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OBJECTIVE: To characterize the circadian features of the trigeminal ganglion in a mouse model of headache. BACKGROUND: Several headache disorders, such as migraine and cluster headache, are known to exhibit distinct circadian rhythms of attacks. The circadian basis for these rhythmic pain responses, however, remains poorly understood. METHODS: We examined trigeminal ganglion ex vivo and single-cell cultures from Per2::LucSV reporter mice and performed immunohistochemistry. Circadian behavior and transcriptomics were investigated using a novel combination of trigeminovascular and circadian models: a nitroglycerin mouse headache model with mechanical thresholds measured every 6 h, and trigeminal ganglion RNA sequencing measured every 4 h for 24 h. Finally, we performed pharmacogenomic analysis of gene targets for migraine, cluster headache, and trigeminal neuralgia treatments as well as trigeminal ganglion neuropeptides; this information was cross-referenced with our cycling genes from RNA sequencing data to identify potential targets for chronotherapy. RESULTS: The trigeminal ganglion demonstrates strong circadian rhythms in both ex vivo and single-cell cultures, with core circadian proteins found in both neuronal and non-neuronal cells. Using our novel behavioral model, we showed that nitroglycerin-treated mice display circadian rhythms of pain sensitivity which were abolished in arrhythmic Per1/2 double knockout mice. Furthermore, RNA-sequencing analysis of the trigeminal ganglion revealed 466 genes that displayed circadian oscillations in the control group, including core clock genes and clock-regulated pain neurotransmitters. In the nitroglycerin group, we observed a profound circadian reprogramming of gene expression, as 331 of circadian genes in the control group lost rhythm and another 584 genes gained rhythm. Finally, pharmacogenetics analysis identified 10 genes in our trigeminal ganglion circadian transcriptome that encode target proteins of current medications used to treat migraine, cluster headache, or trigeminal neuralgia. CONCLUSION: Our study unveiled robust circadian rhythms in the trigeminal ganglion at the behavioral, transcriptomic, and pharmacogenetic levels. These results support a fundamental role of the clock in pain pathophysiology. PLAIN LANGUAGE SUMMARY: Several headache diseases, such as migraine and cluster headache, have headaches that occur at the same time each day. We learned that the trigeminal ganglion, an important pain structure in several headache diseases, has a 24-hour cycle that might be related to this daily cycle of headaches. Our genetic analysis suggests that some medications may be more effective in treating migraine and cluster headache when taken at specific times of the day.
Subject(s)
Cluster Headache , Migraine Disorders , Trigeminal Neuralgia , Mice , Animals , Trigeminal Ganglion , Transcriptome , Trigeminal Neuralgia/genetics , Nitroglycerin , Headache , Gene Expression Profiling , Pain , Circadian Rhythm/genetics , Mice, KnockoutABSTRACT
OBJECTIVE: Micronutrient deficiencies are common complications after bariatric surgery as alterations to the gastrointestinal tract change absorption. Patients are recommended to take supplements including multivitamins, B complex, calcium, vitamin D, and iron after bariatric surgery, and can take these as specifically formulated vitamins for post-bariatric patients or separate vitamin supplements. We investigated the compliance, efficacy, and cost of specifically formulated vitamins for post-bariatric patients in comparison to separate vitamin supplements. METHODS: We surveyed 126 post-bariatric adult patients between February 1, 2022, and August 31, 2022, who had undergone bariatric surgery between 2014 and 2021 to assess the type of supplements taken, compliance, and cost. Demographics, type of bariatric surgery, and serum micronutrient levels were evaluated for all patients. RESULTS: There were 51 patients taking formulated vitamins and 75 patients taking separate vitamins. The formulated vitamin group demonstrated greater adherence to optimal vitamin dosage (formulated vitamin group, 76.5% vs. separate supplement group, 30.7%; p < 0.001) and higher compliance (formulated vitamin group, 90.2% vs. separate supplement group, 66.7%; p = 0.002). The costs associated with both groups were comparable. No significant difference was observed in the incidence of micronutrient deficiency between the groups. CONCLUSIONS: Our study shows that formulated vitamins do not offer significant difference in micronutrient levels or cost compared to separate standard vitamin supplements. However, formulated bariatric vitamins have improved compliance compared to separate vitamin supplements.
