Targeting delivery of lipocalin 2-engineered mesenchymal stem cells to colon cancer in order to inhibit liver metastasis in nude mice

One of the major obstacles in cancer therapy is the lack of anticancer agent specificity to tumor tissues. The strategy of cell-based therapy is a promising therapeutic option for cancer treatment. The specific tumor-oriented migration of mesenchymal stem cells (MSCs) makes them a useful vehicle to deliver anticancer agents. In this study, we genetically manipulated bone marrow-derived mesenchymal stem cells with their lipocalin 2 (Lcn2) in order to inhibit liver metastasis of colon cancer in nude mice. Lcn2 was successfully overexpressed in transfected MSCs. The PCR results of SRY gene confirmed the presence of MSCs in cancer liver tissue. This study showed that Lcn2-engineered MSCs (MSC-Lcn2) not only inhibited liver metastasis of colon cancer but also downregulated the expression of vascular endothelial growth factor (VEGF) in the liver. Overall, MSCs by innate tropism toward cancer cells can deliver the therapeutic agent, Lcn2, and inhibit cancer metastasis. Hence, it could be a new modality for efficient targeted delivery of anticancer agent to liver metastasis. © 2015, International Society of Oncology and BioMarkers (ISOBM)

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Security and searchability in secret sharing based data outsourcing

A major challenge organizations face when hosting or moving their data to the Cloud is how to support complex queries over outsourced data while preserving their confidentiality. In principle, encryption-based systems can support querying encrypted data, but their high complexity has severely limited their practical use. In this paper, we propose an efficient yet secure secret sharing-based approach for outsourcing relational data to honest-but-curious data servers. The problem with using secret sharing in a data outsourcing scenario is how to efficiently search within randomly generated shares. We present multiple partitioning methods that enable clients to efficiently search among shared secrets while preventing inference attacks on the part of data servers, even if they can observe shares and queries. Also, we prove that with some of our partitioning methods the probability of finding a correspondence between a set of shares and their original values is almost equal to that of a random guess. We discuss query processing for different types of queries including equality, range, aggregation, projection, join, and update queries. Our extensive experimentation confirms the practicality and efficiency of our approach in terms of query execution time, storage, and communication overheads

A comparative experimental and molecular simulation study on the mechanical and morphological behaviors of adamantane-based polypropylene composites

The main objectives of this work were to construct and characterize polypropylene and adamantane (PP/ADM) nanocomposites experimentally and to identify their mechanical properties using molecular dynamics (MD) simulation. Samples with different contents of ADMs (0.5, 1, 2 and 4 weight percent (wt%)) were prepared using melt mixing method. It was observed that ADM nanofillers had significant effects on mechanical properties (Young’s modulus) of PP nanocomposites. Furthermore an appropriate simulation model was developed to find mechanisms of dispersion and aggregation of the ADMs and to predict bulk properties of the nanocomposite. While former researches claimed that homogeneous filler dispersion exists only at the intermediate level of interfacial interaction between polymer and nanoparticle, according to results of current study entropy has substantial influence on dispersion process. In other words, entropy which controls the interfacial parameters such as how ADMs attach to the polymer chains (either by chain end or middle of the backbone), is a determining agent in dispersion and aggregation mechanism. Consequently chains entropy plays a significant role in enhancement of the nanocomposites Young’s modulus. The trend of modulus alterations demonstrated that the entrance of ADMs at the chains contact point reinforced the polymer matrix and hence increased the modulus intensively. On the other hand, relative dispersion of ADMs and their small aggregates enhanced the modulus. However, ADMs aggregation caused by attaching to the joined ends, made a dramatic decline in Young’s modulus

Database as a service : towards a unified solution for security requirements

Security of database outsourcing, due to the untrustworthiness of service provider, is a basic challenge to have Database As a Service in a cloud computing environment. Having disparate assumptions to solve different aspects of security such as confidentiality and integrity is an obstacle for an integrated secure solution through the combination of existing approaches. Concentrating on confidentiality and integrity aspects of database outsourcing, this paper proposes an approach in which each attribute value is split up between several data servers using a customized threshold secret sharing scheme. Our approach preserves data confidentiality and at the same time provides the correctness verifiability of query results for clients. The distribution algorithm and redundant shares in the secret sharing scheme are the basis of correctness verification for query results

