SERPINB3/B4 Is Increased in Psoriasis and Rosacea Lesions and Has Proinflammatory Effects in Mouse Models of these Diseases.

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these 2 conditions are poorly understood. In this study, we reveal that both patients with psoriasis and those with rosacea as well as their mouse models have significantly elevated expressions of SERPINB3/B4 (members of serine protease inhibitor) in the lesional skin. Skin inflammation in mice that resembles both psoriasis and rosacea is prevented by SERPINB3/B4 deficiency. Mechanistically, we demonstrate that SERPINB3/B4 positively induces NF-κB signaling activation, thereby stimulating disease-characteristic inflammatory chemokines and cytokines production in keratinocytes and promoting the chemotaxis of CD4+ T cells. Our results suggest that in keratinocytes, SERPINB3/B4 may be involved in the pathogenesis of both psoriasis and rosacea by stimulating NF-κB signaling, and they indicate a possible treatment overlap between these 2 diseases.

Targeting Aquaporin-3 Attenuates Skin Inflammation in Rosacea.

Rosacea is a common inflammatory skin disorder mediated by the dysregulation of both keratinocytes and T cells. Here, we report that aquaporin 3 (AQP3), a channel protein that mediates the transport of water/glycerol, was highly expressed in the epidermis and CD4+ T cells of both rosacea patients and experimental mice. Specifically, AQP3 deletion blocked the development of rosacea-like skin inflammation in model mice with LL37-induced rosacea-like disease. We also present mechanistic evidence showing that AQP3 was essential to the activation of NF-κB signaling and subsequent production of disease-characteristic chemokines in keratinocytes. Moreover, we show that AQP3 was upregulated during T cell differentiation and promotes helper T (Th) 17 differentiation possibly via the activation of STAT3 signaling. Our findings reveal that AQP3-mediated activation of NF-κB in keratinocytes and activation of STAT3 in CD4+ T cells acted synergistically and contributed to the inflammation in rosacea.

Screening for latent infectious disease in patients with alopecia areata before initiating JAK inhibitors therapy: a single-center real-world retrospective study.

Introduction: Although there is growing evidence supporting the effectiveness of Janus kinase (JAK) inhibitors in treating alopecia areata, the high rate of recurrence following drug discontinuation has led to prolonged treatment courses and raised concerns about long-term safety. In clinical practice, caution should be exercised while using JAK inhibitors for various indications, and a comprehensive pre-treatment screening. Methods: This study presents an analysis of screening data collected from real-world settings before the initiation of Janus kinase inhibitors in patients with alopecia areata. Investigators collected retrospective medical data characterizing patients' screening data. Data on demographic and clinical data, including age, sex, disease duration, severity of alopecia tool scale, history of prior treatment, and treatment regimen were recorded. Results: In this cohort (N = 218), JAK inhibitors were initiated for 163 of 218 (74.8%) alopecia areata patients. The numbers of patients positive for antinuclear antibodies, hepatitis B surface antigen, hepatitis C virus antibodies, human immunodeficiency virus antibody, treponema pallidum hemagglutination assay, and thyroid-stimulating hormone were 32 (32/176), 10(10/218), 0 (0/218), 0 (0/218), 3 (3/218) and 9 (9/176), respectively. The number of patients with T-cell spot positive or imaging of the chest indicating tuberculosis was 37 (37/218). Disccusion: Our data provide additional information on the safety profile of JAK inhibitors in patients with alopecia areata. As such, it is necessary and crucial to screen for JAK inhibitors before it is used, particularly for individuals with a high risk of tuberculosis, hepatitis B, and other infections.

Effectiveness of Tofacitinib in Pre-adolescent Alopecia Areata: A Retrospective Case Series and Literature Review.

Alopecia areata (AA) is a common cause of hair loss in children. Despite numerous therapeutic options for paediatric AA, none have been found to be both effective and safe. Recent studies have demonstrated the efficacy and safety of the Janus kinase (JAK) inhibitor tofacitinib in adult patients with AA, whereas data on paediatric patients with AA in real-world practice are limited. This was a single-centre, retrospective study that included 11 pre-adolescent patients with AA treated with tofacitinib between December 2021 and September 2022. Clinical characteristics of patients, clinical response and adverse events were evaluated. Overall, 82% (9/11) of patients experienced hair regrowth and 64% (7/11) of patients experienced over 50% improvement in their Severity of Alopecia Tool (SALT) scores. Adverse events were mild. In the literature, tofacitinib has been used to treat AA in 31 children ≤12 years of age who failed to respond to prior treatments. Eighty-seven percent (27/31) of these patients showed significant responses based on changes in their SALT scores. This case series demonstrates that oral tofacitinib is an effective and safe treatment option for paediatric AA, particularly for children who have failed to respond to traditional treatments or are not suitable for such treatments.

Correlation of SV2C rs1423099 single nucleotide polymorphism with sporadic Parkinson's disease in Han population in Southern China.

BACKGROUND: The synaptic vesicle glycoprotein 2 (SV2) has been implicated in synaptic function throughout the brain. Accumulating evidence investigated that SV2C contributed to dopamine release and the disrupted expression of SV2C was considered to be a unique feature of PD that may facilitate dopaminergic neuron dysfunction. OBJECTIVE: This study aimed to examine the relationship between the SV2C rs1423099 single nucleotide polymorphism and sporadic Parkinson's disease (PD) in the Chinese Han population. MATERIALS AND METHODS: This study enrolled 351 patients with sporadic PD and 240 normal controls in Chinese Han population. Peripheral blood DNA was extracted by DNA extraction kits and the rs1423099 genotype was analyzed by Agena MassARRAY DNA mass spectrometry. The differences in genotype and allele distribution frequencies between PD patients and control groups were compared using chi-squared tests or Fisher's exact tests. RESULTS: No statistical difference was revealed in age and sex distribution between the cases and control groups, and the distribution of genotype and allele frequencies was consistent with the Hardy-Weinberg equilibrium test. In SV2C rs1423099 dominant model, the frequency of the CC/CT genotype was significantly higher in the PD group compared to the control group (OR = 4.065,95% CI: 2.801-10.870, p = 0.002). Nevertheless, in the recessive model, CC or CT/TT genotypes have no statistical difference in the two groups (p = 0.09). Additionally, in allelic analysis, the C allele was investigated to increase the risk of PD (OR = 1.346, 95% CI: 1.036-1.745, p = 0.026); Furthermore, subgroup analysis suggested that those carrying the C allele in the male subgroup were at a higher risk to afflicted with PD (OR = 1.637, 95% CI: 1.147-2.336, p = 0.006). CONCLUSION: SV2C rs1423099 single nucleotide polymorphism was associated with sporadic Parkinson's disease in the Chinese Han population, particularly in males.