A deficiency of complement factor H may lead to excessive consumption of C3 and an increase in C3b deposition, which are important pathological characteristics of lupus nephritis. Complement factor H-related proteins (CFHRs), comprising CFHR1 to CFHR5 (CFHR1–5), are members of the wider factor H/CFHR family. Their role in lupus nephritis remains unclear. In this study, we compared circulating levels of CFHR1–5 in 152 patients diagnosed with lupus nephritis and 20 unrelated healthy individuals to explore the relationship between the expression of CFHR1–5 and development of the disease. We found that plasma levels of CFHR3 and CFHR5 were higher in patients with lupus nephritis than in healthy individuals; also, CFHR3 and CFHR5 concentrations increased with increasing systemic lupus erythematosus disease activity index (SLEDAI) values (P < 0.05). Pearson's and Spearman's correlation test results confirmed that plasma CFHR3 and CFHR5 levels in lupus nephritis patients were positively correlated with proteinuria and levels of creatinine (Cr) and anti-dsDNA (correlation coefficients = 0.491–0.717, P < 0.05), while they were negatively correlated with plasma C3 levels and eGFR [correlation coefficients = –(0.706–0.788), P < 0.05]. Receiver operating characteristic (ROC) curve analysis results confirmed that plasma CFHR3 and CFHR5 levels were predictive of SLEDAI values and disease end points (area under the curve = 0.664–0.884, P < 0.05), with patients with both high CFHR3 and high CFHR5 exhibiting the shortest progression-free survival. Thus, both CFHR3 and CFHR5 are of prognostic value in lupus nephritis status. 相似文献
Introduction: Besifovir (LB80380) is a relatively new oral acyclic nucleotide phosphonate. We reviewed the pharmacokinetic characteristics of LB80380 and discussed its role in the treatment of chronic hepatitis B infection.
Areas covered: LB80380 is a prodrug of LB80331 and LB80317. It is rapidly absorbed when taken orally. Escalating doses of besifovir produce linear increase of the plasma concentration. Doses above 60mg are effective for inhibiting HBV in human. Using 60mg as an example, the maximal concentration of LB80331 in plasma is 397 ng/mL. The time required to reach maximal concentration in plasma and elimination half-life are 2.0 and 3.0 h, respectively. Besifovir and its metabolites are mainly excreted via the kidneys. Its antiviral efficacy is non-inferior to ETV 0.5mg daily. It is generally safe in terms of renal and bone toxicity. The most common adverse event is carnitine depletion which affects almost all patients on besifovir requiring carnitine supplementation.
Expert opinion: Besifovir demonstrated predictable pharmacokinetic characteristics in human subjects. Few clinical studies on besifovir have been conducted. More data are expected particularly for special populations. The adverse events upon long term exposure should be monitored. Large scale head-to-head trials comparing besifovir with existing NA, especially tenofovir alafenamide, should be conducted. 相似文献
To extend the applications of engineered nanomaterials, such as graphene oxide (GO), it is necessary to minimize cytotoxicity. However, the mechanisms underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have been used to illustrate the molecular bases of gene expression, which offers a more sensitive and cutting-edge technology to elucidate complex biological processes associated with epigenetic regulations. In this study, the role of GO-triggered chromatin interactions in the activation of cox2, a hallmark of inflammation, was investigated in normal human cells. Using chromosome conformation capture technology, we showed that GO triggers physical interactions between the downstream enhancer and the cox2 promoter in human embryonic kidney 293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which was required for high cox2 expression. Moreover, tumor necrosis factor-α (TNF-α), located upstream of the p65 signaling pathway, contributed to the regulation of cox2 activation through dynamic chromatin architecture. Compared with pristine GO and aminated GO (GO-NH2), poly (acrylic acid)-functionalized GO (GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin architecture. Our results mechanistically link GO-mediated chromatin interactions with the regulation of cox2 and suggest that GO derivatives may minimize toxicity in practical applications. 相似文献
Although hypodontia, or oligodontia, is one of the most common human dental anomalies observed, there have been few studies on the association of other anomalies occurring with it. The present investigation of 1032 patient records found that 65.7% of patients with hypodontia showed ankylosis of primary molars compared to only 1.5% of control children (P less than 0.001). In addition, taurodontism of the mandibular first permanent molar was observed in 34.3% of hypodontia cases compared to 7.1% in the controls (P less than 0.001). Other dental anomalies significantly associated with hypodontia include enamel hypoplasia (11.9%, P less than 0.01) and conical incisors (8.9%, P less than 0.01). In contrast, there were significantly more impacted teeth in control children compared to the hypodontia group. The results indicate that for patients with missing permanent teeth, clinicians should be alert to the possibility of these associated anomalies and their accompanying clinical implications. 相似文献
Residual monomer contents and surface hardness are important factors in determining the serviceability of provisional restorations. The intent of this study was to systemically evaluate the effects of curing conditions on provisional polymethyl methacrylate (PMMA) resins which utilize a free-radical polymerization reaction. Combinations of the three curing factors of temperature, pressure, curing environment (water/air) were adjusted during the fabrication of autopolymerized specimen disks. The initial hardness of tested materials was measured with a microhardness tester 1 h after disc fabrication, and the amounts of residual methyl methacrylate (MMA) released into water were analyzed by reverse-phase HPLC after 7 d of water immersion. Results from multiple regressions showed that curing temperature was the dominant factor in improving resin surface hardness, whereas curing in water was the key factor for reducing the quantity of residual monomer. The pressure factor, which was thought to be critical for managing autopolymerized resins, showed no significant influences on the properties tested. ANOVA results showed that provisional PMMA resins cured in hot water, with or without pressure, significantly reduced the amount of residual MMA elution (up to 80%) and increased the microhardness values (up to 50%). 相似文献