Dermatitis Score Research Articles

Corydalis Tuber Extract Alleviates Atopic Dermatitis: Transcriptomics-Based Mechanism Prediction and In Vitro/In Vivo Studies

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by recurrent eczema and chronic itching, affecting a significant portion of the global population. This study investigated the effects of Corydalis Tuber 70% ethanol extract (CTE) on tumor necrosis factor-α- and interferon-γ (TI)-stimulated human keratinocytes (HaCaT) and a house dust mite-induced AD mouse model, elucidating its mechanism via transcriptome analysis. A total of 13 compounds, including columbamine, corydaline, dehydrocorydaline, and glaucine, were identified in CTE using ultra performance liquid chromatography-tandem mass spectrometry. CTE downregulated pathways related to cytokine signaling and chemokine receptors in TI-stimulated HaCaT cells. It significantly inhibited C-C motif chemokine ligand (CCL)5, CCL17, and CCL22 levels by blocking the Janus kinase-signal transducers and activators of transcription and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. In the AD mouse model, topical CTE significantly decreased dermatitis scores, epidermal thickening, and inflammatory cell infiltration. Plasma levels of histamine, immunoglobulin E, CCL17, CCL22, corticosterone, and cortisol were reduced. Lesions showed decreased thymic stromal lymphopoietin, CD4+ T cells, interleukin-4, and intercellular adhesion molecule-1 expression. The findings demonstrate that CTE alleviates AD by modulating inflammatory mediators, cytokines, and chemokines, reducing inflammatory cell infiltration, and alleviating stress-related factors.

Intelligent strategy for severity scoring of skin diseases based on clinical decision-making thinking with lesion-aware transformer

Skin diseases are numerous in types and high in incidence, posing a serious threat to human health. Accurately assessing the severity of skin diseases helps dermatologists in making personalized treatment decisions. However, focusing solely on the skin lesion itself and ignoring the true state of the surrounding skin can lead to distorted results. Assessing the severity of the condition should be a holistic process. Specifically, dermatologists need to compare the abnormal skin with surrounding skin to conduct the diagnosis. To imitate such diagnosis practice of dermatologists, we propose LSATrans, a Transformer based framework customized for severity scoring of skin diseases. Different from the Standard Self-Attention module, we propose the Lesion-aware Self-Attention (LSA) module. LSA can capture the visual features of both lesion and normal surrounding skin areas and include their relationship in modeling. In addition to LSA, the proposed LSATrans also introduces a contrastive learning strategy for further optimization. We first evaluated the performance of LSATrans in scar, atopic dermatitis, and psoriasis scoring tasks, and it achieved mean absolute errors of 0.5895, 0.5614, and 0.5416 respectively in these three tasks. Furthermore, we conducted additional validation of LSATrans’s performance in two distinct skin disease diagnosis tasks, where it demonstrated remarkable outcomes with AUCs of 0.9774 and 0.9801, respectively, in the classification of common skin diseases and subtypes of skin diseases. These results are better than existing methods, indicating that LSATrans is expected to become a universal, accurate and objective intelligent tool for scoring the severity of skin diseases.

Effects of Standardized Natural Citrus Extract on Growth, Gut Health, Carcass Quality, and Welfare of Broiler Chickens.

