RESUMEN
Lupus peritonitis (LP) is extremely rare. Acute LP is characterized by rapid onset of ascites and severe abdominal pain, in addition to other well-recognized clinical features of a general systemic lupus erythematosus (SLE) fare. Ascites associated with acute LP has been rarely reported as the prominent feature of a SLE fare. We report a 39-year-old woman who developed massive, painful ascites as the presenting manifestation of a SLE fare. Diagnostic workup ruled out the possibility of hepatic, cardiovascular, infectious, or malignant diseases, and confirmed the presence of a SLE fare. The patient was treated with methyl prednisolone and hydroxychloroquine resulting in dramatic improvement of her condition. During ambulatory follow up, she has remained asymptomatic up to the moment of this writing. Adrenal steroids and hydrocychloroquine may be useful for the management of SLE fares in patients with massive, painful ascites due to acute LP.
Asunto(s)
Ascitis/etiología , Lupus Eritematoso Sistémico/complicaciones , Peritonitis/etiología , Adulto , Ascitis/diagnóstico , Femenino , Humanos , Peritonitis/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Diabetic retinopathy is one of the most common and severe complications of diabetes mellitus. Arctiin, a bioactive compound isolated from the dry seeds of Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on the serum glucose and HBA1c levels, the blood viscosity, and VEGF expression in the retinal tissues of rats with diabetic retinopathy. We first extracted arctiin from Fructus Arctii and then investigated its chemopreventive effect on streptozotocin-induced diabetic retinopathy in male Sprague-Dawley rats. After the induction of diabetes using streptozotocin (30 mg/kg, i. p.), the rats were randomly divided into five groups (n = 20 per group) and treated with intragastric doses of 30, 90, or 270 mg/kg/d wt of arctiin, 100 mg/kg/d wt of calcium dobesilate, or 0.5 % CMC-Na. Twenty nondiabetic sham-treated rats were treated with 0.5 % CMC-Na. The occurrence of diabetic retinopathy did not differ dramatically among the groups. However, at week 16, the glycosylated haemoglobin (HBA1c) level was significantly decreased in all of the arctiin-treated groups when compared with the control group, and the serum glucose level was also decreased in the rats treated with the highest dose of arctiin. In addition, treatment with arctiin ameliorated retinal oedema, detachment of the retina, and VEGF expression in the retina, as detected using histological and immunochemical examinations. Finally, arctiin increased the viability of retinal microvascular endothelial cells in vitro. Together, these findings demonstrate that arctiin decreases the severity of diabetic complications, demonstrating the importance of this compound as an inhibitor of diabetic retinopathy.
Asunto(s)
Retinopatía Diabética/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Furanos/uso terapéutico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Animales , Arctium/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/inducido químicamente , Retinopatía Diabética/etiología , Furanos/aislamiento & purificación , Glucósidos/aislamiento & purificación , Hemoglobina Glucada/efectos de los fármacos , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Semillas/química , EstreptozocinaRESUMEN
Reactive oxygen species (ROS) are essential in regulating various physiological functions. However, overproduction of ROS is implicated in the pathogenesis of various inflammatory diseases. Antioxidant therapy has thus represented an effective strategy for the treatment of oxidative stress relevant inflammatory diseases. Conventional anti-oxidative agents showed limited in vivo effects owing to their non-specific distribution and low retention in disease sites. Over the past decades, significant achievements have been made in the development of antioxidant nanotherapies that exhibit multiple advantages such as excellent pharmacokinetics, stable anti-oxidative activity, and intrinsic ROS-scavenging properties. This review provides a comprehensive overview on recent advances in antioxidant nanotherapies, including ROS-scavenging inorganic nanoparticles, organic nanoparticles with intrinsic antioxidant activity, and drug-loaded anti-oxidant nanoparticles. We highlight the biomedical applications of antioxidant nanotherapies in the treatment of different inflammatory diseases, with an emphasis on inflammatory bowel disease, cardiovascular disease, and brain diseases. Current challenges and future perspectives to promote clinical translation of antioxidant nanotherapies are also briefly discussed.
