Establishment of an immune-related gene prognostic model for head and neck tumors.

This study aimed to screen the key immune-related genes (IRGs) in head and neck squamous cell carcinoma (HNSC) and construct the IRGs-related prognostic model to predict the overall survival (OS) of patients with HNSC. The RNA-seq data and clinical data were downloaded from The Cancer Genome Atlas database, and IRGs were obtained from the Immunology Database and Analysis Portal. Differentially expressed genes (DEGs) between HNSC and normal samples were identified, followed by integration with IRGs to screen differentially expressed IRGs. After univariate and multivariate proportional hazard regression analyses, an IRG-based risk model was constructed. Meanwhile, data chip of GSE65858 as the validation set to assess the predicted performance of established model. Next, univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factor of HNSC, and the Nomogram model was developed to predict patient outcome. Furthermore, the correlation between immune cell infiltration and risk score was analyzed. A total of 65 differently expressed IRGs associated with prognosis of HNSC were screened, and finally a 26-gene IRG signature was identified to construct a prognostic prediction model. The AUC of ROC curve was 0.750. Survival analysis showed that patients in the high-risk group had a worse prognosis. Independent prognostic analysis showed that risk score could be considered as an independent predictor for HNSC prognosis. Nomogram assessment showed that the model had high reliability for predicting the survival of patients with HNSC in 1, 2, 3 years. Ultimately, the abundance of B cells and CD4+ T cell infiltration in HNSC showed negative correlations with risk score. Our IRG-based prognostic risk model may be used to estimate the prognosis of HNSC patients.

Antimicrobial effects of three herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) on membrane permeability and apoptosis in Salmonella.

AIMS: This study aimed synergistic effects of three herbs in Salmonella via increased membrane permeability and apoptosis. METHODS AND RESULTS: Using high-performance liquid chromatography, four types of phenylethyl glycosides and a lignan were detected in the herb mixture (Brassica juncea, Forsythia suspensa, and Inula britannica). During treatment with the herb mixture (1×, 2×, or 4× the MIC), viable cells decreased to 1·87 log CFU per ml (Salmonella Gallinarum) and 2·33 log CFU per ml (Salmonella Enteritidis) after 12 h of incubation according to inhibition of tricarboxylic acid cycle (P < 0·01). In addition, N-phenyl-1-naphthylamine uptake increased from 229·00 to 249·67 AU in S. Gallinarum and from 232·00 to 250·67 AU in S. Enteritidis (P < 0·05), whereas membrane potential decreased from 8855·00 to 3763·25 AU and from 8703·67 to 4300·38 AU, respectively. Apoptotic Salmonella cells were observed by confocal laser scanning microscopy and flow cytometry. Transmission electron microscopy observations with negative staining showed protein leakage from damaged Salmonella. CONCLUSIONS: These results showed the synergistic effect of the three herbs against avian pathogenic Salmonella induced by membrane damage and apoptosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Salmonella causes enormous economic losses in the poultry industry. These results indicated that potency of natural antimicrobial agents due to apoptosis in Salmonella.

[Prenatal diagnosis of women with an adverse reproductive history using both traditional karyotyping and SNP-array].

Objective: To explore the occurrence of fetal chromosomal abnormalities among pregnant women with an adverse reproductive history using traditional karyotyping and single nucleotide polymorphism microarray (SNP-array) technology. Methods: Totally 94 in 2 163 (4.35%) cases of singleton pregnant women with an adverse reproductive history were performed amniocentesis in Jinhua Maternal and Child Health Care Hospital from June 2015 to June 2017. Traditional karyotyping and SNP-array were employed simultaneously for prenatal diagnosis, and the detection rates of the two methods were compared. Results: All of the 94 specimens were successfully analyzed, 11 cases were found with chromosomal anomaly, the overall detection rate was 11.7%(11/94). Seven (7.4%,7/94) abnormalities cases were detected by karyotyping, and 7(7.4%) by SNP-array. The karyotyping results of trisomy 21, and 45,X and the deletion of chromosome 13 were consistent with SNP-array. Only 3 (3.2%, 3/94) microdeletion/duplications (the sizes of duplications and deletions were between 422.4-1 708.4 kb) and 1 (1/4) loss of heterozygosity were detected by SNP-array, but were missed by karyotyping. Furthermore, 2 cases' copy number variation were found pathogenic gene related, while the other 2 were considered benign or variant of uncertain significance. Four cases (4/7) of abnormalities were detected by karyotyping, while confirmed balanced translocation and inversion by SNP-array. All patients were informed and chosen to continue the pregnancy. Conclusions: The rate of abnormal fetal chromosomes in pregnant women with an adverse reproductive history is still high. SNP-array is a new molecular genetic technique, and combined with use of traditional karyotyping, it could improve the detection rate of fetal chromosomal abnormalities and reduce abortion rate, thus providing a basis for genetic counseling and prenatal diagnosis.

