Yan Zhang

Macrophage polarization is a pivotal determinant in the modulation of immune responses and the formation of the tumor-microenvironment (TME), therefore represents a promising avenue for the development of cancer immunotherapy. Recent research highlights the potential of edible mushroom polysaccharides in inducing M1/M2 polarization of macrophages. Here, we report that oral administration of Flammulina velutipes polysaccharide (FVP) reduced the tumor volume of grafted 4T1 mammary and lewis lung carcinoma (LLC), and increased the overall survival rate of mice. Moreover, this polysaccharide induced the generation of CD11b+Ly6ChighF4/80+ macrophage cells in LLC and 4T1 tumor-bearing mice. Further investigation found that FVP decreased the ratio of M2-macrophages and regulatory T cells in TME, which is known to support tumor growth and metastasis. Mechanistically, FVP reversed the IL-4 induced M2-polarization by activating the TLR4/NF-κB axis, and in vitro assays confirmed the expression of pro-inflammatory genes and the antitumor effects of the polysaccharide. Additionally, the expression of Th1 response relative genes was also enhanced by FVP polarized macrophage secretions. In summary, these results suggest that FVP may represent a promising immunomodulatory agent for the reversal of macrophage polarization.

A high-performance powder Ag@CD-MOF surface enhanced Raman Spectroscopy (SERS) substrate with good storage stability was developed utilizing the cavity structure and reducing characteristics of CD-MOF for detecting thiram (THR). In this substrate, Ag NPs were confined in the cavity of cyclodextrin metal-organic framework (CD-MOF). CD-MOF as a template promoted the fabrication of small-size Ag NPs with its cavity limiting the further nucleation of Ag NPs. What’s more, CD-MOF could easily disintegrate to release Ag NPs when dissolving in water. The released Ag NPs were capped with γ-CD which could capture the THR molecule close to the hotspot region of Ag NPs via the host-guest interaction between the hydrophobic cavity of γ-CD and the hydrophobic THR molecule to realize the sensitive detection of THR. As a result, a good linearity was acquired between the SERS signal and the THR concentration from 10-8 to 10-3 mol/L based on the fabricated Ag@CD-MOF substrate with a detection limit as low as 6.47×10-9 mol/L. At the same time, the fabricated Ag@CD-MOF substrate could still reach 85% of its original SERS intensity after three months of storage, and the recovery rate in the actual grain samples was 91%~93%, which could realize the detection of THR in real samples.

Alcoholic liver disease (ALD), a pervasive global health concern, involves multifaceted pathological mechanisms including oxidative stress, lipid dysregulation and inflammatory responses, yet lacks effective multi-target therapies. Carnosic acid (CA), a natural diterpenoid with extensively characterized antioxidant and anti-inflammatory properties, remains underexplored for its systemic therapeutic potential in ALD. This study aimed to comprehensively investigate CA's hepatoprotective efficacy and molecular mechanisms against ALD. Results demonstrated that CA significantly reduced serum total cholesterol, triglycerides, and transaminase levels in ALD mice, concurrently alleviating alcohol-induced histopathological damage. Network pharmacology identified 36 potential targets, with 10 core targets predominantly enriched in lipid metabolism, PPAR signaling and inflammatory response. Molecular docking revealed superior binding affinities of CA to core targets compared to silibinin, a reference hepatoprotectant. RT-qPCR validation further confirmed CA's regulatory effects on apoptosis-related TP53/BCL2 axis, TNF-mediated inflammatory pathways and CYP450 metabolic genes. Through a tripartite strategy integrating phenotypic validation, mechanistic prediction, and experimental confirmation, this study elucidates CA's multi-target therapeutic actions against ALD via coordinated modulation of lipid homeostasis, oxidative stress and inflammatory pathways, providing the groundwork for future mechanism exploration.

