Characterizing the metabolic divide: distinctive metabolites differentiating CAD-T2DM from CAD patients.

OBJECTIVE: To delineate the metabolomic differences in plasma samples between patients with coronary artery disease (CAD) and those with concomitant CAD and type 2 diabetes mellitus (T2DM), and to pinpoint distinctive metabolites indicative of T2DM risk. METHOD: Plasma samples from CAD and CAD-T2DM patients across three centers underwent comprehensive metabolomic and lipidomic analyses. Multivariate logistic regression was employed to discern the relationship between the identified metabolites and T2DM risk. Characteristic metabolites' metabolic impacts were further probed through hepatocyte cellular experiments. Subsequent transcriptomic analyses elucidated the potential target sites explaining the metabolic actions of these metabolites. RESULTS: Metabolomic analysis revealed 192 and 95 significantly altered profiles in the discovery (FDR < 0.05) and validation (P < 0.05) cohorts, respectively, that were associated with T2DM risk in univariate logistic regression. Further multivariate regression analyses identified 22 characteristic metabolites consistently associated with T2DM risk in both cohorts. Notably, pipecolinic acid and L-pipecolic acid, lysine derivatives, exhibited negative association with CAD-T2DM and influenced cellular glucose metabolism in hepatocytes. Transcriptomic insights shed light on potential metabolic action sites of these metabolites. CONCLUSIONS: This research underscores the metabolic disparities between CAD and CAD-T2DM patients, spotlighting the protective attributes of pipecolinic acid and L-pipecolic acid. The comprehensive metabolomic and transcriptomic findings provide novel insights into the mechanism research, prophylaxis and treatment of comorbidity of CAD and T2DM.

GC/QQQ coupling with metabolomics for selection of predicator of tea fermentation.

Fermentation is the most crucial process for manufacture of black tea. Signature components were desired for the establishment of accurate prediction of fermentation degree. In this study, finished black teas were prepared using leaves that had been fermented for various times, and sensory quality evaluation was performed. Tracking analysis of volatiles during fermentation was conducted to discriminate the iconic compounds. On the basis of both the sensory evaluation results and the enzymatic oxidation traits of fermentation, the ratio of ß-cyclocitral to γ-pylpyrone was proposed as an indicator. A positive correlation was observed between this ratio and the sensory score of finished black tea with varied duration of fermentation, and the correlation coefficient was 0.78. Furthermore, widely plant-targeted metabolomics was applied to cognize the fermentation. Comparative analysis of metabolites was conducted by category, and special attention was paid to flavonoids and terpenes. Significant metabolic differences emerged discriminatively. The results would be useful for intelligent modulation of the manufacture of black tea.

Impact of tea leaves categories on physicochemical, antioxidant, and sensorial profiles of tea wine.

Introduction: Tea is the main raw material for preparing tea wine. Methods: In this research, four types of tea wine were prepared using different categories of tea leaves, including green tea, oolong tea, black tea, and dark tea, and the comparative study looking their physicochemical, sensorial, and antioxidant profiles were carried out. Results: The dynamic changes of total soluble solids, amino acids and ethanol concentrations, and pH were similar in four tea wines. The green tea wine (GTW) showed the highest consumption of total soluble solids and amino acids, and produced the highest concentrations of alcohol, malic, succinic, and lactic acid among all tea wines. The analysis of volatile components indicated the number and concentration of esters and alcohols increased significantly after fermentation of tea wines. GTW presented the highest volatile concentration, while oolong tea wine (OTW) showed the highest number of volatile compounds. GTW had the highest total catechins concentration of 404 mg/L and the highest ABTS value (1.63 mmol TEAC/mL), while OTW showed the highest DPPH value (1.00 mmol TEAC/mL). Moreover, OTW showed the highest score of sensory properties. Discussion: Therefore, the types of tea leaves used in the tea wine production interfere in its bioactive composition, sensorial, and antioxidant properties.

Recognition of Gallotannins and the Physiological Activities: From Chemical View.

Gallotannins, characterized with the glycosidic core and galloyl unit, are seemed as vital components of hydrolyzable tannins. Benefit from the more and more discoveries of their bioactivities and edibility, application of gallotannins in food industry, pharmacy industry, and other fields is increasing. Inheriting previous study achievements, chemical structure of gallotannins was illustrated and degradation as well as synthetic routes to gallotannins were summarized. On this basis, distribution in the nature also including the distinction of gallotannins was discussed. More than that, activities involving in antioxidant, anti-inflammatory, enzyme inhibitions, protein binding, and so on, as well as applications in the field of food industry, biopharmaceutical science, agricultural production, etc., were combed. Finally, improvement of bioavailability, chemical modification of the structure, and accurate determination of new gallotannins were pointed out to be the orientation in the future.

Ag2O-mediated Tandem Reaction between Terminal Alkyne and o-Iodibenzoic Acid: Construction of 3-Ethylideneisobenzofuran-1(3H)-ones.

Taking aryl propargyl ether and o-iodibenzoic acid as substrates, a series of aryl cyclolactones bearing an exocyclized C=C bond were constructed with moderate to good yields. Diverse substituent groups could be tolerant in the reaction, which indicated excellent compatibility of the reaction. In this tandem reaction, Ag2O was employed as the media and Et3N was screened as the base to facilitate the reaction. A concise mechanism was proposed on the basis of the expansion of the substrates and theoretical analysis. Sonogashira type coupling coupled with intramolecular nucleophilic addition in one pot to construct the product, 3-ethylideneisobenzofuran-1(3H)-one.

