RESUMEN
Dental caries (DC) is one of the most common oral diseases and is mainly caused by Streptococcus mutans (S. mutans). The use of antibiotics against S. mutans usually has side effects, including developing resistance. N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC), a natural product, has great potential utility in antibacterial agents owing to its low toxicity and good biocompatibility. Thus, the purpose of the present study was to explore the antimicrobial activity of N-2-HACC against S. mutans through the permeability of the cell wall, integrity of cell membrane, protein and nucleic acid synthesis, respiratory metabolism, and biofilm formation. Our results confirmed that the MIC of N-2-HACC against S. mutans was 0.625 mg/mL with a 90.01 ± 1.54% inhibition rate. SEM observed the formation of cavities on the surface of S. mutans after 12 h N-2-HACC treatment. The level of alkaline phosphatase (AKP) activity was higher in the N-2-HACC treatment group than in the control group, indicating that N-2-HACC can improve the permeability of the cell wall. Also, N-2-HACC treatment can destroy the cell membrane of S. mutans by increasing conductivity and absorbance at 260 nm, decreasing cell metabolic activity, and enhancing the fluorescence at 488 nm. Respiratory metabolism revealed that the activities of the Na+-K+-ATP enzyme, pyruvate kinase (PK), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were decreased after N-2-HACC treatment, revealing that N-2-HACC can inhibit glycolysis and the tricarboxylic acid cycle (TCA cycle) of S. mutans. Moreover, N-2-HACC can also decrease the contents of the nucleic acid and solution protein of S. mutans, interfere with biofilm formation, and decrease the mRNA expression level of biofilm formation-related genes. Therefore, these results verify that N-2-HACC has strong antibacterial activity against S. mutans, acting via cell membrane integrity damage, increasing the permeability of cell walls, interfering with bacterial protein and nucleic acid synthesis, perturbing glycolysis and the TCA cycle, and inhibiting biofilm formation. It is suggested that N-2-HACC may represent a new potential synthetically modified antibacterial material against S. mutans.
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Antibacterianos , Biopelículas , Quitosano , Pruebas de Sensibilidad Microbiana , Streptococcus mutans , Streptococcus mutans/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Quitosano/análogos & derivados , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Biopelículas/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/antagonistas & inhibidores , Caries Dental/microbiología , Caries Dental/tratamiento farmacológico , Pared Celular/efectos de los fármacos , Compuestos de Amonio Cuaternario/farmacología , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/síntesis químicaRESUMEN
To investigate the effect of Ginsenoside Rg3 on insulin secretion in mouse MIN6 cells and the possible mechanism. The cultured mouse pancreatic islet MIN6 cells were divided into control group (NC), Rg3 group (Rg3, 50 µg/L), high glucose group (HG, 33 mmol/L), High glucose and Rg3 group (HG + Rg3), after 48 h of continuous culture, CCK-8 was used to detect cell viability; mouse insulin enzyme-linked immunoassay kit to detect insulin release; ATP content detection kit to detect ATP; DCFH-DA to detect intracellular reactive oxygen species (ROS) levels; total glutathione (T-GSH)/oxidized glutathione (GSSG) assay kit to detect the ratio of GSH/GSSG; Using the mitochondrial membrane channel pore (MPTP) fluorescence detection kit in MIN6 cells and collect the intensity of green fluorescence; Western blot to detect the expression of antioxidant proteins Glutathione reductase (GR). The results showed that compared with the NC group, the cell viability of the HG was decreased (P < 0.05), insulin release decreased (P < 0.001), ATP content decreased significantly (P < 0.001), and ROS content increased (P < 0.01), the GSH/GSSH ratio of pancreatic islet cells decreased (P < 0.05),the green fluorescence intensity decreased (P < 0.001), indicating that the permeability of mitochondria increased and the content of antioxidant protein in the cells decreased (P < 0.05). Compared with the HG group, the cell viability of the HG + Rg3 group was significantly increased (P < 0.05), the amount of insulin released was significantly increased (P < 0.001), ATP content was significantly increased (P < 0.01), and the ROS content was significantly decreased (P < 0.01), GSH/GSSH ratio increased significantly (P < 0.05), the green fluorescence intensity was increased (P < 0.001), indicating that the permeability of mitochondria decreased and antioxidant protein GR content increased significantly (P < 0.05). Taken together, our results suggest that Rg3 has an antioxidant protective effect on mouse pancreatic islet cells damaged by high glucose and maintains pancreatic islet cell function and promotes insulin secretion.
