IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps.

The nasal polyps (NPs) microenvironment comprises multiple cell types, including mesenchymal stromal cells (MSCs). Insulin-like growth factor binding protein 2 (IGFBP2) plays crucial roles in cell proliferation, differentiation and more. However, the role of NPs-derived MSCs (PO-MSCs) and IGFBP2 in NPs pathogenesis remains poorly defined. Herein, primary human nasal epithelial cells (pHNECs) and MSCs were extracted and cultured. Extracellular vesicles (EVs) and soluble proteins were isolated to investigate the role of PO-MSCs on epithelial-mesenchymal transition (EMT) and epithelial barrier function in NPs. Our data showed that IGFBP2, but not EVs from PO-MSCs (PO-MSCs-EVs), exhibited a crucial role in EMT and barrier destruction. Moreover, focal adhesion kinase (FAK) signaling pathway is necessary for IGFBP2 to exert its functions in human and mice nasal epithelial mucosa. Altogether, these findings may improve the current understanding of the role of PO-MSCs in NPs microenvironment and ultimately contribute to the prevention and treatment of NPs.

Role of Cell-Cell Junctions in Oesophageal Squamous Cell Carcinoma.

Cell-cell junctions comprise various structures, including adherens junctions, tight junctions, desmosomes, and gap junctions. They link cells to each other in tissues and regulate tissue homeostasis in critical cellular processes. Recent advances in cell-cell junction research have led to critical discoveries. Cell-cell adhesion components are important for the invasion and metastasis of tumour cells, which are not only related to cell-cell adhesion changes, but they are also involved in critical molecular signal pathways. They are of great significance, especially given that relevant molecular mechanisms are being discovered, there are an increasing number of emerging biomarkers, targeted therapies are becoming a future therapeutic concern, and there is an increased number of therapeutic agents undergoing clinical trials. Oesophageal squamous cell carcinoma (ESCC), the most common histological subtype of oesophageal cancer, is one of the most common cancers to affect epithelial tissue. ESCC progression is accompanied by the abnormal expression or localisation of components at cell-cell junctions. This review will discuss the recent scientific developments related to the molecules at cell-cell junctions and their role in ESCC to offer valuable insights for readers, provide a global view of the relationships between position, construction, and function, and give a reference for future mechanistic studies, diagnoses, and therapeutic developments.

Predicting the Risk of Diabetic Foot Ulcers From Diabetics With Dysmetabolism: A Retrospective Clinical Trial.

Background: Diabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2D) often leads to amputation. Early intervention to prevent DFU is urgently necessary. So far, there have been no studies on predictive models associated with DFU risk factors. Our study aimed to quantify the predictive risk value of DFU, promote health education, and further develop behavioral interventions to reduce the incidence of DFU. Methods: Data from 973 consecutive patients with T2D was collected from two hospitals. Patients from the Guangxi Medical University First Affiliated Hospital formed the training cohort (n = 853), and those from the Wuming Hospital of Guangxi Medical University formed the validation cohort (n = 120). Independent variable grouping analysis and multivariate logistic regression analysis were used to determine the risk factors of DFUs. The prediction model was established according to the related risk factors. In addition, the accuracy of the model was evaluated by specificity, sensitivity, predictive value, and predictive likelihood ratio. Results: In total, 369 of the 853 patients (43.3%) and 60 of the 120 (50.0%) were diagnosed with DFUs in the two hospitals. The factors associated with DFU were old age, male gender, lower body mass index (BMI), longer duration of diabetes, history of foot disease, cardiac insufficiency, no use of oral hypoglycemic agent (OHA), high white blood cell count, high platelet count, low hemoglobin level, low lymphocyte absolute value, and high postprandial blood glucose. After incorporating these 12 factors, the nomogram drawn achieved good concordance indexes of 0.89 [95% confidence interval (CI): 0.87 to 0.91] in the training cohort and 0.84 (95% CI: 0.77 to 0.91) in the validation cohort in predicting DFUs and had well-fitted calibration curves. Patients who had a nomogram score of ≥180 were considered to have a low risk of DFU, whereas those having ≥180 were at high risk. Conclusions: A nomogram was constructed by combining 12 identified risk factors of DFU. These 12 risk factors are easily available in hospitalized patients, so the prediction of DFU in hospitalized patients with T2D has potential clinical significance. The model provides a reliable prediction of the risk of DFU in patients with T2D.

