Comparison between synthetic retinoid CD437 and acitretin inhibiting melanoma A375 cell in vitro

Objective： To investigate the effects of synthetic retinoid CD437 and acitretin on cell proliferation, apoptosis, cycle arrest and Bax/ Bcl-2 protein expression of melanoma A375 cell, Methods：MTT assay was used to determine the anti-proliferative effects of CD437 and acitretin on melanoma A375 cell, Flow cytometry was performed to investigate the influence of CD437 and acitretin on cell cycle and cell apoptosis. SABC immunocytochemistry was employed for detection of Bax/bcl-2 protein expressions. Results：10^-5 mol/L CD437 was more effective than acitretin in inhibiting proliferation and inducing apoptosis of A375 cell after 24 h treatment, growth inhibiting ratio and apoptosis ratio（58.6%vs43.25% and 28.03%vs17.13%, P 〈 0.05 respectively）. CD437 promoted G0/G1 arrest in melanoma A375 cell, however acitretin could not. CD437 and acitretin could up-regulate the expression of Bax protein and downregulate the expression of bcl-2 protein（P 〈 0.05）. Conclusion：CD437 is more effective than acitretin in inhibiting proliferation and inducing apoptosis and cycle arrest on A375 cell, CD437 may have more potentialities than acitretin for subsidiary treatment of melanoma. Mitochondrial apoptosis pathway is partially involved in two drugs inducing apoptosis on A375 cell.

A Unique Case? Darier’s Disease Presented as Porcupine-Like Appearance and the Observation on Acitretin Treatment

Dyskeratosis follicularis (Darier’s disease, DD) is rare autosomal dominant disease characterized by hyperkeratotic papules that coalesce into plaques and occur primarily in seborrheic or intertriginous areas. Associated findings include nail abnormalities. A 3-year-old boy presented with porcupine-like appearance for 2 years. The lesion from the back was taken for light microscopy and electron microscopy. He was treated with acitretin (0.31 mg/d to 0.66 mg/d) for 8 years. Light microscopy and electron microscopy showed that the typical features of DD. The patient show good respond to the treatment. During 8 years treatment, the patient had dry mouth and pruritus. The skeletal abnormalities didn’t happen in the patient. The serum lipid profile, liver function and renal function within normal lever after treatment. Our findings showed that porcupine-like appearance is a unique pattern of DD. Acitretin may be a useful therapeutic agent in children with DD and less likely to cause skeletal problems.

Meta-analysis of clinical effect of clearing heat and cooling blood on psoriasis and its effect on inflammatory cytokines

Objective:To evaluate the effect of Qingreliangxue method compared with Acitretin Capsules on clinical efficacy of psoriasis and serum inflammatory cytokines.Methods:The computer searches databases such as CNKI,Wanfang,VIP,PubMed,Embase and Cochrane Library.The search time is from the time the library is built until December 2019.According to the criteria for screening and selection of studies,extract data,use risk assessment tools for quality evaluation,and use Revman 5.3 software to perform meta-analysis on the outcome indicators of the included studis.Results:Finally,20 studies were included,with a total of 1592 patients.The analysis results showed that the total effective rate(OR=3.70,95%CI[2.58,5.30],P<0.00001)and cure rate(OR=2.40,95%CI[1.86,3.10],P<0.00001),PASI score(OR=-2.65,95%CI[-3.60,-1.70],P<0.00001),serum inflammatory cytokines(OR=-8.84,95%CI[-10.52,-7.16],P<0.00001),adverse reactions(OR=0.25,95%CI[0.11,0.57],P=0.001)are superior to Acitretin Capsules.Statistics of the top 10 Chinese medicines in clinical used frequency are,in order,habitat,red peony root,paeonol,honeysuckle,comfrey,soil tuckahoe,salvia miltiorrhiza,buffalo horn,heliotrope,angelica.Conclusion:Based on the current evidence,the treatment of psoriasis with clearing heat and cooling blood as the mainstay of Chinese medicine alone or in combination with Acitretin Capsules can better improve the efficacy,and its mechanism may be related to reducing inflammation.Due to the limitation of the included literature,this conclusion needs to be further verified.

