TGFß-induced EN1 promotes tumor budding of adenoid cystic carcinoma in patient-derived organoid model.

Adenoid cystic carcinoma (ACC) and basal cell adenoma (BCA) share many histological characteristics and often need a differential diagnosis in clinical pathology. Recently, we found homeobox protein engrailed-1 (EN1) was a potential diagnostic marker for ACC in an organoids library of salivary gland tumors (SGTs). Here we aim to confirm EN1 as a differential diagnostic marker for ACC, and further investigate the regulatory mechanism and biological function of EN1 in tumor progression. The transcriptional analysis, quantitative polymerase chain reaction, Western blot and immunohistochemistry staining were performed and revealed that EN1 was specifically and highly expressed in ACC, and accurately differentiated ACC from BCA. Furthermore, TGFß signaling pathway was found associated with ACC, and the regulation of EN1 through TGFß was detected in the human ACC cell lines and patient-derived organoids (PDOs). TGFß-induced EN1 was important in promoting tumor budding in the PDOs model. Interestingly, a high level of EN1 and TGFß1 in the budding tips was observed in ACC clinical samples, and the expression of EN1 and TGFß1 in ACC was significantly associated with the clinical stage. In summary, our study verified EN1 is a good diagnostic marker to differentiate ACC from BCA. TGFß-induced EN1 facilitates the tumor budding of ACC, which might be an important mechanism related to the malignant phenotype of ACC.

Predictors of short-term survival in cardiac valvular surgery patients with intra-aortic balloon pump implantation.

BACKGROUND: Intro-aortic balloon pump (IABP) is widely used in cardiac surgery patients nowadays. This study aimed to analyze the predictor of short-term survival in cardiac valvular surgery patients with intra-aortic balloon pump implantation. METHODS: This was a retrospective study and a total of 102 cardiac valvular surgery patients who received intra-aortic balloon pump implantation were consecutively included. We retrospectively collected the baseline characteristics and short-term outcomes. Baseline characteristics were compared between survivors with non-survivors, and logistic regression was performed to identify predictors for short-term mortality. RESULTS: Among all the patients, there were 71 (69.6%) patients successfully weaned from IABP and survived to discharge, the other 31 (30.4%) patients failed to wean from IABP and died within the first 30 days after surgery. When compared with non-survivors, survivors had a higher proportion of males (62% vs 32.3%, p = 0.006), a lower rate of Atrial fibrillation (38% vs 62%, p < 0.03). After IABP implantation, vasoactive drug use was significantly lower in survivors compared with non-survivors, and survivors showed significant improvements in cardiac function and urine volume. Univariate and multivariate logistic regression analysis indicated that atrial fibrillation and combined use of continuous renal replacement therapy (CRRT) were significant independent predictors for short-term mortality. CONCLUSION: Timely implantation of IABP can improve patients' cardiac and renal function and reduce the dosage of vasoactive drugs. Atrial fibrillation and combined use of CRRT are independent predictors for short-term mortality in patients who underwent cardiac valvular surgery with IABP implantation.

An organoid library of salivary gland tumors reveals subtype-specific characteristics and biomarkers.

BACKGROUND: Salivary gland tumors (SGTs) include a large group of rare neoplasms in the head and neck region, and the heterogeneous and overlapping features among the subtypes frequently make diagnostic difficulties. There is an urgent need to understand the cellular mechanisms underlying the heterogeneity and overlap among the subtypes, and explore the subtype-specific diagnostic biomarkers. METHODS: The tumor tissue and the adjacent normal tissue from the 6 most common types of SGTs were processed for organoid culture which only maintained tumor epithelial cells. Organoids were histologically evaluated based on phenotype markers, followed by transcriptional profiling using RNA-sequencing. The transcriptomic similarities and differences among the subtypes were analyzed by subtype consensus clustering and hierarchical clustering. Furthermore, by comparative transcriptional analysis for these 6 types of SGTs and the matched organoids, the potential diagnostic biomarkers from tumor epithelium were identified, in which two selected biomarkers were evaluated by qPCR and confirmed by immunohistochemistry staining using a tissue microarray. RESULTS: We generated a biobank of patient-derived organoids (PDOs) with 6 subtypes of SGTs, including 21 benign and 24 malignant SGTs. The PDOs recapitulated the morphological and transcriptional characteristics of the parental tumors. The overlap in the cell types and the heterogenous growth patterns were observed in the different subtypes of organoids. Comparing the bulk tissues, the cluster analysis of the PDOs remarkably revealed the epithelial characteristics, and visualized the intrinsic relationship among these subtypes. Finally, the exclusive biomarkers for the 6 most common types of SGTs were uncovered by comparative analysis, and PTP4A1 was demonstrated as a useful diagnostic biomarker for mucoepidermoid carcinoma. CONCLUSIONS: We established the first organoid biobank with multiple subtypes of SGTs. PDOs of SGTs recapitulate the morphological and transcriptional characteristics of the original tumors, which uncovers subtype-specific biomarkers and reveals the molecular distance among the subtype of SGTs.

