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Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on CD100-mediated T-cell morphology and expressed in the immune system. It may play a role in the pathogenesis of psoriasis. To assess the tissue level of plexin-B2 and plexin B2 related gene polymorphism which is signal regulatory protein gamma (SIRPγ-rs71212732) in psoriatic patients before and after NB-UVB, acitretin therapy alone or in combination and to detect correlation between level of tissue plexin B2 and disease severity and improvement. This single blinded randomized controlled trial was carried on 50 psoriatic patients and 50 healthy controls. Psoriasis Area and Severity Index score (PASI) was used to evaluate the disease severity. Tissue plexin-b2 level was measured using ELISA and SIRPγ-rs71212732 (T\\C) was assessed using TaqMan™ assays and real-time PCR. A significant lower tissue plexin-B2 level was observed in control group (2.9 ± 0.6 pg/g) than cases (25.8 ± 2.8, pg/g) (p < 0.001). Also, a significantly higher tissue plexin-B2 level was observed in sever psoriasis (32.7 ± 3.8 pg/ml) in than moderate psoriasis (13.6 ± 2.1 pg/ml, p = 0.001). Tissue plexin B2 was positively correlated with diseases severity. Significantly higher (TC& TT) genotypes and mutant (C) allele among patients compared to the controls, p < 0.001 for all. Tissue plexin-b2 level was high in psoriasis vulgaris with positive correlation with disease severity and decreased after treatment. This may indicate a role of plexin-b2 in psoriasis vulgaris pathogenesis.

Introduction There are no controlled trials comparing etanercept and acitretin efficacy and therapeutic mechanisms in psoriasis. Materials and methods In the present study, 30 patients were given etanercept 50 mg twice weekly and 30 patients acitretin 0.4 mg/kg per day, both for 12 weeks. Before and after treatment, psoriasis area and severity index was calculated, and serum levels of interleukin (IL)-17, IL-22, and IL-23 were investigated. Results After treatment, psoriasis area and severity index was significantly lower for both groups. However, etanercept-treated patients showed lower psoriasis area and severity index than acitretin-treated ones. Psoriasis patients showed higher IL-17 and IL-22 levels than controls, while no IL-23 was found in any serum. Furthermore, a correlation between IL-17 levels and psoriasis severity was found. Only etanercept was able to reduce IL-17 and IL-22 levels. Conclusions Our findings suggest that etanercept is more effective than acitretin in the treatment of psoriasis and that it is able to affect Th17 system.

Background：Few clinical trials have evaluated the efficacy and safety of Tripterygium wilfordii Hook F （TwHF） compared with acitretin in psoriasis.We aimed to compare the efficacy and safety of TwHF compared with acitretin in the treatment of moderate to severe psoriasis vulgaris.Methods：Adults with Psoriasis Area Severity Index （PASI） score ＞ 10 and psoriasis-affected body surface area ＞ 10％ were randomized into a TwHF （20 mg,3 times a day） or acitretin group （30 mg,once a day）.The treatment course lasted for 8 weeks.Patients were assessed at baseline and at 2,4,and 8 weeks.Laboratory tests were performed at baseline,week 4,and week 8.The data were analyzed using paired samples t-test or analysis of variance （ANOVA）.Results：A total of 115 patients was enrolled （58 TwHF; 57 acitretin）.The median PASI score improved in the TwHF group by 50.4％ and in the acitretin group by 42.7％.There was no significant difference in median PASI improvement between two groups at 2,4,and 8 weeks.There was also no significant difference in PASI 25,PASI 50,PASI 75,and PASI 90 response between the two groups at 2,4,and 8 weeks.There was a significant increase in the level of aspartate transaminase and triglycerides in the TwHF group （P =0.026 and P =0.011,respectively）.In the acitretin group,there was a significant increase in the level of alanine transaminase,cholesterol,and high-density lipoprotein （P =0.030,P ＜ 0.01,and P ＜ 0.01,respectively）.Conclusions：There was no significant difference in treatment efficacy between the TwHF and acitretin groups within 8 weeks,but there were fewer treatment-related adverse events in the TwHF group.