RESUMEN
In this work, a noble-metal-free composite electrode was prepared based on PMo12O403- (PMo12), C9H5FeO7 (MIL-100(Fe), a Fe-based metal organic framework) and polyvinylpyrrolidone (PVP), and served as a high performance electrochemical sensor for synchronous detection of dopamine (DA) and uric acid (UA). The PMo12@MIL-100(Fe)@PVP composite electrode was fabricated by a in-situ hydrothermal method. Thanks to the synergistic effect of three active components (PMo12, MIL-100 and PVP), the electrode possesses large specific surface area and high electrical conductivity and therefore it shows high electrocatalytic oxidation performance of DA and UA with a spacing of 0.146 V between the two peak positions. These benefits of the electrode enable its electrochemical sensor to synchronously detect of DA and UA. Namely, the linear ranges can achieve 1-247 µM for DA and 5-406 µM for UA. Meanwhile, the detection limits are 0.586 µM for DA and 0.372 µM for UA. Moreover, the sensor can be applied to simultaneous determination of UA and DA in human serums with satisfactory recovery values.
Asunto(s)
Grafito , Nanocompuestos , Humanos , Ácido Ascórbico , Dopamina , Técnicas Electroquímicas/métodos , Electrodos , Límite de Detección , Povidona , Ácido ÚricoRESUMEN
The gene coding interleukin 6 (IL-6) is a promising candidate in predisposition to type 2 diabetes mellitus (T2DM). This study aimed to meta-analytically examine the association of IL-6 gene -174G/C polymorphism with T2DM and circulating IL-6 changes across -174G/C genotypes. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Twenty-five articles were meta-analysed, with 20 articles for T2DM risk and 9 articles for circulating IL-6 changes. Overall, there was no detectable significance for the association between -174G/C polymorphism and T2DM, and this association was relatively obvious under dominant model (OR: 0.82, 95% CI: 0.56-1.21). Improved heterogeneity was seen in some subgroups, with statistical significance found in studies involving subjects of mixed races (OR: 0.63, 95% CI: 0.46-0.86). Begg's and filled funnel plots, along with Egger's tests revealed week evidence of publication bias. In genotype-phenotype analyses, carriers of -174CC and -174CG genotypes separately had 0.10 and 0.03 lower concentrations (pg/mL) of circulating IL-6 than -174GG carriers. Albeit no detectable significance for the association of -174G/C with T2DM, our findings provided suggestive evidence on a dose-dependent relation between -174G/C mutant alleles and circulating IL-6 concentrations, indicating possible implication of this polymorphism in the pathogenesis of T2DM.
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Diabetes Mellitus Tipo 2/epidemiología , Predisposición Genética a la Enfermedad , Interleucina-6/genética , Polimorfismo de Nucleótido Simple , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Genotipo , Humanos , Factores de RiesgoRESUMEN
We did a systematic review and meta-analysis, aiming to examine the association of available polymorphisms in the receptor for advanced glycation end products (AGER) gene with the risk of type 2 diabetes. Literature search, eligibility assessment, and data extraction were independently performed by two authors. Risk was expressed as by odds ratio (OR) and 95% confidence interval (CI) under the random-effects model. A total of 26 publications, involving 29 independent studies (8,318 patients with type 2 diabetes and 5,589 healthy or orthoglycemic controls) were included in this meta-analysis. Six polymorphisms in AGER gene, rs2070600, rs1800624, rs1800625, rs184003, rs3134940, and rs55640627, were eligible for inclusion. Overall analyses indicated that the mutations of rs1800624 (-374A) and rs55640627 (2245A) were associated with a significantly increased risk of type 2 diabetes (OR = 1.17 and 1.55, 95% CI: 1.00 to 1.38 and 1.21 to 1.98, respectively). Subsidiary analyses revealed that the mutation of rs2070600 was associated with 2.13-folded increased risk of type 2 diabetes in Caucasians (95% CI: 1.28 to 3.55), and the mutation of rs1800624 was associated with 1.57-folded increased risk in South Asians (95% CI: 1.09 to 2.25), with no evidence of heterogeneity (I2: 42.5% and 44.5%). There were low probabilities of publication bias for all studied polymorphisms. Taken together, our findings indicate an ethnicity-dependent contribution of AGER gene in the pathogenesis of type 2 diabetes, that is, rs2070600 was a susceptibility locus in Caucasians, yet rs1800624 in South Asians.
