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1.
Clin Cosmet Investig Dermatol ; 17: 1505-1517, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952411

RESUMEN

Introduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings. Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay. Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent. Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.

2.
Int Immunopharmacol ; 137: 112460, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908082

RESUMEN

There is growing interest in evaluating the safety and therapeutic potential of existing treatments such as tocilizumab (TCZ), an IL-6 receptor antagonist used to treat inflammatory diseases. However, there have been reports of increased inflammation in patients with HTLV-1 uveitis after TCZ treatment, and its ocular safety in the HTLV-1 infected state remains unknown. This study focused on assessing the impact of TCZ on HTLV-1-infected ocular cells using an in vitro model in which retinal pigment epithelial cells were cocultured with irradiated HTLV-1-infected T-cell lines. TCZ did not significantly affect cellular viability, inflammatory markers, or HTLV-1 proviral loads at various concentrations (25/50/100 µg/ml), indicating no increased risk of HTLV-1 viral infection and no exacerbation of the inflammatory aspects of HTLV-1 infection in the ocular cells. These promising results support the potential of TCZ as a safe treatment option for HTLV-1-infected patients, particularly those with eye infections.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Humanos , Infecciones por HTLV-I/tratamiento farmacológico , Infecciones por HTLV-I/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/efectos adversos , Línea Celular , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/virología , Epitelio Pigmentado de la Retina/inmunología , Técnicas de Cocultivo , Supervivencia Celular/efectos de los fármacos , Carga Viral/efectos de los fármacos
3.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38731972

RESUMEN

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.


Asunto(s)
Vacunación , Humanos , Vacunación/efectos adversos , Vacunación/métodos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Ojo/inmunología , SARS-CoV-2/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Vacunas/efectos adversos , Vacunas/inmunología , Animales , Oftalmopatías/inmunología , Oftalmopatías/prevención & control
4.
Int J Mol Sci ; 25(6)2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38542203

RESUMEN

Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5-10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.


Asunto(s)
Glaucoma , Virus Linfotrópico T Tipo 1 Humano , Isoquinolinas , Sulfonamidas , Uveítis , Adulto , Humanos , FN-kappa B , Glaucoma/tratamiento farmacológico , Glaucoma/etiología , Citocinas/uso terapéutico , Interleucina-6 , Quinasas Asociadas a rho
5.
Pathogens ; 12(12)2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38133300

RESUMEN

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32-73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability.

6.
Vaccines (Basel) ; 11(10)2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37897028

RESUMEN

The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt-Koyanagi-Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles-mumps-rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine.

7.
Int Immunopharmacol ; 123: 110782, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37573688

RESUMEN

BACKGROUND: Inflammasome has been reported to play an important role in the pathogenesis and progression of hematologic malignancies. As one of the backbone drugs for treating acute lymphoblastic leukemia (ALL), the anti-inflammatory effect of mercaptopurine (6-MP) and the impact of gut microbiome changes caused by 6-MP on anti-inflammasome remain unclear. OBJECTIVE: We aimed to explore the association between 6-MP therapeutic effects and microbiome-involved inflammatory responses in ALL mice models. STUDY DESIGN: ALL murine model was built by i.v. injecting murine L1210 cells into DBA/2 mice (model group). Two weeks after cell injections, 6-MP was orally administrated for 14 days (6-MP group). Fecal samples of mice were collected at different time points. Cecum short-chain fatty acids (SCFAs) concentrations were determined by LC-MS/MS method. Serum cytokines were measured using a cytometric bead array. Gut microbiota composition in mice was explored using 16S rRNA gene sequencing. RESULTS: The anti-tumor effect of 6-MP was proved in ALL mice models. The levels of pro-inflammatory factors IL-6 and TNFα significantly decreased after the administration of 6-MP. Cecum contents' acetate, propionate, and butyrate levels were negatively correlated with IL-6 (correlation coefficient: acetate, -0.24; propionate, -0.26; butyrate, -0.17) and TNFα (correlation coefficient: acetate, -0.45; propionate, -0.42; butyrate, -0.31) changes. Relative abundance changes of f_Lachnospiraceae.g_ASF356 and f_Peptococcaceae.g_uncultured were in accordance with the changes of butyrate levels and opposite to the changes of pro-inflammatory levels. CONCLUSION: The anti-inflammatory response of 6-MP influenced by intestinal microbiota and its metabolites SCFAs, especially butyrate, played an essential role in improving ALL progression.