This study aimed to investigate the effects of a Standardized Natural Citrus Extract (SNCE) on broiler chickens' growth performance, gut health, carcass quality, and welfare. A total of 756 one-day-old Ross 308 males were randomly assigned to two groups: a control group (CTL) fed with a standard diet, and a citrus group (SNCE) fed with the same standard diet supplemented with 250 g/ton of feed of SNCE. Growth performance was recorded weekly until d 35, while mortality was recorded daily. The feed conversion ratio (FCR) and European Efficiency Index (EEI) of broiler chickens were also calculated weekly. At day 35, 10 birds per group were randomly selected for slaughter performance. In parallel, broiler chickens' welfare was assessed according to the Welfare Quality Assessment Protocol. Caecal digest was also collected post mortem for short-chain fatty acids (SCFA) analyses, and jejunum samples were collected for ex vivo gut permeability assay. SNCE dietary supplementation enhanced broiler chickens' performance, i.e., final bodyweight and EEI, compared to the CTL group. The carcass weight was also significantly higher in the SNCE group. In addition, the fat percentage was lower in the SNCE group. Regarding broiler chickens' welfare and gut health parameters, Footpad Dermatitis (FPD) and gate score were also lower in birds supplemented with SNCE. The SCFA measurement showed a lower concentration of iso-butyric acid, iso-valeric acid, and total putrefactive SCFA in the SNCE group. The differences in gut permeability measured as TEER value indicate that using citrus extract lowered the risk of gut inflammation. This study provides valuable insights into the mechanisms of action that may underlie the observed effects of SNCE on performance, as demonstrated in this study and others. These effects could potentially be attributed to the reduction in inflammation and the enhanced utilization of nutrients. Further studies are needed to confirm these results.

Diaper Dermatitis Algorithm and Scoring Tool in the Neonatal Intensive Care Unit (NICU): A Quality Improvement Project.

The purpose of this quality improvement project was to implement and evaluate an algorithm for management and prevention of diaper dermatitis (DD) embedded in a scoring tool. The specific aim of the project was to decrease DD occurrences with a severity score of 3 to 4 by 25%. Quality improvement participants comprised 164 neonates; 89 were cared for prior to project implementation and 75 post-implementation. Data were collected over a 3-month period. The setting of this quality improvement project was a 98-bed, Level IV neonatal intensive care unit (NICU) located in the Midwestern United States (Oklahoma City, OK). The NICU is part of a freestanding children's hospital affiliated with a university. Diaper dermatitis occurrences and severity scores were collected prior to and 3 months after the protocol was implemented in the NICU. We collected pre-implementation data, followed by staff education concerning the DD protocol. We also provide guidance for protocol implementation at the bedside and in our Electronic Medical Record. Data on DD rates and severity were provided during the National Database for Nurse Quality Indicators (NDNQI) prevalence days the 4th quarter of 2020 and the 1st quarter of 2021. We compared data before and after protocol implementation to evaluate its effect on DD rates and severity. Analysis before and after implementation of the protocol showed no significant differences in DD occurrences or severity scores. The unintended introduction of water-based cleansing wipes was identified as a confounding factor that we believe influenced outcomes. The DD scoring system and algorithm were permanently implemented for DD score quantification, DD management and treatment guidance, and ease of DD documentation with interventions, despite non-significant group differences. Next steps for this project are to implement the water-based cleansing wipes facility wide, along with the scoring tool and DD prevention protocol.

Beneficial effects of ultrafine bubble shower on a mouse model of atopic dermatitis.

Atopic dermatitis (AD) is a common and relapsing skin disease characterized by skin barrier dysfunction, inflammation, and chronic pruritus. Both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of the pathology of AD. Although various anti-inflammatory pharmacological agents, including cytokine inhibitors and signaling pathway blockers, have been developed recently, keeping the skin clean is of utmost importance in maintaining physiological cutaneous barrier function and avoiding an AD flare. Ultrafine bubbles (UFBs) are less than 1 μm in diameter and usually used to clean medical equipment. A UFB shower is expected to keep skin clean with attention to the temperature and strength of the shower. We examined the effects of a UFB shower on two mouse models of AD: Dermatophagoides farinae body (Dfb)- induced AD in NC/Nga mice and interleukin (IL)-33 transgenic (tg) mice. Each model comprised three groups: UFB shower-treated, normal shower-treated, and untreated. We evaluated the mice using a dermatitis score, scratching counts, histology, and the expression of inflammatory cytokines and skin barrier-related proteins. In the Dfb-induced AD mouse model, clinical features improved markedly in the UFB shower-treated mice compared to other groups. IL-4 and IL-13 levels decreased in the skin of normal and UFB shower-treated mice. In addition, in the skin of UFB shower-treated mice, the expression levels of skin barrier-related proteins were increased compared to normal showertreated mice. However, we found no significant differences in IL33tg mice. These results suggest that UFB shower can recover the skin barrier function and improve skin inflammation, especially in conditions such as extrinsic AD.

