Objectives: Nisin is a lantibiotic widely used for the preservation of food and beverages. Recently, investigators have reported that nisin may have clinical applications for treating bacterial infections. The aim of this study was to investigate the effects of ultra pure food grade Nisin ZP (>95% purity) on taxonomically diverse bacteria common to the human oral cavity and saliva derived multi-species oral biofilms, and to discern the toxicity of nisin against human cells relevant to the oral cavity.Methods: The minimum inhibitory concentrations and minimum bactericidal concentrations of taxonomically distinct oral bacteria were determined using agar and broth dilution methods. To assess the effects of nisin on biofilms, two model systems were utilized: a static and a controlled flow microfluidic system. Biofilms were inoculated with pooled human saliva and fed filter-sterilized saliva for 20–22 h at 37°C. Nisin effects on cellular apoptosis and proliferation were evaluated using acridine orange/ethidium bromide fluorescent nuclear staining and lactate dehydrogenase activity assays.Results: Nisin inhibited planktonic growth of oral bacteria at low concentrations (2.5–50 μg/ml). Nisin also retarded development of multi-species biofilms at concentrations ≥1 μg/ml. Specifically, under biofilm model conditions, nisin interfered with biofilm development and reduced biofilm biomass and thickness in a dose-dependent manner. The treatment of pre-formed biofilms with nisin resulted in dose- and time-dependent disruption of the biofilm architecture along with decreased bacterial viability. Human cells relevant to the oral cavity were unaffected by the treatment of nisin at anti-biofilm concentrations and showed no signs of apoptotic changes unless treated with much higher concentrations (>200 μg/ml).Conclusion: This work highlights the potential therapeutic value of high purity food grade nisin to inhibit the growth of oral bacteria and the development of biofilms relevant to oral diseases.

The current study was designed to evaluate the pharmacologic effects of three novel cysteine-containing compounds: S-propyl-l-cysteine (SPC), S-allyl-l-cysteine (SAC), and S-propargyl-l-cysteine (SPRC) on H 2 S production and antioxidant defenses in an acute myocardial infarction (MI) rat model. The enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as glutathione redox status and malonaldehyde (MDA) content, also were determined. All three compounds were found to preserve SOD and GPx activities and also tissue GSH levels while reducing the formation of the lipid peroxidation product MDA in ventricular tissues. With immunfluorescence assays, we observed the expression of CSE and Mn-SOD. The morphologic changes of the cardiac cells are seen with both light and electron microscopy. The corresponding pathologic alterations were characterized mainly as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. Propargylglycine, a selective inhibitor of CSE, abolished the protective effects of each compound used in the current model. Our study provides novel evidence that SPC, SAC, and SPRC have cardioprotective effects in MI by reducing the deleterious effects of oxidative stress by modulating the endogenous levels of H 2 S and preserving the activities of antioxidant defensive enzymes like SOD.

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Achieving satisfactory reconstruction of bone remains an important goal in orthopedic and dental conditions such as bone trauma, osteoporosis, arthritis, osteonecrosis, and periodontitis. Appropriate temporal and spatial differentiation of mesenchymal stem cells (MSCs) is essential for postnatal bone regeneration. Additionally, an acute inflammatory response is crucial at the onset of bone repair, while an adaptive immune response has important implications during late bone remodeling. Various reports have indicated bidirectional interactions between MSCs and inflammatory cells or molecules. For example, inflammatory cells can recruit MSCs, direct their migration and differentiation, so as to exert anabolic effects on bone repair. Furthermore, both pro-inflammatory and anti-inflammatory cytokines can regulate MSCs properties and subsequent bone regeneration. MSCs have demonstrated highly immunosuppressive functions, such as inhibiting the differentiation of monocytes/hematopoietic precursors and suppressing the secretion of pro-inflammatory cytokines. This review emphasizes the important interactions between inflammatory stimuli, MSCs, and bone regeneration as well as the underlying regulatory mechanisms. Better understanding of these principles will provide new opportunities for promoting bone regeneration and the treatment of bone loss associated with immunological diseases.

