The role of interleukin-36 in inflammatory skin diseases

Interleukin (IL)-36 cytokines are new members of the IL-1 family, that include proinflammatory factors, IL-36α, IL-36β and IL-36γ, and a natural receptor antagonist IL-36Ra. IL-36 cytokines are expressed in a specific manner by monocytes/macrophages, dendritic cells (DCs), T cells subsets, keratinocytes, Langerhans cells, and mucosal epithelium. Since IL-36 cytokines are predominantly expressed in keratinocytes it is not surprising that specifically skin disorders have been explored for associations with these cytokines. Several reports have found that IL-36α and IL-36γ are up-regulated in psoriatic and allergic contact dermatitis skin. Over recent years much has been learned on their important functions in the regulation of immune response and, especially, on their involvement in many inflammatory conditions. In this study, we wanted to elucidate the role of these mediators in the pathogenesis of most common inflammatory skin diseases such as, psoriasis, allergic contact dermatitis and polymorphic light eruption

Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage

: The Thyroid Hormone (TH) activating enzyme, type 2 Deiodinase (D2), is functionally required to elevate the TH concentration during cancer progression to advanced stages. However, the mechanisms regulating D2 expression in cancer still remain poorly understood. Here, we show that the cell stress sensor and tumor suppressor p53 silences D2 expression, thereby lowering the intracellular THs availability. Conversely, even partial loss of p53 elevates D2/TH resulting in stimulation and increased fitness of tumor cells by boosting a significant transcriptional program leading to modulation of genes involved in DNA damage and repair and redox signaling. In vivo genetic deletion of D2 significantly reduces cancer progression and suggests that targeting THs may represent a general tool reducing invasiveness in p53-mutated neoplasms

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Psoriatic arthritis onset in psoriatic patients receiving UV phototherapy in Italy

Psoriasis is a chronic, recurrent, and immune-mediated inflammatory disease that affects 2-3% of the world population. A substantial proportion of patients with psoriasis, approximately 40 %, develop a form of inflammatory arthritis known as psoriatic arthritis (PsA), the arthritis follows the development of psoriasis, and it will develop simultaneously or possibly before the appearance of skin lesions. The presence of PsA indicates a need for more active intervention rather than purely topical therapies or UV-based therapies. The aim of this multicenter, retrospective, epidemiological study was to estimate the incidence of PsA in psoriatic patients receiving UV treatment as monotherapy

Q-ball imaging models: comparison between high and low angular resolution diffusion-weighted MRI protocols for investigation of brain white matter integrity

INTRODUCTION: Q-ball imaging (QBI) is one of the typical data models for quantifying white matter (WM) anisotropy in diffusion-weighted MRI (DwMRI) studies. Brain and spinal investigation by high angular resolution DwMRI (high angular resolution imaging (HARDI)) protocols exhibits higher angular resolution in diffusion imaging compared to low angular resolution models, although with longer acquisition times. We aimed to assess the difference between QBI-derived anisotropy values from high and low angular resolution DwMRI protocols and their potential advantages or shortcomings in neuroradiology. METHODS: Brain DwMRI data sets were acquired in seven healthy volunteers using both HARDI (b = 3000 s/mm2, 54 gradient directions) and low angular resolution (b = 1000 s/mm2, 32 gradient directions) acquisition schemes. For both sequences, tract of interest tractography and generalized fractional anisotropy (GFA) measures were extracted by using QBI model and were compared between the two data sets. RESULTS: QBI tractography and voxel-wise analyses showed that some WM tracts, such as corpus callosum, inferior longitudinal, and uncinate fasciculi, were reconstructed as one-dominant-direction fiber bundles with both acquisition schemes. In these WM tracts, mean percent different difference in GFA between the two data sets was less than 5 %. Contrariwise, multidirectional fiber bundles, such as corticospinal tract and superior longitudinal fasciculus, were more accurately depicted by HARDI acquisition scheme. CONCLUSION: Our results suggest that the design of optimal DwMRI acquisition protocols for clinical investigation of WM anisotropy by QBI models should consider the specific brain target regions to be explored, inducing researchers to a trade-off choice between angular resolution and acquisition time

Anti IL-17 therapy rapidly decreases osteoclast activity in psoriatic patients: a novel quality in addition to its efficacy and safety

Psoriasis is a chronic, immune-mediated, inflammatory skin disease where interleukin-17 plays an important role in the underlying pathogenesis. IL-17A is a key driver of pro- osteoclastogenic process, that is abnormal in psoriatic patients. Aim of this study was to investigate in vivo the capability of secukinumab to influence the osteoclastogenesis in psoriatic patients reporting also our experience regarding the effectiveness and safety profile of this biological treatment

Anti IL-17 therapy rapidly decreases osteoclast activity in psoriatic patients: a novel quality in addition to its efficacy and safety

Psoriasis is a chronic, immune-mediated, inflammatory skin disease where interleukin-17 plays an important role in the underlying pathogenesis. IL-17A is a key driver of pro- osteoclastogenic process, that is abnormal in psoriatic patients. Aim of this study was to investigate in vivo the capability of secukinumab to influence the osteoclastogenesis in psoriatic patients reporting also our experience regarding the effectiveness and safety profile of this biological treatment

Noncoding rnas and midbrain da neurons: Novel molecular mechanisms and therapeutic targets in health and disease

Midbrain dopamine neurons have crucial functions in motor and emotional control and their degeneration leads to several neurological dysfunctions such as Parkinson’s disease, addiction, depression, schizophrenia, and others. Despite advances in the understanding of specific altered proteins and coding genes, little is known about cumulative changes in the transcriptional landscape of noncoding genes in midbrain dopamine neurons. Noncoding RNAs—specifically microRNAs and long noncoding RNAs—are emerging as crucial post-transcriptional regulators of gene expression in the brain. The identification of noncoding RNA networks underlying all stages of dopamine neuron development and plasticity is an essential step to deeply understand their physiological role and also their involvement in the etiology of dopaminergic diseases. Here, we provide an update about noncoding RNAs involved in dopaminergic development and metabolism, and the related evidence of these biomolecules for applications in potential treatments for dopaminergic neurodegeneration

Structural connectome with high angular resolution diffusion imaging MRI: assessing the impact of diffusion weighting and sampling on graph-theoretic measures

Purpose: Advances in computational network analysis have enabled the characterization of topological properties of human brain networks (connectomics) from high angular resolution diffusion imaging (HARDI) MRI structural measurements. In this study, the effect of changing the diffusion weighting (b value) and sampling (number of gradient directions) was investigated in ten healthy volunteers, with specific focus on graph theoretical network metrics used to characterize the human connectome. Methods: Probabilistic tractography based on the Q-ball reconstruction of HARDI MRI measurements was performed and structural connections between all pairs of regions from the automated anatomical labeling (AAL) atlas were estimated, to compare two HARDI schemes: low b value (b = 1000) and low direction number (n = 32) (LBLD); high b value (b = 3000) and high number (n = 54) of directions (HBHD). Results: LBLD and HBHD data sets produced connectome images with highly overlapping hub structure. Overall, the HBHD scheme yielded significantly higher connection probabilities between cortical and subcortical sites and allowed detecting more connections. Small worldness and modularity were reduced in HBHD data. The clustering coefficient was significantly higher in HBHD data indicating a higher level of segregation in the resulting connectome for the HBHD scheme. Conclusion: Our results demonstrate that the HARDI scheme as an impact on structural connectome measures which is not automatically implied by the tractography outcome. As the number of gradient directions and b values applied may introduce a bias in the assessment of network properties, the choice of a given HARDI protocol must be carefully considered when comparing results across connectomic studies