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Alston Persson posted an update 1 year, 6 months ago
Liposomes are highly biocompatible and versatile drug carriers with an increasing number of applications in the field of nuclear medicine and diagnostics. So far, only negatively charged liposomes with intercalated radiometals, e.g., 64Cu, 99mTc, have been reported. However, the process of cellular uptake of liposomes by endocytosis is rather slow. Cellular uptake can be accelerated by recently developed cationic liposomes, which exhibit extraordinarily high membrane fusion ability. The aim of the present study was the development of the formulation and the characterization of such cationic fusogenic liposomes with intercalated radioactive [131I]I- for potential use in therapeutic applications. The epithelial human breast cancer cell line MDA-MB-231 was used as a model for invasive cancer cells and cellular uptake of [131I]I- was monitored in vitro. Delivery efficiencies of cationic and neutral liposomes were compared with uptake of free iodide. The best cargo delivery efficiency (~10%) was achieved using cationic fusogenic liposomes due to their special delivery pathway of membrane fusion. Additionally, human blood cells were also incubated with cationic control liposomes and free [131I]I-. In these cases, iodide delivery efficiencies remained below 3%.Privacy protection in electronic healthcare applications is an important consideration, due to the sensitive nature of personal health data. Internet of Health Things (IoHT) networks that are used within a healthcare setting have unique challenges and security requirements (integrity, authentication, privacy, and availability) that must also be balanced with the need to maintain efficiency in order to conserve battery power, which can be a significant limitation in IoHT devices and networks. Data are usually transferred without undergoing filtering or optimization, and this traffic can overload sensors and cause rapid battery consumption when interacting with IoHT networks. This poses certain restrictions on the practical implementation of these devices. In order to address these issues, this paper proposes a privacy-preserving two-tier data inference framework solution that conserves battery consumption by inferring the sensed data and reducing data size for transmission, while also protecting sensitive data from leakage to adversaries. The results from experimental evaluations on efficiency and privacy show the validity of the proposed scheme, as well as significant data savings without compromising data transmission accuracy, which contributes to energy efficiency of IoHT sensor devices.The reduction of female fertility over time is considered as a natural consequence of ovarian aging. The exact mechanism underlying this process is not fully elucidated. However, it is becoming increasingly evident that qualitative and quantitative mitochondrial genome alterations might play a relevant role. Liproxstatin-1 The former include mitochondrial DNA (mtDNA) damage caused by oxidative stress, the accumulation of acquired mtDNA mutations, the effects of inherited mtDNA mutations, and alterations in the mitochondrial stress response mechanism. The latter refer to alterations in the oocytes, granuolosa cells, and embryonic cells mtDNA content. The present review aims to investigate the evidence about (1) the effect of qualitative and quantitative mtDNA alterations on female fertility, paying particular attention to those with a pathophysiology characterized by a relevant role of oxidative stress; (2) the use of oocytes, granulosa cells (GCs), embryonic cells, and peripheral blood cells mtDNA copy number as a female fertility surrogate biomarker; (3) experimental therapies tested to try to subvert the ovarian aging process with particular reference to antioxidant treatments.Parkinson’s disease (PD) is an age-dependent neurodegenerative condition. Leucine-rich repeat kinase 2 (LRRK2) mutations are the most frequent cause of sporadic and autosomal dominant PD. The exact role of LRRK2 protective variants (R1398H, N551K) together with a pathogenic mutant (G2019S) in aging and neurodegeneration is unknown. We generated the following myc-tagged UAS-LRRK2 transgenic Drosophila LRRK2 (WT), N551K, R1398H, G2019S single allele, and double-mutants (N551K/G2019S or R1398H/G2019S). The protective variants alone were able to suppress the phenotypic effects caused by the pathogenic LRRK2 mutation. Next, we conducted RNA-sequencing using mRNA isolated from dopaminergic neurons of these different groups of transgenic Drosophila. Using pathway enrichment analysis, we identified the top 10 modules (p less then 0.05), with “LRRK2 in neurons in Parkinson’s disease” among the candidates. Further dissection of this pathway identified the most significantly modulated gene nodes such as eEF1A2, ACTB, eEF1A, and actin cytoskeleton reorganization. The induction of the pathway was successfully restored by the R1398H protective variant and R1398H-G2019S or N551K-G2019S rescue experiments. The oxidoreductase family of genes was also active in the pathogenic mutant and restored in protective and rescue variants. In summary, we provide in vivo evidence supporting the neuroprotective effects of LRRK2 variants. RNA sequencing of dopaminergic neurons identified upregulation of specific gene pathways in the Drosophila carrying the pathogenic variant, and this was restored in the rescue phenotypes. Using protective gene variants, our study identifies potential new targets and provides proof of principle of a new therapeutic approach that will further our understanding of aging and neurodegeneration in PD.While alterations in bone mineral density (BMD) are of interest in a number of musculoskeletal conditions affecting the knee, their analysis is limited by a lack of tools able to take full advantage of modern imaging modalities. This study introduced a new method, combining computed tomography (CT) and computational anatomy algorithms, to produce standardized three-dimensional BMD quantification in the distal femur and proximal tibia. The method was evaluated on ten cadaveric knees CT-scanned twice and processed following three different experimental settings to assess the influence of different scans and operators. The median reliability (intraclass correlation coefficient (ICC)) ranged from 0.96 to 0.99 and the median reproducibility (precision error (RMSSD)) ranged from 3.97 to 10.75 mg/cc for the different experimental settings. In conclusion, this paper presented a method to standardize three-dimensional knee BMD with excellent reliability and adequate reproducibility to be used in research and clinical applications.

