The aim of this study was to research the expression of IL-37 in systemic lupus erythematosus (SLE) patients and the effect of glucocorticoid on IL-37. Thirty newly diagnosed severe SLE patients receiving prednisone 1 mg/kg/day for 14 consecutive days and 30 healthy subjects were enrolled into this study. The plasma levels of IL-37 and other cytokines were detected by ELISA and the relative mRNA amounts of IL-37 and other cytokines were detected by RT-PCR. The plasma levels of IL-37, IL-18, IL-18BP, IFN-γ, and IL-6 in SLE patients increased significantly compared with healthy controls (p<0.05). The relative amount of IL-37 mRNA increased by 2.45-fold in pre-treatment SLE patients compared with controls (p<0.05). Plasma concentrations of IL-37 correlated with IL-18, IL-18BP, IFN-γ, IL-6 and SLEDAI score in both pre-treatment and post-treatment SLE patients. The plasma levels of IL-37 decreased significantly after treatment of glucocorticoid. The relative amount of IL-37 mRNA decreased by 24.5 % in post-treatment SLE patients compared with pre-treatment ones (p<0.01). In conclusion, IL-37 is upregulated in active SLE patients. IL-37 is correlated with pro-inflammatory cytokines and SLEDAI. Glucocorticoid can downregulate the expression of IL-37 and other cytokines in SLE patients.

Whereas white adipose tissue depots contribute to the development of metabolic diseases, brown and beige adipose tissue has beneficial metabolic effects. Here we show that CDK6 regulates beige adipocyte formation. We demonstrate that mice lacking the CDK6 protein or its kinase domain (K43M) exhibit significant increases beige cell formation, enhanced energy expenditure, better glucose tolerance, and improved insulin sensitivity, and are more resistant to high-fat diet-induced obesity. Re-expression of CDK6 in Cdk6−/− mature or precursor cells, or ablation of RUNX1 in K43M mature or precursor cells, reverses these phenotypes. Furthermore, RUNX1 positively regulates the expression of Ucp-1 and Pgc1α by binding to proximal promoter regions. Our findings indicate that CDK6 kinase activity negatively regulates the conversion of fat-storing cells into fat-burning cells by suppressing RUNX1, and suggest that CDK6 may be a therapeutic target for the treatment of obesity and related metabolic diseases.

No abstract

Progranulin (PGRN) is a widely expressed growth factor that effectively inhibits tumor necrosis factor α (TNFα)-mediated inflammatory response. TNFα is involved in intervertebral disc degeneration (IDD) and plays a key role. This study aims to determine the role of PGRN in the intervertebral disc degeneration process. We collected intervertebral discs (IVDs) from humans and mice with different genetic backgrounds. We examined the expression of PGRN in IVD tissues by immunohistochemistry staining and Western blotting assay. We examined the peripheral serum level of PGRN by ELISA assay. Murine IVD tissue samples were taken to undergo safranin O, HE, and immunohistochemistry staining. Primary human nucleus pulposus cells were used for ELISA and RT-PCR assays. PGRN as well as interlukin-10 (IL-10) and interlukin-17 (IL-17) expressions were elevated in degenerative discs and peripheral blood sera. Loss of PGRN led to accelerated disc degeneration in the animal model, along with decreased expression of IL-10 and increased expression of IL-17. Additionally, the PGRN level was positively related to levels of IL-10 and IL-17. In vitro study suggested that PGRN protected against disc degeneration by inducing IL-10 and reducing IL-17. PGRN is associated with intervertebral disc degeneration through interfering with IL-10 and IL-17; thus, PGRN could be an interesting biomarker for diagnosis and a potential treatment target.