Preclinical and clinical studies on Qin-Zhu-Liang-Xue decoction: insights from network pharmacology and implications for atopic dermatitis treatment.

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.

Preparation of Patchouli Oil Microemulsion Gel and Its Topical Application to Ameliorate Atopic Dermatitis in Mice.

Patchouli oil (PO) is a natural substance famous for its immune-enhancing and anti-inflammatory effects. Atopic dermatitis (AD) is characterized by epidermal gene mutations, skin barrier dysfunction, and immune dysregulation, making patchouli volatile oil a potential candidate for AD treatment. Initially, PO was mixed with ethyl oleate (EO), castor oil ethoxylated ether-40 (EL-40), anhydrous ethanol, and water to form a patchouli oil microemulsion (PO-ME) system. The formulation ratios were optimized using the Box-Behnken design-effect surface method, and their products were characterized for type, particle size, polydispersity index (PDI), and appearance. Additionally, patchouli oil microemulsion gel (PO-MEG) was developed with a specified concentration of 1.5% carbomer-940 as the matrix, and its pH, stability, viscosity, and permeability were evaluated. We assessed the irritation tests of PO-MEG using a rat self-control model and the Cell Counting Kit-8 (CCK-8) assay. The results demonstrated that should be attributed to non-irritating. This study also assessed the efficacy of optimized PO-MEG on AD-like symptoms using a 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mouse model. Compared with the model group, the in vivo efficacy studies have shown the PO-MEG group significantly reduces dermatitis scores, mast cell counts, epidermal thickness, and levels of pro-inflammatory cytokines and immune factors in skin homogenates. This suggests that PO-MEG would become a safer topical formulation for treating atopic dermatitis.

Acupuncture for atopic dermatitis: a systematic review and meta-analysis

ObjectivesAtopic dermatitis is a chronic, relapsing, inflammatory skin disease that impacts patients’ quality of life and imposes substantial economic burdens on their families. Acupuncture holds promise as a viable treatment...

Use of advanced systemic therapy in patients with moderate-to-severe atopic dermatitis in the TARGET-DERM AD Registry

Background Moderate-to-severe atopic dermatitis (AD) significantly impacts quality of life. Advanced systemic therapeutics (AST) represent a new generation of medications targeting AD pathogenesis, but many who may benefit from these medications are AST-naïve. We compared patients in the United States who had started AST with those who had not started AST to evaluate associated characteristics. Methods TARGET-DERM AD, (NCT03661866, “A Longitudinal Observational Study of Patients Undergoing Therapy for IMISC (TARGET-DERM)” launched in 2019, is an ongoing, longitudinal, observational study of patients managed at 37 United States sites. Patients were aged 12 years and above, had moderate-to-severe AD based on validated Investigator Global Assessment (vIGA) at enrollment, at least one follow-up visit post-enrollment, and treatment with any of the following: a topical/systemic corticosteroid, immunomodulator, or phototherapy. AST included dupilumab and upadacitinib. Variables of interest gathered at enrollment included demographics, vIGA and Body Surface Area (BSA), patient-reported outcomes, and all recorded therapeutics. Results Of 3,076 patients, 436 qualified for inclusion, 52 were AST-treated adolescents and 141 AST-treated adults. Both groups had increased likelihood of AST initiation if they had private insurance and higher BSA, vIGAxBSA, or Patient-Oriented SCORing Atopic Dermatitis scores. Adults were more likely to start AST based on minority/ethnicity, more severe vIGA, higher patient-reported outcomes, or if treated at a community clinic. Substantial numbers of adolescent and adult patients (47 and 58%, respectively) with severe disease were AST-naïve. Conclusions Disease severity and patient access to AST are major factors driving AST initiation. However, some patients are undertreated. This analysis supports AD patient advocacy for those inadequately managed with conventional therapies. Further investigations are necessary to delineate AST initiation barriers and relevant outcomes.

