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1.
Brain Res Bull ; 207: 110871, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38211740

RESUMEN

CONTEXT: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been shown to exhibit anti-depressive effects in clinical trials. However, the direct mechanism underlying its effect on neuroinflammation remains unclear. Neuroinflammatory reaction from astrocytes leads to depression, and our previous study found that gap junction disorder between astrocytes aggravated neuroinflammatory reaction in depressed mice. OBJECTIVE: To investigate the potential mechanism of celecoxib's effects on astrocytic gap junctions during the central nervous inflammation-induced depression. MATERIALS & METHODS: Stereotaxic injection of lipopolysaccharide (LPS) into the prefrontal cortex (PFC) to establish a model of major depressive disorder (MDD). Celecoxib was administrated into PFC 15 min after LPS injection. The depressive performance was tested by tail suspension test and forced swimming test, and the levels of proinflammation cytokines were determined at mRNA and protein levels. Resting-state functional connection (rsFC) was employed to assess changes in the default mode network (DMN). Additionally, astrocytic gap junctions were also determined by lucifer yellow (LY) diffusion and transmission electron microscope (TEM), and the expression of connexin 43 (Cx43) was measured by western blotting, quantitative polymerase chain reaction, and immunofluorescence. RESULTS: LPS injection induced significant depressive performance, which was ameliorated by celecoxib treatment. Celecoxib also improved rsFC in the DMN. Furthermore, celecoxib improved astrocytic gap junctions as evidenced by increased LY diffusion, shortened gap junction width, and normalized levels of phosphorylated Cx43. Celecoxib also blocked the phosphorylation of p65, and inhibition of p65 abolished the improvement of Cx43. DISCUSSION & CONCLUSION: Anti-depressive effects of celecoxib are mediated, at least in part, by the inhibition of nuclear factor- kappa B (NF-κB) and the subsequent improvement of astrocytic gap junction function.


Asunto(s)
Trastorno Depresivo Mayor , FN-kappa B , Animales , Ratones , Celecoxib/farmacología , FN-kappa B/metabolismo , Conexina 43/metabolismo , Astrocitos/metabolismo , Trastorno Depresivo Mayor/metabolismo , Lipopolisacáridos/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Uniones Comunicantes
2.
J Coll Physicians Surg Pak ; 33(10): 1130-1135, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37804018

RESUMEN

OBJECTIVE: To determine the clinical efficacy of ultrasonic irrigation combined with epoxy resin-based sealer in single visit root canal treatment of chronic pulpitis. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Stomatology, Hefei BOE Hospital, Hefei, China, from March 2019 to December 2021. METHODOLOGY: Ninety patients with chronic pulpitis, comprising 104 affected teeth, were enrolled. Using a random number table, they were divided into Group A (n = 30, 35 teeth), Group B (n = 30, 35 teeth), and the control group (n = 30, 34 teeth). All underwent single visit root canal treatment. Group A received ultrasonic irrigation followed by sealing with epoxy resin-based paste; Group B had conventional syringe irrigation followed by the same sealing; the control group had syringe irrigation and closure with zinc oxide-eugenol paste. Pain during treatment, posttreatment clinical outcomes, and differences in inflammatory markers (IL-4, IL-6, hs-CRP), and quality of life (QOL) scores pre- and posttreatment over two months were observed. RESULTS: After the treatment, improvement rates for Groups A, B, and the control group were 91.4%, 65.7%, and 61.7%, respectively. Pain occurrence rates were 6.7%, 30.0%, and 36.7%, respectively. Group A outperformed both Group B and the control group in improvement and pain incidence with statistical significance (p<0.016). Posttreatment, Group A had lower IL-4, IL-6, hs-CRP levels than Groups B and the control group (p<0.05), and had higher scores for sleep, mood, and appetite (p<0.05). CONCLUSION: Ultrasonic irrigation combined with epoxy resin-based paste yields better results for chronic pulpitis treatment, reducing postoperative pain, mitigating inflammation levels, and enhancing quality of life. KEY WORDS: Chronic pulpitis, Ultrasonic irrigation, Epoxy resin paste, Root canal treatment, Therapeutic effect.


