Microneedles(MNs)can be used for the topical treatment of skin disorders as they directly deliver therapeutics to the site of skin lesions,resulting in increased therapeutic efficacy while having minimum side effects....Microneedles(MNs)can be used for the topical treatment of skin disorders as they directly deliver therapeutics to the site of skin lesions,resulting in increased therapeutic efficacy while having minimum side effects.MNs are used to deliver different kinds of therapeutics(e.g.,small molecules,macromolecules,nanomedicines,living cells,bacteria,and exosomes)for treating various skin disorders,including superficial tumors,wounds,skin infections,inflammatory skin diseases,and abnormal skin appearance.The therapeutic efficacy of MNs can be improved by integrating the advantages of multiple therapeutics to perform combination therapy.Through careful designing,MNs can be further modified with biomimetic structures for the responsive drug release from internal and external stimuli and to enhance the transdermal delivery efficiency for robust therapeutic outcomes.Some studies have proposed the use of drug-free MNs as a promising mechanotherapeutic strategy to promote wound healing,scar removal,and hair regeneration via a mechanical communication pathway.Although MNs have several advantages,the practical application of MNs suffers from problems related to industrial manufacture and clinical evaluation,making it difficult for clinical translation.In this study,we summarized the various applications,emerging challenges,and developmental prospects of MNs in skin disorders to provide information on ways to advance clinical translation.展开更多
The skin is the largest organ of the body.The establishment of immunological memory in the skin is a crucial component of the adaptive immune response.Once naive T cells are activated by antigen-presenting cells,a sma...The skin is the largest organ of the body.The establishment of immunological memory in the skin is a crucial component of the adaptive immune response.Once naive T cells are activated by antigen-presenting cells,a small fraction of them differentiate into precursor memory T cells.These precursor cells ultimately develop into several subsets of memory T cells,including central memory T(TCM)cells,effector memory T(TEM)cells,and tissue resident memory T(TRM)cells.TRM cells have a unique transcriptional profile,and their most striking characteristics are their long-term survival(longevity)and low migration in peripheral tissues,including the skin.Under physiological conditions,TRM cells that reside in the skin can respond rapidly to pathogenic challenges.However,there is emerging evidence to support the vital role of TRM cells in the recurrence of chronic inflammatory skin disorders,including psoriasis,vitiligo,and fixed drug eruption,under pathological or uncontrolled conditions.Clarifying and characterizing the mechanisms that are involved in skin TRM cells will help provide promising strategies for reducing the frequency and magnitude of skin inflammation recurrence.Here,we discuss recent insights into the generation,homing,retention,and survival of TRM cells and share our perspectives on the biological characteristics of TRM cells in the recurrence of inflammatory skin disorders.展开更多
Inflammatory skin disorders(ISDs),characterized by severe inflammation and impaired skin barrier functions,often requires persistent treatment due to chronic and relapsing natures.To address these issues,we developed ...Inflammatory skin disorders(ISDs),characterized by severe inflammation and impaired skin barrier functions,often requires persistent treatment due to chronic and relapsing natures.To address these issues,we developed a small-molecular self-assembled nanodrug(ECN)that is composed of natural epigallocatechin-3-gallate(EGCG)self-assembled with tripeptide collagen(CTP).By formulating a transdermal enhancer(cationic dendrimer)with ECN,the resulted dendrimers/ECN nanocomplex(DECN)can effectively penetrate into the skin layer,resulting in effective anti-inflammatory response and repair of skin-barrier functions.In animal models of ISDs,including atopic dermatitis(AD)and psoriasis,DECN showed remarkable skin penetration,with high level of drug deposition in the epidermaldermal layer.By using a commercially available spray pump,DECN nanoparticles can be further translated into a spray formulation,which contributes to alleviating visible symptoms,skin lesions,and inflammatory progression of psoriasis and AD.This all-in-one spray nano-formulation offers an effective,safe,and convenient way for ISDs treatment.展开更多
