[Research on the method of loading exosomes onto absorbable stents].

Objective: To explore a method of loading exosomes onto absorbable stents. Methods: By building a stent-(3-aminopropyl) triethoxysilane-1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) 5000]-exosomes connection, the exosomes were loaded onto absorbable stents to obtained the exosome-eluting absorbable stents. The surface conditions of the stents and absorption of exosomes were observed by scanning electron microscope and identified through the time-of-flight mass spectrometry; the roughness of the stents' surfaces was observed by atomic force microscope; the appearances and sizes of the stents were observed by stereomicroscope; and the radial force was tested by tensile test machine. The absorbable stents were used as control. Results: The scanning electron microscope observation showed that the exosome-eluting absorbable stents had some small irregular cracks on the surface where many exosomes could be seen. The atomic force microscopy observation showed that within the range of 5 µm 2, the surface roughness of the absorbable stents was ±20 nm, while the surface roughness of the exosome-eluting absorbable stents was ±70 nm. In the results of time-of-flight mass spectrometry, both the exosome-eluting absorbable stents and exosomes had a peak at the mass charge ratio of 81 (m/z 81), while the absorbable stents did not have this peak. The peak of exosome-eluting absorbable stents at m/z 73 showed a significant decrease compared to the absorbable stents. The stereomicroscope observation showed that the sizes of exosome-eluting absorbable stents met standards and the surfaces had no cracks, burrs, or depressions. The radial force results of the exosome-eluting absorbable stents met the strength standards of the original absorbable stent. Conclusion: By applying the chemical connection method, the exosomes successfully loaded onto the absorbable stents. And the sizes and radial forces of this exosome-eluting absorbable stents meet the standards of the original absorbable stents.

Comparison of Gelatin/Polylysine- and Silk Fibroin/SDF-1α-Coated Mesenchymal Stem Cell-Seeded Intracranial Stents.

Endothelialization of the aneurysmal neck is essential for aneurysm healing after endovascular treatment. Mesenchymal stem cell (MSC)-seeded stents can promote aneurysm repair. The biological effects of coated and uncoated nitinol intracranial stents seeded with MSCs on vascular cells and macrophage proliferation and inflammation are investigated. Two stent coatings that exert pro-aggregation effects on MSCs via different mechanisms are examined: gelatin/polylysine (G/PLL), which enhances cell adhesion, and silk fibroin/SDF-1α (SF/SDF-1α), which enhances chemotaxis. The aim is to explore the feasibility of MSC-seeded coated stents in the treatment of intracranial aneurysms. The G/PLL coating provides the highest cytocompatibility and blood compatibility substrate for MSCs and vascular cells and promotes cell adhesion and proliferation. Moreover, it enhances MSC secretion and regulation of vascular cell and macrophage proliferation and chemotaxis. Although the SF/SDF-1α coating promotes MSC secretion and vascular cell chemotaxis, it induces a greater degree of macrophage proliferation, chemotaxis, and secretion of pro-inflammatory factors. MSC-seeded stents coated with G/PLL may benefit stent surface endothelialization and reduce the inflammatory response after endovascular treatment of intracranial aneurysm. These effects may improve aneurysm healing and increase the cure rate.

Abnormal hubs in global network as neuroimaging biomarker in right temporal lobe epilepsy at rest.

While abnormal neuroimaging features have been reported in patients suffering from right temporal lobe epilepsy (rTLE), the value of altered degree centrality (DC) as a diagnostic biomarker for rTLE has yet to be established. As such, the present study was designed to examine DC abnormalities in rTLE patients in order to gauge the diagnostic utility of these neuroimaging features. In total, 68 patients with rTLE and 73 healthy controls (HCs) participated in this study. Imaging data were analyzed using DC and receiver operating characteristic (ROC) methods. Ultimately, rTLE patients were found to exhibit reduced right caudate DC and increased left middle temporal gyrus, superior parietal gyrus, superior frontal gyrus, right precuneus, frontal gyrus Inferior gyrus, middle-superior frontal gyrus, and inferior parietal gyrus DC relative to HC. ROC analyses indicated that DC values in the right caudate nucleus could be used to differentiate between rTLE patients and HCs with a high degree of sensitivity and specificity. Together, these results thus suggest that rTLE is associated with abnormal DC values in the right caudate nucleus, underscoring the relevance of further studies of the underlying pathophysiology of this debilitating condition.

