Expression Patterns of Clock Gene mRNAs and Clock Proteins in Human Psoriatic Skin Samples

Psoriasis is a systemic inflammatory skin disorder that can be associated with sleep disturbance and negatively influence the daily rhythm. The link between the pathomechanism of psoriasis and the circadian rhythm has been suggested by several previous studies. However, there are insufficient data on altered clock mechanisms in psoriasis to prove these theories. Therefore, we investigated the expression of the core clock genes in human psoriatic lesional and non-lesional skin and in human adult low calcium temperature (HaCaT) keratinocytes after stimulation with pro-inflammatory cytokines. Furthermore, we examined the clock proteins in skin biopsies from psoriatic patients by immunohistochemistry. We found that the clock gene transcripts were elevated in psoriatic lesions, especially in non-lesional psoriatic areas, except for rev-erbα, which was consistently downregulated in the psoriatic samples. In addition, the REV-ERBα protein showed a different epidermal distribution in non-lesional skin than in healthy skin. In cytokine-treated HaCaT cells, changes in the amplitude of the bmal1, cry1, rev-erbα and per1 mRNA oscillation were observed, especially after TNFα stimulation. In conclusion, in our study a perturbation of clock gene transcripts was observed in uninvolved and lesional psoriatic areas compared to healthy skin. These alterations may serve as therapeutic targets and facilitate the development of chronotherapeutic strategies in the future.

The Role of Helper T Cells in Psoriasis

Psoriasis is a complex, chronic relapsing and inflammatory skin disorder with a prevalence of approximately 2% in the general population worldwide. Psoriasis can be triggered by infections, physical injury and certain drugs. The most common type of psoriasis is psoriasis vulgaris, which primarily features dry, well-demarcated, raised red lesions with adherent silvery scales on the skin and joints. Over the past few decades, scientific research has helped us reveal that innate and adaptive immune cells contribute to the chronic inflammatory pathological process of psoriasis. In particular, dysfunctional helper T cells (Th1, Th17, Th22, and Treg cells) are indispensable factors in psoriasis development. When stimulated by certain triggers, antigen-presenting cells (APCs) can release pro-inflammatory factors (IL-23, IFN-α and IL-12), which further activate naive T cells and polarize them into distinct helper T cell subsets that produce numerous cytokines, such as TNF, IFN-γ, IL-17 and IL-22, which act on keratinocytes to amplify psoriatic inflammation. In this review, we describe the function of helper T cells in psoriasis and summarize currently targeted anti-psoriatic therapies.

The Use of HSQoL-24 in an Assessment of Quality-of-Life Impairment among Hidradenitis Suppurativa Patients: First Look at Real-Life Data

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with well-documented effects on patients’ quality of life (QoL). The aim of this study was to evaluate the QoL of patients with HS via the use of a newly developed questionnaire: Hidradenitis Suppurativa Quality of Life-24 (HSQoL-24). This study was performed on a population of 342 HS patients. Their QoL was assessed via the HSQoL-24 questionnaire. The perceived impairment of QoL due to HS in the studied group was considered to be serious (mean HSQoL-24 score: 58.3 ± 21.0 points). Women tended to experience a significantly higher impact from the disease than men (61.6 ± 19.2 points vs. 51.1 ± 23.1 points, p < 0.001). The HS severity had an effect on the perceived QoL, with statistically significant differences being evident between the self-assessed HS severity groups. The level of QoL impairment correlated positively with the number of affected body areas (r = 0.285, p < 0.001) and the duration of the disease (r = 0.173, p = 0.001), while the patients’ age at disease onset correlated negatively with the HSQoL-24 global score (r = −0.182, p = 0.001). Patients living in their family house scored higher than other groups. The least affected were patients who lived alone. The study shows that the HSQoL-24 questionnaire is a reliable, HS-specific tool for measuring the QoL among patients with HS in real-life clinical settings.

