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1.
Allergol. immunopatol ; 51(1): 168-176, ene. 2023. tab
Artigo em Inglês | IBECS | ID: ibc-214038

RESUMO

Objective: To develop a questionnaire and a scoring system for evaluating physicians’ knowledge of allergen immunotherapy (AIT). Methods: Questionnaire was designed using the Questionnaire Star tool. A total of 1024 physicians were assessed, and based on the score divided into accurate judgment and inaccurate judgment groups. Statistical analysis was done, and counting data were expressed as frequencies and percentage values. Chi-square test and multi-factor logistic analysis were used to determine influencing factors on the indications for AIT. Results: Physician’s age, grade of the hospital, and pediatric specialty influenced the accurate judgment of AIT indication after adjustment for independent variables (P < 0.05). In all, 80.5% physicians exercised accurate assessment for allergic rhinitis. Allergic conjunctivitis was judged accurately by 47.0% physicians. Bronchial asthma was judged accurately by 71.0% physicians, and atopic dermatitis by 61.3% physicians, with a higher accuracy rate for pediatricians than nonpediatricians for all the mentioned conditions (P < 0.05). There was no significant difference in the accuracy of judgment between pediatricians and non-pediatricians in terms of AIT for food allergy and dust mite sensitization (P > 0.05). Conclusion: The results of our study demonstrated a high accuracy judgment rate among clinicians for rhinitis, asthma, and dermatitis, and a low accuracy rate for desensitization of healthy people with allergic conjunctivitis, food allergies, and allergen sensitization (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Dessensibilização Imunológica , Rinite Alérgica/terapia , Asma/terapia , Dermatite/terapia , Competência Clínica , Inquéritos e Questionários
2.
Microbiome ; 11(1): 11, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670494

RESUMO

BACKGROUND: Paederus fuscipes is medically the most famous rove beetle, which causes dermatitis or conjunctivitis in humans, as well as gastrointestinal toxicosis in livestock, via releasing toxic hemolymph containing pederin. Pedrin biosynthesis genes have been identified in uncultured Pseudomonas-like endosymbionts that are speculated to be acquired through a horizontal transfer. However, the composition of the P. fuscipes microbial community, especially of the gut and genital microbiome, remains unclear. This study was aimed to characterize the structure and diversity of P. fuscipes-associated bacterial communities in terms of gender, organ, and location using the Illumina HiSeq platform in the southern littorals of Caspian Sea. RESULTS: The OTUs identified from P. fuscipes specimens were collapsed into 40 phyla, 112 classes, 249 orders, 365 families, 576 genera, and 106 species. The most abundant families were Pseudomonadaceae, Spiroplasmataceae, Weeksellaceae, Enterococcaceae, and Rhizobiaceae, respectively. Thirty top genera made up > 94% of the P. fuscipes microbiome, with predominating Pseudomonas, followed by the Spiroplasma, Apibacter, Enterococcus, Dysgonomonas, Sebaldella, Ruminococcus, and Wolbachia. Interesting dissimilarities were also discovered within and between the beetle microbiomes in terms of genders and organs. Analyses showed that Spiroplasma / Apibacter as well as Pseudomonas / Pseudomonas were the most abundant in the genitals / intestines of male and female beetles, respectively. Bacterial richness did not display any significant difference in the three provinces but was higher in male beetles than in females and more in the genitals than intestines. CONCLUSIONS: The present study identified Pseudomonas-like endobacterium as a common symbiont of P. fuscipes beetles; this bacterium begins its journey from gut and genitalia of females to reach the male rove beetles. Additionally, male and female rove beetles were characterized by distinctive microbiota in different organs, likely reflecting different functions and/or adaptation processes. Evidence of the extension of P. fuscipes microbiome from the environmental paradigm to the pathobiome was also presented herein. A comprehensive survey of P. fuscipes microbiome components may eventually lead to ecological insights into the production and utilization of defensive compound of pederin and also the management of linear dermatitis with the use of available antibiotics against bacterial pathogens released by the beetles. Video Abstract.