Asunto(s)
Pulpitis , Materiales de Obturación del Conducto Radicular , Humanos , Pulpitis/tratamiento farmacológico , Pulpitis/cirugía , Resinas Epoxi/uso terapéutico , Calidad de Vida , Ultrasonido , Proteína C-Reactiva , Cavidad Pulpar , Interleucina-4 , Interleucina-6 , Preparación del Conducto Radicular , Dolor Postoperatorio/tratamiento farmacológico , Irrigantes del Conducto Radicular
3.
J Drugs Dermatol ; 22(1): 45-53, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36607763

RESUMEN

BACKGROUND: Rosacea is primarily an inflammatory disease of facial skin associated with impaired skin barrier function. While it is commonly thought of as a Caucasian person's disease, it is likely underdiagnosed in people of color, including Asians, leading to missed and delayed diagnoses and increased morbidity. The purpose of this review is to highlight literature on rosacea in Asian people and the role of non-prescription skincare in managing rosacea. METHODS: Four dermatologists (the panel) completed pre-meeting surveys and participated in a web meeting to discuss the role of skin care in treating rosacea in the Asia Pacific (APAC) region. The survey results were summarized, then presented during the virtual meeting. These survey results and relevant papers identified through a literature review were then discussed. This review shows the fruit of these discussions, as well as the advisors' expert opinions and experiences. RESULTS: The panel crafted 5 consensus statements regarding the role of skin care in the treatment of rosacea in the APAC region. The most common forms of rosacea seen by the advisors are mostly erythematous and papulopustular. Among the panel, doxycycline is the most popular treatment for papulopustular rosacea. The panel prioritize gentleness when choosing skincare products for patients with rosacea. CONCLUSIONS: In Asian patients with rosacea, adjunctive skincare is an important part of treatment, maintenance, and prescription treatment. Given the highly sensitive skin of certain Asian patients with rosacea, avoiding potentially irritating substances is crucial. J Drugs Dermatol. 2023;22(1):45-53. doi:10.36849/JDD.7021.


Asunto(s)
Rosácea , Humanos , Rosácea/diagnóstico , Rosácea/tratamiento farmacológico , Piel , Eritema , Cuidados de la Piel/métodos , Asiático
4.
J Craniofac Surg ; 33(3): 906-909, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-34907949

RESUMEN

ABSTRACT: We aimed to evaluate the quality of life of Chinese patients after immediate reconstruction surgery on individuals with oral cavity cancer. In addition, we compared the differences between radial forearm free flap and pectoralis major myocuta- neous flap. Using the University of Washington quality of life v4 questionnaire, 1:1 matched research was performed on patients received PMM or RFF flap. Chi-square test was used to analyze the variables. One hundred twenty four of 179 questionnaires were returned (69.3%). Age, N stage, and postoperative radiotherapy were similar for both groups. However, there were significant differences between two groups in gender, T stage, operation duration, and complication rate. Oral cavity cancer patients reconstructed with radial forearm free flap had better shoulder and speech functions but worse appearance domains. The results of our research provide important information for patients and physicians during their discussion of treatment programs for oral cavity cancers.


Asunto(s)
Colgajos Tisulares Libres , Neoplasias de la Boca , Colgajo Miocutáneo , Procedimientos de Cirugía Plástica , Antebrazo/cirugía , Colgajos Tisulares Libres/cirugía , Humanos , Neoplasias de la Boca/cirugía , Colgajo Miocutáneo/cirugía , Calidad de Vida , Procedimientos de Cirugía Plástica/métodos
5.
J Drugs Dermatol ; 20(11): 1213-1221, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34784121

