Psoriatic Plaques Research Articles

Deep resolution of clinical, cellular and transcriptomic inflammatory markers of psoriasis over 52 weeks of interleukin-17A inhibition by secukinumab.

Secukinumab, an anti-interleukin (IL)-17A monoclonal antibody, induces histological and molecular resolution of psoriatic plaques by 12 weeks. However, the long-term effects of secukinumab on the molecular resolution of psoriatic inflammation remain unknown. To investigate the molecular resolution of psoriasis following 52 weeks of secukinumab treatment. This was a two-part phase II randomized double-blinded placebo-controlled 52-week study of patients with moderate-to-severe psoriasis receiving secukinumab 300 mg (NCT01537432). Psoriatic lesional and nonlesional skin biopsies were obtained at baseline and at weeks 12 and 52, and the composition of the residual disease genomic profile (RDGP; i.e. 'molecular scar') of biopsies from secukinumab responders analysed. After 52 weeks of treatment, 14 of 24 enrolled patients were considered to be clinical responders [≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75)], 4 of 24 were considered to be nonresponders (< PASI 75) and 6 of 24 patients were lost to follow-up; both the histological and transcriptomic profiles of PASI 75 responders improved from week 12 to week 52. RDGP transcripts of histological responders only partially overlapped between weeks 12 and 52, despite a similar number of transcripts in each RDGP; specifically, four novel transcript subsets showed distinct expression dynamics between weeks 12 and 52 ('slow-resolving', 'recurring', 'persistent' and 'resolved'), with anti-inflammatory and immunomodulatory genes (e.g. SOCS1, CD207 and IL37) notably restored at week 52. Shorter disease duration prior to secukinumab treatment coincided with greater transcript improvements at weeks 12 and 52. Secukinumab improves the histological and molecular phenotype of psoriatic lesional skin up to 52 weeks of treatment; these results suggest possible mechanisms that drive long-term control of psoriasis.

Gasdermin B (GSDMB) in psoriatic patients-a preliminary comprehensive study on human serum, urine and skin.

Psoriasis is one of the most common skin diseases and a crucial issue to manage in contemporary dermatology. The search for the details of its pathogenesis, markers and treatment is continuously ongoing. Our aim was to investigate the role of gasdermin B (GSDMB) in psoriasis, the second protein from the gasdermin family, involved in cell death and proliferation. GSDMB serum and urinary concentrations have never been studied in psoriatics, neither tissue expression of GSDMB by immunohistochemistry. The study included 60 psoriatic patients and 30 volunteers without dermatoses as controls. The serum and urinary GSDMB were evaluated by ELISA. Tissue expression of GSDMB was analyzed by immunohistochemistry. The serum and absolute urine concentrations of GSDMB were significantly higher in psoriatic patients than controls without skin diseases (p = 0.0137, p = 0.039 respectively). Urinary GSDMB/creatinine concentration ratio was significantly lower in patients compared to controls (p = 0.0241). The expression of GSDMB in the dermis and epidermis was significantly more prevalent in psoriatic plaque compared to the non-lesional skin and healthy skin of controls (p = 0.0012, p = 0.017, respectively). Serum GSDMB correlated positively with the age of patients (R = 0.41; p = 0.001). Our study adds to the current state of knowledge about psoriasis concerning the potential involvement of GSDMB. Possibly it could be engaged in keratinocytes migration, which requires further research. Elevated serum GSDMB and decreased urinary GSDMB/creatinine concentration ratio could potentially be investigated as psoriasis biomarkers. GSDMB could be investigated in the future as a potential therapeutic target.

Guselkumab, a Novel Monoclonal Antibody Inhibitor of the p19 Subunit of IL-23, for Psoriatic Arthritis and Plaque Psoriasis: A Review of Its Mechanism, Use, and Clinical Effectiveness.

