucianism is not only an aspect of faith, but also a way of thinking for Chinese individuals. Zhongyong includes two thinking forms: eclectic thinking (ET; i.e., "neither-A-nor-B") and integrated thinking (IT; i.e., "both-A-and-B"). Given the inclination of Asian individuals toward situational cognition, this study used questions about situations familiar to Chinese undergraduates to activate either ET or IT. This was done to investigate the effects of the two divergent thinking forms of zhongyong on performance levels on the Remote Associates Test (RAT). Both behavioral and EEG results found that participants in the IT condition demonstrated higher RAT scores than those in the ET condition. The conclusion was that the RAT and priming tasks shared the same neural mechanism. This meant that the priming tasks of IT allowed participants to enter a state of creative preparation in advance, further affecting resolution of the RAT.

Expression and clinical significance of Vimentin and E-cadherin in breast cancer tissues / 中国肿瘤生物治疗杂志

@#Objective: To study the expression and clinical significance of Vimentin and E-cadherin in human breast cancer tissues. Methods: : The clinical data of 56 cases of breast cancer patients, who underwent radical mastectomy in Chaohu Hospital Affiliated to Anhui Medical University from January 2014 to January 2016, were retrospectively analyzed. The protein and mRNAexpressions of Vimentin and E-cadherin in breast cancer tissues were detected by immunohistochemistry and qPCR, respectively; and the relationship between the expression of Vimentin and E-cadherin in breast cancer tissues and the clinicopathological characteristics was analyzed. Logistic multivariate regression was used to analyze the independent factors affecting the protein expressions of Vimentin and E-cadherin. Spearman was used to analyze the correlation between Vimentin and E-cadherin. Kaplan-Meier was used to analyze the relationship between protein expressions of Vimentin, E-cadherin and prognosis. ROC curve was used to analyze the diagnostic value of Vimentin and E-cadherin on prognosis. Results: The rates of breast cancer tissues with high positive expression of Vimentin and E-cadherin were 76.79% and 19.64%, respectively.Among them, 47 cases (47/56, 83.93%) of breast cancer tissues showed significantly higher Vimentin mRNA expression than adjacent tissues (P<0.05), and 46 cases (46/56, 82.14%) of breast cancer tissues showed significantly lower Ecadherin mRNA expression than adjacent tissues (P<0.05). Vimentin protein expression was associated with tumor size, lymph node metastasis, vascular invasion, histological grade, clinical stage, molecular typing, Ki67+, ER-, PR- and HER2- expression (P<0.05). And E-cadherin protein expression was associated with lymph node metastasis, vascular invasion, histological grade, clinical stage, molecular typing, Ki67+, ER-, PR- and HER2- expression (P<0.05). Tumor size, lymph node metastasis, vascular invasion, histological grading, clinical staging, molecular typing, Ki67+, ER-, PR- and HER2- expression were all independent factors affecting the expression of Vimentin and E-cadherin (P<0.05). There was a negative correlation between Vimentin and E-cadherin expression (P<0.05). The 3-year survival rate of patients with high expression of Vimentin protein was 67.44%, while that of patients with low expression of E-cadherin protein was 68.89%. Conclusion: The high expression of Vimentin and low expression of E-cadherin in breast cancer tissues may be related to the occurrence, development, invasion and metastasis of breast cancer. It can be used as a reliable indicator of clinical diagnosis and prognosis.

Studies of acute and subchronic systemic toxicity associated with a copper/low-density polyethylene nanocomposite intrauterine device.