Assuntos
Besouros , Dermatite , Microbiota , Rhizobiaceae , Humanos , Animais , Masculino , Feminino , Besouros/microbiologia , Enterococcus , Microbiota/genética
3.
J Zoo Wildl Med ; 53(4): 644-653, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36640065

RESUMO

Detection of renal disease in birds is currently reliant on biochemical measures such as uric acid, which is only elevated after significant renal compromise has occurred. Symmetric dimethylarginine (SDMA) production has not been previously evaluated in birds and no reference intervals (RI) for measurement exist in avian species. This study aimed to develop an RI for SDMA in greater flamingos (Phoenicopterus roseus) and evaluate the association between SDMA levels and renal disease. Blood from 60 flamingos was collected for RI development and the RI of SDMA was found to be 11.8-34.2 µg/dl. Symmetric dimethylarginine showed a strong positive correlation with uric acid, a moderate positive correlation with creatine kinase, and moderate negative correlations with total protein, albumin, and glucose. No correlation was found with pododermatitis score or body condition. Using the SDMA RI, six clinical cases were included for assessment of the clinical relevance of SDMA in renally compromised patients. All birds that were euthanized had elevated SDMA levels and severe renal or systemic pathology on necropsy.


Assuntos
Dermatite , Nefropatias , Animais , Ácido Úrico , Nefropatias/veterinária , Dermatite/veterinária , Aves , Biomarcadores
4.
Anticancer Res ; 43(2): 823-830, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36697089

RESUMO

BACKGROUND/AIM: Smoking and alcohol abuse may impair outcomes of chemoradiation for squamous cell head and neck cancer (SCCHN). Potential associations with toxicity, loco-regional control (LRC), and overall survival (OS) were investigated. PATIENTS AND METHODS: Ninety-six patients were retrospectively analyzed for impacts of pre-radiotherapy (pre-RT) smoking history, smoking during radiotherapy, and pre-RT alcohol abuse on toxicity, LRC, and OS. RESULTS: A trend was found for associations between pre-RT smoking history and grade ≥2 dermatitis. Smoking during radiotherapy was significantly associated with grade ≥3 mucositis and showed trends regarding grade ≥2 mucositis and dermatitis. On univariate analyses, smoking during radiotherapy was negatively associated with LRC and OS, pre-RT alcohol abuse with OS, and >40 pack years with LRC and OS. In multivariate analyses, smoking during radiotherapy remained significant for decreased OS, and pack years showed a trend. CONCLUSION: Smoking during radiotherapy was an independent predictor of OS and associated with increased toxicity. Thus, it is important to stop smoking prior to the start of radiotherapy.


Assuntos
Alcoolismo , Carcinoma de Células Escamosas , Dermatite , Neoplasias de Cabeça e Pescoço , Mucosite , Humanos , Carcinoma de Células Escamosas/terapia , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/radioterapia , Fumar/efeitos adversos , Consumo de Bebidas Alcoólicas/efeitos adversos
5.
Medicine (Baltimore) ; 102(3): e32360, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36701719

RESUMO

BACKGROUND: Psoriasis is a chronic, inflammatory, autoimmune skin disease. The aim of this review is to systematically evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used to treat inflammatory skin lesions of psoriasis. METHODS: A comprehensive literature search will be conducted in 3 English databases (PubMed, Cochrane Library, and Embase), 4 Korean databases (Korean Studies Information Service System, Research Information Service System, Oriental Medicine Advanced Searching Integrated System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from their inception until July 29, 2021. Statistical analysis will be performed using R version 4.1.2 and the R studio program using the default settings of the "meta" and "metafor" packages. The primary outcome will be an improvement in the psoriasis area severity index. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. If heterogeneity is detected in the study, the cause will be identified through sensitivity, meta-regression, and subgroup analyses. Methodological quality will be assessed independently using the revised tool for the risk of bias in randomized trials, version 2.0. The overall quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation pro framework. RESULTS: This study will review all available trials on the same subject and arrive at a more statistically robust conclusion based on a sufficient sample size of participants and additional analysis using data mining techniques will be performed on intervention prescription information in clinical studies collected according to rigorous criteria. CONCLUSION: We believe that this study will provide useful knowledge on managing inflammatory skin lesions of psoriasis vulgaris using integrative medicine using East Asian herbal medicine.


