Tormentic acid (TA) has demonstrated potential anti-hepatocellular carcinoma (HCC) effects. This study aimed to explore the anti-HCC effect and underlying mechanisms of TA via network pharmacology, molecular docking, molecular dynamics simulation and in vitro experiments. In this study, HCC-related genes were obtained from the GeneCards OMIM, and GEO databases. The targets of TA were collected from Swiss Target Prediction, TargetNet, and the PharmMapper database. A protein-protein interaction network of TA anti-HCC target genes was constructed using the STRING database and visualized by Cytoscape. The potential anti-HCC targets of TA were then identified through GO and KEGG pathway enrichment analyses using the DAVID database. Molecular docking and molecular dynamics simulation were performed to evaluate the binding affinity and structural stability of TA-target complexes. For the in vitro experiments, the CCK-8 assay was employed to assess the effects of TA on HepG2 cell viability. Apoptosis in HepG2 cells was detected via flow cytometry. Western blotting was used to elucidate the underlying molecular mechanisms of TA. Integrating network pharmacology and bioinformatics analyses revealed that the anti-HCC effect of TA was closely associated with apoptosis and the PI3K/AKT/HSP90 pathway. Molecular docking and molecular dynamics simulation demonstrated that TA-target protein complexes maintained marked structural stability and exhibited favorable kinetic properties. In vitro experiments showed that TA significantly inhibited the proliferation of HepG2 cells and induced apoptosis. Western blot results further indicated that TA treatment increased the expression of Bax while decreasing the expression levels of PI3K, AKT, HSP90, and Bcl-2. TA suppressed the proliferation of HepG2 cells and induced apoptosis, possibly by regulating the PI3K/AKT/HSP90 signaling pathway.

Background: Diabetic wounds present a formidable therapeutic challenge due to their persistent nature and high complication rates. In this study, the new silver alginate dressing was evaluated to determine whether it improves wound healing in type II diabetic rats by comparison with the commercially available silver alginate dressing Biatain (R) in vivo and in vitro. This study demonstrates that the novel dressing may provide a viable alternative approach to the current management of diabetic wounds. Methods: The in vitro part involved the evaluation of its water vapor transmission ability, water-uptake ability, and antibacterial ability. Then, Goto-Kakizaki diabetic rats were selected for in vivo experiments to establish the diabetic infection wound model. The healing rate of wounds and the bacterial count on wounds and wound dressings were studied. Detection of fibrinogen (FIB), procalcitonin (PCT), and high-sensitivity C-reactive protein (hs-CRP) by ELISA, Platelet endothelial cell adhesion molecule-1 (CD31) and Alpha-smooth muscle actin (alpha-SMA) protein expression by histological staining and determination of silver by microwave digestioninductively coupled plasma mass spectrometry. Results: In comparison with the commercially available Biatain (R), The silver alginate ion dressing has about twice the water absorption capacity of Biatain (R) (P < 0.01) and On day 14, the wound healing rate in the sample group demonstrated a significant increase of 15.6 % relative to the model group, with wounds approaching nearcomplete closure. Conclusion: The newly developed silver-ion alginate dressing enhanced wound closure, reduced infection and healing time, and lowered dressing change frequency, demonstrating comparable efficacy to the commercial reference product (Biatain (R)) as a practical alternative for diabetic wound care.

Metabolic associated fatty liver disease (MAFLD) has high morbidity and tragically lacks effective therapeutic remedies. Tormentic acid (TA) has been shown to have therapeutic effect on liver fibrosis, but its role in MAFLD remains unknown. Therefore, we employed multi-omics analyses to investigate the effects of TA on MAFLD. In this study, male C57BL/6J mice were fed a methionine- and choline- deficiency (MCD) diet to induce MAFLD and subsequently treated with TA for 4 weeks. The therapeutic efficacy of TA was then evaluated through histopathological examination and biochemical analysis. In addition, multi-omics analyses including transcriptomics, proteomics and metabolomics were conducted to identify potential pathways associated with TA treatment. Finally, key genes and proteins in the identified pathways were validated by qPCR and Western blot. Our results showed that TA significantly alleviated liver damage and excessive lipid accumulation. Importantly, our integrative multi-omics analyses identified tryptophan metabolism and glycolysis as pivotal pathways associated with TA treatment in our fatty liver mouse model. Subsequent validation demonstrated the TA-induced upregulation of IDO2 and HAAO, suggesting engagement of tryptophan metabolism. Concurrently, TA treatment downregulated HK2, PFKP, and PKM2, indicative of altered rate-limiting glycolytic enzyme expression. These findings suggest that TA alleviates MCD diet-induced MAFLD, potentially involving modulation of enzyme expression in tryptophan metabolism and glycolysis.

