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BACKGROUND: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. RESULTS: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. CONCLUSIONS: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.
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Diabetes Mellitus , Enfermedades de los Perros , Microbioma Gastrointestinal , Enfermedades Metabólicas , Morus , Humanos , Animales , Perros , 1-Desoxinojirimicina/farmacología , Extractos Vegetales/farmacología , Obesidad/tratamiento farmacológico , Obesidad/veterinaria , Diabetes Mellitus/veterinaria , Enfermedades Metabólicas/veterinaria , Hojas de la PlantaRESUMEN
Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin with antioxidant, anti-inflammatory, and antitumor properties. However, as the effects of C3G on the amyloidogenic pathway, autophagy, tau phosphorylation, neuronal cell death, and synaptic plasticity in Alzheimer's disease models have not been reported, we attempted to investigate the same in the brains of APPswe/PS1ΔE9 mice were analyzed. After oral administration of C3G (30 mg/kg/day) for 16 weeks, the cortical and hippocampal regions in the brains of APPswe/PS1ΔE9 mice were analyzed. C3G treatment reduced the levels of soluble and insoluble Aß (Aß40 and Aß42) peptides and reduced the protein expression of the amyloid precursor protein, presenilin-1, and ß-secretase in the cortical and hippocampal regions. And C3G treatment upregulated the expression of autophagy-related markers, LC3B-II, LAMP-1, TFEB, and PPAR-α and downregulated that of SQSTM1/p62, improving the autophagy of Aß plaques and neurofibrillary tangles. In addition, C3G increased the protein expression of phosphorylated-AMPK/AMPK and Sirtuin 1 and decreased that of mitogen-activated protein kinases, such as phosphorylated-Akt/Akt and phosphorylated-ERK/ERK, thus demonstrating its neuroprotective effects. Furthermore, C3G regulated the PI3K/Akt/GSK3ß signaling by upregulating phosphorylated-Akt/Akt and phosphorylated-GSK3ß/GSK3ß expression. C3G administration mitigated tau phosphorylation and improved synaptic function and plasticity by upregulating the expression of synapse-associated proteins synaptophysin and postsynaptic density protein-95. Although the potential of C3G in the APPswe/PS1ΔE9 mouse models has not yet been reported, oral administration of the C3G is shown to protect the brain and improve cognitive behavior.
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Enfermedad de Alzheimer , Antocianinas , Ratones , Animales , Ratones Transgénicos , Antocianinas/farmacología , Antocianinas/uso terapéutico , Antocianinas/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Enfermedad de Alzheimer/patología , Cognición , Encéfalo/metabolismo , Glucósidos/farmacología , Glucósidos/uso terapéutico , Péptidos beta-Amiloides/metabolismoRESUMEN
Microglial polarization to the M1 phenotype (classically activated) or the M2 phenotype (alternatively activated) is critical in determining the fate of immune responses in neurodegenerative diseases (NDs). M1 macrophages contribute to neurotoxicity, neuronal and synaptic damage, and oxidative stress and are the first line of defense, and M2 macrophages elicit an anti-inflammatory response to regulate neuroinflammation, clear cell debris, and promote neuroregeneration. Various studies have focused on the ability of natural compounds to promote microglial polarization from the M1 phenotype to the M2 phenotype in several diseases, including NDs. However, studies on the roles of fatty acids in microglial polarization and their implications in NDs are a rare find. Most of the studies support the role of polyunsaturated fatty acids (PUFAs) in microglial polarization using cell and animal models. Thus, we aimed to collect data and provide a narrative account of microglial types, markers, and studies pertaining to fatty acids, particularly PUFAs, on microglial polarization and their neuroprotective effects. The involvement of only PUFAs in the chosen topic necessitates more in-depth research into the role of unexplored fatty acids in microglial polarization and their mechanistic implications. The review also highlights limitations and future challenges.
