Anthocyanins,but not Anthocyanidins,from Bilberry (Vaccinium myrtillus L.) Alleviate Pruritus via Inhibition of Mast Cell Degranulation

Abstract: We have previously reported that bilberry anthocyanins exhibit an anti‐pruritic effect in a mouse model of allergic contact dermatitis. It has been reported that anthocyanins are particularly sensitive to thermal treatment and are easily hydrolyzed to anthocyanidins when exposed to high temperatures. The objective of this study was to compare the anti‐pruritic effect of anthocyanin‐rich quality‐controlled bilberry extract and anthocyanidin‐rich degraded extract using a mouse model of allergic contact dermatitis. BALB/c mice with allergic contact dermatitis induced by 4 weeks of repeated application of 2,4,6‐trinitro‐1‐chlorobenzene (TNCB) were administered Bilberon‐25 orally for 4 weeks after sensitization with TNCB. The effect of Bilberon‐25 on pruritus was evaluated by measurement of scratching behavior. RBL‐2H3 mast cells were used to investigate the effect of Bilberon‐25 on degranulation in 48/80‐stimulated mast cells. Compared with nonheated Bilberon‐25, the proportion of anthocyanins in heated Bilberon‐25 decreased, and the proportion of anthocyanidins was increased in heated‐time dependent manner. Treatment with non‐heated Bilberon‐25 significantly attenuated the TNCB‐induced increase in scratching behavior, whereas treatment with 2 h‐heated Bilberon‐25 did not. Moreover, 300 μg/mL nonheated Bilberon‐25 showed significant inhibition of degranulation in RBL‐2H3 mast cells, whereas 2 h‐heated Bilberon‐25 had no effect at any concentration studied. It is assumed that the inhibitory effect of bilberry anthocyanins on pruritus might be mediated, at least in part, by its inhibitory effect on mast cell degranulation. In conclusion, the anthocyanin‐rich but not anthocyanidin‐rich bilberry extract may be a useful dietary supplement for skin diseases involving pruritic symptoms, such as chronic allergic contact dermatitis, atopic dermatitis, and rhinitis.     

血液灌流串联血液透析治疗尿毒症顽固性皮肤瘙痒的疗效

目的探讨血液透析（HD）和血液灌流（HP）联合治疗维持性HD尿毒症患者皮肤瘙痒的疗效。方法将45例终末期尿毒症患者按随机数字表法分为2组,观察组（n=23）和对照组（n=22）。2组在营养支持及综合治疗的基础上,对照组采用HD治疗;观察组采用HP＋HD治疗。对2组治疗后3周甲状腺激素（PTH）、β2-微球蛋白（β2-MG）的水平变化以及患者皮肤瘙痒的缓解程度进行比较。结果观察组治疗后3周PTH和β2-MG水平较治疗前及对照组明显下降,皮肤瘙痒症状也较对照组明显改善（均P〈0.05）。结论 HP＋HD联合治疗能显著下降尿毒症患者PTH和β2-MG水平,减轻皮肤瘙痒症状。     

Pruritus: Is there a grain of salty truth?

Hemodialysis patients characteristically suffer from a range of unpleasant symptoms. Uremic pruritus effects close to half of the chronic kidney disease population, reducing quality of life and associated with increased mortality. Its pathophysiology though is poorly understood; currently deployed therapeutic approaches are ineffective. Excessive levels of skin and soft tissue sodium accumulate in dialysis patients, producing a range of biological consequences, including inflammation. We report an index case of a hemodialysis patient with debilitating pruritus and extreme levels of tissue sodium, measured with Sodium-23 magnetic resonance imaging. Both the tissue sodium loading and pruritus responded fully to initiation of expanded hemodialysis therapy with a recently introduced medium cutoff dialysis membrane-based dialyzer.     

Cromolyn sodium: A potential therapy for uremic pruritus?