Inhibitory mechanism of angiotensin-converting enzyme inhibitory peptides from black tea.

The aim of this work is to discover the inhibitory mechanism of tea peptides and to analyse the affinities between the peptides and the angiotensin-converting enzyme (ACE) as well as the stability of the complexes using in vitro and in silico methods. Four peptide sequences identified from tea, namely peptides I, II, III, and IV, were used to examine ACE inhibition and kinetics. The half maximal inhibitory concentration (IC50) values of the four peptides were (210.03±18.29), (178.91±5.18), (196.31±2.87), and (121.11±3.38) µmol/L, respectively. The results of Lineweaver-Burk plots showed that peptides I, II, and IV inhibited ACE activity in an uncompetitive manner, which requires the presence of substrate. Peptide III inhibited ACE in a non-competitive manner, for which the presence of substrate is not necessary. The docking simulations showed that the four peptides did not bind to the active sites of ACE, indicating that the four peptides are allosteric inhibitors. The binding free energies calculated from molecular dynamic (MD) simulation were -72.47, -42.20, -52.10, and -67.14 kcal/mol (1 kcal=4.186 kJ), respectively. The lower IC50 value of peptide IV may be attributed to its stability when docking with ACE and changes in the flexibility and unfolding of ACE. These four bioactive peptides with ACE inhibitory ability can be incorporated into novel functional ingredients of black tea.

Rapid Identification of Different Grades of Huangshan Maofeng Tea Using Ultraviolet Spectrum and Color Difference.

Tea is an important beverage in humans' daily lives. For a long time, tea grade identification relied on sensory evaluation, which requires professional knowledge, so is difficult and troublesome for laypersons. Tea chemical component detection usually involves a series of procedures and multiple steps to obtain the final results. As such, a simple, rapid, and reliable method to judge the quality of tea is needed. Here, we propose a quick method that combines ultraviolet (UV) spectra and color difference to classify tea. The operations are simple and do not involve complex pretreatment. Each method requires only a few seconds for sample detection. In this study, famous Chinese green tea, Huangshan Maofeng, was selected. The traditional detection results of tea chemical components could not be used to directly determine tea grade. Then, digital instrument methods, UV spectrometry and colorimetry, were applied. The principal component analysis (PCA) plots of the single and combined signals of these two instruments showed that samples could be arranged according to grade. The combined signal PCA plot performed better with the sample grade descending in clockwise order. For grade prediction, the random forest (RF) model produced a better effect than the support vector machine (SVM) and the SVM + RF model. In the RF model, the training and testing accuracies of the combined signal were all 1. The grades of all samples were correctly predicted. From the above, the UV spectrum combined with color difference can be used to quickly and accurately classify the grade of Huangshan Maofeng tea. This method considerably increases the convenience of tea grade identification.

Identification of Similar Chinese Congou Black Teas Using an Electronic Tongue Combined with Pattern Recognition.

It is very difficult for humans to distinguish between two kinds of black tea obtained with similar processing technology. In this paper, an electronic tongue was used to discriminate samples of seven different grades of two types of Chinese Congou black tea. The type of black tea was identified by principal component analysis and discriminant analysis. The latter showed better results. The samples of the two types of black tea distributed on the two sides of the region graph were obtained from discriminant analysis, according to tea type. For grade discrimination, we determined grade prediction models for each tea type by partial least-squares analysis; the coefficients of determination of the prediction models were both above 0.95. Discriminant analysis separated each sample in region graph depending on its grade and displayed a classification accuracy of 98.20% by cross-validation. The back-propagation neural network showed that the grade prediction accuracy for all samples was 95.00%. Discriminant analysis could successfully distinguish tea types and grades. As a complement, the models of the biochemical components of tea and electronic tongue by support vector machine showed good prediction results. Therefore, the electronic tongue is a useful tool for Congou black tea classification.

