Abstract Objectives p53 Gene variants BstUI RFLP at codon 72 in exon 4, 16 bp tandem repeat in intron 3 and MspI RFLP in intron 6, which code for two functionally different protein isoforms, have ...been shown to modulate susceptibility to different types of human neoplasms. Methods p53 genotype was assessed in 90 CRC patients, 321 age-matched controls and 322 centenarians. Results The p53 codon 72 arginine, the p53 16 bp deletion, and the MspI RFLP were significantly more frequent in CRC patients in comparison to the controls and to the centenarians (odd ratio 1.44 and 1.93). In the CRC group, the BstUI RFLP polymorphism was the more frequent combination (62.2%), and it was significantly associated with highly infiltrating ( p < 0.01), poorly differentiated ( p < 0.01), and metastatic ( p < 0.05) tumours. Our findings indicate that the p53 codon 72 polymorphisms are associated with a higher risk of CRC and are associated with more advanced and undifferentiated tumours.
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can differentiate into several cell types. Bone marrow (BM)-MSCs mainly differentiate into osteoblasts or adipocytes. MSC ...interactions with their microenvironment directly affect their self-renewal/differentiation program. Here, we show for the first time that Fas ligand (FasL), a well-explored proapoptotic cytokine, can promote proliferation of BM-derived MSCs in vitro and inhibits their differentiation into adipocytes. BM-MSCs treated with a low FasL dose (0.5 ng/ml) proliferated more rapidly than untreated cells without undergoing spontaneous differentiation or apoptosis, whereas higher doses (25 ng/ml) induced significant though not massive BM-MSC death, with surviving cells maintaining a stem cell phenotype. At the molecular level, 0.5 ng/ml FasL induced ERK1/2 phosphorylation and survivin upregulation, whereas 25 ng/ml FasL induced caspase activation. Importantly, 25 ng/ml FasL reversibly prevented BM-MSC differentiation into adipocytes by modulating peroxisome proliferator-activated receptor gamma (PPARγ) and FABP4/aP2 expression induced by adipogenic medium. All such effects were inhibited by anti-Fas neutralizing antibody. The in vitro data regarding adipogenesis were confirmed using Fas(lpr) mutant mice, where higher PPARγ and FABP4/aP2 mRNA and protein levels were documented in whole tibia. These data show for the first time that the FasL/Fas system can have a role in BM-MSC biology via regulation of both proliferation and adipogenesis, and may have clinical relevance because circulating Fas/FasL levels decline with age and several age-related conditions, including osteoporosis, are characterized by adipocyte accumulation in BM.
The prognosis of patients with transfusion-dependent homozygous β-thalassemia (thalassemia major) has been improved by regular transfusion and iron-chelation therapy
1
. Before the introduction of ...therapy with deferoxamine, an iron-chelating agent, in the late 1970s,
2
iron overload from transfusions was a frequent cause of morbidity and mortality in these patients. Death was often due to cardiac failure, which typically began before the patient reached 20 years of age
3
. Previous studies have suggested that deferoxamine therapy, begun early in life, prolongs survival without cardiac disease,
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–
9
but follow-up was too short for unequivocal conclusions. The need for definitive information about the . . .
We report a 7-year-old boy with Menkes disease complicated by rupture of a large splenic artery aneurysm. The aneurysm was successfully embolized with microcoils and n-butyl cyanoacrylate. Further ...angiographic evaluation revealed marked tortuosity of mesenteric and lower extremity vasculature, including the femoral arteries bilaterally, without aneurysm formation. The patient has since been evaluated annually with computed tomography angiography and there have been no additional vascular complications of his disease during 3-year follow up.
Achieving sustainable urban development requires a reorientation in the planning, management, and design of cities based on the use of cross-cutting solutions that can systematically address urban ...problems. The implementation of Nature-based Solutions (NBS) such as green walls in cities contributes to reducing the effects of a systemic issue: climate change. This field of research is constantly evolving, and there is a growing need for systematic analysis to understand the current scenario, identify gaps, and accelerate new lines of research. This review aims to demonstrate the impact of green walls on urban comfort by providing a systematic review of the state of the art in the field of temperature reduction and acoustic absorption, identifying the factors that influence urban comfort through the use of vegetation, and highlighting research gaps that can be further explored. The most relevant results have shown that the temperature reduction is mainly influenced by the shading capacity of the selected vegetation type, the evapotranspiration process of the plants, and the presence of substrate. Also, the acoustic absorption capacity is influenced to a greater extent by the system's configuration, the substrate's characteristics, and the vegetation's density. In both cases, the environmental conditions in which they are found can vary the impact to a greater or lesser extent. The results of this research are relevant for the implementation of green walls as a climate change mitigation tool in cities and the development of new research approaches.
•Green walls have a positive impact on thermal and acoustic urban comfort.•Shading and evapotranspiration reduce from 0.8 °C to 31 °C depending on the system configuration.•80% of the noise absorbed by a green wall is due to the presence of the substrate.•For dense vegetation, the absorption coefficient can increase by 0.2–0.3.•The evapotranspiration impacts temperature reduction if irrigation of 2.5 L/m2/day is ensured.
