5-HT 2 receptor mediates high-fat diet-induced hepatic steatosis and very low density lipoprotein overproduction in rats.

BACKGROUND: 5-HT has been shown to mediate abnormality of hepatic lipid metabolism through activation of mammalian target of rapamycin (mTOR). However, it is unclear whether 5-HT is directly involved in high-fat diet (HFD)-induced hepatic steatosis. MATERIALS AND METHODS: Male rats were allocated into seven groups with control, either HFD feeding, 5-HT treatment, or HFD feeding and 5-HT treatment with or without sarpogrelate treatment, all of which were executed for 4 weeks. HepG2 cells were exposed to 5-HT or palmitic acid (PA) with or without rapamycin or Sar treatment. RESULTS: Rats fed with HFD or exposed to 5-HT led to abnormalities with activated hepatic mTOR-S6K pathway, overproduction of hepatic triglycerides and VLDL with steatosis, and hyperlipidemia, which were exacerbated by a combination of HFD and 5-HT. Sarpogrelate significantly inhibited above abnormalities induced by HFD and 5-HT, alone or in a combination. Additionally, HFD caused up-regulation of 5-HT2 receptors (5-HT2R), including 5-HT2AR and 5-HT2BR, and 5-HT synthesis in the liver, without obvious influence on other 5-HT receptors gene expression. In HepG2 cells, both PA and 5-HT induced overproduction of triglycerides and VLDL with lipid droplets, and PA up-regulated 5-HT2AR and 5-HT2BR expression and 5-HT synthesis as well. Rapamycin fully abolished PA or 5-HT-induced mTOR activation, which was more effective than sarpogrelate. However, the inhibitory effects of rapamycin on PA or 5-HT-induced overproduction of triglycerides and VLDL were less than sarpogrelate. CONCLUSIONS: Up-regulation of hepatic 5-HT2R and 5-HT synthesis by HFD is crucial for HFD-induced overproduction of hepatic triglycerides and VLDL with hyperlipidemia.

Cytotoxicity of the Defensive Secretion from the Medicinal Insect Blaps rynchopetera.

Blaps rynchopetera Fairmaire has long been used as a folk medicine by the Yi and Bai ethnic groups in China to treat fever, cough, gastritis, boils, and tumors. In the present study, the cytotoxicity of the defensive secretion (TDS) of B. rynchopetera against AGS Caco-2, HepG2 U251 and Bel-7402 was tested, and the results revealed that TDS had potent cytotoxicity against testing cells with IC50 values of 45.8, 17.4, 53.6, 98.4 and 23.4 µg/mL, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis was employed to clarify the cytotoxic constituents in TDS of B. rynchopetera and five volatile compounds, including 2-ethyl-2,5-cyclohexadiene-1,4-dione (3, 31.00%), 1-tridecene (5, 28.02%), 2-methyl-2,5-cyclohexadiene-1,4-dione (2, 22.86%), hydroquinone (4, 1.33%), and p-benzoquinone (1, 1.01%), were identified. Chemical constituent investigation on TDS further supported the presence of 5 above compounds. A cytotoxic assay indicated that compounds 1, 2, 3 and 4 exhibited significant cytotoxicity against the testing cell lines, implying that benzoquinones and hydroquinone played important roles in the cytotoxicity of TDS of B. rynchopetera. TDS is a cytotoxic natural material and further studies investigating mechanisms and inhibitory activities on other cell lines is warranted.

Influence of SCARB1 gene SNPs on serum lipid levels and susceptibility to coronary heart disease and cerebral infarction in a Chinese population.

