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1.
Front Immunol ; 15: 1441410, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234260

RESUMO

Mucosal melanoma (MM) poses a significant clinical challenge due to its aggressive nature and limited treatment options. In recent years, immunotherapy has emerged as a promising strategy for MM, with a particular focus on immune checkpoint inhibitors such as PD-1 and CTLA-4 inhibitors. These inhibitors have demonstrated substantial efficacy by harnessing the body's immune response against tumors. Moreover, adoptive cell transfer (ACT), anti-angiogenic therapy, and combination therapies have garnered attention for their potential in MM treatment. ACT involves modifying T cells to target melanoma cells, showing promising antitumor activity. Anti-angiogenic therapy aims to impede tumor growth by inhibiting angiogenesis, while combination therapies, including immune checkpoint inhibitors and targeted therapies, offer a multifaceted approach to overcome treatment resistance. This comprehensive review explores the advancements in immunotherapy for MM, highlighting the role of diverse therapeutic modalities in enhancing treatment outcomes and addressing the challenges posed by this aggressive malignancy.


Assuntos
Inibidores de Checkpoint Imunológico , Imunoterapia , Melanoma , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/terapia , Melanoma/imunologia , Melanoma/tratamento farmacológico , Imunoterapia/métodos , Animais , Resultado do Tratamento , Mucosa/imunologia , Terapia Combinada , Imunoterapia Adotiva/métodos
2.
Cancer Control ; 31: 10732748241283621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39275798

RESUMO

OBJECTIVES: Radiation-induced oropharyngeal injury is a dose-limiting toxicity in head and neck cancer patients. Delineation of the "oropharyngeal mucosa" and limiting its dose to spare the oropharynx was investigated. METHODS: In this retrospective study, computed tomography imaging from eight patients with previously untreated head and neck cancer was employed. An adaptive contouring brush within the planning software Monaco was used to create an air cavity within the oropharynx, and then the air cavity was expanded uniformly 2 mm to create the "oropharyngeal mucosa". Three plans were independently generated for each patient: Plan1: dose constraint was applied for the oropharynx; Plan2: dose constraints were applied for the oropharynx and the "oropharyngeal mucosa"; Plan3: dose constraint was applied for the "oropharyngeal mucosa". T-tests were used to compare the dosimetry variables. RESULTS: All plans had adequate target coverage and there were no statistical differences among plans. The mean dose, D30%, D45%, D50%, D85%, D90%, D95%, D100%, V25 Gy, V30 Gy, V35 Gy, V40 Gy, and V45 Gy of the oropharynx and "oropharyngeal mucosa" in Plan1 were significantly higher than those in Plan2 and Plan3. There were no significant differences between Plan2 and Plan3. There were no significant differences in the dosimetric parameters of any other organs at risk. CONCLUSION: Delineation of the "oropharyngeal mucosa" and limiting its dose should be an easy and effective method to spare the oropharynx.


Radiation-induced oropharyngeal injury is dose-limiting toxicity in head and neck cancer patients. Delineation of "oropharyngeal mucosa" and limiting its dose should be an easy and effective method to spare the oropharynx.


Assuntos
Neoplasias de Cabeça e Pescoço , Orofaringe , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Estudos Retrospectivos , Planejamento da Radioterapia Assistida por Computador/métodos , Orofaringe/efeitos da radiação , Orofaringe/diagnóstico por imagem , Masculino , Órgãos em Risco/efeitos da radiação , Feminino , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Mucosa/efeitos da radiação , Lesões por Radiação/prevenção & controle , Lesões por Radiação/etiologia
3.
Front Immunol ; 15: 1441793, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39301032