Tandem mass tag-based proteomics analysis reveals the effects of Guri Gumu-13 pill on drug-induced liver injury.

The incidence of drug-induced liver injury (DILI) is second only to viral hepatitis and steatohepatitis in China, and DILI has become a serious public health problem that cannot be ignored. Guri Gumu-13 pill (GRGM) is a traditional Chinese medicine (TCM), which has a protective effect on liver diseases. However, the underlying therapeutic mechanisms of GRGM for DILI are still vague. In this study, the protective effect of GRGM on acetaminophen (APAP)-induced DILI was investigated based on the proteomics clues. The effects of GRGM on APAP-induced DILI in rats were studied using tandem mass tag (TMT)-based quantitative proteomics technology. Besides, western blotting was exerted to verify related proteins. Using the TMT-based quantitative proteomics approach, 237 proteins were identified as regulated in APAP-induced DILI and 58 proteins were regulated by GRGM. The 17 overlapping differentially expressed proteins (DEPs) were identified, and 7 proteins were inversely regulated. Enrichment analysis of KEGG indicated that metabolic pathways, linoleic acid metabolism, and retinol metabolism might be affected in DILI. Next, Cyp2c11, Aldh1a1, and Fads2 were verified with molecular biotechnology. GRGM exerts therapeutic effects through multi-pathways regulation in the treatment of DILI. This work may provide proteomics clues for the continuation of research on DILI treatment with GRGM.

A sensitive electrochemical bisphenol A sensor based on molecularly imprinted polydopamine-coated Fe3O4 microspheres.

Bisphenol A (BPA) interferes with the reproduction and endocrine system of humans and wild animals. For the detection of BPA, a sensitive and rapid detection method was established. BPA was imprinted on the surface of Fe3O4 nanoparticles through dopamine self-polymerization. After the removal of BPA, molecularly imprinted microspheres with BPA recognition cavity were formed. The electrochemical impedance response increased with BPA embedded in the molecular imprinting layer. The electrochemical signal was proportional to the concentration of BPA with a linear range from 1 × 10-11 to 1 × 10-3 M and a detection limit of 5.78 × 10-12 M. The proposed biosensor was used to detect the BPA in vegetable oil indicating a promising application in food-field monitoring.

Metal-organic frameworks with peroxidase-like activity for efficient removal of aflatoxin B1.

Aflatoxin B1 (AFB1), a naturally produced toxin existing in major food crops, is highly toxic and carcinogenic to human and animals. In this study, a reusable material, Pd@PCN-222 with great adsorption performance and peroxidase-like activity was synthesized for the removal of AFB1. Pd@PCN-222 exhibited great adsorption performance owing to hierarchical porous structure. Pd@PCN-222 also could catalyze the AFB1 in the presence of H2O2 due to the Fe-tetrakis (4-carboxyphenyl) porphyrin and Pd as effective peroxidase active site, which improved the removal efficiency of AFB1. Pd@PCN-222 was applied for the removal of AFB1 with a removal rate of 96.52% in 2 h. Owing to the advantages of high removal efficiency and reusability, Pd@PCN-222 had great application potential in AFB1 removal.

ZrO2/CeO2/polyacrylic acid nanocomposites with alkaline phosphatase-like activity for sensing.

In the present work, we synthesized ZrO2/CeO2/polyacrylic acid (PAA) nanocomposites (nanozyme) with phosphatase-like activity. ZrO2 evenly distributed in CeO2 nanorods considered as lewis acids to enhance the phosphatase-like activity of CeO2 nanorods. Furthermore, PAA was used to coat ZrO2/CeO2/ nanorods and improve the dispersion, stability and robustness. The ZrO2/CeO2/PAA nanocomposites had 100% enhanced phosphatase-like activity compared with CeO2 nanorods and excellent adaptability in a wide pH range from 4.0 to 12.0. ZrO2/CeO2/PAA nanocomposites could hydrolyze methyl parathion (MP) to p-nitrophenol (p-NP) with bright yellow color for colorimetric detection. The developed colorimetric detection system showed a linear response from 7.60 × 10-11-7.60 × 10-8 M with a detection limit of 0.021 nM and was successfully applied for the determination of MP in corn samples.