Changes in psychological health, subjective food intake ability and oral health-related quality of life during orthodontic treatment.

Assessing changes in patient's psychological health and oral health-related quality of life (OHRQoL) over time during orthodontic treatment may help clinicians to treat patients more carefully. To evaluate changes in mental health, self-reported masticatory ability and OHRQoL during orthodontic treatment in adults, this prospective study included 66 adults (30 men, 36 women; mean age, 24·2 ± 5·2 years). Each patient completed the Korean versions of the State-Trait Anxiety Inventory, Zung Self-Rating Depression Scale, Rosenberg self-esteem scale, key subjective food intake ability (KFIA) test for five key foods and Oral Health Impact Profile-14 (OHIP-14K) at baseline (T0), 12 months after treatment initiation (T1) and debonding (T2). All variables changed with time. Self-esteem and the total OHIP-14K score significantly decreased and increased, respectively, at T1, with a particular increase in the psychological and social disabilities scores. There were no significant differences in any questionnaire scores before and after treatment. The total OHIP-14K score was positively correlated with trait anxiety and depression, and negatively correlated with self-esteem and KFIA at T0, regardless of the treatment duration. Older patients showed a significant increase in the total OHIP-14K score at T1 and T2. OHRQoL worsened with an increase in the treatment duration. Our results suggest that OHRQoL temporarily deteriorates, with the development of psychological and social disabilities, during orthodontic treatment. This is related to the baseline age, psychological health and self-reported masticatory function. However, patients recover once the treatment is complete.

[Feasibility of the 2014 European guidelines risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy in Chinese patients].

Objective: Exploring the feasibility of the 2014 European Society of Cardiology(ESC)guideline's risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD) in Chinese patients. Methods: The study population consisted of a consecutive cohort of 172 Chinese patients with HCM without prior sudden cardiac death (SCD) event who were in patients in Nanjing Drum Tower Hospital from December 2010 to October 2015.The endpoint event was a composite of SCD and appropriate implantable cardioverter-defibrillator (ICD) therapy.Clinical data were collected to calculate the 5-year SCD risk using the HCM Risk-SCD formula and to observe the actual risk during the follow-up.Receiver operating characteristic curves (ROC) and the area under curve (AUC) were calculated for the HCM Risk-SCD and risk stratification methods of the 2011 American Heart Association (AHA) guideline. Results: During follow-up of (2.69±1.36) years, five patients achieved the endpoint event.The predicated rate of SCD event using HCM Risk-SCD was (2.36±1.73)%, (1.93±0.78)%, (5.18±0.65)%, (8.77±2.38)% for all patients, low-risk group, medium-risk group and high-risk group respectively.However, the actual rate of SCD event was 2.91%, 1.27%, 25.00% and 14.29%, respectively.The AUC of 2014 ESC guideline and 2011 AHA guidelinewas 0.93(95%CI 0.85-1.00) vs. 0.87(95%CI 0.75-0.98). Conclusion: The predicated rate of SCD event calculated by HCM Risk-SCD is lower than actual rate of SCD, but the prediction efficiency and indication for ICD implantation of HCM Risk-SCD are better than that of 2011 AHA guideline.

Subjective food intake ability related to oral health-related quality of life and psychological health.

