RESUMEN
Granulocyte transfusion (GT) may be used to treat and prevent infections in patients with severe neutropenia or nonfunctioning granulocytes. For pediatric patients, the volume of granulocyte unit transfused is a crucial consideration given smaller blood volume and increased risk of volume overload compared to adults. There is limited literature on the optimal dosing or the maximum amount of granulocytes that can be tolerated, especially in pediatric patients. Additionally, no consensus exists regarding granulocyte collection method, frequency, or timing of GT initiation. Previous studies have described splitting or limiting collection volume for GT in pediatric patients, but these methods yield lower absolute neutrophil count (ANC) increment. Our blood supplier provides high-volume (0.5-1 L/unit), high-dose apheresis-collected granulocytes from donors stimulated with both granulocyte colony-stimulating factor and steroids. Here, we report cases of two pediatric patients with active infection undergoing bone marrow transplant with dramatic ANC increments (median one-hour ANC increment 5524/µL, interquartile range (IQR) 4417-10087; median 24-hour ANC increment 3880/µL, IQR 2550-5263) after infusing 100 mL plasma-reduced, apheresis collected GT. Our cases indicate that pediatric patients can tolerate 4-6 × 109/kg plasma-reduced GT and have detectable ANC with GT every 3 days.
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Eliminación de Componentes Sanguíneos , Granulocitos , Adulto , Humanos , Niño , Neutrófilos , Transfusión de Leucocitos , Donantes de Sangre , Factor Estimulante de Colonias de Granulocitos/uso terapéuticoRESUMEN
BACKGROUND: Administering platelets through a rapid infuser is proven to be safe. However, the clinical significance of infusing ABO-incompatible platelets with red blood cells (RBCs) in a rapid infuser remains unclear. There is a theoretical risk that isoagglutinin in the plasma of a platelet unit can interact with RBCs and induce hemolysis. MATERIALS AND METHODS: Seven in vitro studies were performed including five cases (type A RBCs and type O platelets) and two controls (type A RBCs and platelets). Anti-A titers were measured in platelet units. An RBC unit and a platelet unit were mixed in the rapid infuser reservoir and incubated for 30 min. The primary outcome was the presence of hemolysis based on the following parameters: free hemoglobin concentration, hemolysis check, direct antiglobulin test (DAT), and direct agglutination. RESULTS: The post-mix DAT was positive for IgG in all test samples (5/5), and weakly positive for complement in 3/5. The changes in free Hb in test cases between measured and calculated post-mix spanned -2.2 to +3.4 mg/dL. Post-mix hemolysis check was negative in 3/5 and slightly positive in 2/5 cases, with no significant differences compared to the control case. Anti-A titers ranged from 16 to 512 and were not associated with hemolysis. All samples were negative for direct agglutination. CONCLUSION: Our study suggested that mixing ABO-incompatible platelets with RBCs in a rapid infuser does not induce in vitro hemolysis. These findings support the use of rapid infusers regardless of platelet compatibility in support of hemostatic resuscitation.