Assuntos
Dermatite , Medicamentos de Ervas Chinesas , Medicina Integrativa , Medicina Tradicional do Leste Asiático , Psoríase , Humanos , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Medicina Tradicional do Leste Asiático/métodos , Psoríase/tratamento farmacológico , Extratos Vegetais , Medicamentos de Ervas Chinesas/uso terapêutico , Literatura de Revisão como Assunto
6.
Medicine (Baltimore) ; 102(4): e32780, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705366

RESUMO

Multimodal molecular imaging technologies have been widely used to optimize medical research and clinical practice. Bibliometric analysis was performed to identify global research trends, hot spots, and scientific frontiers of multimodal molecular imaging technology from 2012 to 2021. The articles and reviews related to multimodal molecular imaging were retrieved from the Web of Science Core Collection. A bibliometric study was performed using CiteSpace and VOSviewer. A total of 4169 articles and reviews from 2012 to 2021 were analyzed. An increasing trend in the number of articles on multimodal molecular imaging technology was observed. These publications mainly come from 417 institutions in 92 countries, led by the USA and China. K. Bailey Freund published the most papers amongst the publications, while R.F. Spaide had the most co-citations. A dual map overlay of the literature shows that most publications were specialized in physics/materials/chemistry, and molecular/biology/immunology. Synergistic therapy in cancer, advanced nanotechnology, and multimodal imaging in ophthalmology are new trends and developing areas of interest. A global bibliometric and visualization analysis was used to comprehensively review the published research related to multimodal molecular imaging. This study may help in understanding the dynamic patterns of multimodal molecular imaging technology research and point out the developing areas of this field.


Assuntos
Pesquisa Biomédica , Dermatite , Humanos , Bibliometria , China , Imagem Molecular
7.
Sci Rep ; 13(1): 1195, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681722

RESUMO

The source of massive magma production at volcanic rifted margins remains strongly disputed since the first observations of thick lava piles in the 1980s. However, volumes of extruded and intruded melt products within rifted continental crust are still not accurately resolved using geophysical methods. Here we investigate the magma budget alongside the South Atlantic margins, at the onset of seafloor spreading, using high-quality seismic reflection profiles to accurately estimate the oceanic crustal thickness. We show that, along ~ 75% of the length of the Early-Cretaceous initial spreading centre, the crustal thickness is similar to regular oceanic thickness with an age > 100 Ma away from hot spots. Thus, most of the southernmost Atlantic Ocean opened without anomalously hot mantle, high magma supply being restricted to the Walvis Ridge area. We suggest that alternative explanations other than a hotter mantle should be favoured to explain the thick magmatic layer of seaward dipping reflectors landward of the initial mid-oceanic ridge.


Assuntos
Dermatite , Hemorroidas , Humanos , Oceano Atlântico , Orçamentos , Temperatura Alta
8.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674974

RESUMO

Sphingolipids are crucial molecules of the mammalian epidermis. The formation of skin-specific ceramides contributes to the formation of lipid lamellae, which are important for the protection of the epidermis from excessive water loss and protect the skin from the invasion of pathogens and the penetration of xenobiotics. In addition to being structural constituents of the epidermal layer, sphingolipids are also key signaling molecules that participate in the regulation of epidermal cells and the immune cells of the skin. While the importance of ceramides with regard to the proliferation and differentiation of skin cells has been known for a long time, it has emerged in recent years that the sphingolipid sphingosine 1-phosphate (S1P) is also involved in processes such as the proliferation and differentiation of keratinocytes. In addition, the immunomodulatory role of this sphingolipid species is becoming increasingly apparent. This is significant as S1P mediates a variety of its actions via G-protein coupled receptors. It is, therefore, not surprising that dysregulation in the signaling pathways of S1P is involved in the pathophysiological conditions of skin diseases. In the present review, the importance of S1P in skin cells, as well as the immune cells of the skin, is elaborated. In particular, the role of the molecule in inflammatory skin diseases will be discussed. This is important because interfering with S1P signaling pathways may represent an innovative option for the treatment of inflammatory skin diseases.


