Predicting the Activity of Oral Lichen Planus with Glycolysis-related Molecules:A Scikit-learn-based Function

Objective Oral lichen planus(OLP)is one of the most common oral mucosa diseases,and is mainly mediated by T lymphocytes.The metabolic reprogramming of activated T cells has been shown to transform from oxidative phosphorylation to aerobic glycolysis.The present study investigated the serum levels of glycolysis-related molecules(lactate dehydrogenase,LDH;pyruvic acid,PA;lactic acid,LAC)in OLP,and the correlation with OLP activity was assessed using the reticular,atrophic and erosive lesion(RAE)scoring system.Methods Univariate and multivariate linear regression functions based on scikit-learn were designed to predict the RAE scores in OLP patients,and the performance of these two machine learning functions was compared.Results The results revealed that the serum levels of PA and LAC were upregulated in erosive OLP(EOLP)patients,when compared to healthy volunteers.Furthermore,the LDH and LAC levels were significantly higher in the EOLP group than in the nonerosive OLP(NEOLP)group.All glycolysis-related molecules were positively correlated to the RAE scores.Among these,LAC had a strong correlation.The univariate function that involved the LAC level and the multivariate function that involved all glycolysis-related molecules presented comparable prediction accuracy and stability,but the latter was more time-consuming.Conclusion It can be concluded that the serum LAC level can be a user-friendly biomarker to monitor the OLP activity,based on the univariate function developed in the present study.The intervention of the glycolytic pathway may provide a potential therapeutic strategy.

Prediction of potential targets and molecular mechanisms of Tripterygium hypoglaucum for oral lichen planus based on network pharmacology and molecular docking

Objective:To explore the potential targets and molecular mechanisms of tripterygium hypoglaucum for oral lichen planus(OLP)by applying network pharmacology and molecular docking technology.Methods:The active ingredients and targets of tripterygium hypoglaucum were screened.OLP-related targets were predicted.The Protein-Protein Interaction(PPI)network was constructed for the intersection targets of tripterygium hypoglaucum and OLP.The“OLP-target-molecule-Tripterygium hypoglaucum”network was constructed and visualized.The intersection genes were screened for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking analysis and visualization were performed.Results:15 active ingredients and 78 targets of tripterygium hypoglaucum were obtained.9109 OLP-related targets were screened,and 54 intersection genes of tripterygium hypoglaucum with OLP were obtained.The top 10 key targets were screened from the constructed PPI network.The top 10 active ingredients of tripterygium hypoglaucum were screened from the constructed“OLP-targets of actionactive ingredients-tripterygium hypoglaucum”network.The GO and KEGG analyses of the 54 intersection targets indicated that tripterygium hypoglaucum may play a therapeutic role by regulating one carbon pool by folate,pathways in cancer,et al.Molecular docking analysis showed that dihydrofolate reductase(DHFR),phosphoribosylglycinamide formyltransferase(GART),estrogen receptor 1(ESR1),et al are the key targets for the treatment of OLP in tripterygium hypoglaucum.Conclusion:The potential key targets and molecular mechanisms of tripterygium hypoglaucum in treating OLP provide a theoretical basis for new drug development and clinical applications.

Unilateral lichen planus with Blaschko line distribution: A case report

BACKGROUND Lichen planus(LP)with distribution of lesions along Blaschko’s lines is a rare entity,accounting for 0.24%-0.62%of all patients.Unilateral distribution of lesions in arm,leg,trunk,and waist is even less common.Approximately 10%of patients with LP manifest nail lesions.CASE SUMMARY A 20-year-old woman presented to our department with polygonal,purpuric,flattopped papules over the right arm,right leg,and right side of trunk and waist for the last 5 mo.The patient initially developed nail deformation in the left middle finger with no obvious cause,followed by development of blue-purple and red maculopapular rash with pruritus.During the disease course,the skin lesions aggravated and spread to several segments due to scratching.The lesions showed unilateral distribution along the Blaschko’s lines.The diagnosis of LP along Blaschko’s lines was established based on dermoscopy and skin biopsy.Her cutaneous lesions considerably improved after 4-wk treatment with intramuscular glucocorticoid,oral acitretin,topical glucocorticoid,and retinoids.CONCLUSION Cases of LP involving multiple segments of the body along the Blaschko’s lines with nail damage are rare.

