Yuhong Lyu

Inflammation is a defensive response of the body to external stimuli. However, excessive or dysregulated inflammatory responses contribute to various chronic diseases, with neurodegenerative disorders accounting for approximately 30% of the global disease burden. Flavonoids are natural polyphenolic compounds widely distributed in plants. Unlike conventional anti-inflammatory drugs, which tend to induce drug resistance and cause severe side effects, these natural dietary components exhibit low toxicity, offering a safer alternative for the intervention of chronic inflammatory diseases, with particularly notable advantages in long-term therapeutic applications. Accumulating evidence indicates that they exert synergistic anti-inflammatory effects through multiple targets and pathways. In neuroinflammatory diseases, the interventional effects of these natural compounds are particularly prominent: nobiletin inhibits β-Amyloid (Aβ) aggregation via the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway to ameliorate Alzheimer’s disease (AD) pathology; baicalin alleviates neuroinflammation through the Nuclear factor erythroid 2-related factor 2-NOD-like receptor thermal protein domain associated protein 3 (Nrf2-NLRP3) axis to protect dopaminergic neurons in Parkinson’s disease (PD) ; luteolin reduces mutant huntingtin protein aggregation to mitigate the progression of Huntington’s disease (HD) ; quercetin activates the Sestrin2/adenosine monophosphate-activated protein kinase/sirtuin 1 (Sestrin2/AMPK/SIRT1) pathway to delay motor neuron degeneration in amyotrophic lateral sclerosis (ALS) . Additionally, this review further analyzes the key challenges in the clinical translation of flavonoids, including insufficient blood-brain barrier penetration, limited bioavailability in vivo, and limitations of experimental models. To address these challenges, this review focuses on food science-oriented strategies, emphasizing two core directions: the construction of nanodelivery systems and molecular structural modification. while integrating advanced approaches such as humanized models, aiming to provide a theoretical basis and translational pathway for the clinical application of flavonoids in neuroinflammatory intervention.

In this study, we constructed an oral vaccine by expressing fusion antigens of African swine fever virus (ASFV) on the surface of Bacillus subtilis spores and explored its immunogenicity. Fusion proteins were designed, and recombinant strains that could stably express target proteins on the spore surface were successfully constructed. After oral immunization of rats, the spleen index and the levels of ASFV-specific IgG, interleukin-2, and interferon-γ were markedly increased, indicating effective activation of humoral and cellular immunity. This study established a reliable spore surface display system. The recombinant spores triggered favorable immune responses in vivo, providing an experimental foundation for the development of novel ASFV oral vaccines.

Objective To elucidate the potential molecular mechanism of baicalein in the treatment of allergic contact dermatitis (ACD). Methods An in vitro inflammatory model was established using human keratinocytes (HaCaT cells) stimulated with tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ). The regulatory effect of baicalein on inflammatory factors was detected by quantitative real time polymerase chain reaction. Network pharmacology was applied to screen the common targets of baicalein and ACD. Key signaling pathways were predicted via a protein protein interaction (PPI) network and pathway enrichment analysis, and the binding capacity of baicalein to core targets was evaluated by molecular docking. Results In vitro experiments showed that baicalein significantly reduced the expression of pro-inflammatory factors in HaCaT cells induced by TNF-α combined with IFN-γ, but had no significant effect on the T helper 1 (Th1)/T helper 17(Th17)cell imbalance, suggesting that its anti inflammatory mechanism was not completely dependent on inflammatory pathways such as T cell activation and Th17 differentiation. A total of 46 potential targets of baicalein for ACD were screened by network pharmacology, and the functional enrichment was associated with inflammatory pathways including T cell activation and Th17 differentiation. Furthermore, 11 core targets were obtained from the 46 potential targets using CytoHubba and MCODE algorithms. Molecular docking results demonstrated that baicalein exhibited high binding affinity to core targets related to the cytochrome P450 (CYP450) family, among which the affinity with CYP1A1 was the highest (binding energy=-10.17 kcal.mol^-1, RMSD=1.14 ). Conclusion Baicalein exhibits significant therapeutic potential against ACD. It can downregulate the expression of inflammatory factors in HaCaT cells induced by TNF-α combined with IFN-γ, and its mechanism may be related to the interactions with CYP450 family-related targets.

The occurrence and progression of liver cancer are closely associated with mitochondrial dysfunction. Mitochondria exhibit characteristics, such as decreased oxidative phosphorylation efficiency, abnormal accumulation of reactive oxygen species in liver cancer and promoting tumor proliferation and drug resistance through the Warburg effect, as the core of energy metabolism and apoptosis regulation. Mutations in mitochondrial DNA (mtDNA) and dysregulation of mitochondrial autophagy (mitophagy) further enhance the invasive and metastatic capabilities of liver cancer. Current targeted therapeutic strategies focus on modulating the activity of respiratory chain complexes, regulating calcium homeostasis, repairing mtDNA, and activating mitochondrial apoptotic pathways. Although these approaches have shown therapeutic effects, challenges persist, such as tumor heterogeneity, insufficient drug specificity, and drug resistance. Future research needs to integrate the concept of precision medicine by focusing on breakthroughs in the molecular mechanisms underlying mitochondrial dysfunction, development of targeted delivery systems, optimization of combination therapy regimens, and screening of biomarkers to provide new pathways for individualized treatment. With advances in technology, targeting mitochondrial dysfunction is expected to become an important breakthrough for improving the prognosis of liver cancer.