Psoriatic arthritis and plaque psoriasisare autoimmune conditions affecting multiple organs, including the skin. The pathophysiology and etiology of these conditions are not fully understood; however, numerous factors are believed to play a critical role, including genetics and environmental risk factors. Furthermore, research suggests the IL-23/IL-17pathway partially mediates these diseases. Once the IL-23 receptor is bound and activated, two subunits, p19, and p40, act through different signaling pathways. Ultimately, inflammation is produced through the effector molecule, IL-17, other cytokines, and tumor necrosis factor (TNF). Traditionally, these chronic conditions have been treated with TNF-α inhibitors and methotrexate, a dihydrofolate reductase inhibitor. Although successful in inhibiting the immune system, these drugs can have many adverse effects due to their broad targets. In recent years, more targeted therapy has become popular. Guselkumab is a monoclonal antibody that inhibits the p19 subunit of IL-23. It has been FDA-approved to treat both plaque psoriasis and psoriatic arthritis. Clinical trials showing guselkumab's efficacy have been promising, even showing improvement in symptoms of plaque psoriasis patients resistant to adalimumab, a TNF-α inhibitor. Guselkumab has also been shown to be well tolerated with a similar safety profile as other biologics inhibiting the immune system. In addition to its efficacy in treating plaque psoriasis and psoriatic arthritis, the mechanism of action offers a targeted approach that may minimize the broad immunosuppressive effects often associated with traditional therapies, providing a potential advantage in the long-term management of these autoimmune conditions.

PSORIATIC ARTHRITIS: PROBLEMS AND SOLUTIONS (CASE REPORT)

The purpose of this study is to evaluate the effectiveness of therapy for psoriatic arthritis with tumor necrosis factor inhibitor α–Adalimumab. Material and methods. Retrospective and prospective analyses of psoriatic arthritis course were performed in a patient along with a comprehensive examination before and after administering therapy with a tumor necrosis factor inhibitor α-Adalimumab. The diagnosis of the patient was made on the basis of psoriatic arthritis classification criteria, the assessment of psoriatic rashes was performed according to PASI index. The laboratory study included complete blood cell count and biochemical blood tests. The patient underwent X-ray examinations of the joints and magnetic resonance imaging of the lumbosacral spine in the STIR mode. Study results. The patient's first manifestations of psoriasis were detected at the age of 12 years. At the age of 22, the patient had pain in the lower back of VAS 2-3 points, as well as enthesites in the area of the lateral epicondyle of humerus, wings of the iliac bones, trochanter major, the upper edge of the patella and tibial tuberosity, the PASI index was 17.3 points. In order to relieve pain, the patient took non-steroidal anti-inflammatory drugs. Against the background of therapy with non-steroidal anti-inflammatory drugs, the intensity of pain in the lower back decreased, but enthesites persisted. At the age of 35, the patient was diagnosed with psoriatic arthritis, activity III, stage II, dactylitis, enthesites, PASI index 38.5 points; right-sided active sacroiliitis, ASDAS ESR index activity was 3.92 points, joint functional insufficiency of the 2nd degree. Methotrexate therapy was prescribed. There was no positive dynamics against the background of treatment, in connection with this, therapy with genetically engineered biological drugs was initiated. We observed positive dynamics in the clinical course of psoriatic arthritis when Adalimumab was included in the treatment: after the 2nd week of treatment, the articular syndrome subsided, joint pain decreased when evaluated on a scale of 2-3 points, the number of psoriatic plaques on the trunk and limbs decreased as well, the index of psoriatic rashes was 5.3 points. After 8 weeks from the start of therapy with Adalimumab, regression of pathological skin rashes was noted, the index of psoriatic rashes was 0 points. Conclusions. Therapy with Adalimumab in the patient resulted in regression of psoriatic manifestations on the skin, suppression of psoriatic arthritis activity. The study showed the clinical effectiveness of a genetically engineered biological drug – Adalimumab in achieving persistent clinical remission of psoriatic arthritis.

Saliva: An Emerging Adjunct Biomarker for Psoriasis –Trends, Scope and Relevance

Psoriasis is a widely prevalent chronic immuno inflammatory dermatological disease resulting from a complex and dynamic interplay of genetic, environmental, and immunological aetiologies. It manifests as characteristic erythematous psoriatic plaques visible to the naked eye, but prognostic biomarkers for disease monitoring and therapeutic effectiveness are still absent. Saliva is a biological fluid that, besides being critical to maintaining oral homeostasis, harbors various salivary microbiota and inflammatory markers. It can be easily collected, stored, and analyzed. Oral fluids offer an excellent advantage for biomarker study as they are non-invasive and fast techniques. Studies showed that the saliva of healthy individuals and those with psoriasis had differences in the levels of inflammatory cytokines, immunoglobulin A, and anti-oxidant biomarkers. In GCF, individuals with psoriasis showed higher levels of S100A8, IL-18, and sE-selectin than healthy individuals, independent of periodontal status. Oxidative stress(OS) is one of the pathogenetic factors of psoriasis. Thus levels of ROS and anti-oxidants can also become important factors in diagnosis.