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Sistema del Grupo Sanguíneo ABO , Hemólisis , Humanos , Transfusión de Plaquetas/efectos adversos , Incompatibilidad de Grupos Sanguíneos , Plaquetas , AnticuerposRESUMEN
INTRODUCTION: Lipoprotein X (Lp-X) is an abnormal lipoprotein found in multiple disease conditions, including liver dysfunction and cholestasis. High Lp-X concentrations can interfere with some laboratory testing that may result in spurious results. The detection of Lp-X can be challenging, and there is currently a lack of consensus regarding the management of Lp-X other than treating the underlying disease. CASE PRESENTATION: A 42-year-old female with Hodgkin's lymphoma treated with dexamethasone, high dose cytarabine and cisplatin and vanishing bile duct syndrome confirmed by liver biopsy presented with cholestasis, pseudohyponatremia (sodium, 113 mmol/L; reference range 136-146 mmL/L; serum osmolality, 303 mOsm/kg), and hypercholesterolemia (> 2800 mg/dL, reference range < 200 mg/dL). Lp-X was confirmed by lipoprotein electrophoresis (EP). Although she did not manifest any specific signs or symptoms, therapeutic plasma exchange (TPE) was initiated based on laboratory findings of extreme hypercholesterolemia, spuriously abnormal serum sodium, and HDL values, and the potential for short- and long-term sequelae such as hyperviscosity syndrome, xanthoma, and neuropathy. During the hospitalization, she was treated with four 1.0 plasma volume TPE over 6 days using 5% albumin for replacement fluid. After the first TPE, total cholesterol (TC) decreased to 383 mg/dL and sodium was measured at 131 mmol/L. The patient was transitioned into outpatient maintenance TPE to eliminate the potential of Lp-X reappearance while the underlying disease was treated. Serial follow-up laboratory testing with lipoprotein EP showed the disappearance of Lp-X after nine TPEs over a 10-week period. LITERATURE REVIEW: There are seven and four case reports of Lp-X treated with TPE and lipoprotein apheresis (LA), respectively. While all previous case reports showed a reduction in TC levels, none had monitored the disappearance of Lp-X after completing a course of therapeutic apheresis. CONCLUSION: Clinicians should have a heightened suspicion for the presence of abnormal Lp-X in patients with cholestasis, hypercholesterolemia, and pseudohyponatremia. Once Lp-X is confirmed by lipoprotein EP, TPE should be initiated to reduce TC level and remove abnormal Lp-X. Most LA techniques are not expected to be beneficial since Lp-X lacks apolipoprotein B. Therefore, we suggest that inpatient course of TPE be performed every other day until serum sodium, TC and HDL levels become normalized. Outpatient maintenance TPE may also be considered to keep Lp-X levels low while the underlying disease is treated. Serum sodium, TC, and HDL levels should be monitored while on maintenance TPE.
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Colestasis , Hipercolesterolemia , Femenino , Humanos , Adulto , Hipercolesterolemia/complicaciones , Hipercolesterolemia/terapia , Lipoproteína X , Intercambio Plasmático , Colestasis/etiología , Colestasis/terapia , Lipoproteínas , Sodio , Conductos BiliaresRESUMEN
OBJECTIVE: Independent assessment of SARS-CoV-2 antigen (COV2Ag) tests remains important as varying performance between assays is common. We assessed the performance of a new high-throughput COV2Ag test compared to SARS-CoV-2 nucleic acid amplification tests (NAAT). METHODS: A total of 347 nasopharyngeal samples collected from January to October 2021 were assessed by NAAT as part of standard-of-care testing (CDC LDT or GeneXpert System, Cepheid) and COV2Ag using the ADVIA Centaur CoV2Ag assay (Siemens Healthineers). RESULTS: Among NAAT positive specimens we found 82.4% agreement and in NAAT negative specimens we found 97.3% agreement (overall agreement 85.6%). In symptomatic persons, COV2Ag agreed with NAAT 90.0% (nâ =â 291), and in asymptomatic persons, 62.5% (nâ =â 56). Agreement between positive NAAT and COV2Ag increased at lower cycle threshold (Ct) values. CONCLUSION: The COV2Ag assay exceeded the World Health Organization minimum performance requirements ofâ ≥â 80% sensitivity andâ ≥â 97% specificity. The COV2Ag assay is helpful for large scale screening efforts due to high-throughput and reduced wait times.