RESUMEN
As the most potent vasoconstrictor in mammals, urotensin II (U II) has recently been demonstrated to play an important role in adverse cardiac remodeling and fibrosis. However, the mechanisms of U II-induced myocardial fibrosis remain to be clarified. We postulated that U II alters transforming growth factor-beta1 (TGF-beta1) expression, and thereby modulates cardiac fibroblast collagen metabolism. Experiments were conducted using cardiac fibroblast from neonatal Wistar rats to determine the expression of TGF-beta1, and the role of U II receptor UT in this process. The functional role of TGF-beta1 and UT in modulating U II effects on type I, III collagen mRNA expression and 3H-proline incorporation was also analyzed. TGF-beta1 gene and protein expression were consistently identified in quiescent cardiac fibroblasts. U II increased the expression of TGF-beta1 mRNA and protein in a time-dependent manner. This effect was UT mediated, because UT antagonist urantide abolished U II-induced TGF-beta1 expression. U II-induced increase in type I, III collagen mRNA expression and 3H-proline incorporation were both inhibited by a specific TGF-beta1 neutralizing antibody and UT receptor antagonist urantide. Hence, our results indicate that TGF-beta1 is upregulated in cardiac fibroblasts by U II via UT and modulates profibrotic effects of U II. These findings provide novel insights into U II-induced cardiac remodeling.
Asunto(s)
Colágeno/metabolismo , Fibroblastos/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Urotensinas/farmacología , Animales , Animales Recién Nacidos , Células Cultivadas , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Miocardio/citología , Miocardio/metabolismo , Fragmentos de Péptidos/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Wound healing is a complex pathophysiological process that occurs frequently in everyday pathology and remains a challenge during the treatment of trauma. Previously, we prepared silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol) (PVA/COS-AgNP) nanofibers via an electrospinning technique. These nanofibers promoted the proliferation of human skin fibroblasts (HSFs) and the expression of transforming growth factor TGF-ß1 in the early stage of wound repair, although the specific mechanisms remain unclear. Therefore, considering that TGF-ß1 has emerged as a major modulator of wound healing, the objective of this study was to further understand whether the molecular mechanisms responsible for PVA/COS-AgNP nanofiber-mediated wound healing include the TGF-ß1/Smad signal transduction pathway. In this study, we used human skin fibroblasts (HSFs) to investigate the molecular and cellular mechanisms underlying PVA/COSAgNP nanofiber-mediated wound healing. Cell adhesion and proliferation experiments, immunofluorescence staining, hydroxyproline content measurements, flow cytometry, quantitative real-time PCR (qRT-PCR), and western blotting (WB) were used to analyze the wound healing mechanisms of human skin fibroblasts treated with various concentrations of PVA/COS-AgNP nanofibers and the combined application of silver nanofibers and SB431542 (an inhibitor of the TGF-ß1 receptor kinase). Our study showed that PVA/COS-AgNP nanofibers markedly promoted fibroblast proliferation, collagen synthesis, and cell adherence. We also found that treating fibroblasts with PVA/COS-AgNP nanofibers stimulated cell cycle progression from G1 into the S and G2 phases, reducing the proportion of cells in the G0/G1 phase and inducing S and G2/M arrest. Importantly, the cell factors associated with the TGF-ß1/Smad signal transduction pathway, such as TGF-ß1, TGFßRI, TGFßRII, pSmad2, pSmad3, collagen I, collagen III, and fibronectin were also up-regulated. Moreover, this enhancing effect was markedly inhibited by the TGFßRI receptor inhibitor, SB431542. Therefore, the PVA/COS-AgNP nanofibers used to accelerate wound healing do so by activating the TGF-ß1/Smad signal transduction pathway.
Asunto(s)
Quitosano/farmacología , Nanopartículas del Metal/química , Nanofibras/química , Plata/farmacología , Cicatrización de Heridas/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Quitosano/química , Técnicas Electroquímicas , Fibroblastos/efectos de los fármacos , Humanos , Alcohol Polivinílico/farmacología , Transducción de Señal/efectos de los fármacos , Plata/química , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Wound healing occupies a remarkable place in everyday pathology and remains a challenging clinical problem. In our previous study, we prepared a silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol) (PVA/COS-AgNPs) nanofiber via electrospinning and revealed that it could promote wound healing; however, the healing mechanism remained unknown. Therefore, we aimed to clarify the mechanism underlying the accelerated healing effect of the PVA/COS-AgNPs nanofiber. The TGFß1/Smad signaling pathway is actively involved in wound healing. Considering the key role of this signaling pathway in wound healing, our preliminary study showed that the TGFß1 level was significantly increased during the early stage of wound healing. Thus, in this study, hematoxylin-eosin, Masson's trichrome, immunofluorescent staining, hydroxyproline content, quantitative real-time polymerase chain reaction, and Western blot analyses were used to analyze the wound healing in a rat model treated with gauze, the PVA/COS-AgNPs nanofiber, and the nanofiber plus SB431542 (an inhibitor of TGFß1 receptor kinase). The results showed that the PVA/COS-AgNPs nanofiber promoted wound healing and upregulated the expression levels of cytokines associated with the TGFß1/Smad signaling pathway such as TGFß1, TGFßRI, TGFßRII, collagen I, collagen III, pSmad2, and pSmad3. Inhibiting this pathway with SB431542 resulted in prevention of the PVA/COS-AgNPs nanofiber-associated salutary effects on the early stage of wound healing and relative cytokines expression. In conclusion, the wound healing effect of the PVA/COS-AgNPs nanofiber involves activation of the TGFß1/Smad signaling pathway.
