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1.
Exp Dermatol ; 33(2): e15018, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38414007

RESUMO

Ferroptosis, a type of programmed cell death, occurs when there is oxidative stress and lipid peroxides. This condition is marked by lipid peroxidation that relies on iron and the reduction of cellular defences against oxidation. To investigate the effect of UVB irradiation on ferroptosis of human keratinocytes HaCaT cells, the cells were pretreated with Ferrostatin 1 (Fer-1, 10 µM), an ferroptosis inhibitor and then irradiated with UVB (20 mJ/cm2 ) for 30 min to detect related indexes of ferroptosis through MTT assay, quantitative real-time polymerase chain reaction, flow cytometry, reactive oxygen species (ROS) assay, western blotting. Results showed that UVB significantly reduced cell activity, promoted apoptosis and ROS level, whereas Fer-1 significantly increased cell activity, and reduced apoptosis and ROS level. In addition, UVB significantly reduced levels of ferroptosis-related proteins and skin barrier-related proteins, and increased levels of γ-H2AX and iron, whereas Fer-1 significantly increased their protein levels, and reduced levels of γ-H2AX and iron. Conjoint analysis of transcriptomic and proteomic revealed that UVB significantly reduced the levels of TIMP metallopeptidase inhibitor 3 (TIMP3), and coagulation factor II thrombin receptor (F2R), whereas Fer-1 significantly promoted the levels of TIMP3, and F2R. Therefore, our results indicated that Fer-1 significantly ameliorates UVB-induced damage of HaCaT cells by regulating the levels of TIMP3 and F2R.


Assuntos
Ferroptose , Células HaCaT , Humanos , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Apoptose , Queratinócitos/metabolismo , Ferro , Raios Ultravioleta/efeitos adversos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38581327

RESUMO

Objective: This study aimed to explore the clinical application of aseptic skin repair dressing in facial dermatitis. Patients and Methods: A total of 80 patients with facial dermatitis admitted to Zhejiang Provincial People's Hospital from February 2020 to May 2021 were enrolled. And randomly assigned to the control group and study group, with 40 cases in each group. The control group received nicotinamide and narrow-band red light, while the study group received nicotinamide, narrow-band red light, and sterile skin repair dressing. The clinical efficacy, symptom score, erythema, transepidermal water loss (TEWL), and adverse reactions were compared after treatment. Results: After treatment, the study group exhibited significantly lower symptom scores, erythema amount, and TEWL value compared to the control group (P < .05). The clinical efficacy rate in the study group (97.5%) was significantly higher than that in the control group (82.5%) (P < .05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (2.5% vs. 5%) (P > .05). Conclusion: Aseptic skin repair dressing, employed as an adjunctive therapy for facial dermatitis, demonstrates a noteworthy capacity to effectively mitigate parameters such as patient symptom scores, facial erythema quantity, and TEWL values. Notably, the application of this dressing does not pose an elevated risk of adverse reactions. These merits substantiate the superior therapeutic efficacy of aseptic skin repair dressing in facilitating the treatment of facial dermatitis.

3.
Mycopathologia ; 189(3): 33, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627263

RESUMO

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.


Assuntos
Dermatomicoses , Humanos , Masculino , Dermatomicoses/patologia , Pele/patologia , Trichophyton , Microscopia , Escroto/microbiologia
4.
Exp Dermatol ; 32(9): 1439-1450, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37293825

