Cholic Acid Research Articles

Pretreatment serum bile acid composition and predictability of subsequent response to odevixibat in patients with bile salt export pump (BSEP) deficiency.

Bile salt export pump (BSEP) deficiency, or progressive familial intrahepatic cholestasis type 2, is a genetic liver disease characterized by defective biliary bile acid secretion. Odevixibat, an ileal bile acid transporter inhibitor (IBATi), impairs intestinal reabsorption of conjugated bile acids, reducing serum bile acid (sBA) concentration in some patients with BSEP deficiency. We evaluated association of pretreatment sBA levels and composition, and subsequent response to odevixibat in patients with BSEP deficiency to improve our understanding of the mechanism. In this blinded post hoc analysis, pretreatment sBAs from 41 odevixibat-treated patients with BSEP deficiency who participated in PEDFIC were analyzed using liquid chromatography-tandem mass spectrometry. Patients were divided into sBA responders (Rs) and non-responders (NRs). Association of pretreatment individual sBAs with subsequent response was evaluated and receiver operating characteristic (ROC) curves were constructed to identify discriminating cutoff values. Rs had higher pretreatment percentages of unconjugated cholic acid (CA; area under the ROC curve [AUC]: 0.70 [95% CI: 0.52-0.87; P=0.03]), unconjugated chenodeoxycholic acid (CDCA; AUC: 0.73 [0.56-0.90]; P=0.01), and concentration of CA + CDCA (AUC: 0.76 [0.61-0.92]; P=0.001). When ≥1 of 3 cutoffs were reached, 36/41 (87.8%) patients with BSEP deficiency were correctly classified as subsequent Rs (17/19; sensitivity: 89.5%) or NRs (19/22; specificity: 86.4%). Higher pretreatment serum levels of unconjugated CA and CDCA are associated with subsequent response to odevixibat in patients with BSEP deficiency. Response to odevixibat may be related to residual biliary bile acid secretion capacity in patients with BSEP deficiency.

DMF, an activator of Nrf2, could mitigate cholic-acid-induced liver damage in high-fat diet

Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread chronic liver condition associated with liver inflammation, fibrosis, and various metabolic disorders. Although cholic acid (CA), a primary bile acid (BA), is known to reduce steatosis when added to a high-fat diet, it may exacerbate hepatocellular injury by promoting oxidative stress and inflammation. Therefore, regulating BA-induced liver toxicity is crucial. Dimethyl fumarate (DMF) is an FDA-approved drug known to activate the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), a transcription factor that induces cytoprotective genes involved in cellular stress. The present study aimed to investigate whether DMF supplementation could attenuate CA-induced liver injury in high-fat diet-fed mice. Methods: To induce liver injury, high-fat diet with and without CA were compared for liver damage and liver fat gain. Following the establishment of the toxic but antisteatotic effect of CA, C57BL/6j mice were fed a high-fat diet supplemented with 0.5% CA (HFDCA) with or without DMF (0.3 mg/mL or 0.6 mg/mL), which was administered via drinking water for 7 weeks. Results: CA was found to be an accelerator of high-fat diet to induce liver damage, but prevented liver fat accumulation. HFDCA mice showed signs of liver damage, including elevated liver enzymes and liver enlargement. However, DMF treatment activated the Nrf2 pathway and partially mitigated the hepatotoxic effect of CA/high-fat diet, although some doses exhibited pro-oxidant effects. Conclusions: The findings suggest that DMF, as an activator of Nrf2, has potential as a therapeutic agent for liver diseases related to high-fat diets and BA-induced injury, though careful dosage management is crucial to maximize its benefits and mitigate BA toxicity.

