Surfaces modified with small molecules that interfere with nucleotide signaling reduce Staphylococcus epidermidis biofilm and increase the efficacy of ciprofloxacin

Article

Author: Xu, Li-Chong ; Sun, Dongxiao ; Allcock, Harry R ; Chen, Chen ; Ochetto, Alyssa ; Siedlecki, Christopher A

Staphylococcus epidermidis are common bacteria associated with biofilm related infections on implanted medical devices.Antibiotics are often used in combating such infections, but they may lose their efficacy in the presence of biofilms.Bacterial intracellular nucleotide second messenger signaling plays an important role in biofilm formation, and interference with the nucleotide signaling pathways provides a possible way to control biofilm formation and to increase biofilm susceptibility to antibiotic therapy.This study synthesized small mol. derivates of 4-arylazo-3,5-diamino-1 H-pyrazole (named as SP02 and SP03) and found these mols. inhibited S. epidermidis biofilm formation and induced biofilm dispersal.Anal. of bacterial nucleotide signaling mols. showed that both SP02 and SP03 significantly reduced cyclic dimeric adenosine monophosphate (c-di-AMP) levels in S. epidermidis at doses as low as 25 μM while having significant effects on multiple nucleotides signaling including cyclic dimeric guanosine monophosphate (c-di-GMP), c-di-AMP, and cyclic adenosine monophosphate (cAMP) at high doses (100 μM or greater).We then tethered these small mols. to polyurethane (PU) biomaterial surfaces and investigated biofilm formation on the modified surfaces.Results showed that the modified surfaces significantly inhibited biofilm formation during 24 h and 7-day incubations.The antibiotic ciprofloxacin was used to treat these biofilms and the efficacy of the antibiotic (2 μg/mL) was found to increase from 94.8% on unmodified PU surfaces to > 99.9% on both SP02 and SP03 modified surfaces (>3 log units).Results demonstrated the feasibility of tethering small mols. that interfere with nucleotide signaling onto polymeric biomaterial surfaces and in a way that interrupts biofilm formation and increases antibiotic efficacy for S. epidermidis infections.

03 Mar 2021·Journal of Agricultural and Food ChemistryQ1 · AGRICULTURAL & FORESTRY SCIENCE

Stichopus japonicus Polysaccharide Stimulates Osteoblast Differentiation through Activation of the Bone Morphogenetic Protein Pathway in MC3T3-E1 Cells

Q1 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Wang, Yanjie ; Liu, Wenzhuan ; Sun, Jinghe ; Yang, Sheng ; Yang, Jingfeng ; Zhang, Yanqi

This study aimed to examine the combined use of bone morphogenetic protein-2 (BMP-2) and polysaccharide isolated from Stichopus japonicus on osteogenic differentiation of MC3T3-E1 cells. Osteogenic differentiation was measured via histochemical staining of alkaline phosphatase (ALP) assay, alizarin red staining of mineralization assay, Western blotting, ELISA, and a qRT-PCR evaluation for the expression of BMP-2, runt-related transcription factor-2 (Runx-2), osteocalcin (OCN), osteopontin (OPN), and collagen type I (Col I) in MC3T3-E1 cells. Immunofluorescence assay was utilized to assess the BMP-2 localized on the cell surface. The results illustrated that SP-2 was able to increase ALP expression and accelerate the mineralization. Osteoblasts cultured on BMP-2/SP-2 substrate increased the expression levels of BMP-2, Runx-2, Col I, OCN, and OPN. SP-2 increased the binding efficiency involving a BMP-2 and its cell surface receptor. The dose of 5 μg/mL SP-2 used showed the best function of inducing osteoblast differentiation. These findings indicated that SP-2 is a more effective enhancer that cooperated with BMP-2 to induce osteoblastic differentiation by utilizing the BMP-2 signaling pathway.

01 Nov 2018·International Urology and NephrologyQ4 · MEDICINE

Relation of serum spondin-2 levels with cardiac morphology and inflammatory parameters in hemodialysis patients

Q4 · MEDICINE

Article

Author: Dogan, Tolga ; Yilmaz, Mehmet Bertan ; Yetim, Mucahit ; Karavelioglu, Yusuf ; Kayadibi, Huseyin ; Eser, Baris ; Kalcik, Macit ; Dogan, Ibrahim

PURPOSECardiovascular diseases are the leading causes of mortality in chronic kidney disease. Spondin-2 (SP-2), an intrinsic cardio-protective factor, prevents maladaptive remodeling. We aimed to determine the relation between serum SP-2 levels and cardiac morphology along with inflammatory parameters in hemodialysis (HD) patients.METHODThe study comprised a total of 95 patients (61 females) receiving HD treatment three times a week for at least 6 months, and a control group consisting of age and gender matched 62 subjects (34 females). SP-2 levels were determined by ELISA. Echocardiography, 24-h ambulatory blood pressure monitoring, and carotid artery intima-media thickness (CIMT) measurement were performed in all subjects. The relation of serum SP-2 levels with CIMT, echocardiographic parameters, CRP, and absolute neutrophil-to-lymphocyte count ratio (NLR) was evaluated by correlation analysis.RESULTSSP-2 levels were found to be significantly higher in the HD group than the control group (16.660 [8.719-20.938] vs. 3.988 [2.702-8.042] ng/L; P < 0.001). CIMT, CRP, and NLR were also higher in HD group (P < 0.005, P < 0.001, and P < 0.001, respectively). Significantly positive correlation was found between SP-2 and left ventricular mass, left ventricular mass index, CRP, and NLR, but no correlation was determined between SP-2 and CIMT. SP-2 was not statistically significant variable for the determination of LVH in univariate logistic regression analysis [Wald = 2.375; OR (95% CI) = 1.000 (0.999-1.000), P = 0.123].CONCLUSIONSerum SP-2 levels were higher in HD patients compared to the population with normal renal functions. The results suggest that SP-2, an uremic toxin, might be effective over a complex pathway in the inflammatory process and in the pathogenesis of cardiovascular diseases of patients under HD treatment.

100 Deals associated with SP02

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Indication	Highest Phase	Country/Location	Organization	Date
Arthritis, Psoriatic	Preclinical	China	Smart Pharmaceutical Shanghai Ltd.	26 Oct 2024
Fasciitis	Preclinical	China	Smart Pharmaceutical Shanghai Ltd.	26 Oct 2024

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