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BACKGROUND: Cervical cancer (CC) remains a significant clinical challenge, even though its fatality rate has been declining in recent years. Particularly in developing countries, the prognosis for CC patients continues to be suboptimal despite numerous therapeutic advances. METHODS: Using The Cancer Genome Atlas database, we extracted CC-related data. From this, 52 methylation-related genes (MRGs) were identified, leading to the selection of a 10 long non-coding RNA (lncRNA) signature co-expressed with these MRGs. R programming was employed to filter out the methylation-associated lncRNAs. Through univariate, least absolute shrinkage and selection operator (i.e. LASSO) and multivariate Cox regression analysis, an MRG-associated lncRNA model was constructed. The established risk model was further assessed via the Kaplan-Meier method, principal component analysis, functional enrichment annotation and a nomogram. Furthermore, we explored the potential of this model with respect to guiding immune therapeutic interventions and predicting drug sensitivities. RESULTS: The derived 10-lncRNA signature, linked with MRGs, emerged as an independent prognostic factor. Segmenting patients based on their immunotherapy responses allowed for enhanced differentiation between patient subsets. Lastly, we highlighted potential compounds for distinguishing CC subtypes. CONCLUSIONS: The risk model, associated with MRG-linked lncRNA, holds promise in forecasting clinical outcomes and gauging the efficacy of immunotherapies for CC patients.
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Adenina/análogos & derivados , RNA Longo não Codificante , Neoplasias do Colo do Útero , Humanos , Feminino , Prognóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , RNA Longo não Codificante/genética , ImunoterapiaRESUMO
Depression, which affects millions of individuals worldwide, is associated with glucocorticoid (GC) impairment, with the FKBP51 protein playing a pivotal role. Ginsenosides, extracted from the root of Panax ginseng C.A. Mey, have demonstrated the potential to mitigate depression associated with GC dysregulation. This study evaluated the therapeutic efficacy of ethanol extract of P. ginseng (PG) in treating depression and its underlying FKBP51-linked mechanism. Using chronic unpredictable stress, a depression model was developed in Kunming mice to test the efficacy of PG by observing changes in behaviors and protein expression in depressed mice. The mechanism of action was investigated through transfection with HEK293T cells. Depressed mice treated with PG demonstrated notable improvements: the rate of weight loss was reduced, sucrose preference and open-field activity were enhanced, and the rate of apoptosis in hippocampal cells was decreased. Additionally, the HPA axis function appeared to be restored. These physiological adjustments coincided with an increase in GR levels and a decrease in FKBP51 levels. Altogether, these results suggested that PG treatment effectively alleviates depressive symptoms in mice. PG also moderated FKBP51-GR interaction, lessening FKBP51's restraint on GR nuclear entry. This modulation may enhance the sensitivity of the GR response, reinforcing the negative feedback regulation of the HPA axis and thereby reducing depressive symptoms in mice. These findings highlight the potential of PG as a promising curative treatment for depression, providing a basis for the development of innovative treatments targeting the FKBP51-GR pathway.
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Depressão , Ginsenosídeos , Sistema Hipotálamo-Hipofisário , Panax , Sistema Hipófise-Suprarrenal , Receptores de Glucocorticoides , Estresse Psicológico , Proteínas de Ligação a Tacrolimo , Animais , Ginsenosídeos/farmacologia , Camundongos , Proteínas de Ligação a Tacrolimo/metabolismo , Receptores de Glucocorticoides/metabolismo , Depressão/tratamento farmacológico , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Masculino , Células HEK293 , Estresse Psicológico/tratamento farmacológico , Panax/química , Modelos Animais de Doenças , Apoptose/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismoRESUMO
This study examined the impact of Semen raphani on the absorption of ginsenosides from Panax ginseng C.A. Meyer (ginseng) using a Caco-2 cell model and Ultra-High-Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS). Six primary ginsenosides (Rg1, Re, Rb1, Rb2, Rc, Rd) were quantified. Results showed that Semen Raphani increased the efflux rate of ginsenosides, particularly at higher concentrations, suggesting it inhibits their absorption. The research elucidates the intestinal absorption process of ginsenosides and the antagonistic mechanism of Semen Raphani against ginseng.