Subject(s)
Bariatric Surgery , Obesity, Morbid , Adult , Humans , Vitamins/therapeutic use , Obesity, Morbid/surgery , Vitamin A , Vitamin KABSTRACT
Introduction: Allodynia, which can be induced by paclitaxel administration, is the presence of pain as a result of a stimulus that does not usually provoke pain. Many studies have investigated the analgesic efficacy of acupuncture, including laser acupuncture (LA) and electroacupuncture (EA). Although pain-related diseases are relatively common, few studies have analyzed the analgesic effects and mechanisms of LA combined with EA. The purpose of this study was to investigate the therapeutic effect and mechanism of manual acupuncture (MA), EA, LA, and combined therapy (LA + EA) in a paclitaxel-induced allodynia rat model. Methods: A total of 56 rats were classified into eight groups: a normal (Nor, n = 7), a control (Con, n = 7), an MA (n = 7), an EA (n = 7), a 650-nm LA (650LA, n = 7), an 830-nm LA (830LA, n = 7), a 650-nm LA combined with EA (650LA + EA, n = 7), and an 830-nm LA combined with EA group (830LA + EA, n = 7). Allodynia was induced by intraperitoneal injection of 2 mg/kg of paclitaxel every other day for a total of four times except the Nor group. Acupuncture treatments were conducted at the points of Jungwan (CV12) and Joksamni (ST36) once every other day for 6 min, for a total of nine times. Withdrawal response reaction times and force intensity of the foot were measured before the start of the experiment, after the 4th paclitaxel administration (day 8), and after the 9th and last treatment (day 15). On the 16th day, mRNA and protein expression in the spinal nerves was assessed, and a metabolome analysis of the animals' feces was performed. Results and discussion: Our analyses show that 650LA + EA treatment resulted in an upregulation of protein expression related to pain relief and nerve regeneration, whereas 830LA + EA treatment led to significant changes in metabolomes. This study demonstrates that a combination treatment of EA and LA can suppress allodynia and promote upregulation of protein expression related to nerve regeneration and is effective in changing the intestinal microbiome. Further large-scale research is required to assess the exact mechanism underlying the therapeutic effect of this combination treatment in pain-related diseases.
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Grifola frondosa (GF), a species of Basidiomycotina, is widely distributed across Asia and has been used as an immunomodulatory, anti-bacterial, and anti-cancer agent. In the present study, the pharmacological activity of the GF extract against an ecotoxicological industrial chemical, bisphenol A (BPA) in normal human dermal fibroblasts (NHDFs), was investigated. GF extract containing naringin, hesperidin, chlorogenic acid, and kaempferol showed an inhibitory effect on cell death and inflammation induced by BPA in the NHDFs. For the cell death caused by BPA, GF extract inhibited the production of reactive oxygen species responsible for the unique activation of the extracellular signal-regulated kinase. In addition, GF extract attenuated the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and the pro-inflammatory cytokine IL-1ß by the suppression of the redox-sensitive transcription factor, nuclear factor-kappa B (NF-κB) in BPA-treated NHDFs. For the inflammation triggered by BPA, GF extract blocked the inflammasome-mediated caspase-1 activation that leads to the secretion of IL-1ß protein. These results indicate that the GF extract is a functional antioxidant that prevents skin fibroblastic pyroptosis induced by BPA.