The effect of high-fat diet on serum metabolites in rats with heart failure: a non-targeted metabolomics approach

ObjectiveThe aim of this study was to explore the potential mechanism underlying the effects of a high-fat diet (HFD) on heart failure (HF), utilizing the integration of serum metabolomics.MethodA Sprague-Dawley rat model for HF induced by pressure overload via abdominal aortic contraction was established. A metabolomics approach based on liquid chromatography–mass spectrometry (LC-MS) was performed to analyze the serum biomarkers from control + chew diet (CCD) group, model + chew diet (MCD) group, and model + HFD(MHFD) group. Principal component analysis (PCA) and orthogonal projection to latent structures-discriminan* t analysis (OPLS-DA) were employed to identify differences in metabolic profiles among the three groups.ResultsThere were significant differences in OPLS-DA scores between the CCD vs. MCD groups and MCD vs. MHFD groups. In comparison to the CCD group, the MCD group demonstrated significant alterations in multiple metabolites, such as Lyso PE (20:4 (5Z, 8Z, 11Z, 14Z))/0:0, Lyso PE (16:0/0:0), L-glutamine, N2-γ-glutamine, butyrylcarnitine, PHOOA-P, and so on. In addition, the levels of metabolites such as cholic acid, (9 S, 10E, 12 S, 13 S) −9,12,13-trihydroxyoctadec-10-enoylcarnitine, and 8-deoxy19,20-epoxycytidine C in the MHFD group were significantly higher than those in the MCD group. 17 metabolites showed a significant restorative trend from HF to a normal condition, implying their significant relationship with the positive effects of HFD on HF. These metabolites can be considered potential biomarkers for HFD treatment.ConclusionsThese results can be used to better understand the effects of HFD on HF rats, which will provide new ideas for treatment.

Integration bile acid metabolomics and gut microbiome to study the anti-liver fibrosis effects of total alkaloids of Corydalis saxicola Bunting

BackgroundBile acids and gut microbiota participate in the pathogenesis of liver fibrosis (LF). The total alkaloids of Corydalis saxicola Bunting (TACS) is a traditional Chinese medicine extract that has been used to treat LF, but the underlying mechanisms are not clear. This study performed integrated metabolomics and gut microbiome analysis to study the anti-LF mechanism of TACS using a rat model.MethodsUltra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to identify the chemical compounds in TACS. Biochemical and histopathological analysis were performed to determine the efficacy of TACS. Bile acid-targeted metabolomics was used to assess changes in the bile acid (BA) profiles in TACS-treated LF rats. 16S rRNA gene sequencing and metagenomics were used to assess changes in the gut microbiota of the TACS-treated LF rats. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) were used to determine the relationship between the gut microbiota and the anti-LF effects of TACS. Metagenomics was used to identify significantly enriched gut microbiota after TACS treatment and its correlation with the anti-LF effects was verified by in vivo experiments.ResultsTACS treatment significantly reduced the levels of serum liver enzymes, fibrosis and pro-inflammatory cytokines in the liver. TACS significantly increased the levels of chenodeoxycholic acid (CDCA) and taurochenodeoxycholic acid (TCDCA) in the cecum and decreased the levels of cholic acid (CA) and deoxycholic acid (DCA) in the liver of the LF rats. TACS significantly increased the abundances of Lactobacillus and Akkermansia in the LF rats. Antibiotic cocktail treatment and FMT have shown that the effect of TACS cure liver fibrosis depends on the gut microbiota. The abundance of Lactobacillus reuteri was significantly increased by TACS. Administration of Lactobacillus reuteri via gavage ameliorated LF.ConclusionsTACS exerted anti-LF effects in rats by modulating bile acid metabolism and gut microbiome.Graphical

A combination of dietary cholesterol and cholic acid induces hepatic expression of proinflammatory genes accompanied by changes in sterol metabolism and redox status.

A combination of dietary cholesterol and cholic acid induces hepatic expression of proinflammatory genes accompanied by changes in sterol metabolism and redox status.

Effectiveness and Safety of Personalized Cholic Acid Treatment in Patients With Bile Acid Synthesis Defects.