PSORIASIS COMBINED WITH SYSTEMIC AMYLOIDOSIS: CLINICAL OBSERVATION

Secondary amyloidosis is a frequent complication of chronic inflammatory processes. That is why comorbid conditions are possible in which the underlying disease is combined with systemic amyloidosis. Once started, secondary amyloidosis becomes an independent process that complicates the course of the underlying disease that caused it and often becomes the main cause of death of the patient. The aim is to present a case report of psoriasis combined with systemic amyloidosis. Material and methods. The material was a clinical case of psoriasis combined with AL-amyloidosis in a 36-year-old patient who was in a state of persistent clinical remission for 12 years after treatment with melphalan in combination with the introduction of autologous stem cells. From the biopsy material of a psoriatic plaque, we made paraffin sections with a thickness of 5 microns, which were stained with hematoxylin and eosin, or hematoxylin and Congo Red, or thioflavin and subjected to light, polarization and luminescence microscopy. Results. Amyloid deposits were found in the dermis of the patient's psoriatic plaque, which were detected by examining sections stained with Congo Red in polarized light and thioflavin under luminescent microscopy. Conclusions. Despite a persistent clinical remission of systemic AL-amyloidosis, comorbid to preceding psoriasis, obtained as a result of the use of a modern pathogenetic method for treating such conditions – a course of melphalan in combination with autologous stem cell support – amyloid deposits in the psoriatic duty plaque were found in the examined patient.

Differences in the skin microbiota spectrum and parameters of local immunity in the areas of inflammation in skin diseases and healthy people

Alteration of microbiota composition is a trigger, and, sometimes, an etiological factor in the development of chronic skin diseases, e.g., psoriasis or eczema. Recognition of microflora by keratinocytes and immune cells leads to the production of antimicrobial peptides, chemokines and growth factors, which contribute to the differentiation of T lymphocytes to autoaggressive effector cells of Th1, Th17 and Th22 types that implement autoimmune inflammation in the psoriatic plaque. The aim of our work was to study the differences in the skin microbiota spectrum and the parameters of local immunity in capillary blood taken near the focus of inflammation in patients with autoimmune (psoriasis) and allergic (eczema) diseases compared with the parameters of healthy people. 24 patients with psoriasis (group 1), 20 patients with eczema (group 2) and 20 healthy adults (group 3) were examined. Biological materials were taken, i.e., the smears taken with sterile dry swab to the Amies transport medium with activated carbon, and capillary blood was taken in 2 microvets, 200 µL each) from the foci of inflammation on affected skin from the hands of patients, or from the fingers of healthy people. Inoculations of diagnostic media, microscopy with Gram staining and microbial identification were performed in a microbiological analyzer. Immunophenotyping of 22 subsets of mononuclear cells was performed by four-color staining of capillary blood with erythrocyte lysis and evaluation of subsets by a flow cytometer. Cytokines in blood plasma were determined by multiplex method. The spectrum of hand skin microflora of the group 3 was more diverse in the species composition. In patients with psoriasis and eczema, the coccal flora dominated, with a shift towards pathobionts in the microbiota spectrum. Activation of T and B cells, production of pro-inflammatory cytokines, IL-23/IL-17/IL-22 axis cytokines and cytokines – markers of epithelial cell damage (IL-25 and IL-33), as well as anti-inflammatory factors insufficiency were detected. Differences in changing parameters of the local immune status in patients with autoimmune (psoriasis) and allergic (eczema) diseases were revealed, thus reflecting the distinct features of immunopathogenesis in these diseases.

Multiple Lentigines in Resolving Psoriatic Plaques After Treatment with Secukinumab in Two Cases

Multiple Lentigines in Resolving Psoriatic Plaques After Treatment with Secukinumab in Two Cases

Exploring the role of growth factors as potential regulators in psoriatic plaque formation.