Subject(s)
Endocrine Disruptors , Grifola , Hesperidin , Antioxidants/pharmacology , Benzhydryl Compounds , Caspase 3 , Chlorogenic Acid , Cytokines/metabolism , Extracellular Signal-Regulated MAP Kinases , Fibroblasts/metabolism , Humans , Inflammasomes , Inflammation/chemically induced , Kaempferols , NF-kappa B/metabolism , Phenols , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-bcl-2 , Reactive Oxygen Species/metabolism , bcl-2-Associated X Protein/metabolismABSTRACT
Dysregulated circadian functions contribute to various diseases, including cardiovascular disease. Much progress has been made on chronotherapeutic applications of drugs against cardiovascular disease (CVD); however, the direct effects of various medications on the circadian system are not well characterized. We previously conducted high-throughput chemical screening for clock modulators and identified an off-patent anti-arrhythmic drug, moricizine, as a clock-period lengthening compound. In Per2:LucSV reporter fibroblast cells, we showed that under both dexamethasone and forskolin synchronization, moricizine was able to increase the circadian period length, with greater effects seen with the former. Titration studies revealed a dose-dependent effect of moricizine to lengthen the period. In contrast, flecainide, another Class I anti-arrhythmic, showed no effects on circadian reporter rhythms. Real-time qPCR analysis in fibroblast cells treated with moricizine revealed significant circadian time- and/or treatment-dependent expression changes in core clock genes, consistent with the above period-lengthening effects. Several clock-controlled cardiac channel genes also displayed altered expression patterns. Using tissue explant culture, we showed that moricizine was able to significantly prolong the period length of circadian reporter rhythms in atrial ex vivo cultures. Using wild-type C57BL/6J mice, moricizine treatment was found to promote sleep, alter circadian gene expression in the heart, and show a slight trend of increasing free-running periods. Together, these observations demonstrate novel clock-modulating activities of moricizine, particularly the period-lengthening effects on cellular oscillators, which may have clinical relevance against heart diseases.
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BACKGROUND/OBJECTIVES: Brain senescence causes cognitive impairment and neurodegeneration. It has also been demonstrated that curcumin (Cur) and hesperetin (Hes), both antioxidant polyphenolic compounds, mediate anti-aging and neuroprotective effects. Therefore, the objective of this study was to investigate whether Cur, Hes, and/or their combination exert anti-aging effects in D-galactose (Dg)-induced aged neuronal cells and rats. MATERIALS/METHODS: SH-SY5Y cells differentiated in response to retinoic acid were treated with Cur (1 µM), Hes (1 µM), or a combination of both, followed by 300 mM Dg. Neuronal loss was subsequently evaluated by measuring average neurite length and analyzing expression of ß-tubulin III, phosphorylated extracellular signal-regulated kinases, and neurofilament heavy polypeptide. Cellular senescence and related proteins, p16 and p21, were also investigated, including their regulation of antioxidant enzymes. In vivo, brain aging was induced by injecting 250 mg/kg body weight (b.w.) Dg. The effects of supplementing this model with 50 mg/kg b.w. Cur, 50 mg/kg b.w. Hes, or a combination of both for 3 months were subsequently evaluated. Brain aging was examined with a step-through passive avoidance test and apoptosis markers were analyzed in brain cortex tissues. RESULTS: Cur, Hes, and their combination improved neuron length and cellular senescence by decreasing the number of ß-gal stained cells, down-regulated expression of p16 and p21, and up-regulated expression of antioxidant enzymes, including superoxide dismutase 1, glutathione peroxidase 1, and catalase. Administration of Cur, Hes, or their combination also tended to ameliorate cognitive impairment and suppress apoptosis in the cerebral cortex by down-regulating Bax and poly (ADP-ribose) polymerase expression and increasing Bcl-2 expression. CONCLUSIONS: Cur and Hes appear to attenuate Dg-induced brain aging via regulation of antioxidant enzymes and apoptosis. These results suggest that Cur and Hes may mediate neuroprotective effects in the aging process, and further study of these antioxidant polyphenolic compounds is warranted.
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Physical inactivity and high-fat diet, especially high saturated fat containing diet are established risk factors for breast cancer that are amenable to intervention. High-fat diet has been shown to induce tumor growth and metastasis by alteration of inflammation but steady exercise has anti-tumorigenic effects. However, the mechanisms underlying the effects of physical activity on high-fat diet stimulated breast cancer initiation and progression are currently unclear. In this study, we examined how the intensity of physical activity influences high fat diet-stimulated breast cancer latency and progression outcomes, and the possible mechanisms behind these effects. Five-week-old female Balb/c mice were fed either a control diet or a high-fat diet for 8 weeks, and then 4T1 mouse mammary tumor cells were inoculated into the mammary fat pads. Exercise training occurred before tumor cell injection, and tumor latency and tumor volume were measured. Mice with a high-fat diet and low-intensity exercise (HFLE) had a longer tumor latency period, slower tumor growth, and smaller tumor volume in the final tumor assessment compared with the control, high-fat diet control (HFDC), and high-fat diet with moderate-intensity exercise (HFME) groups. Steady low- and moderate-intensity exercise had no effect on cell proliferation but induced apoptosis by activating caspase-3 through the alteration of Bcl-2, Bcl-xL, and Bax expression. Furthermore, steady exercise reduced M2 macrophage polarization in breast tumor tissue, which has been linked to tumor growth. The myokine, myostatin, reduced M2 macrophage polarization through the inhibition of the JAK-STAT signaling pathway. These results suggest that steady low-intensity exercise could delay breast cancer initiation and growth and reduce tumor volume through the induction of tumor cell apoptosis and the suppression of M2 macrophage polarization.