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Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptor para Productos Finales de Glicación Avanzada/genética , Frecuencia de los Genes , Genotipo , HumanosRESUMEN
We successfully synthesized {BiW8 }, a 10-nuclear heteroatom cluster modified {BiW8 O30 }. At 24â h post-incubation, the IC50 values of {BiW8 } against HUVEC, MG63, RD, Hep3B, HepG2, and MCF7 cells were 895.8, 127.3, 344.3, 455.0, 781.3, and 206.3â µM, respectively. The IC50 value of {BiW8 } on the MG63 cells was more than 2-fold lower than that of the other raw materials. Through morphological and functional features, we demonstrated pyroptosis as a newly identified mechanism of cell death induced by {BiW8 }. {BiW8 } increased 2-fold reactive oxygen species (ROS) levels in MG63 cells at 24â h post-incubation. Compared with 0â h, the glutathione (GSH) content decreased by 59, 65, 75, 94, and 97 % at 6, 12, 24, 36 and 48â h post-incubation, respectively. Furthermore, multiple antitumor mechanisms of {BiW8 } were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair.
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Antineoplásicos/farmacología , Piroptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Tungsteno/farmacología , Regulación hacia Arriba/efectos de los fármacos , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Compuestos de Tungsteno/químicaRESUMEN
The lytic cold-active bacteriophage VSW-3, belonging to the Podoviridae family and infecting the host Pseudomonas fluorescens SW-3, was isolated from the Napahai plateau wetland in China. With the development of sequencing technology, the study of Pseudomonas genomic diversity has increased; however, knowledge of cold-active phages infecting Pseudomonas is limited. The newly sequenced phage VSW-3 was classified based on virion morphology by transmission electron microscope. Sequence analysis revealed that the genome size was 40,556 bp with an overall GC content of 57.54 % and 46 open reading frames. The genome was organized into several modules containing genes for packaging, structural proteins, replication/transcription, and phage lysis. The sequence contained 45 potential promoters, 3 transcription terminators, and yet no tRNAs. This is the first report of cold-active Pseudomonas fluorescens bacteriophage genome sequencing.
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Genoma Viral , Fagos Pseudomonas/genética , Pseudomonas fluorescens/virología , Análisis de Secuencia de ADN , Biología Computacional , Orden Génico , Sistemas de Lectura Abierta , Filogenia , Fagos Pseudomonas/clasificación , HumedalesRESUMEN
Wetlands are often called the "kidneys of the Earth" and contribute substantially to environmental improvement. Pseudomonas fluorescens is a major contaminant of milk products and causes the spoilage of refrigerated foods and fresh poultry. In this study, we isolated and characterized a lytic cold-active bacteriophage named VSW-3 together with P. fluorescens SW-3 cells from the Napahai wetland in China. Electron microscopy showed that VSW-3 had an icosahedral head (56 nm) and a tapering tail (20 nm × 12 nm) and a genome size of approximate 40 kb. On the basis of the top-scoring hits in the BLASTP analysis, VSW-3 showed a high degree of module similarity to the Pseudomonas phages Andromeda and Bf7. The latent and burst periods were 45 and 20 min, respectively, with an average burst size of 90 phage particles per infected cell. The pH and thermal stability of VSW-3 were also explored. The optimal pH was found to be 7.0 and the activity decreased rapidly when the temperature exceeded 60 °C. VSW-3 is a cold-active bacteriophage, hence, it is important to research its ability to prevent product contamination caused by P. fluorescens and to characterize its relationship with its host P. fluorescens in the future.