Asunto(s)
Microbiota , Leucemia-Linfoma Linfoblástico de Células Precursoras , Ratones , Animales , Propionatos , Factor de Necrosis Tumoral alfa , Mercaptopurina/uso terapéutico , Interleucina-6 , ARN Ribosómico 16S/genética , Cromatografía Liquida , Ratones Endogámicos DBA , Espectrometría de Masas en Tándem , Ácidos Grasos Volátiles/metabolismo , Butiratos , Acetatos , Antiinflamatorios/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico
8.
Int J Nanomedicine ; 18: 79-94, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36636639

RESUMEN

Background: Nanomedicines have significant advantages in enhancing the oral bioavailability of drugs, but a deeper understanding of the underlying mechanisms remains to be interpreted. Hence, the present study aims to explain the uptake and trafficking mechanism for 6-MP nanomedicines we previously constructed. Methods: 6-MP loaded poly(lactide-co-glycolide) (PLGA) nanomedicines (6-MPNs) were prepared by the multiple emulsion method. The transcytosis mechanism of 6-MPNs was investigated in Caco-2 cells, Caco-2 monolayers, follicle associated epithelium (FAE) monolayers and rats, including transmembrane pathway, intracellular trafficking, paracellular transport and the involvement of transporter. Results: Pharmacokinetics in rats showed that the area under the curve (AUC) of 6-MP in the 6-MPNs group (147.3 ± 42.89 µg/L·h) was significantly higher than that in the 6-MP suspensions (6-MPCs) group (70.31 ± 18.24 µg/L·h). The uptake of 6-MPNs in Caco-2 cells was time-, concentration- and energy-dependent. The endocytosis of intact 6-MPNs was mediated mainly through caveolae/lipid raft, caveolin and micropinocytosis. The intracellular trafficking of 6-MPNs was affected by endoplasmic reticulum (ER)-Golgi complexes, late endosome-lysosome and microtubules. The multidrug resistance associated protein 4 (MRP4) transporter-mediated transport of free 6-MP played a vital role on the transmembrane of 6-MPNs. The trafficking of 6-MPNs from the apical (AP) side to the basolateral (BL) side in Caco-2 monolayers was obviously improved. Besides, 6-MPNs affected the distribution and expression of zona occludens-1 (ZO-1). The transport of 6-MPNs in FAE monolayers was concentration- and energy-dependent, while reaching saturation over time. 6-MPNs improved the absorption of the intestinal Peyer's patches (PPs) in rats. Conclusion: 6-MPNs improve the oral bioavailability through multiple pathways, including active transport, paracellular transport, lymphatic delivery and MRP4 transporter. The findings of current study may shed light on the cellular uptake and transcellular trafficking mechanism of oral nanomedicines.


Asunto(s)
Mercaptopurina , Nanopartículas , Humanos , Ratas , Animales , Células CACO-2 , Disponibilidad Biológica , Nanomedicina , Transporte Biológico , Proteínas de Transporte de Membrana , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo
10.
Asia Pac Psychiatry ; 15(1): e12523, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36596718

