Low apolipoprotein M serum levels correlate with Systemic lupus erythematosus disease activity and apolipoprotein M gene polymorphisms with Lupus.

BACKGROUND: Sequence variation in gene promoters is often associated with disease risk. In this study, we tested the hypothesis that common promoter variation in the APOM gene is associated with systemic lupus erythematosus (SLE) risk and SLE-related clinical phenotypes in a Chinese cohort. Meanwhile, we investigated the expression of apolipoprotein M (APOM) in the serum of patients with systemic lupus erythematosus (SLE) and its relationship with disease activity. METHODS: We used a case-control design and genotyped 52 SLE patients and 52 healthy controls for 19 APOM promoter single nucleotide polymorphism (SNP) (rs113947529, rs1143030, rs114826514, rs116715239, rs12525463, rs1266078, rs2273612, rs28432254, rs34490746, rs4947251, rs55880811, rs707921, rs74890500, rs75629491, rs76611345, rs76794541, rs805264, rs805297, rs9267528). Genotyping was done by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The blood serum concentration of APOM was measured by an enzyme-linked immunosorbent assay in SLE patients and controls. RESULTS: The average concentration of APOM in serum was significantly lower in SLE patients compared to controls and APOM levels in SLE patients with positive anti-dsDNA antibodies were dramatically lower than that of patients with negative anti-dsDNA antibodies (P = 0.011). It was interesting that APOM levels correlated with systemic lupus erythematosus disease activity index (SLEDAI) scores (r = -0.396, P = 0.004). No association between APOM and SLE susceptibility was detected in our Han Chinese cohort. CONCLUSIONS: Our results demonstrated that lower APOM levels in SLE patients and correlated with disease activity.

Characteristics of lipid metabolism including serum apolipoprotein M levels in patients with primary nephrotic syndrome.

BACKGROUND: Apolipoprotein M (apoM) is a 26-kD apolipoprotein that is mainly expressed in specific cell types, such as human liver parenchymal cells and kidney proximal renal tubular epithelial cells. ApoM can regulate the formation of pre-ß-HDL and the reverse cholesterol transport and thus plays an important role in the metabolism of lipids and lipoproteins, meaning that it can affect the development of lipid metabolism disorders. Significantly elevated serum apoM levels are detected in patients with hyperlipidemia. However, few studies have shown how apoM is expressed in primary nephrotic syndrome (PNS), which is often accompanied with hyperlipidemia, and the underlying mechanism is poorly understood. This study was aimed at examining the apoM levels in patients with PNS and at determining the effects of PNS on serum apoM levels in these patients. METHODS: This study included patients with hyperlipidemia (n = 37), the PNS with hyperlipidemia group (n = 62), PNS without hyperlipidemia group (n = 33), and healthy controls (n = 73). The age and body-mass index (BMI) matched among the groups of participants. Their serum apoM concentrations were measured by an enzyme-linked immunosorbent assay. Serum levels of conventional lipids and renal function indices were assessed using an automatic biochemical analyzer. The data were analyzed by means of Pearson's correlation coefficient (continuous variables) or Student's t test (mean differences). RESULTS: The average serum apoM concentrations were higher in the hyperlipidemia group (61.1 ± 23.2 mg/L, P = 0.004) than in the healthy controls (31.6 ± 18.92 mg/L). The serum apoM concentrations were lower in the PNS with hyperlipidemia group (25.1 ± 16.31 mg/L, P = 0.007) and in the PNS without hyperlipidemia group (21.00 ± 17.62 mg/L, P = 0.003) than in the healthy controls. The serum apoM concentrations in the PNS with hyperlipidemia group did not differ significantly from those in the PNS without hyperlipidemia group (P = 0.083). Moreover, serum apoM levels positively correlated with serum high-density lipoprotein cholesterol (HDL-C) and apoA1 levels and negatively correlated with proteinuria in PNS patients (r = 0.458, P = 0.003; r = 0.254, P = 0.022; r = -0.414, P = 0.028). CONCLUSION: Serum apoM concentrations are higher in patients with hyperlipidemia than in healthy controls. Low serum apoM levels in patients with PNS are likely caused by PNS.

