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Excess intake of fluoride leads to a serious health issue called fluorosis. Fluorosis patients exhibit the symptom of muscle damage, but the specific mechanism remains unclear. Fibroblast growth factor 21 (FGF21) is a novel myokine that is involved in the regulation of myogenic differentiation, but whether fluoride induces skeletal muscle damage via FGF21 signaling has not been reported yet. In the current study, C2C12 cells were used to investigate the impact of fluoride on myogenic development and the involved regulatory role of FGF21/ERK signaling pathway. The expressions of the markers of myoblasts development and FGF21/ERK signaling pathway-related molecules were detected after fluoride treatment. The results indicated that fluoride notably inhibited the expressions of myogenic regulatory genes MyoD, MyoG and MyHC in C2C12 cells. In addition, fluoride increased the expressions of muscle atrophy-related markers MuRF1 and MAFbx. We proved that fluoride significantly inhibited the expression of FGF21 based on the RNA-seq results, and detected the expressions of downstream molecules FGFR1, KLB, Raf, MEK and ERK. Moreover, FGF21 pretreatment reversed the adverse effect of fluoride on the C2C12 cells and alleviated the atrophy of myotubes. Taken together, these findings indicated that fluoride suppressed differentiation and aggravated atrophy via FGF21/ERK signaling pathway in C2C12 cells. Our study has provided new evidence for the role of FGF21/ERK in fluoride-induced skeletal muscle damage and FGF21 may be one of the potential targets for prevention and treatment of fluorosis. • Fluoride inhibited the differentiation of C2C12 cells and induced the atrophy of myotubes. • Fluoride inhibited the FGF21/ERK signaling pathway in C2C12 cells. • FGF21 pretreatment alleviated the fluoride-induced adverse effects on C2C12 cells. [ABSTRACT FROM AUTHOR]

Abstract: The missense mutations at codons 12 and 13 of KRAS gene have been confirmed as a predictor of nonresponse to EGFR-targeted therapy with monoclonal antibodies cetuximab and panitumumab in patients with metastatic colorectal carcinoma (mCRC). Because of the intra-tumor heterogeneity at genetic levels, it is important to develop sensitive and selective assays to detect above KRAS mutation of rare mutated cells in the presence of large excess of wild-type cells. In the present study, wild-type blocking PCR (WTB-PCR) was developed to detect the aforementioned KRAS mutations, in which a chimera composed of locked nucleic acid (LNA) and DNA was used to inhibit with high sensitivity the amplification of wild-type KRAS alleles whereas it allowed the highly selective amplification of mutated KRAS alleles. Using mutated KRAS from HCT-116 as spiking DNA, the results showed that WTB-PCR could detect mutated alleles in a ratio of 1:10,000 (i.e., 0.01%) wild-type alleles and at a single copy level. For its further applications to detect aforementioned KRAS mutations in 20 cases of mCRC patients, the results showed that the detected mutation percentage of WTB-PCR (60%, 12/20) was higher than that of traditional PCR (45%, 9/20). Moreover, two patients respectively having synonymous mutated codons 13 (i.e., c.39C > T) and missense mutated codons 14 (i.e., c.40G > A) could be also only detected by WTB-PCR. In conclusion, the current WTB-PCR was a rapid, simple, and low-cost method to detect a trace amount of mutated KRAS gene. [ABSTRACT FROM AUTHOR]

• Two unique nitrogenous meroterpenoids were isolated. • ECD calculations were used to determine the absolute configurations. • Compound 2 possessed a novel benzo[ d ]oxazolidine-2-one based on the rearranged drimane scaffold. • Compound 1 showed potential anti-inflammatory activity in both vitro and vivo experiments. Two unique nitrogenous sesquiterpene quinone meroterpenoids, dysidinoid B (1) and dysicigyhone A (2), together with eight known analogues (3 – 10) were isolated and characterized from the marine sponge Dysidea septosa. Their structures with absolute configurations were established by a combination of extensive spectroscopic, electron circular dichroism (ECD) and single-crystal X-ray diffraction data analysis. Structurally, dysicigyhone A (2) possessed a unique benzo[ d ]oxazolidine-2-one unit. Additionally, dysidinoid B (1) exhibited significant anti-inflammatory effect by inhibiting TNF- α and IL-6 generation with IC 50 values of 9.15 μM and 17.62 μM, respectively. Further in vivo anti-inflammatory assay verified that the dysidinoid B (1) alleviated the CuSO 4 -induced robust acute inflammatory response in zebrafish model. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the prognostic value of D3 lymph node (TSLN) for the survival of patients with colorectal cancer. A total of 156 patients with R0 resected colorectal cancer were selected from 2011 to 2015 to carry out a retrospective study. The survival rate according to the groups of positive lymph node number (N: 1-3, N2: 4-6, N3: ≥7) and TSLN (TSLN [-], TSLN [+]) was analyzed. The influences of covariates on the 5-year overall survival (OS) and 5-year disease-free survival (DFS) were determined by the Cox proportional risk model of backward stepwise analysis. Kaplan-Meier survival analysis was used to draw survival curves between and within groups. During the median follow-up period (44.0 months), the 5-year DFS rate and OS rate were 45.0% and 46.0%, respectively. Survival analysis of the TSLN group showed that the 5-year OS rate and 5-year DFS rate in the TSLN (+) group (20.0 and 16.2%, respectively) were significantly lower than those in the TSLN (-) group (68.3 and 51.6%, respectively) (P < 0.001). The 5-year OS rate and DFS rate of the TSLN (+) and TSLN (-) subgroups in the N1 group were 16.7%, 33.3%, 56.7%, and 55.7%, respectively (P < 0.001). Multivariate analysis showed that positive lymph node, TSLN, and Pathological T stage were independent prognostic factors of DFS and OS for 5 years. Patients in the TSLN (+) group had a poorer prognosis. TSLN metastasis is an independent factor influencing the prognosis of patients, and patients with TSLN (+) have a poor prognosis. As an independent prognostic factor, this factor should be considered when evaluating the prognosis of patients. [ABSTRACT FROM AUTHOR]