RESUMO

SIV and HIV-based envelope V1-deleted (ΔV1) vaccines, delivered systemically by the DNA/ALVAC/gp120 platform, decrease the risk of mucosal SIV or SHIV acquisition more effectively than V1-replete vaccines. Here we investigated the induction of mucosal and systemic memory-like NK cells as well as antigen-reactive ILC response by DNA/ALVAC/gp120-based vaccination and their role against SIV/SHIV infection. ΔV1 HIV vaccination elicited a higher level of mucosal TNF-α+ and CD107+ memory-like NK cells than V1-replete vaccination, suggesting immunogen dependence. Mucosal memory-like NK cells, systemic granzyme B+ memory NK cells, and vaccine-induced mucosal envelope antigen-reactive IL-17+ NKp44+ ILCs, IL-17+ ILC3s, and IL-13+ ILC2 subsets were linked to a lower risk of virus acquisition. Additionally, mucosal memory-like NK cells and mucosal env-reactive IFN-γ+ ILC1s and env- reactive IL-13+ ILC2 subsets correlated with viral load control. We further observed a positive correlation between post-vaccination systemic and mucosal memory-like NK cells, suggesting vaccination enhances the presence of these cells in both compartments. Mucosal and systemic memory-like NK cells positively correlated with V2-specific ADCC responses, a reproducible correlate of reduced risk of SIV/HIV infection. In contrast, an increased risk was associated with the level of mucosal PMA/Ionomycin-induced IFN-γ+ and CD107+ NKG2A-NKp44- ILCs. Plasma proteomic analyses demonstrated that suppression of mucosal memory-like NK cells was linked to the level of CCL-19, LT-α, TNFSF-12, and IL-15, suppression of systemic env-reactive granzyme B+ memory-like NK cells was associated with the level of OLR1, CCL-3, and OSM, and suppression of IL-17+ ILCs immunity was correlated with the level of IL-6 and CXCL-9. In contrast, FLT3 ligand was associated with promotion of protective mucosal env-reactive IL-17+ responses. These findings emphasize the importance of mucosal memory-like NK cell and envelope- reactive ILC responses for protection against mucosal SIV/SHIV acquisition.


Assuntos
Memória Imunológica , Células Matadoras Naturais , Vacinas contra a SAIDS , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Células Matadoras Naturais/imunologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vacinas contra a SAIDS/imunologia , Vacinas contra a SAIDS/administração & dosagem , Imunidade nas Mucosas , Macaca mulatta , Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinação , Humanos , Mucosa/imunologia
4.
BMC Cancer ; 24(1): 1154, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289617

RESUMO

OBJECTIVES: The aim of this study was to characterize the microbiome of multiple mucosal organs in cervical cancer (CC) patients. METHODS: We collected oral, gut, urinary tract, and vaginal samples from enrolled study participants, as well as tumor tissue from CC patients. The microbiota of different mucosal organs was identified by 16S rDNA sequencing and correlated with clinical-pathological characteristics of cervical cancer cases. RESULTS: Compared with controls, CC patients had reduced α-diversity of oral and gut microbiota (pOral_Sob < 0.001, pOral_Shannon = 0.049, pOral_Simpson = 0.013 pFecal_Sob = 0.030), although there was an opposite trend in the vaginal microbiota (pVaginal_Pielou = 0.028, pVaginal_Simpson = 0.006). There were also significant differences in the ß-diversity of the microbiota at each site between cases and controls (pOral = 0.002, pFecal = 0.037, pUrine = 0.001, pVaginal = 0.001). The uniformity of urine microbiota was lower in patients with cervical squamous cell carcinoma (pUrine = 0.036) and lymph node metastasis (pUrine_Sob = 0.027, pUrine_Pielou = 0.028, pUrine_Simpson = 0.021, pUrine_Shannon = 0.047). The composition of bacteria in urine also varied among patients with different ages (p = 0.002), tumor stages (p = 0.001) and lymph node metastasis (p = 0.002). In CC cases, Pseudomonas were significantly enriched in the oral, gut, and urinary tract samples. In addition, Gardnerella, Anaerococcus, and Prevotella were biomarkers of urinary tract microbiota; Abiotrophia and Lautropia were obviously enriched in the oral microbiota. The microbiota of tumor tissue correlated with other mucosal organs (except the gut), with a shift in the microflora between mucosal organs and tumors. CONCLUSIONS: Our study not only revealed differences in the composition and diversity of the vaginal and gut microflora between CC cases and controls, but also showed dysbiosis of the oral cavity and urethra in cervical cancer cases.


