Sciadonic acid ameliorates cyclophosphamide-induced immunosuppression by modulating the immune response and altering the gut microbiota.

BACKGROUND: Cyclophosphamide (Cy) is a frequently used chemotherapeutic drug, but long-term Cy treatment can cause immunosuppression and intestinal mucosal damage. The intestinal mucosal barrier and gut flora play important roles in regulating host metabolism, maintaining physiological functions and protecting immune homeostasis. Dysbiosis of the intestinal flora affects the development of the intestinal microenvironment, as well as the development of various external systemic diseases and metabolic syndrome. RESULTS: The present study investigated the influence of sciadonic acid (SA) on Cy-induced immunosuppression in mice. The results showed that SA gavage significantly alleviated Cy-induced immune damage by improving the immune system organ index, immune response and oxidative stress. Moreover, SA restored intestinal morphology, improved villus integrity and activated the nuclear factor κB signaling pathway, stimulated cytokine production, and reduced serum lipopolysaccharide (LPS) levels. Furthermore, gut microbiota analysis indicated that SA increased t beneficial bacteria (Alistipes, Lachnospiraceae_NK4A136_group, Rikenella and Odoribacter) and decreased pathogenic bacteria (norank-f-Oscillospiraceae, Ruminococcus and Desulfovibrio) to maintain intestinal homeostasis. CONCLUSION: The present study provided new insights into the SA regulation of intestinal flora to enhance immune responses. © 2024 Society of Chemical Industry.

Isopimaric acid, an ion channel regulator, regulates calcium and oxidative phosphorylation pathways to inhibit breast cancer proliferation and metastasis.

Breast cancer is the globally most common malignant tumor and the biggest threat to women. Even though the diagnosis and treatment of breast cancer are progressing continually, a large number of breast cancer patients eventually develop a metastatic tumor, especially triple-negative breast cancer (TNBC). Recently, metal ion homeostasis and ion signaling pathway have become important targets for cancer therapy. In this study, We analyzed the effects and mechanisms of isopimaric acid (IPA), an ion channel regulator, on the proliferation and metastasis of breast cancer cells (4 T1, MDA-MB-231and MCF-7) by cell functional assay, flow cytometry, western blot, proteomics and other techniques in vitro and in vivo. Results found that IPA significantly inhibited the proliferation and metastasis of breast cancer cells (especially 4 T1). Further studies on the anti-tumor mechanism of IPA suggested that IPA might affect EMT and Wnt signaling pathways by targeting mitochondria oxidative phosphorylation and Ca2+ signaling pathways, and then inducing breast cancer cell cycle arrest and apoptosis. Our research reveals the therapeutic value of IPA in breast cancer and provides a theoretical basis for the new treatment of breast cancer.

Environmental quality assessment of heavy metals in the Rongcheng offshore area, Shandong Peninsula, China.

Eighteen surface sediment samples collected from the Rongcheng offshore area of China in 2021 were analyzed for heavy metal concentrations, sources, and pollution status. The Cu, Zn, Cr, Cd, As, and total organic carbon (TOC) distributions were similar. In contrast, the distributions of Pb and Hg were irregular, and high concentrations appeared in two or several areas. Occasional adverse effects were observed from pollution caused by Cu, Pb, and As, and none of the heavy metal concentrations exceeded the probable effect level (PEL). The Pearson's correlation coefficient, geoaccumulation index, and principal component analysis were used to distinguish the sources and assess the pollution risk of heavy metals. The results showed that heavy metals did not pollute the surface sediments in the Rongcheng offshore area and that the metals were mainly derived from natural sources.

Sciadonic acid attenuates high-fat diet-induced bone metabolism disorders in mice.

High-fat diet (HFD) has been associated with certain negative bone-related outcomes, such as bone metabolism disruption and bone loss. Sciadonic acid (SC), one of the main nutritional and functional components of Torreya grandis seed oil, is a unique Δ5-unsaturated-polymethylene-interrupted fatty acid (Δ5-UPIFA) that has been claimed to counteract such disorders owing to some of its physiological effects. However, the role of SC in ameliorating bone metabolism disorders due to HFD remains unclear. In the present investigation, we observed that SC modulates the OPG/RANKL/RANK signaling pathway by modifying the lipid metabolic state and decreasing inflammation in mice. In turn, it could balance bone resorption and formation as well as calcium and phosphorus levels, enhance bone strength and bone mineral density (BMD), and improve its microstructure. In addition, SC could inhibit fat vacuoles in bone, reverse the phenomenon of reduced numbers and poor continuity of bone trabeculae, and promote orderly arrangement of collagen fibers and cartilage repair. This study provides some theoretical basis for SC as a dietary intervention agent to enhance bone nutrition.

Sciadonic acid attenuates high-fat diet-induced obesity in mice with alterations in the gut microbiota.

