858 research outputs found

    Effect of enalapril maleate-folic acid tablets on inflammatory response and myocardial endoplasmic reticulum stress-related factors in hypertensive rats

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    Purpose: To determine the effect of enalapril maleate folate on inflammatory reaction and myocardial endoplasmic reticulum stress-related factors in hypertensive rats.Methods: Eighty (80) hypertensive rats with SBP > 140 mmHg were equally assigned to control and study groups. Rats in control group were given normal saline by gavage, while the observation group was given enalapril maleate powder (10 mg/kg/day). After 4 weeks of treatment, 2 mL of inferior vena cava blood was collected from each of the two rat groups. The level of homocysteine (Hcy) was determined with Hcy assay kit, while C-reactive protein (CRP) levels in patients were determined by latex immunoturbidimetry. Serum FBG was assessed using automatic biochemical analyzer. The expression levels of GRP78, CRP94, chop and caspase-12 in aortic smooth muscle cells were assayed immunohistochemically.Results: Central arterial pressure (MAP), aortic media thickness, lvwi, HWI FBG and CRP were significantly higher in the study rats, while Hcy level was lower, than in controls (p < 0.05). There were significantly lower levels of glucose regulatory protein 78 (GRP78), CRP94, CHOP and caspase-12 in study rats than in control rats (p < 0.05).Conclusion: Enalapril maleate-folate slows down inflammatory reaction by reducing the levels of Hcy, CRP and FBG. It inhibits the expressions of GRP78, CRP94, CHOP and caspase-12 in myocardium, reduces damage to myocardial cells, and alleviates or reverses left ventricular hypertrophy in rats with high blood pressure. This provides new insight into the research and development of other drugs

    Combinatorial-Entropy-Driven Aggregation in {DNA}-Grafted Nanoparticles

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    We use computer simulations and experiments to study the interactions between nanoparticles (NPs) grafted with self-complementary DNA strands. Each strand ends with a sticky palindromic single-stranded sequence, allowing it to associate equally favorably with strands grafted on the same particle or on different NPs. Surprisingly we find an attractive interaction between a pair of NPs, and we demonstrate that at low temperature it arises purely from a combinatorial-entropy contribution. We evaluate theoretically and verify numerically this entropic contribution originating from the number of distinct bonding patterns associated with intra- and interparticle binding. This entropic attraction becomes more favorable with decreasing inter-NP distance because more sticky ends can participate in making this choice

    CCL3 and CCL20-recruited dendritic cells modified by melanoma antigen gene-1 induce anti-tumor immunity against gastric cancer ex vivo and in vivo

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    <p>Abstract</p> <p>Background</p> <p>To investigate whether dendritic cell (DC) precursors, recruited by injection of <b>chemokine ligand 3 (CCL3) and CCL20</b>, induce anti-tumor immunity against gastric cancer induced by a DC vaccine expressing melanoma antigen gene-1 (MAGE-1) ex vivo and in vivo.</p> <p>Methods</p> <p>B6 mice were injected with CCL3 and CCL20 via the tail vein. Freshly isolated F4/80<sup>-</sup>B220<sup>-</sup>CD11c<sup>+ </sup>cells cultured with cytokines were analyzed by phenotype analysis and mixed lymphocyte reaction (MLR). For adenoviral (Ad)-mediated gene transduction, cultured F4/80<sup>-</sup>B220<sup>-</sup>CD11c<sup>+ </sup>cells were incubated with Ad-MAGE-1. Vaccination of stimulated DC induced T lymphocytes. The killing effect of these T cells against gastric carcinoma cells was assayed by MTT. INF-γ production was determined with an INF-γ ELISA kit. In the solid tumor and metastases model, DC-based vaccines were used for immunization after challenge with MFC cells. <b>Tumor size, survival of mice, and number of pulmonary metastatic foci were used to assess the therapeutic effect of DC vaccines</b>.</p> <p>Results</p> <p>F4/80<sup>-</sup>B220<sup>-</sup>CD11c<sup>+ </sup>cell numbers increased after <b>CCL3 and CCL20 </b>injection. Freshly isolated F4/80<sup>-</sup>B220<sup>-</sup>CD11c<sup>+ </sup>cells cultured with cytokines were phenotyically identical to typical DC and gained the capacity to stimulate allogeneic T cells. These DCs were transduced with Ad-MAGE-1, which were prepared for DC vaccines expressing tumor antigen. T lymphocytes stimulated by DCs transduced with Ad-MAGE-1 exhibited specific killing effects on gastric carcinoma cells and produced high levels of INF-γ ex vivo. In vivo, tumor sizes of the experimental group were much smaller than both the positive control group and the negative control groups (<it>P </it>< 0.05). Kaplan-Meier survival curves showed that survival of the experimental group mice was significantly longer than the control groups (<it>P </it>< 0.05). In addition, MAGE-1-transduced DCs were also a therapeutic benefit on an established metastatic tumor, resulting in a tremendous decrease in the number of pulmonary metastatic foci.</p> <p>Conclusions</p> <p><b>CCL3 and CCL20</b>-recruited DCs modified by adenovirus-trasnsduced, tumor-associated antigen, MAGE-1, can stimulate anti-tumor immunity specific to gastric cancer ex vivo and in vivo. This system may prove to be an efficient strategy for anti-tumor immunotherapy.</p

