Naked cuticle inhibits wingless signaling in Drosophila wing development.

Wnt signaling is one of the major signaling pathways that regulate cell differentiation, tissue patterning and stem cell homeostasis and its dysfunction causes many human diseases, such as cancer. It is of tremendous interests to understand how Wnt signaling is regulated in a precise manner both temporally and spatially. Naked cuticle (Nkd) acts as a negative-feedback inhibitor for Wingless (Wg, a fly Wnt) signaling in Drosophila embryonic development. However, the role of Nkd remains controversial in later fly development, particularly on the canonical Wg pathway. In the present study, we show that nkd is essential for wing pattern formation, such that both gain and loss of nkd result in the disruption of Wg target expression in larvae stage and abnormal adult wing morphologies. Furthermore, we demonstrate that a thirty amino acid fragment in Nkd, identified previously in Wharton lab, is critical for the canonical Wg signaling, but is dispensable for Wg/planar cell polarity pathway. Putting aside the pleiotropic nature of nkd function, i.e. its role in the Decapentaplegic signaling, we conclude that Nkd universally inhibits the canonical Wg pathway across a life span of Drosophila development.

[Levels of short-chain fatty acids in enterobacteria-related metabolites in the feces of infants with cholestatic hepatopathy].

OBJECTIVE: To compare the levels of short-chain fatty acids in enterobacteria-related metabolites in feces between infants with cholestatic hepatopathy and healthy infants. METHODS: Thirty infants with cholestatic hepatopathy were enrolled in this study as the disease group, while 30 healthy infants were enrolled as the control group. Fecal specimens were collected from the disease group before and after treatment and from the control group. Gas chromatography was used to quantitatively determine the content of short-chain fatty acids in the feces of both groups including acetic acid, propionic acid, butyric acid, isobutyric acid, and isovaleric acid. RESULTS: There were no significant differences in the concentrations of acetic acid and propionic acid between the control and disease groups before and after treatment, as well as no significant changes in the two markers in the disease group after treatment (P>0.05). The disease group had a significantly increased concentration of butyric acid after treatment (P<0.05). The concentrations of isobutyric acid and isovaleric acid in the control group were significantly higher than those in the disease group before and after treatment (P<0.05). CONCLUSIONS: Intestinal protein metabolites in infants with cholestatic hepatopathy are significantly different from those in healthy infants, whereas there is no significant difference with respect to carbohydrate metabolites.

An essential role for PTIP in mediating Hox gene regulation along PcG and trxG pathways.

During Drosophila development, Polycomb-group and Trithorax group proteins function to ensure correct maintenance of transcription patterns by epigenetically repressing or activating target gene expression. To get a deep insight into the PcG and trxG pathways, we investigated a BRCT domain-containing protein called PTIP, which was generally identified as a transcriptional coactivator and belongs to the TRR complex. At the genome scale, we sorted given PTIP-binding peaks into two groups: PTIP/TRR-cobound and PTIP/PC-cobound peaks. In particular, we found that PTIP mediates the molecular switch between H3K4me3/H3K27ac and H3K27me3 histone modifications at TRR or PC occupied regions. Thus, we suggest that PTIP is a mediator rather than a dedicated co-activator along PcG and trxG pathways. Our hypothesis is further supported by the genetic assay: PTIP interacts genetically with either PcG or TrxG in a dosage-dependent manner, suggesting that PTIP functions as a co-factor of PcG/TrxG proteins. In addition, in accordance with the analysis of ChIP-seq, these genetic interactions correlate with modified ectopic HOX protein levels in imaginal discs, which reveals an essential role for PTIP in PcG-mediated Hox gene repression. Hence, we reveal a novel role for PTIP in the epigenetic regulation of gene expression along PcG and trxG pathways.

Meta-analysis of the prognostic value of long non-coding RNA AFAP1-AS1 for cancer patients in China.

LncRNA actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) is often dysregulated in cancer. We performed this meta-analysis to clarify the usefulness of AFAP1-AS1 as a prognostic marker in malignant tumors. The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to Augest 7, 2017. Sixteen studies with a total of 1,386 patients were included in the study. The pooled hazard ratio (HR) suggested high AFAP1-AS1 expression correlated with poor overall survival (OS) (HR = 1.98, 95% confidence interval (CI): 1.71-2.28), disease-free survival (DFS) (HR = 1.54, 95% CI: 1.22-1.95), and progression-free survival (PFS) (HR = 2.17, 95% CI:1.64-2.88) in cancer patients, without obvious heterogeneity. High AFAP1-AS1 expression also correlated with larger tumor size (odds ratio (OR) = 2.04, 95% CI: 1.54-2.72), advanced tumor stage (OR=2.35, 95% CI: 1.70-3.26), poor histological grade (OR =1.39, 95% CI: 1.02-1.90), lymph node metastasis (OR = 2.71, 95% CI: 1.98-3.72) and distant metastasis (OR = 2.96, 95% CI: 2.03-4.32). Thus high AFAP1-AS1 expression is predictive of poor OS, DFS, PFS, lymph node metastasis, distant metastasis, histological grade, larger tumor size and tumor stage, which suggests high AFAP1-AS1 expression may serve as a novel biomarker of poor prognosis in cancer.