Obesity has been reported to be associated with dysbiosis of gut microbiota. Sciadonic acid (SC) is one of the main functional components of Torreya grandis "Merrillii" seed oil. However, the effect of SC on high-fat diet (HFD)-induced obesity has not been elucidated. In this study, we evaluated the effects of SC on lipid metabolism and the gut flora in mice fed with a high-fat diet. The results revealed that SC activates the PPARα/SREBP-1C/FAS signaling pathway and reduces the levels of total cholesterol (TC), triacylglycerols (TG), and low-density lipoprotein cholesterol (LDL-C), but increases the level of high-density lipoprotein cholesterol (HDL-C) and inhibits weight gain. Among them, high-dose SC was the most effective; the TC, TG and LDL-C levels were reduced by 20.03%, 28.40% and 22.07%, respectively; the HDL-C level was increased by 8.55%. In addition, SC significantly increased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels by 98.21% and 35.17%, respectively, decreased oxidative stress, and ameliorated the pathological damage to the liver caused by a high-fat diet. Furthermore, SC treatment altered the composition of the intestinal flora, promoting the relative abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, while simultaneously decreasing the relative abundance of potentially harmful bacteria such as Faecalibaculum, norank_f_Desulfovibrionaceae, and Romboutsia. Spearman's correlation analysis indicated that the gut microbiota was associated with SCFAs and biochemical indicators. In summary, our results suggested that SC can improve lipid metabolism disorders and regulate the gut microbial structure.

Distribution of heavy metals in coastal sediments under the influence of multiple factors: A case study from the south coast of an industrialized harbor city (Tangshan, China).

This research investigated the spatial distribution of heavy metals, including mercury (Hg), cadmium (Cd), copper (Cu), arsenic (As), nickel (Ni), lead (Pb), chromium (Cr), and zinc (Zn), in surface sediments from a coastal area near to an industrial harbor (Tangshan Harbor, China) using 161 sediment samples. According to the geo-accumulation index (Igeo), 11 samples were classified as unpolluted (Igeo≤0). Notably, 41.0 % of the research samples were moderately or strongly polluted (2 < Igeo≤3) with Hg and 60.2 % of the samples were moderately polluted (1 < Igeo≤2) in Cd. The ecological effect evaluation showed that the metals Zn, Cd, and Pb were at the effect range low level, and 51.6 % of the samples for Cu, 60.9 % for Cr, 90.7 % for As, 41.0 % for Hg, and 64.0 % for Ni fell in the range between the effect range-low and the effect range-mean levels, respectively. The correlation analysis showed that the distribution patterns of Cr, Cu, Zn, Ni, and Pb were similar to each other, high in the northwest, southeast, and southwest regions of the study area and low in the northeast region, which corresponded well with sediment size components. Based on principal component analysis (PCA) and positive matrix factorization (PMF), four distinct sources of pollution were quantitatively attributed, including agricultural activities (22.08 %), fossil fuel consumption (24.14 %), steel production (29.78 %), and natural sources (24.00 %). Hg (80.29 %), Cd (82.31 %) and As (65.33 %) in the region's coastal sediments were predominantly contributed by fossil fuel, steel production and agricultural sources, respectively. Cr (40.00 %), Cu (43.63 %), Ni (47.54 %), and Zn (38.98 %) were primarily of natural lithogenic origin, while Pb mainly came from the mixed sources of agricultural activities (36.63 %), fossil fuel (36.86 %), and steel production (34.35 %). Multiple factors played important roles in the selective transportation of sedimentary heavy metals, particularly sediment properties, and hydrodynamic sorting processes in the study area.

Antidiabetic effect of sciadonic acid on type 2 diabetic mice through activating the PI3K-AKT signaling pathway and altering intestinal flora.

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia. The aim of this work was to investigate the effect of sciadonic acid (SA) on disorders of glucolipid metabolism and intestinal flora imbalance and to further investigate its potential molecular mechanism of anti-diabetes. The experimental data indicated that SA could alleviate hyperlipidemia, insulin resistance, oxidative stress, the inflammatory response, repair liver function damage, and promote glycogen synthesis caused by T2DM. SA could also activate the PI3K/AKT/GLUT-2 signaling pathway, promote glucose metabolism gene expression, and maintain glucose homeostasis. Furthermore, 16S rRNA analysis revealed that SA could reduce the Firmicutes/Bacteroidota (F/B) ratio; promote norank_f__Muribaculaceae, Allobaculum, Akkermansia, and Eubacterium_siraeum_group proliferation; increase the levels of major short-chain fatty acids (SCFAs), such as acetic acid, propionic acid, and butyric acid; and maintain the homeostasis of the intestinal flora. In conclusion, these results suggested that SA could reshape the structural composition of intestinal microbes, activate the PI3K/AKT/GLUT2 pathway, improve insulin resistance, and decrease blood glucose levels.