Topical calcineurin inhibitors in the treatment of oral lichen planus: a systematic review and meta-analysis.

BACKGROUND: TCS (topical corticosteroids) are the first-line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, pimecrolimus and ciclosporin for OLP is still controversial. OBJECTIVES: To compare the efficacy and safety of TCI vs. TCS for OLP. METHODS: The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events. RESULTS: Twenty-one trials involving 965 patients were included in the analysis. For the treatment of OLP (3-8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus-TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short-term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious. CONCLUSIONS: The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short-term treatment in recalcitrant OLP. Further well-designed trials are warranted to evaluate the long-term efficacy and safety of TCI. What's already known about this topic? The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS). Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs. Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune-mediated diseases. What does this study add? TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short-term treatment of OLP. The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious. The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short-term and long-term efficacy and safety of TCI compared with TCS.

Hypomethylation of interleukin-6 (IL-6) gene increases the risk of essential hypertension: a matched case-control study.

Essential hypertension (EH) is a chronic disease with clear epigenetic component. Inflammation and endothelial dysfunction have a great role in the development of persistent blood pressure elevation. The aim of this study was to explore an association between EH and DNA methylation in pro-inflammation cytokine gene interleukin-6 (IL-6) during the inflammatory process. We performed methylation analysis of peripheral blood DNA using bisulphite pyrosequencing technology between 96 EH patients and 96 age- and gender-matched healthy controls. The present results showed that three cytosine-phosphate-guanine (CpG) sites of IL-6 promoter CpG island had different lower methylation in EH group compared with controls, but only CpG2 (58.43±7.53 versus 62.34±9.65, P=0.004) and CpG3 (51.52±6.18 versus 57.45±8.29, P<0.001) had statistical difference. Logistic regression analysis found CpG3 hypomethylation was a risk factor of EH (odds ratio=1.111, adjusted P=0.004). In addition, we found hypermethylation of CpG1 (64.84±7.06 versus 61.84±8.61) and CpG2 (62.04±7.40 versus 59.30±9.57) in male compared with female. In male, we found hypomethylation of CpG2 (60.41±7.74 versus 64.28±6.36) and CpG3 (53.70±8.62 versus 57.78±7.87) of smoker versus non-smoker and hypomethylation of CpG2 (60.89±7.32 versus 64.70±7.03) and CpG3 (53.23±7.99 versus 60.48±7.58) of drinker versus non-drinker. Furthermore, the CpG2 and CpG3 had a negative correlation with systolic blood pressure and diastolic blood pressure (P<0.05). Receiver operating characteristic curve analysis showed that CpG2 (area under curve: 0.638, P=0.001) and CpG3 (area under curve: 0.704, P<0.001) had a diagnostic value to predict the risk of EH. In summary, our study revealed hypomethylation of IL-6 was correlated with the risk of EH in the population assessed and we found the differences of IL-6 promoter methylation in gender, smoking and drinking.

Characterization of mullerian inhibiting substance binding on cervical carcinoma cells demonstrated by immunocytochemistry.

Müllerian inhibiting substance (MIS) is a glycoprotein released from Sertoli cells or follicular cells of gonads, responsible for the regression of Müllerian ducts and/or Müllerian-derived tumor cells. Binding of MIS to target cells is essential for initiating regression. A human cervical carcinoma CaSki cell was examined by quantitative immunocytochemistry detected by anti-avian MIS antibody for MIS binding ability. Various treatments of WGA-peroxidase conjugate, enzyme digestion, sodium periodate or exogenous estrogen before antibody recognition were performed. It was found that the WGA partially blocked MIS binding to CaSki cell surfaces. Protease digestion of CaSki cell surfaces prior to addition of MIS or an anticervical carcinoma monoclonal antibody 1H10 (MAb 1H10), blocked the binding of MIS but not MAb 1H10 to cell surfaces. Sodium periodate and overnight exposure of CaSki cells to estrogen or diethylstilbestrol before or after fixation of the cells, did not influence MIS binding ability in vitro. MIS binding was higher on avian Müllerian duct compared with MIS binding to CaSki cells by quantitative immuno-gold labeling analysis. MAb 1H10 immuno-gold complexes binding to CaSki cells was also obtained and compared with MIS immuno-gold bindings. MIS binding site could be a polypeptide which survived sodium periodate treatment. The 'critical window' period, in which developing Müllerian ducts respond to exogenous estrogen protection from MIS regression, is possibly lost in CaSki cell.

Physical properties of some snake plasma albumins.

The albumin-like proteins were purified from the plasma of three terrestrial elapids and two sea snakes. The albumin-like fraction averaged 25% (range: 21-30%) in concentration of the total plasma proteins as determined by densitometer. The physical properties of the albumin-like proteins purified from these snakes were compared. These properties, e.g. electrophoretic mobility, isoelectric point, extinction coefficient, and molecular weight, were shown to be strikingly similar to those of human plasma albumin. The physical properties of the plasma albumins of the snakes studied are similar to one another. This similarity does not explain our previous observation that Naja albumin is considerably remote immunologically from those of other elapids (Mao et al., 1983).

Hemoglobin fingerprint correspondence and relationships of Taiwan common venomous snakes.

Peptide fingerprints of tryptic digests of globins of 6 venomous snakes representing 2 families and 3 subfamilies were compared. The evolutionary relationships of these snakes derived from globin peptide fingerprints are consistent with those based upon morphological criteria. Globins of Trimeresurus mucrosquamatus and Trimeresurus s. stejnegeri are most alike, differing in 19 components. The average from globins of the 2 Trimeresurus compared with Agkistrodon shows a difference of 24 components. The average difference between the 3 crotalines and Vipera is 26. Naja globin is most divergent in structure, differing from those of the 4 viperids by 42-44 peptides, and from that of Bungarus by 32 peptides.