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The precise clinical diagnosis of prostate cancer still presents inherent challenges, and usually a monitoring of multiple biomarkers is required. In this study, a new aggregation-induced emission (AIE)-based bifunctional strategy was developed for the simultaneous detection of prostate cancer-specific in situ membrane antigens (PSMA) and free antigens (PSA). First, a bifunctional fluorescent probe with double sensing sites (a PSA-specific sensing site and a PSMA-targeted ligand) was constructed. In the presence of PSA, it specifically binds to the PSA-specific sensing site of the probe, resulting in the restoration of the fluorescence signal, enabling linear sensing of PSA. For the detection of PSMA, the PSMA-targeted ligand modified on the probe can specifically recognize PSMA, inducing the aggregation of the AIE material and resulting in an enhanced fluorescence signal. Moreover, a liposome-based artificial cell was developed to simulate the real prostate cancer cell, and it was used to investigate the feasibility of monitoring the two types of antigens. Utilizing this bifunctional fluorescent strategy, a dual-analysis of free serum antigen biomarker of PSA and in-situ membrane antigen of PSMA was achieved. The assay exhibited a wide linearity range for PSA detection from 0.0001 to 0.1 µg/mL, with a low limit of detection (LOD) of 6.18 pg/mL. For PSMA, the obtained LOD is 8.79 pg/mL, with a linearity range from 0.0001 to 0.1 µg/mL. This strategy allows us to simultaneously assess the levels of two types of biomarkers in living human prostatic cancer cells, providing a highly accurate and selective tool for early screening and monitoring of prostatic cancer.
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Antígenos de Superfície , Técnicas Biossensoriais , Corantes Fluorescentes , Glutamato Carboxipeptidase II , Antígeno Prostático Específico , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Antígeno Prostático Específico/sangue , Glutamato Carboxipeptidase II/análise , Glutamato Carboxipeptidase II/sangue , Antígenos de Superfície/análise , Antígenos de Superfície/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Limite de Detecção , Espectrometria de Fluorescência/métodos , Linhagem Celular TumoralRESUMO
To address the challenge of signal production and separation for multiple microRNA (miRNA) detection, in this work, a "one-pot" process to self-generate distinguishable fluorescent probes was developed. Based on a long and short probe amplification strategy, the generated G-quadruplex fluorescent dye-free probes can be separated and detected by a high-performance liquid chromatography-fluorescence platform. The free hairpin probes enriched in guanine with different lengths and base sequences were designed and could be opened by the target miRNAs (miRNA-10b, miRNA-21, and miRNA-210). Cleaved G-quadruplex probes with fluorescent signal could be generated in a one-pot process after a duplex-specific nuclease-based cleavage, and the detection of multiple miRNAs could be realized in one run. No solid nanomaterials were applied in the assay, which avoided the blocking of the column. Moreover, without modification of expensive fluorescein, the experimental cost was greatly reduced. The one-pot reaction process also eliminated tedious preparation steps and suggested feasibility of automation. The limits of detection of miRNA-10b, miRNA-21, and miRNA-210 were 2.19, 2.20, and 2.75 fM, respectively. Notably, this method was successfully applied to multiplex detection of miRNAs in serum samples from breast cancer patients within 30 min.
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Técnicas Biossensoriais , Quadruplex G , MicroRNAs , Humanos , MicroRNAs/análise , Corantes Fluorescentes , Fluoresceína , Cromatografia Líquida , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas Biossensoriais/métodosRESUMO
The lack of solid-phase media limits the portability of colorimetric sensing platforms. In this study, a series of transparent polyvinyl alcohol (PVA) hydrogels encapsulated antimony tin oxide nanoparticles (ATO NPs) and 3,3',5,5'-tetramethylbenzidine (TMB) were developed as the solid-phase sensing media for glucose and uric acid. Under the conditions of H2O2 and UV light, the hydrogel presented a multicatalytic ability (photo Fenton-like and peroxidase-like activities), which accelerated the oxidation of TMB, turning the hydrogel from colorless to blue and finally enhancing the detection signal. The plasticity of the hydrogel allowed it to be designed into various shapes (membrane, microsphere etc.) to adapt multiple detection platforms (a liquid/solid-phase UV spectrophotometer, a NanoPhotometer, and smartphone spectroscopy). The hydrogel sensing media exhibited excellent tunability and enhanced the photocatalytic ability. The proposed material was successfully applied to detect glucose and uric acids in real samples by four detection platforms to evaluate its practicability.
