ObjectivesTo confirm the association of previously discovered psoriasis (Ps) risk loci with the disease in a Polish population and to create predictive models based on the combination of these single nucleotide polymorphisms (SNPs).Material and methodsThirty-eight SNPs were genotyped in 480 Ps patients and 490 controls. Alleles distributions were compared between patients and controls, as well as between different Ps sub-phenotypes. The genetic risk score (GRS) was calculated to assess the cumulative risk conferred by multiple loci.ResultsWe confirmed associations of several loci with Ps: HLA-C, REL, IL12B, TRIM39/RPP21, POU5F1, MICA. The analysis of ROC curves showed that GRS combining 16 SNPs at least nominally (uncorrected P<0.05) associated with Ps (GRS-N) had significantly better discriminative power than GRS combining SNPs associated with Ps after the Bonferroni correction (AUC 0.776 vs. 0.750, P = 1 x 10−4) or HLA-C (AUC 0.776 vs. 0.694, P<1 x 10−5). On the other hand, adding additional SNPs to the model did not improve its discriminatory ability (AUC 0.782 for GRS combining all SNPs, P>0.05). In order to assess the total risk conferred by GRS-N, we calculated ORs according to GRS-N quartile ˗ the Ps OR for top vs. bottom GRS-N quartiles was 12.29 (P<1 x 10−6). The analysis of different Ps sub-phenotypes showed an association of GRS-N with age of onset and family history of Ps.ConclusionsWe confirmed the association of Ps with several previously identified genetic risk factors in a Polish population. We found that a GRS combining 16 SNPs at least nominally associated with Ps had a significantly better discriminatory ability than HLA-C or GRS combining SNPs associated with Ps after the Bonferroni correction. In contrast, adding additional SNPs to GRS did not increase significantly the discriminative power.
Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima-media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRS IMT , GRS CP and GRS CAD , comprising intima-media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRS IMT. Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRS IMT among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.
INTRODUCTIONAcne vulgaris (AV) is chronic inflammatory disease of sebaceous glands and hair follicles (so-called folliculosebaceous units) characterized by the presence of both non-inflammatory (i.e. microcomedones, closed comedones and open comedones) and inflammatory lesions (papules, pustules and cysts). AV is the most common skin disease in adolescents, although it is seen more and more often in adults, mostly women. It is estimated that 41% of people aged 25 to 40 suffer from acne lesions for at least 3 to 4 months per year (with a marked predominance in women -female: male ratio of 4:1) [1].AV pathogenesis is complex, involving mostly 4 interdependent pathogenic factors: (i) increased a c t i v i t y o f s e b a c e o u s g l a n d s w i t h s e b u m overproduction; (ii) hyperkeratosis of pilosebaceous duct leading to blockage of pilosebaseous units with excess keratin and sebum, causing comedo formation; (iii) colonization of sebaceous glands ducts with anaerobic bacteria Propionibacterium acnes and increased proliferation of aerobic bacteria Staphylococcus epidermidis and lipophilic yeasts Pityrosporum ovale (which cause irritant action due to free fatty acids derived from hydrolysis of sebum triglycerides); (iv) induction of inflammatory processes in the skin. Other factors involved in the formation of acne lesions include: (i) genetic predisposition (probably polygenic or autosomal dominant with variable penetrance) -genetic factors influence density of androgen receptors in sebaceous glands, 5-α reductase activity, seborrhoea intensity and sebaceous glands size [2,3]; (ii) immunological disturbances -excessive ABSTRACT Background: Acne vulgaris (AV) is a common skin disease with characteristic clinical, chronic course and different etiopathogenesis. AV occurs more and more often among adults, especially women. AV, due to the chronic nature of the skin lesions, often requires many months or even long-term treatment and proper skin care both during the period that does not require administration of drugs, as well as during and after pharmacotherapy. The aim of the study was to evaluate the safety and the anti-acne efficacy of a point-gel containing 2% H2O2 and salicylic acid (0.54%), phytic acid (1%), D-panthenol (1%) and vitamin PP (0.012%). Material and Methods: 24 patients with mild to severe AV used the study product containing hydrogen peroxide for 7 days. The condition of skin patients was assessed instrumentally (VISIA) and clinically by a dermatologist, including assessment of skin lesions visibility in the 10-point analogue scale and the number of particular acne lesions. Results: The product was well tolerated. Dermatological evaluation at day 7 showed a significant decrease in the visibility of acne lesions (P=0.0003) and a significant reduction of number of pustules (P=0.002); an insignificant decrease in numbers of papules and comedones was also observed. Instrumental analysis of VISIA showed insignificant reduction in the number and intensity of skin discolorations, epidermal irregulariti...
