Quantitative Dixon and intravoxel incoherent motion diffusion magnetic resonance imaging parameters in lumbar vertebrae for differentiating aplastic anemia and acute myeloid leukemia

ObjectiveWe sought to evaluate the use of quantitative Dixon (Q-Dixon) and intravoxel incoherent motion diffusion imaging (IVIM) for the differential diagnosis of aplastic anemia (AA) and acute myeloid leukemia (AML).MethodsBetween August 2021 and October 2023, we enrolled 68 diagnosed patients, including 36 patients with AA and 32 patients with AML, as well as 26 normal controls. All patients underwent 3-Tesla magnetic resonance imaging, which included IVIM and T2*-corrected Q-Dixon imaging at the L2–4 level. The iliac crest biopsy’s pathology was used as the diagnostic criterion. The interobserver measurement repeatability was evaluated using the intraclass correlation coefficient (ICC). One-way analysis of variance, Spearman analysis, and receiver operating characteristic curve analysis were used.ResultsThe fat fraction (FF) and perfusion fraction (f) values were statistically significantly different between the three groups (p < 0.001 and p = 0.007). The FF and f values in the AA group were higher than those in the AML group. The true apparent diffusion coefficient (D) value was substantially negatively correlated to the FF and R2* values (r = −0.601, p < 0.001; r = −0.336, p = 0.002). The f value was positively correlated with both FF and pseudo-apparent diffusion coefficient (D*) values (r = 0.376, p < 0.001; r = 0.263, p = 0.017) and negatively correlated with the D value (r = −0.320, p = 0.003). The FF and f values were negatively correlated with the degree of myelodysplasia (r = −0.597, p < 0.001; r = −0.454, p = 0.004), and the D value was positively correlated with the degree of myelodysplasia (r = 0.395, p = 0.001). For the differential diagnosis of AA and AML, the Q-Dixon model’s sensitivity (93.75%) and specificity (84%) confirmed that it outperformed the IVIM model.ConclusionQ-Dixon parameters have the potential to be used as new biomarkers to differentiate AA from AML

Voltammetric behaviour of oligonucleotide lipoplexes adsorbed onto glassy carbon electrodes

The voltammetric behaviour of oligonucleotide lipoplexes (ODN-lipoplexes) prepared from short oligodeoxynucleotides (ODN), with different base compositions, and liposomes of the cationic lipid DOTAP, was studied by differential pulse voltammetry with a glassy carbon mini-electrode. It was found that the ODN base composition influences the ODN-lipoplex voltammetric response. Differential pulse voltammograms for ODN-lipoplexes of the ODN adenosine nucleotides present two different features when compared with the differential pulse voltammograms obtained for free ODN: a new peak appeared and the peak attributed to oxidation of adenosine diminished or was absent, depending on whether the ODN sequence had guanosine nucleotides or not. The presence of guanosine nucleotides in the ODN-lipoplex led to a peak due to guanosine oxidation with similar potential and current to the peak obtained for guanosine oxidation in free ODN. No detectable peaks were recorded in the voltammograms obtained with lipoplexes composed of ODN containing only pyrimidine bases. It was possible to show by voltammetry the occurrence of partial denaturation of short double helices of ODN when mixed with DOTAP liposomes to generate lipoplexes. The extent of denaturation was observed to increase with lipoplex (+/-) charge ratio as shown by the increase in the differential pulse voltammetry peak currents. The electrochemical characterisation of lipoplex properties at a charged interface can be important for understanding and development of these gene therapy vectors.http://www.sciencedirect.com/science/article/B6TGB-4B4RVT3-2/1/80478920c615683b2439ef8a2980898

Applying response surface methodology to optimize nimesulide permeation from topical formulation

Nimesulide is a non-steroidal anti-inflammatory drug that acts through selective inhibition of COX-2 enzyme. Poor bioavailability of this drug may leads to local toxicity at the site of aggregation and hinders reaching desired therapeutic effects. This study aimed at formulating and optimizing topically applied lotions of nimesulide using an experimental design approach, namely response surface methodology. The formulated lotions were evaluated for pH, viscosity, spreadability, homogeneity and in vitro permeation studies through rabbit skin using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of permeation enhancers, namely propylene glycol and polyethylene glycol on percutaneous absorption of nimesulide from lotion formulations. The best fit quadratic model explained that the enhancer combination at equal levels significantly increased the flux and permeability coefficient. The model was validated by comparing the permeation profile of optimized formulations’ predicted and experimental response values, thus, endorsing the prognostic ability of response surface methodology

Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy

Objective. Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods. Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results. 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree=24), GNB3 (degree=23), QSOX1 (degree=21), and APOB (degree=17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion. Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM

Comparison and evaluation of two different methods to establish the cigarette smoke exposure mouse model of COPD

Animal model of cigarette smoke (CS) -induced chronic obstructive pulmonary disease (COPD) is the primary testing methodology for drug therapies and studies on pathogenic mechanisms of disease. However, researchers have rarely run simultaneous or side-by-side tests of whole-body and nose-only CS exposure in building their mouse models of COPD. We compared and evaluated these two different methods of CS exposure, plus airway Lipopolysaccharides (LPS) inhalation, in building our COPD mouse model. Compared with the control group, CS exposed mice showed significant increased inspiratory resistance, functional residual capacity, right ventricular hypertrophy index, and total cell count in BALF. Moreover, histological staining exhibited goblet cell hyperplasia, lung inflammation, thickening of smooth muscle layer on bronchia, and lung angiogenesis in both methods of CS exposure. Our data indicated that a viable mouse model of COPD can be established by combining the results from wholebody CS exposure, nose-only CS exposure, and airway LPS inhalation testing. However, in our study, we also found that, given the same amount of particulate intake, changes in right ventricular pressure and intimal thickening of pulmonary small artery are a little more serious in nose-only CS exposure method than changes in the whole-body CS exposure method.National Natural Science Foundation of China [81630004, 81470246, 81220108001, 81520108001]; Guangdong Department of Science and Technology of China [2016A030311020, 2016A030313606]; Guangzhou Department of Education Yangcheng Scholarship [12A001S]; Guangzhou Department of Education Scholarship [1201630095]; Guangzhou Department of Science and Technology [2014Y2-00167, 201607010358]; Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme, ChinaThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]