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COVID-19 , Ácidos Nucleicos , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Prueba Serológica para COVID-19 , Técnicas de Amplificación de Ácido NucleicoRESUMEN
OBJECTIVES: Acute viral infections and some vaccines have been shown to increase false positivity in serologic assays. We assessed if the messenger RNA coronavirus disease 2019 (COVID-19) vaccines could cause false reactivity in common serologic assays in a pilot longitudinal cohort. METHODS: Thirty-eight participants with sera available prevaccination, 2 weeks after each vaccine dose, and monthly thereafter for up to 5 months were tested for common infectious disease serologies and antiphospholipid syndrome (APS) serology markers on the BioPlex 2200, Sure-Vue rapid plasma reagin (RPR), and Macro-Vue RPR. Twenty-two participants received the Moderna vaccine and 16 received the Pfizer vaccine. RESULTS: Most assays had no change in reactivity over the course of the sample draws, including APS markers. Epstein-Barr virus immunoglobulin G (IgG), measles IgG, and rubella immunoglobulin M all had possible false reactivity in one to two participants. RPR tests demonstrated false reactivity, with baseline nonreactive participant samples becoming reactive following vaccination. There were more false reactive participants (7/38) in the BioPlex RPR than in the Sure-Vue (2/38) and Macro-Vue (1/38) tests. All falsely reactive RPR tests were in participants who received the Moderna vaccine. CONCLUSIONS: Serologic assays with results that do not fit the clinical picture following COVID-19 vaccination should be repeated. Effects of false reactivity can last more than 5 months in some assays. In particular, RPR is susceptible to false reactivity, and there is variability among assays. Larger longitudinal studies are needed to determine the incidence and window of false reactivity.
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COVID-19 , Infecciones por Virus de Epstein-Barr , COVID-19/diagnóstico , COVID-19/prevención & control , Prueba de COVID-19 , Vacunas contra la COVID-19 , Herpesvirus Humano 4 , Humanos , Inmunoglobulina G , ARN Mensajero , Reaginas , Pruebas Serológicas , Serodiagnóstico de la Sífilis/métodos , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
OBJECTIVE: Neutralizing antibodies are among the factors used to measure an individual's immune status for the control of infectious diseases. We aimed to confirm the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody levels in patients who had recovered from coronavirus disease 2019 (COVID-19). METHODS: Plasma donors in South Korea who had completely recovered from SARS-CoV-2 infection had follow-up testing to determine the persistence of neutralizing antibodies using a plaque-reduction neutralization test and ELISA. RESULTS: Of the 111 participants-aged 20-29 years, 37/111 (33.3%); 30-39 years, 17/111 (15.3%); 40-49 years, 23/111 (20.7%); 50-59 years, 21/111 (18.9%); 60-65 years, 13/111 (11.7%); male, 43/111 (38.7%); female, 68/111 (61.3%)-66.1% still had neutralizing antibodies approximately 9 months (range 255-302 days) after confirmation of the diagnosis. CONCLUSIONS: In this study we analysed the titre of neutralizing antibodies associated with predicting immune status in individuals with natural infection. Information about the persistence and change in levels of neutralizing antibodies against SARS-CoV-2 can be utilized to provide evidence for developing vaccination schedules for individuals with previous infection.
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COVID-19 , Adulto , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Formación de Anticuerpos , Femenino , Humanos , Masculino , SARS-CoV-2 , Adulto JovenRESUMEN
BACKGROUND: The skin acts as a barrier to protect organisms against harmful exogenous agents. Compound K (CK) is an active metabolite of ginsenoside Rb1, Rb2 and Rc, and researchers have focused on its skin protective efficacy. In this study, we hypothesized that increased expression of the serine protease inhibitor Kazal type-5 (SPINK5) may improve skin barrier function. METHODS: We screened several ginsenosides to increase SPINK5 gene promoter activity using a transactivation assay and found that CK can increase SPINK5 expression. To investigate the protective effect of CK on the skin barrier, RT-PCR and Western blotting were performed to investigate the expression levels of SPINK5, kallikrein 5 (KLK5), KLK7 and PAR2 in UVB-irradiated HaCaT cells. Measurement of transepidermal water loss (TEWL) and histological changes associated with the skin barrier were performed in a UVB-irradiated mouse model and a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis-like model. RESULTS: CK treatment increased the expression of SPINK5 and decreased the expression of its downstream genes, such as KLKs and PAR2. In the UVB-irradiated mouse model and the DNCB-induced atopic dermatitis model, CK restored increased TEWL and decreased hydration and epidermal hyperplasia. In addition, CK normalized the reduced SPINK5 expression caused by UVB or DNCB, thereby restoring the expression of the proteins involved in desquamation to a level similar to normal. CONCLUSIONS: Our data showed that CK contributes to improving skin-barrier function in UVB-irradiated and DNCB-induced atopic dermatitis-like models through SPINK5. These results suggest that therapeutic attempts with CK might be useful in treating barrier-disrupted diseases.
