Asthma is a heterogeneous disease characterized by chronic airway inflammation and driven by diverse mechanisms, including T2-high, T2-low, and non-immune pathways. In traditional Chinese medicine(TCM), it is viewed as a syndrome of "root deficiency with branch excess", involving the dysfunction of the lung, spleen, and kidney. Animal models serve as crucial tools for investigating asthma mechanisms, screening therapeutic targets, and evaluating potential interventions, and their construction must closely align with disease pathogenesis. This study highlights a mechanism-guided approach to asthma animal modeling. It reviews models that reflect major immune phenotypes in modern medicine (T2-high, T2-low, and non-immune mechanisms)alongside TCM syndromes, including cold asthma, heat asthma, and kidney deficiency with phlegm retention. The construction principles, mechanistic links, and practical limitations of these models are analyzed. Emphasis is placed on optimizing models through a mechanism-oriented perspective and integrating Western and TCM frameworks. Such strategies are proposed to enhance the precision, translational value, and clinical relevance of asthma research using animal models.

Asthma is one of the most common chronic inflammatory airway diseases worldwide. Although current treatments can control symptoms, they are unable to fundamentally regulate the underlying immunopathological processes. Xiao'er Jiangqi Pingxiao Mixture (JPM) is a clinically used empirical prescription for the treatment of asthma. Previous studies have confirmed its efficacy in improving asthma symptoms, but its underlying mechanism remains to be elucidated. In this study, transcriptomic data from nasal brush samples of pediatric asthma patients (GSE152004) and lung tissue transcriptomic data from asthmatic mice (GSE41665) were integrated. Core targets were identified using machine learning, and their association with the immune microenvironment of asthma was explored through immune cell infiltration analysis. Pharmacodynamic evaluation and mechanistic validation were then performed in an ovalbumin (OVA) -induced asthma mouse model. The pharmacodynamic results showed that JPM significantly reduced the levels of interleukin (IL) -4 and IL-5 in bronchoalveolar lavage fluid (BALF) of model mice and alleviated airway inflammatory infiltration, mucus secretion, and collagen deposition. Machine learning identified seven core genes, among which IL-13 and interleukin-1 receptor-like 1 (IL-1RL1) were significantly positively correlated and closely associated with the infiltration of pro-inflammatory immune cells such as activated dendritic cells and type 1 macrophage (M1).Enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and real-time quantitative PCR (RTqPCR) further demonstrated that JPM significantly downregulated the protein expressions of IL-13 and IL-1RL1 in BALF, suppressed the positive expressions of complement C1q subcomponent subunit A (C1QA) and subunit C (C1QC) in lung tissues, and reduced the messenger RNA (mRNA) levels of IL-33, thymic stromal lymphopoietin (TSLP), and the complement receptor low-density lipoprotein receptor-related protein 1 (LRP1). Collectively, these findings suggest that JPM may ameliorate the experimental asthma phenotype by interfering with the "epithelial alarmin-complement-mediated presentation-type 2 immune amplification" cascade axis (specifically through inhibiting IL-33/TSLP release, blocking C1QA/C1QC-LRP1 mediated antigen presentation, and modulating the IL-1RL1/IL-13 axis), thereby systematically restoring the helper T cell 2 (Th2) immune microenvironment homeostasis. This study provides an experimental basis for further mechanistic investigation and clinical application of JPM. All animal experiments were approved by the Animal Ethics Committee of China Academy of Chinese Medical Sciences (approval No.: 2026B039).