INTRODUCTION: The physiologic safety of devices and materials intended for clinical implantation should be evaluated. This study, a logical extension of our previous work, aimed to investigate the safety of a novel contraceptive device, the copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD), through studies of its potential toxicity after acute and subchronic administration in mice and rats. METHODS: For the acute toxicity study, single 50 mL/kg doses of nano-Cu/LDPE IUD extracts were administered to mice via intravenous or intraperitoneal injection. General behavioral adverse effects, mortality, and body weights were evaluated for up to 72 hours. In the 13-week subchronic toxicity study, the nano-Cu/LDPE composite with 10-fold higher than the standard clinical dose was implanted subcutaneously into the dorsal skin of Wistar rats. The control group underwent a sham procedure without material insertion. RESULTS: During all acute study observation times, the biologic reactions of the mice in the nano-Cu/LDPE group did not differ from those observed in the control group. The groups did not differ statistically in terms of body weight gain, and no macroscopic changes were observed in any organs. In the subchronic study, no clinical signs of toxicity or mortality were observed in either the nano-Cu/LDPE or control group during the 13-week period. The nano-Cu/LDPE composite did not cause any alterations in body weight, food consumption, hematologic and biochemical parameters, or organ weight relative to the control for any observed sample group. Histopathologic examinations of the organs revealed normal architecture, indicating that the inserted material did not cause morphologic disturbances in the rats. CONCLUSION: Overall, the results indicate that the nano-Cu/LDPE IUD did not induce systemic toxicity under experimental conditions of the recommended standard practices, suggesting that the novel material IUD is safe and feasible for future contraceptive applications.

Association between IL-17A G197A polymorphism and gastric cancer risk: an updated meta-analysis based on 6,624 cases and 7,631 controls.

PURPOSE: Previous studies investigating the association between interleukin-17A (IL-17A) G197A polymorphism and gastric cancer risk have provided inconsistent results. We, therefore, conducted this meta-analysis to clarify the association between IL-17A G197A polymorphism and gastric cancer risk. METHODS: We searched PubMed, Excerpta Medica Database, and CNKI databases to identify relevant studies up to June 10, 2017. A total of 16 case-control studies including 6,624 cases and 7,631 controls were identified. RESULTS: Overall, significant associations between IL-17A G197A polymorphism and gastric cancer risk were observed (A vs G: OR =1.24, 95% CI =1.14-1.36; AA vs GG: OR =1.63, 95% CI =1.35-1.96; GA vs GG: OR =1.12, 95% CI =1.01-1.25; AA+GA vs GG: OR =1.23, 95% CI =1.11-1.35; AA vs GA+GG: OR =1.54, 95% CI =1.27-1.87). Similar associations were also observed in Asian population (A vs G: OR =1.25, 95% CI =1.15-1.37; AA vs GG: OR =1.62, 95% CI =1.33-1.97; GA vs GG: OR =1.16, 95% CI =1.07-1.25; AA+GA vs GG: OR =1.24, 95% CI =1.15-1.33; AA vs GA+GG: OR =1.51, 95% CI =1.23-1.85), in Caucasian population (AA vs GA+GG: OR =2.19, 95% CI =1.40-3.44), and in the hospital-based controls' subgroup (A vs G: OR =1.30, 95% CI =1.17-1.45; AA vs GG: OR =1.81, 95% CI =1.46-2.25; AA+GA vs GG: OR =1.27, 95% CI =1.12-1.43; AA vs GA+GG: OR =1.71, 95% CI =1.34-2.18). CONCLUSIONS: The current meta-analysis suggests that IL-17A G197A polymorphism might enhance gastric cancer risk.

DlgR2 knockdown boosts dendritic cell activity and inhibits hepatocellular carcinoma tumor in-situ growth.

Tumor-specific hepatic stellate cells (tHSCs) positively participate in human hepatocellular carcinoma (HCC) tumorigenesis and progression. Our previous studies have shown that tHSCs co-culture with dendritic cells (DCs) induced DIgR2 (dendritic cell-derived immunoglobulin receptor 2) expression. The latter is a member of IgSF inhibitory receptor suppressing DCs-initiated antigen-specific T-cell responses. In the current study, we show that hepatic artery injection of DlgR2 siRNA significantly inhibited in-situ HCC xenograft growth in rat livers. Further, 5-FU-medied inhibition of in-situ HCC growth was dramatically sensitized with DlgR2 silence. DlgR2 siRNA injection indeed downregulated DlgR2 in ex-vivo cultured tumor-derived DCs (tDCs). More importantly, tDCs activity was boosted following DlgR2 siRNA. These cells presented with upregulated CD80, CD86 and MHC-II. Production of interleukin-12 and tumor necrosis factor-α was also increased in the DlgR2-silenced tDCs. We propose that DlgR2 knockdown likely boosts the activity of tumor-associated DCs, and inhibits growth of in-situ HCC xenografts.