Effects of a 300 mT static magnetic field on human umbilical vein endothelial cells.

none8This study describes the effects of a static magnetic field (SMF) on cell growth and DNA integrity of human umbilical vein endothelial cells (HUVECs). Fast halo assay was used to investigate nuclear damage; quantitative polymerase chain reaction (QPCR), standard PCR, and real-time PCR were used to evaluate mitochondrial DNA integrity, content, and gene expression. HUVECs were continually exposed to a 300mT SMF for 4, 24, 48, and 72 h. Compared to control samples (unexposed cultures) the SMF-exposed cells did not show a statistically significant change in their viability. Conversely, the static field was shown to be significant after 4 h of exposure, inducing damage on both the nuclear and mitochondrial levels, reducing mitochondrial content and increasing reactive oxygen species. Twentyfour hours of exposure increased mitochondrial DNA content as well as expression of one of the main genes related to mitochondrial biogenesis. No significant differences between exposed and sham cultures were found after 48 and 72 h of exposure. The results suggest that a 300mT SMF does not cause permanent DNA damage in HUVECs and stimulates a transient mitochondrial biogenesis. BioelectromagneticsopenPOTENZA L; MARTINELLI C; POLIDORI E; DONATI ZEPPA, S; CALCABRINI C; STOCCHI L; SESTILI P; STOCCHI V;Potenza, LUCIA ANNA MARIA; Martinelli, Chiara; Polidori, Emanuela; DONATI ZEPPA, Sabrina; Calcabrini, Cinzia; Stocchi, L; Sestili, Piero; Stocchi, Vilbert

O CUIDADO EM SAÚDE E AS IMPLICAÇÕES PARA OS CUIDADORES DOMICILIARES

RESUMO: O artigo trata da temática do cuidado domiciliar em saúde, modalidade de atendimento que tem crescido em vários países, impulsionada pelas transições demográficas e epidemiológicas dos últimos anos. Com foco em duas experiências, o trabalho apresenta os resultados de uma pesquisa com o objetivo de analisar o perfil dos cuidadores de dois programas de atenção em saúde domiciliar sendo, um público e outro privado desenvolvido em cidades localizadas na Região da Grande Florianópolis. Trata-se de uma pesquisa qualitativa com aplicação de entrevistas com cuidadores de pessoas em internação domiciliar. Como principais resultados aponta-se que a família tem sido cada vez mais responsabilizada pelo cuidado em saúde, principalmente as mulheres alterando a dinâmica familiar que implica nas condições objetivas de vida

Supplementing Soy-Based Diet with Creatine in Rats: Implications for Cardiac Cell Signaling and Response to Doxorubicin.

Nutritional habits can have a significant impact on cardiovascular health and disease. This may also apply to cardiotoxicity caused as a frequent side effect of chemotherapeutic drugs, such as doxorubicin (DXR). The aim of this work was to analyze if diet, in particular creatine (Cr) supplementation, can modulate cardiac biochemical (energy status, oxidative damage and antioxidant capacity, DNA integrity, cell signaling) and functional parameters at baseline and upon DXR treatment. Here, male Wistar rats were fed for 4 weeks with either standard rodent diet (NORMAL), soy-based diet (SOY), or Cr-supplemented soy-based diet (SOY + Cr). Hearts were either freeze-clamped in situ or following ex vivo Langendorff perfusion without or with 25 μM DXR and after recording cardiac function. The diets had distinct cardiac effects. Soy-based diet (SOY vs. NORMAL) did not alter cardiac performance but increased phosphorylation of acetyl-CoA carboxylase (ACC), indicating activation of rather pro-catabolic AMP-activated protein kinase (AMPK) signaling, consistent with increased ADP/ATP ratios and lower lipid peroxidation. Creatine addition to the soy-based diet (SOY + Cr vs. SOY) slightly increased left ventricular developed pressure (LVDP) and contractility dp/dt, as measured at baseline in perfused heart, and resulted in activation of the rather pro-anabolic protein kinases Akt and ERK. Challenging perfused heart with DXR, as analyzed across all nutritional regimens, deteriorated most cardiac functional parameters and also altered activation of the AMPK, ERK, and Akt signaling pathways. Despite partial reprogramming of cell signaling and metabolism in the rat heart, diet did not modify the functional response to supraclinical DXR concentrations in the used acute cardiotoxicity model. However, the long-term effect of these diets on cardiac sensitivity to chronic and clinically relevant DXR doses remains to be established

Effects of Reactive Oxygen Species on Mitochondrial Content and Integrity of Human Anastomotic Colorectal Dehiscence: A Preliminary DNA Study

BACKGROUND: Anastomotic dehiscence is one of the most severe complications of colorectal surgery. Gaining insight into the molecular mechanisms responsible for the development of anastomotic dehiscence following colorectal surgery is important for the reduction of postoperative complications. OBJECTIVE: Based on the close relationship between surgical stress and oxidative stress, the present study aimed to determine whether a correlation exists between increased levels of reactive oxygen species and colorectal anastomotic dehiscence. METHODS: Patients who underwent surgical resection for colorectal cancer were divided into three groups: patients with anastomotic dehiscence (group 1); patients without dehiscence who underwent neoadjuvant radiochemotherapy (group 2); and patients without anastomotic dehiscence who did not undergo neoadjuvant radiochemotherapy (group 3). Quantitative polymerase chain reaction and real-time polymerase chain reaction assays were performed to measure nuclear DNA and mitochondrial DNA (mtDNA) content, and possible oxidative damage to nonmalignant colon and rectal tissues adjacent to the anastomoses. RESULTS: mtDNA content was reduced in the colon tissue of patients in groups 1 and 2. Rectal mtDNA was found to be more damaged than colonic mtDNAs in all groups. The 4977 bp common deletion was observed in the mtDNA of tissues from both the colon and rectum of all patients. DISCUSSION: Patients in groups 1 and 2 were more similar to one another than to group 3, probably due to higher levels of reactive oxygen species in the mitochondria; the greater damage found in the rectum suggests that dehiscence originates primarily from the rectal area. CONCLUSIONS: The present study of mtDNA analyses of normal human colon and rectal tissues from patients with colorectal cancer is among the first of its kind

