Songli Shi

Background: Liver injury represents a major global health concern, and effective hepatoprotective agents remain urgently needed. This study investigated the hepatoprotective effects of Amygdalus mongolica oil in a carbon tetrachloride (CCl₄)-induced liver injury model, focusing on two complementary aspects: regulation of the PI3K/AKT/mTOR signaling pathway and modulation of the gut microbiota. Results: A. mongolica oil exerted hepatoprotective effects at all doses tested, with the medium-dose group (OIL-M) showing the greatest overall efficacy. OIL-M attenuated hepatocyte necrosis, inflammatory cell infiltration, and collagen deposition, and improved serum liver function indices, fibrosis-related markers, and inflammatory cytokines. Western blot analysis showed that OIL-M inhibited aberrant activation of the hepatic PI3K/AKT/mTOR pathway, as reflected by reduced p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR ratios. OIL-M also restored gut microbial alpha and beta diversity, shifting the overall community structure toward that of the control group (CON). Linear discriminant analysis effect size (LEfSe) identified ten discriminatory taxa enriched in the OIL-M group, including Dorea , Psychrobacter , Tuzzerella , Oscillibacter , Oligella , HT002, Colidextribacter , Roseburia , Anaerostipes , and Dubosiella . Genus-level analysis showed that OIL-M increased the relative abundances of Roseburia , Anaerostipes , Dubosiella , and Oscillibacter , while reducing Desulfovibrio . Spearman correlation analysis linked microbiota remodeling to improved hepatic phenotypes. PICRUSt2-based functional prediction indicated that OIL-M altered microbial metabolic potential, particularly in pathways related to nicotinate and nicotinamide metabolism and xenobiotic degradation. Conclusions: These findings suggest that A. mongolica oil alleviates CCl ₄ -induced liver injury through gut microbiota remodeling and inhibition of hepatic PI3K/AKT/mTOR signaling, providing evidence for the involvement of the gut-liver axis. Graphical Proposed schematic illustrating the mechanisms potentially involved in the protective effects of Amygdalus mongolica oil against CCl ₄ -induced liver injury. A. mongolica oil may exert hepatoprotective effects by modulating the gut microbiota, characterized by increased relative abundances of Dubosiella , Anaerostipes , Roseburia , and Oscillibacter and a decreased abundance of Desulfovibrio , and by suppressing hepatic PI3K/AKT/mTOR signaling, as reflected by reduced p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR ratios. These coordinated changes were associated with the amelioration of liver injury.

Introduction: Liver cirrhosis is the terminal stage of chronic liver disease, which is marked by high morbidity and mortality in its advanced phases. Although liver biopsy still serves as the gold - standard diagnostic method, the detection of serum and urine metabolites holds great promise for the identification of cirrhosis. Methods: Untargeted metabolomics analysis was carried out using ultra - performance liquid chromatography coupled with quadrupole time - of - flight mass spectrometry (UPLC - QTOF/MS). We compared the serum and urine metabolic profiles between 30 healthy individuals and 28 liver cirrhosis patients to screen for biomarkers associated with liver cirrhosis. Results: A total of 55 endogenous metabolites showed dysregulation in serum, and 51 did so in urine. Four shared differential metabolites—glycoursodeoxycholic acid, urobilin, glycocholic acid, and urobilinogen—were identified in both biofluids. Pathway enrichment analysis revealed three co - regulated metabolic pathways: tryptophan metabolism, glycerophospholipid metabolism, and porphyrin metabolism ( p < 0.05). Discussion: This study delineates the distinct metabolic signatures of cirrhosis and proposes a diagnostic strategy based on dual - biofluid analysis. The intersectional biomarkers and pathways elucidate the mechanisms linking bile acid homeostasis and hemoprotein catabolism to cirrhotic progression, offering a noninvasive approach for clinical detection.

