A Static Magnetic Field Improves Iron Metabolism and Prevents High-Fat-Diet/Streptozocin-Induced Diabetes.
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ABSTRACT:
SUBMITTER: Yu B
PROVIDER: S-EPMC8454665 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveWith the deepening of magnetic biomedical effects and electromagnetic technology, some medical instruments based on static magnetic field (SMF) have been used in orthopedic-related diseases treatment. Studies have shown SMF could combat osteoporosis by regulating the differentiation of mesenchymal stem cells (MSCs), osteoblast and osteoclast. With the development of nanotechnology, iron oxide nanoparticles (IONPs) have been reported to regulate the process of bone anabolism. As for SMF combined with IONPs, studies indicated osteogenic differentiation of MSCs were promoted by the combination of SMF and IONPs. However, there are few reports on the effects of SMF combined with IONPs on osteoclast. Herein, the purpose of this study was to investigate the effects of high static magnetic field (HiSMF) combined with IONPs on unloading-induced bone loss in vivo and osteoclastic formation in vitro, and elucidated the potential molecular mechanisms.MethodsIn vivo, C57BL/6 J male mice were unloaded via tail suspension or housed normally. The hindlimb of mice were fixed and exposed to 1-2 T SMF for 1 h every day, 10 mg/kg of Ferumoxytol or saline were injected by tail vein once a week, last for 4 weeks. Bone microstructure, mechanical properties, and osteoclastogenesis were examined respectively. In vitro, the RAW264.7 cells were used to assess the effects of 1-2 T SMF combined with IONPs in osteoclastogenesis. The iron content was detected by atomic absorption spectrometry and Prussian blue staining. DCFH-DA and MitoSOX™ fluorescence staining were used to assess oxidative stress levels. NF-κB and MAPK signaling pathways were examined by western blot assay.ResultsIn vivo, the results showed 1-2 T SMF and IONPs prevented the damage to bone microstructure and improved the mechanical properties, diminished the number of osteoclasts in unloaded mice, 1-2 T SMF combined with IONPs was found more effective. The iron content in the liver and spleen was reduced by the combination of 1-2 T SMF and IONPs, enhancing iron levels in the femur. In vitro, osteoclast formation was inhibited by 1-2 T SMF and IONPs treatment, and 1-2 T SMF combined with IONPs had a more pronounced effect. Moreover, iron uptake of IONPs in osteoclast was reduced to 1-2 T SMF exposure. Oxidative stress levels were decreased in osteoclast differentiation under 1-2 T SMF combined with IONPs treatment. Molecularly, the expression of NF-κB and MAPK signaling pathways were inhibited under 1-2 T SMF combined with IONPs in osteoclastogenesis.ConclusionsSynthetically, our research illustrated 1-2 T SMF combined with IONPs prevented unloading-induced bone loss by regulating iron metabolism in osteoclastogenesis.Translational potential of this article: As a non-invasive alternative therapy, some medical instruments based on SMF have been used for orthopedic-related diseases treatment for their portability, cheapness and safety. Ferumoxytol (Feraheme™), the first FDA-approved IONP drug for the treatment of iron deficiency anemia, has been also adapted in translational research for osteoporosis. Based on the above-mentioned two points, we found the synergistic effects of SMF and Ferumoxytol for treatment of experimental osteoporosis. These results show translational potentials for clinical application.
| S-EPMC9646753 | biostudies-literature
Project description:ObjectiveGiven that the prevalence rate of type 2 diabetes mellitus (T2DM) continues to increase, it is important to find an effective method to prevent or treat this disease. Previous studies have shown that dietary intervention with a slowly digestible carbohydrate (SDC) diet can improve T2DM with almost no side effects. However, the underlying mechanisms of SDC protect against T2DM remains to be elucidated.MethodsThe T2DM mice model was established with a high-fat diet and streptozocin injection. Then, SDC was administered for 6 weeks. Bodyweight, food intake, organ indices, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), homeostasis model assessment for insulin resistance (HOMA-IR), and other biochemical parameters were measured. Histopathological and lipid accumulation analyses were performed, and the glucose metabolism-related gene expressions in the liver and skeletal muscle were determined. Lastly, colonic microbiota was also analyzed.ResultsSDC intervention alleviated the weight loss in the pancreas, lowered blood glucose and glycosylated hemoglobin levels, and improved glucose tolerance and HOMA-IR. SDC intervention improved serum lipid profile, adipocytokines levels, and lowered the lipid accumulation in the liver, subcutaneous adipose tissue, and epididymal visceral adipose tissue. In addition, SDC intervention increased the expression levels of IRS-2 and GLUT-2 in liver tissues and elevated GLUT-4 expression levels in skeletal muscle tissues. Notably, SDC intervention decreased the Bacteroidetes/Firmicutes ratio, increased Desulfovibrio and Lachnospiraceae genus levels, and inhibited the relative abundance of potentially pathogenic bacteria.ConclusionsSDC intervention can improve hyperglycemia and hyperlipidemia status in diabetic mice, suggesting that this intervention might be beneficial for T2DM.