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Armillaria mellea (Vahl) P. Kumm is commonly used for food and pharmaceutical supplements due to its immune regulatory function, and polysaccharides are one of its main components. The aim of this research is to study the immunological activity of the purified acidic polysaccharide fraction, namely, AMPA, isolated from Armillaria mellea crude polysaccharide (AMP). In this study, a combination of the immune activity of mouse macrophages in vitro and serum metabonomics in vivo was used to comprehensively explore the cell viability and metabolic changes in immune-deficient mice in the AMPA intervention, with the aim of elucidating the potential mechanisms of AMPA in the treatment of immunodeficiency. The in vitro experiments revealed that, compared with LPS-induced RAW264.7, the AMPA treatment elevated the levels of the cellular immune factors IL-2, IL-6, IgM, IgA, TNF-α, and IFN-γ; promoted the expression of immune proteins; and activated the TLR4/MyD88/NF-κB signaling pathway to produce immunological responses. The protein expression was also demonstrated in the spleen of the cyclophosphamide immunosuppressive model in vivo. The UHPLC-MS-based metabolomic analysis revealed that AMPA significantly modulated six endogenous metabolites in mice, with the associated metabolic pathways of AMPA for treating immunodeficiency selected as potential therapeutic biomarkers. The results demonstrate that phosphorylated acetyl CoA, glycolysis, and the TCA cycle were mainly activated to enhance immune factor expression and provide immune protection to the body. These experimental results are important for the development and application of AMPA as a valuable health food or drug that enhances immunity.
Assuntos
Armillaria , Polissacarídeos , Animais , Camundongos , Cromatografia Líquida de Alta Pressão , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico , Polissacarídeos/farmacologia , Ciclofosfamida/efeitos adversosRESUMO
BACKGROUND: The purpose of this study was to investigate the relationships of oral health status and swallowing function with cognitive impairment in community-dwelling older adults from Changsha, Hunan Province, China. METHODS: In this cross-sectional study, we analyzed the data of 215 participants aged ≥ 50 years which were retrieved from the Xiangya and Panasonic mild cognitive impairment (MCI) Study, a community-based study conducted among the residents of the urban areas of Hunan province in China. Demographic information of all participants was collected. We determined oral function by evaluating oral hygiene, oral dryness, occlusal force, tongue pressure, chewing function, swallowing function, remaining teeth number, and other indicators. The mini-mental state examination (MMSE) was used to screen for cognitive function. The relationship between each oral function evaluation item and cognitive function was investigated using correlation analysis. The associations between oral health status and swallowing function with cognitive impairment were inferred using multiple regression analysis. RESULTS: The general characteristics of participants showed statistically significant correlation coefficients in number of teeth remaining (p = 0.003) and number of teeth lost (p < 0.0001). Almost half of the 25 participants (48%) were aged from 70-80 years. Only 25 older adults (11.6% of the participants) were determined to have cognitive impairment by MMSE sores less than 24. Tongue pressure in male participants was the only significant independent variable that was associated with cognitive impairment (p = 0.01971). The results indicate that male participants with lower MMSE scores had a relative deficiency in tongue pressure. CONCLUSIONS: In this cross-sectional study, the oral health status and swallowing function of participants were in relatively good condition and showed low correlations with cognitive impairment. However, lower tongue pressures were associated with lower MMSE scores in males, indicating it could serve as a novel oral function index for evaluating cognitive impairment.
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Disfunção Cognitiva , Deglutição , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Envelhecimento , Disfunção Cognitiva/complicações , Estudos Transversais , Saúde Bucal , Pressão , Língua , Idoso de 80 Anos ou maisRESUMO
CONTEXT: Panax ginseng C. A. Meyer (Araliaceae) is a tonic herb used in ancient Asia. OBJECTIVE: This study investigated the antifatigue effect of P. ginseng on chronic fatigue rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into control, model and EEP (ethanol extraction of P. ginseng roots) (50, 100 and 200 mg/kg) groups (n = 8). The rats were subcutaneously handled with loaded swimming once daily for 26 days, except for the control group. The animals were intragastrically treated with EEP from the 15th day. On day 30, serum, liver and muscles were collected, and the PI3K/Akt/mTOR signalling pathway was evaluated. RESULTS: The swimming times to exhaust of the rats with EEP were significantly longer than that without it. EEP spared the amount of muscle glycogen, hepatic glycogen and blood sugar under the chronic state. In addition, EEP significantly (p < 0.05) decreased serum triglycerides (1.24 ± 0.17, 1.29 ± 0.04 and 1.20 ± 0.21 vs. 1.58 ± 0.13 mmol/L) and total cholesterol (1.64 ± 0.36, 1.70 ± 0.15 and 1.41 ± 0.19 vs. 2.22 ± 0.19 mmol/L) compared to the model group. Regarding the regulation of energy, EEP had a positive impact on promoting ATPase activities and relative protein expression of the PI3K/Akt/mTOR pathway. CONCLUSIONS: Our results suggested that EEP effectively relieved chronic fatigue, providing evidence that P. ginseng could be a potential dietary supplement to accelerate recovery from fatigue.