Psoriasis is a chronic inflammatory skin disease in which growth activity is more prominent than inflammatory activity at the centre of lesional skin (CE skin). This growth activity is partly influenced by growth factors (GFs) that play an important role in cell growth and inflammation during the plaque development. In this study, we identified potential GFs in CE skin and predicted their regulatory functions and biological activity in mediating transcripts in the plaques. Samples of uninvolved skin (UN skin) and CE skin were biopsied from patients with psoriasis vulgaris for RNA-sequencing analysis in order to identify differentially expressed genes (DEGs). Our finding revealed that epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF) signalling were enriched by CE/UN skin-derived DEGs. Additionally, several EGFR ligands, namely EGF, heparin-binding EGF like growth factor (HB-EGF), amphiregulin (AREG) and transforming growth factor (TGF)-α, as well as TGF-β1, TGF-β2, vascular endothelial growth factor-A, FGFs, PDGF-B and HGF, were predicted to be GF regulators. The regulatory pattern and biological activity of these GF regulators on mediating the CE/UN skin-derived DEGs was demonstrated. This study provides a novel hypothesis regarding the overall regulatory function of GFs, which appear to modulate the expression of the transcripts involved in inflammation and growth in the CE skin. In addition, some GFs may exert anti-inflammatory effects. Further investigations on the mechanisms underlying this regulation may contribute to a deeper understanding of psoriasis and the identification of potential therapeutic targets for patients with psoriasis.

Gasdermin E (GSDME)-A New Potential Marker of Psoriasis and Its Metabolic Complications: The First Combined Study on Human Serum, Urine and Tissue.

Psoriasis is a frequent and incurable skin disease whose pathogenesis is still not fully understood. It is characterized by immune disturbances leading to hyperproliferation and improper differentiation of keratinocytes. Gasdermin E (GSDME) is a protein from the gasdermin family involved in the processes of inflammation and cell death based on apoptosis, necroptosis and pyroptosis. It has never been studied in psoriatics' sera or urine before. Our study enrolled 60 patients with psoriasis and 30 volunteers without dermatoses as controls. Serum and urinary GSDME concentrations were examined by ELISA and tissue expression of GSDME by immunohistochemistry. Serum GSDME concentration was significantly higher in patients than controls (p < 0.05). There were no differences in urinary GSDME concentrations between patients and controls. GSDME expression was significantly higher in the psoriatic plaque than non-lesional patients' skin and compared to controls (both p < 0.001). There was no correlation between serum GSDME or its lesional expression and psoriasis severity, age or disease duration. GSDME serum concentration was significantly negatively correlated with BMI, triglycerides and glucose concentrations. The obtained results suggest the engagement of GSDME in psoriasis pathogenesis. It could potentially become a new non-invasive psoriasis marker. Considering its pro-apoptotic influence, GSDME could be compensatively elevated to direct cells towards apoptosis, whereas under other circumstances, it may lead to pyroptosis and sustain inflammation. GSDME may exert a protective influence on the metabolic complications in psoriasis which requires further studies.

A CASE OF DEVELOPING SQUAMOUS CELL AND BASAL-CELL CARCINOMA IN PATIENTS WITH PSORIASIS

The described clinical example illustrates the rare association of psoriasis with basal cell and squamous cell carcinoma. This clinical case may be of interest to dermatologists and oncologists. It illustrates the neglect of the process in view of the late treatment of the patient. The rising incidence rates of skin cancer are caused by exposure to UVB procedures and increasing with age, which emphasizes the importance of thorough dermatological screening among patients with psoriasis and histological examination of old psoriatic plaques. Alertness for the early detection of skin tumors is relevant not only among medical workers, but also among the population.

Gasdermin D (GSDMD) Is Upregulated in Psoriatic Skin-A New Potential Link in the Pathogenesis of Psoriasis.