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Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Animales , Polaridad Celular , Ácidos Grasos/metabolismo , Ácidos Grasos Insaturados/metabolismo , Ácidos Grasos Insaturados/farmacología , Macrófagos/metabolismo , Microglía/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Fármacos Neuroprotectores/farmacologíaRESUMEN
Overweight and obesity, associated with various health complications, refer to abnormal or excessive fat accumulation conditions that harm health. Like humans, obesity is a growing problem in dogs, which may increase the risk of serious diseases such as diabetes and cancer. Mulberry leaf has shown potential anti-obesity and anti-diabetes effects in several studies. Our research studied the impact of mulberry leaf supplements in healthy old overweight dogs for 12 weeks. Blood and fecal samples were collected from the dogs before and after treatment for different analyses, including whole transcriptome and gut microbiome analysis. The Body Condition Score (BCS) and blood glucose levels were significantly decreased in all mulberry treatment groups, which justifies the anti-obesity effect of mulberry leaf in dogs. Throughout the whole transcriptome study, the downregulation of PTX3 and upregulation of PDCD-1, TNFRSF1B, RUNX3, and TICAM1 genes in the high mulberry group were found, which have been associated with anti-inflammatory effects in the literature. It may be an essential gene expression mechanism responsible for the anti-inflammatory and, subsequently, anti-obesity effects associated with mulberry leaf treatment, as confirmed by real-time polymerase chain reaction analysis. In microbiome analysis, Papillibacter cinnamivorans, related to the Mediterranean diet, which may cause anti-inflammatory effects, were abundant in the same treatment group. Further studies may be required to establish the gene expression mechanism and role of abundant bacteria in the anti-obesity effect of mulberry supplements in dogs. Overall, we propose mulberry leaves as a portion of food supplements for improving blood glucose levels and the anti-inflammation of blood in companion dogs.
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Diabetes Mellitus , Morus , Humanos , Perros , Animales , Anciano , Glucemia , Hojas de la Planta/metabolismo , Obesidad/metabolismo , Sobrepeso/complicaciones , Suplementos Dietéticos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Edible insects, Bombyx mori (silkworm; SW), which feed on mulberry leaves, have been consumed by humans for a long time as supplements or traditional medication. Non-alcoholic fatty liver disease (NAFLD) is a liver metabolic disorder that affects many people worldwide. We examined the hepatoprotective effects of SW using in vitro and high-fat and high-fructose (HFHF) diet-induced obese in vivo model mice by real-time PCR, immunoblot analysis, and fecal microbiota analysis. SW significantly reduced lipid accumulation and expression of the lipogenic genes in HepG2 cells and the livers of HFHF-induced mice. SW caused significant reductions in triglycerides, and total cholesterol in serum and upregulation of fatty acid oxidation markers compared to the HFHF group. Besides, SW significantly induced phosphorylation of AMPK and ACC in both models, suggesting roles in AMPK activation and the ACC signaling pathway. Furthermore, the gut microbiota analysis demonstrated that SW treatment reduced Firmicutes to Bacteroidetes ratios and the relative abundance of the Lachnospiraceae family compared to HFHF-induced obese mice. These results provide a novel therapeutic agent of hepatoprotective effects of SW for non-alcoholic hepatic steatosis that targets hepatic AMPK and ACC-mediated lipid metabolism.
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Proteínas Quinasas Activadas por AMP/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Productos Biológicos/farmacología , Bombyx/química , Microbioma Gastrointestinal , Metabolismo de los Lípidos , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Línea Celular , Dieta Alta en Grasa , Células Hep G2 , Humanos , Técnicas In Vitro , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patologíaRESUMEN
Obesity has become a worldwide health problem, and many significant inflammatory markers have been associated with the risk of side effects of obesity and obesity-related diseases. After a normal diet or high-fat diet with high-fructose water (HFHF) for 8 weeks, male Wistar rats were divided randomly into four experimental groups according to body weight. Next, for 8 weeks, a normal diet, HFHF diet, and HFHF diet with L. plantarum strains ATG-K2 or ATG-K6 were administered orally. Compared to the control group, the HFHF diet group showed significantly increased visceral fat, epididymal fat, and liver weight. The mRNA and protein expression levels of FAS and SREBP-1c were higher in the HFHF diet group than in the HFHF diet with L. plantarum strains ATG-K2 and ATG-K6. The HFHF diet with L. plantarum strain ATG-K2 showed significantly decreased inflammatory cytokine expression in the serum and small intestine compared to the HFHF diet group. Furthermore, histological morphology showed minor cell injury, less severe infiltration, and longer villi height in the small intestine ileum of the HFHF diet with L. plantarum strains groups than in the HFHF diet group. These results suggest that L. plantarum strains K2 and K6 may help reduce intestinal inflammation and could be used as treatment alternatives for intestinal inflammatory reactions and obesity.