Assuntos
Microbiota , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/patologia , Pessoa de Meia-Idade , Microbiota/genética , Adulto , Vagina/microbiologia , Vagina/patologia , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Mucosa/microbiologia , Mucosa/patologia , Estudos de Casos e Controles , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Sistema Urinário/microbiologia , Sistema Urinário/patologia , Idoso , Biodiversidade , Boca/microbiologia
5.
Med Mycol ; 62(9)2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39237447

RESUMO

The immunopathogenesis of recurrent vulvovaginal candidiasis (RVVC) is poorly understood. Recently, it was reported that patients with RVVC present a decrease in both the fungicidal capacity of neutrophils and the proliferative capability of peripheral blood mononuclear cells in response to Candida albicans infection, suggesting an alteration in the innate and adaptive immune response. The aim of this study was to determine the in-situ expression, in the vaginal mucosa, of genes associated with the immune response, as well as the serum concentrations of dectin-1, mannose-binding lectin (MBL), and vitamin D in patients with RVVC. A study was carried out on 40 patients with a diagnosis of RVVC and 26 healthy women. Vaginal scrapings were obtained, and the expression of genes that encode cytokines and transcription factors specific for Th1, Th2, Th17, Treg, pro-inflammatory profiles, and enzymes related to oxidative/microbicidal mechanisms was evaluated by quantitiative polymerase chain reaction (qPCR). Additionally, serum levels of vitamin D and the soluble receptors dectin-1 and MBL were determined by enzyme-linked immunosorbent assay (ELISA). In patients with RVVC, a decreased expression of T-bet, RORγ-T, IL-1ß, and IL-17, and an increase in the expression of FOXP3, IL-4, IL-8, IL-10, and IL-18 were observed when compared to healthy women: moreover, decreased levels of MBL were also observed in these patients. These results confirm that patients with RVVC present in-situ alterations in both the specific and adaptive immune response against Candida spp., a fact that could be associated with the exaggerated vaginal inflammatory response.


The study concerns the immune response of women with recurrent vulvovaginal candidiasis; we observed an alteration in the expression of genes that participate in the control of infection, a fact that could be associated with the exaggerated vaginal inflammatory response observed in those patients.


Assuntos
Candidíase Vulvovaginal , Citocinas , Lectinas Tipo C , Vagina , Vitamina D , Humanos , Candidíase Vulvovaginal/imunologia , Candidíase Vulvovaginal/microbiologia , Feminino , Lectinas Tipo C/genética , Adulto , Citocinas/sangue , Vagina/microbiologia , Vagina/imunologia , Vitamina D/sangue , Adulto Jovem , Recidiva , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/genética , Mucosa/imunologia , Mucosa/microbiologia , Candida albicans/imunologia
6.
Biomacromolecules ; 25(9): 5968-5978, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39190052

RESUMO

Effective drug delivery to bacterially infected mucosa remains a challenge due to the combined obstacles of the mucosal barrier, pH variations, and high concentrations of glutathione. However, polysaccharide-based responsive nanogels (NGs) can take advantage of these conditions to deliver specific antimicrobials. We explored the critical features of pH- and redox-responsive NGs to increase drug penetration, residence time, and efficacy in the infected mucosa. We prepared multifunctional NGs using hydroxypropyl cellulose as a template for the cross-linking of methacrylic acid with N,N'-bis(acryloyl)cystamine (BAC) or N,N'-methylenebis(acrylamide) (BIS). Studies of NG-mucin binding and the antibacterial efficacy of doxycycline-loaded NGs revealed the interplay between the response to pH and redox clues. Specifically, higher BAC composition increased mucus binding and controlled release in reductive conditions, while higher BIS composition yielded NGs with higher doxycycline-mediated antibacterial efficacy against Staphylococcus aureus. The findings reveal the potential of multiresponsive NGs in effective antimicrobial delivery in infected mucosa.


