Jing Li

3,4,5,4’-Trans-tetramethoxystilbene (Synonyms: DMU-212) is a resveratrol analogue with stronger antiproliferative activity and more bioavailability. However, the metabolite characterization of this component remains insufficient. An efficient strategy was proposed for the comprehensive in vivo metabolite profiling of DMU-212 after oral administration in Apc^Min/+ mice based on the effectiveness of the medicine. Ultra-high performance liquid chromatography-quadrupole/orbitrap/linear ion trap mass spectrometry (UHPLC-Q/Orbitrap/LTQ MS) in the AcquireX^TM intelligent data acquisition mode, combining the exact mass and structural information, was established for the profiling and identification of the metabolites of DMU-212 in vivo, and the possible metabolic pathways were subsequently proposed after the oral dose of 240mg/kg for 3 weeks in the colorectal adenoma (CRA) spontaneous model Apc^Min/+ mice. A total of 63 metabolites of DMU-212 were tentatively identified, including 48, 48, 34 and 28 metabolites in the Apc^Min/+ mice’s intestinal contents, liver, serum, and colorectal tissues, respectively. The metabolic pathways, including demethylation, oxidation, desaturation, methylation, acetylation, glucuronide and cysteine conjugation were involved in the metabolism. Additionally, further verification of the representative active metabolites was employed using molecular docking analysis. This study provides important information for the further investigation of the active constituents of DMU-212 and its action mechanisms for CRA prevention.

Question Does tirzepatide (TZP) influence appetite, energy intake and fat mass in people with T2D? Methodology This randomized, double-blind, parallel study compared the effects of TZP 15mg (N=45), semaglutide (SEMA) 1mg (N=44) and placebo (N=28) on energy intake (assessed by an ad libitum lunch), appetite (visual analog scale [VAS] ratings of hunger, satiety, prospective food consumption [PFC], and fullness) and body composition (air-displacement plethysmography) at baseline and Week 28. Results At Week 28, reductions in body weight from baseline were observed with TZP 15mg (-11.2kg) and SEMA 1mg (-6.9kg), with significant difference between treatment groups (-4.3kg [95%CI: -6.8, -1.9]; p<0.001). Reductions in fat mass from baseline were observed with TZP 15mg (-9.7 kg) and SEMA 1mg (-5.9kg), with significant difference between treatment groups (-3.8kg [95%CI: -6.2, -1.4]; p=0.002). Energy intake reductions from baseline observed with TZP 15mg (-348.4kcal) and SEMA 1mg (-284.1kcal) did not differ between treatment groups (-64.3kcal [95%CI: -160.3, 31.7]; p=0.187). TZP reduced overall appetite by increasing satiety with decreased PFC (all p<0.05). Appetite ratings did not differ between TZP and SEMA. Conclusion TZP achieved greater weight loss than a selective GLP-1 RA, mostly driven by fat-mass loss. Significant and clinically meaningful reductions in appetite and energy intake were observed with both TZP and selective GLP-1 RA. However, these effects could not totally explain the additional weight loss with TZP. As appetite and energy intake reduction were not significantly different between treatments; additional mechanisms might contribute to the weight loss with TZP. Article published online: 02 May 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

Colorectal cancer (CRC) is common Cancer as well as the third leading cause of mortality around the world; its exact molecular mechanism remains elusive. Although CRC risk is significantly correlated with genetic factors, the pathophysiology of CRC is also influenced by external and internal exposures and their interactions with genetic factors. The field of CRC research has recently benefited from significant advances through Omics technologies for screening biomarkers, including genes, transcripts, proteins, metabolites, microbiome, and lipidome unbiasedly. A promising application of omics technologies could enable new biomarkers to be found for the screening and diagnosis of CRC. Single-omics technologies cannot fully understand the molecular mechanisms of CRC. Therefore, this review article aims to summarize the multi-omics studies of Colorectal cancer, including genomics, transcriptomics, proteomics, microbiomics, metabolomics, and lipidomics that may shed new light on the discovery of novel biomarkers. It can contribute to identifying and validating new CRC biomarkers and better understanding colorectal carcinogenesis. Discovering biomarkers through multi-omics technologies could be difficult but valuable for disease genotyping and phenotyping. That can provide a better knowledge of CRC prognosis, diagnosis, and treatments.

Aging affects the brain function in elderly individuals, and Dushen Tang (DST) is widely used for the treatment of senile diseases. In this study, the protective effect of DST against memory impairment was evaluated through the Morris water maze (MWM) test and transmission electron microscopy (TEM). A joint analysis was also performed using LC‐MS metabolomics and the microbiome. The MWM test showed that DST could significantly improve the spatial memory and learning abilities of rats with memory impairment, and the TEM analysis showed that DST could reduce neuronal damage in the hippocampus of rats with memory impairment. Ten potential biomarkers involving pyruvate metabolism, the synthesis and degradation of ketone bodies, and other metabolic pathways were identified by the metabolomic analysis, and it was found that 3‐hydroxybutyric acid and lactic acid were involved in the activation of cAMP signaling pathways. The 16S rDNA sequencing results showed that DST could regulate the structure of the gut microbiota in rats with memory impairment, and these effects were manifested as changes in energy metabolism. These findings suggest that DST exerts a good therapeutic effect on rats with memory impairment and that this effect might be mainly achieved by improving energy metabolism. These findings might lead to the potential development of DST as a drug for the treatment of rats with memory impairment.