Subject(s)
Diet, High-Fat , Neoplasms , Animals , Cell Proliferation , Diet, High-Fat/adverse effects , Female , Inflammation , Macrophages , Mice , Mice, Inbred BALB CABSTRACT
The objective of this study was to examine the anti-colitis activity of Jakyakgamcho-tang (JGT) in dextran sulfate sodium (DSS)-induced colitis and explore changes of the gut microbial community using 16S rRNA amplicon sequencing and metabolomics approaches. It was found that treatment with JGT or 5-aminosalicylic acid (5-ASA) alleviated the severity of colitis symptoms by suppressing inflammatory cytokine levels of IL-6, IL-12, and IFN-γ. The non-metric multidimensional scaling analysis of gut microbiome revealed that JGT groups were clearly separated from the DSS group, suggesting that JGT administration altered gut microbiota. The operational taxonomic units (OTUs) that were decreased by DSS but increased by JGT include Akkermansia and Allobaculum. On the other hand, OTUs that were increased by DSS but decreased by 5-ASA or JGT treatments include Bacteroidales S24-7, Ruminococcaceae, and Rikenellaceae, and the genera Bacteroides, Parabacteroides, Oscillospira, and Coprobacillus. After JGT administration, the metabolites, including most amino acids and lactic acid that were altered by colitis induction, became similar to those of the control group. This study demonstrates that JGT might have potential to effectively treat colitis by restoring dysbiosis of gut microbiota and host metabolites.
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The purpose of this study was to analyze metabolic differences of ginseng berries according to cultivation age and ripening stage using gas chromatography-mass spectrometry (GC-MS)-based metabolomics method. Ginseng berries were harvested every week during five different ripening stages of three-year-old and four-year-old ginseng. Using identified metabolites, a random forest machine learning approach was applied to obtain predictive models for the classification of cultivation age or ripening stage. Principal component analysis (PCA) score plot showed a clear separation by ripening stage, indicating that continuous metabolic changes occurred until the fifth ripening stage. Three-year-old ginseng berries had higher levels of valine, glutamic acid, and tryptophan, but lower levels of lactic acid and galactose than four-year-old ginseng berries at fully ripened stage. Metabolic pathways affected by different cultivation age were involved in amino acid metabolism pathways. A random forest machine learning approach extracted some important metabolites for predicting cultivation age or ripening stage with low error rate. This study demonstrates that different cultivation ages or ripening stages of ginseng berry can be successfully discriminated using a GC-MS-based metabolomic approach together with random forest analysis.
Subject(s)
Fruit/growth & development , Gas Chromatography-Mass Spectrometry , Metabolome/physiology , Metabolomics , Panax/growth & developmentABSTRACT
Sasang constitutional medicine classifies human beings into four types based on their physical and psychological characteristics. Despite its potential value in achieving personalized medicine, the diagnosis of sasang constitution (SC) type is complex and subjective. In this study, gas chromatography-mass spectrometry and 1H nuclear magnetic resonance-based metabolic analyses were conducted to find maker metabolites in serum and urine according to different SC types. Although some samples were overlapped on orthogonal projection to latent structure discriminant analysis score plots, serum samples showed separation between different SC types. Levels of lactate, glutamate, triglyceride, and fatty acids in serum and glycolic acid in urine of Tae-Eum type were higher than those of So-Eum and So-Yang type. Fatty acids, triglyceride, and lactate levels were found to be metabolites related to body mass index, indicating that marker metabolites for the diagnosis of SC type could be associated with obese. However, Tae-Eum type showed higher lactate levels in serum than So-Yang type for both normal weight and overweight groups, suggesting that the contents of serum lactate might be dependent on the SC type regardless of body weight. These results suggest that metabolomics analysis could be used to determine SC type.