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Nanopartículas , Ácido Úrico , Peróxido de Hidrogênio/química , Hidrogéis , Glucose , Nanopartículas/química , Colorimetria/métodosRESUMO
Biogenic amines (BAs) represent a class of potentially harmful substances in foods and medicines. Their content is thus an important indicator of proper hygiene in food preparation, and purity of medicines. It is of great practical significance to establish accurate and sensitive detection of BAs in food and drugs. In this study, a high performance liquid chromatography (HPLC) method was developed for the simultaneous detection of multiple BAs in fish, pork and antibiotics based on aptamer signal replacement and cyclic amplification strategy. First, non-fluorescent targets were converted into fluorescent nucleic acid probes using a two-step replacement process. Subsequently, a large number of nucleic acid probes with different lengths and base sequences were generated using a double-stranded specific nuclease-assisted signal amplification strategy. Finally, various BAs in real samples were accurately identified using an HPLC platform. The influence of base sequence and nucleic acid probe length on separation via HPLC was studied to improve discrimination among fluorescent signals. Four different sequences were selected as tails to the DNA probe, and their retention times increased in turn. Experimental conditions, including column temperature, flow rate, gradient elution process, reaction temperature, and incubation time, were optimized by orthogonal experiments to further improve signal separation efficiency. Specifically, the methanol gradient was changed from 10% to 20% during 0-20 min, 35 â of column temperature and 1.0 mL/min of flow rate were chosen as the HPLC conditions. The final resolution of chromatographic peaks was 3.44, 3.59 and 2.37, indicating complete separation between peaks. Optimal incubation time for BA capture by aptamer was 120 min, and optimal dosage of duplex specific nuclease (DSN) and Mg2+were 0.9 U and 30 mmol/L. The optimal pH, incubation temperature, and DSN incubation time were 7.0, 40 â and 210 min, respectively. The proposed method exhibited high sensitivity towards BAs, with a linear range of 1 pmol/L-1 µmol/L, and the limits of detection of tyramine, histamine, spermine, and tryptamine were 0.25, 0.21, 0.27 and 0.19 pmol/L, respectively. The feasibility of this method was verified, and contrast experiments indicated that it could achieve highly selective detection of four BAs in one run. The applicability of this integrated method was also investigated for the detection of real samples (gentamycin sulfate, fish and pork). To assess the matrix effect, each BA with different concentrations were spiked into real fish and pork samples. Relative recoveries and relative standard deviations (RSDs) ranged from 101.2% to 104.5% and from 1.5% to 4.3%, respectively. The above detection results for real samples showed that this method could accurately capture, separate, and identify BAs in complex matrix samples. This strategy can effectively improve analyte selectivity and reduce the matrix effect. This assay is thus expected to provide a new approach for food and drug analyses.
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Aminas Biogênicas , Histamina , Animais , Aminas Biogênicas/análise , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão , Histamina/análise , PeixesRESUMO
Saponins from bitter melon (BMS) are well-known to have various biological activities, especially in the field of fat-lowering. However, many gaps remain in our knowledge of BMS-induced fat reduction and health benefits. Here, we aimed to investigate the precise mechanism of BMS in alleviating fat accumulation in C. elegans and HepG2 cell line. Results indicated that BMS showed strong fat-lowering and lifespan-extension properties. Lipidomic analysis illustrated that BMS could alter the lipid profile, especially represented by phosphatidylethanolamine (PE) increase, which plays an essential role in autophagy. Furthermore, we applied gene-deficient mutants and RNAi technology to confirm that BMS largely depended on daf-16/FoxO1 and hlh-30/TFEB mediated lipophagy to reduce fat deposition. In addition, BMS could ameliorate oil acid (OA)-induced fat accumulation in HepG2 cells by induction of autophagy-related proteins, such as the phosphorylated AMPK and LC3B. In conclusion, our results elucidated the underlying mechanism of bitter melon saponins interfering with lipid metabolism from the autophagy point of view, which provide new insights into a nutraceutical to mitigate obesity.