Background/Aim: To investigate the effects of acitretin treatment on insulin resistance (IR) and adipokines, particularly retinol-binding protein (RBP)-4. Methods: Thirty-four patients with chronic plaque psoriasis and a control group of 34 healthy volunteers were recruited in the study. Screening for the parameters was performed before starting and after 3 months of acitretin treatment in the psoriasis group. The control group was only evaluated at the beginning of the study and did not receive placebo. We could not compare our results with a placebo control group because of ethical reasons. Results: Basal adiponectin (p = 0.01), insulin (p < 0.0001) levels and homeostasis model assessment (HOMA) IR (p < 0.0001) were significantly higher in psoriasis patients. After the treatment, insulin (p = 0.014), C peptide (p = 0.011), RBP-4 (p < 0.0001) levels and HOMA-IR (p = 0.008) decreased significantly. Posttreatment leptin (p = 0.036) levels were significantly lower than those of the controls. Posttreatment adiponectin (p = 0.005) and insulin (p = 0.048) levels were higher than those of the controls. Conclusions: This study showed for the first time that RBP-4 levels and IR are decreased significantly with acitretin treatment. This finding is very important in psoriasis patients because psoriasis may cause insulin resistance and diabetes. Further experimental and clinical studies are needed to clarify the effect of acitretin on adipocyte structure and behavior.

ObjectiveTo assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer’s disease.MethodsThe MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses.ResultsNineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI −0.40 to 0.81; I 2=99.8%; minimal important difference 3.1–3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: −0.96, 95% CI −0.99 to −0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit.DiscussionFrom current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.Trial registration numberPROSPERO registration number CRD42019126272.

The goal of the current study was to explore the potential benefits of Acitretin (Act) nanovesicular gel as a prospective antipsoriatic topical delivery system counteracting the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Act-loaded niosomes were successfully developed, entirely characterized, and optimized. Further evaluation of the optimized formula was conducted regarding its stability and ex vivo cytotoxicity on different cell lines. The optimized niosomal vesicles were then incorporated in gel base matrix and investigated by sequential ex vivo (skin permeation and deposition) and in vivo (skin irritation and antipsoriatic activity using mouse tail model) experiments. The optimized Act-loaded niosomes (span 60:cholesterol molar ratio 1:1) were spherical in shape and exhibited the highest entrapment efficiency (90.32±3.80%) with appropriate nanosize and zeta potential of 369.73±45.45 nm and -36.33±1.80 mV, respectively. Encapsulation of the drug in the nanovesicles was further emphasized by differential scanning calorimetric and powder X-ray diffraction studies. After 3 months storage at 4±1°C, the optimized formula preserved its stability. Act nano niosomal gel produced a remarkable enhanced ex vivo permeation profile up to 30 h and significant drug deposition in the viable epidermal-dermal layers compared with those of Act gel. The pronounced antipsoriatic activity of the medicated nano niosomes was proved ex vivo in HaCaT cells (a keratinocyte cell line). Topical application of Act nano niosomal gel to mouse tail model further established its distinct in vivo antipsoriatic superiority in terms of significantly higher orthokeratosis, drug activity, and reduction in epidermal thickness compared with the control and other gel formulations. Also, negligible skin irritation and better skin tolerability of Act nanovesicular gel were revealed by primary irritation index and histopathologic examination.

Acitretin is a synthetic, second-generation retinoid mainly used for the treatment of Darier's disease (DD), which impacts biological processes by binding to a nuclear receptor from the corticosteroid/thyroid receptor superfamily, thereby altering gene expression. Our report outlines the case of a 41-year-old male patient who has received a clinical diagnosis of DD and does not exhibit any other coexisting comorbidities, who developed hypothyroidism posttreatment with acitretin, an unusual and rare side effect of the drug. His baseline routine investigations fell within normal limits before the initiation of acitretin. Acitretin-induced hypothyroidism was treated with thyroxine. Although a good therapeutic response was seen with acitretin, it could not be continued due to the development of side effects and was continued on topical therapy. This case emphasizes the likelihood of adverse effects linked to therapeutic levels of acitretin in patients without any prior history and signifies the critical importance of consistent blood monitoring throughout drug therapy.