Asunto(s)
Quitosano/química , Nanopartículas del Metal/administración & dosificación , Nanofibras/administración & dosificación , Plata/química , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Animales , Vendajes , Western Blotting , Técnica del Anticuerpo Fluorescente , Técnicas para Inmunoenzimas , Masculino , Nanopartículas del Metal/química , Nanofibras/química , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismo , Proteínas Smad/genética , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Hypericin (HY) is a promising photosensitizer (PS) for use in photodynamic therapy (PDT). Port-wine stains (PWSs) are congenital superficial dermal capillary malformations. In this study, we evaluated the photocytotoxic effects of HY for PDT in human vascular endothelial cells and a chicken cockscomb model. HY significantly inhibited the growth of human umbilical vein endothelial cells (HUVECs), as determined by colorimetric assays and morphological observation, and flow cytometry assays indicated induction of apoptosis and collapse of the mitochondrial membrane potential. In addition, HY more effectively inhibited growth of and induced apoptosis in HUVECs compared with hematoporphyrin (HP). Further experiments performed in a Roman chicken cockscomb model also showed a clear photocytotoxic effect on the cockscomb dermal capillary upon intravenous injection of HY. This effect may be due to the role of HY in the induction of apoptosis. Transmission electron microscopical analysis showed mitochondrial morphological changes such as incomplete ridges and swelling, and immunohistochemical assays showed an increase in the release of cytochrome c. In conclusion, HY exhibited a greater photocytotoxic activity than did HP toward the growth of endothelial cells and may thus represent a potent PS for PWS PDT.
Asunto(s)
Apoptosis/efectos de los fármacos , Capilares/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Hematoporfirinas/farmacología , Modelos Biológicos , Perileno/análogos & derivados , Antracenos , Línea Celular , Citocromos c/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/enzimología , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Perileno/farmacología , FotoquimioterapiaRESUMEN
Lupus peritonitis (LP) is extremely rare. Acute LP is characterized by rapid onset of ascites and severe abdominal pain, in addition to other well-recognized clinical features of a general systemic lupus erythematosus (SLE) fare. Ascites associated with acute LP has been rarely reported as the prominent feature of a SLE fare. We report a 39-year-old woman who developed massive, painful ascites as the presenting manifestation of a SLE fare. Diagnostic workup ruled out the possibility of hepatic, cardiovascular, infectious, or malignant diseases, and confirmed the presence of a SLE fare. The patient was treated with methyl prednisolone and hydroxychloroquine resulting in dramatic improvement of her condition. During ambulatory follow up, she has remained asymptomatic up to the moment of this writing. Adrenal steroids and hydrocychloroquine may be useful for the management of SLE fares in patients with massive, painful ascites due to acute LP.
La peritonitis lúpica es rara. El cuadro agudo se caracteriza por ascitis de comienzo rápido, dolor abdominal severo y otras manifestaciones de una recidiva de un lupus eritematoso sistémico (LES). Sólo ocasionalmente e ha informado que la ascitis y peritonitis lúpica sean las principales manifestaciones de una recidiva lúpica. Presentamos a una mujer de 39 años que presentó ascitis masiva y dolorosa como la primera manifestación de una reactivación lúpica. El estudio diagnóstico descartó problemas hepáticos, pulmonares, cardiacos, cáncer o infecciones y confirmó la reactivación lúpica. La paciente se trató con metilprednisolona y cloroquina, resultando en una mejoría dramática. Al momento de preparar este informe, la paciente permanece asintomática en control ambulatorio. Los corticoides y cloroquina pueden ser medicamentos útiles para el tratamiento de pacientes con ascitis dolorosa y masiva secundaria a peritonitis lúpica.