Rosmarinic Acid Ameliorates Dermatophagoides farinae Extract-Induced Atopic Dermatitis-like Skin Inflammation by Activating the Nrf2/HO-1 Signaling Pathway.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. AD pathogenesis is associated with increased oxidative stress, impairment of the skin barrier, and activation of the immune response. Rosmarinic acid (RA), a caffeic acid ester, is known for its anti-inflammatory and antioxidant properties. However, the effects of RA on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation, as well as its ability to regulate oxidative stress through the Nrf2/HO-1 pathway in TNF-α/IFN-γ-treated keratinocytes, remain unclear. We investigated RA activity in a DfE-induced AD-like skin inflammation mouse model and IFN-γ/TNF-α-stimulated keratinocytes. We found that RA attenuates DfE-induced inflammation by decreasing dermatitis scores and serum inflammatory marker levels and mast cell infiltration. Additionally, RA significantly suppressed IFN-γ/TNF-α-induced chemokine production in keratinocytes and reduced Th cytokine levels in concanavalin A-stimulated splenocytes. Importantly, RA also increased Nrf2/HO-1 expression in TNF-α/IFN-γ-treated keratinocytes. In conclusion, this study demonstrated that RA effectively alleviates DfE-induced AD-like skin lesions by reducing the levels of inflammatory cytokines and chemokines. Furthermore, RA promotes Nrf2/HO-1 signaling in keratinocytes, which may help mitigate DfE-induced oxidative stress, thereby alleviating AD-like skin inflammation. These findings highlight the potential of RA as a therapeutic agent for treating AD and other skin inflammation.

Efficacy and safety of lebrikizumab for the treatment of moderate-to-severe atopic dermatitis: a systematic review and meta-analysis.

Lebrikizumab, an IL-13 immunomodulator, has shown recommendable effectiveness and safety in clinical studies for the treatment of moderate-to-severe atopic dermatitis (AD) in adolescents and adults. To evaluate the efficacy and safety of lebrikizumab in the treatment of moderate-to-severe AD through a meta-analysis. PubMed, Embase, Web of Science, Medline, and ClinicalTrials.gov databases were searched up to 8 August 2023. Randomized clinical trials of lebrikizumab treatment for moderate-to-severe AD were included by screening titles, abstracts, and papers. Five studies involving 1,551 patients with AD were identified. Pooled analysis revealed significant improvements in the Eczema Area and Severity Index (EASI) score (SMD = -0.527; 95% CI = [-0.617, -0.436]), Investigator's Global Assessment (IGA) score (RR = 2.122; 95% CI = [1.803, 2.496]), Body Surface Area (BSA) score (SMD = -0.608; 95% CI = [-1.099, -0.118]), SCORing Atopic Dermatitis (SCORAD) score (SMD = -0.441; 95% CI = [-0.633, -0.250]). Moreover, Pruritus Numeric Rating Scale (P-NRS) score, Patient-oriented Eczema Measure (POEM) scores, Sleep-loss score and Dermatology Life Quality Index (DLQI) scores showed similar results. Adverse events (AEs) (RR = 0.984; 95% CI = [0.907, 1.068]) for lebrikizumab showed no statistically significant difference compared to placebo, with similar results for serious adverse events (SAEs) (RR = 0.748; 95% CI = [0.410, 1.364]). This meta-analysis reveals that lebrikizumab has higher efficacy and safety in the treatment of moderate-to-severe AD, with the 250mg Q2W dosage regimen appearing to be more advantageous.