Secondary iron overload Kushner, J P; Porter, J P; Olivieri, N F
Hematology,
2001, Letnik:
2001, Številka:
1
Journal Article
Transfusion therapy for inherited anemias and acquired refractory anemias both improves the quality of life and prolongs survival. A consequence of chronic transfusion therapy is secondary iron ...overload, which adversely affects the function of the heart, the liver and other organs. This session will review the use of iron chelating agents in the management of transfusion-induced secondary iron overload. In Section I Dr. John Porter describes techniques for the administration of deferoxamine that exploit the pharmacokinetic properties of the drug and minimize potential toxic side effects. The experience with chelation therapy in patients with thalassemia and sickle cell disease will be reviewed and guidelines will be suggested for chelation therapy of chronically transfused adults with refractory anemias. In Section II Dr. Nancy Olivieri examines the clinical consequences of transfusion-induced secondary iron overload and suggests criteria useful in determining the optimal timing of the initiation of chelation therapy. Finally, Dr. Olivieri discusses the clinical trials evaluating orally administered iron chelators.
Severe forms of anemia in children in the developing countries may be characterized by different clinical manifestations at particular stages of development. Whether this reflects developmental ...changes in adaptation to anemia or other mechanisms is not clear. The pattern of adaptation to anemia has been assessed in 110 individuals with hemoglobin (Hb) E β-thalassemia, one of the commonest forms of inherited anemia in Asia. It has been found that age and Hb levels are independent variables with respect to erythropoietin response and that there is a decline in the latter at a similar degree of anemia during development. To determine whether this finding is applicable to anemia due to other causes, a similar study has been carried out on 279 children with severe anemia due to Plasmodium falciparum malaria; the results were similar to those in the patients with thalassemia. These observations may have important implications both for the better understanding of the pathophysiology of profound anemia in early life and for its more logical and cost-effective management.
Abstract Background The functional characteristics of circulating angiogenic cells (CACs) are impaired in congestive heart failure (CHF) patients, suggesting that CAC dysfunction could contribute to ...CHF pathogenesis. However, the underlying mechanisms are only partly unraveled. No data are currently available regarding telomere/telomerase system in CACs of CHF patients. Methods CACs were obtained from 80 subjects: 40 healthy control subjects (CTR) median age (IQR), 80 (76–85 yrs) and 40 patients affected by post-ischemic cardiomyopathy CHF median age (IQR), 82 (77–89). CAC and leukocyte telomere length, assessed as T/S ratio, and telomerase (TERT) activity were determined in all the enrolled subjects. Specificity and sensitivity of CAC and leukocyte T/S in discriminating between CHF and CTR were evaluated using Receiver Operator Characteristic (ROC) curve analysis and reported as AUC values. CD34+/VEGFR2+ number and pro-inflammatory cytokines plasma levels, such as IL-6 and TNF-α, were also measured. Results CAC T/S and TERT activity were significantly reduced in CHF patients compared to CTR subjects. In leukocytes, only a significant T/S reduction was observed. AUC values were higher for CAC T/S with respect to leukocyte T/S (AUC = 0.89, and AUC = 0.73, P < 0.01, respectively). In multivariate analysis, leukocyte T/S, CAC T/S, CAC TERT activity and NT-proBNP levels were confirmed as parameters significantly associated with CHF. CD34+/VEGFR2+ number, IL-6 and TNF-α plasma levels were significantly increased in CHF patients. Conclusions CACs from CHF patients are characterized by telomere/telomerase system impairment, providing new insight into the clinical relevance of CACs in CHF pathogenesis.
Mesenchymal stem cells (MSCs), isolated from different adult sources, have great appeal for therapeutic applications due to their simple isolation, extensive expansion potential, and high ...differentiative potential.
In our previous studies we isolated MSCs form amniotic fluid (AF-MSCs) and skin (S-MSCs) and characterized them according to their phenotype, pluripotency, and mRNA/microRNAs (miRNAs) profiling using Card A from Life Technologies.
Here, we enlarge the profiling of AF-MCSs and S-MSCs to the more recently discovered miRNAs (Card B by Life Technologies) to identify the miRNAs putative target genes and the relative signaling pathways. Card B, in fact, contains miRNAs whose role and target are not yet elucidated.
The expression of the analyzed miRNAs is changing between S-MSCs and AF-MSCs, indicating that these two types of MSCs show differences potentially related to their source. Interestingly, the pathways targeted by the miRNAS deriving from Card B are the same found during the analysis of miRNAs from Card A.
This result confirms the key role played by WNT and TGF-β pathways in stem cell fate, underlining as other miRNAs partially ignored up to now deserve to be reconsidered. In addition, this analysis allows including Adherens junction pathways among the mechanisms finely regulated in stem cell behavior.
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