Psoriasis is an important issue in daily dermatological practice. Not only is it an aesthetic defect but it is also a matter of decreased life quality and economic burden. However frequent, the pathogenesis of psoriasis remains uncertain despite numerous investigations. Gasdermins are a family of six proteins. Gasdermin D (GSDMD) is the best-studied from this group and is involved in the processes of inflammation, proliferation, and death of cells, especially pyroptosis. GSDMD has never been studied in psoriatic sera or urine before. Our study involved 60 patients with psoriasis and 30 volunteers without dermatoses as controls. Serum and urinary GSDMD concentrations were examined by ELISA. The tissue expression of GSDMD was assessed by immunohistochemistry. The serum-GSDMD concentration was insignificantly higher in the patients than controls. There were no differences in the urinary-GSDMD concentrations between the patients and controls. Strong tissue expression of GSDMD was significantly more prevalent in psoriatic plaque than in the non-lesional skin and healthy skin of the controls. There was no correlation between the serum-GSDMD concentrations and the psoriasis severity in PASI, age, or disease duration. Taking into consideration the documented role of gasdermins in cell proliferation and death, the increased expression of GSDMD in psoriatic skin may demonstrate the potential involvement of this protein in psoriasis pathogenesis. Neither serum, nor urinary GSDMD can be currently considered a psoriasis biomarker; however, future studies may change this perspective.

Arsenic trioxide liposome gels for the treatment of psoriasis in mice

Psoriasis is a chronic, immune-mediated skin disease with no cure. Intravenous arsenic trioxide (ATO) has been used to treat psoriasis in animal studies. However, the high toxicity of ATO limits its application to clinics for systemic administration. The aim of this study was to fabricate sustained-release ATO liposome gels (ATO-Lip-Gels) to be used for the treatment of psoriasis. The ATO Liposomes were prepared using a zinc acetate gradient method. ATO concentrations were analyzed by HPLC-HG-AFS. The ATO-Lip-Gels were characterized with respect to size, zeta potential, and entrapment efficiency. Stability, in vitro drug release, and in vivo efficacy were also evaluated. The optimal formulation of ATO-Lip was ATO (0.45%), S100 (9%), and cholesterol (1.5%) (W/V) in 0.3 mol/L zinc acetate and incubated for 10 min. In the in vitro drug release study, ATO-Lip-Gels exhibited a slower release profile of ATO than that from Gels only. Compared with the model group, ATO-Lip-Gels-H significantly reduced PASI scores after psoriasis in mice and was superior to tacrolimus at day 5. HE staining showed that the pathological changes caused by psoriasis in mice were significantly improved in the treatment groups, and ATO-Lip-Gels-H had the best effect among the treatment groups. ATO-Lip-Gels applied topologically to imiquimote-induced psoriatic plaque models significantly reduced the levels of key psoriatic cytokines such as IL-6 and TNF-α. We have developed ATO-Lip-Gels for the treatment of psoriasis, which demonstrated higher efficacy with the benchmark, Tacrolimus, and can be an alternative to the conventional treatment with Tacrolimus.

Effect of Narrow-Band Ultraviolet B Therapy of Psoriasis Vulgaris on Skin Directional Reflectance, Skin Density and Epidermal Thickness

Psoriasis is an inflammatory dermatosis manifested by the appearance of brown-red papules on the body, covered with silver scales. One of the most common and effective treatments for psoriasis is narrow-band UVB phototherapy. Narrow-band UVB has a wavelength of 311 nm, which results in shallow skin penetration, is absorbed only by the epidermis and the superficial layers of the dermis. The aim of the study was to assess the effect of narrow-band UVB 311 nm phototherapy on skin covered with psoriatic scales and without psoriatic lesions in patients with psoriasis vulgaris on the total directional hemispherical reflectance (DHR) of the skin, skin density and epidermis thickness. For this purpose, a 410 Solar DHR reflectometer and high-frequency ultrasonography DUB SkinScanner were used. A total of 48 volunteers were enrolled. There was a difference in the reflectance of skin without psoriatic scales and psoriatic skin. Depending on the wavelength range, the skin was characterized by different reflectance values. During the course of phototherapy, the reflectance values decreased, both in the psoriatic skin and skin without psoriatic scales. After the phototherapy, the epidermis thickness and SLEB layer decreased and skin density increased in the area with psoriatic plaque. The density of the skin without psoriasis after a series of 20 irradiations increased, while the thickness of the epidermis did not change.

Cyclodextrin-Coordinated Liposome-in-Gel for Transcutaneous Quercetin Delivery for Psoriasis Treatment.

