Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction.

BackgroundThe extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.Methodology/principal findingsFour peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.Conclusions/significanceWe demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology

Bifurcation of Safe Basins and Chaos in Nonlinear Vibroimpact Oscillator under Harmonic and Bounded Noise Excitations

The erosion of the safe basins and chaotic motions of a nonlinear vibroimpact oscillator under both harmonic and bounded random noise is studied. Using the Melnikov method, the system’s Melnikov integral is computed and the parametric threshold for chaotic motions is obtained. Using the Monte-Carlo and Runge-Kutta methods, the erosion of the safe basins is also discussed. The sudden change in the character of the stochastic safe basins when the bifurcation parameter of the system passes through a critical value may be defined as an alternative stochastic bifurcation. It is founded that random noise may destroy the integrity of the safe basins, bring forward the occurrence of the stochastic bifurcation, and make the parametric threshold for motions vary in a larger region, hence making the system become more unsafely and chaotic motions may occur more easily

Formation of Maillard Reaction Products in Heat-Treated Torreya grandis cv. Merrilli Seed Oil and Their Effects on Two Analytical Methods for the Determination of Total Phenolics

The occurrence of Maillard reaction in heated Torreya grandis cv. Merrilli seed oil was verified by detecting browning index and the contents of the Maillard reaction products (MRPs) 3-deoxyglucosone, methylglyoxal and 5-(hydroxymethyl)furfural, and the effects of the MRPs on the quantification of total phenolics using the Folin-Ciocalteu and Fast Blue BB assays were explored. The Folin-Ciocalteu assay showed that the content of total phenolics in the oil increased after treatment at 150 ℃ for 90 to 120 min, while the Fast Blue BB assay showed the opposite result. It was also observed that the absorbance of the oil at a wavelength of 294 nm increased after long-term low-temperature or high-temperature heat treatment. 3-Deoxyglucosone (0.21–0.47 μg/g) and 5-(hydroxymethyl)furfural (0.06–0.40 μg/g) were detected only in the 150 ℃ treated oil, while methylglyoxal (0.67–1.73 μg/g) existed in both oil samples. In the Folin-Ciocalteu assay, the absorbance at a wavelength of 765 nm of 3-deoxyglucosone and methylglyoxal linearly increased with an increase in their concentrations, and the decreasing order of the absorbance of the MRPs at the same concentration was 3-deoxyglucosone > methylglyoxal > 5-(hydroxymethyl)furfural. In the presence of 3-deoxyglucosone, the Folin-Ciocalteu result was greater than the actual value, and the degree of interference was not related to the content of total phenolics in samples, but instead was positively correlated with the concentration of 3-deoxyglucosone. In the Fast Blue BB assay, there was no significant difference in absorbance at 420 nm among the three MRPs. For food matrices prone to the formation of 3-deoxyglucosone and methylglyoxal during processing, the Fast Blue BB assay can be selected instead of the Folin-Ciocalteu assay to mitigate the interferences from the two substances in the quantification of total phenolics

Anti-inflammatory effect of Zanthoxylum bungeanum-cake-separated moxibustion on rheumatoid arthritis rats

Background: Zanthoxylum bungeanum-cake-separated moxibustion (ZBCS-moxi), a kind of traditional therapy of moxibustion, has been used in China since 340 B.C. However, its mechanism remains unclear. So, this study was attempted to reveal the anti-inflammatory effect of ZBCS-moxi on rheumatoid arthritis (RA) rats.Methods and Materials: Forty health SD female rats were randomly divided into 4 groups  (n=10/group): control group, model group, Zanthoxylum bungeanum-cake-separated moxibustion group (ZBCS-moxi group) and Aconitum carmichaeli-cake-separated moxibustion group (ACCS-moxi group). RA model was induced by injecting 0.1 ml Freund’s complete adjuvant (FCA) into the right hind paw of rats. Eleven days after CFA injection, the rats in ZBCS-moxi group received Zanthoxylum bungeanum- cake-separated moxibustion on Shenshu (BL23), Zusanli (ST36) acupoints and the dorsum right hind paw respectively for 3 weeks. The ACCS-moxi group was used as a positive control, while the rats were treated with Aconitum carmichaeli-cake-separated moxibustion on the same acupoints and courses. After a 3-week treatment, we investigated anti-inflammatory effect by measuring the paw volume,  observing the pathologic morphology of synovial membranes and detecting the concentration of IL-1β and TNF-α in serum.Results: Compared to model group, the swollen paw volumes, the synovial hyperplasia and pannus formation of synovial membranes and the concentration of IL-1β and TNF-α in serum decreased obviously (P<0.01, P<0.05) in ZBCS-moxi group, as well as in ACCS-moxi group. However, the swollen paw volumes, the synovial hyperplasia and pannus formation of synovial membranes and the concentration of IL-1β and TNF-α in serum in ZBCS-moxi and ACCS-moxi group did not show significant differences (P>0.05)Conclusions: ZBCS-moxi displays anti-inflammatory effect on RA rats via suppressing the expression of cytokines and has similar effect to ACCS-moxi.Key words: Anti-inflammatory effect; Zanthoxylum bungeanum-cake-separated moxibustion; Aconitum carmichaeli-cake-separated moxibustion; Rheumatoid Arthritis