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Fermentation by lactic acid bacteria can improve the nutritional value and biological function of cereal. Our previous studies have confirmed that Lactobacillus plantarum fermented barley extract (LFBE) can alleviate obesity caused by high-fat diet (HFD) in rats, while the precise mechanism remains unclear. Herein, we explored the effect of LFBE on the adipose tissue in obese rats and its mechanism via transcriptomics technology. Results showed that administration of LFBE in obese rats for 8 weeks significantly alleviated weight gain, reduced fasting blood glucose, and inhibited lipid accumulation. Transmission electron microscope (TEM) observation of adipose tissue found that LFBE held the ability to maintain mitochondria integrity and functionality. Transcriptomics analysis revealed that LFBE increased the expressions of mitochondrial ß-oxidized-related genes, while inhibiting the expressions of fatty acid synthesis-related genes. Furthermore, KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis and western blotting studies confirmed that LFBE mainly enhanced the energy consumption of adipocytes through the phosphorylation of AMP-Activated Protein Kinase (AMPK) and the mitochondrial proliferation pathway regulated by peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC1α). Taken together, these findings indicated that LFBE could ameliorate HFD-induced obesity by activating AMPK/PGC1α axis regulated signaling pathways.
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Fármacos Antiobesidade , Hordeum , Lactobacillus plantarum , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Hordeum/microbiologia , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Ratos , TranscriptomaRESUMO
BACKGROUND: A reduced level of fatty acid oxidation (FAO) by skeletal muscle leads to the accumulation of intermuscular fat (IMF), which is linked to impaired exercise capacity. Previously, we have reported that Lactiplantibacillus plantarum fermented barley extract (LFBE) has effective anti-obesity properties. In this study, the effects of LFBE on muscle were investigated. RESULTS: LFBE improved running endurance and muscle strength, which was caused by the elevation of FAO in muscle. In addition, LFBE renovated muscle regeneration through the upregulation of paired box 7 and myogenic differentiation 1 expression avoiding the injury of skeletal muscle fibers. Furthermore, total polyphenol isolated from LFBE (FTP) reinforced mobility and showed a significant protective effect on maintaining muscle fiber morphogenesis in Caenorhabditis elegans. Transmission electron microscope observation suggested FTP induced mitophagy in C. elegans body wall muscle, which was strongly connected with enhanced FAO in mitochondria. CONCLUSIONS: Our findings highlighted the beneficial bioactivities of FTP and its potential application for stimulating mitophagy and muscle function in obese individuals. © 2022 Society of Chemical Industry.
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Hordeum , Lactobacillus plantarum , Animais , Caenorhabditis elegans , Dieta Hiperlipídica , Fermentação , Hordeum/química , Humanos , Lactobacillus plantarum/metabolismo , Mitofagia , Músculo Esquelético/metabolismo , Músculos/metabolismo , Obesidade/metabolismo , Extratos Vegetais/químicaRESUMO
The objective of this study was to compare the in vitro digestibility of different buckwheat and wheat starch cultivars and establish the relationship between digestibility and structure of buckwheat starch. Structure of starches were analyzed with size exclusion chromatography and fluorophore-assisted capillary electrophoresis. Results showed that the amylose content of Tartary buckwheat starch (TBS) and common buckwheat starch (CBS) was 3-4% lower than that of wheat starch. However, no significant difference in the digestibility was found between them. The fast digestion rate coefficient of TBS was negatively correlated with the amount of long amylopectin chains (24 < DP ≤ 36), and the total digested starch percentage of CBS was negatively correlated with the amount of medium-long amylopectin chains (13 < DP ≤ 24). This suggests that the digestibility of fully gelatinized starch had no association with the botanical sources but may be more influenced by starch structure.
