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1.
Sci Rep ; 10(1): 21732, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303806

RESUMO

Poor wound closure due to diabetes, aging, stress, obesity, alcoholism, and chronic disease affects millions of people worldwide. Reasons wounds will not close are still unclear, and current therapies are limited. Although stem cell factor (SCF), a cytokine, is known to be important for wound repair, the cellular and molecular mechanisms of SCF in wound closure remain poorly understood. Here, we found that SCF expression in the epidermis is decreased in mouse models of delayed wound closure intended to mimic old age, obesity, and alcoholism. By using SCF conditionally knocked out mice, we demonstrated that keratinocytes' autocrine production of SCF activates a transient c-kit receptor in keratinocytes. Transient activation of the c-kit receptor induces the expression of growth factors and chemokines to promote wound re-epithelialization by increasing migration of skin cells (keratinocytes and fibroblasts) and immune cells (neutrophils) to the wound bed 24-48 h post-wounding. Our results demonstrate that keratinocyte-produced SCF is essential to wound closure due to the increased recruitment of a unique combination of skin cells and immune cells in the early phase after wounding. This discovery is imperative for developing clinical strategies that might improve the body's natural repair mechanisms for treating patients with wound-closure pathologies.

2.
Medicine (Baltimore) ; 99(50): e23479, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327279

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune system disease that mainly affects joints throughout the body, causing joint pain, deformity, and even disability. The use of Chinese herbal medicine (CHM) to treat RA has achieved certain effects, and Duohuo Jisheng decoction (DHJSD) is one of them. But there is no high-level evidence to support this result. The purpose of this work is to evaluate the effectiveness of DHJSD combined with DMARDs compared with isolated DMARDs for RA. METHODS: We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), Chinese databases SinoMed (CBM), PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to October 2020. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. RESULTS: This study will evaluate the efficacy and safety of DHJSD combined with DMARDs compared with isolated DMARDs in the treatment of Rheumatoid arthritis, to provide high-quality, evidence-based clinical recommendations. CONCLUSION: This study will provide reliable evidence on whether Duhuo Jisheng decoction combined with DMARDs compared with isolated DMARDs is more effective in treating RA. TRIAL REGISTRATION NUMBER: INPLASY2020100089.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
3.
J Invest Dermatol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33197483

RESUMO

The outer layer of the epidermis composes the skin barrier, a sophisticated filter constituted by layers of corneocytes in a lipid matrix. The matrix lipids, especially the ceramide-generated sphingosine 1-phosphate (S1P), are the messengers that the skin barrier uses to communicate with the basal layer of epidermis where replicating keratinocytes are located. S1P is a bioactive sphingolipid mediator involved in various cellular functions via S1P receptor (S1PR) 1-5, expressed by keratinocytes. We discovered that the S1pr2 absence is linked to an impairment in skin barrier function. Although S1pr2-/- mouse skin have no difference in its phenotype and barrier function compared to wildtype (wt), after tape stripping, S1pr2-/- mice showed significantly higher transepidermal water loss (TEWL) and required another 24 more hours to normalize their TEWL levels. Moreover, after epicutaneous S. aureus application, impaired S1pr2-/- mouse epidermal barrier function allowed deeper bacterial penetration and denser neutrophil infiltration in the dermis. Microarray and RNA sequence of S1pr2-/- mouse epidermis linked the barrier dysfunction with a decrease in filaggrin 2 and tight junction components. In conclusion, S1pr2-/- mice have compromised skin barrier function and increased bacteria permeability, making them a suitable model for diseases that present similar characteristics, such as atopic dermatitis.

4.
Medicine (Baltimore) ; 99(47): e23262, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217849

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is a kind of degenerative osteoarthropathy, which causes joint pain and limited mobility, seriously affects the quality of life of the patient. Traditional Chinese Medicine acupuncture and moxibustion has been widely used to treat KOA, and acupoint injection is 1 of the acupuncture treatment methods. The purpose of this work is to evaluate the effectiveness of Acupoint injection combined with Hyaluronic Acid injection compared with isolated Hyaluronic Acid injection for KOA. METHODS: We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure, Wanfang Data, Chinese Scientific Journals Database, Chinese databases SinoMed, PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to October 2020. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. RESULTS: This study will evaluate the efficacy and safety of Acupoint injection combined with Hyaluronic Acid injection compared with isolated Hyaluronic Acid injection in the treatment of KOA, to provide high-quality, evidence-based clinical recommendations. TRIAL REGISTRATION NUMBER: INPLASY2020100058 CONCLUSION:: This study will provide reliable evidence on whether Acupoint injection combined with Hyaluronic Acid injection compared with isolated Hyaluronic Acid injection is more effective in treating KOA.

