Knockdown of membrane-bound complement regulatory proteins suppresses colon cancer growth in mice through inducing tumor cell apoptosis.

CD46, CD55 and CD59 are membrane-bound complement regulatory proteins (mCRPs) and highly expressed in many tumor tissues. Our analysis by RNA sequencing and qRT-PCR revealed that the expression of mCRPs was significantly elevated in cancer tissues of 15 patients with colon cancer. To further investigate the role of mCRPs in the development of colon cancer, we suppressed the expression of mCRPs by CD46-shRNA, CD55-shRNA and CD59-shRNA in colon cancer cell lines, SW620 and HT-29 cells. The results indicated that CD46-shRNA, CD55-shRNA and CD59-shRNA effectively reduced the expression of mCRPs, accompanied with the increased LDH release and the percentage of Annexin V + 7-AAD- early phase of apoptotic cells. The similar cytotoxic effects were also observed in the cells treated with CD46 neutralizing antibody (aCD46), associated with the increased C5b-9 deposition, cleaved caspase-3 and Bax expression in the treated cells. The cytotoxic effects by mCRPs knock-down were potentiated in the cells co-treated with doxorubicin (Dox). In addition, STAT3, STAT6, and p38 MAPK inhibitors, including C188-9, AS1517499 and SB203580 effectively reduced the expression of CD46 in the treated colon cells, associated with increased cell apoptosis and LDH release. Further study with mouse model revealed that mCRPs knockdown by mCRPs-shRNA significantly reduced colon cancer growth, associated with increased expression of Bax, cleaved caspase-3 and C5b-9 deposition, but reduced expression of Bcl-2, IL-6 and IL-1beta in tumor tissues of nude mice transplanted with SW620 cells. Thereby, mCRPs expression in human colon cancer cells were upregulated by STAT3/STAT6/p38 MAPK signaling and mCRPs knockdown reduced colon cancer growth in mice through inducing tumor cell apoptosis.

Appraising the Accuracy of Ischaemia-Modified Albumin in Diagnosing Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ischaemia-modified albumin (IMA) is a new, sensitive marker of ischaemic diseases that has been approved for diagnosing myocardial ischaemia. However, the accuracy of IMA in the diagnosis of stroke remains to be clarified. The study's purpose is to assess the potential role of IMA as a diagnostic indicator in stroke. METHODS: We carried out a systematic search in Medline, the Cochrane Library, Embase, Scopus, Science Direct, ISI Web of Knowledge, and the reference lists of relevant articles from the databases' inception to September 1, 2019. Studies that appraised the diagnostic accuracy of IMA for acute stroke patients were included in our study. Two reviewers extracted data independently and assessed the quality of the retrieved studies, and disagreements were resolved through discussions with a third reviewer. Sensitivities and specificities were pooled by using bivariate diagnostic meta-analysis. We calculated I2 to test the heterogeneity and used meta-regression to identify potential sources of heterogeneity. This systematic review and meta-analysis is registered in international prospective register of systematic reviews (number CRD42020149174). RESULTS: Six studies with 605 patients were eligible for inclusion. Our meta-analysis produced the following outcomes: the mean sensitivity of IMA in diagnosing acute stroke was 0.80 (95% confidence interval [CI], 0.69-0.88) and the specificity was 0.80 (95% CI, 0.71-0.87). The area under the receiver operating characteristic curve was 0.86 (95% CI, 0.83-0.89), and the pooled diagnostic odds ratio was 16 (95% CI, 8-33). There was obvious heterogeneity between studies (I2 = 78%, 95% CI, 53-100). Sensitivity analysis and meta-regression could account for the heterogeneity. CONCLUSION: IMA is a helpful marker for consideration in the early diagnosis of stroke.

High-quantum-efficiency ultraviolet solar-blind AlGaN photocathode detector with a sharp spectral sensitivity threshold at 300 nm.

At present, most of the existing practical ultraviolet (UV) solar-blind detectors are based on Te-Cs photocathode image intensifiers. However, limited by their photoemission characteristics, it is difficult for the Te-Cs-based photocathodes to achieve both high quantum efficiency in the application band and high cutoff ratio in the non-applied band simultaneously. In this paper, a high-quantum-efficiency UV solar-blind detector based on AlGaN photocathodes with a sharp spectral sensitivity threshold at 300 nm is reported. The proposed AlGaN photocathode has extremely high quantum efficiency (i.e., 20%) in the 210-275 nm band, while the efficiency curve steeply reduces to 2% at 300 nm, showing obviously superior performance than the existing Te-Cs photocathodes.