RESUMEN

INTRODUCTION: This study aimed to investigate the prevalence of depression and anxiety, and associated factors, among Chinese children and adolescents aged 8-18 years who attend primary or high school. METHODS: A total of 23 005 primary and high school students were recruited from February to December, 2019 for this cross-sectional study. The questionnaire included demographic information, questions assessing suicidality, resilience, depression (Center for Epidemiological Studies Depression Scale for Children), and anxiety (Screen for Child Anxiety Related Disorders). Binary logistic regression was used to analyze the independent correlates of depression and anxiety. RESULTS: Overall, 13.06% of participants experienced depressive symptoms, 22.34% experienced anxiety symptoms, 26.34% experienced transient suicidal ideation, 2.23% had serious suicidal ideation, and 1.46% had a history of suicide attempts. Anxiety (odds ratio [OR], 4.935; 95% confidence interval [CI][4.442-5.485]), suicidality (OR, 2.671; 95% CI[2.203-3.237]), skipping breakfast (OR, 1.920; 95% CI[1.348-2.736]), sleep duration (OR, 0.470; 95% CI[0.398-0.556]) and self-expectations (OR, 1.924; 95% CI[1.550-2.389]) were associated with depression (all p < .05). Depression (OR, 4.424; 95% CI[3.983-4.914]), female sex (OR, 1.903; 95% CI[1.759-2.060]), school-based traumatic experience(s) (OR, 1.905; 95% CI[1.747-2.077]), relationships with teachers (OR, 1.575; 95% CI[1.103-2.249]), and suicidality (OR, 1.467; 95% CI[1.218-1.766]) were associated with anxiety symptoms (all p < .05). DISCUSSION: Depression and anxiety are common among school-age children and adolescents in China. Childhood school- and family-based traumatic experience(s), female sex, and lifestyle factors (eating breakfast, sleep duration, exercising, and Internet use) are significantly associated with mental health among children and adolescents. Developing interventions targeting these factors to protect students from depression and anxiety are needed.


Asunto(s)
Depresión , Pueblos del Este de Asia , Adolescente , Niño , Humanos , Femenino , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , Prevalencia , Factores de Riesgo , Ansiedad/epidemiología , Ansiedad/psicología , Ideación Suicida , Estudiantes/psicología
11.
BMC Cancer ; 21(1): 409, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33858374

RESUMEN

BACKGROUND: Carnitine palmitoyl transferase 1A (CPT1A), the key regulator of fatty acid oxidation, contributes to tumor metastasis and therapeutic resistance. We aimed to identify its clinical significance as a biomarker for the diagnosis and prediction of breast cancer. METHODS: Western blot, ELISA and in silico analysis were used to confirm CPT1A levels in breast cancer cell lines, cell culture medium and breast cancer tissues. Four hundred thirty breast cancer patients, 200 patients with benign breast disease, and 400 healthy controls were enrolled and randomly divided into a training set and a test set with a 7:3 ratio. Training set was used to build diagnostic models and 10-fold cross validation was used to demonstrate the performance of the models. Then test set was aimed to validate the effectiveness of the diagnostic models. ELISA was conducted to detect individual serum CPT1A levels. Receiver operating characteristic (ROC) curves were generated, and binary logistic regression analyses were performed to evaluate the effectiveness of CPT1A as a biomarker in breast cancer diagnosis. CPT1A levels between post-operative and pre-operative samples were also compared. RESULTS: CPT1A was overexpressed in breast cancer tissues, cell lines and cell culture medium. Serum CPT1A levels were higher in breast cancer patients than in controls and were significantly associated with metastasis, TNM stage, histological grading and molecular subtype. CPT1A levels were decreased in post-operative samples compared with paired pre-operative samples. Moreover, CPT1A exhibited a higher efficacy in differentiating breast cancer patients from healthy controls (training set: area under the curve, AUC, 0.892, 95% CI, 0.872-0.920; test set, AUC, 0.904, 95% CI, 0.869-0.939) than did CA15-3, CEA, or CA125. CONCLUSION: CPT1A is overexpressed in breast cancer and can be secreted out of breast cancer cell. Serum CPT1A is positively associated with breast cancer progression and could serve as an indicator for disease monitoring. Serum CPT1A displayed a remarkably high diagnostic efficiency for breast cancer and could be a novel biomarker for the diagnosis of breast cancer.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/enzimología , Carnitina O-Palmitoiltransferasa/metabolismo , Adulto , Anciano , Enfermedades de la Mama/diagnóstico , Enfermedades de la Mama/enzimología , Neoplasias de la Mama/mortalidad , Carnitina O-Palmitoiltransferasa/sangre , Estudios de Casos y Controles , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Curva ROC , Reproducibilidad de los Resultados
12.
J Invest Dermatol ; 141(9): 2141-2150, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33741391

