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Background: Fu-zi decoction (FZD) has a long history of application for treating Rheumatoid arthritis (RA) as a classic formulation. However, its underlying mechanisms have not been fully elucidated. This study aimed to decipher the potential mechanism of FZD in treating RA, with a specific focus on receptor activator of nuclear factor κB/receptor activator of nuclear factor κB ligand (RANK/RANKL) signaling pathway. Methods: The impact of FZD on RA was investigated in collagen-induced arthritis rats (CIA), and the underlying mechanism was investigated in an osteoclast differentiation cell model. In vivo, the antiarthritic effect of FZD at various doses (2.3, 4.6, 9.2 g/kg/day) was evaluated by arthritis index score, paw volume, toe thickness and histopathological examination of inflamed joints. Additionally, the ankle joint tissues were determined with micro-CT and safranin O fast green staining to evaluate synovial hyperplasia and articular cartilage damage. In vitro, osteoclast differentiation and maturation were evaluated by TRAP staining in RANKL-induced bone marrow mononuclear cells. The levels of pro- and anti-inflammatory cytokines as well as RANKL and OPG were evaluated by ELISA kits. In addition, Western blotting was used to investigate the effect of FZD on RANK/RANKL pathway activation both in vivo and in vitro. Results: FZD significantly diminished the arthritis index score, paw volume, toe thickness and weigh loss in CIA rats, alleviated the pathological joint alterations. Consistent with in vivo results, FZD markedly inhibited RANKL-induced osteoclast differentiation by decreasing osteoclast numbers in a dose-dependent manner. Moreover, FZD decreased the levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α, while increasing anti-inflammatory cytokine IL-10 level both in serum and culture supernatants. Treatment with FZD significantly reduced serum RANKL levels, increased OPG levels, and decreased the RANKL/OPG ratio. In both in vivo and in vitro settings, FZD downregulated the protein expressions of RANK, RANKL, and c-Fos, while elevating OPG levels, further decreasing the RANKL/OPG ratio. Conclusion: In conclusion, FZD exerts a therapeutic effect in CIA rats by inhibiting RANK/RANKL-mediated osteoclast differentiation, which suggested that FZD is a promising treatment for RA.
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OBJECTIVE: High altitude hypoxic environment has a certain negative impact on physical fitness of adolescents. We aimed to understand the physical fitness status of Tibetan adolescents in different high-altitude areas in Tibet, China. METHODS: Physical fitness items, such as grip strength, standing long jump, sit and reach, 50 m dash, 1000 m run for boys, and 800 m run for girls were tested on 3806 Tibetan adolescents by using stratified whole group sampling method in class units. The mean age of the participants was (15.51 ± 1.69) years for Tibetan males and (15.54 ± 1.69) years for females. One-way analysis of variance (ANOVA) and other methods were used to make cross-sectional comparisons of physical fitness performance of Chinese Tibetan adolescents in different high-altitude regions. RESULTS: The standing long jump scores of boys (203.37 ± 28.36) were higher than that of girls (152.97 ± 19.46) and the lowest standing long jump scores of adolescents in Shigatse region (166.39 ± 35.04). The highest level of sit and reach was found among boys (10.69 ± 5.34) in Nyingchi and the lowest level of sit and reach was found among girls (8.42 ± 5.84) in Shigatse. Shigatse region adolescents had the lowest performance in 50 m dash (9.09 ± 1.72) while the best performance in 1000 m run (266.23 ± 35.82) and 800 m run (245.40 ± 27.92). CONCLUSION: There is variability in the physical fitness of Tibetan adolescents in different high-altitude regions of Tibet, China. Targeted physical fitness interventions should be carried out for Tibetan adolescents in different high-altitude regions. The focus should be on improving the endurance quality of Tibetan adolescents in Lhasa and the lower limb muscle strength, flexibility, and speed quality of adolescents in Shigatse.
