长春中医药大学

Tranexamic acid, an antifibrinolytic drug, is effective for surgical hemostasis and bleeding-related disorders but may induce neurotoxicity, such as epilepsy. The mechanisms driving TXA-induced epilepsy remain poorly understood, as traditional toxicology approaches fall short in capturing its complex toxicity profile. This study employs network toxicology and molecular docking to elucidate the multi-target molecular mechanisms of TXA-induced epilepsy, aiming to enhance its safe clinical application. TXA toxicity was predicted using ADMETlab2.0, PROTOX3.0, toxCSM, and ADMET-AI, with SMILES sequences obtained from PubChem, and a TXA target library was constructed using databases such as ChEMBL. EP-related targets were screened from databases such as GeneCards, and target intersections were analyzed using R software. Networks were constructed using Cytoscape and STRING, with GO and KEGG analyses performed to investigate molecular pathways. Molecular docking was conducted using the CB-Dock2 platform to analyze TXA binding to core targets. TXA poses a neurotoxicity risk, with 51 intersecting targets identified between TXA and EP, among which GABRA1, GABBR2, GABRA5, GABRA2, and GAD1 exhibited the greatest relevance. Analysis revealed that TXA induces EP by disrupting GABA signaling and synaptic function. The PPI network confirmed five core targets, and GO and KEGG analyses elucidated their roles in neural suppression. Molecular docking demonstrated stable binding of TXA to these targets, with Vina scores ranging from − 5.2 to − 6.9. This study elucidates the mechanisms of TXA-induced EP through network toxicology and molecular docking, confirming its interference with GABA-related targets and neural suppression functions. The study overcomes the limitations of traditional toxicology, providing a scientific basis for the safe use of TXA and prevention of neurotoxicity.

Patchoulol is a widely used sesquiterpenoid in perfumes, cosmetics, foods and pharmaceuticals. The plant-dependent production is suffering from limited growing area, long seasonal cycle, etc. Microbial production represents a sustainable alternative as it is featured with mild operating conditions and eco-friendliness. Herein, we engineered the oleaginous Rhodotorula toruloides toward patchoulol production. First, the patchoulol biosynthesis baseline was constructed by employing a chimeric enzyme of the Pogostemon cablin originated patchoulol synthase and the native FPPS. Second, the supply of essential intermediates was streamlined by redeploying the mevalonate (MVA) pathway while the recycling of NADPH was enhanced through over-expressing related enzymes. Third, the patchoulol production was further enhanced to 724.8 mg/L, 6.0 mg/L/h and 36.2 mg/g glucose by down-regulating the squalene biosynthesis and tuning the cultivation condition in shake flask. Finally, the production of patchoulol was increased to 1.31 g/L and 13.8 mg/g glucose in the minimal medium in a 3-L bioreactor. Our study demonstrated the potential of R. toruloides in producing patchoulol, and should shed light on the microbial synthesis of other sesquiterpenes.

Deep eutectic solvents (DESs) are regarded as sustainable and safe solvents due to their high efficiency, stability, recyclability, and alignment with the principles of green analytical chemistry, demonstrating broad application prospects in the green extraction of natural products. This study employed a combination of a DES and ultrasound-assisted extraction (UAE) for the extraction of ginsenosides from ginseng leaves. After screening, choline chloride-urea (1:2) was identified as the optimal DES. The optimal extraction conditions were determined as follows: water content 52.48 %, liquid-to-solid ratio 8.43 mL/g, extraction time 31.13 min, and temperature 51.85 degrees C. Under identical conditions, the extraction efficiency of this DES surpassed that of conventional solvents. In vitro antioxidant assays confirmed that the DES extract possessed concentration-dependent antioxidant activity. Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) analyses revealed that, compared with traditional solvents, the DES caused more significant disruption to the cellular structure of ginseng leaves, thereby enhancing the ginsenoside extraction yield. This study developed a green DES-UAE method for extracting underutilized ginsenosides from ginseng leaves. The proposed technique demonstrated superior extraction efficiency over conventional approaches. Its extraction mechanism was elucidated through SEM and FT-IR analyses, which revealed the associated microstructural changes and intermolecular interactions. This research provides an eco-friendly alternative to toxic solvents while establishing both theoretical and chemical foundations for natural product extraction and the value-added utilization of ginseng leaves.

OBJECTIVE:Cyclophosphamide(CHOP) is a widely used chemotherapeutic agent belonging to the class of alkylating agents. It primarily inhibits the proliferation of tumor cells by interfering with DNA replication and transcription. CHOP has been approved for the treatment of various types of malignant tumors. The aim of this research is to assess adverse events linked to CHOP using real-world data. METHODS:This research collected and analyzed adverse event reports associated with CHOP from the FAERS(US Food and Drug Administration Adverse Event Reporting System) database spanning from the first quarter of 2004 to the third quarter of 2024. This study leveraged the FAERS database, extracting reports submitted exclusively by healthcare professionals where CHOP was designated as the primary suspect (PS). Four risk signal detection methods were employed: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multiitem Gamma Poisson Shrinker (MGPS), to conduct a comprehensive analysis of CHOP-related ADRs. RESULTS:A total of 3,625 adverse event reports with CHOP as the primary suspect drug were obtained. Across 25 system organ classes (SOCs), four positive Preferred Terms(PTs) signals were detected. The most significant signal in SOCs was "blood and lymphatic system disorders" (ROR = 6.64, 95% CI 6.49-6.79), while the most significant PTs signal was "high grade B-cell lymphoma Burkitt-like lymphoma recurrent" (ROR = 613.63, 95% CI 123.85-3040.40). CONCLUSION:This study provides compelling evidence of the presence of CHOP seven unexpected off-label AEs were also observed, such as mucoepidermoid carcinoma, hypotelorism of orbit, breakthrough COVID-19, airway remodeling, meningitis enteroviral, acute graft versus host disease, and gastrosplenic fistula. Additionally, the combination of CHOP and radiotherapy increased the risk of several severe AEs, such as hemorrhagic cystitis. These findings highlight the importance of caution when prescribing CHOP to high-risk individuals with a history of meningitis, cystitis or airway obstruction.

ObjectiveThis study aimed to assess the therapeutic potential of Yangjing Shugan decoction (YJSGD) in D-galactose (D-gal)-induced Premature Ovarian Failure (POF) mice and to elucidate its underlying mechanisms.MethodsThe main metabolites in YJSGD were characterized. A D-gal-induced POF mouse model was established and intervened with YJSGD at doses of 25, 50, and 100 mg/kg. A comprehensive analysis encompassing ovarian function, oxidative stress, inflammation, the Sirt1/Nrf2 pathway, gut microbiota, short-chain fatty acids (SCFAs), and serum metabolomics was conducted.ResultsThe results demonstrated that YJSGD effectively restored estrous cyclicity, normalized serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, and improved ovarian follicular development. YJSGD treatment also enhanced systemic antioxidant capacity and attenuated inflammation. Mechanistically, the therapeutic effects were associated with the upregulation of the Sirt1/Nrf2 signaling pathway in the ovary, as evidenced by increased protein expression of Sirt1, Nrf2, and HO-1, and suppressed Keap1. Furthermore, YJSGD ameliorated gut microbiota dysbiosis, promoted beneficial SCFAs production, and rectified serum metabolic disturbances involved in amino acid, lipid, and energy metabolism.ConclusionThe results indicate that YJSGD is a promising multi-target agent for POF treatment, and its synergistic effects on reproductive, oxidative, and gut microbiota homeostasis provide a solid basis for its clinical application.