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Fagopyrum , Amido , Amilopectina , Amilose , Estrutura Molecular , TriticumRESUMO
Volvariella volvacea has bioactivities in improving immunity, anti-oxidation, and alleviating obesity, which is an excellent functional food. Polysaccharide from Volvariella volvacea (VPS), one of the main bioactive components, exerts a potential fat-lowering effect, but its exact mechanism remains unclear. In this study, the effects and molecular pathways of VPS regulate the fat deposition of Caenorhabditis elegans. Results showed that VPS at low (250 µg/ml), medium (500 µg/ml) and high (750 µg/ml) concentrations all reduced the overall fat, without inhibitory effects on the growth and movement abilities of nematode. VPS at 500 µg/ml could dramatically decrease the triglyceride (TG) level of wild-type nematode, while no significant changes in TG content were observed in mutants deficient in aak-2 (energy receptor), nhr-49 (nuclear transcription factor), fat-5, and fat-7 genes. VPS declines fat storage of C. elegans, largely through the aak-2/nhr-49-mediated fatty acid synthesis pathway, and partially the acs-2-mediated fatty acid oxidation pathway. PRACTICAL APPLICATIONS: A model illustrates the mechanism of polysaccharide from Volvariella volvacea (VPS) inhibiting fat accumulation in Caenorhabditis elegans. VPS may directly or indirectly activate the energy sensor aak-2, which governs lipid metabolism. Results demonstrate that VPS regulates fat metabolism including fatty acid oxidation (FAO) and fatty acid synthesis (FAS), rather than lipolysis. In the FAO, VPS promotes FAO by up-regulating the mRNA and protein levels of acs-2. In FAS, VPS significantly down-regulated the transcriptional regulator nhr-49 and the downstream targets fat-5, fat-6, and fat-7, thereby declining the overall fat deposition. In conclusion, VPS inhibits the fat accumulation of C. elegans largely dependent on an aak-2/nhr-49-mediated FAS pathway.
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Agaricales , Proteínas de Caenorhabditis elegans , Proteínas Quinases Ativadas por AMP , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Polissacarídeos/farmacologia , Receptores Citoplasmáticos e NuclearesRESUMO
High-fat diet (HFD)-induced obesity is caused by the imbalance between energy intake and expenditure. Here, we studied the inhibitory effects of aqueous extracts of fermented barley with Lactobacillus plantarum dy-1 (LFBE) and beta-glucan (BGL) on the obesity induced by HFD. Both LFBE and BGL significantly decreased body weight, suppressed visceral lipid accumulation, improved blood lipid profile, and glucose tolerance in HFD rats. BGL showed no thermogenic capacity, while LFBE enhanced the expression of Uncoupling Protein 1 (UCP1), and brown-specific mRNA (PRDM16, PGC1-α, and CIDEA) levels in brown adipose tissue (BAT) and white adipose tissues (WAT) of HFD rats. In addition, LFBE increased the expression of key genes involved in mitochondria biosynthesis and the mitochondrial respiration function. Further, we demonstrated that proteins extracted from LFBE (LFBE-P) were responsible for triggering brown markers to some extent. In conclusion, LFBE alleviates HFD-induced obesity by activating thermogenic fat bioenergetics and mitochondria biosynthesis. PRACTICAL APPLICATIONS: Barley is one of the most productive crops with pretty low utilization. Our group committed to exploring the application and nutritional value of barley. This work aimed to explore improvements in nutritional function of barley after fermentation by Lactobacillus plantarum dy-1. Our study found that oral administration of LFBE help turning white adipose tissue into a thermogenesis state and activate heat generation function of brown adipose tissue. Its characteristics mentioned above significantly inhibited the body weight and blood lipid of high-fat diet rats. Further, we evidenced that LFBE-P were responsible for triggering brown markers in 3T3-L1 cells. We believe our research plays a great part to relieving high-fat diet-induced obesity and type 2 diabetes with functional diet supplementation.