RESUMO

Bowenoid papulosis (BP) is a benign and possibly carcinogenic disease associated with human papillomavirus (HPV) infection, which has been increasingly recognised and paid attention to in recent years, but the potential mechanisms still remain unclear. In our study, three patients who were diagnosed with BP were enrolled into our research. Skin biopsies were taken and were separated into two parts, one part was for HE staining and the others were for RNA-sequencing (RNA-seq). All the three patents were human papillomavirus (HPV) positive and HE staining revealed typical skin histopathological changes in BP, including dyskeratosis, hyperplasia and hypertrophy of the granular and spinous layers, atypical keratinocytes. RNA-seq analysis demonstrated that a total of 486 differentially expressed genes (DEGs) were detected between the skin tissues from BP and the controls, among which, 320 genes were significantly upregulated and 166 genes were dramatically downregulated. GO enrichment revealed that antigen binding, cell cycle, immune response and keratinisation to be the most notably altered pathways, whereas KEGG analysis indicated that cell cycle cytokine-cytokine receptor interaction, ECM receptor interaction and p53 signalling pathway to be the most significantly changed signalling pathways in BP. Furthermore, metabolism-associated enrichment analysis showed that cholesterol metabolism, metabolism of xenobiotics by cytochrome p450 and pyrimidine metabolism to be the most dramatically dysregulated metabolic pathways in BP as compared to normal controls. Our study revealed that inflammation, metabolism and cell proliferation signalling pathways might be the most important pathways for BP disease, targeted inhibiting of these signals might be a potential method for BP treatment.


Assuntos
Doença de Bowen , Carcinoma de Células Escamosas , Condiloma Acuminado , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Humanos , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/complicações , Transcriptoma , Doença de Bowen/genética , Doença de Bowen/diagnóstico , Doença de Bowen/patologia
5.
Medicina (Kaunas) ; 58(12)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36557075

RESUMO

Cutaneous nocardiosis is a rare bacterial infection that can result in various dermatologic manifestations such as actinomycetoma, lymphocutaneous infection, superficial skin infection, and secondary infection due to hematogenous dissemination. We report on a Chinese patient with erythema nodosum-like exanthema, possibly secondary to nocardiosis. Our diagnosis for this patient was based on the clinical presentation, histopathological evidence, and microbiological findings. Given the protean manifestation of Nocardia, persistent reports on new presentations of the disease are important for early identification and treatment.


Assuntos
Eritema Nodoso , Nocardiose , Nocardia , Dermatopatias Bacterianas , Humanos , Eritema Nodoso/complicações , Eritema Nodoso/patologia , Nocardiose/complicações , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Pele/patologia , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia
6.
Cerebrovasc Dis ; 49(5): 462-473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877893

RESUMO

BACKGROUND: Hemangioma (Hem) is a benign tumor commonly seen in infancy with a relative high morbidity. Human umbilical vein endothelial cell (HUVEC)-derived extracellular vesicles (EVs) are actively participated in Hem. Therefore, this study is designed to figure out the underlying mechanism of HUVEC-derived EVs in Hem. METHODS: Initially, EVs were separated from HUVECs and identified. HUVEC-derived EVs in normoxia or hypoxia were then cultivated with Hem endothelial cells (HemECs) to test the proliferation, apoptosis, and migration of HemECs. Microarray analysis was performed to select microRNAs (miRs) with differential expression. miR-210 in hypoxia-induced HUVECs was silenced, and the relevant EVs were extracted and then co-cultured with HemECs to perform biological effect experiments. Then, the target relation between miR-210 and homeobox A9 (HOXA9) was identified by the dual luciferase reporter gene assay and RNA immunoprecipitation assay. Moreover, xenograft transplantation was also applied to confirm the in vitro experiments. RESULTS: Hypoxia-induced HUVECs promoted release of EVs, which were absorbed by HemECs. Hypoxia-induced HUVEC-EVs promoted HemEC proliferation and migration and inhibited apoptosis. miR-210 from the hypoxia-induced HUVEC-EVs was highly expressed and promoted HemEC growth. Silencing miR-210 expression in the hypoxia-induced HUVEC-EVs suppresses Hem development in vivo. In addition, miR-210 targeted HOXA9. CONCLUSION: Silencing miR-210 in HUVEC-derived EVs could suppress Hem by targeting HOXA9. This investigation may provide novel insights for Hem treatment.