Assuntos
Dermatite , Dermatopatias , Animais , Esfingosina/metabolismo , Esfingolipídeos/metabolismo , Lisofosfolipídeos/metabolismo , Ceramidas/metabolismo , Dermatopatias/tratamento farmacológico , Dermatopatias/metabolismo , Mamíferos/metabolismo
9.
Molecules ; 28(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36677961

RESUMO

The presence of phenobarbital and formaldehyde in drugs, food, and beverages can lead to various health issues, including inflammation, oncogenesis, and neurological distress. Psychological stress leads to mood fluctuations and the onset of skin inflammation. Skin inflammation has a range of causes, including chemicals, heavy metals, infection, immune-related disorders, genetics, and stress. The various treatments for skin inflammation include medical and cosmetic creams, diet changes, and herbal therapy. In this study, we investigated the effects of Avocom-M and pomegranate seed oil extract (PSOE) against phenobarbital- and formaldehyde-induced skin biochemical changes in rats. We analyzed the constituents of PSOE using gas chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry. We also observed biochemical changes in the skin of human volunteers with and without TROSYD and PSOE as a skin cream. We compared the biochemical changes in human volunteers' skin before treatment and 21 days after the treatment stopped. The outcomes showed an improvement in the rats' biochemical status, due to PSOE and Avocom-M treatment. The human volunteers treated with TROSYD and PSOE showed substantial amelioration of skin inflammation. PSOE, Avocom-M, and TROSYD produced beneficial effects by reducing the levels of cyclooxygenase-2, lipid peroxidation, tyrosinase, hyaluronidase, elastase, collagenase, and nitric oxide in the animals tested on and in human volunteers.


Assuntos
Dermatite , Romã (Fruta) , Humanos , Animais , Ratos , Projetos Piloto , Creme para a Pele/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Óleos Vegetais/farmacologia , Óleos Vegetais/química , Inflamação/tratamento farmacológico , Formaldeído
10.
Viruses ; 15(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36680262

RESUMO

Alaska is a unique US state because of its large size, geographically disparate population density, and physical distance from the contiguous United States. Here, we describe a pattern of SARS-CoV-2 variant emergence across Alaska reflective of these differences. Using genomic data, we found that in Alaska, the Omicron sublineage BA.2.3 overtook BA.1.1 by the week of 27 February 2022, reaching 48.5% of sequenced cases. On the contrary, in the contiguous United States, BA.1.1 dominated cases for longer, eventually being displaced by BA.2 sublineages other than BA.2.3. BA.2.3 only reached a prevalence of 10.9% in the contiguous United States. Using phylogenetics, we found evidence of potential origins of the two major clades of BA.2.3 in Alaska and with logistic regression estimated how it emerged and spread throughout the state. The combined evidence is suggestive of founder events in Alaska and is reflective of how Alaska's unique dynamics influence the emergence of SARS-CoV-2 variants.


Assuntos
COVID-19 , Dermatite , Humanos , Alaska/epidemiologia , SARS-CoV-2/genética , COVID-19/epidemiologia
11.
J Am Anim Hosp Assoc ; 59(1): 7-11, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584311

