The present study investigated the potential therapeutic potential of Ficus carica polysaccharides (FCPS) in type 2 diabetic mellitus (T2DM) mice, focusing on elucidating the underlying molecular mechanisms. Network pharmacology analysis identified 37 shared targets between FCPS and T2DM, including perixisome proliferator activated receptor alpha (PPARα), highlighting the significance of PPAR signaling pathways in FCPS-mediated T2DM treatment. The results demonstrated that FCPS treatment significantly reduced markers of glucose and lipid metabolism (fasting blood glucose (FBG), nonestesterified fatty acid (NEFA), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C)), inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1)), and liver damage (glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT)) in T2DM mice. Additionally, FCPS ameliorated hepatic lipid droplet accumulation, fatty degeneration, and hepatocyte structural abnormalities. Western blot analysis confirmed FCPS-induced upregulation of key proteins in the IRS-1/AKT/PPARα signaling pathway, (insulin receptor substrate 1 (IRS-1), phosphatidyqinositol-3 kinase (PI3K), phospho-protein kinase B (p-AKT), glucose transporter 2 (GLUT2), phospho-glycogen synthase kinase 3 beta (p-GSK-3β), phospho-adenosine 5′-monophosphate-activated protein kinase alpha (p-AMPKα), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), PPARα, peroxisome proliferator-activated receptor gamma (PPARγ)) and downregulation of GSK-3β, sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). 16S rRNA sequencing results revealed FCPS's ability to modulate gut microbiota dysbiosis in T2DM mice by promoting beneficial bacteria (e.g., Lactobacillus_reuteri, Candidatus_Saccharimonas) and suppressing opportunistic pathogens (e.g., Proteobacteria, Gammaproteobacteria, Escherichia-Shigella). These findings collectively suggest that FCPS has a marked effectiveness in improving glucose and lipid metabolism, decreasing inflammatory responses, as well as modulating the gut microbiota in T2DM mice via the gut-hepatic axis, demonstrating its potential as a functional food for diabetes prevention and management.

Although nanodrugs based on antiangiogenic and oxidative stress have received widespread attention in oncotherapy, low delivery efficiency and drug payload have greatly hindered their further applications. The self-targeting carrier-free metal-organic nanodrugs are constructed via the dynamic ligand-driven self-assembly of anti-angiogenesis pseudolaric acid B (PAB), Fenton-like agent copper ion, and the chemo-drug pemetrexed (PEM) to enhance anti-angiogenic-oxidative stress oncotherapy. After intravenous injection, it is found that such nanodrugs can be efficiently accumulated in tumor site and internalized into tumor cells by folate receptors-mediated self-targeting. After that, nanodrugs are disassembled to achieve the burst release of drugs under stimuli of acidic lysosome and endogenous glutathione (GSH). Interestingly, the released Cu^[II] can efficiently decompose the endogenous hydrogen peroxide (H₂O₂) into hydroxyl radicals (·OH) and significantly weaken reactive oxygen species (ROS) elimination by downregulating endogenous GSH to self-amplify intracellular oxidative stress. Meanwhile, the released PAB can obviously inhibit the secretion of vascular endothelial growth factor (VEGF), block the formation of new blood vessels, and regulate the conformation of VEGF receptor 2 (VEGFR2) to inhibit the angiogenesis signaling pathway. After two weeks of treatment, PEM-Cu^[II]-PAB (PCP) nanodrugs achieved a 95% tumor inhibition rate and 100% survival rate in tumor-bearing mice. Taken together, our study can expect to provide a promising method for targeted oncotherapy based on the synergistic therapy of antiangiogenic or oxidative stress.