Photodynamic therapy of oral leukoplakia and orallichen planus using methylene blue:A pilot study

Premalignant lesions like oral lichen planus(OLP),oral leukoplakia(OL)has a fair probability of transforming into malignancy and they are perverse toward conventional therapies.Photody-namic therapy(PDT)has been considered as an alternative/complimentary therapeutic mo-dality for the management of premalignant lesions.In this study,methylene blue mediated photodynamic therapy(MB-PDT)was used as a possible alternative method for the treatment of OLP and OL.A total of 15 OLP lesions and 13 OL lesions were enrolled in the study.The patients were irradiated 1using metal halide lamp filtered at 630土10nm,with a light exposure dose of 120 J/cm^(2) per stting.For the OLP lesions,MB-PDT was performed once a week for four weeks and for the OL lesions,MB-PDT was performed twice a week for three weeks.Lesions were evaluated pre-and post-and at follow-u sessions by changes in sign and symptom scores,and size of lesions.We have observed a 53.3%of complete reduction in the treated OLP lesions and their decrease in size,sign and symptom score after treatment and at follow-up session was statistially signifcant.We have also observed complete response for one OL lesion of the 13 treated lesions.The result indicates that MB-PDT is an effective modality in management of OLP and OL.Among the two types of premalignancies treated with MB-PDT,OLP lesions responded much better than that of OL.

Treatment of cutaneous lichen planus with ALA-mediated topical photodynamic therapy

Purpose:To evaluate the efectiveness of topical 5-aminolevulinie acid(ALA)-mediated pho-todynamic therapy(PDT)for the treatment of cutaneous lichen planus(LP).Methods:A total of 17 symptomatic LP lesions in 7 Chinese patients were assessed.ALA cream(10%)was applied topically to LP lesions for 3h.The lesions were iradiated with a 635 nm diode laser at the dose level of 100J/cm^(2).The treatment was repeated at two week intervals.Clinical assessmnent was conducted before each treatment.Follow-up was performed once a month for up to six months.Results:Lesions showed significant improvement after one to four courses of treatments.Complete response was achieved in 13 lesions(five patients)and partial remission in four lesions(two patients).The complete response rate was 71%.There was no significant side ffects except the feeling of pain that most patients could tolerate.Follow-up of five patients who achieved complete response showed no signs of recurrence.Conclusion:Topical ALA PDT is effective in the treatment of cutaneous LP.

Lichen planus affecting a 12-year-old girl

Lichen planus (LP) is a chronic inflammatory mucocutaneous condition which is relatively common in adults but rarely affects children. In addition, few cases with oral lesions affecting children have been reported in the literature. The purpose of this study is to report an unusual case of oral LP involving the tongue and buccal mucosa in a child. A 12-year-old girl complained of painless oral lesions with 18 months of evolution. On clinical evaluation, multiple white lesions in tongue and buccal mucosa were observed with no cutaneous lesions. Diagnosis was made based on clinical examination and histopathological features. No active treatment was necessary. The patient is currently under regular evaluation. Although rarely reported in childhood, lichen planus should be considered in a differential diagnosis of hyperkeratotic and/or reticular lesions of the oral mucosa in children.