Psoriasis is a chronic inflammatory skin disease that is difficult to treat. Quercetin (QT) is a dietary flavonoid known for its anti-inflammatory effects and safe use in humans. However, the topical application of quercetin for psoriasis treatment presents a significant challenge due to its poor water solubility and low stability in semisolid preparations, where it tends to recrystallize. This work presents a novel liposome-in-gel formulation for the quercetin-based topical treatment of psoriasis. The quercetin-loading liposomes are stabilized by hydroxypropyl-β-cyclodextrin (HPCD), which interacts with phospholipids via hydrogen bonding to form a layer of an HPCD coating on the liposome interface, thus resulting in improved stability. Various analytical techniques, such as FTIR spectroscopy, Raman spectroscopy, and TEM, were used to characterize the molecular coordination patterns between cyclodextrin and liposomes. The results demonstrated that HPCD assisted the liposomes in interfacing with the matrix lipids and keratins of the stratum corneum, thereby enhancing skin permeability and promoting drug penetration and retention in the skin. The in vivo results showed that the topical QT HPCD-liposome-in-gel improved the treatment efficacy of psoriatic plaque compared to free QT. It alleviated the symptoms of skin thickening and downregulated proinflammatory cytokines, including TNF-α, IL-17A, and IL-1β. The results suggested that the HPCD-coordinated liposome-in-gel system could be a stable carrier for topical QT therapy with good potential in psoriasis treatment.

Sericin coated thin polymeric films reduce keratinocyte proliferation via the mTOR pathway and epidermal inflammation through IL17 signaling in psoriasis rat model

Therapeutic treatment forms can play significant roles in resolving psoriatic plaques or promoting wound repair in psoriatic skin. Considering the biocompatibility, mechanical strength, flexibility, and adhesive properties of silk fibroin sheets/films, it is useful to combine them with anti-psoriatic agents and healing stimulants, notably silk sericin. Here, we evaluate the curative properties of sericin-coated thin polymeric films (ScF) fabricated from silk fibroin, using an imiquimod-induced psoriasis rat model. The film biocompatibility and psoriatic wound improvement capacity was assessed. A proteomics study was performed to understand the disease resolving mechanisms. Skin-implantation study exhibited the non-irritation property of ScF films, which alleviate eczema histopathology. Immunohistochemical and gene expression revealed the depletion of β-defensin, caspase-3 and -9, TNF-α, CCL-20, IL-1β, IL-17, TGF-β, and Wnt expressions and S100a14 mRNA level. The proteomics study suggested that ScF diminish keratinocyte proliferation via the mTOR pathway by downregulating mTOR protein, corresponding to the modulation of TNF-α, Wnt, and IL-1β levels, leading to the enhancement of anti-inflammatory environment by IL-17 downregulation. Hematology data demonstrated the safety of using these biomaterials, which provide a potential therapeutic-option for psoriasis treatment due to desirable effects, especially anti-proliferation and anti-inflammation, functioning via the mTOR pathway and control of IL-17 signaling.

Subcutaneous Injection of Allogeneic Adipose-Derived Mesenchymal Stromal Cells in Psoriasis Plaques: Clinical Trial Phase I.

Mesenchymal stromal cells (MSCs) play immunomodulatory role in various autoimmune diseases. Previous pre-clinical and clinical studies have shown that MSCs could be a therapeutic modality for psoriasis. However, the mechanisms of treatment and its possible side effects are under investigation. In this study, the safety and probable efficacy of injecting allogeneic adipose-derived mesenchymal stromal cells (ADSCs) in psoriatic patients were evaluated. In this phase I clinical study with six months of follow-up, total number of 1×106 or 3×106 cells/cm2 of ADSCs were injected into the subcutaneous tissue of each plaque as a single dose in three males and two females (3M/2F) with a mean age of 32.8 ± 8.18. The primary outcome was safety. Changes in clinical and histological indexes, the number of B and T lymphocytes in local and peripheral blood, and serum levels of inflammatory cytokines were assessed. Paired t test was used to compare variables at two time points (baseline and six months after injection) and repeated measures ANOVA test was utilized for variables at three time points in follow-up visits. No major adverse effects such as burning, pain, itching, or any systemic side effects were observed following ADSCs injection, and the lesions showed slight to considerable improvement after injection. The mRNA expression levels of pro-inflammatory factors were reduced in the dermis of the patients after injection. The increased expression level of Foxp3 transcription factor in the patient blood samples suggested modulation of inflammation after ADMSCs administration. Six months after the intervention, no major side effects were reported, but skin thickness, erythema, and scaling of the plaques, as well as the PASI score, were decreased in majority of patients. Our study suggested that ADSC injection could be considered as a safe and effective therapeutic approach for psoriatic plaques (registration number: IRCT20080728001031N24).