The study aims to investigate the potential active ingredients and mechanism of action of XKZ2305 Granules in treating pediatric cough and asthma syndrome. An HPLC-Q-TOF-MS/MS method was established to rapidly identify the chemical constituents in XKZ2305 Granules using electrospray ionization (ESI) source in both positive and negative ion scanning modes. A total of 174 compounds were identified, including 46 flavonoids, 30 terpenoids, 16 alkaloids, 18 phenolic acids, and 64 other components. Integrated with network pharmacology analysis, potential targets of these chemical components and asthma-related disease targets were retrieved from the TCMSP, Swiss Target Prediction, GeneCards, and OMIM databases, respectively. After screening, 451 overlapping targets were obtained. Protein-protein interaction (PPI) analysis was performed using the STRING database, and visualization of the PPI network and the "herb-compound-target" network was conducted using Cytoscape software, leading to the identification of 29 core targets. GO (gene ontology) functional enrichment and KEGG (Kyoto encyclopedia of genes and genomes) pathway analyses via the DAVID database revealed that the therapeutic mechanism of XKZ2305 Granules against pediatric cough and asthma syndrome components, including baicalein, wogonin, quercetin, sinapine thiocyanate, and rhynchophylline, act on targets such as TP53, IL6, IL1B, HIF1A, GAPDH, BCL2, and AKT1, primarily through the HIF-1, PI3K/AKT, AGE-RAGE, and MAPK signaling pathway. Animal experiments demonstrated that XKZ2305 Granules significantly improved behavioral changes in juvenile asthmatic mice induced by ovalbumin (OVA), markedly reduced serum IgE levels and TNF-α content in bronchoalveolar lavage fluid (BALF), showed a trend toward increasing IL-10 levels, alleviated OVAinduced airway inflammation, and consequently mitigated pediatric asthma and cough syndrome. This study comprehensively identified the chemical constituents of XKZ2305 Granules. The animal experiments involved in this study have been approved by the Institutional Animal Care and Use Committee of Tianjin Institute of Pharmaceutical Research (Approval No.: TIPR-2025-2361PD9).

To characterize the material basis of Jiangqi Pingxiao Formula (JQPXF), this study employed feature-based molecular networking (FBMN), identifying a total of 237 chemical components. Based on FBMN, we further compared the chemical profiles of clinical Pediatric Jiangqi Pingxiao Mixture (HJ) and water decoction mixture (JJ) via non-targeted HRMS. The results revealed distinct chemical signatures in iridoids and terpenoids for the mixture, while the decoction showed preferential extraction of glycosides. Notably, in vivo exposure studies demonstrated that 24 components exhibited high pulmonary distribution, suggesting their potential as the direct material basis. Concurrently, 48 components showed delayed exposure in colonic contents, suggesting a potential effect for modulating gut microbiota against asthma through lung-gut axis. Further mechanistic analysis revealed a total of 11 core targets. Beyond classical anti-inflammatory pathways (e. g., TNF signaling), the formula may intervene in oxidative stress and airway remodeling through multiple mechanisms, including the inhibition of programmed cell death, modulation of 14-3-3 protein signaling, and regulation of lipid metabolism and fluid shear stress. This study comprehensively elucidates the "multi-component and multi-pathway" characteristics of JQPXF, providing a scientific foundation for its clinical application and formulation optimization (All animal experiments in this study were approved by the Animal Experimental Ethics Committee of Nanjing University of Chinese Medicine, Ethics No.: 202210A028).

Phenotypic drug discovery (PDD) represents a vital source of first-in-class drug innovation; however, its central bottleneck — demonstrating efficacy without a clear mechanism of action — remains a fundamental challenge in modern medicinal chemistry. This review discusses how chemical biology serves as a critical link between phenotypic screening and target validation, leveraging an integrated technological repertoire — including chemical proteomics, genetically encoded biosensors, and chemical genetics — to seamlessly connect phenotypic assays with target deconvolution, thereby accelerating the iterative cycle of "phenotypic investigation → target identification → medicinal chemistry optimization". Drawing upon cutting-edge modalities such as proteolysis targeting chimera (PROTACs) and molecular glues, we analyze the pivotal role of chemical biology in lead discovery, target deconvolution, mechanistic elucidation, and the design of novel drug modalities. Looking forward, the field is poised to deeply integrate artificial intelligence (AI)-driven drug design and single-cell chemical genomics to tackle previously undruggable targets and drive the modern revival of natural products. Concurrently, its research paradigm is shifting from a narrow focus on molecular mechanisms toward a systems-level regulation of biological networks, ultimately laying a solid technological foundation for precision medicine and the development of next-generation therapeutic modalities.