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Altitude , Aptidão Física , Masculino , Feminino , Humanos , Adolescente , Tibet , Estudos Transversais , China , Aptidão Física/fisiologiaRESUMO
Angiopoietin-like protein 8 (ANGPTL8) is a secreted protein predominantly expressed in liver and adipose tissue. ANGPTL8 modulates the clearance of triglycerides (TGs) by suppressing the activity of lipoprotein lipase (LPL) within the plasma. Previous studies found that circulating ANGPTL8 levels were significantly increased in metabolic disorder-related diseases, such as type 2 diabetes mellitus (T2DM), obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Whether ANGPTL8 has a direct pathogenic role in these diseases remains to be determined. In this review, we summarize the emerging roles of ANGPTL8 in the regulation of inflammation, tumours, circulatory system-related diseases, and ectopic lipid deposition, which may provide new insights into the diverse functions of ANGPTL8 in various diseases beyond its well-established functions in glucose and lipid metabolism.
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Human aging is characterized by gut microbiome alteration and differential loss of gut commensal species associated with the onset of frailty. The administration of cultured commensal strains to replenish lost taxa could potentially promote healthy aging. To investigate the interaction of whole microbiomes and administered strains, we transplanted gut microbiota from a frail or healthy elderly subject into germ-free mice. We supplemented the frail-donor recipient group with a defined consortium of taxa (the "S7") that we identified by analyzing healthy aging subjects in our previous studies and whose abundance correlated with health-promoting dietary intervention. Inoculation with a frail or a healthy donor microbiome resulted in differential microbiota compositions in murine recipients 5 weeks post-transplantation. Fecal acetate levels were significantly higher in healthy donor recipient mice than in frail donor recipient mice after 4 weeks. However, the frailty-related phenotype was not replicated in recipient mice with single-dose microbiota transplantation from a healthy and a frail donor. Five S7 species colonized successfully in germ-free mice, with a relatively high abundance of Barnesiella intestinihominis and Eubacterium rectale. The engraftment of five S7 species in germ-free mice increased fecal acetate levels and reduced colon permeability and plasma TNF-É concentration. Supplementation with the S7 in frail-microbiota recipient mice did not increase alpha-diversity but significantly increased the abundance of Barnesiella intestinihominis. S7 supplementation showed the potential for improving spatial reference memory in frail-microbiota recipient mice. Collectively, these data highlight the challenge of elderly microbiota engraftment in the germ-free mouse model but show promise for modulating the gut microbiome of frail elderly subjects by administering an artificial gut microbe consortium associated with healthy aging.
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Fragilidade , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Idoso , Microbioma Gastrointestinal/genética , Bacteroidetes , Fezes/microbiologia , Transplante de Microbiota Fecal , AcetatosRESUMO
Taurine-respiring gut bacteria produce H2S with ambivalent impact on host health. We report the isolation and ecophysiological characterization of a taurine-respiring mouse gut bacterium. Taurinivorans muris strain LT0009 represents a new widespread species that differs from the human gut sulfidogen Bilophila wadsworthia in its sulfur metabolism pathways and host distribution. T. muris specializes in taurine respiration in vivo, seemingly unaffected by mouse diet and genotype, but is dependent on other bacteria for release of taurine from bile acids. Colonization of T. muris in gnotobiotic mice increased deconjugation of taurine-conjugated bile acids and transcriptional activity of a sulfur metabolism gene-encoding prophage in other commensals, and slightly decreased the abundance of Salmonella enterica, which showed reduced expression of galactonate catabolism genes. Re-analysis of metagenome data from a previous study further suggested that T. muris can contribute to protection against pathogens by the commensal mouse gut microbiota. Together, we show the realized physiological niche of a key murine gut sulfidogen and its interactions with selected gut microbiota members.