Metabolic features of orbital adipose tissue in patients with thyroid eye disease

BackgroundThyroid eye disease (TED) is the most frequent orbital disease in adults and is characterized by the accumulation of orbital adipose tissue (OAT). It can lead to eyelid retraction or even vision loss. Orbital decompression surgery serves as the primary treatment for inactive TED by removing the excess OAT. However, there is a lack of alternative treatments to surgery due to the unclear understanding of the pathogenesis, particularly the metabolic features. Accordingly, our study was implemented to explore the content and features of metabolites of OATs from TED patients.MethodThe OATs used in the current study were obtained from the orbital decompression surgery of seven patients with inactive TED. We also collected control OATs from eye surgical samples of five individuals with no history of autoimmune thyroid diseases, TED, or under non-inflammatory conditions. The liquid chromatography mass spectrometer was used for the measurements of the targeted metabolites. Afterwards, we performed differential metabolite assay analysis and related pathway enrichment analysis.ResultsIn our study, a total of 149 metabolite profiles were detected in all participants. There were significant differences in several metabolite profiles between the TED group and the control group, mainly including uric acid, oxidized glutathione, taurine, dGMP, oxidized glutathione 2, uracil, hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, and uridine 5′-monophosphate (all p-value < 0.05). The TED-related pathways identified included purine metabolism, beta-alanine metabolism, glutathione metabolism (p-values < 0.05). Our study found overlaps and differences including uric acid and uracil, which are in accordance with metabolites found in blood of patients with TED from previous study and several newly discovered metabolite by our study such as hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, compared to those tested from blood, OAT, or urine samples reported in previous studies.ConclusionThe findings of our study shed light on the metabolic features of OAT in individuals with TED. These results may help identify new treatment targets for TED, providing potential avenues for developing alternative treatments beyond ophthalmic surgery

ANTI-INFLAMMATORY EFFECT OF ZANTHOXYLUM BUNGEANUM-CAKE-SEPARATED MOXIBUSTION ON RHEUMATOID ARTHRITIS RATS

Background: Zanthoxylum bungeanum-cake-separated moxibustion (ZBCS-moxi), a kind of traditional therapy of moxibustion, has been used in China since 340 B.C. However, its mechanism remains unclear. So, this study was attempted to reveal the anti-inflammatory effect of ZBCS-moxi on rheumatoid arthritis (RA) rats. Methods and Materials: Forty health SD female rats were randomly divided into 4 groups (n=10/group): control group, model group, Zanthoxylum bungeanum-cake-separated moxibustion group (ZBCS-moxi group) and Aconitum carmichaeli-cake-separated moxibustion group (ACCS-moxi group). RA model was induced by injecting 0.1 ml Freund’s complete adjuvant (FCA) into the right hind paw of rats. Eleven days after CFA injection, the rats in ZBCS-moxi group received Zanthoxylum bungeanum- cake-separated moxibustion on Shenshu (BL23), Zusanli (ST36) acupoints and the dorsum right hind paw respectively for 3 weeks. The ACCS-moxi group was used as a positive control, while the rats were treated with Aconitum carmichaeli-cake-separated moxibustion on the same acupoints and courses. After a 3-week treatment, we investigated anti-inflammatory effect by measuring the paw volume, observing the pathologic morphology of synovial membranes and detecting the concentration of IL-1β and TNF-α in serum. Results: Compared to model group, the swollen paw volumes, the synovial hyperplasia and pannus formation of synovial membranes and the concentration of IL-1β and TNF-α in serum decreased obviously (

Finding nucleolus of flow game

We study the algorithmic issues of finding the nucleolus of a flow game. The flow game is a cooperative game defined on a network D=(V,E; ω). The player set is E and the value of a coalition S ⊆ E is defined as the value of a maximum flow from source to sink in the subnetwork induced by S. We show that the nucleolus of the flow game defined on a simple network (ω(e)=1 for each e ∈ E) can be computed in polynomial time by a linear program duality approach, settling a twenty-three years old conjecture by Kalai and Zemel. In contrast, we prove that both the computation and the recognition of the nucleolus are N℘-hard for flow games with general capacity