Paeonol Inhibits Proliferation of Vascular Smooth Muscle Cells Stimulated by High Glucose via Ras-Raf-ERK1/2 Signaling Pathway in Coculture Model

Paeonol (Pae) has been previously reported to protect against atherosclerosis (AS) by inhibiting vascular smooth muscle cell (VSMC) proliferation or vascular endothelial cell (VEC) injury. But studies lack how VSMCs and VECs interact when Pae plays a role. The current study was based on a coculture model of VSMCs and VECs to investigate the protective mechanisms of Pae on atherosclerosis (AS) by determining the secretory function of VECs and proliferation of VSMCs focusing on the Ras-Raf-ERK1/2 signaling pathway. VECs were stimulated by high glucose. Our data showed that high concentration (35.5 mM) of glucose induced damage in VECs. Injury of VECs stimulated VSMC proliferation in the coculture model. Pae (120 μM) decreased vascular endothelial growth factor (VEGF) and platelet derivative growth factor B (PDGF-B) release from VECs and inhibited overexpression of Ras, P-Raf, and P-ERK proteins in VSMCs. The results indicate that diabetes modulates the inflammatory response in VECs to stimulate VSMC proliferation and promote the development of AS. Pae was beneficial by inhibiting the inflammatory effects of VECs on VSMC proliferation. This study suggests the inhibitory mechanism of Pae due to the inhibition of VEGF and PDGF-B secretion in VECs and Ras-Raf-ERK1/2 signaling pathway in VSMCs

Studies of dopamine oxidation process by atmospheric pressure glow discharge mass spectrometry

An atmospheric pressure glow discharge ionisation source was constructed and utilized to study the dopamine (DA) oxidation process coupling with mass spectrometry. During the DA oxidation process catalysed by polyphenol oxidase (PPO), six cationic intermediates were directly detected by the atmospheric pressure glow discharge mass spectrometry (APGD-MS). Combined with tandem mass spectrometry, the structures of the dopamine o-semiquinone radical (DASQ) and leukodopaminochrome radical (LDAC●) intermediates and structures of the isomers of dopaminochrome (DAC) and 5,6-dihydroxyindole (DHI) were further characterised with the introduction of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) and deuterium oxide (D2O) to APGD-MS. Meanwhile, UV–Vis studies confirmed the important role of PPO in catalyzing the DA oxidation reaction. Based on APGD-MS studies, a possible mechanism could be proposed for DA oxidation catalysed by PPO. Furthermore, APGD-MS could provide possibilities for the effective detection and characterisation of short-lived intermediates, even in complicated systems

Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis

<p>Abstract</p> <p>Background</p> <p>Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of collagens by proteases produces small fragments, so-called neoepitopes, which are released systemically. Technologies investigating MMP-generated fragments of collagens may provide more useful information than traditional serological assays that crudely measure total protein. In the present study, we developed an ELISA for the quantification of a neoepitope generated by MMP degradation of type IV collagen and evaluated the association of this neoepitope with liver fibrosis in two animal models.</p> <p>Methods</p> <p>Type IV collagen was degraded <it>in vitro </it>by a variety of proteases. Mass spectrometric analysis revealed more than 200 different degradation fragments. A specific peptide sequence, 1438'GTPSVDHGFL'1447 (CO4-MMP), in the α1 chain of type IV collagen generated by MMP-9 was selected for ELISA development. ELISA was used to determine serum levels of the CO4-MMP neoepitope in two rat models of liver fibrosis: inhalation of carbon tetrachloride (CCl₄) and bile duct ligation (BDL). The levels were correlated to histological findings using Sirius red staining.</p> <p>Results</p> <p>A technically robust assay was produced that is specific to the type IV degradation fragment, GTPSVDHGFL. CO4-MMP serum levels increased significantly in all BDL groups compared to baseline, with a maximum increase of 248% seen two weeks after BDL. There were no changes in CO4-MMP levels in sham-operated rats. In the CCl₄model, levels of CO4-MMP were significantly elevated at weeks 12, 16 and 20 compared to baseline levels, with a maximum increase of 88% after 20 weeks. CO4-MMP levels correlated to Sirius red staining results.</p> <p>Conclusion</p> <p>This ELISA is the first assay developed for assessment of proteolytic degraded type IV collagen, which, by enabling quantification of basement membrane degradation, could be relevant in investigating various fibrogenic pathologies. The CO4-MMP degradation fragment was highly associated with liver fibrosis in the two animal models studied.</p

Edible Mushroom Cultivation for Food Security and Rural Development in China: Bio-Innovation, Technological Dissemination and Marketing

Mushrooms traditionally collected from forests and now more cultivated have recently become the products of the fifth-largest agricultural sector in China. It was estimated that more than 25 million farmers in China are currently engaged in the collection, cultivation processing and marketing of mushrooms. The total value of mushroom products amounted to 149 billion RMB Yuan (24 billion USD) in 2011. The raw materials have expanded from a few hardwoods to a variety of woods and increasing more into agricultural residues and wastes. The average annual growth rate has been over 10% over the past 30 years in China. This paper describes the rapid growth of mushroom cultivation and its contribution to food security and rural sustainable development. The roles of bio-innovation, technological dissemination, and marketing are also examined. Mushrooms could potentially be very important in future food supplies and in new dimensions of sustainable agriculture and forestry

A causal relationship between panic disorder and risk of alzheimer disease: a two-sample mendelian randomization analysis

Abstract Background Observational studies have suggested a link between panic disorder (PD) and Alzheimer disease (AD). This study aimed to identify the underlying association of PD with the risk of AD using Mendelian randomization. Methods Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests. Results The Cochran’s Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p = 0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p = 0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p = 0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results. Conclusion This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities

A facile preparation of FePt-loaded few-layer MoS2 nanosheets nanocomposites (F-MoS2-FePt NCs) and their application for colorimetric detection of H2O2 in living cells

Abstract Background Rapid and sensitive detection of H2O2 especially endogenous H2O2 is of great importance for series of industries including disease diagnosis and therapy. In this work, uniform FePt nanoparticles are successfully anchored onto Few-layer molybdenum disulfide nanosheets (F-MoS2 NSs). The powder X-ray diffraction, transmission electron microscopy, UV–Vis spectra and atomic force microscopy were employed to confirm the structure of the obtained nanocomposites (F-MoS2-FePt NCs). The prepared nanocomposites show efficient peroxidase-like catalytic activities verified by catalyzing the peroxidation substrate 4,4′-diamino-3,3′,5,5′-tetramethylbiphenyl (TMB) with the existence of H2O2. Results The optimal conditions of the constructed colorimetric sensing platform is proved as 35 °C and pH 4.2. Under optimal catalytic conditions, the detection limit for H2O2 detection reaches 2.24 μM and the linear ranger is 8 μM to 300 μM. Furthermore, the proposed colorimetric sensing platform was successfully utilized to detect the intracellular H2O2 of cancer cells (MCF-7). Conclusions These findings indicated that the F-MoS2-FePt-TMB-H2O2 system provides a potential sensing platform for hydrogen peroxide monitoring in living cells