Assuntos
Vesículas Extracelulares/transplante , Hemangioma/prevenção & controle , Células Endoteliais da Veia Umbilical Humana/transplante , MicroRNAs/genética , Interferência de RNA , Animais , Apoptose , Hipóxia Celular , Movimento Celular , Proliferação de Células , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Feminino , Hemangioma/genética , Hemangioma/metabolismo , Hemangioma/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lactente , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Carga Tumoral , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Mycopathologia ; 183(2): 417-421, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29164434

RESUMO

The incidence of candidiasis due to non-albicans Candida species (especially Candida glabrata) has significantly increased in recent decades. Candida glabrata often invades immunocompromised hosts and causes systemic or mucosal infections, whereas cutaneous infections are rarely reported. We present a rare case of cutaneous infection caused by C. glabrata and review all similar cases available in the PubMed database. A patient was admitted to the hospital with a 2-month history of a plaque on the face. Histopathological examination displayed typical infectious granulomas in the deep dermis, and the pathogen was finally confirmed as C. glabrata using a series of microbial examinations (fungal culture, biochemical test, and PCR-directed sequencing). The patient was completely cured after 4 months of treatment with oral itraconazole combined with topical terbinafine. We reviewed similar reports of cutaneous infection caused by C. glabrata. All the data suggested that an accurate diagnosis of cutaneous candidiasis depends mainly on histological and fungal examinations, especially molecular biological assays. Antifungal agents based on microbial susceptibility tests are the first-line treatment choice for C. glabrata infection, but the prognosis might be more dependent on the basic condition of the host.


Assuntos
Candida glabrata/isolamento & purificação , Candidíase/diagnóstico , Candidíase/patologia , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/patologia , Granuloma/diagnóstico , Granuloma/patologia , Antifúngicos/administração & dosagem , Candidíase/tratamento farmacológico , Dermatoses Faciais/tratamento farmacológico , Feminino , Granuloma/tratamento farmacológico , Histocitoquímica , Humanos , Técnicas Microbiológicas , Microscopia , Pessoa de Meia-Idade , Análise de Sequência de DNA , Resultado do Tratamento
9.
Fungal Genet Biol ; 2016 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-27915049

RESUMO

The COP9 signalosome (CSN) is a multisubunit protein complex, and it now has been found to participate in diverse cellular and developmental processes in various eukaryotic organisms. Cryptococcus neoformans (C. neoformans) is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immune compromised population. Here, we generated CSN deletion mutants to investigate the role in Cryptococcus infection. Compared to other CSN mutants, we identified a CSN1201 mutant exhibited severely attenuated virulence. Deletion of CSN1201 made cryptococcal cells more susceptible to nearly all in vitro stresses. Furthermore, deletion of CSN1201 obviously impaired survival of C. neoformans. At the same time, in vivo virulence assay of mouse infection models demonstrated that CSN1201 significantly enhanced the virulence of C. neoformans compared with the other CSN subunit strains, while ELISA analysis of C. neoformans infection in innate or adaptive immune response showed that deletion of CSN1201 significantly impaired cytokines and interferon expression. In vitro model of the blood-brain barrier (BBB) analysis indicated that deletion of CSN1201 reduced the invasion efficacy of Cryptococcusto cross BBB. Taken together, our findings reveal a novel mechanism of CSN1201, which plays a critical role for the virulence composite of C. neoformans, and also provides an additional yeast survival and propagation advantage in the host.

10.
Clin Cosmet Investig Dermatol ; 17: 785-789, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38616885

RESUMO

Purpose: Verruciform xanthoma (VX) is a rare, chronic, and benign lesion affecting the skin and mucous membranes. We reported a case of VX in the vulva of a female child. Patients and Methods: A 12-year-old female had vulvar lesions for over 10 years without any discomfort. Physical examination revealed red lobulated patches on the left labia majora with a few scales attached to the surface. Histopathological examination indicated excessive and incomplete keratinization, hypertrophic spinous layer hyperplasia, neutrophil infiltration in the epidermis, and foam-like tissue could be seen in the dermal papilla. Lymphocyte-dominated inflammatory cell infiltration was scattered around the blood vessels. Immunohistochemical results showed positive CD68. Results: The final diagnosis confirmed the presence of VX. Conclusion: Surgical intervention proved successful in achieving favorable outcomes for the patient.


