Protein phosphatase 2A (PP2A) is a human tumor suppressor that inhibits cellular transformation by regulating the activity of several signaling proteins critical for malignant cell behavior. PP2A has ...been described as a potential therapeutic target in chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia and B-cell chronic lymphocytic leukemia. Here, we show that PP2A inactivation is a recurrent event in acute myeloid leukemia (AML), and that restoration of PP2A phosphatase activity by treatment with forskolin in AML cells blocks proliferation, induces caspase-dependent apoptosis and affects AKT and ERK1/2 activity. Moreover, treatment with forskolin had an additive effect with Idarubicin and Ara-c, drugs used in standard induction therapy in AML patients. Analysis at protein level of the PP2A activation status in a series of patients with AML at diagnosis showed PP2A hyperphosphorylation in 78% of cases (29/37). In addition, we found that either deregulated expression of the endogenous PP2A inhibitors SET or CIP2A, overexpression of SETBP1, or downregulation of some PP2A subunits, might be contributing to PP2A inhibition in AML. In conclusion, our results show that PP2A inhibition is a common event in AML cells and that PP2A activators, such as forskolin or FTY720, could represent potential novel therapeutic targets in AML.
Abstract
This study presents results from quantum chemical simulations of the synergetic interaction, electronic structure, and optical properties of calcium-silicate hydrates (C-S-H) reinforced by ...graphene-nanoribbons and single-walled carbon nanotubes (SWCNT). The calculations show that C-S-H/graphene-nanoribbon and C-S-H/SWCNT composites are stabilized by electrostatic interaction due to the charge transfer from Ca ions at the interface of C-S-H to the nearby C atoms of the graphene-nanoribbon and SWCNT. Removing Ca ions at the interface drastically decreases the strength of interaction into a weak van der Waals type. The Bader charge transfer analysis and electron distribution topology further confirm these results. Generally, the electronic states of the graphene-nanoribbon and SWCNT are shifted to lower energy in the complex. The electronic structure of graphene-nanoribbon and SWCNT is susceptible to the Ca ions-rich C-S-H environment. The composites’ overall absorption spectra can be considered superimposed of the isolated nanocarbon and C-S-H except in the lower energy region due to charge transfer and realignment of energy states. The results presented here reveal the bonding mechanism of the C-S-H with nanocarbon at the fundamental level. This work serves as a reference for the nanoengineering cement-based material with nanocarbon for the next-generation smart infrastructure.
Over the past decade polyelectrolyte multilayer (PEM)-based membranes have gained a lot of interest in the field of nanofiltration (NF) as an alternative to conventional polyamide-based thin film ...composite membranes. With great variety in fabrication conditions, these membranes can achieve superior properties such as high chemical resistance and excellent filtration performance. Some of the most common polyelectrolytes used to prepare NF membranes are weak, meaning that their charge density depends on pH within the normal window of operation relevant for potential applications (pH 0–14). This might cause a dependency of membrane properties on the pH of filtered solutions, as indicated by other applications of PEMs. In this work, the susceptibility of membrane structure (swelling and surface charge) and performance (permeability, molecular weight cutoff, and salt retention) toward the pH of the filtration solution was studied for four fundamentally different PEM systems: poly(diallyldimethylammonium chloride) (PDADMAC)/poly(sodium-4-styrenesulfonate) (PSS) (strong/strong), poly(allylamine hydrochloric acid) (PAH)/poly(acrylic acid) (PAA) (weak/weak), and PAH/PSS (weak/strong) and PAH/PSS+PAH/PAA (asymmetric). Slight variations in structure and performance of the PDADMAC/PSS-based membranes were observed. On the contrary, structure and performance of PAH/PAA-based membranes are very susceptible to feed solution pH. A continuous change in charge density with variation in pH significantly affects salt retention. An increased swelling at pH 9 translates to variation in permeability and molecular weight cutoff of the membrane. The susceptibility of PAH/PSS-based membranes to pH is less pronounced compared to the PAH/PAA-based membranes since only one of the polyelectrolytes involved is weak. No structural changes were observed, indicating additional specific interactions between the polyelectrolytes other than electrostatic forces that stabilize film structure. A combination of the PAH/PSS and PAH/PAA system (8 + 2 bilayers) also displays a clear dependency of both membrane structure and performance on solution pH, where PAH/PSS is dominating due to a higher bilayer number.