Assuntos
Síndrome de Fadiga Crônica , Panax , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Fosfatidilinositol 3-Quinases , Ratos Sprague-Dawley , Serina-Treonina Quinases TORRESUMO
The excretion of neurotransmitter metabolites in normal individuals is of great significance for health monitoring. A rapid quantitative method was developed with ultra-performance liquid chromatography-tandem mass spectrometry. The method was further applied to determine catecholamine metabolites vanilymandelic acid (VMA), methoxy hydroxyphenyl glycol (MHPG), dihydroxy-phenyl acetic acid (DOPAC), and homovanillic acid (HVA) in the urine. The urine was collected from six healthy volunteers (20-22 years old) for 10 consecutive days. It was precolumn derivatized with dansyl chloride. Subsequently, the sample was analyzed using triple quadrupole mass spectrometry with an electrospray ion in positive and multireaction monitoring modes. The method was sensitive and repeatable with the recoveries 92.7-104.30%, limits of detection (LODs) 0.01-0.05 µg/mL, and coefficients no less than 0.9938. The excretion content of four target compounds in random urine samples was 0.20 ± 0.086 µg/mL (MHPG), 1.27 ± 1.24 µg/mL (VMA), 3.29 ± 1.36 µg/mL (HVA), and 1.13 ± 1.07 µg/mL (DOPAC). In the urine, the content of VMA, the metabolite of norepinephrine and adrenaline, was more than MHPG, and the content of HVA, the metabolite of dopamine, was more than DOPAC. This paper detected the levels of catecholamine metabolites and summarized the characteristics of excretion using random urine samples, which could provide valuable information for clinical practice.
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Dopamina , Espectrometria de Massas em Tandem , Adulto , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ácido Homovanílico , Humanos , Espectrometria de Massas em Tandem/métodos , Adulto JovemRESUMO
Anti-aging is a challenging and necessary research topic. Momordica charantia L. is a common edible medicinal plant that has various pharmacological activities and is often employed in daily health care. However, its anti-aging effect on mice and the underlying mechanism thereof remain unclear. Our current study mainly focused on the effect of Momordica charantia L. on d-galactose-induced subacute aging in mice and explored the underlying mechanism. UHPLC-Q-Exactive Orbitrap MS was applied to qualitatively analyze the chemical components of Momordica charantia L. ethanol extract (MCE). A subacute aging mice model induced by d-galactose (d-gal) was established to investigate the anti-aging effect and potential mechanism of MCE. The learning and memory ability of aging mice was evaluated using behavioral tests. The biochemical parameters, including antioxidant enzyme activity and the accumulation of lipid peroxides in serum, were measured to explore the effect of MCE on the redox imbalance caused by aging. Pathological changes in the hippocampus were observed using hematoxylin and eosin (H&E) staining, and the levels of aging-related proteins in the PI3K/AKT signaling pathway were assessed using Western blotting. The experimental results demonstrated that a total of 14 triterpenoids were simultaneously identified in MCE. The behavioral assessments results showed that MCE can improve the learning and memory ability of subacute mice. The biochemical parameters determination results showed that MCE can improve the activity of antioxidant enzymes and decrease the accumulation of lipid peroxides in aging mice significantly. Furthermore, aging and injury in the hippocampus were ameliorated. Mechanistically, the results showed a significant upregulation in the protein expression of P-PI3K/PI3K and P-AKT/AKT (p < 0.01), as well as a significant reduction in cleaved caspase-3/caspase-3, Bax and P-mTOR/mTOR (p < 0.01). Our results confirm that MCE could restore the antioxidant status and improve cognitive impairment in aging mice, inhibit d-gal-induced apoptosis by regulating the PI3K/AKT signaling pathway, and rescue the impaired autophagy caused by mTOR overexpression, thereby exerting an anti-aging effect.