RESUMEN

BACKGROUND: Acne vulgaris (acne) is a common inflammatory skin disorder prevalent among all ethnic groups. This review aimed to investigate the current literature regarding the potential benefit of over-the-counter (OTC) adjuncts (eg, moisturizers, cleansers) for acne patients focusing on Asian phenotypes. METHODS: An online procedure was employed to review the role of adjunctive OTC acne treatment. A panel consisting of dermatologists with expertise in treating Asian acne patients participated in a pre-meeting survey that collected information regarding their recommendation habits for OTC products in acne patients. Recommendations on using OTC products as an adjunct for treating acne in Asians are based on the pre-meeting survey results, evidence from literature presented during a series of plenary lectures, and discussions conducted during a stepwise program of sessions. RESULTS: Many topical treatments have been associated with adverse events (AEs) (eg, skin dryness, erythema, scaling, stinging, burning, pruritus). Multiple studies on topical acne treatments have found that Asians display greater sensitivity and less tolerability than Caucasians to acne treatment. Skincare as an adjunct to acne treatment may reduce dryness or irritation, particularly important in Asians with acne. CONCLUSIONS: Advisors agreed that cleansers and moisturizers should be considered for their beneficial adjunctive role in the armamentarium of acne treatment and maintenance strategies. J Drugs Dermatol. 2021;20(11): 1213-1221. doi:10.36849/JDD.6259.


Asunto(s)
Acné Vulgar , Acné Vulgar/tratamiento farmacológico , Pueblo Asiatico , Humanos , Medicamentos sin Prescripción/efectos adversos , Cuidados de la Piel , Resultado del Tratamiento
6.
Int J Biochem Cell Biol ; 81(Pt B): 375-382, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27732890

RESUMEN

Autophagy is a recycling program which allows cells to adapt to metabolic needs and to stress. Defects in autophagy can affect metabolism, aging, proteostasis and inflammation. Autophagy pathway genes, including autophagy related 7 (Atg7), have been associated with the regulation of skin pigmentation, and autophagy defects disturb the biogenesis and transport of melanosomes in melanocytes as well as transfer and processing of melanin into keratinocytes. We have previously shown that mice whose melanocytes or keratinocytes lack Atg7 (and thus autophagy) as a result of specific gene knockout still retained functioning melanosome synthesis and transfer, and displayed only moderate reduction of pigmentation. In cell culture the Atg7 deficient melanocytes were prone to premature senescence and dysregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling. To elucidate the biochemical basis of this phenotype, we performed a study on global gene expression, protein secretion and phospholipid composition in Atg7 deficient versus Atg7 expressing melanocytes. In cell culture Atg7 deficient melanocytes showed a pro-inflammatory gene expression signature and secreted higher levels of C-X-C motif chemokine ligand -1,-2,-10 and -12 (Cxcl1, Cxcl2, Cxcl10, Cxcl12), which are implicated in the pathogenesis of pigmentary disorders and expressed higher amounts of matrix metalloproteinases -3 and -13 (Mmp3, Mmp13). The analysis of membrane phospholipid composition identified an increase in the arachidonic- to linoleic acid ratio in the autophagy deficient cells, as well as an increase in oxidized phospholipid species that act as danger associated molecular patterns (DAMPs). The secretion of inflammation related factors suggests that autophagy deficient melanocytes display a senescence associated secretory phenotype (SASP), and we propose oxidized lipid mediators as novel components of this SASP.


Asunto(s)
Envejecimiento , Proteína 7 Relacionada con la Autofagia/genética , Proteína 7 Relacionada con la Autofagia/metabolismo , Metabolismo de los Lípidos , Melanocitos/citología , Melanocitos/metabolismo , Animales , Autofagia/genética , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Regulación de la Expresión Génica , Técnicas de Inactivación de Genes , Humanos , Lípidos/química , Ratones , Fenotipo , Reacción en Cadena de la Polimerasa
7.
Medicine (Baltimore) ; 95(6): e2744, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26871820