| S-EPMC9051025 | biostudies-literature
Project description:Mannose is an important monosaccharide for protein glycosylation in mammals but is an inefficient cellular energy source. Using a C57BL6/J mouse model of diet-induced obesity, we show that mannose supplementation of high-fat-diet-fed mice prevents weight gain, lowers adiposity, reduces liver steatosis, increases endurance and maximal O2 consumption, and improves glucose tolerance. Mannose-supplemented mice have higher fecal energy content, suggesting reduced caloric absorption by the host. Mannose increases the Bacteroidetes to Firmicutes ratio in the gut microbiota, a signature associated with the lean phenotype. These beneficial effects of mannose are observed when supplementation is started early in life. Functional transcriptomic analysis of cecal microbiota revealed profound and coherent changes in microbial energy metabolism induced by mannose that are predicted to lead to reduced energy harvest from complex carbohydrates by gut microbiota. Our results suggest that the gut microbiota contributes to mannose-induced resistance to deleterious effects of a high-fat diet. VIDEO ABSTRACT.
| S-EPMC6207501 | biostudies-literature
Project description:Understanding how a magnetic field affects the interaction of magnetic nanoparticles (MNPs) with cells is fundamental to any potential downstream applications of MNPs as gene and drug delivery vehicles. Here, we present a quantitative analysis of how a pulsed magnetic field influences the manner in which MNPs interact with and penetrate across a cell monolayer. Relative to a constant magnetic field, the rate of MNP uptake and transport across cell monolayers was enhanced by a pulsed magnetic field. MNP transport across cells was significantly inhibited at low temperature under both constant and pulsed magnetic field conditions, consistent with an active mechanism (i.e., endocytosis) mediating MNP transport. Microscopic observations and biochemical analysis indicated that, in a constant magnetic field, transport of MNPs across the cells was inhibited due to the formation of large (>2 ?m) magnetically induced MNP aggregates, which exceeded the size of endocytic vesicles. Thus, a pulsed magnetic field enhances the cellular uptake and transport of MNPs across cell barriers relative to a constant magnetic field by promoting accumulation while minimizing magnetically induced MNP aggregation at the cell surface.
| S-EPMC3609927 | biostudies-literature
Project description:Many studies have indicated that static magnetic fields (SMFs) have positive effects on bone tissue, including bone formation and bone healing process. Evaluating the effects of SMFs on bone cell (especially osteoblast) function and exploring the mechanism, which is critical for understanding the possible risks or benefits from SMFs to the balance of bone remodeling. Iron and magnetic fields have the natural relationship, and iron is an essential element for normal bone metabolism. Iron overload or deficiency can cause severe bone disorders including osteoporosis. However, there are few reports regarding the role of iron in the regulation of bone formation under SMFs. In this study, hypomagnetic field (HyMF) of 500 nT, moderate SMF (MMF) of 0.2 T, and high SMF (HiMF) of 16 T were used to investigate how osteoblast (MC3T3-E1) responses to SMFs and iron metabolism of osteoblast under SMFs. The results showed that SMFs did not pose severe toxic effects on osteoblast growth. During cell proliferation, iron content of osteoblast MC3T3-E1 cells was decreased in HyMF, but was increased in MMF and HiMF after exposure for 48 h. Compared to untreated control (i.e., geomagnetic field, GMF), HyMF and MMF exerted deleterious effects on osteoblast differentiation by simultaneously retarding alkaline phosphatase (ALP) activity, mineralization and calcium deposition. However, when exposed to HiMF of 16 T, the differentiation potential showed the opposite tendency with enhanced mineralization. Iron level was increased in HyMF, constant in MMF and decreased in HiMF during cell differentiation. In addition, the mRNA expression of transferrin receptor 1 (TFR1) was promoted by HyMF but was inhibited by HiMF. At the same time, HiMF of 16 T and MMF of 0.2 T increased the expression of ferroportin 1 (FPN1). In conclusion, these results indicated that osteoblast differentiation can be regulated by altering the strength of the SMF, and iron is possibly involved in this process.
| S-EPMC5992240 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-11-06 | GSE110796 | GEO
Project description:Neural proliferation and differentiation fates of pluripotent stem cells are influenced by external natural forces. Despite the presence of biogenic magnetite nanoparticles in the central nervous system and constant exposure to Earth’s magnetic fields and other sources, there has been scant knowledge regarding the role of electromagnetic stimuli in neurogenesis. Moreover, the emerging application of electrical and magnetic stimulation to treat neurological disorders emphasizes the relevance of understanding the impact and mechanisms behind these stimuli. Here, the effects of magnetic nanoparticles (MNPs) contained in polymeric coatings and the static external magnetic field (EMF, 0.4 Tesla) were investigated on neural induction of murine embryonic stem cells (mESCs) and human induced pluripotent stem cells (hiPSCs) into induced dopaminergic neurons (iDA).
