Synthesis and bioassay of ß-(1,4)-D-mannans as potential agents against Alzheimer's disease.

AIM: Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against Aß peptide toxicity in vitro. METHODS: The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Aß1-40 (2 µmol/L), and the cell viability was detected using a CCK8 assay. RESULTS: A series of ß-(1,4)-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 µmol/L ß-(1,4)-D-mannobiose 6, ß-(1,4)-D-mannotriose 9 or ß-(1,4)-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Aß1-40-induced toxicity. The efficacies were similar to those caused by 10 µmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. CONCLUSION: Synthetic homogeneous short chain ß-(1,4)-D-mannans shows neuroprotective effect against Aß peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.

Small molecule inhibitors of amyloid ß peptide aggregation as a potential therapeutic strategy for Alzheimer's disease.

Amyloid ß (Aß) peptides have long been viewed as a potential target for Alzheimer's disease (AD). Aggregation of Aß peptides in the brain tissue is believed to be an exclusively pathological process. Therefore, blocking the initial stages of Aß peptide aggregation with small molecules could hold considerable promise as the starting point for the development of new therapies for AD. Recent rapid progresses in our understanding of toxic amyloid assembly provide a fresh impetus for this interesting approach. Here, we discuss the problems, challenges and new concepts in targeting Aß peptides.

Degeneration in the Zygapophysial Joint of the Fifth Lumbar Vertebra: The V-Shaped Sign Revealed by Bone Scintigraphy.

OBJECTIVE: The aim of the study was to explore the nature of a V-shaped sign in the backbone of the fifth lumbar vertebra revealed by whole-body bone scintigraphy (WBBS). METHODS: A local single-photon emission computed tomography (SPECT) scan plus a computed tomography (CT) scan were performed on 41 patients in our department who had a V-shaped sign in the backbone of the fifth lumbar vertebra detected by WBBS. Image fusion was conducted to understand the manifestations of the changes in the V-shaped sign in the CT images in WBBS and to determine the nature of the lesion. RESULTS: All 41 patients presented with degenerative changes observed in the bilateral posterior zygapophysial joint of the fifth lumbar vertebra in the CT imaging bone window, bone hyperplasia of the articular process, joint surface hardening, and a joint gap. The vacuum sign could also be seen in some of these patients. CONCLUSION: The typical V-shaped sign in the posterior zygapophysial joint of the fifth lumbar vertebra revealed by WBBS suggests degenerative changes in the zygapophysial joint of the fifth lumbar vertebra.

Radiomics models based on enhanced computed tomography to distinguish clear cell from non-clear cell renal cell carcinomas.

This study was to assess the effect of the predictive model for distinguishing clear cell RCC (ccRCC) from non-clear cell RCC (non-ccRCC) by establishing predictive radiomic models based on enhanced-computed tomography (CT) images of renal cell carcinoma (RCC). A total of 190 cases with RCC confirmed by pathology were retrospectively analyzed, with the patients being randomly divided into two groups, including the training set and testing set according to the ratio of 7:3. A total of 396 radiomic features were computationally obtained and analyzed with the Correlation between features, Univariate Logistics and Multivariate Logistics. Finally, 4 features were selected, and three machine models (Random Forest (RF), Support Vector Machine (SVM) and Logistic Regression (LR)) were established to discriminate RCC subtypes. The radiomics performance was compared with that of radiologist diagnosis. In the testing set, the RF model had an area under the curve (AUC) value of 0.909, a sensitivity of 0.956, and a specificity of 0.538. The SVM model had an AUC value of 0.841, a sensitivity of 1.0, and a specificity of 0.231, in the testing set. The LR model had an AUC value of 0.906, a sensitivity of 0.956, and a specificity of 0.692, in the testing set. The sensitivity and specificity of radiologist diagnosis to differentiate ccRCC from non-ccRCC were 0.850 and 0.581, respectively, with the AUC value of the radiologist diagnosis as 0.69. In conclusion, radiomics models based on CT imaging data show promise for augmenting radiological diagnosis in renal cancer, especially for differentiating ccRCC from non-ccRCC.