Reduced food intake ability can restrict an individual's choice of foods and might have a significant impact on the individual's quality of life and mental health. The aim of this study was to evaluate the correlations between self-reported masticatory ability and oral health-related quality of life (OHRQOL) and psychological health. The study included 72 (26 men, 46 women) adults with a mean age of 26·4 ± 8·6 years. Each participant completed the key subjective food intake ability (KFIA) test for five key foods, the Korean version of the Oral Health Impact Profile-14 (OHIP-14K) and three questionnaires for measuring anxiety, depression and self-esteem. The participants were distributed into two groups by sex (a mean age of 23·9 ± 5·2 for men and 27·9 ± 9·8 for women) and by the median KFIA score. There were no significant differences in any of the variables according to sex. Thirty-two participants (12 men, 20 women) in the lower KFIA group had a higher total OHIP-14K (P < 0·001) and depression level (P < 0·05) than the 40 participants (14 men, 26 women) in the higher KFIA group. As the KFIA decreased, OHRQOL worsened (P < 0·001) and depression increased (P < 0·05). Participants with lower KFIA scores were more than 4·3 times as likely as to have a poor OHRQOL than the reference group (odds ratio, 4·348; 95% confidence interval, 1·554-12·170, P < 0·01). Lower subjective food intake ability is associated with a poor oral health-related quality of life and higher depression level.

Galectin isolated from parasite inhibits remission of experimental autoimmune encephalomyelitis by up-regulating autoantibody.

Recently, parasite infections or parasite-derived products have been suggested as a therapeutic strategy with suppression of immunopathology, which involves the induction of regulatory T cells or/and T helper type 2 (Th2) responses. In a recent study, researchers reported that constructed recombinant galectin (rTl-gal) isolated from an adult worm of the gastrointestinal nematode parasite Toxascaris leonina attenuated clinical symptoms of inflammatory bowel disease in mice treated with dextran sulphate sodium. Noting the role of rTl-gal in inflammatory disease, we attempted to investigate the effect of the parasite via its rTl-gal on neuronal autoimmune disease using experimental autoimmune encephalomyelitis (EAE), a mouse inflammatory and demyelinating autoimmune disease model of human multiple sclerosis. In this model, rTl-gal-treated experimental autoimmune encephalomyelitis (EAE) mice failed to recover after the peak of the disease, leading to persistent central nervous system (CNS) damage, such as demyelination, gliosis and axonal damage. Further, rTl-gal-treated EAE mice markedly increased the number of CD45R/B220(+) B cells in both infiltrated inflammation and the periphery, along with the increased production of autoantibody [anti-myelin oligodendrocyte glycoprotein (MOG)35-55 ] in serum at chronic stage. Upon antigen restimulation, rTl-gal treatment affected the release of overall cytokines, especially interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Our results suggest that galectin isolated from a gastrointestinal parasite can deliver a harmful effect to EAE contrary to its beneficial effect on inflammatory bowel disease.

TLR2-dependent amelioration of allergic airway inflammation by parasitic nematode type II MIF in mice.

In our previous studies, the recombinant type II macrophage migration inhibitory factor homologue (rAs-MIF) secreted from Anisakis simplex suppressed experimental inflammation mouse model through IL-10 production and CD4(+)CD25(+)Foxp3(+) T-cell recruitment. Also, TLR2 gene expression was significantly increased following rAs-MIF treatment. To know the relation between TLR2 and amelioration mechanisms of rAs-MIF, we induced allergic airway inflammation by ovalbumin and alum with or without rAs-MIF under TLR2 blocking systems [anti-TLR2-specific antibody (α-mTLR2 Ab) treatment and using TLR2 knockout mice]. As a result, the amelioration effects of rAs-MIF in allergic airway inflammation model (diminished inflammation and Th2 response in the lung, increased IL-10 secretion, CD4(+)CD25(+)Foxp3(+) T-cell recruitment) were diminished under two of the TLR2 blocking model. The expression of TLR2 on the surface of lung epithelial cell was significantly elevated by rAs-MIF treatment or Pam3CSK (TLR2-specific agonist) treatment, but they might have some competition effect on the elevation of TLR2 expression. In addition, the elevation of IL-10 gene expression by rAs-MIF treatment was significantly inhibited by α-mTLR2 Ab or Pam3CSK pretreatment. In conclusion, anti-inflammatory effects of the rAs-MIF on OVA-induced allergic airway inflammation might be closely related to TLR2.

