Yunli Zhao

Introduction: Hyperlipidemia is a widespread metabolic disorder that places a heavy burden on normal body functions. Given the drawbacks of current lipid-lowering drugs, there is considerable interest in developing alternative nutraceuticals from natural sources. S -2-(2-hydroxypropanamido) benzoic acid ( S -HPABA) is a novel compound obtained for the first time from a marine fungus, which has demonstrated strong lipid-lowering effects in vitro and in vivo with an excellent safety profile. Methods: To investigate S -HPABA’s mechanism of action, an integrated strategy of lipidomics and bioinformatics was adopted to screen candidate targets. The selected targets were then validated through RT-qPCR and western blotting. Results: The results indicated that 57 differential metabolites and 11 metabolic pathways were significantly regulated by S -HPABA. Based on the combined analyses, five targets were initially selected. Validation experiments showed that FASN, PLA2G2A and TYMP play crucial roles in the lipid-lowering process, with FASN being the most prominent. Discussion: Mechanistically, S -HPABA-induced reduction of lipid accumulation was associated with decreased FASN expression and PI3K/AKT/mTOR pathway inhibition. In summary, S -HPABA is a safe and potent lipid-lowering bioactive compound with promise as a functional food ingredient for metabolic health.

Background: Doxorubicin (DOX) is a highly effective chemotherapy drug, but its use is limited by dose-dependent cardiotoxicity, driving the search for protective natural products. Although the herb Viscum coloratum (Kom.) Nakai is known for its cardiovascular benefits, the cardioprotective effects and mechanisms of its isolated compound, DHDK, remain unexplored. Methods: The protective effect of DHDK was first evaluated in DOX-injured H9c2 cardiomyocytes. Subsequently, an integrated network toxicology (incorporating DOX-induced toxicity targets and relevant chronic disease pathways such as aging and lipid metabolism) and pharmacology (DHDK) approach identified core targets, which were then refined through Protein–Protein Interaction (PPI) analysis and molecular docking. The underlying mechanism was investigated using lipidomics and validated through a series of in vitro assays, including CCK-8, q-PCR, biochemical tests, and flow cytometry, as well as in an in vivo rat model. Results: DHDK significantly alleviated DOX-induced cardiomyocyte toxicity. Integrated analysis identified 56 intersecting targets, with PPARG confirmed as the primary target via PPI and molecular docking. Lipidomics revealed that DHDK potently attenuated DOX-induced accumulation of pathogenic lipids (e.g., fatty acids, ceramides). Mechanistically, DHDK activated PPARG, which in turn upregulated CPT1B, a key regulator of fatty acid β-oxidation (FAO). This enhanced cell viability, ATP production, and mitochondrial membrane potential while reducing oxidative stress. These protective effects, which were abolished by the inhibition of PPARG or CPT1B, were further validated in vivo. Conclusion: This study demonstrates that DHDK exerts its cardioprotective effect by activating the PPARG-CPT1B-FAO axis, effectively correcting lipid metabolic disorders. Given that lipid dysregulation is a hallmark of various internal metabolic diseases, DHDK may also hold therapeutic potential for other heart conditions driven by metabolic disturbances, such as diabetic cardiomyopathy, highlighting its broad relevance to the field of internal diseases.

A novel paper-based colorimetric sensor was synthesized based on a core–shell metal–organic framework (MOF) coated with dummy molecularly imprinted polymer (DMIP) for detecting organophosphorus pesticides (OPs). The MOF, used as the core, enhances sensor sensitivity owing to its inherent advantages such as high catalytic activity and stability; meanwhile, the introduction of MIP effectively overcomes the limitation of MOFs in single-substrate detection. This sensor shows great on-site detection potential and superior analytical performance owing to the combination of color response and quantitative analysis via a smartphone. Six OPs were successfully detected in agricultural products with a limit of detection as low as 0.5 ng/mL. Moreover, the consistency between the sensor and HPLC–MS/MS results was verified, yielding satisfactory agreement ranging from 94.4% to 100%. In conclusion, this method is promising for portable, rapid, and on-site food safety detection. Graphical Abstract

