Gut microbiota regulation and anti-inflammatory effect of ß-carotene in dextran sulfate sodium-stimulated ulcerative colitis in rats.

ß-Carotene displays antioxidant and anti-inflammatory activities and prevents the development of cancer. Ulcerative colitis (UC) is a kind of inflammatory bowel disease that is accompanied by a certain risk of colon cancer. However, the role of ß-carotene in the modulation of gut microbiota and UC improvement is unclear. In this research, the properties of ß-carotene on anti-inflammatory and the composition of gut microbiota were evaluated in a rat model of UC induced by dextran sulfate sodium (DSS). The results revealed that ß-carotene significantly (p < 0.05) decreased the severity of colitis in rats, as assessed using body weight (6.00 ± 1.73%), colon length (22.23 ± 0.53%), and disease activity index, and improved the structure of the colon damaged. Moreover, colonic levels of proinflammatory cytokines were significantly lower following ß-carotene supplementation. ß-Carotene intervention also lowered the expression levels of phosphorylated p65 (0.60 ± 0.02), p38 (0.57 ± 0.00), Erk (0.63 ± 0.04), and JNK (0.70 ± 0.00). The result of the relative abundance of gut microbiota showed that DSS administration significantly changed the microbial structure at the phylum and genus levels of rats. Furthermore, ß-carotene treatment significantly increased the abundance of Faecalibacterium, the levels of which negatively correlated with the levels of inflammatory cytokines. Faecalibacterium may be a potential target in the alleviation of DSS-induced UC. ß-Carotene can alleviate DSS-induced UC through the regulation of gut microbiota. This study provides a reference for the rational use of ß-carotene in the treatment of UC. PRACTICAL APPLICATION: ß-Carotene can relieve ulcerative colitis and regulate the gut microbiota; the nutritional intervention of ß-carotene enhancing animal health.

Metabolomics strategy reveals the osteogenic mechanism of yak (Bos grunniens) bone collagen peptides on ovariectomy-induced osteoporosis in rats.

Our previous work demonstrated that yak bone collagen peptides (YBP) possessed excellent osteogenic activity in vitro. However, associations between YBP and osteoporosis were less established, and the positive effect and underlying mechanism of YBP in the treatment of osteoporotic rats in vivo remained unclear. Herein, ovariectomized rats were intragastrically administered with YBP or 17ß-estradiol for 12 weeks. Bone turnover markers, bone biomechanical parameters and bone microarchitecture were investigated to identify the specific changes of potential antagonistic effects of YBP on ovariectomized rats. Then, serum samples were analyzed by UPLC/Q-TOF-MS to identify metabolites. The results showed that YBP treatment remarkably altered the content of serum bone turnover markers and prevented the ovariectomy-induced deterioration of bone mechanical and microarchitecture characteristics. A total of forty-one biomarkers for which levels changed markedly upon treatment have been identified based on non-targeted metabolomics. Among them, twenty-one metabolites displayed a downward expression level, while twenty metabolites showed an upward expression level in the YBP group and finally were selected as potential biomarkers. The levels of these biomarkers displayed significant alterations and a tendency to be restored to normal values in YBP treated osteoporotic rats. A systematic network analysis of their corresponding pathways delineated that the protective or recovery effect of YBP on osteoporosis occurred primarily by regulating the amino acid metabolism and lipid metabolism (especially unsaturated fatty acid). Collectively, these findings highlight that such peptides hold promise in further advancement as a natural alternative for functional and health-promoting foods, which could be potentially used in mediated treatment of osteoporosis.

Yak (Bos grunniens) bones collagen-derived peptides stimulate osteoblastic proliferation and differentiation via the activation of Wnt/ß-catenin signaling pathway.

BACKGROUND: As the world's population is transitioning gradually to an ageing stage, the incidence of osteoporosis is increasing annually. Yak bone is one of the major components of Tibetan medicine and it has mainly been associated with an improvement in bone health, for example against osteoporosis. However, the functional bioactive ingredients and the underlying mechanisms are still unclear. RESULTS: Sequential purification of yak-bone hydrolysates was achieved by ultrafiltration, size exclusion chromatography, and semi-preparative reverse-phase high-performance liquid chromatography. After this, 35 novel peptides were identified by mass spectrometry analysis, of which peptide GPAGPPGPIGNV (GP-12) displayed the highest osteoblast proliferation-promoting activity, with an increase of 42.7% in cell growth. An in vitro stability study demonstrated that GP-12 was digested into smaller peptides (GP-9, GV-9, AV-10 and GP-11) after simulated gastrointestinal digestion and absorption (Caco-2 cell monolayers) experiments. However, some of them still can be absorbed intact through the (Caco-2 cell monolayers by a paracellular route (Papp: 5.36 ± 0.34 cm s-1 ). Flow cytometry results indicated that GP-12 enhanced osteoblastic proliferation by inducing the alteration of the cell-cycle progression both from the G0/G1 to the S phase and from the S to the G2/M phase. Quantitative real-time polymerase chain reaction (PCR) and western blot results revealed that GP-12 induced osteoblastic proliferation and differentiation in a dose-response manner through the activation of a Wnt/ß-catenin signaling pathway. CONCLUSION: These findings highlighted that such peptides hold the promise of discovering candidates for functional and health-promoting foods, which could be potentially used for the treatment of osteoporosis. © 2020 Society of Chemical Industry.

A sequential targeting nanoplatform for anaplastic thyroid carcinoma theranostics.

Effective accumulation of nanoparticles (NPs) in tumor regions is one of the major motivations in nanotechnology research and that the establishment of an efficient targeting nanoplatform for the treatment of malignant tumors is urgently needed for theranostic applications. In this study, we engineered multifunctional sequential targeting NPs for achieving synergistic antiangiogenic photothermal therapy (PTT) and multimodal imaging-guided diagnosis for anaplastic thyroid carcinoma (ATC) theranostics. Antibody bevacizumab with an affinity towards vascular endothelial growth factor (VEGF) on the tumor cell surface was conjugated onto the surface of polymer NPs for VEGF targeting and antiangiogenic therapy. Encapsulated IR825 was employed as a photothermal agent (PTA) with a mitochondrial targeting capability, which further cascades NPs into mitochondria to enhance hyperthermic efficiency in the ablation of tumor cells. Importantly, the combination of bevacizumab and IR825 in a single nanosystem achieved desirable accumulations of NPs and that sequential targeted PTT combined with antiangiogenesis significantly promoted the therapeutic efficiency in eradicating tumors by near-infrared (NIR) laser irradiation. Furthermore, these NPs are extraordinary contrast agents for photoacoustic, ultrasound and fluorescence imaging applications, providing multimodal imaging capabilities for therapeutic monitoring and a precise diagnosis. Therefore, this multifunctional nanoplatform provides a promising theranostic strategy for extremely malignant ATC. STATEMENT OF SIGNIFICANCE: Anaplastic thyroid carcinoma (ATC), with extremely aggressive behavior, lacks a satisfactory therapeutic method and a comprehensive early diagnostic strategy. Herein, we successfully synthesized a sequential targeting nanoplatform (IR825@Bev-PLGA-PFP NPs) with theranostic function, which specifically binds to VEGF on the tumor cell surface and further cascades into mitochondria to achieve effective accumulation of NPs in the tumor regions. As a result, it solves the urgent demand for ATC detection and therapy. By breaking the limitation of traditional target, such as low efficacy and frequent recurrence as the results of low accumulation, sequential targeting combined with synergistic antiangiogenic PTT completely eradicates tumors without any residual tissue and side effect. Therefore, this strategy paves a solid way for further investigation in the theranostic progressing of ATC.