Verruciform xanthoma (VX) is a rare and non-cancerous skin condition that usually appears in the mouth but can occur on the genitals. In this case, a 12-year-old girl had red, warty lesions on her left labia majora for over 10 years. The cause of VX is not well understood but may be linked to inflammation, trauma, or immune disorders rather than lipid metabolism. The girl's condition was confirmed through a biopsy, and she underwent surgical removal with no recurrence after a year. VX in the genital area is known as Vegas xanthomas. Though VX can look like other skin issues, a detailed examination of tissue samples is crucial for an accurate diagnosis. Treatment options include surgery, laser therapy, or topical creams. While VX is generally benign, seeking medical attention is important to rule out other concerns.

11.
Patient Prefer Adherence ; 18: 503-506, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414982

RESUMO

Background: Mucous membrane pemphigoid (MMP), a rare autoimmune vesiculous and erosive disorder, may affect multiple mucous membranes, with the oral cavity being the most commonly affected site. Its treatment depends on the site(s) of mucosal involvement and disease severity. Patients and Methods: A 62-year-old female patient with MMP that predominantly involved the oral cavity strongly rejected systemic corticosteroid or immunosuppressive agents and was successfully treated with abrocitinib, a highly selective JAK-1 inhibitor with a good safety profile. Results: The case demonstrated good efficacy and safety profile of abrocitinib for the treatment of MMP with predominant oral involvement. Conclusion: Abrocitinib is a promising agent for the treatment of MMP with oral involvement.

12.
J Pharm Pharmacol ; 76(6): 710-723, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38517943

RESUMO

OBJECTIVES: This study was designed to investigate the pharmacological activity and therapeutic mechanism of Mahuang Xixin Fuzi decoction (MXFD) on migraine. METHODS: Migraine model rats induced by nitroglycerin were established, and then orally administered with MXFD for 7 days. Blood and urine samples were collected to identify differential metabolites with metabolomics. To integrate the findings from network pharmacology and metabolomics analysis, the metabolites and targets related to MXFD therapy for migraine were filtered. KEY FINDINGS: MXFD was found to alleviate the symptoms of migraines in rats. After treatment with MXFD, nine metabolites were found to be regulated and returned to normal levels. MXFD acted directly on nine key targets including MAOB, MAOA, ADRB1, ADRB2, ADRB3, ADORA2A, ADORA2B, DRD5, and HTR4 and regulated two out of nine metabolites, namely deoxycholic acid and 5-methoxyindoleacetate. CONCLUSIONS: The study found that MXFD can alleviate migraines through multitarget and multicomponent interaction networks.


Assuntos
Medicamentos de Ervas Chinesas , Metabolômica , Transtornos de Enxaqueca , Nitroglicerina , Animais , Masculino , Ratos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica/métodos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/metabolismo , Farmacologia em Rede , Nitroglicerina/farmacologia , Ratos Sprague-Dawley
13.
Inflammation ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38796804

RESUMO

Ultraviolet (UV) irradiation significantly contributes to photoaging. Ferroptosis, an iron-dependent cell death mode recently identified, plays a key role in UVB-induced skin photoaging. This study examines the functions and regulatory mechanisms of ferroptosis in this regard. Characterized by increased intracellular iron and reactive oxygen species (ROS), ferroptosis is associated with mitochondrial function and structure. Through RNA sequencing, we identified NADH: ubiquinone oxidoreductase subunit S4 (NDUFS4), a gene implicated in UVB-mediated photoaging, and explored its role in ferroptosis by NDUFS4 knockdown. In vitro, inhibiting NDUFS4 reduced ferroptosis, decreased ROS and matrix metallopeptidase 1 levels, and increased collagen type I alpha 1 chain, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1, and solute carrier family 7 member 11 levels, suggesting a reinforced ferroptosis protective mechanism. Additionally, NDUFS4 regulates ferroptosis via the mitogen-activated protein kinase (MAPK) pathway, with its knockdown reducing p38 and ERK phosphorylation and elevating GPX4 levels, enhancing ferroptosis resistance. Animal experiments supported these findings, demonstrating that Ferrostatin-1, a ferroptosis inhibitor, significantly mitigated UVB-induced skin photoaging and related protein expression. This study uncovers NDUFS4's novel role in regulating ferroptosis and provides new insights into ferroptosis-mediated UVB-induced skin photoaging.