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The objective of this study was to examine the effects of Jackyakgamcho-tang (JGT) on acute colitis. GC/MS-based metabolomics and NGS-based metagenomics were applied to investigate the alteration of metabolites and microbiota in an acute colitis model. The severity of acute colitis symptoms was alleviated by JGT treatment. Induction of colitis and JGT treatment changed compositions of gut microbiota and inflammatory cytokine levels (TNF-α and IL-6). They also substantially change metabolites (i.e., lactic acid, linoleic acid, monostearin, and palmitoylglycerol). In addition, some clear correlations were observed among metabolites, cytokine, and microbiota. This study highlights the applicability of metabolomics and metagenomics study for evaluating anti-inflammatory effects of a new functional herbal medicine as a therapeutic agent for acute colitis.
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GC/MS coupled with multivariate statistical analysis was performed to identify marker metabolites in serum of mice after healing ovalbumin- (OVA-) induced asthma using Opuntia humifusa. Principal component analysis (PCA) score plot showed separation among groups, with metabolite profiles of serum showing differences according to various treatments for the asthma murine model. Levels of stearic acid and arachidic acid were significantly lower in the serum from OVA-induced group than those from the control group. Dexamethasone treatment group was characterized by higher serum levels of urea, myristic acid, and palmitic acid along with lower levels of aspartic acid compared to OVA-induced group. O. humifusa treatment mice groups showed dose-proportional higher levels of urea and glycerol than OVA-induced group. These results highlight that GC/MS-based metabolomics is a powerful technique for identifying molecular markers of asthma.
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BACKGROUND/OBJECTIVES: The objective of this study was to investigate the effects of vitamin C on inflammation, tumor development, and dysbiosis of intestinal microbiota in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced inflammation-associated early colon cancer mouse model. MATERIALS/METHODS: Male BALB/c mice were injected intraperitoneally with AOM [10 mg/kg body weight (b.w)] and given two 7-d cycles of 2% DSS drinking water with a 14 d inter-cycle interval. Vitamin C (60 mg/kg b.w. and 120 mg/kg b.w.) was supplemented by gavage for 5 weeks starting 2 d after the AOM injection. RESULTS: The vitamin C treatment suppressed inflammatory morbidity, as reflected by disease activity index (DAI) in recovery phase and inhibited shortening of the colon, and reduced histological damage. In addition, vitamin C supplementation suppressed mRNA levels of pro-inflammatory mediators and cytokines, including cyclooxygenase-2, microsomal prostaglandin E synthase-2, tumor necrosis factor-α, Interleukin (IL)-1ß, and IL-6, and reduced expression of the proliferation marker, proliferating cell nuclear antigen, compared to observations of AOM/DSS animals. Although the microbial composition did not differ significantly between the groups, administration of vitamin C improved the level of inflammation-related Lactococcus and JQ084893 to control levels. CONCLUSION: Vitamin C treatment provided moderate suppression of inflammation, proliferation, and certain inflammation-related dysbiosis in a murine model of colitis associated-early colon cancer. These findings support that vitamin C supplementation can benefit colonic health. Long-term clinical studies with various doses of vitamin C are warranted.
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Obesity is a public concern and is responsible for various metabolic diseases. Xylobiose (XB), an alternative sweetener, is a major component of xylo-oligosaccharide. The purpose of this study was to investigate the effects of XB on obesity and its associated metabolic changes in related organs. For these studies, mice received a 60% high-fat diet supplemented with 15% d-xylose, 10% XB, or 15% XB as part of the total sucrose content of the diet for ten weeks. Body weight, fat and liver weights, fasting blood glucose, and blood lipids levels were significantly reduced with XB supplementation. Levels of leptin and adipokine were also improved and lipogenic and adipogenic genes in mesenteric fat and liver were down-regulated with XB supplementation. Furthermore, pro-inflammatory cytokines, fatty acid uptake, lipolysis, and ß-oxidation-related gene expression levels in mesenteric fat were down-regulated with XB supplementation. Thus, XB exhibited therapeutic potential for treating obesity which involved suppression of fat deposition and obesity-related metabolic disorders.