[A1381T and -1793G/C polymorphisms of vWF gene impact the plasma vWF levels in Yugur, Tibetan and Han nationalities of China].

The aim of this study was to investigate the similarities and differences of A1381T (rs216311) and -1793G/C (rs7966230) single nucleotide polymorphisms (SNP) in Chinese Yugur, Tibetan, and Han nationalities and their influence on plasma vWF concentration in order to explore the sensitivity of these 3 nationalities to vWF-related diseases. Peripheral venous blood was obtained from 322 Yugur, 399 Tibetan, and 120 Han healthy people. The DNA were then extracted. vWF gene A1381T and -1793G/C polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequenced when it was necessary. The vWF:Ag level in plasma was determined by ELISA. The results showed that the genotype distribution of vWF gene at both A1381T and -1793G/C loci in Yugur, Tibetan and Han nationalities was different with statistically significance (P < 0.05). GG genotype of A1381T locus accounted for 69.9% in Yugur nationality, which was much higher than 56.6% and 53.3% in Tibetan and Han nationalities respectively(P < 0.01); AA genotype of A1381T locus expressed a low level of vWF in plasma. For the -1793G/C locus, the proportion of CG genotype in Yugur was much higher than that in Han, CC genotype expressed a high level of vWF in plasma. The plasma vWF levels with different nationalities and the polymorphism of vWF gene were significantly different. It is concluded that the polymorphisms of vWF gene at both A1381T and -1793G/C loci in Yugur, Tibetan and Han are significantly different; the polymorphism of vWF gene influences the plasma vWF level; the plasma vWF levels in Yugur and Tibetan are significantly higher than that in Han, which may be associated with the living environment and habits.

[Effects of ICAM-1 gene K469E, K56M polymorphisms on plasma sICAM-1 expression levels in Chinese Yugur, Tibetan and Han nationalities].

This study was purposed to investigate the intercellular cell adhesion molecule-1 (ICAM-1) gene K469E (A/G) (rs5498) and K56M (A/T) (rs5491) single nucleotide polymorphisms (SNP) and soluble ICAM-1 (sICAM-1) levels in plasma in three Chinese populations of Yugur, Tibetan and Han nationalities, to analyze comparatively the genotypes and allele frequencies distribution in different ethnic groups, and to explore the effects of ICAM-1 K469E and K56M polymorphism and sICAM-1 levels in plasma. EDTA-anticoagulant venous blood from Yugur(327 cases), Tibetan (400 cases) and Han (126 cases) people was collected, the DNA was extracted by using whole blood genomic DNA extraction kit, DNA SNP were analyzed by PCR-RFLP, genotype was judged by gel scan imaging system after agarose gel electrophoresis, the gene sequence was determined and the distribution of ICAM-1 genotypes and allele frequencies were compared among different ethnic groups, besides, the group representativeness was tested via the Hardy-Weinberg genetic equilibrium. Finally, the human sICAM-1 plasma levels were detected by using human ICAM-1 ELISA kit. The results showed that DNA sequencing result was consistent with PCR-RFLP analysis. In Yugur, Tibetan and Han nationalities, the KK, KE and EE three genotypes at ICAM-1 K469E gene locus were detected, the genotype distribution was not statistically significantly different, while the K, E allele frequency distribution was statistically significantly different (P < 0.05). Both of genotype and allele frequency distribution between Yugur, Tibetan and Han nationalities were statistically significantly different (P < 0.05). In K56M site only KK, KM two genotypes were detected, but the MM genotype was not detected in the three ethnic groups; the difference of two genotypes and K, M allele frequencies between Yugur and Han population was statistically significantly different (P < 0.05). Among three ethnic groups, the sex ratio and age distribution of K469E, K56M genotypes and allele frequencies of ICAM-1 gene were not significantly different, and distribution was in accordance with Hardy-Weinberg genetic equilibrium (P > 0.05). The plasma sICAM-1 level at ICAM-1 K469E allele locus in K individuals [(253 ± 122), (185 ± 97) µg/L] was higher than that at non-K allele [(145 ± 110) µg/L, P < 0.01]; the plasma sICAM-1 level of ICAM-1 K56M sites with KK genotype [(253 ± 122) µg/L] was higher than that of the KM genotypes [(168 ± 103) µg/L, P < 0.01]. In Yugur and Tibetan groups, the plasma sICAM-1 levels [(224 ± 80), (214 ± 111) µg/L] were higher than that in the Han group [(175 ± 125)µg/L, P < 0.05]. Pairwise comparison indicated that the plasma sICAM-1 levels between Yugur and Han group were statistically significantly different (P < 0.01), that was significantly different between Tibetan and Han group (P < 0.05). It is concluded that in Yugur, Tibetan and Han population, the genotypes and gene frequencies of two amino acid sites K469E and K56M in ICAM-1 were KK/KE-type, KK-type and K allele, moreover, the ratio of them in Yugur and Tibetan group was higher than that in Han, while there is not significant difference in sex ratio and age distribution, therefore, ICAM-1 genotype and allele frequency distribution in this study had ethnic representativeness. ICAM-1 gene K469E and K56M polymorphisms were likely to affect the plasma sICAM-1 expression level. K469E gene K allele may be a genetic risk factor, while K56M gene M allele a may be genetic protective factor for some diseases.