The decreased connectivity in middle temporal gyrus can be used as a potential neuroimaging biomarker for left temporal lobe epilepsy.

Objective: We aimed to explore voxel-mirrored homotopic connectivity (VMHC) abnormalities between the two brain hemispheres in left temporal lobe epilepsy (lTLE) patients and to determine whether these alterations could be leveraged to guide lTLE diagnosis. Materials and methods: Fifty-eight lTLE patients and sixty healthy controls (HCs) matched in age, sex, and education level were recruited to receive resting state functional magnetic resonance imaging (rs-fMRI) scan. Then VHMC analyses of bilateral brain regions were conducted based on the results of these rs-fMRI scans. The resultant imaging data were further analyzed using support vector machine (SVM) methods. Results: Compared to HCs, patients with lTLE exhibited decreased VMHC values in the bilateral middle temporal gyrus (MTG) and middle cingulum gyrus (MCG), while no brain regions in these patients exhibited increased VMHC values. SVM analyses revealed the diagnostic accuracy of reduced bilateral MTG VMHC values to be 75.42% (89/118) when differentiating between lTLE patients and HCs, with respective sensitivity and specificity values of 74.14% (43/58) and 76.67% (46/60). Conclusion: Patients with lTLE exhibit abnormal VMHC values corresponding to the impairment of functional coordination between homotopic regions of the brain. These altered MTG VMHC values may also offer value as a robust neuroimaging biomarker that can guide lTLE patient diagnosis.

Emodin attenuates acute lung injury in Cecal-ligation and puncture rats.

Acute lung injury (ALI) is a major cause of sepsis-induced acute respiratory failure. Emodin has been considered to play a protective role for acute lung edema in cecal ligation and puncture (CLP)-induced sepsis model. In this study we aimed to investigate whether emodin could improve CLP-induced lung sepsis via regulating aquaporin (AQP) and tight junction (TJ), inflammatory factors, and pulmonary apoptosis. The results showed that sepsis-induced pulmonary pathological changes were significantly improved after emodin treatment. Emodin was found to upregulate AQP and TJ expression in the CLP model. Meanwhile, inflammatory cytokine release and pulmonary apoptosis was remarkably reduced after emodin treatment in lung sepsis. Our data demonstrated that emodin could suppresse inflammation, restore pulmonary epithelial barrier and reduce mortality in CLP-induced ALI, suggesting the potential therapeutic application of emodin in sepsis.

Protective effect of emodin on intestinal epithelial tight junction barrier integrity in rats with sepsis induced by cecal ligation and puncture.

The present study investigated the protective effects of emodin on intestinal epithelial tight junction (TJ) barrier integrity in cecal ligation and puncture (CLP)-induced septic rats and its possible mechanisms of action. Healthy male Sprague-Dawley rats were randomly divided into three groups (n=20 per group): Sham group, CLP group and CLP + emodin group. Animals were sacrificed at 12 and 24 h after the model was established. Abdominal aortic blood and specimens of the ileum were harvested for analysis. The histopathological changes in intestinal mucosa and the ultrastructures of intestinal epithelial cells were investigated using light microscopy and transmission electron microscopy. The integrity of the intestinal barrier was assessed by examining plasma diamine oxidase (DAO) levels and the ratio of urine lactulose to mannitol (L/M). The levels of the intestinal TJ proteins claudin-3, zonula occludens (ZO)-1 and occludin were detected using immunohistochemistry, western blotting and reverse transcription-quantitative PCR. The results showed that the pathological damage to intestinal mucosa and the intestinal tissue injury score in the CLP + emodin group were significantly reduced compared to those of the CLP group, and the differences were more obvious at 24 h compared with 12 h. DAO activity and the L/M ratio in the emodin pre-treatment group decreased significantly at 24 h compared with the CLP groups. The protein and mRNA levels of the TJ proteins claudin-3, ZO-1 and occludin in the emodin pre-treatment groups at 12 and 24 h were increased, while occludin mRNA level was found to be decreased compared with the CLP groups. The present study suggested that emodin may significantly reduce the damage to the intestinal epithelial barrier in sepsis, inhibit intestinal barrier permeability and protect intestinal barrier integrity. Emodin may protect intestinal barrier integrity by elevating expression levels of the TJ proteins claudin-3, ZO-1 and occludin in CLP rats.