The biological activities of polysaccharides are affected by a variety of factors such as monosaccharide composition, molecular weight, glycosidic bond type, branching degree, molecular conformation and functional groups, and are closely related to structural features. In order to clarify the structure of polysaccharides as much as possible, it is necessary to characterize and simulate the structure of polysaccharides based on primary structure characterization and further described or visualized to characterize the three-dimensional structure of polysaccharides. A large number of studies have shown that polysaccharides from different sources and structures participate in or directly exert their activities in the fields of anti-tumor, anti-oxidation and immune regulation related to immunology, anticoagulation, hypoglycemia and lipid-lowering, anti-fatigue and other activities. The structural modification/modification of polysaccharides provides the possibility to improve the activity, efficiency or functional specificity of polysaccharides. Due to the diversity and complexity of the structure of polysaccharides, the structural prediction is not complete and high accuracy, and the functional prediction is limited by the diversity of binding receptors, so the downstream pathways involved cannot be accurately located. Therefore, it is necessary to consider the comprehensive results from multiple perspectives in the study of the mechanism of exerting biological activity. Structural detection and analysis of polysaccharides are inextricably linked to the development of polysaccharide biological activities, which can be easily predicted through structural analysis and summarization of structural patterns.

This study investigated the effect and mechanism of Capparis spinosa L. fruit n-butanol extract(CSBE) on the maturation of dendritic cell(DC). DC was treated with 1, 2, 3 mg·mL⁻¹ CSBE. DC surface molecule expression, antigen phagocytosis and cytokine secretion were determined by flow cytometry and ELISA to verify DC maturity. Liquid chromatography-mass spectrometry(LC-MS) was used to identify anti-inflammatory components of CSBE and network pharmacology was utilized to analyze their targets related to rheumatoid arthritis(RA). String database and Cytoscape 3.7.2 software were utilized to construct protein-protein interaction(PPI) network maps of the key targets, and Metascape platform was used for GO and KEGG enrichment analysis and western blot was used to identify the expression of related proteins. The experiment results showed that CSBE alone had no significant effect on the expression of DC co-stimulatory molecules and cytokines, but significantly inhibited the expression of CD40 and CD86, matrix metalloproteinases MMP9 and MMP13, and the secretion of TNF-α and IL-6 induced by bacterial lipopolysaccharides(LPS). CSBE also increased antigen phagocytosis of DC. There were 49 anti-inflammatory compounds in the positive ion mode of LC-MS, and 42 anti-inflammatory compounds in the negative ion mode. Common core targets include AKT1, TNF, SRC and MMP9. Among them, organic acids are mainly associated with Th17-related biological processes such as helper T cell differentiation, Th17 helper cell differentiation, Th17 type immune response, et al.. It involves PI3K-AKT signaling pathway, Th17 cell differentiation, HIF-1 signaling pathway, and IL-17 signaling pathway related to RA. CSBE can inhibit the maturation of DC and the expression of pro-inflammatory cytokines, and inhibit DC migration by reducing the expression of MMP, thus exerting the function of immunosuppression and treatment of RA.

According to the existing researches on bone morphogenetic proteins(BMPs), their mechanism in adipose tissue insulin resistance was discussed. Relevant BMP signaling pathways in white adipose tissue(WAT) and brown adipose tissue(BAT) were reviewed, and BMPs improved the insulin sensitivity by the regulation of adipocyte fate and function through peroxisome proliferators activated receptor γ(PPARγ) activation. In WAT, BMPs can promote adipocyte differentiation, reduce inflammation, enhance insulin signaling and glucose transport; In BAT, brown adipocytes can be increased and their activity can be enhanced to promote thermogenesis. This review summarized and discussed the role of BMPs in adipose tissue insulin resistance in recent years to provide new ideas for the prevention and treatment of insulin resistance.

