Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage.

Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. GPR133 was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that GPR133 expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased GPR133 expression. Increased GPR133 expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of GPR133 resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of GPR133 on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM.

Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice.

Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation. Acox2 knockout (-/-) mice spontaneously developed liver cancer with marked lymphocytic infiltrate. Tandem-affinity purification coupled with mass spectrometry analysis revealed that Acox2 interacted with methylcrotonoyl-CoA carboxylase followed by co-immunoprecipitation confirmation. Here we reported that non-histone lysine crotonylation (Kcr) levels were downregulated in Acox2-/- mice livers. Interestingly, Kcr signals were concentrated in the nucleus of tumor cells but mostly located in the cytoplasm of adjacent normal liver cells of Acox2-/- mice. Quantitative analysis of the global crotonylome further revealed that 54% (27/50) of downregulated non-histone Kcr sites were located in mitochondrial (11/50) and peroxisomal (17/50) enzymes including Ehhadh, Scp2, Hsd17b4, Crot, Etfa, Cpt1a, Eci1/2, Hadha, Etfdh, and Idh2. Subsequent site-directed mutagenesis and transcriptome analysis revealed that Ehhadh K572cr might have site-specific regulatory roles by downregulating TOP3B expression that lead to increased DNA damage in vitro. Our findings suggested Acox2 is a regulator of Kcr that might play critical role on hepatic metabolic homeostasis.

Decreased D2-40 and increased p16INK4A immunoreactivities correlate with higher grade of cervical intraepithelial neoplasia.

BACKGROUND: D2-40 has been shown a selective marker for lymphatic endothelium, but also shown in the benign cervical basal cells. However, the application of D2-40 immunoreactivity in the cervical basal cells for identifying the grade of cervical intraepithelial neoplasia (CIN) has not been evaluated. METHODS: In this study, the immunoreactive patterns of D2-40, compared with p16(INK4A), which is currently considered as the useful marker for cervical cancers and their precancerous diseases, were examined in total 125 cervical specimens including 32 of CIN1, 37 of CIN2, 35 of CIN3, and 21 of normal cervical tissue. D2-40 and p16(INK4A) immunoreactivities were scored semiquantitatively according to the intensity and/or extent of the staining. RESULTS: Diffuse D2-40 expression with moderate-to-strong intensity was seen in all the normal cervical epithelia (21/21, 100%) and similar pattern of D2-40 immunoreactivity with weak-to-strong intensity was observed in CIN1 (31/32, 97.2%). However, negative and/or focal D2-40 expression was found in CIN2 (negative: 20/37, 54.1%; focal: 16/37, 43.2%) and CIN3 (negative: 22/35, 62.8%; focal: 12/35, 34.3%). On the other hand, diffuse immunostaining for p16(INK4A) was shown in 37.5% of CIN1, 64.9% of CIN2, and 80.0% of CIN3. However, the immunoreactive pattern of D2-40 was not associated with the p16(INK4A) immunoreactivity. CONCLUSIONS: Immunohistochemical analysis of D2-40 combined with p16(INK4A) may have a significant implication in clinical practice for better identifying the grade of cervical intraepithelial neoplasia, especially for distinguishing CIN1 from CIN2/3.

Does Chinese culture influence psychosocial factors for heroin use among young adolescents in China? A cross-sectional study.

BACKGROUND: Little empirical research has examined how cultural factors influence psychosocial factors for heroin drug use. The objectives of the study were to investigate the levels of individualism and collectivism among young adolescents and how cultural differences were associated with the constructs of the Theory of Planned Behavior and other psychosocial factors for heroin drug use. METHODS: A cross-sectional study was conducted among young adolescents in an HIV and heroin-stricken area in China. The Individualism-Collectivism Interpersonal Assessment Inventory (ICIAI) was used to measure cultural norms and values in the context of three social groups: family members, close friends, and classmates. RESULTS: A total of 220 boys and 241 girls were recruited and participated in an interview. Compared to boys, girls reported higher levels of the three specific-relationship ICIAIs, as well as higher levels of perceived behavioral control for heroin use, perceived peer control, and communication with parent about heroin use, but a lower level of favorable attitude towards heroin use. The levels of descriptive and subjective norms of heroin use were low in both girls and boys. Among boys, family ICIAI was positively associated with perceived behavioral control, and friend ICIAI was positively associated with perceived peer control and communication with parent. Among girls, family ICIAI was positively associated with perceived behavioral control and communication with parents about heroin use, but negatively with favorable attitudes to heroin use; friend ICIAI was positively associated with perceived peer control, and classmate ICIAI was negatively associated with favorable attitudes toward heroin use. CONCLUSIONS: This study documents that collectivistic aspects of Chinese culture may influence psychosocial factors for heroin use, although the patterns are varied by gender. Findings provide an empirical basis for the development of culturally competent intervention programs for heroin use intervention and prevention.