This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial and also assessed factors and mechanisms related to the efficacy. Thirty-six children (ages 6 months to 20 years old) with CP were enrolled and treated with UCB or a placebo. Muscle strength and gross motor function were evaluated at baseline and 1, 3, and 6 months after treatment. Along with function measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels were quantitated in serial blood samples. The UCB group showed greater improvements in muscle strength than the controls at 1 (0.94 vs. -0.35, respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB group also showed greater improvements in gross motor performance than the control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally, positron emission tomography scans revealed decreased periventricular inflammation in patients administered UCB, compared with those treated with a placebo. Correlating with enhanced gross motor function, elevations in plasma pentraxin 3 and interleukin-8 levels were observed for up to 12 days after treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll-like receptor 4 were noted at 1 day after treatment in the UCB group, and they were correlated with increased muscle strength at 3 months post-treatment. In this trial, treatment with UCB alone improved motor outcomes and induced systemic immune reactions and anti-inflammatory changes in the brain. Generally, motor outcomes were positively correlated with the number of UCB cells administered: a higher number of cells resulted in better outcomes. Nevertheless, future trials are needed to confirm the long-term efficacy of UCB therapy, as the follow-up duration of the present trial was short.
Cellular prion protein, a membrane protein, is expressed in all mammals. Prion protein is also found in human blood as an anchorless protein, and this protein form is one of the many potential sources of misfolded prion protein replication during transmission. Many studies have suggested that β-amyloid1–42 oligomer causes neurotoxicity associated with Alzheimer's disease, which is mediated by the prion protein that acts as a receptor and regulates the hippocampal potentiation. The prevention of the binding of these proteins has been proposed as a possible preventative treatment for Alzheimer's disease; therefore, a greater understanding of the binding hot-spots between the two molecules is necessary. In this study, the epitope mapping immunoassay was employed to characterize binding epitopes within the prion protein and complementary epitopes in β-amyloid. Residues 23–39 and 93–119 in the prion protein were involved in binding to β-amyloid1–40 and 1–42, and monomers of this protein interacted with prion protein residues 93–113 and 123–166. Furthermore, β-amyloid antibodies against the C-terminus detected bound β-amyloid1–42 at residues 23–40, 104–122 and 159–175. β-Amyloid epitopes necessary for the interaction with prion protein were not determined. In conclusion, charged clusters and hydrophobic regions of the prion protein were involved in binding to β-amyloid1–40 and 1–42. The 3D structure appears to be necessary for β-amyloid to interact with prion protein. In the future, these binding sites may be utilized for 3D structure modeling, as well as for the pharmaceutical intervention of Alzheimer's disease.
Escherichia coli O157:H7 (O157) is an enterohemorrhagic pathogenic subtype, causing diarrhea and Hemolytic-uremic syndrome (HUS). Treatment for HUS patients might be accompanied with antibiotics and antispasmodics with analgesics for abdominal pain.Antiperistaltic effect of antispasmodics, however, may increase the risk of infection of O157 through the intestine. If analgesics also have antibacteiral effect, the prevention and cure of O157 could get benefits. Akhter, T. et al. (2010) reported the inhibitory effect of ibuprofen (IBF) on the bacterial isolates from infected urinary tract. Here, we also found that acetaminophen (4-AAP) and its regioisomer, 3-acetamidophenol (3-AAP), constrained the growth of O157. Inhibitory effect was compared with IBF, since they were both COX inhibitors for their inhibitory mechanism. The experiment results showed that O157 growth was reduced in the presence of 4-AAP, 3-AAP, and IBF. Among them, the inhibitory effect of 4-AAP was less than 3-AAP and IBF in 1.8 fold at 10 mM concentrations. In addition, 4-AAP and 3-AAP inhibited the activity of endogenous peroxidase of E. coli, as well as, horseradish peroxidase (HRP), implying its possible inhibitory mechanism. However, IBF did not inhibit peroxidase activity, suggesting the different mechanism to suppress the growth of O157 by 4-AAP and 3-AAP.
Recently, new virulent strain of Escherichia coli (E.coli) bacteria (0104:H4) was identified, causing ongoing outbreak of food poisoning in Europe, infecting up to 1,600 people with 18 deaths, especially in Germany. More common strain of E. coli for the hemorrhagic colitis and hemolytic uremic syndrome in human from food poisoning was E. coli O157:H7 (O157). Hence, various diagnostic methods for detecting O157 using staining procedure, PCR after cell lysis, sandwich ELISA, electrochemical biosonsors, and SPR biosensor were developed to expedite the detection time. In this study, our aim was to detect and monitor O157 non-invasively without lysing cells by using its endogenous membrane peroxidase. The genomic analysis revealed that O157 had seven different peroxidases, however, their expression levels, locations, or activities had not been revealed. Various peroxidase substrates for the detection by absorption, fluorescence and luminescence spectroscopies revealed 3,3′,5,5′ Tetramethylbenzidine (TMB), as the best peroxidase substrate against O157. Using TMB, the membrane peroxidase of O157 could be detected in 30 to 60 min with the detection levels of 10 5 cells/ mL, comparable to current ELISA kits. Since TMB is a well-known colorimetric HRP substrate without using sophisticated equipments and procedures, the quantification of O157 with the hand-held portable device could yield compatible detection limit. In future, in conjunction with conjugated anti-O157 antibody on magnetic beads, the present method of using endogenous membrane peroxidases could be further developed to a simple point of care test system to be used in the field.
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