Dnmt3a is required for the tumor stemness of B16 melanoma cells.

The relationship of carcinogenesis and DNA methyltransferases has attracted extensive attention in tumor research. We reported previously that inhibition of de novo DNA methyltransferase 3a (Dnmt3a) in murine B16 melanoma cells significantly suppressed tumor growth and metastasis in xenografted mouse model. Here, we further demonstrated that knockdown of Dnmt3a enhanced the proliferation in anchor-independent conditions of B16 cells, but severely disrupted its multipotent differentiation capacity in vitro. Furthermore, transforming growth factor ß1, a key trigger in stem cell differentiation and tumor cell epithelial-mesenchymal transition (EMT), mainly induced apoptosis, but not EMT in Dnmt3a-deficient B16 cells. These data suggested that Dnmt3a is required for maintaining the tumor stemness of B16 cells and it assists B16 cells to escape from death during cell differentiation. Thus it is hypothesized that not only extraordinary self-renewal ability, but also the capacity of multipotent differentiation is necessary for the melanoma tumorigenesis. Inhibition of multipotent differentiation of tumor cells may shed light on the tumor treatment.

Fate tracing of hepatocytes in mouse liver.

Hepatocytes perform most of the functions of the liver and are considered terminally differentiated cells. Recently, it has been suggested that hepatocytes might have the potential to transdifferentiate or dedifferentiate under physiological or pathological conditions in vivo. Epithelial-mesenchymal transition of hepatocytes in liver fibrosis has also been proposed. However, these findings have not been fully confirmed. In this study, hepatocytes were genetically labelled for cell fate tracing using lacZ via the tamoxifen-induced CreERT/loxP system. After induction with tamoxifen, alb + cells were permanently marked by lacZ expression, and all progeny lacZ + cells were derived from a single source with no interference. We did not observe transdifferentiation or dedifferentiation of hepatocytes into cholangiocytes or hepatic progenitor cells under conditions of liver homeostasis or following a 2/3 partial hepatectomy. Meanwhile, lacZ/OPN-positive cells were observed in livers of 3,5-diethoxycarbonyl-1,4-dihydrocollidine-fed mice, and lacZ/alpha-smooth muscle actin-positive cells were detected in carbon tetrachloride-induced chronic liver injury models. These results suggested that some existing differentiated alb + cells might have the potential of transdifferentiation/dedifferentiation or epithelial-to-mesenchymal transition in vivo in some liver injury models, but the proportion of these alb + cells in liver was very low, and their significance and actual function during the pathological process remains to be elucidated.

Generation of a human induced pluripotent stem cell line from a 65-year old healthy female donor with Chinese Han genetic background.

Peripheral blood mononuclear cells (PBMC) were collected from a 65-year old healthy woman with Chinese Han genetic background. The PBMCs were reprogrammed with the human OKSM transcription factors using the non-integrating episomal vector system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously toward the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. The iPSC line can be used as control in disease mechanism studies. Resource table.

Combining genomic and network characteristics for extended capability in predicting synergistic drugs for cancer.

The identification of synergistic chemotherapeutic agents from a large pool of candidates is highly challenging. Here, we present a Ranking-system of Anti-Cancer Synergy (RACS) that combines features of targeting networks and transcriptomic profiles, and validate it on three types of cancer. Using data on human ß-cell lymphoma from the Dialogue for Reverse Engineering Assessments and Methods consortium we show a probability concordance of 0.78 compared with 0.61 obtained with the previous best algorithm. We confirm 63.6% of our breast cancer predictions through experiment and literature, including four strong synergistic pairs. Further in vivo screening in a zebrafish MCF7 xenograft model confirms one prediction with strong synergy and low toxicity. Validation using A549 lung cancer cells shows similar results. Thus, RACS can significantly improve drug synergy prediction and markedly reduce the experimental prescreening of existing drugs for repurposing to cancer treatment, although the molecular mechanism underlying particular interactions remains unknown.