ABSTRACT
Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.
ABSTRACT
Objective To explore the role of resveratrol (RES) on cardiomyocyte hypertrophy of rat induced by isoproternol (ISO) and the effect of Res on the expression of GRP78 and GRP94 in endoplasmic reticulum stress of cardiomyocyte hypertrophy.Methods Hypertrophic model of cardiomyocytes was induced by ISO.Cardiomyocytes was divided into four group: control group, the model group, RES+ISO group and RES group.Hypertrophy status of cardiomyocytes was determined by Leica 2Q500 image analysis system measuring the cell surface area and the gene expression of ANP.The content of LDH and MDA was measured in different groups, and the protein expressions of GRP78 and GRP94 were detected by Western blot.Results Compared with control group, ISO induced cardiomyocytes hypertrophy, endoplasmic reticulum stress related factors GRP78 and GRP94 protein expression were increased, compared with ISO group, RES intervention effectively suppressed the cardiomyocytes hyper-trophy induced by ISO, reduced the protein expression of GRP78 and GRP94, at the same time, reduced lactate dehydrogenase (LDH) and malondialdehyde (MDA) release in cell medium.Conclusions Treatment of RES may protect cardiomyocytes hypertrophy, which is partially mediated by inhibiting the expression of ERS factors GRP78 and GRP94.
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OBJECTIVE To investigate the distribution and resistance of commonly encountered pathogens,and provide reference of antimicrobial agents.METHODS For the clinical specimens during the last three years,flora identification and bacteriostatic test were operated with Microscan WalkAway-40.RESULTS Gram-negative bacteria were 252,507 and 742 strains,Gram-positive bacteria were 142,166,and 243 strains,fung were 0,26,and 229 strains from 2002 to 2004,respectively,the most commonly encountered Gram-negative bacteria were Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa,Enterobacter cloacae,and Acinetobacter baumannii;the Gram positive bacteria were Staphylococcus aureus,S.epidermidis,S.haemolyticus,and Enterococcus.CONCLUSIONS It is important for reasonable drug application to know the distribution and resistance of commonly encountered bacteria.
ABSTRACT
OBJECTIVE:To observe the factors that influence the fluctuation of serum concentrations of valproic acid and to improve the effectiveness and usefulness of monitoring the serum concentration.METHODS:The factors that influence the serum concentration of valproic acid were summed up and the countermeasures were put forward.RESULTS:These influencing factors included the drug administration time;the blood sampling time;the right moment for monitoring;the dosage forms and quality of drug;the obedience of patient;combining use of drugs and the physiological and pathological conditions of pa?tients.CONCLUSION:When epileptic patients receive long-term medical treatment,the doctor,the patient and the pharma?cist should communicate mutually,establish the relevant data,pay attention to those factors and ensure the patients safe and effective in use of drug.