Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

Chemoproteomics reveals Sofalcone inhibits the inflammatory response of Caco-2 cells by covalently targeting HMGB1.

Sofalcone (Sof), a synthetic analog of sophoradin, is a type of natural phenol derived from the traditional medicinal herb Sophora subprostrata, with potent anti-inflammatory activity. However, the mechanisms of action of Sof for treating intestinal-associated inflammation are not well known. In this work, we identified high mobility group box 1 (HMGB1) as the key covalent target of Sof for the anti-inflammatory activity in the human colonic epithelial cells through quantitative chemoproteomics profiling.

SETD7 promotes metastasis of triple-negative breast cancer by YY1 lysine methylation.

Breast cancer has gradually become the predominant cause for cancer-associated death in women. The metastatic dissemination and underlying mechanisms of triple-negative breast cancer (TNBC) are not sufficiently understood. (Su(var)3-9, enhancer of zeste, Trithorax) domain-containing protein 7 (SETD7) is vital for promoting the metastasis of TNBC, as demonstrated in this study. Clinical outcomes were significantly worse in primary metastatic TNBC with upregulated SETD7. Overexpression of SETD7 in vitro and in vivo promotes migration of TNBC cells. Two highly conserved lysine (K) residues K173 and K411 of Yin Yang 1 (YY1) are methylated by SETD7. Further, we found that SETD7-mediated K173 residue methylation protects YY1 from the ubiquitin-proteasome degradation. Mechanistically, it was found that the SETD7/YY1 axis regulates epithelial-mesenchymal transition (EMT) and tumor cell migration via the ERK/MAPK pathway in TNBC. The findings indicated that TNBC metastasis is driven by a novel pathway, which may be a promising target for advanced TNBC treatment.

Cocktail Therapy of Fosthiazate and Cupric-Ammoniun Complex for Citrus Huanglongbing.

Huanglongbing (HLB) is a destructive citrus bacterial disease caused by Candidatus Liberibacter asiaticus (Ca.Las) and cannot be cured by current pesticides. Root lesion and Tylenchulus semipenetrans juveniles were observed in HLB-affected citrus tree roots. We hypothesize that root treatment with fosthiazate (FOS) and Cupric-Ammonium Complex (CAC) will improve the root growth and inhibit HLB. CAC is a broad spectrum fungicide and can promote growth of crops. FOS kills Tylenchulus semipenetrans and protects roots from damage by harmful bacteria such as Ca.Las. After 90 days of combination treatment of FOS and CAC through root drenches, the citrus grew new roots and its leaves changed their color to green. The inhibition rate of Ca.Las reached more than 90%. During treatment process, the chlorophyll content and the root vitality increased 396 and 151%, respectively, and starch accumulation decreased by 88%. Transmission electron microscopy (TEM) and plant tissue dyeing experiments showed that more irregular swollen starch granules existed in the chloroplast thylakoid system of the HLB-infected leaves. This is due to the blocking of their secretory tissue by starch. TEM and flow cytometry experiments in vitro showed the synergistic effects of FOS and CAC. A transcriptome analysis revealed that the treatment induced the differential expression of the genes which involved 103 metabolic pathways. These results suggested that the cocktail treatment of FOS and CAC may effectively kill various pathogens including Ca.Las on citrus root and thus effectively control HLB.

Synthesis, Photothermal Effect and Cytotoxicity of Fe3O4@Au Nanocomposites.

It is currently a very active research area to develop multifunctional nanocomposites (NCs) which integrate the novel properties from various nanomaterials for multimodal imaging and simultaneous therapy. These theranostic nanoplatforms can provide complementary information from each imaging modality for accurate diagnosis and, at the same time, afford an imaging-guided focused tumor therapy. Among them, core/shell Fe3O4@Au NCs have attracted wide attention due to their unique advantages in magnetic targeting, multimodal imaging and photothermal therapy. This study developed a layer-by-layer assembling approach to synthesize Fe3O4@Au NCs with high photothermal conversion efficiency. The as-synthesized NCs showed significant photothermal ablation capability to HeLa cells in vitro under near infrared laser irradiation. To ensure the safety for medical applications, the bio-effects of Fe3O4@Au NCs on RAW264.7 cells were carefully assessed, in terms of cell viability, oxidative stress and apoptosis. We have demonstrated that Fe3O4@Au NCs had good biocompatibility in RAW264.7 cells and no significant cytotoxicity was found. Therefore, the Fe3O4@Au NCs synthesized in this study have great potential as an ideal candidate for CT/MR imaging and photothermal therapy.

[Reactivation of hypermethylated GSTP1 promoter activity in MCF-7 cells by treatment with a component of natural drug].

OBJECTIVE: To investigate the reactivation of hypermethylated GSTP1 (glutathione S-transferase P1) promoter activity by a component of natural drug, CDP. METHODS: The recombinant plasmid of pGL3-GSTP1 pro(m) containing hypermethylated GSTP1 gene promoter was constructed and then used to transiently transfect the human breast cancer cell line MCF-7 cell. After treatment with CDP and 5-aza-C, The luciferase activity in cell lysates were assayed. RESULTS: Low promoter activities were found in hypermethylated GSTP1 promoter. The promoter activities were reactivated and in a CDP dose-dependent mode. CONCLUSION: CDP has the ability to reactivate the hypermethylated GSTP1 gene promoter activity.