Pancreatic cancer is one of the digestive system malignancies with the poorest prognosis, with a five-year survival rate of only approximately 13%, and even lower at 8.5% in the Chinese population. Due to difficulties in early diagnosis, most patients are already at an advanced stage at the time of diagnosis, with limited treatment options and a propensity for resistance to radiotherapy and chemotherapy. KRAS (kirsten rat sarcoma viral oncogene homolog) mutations occur in over 90% of pancreatic cancer cases. Mutant KRAS not only drives tumor proliferation but also remodels the immune microenvironment through various mechanisms, such as inducing infiltration of immunosuppressive cells and upregulating immune checkpoint molecules, thereby leading to immune evasion. In recent years, with the introduction of KRAS inhibitors into clinical practice, targeting KRAS has shown potential for remodeling the tumor immune microenvironment. This article systematically reviews the mechanisms by which KRAS mutations contribute to the formation of an immunosuppressive microenvironment in pancreatic cancer, the progress in the development of KRAS-targeted drugs, and the current status and challenges of their combination with immunotherapy, providing new insights for precision treatment of pancreatic cancer.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most prevalent chronic liver disease worldwide. Its pathogenesis involves the interplay of lipid dysregulation, insulin resistance, oxidative stress, inflammation, gut microbiota dysbiosis, and genetic susceptibility variants. Current therapeutic interventions primarily rely on systemic administration, with their hepatic specificity or selectivity remaining to be improved. Small interfering RNA (siRNA) therapy offers a novel strategy by precisely silencing hepatic pathogenic genes to block aberrant protein synthesis. This review outlines the mechanisms of action and the delivery systems of siRNA therapeutics. Focusing on the core pathological drivers of MASLD, it details the clinical progress and mechanistic insights of siRNA therapeutics within three main areas: Genetic risk variants, lipid metabolism regulation, and fibrosis-inflammation pathways. This article provides an updated reference for siRNA drug development in MASLD.

Colorectal cancer (CRC) is a highly prevalent malignant tumor of the digestive system worldwide, and resistance to chemotherapy and immunotherapy constitutes a major challenge in its clinical management. While lipid metabolic reprogramming supports tumor proliferation, it also confers a specific metabolic susceptibility of CRC cells to ferroptosis, an iron-dependent form of programmed cell death driven by the accumulation of lipid peroxides. CRC cells promote the membrane incorporation of polyunsaturated fatty acids (PUFAs) by upregulating acyl-CoA synthetase long-chain family member 4 (ACSL4), reduce membrane lipid unsaturation by activating stearoyl-CoA desaturase 1 (SCD1), and rely on the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) antioxidant system, together with parallel pathways such as ferroptosis suppressor protein 1 (FSP1) and dihydroorotate dehydrogenase (DHODH), to eliminate peroxides and maintain the dynamic balance of the "lipid-ferroptosis axis". Owing to their multi-target regulatory advantages, natural bioactive compounds specifically intervene in this axis by inhibiting fatty acid desaturation, inducing lipophagic substrate mobilization, blocking antioxidant defenses, and disrupting iron homeostasis, thereby triggering ferroptosis in CRC cells. In addition, the combination of natural products with chemotherapeutic agents or immune checkpoint inhibitors can effectively reverse metabolism-adaptive resistance and activate antitumor immunity by inducing immunogenic ferroptosis. Given that clinical translation still faces challenges such as poor druggability and the lack of predictive models for therapeutic efficacy, the authors systematically analyzed the pharmacodynamic material basis and molecular mechanisms by which natural bioactive compounds modulate the lipid-ferroptosis axis, with the aim of providing a theoretical foundation for the development of drugs targeting metabolic remodeling and for the optimization of combination therapeutic strategies.

With the discovery that thalidomide-like drugs induce the ubiquitination and degradation of target effector proteins, drug development based on similar mechanisms, such as proteolysis targeting chimera (PROTAC), has rapidly expanded worldwide, occupying a considerable proportion of the novel drug discovery landscape. As the first clearly identified effector proteins of thalidomide-like drugs, the Ikaros family has also garnered broader attention. Although recent research on this family continues to focus on the development and differentiation of immune cells, a particular shift in interest has been observed toward regulatory T cells (Tregs). Correspondingly, thalidomide-like drugs are now being explored for use in autoimmune diseases, such as systemic lupus erythematosus. As transcription factors, the regulatory mechanisms of Ikaros family proteins have long been a research hotspot. Among various findings, the role of Ikaros in organizing genomic spatial architecture stands out as particularly prominent. Here, we first briefly review the research progress on thalidomide-like drugs, and then summarize newly discovered physiological functions and molecular regulatory mechanisms of Ikaros family proteins. By organizing and analyzing this information, we aim to clarify trends in related research and explore potential strategies for further targeting the Ikaros protein family.