Short communication: Physicochemical and antioxidant properties of milk supplemented with red ginseng extract.

This study investigated the effect of red ginseng extract (RGE) on the physicochemical properties, sensory test, and antioxidant activity of milk. The milk samples with RGE added at 0.5, 1, 1.5, and 2% were analyzed during storage at 4°C. The physicochemical properties included composition of milk, pH, titratable acidity, and color. The antioxidant activity of milk samples was determined using the 2,2-diphenyl-1-picrylhydrazyl method, ß-carotene bleaching assay, and ferric thiocyanate assay. An increase in the amount of RGE in milk resulted in an increase of lactose and total solids content, titratable acidity, and a* and b* values, whereas fat and protein contents remained unchanged. Also, pH and L* value decreased. The antioxidant activity of milk samples supplemented with RGE was higher than that of the control sample. Sensory evaluation was performed using a quantitative descriptive analysis. Two types of samples were used: (1) sterilized milk fortified with RGE (0.5, 1, 1.5, and 2%) and (2) 2% RGE, 2% RGE with oligosaccharide, and 2% RGE with oligosaccharide and cyclodextrin. The addition of oligosaccharide and cyclodextrin could effect an increase of sweetness, a decrease of bitterness and flavor of RGE, and aftertaste. Therefore, milk supplemented with RGE could be useful as a functional food.

A common environmental pollutant, 4-nonylphenol, promotes allergic lung inflammation in a murine model of asthma.

BACKGROUND: Exposure to environmental hormones, such as alkylphenols, has been suggested to be associated with the development of asthma, but the mechanism of action remains unclear. OBJECTIVE: This study examined the effect of 4-nonylphenol (NP), one of the most important alkylphenols, on conventional dendritic cells (cDCs) and adaptive T-cell responses. It also explored the role of aryl hydrocarbon receptor (AhR) in NP's effect. METHODS: NP-conditioned bone marrow-derived DCs (BM-DCs) and splenic CD11c(+) cDCs were assessed regarding function in a murine model under conditions relevant to route and level of exposure in humans. RESULTS: Our results showed that splenic cDCs from NP-exposed mice have potent Th2-skewing ability and secrete increased levels of IL-6 and TNF-α, but not IL-10 and IL-12, at baseline and after stimulation with LPS. Further, bone marrow-derived DCs were cultured in the presence of NP and showed similar cytokine pattern and influenced the antigen-specific T cells secreting significantly less IFN-γ. Importantly, NP-exposed mice developed more severe OVA-induced allergic lung inflammation compared with control group. Interestingly, in a congenic strain of mice carrying low-affinity, ligand-binding mutant AhR (AhR(d) ), NP's effect on DC functions and lung inflammation was not observed in vitro and in vivo. CONCLUSION: These results suggested that NP may disturb physiologic function of DCs through, in part, AhR-dependent mechanisms, supporting the importance of NP exposure on the regulation of DC functions and allergic inflammation.

Effects of Lactobacillus rhamnosus on asthma with an adoptive transfer of dendritic cells in mice.

AIM: This study was designed to investigate whether the protective effects of Lactobacillus rhamnosus (Lcr35) on allergic asthma are associated with the adoptive transfer of dendritic cells (DCs) and regulatory T cells (Tregs), using a mouse experimental model of asthma. METHODS AND RESULTS: BALB/c mice were orally administered Lcr35 or intravenously treated with in vivo Lcr35-treated DCs daily and were then sensitized and challenged with ovalbumin (OVA) in accordance with a model of asthma protocol. Both the oral application of Lcr35 and intravenous administration of Lcr35-treated DCs suppressed all aspects of the asthmatic response, including bronchial hyperresponsiveness (BHR), total cell counts in the bronchoalveolar lavage (BAL) fluid, the production of OVA-specificimmunoglobulin E (IgE), and pulmonary eosinophilic inflammation. The mechanism of action of Lcr35 is related to Tregs, which suppress the Th2 response in the respiratory organs, and this is mediated by DCs in the mouse model of asthma. CONCLUSIONS: These results confirm that the mechanism underlying the effects of Lcr35 on asthma involves the adoptive transfer of DCs. SIGNIFICANCE AND IMPACT OF THE STUDY: This finding broadens the possibility that Lcr35 has potential as an alternative therapeutic approach to the treatment of human asthma.