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Afeto , Salmonella enterica , Humanos , Animais , Camundongos , Ácidos e Sais Biliares , Taurina , EnxofreRESUMO
The development of miniature mass spectrometry (MS) systems with simple analysis procedures is important for the transition of applying MS analysis outside traditional analytical laboratories. Here, we present Mini 14, a handheld MS instrument with disposable sample cartridges designed based on the ambient ionization concept for intrasurgical tissue analysis and surface analysis. The instrumentation architecture consists of a single-stage vacuum chamber with a discontinuous atmospheric interface and a linear ion trap. A major effort in this study for technical advancement is on making handheld MS systems capable of automatically adapting to complex conditions for in-field analysis. Machine learning is used to establish the model for autocorrecting the mass offsets in the mass scale due to temperature variations and a new strategy is developed to extend the dynamic concentration range for analysis. Mini 14 weighs 12 kg and can operate on battery power for more than 3 h. The mass range exceeds m/z 2000, and the full peak width at half-maximum is Δm/z 0.4 at a scanning speed of 700 Th/s. The direct analysis of human brain tissue for identifying glioma associated with isocitrate dehydrogenase mutations has been achieved and a limit of detection of 5 ng/mL has been obtained for analyzing illicit drugs in blood.
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Glioma , Drogas Ilícitas , Humanos , Isocitrato Desidrogenase , Espectrometria de Massas , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
Transition metal doped carbon materials are recognized as promising sensing platforms for glucose detection. Herein, a simple strategy involving crystallinity, nanostructure engineering, and pyrolysis was developed for constructing well-defined Ni nanoparticle embedded on nanoporous carbon nanorods (Ni/NCNs). A three-dimensional nickel-based metal-organic framework (Ni-MOF) was used as both a self-sacrificing template and precursor. Due to the synergistic effects between the uniformly dispersed Ni nanoparticles and the nanoporous carbon matrix, the as-prepared Ni/NCNs exhibited remarkable electrochemical activity. The fabricated Ni/NCNs glucose sensor showed excellent electrocatalytic performance with ultra-low limit of detection, wide linear detection ranges, fast response times (within 1.6 s), superior stability, and anti-interference characteristics. Moreover, the Ni/NCNs sensing platform was successfully applied to analyze glucose concentrations in human blood samples. These results showed that Ni/NCNs hold potential applications in developing enzyme-free glucose sensors.
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Nanopartículas , Nanotubos , Carbono , Glucose , Humanos , NíquelRESUMO
MicroRNA-21 (miR-21) has been widely investigated as important biomarkers for cancer diagnosis and treatment. Herein, a highly sensitive nonenzymatic electrochemical biosensor based on Pd@metal-organic frameworks (Pd@UiO-66) and target-catalytic hairpin assembly (CHA) with target recycling approach has been proposed for the detection of miR-21. The proposed biosensor integrates the efficient CHA strategy and excellent electrocatalytic performance of Pd@UiO-66 nanocomposites. The concentration of miRNA-21 is related to the amount of the adsorbed electrocatalyst, leading to the different electrochemical signals for readout towards paracetamol (AP). This biosensor shows a low limit of detection of 0.713 fM with the dynamic range of 20 fM -600 pM under the optimal experimental conditions, providing a powerful platform for detecting miR-21. Furthermore, the designed biochemical self-assembly strategy of this electrochemical biosensor is promising candidate for potential applications in the analysis of other important genetic biomarkers for early diagnosis of cancers.
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Técnicas Biossensoriais , Estruturas Metalorgânicas , MicroRNAs , Catálise , Técnicas Eletroquímicas , Humanos , Limite de Detecção , MicroRNAs/análiseRESUMO
A hybridization chain reaction (HCR) amplification-based electrochemical impedimetric biosensor is fabricated for the quick, sensitive, and specific detection of miRNA-21 (miR-21) via monitoring of electrode interfacial property changes in real-time. Two sequences of H1 and H2 are adopted to trigger HCR amplification. A large amount of linear DNA concatemer are formed which could change the interfacial properties of the electrode. Interfacial charge transfer resistance difference (Rct) is probed via electrochemical impedance spectroscopy (EIS) and Randles equivalent circuit. After amplifying via HCR, oligonucleotides with negatively charged repelling [Fe(CN)6]3-/4- ions can form a spatial blockage. HCR amplification strategy markedly enhanced the electrochemical signal with a limit of detection (LOD) down to 4.63 fM (S/N = 3). This strategy exhibited excellent selectivity for three different miRNAs: miR-199a, miR-141, and miR-155. Moreover, results show that the proposed method can be applied to miR-21 detection in the total RNA extracted from five cells. This work presents an enzyme-free and label-free EIS nucleic acid sensor for sensitively and selectively detecting miR-21, offering a promising approach in early diseases diagnosis.