RESUMEN
Previous reports have shown that PPARß/δ agonists ameliorate insulin resistance associated with type 2 diabetes mellitus (T2DM). To determine the role of PPARß/δ in tumor necrosis factor α (TNFα)-mediated insulin resistance, we investigated expression levels of adiponectin and insulin receptor (IR) in response to treatment with the PPARß/δ agonist GW501516 with or without TNFα, a proinflammatory cytokine, in differentiated 3T3-L1 adipocytes. GW501516 induced adipocyte differentiation and the expression of adiponectin in a dose-dependent manner in differentiated adipocytes. TNFα treatment reduced adiponectin expression at the end of differentiation. This effect was reversed by GW501516 co-treatment with TNFα. TNFα treatment decreased adipogenic marker genes such as PPARγ, aP2, resistin, and GLUT4, and GW501516 reversed the effects of TNFα. GW501516 treatment increased the expression of insulin receptor and inhibited TNFα-mediated repression of insulin receptor. Our results showed that GW501516 abrogated TNFα-induced insulin resistance. In summary, our study demonstrated that the PPARß/δ agonist, GW501516 reversed TNFα-induced decreases in adipocyte differentiation and adiponectin expression, and improved insulin sensitivity by increasing the expression of insulin receptor. Therefore, PPARδ may be a promising therapeutic target for treatment of insulin resistance in patients with T2DM.
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Adiponectina/metabolismo , PPAR delta/agonistas , PPAR-beta/agonistas , Receptor de Insulina/metabolismo , Tiazoles/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Resistencia a la Insulina , Ratones , PPAR delta/metabolismo , PPAR-beta/metabolismoRESUMEN
Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is the main lipophilic flavonoid obtained from the Artemisia species. Eupatilin has been reported to have anti-apoptotic, anti-oxidative and anti-inflammatory activities. Previously, we found that eupatilin increases transcriptional activity and expression of peroxisome proliferator-activated receptor α (PPARα) in a keratinocyte cell line and acts as an agonist of PPARα. PPARα agonists ameliorate atopic dermatitis (AD) and restore the skin barrier function. In this study, we confirmed that the effects of eupatilin improved AD-like symptoms in an oxazolone-induced AD-like mouse model. Furthermore, we found that eupatilin suppressed the levels of serum immunoglobulin E (IgE), interleukin-4 (IL-4), and AD involved cytokines, such as tumor necrosis factor α (TNFα), interferon-γ (IFN-γ), IL-1ß, and thymic stromal lymphopoietin (TSLP), IL-33, IL-25 and increased the levels of filaggrin and loricrin in the oxazolone-induced AD-like mouse model. Taken together, our data suggest that eupatilin is a potential candidate for the treatment of AD.