AS5 : a secure searchable secret sharing scheme for privacy preserving database outsourcing

Researchers have been studying security challenges of database outsourcing for almost a decade. Privacy of outsourced data is one of the main challenges when the \u201cDatabase As a Service\u201d model is adopted in the service oriented trend of the cloud computing paradigm. This is due to the insecurity of the network environment or even the untrustworthiness of the service providers. This paper proposes a method to preserve privacy of outsourced data based on Shamir\u2019s secret sharing scheme. We split attribute values into several parts and distribute them among untrusted servers. The problem of using secret sharing in data outsourcing scenario is how to search efficiently within the randomly generated pool of shares. In this paper, at first, we customize Shamir\u2019s scheme to have A Searchable Secret Sharing Scheme (AS4) that enables the efficient execution of different kinds of queries over distributed shares. Then, we extend our method for sharing values to A Secure Searchable Secret Sharing Scheme (AS5) to tolerate statistical attacks based on adversary\u2019s knowledge about outsourced data distribution. In AS5 data shares are generated uniformly across a domain to prevent information leakage about the outsourced data

The correlation between cardiac magnetic resonance T2* and left ventricular global longitudinal strain in people with β-thalassemia

Background: Heart failure is the biggest cause of mortality and morbidity in people with thalassemia, and iron deposition in cardiac tissue impairs cardiovascular function. Therefore, early detection of cardiac involvement is important to improve the prognosis in these individuals. Method: Two- and three-dimensional echocardiography was performed to evaluate left ventricular ejection fraction (LVEF), left ventricular volumes and diameters, and global longitudinal strain (GLS) in 130 individuals with β-thalassemia using the speckle tracking method. Magnetic resonance imaging (MRI) was carried out on both the heart and liver. The participants were divided into 2 groups based on cardiac T2* values (normal and abnormal cardiac iron load), and the correlation between cardiac T2* MRI and GLS was evaluated. Results: The statistical analysis showed a significant correlation between cardiac T2* MRI and left ventricular global longitudinal strain. There was a significant difference in global longitudinal strain (P <.0001), liver MRI T2*(P <.0001), and left ventricular ejection fraction (P <.001) between the 2 groups. The optimal cutoff value for GLS was �18.5 with sensitivity and specificity 73.0 and 63.0, respectively (postitive predictive value = 50, negative predictive value = 82.3, AUC = 0.742, std. error = 0.046) which predicts T2* value of <20 ms, according to cardiac MRI. Conclusions: The participants with cardiac iron overload had a lower GLS than those without one. This suggests that GLS may be a useful method to predict myocardial iron overload particularly in β-thalassemia patients with subclinical cardiac involvement. © 2018, Wiley Periodicals, Inc

The correlation between cardiac magnetic resonance T2* and left ventricular global longitudinal strain in people with β-thalassemia

Background: Heart failure is the biggest cause of mortality and morbidity in people with thalassemia, and iron deposition in cardiac tissue impairs cardiovascular function. Therefore, early detection of cardiac involvement is important to improve the prognosis in these individuals. Method: Two- and three-dimensional echocardiography was performed to evaluate left ventricular ejection fraction (LVEF), left ventricular volumes and diameters, and global longitudinal strain (GLS) in 130 individuals with β-thalassemia using the speckle tracking method. Magnetic resonance imaging (MRI) was carried out on both the heart and liver. The participants were divided into 2 groups based on cardiac T2* values (normal and abnormal cardiac iron load), and the correlation between cardiac T2* MRI and GLS was evaluated. Results: The statistical analysis showed a significant correlation between cardiac T2* MRI and left ventricular global longitudinal strain. There was a significant difference in global longitudinal strain (P <.0001), liver MRI T2*(P <.0001), and left ventricular ejection fraction (P <.001) between the 2 groups. The optimal cutoff value for GLS was �18.5 with sensitivity and specificity 73.0 and 63.0, respectively (postitive predictive value = 50, negative predictive value = 82.3, AUC = 0.742, std. error = 0.046) which predicts T2* value of <20 ms, according to cardiac MRI. Conclusions: The participants with cardiac iron overload had a lower GLS than those without one. This suggests that GLS may be a useful method to predict myocardial iron overload particularly in β-thalassemia patients with subclinical cardiac involvement. © 2018, Wiley Periodicals, Inc