RESUMEN

Cryptococcal meningitis (CM) is a global disease with significant morbidity and mortality. Although low peripheral blood cluster of differentiation 4 (CD4) cell counts are found to be related to a high burden of cryptococcus in HIV-infected patients, little is known about possible immune defects in previously healthy patients (PHPs). We performed a retrospective study of 41 CM patients treated from January 2005 to December 2014 who did not have HIV-infection. There were 33 PHPs and 8 not previously healthy patients (non-PHPs). We analyzed clinical test data pertaining to peripheral blood T cells, antibodies, inflammation markers, and cerebral spinal fluid (CSF) completed during the disease onset phase and 5 years following diagnosis. PHPs had significantly higher counts of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), and cluster of differentiation 45 (CD45) cells, and lower percentages of CD8 cells than non-PHPs (P < 0.05). Measurements of inflammatory markers and immunoglobulin in blood were comparable except for lower immunoglobulin A (IgA) levels in non-PHPs (P = 0.0410). Examination of CSF revealed lower white blood cell (WBC) counts in non-PHPs. Five-year mortality in PHPs was higher than in non-PHPs (22.0% vs 12.5%) but this was not statistically significant (P > 0.05). Multivariate analysis revealed that higher immunoglobulin G (IgG) levels in serum during disease onset may be an independent predictor of mortality (P = 0.015). In conclusion, PHPs demonstrate an immunophenotype that is distinct from that of non-PHPs, leading to an improved understanding of the immunology of cryptococcal meningitis.


Asunto(s)
Meningitis Criptocócica/inmunología , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina G/sangre , Recuento de Linfocitos , Masculino , Meningitis Criptocócica/metabolismo , Meningitis Criptocócica/mortalidad , Persona de Mediana Edad , Fenotipo , Estudios Retrospectivos , Adulto Joven
10.
PLoS One ; 10(4): e0123320, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25875494

RESUMEN

OBJECTIVES: To analyze the gender difference in life expectancy in Chinese urban people and explore the age-specific and cause-specific contributions to the changing gender differences in life expectancy. METHODS: Data of life expectancy and mortality were obtained from "Annual statistics of public health in China." The gender difference was analyzed by decomposition method, including age-specific decomposition and cause-specific decomposition. RESULTS: Women lived much longer than men in Chinese urban areas, with remarkable gains in life expectancy since 2005, respectively. The gender difference reached a peak in 2007. Mortality difference between men and women in the 60-79 age group made the largest contributions to the gender gap in life expectancy in all 6 years. Among causes of death, cancers, circulatory diseases and respiratory diseases made the largest contributions to the gender gap. 33-38% of the gender gap were caused by cancers, among which lung cancer contributed 0.6 years of the overall gap. The contribution of cancers to the gender gap reduced over time, mostly influenced by the narrowing effect of liver cancer on gender gap. Traffic accidents and suicide were the external causes influencing the gender gap, contributing 10-16% of the overall difference. CONCLUSION: Public health efforts to reduce excess mortalities for cancers, circulatory disease, respiratory diseases, and suicide among men in particular might further narrow the gender gap in life expectancy in Chinese cities.


Asunto(s)
Pueblo Asiatico/estadística & datos numéricos , Ciudades , Esperanza de Vida/tendencias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Femenino , Historia del Siglo XXI , Humanos , Lactante , Recién Nacido , Esperanza de Vida/historia , Masculino , Persona de Mediana Edad , Vigilancia en Salud Pública , Factores de Riesgo , Factores Sexuales , Adulto Joven
11.
J Invest Dermatol ; 135(5): 1348-1357, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25290687

RESUMEN

Autophagy is the central cellular mechanism for delivering organelles and cytoplasm to lysosomes for degradation and recycling of their molecular components. To determine the contribution of autophagy to melanocyte (MC) biology, we inactivated the essential autophagy gene Atg7 specifically in MCs using the Cre-loxP system. This gene deletion efficiently suppressed a key step in autophagy, lipidation of microtubule-associated protein 1 light chain 3 beta (LC3), in MCs and induced slight hypopigmentation of the epidermis in mice. The melanin content of hair was decreased by 10-15% in mice with autophagy-deficient MC as compared with control animals. When cultured in vitro, MCs from mutant and control mice produced equal amounts of melanin per cell. However, Atg7-deficient MCs entered into premature growth arrest and accumulated reactive oxygen species (ROS) damage, ubiquitinated proteins, and the multi-functional adapter protein SQSTM1/p62. Moreover, nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent expression of NAD(P)H dehydrogenase, quinone 1, and glutathione S-transferase Mu 1 was increased, indicating a contribution of autophagy to redox homeostasis in MCs. In summary, the results of our study suggest that Atg7-dependent autophagy is dispensable for melanogenesis but necessary for achieving the full proliferative capacity of MCs.