2021-12-17 | GSE190686 | GEO
Project description:BackgroundThe therapeutic potential of exosomes derived from stem cells has attracted increasing interest recently, because they can exert similar paracrine functions of stem cells and overcome the limitations of stem cells transplantation. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been confirmed to promote osteogenesis and angiogenesis. The magnetic nanoparticles (eg. Fe3O4, γ-Fe2O3) combined with a static magnetic field (SMF) has been commonly used to increase wound healing and bone regeneration. Hence, this study aims to evaluate whether exosomes derived from BMSCs preconditioned with a low dose of Fe3O4 nanoparticles with or without the SMF, exert superior pro-osteogenic and pro-angiogenic activities in bone regeneration and the underlying mechanisms involved.MethodsTwo novel types of exosomes derived from preconditioned BMSCs that fabricated by regulating the contents with the stimulation of magnetic nanoparticles and/or a SMF. Then, the new exosomes were isolated by ultracentrifugation and characterized. Afterwards, we conducted in vitro experiments in which we measured osteogenic differentiation, cell proliferation, cell migration, and tube formation, then established an in vivo critical-sized calvarial defect rat model. The miRNA expression profiles were compared among the exosomes to detect the potential mechanism of improving osteogenesis and angiogenesis. At last, the function of exosomal miRNA during bone regeneration was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro.Results50 µg/mL Fe3O4 nanoparticles and a 100 mT SMF were chosen as the optimum magnetic conditions to fabricate two new exosomes, named BMSC-Fe3O4-Exos and BMSC-Fe3O4-SMF-Exos. They were both confirmed to enhance osteogenesis and angiogenesis in vitro and in vivo compared with BMSC-Exos, and BMSC-Fe3O4-SMF-Exos had the most marked effect. The promotion effect was found to be related to the highly riched miR-1260a in BMSC-Fe3O4-SMF-Exos. Furthermore, miR-1260a was verified to enhance osteogenesis and angiogenesis through inhibition of HDAC7 and COL4A2, respectively.ConclusionThese results suggest that low doses of Fe3O4 nanoparticles combined with a SMF trigger exosomes to exert enhanced osteogenesis and angiogenesis and that targeting of HDAC7 and COL4A2 by exosomal miR-1260a plays a crucial role in this process. This work could provide a new protocol to promote bone regeneration for tissue engineering in the future.
| S-EPMC8278669 | biostudies-literature
Project description:Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (T2DM). This study was performed to investigate the antidiabetic effect of Bacillus toyonensis SAU-19 and its possible mechanisms of action in mice with type 2 diabetes mellitus (T2DM). Thirty SPFKM mice were randomly assigned to three groups: control, diabetic model, and diabetes + Bacillus toyonensis SAU-19 group. After 35 days, blood was collected for biochemical analysis and liver tissue samples for histopathological analysis using H&E staining, qPCR, and ELISA. The results showed that the administration of B. toyonensis SAU-19 significantly improved the blood glucose, hepatic insulin resistance, and morphological changes of the liver characterized by significant improvement of dyslipidemia, glycogen synthesis, and antioxidant status (p < 0.05), indicating the strains' ameliorating effects on hepatic insulin resistance in T2DM. In conclusion, the probiotic strain (B. toyonensis SAU-19) inhibits T2DM by reducing insulin resistance, improving antioxidant status, and downregulating genes related to glucose synthesis; hence, it may be used in treating diabetes and other metabolic disorders. This study provides the basis for further studies into the molecular mechanisms of B. toyonensis SAU-19 in treating T2DM.
| S-EPMC8703646 | biostudies-literature
Project description:Ginsenoside is a major active component of ginseng, which exhibits various pharmacological properties such as hepatoprotection, tumor suppression and diabetes resistance. In this study, the anti-diabetic effects of protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins were explored and compared in high-fat diet/streptozocin-induced type 2 diabetes mellitus (T2DM) mice. Our results showed that low or high dose (50 mg/kg bodyweight or 150 mg/kg bodyweight) PPD and PPT significantly reduced fasting blood glucose, improved glucose tolerance and insulin resistance in T2DM mice. PPD and PPT also regulated serum lipid-related markers such as reduced total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol in T2DM mice. In addition, PPD and PPT dramatically ameliorated the inflammatory responses by suppressing the secretion of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-6 in serum level and gene expression in liver level, and improved the antioxidant capacity by increasing the superoxide dismutase and decreasing malondialdehyde levels in the serum of T2DM mice. Moreover, the anti-diabetic effect of PPD and PPT appeared to be partially mediated by the suppression of hepatic metabolism genes expression such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase, as well as facilitating lipid metabolism genes expression such as microsomal TG transfer protein in the liver tissues of T2DM mice. Taken together, our results indicated that PPD and PPT might potentially act as natural anti-diabetic compounds to be used for preventing and treating the T2DM and its complications in the future.
| S-EPMC5539091 | biostudies-other