Amyloid precursor protein in peripheral granulocytes as a potential biomarker for Alzheimers disease

The aim of this study was to assess the potential of amyloid precursor protein in peripheral granulocytes as a diagnostic biomarker for early detection of Alzheimers disease. Immunohistochemistry and flow cytometry were used to evaluate amyloid precursor protein expression levels and subcellular localization in Alzheimers disease. Much higher amyloid precursor protein expression was observed in some leukocytes from Alzheimers disease patients, compared with samples from non-Alzheimers disease controls. In addition, flow cytometry data indicated significantly higher amyloid precursor protein  expression in granulocytes from Alzheimers disease patients compared with control values. No statistically significant differences in amyloid precursor protein  expression were obtained in lymphocytes or monocytes between the patient groups. In conclusion, amyloid precursor protein expression level in peripheral blood granulocyte is a potential biomarker for early diagnosis of Alzheimers disease.

BMPRIA mediated signaling is essential for temporomandibular joint development in mice

The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development

Potential mechanism of tea for treating osteoporosis, osteoarthritis, and rheumatoid arthritis

Osteoporosis (OP), osteoarthritis (OA), and rheumatoid arthritis (RA) are common bone and joint diseases with a high incidence and long duration. Thus, these conditions can affect the lives of middle-aged and elderly people. Tea drinking is a traditional lifestyle in China, and the long-term intake of tea and its active ingredients is beneficial to human health. However, the mechanisms of action of tea and its active ingredients against OP, OA, and RA are not completely elucidated. This study aimed to assess the therapeutic role and related mechanisms of tea and its active ingredients in OP, OA, and RA. Moreover, it expanded the potential mechanisms of tea efficacy based on network pharmacology and molecular docking. Results showed that tea has potential anti-COX properties and hormone-like effects. Compared with a single component, different tea components synergize or antagonize each other, thereby resulting in a more evident dual effect. In conclusion, tea has great potential in the medical and healthcare fields. Nevertheless, further research on the composition, proportion, and synergistic mechanism of several tea components should be performed

The association of lesion eccentricity with plaque morphology and components in the superficial femoral artery: a high-spatial-resolution, multi-contrast weighted CMR study

<p>Abstract</p> <p>Background</p> <p>Atherosclerotic plaque morphology and components are predictors of subsequent cardiovascular events. However, associations of plaque eccentricity with plaque morphology and plaque composition are unclear. This study investigated associations of plaque eccentricity with plaque components and morphology in the proximal superficial femoral artery using cardiovascular magnetic resonance (CMR).</p> <p>Methods</p> <p>Twenty-eight subjects with an ankle-brachial index less than 1.00 were examined with 1.5T high-spatial-resolution, multi-contrast weighted CMR. One hundred and eighty diseased locations of the proximal superficial femoral artery (about 40 mm) were analyzed. The eccentric lesion was defined as [(Maximum wall thickness- Minimum wall thickness)/Maximum wall thickness] ≥ 0.5. The arterial morphology and plaque components were measured using semi-automatic image analysis software.</p> <p>Results</p> <p>One hundred and fifteen locations were identified as eccentric lesions and sixty-five as concentric lesions. The eccentric lesions had larger wall but similar lumen areas, larger mean and maximum wall thicknesses, and more calcification and lipid rich necrotic core, compared to concentric lesions. For lesions with the same lumen area, the degree of eccentricity was associated with an increased wall area. Eccentricity (dichotomous as eccentric or concentric) was independently correlated with the prevalence of calcification (odds ratio 3.78, 95% CI 1.47-9.70) after adjustment for atherosclerotic risk factors and wall area.</p> <p>Conclusions</p> <p>Plaque eccentricity is associated with preserved lumen size and advanced plaque features such as larger plaque burden, more lipid content, and increased calcification in the superficial femoral artery.</p

Self-Assembly and Soft Material Preparation of Binary Organogels via Aminobenzimidazole/Benzothiazole and Acids with Different Alkyl Substituent Chains

The gelation behaviors of binary organogels composed of aminobenzimidazole/benzothiazole derivatives and benzoic acid with single-/multialkyl substituent chain in various organic solvents were designed and investigated. Their gelation behaviors in 20 solvents were tested as new binary organic gelators. This showed that the number and length of alkyl substituent chains and benzimidazole/benzothiazole segment have played a crucial role in the gelation behavior of all gelator mixtures in various organic solvents. More alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. The length of alkyl substituent chains has also played an important role in changing the gelation behaviors and assembly states. Morphological studies revealed that the gelator molecules self-assemble into different aggregates from wrinkle, lamella, belt, to fiber with change of solvents. Spectral studies indicated that there existed different H-bond formation and hydrophobic force, depending on benzimidazole/benzothiazole segment and alkyl substituent chains in molecular skeletons. The prepared nanostructured materials have wide perspectives and many potential applications in nanoscience and material fields due to their scientific values. The present work may also give new clues for designing new binary organogelators and soft materials