The cure rate for chronic neurodegenerative diseases remains low, creating an urgent need for improved intervention methods. Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases. This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases, aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options. We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy, inhibiting mitochondrial fission, enhancing mitochondrial biogenesis, applying mitochondria-targeting antioxidants, and transplanting mitochondria. Each method has unique advantages and potential limitations, making them suitable for various therapeutic situations. Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression, especially in the early stages. In contrast, those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism. Mitochondrial transplantation, while still experimental, holds great promise for restoring the function of damaged cells. Future research should focus on exploring the mechanisms and effects of these intervention strategies, particularly regarding their safety and efficacy in clinical settings. Additionally, the development of innovative mitochondria-targeting approaches, such as gene editing and nanotechnology, may provide new solutions for treating chronic neurodegenerative diseases. Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.

Purpose: To explore the protective effects and mechanisms of Jiawei Qifuyin on APP/PS1 mice, a model for Alzheimer’s disease (AD). Methods: Network pharmacology tools were used to predict anti-AD targets and signaling pathways affected by Jiawei Qifuyin. In vitro studies assessed antioxidant and oxygen radical scavenging abilities, immune cell proliferation, and inflammatory cytokine levels in lipopolysaccharide-induced BV2 microglial cells. Cognitive ability in APP/PS1 mice was evaluated using the Morris Water Maze test. mRNA expression of neuroinflammatory factors, changes in intestinal microbiota, and short-chain fatty acid content were analyzed post-treatment. Results: Network pharmacology predicted that Jiawei Qifuyin affects AKT1, TNF-α, and AGE/RAGE pathways. It showed concentration-dependent antioxidant effects and modulated immune cell proliferation. IL-2, IL-6, and TNF-α levels in LPS-induced BV2 cells were significantly reduced. Treated animals exhibited improved cognitive performance, decreased brain amyloid-beta levels, and downregulated expression of IL-1β, IL-6, RAGE, and NF-κB. Significant changes in intestinal microbiota composition and SCFA content were observed. Conclusion: Jiawei Qifuyin may enhance immunity and improve cognitive impairment in APP/PS1 mice through regulation of inflammatory factors, gut microbiota, and the gut-brain axis.

The Qa-1 in mice is homologous to human leukocyte antigen E(HLA-E), and both of them belong to the non-classical major histocompatibility complex I b(MHC-I b) molecules. Qa-1 is capable of presenting self or exogenous antigen peptides to interact with two distinct receptors, namely T cell receptor (TCR) and natural killer cell group 2 member A (or C) (NKG2A/C), thus playing an important role in immune response and regulation. Qa-1-restricted regulatory CD8⁺ T cell (CD8⁺ Treg) is one of the most studied CD8⁺ Treg subgroups, which can maintain immune homeostasis and autoimmune tolerance by exerting immunosuppressive effects. Consequently, Qa-1-restricted CD8⁺Treg cells are closely associated with the occurrence and development of various clinical diseases, such as tumors, infections, autoimmune diseases, and transplant rejections. This paper provides a comprehensive review of the phenotypic characteristics, functional effects, regulatory mechanisms of Qa-1-restricted CD8⁺ Treg cells, as well as the latest research progresses of Qa-1-restricted CD8⁺ Treg cells involved in the pathogenesis of infectious diseases.

Objective: To explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia.Methods: ELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC–MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention.Results: The content of GABA and L-theanine in 7 L fermentation products was 12.555 μmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p < 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p < 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1β and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids.Conclusion: Probiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.

Previous investigations have illuminated the significant association between the gut microbiome and a broad spectrum of health conditions, including obesity, diabetes, cardiovascular diseases, and psychiatric disorders. Evidence from certain studies suggests that dysbiosis of the gut microbiota may play a role in the etiology of obesity and diabetes. Moreover, it is acknowledged that dietary habits, pharmacological interventions, psychological stress, and other exogenous factors can substantially influence the gut microbial composition. For instance, a diet rich in fiber has been demonstrated to increase the population of beneficial bacteria, whereas the consumption of antibiotics can reduce these advantageous microbial communities. In light of the established correlation between the gut microbiome and various pathologies, strategically altering the gut microbial profile represents an emerging therapeutic approach. This can be accomplished through the administration of probiotics or prebiotics, which aim to refine the gut microbiota and, consequently, mitigate the manifestations of associated diseases. The present manuscript evaluates the recent literature on the relationship between gut microbiota and metabolic syndrome published over the past three years and anticipates future directions in this evolving field.

Previous investigations have illuminated the significant association between the gut microbiome and a broad spectrum of health conditions, including obesity, diabetes, cardiovascular diseases, and psychiatric disorders. Evidence from certain studies suggests that dysbiosis of the gut microbiota may play a role in the etiology of obesity and diabetes. Moreover, it is acknowledged that dietary habits, pharmacological interventions, psychological stress, and other exogenous factors can substantially influence the gut microbial composition. For instance, a diet rich in fiber has been demonstrated to increase the population of beneficial bacteria, whereas the consumption of antibiotics can reduce these advantageous microbial communities. In light of the established correlation between the gut microbiome and various pathologies, strategically altering the gut microbial profile represents an emerging therapeutic approach. This can be accomplished through the administration of probiotics or prebiotics, which aim to refine the gut microbiota and, consequently, mitigate the manifestations of associated diseases. The present manuscript evaluates recent literature on the relationship between gut microbiota and metabolic syndrome published over the past three years and anticipates future directions in this evolving field.