Bile acid synthesis defects (BASDs) comprise a group of rare, often severe, metabolic disorders. Bile acid replacement therapy decreases toxic bile acid intermediates production and improves biochemical profiles, potentially delaying or stabilizing disease progression. An open label, non-randomized trial with cholic acid (CA) supplementation included six patients with α-methylacyl-CoA racemase (AMACR) deficiency and one patient with 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. Patients received up to 20 mg/kg/day CA for 3.5 years, adjusted for biochemical response, side effects, and clinical evaluation. Bile acid metabolites, liver enzymes, liver stiffness, and neurological symptoms were evaluated at baseline and during follow-up. CA was well tolerated in children (n = 3), allowing for higher doses. Adults (n = 4) experienced more side effects, primarily diarrhea and other gastrointestinal symptoms. Children's transaminase levels normalized during treatment, while adults' levels remained normal throughout. Elevated C27-bile acid intermediates, C29-dicarboxylic acid, and pristanic acid were observed in all AMACR patients. C27-bile acids and C29-dicarboxylic acid decreased with treatment, while pristanic acid fluctuated and remained elevated. No clinically relevant changes were observed in liver elasticity, fat-soluble vitamin levels, neurological assessment, or growth (in children). One adult developed hepatocellular carcinoma during treatment. CA treatment is generally safe, with acceptable tolerance and a marked biochemical response observed in children, although biomarker levels remained markedly elevated. In adults, however, the balance shifts negatively, with side effects outweighing the (biochemical) benefits. A longer study is necessary to evaluate the impact of CA treatment on the clinical relevance of the observed biochemical response.

Methylcobalamin-loaded ultra-flexible liposomes: a nanocarrier approach for modulating melanocyte homeostasis and addressing pigmentation imbalances.

Methylcobalamin-loaded ultra-flexible liposomes: a nanocarrier approach for modulating melanocyte homeostasis and addressing pigmentation imbalances.

Integrated transcriptome and metabolome analyses unraveled critical roles of small intestine during the weaning period of Vespertilio sinensis

BackgroundWeaning represents a critical period during which mammals adapt to solid food and develop their immune systems. The intestine, as the primary digestive and immune organ, is central to successful weaning. Bats are the only flying mammals and undergo ontogenetic shifts in flight and diet in response to substantial energy and immune demands. However, the transcriptomic and metabolomic changes in bat intestines during the weaning transition remain unexplored.ResultsIn this study, 24 small intestinal tissue samples were collected from Vespertilio sinensis across four developmental stages, ranging from new-born to weaned. The analysis identified 7,545 significantly differentially expressed genes (DEGs) and 1,006 metabolites, which were enriched in metabolomic pathways related to nutrient digestion, signal transduction, and immunity. Several highly expressed genes were identified in carbohydrate digestion (TREH, MGAM, and SI), lipid metabolism (CD36, ABCG5, ABCG8), protein digestion (CPA1 and CPB1), taste transduction (SCNN1B and SCNN1G), and immune response (FUT2 and SUCNR1). Additionally, major metabolites, including cholic acid, acetylcholine, serotonin, and uric acid, were implicated in dietary shifts in young V. sinensis during weaning.ConclusionsThis is the first study to investigate transcriptomic and metabolomic changes in the small intestine of insectivorous bats during weaning. These findings enhance our understanding of the small intestine’s role in ontogenetic dietary shifts and provide novel insights into the molecular mechanisms underlying weaning in wild mammals.

An NTCP-mediated liver-targeting chimeras (NTLiverTac) design strategy and its application to hepatoblastoma models.

An NTCP-mediated liver-targeting chimeras (NTLiverTac) design strategy and its application to hepatoblastoma models.

A novel molecularly imprinted technology-based approach for cholic acid detection in complex matrices

A novel molecularly imprinted technology-based approach for cholic acid detection in complex matrices

Gut-to-Bile transfer of microbially amidated minor bile acids in patients with hepatopancreatobiliary disorders.

During bile acid (BA) intestinal transit, microbially amidated BAs (MABAs) are produced. This study investigated their cholephilic behavior and their presence in the bile of patients with hepatopancreatobiliary diseases. Bile samples were collected during surgical or endoscopic procedures and analyzed using HPLC-MS/MS, with cholic acid (CA) and chenodeoxycholic acid (CDCA) chemically amidated with leucine (Leu), phenylalanine (Phe), or tyrosine (Tyr) as standards. Gut-to-bile transfer was investigated in cellular and animal models. MABAs (Leu>Phe>Tyr) were detected (<1 µM) in the bile of ≈50% of patients with hepatopancreatobiliary disorders. Their levels were positively correlated with total BA concentrations and inversely correlated with the proportion of major conjugated BAs, but not with age, fat-soluble vitamin levels, or disease outcomes. Oral gavage of D- and L-enantiomers of Tyr-CA in mice resulted in intestinal hydrolysis and limited access of L-Tyr-CA to the enterohepatic circulation. In rats, the intravenous injection of glycocholic acid (GCA) and MABAs resulted in similarly rapid biliary outputs. The time course of biliary secretion after infusing MABAs and GCA into the microbiota-free rat ileum in situ was also similar. Docking studies predicted the interaction of BA transporters and MABAs with binding energies comparable to those of taurocholic acid (TCA) and GCA. In cells expressing BA transporters, MABA uptake was efficient (NTCP>ASBT>OATP1B3) and inhibitable by TCA. Like major conjugated BAs, MABAs are transferred from the gut, where they are produced, to the bile of patients with hepatopancreatobiliary diseases, suggesting gut dysbiosis that favors species generating these compounds.