Clinical efficacy and target signaling pathways of natural products in psoriasis treatment: a systematic review

Background: Psoriasis is a common chronic inflammatory skin disorder, which has adverse effects on patients’ quality of life. Natural products exhibit significant therapeutic capacities with small side effects and might be preferable alternative treatments for patients with psoriasis. Aim of the review: This study summarizes the clinical efficacy of natural products and signaling pathways with the potential targets for psoriasis treatment. Methods: The literature for this article was acquired from PubMed and Web of Science, from Jan 2010 to Dec 2020. The keywords for searching included “psoriasis” and “natural product”, “herbal medicine”, “herbal therapy”, “medicinal plant”, “medicinal herb”, or “pharmaceutical plant”. Results: The anti-psoriatic effect of natural products in clinical studies was summarized. Herbal extracts, natural compounds, and herbal prescriptions could regulate the signaling pathways to alleviate psoriasis symptoms, such as Th17 differentiation, JAK/STAT, NF-κB, MAPK, PI3K/Akt/mTOR, and other signaling pathways, which are involved in the inflammatory response and keratinocyte hyperproliferation. Conclusion: Natural products exerted the anti-psoriatic effect by targeting multiple signaling pathways, providing evidence for the investigation of novel drugs. Further experimental research should be performed to screen and characterize the therapeutic targets of natural products for application in psoriasis treatment.

The New Era of Biologics in Atopic Dermatitis: A Review

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder affecting all ages and ethnic groups. The age-dependent varying appearance and extent of pruritic lesions are accompanied by distinct individual suffering, highlighting the importance of effective treatment options. Over the past years, systemic drugs have considerably extended therapeutic approaches of patients with moderate to severe AD, in particular, new biologics, most notably dupilumab has appeared as major breakthrough. In addition to monoclonal blockade of IL-4 and IL-13 pathway, more cytokines have been found to play a substantial role in AD pathogenesis, presenting potential targets for new therapy options.

Colchicine Improves Clinical Outcomes and Quality of Life in Hidradenitis Suppurativa Patients: A Retrospective Study

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the follicular epithelium. The aim of the study was to investigate the effectiveness of colchicine on the clinical outcomes of HS patients, and to evaluate wither colchicine as monotherapy or in combination with doxycycline would provide better outcomes. Methods: A retrospective study was conducted including 44 patients with established HS, divided into three groups. The first group (n = 15 patients) received colchicine as monotherapy, the second group (n = 14 patients) received colchicine and doxycycline 100 mg/d, while the third group (n = 15 patients) received colchicine and doxycycline 40 mg/d. Disease severity during treatment was assessed at baseline and follow-up, using the Hurley Scoring System and the International Hidradenitis Suppurativa Severity Score System (IHS4). All patients were also asked to complete a Dermatology Life Quality Index (DLQI) questionnaire. These scores were compared among the study groups. Results: The DLQI and IHS4 scores significantly improved after treatment with colchicine (p < 0.001) in all groups. All colchicine regimes, including the single colchicine regime, colchicine plus doxycycline 100 mg regime, and colchicine plus doxycycline 40 mg regime, resulted in significant improvements in the DLQI and IHS4 scores (p < 0.001). Clinical improvement based on DLQI and IHS4 scores was similar in all groups. None of the patients had to discontinue the treatment due to adverse events. Discussion: In conclusion, our findings suggest that colchicine may improve clinical severity and quality of life in HS patients, either as monotherapy or in combination with doxycycline, both at antimicrobial (100 mg) and sub-antimicrobial (40 mg) doses.

Salvianolic Acid A Suppresses DNCB-Induced Atopic Dermatitis-Like Symptoms in BALB/c Mice

Prevalence of atopic dermatitis (AD), a chronic, pruritic, and relapsing inflammatory skin disorder, is growing. Because available therapeutics is limited, immune regulators from natural resources could be helpful for treating AD symptoms. The root of Salvia miltiorrhiza Bunge (Lamiaceae) has been studied for the treatment of inflammatory diseases, including dermatologic disorders in Korea. This study examined the effect of salvianolic acid A on AD-like symptoms. Sensitization on the dorsal skin and repeated application on the ears with 2,4-dinitrochlorobenzene (DNCB) were performed in BALB/c mice to induce AD-like skin lesions. After induction of atopic dermatitis, salvianolic acid A (5 and 10 mg/kg) or dexamethasone (10 mg/kg) were administrated via intraperitoneal injection for 3 weeks. Salvianolic acid A suppressed DNCB-induced AD-like symptoms like ear skin hypertrophy and decreased mast cell infiltration into skin lesions. Salvianolic acid A not only reduced DNCB-induced increase of serum IgE but also lowered levels of the Th2 cytokines (IL-4 and IL-13), Th1 cytokine (interferon-γ), and Th17 cytokine (IL-17A). Furthermore, salvianolic acid A blocked DNCB-induced lymph node enlargement. In summary, these results suggest that salvianolic acid A might have a therapeutic potential for the treatment of AD.