Variations of brain functional connectivity in alcohol-preferring and non-preferring rats with consecutive alcohol training or acute alcohol administration

Alcohol addiction is regarded as a series of dynamic changes to neural circuitries. A comparison of the global network during different stages of alcohol addiction could provide an efficient way to understand the neurobiological basis of addiction. Two animal models (P-rats screened from an alcohol preference family, and NP-rats screened from an alcohol non-preference family) were trained for alcohol preference with a two-bottle free choice method for 4 weeks. To examine the changes in the neural response to alcohol during the development of alcohol preference and acute stimulation, different trials were studied with resting-state fMRI methods during different periods of alcohol preference. The correlation coefficients of 28 regions in the whole brain were calculated, and the results were compared for alcohol preference related to the genetic background/training association. The variety of coherence patterns was highly related to the state and development of alcohol preference. We observed significant special brain connectivity changes during alcohol preference in P-rats. The comparison between the P- and NP-rats highlighted the role of genetic background in alcohol preference. The results of this study support the alterations of the neural network connection during the formation of alcohol preference and confirm that alcohol preference is highly related to the genetic background. This study could provide an effective approach for understanding the neurobiological basis of alcohol addiction

Altered FGF Signaling Pathways Impair Cell Proliferation and Elevation of Palate Shelves

In palatogenesis, palatal shelves are patterned along the mediolateral axis as well as the anteroposterior axis before the onset of palatal fusion. Fgf10 specifically expressed in lateral mesenchyme of palate maintains Shh transcription in lateral epithelium, while Fgf7 activated in medial mesenchyme by Dlx5, suppressed the expansion of Shh expression to medial epithelium. How FGF signaling pathways regulate the cell behaviors of developing palate remains elusive. In our study, we found that when Fgf8 is ectopically expressed in the embryonic palatal mesenchyme, the elevation of palatal shelves is impaired and the posterior palatal shelves are enlarged, especially in the medial side. The palatal deformity results from the drastic increase of cell proliferation in posterior mesenchyme and decrease of cell proliferation in epithelium. The expression of mesenchymal Fgf10 and epithelial Shh in the lateral palate, as well as the Dlx5 and Fgf7 transcription in the medial mesenchyme are all interrupted, indicating that the epithelial-mesenchymal interactions during palatogenesis are disrupted by the ectopic activation of mesenchymal Fgf8. Besides the altered Fgf7, Fgf10, Dlx5 and Shh expression pattern, the reduced Osr2 expression domain in the lateral mesenchyme also suggests an impaired mediolateral patterning of posterior palate. Moreover, the ectopic Fgf8 expression up-regulates pJak1 throughout the palatal mesenchyme and pErk in the medial mesenchyme, but down-regulates pJak2 in the epithelium, suggesting that during normal palatogenesis, the medial mesenchymal cell proliferation is stimulated by FGF/Erk pathway, while the epithelial cell proliferation is maintained through FGF/Jak2 pathway

Myocardial tissue and metabolism characterization in men with alcohol consumption by cardiovascular magnetic resonance and 11C-acetate PET/CT

Background: Chronic alcohol consumption initially leads to asymptomatic left ventricular dysfunction, but can result in myocardial impairment and heart failure if ongoing. This study sought to characterize myocardial tissues and oxidative metabolism in asymptomatic subjects with chronic alcohol consumption by quantitative cardiovascular magnetic resonance (CMR) and 11C-acetate positron emission tomography (PET)/computed tomography (CT). Methods: Thirty-four male subjects (48.8 +/- 9.1 years) with alcohol consumption > 28 g/day for > 10 years and 35 age-matched healthy male subjects (49.5 +/- 9.7 years) underwent CMR and 11C-acetate PET/CT. Native and post T1 values and extracellular volume (ECV) from CMR and Kmono and K1 from PET imaging were measured. Quantitative measurements by CMR and PET imaging were compared between subjects with moderate to heavy alcohol consumption and healthy controls, and their correlations were also analyzed. Results: Compared to healthy controls, subjects with alcohol consumption showed significantly shorter native T1 (1133 +/- 65 ms vs. 1186 +/- 31 ms, p 0.05). In contrast, subjects with heavy alcohol consumption showed significantly lower Kmono values compared to those with moderate alcohol consumption (52.9 +/- 12.1 min(- 1) x 10(- 3) vs. 63.7 +/- 9.2 min(- 1) x 10(- 3), p = 0.012). Strong and moderate correlations were found between K1 and ECV in healthy controls (r = 0.689, p = 0.013) and subjects with moderate alcohol consumption (r = 0.518, p = 0.048), respectively. Conclusion: Asymptomatic men with heavy alcohol consumption have detectable structural and metabolic changes in myocardium on CMR and 11C-acetate PET/CT. Compared with quantitative CMR, 11C-acetate PET/CT imaging may be more sensitive for detecting differences in myocardial damage among subjects with moderate to heavy alcohol consumption.</div

A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear.MethodsWe describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated.ResultsOur signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group.ConclusionOur signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC