Resistance becomes major clinical issue in cancer treatment, which strongly limits patients to benefit from oncotherapy. Growing evidences have been indicative of the critical role of fibroblast growth factor (FGF)/receptor (FGFR) signaling played in resistance to oncotherapy. In this review we discussed the underlying mechanisms of FGF/FGFR signaling mediated resistance to chemotherapy, radiotherapy and target therapy in various cancers. Meanwhile, we summarized the reported mechanism of FGF/FGFR inhibitors resistance in cancers.

Background: N6-methyladenosine (m 6 A) RNA methylation is dynamically and reversibly regulated by methyl-transferases ("writers"), binding proteins ("readers"), and demethylases ("erasers"). The m 6 A is restored to adenosine and thus to achieve demethylation modification. The abnormality of m 6 A epigenetic modification in cancer has been increasingly attended. However, we are rarely aware of its diagnostic, progressive and prognostic performance in lung adenocarcinoma (LUAD). Methods and Results: The expression of 13 widely reported m 6 A RNA regulators in LUAD and normal samples were systematically analyzed. There were 12 m 6 A RNA methylation genes displaying aberrant expressions, and an 11-gene diagnostic score model was finally built (Diagnostic score

The role of an extracellular matrix- (ECM-) receptor interaction signature has not been fully clarified in gastric cancer. This study performed comprehensive analyses on the differentially expressed ECM-related genes, clinicopathologic features, and prognostic application in gastric cancer. The differentially expressed genes between tumorous and matched normal tissues in The Cancer Genome Atlas (TCGA) and validation cohorts were identified by a paired t -test. Consensus clusters were built to find the correlation between clinicopathologic features and subclusters. Then, the least absolute shrinkage and selection operator (lasso) method was used to construct a risk score model. Correlation analyses were made to reveal the relation between risk score-stratified subgroups and clinicopathologic features or significant signatures. In TCGA (26 pairs) and validation cohort (134 pairs), 25 ECM-related genes were significantly highly expressed and 11 genes were downexpressed in gastric cancer. ECM-based subclusters were slightly related to clinicopathologic features. We constructed a risk score model = 0.081 ∗ log 2   CD 36 + 0.043 ∗ log 2   COL 5 A 2 + 0.001 ∗ log 2   ITGB 5 + 0.039 ∗ log 2   SDC 2 + 0.135 ∗ log 2   SV 2 B + 0.012 ∗ log 2   THBS 1 + 0.068 ∗ log 2   VTN + 0.023 ∗ log 2   VWF . The risk score model could well predict the outcome of patients with gastric cancer in both training ( n = 351 , HR: 1.807, 95% CI: 1.292-2.528, P = 0.00046 ) and validation ( n = 300 , HR: 1.866, 95% CI: 1.347-2.584, P = 0.00014 ) cohorts. Besides, risk score-based subgroups were associated with angiogenesis, cell adhesion molecules, complement and coagulation cascades, TGF-beta signaling, and mismatch repair-relevant signatures ( P < 0.0001 ). By univariate (1.845, 95% CI: 1.382-2.462, P < 0.001 ) and multivariate (1.756, 95% CI: 1.284-2.402, P < 0.001 ) analyses, we regarded the risk score as an independent risk factor in gastric cancer. Our findings revealed that ECM compositions became accomplices in the tumorigenesis, progression, and poor survival of gastric cancer.

Nowadays, a large number of consumers have a strong preference for the "functional foods" for the improvement of their eating diet and maintenance of their health (Jeffery, 2005;Shashirekha et al., 2015).Accordingly, fruits and vegetables are important parts of the healthy diet with the capacity of preventing several diseases (Jeffery, 2005;Shashirekha et al., 2015). In recent years, the beetroot (Beta vulgaris L.) has become popular as a potential "functional food" within this context (Frank et al., 2005). In spite of the fact that the beetroot has long been used as a traditional cuisines in Europe, the understanding of the applied value is very limited. Today, with the development of preclinical trials, consumers have increased knowledge about the biological activity of beetroot. The beetroot is now widely cultivated to meet the increase in demand (Maity et al., 2016). In addition to being known as fresh vegetables, or as food additives in cattle products, beverages, candies, and dairy products (Georgiev et al., 2010;Vieira Teixeira da Silva et al., 2019), beetroot has also been found to possess the potential of treating and preventing multiple diseases. According to the database displays in the US Department of Agriculture Agricultural Research Service, beetroot is not only rich in proteins (1.68 g), carbohydrates (9.96 g), fat (0.18 g), amino acids (1.216 g), fatty acids (0.119 g), phytosterols (0.025 g), minerals (0.483 g), and fibers (2 g) per 100 g of wet weight, but also contains

Background and Purpose Migration and differentiation of epidermal cells are essential for epidermal regeneration during wound healing. Fibroblast growth factor 21 (FGF21) plays key roles in mediating a variety of biological activities. However, its role in skin wound healing remains unknown. Experimental Approach Fgf21 knockout (Fgf21 KO) mice were used to determine the effect of FGF21 on wound healing. The source of FGF21 and its target cells were determined by immunohistochemistry, immunoblotting, and ELISA assay. Moreover, Sirt1flox/flox and Atg7flox/flox mice were constructed and injected with the epidermal‐specific Cre virus to elucidate the underlying mechanisms. Migration and differentiation of keratinocytes were evaluated in vitro by cell scratch assays, immunofluorescence, and qRT‐RCR. The effects were further assessed when SIRT1, ATG7, ATG5, BECN1, and P53 were silenced. Interactions between SIRT1 and autophagy‐related genes were assessed using immunoprecipitation assays. Key Results FGF21 was active in fibroblasts and promoted migration and differentiation of keratinocytes following injury. After wounding, SIRT1 expression and autophagosome synthesis were lower in Fgf21 KO mice. Depletion of ATG7 in keratinocytes counteracted the FGF21‐induced increases in migration and differentiation, suggesting that autophagy is required for the FGF21‐mediated pro‐healing effects. Furthermore, epithelial‐specific Sirt1 knockout abolished the FGF21‐mediated improvements of autophagy and wound healing. Silencing of SIRT1 in keratinocytes, which decreased deacetylation of p53 and autophagy‐related proteins, revealed that FGF21‐induced autophagy during wound healing was SIRT1‐dependent. Conclusions and implications FGF21 is a key regulator of keratinocyte migration and differentiation during wound healing. FGF21 may be a novel therapeutic target to accelerate would healing.

Background and Aims: Chronic liver diseases are associated with the development of liver fibrosis. Without treatment, liver fibrosis commonly leads to cirrhosis and HCC. FGF12 is an intracrine factor belonging to the FGF superfamily, but its role in liver homeostasis is largely unknown. This study aimed to investigate the role of FGF12 in the regulation of liver fibrosis.Approach and Results: FGF12 was up-regulated in bile duct ligation (BDL)-induced and CCL 4 -induced liver fibrosis mouse models. Expression of FGF12 was specifically up-regulated in nonparenchymal liver cells, especially in hepatic macrophages. By constructing myeloid-specific FGF12 knockout mice, we found that deletion of FGF12 in macrophages protected against BDL-induced and CCL 4 -induced liver fibrosis. Further results revealed that FGF12 deletion dramatically decreased the population of lymphocyte antigen 6 complex locus C high macrophages in mouse fibrotic liver tissue and reduced the expression of proinflammatory cytokines and chemokines. Meanwhile, loss-of-function and gain-of-function approaches revealed that FGF12 promoted the proinflammatory activation of macrophages, thus inducing HSC activation mainly through the monocyte chemoattractant protein-1/chemokine (C-C motif) receptor 2 axis. Further experiments indicated that the regulation of macrophage activation by FGF12 was mainly mediated through the Janus kinase-signal transducer of activators of transcription pathway. Finally, the results revealed that FGF12 expression correlates with the severity of fibrosis across the spectrum of fibrogenesis in human liver samples.

Background Cancer stem cell (CSC) promotes angiogenesis which plays an important role in tumor occurrence, growth, and metastasis. Accurately, quantifying the tumor vasculature can help understanding CSC characteristics and improve cancer diagnosis, therapy planning, and evaluation. The objective of this study is to present a method for improved angiogenesis assessment. Methods We proposed a three-dimensional microvessel density (3D MVD) to evaluate tumor angiogenesis and tested it in animal models. Six male Balb/c nude mice were divided into normal group and tumor group. The mice in tumor group were orthotopically implanted human gastric cancer, cell line BGC-823. The phase-contrast images were collected at Shanghai Synchrotron Radiation Facility BL13W beamline, which has much higher soft-tissue contrast and spatial resolution than conventional X-ray. After volume reconstruction and vessel extraction, the 3D models of the angiogenesis were established for MVD calculation. Results The results showed that the proposed 3D MVD is positively correlated with the pathological changes of the microvessels. It took the advantage of high resolution of the phase-contrast imaging and added three-dimensional information to the existing MVD measure. Conclusions Our study presents a feasible approach for better understanding of tumor angiogenesis. It may provide doctors and scientists a better tool for cancer investigation and improving medical outcomes.

Renying pulse AI can effectively predict arterial stiffness in synchrony with the manifestations of Cunkou pulse in elderly patients with hypertension. Cunkou pulse apparatus is a valuable tool for evaluating AI in clinical practice. The close correlations reported above reflect the holistic concept of Traditional Chinese Medicine.