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Diabetes Mellitus Tipo 2 , Hordeum , Lactobacillus plantarum , Adipócitos Brancos , Animais , Dieta Hiperlipídica/efeitos adversos , Obesidade/etiologia , Extratos Vegetais/farmacologia , RatosRESUMO
Fermented barley (FB) flour by Lactobacillus plantarum is richer in dietary fiber, polyphenols, gamma-aminobutyric acid, and other biologically active ingredients. This study aimed to determine the impacts of fermented barley - wheat flour compound noodle (FBWN) on glucose and fat metabolism in subjects with metabolic syndrome. This was a single-blinded and parallel 10-week clinical trial study. Subjects were randomly assigned into the trial group (FBWN) and whole wheat noodles group (WWN), and were measured on the beginning of week 3 and the ending of week 10. The glucose level at 30 and 60 min was significantly decreased after FBWN intervention. Levels of fasting blood glucose, HbA1c, and TG were all declined after FBWN intervention compared to before in the trial group. Moreover, the fat mass, fat rate, and visceral fat were decreased by 6.48, 7.19, 6.3 kg after FBWN intervention, respectively, while muscle mass and basal metabolic rate rose 7.44 kg and 252.60 kcal. PRACTICAL APPLICATIONS: Many studies have illustrated that the extraction of fermented barley held the activities of anti-obesity, antitumor, and so on. Moreover, this present study evaluated the effects of fermented barley by Lactobacillus plantarum on patients with metabolic syndrome. Results indicated that FB benefits the subjects on improving plasma glycolipids and insulin sensitivity, decreasing visceral fat level, and increasing satiety. The findings showed that the products of FB may be beneficial to dietary manipulations, thus, reducing the burden of patients.
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Hordeum , Resistência à Insulina , Lactobacillus plantarum , Síndrome Metabólica , Fermentação , Farinha , Glicolipídeos , Humanos , Síndrome Metabólica/terapia , TriticumRESUMO
This report demonstrated the utility of high-performance liquid chromatography (HPLC)-fluorescence detection for selective separation and sensitive quantification of multiple microRNAs (miRNAs). A duplex specific nuclease (DSN)-assisted target recycling amplification strategy was developed to enhance the signals of miRNAs, which alleviates the low sensitivity of conventional HPLC to nucleic acids. To separate the signals of different miRNAs, DNA probes with different lengths and base sequences were immobilized on magnetic beads. The application of an effective magnetic separation minimized the background signal and extended the dynamic range. This assay achieved a limit of detection of 0.39 fM for miRNA-122, 0.30 fM for miRNA-155, and 0.26 fM for miRNA-21, respectively. The proposed assay was successfully applied to detect simultaneously miRNA-122, miRNA-155, and miRNA-21 in serum samples from healthy persons and cervical cancer patients, and the results were then compared with those of quantitative real-time-polymerase chain reaction amplification.
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Sondas de DNA/química , MicroRNAs/análise , Neoplasias do Colo do Útero/diagnóstico por imagem , Cromatografia Líquida de Alta Pressão , Feminino , Fluorescência , Humanos , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico , Neoplasias do Colo do Útero/genéticaRESUMO
Following publication of the original article [1], the Authors' Contributions statement need to be changed.