5.
Medicine (Baltimore) ; 99(43): e22767, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120786

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) causes joint pain and limited mobility, which affects the quality of life. The use of Chinese herbal medicine to treat KOA has achieved certain effects, and Wutou decoction (WTD) is one of them. But there is no high-level evidence to support this result. The purpose of this work is to evaluate WTD's efficacy and safety in the management of KOA. METHODS: We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), Chinese databases SinoMed (CBM), PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to September 2020. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. RESULTS: This study will evaluate the current efficacy and safety of WTD in the treatment of KOA, to provide high-quality, evidence-based clinical recommendations. CONCLUSION: This study will provide reliable evidence on whether WTD is safe and effective in treating KOA. TRIAL REGISTRATION NUMBER: INPLASY202090022.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
6.
Medicine (Baltimore) ; 99(34): e21764, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846803

RESUMO

RATIONALE: Triple or more primary malignancies are rare, with only 23 previous cases including breast cancer reported in the English language studies between January 1990 and December 2019. PATIENT CONCERNS: The patient was a 67-year-old woman with a mass in her right breast. She had a previous history of uterine and colon cancer. Both ultrasonography and mammography revealed a Breast Imaging Reporting and Data System (BI-RADS) category 3 breast lesion, in which proliferative nodules are more likely. Given her previous history of 2 malignancies, her doctors strongly recommended a biopsy. DIAGNOSIS AND INTERVENTIONS: The biopsy pathology suggested intraductal breast cancer. Mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological diagnosis was invasive ductal carcinoma, grade II, stage I. The sample was positive for estrogen receptor and progesterone receptor and negative for cerbB-2. No radiotherapy or chemotherapy was administered except for endocrine therapy. A follow-up at 19 months showed no breast recurrence or distant metastases. OUTCOMES: No recurrence or distant metastasis occurred within the 19-month, 11-year, and 20-year follow-ups for breast, colon, and uterine cancers, respectively. LESSONS: To our knowledge, this is the first review of triple or more primary malignancies including breast cancer. These malignancies occur predominantly in older female patients. The most prevalent tumors of triple or more primary malignancies including breast cancer occur in the colon, uterus, and lung. A favorable prognosis is associated with early-stage malignancies.


Assuntos
Neoplasias da Mama/complicações , Neoplasias do Colo/complicações , Neoplasias Uterinas/complicações , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Humanos , Mamografia , Mastectomia , Biópsia de Linfonodo Sentinela
7.
Appl Biochem Biotechnol ; 192(4): 1176-1190, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32700203

RESUMO

The recyclable aqueous two-phase systems (ATPS) responding to environmental stimuli have been widely studied in the purification of biologics. In this study, a thermo-responsive polymer PNE was copolymerized after optimization of monomer ratio. In addition, its lower critical solution temperature (LCST, 31 °C) and first recovery (99.43%) were determined. Then, PNE was used to form two recyclable ATPS with another thermo-responsive polymer PNDBN and a pH-responsive polymer PADB4.91, which were polymers already prepared in the lab. Meanwhile, the partition behavior of microbial transglutaminase (MTG) was explored using these two ATPS. The result showed that the PNE/PADB4.91 ATPS was superior to PNDBN/PNE ATPS owing to its faster phase formation and better partition performance. In order to optimize the partition behavior, several parameters were investigated based on PNE/PADB4.91 ATPS. In the ATPS constructed with 2.5% (w/v) PNE and 3.5% (w/v) PADB4.91, the maximal partition coefficient (1/KE) and enzymatic recovery (ERB) of MTG were 12.9 and 95.21% in the presence of 10 mM KCl when the temperature, pH, and the addition amount of MTG were 25 °C, 7.0, and 2 mg/mL, respectively.