Subject(s)
Adipose Tissue/metabolism , Adiposity/drug effects , Disaccharides/pharmacology , Disaccharides/therapeutic use , Obesity/drug therapy , Obesity/metabolism , Adipogenesis/drug effects , Adipogenesis/genetics , Adipose Tissue/drug effects , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Cytokines/metabolism , Diet, High-Fat , Fatty Acids/metabolism , Gene Expression Regulation/drug effects , Inflammation Mediators/metabolism , Lipids/blood , Lipogenesis/drug effects , Lipogenesis/genetics , Lipolysis/drug effects , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Obesity/genetics , Obesity/prevention & control , Organ Size/drug effects , Oxidation-ReductionABSTRACT
Phyllodulcin is a natural sweetener found in Hydrangea macrophylla var. thunbergii. This study investigated whether phyllodulcin could improve metabolic abnormalities in high-fat diet (HFD)-induced obese mice. Animals were fed a 60% HFD for 6 weeks to induce obesity, followed by 7 weeks of supplementation with phyllodulcin (20 or 40 mg/kg body weight (b.w.)/day). Stevioside (40 mg/kg b.w./day) was used as a positive control. Phyllodulcin supplementation reduced subcutaneous fat mass, levels of plasma lipids, triglycerides, total cholesterol, and low-density lipoprotein cholesterol and improved the levels of leptin, adiponectin, and fasting blood glucose. In subcutaneous fat tissues, supplementation with stevioside or phyllodulcin significantly decreased mRNA expression of lipogenesis-related genes, including CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator activated receptor γ (PPARγ), and sterol regulatory element-binding protein-1C (SREBP-1c) compared to the high-fat group. Phyllodulcin supplementation significantly increased the expression of fat browning-related genes, including PR domain containing 16 (Prdm16), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), compared to the high-fat group. Hypothalamic brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) signaling was upregulated by phyllodulcin supplementation. In conclusion, phyllodulcin is a potential sweetener that could be used to combat obesity by regulating levels of leptin, fat browning-related genes, and hypothalamic BDNF-TrkB signaling.
Subject(s)
Adipose Tissue, Brown/drug effects , Diet, High-Fat , Energy Metabolism/drug effects , Isocoumarins/pharmacology , Obesity/drug therapy , Subcutaneous Fat/drug effects , Sweetening Agents/pharmacology , Adiponectin/blood , Adipose Tissue, Brown/metabolism , Adipose Tissue, Brown/physiopathology , Adiposity/drug effects , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Disease Models, Animal , Gene Expression Regulation , Hypothalamus/drug effects , Hypothalamus/metabolism , Leptin/blood , Lipids/blood , Male , Membrane Glycoproteins/metabolism , Mice, Inbred C57BL , Obesity/genetics , Obesity/metabolism , Obesity/physiopathology , Protein-Tyrosine Kinases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction/drug effects , Subcutaneous Fat/metabolism , Subcutaneous Fat/physiopathologyABSTRACT
Type 2 diabetes is a major public health concern worldwide. Xylobiose (XB) consists of two molecules of d-xylose and is a major disaccharide in xylooligosaccharides that are used as prebiotics. We hypothesized that XB could regulate diabetes-related metabolic and genetic changes via microRNA expression in db/db mice. For six weeks, C57BL/KsJ-db/db mice received 5% XB as part of the total sucrose content of their diet. XB supplementation improved glucose tolerance with reduced levels of OGTT AUC, fasting blood glucose, HbA1c, insulin, and HOMA-IR. Furthermore, XB supplementation decreased the levels of total triglycerides, total cholesterol, and LDL-C. The expression levels of miR-122a and miR-33a were higher and lower in the XB group, respectively. In the liver, expressions of the lipogenic genes, including, fatty acid synthase (FAS), peroxisome proliferator activated receptor γ (PPARγ), sterol regulatory element-binding protein-1C (SREBP-1C), sterol regulatory element-binding protein-2 (SREBP-2), acetyl-CoA carboxylase (ACC), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter G5/G8 (ABCG5/8), cholesterol 7 alpha-hydroxylase (CYP7A1), and sterol 12-alpha-hydroxylase (CYP8B1), as well as oxidative stress markers, including superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), glutathione peroxidase (GPX), and catalase, were also regulated by XB supplementation. XB supplementation inhibited the mRNA expressions levels of the pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1, as well as phosphorylation of c-Jun N-terminal kinase/stress activated protein kinase (JNK/SAPK), p38 mitogen-activated protein kinases (MAPK), and extracellular signal-regulated kinases 1/2 (ERK1/2). These data demonstrate that XB exhibits anti-diabetic, hypolipogenic, and anti-inflammatory effects via regulation of the miR-122a/33a axis in db/db mice.