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BACKGROUND: Lipid metabolism imbalance has been recognized as one of the major drivers of impaired glucose metabolism in the context of type 2 diabetes mellitus (T2DM), the rates of which are steadily increasing worldwide. Impaired glucose regulation (IGR) plays a vital role in the prevention and treatment of T2DM. The goal of this study was to further clarify whether the combination of plant sterols (PS) and omega-3 fatty acids yields any synergistic effect that enhances the prevention and treatment of IGR. METHODS: A total of 200 participants were randomized to receive PS and omega-3 fatty acids (n = 50), PS alone (n = 50), omega-3 fatty acids alone (n = 50), or placebo soy bean powder plus placebo capsules (n = 50) for 12 weeks. Patient characteristics including body composition, blood pressure, glucose metabolism (Fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)), lipid metabolism (TG, TC, HDL-C, LDL-C) and inflammatory factors (Hs-CRP, IL-6) were all monitored in these IGR individuals. RESULTS: Compared to the placebo group, the group receiving the combined intervention exhibited significantly decreased TG, HDL-C, FBG, HOMA-IR and HbA1c. Omega-3 fatty acids alone were associated with significant reductions in waistline, TG, FBG, HOMA-IR and Hs-CRP. PS alone was only associated with decreased TG and Hs-CRP. No interventions produced significant changes in body weight, BMI, blood pressure, FINS, body fat percentage, visceral fat rating, TC, LDL-C or IL-6. CONCLUSIONS: In summary, this study has demonstrated for the first time that PS, omega-3 fatty acids or the combination thereof significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. These findings may provide a scientific basis for the development of nutritional products incorporating PS and omega-3 fatty acids, and also for the development of nutritional supplement strategies aimed at preventing the development of disease in the IGR population.
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Glicemia/metabolismo , Ácidos Graxos Ômega-3/uso terapêutico , Intolerância à Glucose/sangue , Intolerância à Glucose/tratamento farmacológico , Metabolismo dos Lipídeos , Fitosteróis/uso terapêutico , Citocinas/metabolismo , Quimioterapia Combinada , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fitosteróis/farmacologiaRESUMO
BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8), a newly identified hormone, has been recently characterized as a metabolic regulator which can affect energy homeostasis and has interesting potentials as a metabolic disease therapy. However, little is as yet known as to whether circulating ANGPTL8 levels are altered in thyroid dysfunction. This study measured serum ANGPTL8 levels in patients with Graves' disease and explored the correlations between its serum levels and thyroid index in Graves' disease. METHODS: The concentration of ANGPTL8 was analyzed in blood samples of 128 well-characterized individuals whose anthropometric parameters, biochemical parameters, and thyroid index were measured. The participants were divided into Graves' disease patients (n = 60) and healthy control subjects (n = 68). Logistic regression was used to evaluate the relationship between ANGPTL8 and Graves' disease. RESULTS: Serum ANGPTL8 levels were more significantly decreased in Graves' disease patients than in healthy control subjects (177.67 ± 135.07 vs 326.41 ± 194.72 pg/mL; p < 0.001). Serum ANGPTL8 was negatively correlated with free triiodothyronine (FT3), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOAb) while being positively correlated with thyrotropin (TSH). Logistic regression analyses demonstrated that serum ANGPTL8 was significantly associated with Graves' disease (p < 0.05). CONCLUSIONS: Circulating concentrations of ANGPTL8 showed a significant reduction in Graves' disease patients. Thus, it is suggested that thyroid function should be taken into consideration when evaluating the results of ANGPTL8.