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Dermatitis Atópica/tratamiento farmacológico , Fármacos Dermatológicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , PPAR alfa/genética , Animales , Línea Celular Tumoral , Citocinas/genética , Citocinas/inmunología , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Relación Dosis-Respuesta a Droga , Femenino , Proteínas Filagrina , Regulación de la Expresión Génica , Inmunoglobulina E/sangre , Inmunoglobulina E/genética , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-33/genética , Interleucina-33/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Interleucinas/genética , Interleucinas/inmunología , Proteínas de Filamentos Intermediarios/genética , Proteínas de Filamentos Intermediarios/inmunología , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos BALB C , Oxazolona , PPAR alfa/inmunología , Ratas , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Linfopoyetina del Estroma TímicoRESUMEN
Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a flavonoid compound exhibiting several beneficial biological activities, including neuroprotection, anti-cancer, antinociception, chondroprotection, anti-oxidation, and anti-inflammation. Our previous study demonstrated that eupatilin specifically activates peroxisome proliferator-activated receptor alpha (PPARα) through direct binding. The PPAR subfamily includes ligand-dependent transcription factors that consist of three isotypes: PPARα, PPARß/δ, and PPARγ. All isotypes are involved in inflammation, epidermal proliferation/differentiation and skin barrier function. Among them, PPARα regulates lipid and glucose metabolism and skin homeostasis. In this study, we confirm that the ability of eupatilin as a PPARα activator significantly inhibited tumor necrosis factor-alpha (TNFα)-induced matrix metalloproteinase (MMP)-2/-9 expression and proteolytic activity in HaCaT human epidermal keratinocytes. Furthermore, we found that eupatilin subsequently suppressed IκBα phosphorylation, blocked NF-κB p65 nuclear translocation and down-regulated MAPK/AP-1 signaling via PPARα activation. Taken together, our data suggest that eupatilin inhibits TNFα-induced MMP-2/-9 expression by suppressing NF-κB and MAPK/AP-1 pathways via PPARα. Our findings suggest the usefulness of eupatilin for preventing skin aging.
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Flavonoides/administración & dosificación , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , FN-kappa B/metabolismo , PPAR alfa/agonistas , Factor de Necrosis Tumoral alfa/administración & dosificación , Línea Celular , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , PPAR alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
In this study, we aimed to demonstrate the antidiabetic potential of (E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxyphenyl)acryloyl) phenyl)-4-tert-butylbenzamide (SN158) through peroxisome proliferator-activated receptor (PPAR)-α/γ dual activation. SN158 interacted with both PPARα and PPARγ, and increased their transcriptional activities. Simultaneously, SN158 treatment led to an increase in adipogenic differentiation of 3T3-L1 preadipocytes and fatty acid oxidation in hepatocytes. In addition, glucose uptake in myotubes was significantly increased by SN158 treatment. Finally, SN158 significantly lowered the plasma levels of glucose, triglycerides, and free fatty acids in ob/ob mice without severe weight gain and hepatomegaly. These results suggest that SN158 can be useful as a potential therapeutic agent against type 2 diabetes and related metabolic disorders by alleviating glucose and lipid abnormalities.
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Benzamidas/farmacología , Chalconas/farmacología , Hipoglucemiantes/farmacología , PPAR alfa/agonistas , PPAR delta/agonistas , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adiponectina/genética , Animales , Benzamidas/administración & dosificación , Glucemia/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Diferenciación Celular/efectos de los fármacos , Chalconas/administración & dosificación , Ácidos Grasos/metabolismo , Ácidos Grasos no Esterificados/sangre , Hipoglucemiantes/administración & dosificación , Masculino , Ratones Endogámicos C57BL , Oxidorreductasas/metabolismo , Pioglitazona , ARN Mensajero/metabolismo , Estereoisomerismo , Tiazolidinedionas/farmacología , Transcripción Genética , Triglicéridos/sangreRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jawoongo is a traditional drug ointment (with a traditional botanic formula) used for the treatment of burns and wounds in Korea. One of the components of Jawoongo is Lithospermi Radix (LR, the dried root of Lithospermum erythrorhizon Siebold & Zucc., also known as Zicao or Gromwell), which contains deoxyshikonin and its derivatives. OBJECTIVE: The aim of the present study was to investigate the effects of deoxyshikonin on wound healing. MATERIALS AND METHODS: The effects of LR extract and deoxyshikonin on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVEC) and HaCaT cells, respectively. We evaluated protein expression of mitogen-activated protein kinase (MAPK) activation by Western blotting. The wound healing effects of deoxyshikonin was assessed in a mouse model of cutaneous wounds. RESULTS: The results showed that deoxyshikonin enhanced tube formation in HUVEC and migration in HaCaT cells. From the western blot analysis, we found that deoxyshikonin stimulated the phosphorylation of p38 and extracellular signal-regulated kinase (ERK) in HaCaT cells. Moreover, 20µm deoxyshikonin-treated groups showed accelerated wound closure compared with the controls in a mouse model of cutaneous wounds. CONCLUSION: In conclusion, the current data indicate that deoxyshikonin treatment elevated tube formation in HUVECs, and that deoxyshikonin-induced proliferation and migration in HaCaT cells were mediated by the activation of ERK and p38 MAPKs, respectively. Collectively, these data suggest that deoxyshikonin in Jawoongo must be an active compound for may be wound healing.
