Obesity is associated with numerous immunological disorders. The present study investigated the proportion and phenotype of myeloid‑derived suppressor cells (MDSCs) in the plasma of obese subjects and the association of these cells with the level of liver enzymes. Certain features of the immune response in obese subjects were examined by analyzing the expression of T cell receptor‑ζ (TCRζ) molecules on the surface of T cells. The expression and secretion of S100A9, a possible marker for MDSCs, were detected in the peripheral blood of obese subjects and compared with levels in lean controls. Results showed that the percentage of monocytic MDSCs, with the phenotype CD33+CD11b+CD14+HLADRlow/‑, was significantly increased in obese subjects compared with lean controls. The circulating level of monocytic MDSCs was positively correlated with the levels of liver enzymes in serum. The expression of the TCRζ molecule in the resting T cells was significantly lower in obese individuals than that of lean controls. The expression of S100A9 was detected in the majority of monocytes in peripheral blood mononulear cells, but no difference was identified in the frequency of CD14+S100A9+ cells between the obese and lean groups. However, the plasma level of S100A8/9 was significantly increased in obese compared with lean subjects. These observations suggested that the increased frequency of CD33+CD11b+CD14+HLADRlow/‑ cells may be responsible for the impaired T‑cell function and liver injury observed in obesity.

Protein Z-dependent protease inhibitor (ZPI) 2 was recently identified as a serpin that potently inhibits activated blood coagulation factor X (FXa) (EC 3.4.21.6) in a manner dependent on protein Z, Ca 2ϩ , and phospholipids (1-3) and the action of which is largely ablated in the presence of FVa (3). ZPI is estimated to be present at 3.8 g/ml (53 nM) in plasma, forms non-covalent complexes with protein Z in plasma, and has an apparent mobility of 72 kDa on SDS-PAGE (3, 4). ZPI is 25-35% homologous to human serpins (2) and 70% homologous to rat liver regeneration protein rasp-1 (5). It has an unusual P1 residue of Tyr-387, and the mutant Y387A did not inhibit FXa (2). Besides inhibiting FXa, ZPI inhibits FXIa (EC 3.4.21.27) in a reaction stimulated 2-fold by heparin and not requiring protein Z (3). Recently, mutations in ZPI that generate stop codons at residues Arg-67 or Trp-303 were found to be significantly associated with venous thrombosis (6), although a different study found no association between ZPI or protein Z levels and venous thrombosis (7).Protein Z is a 62-kDa vitamin K-dependent plasma protein that circulates almost entirely as a complex with protein Z-dependent protease inhibitor and has a wide range in plasma of 2.6 Ϯ 1 g/ml (4, 8). The cofactor role of protein Z in FXa inhibition by ZPI is the first clearly identified function for human protein Z, although bovine and not human protein Z enhances the binding of thrombin to membrane surfaces (9).Protein Z gene knock-out mice have no gross abnormalities, but thrombotic manifestations are exacerbated in an FV Leiden pedigree (10). For humans with FV Leiden, low protein Z is associated with an earlier age of first thrombosis and more frequent thrombotic events (11). Protein Z genetic polymorphisms that are associated with reduced protein Z plasma levels were recently reported (12, 13). Low protein Z was reported to be associated with ischemic stroke (14 -16), although there are conflicting reports of high protein Z in association with stroke (17) or with large artery stroke (18) and one report of no relationship between protein Z levels and stroke (19). Low protein Z is associated with anti-protein Z antibodies and unexplained early fetal loss, which could involve thrombosis (20). Low protein Z levels are associated with antiphospholipid antibodies in women (21) and with a 7-fold increased risk of arterial thrombosis in patients with antiphospholipid syndrome (22).Although ZPI was reported in preliminary studies not to inhibit FIXa (3) (EC 3.4.21.22), we investigated whether ZPI might inhibit FIXa in the FXase complex, as well as FXa in the prothrombinase complex. If so, we wondered whether FVIIIa might protect FIXa from ZPI inhibition, as FVa protects FXa from ZPI inhibition, and whether protein Z might be required for inhibition of FIXa. The homologous prothrombinase and FXase complexes work in tandem to generate thrombin (EC 3.4.21.5), and a physiologic inhibitor of both complexes could be particularly significant. EXPERIMENTAL PROCEDURESPlasma-de...

Hepatitis B virus (HBV) infection is a major risk factor for the development of hepatic cirrhosis (HC) and hepatocellular carcinoma (HCC), which are associated with very high morbidity and mortality rates worldwide. Many studies have shown that long noncoding RNAs (lncRNAs) that are highly expressed in HCC (lncRNA-HEIH) and highly upregulated in liver cancer (lncRNA-HULC) have been implicated in the development and progression of hepatitis B-related HC and HCC. In this study, reverse transcription and quantitative PCR were used to detect the expression of lncRNA-HEIH and lncRNA-HULC and western blot analysis to detect the expression of hepatitis B X-interacting protein (HBXIP). RNA immunoprecipitation was used to detect the interaction of HBXIP with lncRNA-HULC and lncRNA-HEIH. The results showed that lncRNA-HEIH, lncRNA-HULC, and HBXIP were upregulated in hepatitis B patients, particularly those with hepatitis B-related HCC. Both lncRNA-HEIH and lncRNA-HULC interacted with HBXIP. These results suggest that lncRNA-HEIH and lncRNA-HULC interact with HBXIP in hepatitis B-related diseases.

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