Maintaining intracellular purine nucleotide homeostasis is critical for sustaining normal cellular physiology. Inosine-5′-monophosphate dehydrogenase (IMPDH) acts as the rate-limiting enzyme in the de novo purine nucleotide biosynthesis (DNPNB) pathway, directly regulating intracellular guanine nucleotide synthesis levels. In rapidly proliferating tumor cells, IMPDH is aberrantly activated to meet heightened nucleic acid demands, rendering it a promising target for cancer therapy. Despite the advancement of several candidates — including tiazofurin — into clinical trials, no IMPDH-targeted antitumor drugs have been approved for marketing, highlighting the need for more rigorous and systematic investigation in this field. This review summarizes the structural and functional properties of IMPDH and the progress in developing IMPDH-targeting anticancer drugs, with the aim of providing insights for future research.

Sepsis is a life-threatening organ dysfunction caused by infection-induced dysregulation of the host response. Its pathological mechanism is complex, involving excessive inflammatory response, immunosuppression and oxidative stress. Current clinical treatments mainly rely on anti-infection and supportive strategies, but the therapeutic efficacy is limited and the mortality remains high. Traditional Chinese medicine (TCM) monomers show great potential in sepsis treatment due to their multi-target, anti-inflammatory, antioxidant and immunomodulatory properties. Nevertheless, their clinical application is restricted by poor water solubility, low bioavailability and weak targeting ability. As an emerging nanoscale porous material, metal-organic frameworks (MOFs) have become ideal drug delivery carriers for their tunable pore size, high specific surface area and good biocompatibility. This review systematically elaborates the core advantages and mechanisms of MOFs as targeted drug delivery.

Sudden respiratory infectious diseases spread rapidly and pose significant challenges for prevention and control, representing a major public health concern globally. Xinjiang is rich in ethnic medical resources, with traditional medicinal materials such as Uyghur and Kazakh herbs demonstrating unique potential in antiviral, anti-inflammatory, antimicrobial, and immunomodulatory effects. This article reviews the chemical components, pharmacological effects and applications in respiratory infectious diseases of characteristic Xinjiang medicinal materials such as Fomes officinalis, Hyssopus officinalis, and Artemisia rupestris, as well as commonly used clinical preparations. Studies have found that ethnic medicinal materials and preparations exhibit synergistic mechanisms involving multiple components, targets, and pathways, which inhibit viral replication, modulate immune responses and mitigate inflammatory damage. They have demonstrated favorable efficacy and safety in clinical practice. This review further discusses the challenges faced in modernization, formulation optimization, and clinical validation of Xinjiang ethnic medicines, aiming to provide new medicinal resources and prevention strategies for addressing sudden respiratory infectious diseases.

The study employed a serum pharmacology approach to investigate the mechanism by which the blood-absorbed components of Dengzhan Shengmai Formula (DZSM) promote angiogenesis in mouse brain microvascular endothelial cells (bEND.3) following oxygen-glucose deprivation/reoxygenation (OGD/R) injury. The blood-absorbed constituents of DZSM were identified using ultra-high performance liquid chromatography coupled with quadrupole electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive-Orbitrap). An OGD/R-injured bEND.3 cell model was established. Cell viability was measured by CCK-8 assay, cellular injury was assessed by lactate dehydrogenase (LDH) levels, reactive oxygen species (ROS) expression was detected by confocal microscopy, and the apoptosis rate was determined by flow cytometry. The pro-angiogenic effect of DZSM-medicated serum was evaluated through wound healing assay, Transwell migration assay, tube formation assay, transepithelial electrical resistance (TEER), and NaF permeability test. Protein expression related to the hypoxia inducible factor-1/vascular endothelial growth factor A (HIF-1α/VEGFA) signaling pathway was detected by Western blot, and molecular docking was performed to screen key active components. The results showed that twelve components, including scutellarin, 4, 5-dicaffeoylquinic acid, and ginsenoside Rb2, were absorbed into the blood. The optimal concentration of DZSM-medicated serum for intervening in OGD/R-injured bEND.3 cells was 20% (v/v). Compared with the control group, the model group exhibited significantly decreased cell viability, migration rate, tube formation ability, and expression of pathway-related proteins, while ROS content and apoptosis rate were markedly increased (P < 0.05). Compared with the model group, the DZSM blood-absorbed components group showed significantly increased cell viability, migration rate, tube formation ability, and expression of tight junction proteins, as well as significantly decreased ROS content and apoptosis rate (P < 0.05). Moreover, the protein expression levels of HIF-1α and VEGFA were notably upregulated. Molecular docking results indicated strong binding affinities between the blood-absorbed components (e.g., scutellarin) and the HIF-1α/VEGFA targets. In conclusion, the blood-absorbed components of DZSM promote angiogenesis in OGD/R-injured bEND.3 cells, and the mechanism is closely related to activation of the HIF-1α/VEGFA signaling pathway and upregulation of its associated proteins. The experimental protocol strictly adhered to the guidelines of the Ethics Committee of Animal Research of Guangdong Pharmaceutical University (approval No.: gdpulacspf2022137).

This study aimed to investigate the mechanism of the traditional Chinese medicine compound Shengmai Yin (SMY) in exerting anti-myocardial ischemia (MI) effects through the synergistic regulation of the gut microbiota and the MAPK signaling pathway. First, network pharmacology combined with GO and KEGG enrichment analysis was used to predict the potential targets and signaling pathways of SMY against MI. Secondly, an acute myocardial ischemia model was established in SD rats by intraperitoneal injection of pituitrin (25 U·kg^-1), while SMY was administered by intragastric gavage for intervention for 7 days, with daily body weight recording. Subsequently, electrocardiogram and cardiac histopathological changes were detected. The levels of myocardial injury markers [aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), lactic acid (LD), and cardiac troponin-Ⅰ (cTn-Ⅰ)], oxidative stress indicators [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA)] and inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β)] were measured. Immunohistochemistry was used to detect the expression of key apoptosis-related proteins in myocardial tissue, including Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and B-cell lymphoma-2 (Bcl-2). TUNEL staining was used to detect cardiomyocyte apoptosis. Western blot was used to detect the expression levels of key proteins in the mitogen-activated protein kinase (MAPK) signaling pathway. 16S rRNA sequencing was used to analyze the structural changes of the gut microbiota. The experimental animals were approved by the Experimental Animal Management Committee Ethics Committee of Chengdu University of Traditional Chinese Medicine (Approval No.: 2014 DL-023). Network pharmacology analysis identified pivotal targets including TP53, TNF, MAPK1, MAPK3, and CTNNB1, which are predominantly involved in the MAPK and PI3K-AKT signaling pathways. In vivo studies demonstrated that SMY ameliorated electrocardiographic abnormalities and histopathological lesions, reduced serum levels of myocardial injury biomarkers and pro-inflammatory cytokines, suppressed the phosphorylation of the key MAPK protein p38, downregulated the expression of Bax and Caspase-3, and upregulated Bcl-2. Furthermore, 16S rRNA sequencing revealed that SMY modulated gut microbiota diversity and compositional structure. These findings suggest that SMY exerts cardioprotective effects against myocardial ischemia, potentially by suppressing inflammatory responses and cardiomyocyte apoptosis. This therapeutic effect is associated with the modulation of the MAPK signaling pathway and alterations in gut microbiota composition; however, the precise mechanisms and causal relationships warrant further investigation.

Huanglian Jiedu Decoction (HLJDT) is a classic fever-clearing detoxification prescription, with clear clinical evidence to support its anti-tumor activity. However, its effect on melanoma metastasis and its potential molecular mechanism have not been systematically clarified. In this study, network pharmacology is used to predict the potential active components, therapeutic targets and key signaling pathways of HLJDT that may have an anti-melanoma transfer effect. Based on these findings, a mouse melanoma lung metastasis model was established, and in vivo and in vitro experiments were carried out to verify the anti-transfer effect of HLJDT and explore its potential mechanism. The results show that network pharmacology analysis indicates that HLJDT contains multiple potential anti-melanoma active ingredients and may exert a synergistic anti-tumor effect by regulating multiple key signaling pathways, including cancer-related pathways and JAK-STAT pathways. In vivo experiments showed that HLJDT significantly inhibited melanoma lung metastasis, reduced the number of lung metastasis nodules, and enhanced the anti-tumor immune response. In vitro experiments further confirmed that HLJDT significantly inhibits the proliferation and migration of melanoma cells and induces cell apoptosis, which is closely related to the enhancement of ROS generation and mitochondrial membrane potential destruction. Mechanism research shows that HLJDT inhibits the activation of signal transducer and activator of transcription 3 (STAT3) and its phosphorylation, downgrades the expression of PD-L1 and N-cadherin, and upregulates the expression of E-cadherin, thus inhibiting the invasion and metastasis of melanoma cells and improving the immune microenvironment of tumors. Overall, these findings show that HLJDT has potential in inhibiting melanoma metastasis and reshaping the tumor immune microenvironment, providing a systematic experimental basis for its application as an auxiliary treatment of malignant tumors. This experiment was approved by the Experimental Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (approval No.: SDUTCM20220302025).

This study investigated the anti-malignant effects and molecular mechanisms of glabridin (GLA), a licorice-derived flavonoid, in esophageal cancer. The effects of glabridin on the esophageal cancer cell lines KYSE150 and TE1 were evaluated using CCK-8 assays, colony formation assays, wound-healing assays, and flow cytometry. A systematic analysis was further conducted by integrating RNA sequencing, multi-platform pharmacological prediction, protein-protein interaction (PPI) network analysis, Western blot (WB) validation, molecular docking, cellular thermal shift assay (CETSA) and database mining. Glabridin concentration dependently suppressed cell viability, with 48-hour IC₅₀ values of 37.85 and 20.00 μmol·L^-1 in KYSE150 and TE1 cells, respectively. Notably, 5 μmol·L^-1 inhibited colony formation, while 20 μmol·L^-1 induced G0/G1 arrest (59.99% and 56.68% of cells) and reduced 24-hour migration rates to 30% and 25% (P < 0.000 1). Transcriptomics identified 2 104 differentially expressed genes enriched in ferroptosis, autophagy, and cell cycle pathways. Integrated analysis filtered 66 core targets. PPI network topology revealed cyclin A2 (CCNA2), heat shock protein 90 alpha family class A member 1 (HSP90AA1), cyclin-dependent kinase 2 (CDK2), and mechanistic target of rapamycin kinase (MTOR) as hub genes, with CCNA2 and HSP90AA1 synergizing with obesity to affect prognosis in TCGA esophageal cancer cohorts. WB confirmed downregulation of CCNA2, CDK2, cyclin-dependent kinase 1 (CDK1), snail family transcriptional repressor 2 (SNAI2), and phosphorylated protein kinase B (p-AKT), whereas HSP90AA1 protein levels remained unchanged. Molecular docking demonstrated stable binding of glabridin to the CCNA2 active pocket via hydrogen bonding, π-alkyl, and π-anion interactions. CETSA demonstrated that glabridin enhanced CCNA2 thermal stability, and the proteasome inhibitor MG132 blocked glabridin-induced CCNA2 degradation. DepMap and LinkedOmics Database analyses revealed that CCNA2 promotes esophageal cancer cell proliferation and is associated with cell cycle progression. Collectively, glabridin suppresses esophageal cancer cell proliferation and migration, potentially through modulation of the cell cycle and epithelial-mesenchymal transition (EMT) processes, and CCNA2 may represent a promising therapeutic target for esophageal cancer.

This study investigated the effects of different doses of benzo[a]pyrene (BaP) on the expression of fibroblast growth factor 21 (FGF-21), lipid metabolism, and related genes in HepG2 cells, as well as whether these effects are mediated by the aryl hydrocarbon receptor (AhR). HepG2 cells were treated with 15, 30, and 60 μmol·L^-1 BaP for 24 h. The levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in HepG2 cells were measured. The mRNA and protein expression levels of FGF-21, β-oxidation-related genes [peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1α (CPT-1α), and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α)], and lipid synthesis-related genes [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and stearoyl-CoA desaturase 1 (SCD1)] were detected by qPCR and Western blot. A stable cell line with AhR silencing was established via lentiviral transduction, and the cells were treated with 30 μmol·L^-1 BaP. Lipid content was assessed by oil red O staining, and the mRNA and protein expression levels of FGF-21, β-oxidation-related genes, and lipid synthesis-related genes were measured. Compared with the control group, all three doses of BaP (15, 30, and 60 μmol·L^-1) increased the levels of TC, TG, and LDL-C in HepG2 cells. Compared with the 30 μmol·L^-1 BaP group, the 60 μmol·L^-1 BaP group showed higher levels of TC, TG, and LDL-C, lower mRNA and protein expression of FGF-21 and β-oxidation-related genes, and higher mRNA and protein expression of lipid synthesis-related genes. Following AhR silencing and treatment with 30 μmol·L^-1 BaP, lipid content, as well as the levels of TC, TG, and LDL-C, decreased in HepG2 cells, and the mRNA and protein expression levels of FGF-21, β-oxidation-related genes, and lipid synthesis-related genes were all reduced. Different doses of BaP increased lipid content in HepG2 cells. However, low-dose BaP activated AhR, thereby relatively increasing FGF-21 expression, reducing lipid synthesis, and enhancing fatty acid β-oxidation. In contrast, high-dose BaP activated AhR but relatively decreased FGF-21 expression, increased lipid synthesis, and reduced fatty acid β-oxidation. The effects of BaP on FGF-21, lipid metabolism, and related genes are all mediated by AhR.