An Individualised Homoeopathic Approach to Chronic Atopic Dermatitis: A Case Report

AbstractAtopic dermatitis is a chronic inflammatory skin disease affecting about one-fifth of all individuals during their lifetime. It has substantial impact on the quality of life of the affected individual. Not only patient is affected by the social stigma of a visible skin condition but also the characteristic itch-scratch cycle often leads to skin trauma and significant sleep disruption. Though there is multitude of treatment options in modern medicine, the recurrence, and adverse effects of medications cannot be ruled out. Therefore, an alternative approach is required. The case presented here reported with the complaint of severe generalised itching eruptions for the last 8 years with a history of atopy. After thorough evaluation from the clinical and homoeopathic standpoint, a single homoeopathic medicine Arsenicum iodatum was prescribed in different potencies at different timepoints as the symptomatology corresponds. Following the administration of individualised homoeopathic (IH) medicine, there was gradual improvement in the case with disappearance of skin lesions which was also evaluated through reduction in SCORing Atopic Dermatitis and Dermatology Life Quality Index scores. During the treatment, old symptoms also reappeared indicating improvement in accordance with Hering's law of cure and Kent's 11th observation. The modified Naranjo criteria score after the treatment course was 10 which exclusively shows positive causal attribution of the IH in this case.

Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis

The Measure Up 1, Measure Up 2, and AD Up studies demonstrated the efficacy and adverse events of upadacitinib through 52 weeks in adults and adolescents with atopic dermatitis (AD); however, longer-term outcomes (longer than 1 year) in adolescents have not previously been available. To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks. The Measure Up 1, Measure Up 2, and AD Up trials are ongoing double-blind, placebo-controlled phase 3 randomized clinical trials including adolescents (aged 12 to 17 years) with moderate to severe AD. Data were collected from August 2018 to April 2022, and data were analyzed from June 2022 to September 2023. Adolescents were randomized 1:1:1 to receive once-daily oral upadacitinib, 15 mg; upadacitinib, 30 mg; or placebo, either alone (Measure Up 1 and Measure Up 2 trials) or with topical corticosteroids (AD Up). At week 16, placebo-treated patients were rerandomized to receive upadacitinib, 15 mg, or upadacitinib, 30 mg, daily. Coprimary end points assessing efficacy included achievement of 75% reduction or more in the Eczema Area and Severity Index Score (EASI-75) from baseline, Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with 2 grades or more of improvement, and Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 points or greater through week 76 for participants with a WP-NRS score of 4 points or higher at baseline. From all studies, 542 adolescents were included; of these, 284 (52.4%) were female. At week 76, among patients in the Measure Up 1, Measure Up 2, and AD Up trials, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of adolescents taking upadacitinib, 15 mg, respectively, and by 96.1%, 93.6%, and 82.7% of adolescents taking upadacitinib, 30 mg, indicating maintenance or improvement of EASI-75 across 76 weeks with upadacitinib. Efficacy measured by achievement of vIGA-AD score of 0 or 1 and WP-NRS improvement of 4 points or more from baseline was similarly maintained or improved through week 76 for adolescents taking upadacitinib, 15 mg or 30 mg. Long-term outcomes in Measure Up 1, Measure Up 2, and AD Up participants were consistent with the known adverse event profile of upadacitinib (herpetic infection: 4.0, 1.9, and 1.1 events per 100 patient-years, respectively; creatine kinase elevation: 11.6, 11.0, and 7.1 events per 100 patient-years); no new signals were observed with either dose. In this study assessing 3 randomized clinical trials, long-term treatment of adolescents with moderate to severe AD with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 76 weeks. Measure Up 1 trial: ClinicalTrials.gov Identifier: NCT03569293; Measure Up 2 trial: NCT03607422; AD Up trial: NCT03568318.