Asunto(s)
Envejecimiento Prematuro/fisiopatología , Antioxidantes/metabolismo , Autofagia/fisiología , Senescencia Celular/fisiología , Melanocitos/metabolismo , Melanocitos/patología , Envejecimiento Prematuro/metabolismo , Animales , Proteína 7 Relacionada con la Autofagia , Proliferación Celular/fisiología , Células Cultivadas , Homeostasis/fisiología , Humanos , Técnicas In Vitro , Peroxidación de Lípido/fisiología , Melaninas/metabolismo , Ratones , Ratones Noqueados , Proteínas Asociadas a Microtúbulos/deficiencia , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Modelos Animales , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo
12.
Exp Ther Med ; 8(3): 737-741, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25120591

RESUMEN

The present study was performed in order to define the clinical manifestations of porokeratosis, with particular emphasis on genital porokeratosis. A total of 55 cases of porokeratosis were retrospectively reviewed between 2000 and 2007 from Huashan Hospital (Shanghai, China). Out of 55 cases, there were 22 cases of porokeratosis of Mibelli, 17 cases of disseminated superficial actinic porokeratosis (DSAP), 15 cases of disseminated superficial porokeratosis and one case of linear porokeratosis. The ratio of males to females was 39:16. Among them, 12 cases had a family history of porokeratosis. During the five-year follow-up period, no malignant transformation was observed and no further aggravation of lesions was detected. The results indicated that the initial region of DSAP in the Chinese population may differ from Caucasians. In combination with other studies, the present study found that genital porokeratosis in the Chinese population is often associated with pruritus. Since no recurrence was observed in cases treated with surgical excision, it was suggested that surgical excision is a viable treatment strategy and should be used for porokeratotic lesions if possible. In addition, regular follow-ups are required, since the aggravation of porokeratosis may cause the development of malignancy transformation.

13.
J Dermatol Sci ; 71(1): 67-75, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23669018

RESUMEN

BACKGROUND: Cornification of keratinocytes involves the degradation of intracellular constituents which has led to the hypothesis that autophagy plays a role in this process. Mice, in which essential autophagy-related genes such as Atg7 are deleted systemically, die after birth and have not been characterized for potential epidermal defects. OBJECTIVE: This study tested whether autophagy is essential for epidermal barrier formation and function. METHODS: Atg7 was inactivated in epidermal keratinocytes by the Cre-loxP system under the control of the keratin K14 promoter (Atg7Δepi mice). Autophagic activity was detected using the GFP-microtubule-associated protein light chain 3 (GFP-LC3) reporter construct and Western blot analysis of LC3. Epidermal morphology was examined by histological and ultrastructural analyses, and barrier functions were assessed by dye diffusion and water loss assays. RESULTS: Suprabasal epidermal cells of normal mice contained GFP-LC3-labeled autophagosomes and epidermal lysates of these mice showed an excess of lipidated over non-lipidated LC3. These features of active autophagy were efficiently suppressed in Atg7Δepi epidermis. Atg7Δepi mice survived the perinatal period and were apparently healthy. Histologically, their epidermis was inconspicuous and ultrastructural analysis revealed no significant defect in cornification. There was however, an increase in the thickness of corneocytes in the back skin of mutant mice. Nevertheless, resistance to dye penetration into the skin and transepidermal water loss were normal in Atg7Δepi mice. CONCLUSION: This study demonstrates that autophagy is constitutively active in the epidermis but not essential for the barrier function of the skin.