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Momordica charantia , Envelhecimento , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Caspase 3/metabolismo , Galactose/efeitos adversos , Peróxidos Lipídicos , Camundongos , Momordica charantia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
This work aimed at improving the water solubility of Ginsenoside (G)-Re by forming an inclusion complex. The solubility parameters of G-Re in alpha (α), beta (ß), and gamma (γ) cyclodextrin (CD) were investigated. The phase solubility profiles were all classified as AL-type that indicated the 1:1 stoichiometric relationship with the stability constants Ks which were 22 M-1 (α-CD), 612 M-1 (ß-CD), and 14,410 M-1 (γ-CD), respectively. Molecular docking studies confirmed the results of phase solubility with the binding energy of -4.7 (α-CD), -5.10 (ß-CD), and -6.70 (γ-CD) kcal/mol, respectively. The inclusion complex (IC) of G-Re was prepared with γ-CD via the water-stirring method followed by freeze-drying. The successful preparation of IC was confirmed by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In-vivo absorption studies were carried out by LC-MS/MS. Dissolution rate of G-Re was increased 9.27 times after inclusion, and the peak blood concentration was 2.7-fold higher than that of pure G-Re powder. The relative bioavailability calculated from the ratio of Area under the curve AUC0-∞ of the inclusion to pure G-Re powder was 171%. This study offers the first report that describes G-Re's inclusion into γ-CD, and explored the inclusion complex's mechanism at the molecular level. The results indicated that the solubility could be significantly improved as well as the bioavailability, implying γ-CD was a very suitable inclusion host for complex preparation of G-Re.
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Ginsenosídeos/síntese química , Ginsenosídeos/farmacologia , gama-Ciclodextrinas/farmacologia , Administração Oral , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Fenômenos Químicos , Ginsenosídeos/química , Ginsenosídeos/farmacocinética , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , gama-Ciclodextrinas/químicaRESUMO
Panax ginseng was employed in the treatment of "Xiao-Ke" symptom, which nowadays known as diabetes mellitus, in traditional Chinese medicine for more than a thousand years. Ginsenoside Re was the major pharmacologic ingredient found abundantly in ginseng. However, the anti-diabetic of Ginsenoside Re and its underlying mechanism in metabolic level are still unclear. Serum and urine metabolomic method was carried out to investigate the anti-diabetic pharmacological effects and the potential mechanism of Ginsenoside Re on high-fat diet combined streptozotocin-induced type 2 diabetes mellitus (T2DM) rats based on ultra-high-performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). Serum and urine samples were collected from the control group (CON), T2DM group, metformin (MET) treatment group, and ginsenoside Re treatment group after intervention. The biochemical parameters of serum were firstly analyzed. The endogenous metabolites in serum and urine were detected by UHPLC-MS. The potential metabolites were screened by multivariate statistical analysis and identified by accurate mass measurement, MS/MS, and metabolite databases. The anti-diabetic-related metabolites were analyzed by KEGG metabolic pathway, and its potential mechanism was discussed. The treatment of ginsenoside Re significantly reduced the blood glucose and serum lipid level improved the oxidative stress caused by T2DM. Biochemical parameters (urea nitrogen, uric acid) showed that ginsenoside Re could improve renal function in T2DM rats. Respective 2 and 6 differential metabolites were found and identified in serum and urine of ginsenoside Re compared with T2DM group and enriched in KEGG pathway. Metabolic pathways analysis indicated that the differential metabolites related to T2DM were mainly involved in arachidonic acid metabolism, Vitamin B6, steroid hormone biosynthesis, and bile secretion metabolic pathways. This study verified the anti-diabetic and anti-oxidation effects of ginsenoside Re, elaborated that ginsenoside Re has a good regulation of the metabolic disorder in T2DM rats, which could promote insulin secretion, stimulated cannabinoid type 1 receptor (CB1), and CaMKK ß to activate AMPK signaling pathway, inhibited insulin resistance, and improved blood glucose uptake and diabetic nephropathy, so as to play the role of anti-diabetic.
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Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ginsenosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metabolômica , Animais , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Ginsenosídeos/análise , Ginsenosídeos/metabolismo , Hipoglicemiantes/análise , Hipoglicemiantes/metabolismo , Masculino , Espectrometria de Massas , Panax/química , Ratos , Ratos Wistar , EstreptozocinaRESUMO
Protein enhancer of sevenless 2B, E(sev)2B, is a key adapter protein in the Ras/MAPK signaling pathway which has been reported to be involved in innate immunity. In this study, the gene that encodes AsE(sev)2B was isolated from A. sinica. It was found to contain a 636 bp open reading frame encoding 211 amino acids with a calculated molecular mass of 24.357â¯kDa and a predicted isoelectric point of 5.39. The predicted protein contains a N-terminal Src homology 3 domain (SH3), a central Src homology 2 domain (SH2), and a C-terminal Src homology 3 domain (SH3). Homology analysis revealed that AsE(sev)2B shares 49%-95% identity with E(sev)2B homologs from other species. In this study, the expression pattern and location of AsE(sev)2B during different stages of embryonic development and bacterial challenge were investigated by means of real-time qPCR, Western blotting and immunohistochemistry. Results showed that the highest expression level of AsE(sev)2B was at 0â¯h. After challenged by Gram-positive bacteria and Gram-negative bacteria, AsE(sev)2B was remarkably upregulated at 106 cellsL-1 bacterial concentrations. These results suggested that AsE(sev)2B plays a vital role during early embryonic development and in immune responses against bacterial challenge.