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Podoviridae/aislamiento & purificación , Fagos Pseudomonas/aislamiento & purificación , Pseudomonas fluorescens/virología , Frío , Podoviridae/crecimiento & desarrollo , Fagos Pseudomonas/crecimiento & desarrollo , HumedalesRESUMEN
Withaferin A (WA), a natural product derived from Withania somnifera, has been used in traditional oriental medicines to treat neurological disorders. Recent studies have demonstrated that this compound may have a potential for cancer treatment and a clinical trial has been launched to test WA in treating melanoma. Herein, WA's chemopreventive potential was tested in a chemically-induced skin carcinogenesis mouse model. Pathological examinations revealed that WA significantly suppressed skin tumor formation. Morphological observations of the skin tissues suggest that WA suppressed cell proliferation rather than inducing apoptosis during skin carcinogenesis. Antibody Micro array analysis demonstrated that WA blocked carcinogen-induced up-regulation of acetyl-CoA carboxylase 1 (ACC1), which was further confirmed in a skin cell transformation model. Overexpression of ACC1 promoted whereas knockdown of ACC1 suppressed anchorage-independent growth and oncogene activation of transformable skin cells. Further studies demonstrated that WA inhibited tumor promotor-induced ACC1 gene transcription by suppressing the activation of activator protein 1. In melanoma cells, WA was also able to suppress the expression levels of ACC1. Finally, results using human skin cancer tissues confirmed the up-regulation of ACC1 in tumors than adjacent normal tissues. In summary, our results suggest that withaferin A may have a potential in chemoprevention and ACC1 may serve as a critical target of WA. © 2015 Wiley Periodicals, Inc.
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Acetil-CoA Carboxilasa/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Regulación hacia Arriba/efectos de los fármacos , Witanólidos/administración & dosificación , Acetil-CoA Carboxilasa/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Factor de Transcripción AP-1/genética , Witanólidos/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Freshwater fish were caught from Nenjiang River in Qiqihaer City, and examined for metacercariae of Clonorchis sinensis by the artificial digestion (pepsin-HCl) method. The metacercariae (35-40) were given orally into stomach to each Kunming mouse of infection group (50 mice). The mice in control group were given the same amount of normal saline. The mice were sacrificed on the 5th, 10th, 15th, 20th, 25th, and 30th day after infection. Worms were collected, fixed and stained with carmine acetate, and observed under microscope. The egg-laying capacity of C. sinensis was observed in mice. 96%(48/50) mice were infected with metacercariae of C. sinensis. The recovery rate of adult worms on the 5th, 10th, 15th, 20th, 25th, and 30th day post-infection was 42.1%, 52.6%, 63.2%, 62.2%, 63.3%, and 63.2%, respectively. The first appearance of eggs in utero and feces was on the 15th and 20th day after infection, respectively. The branch of testis in worms was observed after 20 days of infection.
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Clonorquiasis , Animales , Clonorchis sinensis , Heces , Peces , Masculino , Ratones , Ríos , TestículoRESUMEN
Oral vaccines are generally perceived to be safe, easy to administer, and have the potential to induce both systemic and mucosal immune responses. However, given the challenges posed by the harsh gastrointestinal environment and mucus barriers, the development of oral vaccines necessitates the employment of a safe and efficient delivery system. In recent years, nanoparticle-based delivery has proven to be an ideal delivery vector for the manufacture of oral vaccines. Hence, considering the above, the sucralfate acidified (SA) encapsulated N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC)/N,O-carboxymethyl chitosan (CMCS) nanoparticles (SA@N-2-HACC/CMCS NPs) were prepared, and the BSA was used as a model antigen to investigate the immune responses. The SA@N-2-HACC/CMCS NPs had a particle size of 227 ± 7.0 nm and a zeta potential of 8.43 ± 2.62 mV. The NPs displayed slow and sustained release and high stability in simulated gastric juice and intestinal fluid. RAW 264.7 macrophage-like cell line demonstrated enhanced uptake of the SA@N-2-HACC/CMCS/BSA Nps. The vaccine via oral administration markedly enhanced the residence time of BSA in the intestine for more than 12 h and elicited the production of IgG and sIgA. The SA@N-2-HACC/CMCS NPs developed here for oral administration is an excellent technique for delivering antigens and provides a path of mucosal vaccine research.