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Lithospermum , Naftoquinonas/farmacología , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Línea Celular Transformada , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Relación Dosis-Respuesta a Droga , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Naftoquinonas/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Distribución Aleatoria , Cicatrización de Heridas/fisiologíaRESUMEN
Peroxisome proliferator-activated receptors (PPARs) are key nuclear receptors and therapeutic targets for the treatment of metabolic diseases through the regulation of insulin resistance, diabetes, and dyslipidemia. Although a few drugs that target PPARs have been approved, more diverse and novel PPAR ligands are necessary to improve the safety and efficacy of available drugs. To expedite the search for new natural agonists of PPARs, we developed a screening assay based on ultrafiltration liquid chromatography-mass spectrometry (LC-MS) that is compatible with complex samples such as dietary foods or botanical extracts. The known PPARα and/or PPARγ ligands resveratrol and rosiglitazone were used as positive controls to validate the developed method. When applied to the screening of an Artemisia argyi extract, eupatilin was identified as a selective PPARα ligand. A PPAR competitive binding assay based on FRET detection also confirmed eupatilin as a selective PPARα agonist exhibiting a binding affinity of 1.18 µM (IC50). Furthermore, eupatilin activation of the transcriptional activity of PPARα was confirmed using a cell-based transactivation assay. Thus, ultrafiltration LC-MS is a suitable assay for the identification of PPAR ligands in complex matrixes such as extracts of dietary foods and botanicals.
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Artemisia/química , Flavonoides , PPAR alfa , Activación Transcripcional/efectos de los fármacos , Línea Celular , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacocinética , Flavonoides/farmacología , Humanos , PPAR alfa/agonistas , PPAR alfa/química , PPAR alfa/metabolismo , Unión ProteicaRESUMEN
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and consist of three isotypes: PPARα, PPARß/δ and PPARγ. PPARs are expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, these receptors are highly studied in dermato-endocrine research, and their ligands are targets for the treatment of various skin disorders, such as photoageing and chronological ageing of skin. Intensive studies have revealed that PPARα/γ functions in photoageing and age-related inflammation by regulating matrix metalloproteinases (MMPs) via nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). However, the detailed mechanism of PPARα/γ's role in photoageing has not yet been elucidated. In this study, we confirmed that abietic acid (AA) is a PPARα/γ dual ligand and significantly decreased UVB-induced MMP-1 expression by downregulating UVB-induced MAPK signalling and downstream transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in Hs68 human dermal fibroblast cells. Treatment of cells with AA and GW6471 or bisphenol A diglycidyl ether (BADGE), PPARα or PPARγ antagonists, respectively, reversed the effect on UVB-induced MMP-1 expression and inflammatory signalling pathway activation. Taken together, our data suggest that AA acts as a PPARα/γ dual activator to inhibit UVB-induced MMP-1 expression and age-related inflammation by suppressing NF-κB and the MAPK/AP-1 pathway and can be a useful agent for improving skin photoageing.