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Dieta Alta en Grasa/efectos adversos , Fructosa/toxicidad , Inflamación/prevención & control , Intestinos/efectos de los fármacos , Lactobacillus plantarum/química , Probióticos/farmacología , Animales , Inflamación/etiología , Inflamación/patología , Intestinos/patología , Lactobacillus plantarum/clasificación , Masculino , Ratas , Ratas Wistar , Edulcorantes/toxicidadRESUMEN
Delphinidin-3-O-ß-glucoside (D3G) is a health-promoting anthocyanin whose anti-obesity activity has not yet been thoroughly investigated. We examined the effects of D3G on adipogenesis and lipogenesis in 3T3-L1 adipocytes and primary white adipocytes using real-time RT-PCR and immunoblot analysis. D3G significantly inhibited the accumulation of lipids in a dose-dependent manner without displaying cytotoxicity. In the 3T3-L1 adipocytes, D3G downregulated the expression of key adipogenic and lipogenic markers, which are known as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty acid synthase (FAS). Moreover, the relative protein expression of silent mating type information regulation 2 homolog 1 (SIRT1) and carnitine palmitoyltransferase-1 (CPT-1) were increased, alongside reduced lipid levels and the presence of several small lipid droplets. Furthermore, D3G increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which suggests that D3G may play a role in AMPK and ACC activation in adipocytes. Our data indicate that D3G attenuates adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling, and, hence, could have a therapeutic role in the management and treatment of obesity.
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Adipocitos/citología , Adipogénesis/efectos de los fármacos , Antocianinas/farmacología , Glucósidos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos Blancos/citología , Adipocitos Blancos/enzimología , Animales , Proteínas Potenciadoras de Unión a CCAAT/genética , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , PPAR gamma/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
Of 608 Streptococcus pneumoniae clinical strains isolated at a hospital in South Korea during 2009-2014, sixteen (2.6%) were identified as levofloxacin resistant. The predominant serotype was 11A (9 isolates). Two novel sequence types of multidrug-resistant S. pneumoniae with serotype 11A were identified, indicating continuous diversification of resistant strains.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Levofloxacino/farmacología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Serogrupo , Streptococcus pneumoniae/clasificación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , República de Corea/epidemiología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/genéticaRESUMEN
The extensive utilization of bismuth and its derivatives in many industries, such as chemical, semiconductor, pharmaceutical, and cosmetics, leads to their accumulation in wastewater, posing a risk to both human health and the environment. Carbon nanorods (CNR) are fluorescent nanoparticles with an ability to detect various analytes as sensing probes. This study focuses on the production, structure, and chemical composition characterization of silkworm-derived CNR (swCNR) and their ability to detect bismuth ions (Bi3+) and inhibit radicals. The optimum wavelength for exciting the fluorescence of swCNR was 370 nm, and the resulting emission peak was observed at 436 nm. The prepared swCNR showed static fluorescence quenching mechanism-based sensing of Bi3+ ions with a limit of detection of 175 nM and two linear ranges from 0.5 to 5 µM (R2 = 0.9997) and 10-50 µM (R2 = 0.9995). The swCNR demonstrated high selectivity in detecting Bi3+ ions in the spiked river water samples, thus establishing the swCNR's role as a nano fluorescence probe designed for the selective detection of Bi3+ ions among other metal ions. Favorable results for the antiradical ability of swCNR were obtained against hydroxyl, 2,2 diphenyl-1 picrylhydrazyl, and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals with scavenging percentages of 15, 32, and 90, respectively. The possible applications of swCNR in the environmental and antioxidant sectors are proposed in this study.
