913 research outputs found
TNF-related apoptosis-inducing ligand (TRAIL): a potential candidate for combined treatment of hematological malignancies.
Inflammation and Cardiovascular Cross Talk in Ischemic Vascular Diseases
Ischemic vascular diseases include different pathological events characterized by distinctive features but share the common hallmark of inflammation. In this light, myocardial infarction can be a good paradigm to summarize the different connections linking inflammation and the cardiovascular system during an ischemic event. The immune system and inflammation, through several cellular and soluble inflammatory mediators, play a crucial role in the local tissue structural changes of ischemic heart disease, with a different impact and outcome during acute myocardial infarction compared to the more chronic long-term inflammation. In response to acute damage and hemodynamic stress, there is expansion of resident immune cells and recruitment of extra cells involved in a critical cross talk with parenchymal cells. In other words, postischemic tissue repair is crucial to survival. Recruited inflammatory cells can remove debris and facilitate the repair process; conversely, unrestrained inflammation inhibits optimal healing leading to adverse events. Moreover, other mediators such as some key coagulation factors might influence innate immunity as well as cell-mediated reactions like healing, response to tissue injury, or inflammatory processes. Overall, as recently suggested, the different immune/inflammatory cell subsets act as messengers implicated in novel inflammatory networks that link different organ systems enlarging the continuum beyond the myocardium and blood vessels in a more integrative pathophysiology standpoint. This special issue aims to collect insights about this cross talk with a dual purpose: on the one hand to expand the comprehension on the mechanisms of action and impact of “old” inflammatory mediators and on the other to bring out “new” potential pathways and intermediates. The overall aim is to increase knowledge on the pathophysiological processes of ischemic vascular disease to improve diagnosis and treatment
Treatment With Recombinant Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Alleviates the Severity of Streptozotocin-Induced Diabetes
OBJECTIVE: To evaluate the potential therapeutic effect of recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) treatment in a model of type 1 diabetes. RESEARCH DESIGN AND METHODS: Recombinant TRAIL was added in vitro to primary human and mouse peripheral blood mononuclear cells (PBMCs) and isolated human islets to evaluate the expression of the immunoregulatory gene SOCS1. Diabetes was induced by five consecutive daily injections of low-concentration (50 mg/kg) streptozotocin (STZ) in C57 black mice (n = 24). A group of these mice (n = 12) was co-injected with recombinant TRAIL (20 microg/day) for 5 days, and the diabetic status (glycemia and body weight) was followed over time. After 6 weeks, circulating levels of insulin, TNF-alpha, and osteoprotegerin (OPG) were measured, and animals were killed to perform the histological analysis of the pancreas. RESULTS: The in vitro exposure of both PBMCs and human islets to recombinant TRAIL significantly upregulated the expression of SOCS1. With respect to STZ-treated animals, mice co-injected with STZ+TRAIL were characterized by 1) lower levels of hyperglycemia, 2) higher levels of body weight and insulinemia, 3) a partial preservation of pancreatic islets with normal morphology, and 4) a lower expression of both systemic (TNF-alpha and OPG) and pancreatic (vascular cell adhesion molecule [VCAM]-1) inflammatory markers. CONCLUSIONS: Overall, these data demonstrate that the administration of recombinant TRAIL ameliorates the severity of STZ-induced type 1 diabetes, and this effect was accompanied by the upregulation of SOCS1 expressio
Guidelines for the monitoring of Lucanus cervus
Lucanus cervus is one of the most charismatic saproxylic beetles, widely distributed in Europe. The species is typical of mature deciduous forests, especially oak woodlands. Loss and fragmentation of suitable habitats is one of the major threats for this species which is included in Annex II of the Habitats Directive. Despite several studies carried out in the last years for the monitoring methods of the species, an analytical comparison between them is still lacking. The aims of this paper are (i) to review the current knowledge about systematics, ecology and conservation practices on L. cervus and (ii) to present the research carried out during the Life MIPP project, in order to define a standard monitoring method with a suitable protocol to be used for addressing the obligations of the Habitats Directive. Overall, five methods were tested during three years in two different study areas. Based on these results, a suitable standard method for L. cervus is proposed in this paper and, in order to assess the conservation status of populations and to compare them over time, a simple method for the calculation of a reference value is provided
Fine tuning of protein kinase C (PKC) isoforms in cancer: shortening the distance from the laboratory to the bedside
Serum TRAIL levels increase shortly after insulin therapy and metabolic stabilization in children with type 1 diabetes mellitus
COVID-19 and individual genetic susceptibility/receptivity: Role of ACE1/ACE2 genes, immunity, inflammation and coagulation. might the double x-chromosome in females be protective against SARS-COV-2 compared to the single x-chromosome in males?