Dietary supplements, with nutritional and health benefits, are widely used worldwide. Ensuring the quality of dietary supplements has become particularly important as demand increases. Current traditional methods of quality assessment tend to concentrate solely on the content of certain active ingredients; nevertheless, the bioactivity of a product, which serves as a more direct indicator of its quality, is frequently overlooked. Thus, a comprehensive "Content-Extractives-Activity" quality evaluation system was developed for dietary supplements using a portable near-infrared spectrometer combined with entropy weight method in this study. Taking Eucommia ulmoides granules as the object of study, near-infrared spectroscopy (NIRS) was used to predict the pinoresinol diglucoside content, ethanol-soluble extractives content, bioactivity indicators related to antioxidant damage such as cell viability value and intracellular malondialdehyde content, as well as comprehensive index. The best models all obtained satisfactory prediction results with correlation coefficient of prediction in the range of 0.89-0.97 and residual predictive deviation in the range of 1.81-4.19, which demonstrated the feasibility of the method for the rapid evaluation of the integrated quality of dietary supplements by NIRS.

Background and Aims: Voriconazole (VRC), a widely used antifungal drug, often causes hepatotoxicity, which presents a significant clinical challenge. Previous studies demonstrated that Astragalus polysaccharide (APS) can regulate VRC metabolism, thereby potentially mitigating its hepatotoxic effects. In this study, we aimed to explore the mechanism by which APS regulates VRC metabolism. Methods: First, we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale. Second, we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism. Various in vitro and in vivo assays, including cytokine profiling, immunohistochemistry, quantitative polymerase chain reaction, metabolite analysis, and drug concentration measurements, were performed using a lipopolysaccharideinduced rat inflammation model. Finally, experiments such as intestinal biodiversity analysis, intestinal clearance as sessments, and Bifidobacterium bifidum replenishment were performed to examine the ability of B. bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut-liver axis. Results: The results indicated that APS does not have a direct effect on hepatocytes. However, the assessment of gut microbiota function revealed that APS significantly increases the abundance of B. bifidum, which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism. The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-KB signaling pathway. Conclusions: The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage, highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

BACKGROUND:Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation, and purification. It is associated with immunomodulatory effects, but the underlying mechanisms are not known. This study therefore combined proton nuclear magnetic resonance (1H-NMR) urinary metabolomics and 16S rRNA gene sequencing of the gut microbiome to determine the immunoprotective mechanisms of OP in rats subjected to cyclophosphamide-induced immunosuppression. RESULTS:Oyster polypeptide restored the body weight and the structure of spleen and thymus in rats with cyclophosphamide-induced immunosuppression. It upregulated the levels of white blood cells (WBCs), hemoglobin (HGB), platelets (PLT), red blood cells (RBCs), immunoglobulin G (IgG), immunoglobulin M (IgM), cytokines such as interleukin‑6 (IL-6) and tumor necrosis factor-α (TNF-α), and increased the numbers of CD3+ and CD4+ T cells in the immunosuppressed rats. The 1H-NMR metabolomics results showed that OP significantly reversed the levels of ten metabolites in urine, including 2-oxoglutarate, citrate, dimethylamine, taurine, N-phenylacetylglycine, alanine, betaine, creatinine, uracil, and benzoate. The 16S rRNA gene sequencing results showed that OP restored the gut microbiome homeostasis by increasing the abundance of beneficial bacteria and reducing the abundance of pathogenic bacteria. Finally, a combination of metabolomics and microbiomics found that the metabolism of taurine and hypotaurine, and the metabolism of alanine, aspartate, and glutamate were disturbed, but these metabolic pathways were restored by OP. CONCLUSION:This study demonstrated that OP had immunoprotective effects in rats with cyclophosphamide-induced immunosuppression by restoring key metabolic pathways and the gut microbiome homeostasis. Our findings provide a framework for further research into the immunoregulatory mechanisms of OP and its potential use in drugs and nutritional supplements. © 2024 Society of Chemical Industry.

Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation, and purification. It is associated with immunomodulatory effects, but the underlying mechanisms are not known. This study therefore combined proton nuclear magnetic resonance (

This study investigates the role of the deubiquitinating enzyme USP14 in alleviating doxorubicin (DOX)-induced cardiotoxicity (DIC), particularly concerning its mechanism of regulating pyroptosis through the stabilization of the mitochondrial protein SIRT3. Using in vivo and in vitro models, the research demonstrated that USP14 overexpression protects against DOX-induced cardiac damage by modulating pyroptosis. Silencing SIRT3 via siRNA revealed that SIRT3 is a key intermediary molecule in USP14-mediated regulation of pyroptosis. Notably, DOX exposure resulted in decreased USP14 expression, while its overexpression preserved mitochondrial function and reduced oxidative stress by stabilizing SIRT3. Immunoprecipitation confirmed that USP14 stabilizes SIRT3 through deubiquitination. These findings position USP14 as a promising therapeutic target for mitigating DOX-induced cardiotoxicity by stabilizing SIRT3 and maintaining mitochondrial integrity, suggesting potential novel strategies for cardio-protection in chemotherapy.