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Astrocytes are the major glial cells in the human brain and provide crucial metabolic and trophic support to neurons. The amyloid-ß peptide (Aß) alter the morphological and functional properties of astrocytes and induce inflammation and calcium dysregulation, contributing to Alzheimer's disease (AD) pathology. Recent studies highlight the role of Toll-like receptor (TLR) 4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in inflammation. Reactive oxygen species (ROS) generated due to Aß, induce apoptosis in the brain cells worsening AD progression. Astrocytic cell surface receptors, such as purinergic receptors (P2Y1 and P2Y2), metabotropic glutamate receptor (mGLUR)5, α7 nicotinic acetylcholine receptor (α7nAChR), and N-methyl-d-aspartate receptors (NMDARs), have been suggested to interact with inositol trisphosphate receptor (IP3R) on the endoplasmic reticulum (ER) to induce Ca2+ movement from ER to cytoplasm, causing Ca2+ dysregulation. We found that the citrus flavonoid nobiletin (NOB) protected primary astrocytes from Aß42-induced cytotoxicity and inhibited TLR4/NF-κB signaling in Aß42-induced primary rat astrocytes. NOB was found to regulate Aß42-induced ROS levels through Keap1-Nrf2 pathway. The receptors P2Y1, P2Y2, mGLUR5, α7nAChR, and NMDARs induced intracellular Ca2+ levels by activating IP3R and NOB regulated them, thereby regulating intracellular Ca2+ levels. Molecular docking analysis revealed a possible interaction between NOB and IP3R in IP3R regulation. Furthermore, RNA sequencing revealed various NOB-mediated biological signaling pathways, such as the AD-presenilin, AD-amyloid secretase, and Wnt signaling pathway, suggesting possible neuroprotective roles of NOB. To conclude, NOB is a promising therapeutic agent for AD and works by modulating AD pathology at various levels in Aß42-induced primary rat astrocytes.
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Péptidos beta-Amiloides , Astrocitos , Calcio , Flavonas , Receptores de Inositol 1,4,5-Trifosfato , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Animales , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Ratas , Calcio/metabolismo , Flavonas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Fragmentos de Péptidos/farmacología , Fragmentos de Péptidos/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Humanos , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patologíaRESUMEN
The growing number of companion dogs has contributed to a rapidly growing market for pet products, including dog toys. However, little is known about the hazardous substances released from dog toys. This study aims to examine the potential presence of obesogens, a subset of endocrine-disrupting chemicals (EDCs) that are widely utilized as raw materials in the manufacture of dog toy components, and their effects on dog health. To achieve this, we adapted and employed a migration method typically used for children's products to simulate obesogen exposure in dogs through sucking or chewing toys. We demonstrated that out of various obesogens, bisphenol A (BPA) was released from dog toys into synthetic saliva, whereas phthalates and azo dyes were not detected in any of the leachates. Additionally, we found that BPA induced adipogenic differentiation in canine adipose-derived stem cells (cADSCs). Our RNA sequencing experiments revealed that BPA alters the adipogenesis-related gene signature in cADSCs by elevating the expression levels of ADIPOQ, PLIN1, PCK1, CIDEC, and FABP4. The associated transcriptional changes are involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which may contribute to the promotion of adipogenesis by BPA. Our findings suggest that companion dogs are at risk of BPA exposure, which may contribute to obesity in dogs. Therefore, the implementation of precautionary measures is crucial.
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Adipogénesis , Compuestos de Bencidrilo , Disruptores Endocrinos , Obesidad , Fenoles , Células Madre , Animales , Perros , Compuestos de Bencidrilo/toxicidad , Fenoles/toxicidad , Adipogénesis/efectos de los fármacos , Obesidad/metabolismo , Disruptores Endocrinos/toxicidad , Células Madre/efectos de los fármacos , Tejido Adiposo/metabolismo , Diferenciación Celular/efectos de los fármacosRESUMEN
Silver nanoparticles (AgNPs) have inconsistent findings against inflammation. Although a wealth of literature on the beneficial effects of green-synthesized AgNPs has been published, a detailed mechanistic study of green AgNPs on the protective effects against lipopolysaccharide (LPS)-induced neuroinflammation using human microglial cells (HMC3) has not yet been reported. For the first time, we studied the inhibitory effect of biogenic AgNPs on inflammation and oxidative stress induced by LPS in HMC3 cells. X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and transmission electron microscopy were used to characterize AgNPs produced from honeyberry. Co-treatment with AgNPs significantly reduced mRNA expressions of inflammatory molecules such as interleukin (IL)-6 and tumor necrosis factor-α, while increasing the expressions of anti-inflammatory markers such as IL-10 and transforming growth factor (TGF)-ß. HMC3 cells were also switched from M1 to M2, as shown by lower expression of M1 markers such as cluster of differentiation (CD)80, CD86, and CD68 and higher expression of M2 markers such as CD206, CD163, and triggering receptors expressed on myeloid cells (TREM2). Furthermore, AgNPs inhibited LPS-induced toll-like receptor (TLR)4 signaling, as evidenced by decreased expression of myeloid differentiation factor 88 (MyD88) and TLR4. In addition, AgNPs reduced the production of reactive oxygen species (ROS) and enhanced the expression of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), while decreasing the expression of inducible nitric oxide synthase. The docking score of the honeyberry phytoconstituents ranged from -14.93 to - 4.28 KJ/mol. In conclusion, biogenic AgNPs protect against neuroinflammation and oxidative stress by targeting TLR4/MyD88 and Nrf2/HO-1 signaling pathways in a LPS-induced in vitro model. Biogenic AgNPs could be utilized as potential nanomedicine against LPS-induced inflammatory disorders.