Asunto(s)
Autofagia , Epidermis/metabolismo , Queratinocitos/metabolismo , Proteínas Asociadas a Microtúbulos/deficiencia , Absorción Cutánea , Animales , Proteína 7 Relacionada con la Autofagia , Diferenciación Celular , Células Cultivadas , Difusión , Epidermis/ultraestructura , Proteínas Fluorescentes Verdes , Queratina-14/genética , Queratinocitos/ultraestructura , Ratones , Ratones Endogámicos CBA , Ratones Noqueados , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Permeabilidad , Regiones Promotoras Genéticas , Pérdida Insensible de Agua
14.
J Invest Dermatol ; 133(6): 1629-37, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23340736

RESUMEN

The skin is exposed to environmental insults such as UV light that cause oxidative damage to macromolecules. A centerpiece in the defense against oxidative stress is the Nrf2 (nuclear factor (erythroid-derived-2)-like 2)-mediated transcriptional upregulation of antioxidant and detoxifying enzymes and the removal of oxidatively damaged material. Autophagy has an important role in the intracellular degradation of damaged proteins and entire organelles, but its role in the epidermis has remained elusive. Here, we show that both UVA and UVA-oxidized phospholipids induced autophagy in epidermal keratinocytes. Oxidative stressors induced massive accumulation of high-molecular-weight protein aggregates containing the autophagy adaptor protein p62/SQSTM1 in autophagy-deficient (autophagy-related 7 (ATG7) negative) keratinocytes. Strikingly, even in the absence of exogenous stress, the expression of Nrf2-dependent genes was elevated in autophagy-deficient keratinocytes. Furthermore, we show that autophagy-deficient cells contained significantly elevated levels of reactive oxidized phospholipids. Thus, our data demonstrate that autophagy is crucial for both the degradation of proteins and lipids modified by environmental UV stress and for limiting Nrf2 activity in keratinocytes. Lipids that promote inflammation and tissue damage because of their reactivity and signaling functions are commonly observed in aged and diseased skin, and thus targeting autophagy may be a promising strategy to counteract the damage promoted by excessive lipid oxidation.


Asunto(s)
Autofagia/efectos de la radiación , Queratinocitos/patología , Queratinocitos/efectos de la radiación , Estrés Oxidativo/efectos de la radiación , Fosfolípidos/metabolismo , Rayos Ultravioleta/efectos adversos , Animales , Autofagia/fisiología , Proteína 7 Relacionada con la Autofagia , Células Cultivadas , Epidermis/patología , Epidermis/efectos de la radiación , Ratones , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción , Estrés Oxidativo/fisiología , Fosfolípidos/genética , Regulación hacia Arriba/fisiología , Regulación hacia Arriba/efectos de la radiación
15.
PLoS One ; 7(6): e38933, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22719991

RESUMEN

The thymic epithelium plays critical roles in the positive and negative selection of T cells. Recently, it was proposed that autophagy in thymic epithelial cells is essential for the induction of T cell tolerance to self antigens and thus for the prevention of autoimmune diseases. Here we have tested this hypothesis using mouse models in which autophagy was blocked specifically in epithelial cells expressing keratin 14 (K14), including the precursor of thymic epithelial cells. While the thymic epithelial cells of mice carrying the floxed Atg7 gene (ATG7 f/f) showed a high level of autophagy, as determined by LC3 Western blot analysis and fluorescence detection of the recombinant green fluorescent protein (GFP)-LC3 reporter protein on autophagosomes, autophagy in the thymic epithelium was efficiently suppressed by deletion of the Atg7 gene using the Cre-loxP system (ATG7 f/f K14-Cre). Suppression of autophagy led to the massive accumulation of p62/sequestosome 1 (SQSTM1) in thymic epithelial cells. However, the structure of the thymic epithelium as well as the organization and the size of the thymus were not altered in mutant mice. The ratio of CD4 to CD8-positive T cells, as well as the frequency of activated (CD69+) CD4 T cells in lymphoid organs, did not differ between mice with autophagy-competent and autophagy-deficient thymic epithelium. Inflammatory infiltrating cells, potentially indicative of autoimmune reactions, were present in the liver, lung, and colon of a similar fraction of ATG7 f/f and ATG7 f/f K14-Cre mice. In contrast to previously reported mice, that had received an autophagy-deficient thymus transplant, ATG7 f/f K14-Cre mice did not suffer from autoimmunity-induced weight loss. In summary, the results of this study suggest that autophagy in the thymic epithelium is dispensable for negative selection of autoreactive T cells.