Eruptive Keratoacanthomas within a Red Ink Tattoo: A Case Report

Background: There has been a longstanding debate regarding whether keratoacanthomas (KAs) are neoplastic or reactive/inflammatory lesions. Aim: The aim of this case report is to, within the aforementioned debate, offer support in favor of the potential reactive nature of keratoacanthomas. Case Presentation: A 64-year-old male presented with an eruption of 25 keratoacanthomas within a red ink tattoo. Eruptions were partially resolved over a matter of months, and completely resolved with treatment using oral Acitretin therapy. We believe this to be the third such reported case of eruptive KAs within only the red ink portions of a tattoo. Prior cases involved 2 and 8 KAs each. Discussion: Multiple studies suggest that KAs are neoplastic in nature and very distinct from cutaneous squamous cell carcinoma. Especially interesting is the finding that KAs have increased expression of apoptotic genes;this is particularly notable because of the tendency for these lesions to spontaneously involute. Skin tumorigenesis can occur in predisposed individuals after carcinogen exposure, thus red ink possesses theoretical potential as a carcinogen. KAs could be seen in this case as in fact a reactive neoplasm.

Impact of Adverse Events Associated With Acitretin Treatment of Moderate-to-Severe Plaque Psoriasis:Based on an Observational,Single-Center Study in Shanghai,China

Objective:Acitretin is a widely used systemic retinoid that is to treat psoriasis but has significant variations in efficacy and adverse events(AEs)among individuals.This study aimed to determine the impact of AEs associated with acitretin treatment of moderate-to-severe plaque psoriasis on the Dermatology Life Quality Index(DLQI)and Hospital Anxiety and Depression Scale(HADS)scores.Methods:This prospective,observational,single-center study was conducted from March 2021 to June 2022 and analyzed 116 patients with moderate-to-severe plaque psoriasis treated with acitretin who were followed up for 12 weeks.The primary outcome was the incidence of AEs related to acitretin,and the secondary objective was to investigate the effect of AEs on the DLQI and HADS scores.The generalized linear models were used to assess the association between AEs related to acitretin and DLQI scores or HADS scores,and the association between the involved system/tissue and DLQI scores or HADS scores.Results:A final total of 45 patients were included in the analysis,and a total of 157 treatment-related AEs involving nine organs or systems were reported in 41 patients.The most common AE was skin-or mucosa-related,with 72 cumulative events in 31 patients.AEs also commonly affected the endocrine,digestive,and genitourinary systems.Compared with the group with 0-2 AEs,the group with 3-5 AEs had a significantly increased DLQI score by 5.49 points(95%CI,1.47-9.51)(P=0.0089).Compared with AEs involving 0 to 1 system,AEs affecting 2 to 3 systems resulted in a significant increase in the DLQI score by 5.75 points(95%CI,1.67-9.83)(P=0.0071).Generalized linear models showed no statistically significant associations between AEs and the HADS scores.Conclusion:Our study demonstrates a high incidence of acitretin-related AEs.These AEs may affect quality of life but rarely cause psychological problems such as anxiety and depression.

Efficacy and Safety of Tripterygium wilfordii Hook F Versus Acitretin in Moderate to Severe Psoriasis Vulgaris：A Randomized Clinical Trial

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.

Effect of Chinese Herbal Medicine Combined with Acitretin Capsule in Treating Psoriasis of Blood-Heat Syndrome Type

Objective:To observe the clinical curative effect of Chinese herbal medicine combined with acitretin capsule in treating psoriasis of blood-heat syndrome(P-BH).Methods:Eighty patients of P-BH were randomly assigned to two groups,39 in Group A and 41 in Group B.Both was treated with Chinese herbal medicines for clearing heat,cooling blood and removing toxic substance,and acitretin capsule was given to Group A additionally,with 8 weeks as one therapeutic course.The clinical curative effect was compared betwee...