Esophageal lichen planus:Current knowledge,challenges and future perspectives

Lichen planus(LP)is a frequent,chronic inflammatory disease involving the skin,mucous membranes and/or skin appendages.Esophageal involvement in lichen planus(ELP)is a clinically important albeit underdiagnosed inflammatory condition.This narrative review aims to give an overview of the current knowledge on ELP,its prevalence,pathogenesis,clinical manifestation,diagnostic criteria,and therapeutic options in order to provide support in clinical management.Studies on ELP were collected using PubMed/Medline.Relevant clinical and therapeutical characteristics from published patient cohorts including our own cohort were extracted and summarized.ELP mainly affects middle-aged women.The principal symptom is dysphagia.However,asymptomatic cases despite progressed macroscopic esophageal lesions may occur.The pathogenesis is unknown,however an immune-mediated mechanism is probable.Endoscopically,ELP is characterized by mucosal denudation and tearing,trachealization,and hyperkeratosis.Scarring esophageal stenosis may occur in chronic courses.Histologic findings include mucosal detachment,T-lymphocytic infiltrations,epithelial apoptosis(Civatte bodies),dyskeratosis,and hyperkeratosis.Direct immuno-fluorescence shows fibrinogen deposits along the basement membrane zone.To date,there is no established therapy.However,treatment with topical steroids induces symptomatic and histologic improvement in two thirds of ELP patients in general.More severe cases may require therapy with immunosuppressors.In symptomatic esophageal stenosis,endoscopic dilation may be necessary.ELP may be regarded as a precancerous condition as transition to squamous cell carcinoma has been documented in literature.ELP is an underdiagnosed yet clinically important differential diagnosis for patients with unclear dysphagia or esophagitis.Timely diagnosis and therapy might prevent potential sequelae such as esophageal stenosis or development of invasive squamous cell carcinoma.Further studies are needed to gain more knowledge about the pathogenesis and treatment options.

Treatment of oral lichen planus by surgical excision and acellular dermal matrix grafting:Eleven case reports and review of literature

BACKGROUND Oral lichen planus(OLP)is a chronic inflammatory disorder,and it can affect normal oral function.The conventional treatments for OLP are not always effective,and relapse easily occurs.Therefore,treatment of OLP is difficult and challenging.In this study,we evaluated over a long period the clinical efficacy of surgical excision and acellular dermal matrix(ADM)grafting in patients with refractory OLP.CASE SUMMARY Eleven patients with refractory OLP underwent a standardized protocol of surgical excision and ADM grafting.The condition of the area of the grafted wound,the intraoperative maximum mouth opening,pain,and clinical healing were assessed at postoperative follow-up visits.All patients had a flat surgical area with similar mucosal tissue coverage and local scar formation.Patients had no irritation and pain in their mucous membranes when eating acidic and spicy food.All patients’mouth openings returned to normal within 2-6 mo after surgery.During follow-up,none of the patients had recurrence of OLP after surgery.The longest follow-up was 11 yr and the shortest was 6 mo,and none of the patients relapsed during follow-up.CONCLUSION Surgical excision and ADM grafting could be an effective method to treat refractory OLP.

Histopathological and Immunohistochemical Study of the Distinction between Oral Lichen Planus and Oral Lichenoid Lesions

Background: Oral potentially malignant disorders, which include oral lichen planus (OLP), are clinical presentations that carry a risk of development to cancer in the oral cavity. Oral lichenoid lesions (OLLs) are also termed interface/lichenoid mucositis. Malignant transformation of them remains controversial, but distinct clinical and histological criteria for how to differentiate OLP from OLLs have not been developed. Objectives: The purpose of this study was to elucidate findings that can allow histopathological differentiation of OLP and OLLs using histomorphological and immunohistochemical analyses. Materials and Methods: Analyses were performed in 10 cases diagnosed with OLP and 9 cases diagnosed with OLLs. Cytokeratin 19 (CK19), Ki-67 and CD3 were used as primary antibodies to detect basal cells, proliferative activity and T-cell distribution, respectively, and Perlecan and COX-2 to evaluate epithelial intracellular arrangements and interstitial distributions of proteoglycans and enzymes. Results: For CK19, positive cells were significantly found in OLLs at both the prominent area and site adjacent to the lesion comparison with those of OLP’s. The number of COX-2 positive cells was significantly higher in spinous and basal layers in OLLs of the prominent area. Additionally, OLLs showed mild to moderate expression for perlecan in the basal to spinous layers and in subepithelial tissue. Conclusion: Almost no basal cells were noted in the prominent area in OLP. COX-2 and perlecan were found in the basal to spinous layers in OLLs. Although there are restrictions, these suggested the possibility of helping to distinguish between OLP and OLLs.