To explore the mechanism of Mongolian medicine Zixin Dropping Pills (ZXDW) in treating non-alcoholic fatty liver disease (NAFLD), we combined network pharmacology with animal experiments. Network pharmacology identified 59 core targets of ZXDW for NAFLD, and functional enrichment analysis revealed that lipid metabolism pathway and phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT) signaling pathway were the key involved pathways. Pharmacodynamic experiments on high-fat diet-induced NAFLD in ApoE^-/- mice confirmed that ZXDW alleviated hepatic lipid deposition, fibrosis and inflammation. Immunofluorescence and Western blot verified key targets in the functional pathways, showing that ZXDW significantly upregulated hepatic peroxisome proliferator-activated receptor gamma (PPARγ), liver X receptor alpha (LXRα), ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1) protein expression, while downregulating PI3K, AKT and nuclear factor-kappa B (NF-κB) expression in ApoE^-/- mice. Molecular docking between main components of ZXDW and the above targets indicated that costunolide, taurocholic acid and taurodeoxycholic acid might be the main active components. This study preliminarily confirms that ZXDW alleviates NAFLD through lipid metabolism and PI3K-AKT pathways, providing a theoretical basis for its clinical application. The experiment was approved by the Animal Ethics Committee of Inner Mongolia Medical University (approval No. YKD202401262).

Using a molecular hybridization strategy, 17 peptidomimetic derivatives of phenylalanine were designed and synthesized by combining an aminothiazole oxime scaffold with phenylalanine for antibacterial activity studies. The results showed that these compounds exhibited varying degrees of inhibitory activity against the tested bacterial strains, with compound 8p being particularly outstanding. It demonstrated minimal inhibitory concentrations (MIC) of 2 μg·mL^-1 against E. coli, P. aeruginosa, and fluoroquinolone-resistant E. coli (FREC). Its activity against E. coli and P. aeruginosa was comparable to that of the reference drug ciprofloxacin, while its efficacy against FREC was significantly superior to the reference drug. Meanwhile, compound 8p exhibited synergistic effects when combined with certain antibacterial agents. Its relatively significant antibacterial activities and synergistic enhancement warrant further investigation.

The chemical constituents of petroleum ether extracts from the whole plant of Ferula bungeana were isolated using chromatographic techniques such as SiO₂, Sephadex LH-20, and thin-layer chromatography. Their structures were determined through the analysis of their spectral data. Five sesquiterpenoids were identified from the petroleum ether extracts of Ferula bungeana whole plant, namely buntone A (1), caryophyllene oxide (2), eudesol (3), mesoferulone (4), and jaeschkeanadiol (5). Among them, compound 1 was a new sesquiterpene lactone, while compounds 2 and 3 were isolated for the first time from the genus Ferula. Compounds 1-3 were screened for in vitro anti-inflammatory activity, and the results showed that compounds 1-3 exhibited varying degrees of NO inhibitory activity at a concentration of 10 μmol·L^-1, with inhibition rates of 89.8% ± 1.2%, 76.4% ± 0.8% and 80.4% ± 0.9%, respectively.

Thirteen compounds were isolated from Armeniacae Semen Amarum using macroporous resin column chromatography combined with semipreparative high performance liquid chromatography. Their structures were identified as trans-4-O-(β-D-gentiobiosyl)-p-coumaric acid (1), trans-4-O-(β-D-gentiobiosyl) ferulic acid (2), hazelnutin F (3), amygdalinamide (4), prunasinamide (5), benzyl-β-gentiobioside (6), (S)-mandelamide (7), amygdalinic acid (8), L-phenylalanine (9), L-tryptophan (10), amygdalin (11), L-amygdalin (12), and prunasin (13) by spectroscopic methods including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR), as well as comparison with literature data. Among them, compounds 1 and 2 were identified as new compounds.