Spices have long been popular worldwide. Besides serving as aromatic and flavorful food and cooking ingredients, many spices exhibit notable bioactivity. Quality evaluation methods are essential for ensuring the quality and flavor of spices. However, existing methods typically focus on the content of particular components or certain aspects of bioactivity. For a systematic evaluation of spice quality, we herein propose a comprehensive "quality-quantity-activity" approach based on portable near-infrared spectrometer and membership function analysis. Cinnamomum cassia was used as a representative example to illustrate this approach. Near-infrared spectroscopy and chemometric methods were combined to predict the geographical origin, cinnamaldehyde content, ash content, antioxidant activity, and integrated membership function value. All the optimal prediction models displayed good predictive ability (correlation coefficient of prediction > 0.9, residual predictive deviation > 2.1). The proposed approach can provide a valuable reference for the rapid and comprehensive quality evaluation of spices.

A novel multi-functional micelle delivery system was developed for enhancing the oral absorption of paclitaxel (PTX). The delivery carriers were constructed by modifying chitosan-stearic acid (CS-SA) micelles with L-carnitine (LC) and co-encapsulating quercetin (Que), and the PTX-loaded micelles were prepared by film-sonication dispersing technique. The as-prepared micelles showed homogeneous spherical shapes with a small particle size of 148.3 ± 1.7 nm, high drug loading of 7.05

Ovarian cancer is a significant challenge in women's health due to the lack of effective screening and diagnostic methods, often leading to late detection and the highest mortality rate among all gynecologic tumors worldwide. Recent research has shown that ovarian cancer has an "iron addiction" phenotype which makes it vulnerable to ferroptosis inducers. We tested the combination of NRF2-targeted inhibitors with GPX4-targeted inhibitors in ovarian cancer through in vitro and in vivo experiment. The data showed that combination treatment effectively suppressed adherent cell growth, inhibited suspended cell spheroid formation, and restrained the ability of spheroid formation in 3D-culture. Mechanistically, the combination induced accumulation of ROS, 4-HNE, as well as activation of caspase-3 which indicates that this combination simultaneously increases cell ferroptosis and apoptosis. Notably, inhibition of GPX4 or NRF2 can suppress ovarian cancer spreading and growth in the peritoneal cavity of mice, while the combination of NRF2 inhibitor ML385 with GPX4 inhibitors showed a significant synergistic effect compared to individual drug treatment in a syngeneic mouse ovarian cancer model. Overall, these findings suggest that combining NRF2 inhibitors with GPX4 inhibitors results in a synergy suppression of ovarian cancer in vitro and in vivo, and maybe a promising therapeutic strategy for the treatment of ovarian cancer.

BACKGROUND:Effective drugs for the treatment of hepatic fibrosis have not yet been identified. Isovitexin (IVT) is a promising hepatoprotective agent owing to its efficacy against acute liver injury. However, the role of IVT in liver fibrosis has not been reported.PURPOSE:To explore the effect of IVT on liver fibrosis both in vitro and in vivo.STUDY DESIGN AND METHODS:A mouse model of liver fibrosis induced by carbon tetrachloride (CCl4) and two types of hepatic stellate cell models induced by platelet-derived growth factor-BB (PDGF-BB) were established to evaluate the effect of IVT on hepatic fibrosis. Transcriptomics and metabolomics were used to predict the underlying targets of IVT and were validated by a combination of in vitro and in vivo experiments. Exploration of miRNA and N6-methyladenosine (m6A) modifications was also carried out to detect the key upstream targets of the above targets.RESULTS:IVT reduced collagen deposition and hepatic stellate cell activation to alleviate liver fibrosis. The transcriptomics and metabolomics analyses showed that phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling and the glutathione (GSH) metabolic pathway may be the main regulatory processes of IVT in hepatic fibrosis. Both the in vitro and in vivo experiments confirmed the inhibitory effect of IVT on the PTEN-PI3K-Akt-mTOR axis and activation of the GSH metabolic pathway. A miR-21 mimic inhibited the effects of IVT on these two pathways, suggesting that miR-21 is the hub for IVT regulation of PI3K-Akt signaling and the GSH metabolic pathway. IVT also increased pri-miR-21 level and reduced the m6A enrichment of pri-miR-21, demonstrating that IVT may regulate pri-miR-21 through m6A modification, thereby affecting the maturation of miR-21.CONCLUSION:This study is the first to propose a protective effect of IVT against liver fibrosis. The mechanism of IVT against hepatic fibrosis is based on the regulation of miR-21, targeting PTEN-Akt signaling and the GSH metabolic pathway, which is also a novel discovery.