Lichen Planus Pigmentosus Inversus:Two Case Reports

Introduction:Lichen planus pigmentosus inversus(LPPI)is a rare a rare variant of lichen planus characterized by hyperpigmented patches with predominating localization in intertriginous areas.Due to its rarity,only a few LPPI cases are reported.We herein describe two rare cases of LPPI.Case presentation:The two patients were all with a brownish macular lesion on the intertriginous area.A diagnosis of LPPI was made based on their clinical manifestations,dermoscopic features,and histopathologic features,which revealed an interface change,lichenoid infiltration,and pigmentary incontinence.Discussion:LPPI is pruritic or asymptomatic,hyperpigmented macules and patches on the flexural folds.The axillae and flanks were the most commonly affected areas,followed by the groin and genitalia.About half of the female patients had inframammary fold lesions.LPPI shows higher female predominance than Lichen planus pigmentosus.There were fewer cases that lasted more than 3 years compared to LPP.Conclusion:LPPI is a rare variant of lichen planus,with a locational characteristic and female predominance.Therefore,in the case of a pigmented disease occurring in the flexural folds,it should be placed in the differential diagnosis.

Research Progress of MicroRNAs and Related Factors in the Pathogenesis of Lichen Planus

More evidences show that microRNAs play an important role in the pathogenesis of infiammation and autoimmune diseases including Lichen planus,and are an attractive therapeutic target.MicroRNA family plays an important role in the regulation of gene expression,which involves cell proliferation,apoptosis,growth,differentiation and metabolism,vascularization,immune response and other biological processes.The changes of expression profile and expression level are closely related to the occurrence and development of many diseases,such as tumor,inflammatory disease and autoimmune disease relevant.However,there are few reports on microRNA in the pathogenasis of LP.This review summarizes the research advance of microRNAs(microRNAs-137,microRNAs-125b,microRNAs-138,microRNAs-27b,microRNAs-203)and their downstream proteins in LP.

Mechanism of Huashi Xingyu Qingre recipe(化湿行淤清热方)in treating oral lichen planus based on network pharmacology and clinical trial verification

OBJECTIVE:To identify the main active components and targets of Huashi Xingyu Qingre recipe(化湿行淤清热方,HXQR)and to investigate its mechanism in the treatment of oral lichen planus(OLP).METHODS:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was searched to identify the active ingredients and corresponding targets of HXQR.Disease genes were obtained from the Gene Cards database,and a“drugdisease regulatory network”was constructed using Cytoscape software and PERL programming language.The STRING database was used to build a protein-protein interaction network.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)terms were analyzed using R software with a Bioconducter plugin.Finally,the results and the efficacy of HXQR in treating OLP were validated in a clinical trial that included enzyme-linked immunosorbent assay(ELISA)testing and observations of the post-treatment changes in clinical symptoms.RESULTS:HXQR contained 167 active components and 261 targets,with 391 disease targets.The intersection of these two categories in a Venn diagram revealed 57 drugdisease common targets.A compound-target network was constructed and revealed that the six key pharmaceutical ingredients of HXQR were quercetin,luteolin,wogonin,kaempferol,beta-carotene,and baicalein.The protein-protein interaction network mainly involved core proteins such as ALB,interleukin-6,and AKT1.Drug-disease common targets were enriched in 1628 GO terms and 117 KEGG terms,mainly involving inflammatory responses,viral infections,and tumorrelated pathways.ELISA testing indicated that HXQR inhibited the tumor necrosis factor(TNF)signaling pathway by reducing the expression of interleukin-6,matrix metalloproteinase-9,and intercellular adhesion molecule-1.The clinical symptoms of the patients with OLP were significantly improved after 8 weeks of treatment with HXQR.CONCLUSION:HXQR treats OLP by regulating the TNF signaling pathway,resulting in a marked treatment effect with few adverse effects.