Pegylated recombinant human granulocyte colony-stimulating factor regulates the immune status of patients with small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive disease involving immunodeficiency for which chemotherapy is the standard treatment. Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is widely used for primary or secondary prophylaxis of febrile neutropenia (FN) in chemotherapy. However, whether PEG-rhG-CSF influences immune cells, such as lymphocytes, remains unclear. METHODS: A total of 17 treatment-naïve SCLC patients were prospectively enrolled and divided into the PEG-rhG-CSF and control groups according to their FN risk. Longitudinal sampling of peripheral blood was performed before, after and 4-6 days after the first cycle of chemotherapy. Flow cytometry was used to assess lymphocyte subsets, including CD3+ T, CD4+ T, CD8+ T, NK, and B cells. The diversity and clonality of the T-cell receptor (TCR) repertoire was analyzed by next-generation sequencing. RESULTS: In the PEG-rhG-CSF group, the proportions of CD3+ T and CD4+ T cells had increased significantly (P = 0.002, P = 0.020, respectively), whereas there was no increase in CD8+ T cells. Further, TCR diversity increased (P = 0.009) and clonality decreased (P = 0.004) significantly after PEG-rhG-CSF treatment. However, these factors showed opposite trends before and after chemotherapy. Vß and Jß gene fragment types, which determine TCR diversity, were significantly amplified in the PEG-rhG-CSF group. The change in TCR diversity was significantly correlated with changes in the CD3+ T or CD4+ T cell proportions, but not the CD8+ T cell proportion. CONCLUSIONS: PEG-rhG-CSF regulates the immune status of SCLC patients; CD4+ T cells may be the main effector cells involved in this process. These findings may optimize the treatment of SCLC. KEY POINTS: PEG-rhG-CSF regulates SCLC immunity. PEG-rhG-CSF increased CD3+ T and CD4+ T cell proportions. PEG-rhG-CSF increased TCR diversity and decreased clonality in peripheral blood. Change in TCR diversity were correlated with CD3+ T or CD4+ T changes.

Comb-assisted, Pound-Drever-Hall locked cavity ring-down spectrometer for high-performance retrieval of transition parameters.

Fast and high-performance cavity ring-down spectrometer (CRDS) is highly desired to precisely extract spectral parameters. In this paper, we present our comb-assisted Pound-Drever-Hall (PDH) locked CRDS setup, aiming to retrieve molecular parameters. In the setup, a dynamic feedback is used to keep the tight PDH locking even under strong absorption in the spectral measurement. PDH light and probing light enter the ring-down cavity simultaneously under orthogonal polarization, which enables a fast acquisition of ring-down events without interrupting PDH locking. Ultra-stable cavity temperature is realized, which has an accuracy below 0.5 mK in 27 minutes. The optical frequency comb (OFC) system is developed to rapidly and automatically measure the frequency axis with a relatively wide beat-note range. The minimum detectable absorption coefficient and noise-equivalent absorption coefficient (NEA) are 7.6×10-12cm-1 and 5.3×10-12cm-1Hz-1/2, respectively. The spectrometer is implemented to measure CO2 transition and extract line parameters. The uncertainty for line position is evaluated to be 120 kHz. An accuracy of 0.31% for line intensity is beneficial to the precise determination of CO2 content for the purpose of environment protection and other applications.

Omentin-1 protects renal function of mice with type 2 diabetic nephropathy via regulating miR-27a-Nrf2/Keap1 axis.

Omentin-1, a novel identified adipokine, always significantly decreases in patients with metabolic syndrome. However, the functional roles of omentin-1 in diabetic nephropathy (DN) remains largely unknown. In the present study, we found that omentin-1 treatment could improve renal function of type 2 diabetic db/db mice. ELISA assay and immunohistochemistry staining showed that omentin-1 reduced the productions of proinflammatory cytokines (IFN-γ, TNF-α, MCP-1 and IL-8), and improved oxidative stress level (CAT, MDA and SOD) in the kidney tissue, indicating omentin-1 could relieved the inflammatory response and suppressed oxidative stress. Mechanistic analysis demonstrated that omentin-1 down-regulated miR-27a expression, and subsequently inhibited oxidative stress and inflammation. Luciferase reporter assay and western blot further revealed that miR-27a directly targeted the 3' untranslated region (UTR) of nuclear factor erythroid 2-like 2 (Nrf2) and reduced its expression in type 2 DN. Taken together, these findings provide a new function of omentin-1 in renal protection and also delineate multiple potential targets for therapeutic intervention for type 2 DN.