Asunto(s)
Autofagia , Modelos Animales , Autotolerancia , Timo/inmunología , Animales , Western Blotting , Femenino , Proteínas Fluorescentes Verdes/genética , Ratones
16.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(1): 118-22, 2012 Jan.
Artículo en Chino | MEDLINE | ID: mdl-22497141

RESUMEN

In the present work, we prepared nylon 6 crystals via crystallization of nylon from phosphoric acid by using the vapors of ammonium hydroxide as a precipitation regent. Both XRD and FTIR results demonstrate that the obtained nylon 6 sample exhibit characteristic peaks of nylon 6 in gamma form. In addition, treatment of nylon 6 in boiling water for half an hour followed by FTIR and XRD characterization shows that the obtained nylon 6 sample is in gamma form rather than in meta-stable b form. DSC characterization indicates that the nylon 6 sample exhibits two melting peaks (213 and 220 degrees C) when the sample is heated at a heating rate of 10 degrees C x min(-1). The reason for this phenomenon is that the nylon 6 sample has different lamellar thickness. To investigate the thermal behavior of the nylon 6 sample, the sample underwent the following thermal treatment procedure. First, the sample was heated to a pre-set temperature (T(s)) and kept at that temperature for an hour. Subsequently, the sample was cooled down to 100 degrees C at a cooling rate of 1 degrees C x min(-1), and then cooled down to room temperature at a cooling rate of 10 degrees C x min(-1). The treated samples were characterized by FTIR and DSC method. Experimental results show that the treated nylon 6 samples exhibit different crystalline behavior. When T. ranges from 130 to 160 degrees C, no significant changes were observed. When T(s) is 170 degrees C, a small fraction nylon 6 crystals is destroyed and recrystallized into thin lamellae in a form. As a result, a pre-melting peak appears in DSC result. The pre-melting peak moves to higher temperature and its peak area increases significantly upon increasing T(s) from 170 to 198 degrees C. When T(s) amounts to 200 degrees C, the pre-melting peak and the melting peaks 213 degrees C merge into one melting peak and two melting peaks are observed at 212 and 220 degrees C in the DSC results. FTIR spectra indicate that significant amount of crystalline nylon 6 in a form appears but the majority of crystalline phase of the sample is still gamma phase. As T(s) increases from 200 to 209 degrees C, the melting peak at lower temperature moves to higher temperature with increasing its peak area. On the other hand, the melting peak at 220 degrees C decreases in intensity but does not show any peak shift. As T(s) reaches 209 degrees C, the two melting peaks merge into one peak and FTIR results demonstrate that nylon 6 in a form becomes dominate phase in the sample. In the whole heat-treatment process, the gamma phase nylon 6 sample began to transform to a phase at the heat-treatment temperature of 170 degrees C, which is far below the melting point of the original sample (221 degrees C). This is different from the results reported in the literature, which state that gamma phase nylon 6 will not transform to alpha-phase until nylon is melt.