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Técnicas Biossensoriais , MicroRNAs , Espectroscopia Dielétrica , Técnicas Eletroquímicas , Limite de Detecção , MicroRNAs/genética , Hibridização de Ácido NucleicoRESUMO
Glucose is a popular biosensor target due to its closely with diabetes or hypoglycemia in blood. Designing efficiency electrocatalysts for the determination of glucose is vital to develop glucose detection devices. CoMoO4, as a kind of bimetallic oxide material, exhibits unique electrochemical properties. 3D macroporous carbon (MPC) has large specific surface area and excellent electrical conductivity, providing an effective support for loading other nano-entities to form novel composite with good synergetic effects. Herein, nanorod-like CoMoO4 anchored onto MPC support was synthesized for the development of a promising electrochemical sensing platform for glucose. Attributing to the synergic effects between the good electrocatalytic performance of CoMoO4 nanorods and the extraordinary electrical conductivity of 3D layered MPC, the novel CoMoO4/MPC composites non-enzymatic sensor shows excellent electrocatalytic performance for oxidation of glucose. Under the optimum conditions, the proposed CoMoO4/MPC hybrids provided a reliable linear range of 5â¯×â¯10-7 to 1.08â¯×â¯10-4â¯M with a low limit of detection (0.13⯵M) for the detection of glucose. Meanwhile, the CoMoO4/MPC sensing platform shows fast response time of 1.76â¯s, good stability and selectivity for detecting glucose. Moreover, this non-enzymatic sensor also has been successfully applied to measure glucose level in human blood samples. Therefore, the developed sensor holds a new promise for the construction of facile and sensitive non-enzymatic glucose analytical platform.
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Carbono/química , Cobalto/química , Eletrodos , Glucose/análise , Molibdênio/química , Nanotubos/química , Técnicas Biossensoriais , Catálise , Técnicas Eletroquímicas , Humanos , Limite de Detecção , OxirreduçãoRESUMO
This study evaluated the effects of high-grain diets on the rumen fermentation, epithelial bacterial community, morphology of rumen epithelium, and local inflammation of goats during high-grain feeding. Twelve 8-month-old goats were randomly assigned to two different diets, a hay diet or a high-grain diet (65% grain, HG). At the end of 7 weeks of treatment, samples of rumen content and rumen epithelium were collected. Rumen pH was lower (P < 0.05), but the levels of volatile fatty acids and lipopolysaccharides were higher (P < 0.05) in the HG group than those in the hay group. The principal coordinate analysis indicated that HG diets altered the rumen epithelial bacterial community, with an increase in the proportion of genus Prevotella and a decrease in the relative abundance of the genera Shuttleworthia and Fibrobacteres. PICRUSt analysis suggested that the HG-fed group had a higher (P < 0.05) relative abundance of gene families related to energy metabolism; folding, sorting, and degradation; translation; metabolic diseases; and immune system. Furthermore, HG feeding resulted in the rumen epithelial injury and upregulated (P < 0.05) the gene expressions of IL-1ß and IL-6, and the upregulations were closely related to the rumen pH, LPS level, and rumen epithelial bacteria abundance. In conclusion, our results indicated that the alterations in the rumen environment and epithelial bacterial community which were induced by HG feeding may result in the damage and local inflammation in the rumen epithelium, warranting further study of rumen microbial-host interactions in the HG feeding model.