Inflammatory skin diseases are characterized by the activation of the innate and adaptive immune system via the production of pro-inflammatory cytokines. The main proinflammatory cytokines responsible for this develop...Inflammatory skin diseases are characterized by the activation of the innate and adaptive immune system via the production of pro-inflammatory cytokines. The main proinflammatory cytokines responsible for this development include TNF-alpha, Interleukin 1, 6 and 17, also the transcription factor NF-kappa B. Small molecule anti-inflammatory compounds such as those detailed in the paper, show much promise in dealing with these skin disorders. Four nutraceutical molecules that are well characterized by their capacity to interact with many of the pro-inflammatory cytokines, importantly IL-17, are found in an Australian product, Koena. Koena has been shown to not only decrease these cytokines but also help increase the production of Interleukin 10 and important anti-inflammatory cytokines. This paper reports clinical benefits of Koena in a variety of circumstances;eczema and psoriasis;insect bites and sting;solar damaged skin and keratosis. An analysis of patient/purchaser reviews via the website Koena.com.au to ascertain what condition they purchased the product for, if any, and the satisfaction rating after use. More than 35% of reviewers reported purchasing Koena to help with inflamed skin. Those reporting being satisfied with the result was 95% for this use. This paper reports on the benefit of small molecule anti-inflammatories in modulating and not blocking an immune response. It also illustrates the benefits of multitherapy when dealing with complex inflammatory responses as opposed to monotherapy.展开更多
Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit,which brings serious physical and mental burden to patients.Despite decades of research,its pathogenesis remains multifactorial and incomplete...Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit,which brings serious physical and mental burden to patients.Despite decades of research,its pathogenesis remains multifactorial and incompletely elucidated.Conventional therapeutic approaches still have limitations in meeting clinical demands due to limited skin penetration,systemic side effects,and the emergence of antimicrobial resistance.Microneedles based drug delivery systems offer a minimally invasive strategy to overcome the stratum corneum barrier,achieve controlled intradermal drug release,and enhance local therapeutic efficacy while reducing systemic toxicity.This review systematically summarizes the latest research of microneedles for the treatment of acne.We first introduce the pathological mechanisms underlying acne development,followed by an overview of the latest advances in microneedle technologies for targeted acne therapy,including dissolving,hydrogel,solid,hollow,coated microneedles and stimuli-responsive designs.Finally,we highlight ongoing limitations and propose future strategies to enhance the development and clinical application of microneedle therapies in acne management.展开更多
To the Editor:Bullous pemphigoid(BP)is a rare autoimmune skin disorder characterized by significant mortality,with BP prevalence ranging from 1.46 to 47.99 cases per 100,000 people.[1]The pathogenic mechanism of BP is...To the Editor:Bullous pemphigoid(BP)is a rare autoimmune skin disorder characterized by significant mortality,with BP prevalence ranging from 1.46 to 47.99 cases per 100,000 people.[1]The pathogenic mechanism of BP is attributed to pathogenic autoantibodies targeting BP180 and BP230 antigens,resulting in the formation of subepidermal blisters.[1]Reports indicate that some BP patients also have circulating anti-desmoglein(Dsg)autoantibodies,which are pathogenic antibodies in pemphigus.[2]However,it remains uninvestigated whether the concomitant anti-Dsg antibodies in BP are pathogenic and thereby represent a coincidental occurrence or signify the coexistence of the two diseases.This knowledge gap introduces uncertainty in patient care management.Therefore,a comprehensive analysis was performed to explore the clinicohistopathological characteristics,human leukocyte antigen(HLA)genetic risk factors,and pathogenicity of anti-Dsg antibodies in BP patients with anti-Dsg antibodies compared to those without.展开更多
Objective:Interleukin-1β(IL-1β)and high-mobility group box 1(HMGB1)are widely known damage-associated molecular patterns(DAMPs).However,their expression and secretion in different skin diseases,especially in inflamm...Objective:Interleukin-1β(IL-1β)and high-mobility group box 1(HMGB1)are widely known damage-associated molecular patterns(DAMPs).However,their expression and secretion in different skin diseases,especially in inflammatory skin disorders,remain to be further elucidated.This study was performed to explore and compare the transcriptional and secretory levels of IL-1β and HMGB1 in keratinocytes under 3 types of stimulation:ultraviolet B(UVB)irradiation;co-stimulation by tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)(simulation of T helper 1 cell inflammatory challenge);and psoriasis-like stimulation by M5,a mixture of 5 proinflammatory cytokines.Methods:We used quantitative reverse-transcription polymerase chain reaction to determine the transcription levels of IL-1β and HMGB1.Western blotting and enzyme-linked immunosorbent assay were used to detect the secretion levels of IL-1β and HMGB1.The results were statistically analyzed by t test.Results:A rapid transcriptional and secretory response of IL-1β from keratinocytes occurred in all 3 types of stimulation mimicking common inflammatory environments(P<0.05).Transcription of HMGB1 was inhibited in all 3 types of stimulation(P<0.05),but secretion was increased after exposure to UVB irradiation and co-stimulation by TNF-α and IFN-γ(P<0.05).We observed no change in the secretion level of HMGB1 after treatment with M5(P=0.196).Conclusion:IL-1β is a critical cytokine for the immunomodulatory functions of keratinocytes in inflammatory responses.In this study,keratinocytes restrained transcription of HMGB1 when the secretion of HMGB1 was induced in certain stimulations(eg,by UVB exposure or stimulation by TNF-α and IFN-γ).展开更多