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Lipopolisacáridos , Nanopartículas del Metal , Humanos , Lipopolisacáridos/toxicidad , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/farmacología , Simulación del Acoplamiento Molecular , Plata/farmacología , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/farmacología , Enfermedades Neuroinflamatorias , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/farmacología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Nanopartículas del Metal/uso terapéutico , Transducción de Señal , Fenotipo , Línea Celular , Inflamación/inducido químicamente , Inflamación/metabolismo , Encéfalo/metabolismoRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM), a growing health problem worldwide, is a metabolic disorder characterized by hyperglycemia due to insulin resistance and defective insulin secretion by pancreatic ß-cells. The skeletal muscle is a central organ that consumes most of the insulin-stimulated glucose in the body, and insulin resistance can damage muscles in T2DM. Based on a strong correlation between diabetes and muscles, we investigated the effects of stevia extract (SE) and stevioside (SV) on the skeletal muscle of diabetic db/db mice. METHODS: The mice were administered saline, metformin (200 mg/kg/day), SE (200 and 500 mg/kg/day), and SV (40 mg/kg/day) for 35 days. During administration, we checked the levels of fasting blood glucose twice a week and conducted the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). After administration, we analyzed serum biochemical parameters, triglyceride (TG), total cholesterol (TC), insulin and antioxidant enzymes, and the cross-sectional area of skeletal muscle fibers of db/db mice. Western blots were conducted using the skeletal muscle of mice to examine the effect of SE and SV on protein expression of insulin signaling, mitochondrial function, and oxidative stress. RESULTS: SE and SV administration lowered the levels of fasting blood glucose, OGTT, and ITT in db/db mice. The administration also decreased serum levels of TG, TC, and insulin while increasing those of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Interestingly, muscle fiber size was significantly increased in db/db mice treated with SE500 and SV. In the skeletal muscle of db/db mice, SE and SV administration activated insulin signaling by increasing the protein expression of insulin receptor substrate, Akt, and glucose transporter type 4. Furthermore, SE500 administration markedly increased the protein expression of AMP-activated protein kinase-α, sirtuin-1, and peroxisome proliferator-activated receptor-γ coactivator-1α. SV administration significantly reduced oxidative stress by down-regulating the protein expression of 4-hydroxynonenal, heme oxygenase-1, SOD, and GPx. In addition, SE500 and SV administration suppressed the expression of apoptosis-related proteins in the skeletal muscle of db/db mice. CONCLUSION: SE and SV administration attenuated hyperglycemia in diabetic mice. Moreover, the administration ameliorated insulin resistance by regulating mitochondrial function and oxidative stress, increasing muscle fiber size. Overall, this study suggests that SE and SV administration may serve as a potential strategy for the treatment of diabetic muscles.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hiperglucemia , Resistencia a la Insulina , Stevia , Ratones , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Stevia/metabolismo , Glucemia , Diabetes Mellitus Experimental/tratamiento farmacológico , Insulina , Estrés Oxidativo , Músculo Esquelético , Glutatión Peroxidasa/metabolismo , Mitocondrias/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
INTRODUCTION: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent. METHODS: To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls. RESULTS: In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14). CONCLUSIONS: This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.