Assuntos
Nanogéis , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Nanogéis/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Mucosa/metabolismo , Doxiciclina/farmacologia , Doxiciclina/química , Doxiciclina/administração & dosagem , Doxiciclina/farmacocinética , Celulose/química , Celulose/análogos & derivados , Polietilenoglicóis/química , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química , Humanos
7.
Int J Pediatr Otorhinolaryngol ; 184: 112079, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39173268

RESUMO

OBJECTIVE: In recent years, the clinical efficacy of medications for adenoid hypertrophy has been demonstrated. Topical nasal steroids have effects to shrink hypertrophic adenoids and improve symptoms of associated diseases. However, the mechanism which topical steroid administrations cause adenoid shrinkage remains unclear, herein, sensitivity for topical steroids in the mucosal epithelium of adenoids was evaluated histologically by comparing with tonsils. METHODS: Histological analysis was performed on adenoids and tonsils removed from 32 pediatric patients with adenoid hypertrophy. In hematoxylin-eosin-stained specimens, the morphology of the mucosal epithelium and eosinophil infiltration were evaluated. The expression of the glucocorticoid receptor (GR), interleukin (IL)-4, and IL-25 in the mucosal epithelium was evaluated, and the staining intensity was scored as 0 (none), 1 (weak), and 2 (strong). The number of eosinophils and expression scores of GR, IL-4, and IL-25 were statistically compared between adenoids and tonsils and analyzed correlations with adenoids sizes. RESULTS: Adenoids were covered with ciliated epithelium, and eosinophils in the mucosal epithelium and submucosal area was higher than tonsils (p < 0.05). GR expression in the most superficial layer of the mucosal epithelium was observed in adenoids, and the expression intensity score was higher than that in tonsils (p < 0.05). IL-4 and IL-25 were more widely expressed in the mucosal epithelium of adenoids than in tonsils, and their expression intensity scores were also higher than in tonsils (p < 0.05). A correlation was found between adenoid size and the intensity of IL-25 expression in the adenoid epithelium (p < 0.05). CONCLUSION: Eosinophilic inflammations in adenoids mucosal epithelium could be one of etiology of adenoid hypertrophy, and the GR and eosinophilic inflammation in the adenoids mucosal epithelium might be target of topical nasal steroids to shrink hypertrophic adenoids.


Assuntos
Tonsila Faríngea , Eosinófilos , Hipertrofia , Tonsila Palatina , Receptores de Glucocorticoides , Humanos , Tonsila Faríngea/patologia , Tonsila Faríngea/metabolismo , Receptores de Glucocorticoides/metabolismo , Masculino , Criança , Feminino , Eosinófilos/metabolismo , Pré-Escolar , Tonsila Palatina/patologia , Interleucina-17/metabolismo , Mucosa/patologia , Mucosa/metabolismo , Interleucina-4/metabolismo , Epitélio/patologia , Epitélio/metabolismo , Glucocorticoides , Citocinas/metabolismo , Adolescente
8.
Sci Rep ; 14(1): 18644, 2024 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-39128895

RESUMO

To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery (P = 0.031) and age (P < 0.001), both of which were negatively associated. And vaginal mucosa thickness demonstrated no significant correlation with body mass index (BMI) (P = 0.325), times of abortions (P = 0.511), times of gestation (P = 0.101), menstrual cycle (P = 0.533), or types of delivery (P = 0.056); epithelial thickness showed significant associations with age (P < 0.001) and types of delivery (P = 0.017), both of which were negative correlations. Moreover, BMI (P = 0.429), times of abortions (P = 0.764), delivery (P = 0.079), gestation (P = 0.475), and menstrual cycle (P = 0.950) were nonassociated with epithelial thickness; lamina propria thickness displayed a significant correlation only with age (P = 0.002), and there were no obvious correlations observed between lamina propria thickness and BMI (P = 0.374), times of abortion (P = 0.417), delivery (P = 0.053), gestation (P = 0.101), types of delivery (P = 0.132) and menstrual cycle (P = 0.495). Moreover, when the age segmentation was thresholded at 35 and 50 years, both epithelial thickness and vaginal mucosa thickness were significantly correlated with age (P < 0.05). Lamina propria thickness was associated with age when the age threshold was set at 35 years (P = 0.007), whereas it showed no strong link with age when the age threshold was 50 years (P = 0.072). This study has innovatively established percentile reference values for vaginal mucosa thickness based on histopathology, furnishing clinicians with objective evidence of variations in vaginal mucosal thickness to facilitate personalized medical decisions for patients. The findings demonstrated a strong link between vaginal mucosa thickness and age, with epithelium likely playing a predominant role, while the association with lamina propria appeared to be less significant. Further research involving a larger sample size is warranted to elucidate the potential relationship with the lamina propria.