Psoriasis as initiator or amplifier of the systemic inflammatory march: impact on development of severe vascular events and implications for treatment strategy.

BACKGROUND: Psoriasis is a systemic disease associated with metabolic disorders and vascular complications. Both psoriasis and metabolic disorders are associated with systemic inflammation. We hypothesized that the sequence of events between the onset of psoriasis and metabolic disorder may affect the risk for subsequent development of vascular complications. METHODS: Nested case-control study was performed using the Taiwan National Health Insurance database. Accordingly, a total of 8180 psoriatic patients and 163,600 controls were included. Psoriasis was considered as the initiator of inflammatory march if metabolic disorder, including hypertension, diabetes mellitus and dyslipidemia, developed after onset of psoriasis. In patients with pre-existing metabolic disorder, psoriasis was considered as the amplifier of inflammatory march. RESULTS: In patients whose psoriasis served as the disease initiator, a lower risk for developing vascular disease (HR = 1.49; 95% CI = 1.11-2.00 and HR = 1.64; 95% CI = 1.31-2.05 for cerebrovascular and cardiovascular events, respectively) was found compared with patients whose psoriasis served as the disease amplifier (HR = 2.26; 95% CI = 1.72-2.97 and HR = 2.78; 95% CI = 2.26-3.42 for cerebrovascular and cardiovascular events, respectively) after adjusting for age and gender. In terms of treatment implications, methotrexate was associated with reduced risk for developing cerebrovascular event (HR = 0.22; 95% CI = 0.05-0.88) only in patients with psoriasis serving as the disease amplifier. CONCLUSIONS: Our results suggested that two scenarios of systemic inflammatory marches are present among psoriatic patients with metabolic disorder and judicious use of methotrexate may reduce the risk of cerebrovascular event, especially when psoriasis served as the disease amplifier of the systemic inflammatory march.

Mechanistic correlations between two itch biomarkers, cytokine interleukin-31 and neuropeptide ß-endorphin, via STAT3/calcium axis in atopic dermatitis.

BACKGROUND: Itch is the cardinal symptom of atopic dermatitis (AD). ß-Endorphin, a neuropeptide, is increased in both AD skin and sera. Interleukin (IL)-31, an itch-relevant cytokine, activates IL-31 receptors in keratinocytes. However, how IL-31 and ß-endorphin interact in AD skin remains elusive. OBJECTIVES: To investigate the mechanistic interaction of IL-31 and ß-endorphin in AD. METHODS: This was a prospective cross-sectional study. We recruited adult patients with AD and controls according to Hanifin's AD criteria. Serum levels of IL-31 and ß-endorphin were measured by enzyme-linked immunosorbent assay. Expressions of IL-31 receptor A (IL-31RA) and ß-endorphin in the skin were assessed by immunohistochemistry. Their expression in the skin and blood was compared and correlated in patients with AD and in controls. We also treated primary keratinocytes with IL-31 and measured calcium influx, ß-endorphin production and signalling pathways to define their mechanistic interactions. RESULTS: ß-Endorphin was increased in the supernatant from IL-31-treated keratinocytes. IL-31 receptor activation resulted in calcium influx and STAT3 activation; pretreatment with STAT3 inhibitor stopped the increase of ß-endorphin. Notably, either replacement of extracellular calcium or treatment with 2-aminoethoxydiphenyl borate, an inhibitor for the store-operated channel, blocked STAT3 activation. We found higher levels of blood ß-endorphin and IL-31, which were significantly correlated, in patients with AD. Moreover, IL-31RA and ß-endorphin were increased and colocalized both in AD human skin and TPA-painted mouse skin. CONCLUSIONS: IL-31 receptor activation in keratinocytes induces calcium influx and STAT3-dependent production of ß-endorphin. These results might contribute to an understanding of the regulatory mechanisms underlying peripheral itch.