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Neoplasias de la Mama/genética , Cromosomas Humanos Par 2 , Receptores ErbB/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Oportunidad Relativa , Receptor ErbB-4 , Reproducibilidad de los Resultados , República de CoreaRESUMEN
Mulberry (Morus alba L.) leaves have been used to lower blood glucose in patients with diabetes. We evaluated the effects of mulberry leaves extract (MLE) and 1-deoxynojirimycin (1-DNJ) in improving insulin resistance through the activation of the IRS-1/PI3K/Akt pathway in the skeletal muscle of db/db mice. Histological analysis revealed an amelioration of muscle deformation and increased muscle fiber size. MLE and 1-DNJ positively raised the protein expression of related glucose uptake and increased the translocation of glucose transporter type 4 (GLUT4) to the membrane. Furthermore, MLE and 1-DNJ activated the IRS-1/PI3K/Akt pathway in the skeletal muscle and, subsequently, modulated the protein levels of glycogen synthase kinase-3beta (GSK-3ß) and glycogen synthase (GS), leading to elevated muscle glycogen content. These findings suggest that MLE and 1-DNJ supplementation improves insulin resistance by modulating the insulin signaling pathway in the skeletal muscle of db/db mice.
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Microglial polarization plays an essential role in the progression and regression of neurodegenerative disorders. Cyanidin-3-O-glucoside (C3G), a dietary anthocyanin found in many fruits and vegetables, has been reported as an antioxidant, anti-inflammatory, and antitumor agent. However, there have been no reports on whether C3G can regulate the M1/M2 shift in an Alzheimer's disease model. We attempted to investigate the effects of C3G on M1/M2 polarization and the mechanism to regulate anti-inflammation and phagocytosis, both in vitro and in vivo. HMC3 cells were treated with ß-amyloid (Aß42) in the presence or absence of 50 µM C3G for different time intervals, and APPswe/PS1ΔE9 mice were orally administered 30 mg/kg/day of C3G for 38 weeks. The in vitro data revealed that C3G could shift the M1 phenotype of microglia to M2 by reducing the expression of M1-specific markers (CD86 and CD80), inflammatory cytokines (IL-Iß, IL-6, TNF-α), reactive oxygen species, and enhancing the expression of M2-specific markers (CD206 and CD163). The APPswe/PS1ΔE9 mice results were consistent with the in vitro data, indicating a significant reduction in inflammatory cytokines and higher expression of M2-specific markers such as CD206 and Arg1 in C3G-treated Alzheimer's disease model mice. Additionally, C3G was found to upregulate PPARγ expression levels both in vitro and in vivo, whereas a PPARγ antagonist (GW9662) was found to block C3G-mediated effects in vitro. In this study, we confirmed that C3G could regulate microglial polarization by activating PPARγ and eliminating accumulated ß-amyloid by enhancing Aß42 phagocytosis through the upregulation of TREM2.
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Enfermedad de Alzheimer , Microglía , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides , Animales , Antocianinas/farmacología , Antocianinas/uso terapéutico , Citocinas/metabolismo , Glucósidos/farmacología , Glucósidos/uso terapéutico , Glicoproteínas de Membrana/metabolismo , Ratones , Microglía/metabolismo , PPAR gamma/metabolismo , Fragmentos de Péptidos , Fagocitosis , Receptores Inmunológicos/metabolismo , Transducción de SeñalRESUMEN
Stevioside, the primary sweetener in stevia, is a glycoside with numerous beneficial biological activities. However, its anti-adipogenic effects on tissue differentiation and adipose tissues remain to be thoroughly investigated. In this study, the anti-adipogenic effects of stevioside during the differentiation of 3T3-L1 cells and epididymal adipose tissues of db/db mice were investigated by measuring the lipid droplets stained with Oil Red O and an immunoblot assay. Immunoblot analysis revealed that stevioside downregulated the expression of peroxisome proliferator-activated receptor-gamma (PPARγ), sterol regulatory element-binding protein-1c (SREBP-1c), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty acid synthase (FAS). Additionally, the protein expression of carnitine palmitoyltransferase 1 (CPT1), silent mating type information regulation 2 homolog 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) increased following treatment with stevioside. Furthermore, stevioside increased the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), both in vitro and in vivo. The activity of AMPK in stevioside-treated 3T3-L1 cells was further confirmed using agonists and antagonists of AMPK signaling. Our data indicate that stevioside ameliorates anti-adipogenic effects and promotes ß-oxidation in adipocytes by activating AMPK-mediated signaling. The results of this study clearly demonstrated the inhibitory effect of stevioside on the differentiation of adipocytes and the reduction of lipid accumulation in the epididymal adipose tissues of db/db mice.