Efficacy of topical 30% salicylic acid in combination with minocycline in moderate to severe acne.

To evaluate the efficacy of topical 30% salicylic acid plus minocycline in moderate to severe acne. One hundred patients with moderate to severe acne from February 2020 to February 2021 were retrospectively analyzed. They were assigned (1:1) to receive either topical 30% salicylic acid plus minocycline (combination group) or minocycline (mono therapy group). The acne scores, physician subjective and objective scores, efficacy, quality of life, incidence of adverse reactions, recurrence and satisfaction in both groups were compared. The combination group had lower Global Acne Grading System (GAGS) scores, erythema scores and papulopustular scores than the mono therapy group. Combined therapy was associated with lower erythema absolute value and erythema index, more skin water content and less transcutaneous water loss versus minocycline. Higher efficacy, acne symptoms scores, and quality of life were observed with combination therapy versus mono therapy (P<0.05). The two groups had a similar incidence of adverse reactions and recurrence. Combination therapy showed a higher appearance satisfaction versus mono therapy. The efficacy of topical 30% salicylic acid plus minocycline for moderate to severe acne was better versus minocycline.

Efficacy of supramolecular salicylic acid in combination with doxycycline in the treatment of acne.

To determine the efficacy of supramolecular salicylic acid combined with doxycycline on acne, totally 70 patients with acne treated in our dermatology department from May 2020 to May 2021 were enrolled and randomized (1:1) into control or experimental groups using the random number table method. The control group was given doxycycline for oral administration while the experimental group was given oral doxycycline combined with supramolecular salicylic acid for topical administration. The overall effective rate of treatment was significantly higher in the experimental group versus control group (97.14% vs. 82.86%, P<0.05). Patients in the control group had significantly longer mean acne regression time after treatment versus experimental group (P<0.05). After treatment, patients in the experimental group had significantly lower self-rating depression scale (SDS) scores and self-perceived burden (SPB) scores than the control group, while Short Form 36-item health survey (SF-36) scores were significantly higher than the control group (P<0.05). The overall incidence of adverse reactions was significantly lower in the experimental group versus control group (5.71% vs. 17.14%, P<0.05). Supramolecular salicylic acid in combination with doxycycline in the treatment of patients with acne is an optimal option, as it could better promote acne regression, reduce the level of depression and reduce the patient's self-perceived burden.

Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROS-mediated JAK2/STAT5 signaling pathway.

BACKGROUND AND PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritus and impaired skin barrier function. The pathology of AD involves in immune dysfunction and epidermal barrier disruption. Reactive oxygen species (ROS) are found to be associated with AD, and play a role in the immunological abnormalities and dysfunctional skin barrier. Nicotinamide mononucleotide (NMN) plays an important role in oxidative stress related diseases, but its role in AD is unclear. METHODS: KM mice were treated with DNFB to induce AD-like lesion and typical applied with NMN for two weeks. The dermatitis score, the degree of itching and TEWL were evaluated during modeling. Epidermal thickness of skin lesions and histopathological changes were detected. Further, inflammatory factors, epidermal differentiation-related genes, oxidative stress indicators and JAK2/STAT5 signaling pathway were evaluated. NHEK cells were stimulated by TNF-α/IFN-γ after pre-treatment with NMN, then ROS levels, inflammatory factors and JAK2/STAT5 signaling pathway were detected. RESULTS: NMN exhibited potent anti-atopic activities, shown by alleviated AD-like symptoms, inhibited the increased expression of inflammatory cytokines and restored proteins and mRNA level of skin barrier genes. In addition, NMN inhibited TNF-α/IFN-γ-stimulated elevation of inflammatory chemokines, which was associated with blocking the activation of ROS-mediated JAK2/STAT5 pathway. CONCLUSION: NMN may have a positive effect on relieving symptoms of AD.

Dual specificity phosphatase 22 relates to skin lesion degree and biologics history, while its longitudinal elevation during treatment reflects better outcome in psoriasis patients.

BACKGROUND: Dual specificity phosphatase 22 (DUSP22) plays an important role in the regulation of immune and inflammation, but its correlation with clinical features and treatment outcome in psoriasis patients is still unclear. This study was to investigate the longitudinal change of DUSP22 with time, as well as its association with disease activity and treatment response in psoriasis patients. METHODS: Totally, 120 psoriasis patients, 50 patients with other skin inflammations as disease controls (DCs), and 50 health controls (HCs) were recruited. Serum samples were collected from psoriasis patients at baseline, month (M)1, M3, and M6 after initiation of etanercept-based treatment as well as from DCs and HCs after enrollment to assess DUSP22 level by enzyme-linked immunosorbent assay. RESULTS: DUSP22 was lower in psoriasis patients than in HCs and DCs (both p < 0.001). Besides, in psoriasis patients, DUSP22 was associated with lower psoriasis area severity index (PASI) score (p = 0.001) and systemic biological treatment history (p = 0.023), but not with other demographics, disease characteristics, or treatment history (all p>0.05). In addition, DUSP22 was increased with time (p < 0.001) in total patients. Moreover, DUSP22 at M3 (p = 0.004) and M6 (p < 0.001) was higher in response patients than in non-response patients evaluated by PASI 75. Additionally, DUSP22 at M3 (p < 0.001) and M6 (p = 0.003) was also increased in response patients compared with non-response patients evaluated by PASI 90. CONCLUSION: DUSP22 decreases and negatively correlates with disease activity, while its longitudinal elevation with time reflects satisfactory treatment response in psoriasis patients.