Assuntos
Mucosa , Vagina , Humanos , Feminino , Vagina/patologia , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Mucosa/patologia , Adulto Jovem , Idoso , China , Fatores Etários , Adolescente , Índice de Massa Corporal , Epitélio/patologia
9.
Pediatr Surg Int ; 40(1): 215, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39102122

RESUMO

PURPOSE: We investigated the relationship between bile amylase (AMY) levels and biliary epithelial changes in pancreaticobiliary maljunction (PBM), a congenital anomaly characterized by pancreaticobiliary reflux due to duct fusion outside the duodenal wall. METHODS: We enrolled 43 children with congenital biliary dilatation (CBD) of Todani types Ia, Ic, and IVa who underwent surgery at the Hokkaido Medical Center for Child Health and Rehabilitation between November 2007 and June 2023. We defined total AMY exposure in bile as bile AMY levels multiplied by the patient's age (months), representing amount of estimated AMY exposure until surgery. We retrospectively investigated the relationships between bile AMY levels and clinicopathological findings. RESULTS: All patients exhibited hyperplasia in the gallbladder and bile duct epithelium, with dysplasia observed in 13 cases, but no carcinoma. Exposure to bile AMY ≥ 662,400 IU/L × months was an independent risk factor for dysplasia. CONCLUSION: The amount of estimated AMY exposure in bile rather than AMY levels in the bile is an independent risk factor for dysplasia in the biliary mucosa.


Assuntos
Amilases , Vesícula Biliar , Humanos , Masculino , Feminino , Vesícula Biliar/patologia , Vesícula Biliar/anormalidades , Estudos Retrospectivos , Lactente , Amilases/metabolismo , Dilatação Patológica , Pré-Escolar , Bile/metabolismo , Má Junção Pancreaticobiliar , Mucosa/patologia , Criança , Ductos Biliares/anormalidades , Ductos Biliares/patologia , Recém-Nascido , Fatores de Risco
10.
J Otolaryngol Head Neck Surg ; 53: 19160216241267724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104022

RESUMO

BACKGROUND: This study aimed to explore the impacts of different middle-ear mucosal conditions on the outcomes of type I tympanoplasty. METHODS: A retrospective analysis of 164 patients with chronic otitis media was carried out. The patients were divided into 4 groups according to their mucosal condition. Preoperative hearing levels and air-bone gap (ABG) before and after surgery were compared via the Kruskal‒Wallis H test. The chi-squared test and Fisher's exact test were used to assess the postoperative complications and impact factors of functional success. RESULTS: Preoperatively, neither the air conduction nor bone conduction values differed significantly among groups with different mucosal conditions. All of the ABG closed dramatically after type I tympanoplasty (P < .05) regardless of the mucosal conditions. The functional success rates were lower when the intratympanic mucosa was moderately or severely edematous compared with mildly edematous or normal (P < .05). The disease course, perforation site, and perforation size, as well as the status of the opposite ear, were not related to the auditory functional outcome. The differences in postoperative reotorrhea and reperforation among the 4 groups were not statistically significant. CONCLUSION: Preoperative hearing levels were not affected by middle-ear mucosal conditions. The functional success rate was influenced by mucosal conditions, but hearing levels were significantly enhanced after surgical intervention regardless of the mucosal status. Postoperative complications were not related to the mucosal conditions. Thus, type I tympanoplasty is adoptable for mucosal abnormalities when pharmacotherapy cannot result in a healthy tympanum.