In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex-or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection
IMP dehydrogenase inhibitor, tiazofurin, induces apoptosis in K562 human erythroleukemia cells.
none8Tiazofurin, an anticancer drug which inhibits IMP dehydrogenase, decreases cellular GTP concentration,
induces differentiation and down-regulates ras and myc oncogene expression, caused apoptosis of K562
cells in a time- and dose-dependent fashion. Apoptotic cells were detected by (1) flow cytometry, (2) electron
microscopy, and (3) fluorescence in situ nick translation and confocal microscopy, while the DNA ladder was
not detectable. The induced apoptosis was abrogated by guanosine which replenishes GTP pools through the
guanosine salvage pathways, while it was enhanced by hypoxanthine, a competitive inhibitor of GPRT. The
tiazofurin-mediated apoptosis may therefore be linked with the decrease of GTP and the consequent
impairment of specific signal transduction pathways. Tiazofurin induced apoptosis also in lymphoblastic
MOLT-4 cells, suggesting that this action is not confined to cells of the myeloid lineage, where the
differentiating effects of the drug are more pronounced.openVITALE M; ZAMAI L; FALCIERI E; ZAULI G; GOBBI P.; SANTI S; CINTI C; WEBER GVitale, M; Zamai, Loris; Falcieri, Elisabetta; Zauli, G; Gobbi, Pietro; Santi, S; Cinti, C; Weber, G
Improving water use efficiency in vertical farming: Effects of growing systems, far-red radiation and planting density on lettuce cultivation
Vertical farms (VFs) are innovative urban production facilities consisting of multi-level indoor systems equipped with artificial lighting in which all the environmental conditions are controlled independently from the external climate. VFs are generally provided with a closed loop fertigation system to optimize the use of water and nu-trients. The objective of this study, performed within an experimental VF at the University of Bologna, was to quantify the water use efficiency (WUE, ratio between plant fresh weight and the volume of water used) for a lettuce (Lactuca sativa L.) growth cycle obtained in two different growing systems: an ebb-and-flow substrate culture and a high pressure aeroponic system. Considering the total water consumed (water used for irrigation and climate management), WUE of ebb-and-flow and aeroponics was 28.1 and 52.9 g L-1 H2O, respectively. During the growing cycle, the contribution generated by the recovery of internal air moisture from the heating, ventilation and air conditioning (HVAC) system, was quantified. Indeed, by recovering water from the dehu-midifier, water use decreases dramatically (by 67 %), while WUE increased by 206 %. Further improvement of WUE in the ebb-and-flow system was obtained through ameliorated crop management strategies, in particular, by increasing planting densities (e.g., 153, 270 and 733 plants m-2) and by optimizing the light spectrum used for plant growth (e.g., adjusting the amount of far-red radiation in the spectrum). Strategies for efficient use of water in high-tech urban indoor growing systems are therefore proposed
TRAIL treatment prevents renal morphological changes and TGF-\u3b2-induced mesenchymal transition associated with diabetic nephropathy
BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) has attracted attention not only as an anti-cancer agent, but also as a potential treatment for diabetes. Animal studies have shown that TRAIL delivery ameliorated glucose control in type 1 and type 2 diabetes. It is currently unknown whether TRAIL positive effects are maintained in more severe forms of type 2 diabetes, and whether they include renoprotection. Our study aimed at evaluating TRAIL effects in a severe form of type 2 diabetes with nephropathy. MATERIALS AND METHODS: A total of 20 db/db mice were treated with saline or TRAIL twice per week for 12 weeks. In parallel, renal tubular epithelial cells were cultured with TGF-\u3b21 in the presence and absence of TRAIL, with and without silencing TRAIL-specific receptor (DR5) and leptin receptor. RESULTS: TRAIL did not improve glucose control, but it significantly reduced circulating interleukin (IL)-6 and resistin. In the kidney, TRAIL treatment significantly ameliorated glomerular and tubular morphology with an improvement in kidney function, but no effect on proteinuria. Our in vitro studies on TGF-\u3b21-treated cells, showed that by binding to DR5, TRAIL rescued normal tubular cell morphology, increasing E-cadherin and reducing \u3b1-smooth muscle actin (SMA) expression, with no effects on cell viability. Interestingly, both in vivo and in vitro, TRAIL reduced the accumulation of the autophagy substrate p62. CONCLUSIONS: Our data confirm TRAIL protective effects against organ damage and shed light on to promising anti-fibrotic actions, which are independent of glucose control. TRAIL anti-fibrotic actions might be due to the rescue of autophagy in diabetes
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