Literature Overview of the IL-17 Inhibition from Psoriasis to COVID-19.

The COVID-19 pandemic has posed a serious problem for drug anti-viral efficacy in combatting the cytokine storm triggered by SARS-CoV-2. From dermato-epidemiological studies conducted on psoriatic and other rheumatological patients, IL-17 inhibitors seem to attenuate or even prevent the cytokine storm and thus ICU referral. Furthermore, both in-vivo and in-vitro experiments suggest that IL-17 plays a key role in SARS-CoV-2 infection progression. Due to this evidence, we decided to summarize the literature findings on IL-17 inhibitors and COVID-19, maintaining psoriasis as the referral disease to better understand the extent of drug effects on the immune system.

Circ-IGF1R plays a significant role in psoriasis via regulation of a miR-194-5p/CDK1 axis.

Psoriasis is a skin disorder that is classed as an autoimmune disease. It is characterized by excessive proliferation, abnormal migration and differentiation of keratinocytes, as well as inflammatory cell infiltration. Circular RNAs (circRNAs/circ) have been reported to play an important role in several aspects of psoriasis. Thus in the present study, the role of circ-insulin-like growth factor 1 receptor (circ-IGF1R) in the development of psoriasis was assessed, and the involvement of microRNA (miR)-194-5p was also investigated as its expression was downregulated in psoriasis. StarBase analysis and dual luciferase reporter assays confirmed the interaction between circ-IGF1R with miR-194-5p. The increased expression of circ-IGF1R and decreased expression of miR-194-5p were further confirmed by reverse transcription-quantitative polymerase chain reaction in interleukin (IL-22)-stimulated HaCaT cells. The increased proliferation, migration and invasion, as well as decreased apoptosis, caspase 3 activity and cleaved-caspase 3/caspase 3 ratio were observed in IL-22-stimulated HaCaT cells. Conversely, transfection of circ-IGF1R-small interfering (si)RNA resulted in significantly increased expression of miR-194-5p with or without stimulation of IL-22 in HaCaT cells, and also overcame the effects of the miR-194-5p inhibitor. Additionally, transfection of circ-IGF1R-siRNA inhibited cell proliferation, migration and invasion, which were reversed by transfection of a miR-194-5p inhibitor. Similarly, circ-IGF1R-siRNA promoted apoptosis, caspase 3 activity and the cleaved-caspase 3/caspase 3 ratio, which were reversed by miR-194-5p inhibitor. These results showed that circ-IGF1R could affect the proliferation, apoptosis, migration and invasion of IL-22-stimulated HaCaT cells by regulating the expression of miR-194-5p. Based on TargetScan prediction and dual luciferase reporter assays, it was shown that cyclin-dependent kinase (CDK)1 was targeted by miR-194-5p. Additionally, the expression of CDK1 was upregulated following stimulation with IL-22 in HaCaT cells at the mRNA and protein levels. Transfection of miR-194-5p mimic or miR-194-5p inhibitor negatively regulated CDK1 expression in the IL-22 induced HaCaT cells. In conclusion, circ-IGF1R-siRNA could inhibit the cell proliferation, migration and invasion, and induce apoptosis by regulating the miR-194-5p/CDK1 axis. circ-IGF1R may thus serve as a potential treatment target for psoriasis.

Body Mass Index, Disease Duration and Tumor Necrosis Factor Inhibitor History Predict Reduced Ustekinumab Response in Chinese Psoriasis Patients: A Real-World Study.