RESUMEN

In skin lesions caused by pemphigus, a group of life-threatening autoimmune bullous diseases, an over-representation of CD4+ tissue-resident memory T (TRM) cells was found. We sought to investigate the contributions of CD4+ TRM cells to the severity and refractoriness of pemphigus and their role in local immunological pathogenesis. Our data showed that CD4+ TRM cells accumulated significantly in pemphigus skin lesions. These CD4+ TRM cells expressed a specific set of T follicular helper cell‒related costimulatory molecules. We also found that CD4+ TRM cells remaining in the lesions produced IL-17A and IL-21. In vitro, CD4+ TRM cells exhibited strong support and assistance to autoantibody production. Through transcriptomic sequencing and bioinformatics analysis, we identified that the transcription factor IRF4 was responsible for IL-21 overexpression and autoantibody production. Our results showed that T follicular helper-like CD4+ TRM cells in pemphigus lesions promoted local autoantibody production, resulting in the formation and recurrence of lesions, which supports targeting this cell subset in pemphigus treatment. IRF4 might serve as a potential therapeutic target.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Centro Germinal/inmunología , Pénfigo/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Anciano , Anciano de 80 o más Años , Células Cultivadas , Femenino , Perfilación de la Expresión Génica , Humanos , Memoria Inmunológica , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/metabolismo , Interleucina-17/metabolismo , Interleucinas/metabolismo , Masculino , Persona de Mediana Edad , Fenotipo
13.
Int J Nanomedicine ; 16: 1127-1141, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603372

RESUMEN

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. It requires a long and rigorous course of chemotherapy treatments. 6-Mercaptopurine (6-MP) is one of the primary drugs used in chemotherapy. Unfortunately, its efficacy has been limited due to its insolubility, poor bioavailability and serious adverse effects. To overcome these drawbacks, we constructed 6-mercaptopurine (6-MP)-loaded nanomedicines (6-MPNs) with biodegradable poly(lactide-co-glycolide) (PLGA) to enhance the anticancer efficacy of 6-MP. METHODS: We prepared the 6-MPNs using a double-emulsion solvent evaporation method, characterizing them for the physicochemical properties. We then investigated the plasma, intestinal region and other organs in Sprague Dawley (SD) rats for pharmacokinetics. Additionally, we evaluated its anticancer efficacy in vitro on the human T leukemia cell line Jurkat and in vivo on the ALL model mice. RESULTS: The 6-MPNs were spherical in shape with uniform particle size and high encapsulation efficiency. The in vitro release profile showed that 6-MPNs exhibited a burst release that a sustained release phase then followed. The apoptosis assay demonstrated that 6-MPNs could improve the in vitro cytotoxicity in Jurkat cells. Pharmacokinetics profiles revealed that 6-MPNs had improved oral bioavailability. Tissue distribution experiments indicated that 6-MPNs increased the duodenum absorption of 6-MP, at the same time having a low accumulation of the toxic metabolites of 6-MP. The in vivo pharmacodynamics study revealed that 6-MPNs could prolong the survival time of the ALL model mice. The prepared 6-MPNs, therefore, have superior properties in terms of anticancer efficacy against ALL with reduced systemic toxicity. CONCLUSION: Our nanomedicines provide a promising delivery strategy for 6-MP; they offer a simple preparation method and high significance for clinical translation.