The CD90 gene encodes a cell surface glycoprotein that plays an important role in the development and progression of cancer. Regarding CD90 gene, pan-cancer analysis of investigating the correlation between CD90 and immune filtration, patients prognosis is still unclear. TCGA, GTEx, TIMER 2.0, GEPIA2 databases and web tool were used for analyzing CD90 gene impacts among multiple cancer types. The data visualization of KEGG and GO enrichment analysis were achieved through R codes. In addition, molecular docking and molecular dynamics showed the binding ability of the candidate compounds to proteins, which was verified by in vitro experiments. On the whole, CD90 expression differences exist between tumor tissues and their corresponding normal controls. Meanwhile, CD90 has a significant impact on patient prognosis in multiple cancers. Specifically, CD90 high expression levels are correlated with poor Overall survival (OS) and Disease-free survival (DFS), Disease specific survival (DSS) in the TCGA KIRP and UVM cancer datasets. Additionally, it is worth mentioning that the highest CD90 gene mutation frequency occurs on the cancer type of UVM. Moreover, CD90 expression levels were significantly associated with immune cell infiltration, including cancer associated fibroblast and Endothelial cells. (1E,4E)- 1,7-bis(4-hydroxyphenyl) Hepta- 1,4-dien- 3-one (DHDK) docked well with CD90 protein and the experimental results showed that DHDK interfered with the expression of CD90 in cancer cells. Preliminary experimental results indicate that DHDK holds potential in the future targeted therapy of the CD90 gene.

Purpose Etomidate, which is a psychoactive drug with an anesthetic effect, is used as a substitute for expensive mainstream drugs. There has been a trend toward abuse of etomidate and its emerging structural analogues now. Faced with a large number of samples, a rapid and effective detection method is needed. Methods In this study, ambient flame ionization (AFI) coupled with LTQ-Orbitrap mass spectrometry was used to analyze etomidate and its structural analogues in urine. It can realize detection in less than 0.2 min without sample preparation. Results Ideal analysis conditions were obtained by optimizing various parameters and analytical performance was validated. The isomers (isopropoxate and propoxate) can be distinguished by ion abundance ratios. Positive samples (n = 75) were analyzed very efficiently and successfully from plenty of authentic specimens (n = 116). Statistical analysis was conducted on drug types, age, and gender of drug users. A new structural analogue was discovered in one of the samples, which was a very crucial discovery. That meant the market may face with the emergence of new structural analogues. Conclusions This study can satisfy both targeted and non-targeted screening, which provides support for timely monitoring and detection of novel drugs and offers a wider range of method choices for forensic laboratories. It can also better cope with the current situation of drug control and combat crimes related to new types of drugs.

Breast cancer is the most common cancer among women. Currently, most treatments involve combinations of multiple therapies. However, existing drug therapies remain limited by side effects and drug resistance. (1E,4E)- 1,7-bis(4-hydroxyphenyl)hepta- 1,4-dien- 3-one (DHDK) is a safer, potential targeted drug with strong anti-cancer activity, derived from mistletoe. However, few studies have explored its related treatment mechanisms. This study combined network pharmacology, bioinformatics, molecular docking, and experimental verification to elucidate the mechanism of action of DHDK in treating breast cancer. The SwissTargetPrediction database, Therapeutic Target Databases, and Comparative Toxicogenomics Databases were used for drug target identification. The Gene Expression Omnibus (GEO) database was employed for differential gene screening. The GeneCards, Online Mendelian Inheritance in Man (OMIM) database, and Therapeutic Target Databases (TTD) were utilized to identify DHDK’s breast cancer treatment targets. Nexus genes were identified using Cytoscape software after protein–protein interaction (PPI) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) Resource were conducted to investigateunderlying mechanisms. Target were identified through molecular docking, and the selected signaling pathway was validatedby qPCR. Comprehensive analysis yielded possible targets and mechanisms: DHDK binds to JAK1, inhibiting the phosphorylation of tyrosine residues in downstream target proteins, recruiting and phosphorylating the transcription factor STAT, downregulating STAT1, and further inhibiting the downstream effector BCL2, ultimately inhibits the anti-apoptotic effect of tumor cells. Therefore, DHDK is a highly promising targeted anti-cancer drug. Clinical trial number: not applicable. Graphical abstract