Exploring the Potential of Glycolytic Modulation in Myeloid-Derived Suppressor Cells for Immunotherapy and Disease Management.

Recent advancements in various technologies have shed light on the critical role of metabolism in immune cells, paving the way for innovative disease treatment strategies through immunometabolism modulation. This review emphasizes the glucose metabolism of myeloid-derived suppressor cells (MDSCs), an emerging pivotal immunosuppressive factor especially within the tumor microenvironment. MDSCs, an immature and heterogeneous myeloid cell population, act as a double-edged sword by exacerbating tumors or mitigating inflammatory diseases through their immune-suppressive functions. Numerous recent studies have centered on glycolysis of MDSC, investigating the regulation of altered glycolytic pathways to manage diseases. However, the specific changes in MDSC glycolysis and their exact functions continue to be areas of ongoing discussion yet. In this paper, we review a range of current findings, including the latest research on the alteration of glycolysis in MDSCs, the consequential functional alterations in these cells, and the outcomes of attempts to modulate MDSC functions by regulating glycolysis. Ultimately, we will provide insights into whether these research efforts could be translated into clinical applications.

Lactobacillus plantarum isolated from kimchi regulates inflammation by increasing interleukin-10 secretion by antigen-presenting cells, leading to diminishing of STAT5 phosphorylation in Th2 cells.

The relationship between allergic inflammation and gut microbiota has been elucidated, and the effect of probiotics on immune disorders has been studied as well. Identifying the role of probiotics in individual diseases and immune responses and selecting and applying specific microorganisms based on these findings can be an effective strategy for using probiotics. Herein, lactobacilli isolated from kimchi were investigated in depth, focusing on their immune regulatory effects and the mechanisms involved. Lactic acid bacteria (LAB) effectively diminished the increased secretion of T helper 2 cytokines, such as IL-4, IL-5, and IL-13, from ovalbumin (OVA)-sensitized mouse splenocytes. The gene expression of GATA3, IL-4, IL-5, IL-9, and IL-13 was confirmed to be regulated by LAB. LAB also suppressed IL-2 production and STAT5 phosphorylation. An IL-10-neutralizing antibody attenuated these effects, indicating that LAB-induced upregulation of IL-10 in antigen-presenting cells was responsible at least partially for the increased IL-2 production and STAT5 phosphorylation in CD4+ T cells. In conclusion, the current study identified one immunomodulatory mechanism that allows LAB to regulate allergic immune reactions and the potential of LAB from kimchi to modulate various immune reactions.

Neuroprotective Effects of Davallia mariesii Roots and Its Active Constituents on Scopolamine-Induced Memory Impairment in In Vivo and In Vitro Studies.

Beta-amyloid (Aß) proteins, major contributors to Alzheimer's disease (AD), are overproduced and accumulate as oligomers and fibrils. These protein accumulations lead to significant changes in neuronal structure and function, ultimately resulting in the neuronal cell death observed in AD. Consequently, substances that can inhibit Aß production and/or accumulation are of great interest for AD prevention and treatment. In the course of an ongoing search for natural products, the roots of Davallia mariesii T. Moore ex Baker were selected as a promising candidate with anti-amyloidogenic effects. The ethanol extract of D. mariesii roots, along with its active constituents, not only markedly reduced Aß production by decreasing ß-secretase expression in APP-CHO cells (Chinese hamster ovary cells which stably express amyloid precursor proteins), but also exhibited the ability to diminish Aß aggregation while enhancing the disaggregation of Aß aggregates, as determined through the Thioflavin T (Th T) assay. Furthermore, in an in vivo study, the extract of D. mariesii roots showed potential (a tendency) for mitigating scopolamine-induced memory impairment, as evidenced by results from the Morris water maze test and the passive avoidance test, which correlated with reduced Aß deposition. Additionally, the levels of acetylcholine were significantly elevated, and acetylcholinesterase levels significantly decreased in the brains of mice (whole brains). The treatment with the extract of D. mariesii roots also led to upregulated brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding protein (p-CREB) in the hippocampal region. These findings suggest that the extract of D. mariesii roots, along with its active constituents, may offer neuroprotective effects against AD. Consequently, there is potential for the development of the extract of D. mariesii roots and its active constituents as effective therapeutic or preventative agents for AD.

Anti-Amyloidogenic Effects of Metasequoia glyptostroboides Fruits and Its Active Constituents.

Alzheimer's disease (AD) is a serious neurodegenerative brain disease that interferes with daily life. The accumulation of beta-amyloid (Aß), along with oxidative stress-inducing neurocellular apoptosis, has been considered one of the causes of AD. Thus, the purpose of this study is to find natural products that can reduce Aß accumulation. The ethanol extract of Metasequoia glyptostroboides Hu & Cheng fruits (Cupressaceae) significantly reduced the aggregation of Aß into oligomers and fibrils determined by Thioflavin T (ThT) assay. The solvent-partitioned ethyl acetate layer was further separated based on the bioassay-guided isolation method combined with the ThT assay. As a result, five compounds were isolated and elucidated as taxoquinone (1), sugiol (2), suginal (3), sandaracopimarinol (4), and sandaracopimaradien-19-ol (5) by comparing NMR data with references. All the compounds significantly reduced the aggregation of Aß and enhanced the disaggregation of pre-formed Aß aggregates in a dose-dependent manner. Furthermore, the inhibition of Aß aggregation by the compounds protected PC12 cells from Aß aggregate-induced toxicity. Among the five compounds, sandaracopimarinol (4) and sandaracopimaradien-19-ol (5) were the most effective. These results suggest that M. glyptostroboides and isolated five compounds have a potential for further study to be developed as anti-AD agents.