Physicochemical insights into thymidine-bile salt interactions: a comprehensive study on micellization and binding properties

This study investigates the interaction of thymidine with bile salts, sodium deoxycholate (NaDC), and sodium cholate (NaC), using a range of physicochemical techniques. The critical micelle concentration (CMC) was determined through UV–Vis spectroscopy, conductivity, surface tension, and viscosity measurements. NaDC exhibited a lower CMC than NaC, attributed to its greater hydrophobicity. The presence of thymidine reduced the CMC values for both bile salts. Thermodynamic parameters of micellization ( ∆ G m ο , α, β) and interfacial properties (ᴦ max, A min, π CMC, ∆ G ads ο ) were evaluated using conductivity and surface tension measurements, while the free energy of the surface at equilibrium (G min) was also determined. UV–Vis spectroscopy was employed to calculate the partition coefficient (K x), free energy of partition (ΔG x), binding constant (K b), and free energy of binding (ΔG b) using the Benesi–Hildebrand and pseudo-phase models. Additionally, physicochemical properties, such as the aggregation number (N agg), micelle volume were analyzed. These findings provide valuable insights into the interaction mechanisms between thymidine and bile salts, highlighting their potential in drug delivery applications.

Compression Isotherms of Monomolecular Films of 7β-alkyl Cholic Acid Derivatives on an Acidic Aqueous Substrate and Their Interactions with Lecithin Reveal the Conformations of the Alkyl Chain and Steroid Skeleton.

This study analyzed the compression isotherms of 7β-alkyl cholic acid derivatives and compared them to those of cholic and deoxycholic acids to elucidate their orientation and molecular interactions (acidic aqueous substrate-pH 2; NaCl concentration-3 M; temperature-T = 298.15 K). It was found that the compression isotherm of the 7β-octyl derivative of cholic acid in the monomolecular layer is most similar to the compression isotherm of deoxycholic acid. In 7β-alkyl derivatives of cholic acid, the hydrophobic interaction energy in their aggregates from a monomolecular film increased with the length of the alkyl chain. However, this energy did not increase linearly with C atoms, suggesting the existence of a conformational equilibrium. In binary mixtures of the tested bile acids and lecithin, only the 7β-octyl derivatives of cholic acid and deoxycholic acid had orientations in which the steroid skeleton had a "vertical" position, i.e., only the C3 OH group was immersed in the aqueous substrate, which resulted in the maximum hydrophobic interaction with lecithin. In 7β-octyl derivatives, part of the octyl chain probably also participated in the interaction with lecithin. In 7β-propyl and 7β-butyl derivatives, C7 alkyl groups sterically shielded the C7 α-axial OH group. However, in the 7β-ethyl derivative the C7 OH group was not additionally sterically shielded, so this derivative, similarly to cholic acid, partially dissolved in the aqueous substrate after the collapse point.

Pulmonary microbiome and metabolome signatures associate with chemotherapy response in lung cancer patients