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Proteínas Semelhantes a Angiopoietina/sangue , Doença de Graves/sangue , Hormônios Peptídicos/sangue , Adulto , Proteína 8 Semelhante a Angiopoietina , Biomarcadores/sangue , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função TireóideaRESUMO
This study aimed to conduct a network meta-analysis of the efficacy and safety of different doses of alirocumab in reducing low-density lipoprotein cholesterol levels. In the present study, a total of 16 studies were selected, published between January 2012 and October 2016. Pair-wise and network meta-analyses was used to carry out a direct and indirect comparison of the three treatment strategies of alirocumab in patients with hypercholesterolemia. The efficacy and safety of these different treatment strategies were analyzed. Results revealed that alirocumab could significantly reduce LDL-c levels, compared with placebo (relative effect 95 % CI: -71.45 [-91.16, -50.44], -74.32 [-90.40, -58.63] and -77.28 [-92.21, -61.90]) and ezetimibe (EZE) (relative effect 95 % CI: -37.2 [-61.21, -12.41], -40.07 [-56.92, -24.22] and -43.00 [-68.39, -17.91]). The comparison of the three treatment strategies of alirocumab indicated no significant differences in reducing the levels of LDL-c, TGs, TC, Lp (a), Apo B and SAEs, LTTD, IST, ACE, MD and NC. For the probabilities of 75 mg, 75-150 mg and 150 mg of alirocumab, the best treatment for EZE and placebo were 50 %, 68 %, 82 %, 1 % and 0 %, according to LDL-c level. The results of the benefit-risk analysis of efficacy and safety revealed that the logarithmic scale was 0.016 for 75 mg vs. 75-150 mg of alirocumab and 0.125 for 75-150 mg vs. 150 mg of alirocumab. The PCSK9 inhibitor alirocumab presents a significantly greater reducing effect on the levels of LDL-c compared with EZE, and the different doses of alirocumab exhibited no significant difference in the efficacy of LDL-c for hypercholesterolemia. An alirocumab dose of 75-150 mg Q2W might be the best choice due to its most favorable balance between efficacy and safety.
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Anticorpos Monoclonais/administração & dosagem , Anticolesterolemiantes/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Ezetimiba/uso terapêutico , Humanos , Metanálise em Rede , Inibidores de PCSK9RESUMO
OBJECTIVES: Betatrophin is a widely used diagnostic marker for type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational DM (GDM) is unclear. We evaluated the relationship between betatrophin and the risk of GDM as well as the ability of betatrophin to predict postpartum type 2 DM (PDM). METHODS: In total, 386 patients were categorized into those with and without PDM. All underwent the oral glucose tolerance test while pregnant. Betatrophin was assessed to examine the diagnostic characteristics of GDM. RESULTS: The betatrophin concentration was remarkably higher in patients with than without GDM. The patients were categorized into three groups; those with a betatrophin concentration of 300 to 600 pg/mL and >600 pg/mL had a higher risk of GDM after adjusting for body mass index, age, homeostatic model assessment-insulin resistance (HOMA-IR) concentration, and betatrophin concentration than those with a betatrophin concentration of <300 pg/mL. The HOMA-IR concentration tended to increase as the betatrophin concentration increased, and betatrophin was independently associated with GDM after adjusting for confounders. The betatrophin concentration was higher among pregnant patients with than without PDM. CONCLUSIONS: Betatrophin has high sensitivity but low specificity for diagnosing GDM and may be a promising predictor of PDM.
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Proteínas Semelhantes a Angiopoietina/metabolismo , Biomarcadores/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Gestacional/diagnóstico , Hormônios Peptídicos/metabolismo , Adulto , Proteína 8 Semelhante a Angiopoietina , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Mães , Gravidez , PrognósticoRESUMO
INTRODUCTION: Sanghuang is one of mystical traditional Chinese medicines recorded earliest 2000 years ago, that included various fungi of Inonotus genus and was well-known for antitumor effect in modern medicine. Inonotus vaninii is grown in natural forest of Northeastern China merely and used as Sanghuang commercially, but it has no quality control specification until now. This study was to establish a rapid method of two-phase acid hydrolysis followed by reversed phase-high performance liquid chromatography-ultra violet (RP-HPLC-UV) to quantify naringenin in the fruit body of I. vaninii. MATERIALS AND METHODS: Sample solution was prepared by pretreatment of raw material in two-phase acid hydrolysis and the hydrolysis technology was optimized. After reconstitution, analysis was performed using RP-HPLC-UV. The method validation was investigated and the naringenin content of sample and comparison were determined. RESULTS: The naringenin was obtained by two-phase acid hydrolysis method, namely, 10.0 g of raw material was hydrolyzed in 200 mL of 1% sulfuric acid aqueous solution (v/v) and 400 mL of chloroform in oil bath at 110°C for 2 h. Good linearity (r = 0.9992) was achieved between concentration of analyte and peak area. The relative standard deviation (RSD) of precision was 2.47% and the RSD of naringenin contents for repeatability was 3.13%. The accuracy was supported with recoveries at 96.37%, 97.30%, and 99.31%. The sample solution prepared using the proposed method contained higher content of naringenin than conventional method and was stable for 8 h. CONCLUSION: Due to the high efficiency of sample preparation and high reliability of the HPLC method, it is feasible to use this method for routine analysis of naringenin in the fungus. SUMMARY: A convenient two-phase acid hydrolysis was employed to produce naringenin from raw material, and then an efficient and reliable reversed phase-high performance liquid chromatography-ultra violet method was established to monitor naringenin in the fruit bodies of Inonotus vaninii. The newly established method could be used to control the quality of the herb. Abbreviations used: RP-HPLC-UV: Reversed Phase-High Performance Liquid Chromatography-Ultra Violet, RSD: Relative Standard Deviation, EtOAc: Ethyl acetate, ACN: Acetonitrile, MeOH: Methanol, RH: Relative Humility.