Objective:Lichen planopilaris(LPP)is a rare skin disorder,but it is also the most common cause of scarring alopecia in adults.The main cause of this disease is unknown,but it is considered to be related to the immune ...Objective:Lichen planopilaris(LPP)is a rare skin disorder,but it is also the most common cause of scarring alopecia in adults.The main cause of this disease is unknown,but it is considered to be related to the immune status of the body.Several comorbidities are reportedly associated with LPP,such as hypertension,depression,thyroiditis,diabetes,and vitiligo.In the present study,we aimed to investigate the frequency of comorbidities in patients with LPP who were referred to Razi Hospital in Rasht,Iran,from 2016 to 2019.Methods:This cross-sectional study involved 60 patients with cicatricial alopecia patches(scarring and irreversible)and clinical signs and symptoms consistent with active LPP.The association between demographic data and comorbidities in patients with LPP was evaluated with the chi-square test andt test.Results:The results showed that the most common comorbidities were vitamin D deficiency(24.3%),hypothyroidism(17.6%),anemia(16.2%),asthma and allergy(14.8%),hypertension(13.5%),diabetes(9.5%),and vitiligo(4.5%).There was no statistically significant association of sex,age,or body mass index with LPP according to the presence or absence of underlying disease(P=0.440,P=0.108,andP=0.340,respectively);however,there was a statistically significant difference in the presence of comorbidities according to age(P=0.018).Conclusion:The results illustrated that women with vitamin D deficiency are more prone to LPP than are patients with other pre-existing underlying diseases.展开更多
基金financially supported by the National Natural Science Foundation of China(82104071)Natural Science Foundation of Guangdong Province(2022B1515020085)Leading Entrepreneurship Team Project of Zengcheng District(202001004)。
文摘Microneedles(MNs)can be used for the topical treatment of skin disorders as they directly deliver therapeutics to the site of skin lesions,resulting in increased therapeutic efficacy while having minimum side effects.MNs are used to deliver different kinds of therapeutics(e.g.,small molecules,macromolecules,nanomedicines,living cells,bacteria,and exosomes)for treating various skin disorders,including superficial tumors,wounds,skin infections,inflammatory skin diseases,and abnormal skin appearance.The therapeutic efficacy of MNs can be improved by integrating the advantages of multiple therapeutics to perform combination therapy.Through careful designing,MNs can be further modified with biomimetic structures for the responsive drug release from internal and external stimuli and to enhance the transdermal delivery efficiency for robust therapeutic outcomes.Some studies have proposed the use of drug-free MNs as a promising mechanotherapeutic strategy to promote wound healing,scar removal,and hair regeneration via a mechanical communication pathway.Although MNs have several advantages,the practical application of MNs suffers from problems related to industrial manufacture and clinical evaluation,making it difficult for clinical translation.In this study,we summarized the various applications,emerging challenges,and developmental prospects of MNs in skin disorders to provide information on ways to advance clinical translation.
基金The National Natural Science Foundation of China(no.81573054,81371729,81771783)the Clinical Research and Translation Key Project of Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital(no.2016LZ02)the Sichuan Science and Technology Program(no.2019JDTD0027).
文摘The skin is the largest organ of the body.The establishment of immunological memory in the skin is a crucial component of the adaptive immune response.Once naive T cells are activated by antigen-presenting cells,a small fraction of them differentiate into precursor memory T cells.These precursor cells ultimately develop into several subsets of memory T cells,including central memory T(TCM)cells,effector memory T(TEM)cells,and tissue resident memory T(TRM)cells.TRM cells have a unique transcriptional profile,and their most striking characteristics are their long-term survival(longevity)and low migration in peripheral tissues,including the skin.Under physiological conditions,TRM cells that reside in the skin can respond rapidly to pathogenic challenges.However,there is emerging evidence to support the vital role of TRM cells in the recurrence of chronic inflammatory skin disorders,including psoriasis,vitiligo,and fixed drug eruption,under pathological or uncontrolled conditions.Clarifying and characterizing the mechanisms that are involved in skin TRM cells will help provide promising strategies for reducing the frequency and magnitude of skin inflammation recurrence.Here,we discuss recent insights into the generation,homing,retention,and survival of TRM cells and share our perspectives on the biological characteristics of TRM cells in the recurrence of inflammatory skin disorders.