Uremic pruritus occurs in up to 50% of patients undergoing chronic hemodialysis. The pathogenesis of this disabling condition is unknown but likely involves multiple pathways involving the peripheral and central nervous system as well as local chemical and inflammatory mediators. Therapy has involved modification of the dialysis procedure, topical medications such as emollients, physical treatments such as ultraviolet light, and several oral medications such as antihistamines, activated charcoal, and gabapentin. Unfortunately, most of these therapies have not been subjected to rigorous clinical trials and clinical success has been variable. Two patients with disabling uremic pruritus refractory to multiple interventions are reported, who showed significant improvement in pruritus severity as assessed by a visual analog scale when they were treated with the mast cell stabilizer cromolyn sodium. Cessation of cromolyn resulted in return of pruritus, which improved with rechallenge with the medication. Cromolyn sodium may offer an alternative therapy for patients with refractory uremic pruritus, and should be subjected to a randomized placebo-controlled trial.     

Molecular Aspects of Pruritus Pathogenesis in Psoriasis

Psoriasis is a chronic, systemic inflammatory disease with a genetic background that involves almost 3% of the general population worldwide. Approximately, 70–90% of patients with psoriasis suffer from pruritus, an unpleasant sensation that provokes a desire to scratch. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the pathogenesis of psoriasis-related pruritus still remains unclear. In order to improve patients’ quality of life, development of more effective and safer antipruritic therapies is necessary. In turn to make it possible, better understanding of complexed and multifactorial pathogenesis of this symptom is needed. In this article we have systematized the current knowledge about pruritus origin in psoriasis.     

Psoriasis: Pathogenesis,Comorbidities, and Therapy Updated

Psoriasis is a chronic inflammatory skin disease characterized by IL-17-dominant abnormal innate and acquired immunity, and the hyperproliferation and aberrant differentiation of epidermal keratinocytes, and comorbid arthritis or cardiometabolic diseases. This Special Issue presented updated information on pathogenesis, comorbidities, and therapy of psoriasis. The pathogenesis of psoriasis may involve the dysfunction of indoleamine 2,3-dioxygenase 2 or of UBA domain containing 1-mediated regulation of CARD14/CARMA2sh. The blood cells of psoriasis patients showed the enhanced oxidative stress/autophagy flux and decreased 20S proteasome activity. Elafin, clusterin, or selenoprotein P may act as biomarkers for psoriasis and comorbid metabolic diseases. The proteomic profile of psoriasis lesions showed the dysfunction of dermal fibroblasts; up-regulation of proinflammatory factors and signal transduction or down-regulation of structural molecules. The skin inflammation in psoriasis may populate certain gut bacteria, such as Staphylococcus aureus and Streptococcus danieliae, which worsen the skin inflammation in turn. The psoriasis-associated pruritus may be caused by immune, nervous, or vascular mechanisms. In addition to current oral treatments and biologics, a new treatment option for psoriasis is now being developed, such as retinoic-acid-receptor-related orphan nuclear receptor γt inhibitors, IL-36 receptor antagonist, or aryl hydrocarbon receptor agonist. Antimicrobial peptides and innate immune cells, involved in the pathogenesis of psoriasis, may be novel therapeutic targets. The pathomechanisms and responses to drugs in collagen diseases are partially shared with and partially different from those in psoriasis. Certain nutrients can exacerbate or regulate the progress of psoriasis. The articles in this Special Issue will encourage attractive approaches to psoriasis by future researchers.     

Deacetylasperulosidic Acid Ameliorates Pruritus,Immune Imbalance,and Skin Barrier Dysfunction in 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis NC/Nga Mice

The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1β, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.     