8.
Chemistry ; 26(29): 6694-6702, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32227533

RESUMO

Hybridizing graphene and molecules possess a high potential for developing materials for new applications. However, new methods to characterize such hybrids must be developed. Herein, the wet-chemical non-covalent functionalization of graphene with cationic π-systems is presented and the interaction between graphene and the molecules is characterized in detail. A series of tricationic benzimidazolium salts with various steric demand and counterions was synthesized, characterized and used for the fabrication of graphene hybrids. Subsequently, the doping effects were studied. The molecules are adsorbed onto graphene and studied by Raman spectroscopy, XPS as well as ToF-SIMS. The charged π-systems show a p-doping effect on the underlying graphene. Consequently, the tricationic molecules are reduced through a partial electron transfer process from graphene, a process which is accompanied by the loss of counterions. DFT calculations support this hypothesis and the strong p-doping could be confirmed in fabricated monolayer graphene/hybrid FET devices. The results are the basis to develop sensor applications, which are based on analyte/molecule interactions and effects on doping.

9.
Angew Chem Int Ed Engl ; 59(32): 13657-13662, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32315109

RESUMO

The thermal decomposition of graphene oxide (GO) is a complex process at the atomic level and not fully understood. Here, a subclass of GO, oxo-functionalized graphene (oxo-G), was used to study its thermal disproportionation. We present the impact of annealing on the electronic properties of a monolayer oxo-G flake and correlated the chemical composition and topography corrugation by two-probe transport measurements, XPS, TEM, FTIR and STM. Surprisingly, we found that oxo-G, processed at 300 °C, displays C-C sp3 -patches and possibly C-O-C bonds, next to graphene domains and holes. It is striking that those C-O-C/C-C sp3 -separated sp2 -patches a few nanometers in diameter possess semiconducting properties with a band gap of about 0.4 eV. We propose that sp3 -patches confine conjugated sp2 -C atoms, which leads to the local semiconductor properties. Accordingly, graphene with sp3 -C in double layer areas is a potential class of semiconductors and a potential target for future chemical modifications.

10.
Chemistry ; 26(29): 6484-6489, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31851390

RESUMO

In recent years, graphene oxide has been considered as a soluble precursor of graphene for electronic applications. However, the performance lags behind that of graphene due to lattice defects. Here, the relation between the density of defects in the range of 0.2 % and 1.5 % and the transport properties is quantitatively studied. Therefore, the related flakes of monolayers of graphene were prepared from oxo-functionalized graphene (oxo-G). The morphologic structure of oxo-G was imaged by atomic force microscopy (AFM) and scanning tunneling microscopy (STM). Field-effect mobility values were determined to range between 0.3 cm2 V-1 s-1 and 33.2 cm2 V-1 s-1 , which were inversely proportional to the density of defects. These results provide the first quantitative description of the density of defects and transport properties, which plays an important role for potential applications.

12.
Colloids Surf B Biointerfaces ; 182: 110352, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306831

RESUMO

Psoriasis is a severe disfiguring skin disease affecting approximately 3% of people worldwide and negatively affecting their daily lives. The pathogenesis of psoriasis is complicated, and typical therapeutic strategies for psoriasis mainly focus on anti-inflammation. Considering the side effects, withdrawal rebound, high cost, and many other disadvantages of existing treatments, we developed a new topical therapeutic formulation consisting of niosomes loaded with celastrol, a triterpenoid extracted from Tripterygium. Celastrol niosomes were prepared by the thin film hydration method and probe sonication. The niosomes were composed of Span 20, Span 60, and cholesterol at a weight ratio of 3:1:1. The particle size of the niosomes was approximately 147 nm, with yield of up to 90%. Celastrol niosomes showed improved in vitro permeation ability compared to the raw drug. In our in vivo study, celastrol niosomes effectively alleviated erythema and scaling on the dorsal skin of psoriasis mouse models. Spleen weight and the levels of cytokines, including IL-22, IL-23, and IL-17, decreased after the treatment, indicating the high therapeutic potential of this formulation for psoriasis. In conclusion, encapsulation of celastrol by niosomes increased the water-solubility and permeation of celastrol into the skin, significantly improving its anti-psoriasis activity in mice.


