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Aberrant DNA methylation has been identified as biomarkers for breast cancer detection. Coiled-coil domain containing 12 gene (CCDC12) implicated in tumorigenesis. This study aims to investigate the potential of blood-based CCDC12 methylation for breast cancer detection. DNA methylation level of CpG sites (Cytosine-phosphate Guanine dinucleotides) in CCDC12 gene was measured by mass spectrometry in 255 breast cancer patients, 155 patients with benign breast nodules and 302 healthy controls. The association between CCDC12 methylation and breast cancer risk was evaluated by logistic regression and receiver operating characteristic curve analysis. A total of eleven CpG sites were analyzed. The CCDC12 methylation levels were higher in breast cancer patients. Compared to the lowest tertile of methylation level in CpG_6,7, CpG_10 and CpG_11, the highest quartile was associated with 82, 91 and 95% increased breast cancer risk, respectively. The CCDC12 methylation levels were associated with estrogen receptor (ER) and human epidermal growth factor 2 (HER2) status. In ER-negative and HER2-positive (ER-/HER2+) breast cancer subtype, the combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER−/HER2+ breast cancer from the controls (AUC = 0.727). The hypermethylation levels of CCDC12 in peripheral blood could be used for breast cancer detection. Breast cancer detection could be facilitated by novel blood-based DNA methylation biomarkers. The methylation levels of CpG sites in CCDC12 were higher in breast cancer than those in controls. The combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER-/HER2+ breast cancer subtype from the controls. [ABSTRACT FROM AUTHOR]

Objective. Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton. Early and accurate diagnosis is necessary for the timely and effective treatment of this disease and its common complications. Lipid metabolites form various kinds of bioactive molecules that regulate the initiation and progression of inflammation. However, there are currently few studies that investigate the alteration of serum lipid in AS patients. Methods. Blood samples were collected from 115 AS patients and 108 healthy controls (HCs). Serum-untargeted lipidomics were performed using ultrahigh-performance liquid chromatography coupled with Q-Exactive spectrometry, and the data were determined by multivariate statistical methods to explore potential lipid biomarkers. Results. Lipid phenotypes associated with disease activity were detected in the serum of patients with AS. Of all 586 identified lipids, there are 297 differential lipid metabolites between the AS and HC groups, of which 15 lipid metabolites are significant. In the AS groups, the levels of triacylglycerol (TAG) (18:0/18:1/20:0) were increased, and the levels of phosphatidylcholine (PC) (16:0e/26:4) and PC (18:1/22:6) were decreased. The areas under the receiver operating characteristic curve (AUC) of TAG (18:0/18:1/20:0), PC (16:0e/26:4), and PC (18:1/22:6) were 0.919, 0.843, and 0.907, respectively. Conclusion. Our findings uncovered that lipid deregulation is a crucial hallmark of AS, thereby providing new insights into the early diagnosis of AS. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is the leading cause of cancer-related morbidity and mortality in China. Exploring novel biomarkers for the early detection of LC is important. We quantified DNA methylation levels of three CpG sites of FYB gene in peripheral blood in 163 early-stage LC cases (88.3% at stage I) and 187 age- and gender-matched healthy controls. Covariates-adjusted odds ratios (ORs) for −10% methylation were calculated by binary logistic regression. With multiple testing corrections, hypomethylation of FYB_CpG_4 was significantly associated with LC (OR = 2.04, p = 4.50E-04) even with LC at stage I (OR = 1.41, p = 0.003) without obvious bias between genders, but it mainly affected the subjects older than 55 years (OR = 2.04, p = 0.015). Hypomethylation of FYB_CpG_2 was also associated with LC, but only for the males (OR = 1.76, p = 0.018). FYB_CpG_3 methylation had no association with LC, but interestingly its methylation level in the males was only half of that in the females. We proposed a novel association between blood-based abnormal FYB methylation and very early-stage LC. The age- and gender-related DNA methylation patterns also revealed the diversity and precision of epigenetic regulations. [ABSTRACT FROM AUTHOR]

