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Icaritin, a small molecule currently being investigated in phase III clinical trials in China (NCT03236636 and NCT03236649) for treatment of advanced hepatocellular carcinoma (HCC), is a prenylflavonoid derivative obtained from the Epimedium genus. Previously, it was found that Icaritin decreased the expression of PD‐L1, but its direct molecular targets and the underlying mechanisms have not been identified. In this study, we report the identification of IKK‐α as the protein target of Icaritin by biotin‐based affinity binding assay. The further mutagenesis assay has provided evidence that C46 and C178 in IKK‐α were essential amino acids for Icaritin binding to IKK‐α, revealing the binding sites of Icaritin to IKK‐α for the first time. Functionally, Icaritin inhibited the NF‐κB signalling pathway by blocking IKK complex formation, which led to decreased nuclear translocation of NF‐κB p65, and subsequent downregulation of PD‐L1 expression in a dose–dependent manner. More importantly, PD‐L1‐positive patients exhibited longer overall survival upon Icaritin therapy. Finally, Icaritin in combination with checkpoints antibodies, such as α‐PD‐1, has demonstrated much better efficacy than any single therapy in animal models. This is the first report that anticancer effects of Icaritin are mediated, at least in part, by impairing functions of IKK‐α. [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) was a devastating contagion of swine that could cause 100% mortality of infected animals. The outbreak of ASFV in China in 2019 had caused great economic losses in the pig industry. Therefore, simple and rapid diagnostic technology was highly needed for ASFV prevention. However, most of the current detection methods, such as protein-based technology and fluorescent quantitative polymerase chain reaction (PCR) technology, required complicated and expensive instruments, as well as professional technicians. Isothermal amplification technology did not require complex instruments but needed expensive reagents, which also limited its widespread usage, especially for laboratories with limited resources. In order to meet the needs of laboratories with limited resources to detect ASFV, a new low-cost lateral flow nucleic acid assay (LFNAA) was developed by combining the traditional PCR technique and the colloid gold lateral flow technique. LFNAA could observe the test results with naked eyes. A unique tailed-primer was designed to avoid the need for complicated antigen-labeling and expensive antibody, thus the PCR could produce a double-stranded DNA product with a single-strand oligonucleotide tail at one end, then the PCR product could hybridize with a colloidal gold-labeled oligonucleotide capture probe. In the presence of the positive product, the biotin on the other end of the product would bind to the streptavidin pre-immobilized on the test line of the strip and formed a sandwich structure of "streptavidin - biotin – PCR product - oligonucleotide tail - gold-labeled capture probe", so the test line of the strip would show a red color to indicate the positive result. On the other hand, if there was no positive product in the sample, the test line would show no red color. So, the detection result could be judged by observing whether the test line has a red color. Besides, the excess gold-labeled capture probe would hybridize with the control probe on the control line, showing a red color as an assay valid control. As a verification of the assay specificity, the LFNAA system was used to identify the presence of ASFV in actual samples of CSFV, PRRSV, PCV1 and PCV2, PRV, PPV. The result showed that the LFNAA could specifically detect ASFV, which was consistent with the fluorescent quantitative PCR. And the sensitivity of the LFNAA was the same with the agarose gel electrophoresis, both could reach to 10³ copies/μL. Therefore, the LFNAA can meet the requirements of rapid and sensitive ASFV identification with only a common PCR instrument. Its rapidity (<2 h), low-cost, and simple-operation are greatly suitable for the non-professionals in the laboratories with limited resources. LFNAA avoids the usage of the expensive antibody and the complicated process of AuNP-antibody conjugation. Furthermore, due to the generality of the technique, the more simple isothermal amplification technology is expected to replace the current PCR method to make it more convenient and simple, and realizes faster and easier field testing in food safety testing and medical diagnosis. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present investigation was to explore the expression and significance of Gal-3 and MUC1 in colorectal cancer tissue and tissue adjacent to carcinoma. Methods: In this study we collected colorectal cancer tissues and the tissues adjacent to carcinoma from 45 cases from the Colorectal Cancer Surgery Department of Zhengzhou People's Hospital from December of 2009 to June of 2010. At the same time, this study also collected nontumor tissues adjacent to carcinoma from 20 cases as the control group. The expression of Gal-3 and MUC1 of these tissues was detected by using immunohistochemistry streptavidin-peroxidase method, and the correlation between colorectal cancer and expression of Gal-3 and MUC1 was analyzed. Results: The positive expression rates of Gal-3 in the tissues adjacent to carcinoma and colorectal cancer were 15.0% and 73.3%, respectively. The positive expression rate of Gal-3 in colorectal cancer was significantly higher than that in the tissue adjacent to carcinoma. The positive expression rate of Gal-3 of the patients without lymph node metastasis was 61.5% (16/26). The positive expression rate of Gal-3 in the patients with lymph node metastasis was 89.5% (17/19), and the difference was statistically significant (P=0.0363). The positive expression rates of MUC1 in the tissues adjacent to carcinoma and in colorectal cancer tissues were 0.0% and 54.5%, respectively. The positive expression rate of MUC1 in colorectal cancer tissues was significantly higher than that in the normal tissues adjacent to carcinoma (P<0.05); the positive expression rate of MUC1 in the patients without lymph node metastasis was 34.6% (9/26). The positive expression rate of MUC1 in the patients with lymph node metastasis was 84.2% (16/19), and the expression difference was statistically significant (P=0.0009). Conclusion: The expression of Gal-3 and MUC1 was significantly higher than that in the nontumor tissue adjacent to carcinoma. There was a correlation between Gal-3 and MUC1 expression and lymphatic metastasis. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to present 12 additional cases of glandular odontogenic cyst (GOC) in the Department of Oral Pathology, School of Stomatology, Wuhan University, People's Republic of China, and to investigate their immunohistochemical cytokeratins (CKs) expression in the epithelial components. Methods: A total of 12 GOCs were reviewed clinically and radiographically, and immunohistologic CKs AE1, 7, 8/18, 10/13, 14, 16, 19 and 20 were performed by using a standard biotin-streptavidin immunoperoxidase technique on paraffin sections. Results: The present series showed that eight occurred in males and four in females. The mean age was 37.6 years with a peak incidence occurring in the third decades (six of 12). Mandibles were more affected than maxillas (7:5), especially anterior mandible (four of seven). Radiographically, ratio multilocular to unilocular radiolucencies was 5:7 usually with well-defined borders. Histologically, cystic spaces were lined by non-keratinized stratified epithelia containing focal plaque-like or whirlpool-like thickenings; surface epithelial layer-containing eosinophilic cuboidal cells; mucous cells; and mucin pools of microcystic areas in the epithelium. Immunohistochemistry showed that epithelium of GOCs stained for CKs AE1, 7, 8/18, 10/13, 14 and 19 with slight changes in their patterns, and no reaction to CKs 16 and 20. Conclusions: Most clinical and histologic features in this study were analogous to those reported west population, although with slight difference between them. Histologically, the morphology of the epithelium strongly suggested an odontogenic origin, and CKs expression of GOC was similar to that of odontogenic epithelium, suggesting histochemically that GOC might be derived from odontogenic epithelium. [ABSTRACT FROM AUTHOR]

Investigates cathepsin D (CD) expression in patients with lung tumor in China. Use of streptavidin-peroxidase conjugated method; Distribution of CD in the tumor cell cytoplasm; Relation of immunohistochemical staining frequency on clinical and histopathologic parameters.