Assuntos
Otite Média , Timpanoplastia , Humanos , Timpanoplastia/métodos , Estudos Retrospectivos , Masculino , Feminino , Adulto , Otite Média/cirurgia , Pessoa de Meia-Idade , Resultado do Tratamento , Orelha Média/cirurgia , Doença Crônica , Condução Óssea , Mucosa/cirurgia , Adulto Jovem , Adolescente , Idoso , Perfuração da Membrana Timpânica/cirurgia , Perfuração da Membrana Timpânica/fisiopatologia , Complicações Pós-Operatórias
11.
Glycobiology ; 34(9)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39107988

RESUMO

Infections pose a challenge for the fast growing aquaculture sector. Glycosphingolipids are cell membrane components that pathogens utilize for attachment to the host to initiate infection. Here, we characterized rainbow trout glycosphingolipids from five mucosal tissues using mass spectrometry and nuclear magnetic resonance and investigated binding of radiolabeled Aeromonas salmonicida to the glycosphingolipids on thin-layer chromatograms. 12 neutral and 14 acidic glycosphingolipids were identified. The glycosphingolipids isolated from the stomach and intestine were mainly neutral, whereas glycosphingolipids isolated from the skin, gills and pyloric caeca were largely acidic. Many of the acidic structures were poly-sialylated with shorter glycan structures in the skin compared to the other tissues. The sialic acids found were Neu5Ac and Neu5Gc. Most of the glycosphingolipids had isoglobo and ganglio core chains, or a combination of these. The epitopes on the rainbow trout glycosphingolipid glycans differed between epithelial sites leading to differences in pathogen binding. A major terminal epitope was fucose, that occurred attached to GalNAc in a α1-3 linkage but also in the form of HexNAc-(Fuc-)HexNAc-R. A. salmonicida were shown to bind to neutral glycosphingolipids from the gill and intestine. This study is the first to do a comprehensive investigation of the rainbow trout glycosphingolipids and analyze binding of A. salmonicida to glycosphingolipids. The structural information paves the way for identification of ways of interfering in pathogen colonization processes to protect against infections in aquaculture and contributes towards understanding A. salmonicida infection mechanisms.


Assuntos
Aeromonas salmonicida , Glicoesfingolipídeos , Oncorhynchus mykiss , Animais , Oncorhynchus mykiss/microbiologia , Oncorhynchus mykiss/metabolismo , Aeromonas salmonicida/metabolismo , Aeromonas salmonicida/química , Glicoesfingolipídeos/metabolismo , Glicoesfingolipídeos/química , Mucosa/microbiologia , Mucosa/metabolismo
12.
PLoS One ; 19(8): e0308609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39121037

RESUMO

Current prophylactic and disease control measures in aquaculture highlight the need of alternative strategies to prevent disease and reduce antibiotic use. Mucus covered mucosal surfaces are the first barriers pathogens encounter. Mucus, which is mainly composed of highly glycosylated mucins, has the potential to contribute to disease prevention if we can strengthen this barrier. Therefore, aim of this study was to develop and characterize fish in vitro mucosal surface models based on commercially available cell lines that are functionally relevant for studies on mucin regulation and host-pathogen interactions. The rainbow trout (Oncorhynchus mykiss) gill epithelial cell line RTgill-W1 and the embryonic cell line from Chinook salmon (Oncorhynchus tshawytscha) CHSE-214 were grown on polycarbonate membrane inserts and chemically treated to differentiate the cells into mucus producing cells. RTGill-W1 and CHSE-214 formed an adherent layer at two weeks post-confluence, which further responded to treatment with the γ-secretase inhibitor DAPT and prolonged culture by increasing the mucin production. Mucins were metabolically labelled with N-azidoacetylgalactosamine 6 h post addition to the in vitro membranes. The level of incorporated label was relatively similar between membranes based on RTgill-W1, while larger interindividual variation was observed among the CHSE in vitro membranes. Furthermore, O-glycomics of RTgill-W1 cell lysates identified three sialylated O-glycans, namely Galß1-3(NeuAcα2-6)GalNAcol, NeuAcα-Galß1-3GalNAcol and NeuAcα-Galß1-3(NeuAcα2-6)GalNAcol, resembling the glycosylation present in rainbow trout gill mucin. These glycans were also present in CHSE-214. Additionally, we demonstrated binding of the fish pathogen A. salmonicida to RTgill-W1 and CHSE-214 cell lysates. Thus, these models have similarities to in vivo mucosal surfaces and can be used to investigate the effect of pathogens and modulatory components on mucin production.


