- Mesoporous composite nanoparticles for dual-modality ultrasound/magnetic resonance imaging and synergistic chemo-/thermotherapy against deep tumors. [Journal Article]
- IJInt J Nanomedicine 2017; 12:7273-7289
- High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment for solid tumors, which has been explored for potential clinical applications. However, the clinical applications of ...
High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment for solid tumors, which has been explored for potential clinical applications. However, the clinical applications of HIFU for large and deep tumors such as hepatocellular carcinoma (HCC) are severely limited by unsatisfactory imaging guidance, long therapeutic times, and damage to normal tissue around the tumor due to the high power applied. In this study, we developed doxorubicin/perfluorohexane-encapsulated hollow mesoporous Prussian blue nanoparticles (HMPBs-DOX/PFH) as theranostic agents, which can effectively guide HIFU therapy and enhance its therapeutic effects in combination with chemotherapy, by decreasing the cavitation threshold. We investigated the effects of this agent on ultrasound and magnetic resonance imaging in vitro and in vivo. In addition, we showed a highly efficient HIFU therapeutic effect against HCC tumors, as well as controlled drug release, owing to the phase-transitional performance of the PFH. We therefore conclude that HMPB-DOX/PFH is a safe and efficient nanoplatform, which holds significant promise for cancer theranostics against deep tumors in clinical settings.
- Oral Glycine and Sodium Thiosulfate for Lethal Cyanide Ingestion. [Journal Article]
- JCJ Clin Toxicol 2017; 7(3)
- CONCLUSIONS: Oral sodium thiosulfate with gastric alkalization rescued animals from lethal doses of ingested cyanide. The combination of oral glycine and sodium thiosulfate may have potential for treating high dose acute cyanide ingestion and merits further investigation. The combination of systemic and oral therapy may provide further options.
- Bactericidal activity of alpha-bromocinnamaldehyde against persisters in Escherichia coli. [Journal Article]
- PlosPLoS One 2017; 12(7):e0182122
- Persisters are tolerant to multiple antibiotics, and widely distributed in bacteria, fungi, parasites, and even cancerous human cell populations, leading to recurrent infections and relapse after the...
Persisters are tolerant to multiple antibiotics, and widely distributed in bacteria, fungi, parasites, and even cancerous human cell populations, leading to recurrent infections and relapse after therapy. In this study, we investigated the potential of cinnamaldehyde and its derivatives to eradicate persisters in Escherichia coli. The results showed that 200 μg/ml of alpha-bromocinnamaldehyde (Br-CA) was capable of killing all E. coli cells during the exponential phase. Considering the heterogeneous nature of persisters, multiple types of persisters were induced and exposed to Br-CA. Our results indicated that no cells in the ppGpp-overproducing strain or TisB-overexpressing strain survived the treatment of Br-CA although considerable amounts of persisters to ampicillin (Amp) and ciprofloxacin (Cip) were induced. Chemical induction by carbonyl cyanide m-chlorophenylhydrazone (CCCP) led to the formation of more than 10% persister to Amp and Cip in the entire population, and Br-CA still completely eradicated them. In addition, the cells in the stationary phase, which are usually highly recalcitrant to antibiotics treatment, were also completely eradicated by 400 μg/ml of Br-CA. Further studies showed that neither thiourea (hydroxyl-radical scavenger) nor DPTA (Fe3+ chelator to block the hydroxyl-radical) affected the bactericidal efficiency of the Br-CA to kill E. coli, indicating a ROS-independent bactericidal mechanism. Taken together, we concluded that Br-CA compound has a novel bactericidal mechanism and the potential to mitigate antibiotics resistance crisis.
- Correlation between serum ferritin and bone marrow iron stores. [Journal Article]
- TDTrop Doct 2017; 47(3):217-221
- Bone marrow aspirate examination is a gold standard to assess bone marrow iron stores. The correlation between serum ferritin and bone marrow iron has not been established in detail, as the cutoff va...
Bone marrow aspirate examination is a gold standard to assess bone marrow iron stores. The correlation between serum ferritin and bone marrow iron has not been established in detail, as the cutoff value for iron stores have not been uniformly established. Ours was a cross-sectional study. Perl's Prussian blue stain was used to stain bone marrow, assessed by Gale's grading. Receiver operating characteristic curve analysis and Spearman's correlation coefficient calculated. Gale's grading revealed iron store deficiency in 26 and sufficiency in 13. Spearman's correlation coefficient of 0.90 showed a significant relation between serum ferritin and bone marrow iron stores. A serum ferritin of 228 pmol/L had high sensitivity and specificity for iron deficiency; our study suggests that this level be taken as the cutoff value to predict iron store deficiency in bone marrow.
- Intraosseous administration of antidotes - a systematic review. [Review]
- CTClin Toxicol (Phila) 2017; 55(10):1025-1054
- CONCLUSIONS: The evidence supporting the use of IO route for the administration of antidotes in a context of poisoning is scarce. The majority of the evidence consists of case reports and animal experiments. Common antidotes such as acetylcysteine, fomepizole, and digoxin-specific antibody fragments have not been studied or reported with the use of the IO route. Despite the low-quality evidence available, IO access is a potential option for antidotal treatments in toxicological resuscitation when IV access is unavailable.
- Electrochemical sensor for detection of hydrogen peroxide modified with prussian blue electrodeposition on nitrogen, phosphorus and sulfur co-doped porous carbons-chitosan. [Journal Article]
- MSMater Sci Eng C Mater Biol Appl 2017 Aug 01; 77:1242-1246
- Nitrogen, phosphorus and sulfur co-doped porous carbons (N, P, S@PC) were well dispersed in the chitosan (CS) acid solution, in particular via covalently interaction, which could avoid the aggregatio...