目的 应用代谢组学与体内实验验证并结合分子对接技术的方法,探讨异牡荆素(isovitexin,IVT)对酒精性脂肪肝(alcoholic fatty liver disease,AFLD)的影响及其作用机制.方法 将8周龄雄性C57BL/6J小鼠随机分为对照组、模型组及IVT组,每组6只.对照组用酒精液体饲料对照饲料喂养,模型组和IVT组用酒精液体饲料模型饲料喂养,IVT组每日灌胃IVT(100 mg·kg-1).30 d后,检测与AFLD相关的关键指标,包括血生化指标、氧化应激指标和肝组织病理变化等,同时采用UPLC-Q-TOF/MS技术和分子对接技术,以探讨IVT对AFLD的影响及其作用机制.结果 IVT可以明显降低AFLD小鼠血生化异常并且改善相关症状.通过代谢组学分析确定了 34个生物标志物及5条代谢通路.通过分子对接进一步分析表明,IVT可能通过调控甘油磷脂代谢而起到治疗AFLD的作用.结论 IVT能有效改善AFLD,对其具有一定的保护作用,其机制可能与激活甘油磷脂代谢通路有关.

This study examined the effect of Asiatic acid from Potentilla chinensis (AAPC) on chronic ethanol-induced hepatic injury. Rats underwent intragastric administration of ethanol (5.0–9.0 g/kg) once a day for 12 weeks. A subset of rats were also intragastrically treated with AAPC (2, 4 or 8 mg/kg) once a day. In the end, AAPC treatment significantly protected against ethanol-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases levels and the attenuation of histopathological changes in rats. Additionally, AAPC significantly decreased blood alcohol and acetaldehyde concentrations by enhancing alcohol dehydrogenase and aldehyde dehydrogenase activities. Mechanistically, studies showed that AAPC remarkably alleviated the formations of malondialdehyde and myeloperoxidase, restored impaired antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase, and inhibited cytochrome P450 (CYP)2E1 activity. Moreover, the over-expression of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the elevated plasma endotoxin level and the up-regulated Toll-like receptor 4 (TLR4), CD14 and myeloid differentiation factor 88 (MyD88) as well as nuclear factor-κB were also suppressed by AAPC in ethanol-intoxicated rats. In conclusion, the protective effect of AAPC on ethanol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress and inhibit Kupffer cell activation by decreasing the level of plasma endotoxin and the expression of TLR4, CD14 and MyD88.

Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4‑dione (DMDD, i.e., Averrhoa carambola extractive) liposomes (HA/TN-DLP) were conducted and assessed. HA/TN-DLP showed controllable drug loading (up to 83%) with high stability. In vitro and in vivo studies showed good cell uptake behavior and high inhibition rate of breast cancer compared to free DMDD. HA/TN-DLP might be the suitable for DMDD due to its better advantages in delivery, penetrability, and targeting-tumor capability. For in vivo mouse model tests, HA/TN-DLP effectively inhibited tumor growth compared to free DMDD. Further analyses indicated that HA/TN-DLP inhibited the glycerophospholipid metabolism pathway by reducing the biosynthesis of phosphatidylcholine and 1-acyl-sn‑glycero-3-phosphocholine through regulating the expressions of CEPT1 and LYPLA1, and inhibited tumor cell growth by regulating the PI3K/Akt and NF-κB signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent.

Oysters are extensively cultivated worldwide. However, significant variations in chemical composition, quality, and price exist between oysters from different geographical origins. This study employed portable near-infrared spectroscopy in conjunction with chemometric analysis to determine the geographical origin and glycogen content of oysters. Pretreatment methods (multiplicative scattering correction, first derivative, and second derivative) were used to preprocess the raw spectra. Partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA), and support vector machine (SVM) were then adopted to establish the qualitative models. Partial least squares regression (PLSR) and support vector machine regression (SVMR) were compared for predicting the glycogen content. The results revealed that the PLS-DA, OPLS-DA, and SVM models classified the geographical origin of oysters with 100% accuracy. For quantitative analysis, the regression equations displayed high predictive ability. The SVMR model was superior to the PLSR model for glycogen content prediction, with a coefficient of determination of prediction (R2P) of 0.9253 and a residual prediction deviation (RPD) of 3.62. Therefore, the proposed approach is suitable for the accurate and environmentally friendly determination of the geographical origin and glycogen content of oysters, thus representing an attractive alternative method for the traceability supervision and quantitative analysis of seafood products.