Folates are group of water-soluble B-vitamins indispensable to one carbon metabolism as acceptor and donor of methyl group during purine and pyrimidine biosynthesis, DNA and histone methylations, and in mitochondrial protein translation. The deficiencies associated with risk of neural tube defect, cancer, cardiac and psychiatric disorders. Thus, detecting and quantifying folate species accurately become a crucial step in food omics, disease metabolomics, proteomics, genomics, toxicology, and pharmacokinetics, and regulatory sciences. However, the detection and quantitative determination of folate species yet subjected to analytical challenges due to physio-chemical instability, structural similarity, ultra-trace availability. Advances in liquid chromatography tandem mass spectrometry (LC-MS/MS) method enabled the detection and quantification of folate species in short span of time using low sample volume. However, risk of inter conversion, degradation or loss during sample preparation, coupled with folate isomers and isobars challenged the selectivity, specificity and sensitivity for quantification by LC-MS/MS at trace level. Systematic literature search was conducted through major indexing databases such as Pub med, Embase, and Google Scholar to include the most relevant articles published 2010-2025 in preparing the review highlighting the challenges of folate species analysis in food and biological matrices from sample preparation to mass spectrometry detection with a future perspective on innovative optimization methods.

Gastric intestinal metaplasia (GIM) is a precancerous lesion and the key risk factor in the development of gastric cancer (GC), but early detection and treatment remain challenging. The traditional endoscopic diagnosis of metaplastic lesions is complicated by an increased rate of inappropriateness and false negativity. Although early interventions with H. pylori eradication, as well as endoscopic therapy results, were promising, there is still a significant unmet need to control GIM progression and recurrences. Molecular alterations, such as an increased DNA methylation index, have been identified as a crucial factor in the downregulation of tumor suppressor genes, such as the caudal-type homeobox (CDX2) gene, which regulates epithelial cell proliferation and GIM progression and is associated with treatment failure. CDX2 is downregulated by promoter hypermethylation in the colonic-type epithelium, in which the methylation was correlated with reduced intake of dietary folate sources. Tumor cells alter to dietary methionine sources in the biosynthesis of S-Adenosylmethionine, a universal methyl donor for transmethylation, under the conditions of limited folate and B12 availability. The gut microbiota also exhibited a shift in microbial composition, which could influence the host’s dietary methionine metabolism. Meanwhile, activated oncogenic signaling via the PI3K/Akt/mTORC1/c-MYC pathway could promotes rewiring dietary methionine and cellular proliferation. Tumor methionine dependence is a metabolic phenotype that could be helpful in predictive screening of tumorigenesis and as a target for preventive therapy to enhance precision oncology. This review aimed to discuss the molecular alterations in GIM to shed light on the alteration of methionine metabolism, with insight into new diagnostic and treatment approaches and future research directions.

Gastric cancer (GC) is one of the most malignant tumors with high morbidity and mortality in the world. Compound a2, a Jiyuan oridonin derivative, exhibited excellent anti-proliferative activity against GC cells. To investigate the gastric cellular response to a2 therapy as a novel drug candidate, we adopted a pseudotargeted metabolomics method to explore metabolic variation in a2-induced MGC-803 gastric cells using liquid chromatography tandem mass spectrometry combined with multivariate statistical analysis. The results showed that a2 treatment induced significant metabolic changes in the levels of aminoacyl-tRNA biosynthesis, alanine, aspartate and glutamate metabolism, pyrimidine metabolism, and tricarboxylic acid cycle, approximately 80% of the metabolites were down-regulated in the low-dose and high-dose groups including aspartate, tryptophan, sedoheptulose 7-phosphate, succinate, 2′-deoxyadenosine, uridine, cytidine, etc. which can provide evidence for a new therapy of GC.

Atractylodis lancea (Cangzhu) and Atractylodes macrocephala (Baizhu) are two traditional Chinese medicines with complex chemical compositions. However, a comprehensive comparative analysis of their constituents remains lacking. In this work, an ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap tandem mass spectrometry (UPLC-Q-Orbitrap-MS/MS) method was developed for the rapid characterization and differentiation of chemical components in Cangzhu and Baizhu. Chromatographic separation was achieved on a C18 column with gradient elution, and compounds were detected using electrospray ionization in both positive and negative modes. By analyzing characteristic fragmentation patterns and neutral losses, a total of 111 compounds were tentatively identified, including 14 common components (present in both species) and 97 differential components (unique to one species). This study presents the first comprehensive comparative chemical profiling of the two Atractylodes species, offering valuable references for pharmacodynamic material basis studies and quality control.