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The neurohypophysial hormone, oxytocin, is involved in the regulation of energy metabolism. Adiponectin (APN) is an adipose tissue-specific serum protein that inversely associates with metabolic syndrome (MetS). High-molecular-weight adiponectin (HMW APN) is considered the active form. In the present study, we aimed to determine the relationships of oxytocin and HMW APN to MetS and investigate whether or not the combination of oxytocin and HMW APN is associated with further metabolic abnormalities compared to each of them alone. A total of 170 subjects (75 with MetS and 95 non-MetS) were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT), blood lipids, hs-CRP, oxytocin and HMW APN levels were measured. Compared with non-MetS subjects, serum oxytocin and HMW APN levels were significantly lower in subjects with MetS (P<0.01). We then classified the subjects into three groups: high oxytocin and high HMW APN levels (high score group), low oxytocin and low HMW APN levels (low score group) and others. Participants in low score group showed the worst metabolic profiles and were more likely to have MetS compared to the other two group. In Spearman rank correlation coefficient, the classification by the combination of oxytocin and HMW APN was significantly correlated with a larger number of metabolic risk factors compared with classification by each of them alone. Individuals with low circulating oxytocin levels coupled with low HMW APN levels were at significantly increased risk of MetS. The combination of both markers would be useful for identifying MetS high risk patients.
Assuntos
Adiponectina/sangue , Síndrome Metabólica/sangue , Ocitocina/sangue , Adiponectina/química , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Peso Molecular , Fatores de RiscoRESUMO
Fibroblast growth factor 1 (FGF1) has been recently characterized as a potent insulin sensitizer that regulates adipose tissue remodeling, but the physiological role of FGF1 remains unclear. This study measured serum FGF1 levels for the first time in patients with newly diagnosed type 2 diabetes mellitus (T2DM), and further explored the correlations between FGF1 levels and various metabolic parameters in T2DM. Serum FGF1 levels were determined using ELISA in age-, sex- and BMI- matched subjects with normal glucose tolerance (NGT) (n=80) and newly diagnosed T2DM (n=80). Oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1C), blood lipids, and insulin secretion were also measured. Insulin resistance and pancreatic ß-cell function were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta cell function (HOMA-ß), respectively. Serum FGF1 levels were significantly higher in T2DM patients than in normal glucose tolerance subjects (74.52 [55.91â¼101.34] vs. 60.31 [48.99â¼83.91] pg/mL; P<0.05). In addition, serum FGF1 level positively correlated with body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), fasting plasma glucose (FPG), 2-h post-OGTT glucose (2h PG), and HbA1C (all P values <0.05) in T2DM subjects. Multivariate regression analyses showed that BMI and HbA1C were the independent factors influencing serum FGF1 levels. Logistic regression analyses demonstrated that serum FGF1 was significantly associated with type 2 diabetes (P<0.01). Circulating concentrations of FGF1 are significantly increased in T2DM patients. Our results suggest that FGF1 may play a role in the pathogenesis of T2DM.