Introduction
CD is characterized by at least three features: its duration is prolonged, it does not resolve spontaneously and it is rarely completely cured. Approximately 10-15% of young people have ...CD. Adolescents with CD often have emotional and behavioral problems.
Objectives
To assess risk factors, derived psychiatric pathologies and coping strategies for a CD diagnosis in adolescence.
Methods
An extensive literature review was carried out on the subject in question, extracting information mainly from scientific articles, manuals and books.
Results
The main risk factors are those related with the CD in question, physical sequelae, the need for long-term hospital admissions or the use of drugs whose side effects include affective or behavioral symptoms; those related to the personality traits of the affected child or adolescent. In addition, as far as the family is concerned, the presence of a low level of education, lack of support or communication, as well as the presence of psychiatric disorders or serious medical conditions in parents. Among the most frequent psychiatric disorders associated with CD are affective and anxiety disorders, adaptive disorders, somatoform disorders, eating disorders and behavioral disorders. Whatever the CD is, it generates high levels of stress and uncertainty in the patient and family, which must be dealt together from a flexible perspective, allowing child or adolescent to adapt to the changes, reorganize and facing them with adaptive patterns of behavior. For this, it will be essential to have adequate social and family support with relational style based on communication, trust and acceptance.
Conclusions
In general, both adolescents with CD and their families have an adequate capacity to adapt to the repercussions and effects derived from the disease. Nevertheless, in case of possible emotional difficulties that may appear, a comprehensive and individualized approach to these adolescents and their families is necessary to provide them resources and coping strategies in different areas and contexts in which the disease debuts.The comprehensive therapeutic approach will consist of interventions at the individual and family level. Among the main objectives of these interventions are to achieve acceptance and adaptation to CD provinding adequate psychosocial support to enable them to cope with CD in the best possible way and to detect and address the emotional implications, even coexisting psychopathology.
Disclosure of Interest
None Declared
Protein phosphatase 2A (PP2A) is a tumour suppressor frequently inactivated in human cancer and its tyrosine-307 phosphorylation has been reported as a molecular inhibitory mechanism.
Expression of ...phosphorylated PP2A (p-PP2A) was evaluated in 250 metastatic colorectal cancer (CRC) patients. Chi-square, Kaplan-Meier and Cox analyses were used to determine correlations with clinical and molecular parameters and impact on clinical outcomes.
High p-PP2A levels were found in 17.2% cases and were associated with ECOG performance status (P=0.001) and presence of synchronous metastasis at diagnosis (P=0.035). This subgroup showed substantially worse overall survival (OS) (median OS, 6.0 vs 26.2 months, P<0.001) and progression-free survival (PFS) (median PFS, 3.8 vs 13.3 months, P<0.001). The prognostic impact of p-PP2A was particularly evident in patients aged <70 years (P<0.001). Multivariate analysis revealed that p-PP2A retained its prognostic impact for OS (hazard ratio 2.7; 95% confidence interval, 1.8-4.1; P<0.001) and PFS (hazard ratio 3.0; 95% confidence interval, 1.8-5.0; P<0.001).
Phosphorylated PP2A is an alteration that determines poor outcome in metastatic CRC and represents a novel potential therapeutic target in this disease, thus enabling to define a subgroup of patients who could benefit from future treatments based on PP2A activators.