BackgroundLung cancer is a leading cause of cancer-related mortality worldwide, with chemotherapy response varying significantly among patients. Emerging evidence suggests that the pulmonary microbiota and metabolome may influence treatment outcomes, but their roles remain unclear.MethodsThis study enrolled 25 lung cancer patients undergoing chemotherapy, categorized into chemotherapy-sensitive (n = 15) and chemotherapy-insensitive (n = 10) groups. Bronchoalveolar lavage fluid (BALF) was collected for 16S rDNA sequencing and untargeted metabolomics (LC-MS). Serum bile acids were also analyzed.ResultsThe study identified 92 significantly altered metabolites in BALF between the two groups. Trans-urocanate showed the highest increase, while phenylalanylphenylalanine exhibited the greatest decrease in sensitive patients. Key metabolic pathways, including ABC transporters, glutathione metabolism, and bile acid biosynthesis, were enriched. Microbiome analysis revealed differential abundances of specific bacterial genera, particularly increased Caulobacter and decreased Acinetobacter in sensitive patients. Notably, serum levels of four bile acids (chenodeoxycholic acid, cholic acid, deoxycholic acid, and ursodeoxycholic acid) were significantly elevated in chemotherapy-sensitive patients, demonstrating good predictive value with AUCs ranging from 0.633 to 0.830.ConclusionThe study highlights distinct microbial and metabolic signatures associated with chemotherapy response, suggesting potential biomarkers for personalized therapy.

Association of plasma n-3 polyunsaturated fatty acid with gut mycobiome and implications for glucose homeostasis.

The pivotal role of gut fungi (i.e., mycobiome) in host health is increasingly recognized. Diet is a critical determinant factor for both gut fungi and host metabolic health. This study aimed to investigate the associations of plasma n-3 polyunsaturated fatty acids (PUFAs), an important dietary lipid component, with gut mycobiome and explore the relationship of n-3 PUFA-related gut fungi with type 2 diabetes (T2D) and glycemic phenotypes. Here, we identified four fungal genera that were inversely associated with plasma total n-3 PUFA in the discovery cohort. Among these, Debaryomyces, Kodamaea, and Wickerhamomyces were consistently associated with total n-3 PUFA in the metaanalysis of 4 human cohorts (FDR-meta<0.1). We also found that Wickerhamomyces was positively associated with host fasting blood glucose and glycated hemoglobin (FDR<0.05). Moreover, we observed an interaction between n-3 PUFA and Kodamaea on T2D (P-interaction=0.02), which was confirmed in the mice study. In human and mice studies, the inverse associations between n-3 PUFA and glycemic phenotypes were only observed in the Kodamaea-free population. Additionally, the enrichment of specific primary bile acids, namely cholic acid and its conjugated forms, was associated with Kodamaea colonization. Our results indicate that n-3 PUFA is associated with specific gut fungal genera, which may, in turn, affect host glucose homeostasis.

Critical Role of Cholic Acid in the Development of iHFC Diet-induced MASH in TSNO Mice.

A high-fat/cholesterol/cholate-based (iHFC) diet induces pathological changes in Tsumura-Suzuki non-obese (TSNO) mice, resembling human metabolic dysfunction associated steatohepatitis (MASH), along with advanced liver fibrosis. In this study, we investigated the role of cholic acid (CA) in the development of iHFC diet-induced MASH development. In mice receiving an iHFC diet without CA (CA(-) iHFC diet), both lobular inflammation and fibrosis progression in the liver were attenuated compared to those on the standard iHFC diet. Notably, hepatocyte ballooning was significantly improved in the CA(-) iHFC diet group. The expression levels of genes associated with inflammation and fibrosis were lower in the livers of CA(-) iHFC diet-fed mice compared to those fed the iHFC diet. Furthermore, there were no significant changes in the proportion and number of monocyte-derived macrophages in the livers of CA(-) iHFC diet-fed mice relative to those in the ND (normal diet)-fed group. The co-localization of CD11c+ macrophages with collagen fibers in the livers of CA(-) iHFC diet-fed mice did not significantly differ from that of the ND-fed group. Moreover, the CA(-) iHFC-fed mice exhibited a distinct microbial composition relative to both ND- and iHFC-fed mice. Finally, the increase in deoxycholic acid in fecal samples and the reduced hepatic expression of Cyp27a1 and Cyp7a1 induced by the iHFC diet were less in the CA(-) iHFC-fed group. These results suggest that CA modulates iHFC diet-induced MASH development by influencing the accumulation of monocyte-derived macrophages in the liver and shaping the gut microbiota composition and bile acid profile.