Subject(s)
Diabetes Mellitus, Experimental/therapy , Disaccharides/administration & dosage , Lipogenesis/physiology , MicroRNAs/metabolism , Sweetening Agents/administration & dosage , Animals , Diabetes Mellitus, Experimental/metabolism , Dietary Supplements , Lipogenesis/genetics , Liver/metabolism , Mice , Mice, Inbred C57BL , Prebiotics/administration & dosageABSTRACT
Zerovalent iron nanoparticles (Fe(0) NPs or nZVI) synthesized by reductive precipitation in aqueous solution (Fe/FeO) differ in composition and reactivity from the NPs obtained by reductive precipitation in the presence of a S-source such as dithionite (Fe/FeS). To compare the redox properties of these types of NPs under a range of environmentally relevant solution conditions, stationary powder disk electrodes (PDEs) made from Fe/FeO and Fe/FeS were characterized using a series of complementary electrochemical techniques: open-circuit chronopotentiometry (CP), linear polarization resistance (LPR), electrochemical impedance spectroscopy (EIS), and linear sweep voltammetry (LSV). The passive films on these materials equilibrate within minutes of first immersion and do not show further breakdown until >1 day of exposure. During this period, the potentials and currents measured by LPR and LSV suggest that Fe/FeS undergoes more rapid corrosion and is more strongly influence by solution chemical conditions than Fe/FeO. Chloride containing media were strongly activating and natural organic matter (NOM) was mildly passivating for both materials. These effects were also seen in the impedance data obtained by EIS, and equivalent circuit modeling of the electrodes composed of these powders suggested that the higher reactivity of Fe/FeS is due to greater abundance of defects in its passive film.
Subject(s)
Ferric Compounds/chemistry , Iron Compounds/chemistry , Metal Nanoparticles/chemistry , Sulfides/chemistry , Adsorption , Corrosion , Dielectric Spectroscopy , Electrochemical Techniques , Electrodes , Electrolytes/chemistry , Potentiometry , Solutions , Time FactorsABSTRACT
Natural organic coagulants (NOCs) such as chitosan and Moringa oleifera seeds have been extensively characterized for potential application in water treatment as an alternative to metal-based coagulants. However, the action of both chitosan and M. oleifera seeds is mainly restricted to anionic organic pollutants because of their cationic functional groups affording poor cationic pollutant coagulation by electrostatic repulsion. In this study, we employed ethanolic grape seed extract (GSE) and grape seed-derived polyphenols such as tannic acid and catechin in an effort to find novel NOCs showing stable anionic forms for removal of cationic organic pollutants. The target substances tested were malachite green (MG) and crystal violet (CV), both mutagenic cationic dyes. Polyphenol treatment induced fast decolorization followed by gradual floc formation concomitant with red or blue shifts in maximum absorbance wavelengths of the cationic dyes. Liquid chromatography analysis of flocs formed by polyphenols directly showed that initial supramolecular complexes attributed mainly to electrostatic attraction between polyphenol hydroxyphenyl groups and cationic dyes further progressed into stronger aggregates, leading to precipitation of dye-polyphenol complexes. Consistent with the results obtained using catechin and tannic acid, use of GSE also resulted in effective decolorization and coagulation of soluble MG and CV in aqueous solutions. Screening of several organic GSE components for NOC activity strongly suggested that natural polyphenols are the main organic ingredients causing MG and CV removal via gradual floc formation. The treatment by natural polyphenols and GSE decreased toxicity of MG- or CV-contaminated water.