Mast cell (MC) functions in vivo have been analyzed by using MC-deficient mice with Kit mutations such as Kit W-sh/W-sh. However, these mice reportedly had other hematopoietic abnormalities. To use bona fide solely MC-deficient mice, Cpa3 Cre/+ mice were established using Cre under the control of a promoter of MC-specific Carboxypeptidase A3 (Cpa3) gene and are now used to study MC functions in vivo. We confirmed that peritoneal MCs in both mice were undetectable by flow cytometry and were detectable upon reconstitution of MCs by injecting bone marrow-derived MC (BMMC) from wild type (WT) mice. While analyzing peritoneal MCs in a CD45 + cell population, we discovered that F4/80 hi CD11b hi peritoneal macrophages (mFs) were reduced in both mice compared to WT mice, and were restored to the level of WT mice by the MC reconstitution. We also discovered that c-Kit + CD11b + cells were undetectable in both mice and significantly increased upon the MC reconstitution. We further found that c-Kit+CD11b+ cells expressed CD34, Sca-1, and CD135, indicating the expression of multipotent progenitor (MPP) phenotypes. We termed these cells "MPP-like cells". Upon the MC reconstitution in Cpa3 Cre/+ (CD45.2) mice by CD45.1 BMMC, we identified MPP-like cells were recipient-derived, while upon the MC reconstitution in Kit W-sh/W-sh (CD45.1) mice by CD45.2 BMMC, they were totally donor-derived. These results indicated that MCs are required for the development of MPP-like cells in Cpa3 Cre/+ mice and MCs per se in Kit W-sh/W-sh mice transform into MPP-like cells. We next tested whether the similar phenomenon was observed in the skin. To do so, we reconstituted MCs in both mice by the i.d. injection of WT-derived BMMC. In both, MCs in the skin were restored to the WT level, whereas CD206 + dermal mFs were significantly increased compared to non-reconstituted mice. Taken together, these results suggest that MCs play a role in controlling a population of MPP-like cells as a mF progenitor cell-type to regulate mF homeostasis in terms of its number and phenotype in a tissue-dependent manner. 323 IL-36y stimulation induces proinflammatory effects on human endothelial cells
Mast cell (MC) functions in vivo have been analyzed by using MC-deficient mice with Kit mutations such as Kit W-sh/W-sh. However, these mice reportedly had other hematopoietic abnormalities. To use bona fide solely MC-deficient mice, Cpa3 Cre/+ mice were established using Cre under the control of a promoter of MC-specific Carboxypeptidase A3 (Cpa3) gene and are now used to study MC functions in vivo. We confirmed that peritoneal MCs in both mice were undetectable by flow cytometry and were detectable upon reconstitution of MCs by injecting bone marrow-derived MC (BMMC) from wild type (WT) mice. While analyzing peritoneal MCs in a CD45 + cell population, we discovered that F4/80 hi CD11b hi peritoneal macrophages (mFs) were reduced in both mice compared to WT mice, and were restored to the level of WT mice by the MC reconstitution. We also discovered that c-Kit + CD11b + cells were undetectable in both mice and significantly increased upon the MC reconstitution. We further found that c-Kit+CD11b+ cells expressed CD34, Sca-1, and CD135, indicating the expression of multipotent progenitor (MPP) phenotypes. We termed these cells "MPP-like cells". Upon the MC reconstitution in Cpa3 Cre/+ (CD45.2) mice by CD45.1 BMMC, we identified MPP-like cells were recipient-derived, while upon the MC reconstitution in Kit W-sh/W-sh (CD45.1) mice by CD45.2 BMMC, they were totally donor-derived. These results indicated that MCs are required for the development of MPP-like cells in Cpa3 Cre/+ mice and MCs per se in Kit W-sh/W-sh mice transform into MPP-like cells. We next tested whether the similar phenomenon was observed in the skin. To do so, we reconstituted MCs in both mice by the i.d. injection of WT-derived BMMC. In both, MCs in the skin were restored to the WT level, whereas CD206 + dermal mFs were significantly increased compared to non-reconstituted mice. Taken together, these results suggest that MCs play a role in controlling a population of MPP-like cells as a mF progenitor cell-type to regulate mF homeostasis in terms of its number and phenotype in a tissue-dependent manner. 323 IL-36y stimulation induces proinflammatory effects on human endothelial cells
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