Effects of lactoferrin and lactoperoxidase‐containing food on the oral microbiota of older individuals

The oral microbiota influences health and disease states. Some gram‐negative anaerobic bacteria play important roles in tissue destruction associated with periodontal disease. Lactoferrin (LF) and lactoperoxidase (LPO) are antimicrobial proteins found in saliva; however, their influence on the whole oral microbiota currently remains unknown. In this randomized, double‐blinded, placebo‐controlled study, the effects of long‐term ingestion of LF and LPO‐containing tablets on the microbiota of supragingival plaque and tongue coating were assessed. Forty‐six older individuals ingested placebo or test tablets after every meal for 8 weeks. The relative abundance of bacterial species was assessed by 16S rRNA gene high‐throughput sequencing. Most of the bacterial species in supragingival plaque and tongue coating that exhibited significant decreases in the test group were gram‐negative bacteria, including periodontal pathogens. Decreases in the total relative abundance of gram‐negative organisms in supragingival plaque and tongue coating correlated with improvements in assessed variables related to oral health, such as oral malodor and plaque accumulation. Furthermore, there was significantly less microbiota diversity in supragingival plaque at 8 weeks in the test group than in the placebo group and low microbiota diversity correlated with improvements in assessed variables related to oral health. These results suggest that LF and LPO‐containing tablets promote a shift from a highly diverse and gram‐negative‐dominated to a gram‐positive‐dominated community in the microbiota of supragingival plaque and tongue coating. This microbial shift may contribute to improvements in oral health, including oral malodor and state of the gingiva.

     

Molecular cloning of putative chloroplastic cysteine synthase in Leucaena leucocephala

Journal of Plant Research - Cysteine biosynthesis is directed by the successive commitments of serine acetyltransferase, and O-acetylserine (thiol) lyase (OASTL) compounds, which subsequently frame...     

X-ray Crystallographic Study of an HIV-1 Fusion Inhibitor with the gp41 S138A Substitution

The S138A substitution of fusion inhibitory peptides derived from the C-terminal heptad repeat (C-HR) of the human immunodeficiency virus type 1 (HIV-1) gp41 leads to enhanced binding affinity to the N-terminal heptad repeat (N-HR). As such, these peptides exhibit highly potent anti-HIV-1 activity. X-ray crystallographic analysis was performed to understand the effect of the substitution on binding affinity. The comparison of the native and S138A crystal structures indicated that the increase in the hydrophobicity of the S138A substitution may aid the stabilization of the N-HR/C-HR complex through additional hydrophobic contacts. Free-energy calculations suggest that the difference between the desolvation free energies of the C-HR-derived peptides with and without the S138A mutation dominates the observed difference in anti-HIV-1 activity.     

A mathematical design of vector vaccine against autoimmune disease

Viruses have been implicated in the initiation, progression, and exacerbation of several human autoimmune diseases. Evidence also exists that viruses can protect against autoimmune disease. Several proposed mechanisms explain the viral effects. One mechanism is “molecular mimicry” which represents a shared immunologic epitope with a microbe and the host. We consider, using a simple mathematical model, whether and how a viral infection with molecular mimicry can be beneficial or detrimental for autoimmune disease. Furthermore, we consider the possibility of development of a vector therapeutic vaccine that can relieve autoimmune disease symptoms. Our findings demonstrate that vaccine therapy success necessitates (i) appropriate immune response function, (ii) appropriate affinities with self and non-self antigen, and (iii) a replicative vector vaccine. Moreover, the model shows that the viral infection can cause autoimmune relapses.     

Mesenchymal Stromal Cell Secretome Up-Regulates 47 kDa CXCR4 Expression,and Induce Invasiveness in Neuroblastoma Cell Lines

Neuroblastoma accounts for 15% of childhood cancer deaths and presents with metastatic disease of the bone and the bone marrow at diagnosis in 70% of the cases. Previous studies have shown that the Mesenchymal Stromal Cell (MSC) secretome, triggers metastases in several cancer types such as breast and prostate cancer, but the specific role of the MSC factors in neuroblastoma metastasis is unclear. To better understand the effect of MSC secretome on chemokine receptors in neuroblastoma, and its role in metastasis, we studied a panel of 20 neuroblastoma cell lines, and compared their invasive potential towards MSC-conditioned-RPMI (mRPMI) and their cytokine receptor expression profiles. Western blot analysis revealed the expression of multiple CXCR4 isoforms in neuroblastoma cells. Among the five major isoforms, the expression of the 47 kDa isoform showed significant correlation with high invasiveness. Pretreatment with mRPMI up-regulated the expression of the 47 kDa CXCR4 isoform and also increased MMP-9 secretion, expression of integrin α3 and integrin β1, and the invasive potential of the cell; while blocking CXCR4 either with AMD 3100, a CXCR4 antagonist, or with an anti-47 kDa CXCR4 neutralizing antibody decreased the secretion of MMP-9, the expression of integrin α3 and integrin β1, and the invasive potential of the cell. Pretreatment with mRPMI also protected the 47 kDa CXCR4 isoform from ubiquitination and subsequent degradation. Our data suggest a modulatory role of the MSC secretome on the expression of the 47 kDa CXCR4 isoform and invasion potential of the neuroblastoma cells to the bone marrow.     

Glycine amide shielding on the aromatic surfaces of lysozyme: implication for suppression of protein aggregation

Glycine amide (GlyAd), a typically amidated amino acid, is a versatile additive that suppresses protein aggregation during refolding, heat treatment, and crystallization. In spite of its effectiveness, the exact mechanism by which GlyAd suppresses protein aggregation remains to be elucidated. Here, we show the crystal structure of the GlyAd–lysozyme complex by high resolution X-ray crystallographic analysis at a 1.05 Å resolution. GlyAd bound to the lysozyme surface near aromatic residues and decreased the amount of bound waters and increased the mobility of protein. Arg and GlyAd molecules are different in binding sites and patterns from glycerol and related compounds, indicating that decreasing hydrophobic patches might be involved in suppression of protein aggregation.     

Design, synthesis, and biological activity of folate receptor-targeted prodrugs of thiolate histone deacetylase inhibitors

Aiming to develop selective anticancer drugs, we designed and synthesized three disulfides bearing a folic acid moiety as candidate folate receptor (FR)-targeted prodrugs of thiolate histone deacetylase inhibitors. Among them, compound 1 displayed growth-inhibitory activity toward folate receptor-positive MCF-7 breast cancer cells. The activity of 1 was significantly reduced by free folic acid, suggesting that cellular uptake of 1 is mediated by FR.