基金supported by National Natural Science Foundation of China(32261143727,82073779,32000992)National Key Research and Development Program of China(2018YFA0901800)Natural Science Foundation of Zhejiang Province(Natural Science Foundation of Zhejiang Province Distinguished Young Scholar Program,LR21H300002)。
文摘Inflammatory skin disorders(ISDs),characterized by severe inflammation and impaired skin barrier functions,often requires persistent treatment due to chronic and relapsing natures.To address these issues,we developed a small-molecular self-assembled nanodrug(ECN)that is composed of natural epigallocatechin-3-gallate(EGCG)self-assembled with tripeptide collagen(CTP).By formulating a transdermal enhancer(cationic dendrimer)with ECN,the resulted dendrimers/ECN nanocomplex(DECN)can effectively penetrate into the skin layer,resulting in effective anti-inflammatory response and repair of skin-barrier functions.In animal models of ISDs,including atopic dermatitis(AD)and psoriasis,DECN showed remarkable skin penetration,with high level of drug deposition in the epidermaldermal layer.By using a commercially available spray pump,DECN nanoparticles can be further translated into a spray formulation,which contributes to alleviating visible symptoms,skin lesions,and inflammatory progression of psoriasis and AD.This all-in-one spray nano-formulation offers an effective,safe,and convenient way for ISDs treatment.
文摘Inflammatory skin diseases are characterized by the activation of the innate and adaptive immune system via the production of pro-inflammatory cytokines. The main proinflammatory cytokines responsible for this development include TNF-alpha, Interleukin 1, 6 and 17, also the transcription factor NF-kappa B. Small molecule anti-inflammatory compounds such as those detailed in the paper, show much promise in dealing with these skin disorders. Four nutraceutical molecules that are well characterized by their capacity to interact with many of the pro-inflammatory cytokines, importantly IL-17, are found in an Australian product, Koena. Koena has been shown to not only decrease these cytokines but also help increase the production of Interleukin 10 and important anti-inflammatory cytokines. This paper reports clinical benefits of Koena in a variety of circumstances;eczema and psoriasis;insect bites and sting;solar damaged skin and keratosis. An analysis of patient/purchaser reviews via the website Koena.com.au to ascertain what condition they purchased the product for, if any, and the satisfaction rating after use. More than 35% of reviewers reported purchasing Koena to help with inflamed skin. Those reporting being satisfied with the result was 95% for this use. This paper reports on the benefit of small molecule anti-inflammatories in modulating and not blocking an immune response. It also illustrates the benefits of multitherapy when dealing with complex inflammatory responses as opposed to monotherapy.
基金The National Natural Science Foundation of China(52403189)the Natural Science Foundation of Jiangsu Province(BK20220170)the Wenzhou Institute UCAS startup fund(WIUCASQD2024009).
文摘Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit,which brings serious physical and mental burden to patients.Despite decades of research,its pathogenesis remains multifactorial and incompletely elucidated.Conventional therapeutic approaches still have limitations in meeting clinical demands due to limited skin penetration,systemic side effects,and the emergence of antimicrobial resistance.Microneedles based drug delivery systems offer a minimally invasive strategy to overcome the stratum corneum barrier,achieve controlled intradermal drug release,and enhance local therapeutic efficacy while reducing systemic toxicity.This review systematically summarizes the latest research of microneedles for the treatment of acne.We first introduce the pathological mechanisms underlying acne development,followed by an overview of the latest advances in microneedle technologies for targeted acne therapy,including dissolving,hydrogel,solid,hollow,coated microneedles and stimuli-responsive designs.Finally,we highlight ongoing limitations and propose future strategies to enhance the development and clinical application of microneedle therapies in acne management.
基金supported by grants from the Central Guidance for Local Scientific and Technological Development Projects of Shandong Province(No.YDZX2023058)the Shandong Province Taishan Scholar Project(No.tsqn201909141).