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Abietanos/química , Fibroblastos/citología , Metaloproteinasa 1 de la Matriz/metabolismo , PPAR alfa/metabolismo , PPAR gamma/metabolismo , Piel/metabolismo , Factor de Transcripción AP-1/metabolismo , Transporte Activo de Núcleo Celular , Línea Celular , Fibroblastos/metabolismo , Humanos , Inflamación , Ligandos , Luz , Transducción de Señal , Piel/efectos de los fármacos , Envejecimiento de la Piel , Fenómenos Fisiológicos de la Piel , Factor de Transcripción ReIA/metabolismo , Rayos UltravioletaRESUMEN
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, their ligands are targets for the treatment of various skin disorders, such as photo-aging and chronological aging of skin. Intensive studies have revealed that PPARα/γ functions in photo-aging and age-related inflammation by regulating matrix metalloproteinases (MMPs) via activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). However, the detailed mechanism of PPARα/γ's role in skin aging has not yet been elucidated. In this study, we confirmed that sargahydroquinoic acid (SHQA) as a PPARα/γ ligand significantly decreased Tumor Necrosis Factor-alpha (TNFα)-induced MMP-2/-9 expression by downregulating TNFα-induced transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in HaCaT human epidermal keratinocyte cells. Treatment of cells with SHQA and GW6471 (PPARα antagonist) not bisphenol A diglycidyl ether (PPARγ antagonists), reversed the effect on TNFα-induced inflammatory signaling pathway activation. Taken together, our data suggest that SHQA inhibit TNFα-induced MMP-2/-9 expression and age-related inflammation by suppressing AP-1 and NF-κB pathway via PPARα.
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Alquenos/farmacología , Benzoquinonas/farmacología , FN-kappa B/metabolismo , PPAR alfa/agonistas , Transducción de Señal/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo , Factor de Necrosis Tumoral alfa/fisiología , Secuencia de Bases , Línea Celular , Cartilla de ADN , Humanos , FosforilaciónRESUMEN
The present study investigated the presence and mechanism of esculin-mediated renoprotection to assess its therapeutic potential. Esculin was orally administered at 20 mg/kg/day for 2 weeks to streptozotocin-induced diabetic mice, and its effects were compared with those of the vehicle in normal and diabetic mice. After oral administration of esculin to mice, the concentrations of esculin and esculetin in blood were 159.5 ± 29.8 and 9.7 ± 4.9 ng/mL at 30 min, respectively. Food and water intake were significantly increased in the diabetic mice compared to normal mice but attenuated in mice receiving esculin. The elevated blood glucose level and hepatic glucose-6-phosphatase expression were significantly reduced in esculin-treated diabetic mice, supporting the antidiabetic effect of esculin. Esculin also increased the uptake of glucose and induced the insulin-evoked phosphorylation of insulin receptor, Akt, and glycogen synthase kinase 3ß in C2C12 myotubes, indicating a potential for improvement of insulin sensitivity. In addition, esculin lessened the elevated blood creatinine levels in diabetic mice and ameliorated diabetes-induced renal dysfunction by reducing caspase-3 activation in the kidney. Data support the beneficial effect of esculin against diabetes and oxidative stress-related inflammatory processes in the kidney.