TO STUDY THE EPIDEMIOLOGICAL PROFILE OF PITYRIASIS ROSEA

Background: Pityriasis rosea (PR) is an acute inflammatory skin disorder. Though self-limiting but the bothersome symptoms often have a significant impact on the quality-of-life of patients. To study the epidemiological profile of pityriasis rosea. Methods: A prospective controlled study was conducted on 60 patients of pityriasis rosea attending outdoor patient department of Dermatology, Venereology and Leprosy, SP Medical College and PBM Hospital, Bikaner. Results: Mean age of patients in study group was 21.26±10.19 years. 39 patients were female and 21 patients were male. Acute onset of disease was present in 88.30 % of patients. Mother patch was present in 40% patients. Conclusion: We concluded from the present study that pityriasis rosea is common in 20-30 years age group with male predominance. Keywords: Pityriasis rosea (PR), Clinical profile, Skin disorder.

A comprehensive review of therapeutic approaches available for the treatment of dermatitis

: Dermatitis or eczema is a prevalent skin disorder worldwide and is also very common as a pediatric inflammatory skin disorder. Its succession gets worse with the multiple comorbidities which exhibit mechanisms that are poorly understood. Its management further becomes a challenge due to the limited effective treatment options available. However, the novel drug delivery systems (NDDS) along with new targeting strategies can easily bypass the issues associated with dermatitis management. If we compare the active constituents against phytoconstituents effective against dermatitis then phytoconstituents can be perceived to be more safe and gentle. Administration of NDDS of plant extract or actives displays improved absorption behavior, which helps them to permeate through lipid-rich biological membrane leading to increased bioavailability. The newer efficient discoveries related to eczema can face various exploitations. This can be intervened by the subjection of patent rights, which not only safeguard the novel works of individual(s) but also give them the opportunity to share details of their inventions with people globally. The present review focuses on the available research about the use of nanoformulations in the topical delivery. It further elaborates the use of different animal models as the basis to characterize the different features of dermatitis. The review also highlights the recent nanoformulations which have the ability to amplify the delivery of active agents through their incorporation in transfersomes, ethosomes, niosomes or phytosomes, etc.

Skin Mast Cell-Driven Ceramides Drive Early Apoptosis in Pre-Symptomatic Eczema in Mice

Atopic dermatitis (AD or eczema) is the most common chronic inflammatory skin disorder worldwide. Ceramides (Cer) maintain skin barrier functions, which are disrupted in lesional skin of AD patients. However, Cer status during the pre-lesional phase of AD is not well defined. Using a variation of human AD-like preclinical model consisting of a 7-day topical exposure to ovalbumin (OVA), or control, we observed elevation of Cer C16 and C24. Skin mRNA quantification of enzymes involved in Cer metabolism [Cer synthases (CerS) and ceramidases (Asah1/Asah2)], which revealed augmented CerS 4, 5 and 6 and Asah1. Given the overall pro-apoptotic nature of Cer, local apoptosis was assessed, then quantified using novel morphometric measurements of cleaved caspase (Casp)-3-restricted immunofluorescence signal in skin samples. Apoptosis was induced in response to OVA. Because apoptosis may occur downstream of endoplasmic reticulum (ER) stress, we measured markers of ER stress-induced apoptosis and found elevated skin-associated CHOP protein upon OVA treatment. We previously substantiated the importance of mast cells (MC) in initiating early skin inflammation. OVA-induced Cer increase and local apoptosis were prevented in MC-deficient mice; however, they were restored following MC reconstitution. We propose that the MC/Cer axis is an essential pathogenic feature of pre-lesional AD, whose targeting may prevent disease development.