Nitrogen, phosphorus and sulfur co-doped porous carbons (N, P, S@PC) were well dispersed in the chitosan (CS) acid solution, in particular via covalently interaction, which could avoid the aggregation of N, P, S@PC in most solvents. Moreover, CS could also avoid N, P, S@PC leakage from the modified electrode. A novel electrochemical sensor was then developed through prussian blue (PB) was electrodeposited on the glass carbon (GC) electrode modified with N, P, S@PC-CS composite. Results with scanning electron microscopy image, illustrate that PB/N, P, S@PC-CS composite distributes very uniformly on the substrate surface, which is hoped to be very attractive for determination of hydrogen peroxide (H2O2). Due to synergistic effect between PB and N, P, S@PC, the PB/N, P, S@PC-CS/GC electrode exhibited excellent conductive and electrocatalytical activity towards H2O2. Under a low applied potential of -0.174V, H2O2 could be linearly detected from 0.4μM to 2.0mM with a low detection limit of 0.2μM (S/N=3) and fast response time of 2s. These results indicate that the electrochemical sensor prepared with PB/N, P, S@PC- CS composite has promising applications for real analysis applications of H2O2.
- Suicide attempt with acetonitrile ingestion in a nursing mother. [Case Reports]
- CTClin Toxicol (Phila) 2017; 55(8):929-933
- CONCLUSIONS: The clinical management must involve the use of CN antidotes for more than 24 h depending on the symptoms and blood levels of ACN. Furthermore, our data showed the possible existence of a close relationship between plasma and breast milk levels.
- Cisplatin Analogs Confer Protection against Cyanide Poisoning. [Journal Article]
- CCCell Chem Biol 2017 May 18; 24(5):565-575.e4
- Cisplatin holds an illustrious position in the history of chemistry most notably for its role in the virtual cure of testicular cancer. Here we describe a role for this small molecule in cyanide deto...
Cisplatin holds an illustrious position in the history of chemistry most notably for its role in the virtual cure of testicular cancer. Here we describe a role for this small molecule in cyanide detoxification in vivo. Cyanide kills organisms as diverse as insects, fish, and humans within seconds to hours. Current antidotes exhibit limited efficacy and are not amenable to mass distribution requiring the development of new classes of antidotes. The binding affinity of the cyanide anion for the positively charged metal platinum is known to create an extremely stable complex in vitro. We therefore screened a panel of diverse cisplatin analogs and identified compounds that conferred protection from cyanide poisoning in zebrafish, mice, and rabbits. Cumulatively, this discovery pipeline begins to establish the characteristics of platinum ligands that influence their solubility, toxicity, and efficacy, and provides proof of concept that platinum-based complexes are effective antidotes for cyanide poisoning.
- In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and common laboratory animals. [Journal Article]
- TLToxicol Lett 2017 May 15; 274:64-68
- Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad applications in manufacturing and history as an agent of warfare/terror highlight the limitations in approved cyanide antid...
Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad applications in manufacturing and history as an agent of warfare/terror highlight the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a pre-clinical antidote for cyanide poisoning, exploits an endogenous detoxification pathway and should be amenable to mass-casualty scenarios. Because human studies are unethical, determination of appropriate animal species as models in translational studies for FDA approval under the "Animal Rule" are critical. Here, we compared the specific activities of mercaptopyruvate sulfurtransferase (MST, required for sulfanegen's activity), across common laboratory models of cyanide intoxication, and humans. Human MST activities in erythrocytes (measured as micromole pyruvate/min/10(6) rbc) were closest to those of Swiss-Webster mice and NZW rabbits. Similar species were selected for a more detailed tissue-specific comparison of MST activities. NZW Rabbits were closest to humans in the liver and kidney mitochondrial fractions, the Swiss-Webster mouse was closest to humans in the liver cytosolic fraction, while C57BL/6 mouse was closest in the kidney cytosolic fraction. These data comparing MST activities in animal models will help justify the use of those specific animals per the animal rule. Interestingly, statistically significant differences were found in MST activities of liver mitochondria between human smokers and non-smokers (p=0.0030).
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- A concentration-dependent multicolor conversion strategy for ultrasensitive colorimetric immunoassay with the naked eye. [Journal Article]
- ACAnal Chim Acta 2017 Apr 22; 963:129-135
- Colorimetric immunoassays have been attracting more attention for use in practical applications, especially in point-of-care diagnostics. In comparison with a single color immunoassay, the dose-depen...
Colorimetric immunoassays have been attracting more attention for use in practical applications, especially in point-of-care diagnostics. In comparison with a single color immunoassay, the dose-dependent multicolor strategy greatly improves the detection resolution and accuracy of visual inspection. In the current study, a concentration-dependent multicolor conversion strategy was developed based on gold nanoparticle (AuNP)-mediated copper deposition for signal amplification and Prussian blue for color generation. Under optimal conditions, a dose-dependent multicolor from yellow through green to blue were successfully achieved, which was easier to be differentiated from each other by the naked eyes. With rabbit IgG and prostate specific antigen (PSA) as model analytes, semi-quantitative evaluations were demonstrated in lab buffer and serum by direct readout with the naked eyes. Quantitative detections were also accomplished by measurement of absorbance of Prussian blue with a common UV-Vis spectrophotometer. A limit of detection (LOD) down to sub-picogram per milliliter was determined. In addition, this newly developed colorimetric assay method can be easily adapted for the detection of other biomolecules by simply changing the recognition pairs.