Asunto(s)
Mercaptopurina/química , Mercaptopurina/farmacocinética , Nanomedicina , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Administración Oral , Animales , Apoptosis , Proliferación Celular , Femenino , Humanos , Mercaptopurina/administración & dosificación , Ratones , Ratones Endogámicos NOD , Ratones SCID , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
14.
J Control Release ; 324: 341-353, 2020 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-32422212

RESUMEN

Chemotherapy post cancer surgery has important clinical significance for reducing the chance of recurrent-metastasis. However, postoperative chemotherapy efficacy is hampered by poor targeting capability and dose-limiting toxicity of chemo-drugs. Herein, we report a bio-mimetic platelet membrane-cloaked paclitaxel nanocrystal system (PPNCs), which consists of spherical paclitaxel nanocrystals (PNCs) as a high-dose drug core, polyethylene glycol-conjugated paclitaxel (PEG-PTX) as an amphiphilic molecule to adjust the surface hydrophilicity of PNCs and the shell of platelet membrane that can target surgical coagulation site. The in vitro characterization of PPNCs exhibited uniform particle size distribution, high drug loading, and good stability, which are crucial for effective drug delivery. At cell levels, PPNCs showed greater cellular uptake and higher cytotoxicity in 4T1 breast cancer cells than bare PNCs. In vivo, the nanoparticles could deliver high-dose chemo-drugs and target the coagulation site caused by surgery or vascular disrupting agents, resulting in enhanced anti-tumor efficacy and reduced systemic toxicities. In general, the PPNCs system can be served as a promising and efficient drug delivery system for postoperative chemotherapy.


Asunto(s)
Antineoplásicos , Nanopartículas , Línea Celular Tumoral , Paclitaxel , Tamaño de la Partícula , Polietilenglicoles
15.
JAAD Case Rep ; 6(3): 192-194, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32149175
16.
Microbiologyopen ; 9(3): e991, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31961499

RESUMEN

Pseudomonas aeruginosa encodes three type VI secretion systems (T6SSs), namely H1-, H2-, and H3-T6SS. P. aeruginosa hemolysin-coregulated protein (Hcp) is the effector protein and the hallmark of T6SS. Although T6SS is ubiquitous and affects ecology and human health, its general mechanism and physiological role are still not fully understood. Therefore, in this study, we investigated the impact of the P. aeruginosa T6SS on biofilm formation and environmental adaptation. To this end, we collected P. aeruginosa clinical isolates, divided them into strong biofilm formation (SBF) and nonbiofilm formation (NBF) groups based on their biofilm-forming ability, and compared their associated clinical characteristics. The duration of hospitalization was longer in patients infected with SBF than those infected with NBF strains. The expression levels of T6SS-related genes (hcp1 and hcp3) and a quorum-sensing gene (lasR) were higher in the SBF group as compared to those in the NBF group. In addition, the expression level of lasR was negatively associated with that of hcp1, but was positively associated with those of hcp2 and hcp3. Moreover, we evaluated the expression of T6SS- and biofilm-associated genes in planktonic and biofilm cells of the P. aeruginosa strain PAO1, and constructed strain PAO1△clpV1 to study the adaptation characteristics of H1-T6SS. The expression levels of hcp1, hcp2, hcp3, lasR, and other biofilm-associated genes were significantly higher in PAO1 biofilm cells as compared to those of planktonic cells. However, except for swarming ability as a vital feature for biofilm formation, there were no significant differences in the biofilm-forming ability and expression of biofilm-associated genes, adherence ability, growth characteristics, resistance to acid and osmotic pressure, surface structure, and morphology between the PAO1△clpV1 and PAO1 wild-type strains. Collectively, our results suggest that T6SS might play a role in biofilm formation and that H1-T6SS does not contribute to environmental adaptation in P. aeruginosa.