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Ração Animal/efeitos adversos , Bactérias/isolamento & purificação , Grão Comestível/efeitos adversos , Cabras/microbiologia , Microbiota , Animais , Clostridiales/isolamento & purificação , Citocinas/metabolismo , Dieta/efeitos adversos , Dieta/veterinária , Epitélio/metabolismo , Epitélio/microbiologia , Ácidos Graxos Voláteis/análise , Fermentação , Cabras/metabolismo , Inflamação/veterinária , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Lipopolissacarídeos/análise , Masculino , Prevotella/isolamento & purificação , Distribuição Aleatória , Rúmen/metabolismo , Rúmen/microbiologiaRESUMO
A simple and highly efficient interface to couple capillary electrophoresis with inductively coupled plasma mass spectrometry by a microflow polyfluoroalkoxy nebulizer and a quadruple ion deflector was developed in this study. By using this interface, six arsenic species, including arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine, and arsenocholine, were baseline-separated and determined in a single run within 11 min under the optimized separation conditions. The instrumental detection limit was in the range of 0.02-0.06 ng/mL for the six arsenic compounds. Repeatability expressed as the relative standard deviation (n = 5) of both migration time and peak area were better than 2.5 and 4.3% for six arsenic compounds. The proposed method, combined with a closed-vessel microwave-assisted extraction procedure, was successfully applied for the determination of arsenic species in the Solanum Lyratum Thunb samples from Anhui province in China with the relative standard deviations (n = 5) ≤4%, method detection limits of 0.2-0.6 ng As/g and a recovery of 98-104%. The experimental results showed that arsenobetaine was the main speciation of arsenic in the Solanum Lyratum Thunb samples from different provinces in China, with a concentration of 0.42-1.30 µg/g.
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Arsenicais/química , Espectrometria de Massas/métodos , Solanum/química , China , Eletroforese CapilarRESUMO
Remarkably little information is available about the impact of high-grain (HG) feeding on colonic mucosa-associated bacteria and mucosal morphology. In the present study, 12 male goats were randomly assigned to either a hay diet (n = 6) or an HG diet (65% grain; n = 6) to characterise the changes in the composition of the bacterial community in colonic mucosa and the mucosal morphology of the colon. The results showed that HG feeding decreased the colonic pH and increased the concentrations of total short chain fatty acids and lipopolysaccharides in colonic digesta. The principal coordinate analysis results showed that the HG diet altered the colonic mucosal bacterial communities, with an increase in the abundance of genus Blautia and a decrease in the abundance of genera Bacillus, Enterococcus, and Lactococcus. The HG-fed goats showed sloughing of the surface layer epithelium, intercellular tight junction erosion, cell mitochondrial damage, and upregulation of the relative mRNA expression of IL-2 and IFN-γ in colonic mucosa. Collectively, our data indicate that HG feeding induced changes in colonic mucosal morphology and cytokines expression that might be caused by excessive fermentation and dramatic shifts in the bacterial populations in the colon.
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Colo/microbiologia , Grão Comestível/efeitos adversos , Mucosa Intestinal/microbiologia , Ração Animal/efeitos adversos , Animais , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Clostridiales/genética , Clostridiales/isolamento & purificação , Colo/metabolismo , Colo/patologia , Ácidos Graxos/metabolismo , Cabras , Concentração de Íons de Hidrogênio , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lipopolissacarídeos/metabolismo , Masculino , Microbiota , Proteobactérias/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Análise de Sequência de DNA , Spirochaetales/genética , Spirochaetales/isolamento & purificação , Junções Íntimas/patologiaRESUMO
In order to support the increasing need to share electronic health data for research purposes, various methods have been proposed for privacy preservation including k-anonymity. Many k-anonymity models provide the same level of anoymization regardless of practical need, which may decrease the utility of the dataset for a particular research study. In this study, we explore extensions to the k-anonymity algorithm that aim to satisfy the heterogeneous needs of different researchers while preserving privacy as well as utility of the dataset. The proposed algorithm, Attribute Utility Motivated k-anonymization (AUM), involves analyzing the characteristics of attributes and utilizing them to minimize information loss during the anonymization process. Through comparison with two existing algorithms, Mondrian and Incognito, preliminary results indicate that AUM may preserve more information from original datasets thus providing higher quality results with lower distortion.