艾司氯胺酮和布托啡诺对剖宫产产妇吗啡所致瘙痒影响的随机对照临床研究

目的：评估艾司氯胺酮、布托啡诺对剖宫产产妇吗啡硬膜外注射所致术后不同时限瘙痒的影响。方法：选取台州市中心医院（台州学院附属医院）妇产科行连续硬膜外麻醉下择期剖宫产手术的产妇162例，随机分为艾司氯胺酮组（K组）、布托啡诺组（B组）和空白对照组（C组）。待胎儿剖出断脐5 min后，K组予以3 mg吗啡稀释液经硬膜外导管注射，同时静脉注射艾司氯胺酮0.2 mg/kg，B组、C组予以相同剂量吗啡，同时分别静脉注射布托啡诺10 μg/kg或同体积生理盐水。比较三组产妇术后不同时间瘙痒发生率、瘙痒程度和其他不良反应发生率。结果：产妇瘙痒在术后4 h内发生率最高。K组和B组产妇术后4 h瘙痒发生率明显低于C组（3.7% vs. 3.7% vs. 29.6%，P<0.05），术后48 h瘙痒总发生率明显低于C组（13.0% vs. 11.1% vs. 40.7%，P<0.05），且中重度瘙痒发生率也明显低于C组（5.6% vs. 3.7% vs. 31.5%，P<0.05）；而K组与B组间比较差异均无统计学意义（均P>0.05）。三组产妇术后恶心、呕吐、头晕的发生率和术后疼痛评分比较差异均无统计学意义（均P>0.05）。结论：艾司氯胺酮、布托啡诺均可降低产妇吗啡硬膜外注射所致瘙痒的发生率及瘙痒程度，不影响吗啡镇痛效果且未增加不良反应发生率。艾司氯胺酮对剖宫产术后瘙痒的预防效果、安全性与布托啡诺相当。     

Mesenchymal Stem Cells and Extracellular Vesicles Derived from Canine Adipose Tissue Ameliorates Inflammation,Skin Barrier Function and Pruritus by Reducing JAK/STAT Signaling in Atopic Dermatitis

Canine atopic dermatitis (AD) is a common chronic inflammatory skin disorder resulting from imbalance between T lymphocytes. Current canine AD treatments use immunomodulatory drugs, but some of the dogs have limitations that do not respond to standard treatment, or relapse after a period of time. Thus, the purpose of this study was to evaluate the immunomodulatory effect of mesenchymal stem cells derived from canine adipose tissue (cASCs) and cASCs-derived extracellular vesicles (cASC-EVs) on AD. First, we isolated and characterized cASCs and cASCs-EVs to use for the improvement of canine atopic dermatitis. Here, we investigated the effect of cASCs or cASC-EVs on DNCB-induced AD in mice, before using for canine AD. Interestingly, we found that cASCs and cASC-EVs improved AD-like dermatitis, and markedly decreased levels of serum IgE, (49.6%, p = 0.002 and 32.1%, p = 0.016 respectively) epidermal inflammatory cytokines and chemokines, such as IL-4 (32%, p = 0.197 and 44%, p = 0.094 respectively), IL-13 (47.4%, p = 0.163, and 50.0%, p = 0.039 respectively), IL-31 (64.3%, p = 0.030 and 76.2%, p = 0.016 respectively), RANTES (66.7%, p = 0.002 and 55.6%, p = 0.007) and TARC (64%, p = 0.016 and 86%, p = 0.010 respectively). In addition, cASCs or cASC-EVs promoted skin barrier repair by restoring transepidermal water loss, enhancing stratum corneum hydration and upregulating the expression levels of epidermal differentiation proteins. Moreover, cASCs or cASC-EVs reduced IL-31/TRPA1-mediated pruritus and activation of JAK/STAT signaling pathway. Taken together, these results suggest the potential of cASCs or cASC-EVs for the treatment of chronic inflammation and damaged skin barrier in AD or canine AD.     

骨胶原清本润肌润体露治疗皮肤瘙痒症的临床疗效和安全性研究

本研究主要评价外用蒽菲优生骨胶原清本润肌润体露产品治疗皮肤瘙痒症的临床疗效和安全性研究,采用CallegariS.P.A.SOFT5.5检测皮肤的pH、皮肤油脂含量及皮肤含水量,用问卷量表方式比较治疗前、后受试者与皮肤干燥相关的症状以及前后疗效评价等方法。