RESUMO

Malassezia pachydermatis is a commensal of canines associated with Malassezia dermatitis. Consensus guidelines recommend topical and/or systemic treatment, but resistance to antifungals has been reported. The objective of this pilot study was to determine the efficacy of a 0.003% colloidal silver nanoparticle-based shampoo in the treatment of canine Malassezia dermatitis. Dogs were included based on compatible history, presentation, and at least one positive cytology. Fourteen privately owned dogs were bathed every 48 hr for up to 28 days, allowing 5-10 min of contact time. The mean Malassezia organisms for 10 oil immersion fields at each Malassezia dermatitis-affected body area was recorded at days 0 and 14. Dogs positive on day 14 had cytologies performed on day 28. Eleven dogs (78.6%) were cytologically negative by day 28. Nine (81.8%) of these were negative by day 14. One dog (7.14%) had partial resolution (negative in 3/4 Malassezia dermatitis areas) by day 28. These results suggest that silver nanoparticle-based shampoo may be effective in the treatment of canine Malassezia dermatitis. Larger, controlled studies are needed to further investigate efficacy, optimal concentration, and ideal application frequency.


Assuntos
Dermatite , Dermatomicoses , Doenças do Cão , Malassezia , Nanopartículas Metálicas , Cães , Animais , Projetos Piloto , Prata/uso terapêutico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/veterinária , Nanopartículas Metálicas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Dermatite/veterinária
12.
J Am Anim Hosp Assoc ; 59(1): 1-6, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584317

RESUMO

A 7 yr old castrated male Cavalier King Charles spaniel presented for evaluation of liver enzyme elevations. Abdominal ultrasound revealed a small liver with mixed echogenicity, small hypoechoic nodules, and an irregular surface. Histologic examination and copper quantification of the liver obtained by laparoscopy diagnosed copper-associated hepatitis. One month later the dog developed hyperkeratosis of all four foot pads and ulcerations of feet, legs, and rectum. Punch biopsies confirmed superficial necrolytic dermatitis. After a total of 2 mo of chelation with no changes to medications, skin lesions began to improve, continuing over the following 6 wk to almost complete resolution. At this point the skin lesions returned and had minimal response to four amino acids infusions. The dog was switched from penicillamine to trientine. Zinc acetate was initiated 6 wk after the switch to trientine, and skin improvement was noted soon thereafter. At the time of death, skin lesions were improving and the dog was clinically comfortable. Copper-associated hepatitis should be considered as a possible etiology for superficial necrolytic dermatitis. Treatment of superficial necrolytic dermatitis is often unrewarding, and copper chelation, when copper-associated hepatitis has been confirmed, represents another therapeutic option.


Assuntos
Dermatite , Doenças do Cão , Hepatite , Dermatopatias , Cães , Masculino , Animais , Dermatite/tratamento farmacológico , Dermatite/veterinária , Dermatite/diagnóstico , Cobre , Trientina/uso terapêutico , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Doenças do Cão/diagnóstico , Dermatopatias/veterinária , Hepatite/complicações
13.
Int J Biol Macromol ; 227: 736-748, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549615

RESUMO

Piperine is an alkaloid mostly found in the fruits of several species of the Piper genus, and its anti-inflammatory potential is already known. However, its therapeutic applications still need to be better explored due to the low aqueous solubility of this active. To overcome this drawback, the objective of this work was to evaluate the efficiency of the nanoencapsulation of the compound as well as its incorporation into hyaluronic acid/alginate-based biomembranes. Polymeric nanoparticles composed of Eudragit S100 and Poloxamer 188 were obtained by the nanoprecipitation technique, obtaining spherical nanosized particles with an average diameter of 122.1 ± 2.0 nm, polydispersity index of 0.266, and encapsulation efficiency of 76.2 %. Hyaluronic acid/sodium alginate membranes were then prepared and characterized. Regarding permeation, a slow passage rate was observed until the initial 14 h, when an exponential increase in the recovered drug concentration began to occur. The in vivo assay showed a reduction in inflammation up to 43.6 %, and no cytotoxicity was observed. The results suggested the potential of the system developed for the treatment of inflammatory skin diseases.