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Nefropatías Diabéticas/prevención & control , Esculina/administración & dosificación , Riñón/efectos de los fármacos , Animales , Glucemia/metabolismo , Caspasa 3/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Humanos , Insulina/metabolismo , Riñón/enzimología , Masculino , Ratones , Ratones Endogámicos ICR , Estreptozocina/efectos adversosRESUMEN
Thin pDMAEMA shells were formed on the surface of silica nanoparticles via vapor deposition polymerization. Scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and elemental analysis have been used to characterize the resulting pDMAEMA-coated silica nanoparticles. Electron microscopy studies reveal that the thin polymer shell is formed on the silica surface. In this work, the particle diameter can be controlled (from ~19 to ~69 nm) by varying the size of silica core. The antibacterial performance of the core-shell nanoparticles was investigated against both Gram-positive (Escherichia coli) and Gram-negative (Staphylococcus aureus) bacteria. Importantly, the nano-sized pDMAEMA particles presented antibacterial activity against both bacteria without additional quaternization due to its enlarged surface area. Additionally, the bactericidal efficiency was enhanced by reducing the particle size, because the expanded surface area of the cationic polymer nanoparticles provides more active sites that can kill the bacteria.
Asunto(s)
Antibacterianos/química , Metacrilatos/química , Nanopartículas/química , Nylons/química , Dióxido de Silicio/química , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Staphylococcus aureus/efectos de los fármacosRESUMEN
Obesity is an important and preventable risk factor for renal disease. The administration of an antioxidant with a lipid-lowering effect is an important therapeutic approach for kidney disease in obese patients. The present study was conducted to examine whether methanolic extract of Dendrobium moniliforme (DM), one of the most famous traditional medicines used in many parts of the world, has an antioxidant effect in vitro and an ameliorative effect on high-fat diet (HFD)-induced alterations such as renal dysfunction and lipid accumulation in vivo. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of DM extract (IC(50) = 29.6 µg/mL) was increased in a dose-dependent manner. The LLC-PK1 kidney cell damage induced by oxidative stress was significantly inhibited by the treatments with DM extract. In the animal study, DM extract (200 mg/kg) was orally administered every day for nine weeks to HFD-fed mice, and its effect was compared with that of metformin. The administration of DM extract decreased the elevated serum glucose, total cholesterol concentration and renal lipid accumulation in HFD-fed mice. It also ameliorated renal dysfunction biomarkers including serum creatinine and renal collagen IV deposition. Taken together, these results provide important evidence that DM extract exhibits a pleiotropic effect on obesity induced parameters and exerted a renoprotective effect in HFD-fed mice.
Asunto(s)
Dendrobium/química , Grasas de la Dieta/administración & dosificación , Riñón/efectos de los fármacos , Estrés Oxidativo , Extractos Vegetales/farmacología , Animales , Glucemia/análisis , Riñón/metabolismo , Células LLC-PK1 , Masculino , Ratones , Ratones Endogámicos C57BL , PorcinosRESUMEN
The aim of the present study was to verify the important role of Maillard reaction in the protective effect of heat-processed ginsenoside Re-serine mixture against oxidative stress-induced nephrotoxicity. The free radical-scavenging activity of ginsenoside Re-serine mixture was increased by heat-processing. Ginsenoside Re was transformed into less-polar ginsenosides such as Rg(2), Rg(6) and F(4) by heat-processing, and the glucose molecule at carbon-20 was separated. The improved-free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant Maillard reaction products (MRPs) from the reaction of glucose with serine. Moreover, MRPs from ginsenoside Re-serine mixture showed protective effect against cisplatin-induced renal epithelial cell damage.
Asunto(s)
Antineoplásicos/toxicidad , Antioxidantes/farmacología , Cisplatino/toxicidad , Citoprotección/efectos de los fármacos , Ginsenósidos/farmacología , Serina/farmacología , Animales , Antioxidantes/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citotoxinas/toxicidad , Ginsenósidos/química , Calor , Riñón/citología , Riñón/efectos de los fármacos , Células LLC-PK1 , Reacción de Maillard/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Panax/química , Serina/química , PorcinosRESUMEN
Novel ZnO/TiO(2) composite nanofibers were fabricated by an electrospinning method and showed excellent antimicrobial activity against gram-negative Escherichia coli and gram-positive Staphylococcus aureus under UV irradiation and in the absence of light.