Background and purpose: Kaposi's sarcoma–associated herpes virus (KSHV) vIL‐6 is sufficient to induce lymphatic reprogramming of vascular endothelial cells, which is a key event in Kaposi's sarcoma (KS) development. This study was aimed to investigate the effect of Chinese herb oroxylin A on lymphatic reprogramming and neovascularization by KSHV vIL‐6 in vitro and in vivo. Methods: The lymphatic‐phenotype endothelial cell line was generated by lentiviral KSHV vIL‐6 infection. Cell viability and apoptosis were determined by MTT assay or flow cytometry with annexin V/propidium iodide staining. Migration, invasion, and neovascularization of the vIL‐6‐expressing lymphatic‐phenotype endothelial cells were determined by wound healing assay, transwell chamber assay, microtubule formation assay, and chick chorioallantoic membrane assay, respectively. Quantitative polymerase chain reaction and Western blot analysis were used to test the expression of Prox1, VEGFR3, podoplanin, LYVE‐1, and PPARγ in cells. Co‐localization of Prox1 and PPARγ was determined by immunofluorescence. Ubiquitination of Prox1 was detected by in vivo ubiquitination assay. Results: The lymphatic‐phenotype endothelial cell line expressing KSHV vIL‐6 was successfully generated. Oroxylin A induced cellular invasion abrogation, apoptosis induction, and neovascularization inhibition of the vIL‐6‐expressing endothelial cells. Mechanically, oroxylin A elevated PPARγ expression, which in turn interacted with and facilitated Prox1 to undergo ubiquitinational degradation, and subsequently leads to VEGFR3, LYVE‐1, and podoplanin reduction. Conclusion: Through modulating PPARγ/Prox1 axis, oroxylin A inhibits lymphatic reprogramming and neovascularization of KSHV vIL‐6. Thus, oroxylin A may serve as a candidate for the treatment of KS as well as other aggressive angiomas. Highlights: Kaposi's sarcoma associated herpes virus (KSHV) encoded viral interleukin (IL)‐6 is sufficient to induce lymphatic reprogramming of endothelial cells, which is a pivotal event in Kaposi's sarcoma (KS) development. The study demonstrates that the Chinese herb Oroxylin A inhibits lymphatic reprogramming and neovascularization of KSHV vIL‐6 by modulating PPAR?/Prox1 axis. Oroxylin A may have a potential in treatment of KS as well as other aggressive angiomas. [ABSTRACT FROM AUTHOR]

Background: To establish a reference interval of alkaline phosphatase for healthy children of various ethnicities, aged 0 years to 12 years in China. Methods: According to the Clinical and Laboratory Standards Institute guideline C28-A3, blood specimens were collected in the morning after overnight fasting from 502 healthy children to determine the alkaline phosphatase (ALP) level, using the Beckman AU5800 automatic biochemical analyzer. Children were grouped by sex and age. The age groups were as follows: 0 to 1 year, 1 to 3 years, 3 to 6 years, and 6 to 12 years. Results: There were no significant differences between the sex and age groups for the age groups of 0 to 1 year, 1 to 3 years, and 3 to 6 years; as a result, we combined those groups into a single group. The reference interval of ALP is 81.9 to 350.3 U per L in the group aged 0 to 6 years and 48.8 to 445.9 U per L in the group aged 6 to 12 years. Conclusions: The results of this study establish a reference interval for ALP in healthy children, which will provide a basis for screening, diagnosing, and monitoring bone or liver-related diseases in children. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsRUNX3 is hypermethylated in multiple cancers. TIMP2 also functions as a regulator of tumors. However, there are only very few reports on the association of methylation of RUNX3 and TIMP2 with lung cancer (LC) in peripheral blood.426 LC patients and 428 age- and sex-matched healthy controls were recruited. DNA methylation in blood was semi-quantitively assessed by mass spectrometry. For the association analysis, binary logistic regression analysis adjusted covariant was applied, and ORs were presented as per +10% methylation.Hypermethylation of CpG_1, CpG_5 and CpG_8 in RUNX3 was significantly associated with LC (ORs = 1.45, 1.35 and 1.35, respectively, adjusted p < 0.05), and even stage I LC. The association between the three RUNX3 CpG sites and LC was enhanced by increased age (> 55 years, ORs ranged from 1.43 to 1.75, adjusted p < 0.05), male gender (ORs ranged from 1.47 to 1.59, adjusted p < 0.05) and tumor stage (stage II&III&IV, ORs ranged from 1.86 to 3.03, adjusted p < 0.05).This study suggests a significant association between blood-based RUNX3 hypermethylation and LC, especially in elder people, in males and in LC patients with advanced stage. [ABSTRACT FROM AUTHOR]

Nowadays, the simultaneous inhibition of two or more pathways plays an increasingly important role in cancer treatment due to the complex and diverse pathogenesis of cancer, and the combination of the cyclin-dependent kinase 6 (CDK6) inhibitor and PIM1 inhibitor was found to generate synergistic effects in acute myeloid leukemia (AML) treatment. Therefore, we discovered a novel lead 1 targeting CDK6/PIM1 via pharmacophore-based and structure-based virtual screening, synthesized five different series of new derivates, and obtained a potent and balanced dual CDK6/PIM1 inhibitor 51 , which showed high kinase selectivity. Meanwhile, 51 displayed an excellent safety profile and great pharmacokinetic properties. Furthermore, 51 displayed stronger potency in reducing the burden of AML than palbociclib and SMI-4a in vivo . In summary, we offered a new direction for AML treatment and provided a great lead compound for AML preclinical studies.