[Fabrications of a poly (methyl methacrylate) (PMMA) microfluidic chip-based DNA analysis device].

A DNA analysis device based on poly(methyl methacrylate) (PMMA) microfluidic chips was developed. A PMMA chip with cross microchannels was fabricated by a simple hot embossing. Microchannels were modified with a static adsorptive coating method using 2% hydroxyethyl cellulose. A high-voltage power unit, variable in the range 0-1 800 V, was used for on-chip DNA sample injection and gel electrophoretic separation. High speed, high resolution DNA analysis was obtained with the home-built PMMA chip in a sieving matrix containing 2% hydroxyethyl cellulose with a blue intercalating dye, TO-PRO-3 (TP3), by using diode laser induced fluorescence detection based on optical fibers with a 670 nm long-pass filter. The DNA analysis device was applied for the separation of phiX-174/HaeIII DNA digest sample with 11 fragments ranging from 72 to 1 353 bp. A separation efficiency of 1.14 x 10(6) plates/m was obtained for the 603 bp fragments, while the R of 271/281 bp fragments was 1.2. The device was characterized by simple design, low cost for fabrication and operation, reusable PMMA chips, and good reproducibility. A portable microfluidic device for DNA analysis can be developed for clinical diagnosis and disease screening.

Clinical relevance of lysyl oxidase-like 2 and functional mechanisms in glioma.

INTRODUCTION: Glioma is the most frequent malignancy of the adult central nervous system with high recurrence risk and poor prognosis. Understanding the biological molecular mechanisms involved in glioma progression is critical for studying oncogenic mechanisms and improving prognosis. Lysyl oxidase-like 2 (LOXL2) is a kind of lysyl oxidase catalyzing the formation of peptidyl-lysine residues and promoting intramolecular cross-linking, especially for proteins in extracellular matrix. Our study explored the expression pattern of LOXL2 in glioma for the first time and found that its high expression was associated with larger tumor size and advanced tumor grade (P<0.05). Moreover, univariate and multivariate analyses revealed LOXL2 as a novel independent prognostic factor for the overall survival of glioma patients. METHODS: To evaluate the detailed functional roles of LOXL2, we tested its oncobiology characteristics in U87-MG cells with overexpression and knockdown experiments. RESULTS: Cellular results demonstrated that LOXL2 overexpression enhanced cell proliferation and invasion, while LOXL2-siRNA attenuated cell viability. Furthermore, our data identified the participation of E-cadherin, Snail1, Src, and FAK proteins downstream of LOXL2. Notably, by using immunoprecipitation and mass spectrometry strategies, we initially verified the interaction between LOXL2 and HDAC2, indicating the existence of a protein complex containing LOXL2/Snail1/HDAC2. Additionally, the expression of HDAC2 protein was highly correlated with that of LOXL2 in clinical glioma tissues (P=0.02), further implying the synergic oncogenic roles of these 2 proteins. CONCLUSION: LOXL2 is a promising prognostic biomarker and may be further evaluated as a potential drug target for patients with glioma.

Static adsorptive coating of poly(methyl methacrylate) microfluidic chips for extended usage in DNA separations.

A simple and robust static adsorptive (dynamic) coating process using 2% hydroxyethylcellulose was developed for surface modification of poly(methyl methacrylate) (PMMA) microfluidic chips for DNA separations, suitable for usage over extended periods, involving hundreds of runs. The coating medium was also used as a sieving matrix for the DNA separations following the coating process. Four consecutive static treatments, by simply filling the PMMA chip channels with sieving matrix once every day, were required for obtaining a stable coating and optimum performance. The performance of the coated chips at different phases of the coating process was studied by consecutive gel electrophoretic separations with LIF detection using a PhiX-174/HaeIII DNA digest sample. The coated chip, with daily renewal of the sieving matrix, showed high stability in performance during a 25-day period of systematic study, involving more than 100 individual runs. The performance of the coated chip also remained almost the same after 3 months of continuous usage, during which over 200 separations were performed. The average precision of migration time for the 603-bp fragment was 1.31% RSD (n = 6) during the 25-day study, with a separation efficiency of 6.5 x 10(4) plates (effective separation length 5.4 cm).