A harlequin ichthyosis pig model with a novel ABCA12 mutation can be rescued by acitretin treatment

Harlequin ichthyosis (HI) is a severe genetic skin disorder and caused by mutation in the ATP-binding cassette A12 (ABCA12) gene. The retinoid administration has dramatically improved long-term survival of HI, but improvements are still needed. However, the ABCA12 null mice failed to respond to retinoid treatment, which impedes the development of novel cure strategies for HI. Here we generated an ethylnitrosourea mutagenic HI pig model (named Z9), which carries a novel deep intronic mutation IVS49-727 A>G in the ABCA12 gene, resulting in abnormal mRNA splicing and truncated protein production. Z9 pigs exhibit significant clinical symptom as human patients with HI. Most importantly, systemic retinoid treatment significantly prolonged the life span of the mutant pigs via improving epidermal maturation, decreasing epidermal apoptosis, and triggering the expression of ABCA6. Taken together, this pig model perfectly resembles the clinical symptom and molecular pathology of patients with HI and will be useful for understanding mechanistic insight and developing therapeutic strategies.

Assessment by HPLC of the degradation behavior of acitretin under hydrolytic,oxidative,photolytic and thermal stress conditions

Acitretin is a photosensitive oral retinoid with very limited data available on its degradation.The official HPLC method for acitretin determination was insufficient to resolve the degradation products generated during stability studies.Therefore,an isocratic RP-HPLC-UV method was developed for the determination of acitretin in the presence of its related impurities and degradation products.Efficient chromatographic separation was achieved on a Thermo beta-basic column C18(100 mm
4.6 mm,5μm)with mobile phase containing 0.3%(v/v)glacial acetic acid with acetonitrile(ACN)and isopropyl alcohol(IPA)in an isocratic ratio of 70:30 at a flow rate of 1.0 mL/min with the eluent monitored at 360 nm.The method was validated for specificity,linearity,precision,accuracy and robustness.The calibration plot was linear over the concentration range of 50-150μg/mL with a correlation coefficient(r2)of 0.999.The proposed method was used to investigate the degradation kinetics of acitretin under the different degradative conditions.The degradation rate constant(K),half-life(t1/2),and t90 were calculated.Degradation of acitretin followed pseudo-first-order kinetics.The drug was found to be less stable under acidic and photolytic degradation conditions:the photolytic degradation constants for acitretin in sunlight and UV light were 0.002698%and 0.0008402%min1,respectively.The LOD for acitretin and the known impurities were at a level below 0.02%.The method shows consistent recoveries for ACTR(99.8%-101.2%)and also for its known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and useful for characterizing the stability of this chemical.

Efficacy of Acitretin Monotherapy on Basal Cell Carcinoma:A Case Report

Introduction:Basal cell carcinoma(BCC)is the most common skin cancer which mainly affects the population over 50 years of age.In addition to surgical treatment,nonsurgical treatment is also an attractive option for some patients.We herein report a case of an 82-year-old man with BCC successfully treated with acitretin.Case presentation:An 82-year-old man presented with BCC on his left nose wing more than 2 years ago.Due to his unwillingness to accept treatment that may lead to pain,discomfort,or trauma,the patient was prescribed oral acitretin 25 mg twice daily[0.8 mg/(kg·d)]and was instructed to apply 2%fusidic acid cream topically once daily for trauma protection.The lesion progressively shrank in size after 4 weeks of treatment,and was almost completely resolved after 28 weeks of follow-up.The patient reported mild adverse effects,such as mild skin fragility and cheilitis,and apparent scaling skin,which caused minor discomfort but did not affect the continuation of treatment.Discussion:The pathogenesis of BCC is still unclear,but it has been demonstrated to be linked to overactive hedgehog signaling and its crosstalk with other pathways such as phosphoinositide 3-kinase and mammalian target of rapamycin.Acitretin could obviously inhibit cell growth and proliferation and down-regulate AMP-dependent protein kinases that plays critical role in the blocking of malignant progression of several tumors including BCC.Conclusion:We provide an effective alternative for the patients with BCC who are unwilling to receive surgical therapy.