Small nucleolar RNA host gene 3 (SNHG3), a long noncoding RNA (lncRNA), acts as an oncogene in hepatocellular carcinoma (HCC), whereas microRNA (miR)-326 plays an inhibitory role in some types of human cancers, including melanoma, osteosarcoma, and gastric cancer. In the present study, by analyzing 47 tissue specimens of human HCC, we found that the relative expression levels of SNHG3 were significantly higher in HCC tissues than those in the adjacent noncancerous tissues, whereas the relative expression levels of miR-326 were significantly lower in HCC tissues. Furthermore, the relative mRNA levels of Sma and Mad Related Family 3 (SMAD3) and zinc finger E-box binding homeobox 1 (ZEB1) were significantly higher in HCC tissues compared with the adjacent noncancerous tissues. In human HCC cell lines, SNHG3 overexpression promoted the proliferation, migration, and epithelial-mesenchymal transition and inhibited apoptosis, whereas knockdown of SNHG3 expression exerted the opposite effects. Importantly, miR-326 or miR-326 inhibitor restored the aforementioned effects of SNHG3 overexpression or SNHG3 knockdown. We thus found that the miR-326-response element is present in SNHG3 and the 3'-untranslated region of SMAD3 mRNA. In fact, SNHG3 overexpression increased the expression levels of SMAD3 and ZEB1, while miR-326 decreased the expression levels of SMAD3. These results suggest that SNHG3 may function as a competing endogenous RNA (ceRNA) for miR-326, which in turn enhances SMAD3 and ZEB1 expression. In conclusion, we propose that SNHG3 promotes HCC progression via the miR-326/SMAD3/ZEB1 signaling pathway. The findings may provide novel targets for the diagnosis and treatment of HCC.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. The current standard treatment with glucocorticoids (GCs) leads to many adverse effects, and its effectiveness is questionable. Thus, it is critical and urgent to find new drug(s) for treatment of IPF. Baicalin (BAI) is an attractive candidate for this purpose. Herein, utilizing shotgun lipidomics, we revealed that IPF could lead to a lipid disorder of the liver in an animal model induced by bleomycin and confirmed through histopathological studies of the lung. Lipidomics further demonstrated that this disorder could virtually be corrected after treatment with BAI, but not with dexamethasone (DEX) (a commonly used GC for treatment of IPF). In contrast, the treatment with DEX did not improve IPF but led to tremendous alterations in hepatic lipidomes and accumulation of fat in the liver, which was very different from the lipid disorder induced by IPF. The underpinning mechanisms of the IPF-resultant lipid disorder and DEX-induced lipotoxicity as revealed by shotgun lipidomics were extensively discussed. Taken together, the current study showed that IPF could lead to hepatic lipid disorder, which can be treated with BAI, and demonstrated that lipidomics could be a powerful tool for drug screening.

Publications by Chinese researchers in scientific journals have dramatically increased over the past decade; however, academic misconduct also becomes more prevalent in the country. The aim of this prospective study was to understand the perceptions of Chinese biomedical researchers towards academic misconduct and the trend from 2010 to 2015. A questionnaire comprising 10 questions was designed and then validated by ten biomedical researchers in China. In the years 2010 and 2015, respectively, the questionnaire was sent as a survey to biomedical researchers at teaching hospitals, universities, and medical institutes in mainland China. Data were analyzed by the Chi squared test, one-way analysis of variance with the Tukey post hoc test, or Spearman's rank correlation method, where appropriate. The overall response rates in 2010 and 2015 were 4.5% (446/9986) and 5.5% (832/15,127), respectively. Data from 15 participants in 2010 were invalid, and analysis was thus performed for 1263 participants. Among the participants, 54.7% thought that academic misconduct was serious-to-extremely serious, and 71.2% believed that the Chinese authorities paid no or little attention to the academic misconduct. Moreover, 70.2 and 65.2% of participants considered that the punishment for academic misconduct at the authority and institution levels, respectively, was not appropriate or severe enough. Inappropriate authorship and plagiarism were the most common forms of academic misconduct. The most important factor underlying academic misconduct was the academic assessment system, as judged by 50.7% of the participants. Participants estimated that 40.1% (39.8 ± 23.5% in 2010; 40.2 ± 24.5% in 2015) of published scientific articles were associated with some form of academic misconduct. Their perceptions towards academic misconduct had not significantly changed over the 5 years. Reform of the academic assessment system should be the fundamental approach to tackling this problem in China.

The alpha‐proteobacteria of the genus Wolbachia is a widespread group of maternally inherited endosymbionts of arthropod and nematode hosts. Wolbachia infection induces a range of host phenotypes, including cytoplasmic incompatibility, male killing, feminization, and induction of thelytokous parthenogenesis. Heterogony (cyclical parthenogenesis) is a remarkable characteristic of oak gallwasps, Cynipini, the largest tribe of the Cynipidae. A few species of Cynipini are exceptional in that they are univoltine and exhibit thelytokous parthenogenesis, probably because they lost the arrhenotokous generation of their heterogonic ancestor species due to Wolbachia infection. In this study, the presence of Wolbachia was detected using polymerase chain reaction primers for the wsp genes in a thelytokous parthenogenetic species [Dryocosmus kuriphilus (Yasumatsu)] (Hymenoptera: Cynipidae: Cynipini). Approximately 29.8 and 87.1% of adults of the Zhuzhou and Fuzhou strains, respectively, were infected with Wolbachia while all females of the remaining four strains collected from other localities in China were Wolbachia free. The length of the wsp fragment of Zhuzhou and Fuzhou strains was found to be 573 and 561 bp, respectively. The nucleotide sequence of the bacterial wsp fragment indicated that the endosymbiotic bacteria of the Zhuzhou and Fuzhou strains are members of supergroup A, but belong to different clades; they probably originated from two independent infection events. In conclusion, thelytokous parthenogenesis of D. kuriphilus is not caused by Wolbachia infection and the deletion of the arrhenotokous generation is thus not associated with such an infection.