Adiponectin and its receptors are involved in hypertensive vascular injury.

Adipocyte-derived adiponectin (APN) is involved in the protection against cardiovascular disease, but the endogenous APN and its receptor expression in the perivascular adipocytes and their role in hypertensive vascular injury remain unclear. The present study aimed to detect endogenous APN and its receptor expression and their protective effects against hypertensive vascular injury. APN was mainly expressed in the perivascular adipocytes, while its receptors AdipoR1 and AdipoR2 were ubiquitously expressed in the blood vessels. Angiotensin II (Ang II)­induced hypertension resulted in a significant decrease of APN and AdipoR1 and AdipoR2 in the perivascular adipocytes and vascular cells. The migration assay used demonstrated that APN attenuated Ang II­induced vascular smooth muscle cells migration and p38 phosphorylation Furthermore, the in vivo study demonstrated that APN receptor agonist AdipoRon attenuated Ang II­induced hypertensive vascular hypertrophy and fibrosis. Taken together, the present study indicated that perivascular adipocytes­derived APN attenuated hypertensive vascular injury possibly via its receptor­mediated inhibition of p38 signaling pathway.

Optical amplification in Er/Yb silicate slot waveguide.

Active slot waveguides were fabricated by embedding low-index Er/Yb silicate material in high-index silicon. A 1.7 dB signal enhancement at 1.53 µm in a 6 mm-long slot waveguide was observed through 1476 nm pumping. The peak Er emission cross-section is determined as 7.53×10(-21) cm2 and the excited Er ion fraction is 0.17. Our experiment shows that the defects in upper c-Si of Si-on-insulator (SOI) and deposited α-Si distorts photoluminescence spectrum and prevents further optical amplification. This negative effect can be partly corrected through annealing treatment, which allows better propagation of the pump light, therefore, stronger excitation in the sandwiched Er/Yb silicate. The defects also affect the 1.53 µm decay curve and are the dominant lifetime reduction mechanism in the active slot waveguide.

Active metal strip hybrid plasmonic waveguide with low critical material gain.

An active metal strip hybrid plasmonic waveguide (MSHPW) using gain materials as loss compensation is proposed with an extremely simple fabrication procedure. Gain materials are introduced either in the low-index layer or in the high-index layer of MSHPW. The effects of waveguide dimensions and material gain coefficients on loss compensation are analyzed at the communication wavelength. For one configuration presented here, a critical material gain as low as 3.8cm(-1) is sufficient for fully compensation of the loss when using a high-index gain material. The active MSHPW with low critical material gain opens up opportunities for practical plasmonic devices in active applications such as amplifiers, sources, and modulators.

[Incidence of metabolic disorders in patients with essential hypertension and patients with primary aldosteronism].

OBJECTIVE: To compare the incidence of metabolic disorders (MS) in patients with primary aldosteronism (PA) and essential hypertension (EH). METHODS: MS prevalence was observed in 200 EH patients (male 104) and 220 PA patients (male 117) hospitalized to our hospital from August 2005 to March 2007. RESULTS: (1) The prevalence of MS in PA group was significantly higher than that of EH group (47.3% vs. 31.5%, P = 0.009). (2) Blood pressure was significantly higher in PA group than that of EH [SBP: (150.67 +/- 15.45) mm Hg vs. (145.69 +/- 17.13) mm Hg, P = 0.042; DBP: (93.03 +/- 10.51) mm Hg vs. (85.83 +/- 14.44) mm Hg, P = 0.037]. (3) Incidences of abdominal obesity (86.8% vs. 78.5%, P = 0.024) and insulin resistance (insulin sensitivity index: 42.42 +/- 16.11 vs. 49.58 +/- 22.43, P = 0.008) were significantly higher in PA group than in EH group. CONCLUSION: The prevalence of MS in hospitalized PA patients was significantly higher than that of EH patients characterized by prevalent abdominal obesity, insulin resistant and severe hypertension.