Narrow-band UVB irradiation stimulates the migration and functional development of vitiligo-IgG antibodies-treated pigment cells.

BACKGROUND: The pathogenesis of vitiligo remains unclear. Most authorities favoured the autoimmune cause for the strong associations of vitiligo with multiple autoimmune diseases and the presence of autoantibodies in vitiligo patients. Narrow-band UVB (NBUVB) irradiation has been considered to be an effective treatment for vitiligo with simple treatment procedure and decreased accumulated ultraviolet exposure doses. OBJECTIVES: The aim this study was to investigate the effects of NBUVB irradiation on normal IgG antibodies (N-IgG) or vitiligo IgG antibodies (V-IgG)-treated NCCmelan5 cells in terms of proliferation, migration and melanin formation. METHODS: Cultured NCCmelan5 cells were treated with (i) NBUVB irradiation alone, (ii) N-IgG or V-IgG alone, and (iii) combination of N-IgG or V-IgG with NBUVB irradiation. The proliferation of NCCmelan5 cells were evaluated using BrdU incorporation assay. Western blotting was used to determine the expressions of phosphorylated p125(FAK) (pp125(FAK)) and tyrosinase in NCCmelan5 cells. The locomotion of NCCmelan5 cells was assessed using time-lapse assay and in vitro wound scratch assay. RESULTS: Neither N-IgG nor V-IgG significantly affected the proliferation of NCCmelan5 cells. The migration, melanin formation and tyrosinase expression in NCCmelan5 cells were decreased by V-IgG. NBUVB irradiation increased the proliferation of V-IgG treated NCCmelan5 cells. In addition, NBUVB irradiation enhanced the mobility of V-IgG-treated NCCmelan5 cells via upregulation of pp125(FAK). The melanogenesis and tyrosinase expression in V-IgG-treated NCCmelan5 cells were promoted using NBUVB irradiation. CONCLUSIONS: Our study demonstrated that the deleterious effects of V-IgG in the pathogenesis of vitiligo might be overcome by NBUVB irradiation.

FK506 (tacrolimus) and endothelin combined treatment induces mobility of melanoblasts: new insights into follicular vitiligo repigmentation induced by topical tacrolimus on sun-exposed skin.

BACKGROUND: Topical tacrolimus (FK506) has been considered as a treatment option for treating vitiligo, a dermatosis characterized by disappearance of melanocytes (MCs). Previous reports have shown that a significant portion of treated patients demonstrated follicular repigmentation, indicating that the activation of MC precursor cells residing in the outer root sheath of hair follicles played an important role during the tacrolimus-induced repigmentation process. OBJECTIVES: To investigate the mechanisms involved in follicular pigmentation induced by topical tacrolimus. METHODS: As stem cells of MC lineage are identified in the lower portion of mouse hair follicles throughout the hair cycle, immature mouse melanoblasts (MBs) derived from neural crest cells (NCCmelb4) were used for this study. Relevant maturation parameters were evaluated. RESULTS: Our results revealed that FK506 stimulated the expressions of protein kinase A, protein kinase C and phosphorylated p38 mitogen-activated protein kinase. However, cell motility, a parameter associated with MB differentiation, was not enhanced by FK506 treatment. Endothelin (ET)-3, a prodifferentiation factor of MBs, also failed to promote NCCmelb4 cell locomotion. Combining ET-3 and FK506, however, stimulated cell mobility. ET B receptor, which was not present in NCCmelb4 cells, was induced after FK506 treatment. CONCLUSIONS: In summary, we have shown that FK506 is an efficient differentiation-stimulating agent, especially for cells of neural origin. The clinical efficacy of topical tacrolimus on vitiligo may be enhanced by combination with ET-3.

Lifetime exposure to cigarette smoking and the development of adult-onset atopic dermatitis.

BACKGROUND: Adult-onset atopic dermatitis (AD) has recently been recognized as a distinct disease entity, but its risk factors have not yet been clearly defined. Although gestational and perinatal exposure to tobacco smoking may be associated with the development of classic AD, the association between active/passive smoking and adult-onset AD remains controversial. OBJECTIVES: To determine if exposure to smoking, including environmental tobacco smoke (ETS), is associated with the risk of adult-onset AD. METHODS: Tobacco smoking and exposure to ETS were measured in a case-control association analysis in 83 patients with physician-diagnosed adult-onset AD and 142 age- and sex-matched controls. RESULTS: Multiple logistic regression analyses showed that, among the potential environmental risk factors, both current and ever smoking were significant risk factors for adult-onset AD [odds ratio (OR) 4·994 and 3·619, respectively], compared with never smoking. Also, packs per year was significantly associated with adult-onset AD (OR 1·058, 95% confidence interval 1·028-1·089), suggesting a lifelong cumulative risk in current smokers. Moreover, nonsmokers with adult-onset AD reported significantly more exposure to ETS. CONCLUSIONS: Early and/or current exposure to cigarette smoking may contribute cumulatively to the development of adult-onset AD. Exposure to ETS in childhood is associated with the development of adult-onset AD. Adults should be discouraged from smoking to prevent adult-onset AD in themselves and their family members.

Noninvasive cutaneous blood flow as a response predictor for visible light therapy on segmental vitiligo: a prospective pilot study.

BACKGROUND: Visible light is a treatment option for segmental vitiligo (SV), and visible light-induced repigmentation is associated with normalization of sympathetic dysfunction. Currently, it is difficult to predict individual patients' response to visible light therapy. OBJECTIVES: To test whether cutaneous blood flow can serve as a response predictor for visible light on treating SV. METHODS: Fourteen patients with SV were recruited in this prospective pilot study. Laser Doppler flowmetry was used to evaluate the cutaneous blood flow over SV lesions and contralateral normal skin. The pretreatment blood flow evaluation consisted of two stages: stage 1, following cold stress without prior visible light irradiation, and stage 2, following cold stress with prior visible light irradiation. Subsequently, the patients received regular visible light treatment for 3months, and a comparison of the pretreatment blood flow patterns between the visible light responding and nonresponding groups was carried out at the end of the study period. RESULTS: The SV lesions showed different blood flow profiles as compared with the contralateral normal skin. At the end of the 3-month study period, seven (50%) patients showed clinical repigmentation of >25%. The visible light responding group showed a more consistent occurrence of increased blood flow after stage 2 of the pretreatment evaluation while the nonresponding counterpart showed no significant changes. CONCLUSIONS: Normalization of sympathetic dysfunction may account for the efficacy of visible light in treating SV. Evaluation of cutaneous blood flow with and without prior visible light irradiation on cold-stressed SV lesions may serve as a treatment response predictor.

Amelioration of intestinal colitis by macrophage migration inhibitory factor isolated from intestinal parasites through toll-like receptor 2.

In a previous study, we cloned type II MIFs (As-MIF) from Anisakis simplex 3rd stage larva and expressed a recombinant protein that suppressed allergic airway inflammation via regulatory T (CD4(+) CD25(+) Foxp3(+) T; T(reg) )-cell recruitment. In this study, in an effort to evaluate the function of rAs-MIF on another immune disease, we induced intestinal inflammation in mice using dextran sodium sulphate (DSS) with or without the application of rAs-MIF treatment to the mice. As a consequence, weight losses were recovered, and the value of disease activity index (DAI) was reduced by rAs-MIF treatment during the experimental period. The levels of TGF-ß and IL-10 in the spleens and mesenteric lymph nodes (MLN) from the rAs-MIF-treated mice were higher, but the levels of IFN-γ, IL-6 and IL-13 were lower than those of the mice treated with DSS but not with rAs-MIF. Additionally, the T(reg) cells observed were greatly increased in the MLNs of the rAs-MIF-treated mice than those of mice not treated with rAs-MIF. The results of our in vitro experiments showed that the elevated IL-10 production induced by rAs-MIF was generated via toll-like receptor 2. In conclusion, rAs-MIF appears to ameliorate DSS-induced colitis and may prove useful as a therapeutic agent for the treatment of intestinal inflammatory disease.