This study established a discrete element method (DEM) parameter calibration approach for fermented Cordyceps powder and investigated the mechanism by which binary mixture systems affect flowability. The angle of repose, measured via physical experiments, served as the response value. Using the Hertz-Mindlin with JKR V2 contact model, the optimal DEM simulation parameters were identified through a sequential methodology comprising Plackett-Burman design, steepest ascent experiments, and Box-Behnken response surface methodology. Based on this calibrated model, binary angle of repose simulations was constructed with large particles (1.404 mm) as the skeleton and small particles (0.228 mm) as the filling phase, at mass ratios of 85∶15, 90∶10, and 95∶5. A mesoscopic mechanical analysis was subsequently performed. Simulation results indicate that the binary mixing method effectively optimizes the fermented Cordyceps powder's flowability. Furthermore, appropriately reducing the proportion of small particles contributes to enhancing the overall system flowability, with the 95∶5 mass ratio representing the optimal balanced state. From a mesoscopic perspective, the observed macroscopic trend is closely related to the reconstruction of the internal force chain architecture from a "weak connection network" to a "strong force chain skeleton". Concurrently, a decrease in the coordination number suggests a reduction in geometric constraints between particles, while the contact stress ratio (Ft/Fn) remains in a subcritical stable state. These factors collectively contribute to the optimized flowability. This study successfully established a DEM model for the flow behavior of fermented Cordyceps powder, elucidated the mechanism of binary mixture systems from the mesoscopic level, and provided a reference for the binary simulation of other fermented Cordyceps powder systems.

Ketorolac tromethamine (KT) is characterized by a short half-life and rapid systemic clearance, necessitating frequent dosing when administered via traditional oral or injectable routes, and is associated with pronounced first-pass metabolism and gastrointestinal adverse effects. To mitigate these limitations, this study developed ketorolac tromethamine microneedles (KTMN) for buccal mucosal delivery and evaluated their analgesic efficacy. The microneedle tips were fabricated using a photosensitive hyaluronic acid methacrylate solution as the matrix, which was cast into polydimethylsiloxane molds, followed by drying and UV crosslinking to yield well-formed KTMNs. Each microneedle exhibited a mechanical strength of 0.70 N and achieved a penetration depth of 120 μm in rat buccal mucosa. In artificial saliva, KTMNs demonstrated sustained and stable drug release, with an in vitro release rate of 55.33% at 2 h and 76.77% at 12 h. Pharmacokinetic analysis revealed a peak plasma concentration of 5.91 μg·mL^-1 at 2 h post-administration, with an average residence time extending up to 15.52 h. In vivo, KTMN administration significantly attenuated pain responses in both the formalin-induced pain model and the carrageenan-induced inflammatory pain model in rats. Overall, buccal mucosal delivery of KTMNs represents a safe, rapid, and efficient formulation, offering a promising new strategy for fast-acting, long-lasting, and convenient analgesia.

α-Humulene is a natural sesquiterpenoid with multiple pharmacological activities including anti-inflammatory, antibacterial and antitumor effects, and also serves as the key precursor for zerumbone biosynthesis. In this study, Saccharomyces cerevisiae was used as the chassis for heterologous production of α-humulene. One novel α-humulene synthase gene, AsTPS8, was mined from the transcriptome of Aquilaria sinensis. Compared with the reported ZSS1 from Zingiber zerumbet, AsTPS8 exhibited higher catalytic efficiency. Furthermore, fusion expression of ERG20 with AsTPS8 via a (GGGS)₂ linker combined with multi-copy integration at the TY1 locus increased the α-humulene titer to 1.41 g·L^-1 in shake flasks. On this basis, the bypass phosphatase gene LPP1 was knocked out using CRISPR/Cas9, and the transcriptional regulators IME4 and UPC2-1 were simultaneously introduced, further elevating the titer to 1.80 g·L^-1. Finally, fed-batch high-density fermentation in a 5 L bioreactor achieved an α-humulene titer of 22.02 g·L^-1 at 144 h, representing the highest reported level to date. This study provides an efficient chassis strain and technical support for the industrial production of α-humulene and downstream zerumbone.