Online LC-ESI-MS/MS comparative analysis of N/O-glycopatterns in human colostrum from different ethnic groups in Northwest China.

Human milk oligosaccharides, including free oligosaccharides and glycoconjugates, exert a key role in neonatal health and development. Changes in free oligosaccharides of milk from different ethnic groups have been documented. In this study, human milk was collected from Han, Hui, and Tibetan populations in northwest China, and differences in N/O-glycome among these three ethnic groups were systematically compared using online high-performance liquid chromatography-tandem mass spectrometry. Among the 63 detected N-glycans, 35 showed significant differences between the three ethnic groups (p < 0.05). Among the 70 detected O-glycans, four neutral O-glycans and six acidic O-glycans exhibited significant differences among the three ethnic groups (p < 0.05), with six acidic O-glycans reported for the first time. Overall, the extent of milk N/O-glycosylation was higher in the Han population than in the Hui or Tibetan groups. This trend was particularly pronounced for the main sialylated N/O-glycans. Except for sulfated O-glycans, which were higher in the milk from Tibetan mothers, the other types of N/O-glycans were present in similar proportions across all ethnic groups. Understanding the composition of N/O-glycans in human milk can help research on the structure-function relationship of glycans.

Tannins in Phyllanthus emblica L. improves cisplatin efficacy in lung cancer cells by boosting endoplasmic reticulum stress to trigger immunogenic cell death.

BACKGROUND: Lung cancer is one of the deadliest cancers world-wide and immunotherapy has been considered as a promising therapeutic strategy. Previously, our study found that tannins in Phyllanthus emblica L. (PTF) could inhibit the growth of tumor by activating the immune response in liver cancer, and also exhibited a cytotoxicity on human lung cancer cells A549, H460, H1703 in vitro. OBJECTIVE: To explore whether PTF inhibited the growth of lung cancer through its immune-regulating function and to clarify underlying mechanisms. METHODS: The induction of immunogenic cell death (ICD) were characterized by calreticulin exposure, extracellular ATP secretion, and High Mobility Group Box 1(HMGB1) release both in vivo using LLC-derived xenograft tumor model and in vitro using both mouse LLC and human A549 cancer cells. RESULTS: PTF inhibited lung cancer cells growth and tumorigenesis in vivo/vitro and promoted anti-tumor immune responses. We further found that PTF could induce ICD, which then activated Type I interferon responses and CXCL9/10-mediated chemotaxis. Mechanistically, PTF induced the formation of intracellular protein aggregates and following activation of PERK/ATF4/CHOP-dependent endoplasmic reticulum stress-related ICD. Moreover, PTF improved the antitumor efficacy of cisplatin by inducing ICD both in vitro and in vivo. Finally, we screened out 5 components from PTF, including gallocatechin, gallic acid, methyl gallate, ethyl gallate and ellagic acid, which could induce ICD in vitro and might be considered as the potential antitumor pharmacodynamic substances. CONCLUSION: In conclusion, PTF inhibits the growth of lung cancer by triggering ICD and remodeling the tumor microenvironment, suggesting that PTF may have promising prospects as an adjacent immunotherapy for cancers.

Enhanced TSG stability through co-assembly with C3G: the mechanism behind processing Polygonum multiflorum Thunb with black beans via supramolecular analysis.

Elucidating the underlying mechanism of the processing of Chinese herbal medicine (CHM) is crucial and also challenging for the modernization of Traditional Chinese Medicine (TCM). Herein, inspired by the traditional method for processing the Chinese herb Polygonum multiflorum (PM) Thunb with excipient black beans, the representative herbal components trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-D-glucopyranoside (TSG) and cyanidin-3-O-ß-glucoside (C3G) from each herbal medicine were selected to investigate the processing mechanism at the supramolecular level. The co-assemblies of TSG/C3G were found to be formed, and their structure was characterized by electronic microscopy and a small angle X-ray scattering (SAXS) technique. In addition, the supramolecular interactions between TSG and C3G were fully probed with UV-Vis, fluorescence, XRD, and NMR spectroscopy. Molecular dynamics were further performed to simulate the assembly processes of TSG and C3G. Notably, the formation of TSG/C3G co-assemblies was found to significantly enhance the stability of TSG against light, Fe3+, and simulated intestinal fluids. The co-assembly of TSG and C3G that leads to supramolecular aggregates discovered here may imply the underlying mechanism of processing PM with black beans. Our results may also suggest that a new effective form of TCM is supramolecular aggregates rather than each component.