14.
Dermatol Ther (Heidelb) ; 14(5): 1229-1243, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38748345

RESUMO

INTRODUCTION: Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2 years with mild to moderate AD. METHODS: We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28 days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. RESULTS: Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. CONCLUSION: Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2 years with mild to moderate AD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04360187.

15.
J Ethnopharmacol ; 334: 118464, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908492

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonol (PAE) and glycyrrhizic acid (GLY) are predominate components of 14 blood-entering ones of Piantongtang No. 1, which is a traditional Chinese medicine prescription for chronic migraine with minimal side effects. Both paeonol and glycyrrhizic acid exhibit analgesic, neuroprotective and anti-inflammatory properties individually. Our previous research has highlighted their combined effect (PAE + GLY) in ameliorating migraine symptoms. However, there are not yet any studies exploring the mechanism of action of PAE + GLY in the treatment of migraine. AIM OF THE STUDY: This research aimed to determine the mechanism of PAE + GLY in ameliorating the recurrent nitroglycerin-induced migraine-like phenotype in rats. MATERIALS AND METHODS: Using a nitroglycerin-induced migraine model via subcutaneous injection in the neck, we evaluated the effect of PAE + GLY on migraine-like symptoms. Behavioural tests and biomarkers analysis were employed, alongside transcriptome sequencing (RNA-seq). Mechanistic insights were further verified utilising reverse transcription quantitative PCR (RT-qPCR), Western blot (WB), ELISA and immunofluorescence (IF) techniques. RESULTS: Following treatment with PAE + GLY, hyperalgesia threshold and 5-hydroxytryptamine (5-HT) levels increased, and migraine-like head scratching, histamine and calcitonin gene-related peptide (CGRP) levels were reduced. RNA-Seq experiments revealed that PAE + GLY upregulated the expression of Glutamate decarboxylase 2 (GAD2) and γ-aminobutyric acid type B receptor subunit 2 (GABBR2) genes. This upregulation activated the GABAergic synapse pathway, effectively inhibiting migraine attacks. Further validation demonstrated an increase in γ-aminobutyric acid (GABA) content in cerebrospinal fluid post PAE + GLY treatment, coupled with increased expression of dural GAD2, GABBR2 and transient receptor potential channel M8 (TRPM8). Consequently, this inhibited the expression of dural cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and transient receptor potential channel type 1 (TRPV1), subsequently downregulating p-ERK1/2, p-AKT1, IL-1ß and TNF-α. CONCLUSIONS: Our findings underscore that PAE + GLY ameliorates inflammatory hyperalgesia migraine by upregulating inhibitory neurotransmitters and modulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

16.
Chin Med J (Engl) ; 137(2): 200-208, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-37482623

RESUMO

BACKGROUND: Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. RESULTS: At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CONCLUSION: CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.