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Adipogénesis , Células 3T3-L1 , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Diterpenos de Tipo Kaurano , Glucósidos/farmacología , RatonesRESUMEN
Many individuals are suffering from depression, and various improvements are being proposed. This study was conducted on young people diagnosed with depression and aimed to assess the effects of flavonoid-rich orange juice on the major depressive disorder (MDD) using a randomized controlled trial. In all, 40 young men and women with MDD aged 18−29 years were randomly assigned to a flavonoid-rich orange juice group (FR group) and a flavonoid-low orange cordial group (FL group). The subjects drank the corresponding juice three times a day (190 mL per bottle) for 8 weeks. The blood BDNF, zonulin, and claudin-5 levels significantly increased (p < 0.0001, p < 0.01, and p < 0.05, respectively) in the FR group, and the fatty acid binding protein 2 (FABP2) level was significantly decreased (p < 0.0001) in the FR group after the juice intervention. The FABP2, LPS, and valeric acid levels were negatively correlated with the abundance of Butyricicoccus pullicaecorum, which was higher in the FR group. Orange juice intake improved depressive symptoms in young adults with MDD in the FR group. This B. pullicaecorum can be a potential biomarker for clinical improvement in young adults with MDD patients.
Asunto(s)
Citrus sinensis , Trastorno Depresivo Mayor , Masculino , Humanos , Femenino , Adulto Joven , Adolescente , Flavonoides , Jugos de Frutas y VegetalesRESUMEN
Lipophagy, a type of autophagy that breaks down lipid droplets, is essential in the regulation of intracellular lipid accumulation and intracellular free fatty acid levels in numerous organisms and metabolic conditions. We investigated the effects of Stevia rebaudiana Bertoni (S), a low-calorie sweetener, and stevioside (SS) on hepatic steatosis and autophagy in hepatocytes, as well as in db/db mice. S and SS reduced the body and liver weight and levels of serum triglyceride, total cholesterol, and hepatic lipogenic proteins. In addition, S and SS increased the levels of fatty acid oxidase, peroxisome proliferator-activated receptor alpha (PPARα), and microtubule-associated protein light chain 3 B but decreased that of sequestosome 1 (p62) in the liver of db/db mice. Additionally, Beclin 1, lysosomal associated membrane protein 1, and phosphorylated adenosine monophosphate-activated protein kinase protein expression was augmented following S and SS treatment of db/db mice. Furthermore, the knockdown of PPARα blocked lipophagy in response to SS treatment in HepG2 cells. These outcomes indicate that PPARα-dependent lipophagy is involved in hepatic steatosis in the db/db mouse model and that SS, a PPARα agonist, represents a new therapeutic option for managing associated diseases.
RESUMEN
Insufficient glucose control remains a critical challenge for type 2 diabetes mellitus (T2DM) patients with currently used therapeutic drugs, which can also have detrimental side effects. The facile synthesis of nitrogen-doped carbon nanorods (N-CNRs) as therapeutic agents in a T2DM transgenic db/db mouse model is reported herein. N-CNRs are synthesized from silkworm powder without the assistance of any template and possess a hollow graphitic nature, rough surface, and good aqueous solubility, which make them ideal candidates for fabricating nanomedicines. N-CNRs are employed to reduce fasting blood glucose and ameliorate serum biomarker levels linked to oxidative stress and inflammation. Interestingly, through the downregulation of enhanced expression of glutathione peroxidase, superoxide dismutase, and catalase as well as inflammatory responses, N-CNRs reverse pancreatic dysfunction and normalize the secretory functions of pancreatic cells. Moreover, hepatic steatosis is attenuated by downregulating lipogenesis and increasing fatty acid oxidation. This finding may help in designing novel therapeutics for T2DM treatment.