Apolipoprotein M Serum Levels Correlate with IgA Vasculitis and IgA Vasculitis Nephritis.

OBJECTIVE: IgA vasculitis (lgAV) is the most frequent vessel vasculitis in children, and the prognosis is related to the children's age and degree of nephritis. This study is aimed at investigating serum apolipoprotein M (apoM) levels in patients with lgAV patients and at evaluating the association between apoM and disease severity. METHODS: A total of 109 lgAV patients and 76 age- and sex-matched healthy controls were included. The age and gender of the study participants were matched. ApoM levels were measured by an enzyme-linked immunosorbent assay. Additionally, the serum levels of lipids, apolipoproteins, kidney biochemical profiles, immunoglobulins (IgA, IgG, IgM, and IgE), and the complements (C3 and C4) were assessed using an automatic biochemical analyzer. RESULTS: ApoM was increased significantly in lgAV patients compared to healthy controls. ApoM, meanwhile, was lower in patients with nephritis than in those without nephritis. The apoM levels were higher in classes I and II IgA vasculitis nephritis (lgAVN) patients than in classes III and IV. Besides, the apoM serum level < 24.81 mg/L was an independent predictive factor for lgAVN and can be independently associated with the presence of nephritis in lgAV patients. Meanwhile, the serum apoM concentration negatively correlated with the ISKDC grading score in lgAVN patients. CONCLUSIONS: Serum apoM was elevated in lgAV patients and decreased gradually with the ISKDC grading score. ApoM (OR = 0.32, 95%CI = 0.12-0.85, p = 0.023) was identified as a protective factor for nephritis in all lgAV patients.

Diagnostic value of serum PIVKA-II levels for BCLC early hepatocellular carcinoma and correlation with HBV DNA.

BACKGROUND: It is reported that prothrombin induced by vitamin K absence-II (PIVKA-II) has a better performance of diagnosis for HCC, and has also been known to be an independent risk factor for vascular invasion. Few studies study the relationship between PIVKA-II and HBV DNA. OBJECTIVE: To determine the clinical value of serum Prothrombin induced by vitamin K absence-II (PIVKA-II) in early hepatocellular carcinoma (HCC), and to explore its relationship with vascular invasion and HBV DNA. METHODS: In a Chinese cohort, we conducted a case-control study to compare the performances of a-fetoprotein (AFP) and PIVKA-II serum levels for diagnosis of HCC and early HCC. Fifty one healthy controls, 37 chronic hepatitis patients, 43 cirrhotic patients and 143 HCC cases of which 48 (33.57%) had early stage HCC (n= 19 very early, n= 29 early) were enrolled. We explored the correlation between PIVKA-II serum level and several pathological features such as vascular invasion. The serum levels of and AFP were measured by chemiluminescence assay (CLIA) and electrochemiluminescence assay (ECLA). RESULTS: The serum levels of both PIVKA-II and AFP in HCC group were higher than that in chronic hepatitis, cirrhosis and healthy control groups. The sensitivity, specificity, positive predictive value, negative predictive value and kappa of PIVKA-II were higher than AFP in the diagnosis of HCC. Serum PIVKA-II level was correlated with tumor size, tumor cell differentiation and BCLC staging (P< 0.05). For the diagnosis of early HCC, the combination of PIVKA-II (AUC 0.812; 95% CI, 0.702-0.894) and AFP (0.797; 95% CI, 0.686-0.883) slightly improve the diagnostic performance for early HCC(AUC 0.849; 95% CI, 0.745-0.923). PIVKA-II > 166 mAU/ml is an independent risk factor for vascular invasion. The serum HBV DNA level in cirrhosis and HCC patients was significantly higher than in chronic hepatitis patients. We detected a negative association between serum PIVKA-II and serum HBV DNA levels. CONCLUSIONS: PIVKA-II was more efficient than AFP for the diagnosis of early HCC and has no correlation with serum HBV DNA levels.