文摘To the Editor:Bullous pemphigoid(BP)is a rare autoimmune skin disorder characterized by significant mortality,with BP prevalence ranging from 1.46 to 47.99 cases per 100,000 people.[1]The pathogenic mechanism of BP is attributed to pathogenic autoantibodies targeting BP180 and BP230 antigens,resulting in the formation of subepidermal blisters.[1]Reports indicate that some BP patients also have circulating anti-desmoglein(Dsg)autoantibodies,which are pathogenic antibodies in pemphigus.[2]However,it remains uninvestigated whether the concomitant anti-Dsg antibodies in BP are pathogenic and thereby represent a coincidental occurrence or signify the coexistence of the two diseases.This knowledge gap introduces uncertainty in patient care management.Therefore,a comprehensive analysis was performed to explore the clinicohistopathological characteristics,human leukocyte antigen(HLA)genetic risk factors,and pathogenicity of anti-Dsg antibodies in BP patients with anti-Dsg antibodies compared to those without.
基金supported by grants from the National Natural Science Foundation of China(81972952,81872531,82173438,and 82273550)Nanjing Incubation Program for National Clinical Research Center(2019060001)+2 种基金CAMS Innovation Fund for Medical Sciences(2021-1-I2M-059,2017-I2M-1-017)Jiangsu Province Foundation(LGY2018095,WSW-016)PhD Programs Foundation of Ministry of Education of China(No.20131106120046)
文摘Objective:Interleukin-1β(IL-1β)and high-mobility group box 1(HMGB1)are widely known damage-associated molecular patterns(DAMPs).However,their expression and secretion in different skin diseases,especially in inflammatory skin disorders,remain to be further elucidated.This study was performed to explore and compare the transcriptional and secretory levels of IL-1β and HMGB1 in keratinocytes under 3 types of stimulation:ultraviolet B(UVB)irradiation;co-stimulation by tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)(simulation of T helper 1 cell inflammatory challenge);and psoriasis-like stimulation by M5,a mixture of 5 proinflammatory cytokines.Methods:We used quantitative reverse-transcription polymerase chain reaction to determine the transcription levels of IL-1β and HMGB1.Western blotting and enzyme-linked immunosorbent assay were used to detect the secretion levels of IL-1β and HMGB1.The results were statistically analyzed by t test.Results:A rapid transcriptional and secretory response of IL-1β from keratinocytes occurred in all 3 types of stimulation mimicking common inflammatory environments(P<0.05).Transcription of HMGB1 was inhibited in all 3 types of stimulation(P<0.05),but secretion was increased after exposure to UVB irradiation and co-stimulation by TNF-α and IFN-γ(P<0.05).We observed no change in the secretion level of HMGB1 after treatment with M5(P=0.196).Conclusion:IL-1β is a critical cytokine for the immunomodulatory functions of keratinocytes in inflammatory responses.In this study,keratinocytes restrained transcription of HMGB1 when the secretion of HMGB1 was induced in certain stimulations(eg,by UVB exposure or stimulation by TNF-α and IFN-γ).
文摘Objective:Lichen planopilaris(LPP)is a rare skin disorder,but it is also the most common cause of scarring alopecia in adults.The main cause of this disease is unknown,but it is considered to be related to the immune status of the body.Several comorbidities are reportedly associated with LPP,such as hypertension,depression,thyroiditis,diabetes,and vitiligo.In the present study,we aimed to investigate the frequency of comorbidities in patients with LPP who were referred to Razi Hospital in Rasht,Iran,from 2016 to 2019.Methods:This cross-sectional study involved 60 patients with cicatricial alopecia patches(scarring and irreversible)and clinical signs and symptoms consistent with active LPP.The association between demographic data and comorbidities in patients with LPP was evaluated with the chi-square test andt test.Results:The results showed that the most common comorbidities were vitamin D deficiency(24.3%),hypothyroidism(17.6%),anemia(16.2%),asthma and allergy(14.8%),hypertension(13.5%),diabetes(9.5%),and vitiligo(4.5%).There was no statistically significant association of sex,age,or body mass index with LPP according to the presence or absence of underlying disease(P=0.440,P=0.108,andP=0.340,respectively);however,there was a statistically significant difference in the presence of comorbidities according to age(P=0.018).Conclusion:The results illustrated that women with vitamin D deficiency are more prone to LPP than are patients with other pre-existing underlying diseases.