Precancerous lesions of oral mucosa

Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaquelike, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary.The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used.

Effect of treating chronic hepatitis C with direct-acting antivirals on extrahepatic cutaneous manifestations

BACKGROUND Hepatitis C virus(HCV)is a disease with a significant global impact,affecting approximately 2%-2.5%of the world’s population.New direct-acting antivirals(DAAs)have been introduced over the past few years with great success in viral eradication.The association of chronic HCV infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature.AIM To assess the effect of treating HCV with DAAs on the extrahepatic cutaneous manifestations of HCV.METHODS This prospective observational study included 1039 HCV positive Egyptian patients who were eligible to receive DAAs.A total of 30 patients were diagnosed with extrahepatic cutaneous manifestations and fulfilled the inclusion criteria of the study.Of these patients,6 had classic lichen planus,8 were diagnosed with psoriasis vulgaris and 16 had pruritus.All patients received DAAs from October 2018 to July 2019 in the form of a three-month course of sofosbuvir/daclatasvir combination.Patients with lichen planus or psoriasis were dermoscopically evaluated before treatment and 6 mo after treatment,while patients with hepatic pruritus were assessed using the 12-Item Pruritus Severity Scale over the same period.RESULTS All patients with psoriasis showed significant improvement in all psoriatic plaques,and all patients with hepatic pruritus scored 0 on the 12-Item Pruritus Severity Scale indicating total improvement of pruritus.In addition,four of six patients with lichen planus showed complete improvement.CONCLUSION Treatment of HCV with DAAs was significantly effective in improving virusrelated extrahepatic cutaneous manifestations.

Dermatologic Extrahepatic Manifestations of Hepatitis C

Hepatitis C virus (HCV) affects millions of people worldwide,and an estimated 3.2 million people in the United States.HCV is a hepatotropic and lymphotropic virus that causes not only liver disease,but also a significant number of extrahepatic manifestations (EHMs).Up to 74% of patients affected by HCV will have HCV-related EHMs of some severity in their lifetime.The EHMs vary from simple cutaneous palpable purpura to complex lymphoproliferative disorders,including lymphomas and immune-complex deposit diseases causing local and/or systemic complications.Mixed cryoglobulinemia (MC) is manifested by multiple systemic organ involvement,mainly skin,kidney,peripheral nerves,and salivary glands,and less frequently causes widespread vasculitis and malignant lymphoma.MC affects up to 3% of HCV-infected patients with cryoglobulinemia of clinical significance,i.e.>6%.Severe disease requires immunosuppressive or plasma exchange therapy.HCV prevalence in the United States in patients with porphyria cutanea tarda (PCT) was reported to be 66%,much higher than that in general population.Therefore,all patients with PCT should be screened for HCV.The skin rash of PCT varies from large blisters to small vesicles and/or milia on the hands.Skin manifestations due to PCT usually respond to anti-HCV treatment together with reducing skin sun exposure,avoiding triggers,having routine phlebotomy (especially for people with chronic iron overload states),and using chloroquine.Lichen planus (LP),which typically affects both the skin and oral mucosa is a chronic inflammatory disease of squamous cell origin affecting about 1% of the worldwide population.The prevalence of HCV in patients with LP varies based on geographic location.We review here the basic pathophysiology,clinical features,and management of dermatologic manifestations of HCV.