Copolymerization of Hydrophilic and Hydrophobic Monomers in Water Assisted by Cyclodextrins

ABSTRACTTo facilitate the copolymerization of both hydrophobic and hydrophilic monomers in aqueous media, cyclodextrins (CDs) are introduced to form inclusion complexes with the hydrophobic monomers. As a proof of concept, β‐CD is used to solubilize a hydrophobic acrylamide derivative of cholic acid (CAAM) in water, enabling its copolymerization with acrylamide to occur in a common and benign solvent, that is, water. An excess of β‐CD is needed to effectively solubilize the cholic acid monomer CAAM in water, leading to the synthesis of a thermoresponsive polymer. The CAAM content in the final copolymer is ca. 2.5 mol%, in contrast to the 5 mol% contained in the feed. Notably, this investigation underscores the usefulness of inclusion complexation in the copolymerization process. The same monomer formed a looser inclusion complex with γ‐CD, which has a larger cavity than β‐CD, and produced a copolymer with only 0.74 mol% of CAAM, indicating the importance of the stability of complexation.

Investigating the binding products between human apolipoproteins and oxidized 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine by micellar electrokinetic chromatography.

Investigating the binding products between human apolipoproteins and oxidized 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine by micellar electrokinetic chromatography.

Qishiwei Zhenzhu Pills Protect Against Cerebral Ischemia via the P53/Cytochrome C/Apoptotic Protease Activating Factor 1-Mediated Mitochondrial Apoptosis Pathway.

Qishiwei Zhenzhu pills (QSWZZP, Tibetan name: ) originated from Ershiwuwei Zhenzhu mother pills in the eighth century AD and are currently included in the Chinese Pharmacopoeia (2020). QSWZZP calm the mind, activate the medians, regulate qi, and harmonize the blood. QSWZZP have significant therapeutic effects in cerebral ischemia. However, QSWZZP's complex and diverse multi-herb chemical composition has presented challenges in identifying their active ingredients, which have hitherto remained unclarified. Therefore, the present study focusses on the identification of QSWZZP's active ingredients and their therapeutic mechanisms. To analyze the distribution of QSWZZP's components in the blood and tissues for the treatment of cerebral ischemia, to identify the biomarkers after drug intervention, and to explore the mechanism of action of QSWZZP in terms of the mitochondrial apoptosis pathway. Ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was used for qualitative and metabolomic analysis of the distribution of QSWZZP's components in the blood and tissues. A middle cerebral artery occlusion (MCAO) rat model was used to evaluate and measure neurobehavioral changes, the ratio of cerebral infarction, the rate of apoptosis-positive cells in the brain tissue, and the pathological changes in the cerebral cortex, hippocampus, and diencephalon. mRNA, protein, and fluorescence expressions of apoptosis-inducing factor (AIF), P53, cytochrome C (Cyt C), apoptotic protease activating factor-1 (APAF-1), cleaved caspase-8, B-cell lymphoma-extra-large, and N-myc downstream-regulated gene family member 4 (NDRG4) were determined in the rat brain tissues via real-time polymerase chain reaction, western blotting, and immunofluorescence. In addition, molecular docking was used to screen the active components of QSWZZP against mitochondria-mediated apoptosis. Thirty-three new compounds were identified, including 13 triterpenoids and nine flavonoids. Among them, 15 blood-entry, 21 urine-entry, three brain-entry, seven liver-entry, and four kidney-entry components were identified. QSWZZP significantly improved neurobehavioral abnormalities and reduced the cerebral infarction rate in the MCAO rats by significantly decreasing AIF, P53, Cyt C, APAF-1, and cleaved caspase-8 mRNA expressions and Cyt C and APAF-1 protein expressions, as well as increasing NDRG4 protein expression in the rat brain tissues. Molecular docking revealed that the active ingredients of QSWZZP against mitochondrial-mediated apoptosis were arjunic acid, cholic acid, and phyllaemblic acid. In this study, 45 components of QSWZZP were qualitatively analyzed, and the metabolic pathways of the related products were clarified. The potential treatment mechanism of QSWZZP may be related to the modulation of the folate biosynthesis metabolic and P53/Cyt C/APAF-1-mediated mitochondrial apoptosis pathways. This study may serve as the foundation for subsequent pharmacokinetic experiments and analysis of the material basis of the drug effect of QSWZZP in cerebral ischemia treatment.

Enterohepatic circulation-inspired nano-platform for less-hepatotoxicity hepatocellular carcinoma therapy.

Enterohepatic circulation-inspired nano-platform for less-hepatotoxicity hepatocellular carcinoma therapy.