Anti-inflammatory Capacity of a Medicinal herb extract, Anemarrhena asphodeloides, on In vivo and In vitro models-induced atopic dermatitis

Anemarrhena asphodeloides (AA) Bunge, a rhizomatous plant from the Liliaceae family, is traditionally utilized to manage inflammatory conditions. Nevertheless, its impact on atopic dermatitis (AD) and the associated molecular pathways have not yet been fully explored. This study explored the therapeutic effects of AA on AD both in vivo, using 2,4-dinitrofluorobenzene-induced NC/Nga mice, and in vitro, with tumor necrosis factor-α/interferon-γ-stimulated HaCaT keratinocytes. Topical application of AA ointment on the dorsal skin notably alleviated AD symptoms and skin lesions, enhanced the dermatitis score, and improved parameters such as the rate of trans-epidermal water loss, epidermal thickness, mast cell infiltration, systemic IgE levels, and cytokine expression. Furthermore, AA treatment significantly reduced serum levels of thymic stromal lymphopoietin (TSLP) and locally suppressed mRNA expression of thymus and activation-regulated chemokine (TARC) along with other relevant cytokines in affected skin. Both in vivo and in vitro applications of AA curtailed TSLP levels by inhibiting the expression of signal transducer and activator of transcription 6, a key regulator of pruritus and an initiator of mitogen-activated protein kinase signaling pathways. Additionally, AA affected the expression of tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible 14, a pathway of interest in the study of cutaneous inflammatory diseases. Collectively, these findings propose that AA holds potential as an effective therapeutic agent for treating AD-induced skin inflammation.

Enoximone alleviates atopic dermatitis-like skin inflammation via inhibition of type 2 T helper cell development

Atopic dermatitis (AD) is an inflammatory skin disease that affects approximately 15-20% of the children and 1-3% of the adults worldwide. Corticosteroids and calcineurin inhibitors are used in AD therapy; however, they cause various side effects. Current studies focus on novel therapeutic targets such as phosphodiesterases (PDEs) to mitigate AD. However, the relationship between PDE3 inhibitors and AD has not yet been reported. This study aimed to investigate the therapeutic effects and pharmaceutical mechanisms of enoximone (Enox), a PDE3 inhibitor. Mice were stimulated with 2,4-dinitrochlorobenzene (DNCB) to induce AD-like skin inflammation and were topically treated with Enox for 2weeks. Treatment with Enox reduced the dermatitis score, skin water loss, IgE production, and expression of cytokines and chemokines that were elevated by DNCB. Histologically, Enox treatment reduced the skin thickness and the infiltration of various inflammatory cells, including macrophages, mast cells, eosinophils, and type 2T helper (Th2) cells. HuT78, a human T cell line, was used to investigate the differentiation of T cells into Th2 cells. Enox treatment decreased the expression of Th2 cytokines and GATA3, a Th2 cell marker in HuT78, and suppressed signaling pathways that play a crucial role in Th2 cell differentiation. Collectively, the results demonstrate that Enox alleviates AD-like skin inflammation by inhibiting T-cell development. Thus, Enox may be a therapeutic candidate for the treatment of AD.

PSXI-6 Effects of termite frass inclusion in free range broiler beddings on growth, footpad dermatitis score, and blood profiles