Assuntos
Anti-Inflamatórios/farmacologia , Lipossomos/química , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Tripterygium/química , Triterpenos/farmacologia , Administração Cutânea , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/metabolismo , Biomarcadores/metabolismo , Colesterol/química , Modelos Animais de Doenças , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Feminino , Hexoses/química , Imiquimode/farmacologia , Indutores de Interferon/farmacologia , Interleucinas/antagonistas & inibidores , Interleucinas/imunologia , Interleucinas/metabolismo , Lipossomos/administração & dosagem , Lipossomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Psoríase/imunologia , Psoríase/metabolismo , Psoríase/patologia , Pele/imunologia , Pele/patologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Triterpenos/isolamento & purificação , Triterpenos/metabolismo
13.
Anesthesiology ; 131(1): 132-147, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31225809

RESUMO

BACKGROUND: As the meningeally derived, fibroblast-rich, mass-produced by intrathecal morphine infusion is not produced by all opiates, but reduced by mast cell stabilizers, the authors hypothesized a role for meningeal mast cell/fibroblast activation. Using the guinea pig, the authors asked: (1) Are intrathecal morphine masses blocked by opiate antagonism?; (2) Do opioid agonists not producing mast cell degranulation or fibroblast activation produce masses?; and (3) Do masses covary with Mas-related G protein-coupled receptor signaling thought to mediate mast cell degranulation? METHODS: In adult male guinea pigs (N = 66), lumbar intrathecal catheters connected to osmotic minipumps (14 days; 0.5 µl/h) were placed to deliver saline or equianalgesic concentrations of morphine sulfate (33 nmol/h), 2',6'-dimethyl tyrosine-(Tyr-D-Arg-Phe-Lys-NH2) (abbreviated as DMT-DALDA; 10 pmol/h; µ agonist) or PZM21 (27 nmol/h; biased µ agonist). A second pump delivered subcutaneous naltrexone (25 µg/h) in some animals. After 14 to 16 days, animals were anesthetized and perfusion-fixed. Drug effects on degranulation of human cultured mast cells, mouse embryonic fibroblast activation/migration/collagen formation, and Mas-related G protein-coupled receptor activation (PRESTO-Tango assays) were determined. RESULTS: Intrathecal infusion of morphine, DMT-DALDA or PZM21, but not saline, comparably increased thermal thresholds for 7 days. Spinal masses proximal to catheter tip, composed of fibroblast/collagen type I (median: interquartile range, 0 to 4 scale), were produced by morphine (2.3: 2.0 to 3.5) and morphine plus naltrexone (2.5: 1.4 to 3.1), but not vehicle (1.2: 1.1 to 1.5), DMT-DALDA (1.0: 0.6 to 1.3), or PZM21 (0.5: 0.4 to 0.8). Morphine in a naloxone-insensitive fashion, but not PZM21 or DMT-DALDA, resulted in mast cell degranulation and fibroblast proliferation/collagen formation. Morphine-induced fibroblast proliferation, as mast cell degranulation, is blocked by cromolyn. Mas-related G protein-coupled receptor activation was produced by morphine and TAN67 (∂-opioid agonist), but not by PZM21, TRV130 (mu biased ligand), or DMT-DALDA. CONCLUSIONS: Opiates that activate Mas-related G protein-coupled receptor will degranulate mast cells, activate fibroblasts, and result in intrathecal mass formation. Results suggest a mechanistically rational path forward to safer intrathecal opioid therapeutics.