Assuntos
Dermatite Atópica , Adulto , Humanos , Dermatite Atópica/tratamento farmacológico , Resultado do Tratamento , Índice de Gravidade de Doença , Anticorpos Monoclonais Humanizados/uso terapêutico , Injeções Subcutâneas , Método Duplo-Cego
17.
Infect Drug Resist ; 16: 391-401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36714352

RESUMO

Skin infections are common diseases for which patients seek inpatient and outpatient medical care. Globally, an increasing number of people are affected by skin infections that could lead to physical and psychological damage. Skin infections always have a broad spectrum of clinical presentations that require physicians to make an aggressive and accurate diagnosis for prescribing the proper symptomatic antimicrobials. In most instances, the treatment for skin infections mainly includes oral or topical anti-infective drugs. However, some of the classical anti-infective drugs have limitations, such as poor water solubility, low bioavailability, and poor targeting efficiency, which can lead to poor efficacy, adverse effects, and drug resistance. Therefore, research priorities should focus on the development of more effective drug delivery systems with new materials. Hydrogels are a highly multifunctional class of medical materials with potential applications in dermatology. Several hydrogel dressings with anti-infective functions have been formulated and demonstrated to improve the efficacy and tolerance of oral or topical classical anti-infective drugs to a certain degree. In this study, the medical applications of hydrogels for the treatment of various skin infections are systematically reviewed to provide an important theoretical reference for future research studies on the treatment options for skin infections.

18.
J Inflamm Res ; 16: 3519-3522, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37636274

RESUMO

Drug-induced alopecia areata is a rare adverse event wherein medications such as antimicrobials, anticonvulsants, and biologics, trigger the premature transition of actively growing hairs into the telogen phase. Herein, a unique case of alopecia universalis observed during a clinical trial involving sacubitril/alisartan, a novel angiotensin receptor-neprilysin inhibitor (ARNI) has been reported. This case contributes to the range of cutaneous reactions that might be observed in association with ARNI therapy.

19.
Clin Cosmet Investig Dermatol ; 16: 1079-1087, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37123625

RESUMO

Purpose: To investigate the expression of Plasmacytoid Dendritic Cells (pDCs) and TLR7/9-MyD88-IRAKs pathway in chronic eczema lesions. Patients and Methods: Lesional tissues and the surrounding healthy tissues were collected from 25 individuals with chronic eczema, and immunohistochemistry was used to detect and comparatively analyze the expression profile of CD123, CD2AP, toll-like receptor 7 (TLR7), toll-like receptor 9 (TLR9) along with interleukin-1 receptor-associated kinase 1 (IRAK1) and interferon regulatory factor 7 (IRF7) in signaling pathways. Results: The positive rates of CD2AP + pDC and CD123 + pDC in lesional tissues were significantly elevated compared to the surrounding healthy tissues (P < 0.05). They were distributed in both the epidermal and dermal layers of the lesional tissue, but the majority were in the dermal layer. The TLR7, TLR9, IRAK1 and IRF7 were more expressed in dermal layers of the lesional tissue with higher positive rates of expression compared to the surrounding healthy tissues (P < 0.05). IRAK1 and IRF7 were expressed in a small amount in the epidermal layer with higher positive rates of expression than in the surrounding healthy tissues (P < 0.05), while the positive rates of TLR7 and TLR9 expression in the epidermal layer were not statistically different from those in the surrounding healthy tissues (P > 0.05). Conclusion: PDC and TLR7/9-MyD88-IRAKs pathways are actively expressed in chronic eczema lesions and may be involved in pathogenesis and disease progression.

20.
Methods Mol Biol ; 2695: 247-262, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37450124

RESUMO

Liquid biopsy, also known as fluid biopsy or fluid-phase biopsy, is the sampling and analysis of the blood, cerebrospinal fluid, saliva, pleural fluid, ascites, and urine. Compared with tissue biopsy, liquid biopsy technology has the advantages of being noninvasive, having strong repeatability, enabling early diagnosis, dynamic monitoring, and overcoming tumor heterogeneity. However, interest in cfDNA and skin diseases has not expanded until recently. In this review, we present an overview of the literature related to the basic biology of cfDNA in the field of dermatology as a biomarker for early diagnosis, monitoring disease activity, predicting progression, and treatment response.


Assuntos
Ácidos Nucleicos Livres , Neoplasias , Dermatopatias , Humanos , Ácidos Nucleicos Livres/genética , Neoplasias/genética , Biópsia Líquida , Biópsia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Dermatopatias/diagnóstico
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