Co-delivery of PSMA antigen epitope and mGM-CSF with a cholera toxin-like chimeric protein suppressed prostate tumor growth via activating dendritic cells and promoting CTL responses.

Subunit vaccines derived from tumor antigens play a role in tumor therapy because of their unique advantages. However, because of the weak immunogenicity of peptides in subunit vaccines, it is difficult to trigger an effective cytotoxic T lymphocyte (CTL) response, which is critical for cancer therapy. A requirement for the activation of CTL cells by exogenous antigens is the stimulation of antigen presenting cells (APC) with the help of adjuvants and cross-presentation to T lymphocytes. Standard nonconjugated adjuvant-peptide mixtures do not ensure co-targeting of the antigen and the adjuvant to the same APC, which limits the effects of adjuvants. In this study, a fusion protein consisting of murine granulocyte-macrophage colony stimulating factor (mGM-CSF) fused with CTA2 (A2 subunit of cholera toxin) was generated and assembled with CTB-PSMA624-632 (prostate specific membrane antigen (PSMA) peptide 624-632 fused to CTB) to obtain a cholera toxin-like protein. The chimeric protein retained the biological activity of mGM-CSF and had stronger GM1 binding activity than (CTB-PSMA624-632)5. C57BL/6J mice immunized with the CT-like chimeric protein exhibited delayed tumor growth following challenge with human PSMA-EGFP-expressing RM-1 cells. Experiment results showed that the CT-like chimeric protein could induce the maturation of DC cells and improve CTL responses. Overall, these results indicate that the nasal administration of a CT-like chimeric protein vaccine results in the development of effective immunity against prostate tumor cells and might be useful for future clinical anti-tumoral applications.

An in vitro and in vivo study of the brain-targeting effects of an epidermal growth factor-functionalized cholera toxin-like chimeric protein.

The development of neuroprotective drugs has proven to be extremely difficult because of the blood-brain barrier. Intranasal administration is thought to transport the drug from the nasal cavity along the olfactory and trigeminal nerves to the brain, thus bypassing the blood-brain barrier. However, macromolecular protein drugs have low delivery efficiency via this route in general. We hypothesized that an innocuous cholera toxin-like chimeric protein could better enhance the efficiency of protein delivery through the intranasal route. To test this hypothesis, we designed an enhanced green fluorescent protein (EGFP) chimera to evaluate the effect of the cholera toxin (CT) as a carrier for drug delivery into the brain. Then, the EGFP was replaced with epidermal growth factor (EGF) in the chimeric protein, and the therapeutic effect of the new chimeric protein was studied in an LPS-induced neuritis mouse model. The results suggest that the CT-like chimeric protein can bypass the blood-brain barrier and enter the brain in approximately 30 min. This EGF chimeric protein can effectively protect the spatial cognitive ability of and confer anti-anxiety protection to mice. The results indicate that cholera toxin-like chimeric proteins are potential tools for effectively delivering macromodecular drugs into the brain through intranasal administration.

Gallotannin 1,2,6-tri-O-galloyl-ß-d-glucopyranose: Its availability and changing patterns in tea (Camellia sinensis).

Gallotannin 1,2,6-tri-O-galloyl-ß-d-glucopyranose (1,2,6-TGGP) plays multiple roles against multidrug-resistant bacteria and other diseases. Nevertheless, its availability in tea (Camellia sinensis) has rarely been reported. Herein, the identification and verification of 1,2,6-TGGP from Camellia sinensis using ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-qTOF MS/MS), electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) were reported. The isolated 1,2,6-TGGP was used for the chemotaxonomy analysis of 17 tea cultivars. The contents of 1,2,6-TGGP ranged from 1.96 to 43.20 mg g-1, with a mean of 13.75 mg g-1. Relatively high 1,2,6-TGGP contents (>30 mg g-1) in two tea cultivars indicate that the beneficial effects of 1,2,6-TGGP can be obtained by consuming these teas. The chemotaxonomy analysis showed a biosynthetic relation between 1,2,6-TGGP and gallic acid. Further analysis showed that the 1,2,6-TGGP contents significantly decreased with the plucking times irrespective of the cultivars. Moreover, a positive and significant correlation was also observed between 1,2,6-TGGP and gallic acid. The identification of tea cultivars that are rich in 1,2,6-TGGP was first reported and the obtained results should boost their potential use in food and medicine.

Research progress on theaflavins: efficacy, formation, and preparation.

Background: Theaflavins (TFs) are a category of natural compounds characterized with the benzotropolone skeleton. The prominent benefits of TFs have been well documented. Amount of research were conducted and excellent achievements were disclosed during the past years. However, as far as we know, there is no comprehensive review about TFs. Scope and approach: This review summarized the recent research progress. The activity of TFs on anti-oxidation, anti-mutagenicity, hypolipidemic, anti-inflammatory, anti-cancer, anti-viral effect as well as the epidemiological cure were sorted. Converging pioneer literature and deduction, the underlying formation mechanism of TFs was proposed. Subsequently, acquisition of TFs was pointed out to be the fundament for further research. Accelerated by enzyme, bio-synthesis of TFs were reviewed simultaneously. At the end, employing modern analysis instrument and technology, isolations of TFs were enumerated. Key findings and conclusions: Structure of the skeleton as well as functional groups were paramount related with the bio-activity of TFs. Meanwhile, oxidation pathway of two catechin molecules to form TFs were hypothesized. Also, ascertainment of the several therapeutic efficiency of the family members of TFs would be the next step in the future.