Antifungal activity of spider venom-derived peptide lycosin-I against Candida tropicalis.

Candida species are a major cause of human mucosal and deep tissue fungal infections, but few antifungal treatments are available. Here, we showed that lycosin-I, a peptide isolated from venom of the spider Lycosa singoriensis, acted as a potent antifungal inhibitor against Candida species. The MIC50 values of lycosin-I reached 8 µg/mL to treat fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates. Time-kill kinetics assays revealed that after a 2-hour exposure, lycosin-I reduced colony-forming units/mL in fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates approximately 70%. Furthermore, salinity tolerance assays suggested that even in the presence of Mg2+, lycosin-I maintained its potent antifungal ability at a high concentration. When the concentration of lycosin-I was increased from 1 × MIC to 8 × MIC, a significant decrease of the biofilm metabolic activity was observed in both fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates. Moreover, the biofilm inhibitory concentration 50 (BIC50) and the biofilm eradicating concentration 50 (BEC50) were approximately 32 µg/mL and 128 µg/mL, respectively. Confocal laser scanning microscopy showed the localization of CY5-labeled lycosin-I mainly in the cell cytoplasm, and lycosin-I was likely to be localized in the cytoplasm after its transportation across the cell wall and membrane. Overall, our work shows that lycosin-I is a potent antifungal agent with a high efficacy, a high salinity tolerance, and potent anti-biofilm properties.

Urinary NGAL for the diagnosis of the renal injury from multiple myeloma.

OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) has been proved as a sensitive biomarker in acute and chronic renal injury. Renal impairment is a common complication of multiple myeloma (MM). We attempt to assess the value of NGAL for the early and accurate diagnosis of renal injury in MM patients. METHODOLOGY: Forty-five MM patients with CKD stage I to V(MM-renal group), 20 MM patients with normal kidney function (MM-non-renal group), and 37 healthy volunteers (healthy control) were compared for serum and urinary NGAL and other renal injury biomarkers (Creatinine[CRE]; Cystatin-C [CysC]; N-acetyl-beta-D-glucosaminidase [NAG]). Other biomarkers reflect the inflammation and tumor burden like high-sensitivity C-reactive protein(hs-CRP) and urine free light chain were also detected. RESULTS: Among the biomarkers of renal injury, the assessment of serum CysC, CRE and NGAL was a reliable tool to distinguish MM-renal from MM-non-renal. Both serum and urinary NGAL levels were higher in MM-renal patients than in MM-non-renal or healthy controls (187.10 (45.60-699.60) vs 136.70 (47.70-216.50) vs 117.7 (69.3-192.3), P< 0.01; 37.50 (6.30-412.10) vs 18.00 (0.50-66.50) vs 11.2 (0.9-69.1), P< 0.01). Univariate analysis showed that both serum (Odds Ratio = 1.009; 95%CI 1.002-1.017; P= 0.018) and urinary NGAL (Odds Ratio = 1.038; 95%CI 1.003-1.073; P= 0.031) as well as serum CysC (Odds Ratio = 9.875; 95%CI 1.685-57.882; P= 0.011) were strong predictors for the risk of renal injury in MM patients. Moreover, the urinary NGAL level was negatively correlated with estimated glomerular filtration rate (eGFR) (r= -0.586, P= 0.00003) and has a tendency towards positive correlation with urine free light chain (r = 0.235, P = 0.124) and hs-CRP (r = 0.379, P = 0.074). CONCLUSIONS: The present study demonstrated that urinary NGAL was not superior to serum NGAL in distinguishing MM-renal group from MM-non-renal group. And it could be considered an independent predictor of renal injury from multiple myeloma reflecting active kidney damage, tumor burden, and inflammation.