OBJECTIVE:To screen novel diagnostic marker or therapeutic target for multiple myeloma (MM). METHODS:Sel1L, SPAG4, KCNN3 and PARM1 were identified by bioinformatics method based on GEO database as high expression genes in MM. Their RNA and protein expression levels in bone marrow mononuclear cells from myeloma cell lines U266, NCI-H929, MM.1s, RPMI8226 and leukemia cell line THP1, as well as 31 MM patients were evaluated by RT-PCR and Western blot, respectively. Meanwhile, 5 samples of bone marrow from healthy donors for allogeneic hematopoietic stem cell transplantation were employed as controls. RESULTS:Compared with leukemia cell line THP1, the expression levels of KCNN3, PARM1 and Sel1L mRNA were significantly increased in myeloma cell lines U266, NCI-H929 and MM.1s, while PARM1 was further increased in myeloma cell lines 8226. Western blot showed that the 4 genes were all expressed in the 4 myeloma cell lines. Compared with healthy controls, the expression levels of Sel1L, SPAG4, KCNN3 and PARM1 mRNA were significantly higher in MM patients (all P < 0.05). Western blot showed that the 4 genes were all expressed in MM patients, and the protein expression level of Sel1L and KCNN3 were significantly different compared with healthy donors (all P < 0.01). CONCLUSION:Sel1L, SPAG4, KCNN3 and PARM1 may be potential diagnostic markers and therapeutic targets for MM.

Objectives: Atherosclerosis is a primary medical concern due to the increasing prevalence and lack of effective treatment that reverses the disease progression. While multiple genetic mutations/variations have been associated with atherosclerotic risk, the development of atherosclerosis in response to risk factors is also contributed by factors at the epigenetic and chromatin level. The SWI/SNF chromatin remodeling complex alters DNA accessibility and chromatin structure to modulate gene expression in response to external and internal cellular environments, potentially serving as an underexplored compartment of CVD and atherosclerosis development. Approach and Results: In an effort to identify key chromatin remodeling compartments involved in atherosclerotic foam cell formation, primary bone marrow-derived macrophages (BMDMs) were exposed to a pro-atherogenic environment, specifically to oxidized Low-density lipoprotein (oxLDL). We observed drastically and time-dependent decrease in the protein abundance of BAF60a, a transcription factor interacting subunit of the SWI/SNF chromatin remodeling complex. Macrophage-specific Baf60a deletion in ApoE deficient mice showed over 30% increase in aortic plaque formation after 16-weeks of western diet feeding (N=12, p=0.0097). Integrated analysis of RNA-seq and ATAC-seq regulatory network in oxLDL treated BAF60a deficient BMDMs identified a shift of chromatin accessibility, transcription factor footprint, and a reshape in gene expression patterns that regulate extracellular matrix organization, focal adhesion, integrin signaling, inflammation, and lead to foam cell formation which ultimately contribute to the atherosclerotic plaque build-up. Conclusions: Our data demonstrated the role of macrophage BAF60a in atherogenesis and suggested a potential therapeutic target to treat atherosclerosis, presumably by compensating for the loss of Baf60a.

OBJECTIVE:To investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT).METHODS:30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured.RESULTS:Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05).CONCLUSION:Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

A further investigation of the lipolysis induced by medium-chain triglyceride (MCT) was conducted on C57BL/6J mice fed with a diet containing 2% MCT or 2% long-chain triglyceride (LCT). Blood norepinephrine, body fat and blood lipid variables, and the protein or mRNA expression of the genes relevant to lipolysis were measured and analyzed in the white and brown adipose tissue (WAT, BAT). Decreased body fat and improved blood lipid profiles attributable to MCT were confirmed. A higher level of blood norepinephrine was observed with the MCT diet. The adipose triglyceride lipase (ATGL) activity and its mRNA expression, the expression of protein and mRNA of the beta 3 adrenergic receptor (β3-AR) in both WAT and BAT, and the hormone-sensitive lipase (HSL) activity and its mRNA expression in BAT were significantly increased in the mice with MCT feeding. The lipolysis induced by MCT might be partially mediated by increasing norepinephrine, thereafter signaling the up-regulation of β3-AR, ATGL, and HSL in WAT and BAT.