Assuntos
Degranulação Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Morfina/farmacologia , Receptores Acoplados a Proteínas-G/fisiologia , Coluna Vertebral/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Animais , Cobaias , Humanos , Infusão Espinal , Masculino , Modelos Animais , Morfina/administração & dosagem , Transdução de Sinais/fisiologia
14.
Int J Mol Sci ; 20(10)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091692

RESUMO

Mast cells (MCs) play a significant role in the innate immune defense against bacterial infection through the release of cytokines and antimicrobial peptides. However, their antimicrobial function is still only partially described. We therefore hypothesized that MCs express additional antimicrobial peptides. In this study, we used FANTOM 5 transcriptome data to identify for the first time that MCs express lipocalin 2 (LCN2), a known inhibitor of bacterial growth. Using MCs derived from mice which were deficient in LCN2, we showed that this antimicrobial peptide is an important component of the MCs' antimicrobial activity against Escherichia coli (E. coli). Since sphingosine-1-phosphate receptors (S1PRs) on MCs are known to regulate their function during infections, we hypothesized that S1P could activate LCN2 production in MCs. Using an in vitro assay, we demonstrated that S1P enhances MCs antimicrobial peptide production and increases the capacity of MCs to directly kill S. aureus and E. coli via an LCN2 release. In conclusion, we showed that LCN2 is expressed by MCs and plays a role in their capacity to inhibit bacterial growth.


Assuntos
Lipocalina-2/metabolismo , Mastócitos/imunologia , Animais , Células Cultivadas , Escherichia coli/efeitos dos fármacos , Humanos , Imunidade Inata , Lipocalina-2/genética , Lipocalina-2/farmacologia , Lisofosfolipídeos/farmacologia , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Lisoesfingolipídeo/metabolismo , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Receptores de Esfingosina-1-Fosfato , Staphylococcus aureus/efeitos dos fármacos
15.
Cancer Manag Res ; 11: 2313-2320, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30962719

RESUMO

Background: There have been no reliable scientific studies examining whether the interval between induction chemotherapy (IC) and initiating radiotherapy is associated with poor outcomes of nasopharyngeal carcinoma (NPC). Patients and methods: In this retrospective study, we included a total of 239 local advanced NPC patients who underwent concurrent chemoradiotherapy and IC. Based on the interval between IC and intensity-modulated radiation therapy (IMRT), the patients were classified into three groups as follows: Group A (≤7 vs >7 days), Group B (≤14 vs >14 days), and Group C (≤ 21 vs >21 days). Univariate and multivariate regression analyses were performed to determine the prognostic factors of survival outcomes. The differences between the two groups were compared by the log-rank test. Results: The median IC-IMRT interval was 9 days (range, 1-76 days). The median follow-up time was 40 months (range, 4-58 months). The IC-IMRT interval including Group A, Group B, and Group C was not significantly associated with overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), or disease-free survival (DFS). Multivariate analysis showed that the tumor stage was the independent significant predictor for OS, DMFS, LRFS, and DFS. But it appears that there was a trend toward improvement in the outcome of ≤7 days group in OS from the Kaplan-Meier curves. Conclusion: It is also feasible to postpone radiotherapy for 1-3 weeks if patients were unable to receive treatment immediately due to chemotherapy complications such as bone marrow suppression. However, we suggest that patients should start IMRT as soon as possible after IC.

17.
J Invest Dermatol ; 139(8): 1743-1752.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30807768

RESUMO

Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator generated when a cell membrane or its components are damaged by various factors. S1P regulates diverse cell activities via S1P receptors (S1PRs). Keratinocytes express S1PR1-5. Although it is known that S1PRs control keratinocyte differentiation, apoptosis, and wound healing, S1PR functions in keratinocyte infections have not been fully elucidated. We propose that the S1P-S1PR axis in keratinocytes works as a biosensor for bacterial invasion. Indeed, in human impetigo infection, we found high epidermal expression of S1PR1 and S1PR2 in the skin. Furthermore, in normal human epidermal keratinocytes in vitro, treatment with Staphylococcus aureus bacterial supernatant not only induced S1P production but also increased the transcription of S1PR2, confirming our in vivo observation, as well as increased the levels of TNFA, IL36G, IL6, and IL8 mRNAs. However, direct treatment of normal human epidermal keratinocytes with S1P increased the expressions of IL36G, TNFA, and IL8, but not IL6. In both S1P- and S. aureus bacterial supernatant-treated normal human epidermal keratinocytes, S1PR1 knockdown reduced IL36G, TNFA, and IL8 transcription, and the S1PR2 antagonist JTE013 blocked the secretion of these cytokines. Overall, we have proven that during infections, keratinocytes communicate damage by using S1P release and tight control of S1PR1 and 2.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Impetigo/imunologia , Queratinócitos/imunologia , Lisofosfolipídeos/metabolismo , Pele/imunologia , Esfingosina/análogos & derivados , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Impetigo/microbiologia , Impetigo/patologia , Queratinócitos/metabolismo , Queratinócitos/microbiologia , Cultura Primária de Células , Pirazóis/farmacologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Pele/citologia , Pele/patologia , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , Receptores de Esfingosina-1-Fosfato/genética , Receptores de Esfingosina-1-Fosfato/metabolismo , Staphylococcus aureus/imunologia
18.
J Dermatol Sci ; 93(1): 58-64, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30658871