Abstract Research on insects as feed has gained attention in the last decade. Among insect species, we have focused on termites, which degrade lignocellulose and synthesize protein by employing gut microbiota. In particular, the damp-wood termite Hodotermopsis sjostedti subsisting on rotten wood, excretes a substantial portion of wood as frass, serving as their primary nest material. Termite frass, a by-product of termite production, has been found to comprise approximately 83% lignin, suggesting potential antibacterial properties. In this study, the effects of termite frass inclusion in free-range broiler chicken bedding on growth, meat and organ weights, blood profile, and footpad dermatitis (FPD) score were examined. Broiler chicks [n = 30; 0 d of age and initial body weight (BW) = 47.1 ± 0.51 g] were divided into three groups and resided in a 1.3 m2 pen fed on a commercial diet. The groups were subjected to one of the three bedding treatments: 7.5 kg sawdust (0% frass), 7.5 kg sawdust plus 7.5 kg termite frass (100% frass), and 7.5 kg sawdust plus 15.0 kg termite frass (200% frass). Intakes and BW were measured weekly, and the FPD score was assessed at 3, 5, 6, and 7 wk. At 50 d of age, the chickens were slaughtered for meat and organ weights and blood profile analyses. Growth data, meat and organ weights, and blood profiles were analyzed by GLM of SAS, and the weekly FPD score was analyzed by GLIMMIX as binomial data. Average daily gain and final BW were greater (P < 0.001 and P = 0.003, respectively) in chickens for 0% and 200% frass treatments than in 100%. Thigh and fillet meat weights were similar among the treatments, whereas breasts tended to be lighter (P = 0.064) for 100%. Footpad dermatitis scores tended to be greater (P = 0.085) for 200% than for 100%. Among organ weights tested (e.g., liver, heart, spleen, ventriculus, proventriculus, pancreas, cecum, intestine), heart weight was heavier (P = 0.044), whereas proventriculus was lighter (P = 0.022) for 200% than for 100%. On the other hand, cecum weight tended to be heavier (P = 0.075), and intestine tended to be lighter (P = 0.093) for 0% than for 100% and 200% treatments. Plasma alanine transaminase (ALT) and lactate dehydrogenase (LD) were less (P < 0.001 and P = 0.04, respectively) for 100% and 200% than for 0%. In conclusion, termite frass inclusion in free-range chicken bedding had slightly adverse trends on FPD; however, 200% inclusion did not alter the growth performances of chickens. It also suggested that frass inclusion would have preferable effects on chicken health based on plasma ALT and LD values. Further investigation is required for the different organ weights and their effects, such as heart, proventriculus, cecum, and intestine.

Crisaborole combined with vitamin D demonstrates superior therapeutic efficacy over either monotherapy in mice with allergic contact dermatitis

This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis.

Reducing Radiation Dermatitis for PBS Proton Therapy Breast Cancer Patients Using SpotDelete

The purpose of this work was toreduce the severity of radiation dermatitis for breast cancer patients receiving pencil beam scanningproton therapy. Thehypothesis was that eliminating proton spots (SpotDelete) in the 0.5cm skin rind would reduce the potentially higher relative biological effectiveness (RBE) known to occur at the Bragg Peak. Our center has been using an in-house developed Python script in RayStation since 2021 to remove spots from the skin rind of breast patients. In this work, we retrospectively reviewed the on-treatment visitdata from a cohort of breast patients treated with hypofractionation (16 fractions) before this technique (MinDepth) and after (SpotDelete) to acquire the physician-reported radiation dermatitis scores. We evaluated the delivered treatment plans, calculating the linear energy transfer (LET) and applying 3 variable RBE models, Carabe-Fernandez, Wedenberg, and McNamara. An α/β of 10 was assumed for the skin. In the MinDepth cohort (n=28), grade 1, 2,and 3 dermatitis accounted for 57%, 36%, and 7% of the cases, respectively. For SpotDelete (n=27), the incidence rate of grade 1 and 2 acute radiation dermatitis was 67% and 37%, respectively. There were 0instances of grade 3 dermatitis observed in the SpotDelete cohort. The onset of radiation dermatitis in the SpotDelete cohort was delayed compared to MinDepth, occurring 1 week later in the course of treatment. There was no significant difference in LET or in any of the variable RBE models when analyzing the 0.5cm skin rind between the cohorts. Despite the lack of correlation in LET or RBE, SpotDelete has been shown to reduce the severity and onset of radiation dermatitis. Possibly, more research into the α/β for skinand RBE models based on skin cell linescould provide insight into the efficacy of the SpotDelete technique.

