Vasoactive Intestinal Peptide Immunoregulatory Role at the Periapex: Associative and Mechanistic Evidences from Human and Experimental Periapical Lesions

IntroductionThe balance between the host proinflammatory immune response and the counteracting anti-inflammatory and reparative responses supposedly determine the outcome of periapical lesions. In this scenario, the vasoactive intestinal peptide (VIP) may exert a protective role because of its prominent immunoregulatory capacity. In this study, we investigated (in a cause-and-effect manner) the potential involvement of VIP in the development of human and experimental periapical lesions.MethodsPeriapical granulomas (n = 124) and control samples (n = 48) were comparatively assessed for VIP and multiple immunologic/activity marker expression through real-time polymerase chain reaction. Experimental periapical lesions (C57Bl/6 wild-type mice) were evaluated regarding endogenous VIP expression correlation with lesion development and the effect of recombinant VIP therapy in lesion outcome. CCR4KO and IL4KO strains and anti-glucocorticoid-induced TNFR-related protein inhibition were used to test the involvement of Treg and Th2 cells in VIP-mediated effects.ResultsVIP expression was more prevalent in periapical granulomas than in controls, presenting a positive association with immunoregulatory factors and an inverse association/correlation with proinflammatory mediators and the receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio. Endogenous VIP expression up-regulation was temporally associated with lesion immunoregulation and a decline of bone loss. VIP therapy in mice prompted the arrest of lesion development, being associated with an anti-inflammatory and proreparative response that limits the proinflammatory, Th1, Th17, and osteoclastogenic response in the periapex. The VIP protective effect was dependent of Treg migration and activity and independent of interleukin 4.ConclusionsOur results show that VIP overexpression in human and experimental periapical lesions is associated with lesion inactivity and that VIP therapy results in the attenuation of experimental lesion progression associated with the immunosuppressive response involving Treg cells.     

Fibrous dysplasia of the jaws: Integrating molecular pathogenesis with clinical,radiological, and histopathological features

Fibrous dysplasia is a non‐neoplastic developmental process that affects the craniofacial bones, characterized by painless enlargement as a result of bone substitution by abnormal fibrous tissue. Postzygotic somatic activating mutations in the GNAS1 gene cause fibrous dysplasia and have been extensively investigated, as well as being helpful in the differential diagnosis of the disease. Fibrous dysplasia may involve one (monostotic) or multiple bones (polyostotic), sporadically or in association with McCune‐Albright syndrome, Jeffe‐Lichenstein syndrome, or Mazabreud syndrome. This review summarizes the current knowledge on fibrous dysplasia, emphasizing the value of integrating the understanding of its molecular pathogenesis with the clinical, radiological, and histopathological features. In addition, we address important aspects related to the differential diagnosis and patient management.     

探讨1.2ml SONOVUE剂量对肝脏占位病变时间-强度曲线灌注参数的影响

目的：探讨1.2ml SONOVUE剂量对肝脏占位病变时间-强度曲线(time-intensity curve，TIC)灌注参数的影响。方法：选取52例1.2ml和83例2.4ml SONOVUE（声诺维）对肝脏占位病变的超声造影的资料，对两组肝脏占位病变超声造影(contrast-enhanced ultrasonography，CEUS)的动脉相血流灌注主要方式增强进行比较。采用QLab9.0软件生成TIC及血流灌注参数。对比肝脏良恶性占位病变的TIC形态特征，分析肝脏占位病灶与周围肝实质血流灌注参数，以及两组肝脏占位病灶血流灌注参数的差异。结果：两种剂量造影下恶性和良性占位病变的主要增强方式相同，恶性占位病变的增强方式都主要是整体型和周边增强型，其CEUS TIC的波峰较尖锐。1.2ml组肝占位病变与周围肝实质的CEUS TIC灌注参数AT、TTP、Δt、Ib、Ip、ΔI/Δt均存在显著差异（P<0.05），提示1.2ml SonoVue剂量可以用于肝占位病变与周围组织的鉴别。与2.4ml组相比，1.2ml组无论肝实质还是肝占位病变的TIC灌注参数AT、TTP、Ib测值大小均存在显著差异（P<0.05）。与2.4ml组相比，1.2ml组HCH的CEUS TIC灌注参数只有AT测值存在显著差异（P<0.05），肝癌（HCC和MLC）的CEUS TIC灌注参数只有Ib测值存在显著差异（P<0.05）。 【结论】：1.2ml SonoVue CEUS可以良好地显示肝脏占位病变，特别是对肝癌和血管瘤的显示。     

The infantile cutaneous microbiome: A review

Recent focus on the neonatal intestinal microbiome has advanced our knowledge of the complex interplay between the intestinal barrier, the developing immune system, and commensal and pathogenic organisms. Despite the parallel role of the infant skin in serving as both a barrier and an interface for priming the immune system, large gaps exist in our understanding of the infantile cutaneous microbiome. The skin microbiome changes and matures throughout infancy, becoming more diverse and developing the site specificity known to exist in adults. Delivery method initially determines the composition of the cutaneous microbiome, though this impact appears transient. Cutaneous microbes play a critical role in immune system development, particularly during the neonatal period, and microbes and immune cells have closely intertwined, reciprocal effects. The unique structure of newborn skin influences cutaneous microbial colonization and the development of dermatologic pathology. The development of the infantile skin barrier and cutaneous microbiome contributes to future skin pathology. Atopic dermatitis flares and seborrheic dermatitis have been linked to dysbiosis, while erythema toxicum neonatorum is an immune response to the establishment of normal bacterial skin flora. Physicians who care for infants should be aware of the impact of the infantile skin microbiome and its role in the development of pathology. A better understanding of the origin and evolution of the skin microbiome will lead to more effective prevention and treatment of pediatric skin disease.     

Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

3‐O‐Laurylglyceryl ascorbate improves the development of sensitive skin through the reduction of oxidative stress

Skin sensitivity is a serious problem for many people, and it can be induced by various factors such as UV irradiation, physical and mental stresses, air pollution, dry air and so on. Skin dryness triggered by UV and dry air is one of the most important causes inducing the development of sensitive skin, and it has been reported that oxidative stress contributes to skin dryness. In this study, we investigated whether treatment with 3‐O‐laurylglyceryl ascorbate (VC‐3LG), which is an amphipathic ascorbic acid derivative, can suppress the development of sensitive skin. The results demonstrate that VC‐3LG restores the expression levels of interleukin‐1α, nerve growth factor and matrix metalloprotease‐9 in the dry skin models of reconstructed human epidermal equivalents (RHEEs) and in H₂O₂‐treated keratinocytes. In addition, VC‐3LG suppresses the dendrite elongation of nerve cells induced in RHEEs by dry skin conditions and by H₂O₂ treatment of keratinocytes. Therefore, we consider that treatment of the skin with VC‐3LG is an effective approach to improve the development of sensitive skin.     

Cutaneous nociception: Role of keratinocytes

Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra‐epidermal nerve endings were classically considered as the exclusive transducers of cutaneous noxious stimuli, it has now been demonstrated that epidermal keratinocytes can initiate nociceptive responses, like Merkel cells do for the innocuous mechanotransduction. In the light of recent in vivo findings, this article outlines this paradigm shift that points to a not yet considered population of sensory epidermal cells.