    Large-area alginate/PEO-PPO-PEO hydrogels with thermoreversible rheology at physiological temperatures

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    Alginate hydrogels have shown great promise for applications in wound dressings, drug delivery, and tissue engineering. Here, we report the fabrication, rheological properties, and dynamics of a multicomponent hydrogel consisting of alginate and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, and the achievement of thick, castable gels with tunable, thermoreversible behavior at physiological temperatures (Figure 1). PEO-PPO-PEO triblock copolymers can form temperature-sensitive hydrogels that exist as liquids at low temperatures and soft solids at high temperatures. In this work, we have employed PEO-PPO-PEO triblock copolymers to impart thermoresponsive properties to alginate hydrogels in the form of a multicomponent hydrogel. These systems can transition between a weak gel and a stiff gel, with a corresponding increase in the viscoelastic moduli of approximately two orders of magnitude as temperature is increased. The temperatures corresponding to the upper and lower boundaries of the stiff gel region, as well as the storage modulus at physiological temperatures (e.g., 36 – 40 C), can be controlled through the PEO-PPO- PEO concentration. Additionally, we explore the properties of these materials under compression and large deformations, and describe how alginate and F127 concentration can be used to control the fracture stress and strain. Finally, we compare the results from bulk rheology to the structure and dynamics of the gels measured via small-angle X-ray scattering (SAXS) and X-ray photon correlation spectroscopy (XPCS) experiments. Please click Additional Files below to see the full abstract

    Association Between Participation in Annual Physical Examinations and Risk Factors for Noncommunicable Diseases in Adults with Disabilities: Evidence from Shanghai, China

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    The relationships between regular participation in annual physical examinations and the risk factors for noncommunicable diseases (NCDs) among adults with disabilities remains unclear. To address this gap, we used data from 130,899 individuals with disabilities in Shanghai (2014-2016) and evaluated four risk factors for NCDs: hypertension, hyperglycemia, hyperlipidemia, and being overweight. Overall, 4540 individuals participated in annual physical examinations across all three years and 11,388 missed examinations in 2015 (group without regular participation). Chi-squared tests and binary logistic regression were used to assess differences in patient characteristics and explore correlations between variables. Significant differences in age (χ2 = 102.620, p \u3c 0.01), place of residence (χ2 = 94.308, p \u3c 0.01), educational level (χ2 = 59.884, p \u3c 0.01), marital status (χ2 = 16.414, p \u3c 0.01) and disability type (χ2 = 56.499, p \u3c 0.01) and severity (χ2 = 45.464, p \u3c 0.01) were found between those who participated in regular physical examinations and those who did not. Regular participation was associated with reduced incidences of hypertension (odds ratio 0.799, 95% confidence interval (CI): 0.733-0.871) and hyperlipidemia (0.347, 95% CI: 0.307-0.392), but not with the incidence of diabetes (1.049, 95% CI: 0.944-1.166) or being overweight (0.907, 95% CI: 0.812-1.014). Hence, regular participation in annual physical examinations had different associations with risk factors for NCDs
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