Molybdenum Nanoparticles Alleviate MC903-Induced Atopic Dermatitis-Like Symptoms in Mice by Modulating the ROS-Mediated NF-κB and Nrf2 /HO-1 Signaling Pathways.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that can affect individuals of all ages. Recent research has shown that oxidative stress plays a crucial role in the development of AD. Therefore, inhibiting oxidative stress may be an effective therapeutic approach for AD. Nano-molybdenum is a promising material for use as an antioxidant. We aimed to evaluate the therapeutic effects and preliminary mechanisms of molybdenum nanoparticles (Mo NPs) by using a murine model of chemically induced AD-like disease. HaCaT cells, a spontaneously immortalized human keratinocyte cell line, were stimulated by tumor necrosis factor-alpha /interferon-gamma after pre-treatment with Mo NPs. Reactive oxygen species levels, production of inflammatory factors, and activation of the nuclear factor kappa-B and the nuclear factor erythroid 2-related factor pathways were then evaluated. Mo NPs was topically applied to treat a murine model of AD-like disease induced by MC903, a vitamin D3 analog. Dermatitis scores, pruritus scores, transepidermal water loss and body weight were evaluated. AD-related inflammatory factors and chemokines were evaluated. Activation of the nuclear factor kappa-B and nuclear factor erythroid 2-related factor / heme oxygenase-1 pathways was assessed. Our data showed that the topical application of Mo NPs dispersion could significantly alleviate AD skin lesions and itching and promote skin barrier repair. Further mechanistic experiments revealed that Mo NPs could inhibit the excessive activation of the nuclear factor kappa-B pathway, promote the expression of nuclear factor erythroid 2-related factor and heme oxygenase-1 proteins, and suppress oxidative stress reactions. Additionally, they inhibited the expression of thymic stromal lymphopoietin, inflammatory factors, and chemokines, thereby alleviating skin inflammation. Mo NPs present a promising alternative treatment option for patients with AD as they could address three pivotal mechanisms in the pathogenesis of AD concurrently.

Topical application of Artemisia annua L. essential oil ameliorates 2,4-dintrochlorobenzene-induced atopic dermatitis in mice

Volatile oil is widely used in traditional Chinese medicine owing to its unique hydrophobic and lipophilic properties and rapid skin absorption. Artemisia annua L. (A.annua) essential oil (AAEO), a volatile oil extracted from A. annua, exhibits anti-inflammatory properties. However, few studies have investigated its effects on skin inflammation. To investigate and elucidate the mechanisms of action of AAEO in the treatment of atopic dermatitis (AD). Network pharmacology was used to predict the targets and pathways of AAEO for the treatment of AD. The AD mouse model was established by topical application of 2,4-dintrochlorobenzene (DNCB), AAEO, and the positive control drug hydrocortisone butyrate cream (HBC). We evaluated the symptoms of AD, SCORAD scores, histological analysis, and serum IgE and TNF-α levels in mice. Immunofluorescence, western blotting, and qPCR were used to investigate the signaling pathways. Network pharmacology analysis indicated that AAEO may exert its effects via the MAPK/NF-κB signaling pathway. Animal experiments demonstrated that topical application of AAEO and HBC significantly ameliorated skin lesions, reduced dermatitis score, and decreased spleen weight compared to DNCB treatment. AAEO reduced skin epidermal thickness and mast cell infiltration. DNCB markedly reduced the protein levels of filaggrin (FLG) and loricrin (LOR), whereas AAEO reversed these changes. Notably, the 5% concentration of AAEO demonstrated substantial improvement in skin barrier function. Compared to the DNCB group, the levels of FLG and LOR remained almost unchanged following HBC treatment. DNCB markedly elevated IgE and TNF-α levels, which were reversed by AAEO and HBC treatment. Among the inflammatory cytokines, DNCB increased mRNA expression of TNF-α, IL-1β, and IL-6, however, it reduced IL-10, with AAEO and HBC reversing these changes to various degrees. Additionally, DNCB-induced ERK, JNK, and P38 phosphorylation, associated with the upregulation of phosphorylation of NF-κB, whereas, AAEO and HBC exhibited potent inhibition of the MAPK/NF-κB signaling pathway. This study systematically demonstrated the possible therapeutic effects and mechanisms of AAEO in AD via network pharmacological analysis and experimental confirmation. These results revealed that topical application of AAEO can suppress skin inflammation and restore skin barrier function. These findings provide the potential application of AAEO in synthesizing external preparations for both pharmacological and cosmetic industries.