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The resistance of bacteria to antibiotics is a major public health issue. Klebsiella pneumoniae is a type exemplification of multi-resistant enterobacteria. Its high biofilm forming capacity is a major factor in the recurrent infection of the intestinal tract. In this study, the intrinsic mechanism of secondary growth of K. pneumoniae in response to antibiotics and the inhibition effect of probiotic supernatant on biofilm formation after antibiotic treatment were investigated in a polyester nonwoven chemostat bioreactor. The experimental results showed that the c-di-GMP content in the cells increased after treatment with levofloxacin, leading to the formation of a thick biofilm due to an increase in the production of extracellular polymer substance (EPS) and type 3 fimbriae. Biofilm prevents the mass transfer of levofloxacin and protects K. pneumoniae cells from being killed by levofloxacin. Under suitable conditions, K. pneumoniae cells on the biofilm enter into the suspension for secondary growth. Moreover, the inhibition of probiotic supernatant on the biofilm formation was mainly due to the reduced expression of yfiN and mrkJ genes, and the decreased concentration of c-di-GMP in cells, as well as the less secretion of EPS. At the same time, the decrease in the concentration of c-di-GMP also reduced the expression of the mrkABCDF gene and prevented the synthesis of the type 3 fimbriae. The results would help to understand the mechanism of antibiotic resistance of pathogenic bacteria and to provide evidence to address this problem through the use of probiotics.The above ESNR 2020 abstract supplement was published with an incorrect affiliation for the abstract 1-P21 VARICELLA-ZOSTER VIRUS INFECTION MANIFESTING AS LIMBIC ENCEPHALITIS on page S40 of the supplement.Protein kinase C inhibitor tamoxifen reduces symptoms of acute mania in bipolar patients and mania-like behaviors in animals. Memory impairment and altered levels of glutamate and glutamate/glutamine ratio have been reported in mania. Tamoxifen suppresses glutamate release which plays an important role in memory. The present study evaluated whether tamoxifen's activity participates in its antimanic efficacy in repeated sleep deprivation mania model. Mice were divided into control and 24-h sleep-deprived groups and were treated with vehicle or 1 mg/kg tamoxifen twice daily for 8 days. Sleep deprivation was repeated three times at intervals of 2 days. Square crossing and rearing were recorded as measures of locomotor activity. Memory and risk taking behavior were evaluated using novel object recognition and staircase tests, respectively. Glutamate and glutamine levels were measured in the frontal cortex and hippocampus. Behavioral tests were conducted 24 h after the second or immediately after the third sleep deprivations. Sleep deprivation increased locomotor activity and risk taking. Glutamate and glutamine levels and glutamate/glutamine ratio in the frontal cortex and hippocampus were unaffected. Locomotor hyperactivity was prevented by tamoxifen treatment. No change in the recognition index suggested lack of memory impairment in the model. These findings confirm the relevance of repeated sleep deprivation as a mania model and tamoxifen as an antimanic agent. However, future research is needed to further address lack of memory impairment in the model and lack of glutamatergic influence on the model and antimanic effect of tamoxifen.Nanotechnology has become a promising approach for addressing cancer therapy limitations because it reduces side effects and increases the efficacy of antineoplastic agents. Therefore, this research was designed to compare the in vitro therapeutic efficacy and in vivo adverse effects of gemcitabine (GEM) and gemcitabine-loaded silver nanoparticles (GEM-AgNPs). GEM molecules were successfully attached to AgNP surfaces with a homogenous and spherical shape. The zeta size of AgNPs and GEM-AgNPs was 79.35 ± 3.2 and 75.1 ± 7 nm, respectively. selleck kinase inhibitor The anticancer effect of AgNPs and GEM-AgNPs was investigated against a human hepatocellular carcinoma cell line (HepG2), and cytotoxic activity was evaluated by MTT assay. Apoptosis/necrosis and cell cycle arrest were also assessed. The cytotoxic activity was recorded in a concentration-dependent way. The findings have shown that GEM-AgNPs induced a better cytotoxic effect with an IC50 value of 13.63 μg/mL compared to GEM (IC50 value of 24.19 μg/mL) or AgNPs alone (IC50 value of 50.6 μg/mL). GEM-AgNPs induced pre-G1 arrest and apoptotic/necrotic cell death. Our in vivo analysis involved the use of 40 male rats assigned equally into the control rats, and rats injected intraperitoneally with GEM (134 mg/kg), AgNPs (1 mg/kg), and GEM-AgNPs (134 mg/kg). GEM and GEM-AgNPs were administered on the 1st, 7th, and 14th day of the experiment. Intraperitoneal GEM injection induced marked hematological, biochemical, hepatorenal, and histopathological alterations, while the loading of GEM in AgNPs to some extent ameliorated these alterations and significantly improved its therapeutic efficacy against HepG2 cells. These findings indicate the potential use of GEM-AgNPs in the clinical setting for anticancer treatment.In recent years, there have been efforts to develop therapeutic agents that target metabolic enzyme systems in addition to existing treatment in possible cancer treatments. Cyclophosphamide (CYP) is an anticancer drug commonly used in various cancer treatments. Chrysin (CH) and naringin (NR) are natural flavonoids that possess many medicinal and pharmacological properties. In the present study, we aimed to investigate the effect of CH and NR against CYP-induced toxicity on some metabolic enzyme activities. For this purpose, 56 male rats were randomly divided into 8 groups in our in vivo study. The rats were pretreated with CH (25 and 50 mg/kg bw) and NR (50 and 100 mg/kg bw) for 7 days before administering a single dose of CYP (200 mg/kg bw) on the seventh day. According to the in vivo results of our study, it was observed that CH and NR regulated abnormal changes in CYP-induced enzyme activities. In addition, our in vitro study, G6PD enzyme was purified from rat erythrocyte using affinity chromatography. The effects of CH, NR, and CYP were investigated on the purified enzyme.
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