Natural lysozyme (N‐Lyso) is an important natural preservative widely used in the food industry and biomedical fields. However, the specific properties and safety of lysozyme after secondary structure modification (M‐Lyso) are still poorly understood. Compared to N‐Lyso, M‐Lyso at the same concentration exhibits increased protease sensitivity, reduced enzymatic activity, but no significant change in antibacterial activity. Multispectral analysis combined with cell experiments revealed that M‐Lyso, characterized by a decreased α‐helix content and increased β‐sheet structure, induced an increase in PDE4D expression in vascular smooth muscle cells (VSMCs) and elevated levels of PDE4D and IL‐6 in the cell culture supernatants, accompanied by a decrease in cell viability. However, treating M‐Lyso with glycyrrhizic acid (GL) or glycyrrhetinic acid (GA) from liquorice reversed the above phenomena. Molecular docking results indicated GL and GA formed supramolecular complexes with lysozyme. The understanding of specific properties of N‐Lyso and M‐Lyso not only provides valuable insights into the safety profile of lysozyme but also offers for the prevention and treating diseases related to alterations in the protein secondary structure.

Cornus officinalis Sieb. et Zucc., a valuable Chinese medicine resource, has a long clinic utilization history. In recent years, more researches focus on the chemical composition and pharmacological activity of C. officinalis which was used as health foods and drugs. This paper summarized the active ingredients, pharmacological activities and molecular mechanisms of C. officinalis in recent 5 years to provide reference for the development and utilization of C. officinalis. One hundred and forty-nine active constituents of C. officinalis were summarized, including iridoids (64), flavonoids (18), lignin (17), tannins (16), organic acids and phenolic acids (14), triterpenes (11) and others (9), which were further subdivided according to their pharmacological effects. It was found that the pharmacological effects of C. officinalis were very extensive, mainly including antioxidant, anti-inflammatory, anti-tumor, neuroprotective and other biological activities. Among these activities, the anti-inflammatory and hypoglycemic mechanisms showed multi-pathway and multi-target characteristics, which were elaborated systematically. However, there are still many compounds in C. officinalis that have not been studied for biological activity, which means that it still has potential pharmacological activity to be further studied. C. officinalis not only has high medicinal value, but also has a potential edible resource. However, limited by people's understanding of the nutritional value of C. officinalis, few product types and incomplete processing technology, people's acceptance of the edible value of C. officinalis is not high, and it needs to be further developed and utilized.

This study established a method using gas chromatography-electrostatic field Orbitrap high-resolution mass spectrometry (Orbitrap GC-MS) for the simultaneous determination of 70 organic pollutants across four categories: organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and phthalates (PAEs) in infant cereal-based supplementary foods. Techniques integrating cryogenic centrifugation and lipid and protein adsorbent (LPAS) purification were employed. The precise mass numbers of target compounds were determined by Orbitrap GC-MS in full-scan mode (Full MS), which effectively minimized matrix interferences in these foods. Method validation on rice flour samples demonstrated that the 70 compounds exhibited excellent linearity within their respective mass concentration ranges, with correlation coefficients all exceeding 0.995. The detection limits for this method ranged from 0.10-1.0 μg/kg, while the quantification limits varied from 0.3-3.0 μg/kg, meeting the established detection requirements. The average spike recovery of the 70 compounds at three spiked levels (5, 20, and 100 μg/kg) ranged from 75.3%-119.3%, with relative standard deviations ranging from 1.8%-10.8%. Both inter-day and intra-day precision demonstrated relative standard deviation values below 15%. This method was applied to analyze 100 samples of commercial infant cereal-based supplementary food, revealing the presence of PAEs and PAHs in 12.0% of the samples. Notably, no OCPs or PCBs were detected. The detected concentrations of benzo[a]pyrene (BaP) and dibutyl phthalate (DBP) were (4.2 ± 0.1) μg/kg and (1.8 ± 0.3) μg/kg, respectively. This method is straightforward, highly sensitive, and suitable for the rapid screening and confirmation of 70 organic pollutants in infant cereal-based supplementary foods.