18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(5): 1184-8, 2010 May.
Artículo en Chino | MEDLINE | ID: mdl-20672597

RESUMEN

In the present paper, the authors developed a new approach by constructing two-dimensional (2D) UV-Vis/fluorescence heterogeneous synchronous spectrum based on the orthogonal sample design scheme (OSD) developed in our previous works to characterize energy transfer among different lanthanide ions during the luminescence process. The authors use the EuCl3-NdCl3 system as an example. The preliminary experimental results on the 2D synchronous spectra of EuCl3-NdCl3 mixture solutions have demonstrated that cross peaks can be observed among the UV-Vis absorption bands from Nd3+ and fluorescence emission bands from Eu3+. The cross peaks in the 2D synchronous spectra of EuCl3-NdCl3 mixture solutions manifested the interaction between the fluorescence emission from Eu3+ and UV-Vis absorbance from Nd3+, and therefore gives out experimental evidences for the occurrence of energy transfer between Eu3+ and Nd3+ ions. The cross peaks are not from the interaction between the solvent, water, and the solute, Eu3+ or Nd3+ ions. Mathematical analysis performed on 2D synchronous spectra using variable concentration as an external perturbation shows that the orthogonal sample design scheme is indispensable in removing the interfering cross peaks in 2D synchronous spectra. In fact, if the authors detect, respectively, the fluorescence emission spectra of pure Eu3+ solutions and the UV-Vis absorbance spectra of pure Nd3+ solutions, then use these spectra data to construct a series of synthesized spectra of an assumed mixture solution in which Eu3+ and Nd3+ are not mixed together, because Eu3+ and Nd3+ ions are spatially separated, there are no intermolecular interactions that should have occurred. Therefore, there are no cross-peaks that can be observed in the comparative 2D synchronous spectra. The cross peaks in 2D synchronous correlation spectra gives out a new approach to characterizing energy transfer among different lanthanide ions during the luminescence process.

19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(5): 1308-12, 2009 May.
Artículo en Chino | MEDLINE | ID: mdl-19650478

RESUMEN

Fluorescence and UV-Vis spectra of ofloxacin (OFL) in sulfuric acid were studied. In the present paper, a new protonation state of OFL was observed. In hydrochloric acid, OFL produced bright green fluorescence upon excitation by UV radiation. The maximal emission wavelength of OFL is about 505 nm. However, OFL produces violet fluorescence when dissolved in concentrated sulfuric acid. The maximal emission wavelength changes into 400 nm. Further analysis demonstrated that the above changes arise from the variation of protonation states of OFL molecule. In dilute sulfuric acid, OFL accepted one proton, resulting in a protonation state that is similar to the OFL molecule dissolved HCl solution. The corresponding fluorescence band occurs at 505 nm. In concentrated sulfuric acid solution, OFL might accept additional protons. As a result, the size of the conjugated system is reduced and the fluorescence band exhibits a blue shift. In sulfuric acid of moderate concentrations, two bands at 505 and 400 nm respectively were found in the fluorescence emission spectra, indicating that OFL in two different protonation states coexists in the solution. In addition, both excitation band in excitation spectra and absorption bands in UV-Vis spectra exhibit red-shifted with the decrease in the concentration of sulfuric acid. Based on the above result, OFL can be used as a spectral probe to reflect the variation of H+ in strong acid environment.

20.
Dermatoendocrinol ; 1(2): 108-13, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20224693

RESUMEN

BACKGROUND: Pigment epithelium-derived factor (PEDF) was first isolated from the medium conditioned by human fetal retinal pigment epithelial cells and has been detected in a broad range of human fetal and adult tissues. Recent studies have indicated that PEDF activity is inhibitory to angiogenesis. OBJECTIVE: To study the expression and distribution of pigment epithelium-derived factor (PEDF) in human melanocytes, malignant melanoma cells and tissues. RESULTS: PEDF was expressed in human melanocytes. The expression of PEDF protein diminished in the following orders healthy skin, pigmented nevus and human malignant melanoma (p < 0.001). Both the expression of PEDF mRNA and protein was much lower or almost absent in the malignant melanoma cell line A375 than that in human melanocytes (p < 0.001). METHODS: The expression and distribution of PEDF in human healthy skin, pigmented nevus and malignant melanoma were studied. The expression of PEDF mRNA in human melanocytes and malignant melanoma cell line A375 was measured by reverse transcription polymerase chain reaction (RT-PCR) and PEDF protein was detected by immunohistochemical method and Western blotting analysis. CONCLUSION: The lack of PEDF expression may contribute to the pathogenesis of malignant melanoma.

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