The SCARB1 gene encodes human scavenger receptor class B type I (SR-BI), the primary receptor for high-density lipoprotein (HDL)- cholesteryl ester uptake, and polymorphisms in this gene may influence SR-BI protein expression and serum lipid levels, modulating susceptibility to coronary heart disease (CHD) and cerebral infarction (CI). Therefore, we investigated the association between singlenucleotide polymorphisms (SNPs) in the SCARB1 gene and serum lipid levels as well as risk of CHD and CI in the Chinese Han population. Genotypes in 295 CHD patients, 302 CI patients and 312 healthy controls matched for age and gender were determined by high-resolution melting (HRM). Among the 5 SNPs investigated in this study, rs10846744 and rs2278986 were significantly associated with CHD risk. The frequency of the C allele for rs10846744 and that of the T allele for rs2278986 appeared to be significantly increased in the CHD group (OR: 1.416, 95%CI: 1.128-1.778, P=0.0058 and OR: 1.681, 95%CI: 1.327-2.130, P<0.0001, respectively). CHD patients with genotypes CC and CG for rs10846744 had a higher HDL-c level than those with genotype GG, and CHD patients with genotypes CC and CT for the rs2278986 SNP had a higher HDL-c level compared to those with the TT allele. The other 3 SNPs, rs5888, rs10744182 and rs838893, showed no significant association with serum lipid levels and CHD or CI risk in the Chinese population. The CCCTT and CCTTC haplotypes of rs5888, rs10846744, rs10744182, rs2278986 and rs838893 appear to significantly increase CHD risk, whereas the CGTTC, CCTCT and TGCTC haplotypes appear to significantly reduce risk. Overall, the CCTTC and TGTTC haplotypes acted as a significant risk for CI, with the CGCTC and CCCCT haplotypes conferring significantly reduced risk. These results suggest that SCARB1 gene polymorphisms may contribute to genetic susceptibility to CHD; in particular, the C allele of rs10846744 and the C allele of rs2278986 may serve as risk and protective factors for CHD, respectively.

[Imbalance of Th17 and Treg cells in peripheral blood from multiple myeloma patients].

OBJECTIVE: To investigate the ratio of Th17 cells and CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells in peripheral blood from patients with multiple myeloma (MM) and explore its pathological effects. METHODS: 70 MM patients were divided into three groups: newly diagnosed group (n=30), plateau stage group (n=23) and relapsed/refractory group (n=17). The controls consisted of 20 healthy donors. The frequencies of Th17 and Treg cells were detected by flow cytometry. RESULTS: Compared with controls [(0.72±0.33)%] and plateau stage group [(0.74±0.29)%], frequencies of Th17 cells were higher in newly diagnosed group [(1.62±0.65)%] and relapsed/refractory group [(1.45±0.51)%], respectively (P<0.05). Compared with controls [(2.33±0.90)%] and plateau stage group [(1.69±0.70)%], frequencies of Treg cells were significantly lower in newly diagnosed group [(0.55±0.23)%] and relapsed/refractory group [(0.82±0.54)%], respectively (P<0.05). The ratios of Th17/Treg in newly diagnosed group and relapsed/refractory group were higher than those in controls (P<0.05). There were no differences of the frequencies of CD3⁺CD4⁺ T cells and Th17 cells between plateau stage group and controls. The frequencies of Treg cells were significantly lower in plateau stage group than that in controls (P<0.05), and the ratio of Th17/Treg was significantly higher in plateau stage group than that in controls (P<0.05). CONCLUSION: The remarkable abnormality of T cells subsets was reduction of CD4⁺ T cells in MM. Higher frequency of Th17 and lower ratio of Treg could lead to imbalance of Th17/Treg, which may play a critical role in the pathogenesis of MM.

[Ratio balance of Th17 and Treg cells in peripheral blood of patients with chronic lymphocytic leukemia].

This study was purposed to investigate the ratio of Th17 cells and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood of patients with chronic lymphocytic leukemia (CLL) and to explore their roles in the pathogenesis and clinical diagnosis. Based on the number of peripheral lymphocytes and treatment condition, the CLL patients were divided into 2 groups: untreated group (n = 30) and remission group (n = 15), the healthy control group (n = 20) was set up as well. The frequencies of Th17 and Treg cells of all cases were detected by flow cytometry (FCM). The results showed that frequencies of CD3(+)CD4(+)T cells and Th17 cells were significantly higher in untreated group than that in healthy control group (P < 0.05), the frequencies of CD3(+)CD8(+)T cells and Treg cells were significantly lower in untreated group than that in healthy control group (P < 0.05), the ratio of Th17/Treg was significantly higher in untreated group than that in healthy control group (P < 0.05). The frequencies of Th17 were not statistically different between remission and healthy control groups, the frequencies of Treg cells were significantly lower in remission group than that in healthy control group (P < 0.05), the ratio of Th17/Treg was significantly higher in remission group than that in healthy control group (P < 0.05), frequencies of Th17 cells were markedly lower in remission group than that in untreated group (P < 0.05). It is concluded that Th17/Treg imbalance exists in patients with CLL, which may play a key role in pathogenesis and development of CLL.