Inflammation caused by obesity, particularly in adipose tissue and the liver, can lead to insulin resistance (IR) and trigger type 2 diabetes (T2DM). It is crucial to identify therapeutic agents that alleviate IR by reducing inflammation. Here, we report that isobavachromene (IB), a flavonoid derived from Psoralea corylifolia Linn., ameliorates IR in 3T3-L1 adipocytes by inhibiting the MAPK/NF-κB signaling pathway. We first found that IB could promote glucose uptake in 3T3-L1 adipocytes by activating the PI-3K/Akt signaling pathway and was more effective than the positive control sodium orthovanadate at concentrations ranging from 25 to 100 μmol/L. Additionally, IB inhibited RAW264.7 macrophage infiltration into 3T3-L1 adipocytes and suppressed the secretion of inflammatory factors from RAW264.7 macrophages, as well as the phosphorylation levels of key proteins (NF-κB P65, ERK1/2, JNK, and P38) in the NF-κB and MAPK signaling pathways. In summary, IB improves glucose uptake in IR adipocytes, activates the PI-3K/Akt signaling pathway, inhibits the JNK and NF-κB inflammatory signaling pathways, and reduces adipocyte inflammation, thereby improving of IR in 3T3-L1 adipocytes.

Vascular oxidative stress serves as a pathological foundation for various vascular injury-related diseases, including atherosclerosis, hypertension, restenosis, and abdominal aortic aneurysms. Recent studies have indicated that the intestinal flora-derived metabolites phenylacetylglutamine (PAGln) and phenylacetylglycine (PAGly) may contribute to the promotion of thrombosis, heart failure, and other related conditions. Aucubin (AU), an iridoid glycoside, has been shown to exhibit anti-cardiovascular properties. Nevertheless, the precise role and underlying mechanisms by which AU mitigates PAGly-induced vascular injury remain poorly understood. Our results indicated that PAGln/PAGly promoted oxidative stress in vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vitro and in vivo. Network pharmacology suggest that AU may possess the capacity to regulate lipid and atherosclerosis, and reactive oxygen species (ROS) processes. We found that AU penetrated the blood vessels and mitigated oxidative stress induced by PAGln/PAGly. Mechanistically, combined the results from intersections analysis between the targets of AU and vascular diseases and molecular docking, we found that TNF may be the potential target of AU. Further DARTS and molecular docking analysis demonstrated that AU bound to recombinant TNF-α, and AU could interact with multiple amino acid residues of TNF-α including Asn-92 and Phe-144. Additionally, PAGly upregulated the level of soluble TNF-α (sTNF-α) in mouse VSMCs and plasma, and promoted the interaction between sTNF-α and TNF receptor 1 (TNFR1), whereas AU inhibited this interaction. Both AU and Infliximab, a specific monoclonal antibody of TNF-α, inhibit TNF-α-induced ROS production. In summary, our results revealed that TNF-α is a cellular target of AU, and the interaction between AU and sTNF-α may mitigate PAGln/PAGly-induced vascular oxidative stress by inhibiting the interaction of TNF-α-TNFR1.

Background: Cholinomimetic compounds are a class of organic compounds found in natural plants that have significant biological activity as well as toxicity, and their dosage must be controlled, with side effects occurring in case of accidental ingestion or excessive intake. Accurate determination of four cholinomimetic compounds in edible fungi and areca nut can provide technical support to the relevant monitoring organizations, which is conducive to the protection of consumer health. In this study, we have established a workflow for the rapid screening and confirmation of four cholinomimetics in edible fungi and areca nut by using the QuEChERS pretreatment method and ultra‐high performance liquid chromatography coupled with quadrupole/time‐of‐flight mass spectrometry (UPLC‐Q‐TOF/MS) for the first time. Methods: The samples were extracted with acetonitrile, and separation was achieved on a HILIC column (2.1 mm × 100 mm, 1.6 μm) with acetonitrile and 20 mM ammonium formate aqueous solution as mobile phase with gradient elution. UPLC‐Triple TOF™6600 ⁺ was used to collect the data of the target analytes in the mode of TOF‐MS‐IDA‐MS/MS, and the data were analyzed by SCIEX OS software to realize the qualitative screening and confirmation of samples. Results: The mass accuracy error of 4 cholinomimetics was lower than 5.0 × 10 ⁻⁶ . All four cholinomimetic compounds had good linearity in a certain range, and the correlation coefficient ( R ² ) was higher than 0.998. The limits of detection and limits of quantification of the method were 2.5–25.0 μg/kg and 5.0–50.0 μg/kg, respectively. The recoveries were between 81.0% and 99.1% at spiked level 5.0–500.0 μg/kg, with the relative standard deviation of 0.41%–4.00%. Conclusion: The method is sensitive, accurate, and suitable for rapid screening and confirmation of 4 cholinomimetics in edible fungi and areca nut.