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Adyuvantes Inmunológicos , Quitosano , Inmunidad Mucosa , Nanopartículas , Sucralfato , Quitosano/química , Animales , Ratones , Nanopartículas/química , Administración Oral , Células RAW 264.7 , Sucralfato/química , Inmunidad Mucosa/efectos de los fármacos , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/administración & dosificación , Vacunas/química , Vacunas/administración & dosificación , Vacunas/inmunología , Tamaño de la Partícula , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/inmunología , Portadores de Fármacos/químicaRESUMEN
SCOPE: Tolypocladium sinense is a fungus isolated from Cordyceps. Cordyceps has some medicinal value and is also a daily health care product. This study explores the preventive effects of T. sinense mycelium polysaccharide (TSMP) on high-fat diet-induced obesity and chronic inflammation in mice. METHODS AND RESULTS: Here, the study establishes an obese mouse model induced by high-fat diet. In this study, the mice are administered TSMP daily basis to evaluate its effect on alleviating obesity. The results show that TSMP can significantly inhibit obesity and alleviate dyslipidemia by regulating the expression of lipid metabolism-related genes such as liver kinase B1 (LKB1), phosphorylated AMP-activated protein kinase (pAMPK), peroxisome proliferator activated receptor α (PPARα), fatty acid synthase (FAS), and hydroxymethylglutaryl-CoA reductase (HMGCR) in the liver. TSMP can increase the protein expression of zona occludens-1 (ZO-1), Occludin, and Claudin-1 in the colon, improve the intestinal barrier dysfunction, and reduce the level of serum LPS, thereby reducing the inflammatory response. 16S rDNA sequencing shows that TSMP alters the intestinal microbiota by increasing the relative abundance of Akkermansia, Lactobacillus, and Prevotellaceae_NK3B31_group, while decreasing the relative abundance of Faecalibaculum. CONCLUSION: The findings show that TSMP can inhibit obesity and alleviates obesity-related lipid metabolism disorders, inflammatory responses, and oxidative stress by modulating the gut microbiota and improving intestinal barrier.
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Dieta Alta en Grasa , Microbioma Gastrointestinal , Inflamación , Ratones Endogámicos C57BL , Micelio , Obesidad , Dieta Alta en Grasa/efectos adversos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Obesidad/tratamiento farmacológico , Masculino , Micelio/química , Inflamación/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Ratones , Metabolismo de los Lípidos/efectos de los fármacos , Polisacáridos/farmacología , Hypocreales , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Polisacáridos Fúngicos/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismoRESUMEN
The agaricoglyceride is a new fungal secondary metabolite that constitutes esters of chlorinated 4-hydroxy benzoic acid and glycerol. The objective of this study was to explore whether the administration of agaricoglyceride could correct hepatic glycemic metabolism dysfunction by attenuating inflammation in the liver. The effects of agaricoglycerides on tumor necrosis factor-α, interleukin-1ß, vascular endothelial growth factor-α, interleukin-17, insulin secretion, adiponectin, leptin, hepatic glycogen, nuclear factor-κB activation, and total antioxidant activity were studied respectively. We demonstrated that administration of agaricoglycerides alleviated glycemic metabolism dysfunction, inflammation, and oxidative stress in mice. These data indicate that agaricoglyceride supplementation could restrain metabolic dysfunction through suppressing the nuclear factor-κB pathway as well as decreasing the levels of inflammatory cytokines and total antioxidant activities.
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Agaricus/química , Antiinflamatorios , Benzoatos/farmacología , Diabetes Mellitus/tratamiento farmacológico , Glicéridos/farmacología , Hígado/metabolismo , Adiponectina/sangre , Adiponectina/metabolismo , Animales , Benzoatos/química , Glucemia/efectos de los fármacos , Femenino , Glicéridos/química , Insulina/sangre , Insulina/metabolismo , Leptina/sangre , Leptina/metabolismo , Glucógeno Hepático/metabolismo , Ratones , Distribución AleatoriaRESUMEN
Chitosan is derived from chitin polysaccharide, the main component of crustacean shells. Chitosan is a biocompatible, nontoxic, and biodegradable polymer soluble in acidic solutions. It is widely used in the medical and pharmaceutical fields. Antimicrobial activities of chitosan against different bacterial, fungal, and viral pathogens have been considered one of its attractive properties, making chitosan valuable for biological applications, including textile, food, tissue engineering, agriculture, and environmental protection. Additionally, chitosan has beneficial effects on livestock, poultry, fish, and crustaceans, which can enhance immunity, improve feed conversion, and promote growth. However, the water solubility of chitosan influences antimicrobial capabilities, limiting its application. In the present work, we reviewed the preparation, factors affecting antimicrobial activity, morphological structure, antimicrobial mechanism, and application of chitosan derivatives, and the problems and prospects were pointed out. Collectively, this review provided an update on the application of chitosan derivatives and their potential for further advanced applications in the antimicrobial field.