Assuntos
Alcaloides , Dermatite , Nanopartículas , Humanos , Ácido Hialurônico , Alginatos , Alcaloides/farmacologia , Tamanho da Partícula
14.
Biochim Biophys Acta Mol Basis Dis ; 1869(3): 166629, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36563916

RESUMO

Recurrent streptococcal tonsillitis exacerbates psoriasis. Studies have indicated that T cells responding to streptococcal antigens in the skin are involved in the pathogenesis of the disease. However, a direct link between streptococcal tonsillitis and psoriasis has not been evidenced. In the present study, the impact of intranasal (i.n.) streptococcal infection on psoriasis was investigated using the imiquimod (IMQ) psoriasis mouse model. The results showed that repeated i.n. infection with group A Streptococcus (GAS) induced a robust and persistent Th17 response in the nasal-associated lymphoid tissue (NALT) and exacerbated IMQ-mediated psoriatic skin lesions. ELISpot and flow cytometry analyses revealed that GAS-reactive tissue-resident memory T cells (TRM) were present in the skin of GAS-infected mice and produced IL-17/IL-23 axis cytokines in response to IMQ, compared to mice uninfected with GAS. In addition, i.n. infection with Streptococcus pneumoniae (Sp), a pathogen not associated with the development of psoriasis, also induced a persistent Th17 response in NALT but did not exacerbate IMQ-induced psoriatic inflammation nor elicited Sp-specific T cells in the skin. The results provide in vivo evidence that GAS-associated psoriasis is dependent on the skin GAS-specific TRM cells induced by GAS nasopharyngeal infection and can be later activated by environmental triggers, leading to psoriatic inflammation. Reducing the reservoir of Th17 cells, which are source of skin TRM cells, may constitute a promising treatment for psoriasis.


Assuntos
Dermatite , Psoríase , Infecções Estreptocócicas , Tonsilite , Animais , Camundongos , Células T de Memória , Psoríase/patologia , Imiquimode/efeitos adversos , Infecções Estreptocócicas/complicações , Inflamação
16.
Can Vet J ; 63(12): 1255-1257, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36467373

RESUMO

A 16-year-old Quarter Horse was examined and observed to have acute signs of colic, pyrexia, and diarrhea. A nephrosplenic entrapment was detected via rectal palpation and confirmed with abdominal ultrasound. The nephrosplenic entrapment was resolved non-surgically with jogging and anti-inflammatory medication. Concurrent colitis, toxic laminitis, and inappetence were managed and the horse made a full recovery.


Correction non chirurgicale d'emprisonnement néphro-splénique et de la colite chez un Quarter Horse. Un Quarter Horse âgé de 16 ans a été examiné et on a observé des signes aigus de coliques, de pyrexie et de diarrhée. Un piégeage néphro-splénique a été détecté par palpation rectale et confirmé par échographie abdominale. L'emprisonnement néphro-splénique a été résolu de manière non chirurgicale avec du jogging et des médicaments anti-inflammatoires. La colite concomitante, la fourbure toxique et l'inappétence ont été gérées et le cheval s'est complètement rétabli.(Traduit par Dr Serge Messier).


Assuntos
Colite , Dermatite , Doenças dos Cavalos , Cavalos , Animais , Colite/cirurgia , Colite/veterinária , Dermatite/veterinária , Diarreia/veterinária , Febre/veterinária , Doenças dos Cavalos/terapia
17.
Cell Rep ; 41(13): 111897, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36577385

RESUMO

Psoriasis is an inflammatory skin disease characterized by keratinocyte proliferation and inflammatory cell infiltration induced by IL-17. However, the molecular mechanism through which IL-17 signaling in keratinocytes triggers skin inflammation remains not fully understood. Pyruvate kinase M2 (PKM2), a glycolytic enzyme, has been shown to have non-metabolic functions. Here, we report that PKM2 mediates IL-17A signaling in keratinocytes triggering skin psoriatic inflammation. We find high expression of PKM2 in the epidermis of psoriatic patients and mice undergoing psoriasis models. Specific depletion of PKM2 in keratinocytes attenuates the development of experimental psoriasis by reducing the production of pro-inflammatory mediators. Mechanistically, PKM2 forms a complex with Act1 and TRAF6 regulating NF-κB transcriptional signaling downstream of the IL-17 receptor. As IL-17 also induces PKM2 expression in keratinocytes, our findings reveal a sustained signaling circuit critical for the psoriasis-driving effects of IL-17A, suggesting that PKM2 is a potential therapeutic target for psoriasis.