BACKGROUND: Ustekinumab, as a monoclonal antibody against interleukin (IL)-12 and IL-23, gets approved in China since 2019, therefore fewstudies report the application of ustekinumab in treating Chinese psoriasis patients in the real clinical settings until now. AIMS: Thus, this study aimed to evaluate treatment efficacy, treatment response-related factors, and safety of ustekinumab in treating Chinese psoriasis patients. MATERIALS AND METHODS: Totally, 72 moderate-to-severe plaque psoriasis patients who underwent ustekinumab treatment were analyzed. Their clinical data were recorded. Furthermore, improvement of psoriasis area severity index (PASI) score more than 75% (PASI75) and improvement of PASI score more than 90% (PASI90) at week 12 and week 24 were retrieved. Besides, the adverse events were reviewed. RESULTS: There were 72.2% and 37.5% psoriasis patients who achieved PASI75 response and PASI90 response at week 12. Meanwhile, 86.7% and 46.7% psoriasis patients realized PASI75 response and PASI90 response at week 24. Besides, multivariant logistic regression analyses revealed that body mass index (BMI), disease duration, and history of tumor necrosis factor (TNF) inhibitors could independently predict reduced ustekinumab response in psoriasis patients. Additionally, the most common adverse events of ustekinumab treatment in psoriasis patients were infection (12.5%) and nasopharyngitis (9.7%), followed by headache (4.2%), cough (4.2%), abnormal hepatic function (4.2%), injection site reactions (2.8%), and eosinophilia (1.4%), which were all mild and manageable. CONCLUSIONS: Ustekinumab is an effective and safe immunotherapy drug for treating Chinese psoriasis patients. Furthermore, BMI, disease duration, and history of TNF inhibitors are predictors of poor ustekinumab response.

IL-1ß, IL-17A and combined phototherapy predicts higher while previous systemic biologic treatment predicts lower treatment response to etanercept in psoriasis patients.

BACKGROUND: This study aimed to explore the correlation of circulating inflammatory cytokines' levels with treatment response to etanercept (ETN) treatment in psoriasis patients. METHODS: 97 moderate-to-severe plaque-psoriasis patients were continuously recruited in this prospective cohort study, and all patients received ETN treatment. Serum samples were collected before and at 6 months (M6) after treatment, and nine inflammatory cytokines expressions were detected by enzyme-linked immuno sorbent assay. Psoriasis Area and Severity Index (PASI) score was evaluated at baseline (M0), 1 month (M1), 3 months (M3) and M6 after treatment, and the corresponding PASI 75/90 responses' rates were calculated. RESULTS: Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-12, IL-17A, IL-22, IL-23, and IL-32 levels were reduced, while IL-10 level was elevated at M6 after ETN treatment compared to baseline. PASI 75/90 responses' rates to ETN were 69.1 and 38.1% at M6, respectively. IL-1ß and IL-17A levels were elevated in PASI 75-response patients compared to PASI 75 non-response patients, while IL-17A level was also increased in PASI 90-response patients compared to PASI 90 non-response patients. Multivariate logistic regression revealed that IL-1ß, IL-17A and combined phototherapy during study predicted higher, while previous systemic biologic treatment predicted lower PASI 75 response to ETN independently. In addition, IL-17A independently predicted higher PASI 90 response to ETN as well. CONCLUSIONS: IL-1ß, IL-17A, and combined phototherapy predicts higher while previous systemic biologic treatment predicts lower treatment response to ETN independently in psoriasis patients.

Effects of RNA interference-mediated E-selectin gene silencing on cell adhesion molecule expression and cell-cell adhesion in vascular endothelial cells in mice with immunologic contact urticaria.

Contact urticaria is recognized as the wheal and flare reaction at a site from direct contact with a chemical or protein agent. Ongoing studies have proposed that gene silencing may have a promising future in finding optimal treatment of a variety of disease; hence, the aim of the study was to investigate the effect of RNA interference-mediated E-selectin ( SELE) gene silencing on cell adhesion molecule expression and on cell-cell adhesion in vascular endothelial cells (VECs) in a mouse model of immunologic contact urticaria (ICU). Following the successful establishment of mouse models of ICU induced by antidinitrophenol immunoglobulin E (IgE) combining 2,4-dinitrofluorobenzene challenge, enzyme-linked immunosorbent assay and immunohistochemistry were used to measure the levels of IgE, interleukin 4 (IL-4), interferon-γ (IFN-γ), and histamine as well as the positive expression rate of SELE, respectively. The siRNA- SELE vector was constructed and transfection efficiency was estimated prior to performing quantitative reverse-transcription polymerase chain reaction and Western blot assay to determine the relative expression of SELE, eosinophil cationic protein (ECP), intercellular adhesion molecule 1 (ICAM-1), L-selectin (CD62L), and the alpha chain of leukocyte function-associated antigen-1 (CD11a). Adhesion assay was then performed to assess the cell adhesion ability in VECs. Elevated levels of IgE, IL-4, IFN-γ, and histamine and increased positive expression rate of SELE were indicative of successful establishment of mouse models of ICU. Furthermore, the relative expression levels of SELE, ECP, ICAM-1, CD62L, and CD11a were highest in the OE- SELE group. Besides, cell adhesion ability of VECs was notably promoted. Collectively, the current study define the potential role of SELE silencing as an inhibitor to ICU development by inhibiting cell adhesion ability of VECs.