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Antiinfecciosos , Quitosano , Nanocompuestos , Animales , Quitosano/farmacología , Quitosano/química , Bacterias , Antiinfecciosos/farmacología , Antiinfecciosos/química , TextilesRESUMEN
Physalis alkekengi L. calyx (PC) extract can relieve insulin resistance and has glycemic and anti-inflammatory effects; however, the potential mechanisms related to gut microbiota and metabolites remain elusive. This study aimed to understand how PC regulates gut microbiota and metabolites to exert anti-obesogenic effects and relieve insulin resistance. In this study, a high-fat high-fructose (HFHF)-diet-induced obesity C57BL/6J male mice model with glycolipid metabolism dysfunction was established, which was supplemented with the aqueous extract of PC daily for 10 weeks. The results showed that the PC supplementation could effectively cure the abnormal lipid metabolism and maintain glucose metabolism homeostasis by regulating the expression of adipose metabolic genes and glucose metabolism genes in the liver, thereby effectively alleviating the inflammatory response. PC treatment also increased the contents of fecal short-chain fatty acids (SCFAs), especially butyric acid. PC extract could restore the HFHF-disrupted diversity of gut microbiota by significantly increasing the relative abundance of Lactobacillus and decreasing those of Romboutsia, Candidatus_Saccharimonas, and Clostridium_sensu_stricto_1. The negative effects of the HFHF diet were ameliorated by PC by regulating multiple metabolic pathways, such as lipid metabolism (linoleic acid metabolism, alpha-linolenic acid metabolism, and sphingolipid metabolism) and amino acid metabolism (histidine and tryptophan metabolism). Correlation analysis showed that among the obesity parameters, gut microbiota and metabolites are directly and closely related. To sum up, this study suggested that PC treatment exhibited therapeutic effects by regulating the gut microbiota, fecal metabolites, and gene expression in the liver to improve glucose metabolism, modulate adiposity, and reduce inflammation.
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Microbioma Gastrointestinal , Resistencia a la Insulina , Physalis , Masculino , Animales , Ratones , Ratones Obesos , Glucolípidos/farmacología , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Inflamación/tratamiento farmacológico , Metabolismo de los Lípidos , Glucosa/farmacología , Expresión Génica , Dieta Alta en Grasa/efectos adversosRESUMEN
Hepatocellular carcinoma (HCC), the most prevalent type of aggressive liver cancer, accounts for the majority of liver cancer diagnoses and fatalities. Despite recent advancements in HCC treatment, it remains one of the deadliest cancers. Radiation therapy (RT) is among the locoregional therapy modalities employed to treat unresectable or medically inoperable HCC. However, radioresistance poses a significant challenge. It has been demonstrated that RT induced the upregulation of programmed death ligand 1 (PD-L1) on tumor cells, which may affect response to PD-1-based immunotherapy, providing a rationale for combining PD-1/PD-L1 inhibitors with radiation. Here, we utilized attenuated Salmonella as a carrier to explore whether attenuated Salmonella carrying siRNA-PD-L1 could effectively enhance the antitumor effect of radiotherapy on HCC-bearing mice. Our results showed that a combination of siRNA-PD-L1 and radiotherapy had a synergistic antitumor effect by inhibiting the expression of PD-L1 induced by radiation therapy. Mechanistic insights indicated that the combination treatment significantly suppressed tumor cell proliferation, promoted cell apoptosis, and stimulated immune cell infiltration and activation in tumor tissues. Additionally, the combination treatment increased the ratios of CD4+ T, CD8+ T, and NK cells from the spleen in tumor-bearing mice. This study presents a novel therapeutic strategy for HCC treatment, especially for patients with RT resistance.
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A novel quartz crystal microbalance (QCM) sensor with a high selectivity and sensitivity has been developed for bilirubin determination, based on the modification of bilirubin-imprinted titania film onto a quartz crystal by molecular imprinting and surface sol-gel techniques. The performance of the developed bilirubin biosensor was evaluated and the results indicated that a sensitive bilirubin biosensor could be fabricated. The obtained bilirubin biosensor presents high-selectivity monitoring of bilirubin, better reproducibility, shorter response time (30 min), wider linear range (0.1-50 µM), and lower detection limit (0.05 µM). The analytical application of the bilirubin biosensor confirms the feasibility of bilirubin determination in serum sample.