To investigate the mechanism of cell apoptosis in human esophageal carcinoma cells Eca109 induced by 85% ethanol elution fraction of Artemisia absinthium L. extract with macroporous resin(AEMV), in this study, the effect on the proliferation of Eca109 cells induced by AEMV was detected by MTT assay in vitro. Flow cytometry was used to detect the change of cell cycle and apoptosis ratio. The change of related proteins expression was detected by Western Blot. The results showed that AEMV could significantly inhibit cell proliferation in a concentration dependent manner, which compared with the DMSO group(P <0.001). The IC50 is 57.76 μg/mL. AEMV could induce apoptosis(P <0.001) and chromatin condensation of Eca109 cells. The cell cycle was arrested by down regulating the expression of cyclin B1. 50 μg/mL AEMV induced arrest cell cycle at the G0/G1 phase, 100 μg/mL AEMV induced cell cycle arrest at the G2/M phase. 100 μg/mL AEMV can increase the level of intracellular reactive oxygen species(P <0.001), decrease the mitochondrial membrane potential(P <0.001) and activate the mitochondrial-mediated intrinsic caspase-dependent pathway by increasing the expression of cleaved caspase-9, caspase-3 and PARP in a dose-dependent manner. This study also found that AEMV could activate endoplasmic reticulum stress(ER stress) in Eca109 cells by up regulating the expression of GRP78, p-PERK, p-eIF-2α and CHOP. In conclusion, AEMV induces ROS production, activates endoplasmic reticulum stress and induces apoptosis of Eca109 cells through mitochondrial-mediated intrinsic caspase-dependent pathway. It is suggested that AEMV may be a potential candidate drug for the treatment of esophageal carcinoma.

To investigate the effect of eriodictyol on dendritic cell(DC) maturation and the molecular mechanism, based on network pharmacology, the related targets for DC, immunosuppression and inflammatory response were obtained through multiple data platforms. Cytoscape 3.6.1 software was used to construct the active component-potential target network, and the String was used to construct the protein interaction(PPI) network. GO and KEGG enrichment analysis were performed using Metascape, and the molecular docking was performed using Autodock Vina software. DCs were treated with different concentrations(210 μM, 280 μM and 350 μM) of eriodictyolin the absence or presence of lipopolysaccharides(LPS). The expression of cell surface molecules was detected by flow cytometry, cytokine secretion was detected by ELISA, and matrix metalloprotein MMP9 expression was detected by Western blot. 96 related targets were screened, 72 of them related to DC, 14 of them related to immunosuppression, and 48 of them related to inflammatory response. The core targets included AKT1, SRC, MMP9 and MMP2, etc., which were involved in biological processes such as the oxidative stress and the cell migration and signaling pathways including pathways in cancer, Ras signaling pathway, EGFR tyrosine kinase inhibitor resistance, c-type lectin receptor signaling pathway and TNF signaling pathway. The molecular docking showed that eriodictyol had stronger binding effect with MMP9. In vitro, eriodictyol significantly suppressed LPS-induced DC maturation characterized by the decreased levels of CD40 (P<0.01), CD86 (P<0.001), TNF-α (P<0.001), IL-6 (P<0.001) and MMP9 (P<0.01). Eriodictyol inhibited the maturation and migration of DC through co-stimulatory molecules CD40 and CD86, pro-inflammatory cytokines TNF-α and IL-6, and MMP9.

Salt severely restricts cotton (Gossypium hirsutum) growth and production. The present study was undertaken to study the effect of salt-induced hydrogen peroxide (H₂O₂) on antioxidant enzymes in cotton. NaCl treatment or exogenous H₂O₂ was used to investigate the relationship between H₂O₂ content and levels of antioxidant enzymes including superoxide dismutase (SOD), ascorbate peroxidase (APX), peroxidase (POD), and catalase (CAT), as well as the transcriptional levels of corresponding genes. H₂O₂ content increased within 24h following 200mmol L^–1 NaCl treatment. Both NaCl-induced and exogenous H₂O₂ increased the activity of antioxidant enzymes including APX and SOD and upregulated the transcriptional levels of GhcAPX1, GhFeSOD, and GhchlCSD. These increased activities and upregulated transcriptional levels were inhibited when the salt-induced H₂O₂ was scavenged by NAC. These results indicate that salt-induced H₂O₂ as a second signaling messenger modulates APX and SOD activities by regulating the transcription levels of corresponding genes, alleviating oxidative stress, and increasing salt tolerance in cotton.