Introduction One of the most important functions of sleep may be the promotion of brain development. The non-REM and REM sleep sequences show the succession of cerebral processing phenomena that ...underlie memory consolidation. The negative consequences of sleep loss on neural and behavioral plasticity has been examined. On the other hand, sleep disruption can be a crucial symptom to develop depression disorders. Recent literature suggests that maintenance insomnia may be a risk factor for dementia. It would be important to elucidate which factors may increase the risk of developing dementia and aggravating its progression. Objectives The aim of this scoping review is to point out the increased risk of developing dementia related to insomnia and depression. Methods Relevant literature was searched with PUBMED as electronic database. We used and combined the following MeSH terms: depression, insomnia, cognitive impairment and dementia. We chose sixteen recent studies from 2009 to 2021. Four of them were ruled out because the methodology and conclusions were not enough evident. Results We underlined an interesting research which was carried out with Chinese population in 2021. A total of 256 patients with insomnia disorder were diagnosed by neurologists, 45 of whom were diagnosed with amnesic mild cognitive impairment (aMCI) and 45 participants with intact cognition were chosen as controls matched for age and education. A case-control study was conducted to compare sleep structure between aMCI and control patients with insomnia disorder. An American prospective research in 2016 founded a statistically significant association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs.7 hours/night). The relationships between depression, cognitive function, serum brain-derived neurotrophic factor (BDNF) and volumetric MRI measurements in older adults were investigated. A total of 4352 individuals aged 65 years or older (mean age 72 years) participated in this Japanese study. Conclusions According to these researches, we emphasize the importance of detecting sleep disturbances as potential risk factors for MCI and dementia. All of them provide evidences that future studies should investigate dementia prevention among elderly individuals through the management of insomnia. At that point we have to consider personalized medicine and machine learning techniques for sleep and cognitive or mood symptoms. Disclosure of InterestNone Declared
Due to mounting environmental and public health concerns about the toxicity of Arsenic (As) contamination, there is a strong drive to develop ultrasensitive sensors and adsorbent material for As. ...Herein, we present results from density functional theory, the fundamental operating principle of the interaction of SWCNT with atomic As and Arsenous acid (H
3
AsO
3
), and its corresponding electronic-optical response. The calculations indicate that atomic As can strongly interact with SWCNT with significant induced structural deformation on the SWCNT's C–C bond. This bonding modifies the prototype SWCNT's intrinsic electronic structure and optical absorption spectra. Hence, SWCNT is indeed a competitive adsorbent and sensing material for atomic As. On the other hand, H
3
AsO
3
interacts weakly with the SWCNT, with no significant modification observed in the SWCNT's atomic configuration, electronic structure, and optical absorption spectra. The interaction and sensitivity with H
3
AsO
3
significantly improved after doping the SWCNT with Fe. Furthermore, the changes in the band structure patterns and optical absorption spectra of Fe-doped SWCNT are also prominent upon exposure to H
3
AsO
3
. The results presented here provide fundamental insights into the interaction of SWCNT and As, which serve as a reference for fabricating SWCNT-based adsorbent and sensing platforms of heavy metals. The findings further give insights into the chemical sensing performance of metal-doped SWCNT.
Abstract Combined oral contraceptives (COC) are the most popular contraceptive method in developed countries. Since their introduction there have been numerous changes and modifications in its ...composition with the aim to improve safety and tolerability while maintaining contraceptive efficacy. Most of the changes have been conducted on the progestin component, since most of the combinations include ethinyl estradiol as oestrogen. One of the adverse effects of COC is the increased risk of venous thromboembolism (VTE) in two clinical forms of presentation: deep vein thrombosis or pulmonary embolism. This review details the changes in haemostasis induced by progestin-only contraceptives and the risk of VTE in women who utilize this type of contraception; the relationship with other risk factors such as thrombophilia; the interactions of these contraceptives with anticoagulant treatment and finally the eligibility criteria for the use of hormonal contraception in women with previous VTE or thrombophilia carriers.
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