Background/Objectives The mechanism of action of treatment drugs for psoriasis is based on anti-inflammation and the inhibition of epidermal proliferation, and retinoids and vitamin D3 derivatives are first-line therapy drugs for psoriasis. This meta-analysis aimed to comprehensively evaluate the efficacy and safety of calcipotriol–acitretin combination therapy for psoriasis and investigate its effect on serum inflammatory factors. Methods A systematic search of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese biomedical literature service system (SinoMed), and Chinese Biomedical Journal Database (VIP), from the earliest record until Dec.13, 2024, was conducted. The outcomes were overall effective rate, Psoriasis Area and Severity Index (PASI) scores, inflammatory factor level and side effects. Results A total of 13 studies with 1196 patients were included in this meta-analysis. The results of this study show that the calcipotriol–acitretin combination therapy could improve the total effective rate when compared with acitretin [RR = 1.25, 95% CI (1.18, 1.33)] or calcipotriol [RR = 1.36, 95% CI (1.20, 1.56)] monotherapy. The combined therapy could decrease the PASI score observably when compared with acitretin monotherapy [SMD =  − 2.26, 95% CI (−3.24, −1.28)] or calcipotriol monotherapy [SMD =  − 3.79, 95% CI (−5.78, −1.79)]. Calcipotriol–acitretin combination therapy remarkably reduced the levels of TNF-α, IL-23, IL-17, INF-γ and IL-6 in serum, while increasing the levels of IL-4 and IL-10 within the serum, compared to acitretin monotherapy. This combination therapy did not increase the risk of skin irritation & burning pain, dry skin and perioral dermatitis. Notably, the incidence of perioral dermatitis was lower in combination therapy than acitretin monotherapy [P = 0.04, RR = 0.24, 95% CI (0.06, 0.93)]. Conclusions The calcipotriol–acitretin combination therapy could be a safe and effective therapeutic strategy in the treatment of psoriasis. However, the lack of PROSPERO registration and the high heterogeneity in this study limited the conclusion, and more high-quality RCTs were needed for further evaluation.

Generalized pustular psoriasis (GPP) is characterized by painful and occasionally disfiguring cutaneous manifestations with sepsis-like systemic symptoms, and is a rare severe variant of psoriasis. Currently, there is no standard treatment for GPP. Here, we report a case of a female patient with ankylosing spondylitis (AS) and mild scalp psoriasis, who developed GPP and alopecia following three courses of adalimumab therapy. The patient’s condition gradually improved following cessation of adalimumab and treatment with secukinumab and acitretin. After eight weeks of treatment, the patient achieved almost complete clearance of her psoriasis, her alopecia improved, and her AS was relieved. Therefore, we believe that a combination of secukinumab with acitretin may be a rational approach for the treatment of severe GPP.

The metalloprotease ADAM10 is a drug target in Alzheimer's disease, where it cleaves the amyloid precursor protein (APP) and lowers amyloid‐beta. Yet, ADAM10 has additional substrates, which may cause mechanism‐based side effects upon therapeutic ADAM10 activation. However, they may also serve—in addition to APP—as biomarkers to monitor ADAM10 activity in patients and to develop APP‐selective ADAM10 activators. Our study demonstrates that one such substrate is the neuronal cell adhesion protein NrCAM. ADAM10 controlled NrCAM surface levels and regulated neurite outgrowth in vitro in an NrCAM‐dependent manner. However, ADAM10 cleavage of NrCAM, in contrast to APP, was not stimulated by the ADAM10 activator acitretin, suggesting that substrate‐selective ADAM10 activation may be feasible. Indeed, a whole proteome analysis of human CSF from a phase II clinical trial showed that acitretin, which enhanced APP cleavage by ADAM10, spared most other ADAM10 substrates in brain, including NrCAM. Taken together, this study demonstrates an NrCAM‐dependent function for ADAM10 in neurite outgrowth and reveals that a substrate‐selective, therapeutic ADAM10 activation is possible and may be monitored with NrCAM. Synopsis The authors provide new insights into the neurobiology of the α‐secretase ADAM10 and show that its therapeutic activation in Alzheimer's disease may be feasible without causing mechanism‐based side effects. Importantly, in human CSF ADAM10 activation may be monitored with its substrate NrCAM as a new biomarker. NrCAM is sequentially cleaved by furin, ADAM10 and γ‐secretase. ADAM10 regulates neurite outgrowth by controlling NrCAM's cell surface expression. Substrate selective ADAM10 activation is feasible and may be monitored by using NrCAM as a companion diagnostic. Graphical Abstract The authors provide new insights into the neurobiology of the α‐secretase ADAM10 and show that its therapeutic activation in Alzheimer's disease may be feasible without causing mechanism‐based side effects. Importantly, in human CSF ADAM10 activation may be monitored with its substrate NrCAM as a new biomarker.