Complete genome sequencing and comparative genomic analysis of Lactobacillus acidophilus C5 as a potential canine probiotics.

Lactobacillus acidophilus is a gram-positive, microaerophilic, and acidophilic bacterial species. L. acidophilus strains in the gastrointestinal tracts of humans and other animals have been profiled, but strains found in the canine gut have not been studied yet. Our study helps in understanding the genetic features of the L. acidophilus C5 strain found in the canine gut, determining its adaptive features evolved to survive in the canine gut environment, and in elucidating its probiotic functions. To examine the canine L. acidophilus C5 genome, we isolated the C5 strain from a Korean dog and sequenced it using PacBio SMRT sequencing technology. A comparative genomic approach was used to assess genetic relationships between C5 and six other strains and study the distinguishing features related to different hosts. We found that most genes in the C5 strain were related to carbohydrate transport and metabolism. The pan-genome of seven L. acidophilus strains contained 2,254 gene families, and the core genome contained 1,726 gene families. The phylogenetic tree of the core genes in the canine L. acidophilus C5 strain was very close to that of two strains (DSM20079 and NCFM) from humans. We identified 30 evolutionarily accelerated genes in the L. acidophilus C5 strain in the ratio of non-synonymous to synonymous substitutions (dN/dS) analysis. Five of these thirty genes were associated with carbohydrate transport and metabolism. This study provides insights into genetic features and adaptations of the L. acidophilus C5 strain to survive the canine intestinal environment. It also suggests that the evolution of the L. acidophilus genome is closely related to the host's evolutionary adaptation process.

Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway.

Manumycin A (Manu A) is a natural product isolated from Streptomyces parvulus and has been reported to have anti-carcinogenic and anti-biotic properties. However, neither its molecular mechanism nor its molecular targets are well understood. Thus, the aim of the present study was to explore the possibility that Manu A has cancer preventive and chemotherapeutic effects on malignant pleural mesothelioma (MPM) through regulation of Sp1 and induction of mitochondrial cell death pathway. Manu A inhibited the cell viability of MSTO-211H and H28 cells in a concentration­dependent manner as determined by MTS assay. IC50 values were calculated as 8.3 and 4.3 µM in the MSTO-311H and H28 cells following 48 h incubation, respectively. Manu A induced a significant increase in apoptotic indices as shown by DAPI staining, Annexin V assay, multi-caspase activity and mitochondrial membrane potential assay. The downregulation of Sp1 mRNA and protein expression by Manu A led to apoptosis by suppressing Sp1-regulated proteins (cyclin D1, Mcl-1 and survivin). Manu A decreased the protein levels of BID, Bcl-xL and PARP while it increased Bax levels. Manu A caused depolarization of the mitochondrial membrane with induction of CHOP, DR4 and DR5. Our results demonstrated that Manu A exerted anticancer effects by inducing apoptosis via inhibition of the Sp1-related signaling pathway in human MPM.

Specificity protein 1 is a novel target of 2,4-bis (p-hydroxyphenyl)-2-butenal for the suppression of human oral squamous cell carcinoma cell growth.

BACKGROUND: The Maillard reaction is a chemical reaction occurring between a reducing sugar and an amino acid, generally requiring thermal processing. Maillard reaction products (MRPs) have antioxidant, antimutagenic, and antibacterial effects though 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242), a fructose-tyrosine MRP, appears to inhibit proliferation of cancer cells, its mechanism of action has not been studied in detail. The purpose of this study was to investigate the anti-proliferative effects of 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242) on two oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, through regulation of specificity protein 1 (Sp1). RESULTS: HPB242 treatment dramatically reduced the cell growth rate and apoptotic cell morphologies. Sp1 was significantly inhibited by HPB242 in a dose-dependent manner. Furthermore, cell cycle regulating proteins and anti-apoptotic proteins, which are known as Sp1 target genes, were altered at the molecular levels. The key important regulators in the cell cycle such as p27 were increased, whereas cell proliferation- and survival-related proteins such as cyclin D1, myeloid leukemia sequence 1 (Mcl-1) and survivin were significantly decreased by HPB242 or suppressed Sp1 levels, however pro-apoptotic proteins caspase3 and PARP were cleaved in HN22 and HSC4. CONCLUSIONS: HPB242 may be useful as a chemotherapeutic agent for OSCC for the purpose of treatment and prevention of oral cancer and for the improvement of clinical outcomes.