The Potential Role of Hyperbaric Oxygen Therapy in Psoriasis Treatment: A Review of PI3K/AKT/FOXO Signaling Cascade and Interleukin-1β

Psoriasis is a chronic, immune-mediated inflammatory skin disorder that affects 2-3% of the population worldwide. Current therapies, including biologic agents, often have adverse effects and incomplete efficacy. Recent studies suggest that the PI3K/AKT/FOXO signalling cascade and interleukin-1 β play a crucial role in the pathogenesis of psoriasis. Hyperbaric oxygen therapy, a safe and well-tolerated procedure, has been suggested as a potential treatment for psoriasis due to its ability to increase tissue oxygenation and reduce inflammation. This review article summarizes the current understanding of the pathophysiology of psoriasis and the potential benefits of hyperbaric oxygen therapy as a treatment modality. The authors suggest that hyperbaric oxygen therapy may modulate the PI3K/AKT/FOXO signalling cascade, reduce interleukin-1 β levels, and improve skin oxygenation, leading to the attenuation of psoriatic plaques. Further clinical studies are needed to confirm the safety and efficacy of hyperbaric oxygen therapy in psoriasis treatment.

Complimentary electrostatics dominate T-cell receptor binding to a psoriasis-associated peptide antigen presented by human leukocyte antigen C∗06:02

Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the human leukocyte antigen (HLA) C∗06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Vα3S1/Vβ13S1) isolated from psoriatic plaques is selective for HLA-C∗06:02, presenting a peptide derived from the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR-HLA-C∗06:02 ADAMTSL5 complex with a stabilized peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C∗06:02 α1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide-binding groove of HLA-C∗06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding the engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis while simultaneously expanding our knowledge of how TCRs engage HLA-C.

Data dynamics of angiogenesis visualization instrumental methods in patients with psoriasis during methotrexate therapy: Clinical and prognostic value of dermatoscopy and ultrasound dopplerography

BACKGROUND: Pathological angiogenesis is one of the important pathogenetic links of psoriasis. At the same time, the prognostic significance of instrumental methods for studying the severity of angiogenesis in psoriatic plaques remains poorly understood.&#x0D; AIM: Clinical assessment of the correlation between the dynamics of angiogenesis parameters (morphometric parameters of vascular glomeruli and Doppler blood flow in the skin and nail bed) and indicators of the methotrexate clinical efficacy during 12 months of therapy.&#x0D; MATERIALS AND METHODS: The work is based on the clinical data analysis of 82 patients with moderate and severe psoriasis vulgaris in the acute stage, who were prescribed methotrexate after initial examination. Patients underwent Doppler ultrasound examination of the skin in psoriatic plaques area and digital dermatoscopy to study the characteristics of vascular angiogenesis loci before treatment and at 1, 3 and 12 months of methotrexate therapy.&#x0D; RESULTS: As a result of comparative correlation analysis of dermatoscopy and ultrasonographic Dopplerography indicators dynamics and psoriasis clinical index values during the treatment of patients with methotrexate, moderate and strong correlations were established between the values of the average diameter of the vascular glomerulus and the degree of increased blood flow in psoriatic plaque area after 1 month of methotrexate treatment and the values of PASI at 3, 6 and 12 months from the start of treatment (r=0.540.76, p=0.0020.005), as well as between the mean vascular glomerulus diameter values and the degree of skin blood flow increase after 3 months and PASI and BSI indices after 6 and 12 months (r=0.360.74, p=0.0010.036). Disappearance of Doppler signals in psoriatic plaques skin and decrease in vascular glomeruli average diameter after 1 month from the start of therapy in 1.76 [1.38; 2.30] and 1.30 [1.38; 2.30] times increase the probability of achieving clinical improvement after three months of methotrexate treatment. The correlation coefficient between the degree of NAPSI reduction after 6 and 12 months of treatment and the dynamics of Doppler blood flow in the nail bed and resistance index of arterial vessels in the nail bed after three months from the start of treatment varied from 0.53 to 0.73.&#x0D; CONCLUSIONS: The dynamics of instrumental methods indicators for studying pathological angiogenesis correlates with the probability of achieving clinical improvement in psoriasis symptoms during systemic methotrexate therapy.