In this study, we determined the cardioprotective effects of S-propargyl-cysteine (SPRC), a structural analog of S-allylcysteine (SAC), using in vivo models of acute myocardial infarction (MI) and in vitro hypoxic cardiomyocytes models. MI was created in rats by ligating the left anterior descending coronary artery. Plasma enzymes levels and cystathionine-gamma-lyase (CSE) activities were determined. Primary cultures of newborn rats' cardiomyocytes were injured by hypoxia for 6 h. Cell viabilities were measured with the thiazolyl blue assay. RT-PCR and western blot analysis revealed the expression of CSE in both models. The protective effects of SPRC were associated with an observed reduction in infarct size (20.8 +/- 2.4% vs. 36.0 +/- 1.3%), decreased plasma enzymes levels and reduced malondialdehyde levels when compared to the MI vehicle group (P < 0.05); cardiac function was also improved. SPRC increased CSE activity and plasma H2S concentration by 1.6-fold and 1.3-fold, respectively, in MI rats. Decreased cell viability (64.5 +/- 5.4%) in hypoxic cardiomyocytes could be rescued with use of SPRC (81.0 +/- 3.1%). Similarly, mRNA and protein expression of CSE were upregulated in the SPRC group. Treatment with the CSE inhibitor propargylglycine abolished the protective effects of SPRC. Our study provides novel evidence that SPRC is protective in myocardial infarctions via a H2S-related pathway.

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Background: Primary Sjögren’s syndrome (PSS) is associated with various histological patterns of interstitial lung disease. Although chest images and lung function studies showed that lung involvement predominantly occurs in small airways, pathological findings were not consistent with the results of high-resolution CT (HRCT) and lung function tests. Objectives: To investigate the pathological characteristics of PSS-associated interstitial lung disease (PSS-ILD) and their relationship with HRCT lung function tests. Methods: Fourteen patients diagnosed as PSS who underwent surgical lung biopsy in Peking Union Medical College Hospital from October 2000 to October 2006 were reviewed. Histopathologic findings, radiologic findings and lung function tests were analyzed. Results:The study included 13 women. The median age was 46 years. Most patients presented with dyspnea and cough. CT scans revealed bilateral ground-glass, consolidative, reticular and nodular opacities and cyst lesions. The histological patterns included nonspecific interstitial pneumonia (NSIP) cellular pattern associated with organizing pneumonia (OP), NSIP mixed pattern associated with OP, noncaseating granulomas, chronic bronchiolitis, follicular bronchiolitis, constrictive bronchiolitis, lymphocytic interstitial pneumonia associated with follicular bronchiolitis, NSIP mixed pattern associated with follicular bronchiolitis, NSIP mixed pattern coexisting with chronic bronchiolitis, OP associated with chronic bronchiolitis, and noncaseating granulomas coexisting with OP. Treatment included prednisone and cyclophosphamide. During the follow-up period (median 38 months), most patients improved or remained stable. The patient with constrictive bronchiolitis died from progression of primary disease. Conclusions: The histopathologic patterns of PSS-ILD included lung interstitial involvement and small airway involvement or both. Corticosteroid therapy combined with cyclophosphamide was administered with a favorable response in the majority of patients.

Bone morphology protein-2 (BMP-2) encapsulated chitosan/chondrotin sulfate nanoparticles (CHI/CS NPs) are developed to enhance ectopic bone formation on biphasic calcium phosphate (BCP) scaffolds. BMP-2 contained CHI/CS NPs were prepared by a simple and mild polyelectrolyte complexation process. It does not involve harsh organic solvents and high temperature, and therefore retain growth factors activity. These NPs were immobilized on BCP scaffolds, and realize the sustained release of growth factors from the scaffolds. The bare BCP scaffolds, NP loaded scaffolds (BCP-NP), and NP loaded and polydopamine coated scaffolds (BCP-Dop-NP) were seeded with bone marrow stroma cells (BMSC) to evaluate the osteoinductivity of the scaffolds. BMSC culture results indicate that all scaffolds favor cell adhesion, proliferation, differentiation. Afterwards, the bare BCP, BCP-NP, and BCP-Dop-NP scaffolds were implanted into rabbits intramuscularly to evaluate the ectopic bone formation of scaffolds. In vivo results indicate that the BCP-NP and BCP-Dop-NP scaffolds enhance more ectopic bone formation than the bare BCP scaffolds. Both the in vitro and in vivo results demonstrate that BMP-2 encapsulated polysaccharide NPs are effective to improve the osteoinductivity of the scaffolds. In addition, BCP-NP scaffolds induce more bone formation than BCP-Dop-NP scaffolds. This is because BCP-NP scaffolds harness the intrinsic osteoinductivity BCP and BMP-2, whereas BCP-Dop-NP scaffolds have polydopamine coatings that inhibit the surfaces biological features of BCP scaffolds, and therefore weaken the bone formation ability of scaffolds.