Assuntos
Dermatite , Psoríase , Camundongos , Animais , Interleucina-17/metabolismo , Piruvato Quinase/metabolismo , Queratinócitos/metabolismo , Psoríase/induzido quimicamente , Inflamação/metabolismo , Pele/metabolismo
19.
Science ; 378(6625): 1201-1207, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36520901

RESUMO

Cell death induced by tumor necrosis factor (TNF) can be beneficial during infection by helping to mount proper immune responses. However, TNF-induced death can also drive a variety of inflammatory pathologies. Protectives brakes, or cell-death checkpoints, normally repress TNF cytotoxicity to protect the organism from its potential detrimental consequences. Thus, although TNF can kill, this only occurs when one of the checkpoints is inactivated. Here, we describe a checkpoint that prevents apoptosis through the detoxification of the cytotoxic complex IIa that forms upon TNF sensing. We found that autophagy-related 9A (ATG9A) and 200kD FAK family kinase-interacting protein (FIP200) promote the degradation of this complex through a light chain 3 (LC3)-independent lysosomal targeting pathway. This detoxification mechanism was found to counteract TNF receptor 1 (TNFR1)-mediated embryonic lethality and inflammatory skin disease in mouse models.


Assuntos
Apoptose , Proteínas Relacionadas à Autofagia , Proteínas de Membrana , Fator de Necrose Tumoral alfa , Proteínas de Transporte Vesicular , Animais , Camundongos , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Dermatite/genética , Dermatite/metabolismo , Dermatite/patologia , Modelos Animais de Doenças , Perda do Embrião/genética , Perda do Embrião/metabolismo , Perda do Embrião/patologia , Lisossomos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
20.
Mar Drugs ; 20(12)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36547895

RESUMO

The dinoflagellate Ostreopsis cf. ovata produces several families of toxic polyketides. Despite only a few field measurements of these phycotoxins in seawater and aerosols, they are believed to be responsible for dermatitis and the toxic inhalations reported during blooms of this species. Therefore, the stability of these compounds in seawater is essential to understanding the causes of these symptoms, however, this has never been assessed. In the current study, the optimization of a solid phase extraction (SPE) procedure was first performed to ensure the most efficient extraction of all phycotoxins known to be produced by this strain, including the recently described liguriatoxins. The SPE cartridge SDBL® under non acidified conditions offered the best option. The stability of the ovatoxins and the liguriatoxins under biotic and abiotic stress was assessed by exposing the spent medium of a culture of Ostreopsis cf. ovata to its bacterial consortium and natural sunlight. A rapid biotic transformation was detected for both families of compounds. When exposed to bacteria, the half-lives of the ovatoxins were reached before 10 h and at 36 h, 97% of these toxins had been transformed. The half-lives of the liguriatoxins were 10 h under these conditions. Photolysis (abiotic degradation) of the ovatoxins (T1/2 < 36 h) was faster than for the liguriatoxins (T1/2 > 62 h). Although none of the catabolites of these phycotoxins were thoroughly identified, an untargeted metabolomics approach combined with molecular networking highlighted the presence of several compounds exhibiting structural similarities with the ovatoxins. Additional work should confirm the preliminary findings on these potential ovatoxins' catabolites and their biological properties. The rapid transformation of O. cf. ovata's phycotoxins introduces questions concerning their presence in seawater and their dispersion in the sea spray aerosols. The compounds involved in the toxic inhalations and dermatitis often experienced by beachgoers may stem from the catabolites of these toxins or even unrelated and as yet unidentified compounds.


Assuntos
Venenos de Cnidários , Dermatite , Dinoflagelados , Humanos , Toxinas Marinhas/química , Dinoflagelados/química , Venenos de Cnidários/metabolismo , Aerossóis , Bactérias
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