Assuntos
Interações Hospedeiro-Patógeno , Mucinas , Oncorhynchus mykiss , Animais , Mucinas/metabolismo , Oncorhynchus mykiss/metabolismo , Linhagem Celular , Mucosa/metabolismo , Salmão/metabolismo , Brânquias/metabolismo , Células Epiteliais/metabolismo , Muco/metabolismo
15.
J Drugs Dermatol ; 23(8): 683-685, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39093653

RESUMO

Melanomas affecting acral and mucosal sites have distinct features and are associated with poorer prognosis. Patients of color may be disproportionately affected. Herein we discuss six ethnically diverse cases of acral and mucosal melanoma (AMM). More data on clinical, genetic, and environmental features of AMM are needed, but thorough physical examination can reduce the burden of disease now. J Drugs Dermatol. 2024;23(8):683-685. doi:10.36849/JDD.8311.


Assuntos
Melanoma , Mucosa , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Melanoma/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Mucosa/patologia , Idoso , Adulto
16.
Curr Opin Immunol ; 89: 102456, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39173414

RESUMO

The unconventional type I interferons IFNε and IFNω and type III interferon IFNλ are gradually emerging as tissue-specific cytokines in defence of mucosal tissues. This review provides an overview of the distinct features and functions that define these IFNs as protective factors in the respiratory, gastrointestinal and reproductive tracts, highlighting their immunoregulatory roles against pathogens while maintaining tolerance against commensal microbes. In particular, we discuss recent advances in our understanding of the constitutively expressed IFNε and its role in protecting against mucosal infections, inflammation and cancers. We identify an emerging theme for this unique cytokine as a key contributor to the 'first line of defence' against pathogens and maintenance of mucosal tissue homeostasis, primarily through its regulation of immune cell populations.


Assuntos
Interferons , Mucosa , Humanos , Animais , Mucosa/imunologia , Mucosa/metabolismo , Interferons/metabolismo , Interferons/imunologia , Imunidade nas Mucosas , Interferon Tipo I/metabolismo , Interferon Tipo I/imunologia
17.
Int J Biol Macromol ; 277(Pt 4): 134531, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116977

RESUMO

Recently, transmucosal drug delivery systems (TDDSs) have been extensively studied because they protect therapeutic agents from degradation; improve drug residence time at the mucosal membranes; and facilitate sustained drug release for a prolonged period. Chitosan is a well-researched polymeric excipient due to its biocompatibility, non-toxicity, biodegradability, mucoadhesive, antimicrobial, and low immunogenicity. Its limited mucoadhesiveness in the physiological environment necessitated its chemical modification. This review highlights the recent advances in the chemical modification of chitosan with various chemical groups to generate various functionalized chitosan derivatives, such as thiolated, acrylated, methacrylated, boronated, catechol, and maleimide-functionalized chitosans with superior mucoadhesive capabilities compared to the parent chitosan. Moreover, it presents the different prepared dosage forms, such as tablets, hydrogels, films, micro/nanoparticles, and liposomes/niosomes for drug administration within various mucosal routes including oral, buccal, nasal, ocular, colonic, intravesical, and vaginal routes. The reported data from preclinical studies of these pharmaceutical formulations have revealed the controlled and target-specific delivery of therapeutics because of their formation of covalent bonds with thiol groups on the mucosal surface. All functionalized chitosan derivatives exhibited long drug residence time on mucosal surfaces and sustainable drug release with excellent cellular permeability, drug efficacy, and biocompatibility. These promising data could be translated from the research laboratories to the clinics with consistent and intensive research effort.


