Doxorubicin-Induced Cardiotoxicity: From Mechanisms to Development of Efficient Therapy

First isolated in the early 1960s, doxorubicin (DOX) is among the most effective anticancer agents ever developed. DOX has been used mainly for the treatment of breast cancer, solid tumors in children, soft tissue sarcomas, and aggressive lymphomas. However, the use of DOX may have dose-dependent cardiotoxic effects that generate changes in myocardial structure, which can develop into severe and irreversible cardiomyopathy. Here, we describe the incidence of DOX-induced cardiotoxicity (DIC); the progress made over the past four decades in understanding the molecular mechanisms of the pathogenesis of acute and chronic DIC; the current strategies for heart protection; and the major breakthroughs and challenges in basic and clinical research to the development of efficient targeted therapy for DIC

Junction communication in the immune system: modulation of the GAP junctions by infection with Toxoplasma gondii / Comunicação juncional no sistema imunológico: modulação das junções GAP em infecção por Toxoplasma gondii

RETOMARO Toxoplasma gondii é um protozoário parasita responsável pela toxoplasmose, podendo estar causando problemas em diferentes sistemas. Algumas dessas complicações estão associadas à alteração da comunicação intercelular mediada por Junctions Communicators que permite a comunicação direta entre os tecidos. No entanto, ainda existem sistemas que não são totalmente consistentes com a comunicação juncional, incluindo o sistema imunológico inato, representado pelos macrófagos. Assim, neutralizou a cultura da linha celular do macrófago J774-G8 infectada pela cepa RH de Toxoplasma em sua forma de taquizoíta.Os resultados revelaram que nas células J774-G8 as proteínas Cx43 e Phalloidina interagem na membrana plasmática da linhagem J774-G8, sofrendo uma sensibilidade redução na membrana após 72 horas da infecção pelo parasita. Toxoplasma gondii . A avaliação da expressão da proteína Cx43 por transferência imunoeletroforética alterada (elevada) em células de macrófagos J774-G8 infectadas com o parasita Toxoplasma gondii 24 e 48 horas em comparação com células não infectadas

Morphological evaluation of macrophage infected with Toxoplasma Gondii / Avaliação morfológica de macrófagos infectados com Toxoplasma Gondii

O Toxoplasma gondii é o parasita causador da toxoplasmose, doença negligenciada que ainda carece de estudos que visem elucidar a relação entre a parasitemia e o sistema imunológico. Uma das principais células do sistema imunológico são os macrófagos e estes possuem linhagens celulares imortalizadas que fornecem um modelo de estudo acessível para experimentos in vitro . Com isso, este trabalho pretende enfatizar a importância da linhagem de macrófagos J774G8 em estudos com protozoários, destacando a viabilidade e alterações morfológicas da cultura de células infectadas com Toxoplasma gondii

Morphological evaluation of intestinal epithelial cells infected with toxoplasma gondii: Avaliação morfológica de células do epitelial intestinal infectadas com toxoplasma gondii

Toxoplasmosis is a disease caused by intracellular obligate protozoan, Toxoplasma gondii. And it can be obtained mainly through the oral route, through the ingestion of oocysts or tissue cysts. For this reason, the intestinal epithelium is a cellular model that makes it possible to study the first line of defense against this type of infection. After infection, the protozoan invades intestinal cells, changing the physiology and functions of the intestinal epithelial barrier. In view of this, we analyzed the morphological changes and the microenvironment, in vitro, which are modified in the intestinal epithelial cell during the process of infection and evasion of Toxoplasma gondii

Intrinsic Angiogenic Potential and Migration Capacity of Human Mesenchymal Stromal Cells Derived from Menstrual Blood and Bone Marrow

Several therapies are being developed to increase blood circulation in ischemic tissues. Despite bone marrow-derived mesenchymal stromal cells (bmMSC) are still the most studied, an interesting and less invasive MSC source is the menstrual blood, which has shown great angiogenic capabilities. Therefore, the aim of this study was to evaluate the angiogenic properties of menstrual blood-derived mesenchymal stromal cells (mbMSC) in vitro and in vivo and compared to bmMSC. MSC’s intrinsic angiogenic capacity was assessed by sprouting and migration assays. mbMSC presented higher invasion and longer sprouts in 3D culture. Additionally, both MSC-spheroids showed cells expressing CD31. mbMSC and bmMSC were able to migrate after scratch wound in vitro, nonetheless, only mbMSC demonstrated ability to engraft in the chick embryo, migrating to perivascular, perineural, and chondrogenic regions. In order to study the paracrine effects, mbMSC and bmMSC conditioned mediums were capable of stimulating HUVEC’s tube-like formation and migration. Both cells expressed VEGF-A and FGF2. Meanwhile, PDGF-B was expressed exclusively in mbMSC. Our results indicated that mbMSC and bmMSC presented a promising angiogenic potential. However, mbMSC seems to have additional advantages since it can be obtained by non-invasive procedure and expresses PDGF-B, an important molecule for vascular formation and remodeling

Safety and Localization of Mesenchymal Stromal Cells Derived from Human Adipose Tissue-Associated Hyaluronic Acid: A Preclinical Study

Millions of plastic surgeries are performed worldwide every year with the objective of correcting lipodystrophies stemming from lesions, tumor resections, birth defects, and AIDS-associated antiretroviral therapy. Besides that, a large number of clinical research have assessed the outcome of procedures that rely on combinations of dermal fillers and autologous cells. However, little is known about the safety of these combinations and the localization of the injected cells. The aim of this study was to test the toxicity of a solution containing 1% hyaluronic acid (HA) and adipose-derived stromal cells (ASCs) from the human adipose tissue and to assess the localization of the injected cells, with and without HA, labeled with technetium-99m. Rats received subcutaneous and intraperitoneal injections of a solution containing 1% HA/adipose-derived stromal cells isolated from the human fat tissue. The animals were then observed for up to forty-two days. The solution tested in this study did not result in systemic, biochemical, or anatomic alterations that could represent toxicity symptoms. The association of HA and ASCs labeled with technetium-99m remained at the site of the injection within a period of twenty-four hours, as demonstrated by a whole-body imaging software fusion of SPECT and CT. In conclusion, our study shows that the subcutaneous and intraperitoneal injection of HA associated with adipose-derived stromal cells (ASCs) is safe. The association of HA and ASCs did not induce local or systemic toxicity. Thus, the administration of volume equal to or less than 0.2 mL of the agent filler (1×106 ASC+HA 1%) should be considered for subsequent studies and may be an alternative to dermal fillers due to the expected lasting effects

Gene expression changes associated with myocarditis and fibrosis in hearts of mice with chronic chagasic cardiomyopathy

Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries. About 30% of Trypanosoma cruzi-infected individuals develop this severe symptomatic form of the disease, characterized by intense inflammatory response accompanied by fibrosis in the heart.We performed an extensive microarray analysis of hearts from a mouse model of this disease and identified significant alterations in expression of ~12% of the sampled genes. Extensive up-regulations were associated with immune-inflammatory responses (chemokines, adhesion molecules, cathepsins, and major histocompatibility complex molecules) and fibrosis (extracellular matrix components, lysyl oxidase, and tissue inhibitor of metalloproteinase 1). Our results indicate potentially relevant factors involved in the pathogenesis of the disease that may provide newtherapeutic targets in chronic Chagas disease. © 2010 by the Infectious Diseases Society of America