RESUMO

BACKGROUND: Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown. OBJECTIVES: To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions. METHODS: Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by ß-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections. RESULTS: Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers. CONCLUSIONS: These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Degranulação Celular/efeitos dos fármacos , Eritema/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Rosácea/tratamento farmacológico , Inibidores da Liberação da Acetilcolina , Animais , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/imunologia , Biópsia , Toxinas Botulínicas Tipo A/uso terapêutico , Degranulação Celular/imunologia , Células Cultivadas , Modelos Animais de Doenças , Eritema/imunologia , Eritema/patologia , Humanos , Injeções Intradérmicas , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de Células , Rosácea/imunologia , Rosácea/patologia , Pele/citologia , Pele/imunologia , Pele/patologia , p-Metoxi-N-metilfenetilamina/farmacologia
19.
Angew Chem Int Ed Engl ; 58(11): 3599-3603, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30570208

RESUMO

The development of versatile functionalization concepts for graphene is currently in the focus of research. Upon oxo-functionalization of graphite, the full surface of graphene becomes accessible for C-C bond formation to introduce out-of-plane functionality. Herein, we present the arylation of graphene with arylazocarboxylic tert-butyl esters, which generates aryl radicals after activation with an acid. Surprisingly, the degree of functionalization is related to the concentration of lattice vacancy defects in the graphene material. Consequently, graphene materials that are free from lattice defects are not reactive. The reaction can be applied to graphene dispersed in solvents and leads to bitopic functionalization as well as monotopic functionalization when the graphene is deposited on surfaces. As the arylazocarboxylic tert-butyl ester moiety can be attached to various molecules, the presented method paves the way to functional graphene derivatives, with the density of defects determining the degree of functionalization.

20.
Photodermatol Photoimmunol Photomed ; 34(6): 405-414, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29974533

RESUMO

BACKGROUND/PURPOSE: Skin commensal bacteria have been described to help orchestrate skin homeostasis, signaling through innate immunity pathways. This study for the first time aimed at studying the relationship between skin commensals and melanocytes after UVB exposure. METHODS: An in vitro UVB radiation model with normal human epidermal melanocytes (NHMs) and skin commensal bacteria supernatant from Staphylococcus epidermidis and Propionibacterium acnes was established. Melanocytes DNA damage, cyclobutane pyrimidine dimers (CPD), and cellular proliferation marker Ki-67 were measured by ELISA and immunofluorescence staining. Cell apoptosis was assessed by flow cytometry and PCR array and RT-qPCR. RESULTS: Normal human epidermal melanocytes are able to survive and proliferate while bearing DNA damage after UVB radiation. Skin commensal bacteria S. epidermidis and its by-product LTA promote melanocytes survival by inducing upregulation of TRAF1, CASP14, CASP5, and TP73. On the other hand, P. acnes can inhibit UVB-irradiated melanocytes survival by increasing apoptosis. CONCLUSION: Our studies show different aspects of commensal activity on melanocytes during irradiation. The possible balance achieved by the different skin commensal can influence NHM potential to become cancer cells.


Assuntos
Apoptose/efeitos da radiação , Dano ao DNA , Melanócitos , Propionibacterium acnes/metabolismo , Pele , Staphylococcus epidermidis/metabolismo , Raios Ultravioleta/efeitos adversos , Adulto , Sobrevivência Celular/efeitos da radiação , Feminino , Humanos , Masculino , Melanócitos/metabolismo , Melanócitos/microbiologia , Melanócitos/patologia , Pele/metabolismo , Pele/microbiologia , Pele/patologia
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