Assuntos
Quitosana , Sistemas de Liberação de Medicamentos , Mucosa , Quitosana/química , Humanos , Mucosa/metabolismo , Animais , Portadores de Fármacos/química , Liberação Controlada de Fármacos
19.
Sci Rep ; 14(1): 15035, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951580

RESUMO

Intermittent catheterization (IC) utilizing conventional eyelets catheters (CECs) for bladder drainage has long been the standard of care. However, when the tissue of the lower urinary tract comes in close proximity to the eyelets, mucosal suction often occurs, resulting in microtrauma. This study investigates the impact of replacing conventional eyelets with a drainage zone featuring multiple micro-holes, distributing pressure over a larger area. Lower pressures limit the suction of surrounding tissue into these micro-holes, significantly reducing tissue microtrauma. Using an ex vivo model replicating the intra-abdominal pressure conditions of the bladder, the intra-catheter pressure was measured during drainage. When mucosal suction occurred, intra-catheter images were recorded. Subsequently affected tissue samples were investigated histologically. The negative pressure peaks caused by mucosal suction were found to be very high for the CECs, leading to exfoliation of the bladder urothelium and breakage of the urothelial barrier. However, a micro-hole zone catheter (MHZC) with a multi-eyelet drainage zone showed significantly lower pressure peaks, with over 4 times lower peak intensity, thus inducing far less extensive microtraumas. Limiting or even eliminating mucosal suction and resulting tissue microtrauma may contribute to safer catheterizations in vivo and increased patient comfort and compliance.


Assuntos
Bexiga Urinária , Cateteres Urinários , Cateteres Urinários/efeitos adversos , Animais , Humanos , Pressão , Mucosa/lesões , Suínos , Sistema Urinário , Cateterismo Uretral Intermitente , Sucção , Urotélio , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/métodos , Cateterismo Urinário/instrumentação
20.
BMC Cancer ; 24(1): 886, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044133

RESUMO

BACKGROUND: Mucosa melanoma is a rare condition with aggressive behavior and a less favorable prognosis compared to cutaneous melanoma. The objective of this study was to estimate the overall survival and clinical outcomes of patients diagnosed with mucosal melanoma in a Colombian hospital. METHODS: A retrospective cohort study was conducted at Fundación Valle del Lili, a single center located in Cali, Colombia. Patients aged ≥ 18 years, both sexes, diagnosed with mucosal melanoma by histopathology study were included between 2010-2019. Patients who received extra-institutional treatment or whose vital status was unknown during follow-up were excluded. Demographic, clinical and laboratory data were obtained from medical records and laboratory and pathology databases. A descriptive analysis was performed. Survival analysis was conducted using the Kaplan-Meier method. RESULTS: A total of 23 patients were included. Median age was 63 years old (IQR: 57-68) and 52.2% were woman. Clinical stage was 34.8% early, 26.1% locally advanced and 39.1% metastatic. The main primary locations were nasopharynx (30.4%), genitals (26.1%), rectum (21.7%), oral cavity (13%) and paranasal sinuses (8.7%). The majority received surgery (30.4%) and immunotherapy (26.1%) as first line treatment. Overall survival at one year was 80.8%, at three years 44.3%, and at five years 36.9%. CONCLUSION: Mucosal melanoma is a rare, aggressive disease with adverse oncological outcomes due to late diagnosis and limited treatment options. This study provides real-world data in a single-center of Colombia.


Assuntos
Melanoma , Mucosa , Humanos , Melanoma/mortalidade , Melanoma/patologia , Melanoma/terapia , Melanoma/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Colômbia/epidemiologia , Idoso , Mucosa/patologia , Prognóstico , Taxa de Sobrevida , Estadiamento de Neoplasias , Estimativa de Kaplan-Meier
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