The flavor substances changes in Fuliang green tea during storage monitoring by GC-MS and GC-IMS.

To study the effect of storage (for 0, 3, 6, and 12 months) on the flavor of green tea (GT), we monitored the volatile organic compounds (VOCs) in GT through gas chromatography (GC) combined with ion mobility spectrometry and headspace solid-phase micro extraction, GC-MS (mass spectrometry). Then, relative odor activity value (ROAV) was applied to analyze the aroma contribution of the VOCs. During storage, the polyphenol and caffeine contents gradually decreased from 22.38 % to 18.51 % and from 4.37 % to 3.74 %, respectively, and the total soluble sugar first increased and then decreased (from 4.89 % to 7.16 % and then 5.02 %). Although the total free amino acid contents showed a fluctuating trend, the content of cysteamine increased gradually. The contents of VOCs with positive contribution to GT aroma, including linalool, geraniol, nonanal, and 6-methyl-5-hepten-2-one, decreased. They also contributed less in the ROAV after storage. The ROAVs of nonanal, linalool, and geraniol decreased from 3.37 to 0.79, from 100 to 38.21, and from 2.98 to 1.8, respectively, after 12 months of storage. Principal component analysis can be used to identify the samples with different storage durations based on these data. Given the increase in amount of cysteamine and decrease in that of linalool oxide, oxidation may be not the only factor responsible for tea quality in storage.

Low concentration Tetrabromobisphenol A (TBBPA) elevating overall metabolism by inducing activation of the Ras signaling pathway.

Tetrabromobisphenol A (TBBPA), one of the most common flame retardants, affects neurodevelopment, disrupts the endocrine system, and increases the possibility of tumorigenesis. This study investigates the cytotoxic effects, genetic effects, and metabolic effects from exposure to low concentration TBBPA. The cell exposure was measured by mimicking the residual TBBPA concentrations in human plasma, specifically in occupational populations. Our results revealed that long-term TBBPA exposure, especially at 1 nM concentration, significantly promoted the proliferation of HepG2 cells. Furthermore, long-term TBBPA exposure can double the levels of reactive oxygen species (ROS) released from mitochondria, thereby increasing Adenosine Monophosphate activated Protein kinase (AMPK) gene expression level to promote cellular proliferation. However, ROS can also mediate the apoptosis process through the mitochondrial membrane potential (MMP). The RNA-seq analysis confirmed that the Ras signaling pathway was activated by the growth factor to mediate cell detoxification mechanism, increasing lipid and vitamin metabolic rate. Our work uncovers a cellular mechanism by which long-term exposure to low concentration TBBPA can induce the activation of the Ras signaling pathway and demonstrates potential metabolic disorder in the human hepatic cells upon plasma TBBPA exposure.

[Analysis of HEXB gene mutations in an infant with Sandhoff disease].

OBJECTIVE: To detect potential mutations of HEXB gene in an infant with Sandhoff disease (SD). METHODS: Genomic DNA was extracted from peripheral blood sample of the infant. All coding exons (exons 1 to 14) and splicing sites of the HEXB gene were subjected to PCR amplification and direct sequencing.PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. PubMed BLAST CD-search was performed to identify functional domains destroyed by thecandidate mutations. Impact of the mutations was analyzed with software including PolyPhen-2, Mutation Taster and SIFT. Whole-exome sequencing was carried out to identify additional mutations. RESULTS: The infant was found to carry compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) of the HEXB gene. The c.1389C>G (p.Tyr463*) mutation may lead to destruction of two functional domains in ß subunit of the Hex protein. The c.1652G>A(p.Cys551Tyr) mutation, unreported previously,was predicted to be probably damaging by Bioinformatic analysis. CONCLUSION: Compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) in the HEXB gene probably underlie the disease in this patient.

Activation of NF-κB pathways mediating the inflammation and pulmonary diseases associated with atmospheric methylamine exposure.

The effects of methylamine on human health have been debated for several years, but the exact adverse outcomes and definite signaling cascades have not been elucidated yet. Herein, a NF-κB signal pathway, a positive regulator of inflammation was identified as the main pathway of methylamine exposure induced adverse effects in bronchial airway cells (16HBE) for the first time. The results indicated that methylamine could stimulate the overproduction of reactive oxygen species (ROS) in cytoplasm and mitochondria of 16HBE cells. Moreover, ROS accelerate the translocation and phosphorylation of NF-κB in nucleic and promote the expression of inflammatory, such as IL-8 and IL-6. As a result, methylamine was found to be increased ROS-mediated NF-κB activation in cells, leading to the production of inflammatory cytokine. Furthermore, the results also showed that methylamine could affect the expression of cytokines related genes, p53, STAT3, Bcl2, c-myc, Cyclin D, Hes1, Mcl-1, TGF-ß2. The breakdown of those cell proliferation and apoptosis related genes were leading to a common toxic mechanism of cell death. In summary, our work uncovers a mechanism by which methylamine can induce the formation of inflammation response and demonstrates potential inflammation and carcinogenesis in human airway cell upon the methylamine inhaled.

Myeloid-derived suppressor cells expansion is closely associated with disease severity and progression in HBV-related acute-on-chronic liver failure.

Dysregulation of the host immune responses induced by host hepatitis B virus (HBV) interactions has been observed in acute-on-chronic liver failure (ACLF). Myeloid-derived suppressor cells (MDSCs), well known for their immunomodulatory properties, can suppress T-cell function by regulating the expression of CD3 ζ chain in cancer and autoimmune/infectious diseases while rarely have been studied in ACLF. In this study, MDSCs, CD4+ /CD8+ T cells, and CD3 ζ chain were analyzed by flow cytometry in peripheral blood mononuclear cells obtained from HBV-related ACLF patients, chronic hepatitis B (CHB) patients and healthy controls. ACLF patients were followed up for dynamic detection of MDSCs and observation of outcomes after treatment. Interestingly, peripheral CD14+ CD33+ CD11b+ HLA-DR-/low MDSCs from ACLF patients were significantly increased compared to those from CHB patients and healthy controls. CD4+ /CD8+ T cell frequency and CD3 ζ chain expression in T cells were decreased in ACLF patients compared to those of healthy controls and were negatively correlated with matched MDSC frequency. Meanwhile, the frequency of MDSCs was closely correlated with biochemical parameters that are relevant for liver injury rather than virological parameters. Moreover, a lower level of MDSCs was correlated with a better short-term prognosis (within 4 weeks but not at 8 weeks), and MDSCs remained high in ACLF patients whose conditions worsened within a 4-week follow-up period after treatment. These results suggest that MDSCs are closely involved in cell-mediated immunity in HBV-related ACLF and that peripheral MDSC expansion is closely associated with disease severity and progression in HBV-related ACLF, which may serve as a predictor of short-term prognosis.

Expression and clinical significance of myeloid derived suppressor cells in chronic hepatitis B patients.

We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/ PBMC median (X(2)=11.877, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/ PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference (X(2)=17.198, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.