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Bilirrubina/análisis , Técnicas Biosensibles/métodos , Bilirrubina/sangre , Bilirrubina/química , Técnicas Biosensibles/estadística & datos numéricos , Técnicas Electroquímicas , Humanos , Concentración de Iones de Hidrógeno , Impresión Molecular , Transición de Fase , Tecnicas de Microbalanza del Cristal de Cuarzo , Propiedades de Superficie , TitanioRESUMEN
Culinary-medicinal Royal Sun mushroom, Agaricus brasiliensis (AbS), has traditionally been used for the prevention of a range of diseases, including cancer, hepatitis, atherosclerosis, hypercholesterolemia, diabetes, and dermatitis. The hepatoprotective effect of the fermented mushroom of A. brasiliensis (FMAE) and wild-growing A. brasiliensis (WMAE) were studied in this paper. An in vivo study of carbon tetrachloride (CCl4)-induced antioxidant activity in 2-month-old rats was conducted by examining the levels of activities of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) and the antioxidant enzymes, including glutathione peroxidase (GSHPx) and catalase (CAT). Rats were divided into four groups, each containing six rats. The first group served as a control group. The second group was the CCl4 group. Group I and group II were treated orally with distilled water for 14 days respectively. Group III and Group IV were treated orally by WMAE and FMAE at oral doses of 50 mg/kg-day, respectively. Both WMAE and FMAE could reduce CCl4-induced toxicity, particularly hepatotoxicity, by suppressing ALT and AST activities, and increasing antioxidant enzyme activity. The studies demonstrate that both the fermented and wild-growing A. brasiliensis could protect the liver against CCl4-induced oxidative damage in rats.
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Agaricus/química , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Alanina Transaminasa/genética , Alanina Transaminasa/metabolismo , Animales , Catalasa/genética , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Fermentación , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Hígado/enzimología , Masculino , Ratas , Ratas Wistar , AguaRESUMEN
The present paper is mainly aimed at optimization of cultivation conditions of fermented mushrooms of Coprinus comatus rich in vanadium (CCRV). Initial screening of effects of carbon source, temperature, pH, and inoculum size were done by using a one-factor-at-a-time method. The results obtained in that study showed that the optimal medium composition was 30 g glucose/Lin YEPG medium, initial pH 6.0, inoculum volume 10%, and incubation time 120 h. Then the medium was subjected to screening of the most significant parameters using the L9 orthogonal array to solve multivariable equations simultaneously. The results obtained in this study showed that the optimal medium composition was 0.4% V and 30 g glucose/Lin YEPG medium, initial pH 5.0, inoculum volume 15%, and incubation time 120 h. At this medium composition, the mycelial biomass and V content were 7.18 ± 0.24 g/L and 3786.0 ± 17 µg/g, respectively. The anti-diabetic potential of CCRV produced with the optimal level was tested in alloxan-induced diabetes. After the mice were administered (i.g.) with CCRV, the level of blood sugar in the CCRV group was very close to that of the control group. These findings suggested that CCRV produced with the optimal level is useful in the control of diabetes mellitus.
Asunto(s)
Coprinus/fisiología , Vanadio/química , Vanadio/toxicidad , Animales , Biodegradación Ambiental , Glucemia , Diabetes Mellitus Experimental/terapia , Concentración de Iones de Hidrógeno , RatonesRESUMEN
With the support of modern biotechnology, vaccine technology continues to iterate. The safety and efficacy of vaccines are some of the most important areas of development in the field. As a natural substance, chitosan is widely used in numerous fields-such as immune stimulation, drug delivery, wound healing, and antibacterial procedures-due to its good biocompatibility, low toxicity, biodegradability, and adhesion. Chitosan-based nanoparticles (NPs) have attracted extensive attention with respect to vaccine adjuvants and delivery systems due to their excellent properties, which can effectively enhance immune responses. Here, we list the classifications and mechanisms of action of vaccine adjuvants. At the same time, the preparation methods of chitosan, its NPs, and their mechanism of action in the delivery system are introduced. The extensive applications of chitosan and its NPs in protein vaccines and nucleic acid vaccines are also introduced. This paper reviewed the latest research progress of chitosan-based NPs in vaccine adjuvant and drug delivery systems.