Hepatic fibrosis (HF), a reversible yet critical pathological stage in chronic liver disease progression, represents a major global public health challenge. This study systematically investigated the antifibrotic mechanism of Prunus mongolica oil (OIL), an active component derived from traditional medicinal plants, through an integrated approach combining pharmacodynamics, transcriptomics, and molecular biology in carbon tetrachloride (CCl₄)-induced Sprague–Dawley rat models. Dose–response evaluation revealed optimal antifibrotic efficacy at the medium dosage (5 g kg⁻¹) compared with other concentrations (2.5 and 7.5 g kg⁻¹). Transcriptomic profiling identified 1734 differentially expressed mRNAs, 121 lncRNAs, and 82 miRNAs among model (MOD), control (CON), and OIL-treated groups. Construction of competing endogenous RNA (ceRNA) networks and functional enrichment analysis highlighted the potential association of the PPAR signaling pathway (P = 0.012, FDR = 0.27). Topological assessment using Cytoscape (v3.9.1) and the STRING database identified the Gck/rno-miR-667-5p/Cyp8b1 axis as the central regulatory node. Mechanistically, OIL exerted dual therapeutic effects: (1) upregulating PGC-1α/PPARγ expression to enhance metabolic reprogramming, and (2) suppressing TGF-β/Smad3 phosphorylation activation, thereby inhibiting hepatic stellate cell (HSC) activation and extracellular matrix (ECM) deposition. Immunohistochemical and western blot analyses validated these protein-level modulations. Our findings revealed a novel ceRNA-network-mediated mechanism wherein OIL attenuates hepatic fibrosis through coordinated regulation of PPAR and TGF-β/Smad3 pathways via the Gck/rno-miR-667-5p/Cyp8b1 axis, providing a theoretical foundation for developing multitarget phytopharmaceuticals against liver fibrosis.

Amygdalus mongolica is a traditional Chinese and Mongolian medicine and is quite effective in relieving cough and eliminating phlegm. In this study, ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to perform metabolomics analysis, combined with transcriptomic sequencing, to study the samples of A. mongolica at early, middle and late growth stages. A comprehensive analysis was conducted to systematically investigate the dynamic changes and developmental trajectories of kernel progression across distinct growth stages, utilizing differential expression analysis and pathway enrichment approaches. A total of 104 significant differential metabolites were identified across different growth stages: the early growth stage (E), the middle growth stage (M), and the late growth stage (L). Specifically, 68 and 36 differential metabolites were detected in the comparisons of E vs. M and M vs. L, respectively. Among them, 29 and 21 metabolites exhibiting up-regulation. In comparison, 39 and 15 metabolites demonstrated down-regulation. Transcriptomic analysis identified 133 differentially expressed genes associated with 62 pathways in the E vs. M. Simultaneously, 14 differentially expressed genes linked to 13 pathways in the M vs. L. The accumulation of various metabolites varied across the growth stages, with a marked increase in amino acids during the middle and late developmental phases, alongside fluctuations in the levels of flavonoid compounds. In conclusion, the study reveals significant variations in the content and types of amino acid compounds and the expression levels of key genes within relevant pathways of A. mongolica kernels throughout different growth stages. Especially, the increase in flavonoid compound expression with advancing growth stages highlights their substantial medicinal potential. These findings provide a foundation for future developing and utilizing valuable medicinal ingredients in A. mongolica kernels.

Introduction: The intricate pathogenesis of renal fibrosis necessitates identifying biomarkers at various stages to facilitate targeted therapeutic interventions, which would enhance patient survival rates and significantly improve prognosis.Methods: We investigated the changes in gut microbiota and serum metabolites during the early, middle, and late stages of renal fibrosis in rats using 16S rDNA sequencing and UPLC-QTOF/MS-based metabolomics.Results: We identified 5, 21, and 14 potential gut microbial markers and 19, 23, and 31 potential metabolic markers in the MOD1, MOD2, and MOD4 groups, respectively. Bifidobacterium was identified as a shared microbial marker between the MOD1 and MOD2 groups; Prevotellaceae_NK3B31_group and Bacteroides were identified as shared microbial markers between the MOD2 and MOD4 groups. The pathways of arachidonic acid metabolism and retinol metabolism were found to play a significant role in the modulation of renal fibrosis at 1, 2, and 4 weeks. Notably, the metabolic biomarkers 8,9-EET and 5(S)-HPETE within these pathways emerged as critical determinants influencing renal fibrosis.Discussion: Our findings demonstrated that the severity of renal fibrosis is associated with dysbiosis of the gut microbiota and alterations in serum metabolites.

The main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1β, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.