Objective： To observe the effects of different doses of acitretin on the transcription of FGF10 mRNA and the translation of FGF10 protein in cultured HaCaT cells. Methods： HaCaT cells were treated with different dos...Objective： To observe the effects of different doses of acitretin on the transcription of FGF10 mRNA and the translation of FGF10 protein in cultured HaCaT cells. Methods： HaCaT cells were treated with different doses of acitretin for 48 h, then the changes on the transcription of FGF10 mRNA and the translation of FGF10 protein in these cells were detected by immunofluorescence and in situ hybridization assay. Results： Compared with the control group, the transcription of FGF10 mRNA and the translation of FGF10 protein were gradually decreased along with the increasing dose of aeitretin. There were significant differences between different groups （P〈0.01）. Conclusion： Aeitretin could inhibit the transcription of FGF10 mRNA and the translation of FGF10 protein in HaCaT cells. With the dose of aeitretin increased, the stains of both FGF10 mRNA and FGF10 protein in HaCaT cells are reduced.展开更多
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 d...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.展开更多
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. Associ...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.展开更多
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 a...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.展开更多
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...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...展开更多
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 imp...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.展开更多
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 durin...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 mm4.6 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.展开更多
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 ass...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.展开更多
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 so...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.展开更多
基金Supported by the Shaanxi Youth Science Fund (No.2003K10-G56)
文摘Objective： To observe the effects of different doses of acitretin on the transcription of FGF10 mRNA and the translation of FGF10 protein in cultured HaCaT cells. Methods： HaCaT cells were treated with different doses of acitretin for 48 h, then the changes on the transcription of FGF10 mRNA and the translation of FGF10 protein in these cells were detected by immunofluorescence and in situ hybridization assay. Results： Compared with the control group, the transcription of FGF10 mRNA and the translation of FGF10 protein were gradually decreased along with the increasing dose of aeitretin. There were significant differences between different groups （P〈0.01）. Conclusion： Aeitretin could inhibit the transcription of FGF10 mRNA and the translation of FGF10 protein in HaCaT cells. With the dose of aeitretin increased, the stains of both FGF10 mRNA and FGF10 protein in HaCaT cells are reduced.
基金supported by the National Natural Science Foundation of China(No.30371295).
文摘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.
文摘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.
文摘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.
文摘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...
基金the Strategic Priority Research Programs of CAS(XDA16030300)the National Natural Science Foundation of China(81671274,31272440,and 31801031)+1 种基金the National Transgenic Project of China(2016ZX08009003-006-007)the Elite Youth Program of the Chinese Academy of Agricultural Sciences(ASTIP-IAS05).
文摘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.
文摘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 mm4.6 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.
基金sponsored by the National Natural Science Foundation of China(Nos.81872522,82073429,82203913)Youth Program of National Natural Science Foundation of China(No.82003335)+5 种基金Innovation Program of Shanghai Municipal Education Commission(No.2019-01-07-00-07-E00046)Clinical Research Plan of SHDC(Nos.SHDC2020CR1014B and SHDC2020CR6022),Program of Shanghai Academic Research Leaders(No.20XD1403300)Program of Science and Technology Commission of Shanghai Municipality(No.18140901800)Excellent Subject Leader Program of Shanghai Municipal Commission of Health and Family Planning(No.2018BR30)Clinical Training Program(No.lcfy2020-02)Fundamental Research Funds for the Central Universities(22120220602).
文摘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.
基金the Natural Science Foundation of Guangdong(No.2020A1515010275)Characteristic Clinic Project of Guangzhou Health Commission(No.2019TS68)the Medical and Health Technology Projects of Guangzhou(No.20191A010052).
文摘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.