Marine Sponge Natural Products with Anticancer Potential: An Updated Review

Despite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored in the oncological field because of the possibility of identifying novel molecular therapeutics. Marine sponges are a prolific source of secondary metabolites, a number of which showed intriguing tumor chemopreventive and chemotherapeutic properties. Recently, Food and Drug Administration-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin’s disease. The chemopreventive and potential anticancer activity of marine sponge-derived compounds could be explained by multiple cellular and molecular mechanisms, including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory activities as well as their ability to chemosensitize cancer cells to traditional antiblastic chemotherapy. The present article aims to depict the multiple mechanisms involved in the chemopreventive and therapeutic effects of marine sponges and critically explore the limitations and challenges associated with the development of marine sponge-based anticancer strategy

Nrf2: a potential therapeutic target for naturally occurring anticancer drugs?

Nuclear factor (erythroid-derived-2)-like 2 is one of the most efficient cytoprotective rheostats against exogenous or endogenous oxidative insults. At present, the modulation of the Nrf2 pathway represents an interesting and highly explored strategy in the oncological area. Area covered: In this review, we present and discuss the different modulation of the Nrf2 pathway by some natural compounds with a well demonstrated anticancer activity, and critically analyze the challenges associated with the development of an Nrf2-based anticancer strategy. Expert opinion: Many natural compounds with a well-defined anticancer activity are able to modulate this pathway. Both Nrf2 inducers and inhibitors can be useful as anticancer strategy. However, since Nrf2 modulates many networks potentially involved in the detoxification process of anticancer drugs, its activation in cancer cells could lead to chemoresistance. The switch between a beneficial or detrimental role of Nrf2 in cancer cells essentially depends on the tight control of its activity, the specific conditions of tumor microenvironment, and cell type. In line with the paucity of clear data related to the mechanisms underpinning the role of Nrf2 in cancer development and chemoresistance, discovery and development of Nrf2-based strategies is one of the most critical and challenging assignments for fighting cancers

Marine sponge natural products with anticancer potential: An updated review

Despite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored in the oncological field because of the possibility of identifying novel molecular therapeutics. Marine sponges are a prolific source of secondary metabolites, a number of which showed intriguing tumor chemopreventive and chemotherapeutic properties. Recently Food and Drug Administration-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin's disease. The chemopreventive and potential anticancer activity of marine sponge-derived compounds could be explained by multiple cellular and molecular mechanisms, including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory activities as well as their ability to chemosensitize cancer cells to traditional antiblastic chemotherapy. The present article aims to depict the multiple mechanisms involved in the chemopreventive and therapeutic effects of marine sponges and critically explore the limitations and challenges associated with the development of marine sponge-based anticancer strategy

Pharmacokinetic Interactions in Combination Therapies for Acute Myeloid Leukemia

Acute myeloid leukemia is characterized by a malignant proliferation of hematopoietic progenitor cells of the myeloid lineage. The lack of differentiation of precursor cells causes their inability to function normally and the disruption of normal hematopoiesis. This review provides a brief overview of the most important pharmacological strategies that impact on acute myeloid leukemia cure rates and highlights their pharmacokinetic interactions and limitations when used in association. The widespread molecular heterogeneity of acute myeloid leukemia might lead to the identification of \u201cdruggable\u201d targets and thus to drugs with an improved therapeutic profile. However, a great deal of focus has to be given to the identification of drug associations with a favourable pharmacokinetic profile that will ultimately contribute to the improved outcomes so cogently needed in acute myeloid leukemia

PAT proteins in the lipid storage regulation in Tuber: T. melanosporum and T. aestivum/uncinatum comparison

Tuber aestivum/uncinatum is a truffle largely widespread in much of Europe. To date, there are many dilemmas about its cultivation, especially in relation to two morphological entities T. aestivum Vitt. "sensu stricto" and in T. uncinatum Chatin "sensu stricto", also characterized by different ecological and organoleptic features (differences in sporal morphology, taste and smell). The study of its biology could provide useful information to develop, in perspective, tools to define new mycorrhization techniques, and experimental fruiting and cultivation methods. For these reasons the aim of the present study was to search genes important in truffle life cycle and probably involved in T. aestivum mycorrhiza development. It has been reported that PAT (Perilipin/ADRP/TIP47) family proteins regulate the production of lipid droplets, at the bases of the typical appressorial turgor pressure. Analogously, a similar mechanism could be occurring also in Tuber, and for these reasons we focused our attention on a perilipin-like protein in T. aestivum. Starting from the sequence of Metarhizium anisopliae gene, T. melanosporum and T. aestivum perilipin-like genes were characterized. More interestingly, PCR analyses on T. melanosporum and T. aestivum fruitbody cDNAs revealed for the first time a perilipin-like gene expression in ectomycorrhizal fungi. The role of this gene/protein could be studied through gene expression analyses on in vitro cultivations performed in nutritional starvation, in order to understand the activation mechanisms of lipid metabolism during mycelial hyphal growth and mycorrhization. The knowledge on molecular mechanisms that lead to the formation of ectomycorrhiza represents an interesting challenge necessary to improve the mycorrhization technologies, as well as the carpophores productions