Asunto(s)
Adaptación Fisiológica , Biopelículas/crecimiento & desarrollo , Ambiente , Pseudomonas aeruginosa/fisiología , Sistemas de Secreción Tipo VI , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Concentración de Iones de Hidrógeno , Mutación , Pseudomonas aeruginosa/ultraestructura , Factores de Virulencia/genética
17.
J Invest Dermatol ; 140(2): 309-318.e8, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31476317

RESUMEN

Pemphigus is an organ-specific autoimmune disease that targets skin and/or mucous membranes. Our previous study showed that infiltrating lymphocytes in pemphigus vulgaris (PV) lesions produce anti-desmoglein (Dsg) 1/3 antibodies after in vitro culture. In this study, we found diffuse ectopic lymphoid-like structures (ELSs) commonly present in the lesions of both PV and pemphigus foliaceus. Notably, pemphigus lesions contained centroblasts, plasmablasts, and plasma cells, which recapitulated the different stages of B cell differentiation. Elevated mRNA expression levels of the differentiation-related transcription factors BLIMP-1, IRF4, and BCL-6 were observed in pemphigus lesions. Moreover, B cell receptor repertoire analysis revealed the clonal expansion of the lesional B cells. Lesional B cells might recirculate among lesions, lymph nodes, and peripheral blood. Increased mRNA expression levels of multiple chemokines in pemphigus lesions and elevated expression levels of chemokine receptors on lesional B cells were also observed. Collectively, these results show that the ELSs in pemphigus lesions might act as a niche, supporting in situ B cell differentiation and clonal expansion.


Asunto(s)
Linfocitos B/inmunología , Diferenciación Celular/inmunología , Pénfigo/inmunología , Piel/inmunología , Estructuras Linfoides Terciarias/inmunología , Adulto , Anciano , Animales , Biopsia , Diferenciación Celular/genética , Células Cultivadas , Selección Clonal Mediada por Antígenos/genética , Selección Clonal Mediada por Antígenos/inmunología , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Factores Reguladores del Interferón/metabolismo , Activación de Linfocitos/genética , Activación de Linfocitos/inmunología , Masculino , Ratones SCID , Persona de Mediana Edad , Pénfigo/sangre , Pénfigo/patología , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Piel/citología , Piel/patología
20.
Oncotarget ; 8(25): 41518-41528, 2017 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-28514747

RESUMEN

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/CT have become two of the most powerful tools for malignant lymphoma exploration, but their diagnostic role in primary central nervous system lymphoma (PCNSL) is still disputed. The purpose of our study is to identify the usefulness of 18F-FDG PET and PET/CT for detecting PCNSL. RESULTS: A total of 129 patients, obtained from eight eligible studies, were included for this systematic review and meta-analysis. The performance of 18F-FDG PET and PET/CT for diagnosing PCNSL were as follows: the pooled sensitivity was 0.88 (95% CI: 0.80-0.94), specificity was 0.86 (95% CI: 0.73-0.94), positive likelihood ratio (PLR) was 3.99 (95% CI: 2.31-6.90), negative likelihood ratio (NLR) was 0.11 (95% CI: 0.04-0.32), and diagnostic odds ratio (DOR) was 33.40 (95% CI: 10.40-107.3). In addition, the area under the curve (AUC) and Q index were 0.9192 and 0.8525, respectively. MATERIALS AND METHODS: PubMed/MEDLINE, Embase and Cochrane Library were systematically searched for potential publications (last updated on July 16th, 2016). Reference lists of included articles were also checked. Original articles that reported data on patients who were suspected of having PCNSL were considered suitable for inclusion. The sensitivities and specificities of 18F-FDG PET and PET/CT in each study were evaluated. The Stata software and Meta-Disc software were employed in the process of data analysis. CONCLUSIONS: 18F-FDG PET and PET/CT showed considerable accuracy in identifying PCNSL in immunocompetent patients and could be a valuable radiological diagnostic tool for PCNSL.


Asunto(s)
Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Linfoma/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Neoplasias del Sistema Nervioso Central/inmunología , Neoplasias del Sistema Nervioso Central/patología , Humanos , Inmunocompetencia , Linfoma/inmunología , Linfoma/patología , Radiofármacos
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