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Artemia/genética , Artemia/imunologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Sequência de Bases , Perfilação da Expressão Gênica , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/fisiologia , Filogenia , Alinhamento de SequênciaRESUMO
Urothelial Carcinoma Antigen 1 (UCA1) is a cell and tissue specific long non-coding RNA (lncRNA) associated with the tumorigenesis and invasion of bladder cancer. However, the mechanism driving the over-transcription of UCA1 in bladder cancer cells remains unclear. It has been reported that C/EBPß has a significant role of regulation in tumorigenesis. Here we report that the expression of UCA1 was dramatically inhibited in 5637â¯cells with C/EBPß down-regulation. Additionally, the function tests indicated that C/EBPß could promote 5637â¯cells growth and colony formation by inducing the expression level of UCA1. These data suggest that C/EBPß was involved in transcriptional regulation of UCA1 and contributed substantially to its high expression and proliferation promoting in bladder cancer cells.
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Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , RNA Longo não Codificante/genética , Transcrição Gênica , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Regiões Promotoras Genéticas/genética , Ligação Proteica , RNA Longo não Codificante/metabolismoRESUMO
INTRODUCTION: Panax ginseng has received much attention as a valuable health supplement with medicinal potential. Its chemical diversity and multiple pharmacological properties call for comprehensive methods to better understand the effects of ginseng and ginsenosides. Liquid chromatography-mass spectrometry (LC-MS) based metabonomic approaches just fit the purpose. OBJECTIVE: Aims to give a review of recent progress on LC-MS based pharmacokinetic, metabolic, and phytochemical metabolomic studies of ginseng, and metabonomic studies of ginseng intervention effects. METHODS: The review has four sections: the first section discusses metabolic studies of ginsenosides based on LC-MS, the second focuses on ginsenoside-drug interactions and pharmacokinetic interaction between herb compounds based on LC-MS, the third is phytochemical metabolomic studies of ginseng based on LC-MS, and the fourth deals with metabonomic studies of ginseng intervention effects based on LC-MS. RESULTS: LC-MS based metabonomic research on ginseng include analysis of single ginsenoside and total ginsenosides. The theory of multi-components and multi-targeted mechanisms helps to explain ginseng effects. CONCLUSION: LC-MS based metabonomics is a promising way to comprehensively assess ginseng. It is valuable for quality control and mechanism studies of ginseng.
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Cromatografia Líquida/métodos , Metabolômica , Panax/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Interações Medicamentosas , Humanos , Panax/química , Extratos Vegetais/análise , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacocinéticaRESUMO
BACKGROUND: Glycated albumin (GA) reflects serum glucose of the preceding 2 - 3 weeks and plays an important role in diabetes mellitus (DM). This study aimed at investigating whether GA can assess renal dysfunction in population. METHODS: 3818 individuals attending physical examination were enrolled in this cross-sectional study and divided into five groups: healthy controls, impaired fasting glucose, DM without renal complications, DM with albuminuria, and nondiabetic chronic kidney disease patients. All analyses were conducted using the subjects with both fasting venous blood and morning urine samples. RESULTS: Among all groups, mean GA, hemoglobin A1c, fasting plasma glucose, and serum creatinine were the highest and estimated glomerular filtration rate (eGFR) was the lowest in DM with albuminuria group. When eGFR was 90 - 105 mL/minute/1.73 m2 or mildly decreased to 60 - 90 mL/minute/1.73 m2, GA increased significantly with elevating albumin-to-creatinine ratio (ACR) from 0 - 10 mg/g to 10 - 30 mg/g to > 30 mg/g (p < 0.001 and p < 0.001). GA increased further when eGFR decreased moderately to severely as a result of renal function continuing to deteriorate (eGFR ≤ 60 mL/minute/1.73 m2).When ACR ≤ 30 mg/g and eGFR ≤ 60 mL/minute/ 1.73 m2, more than 50% subjects were DM patients and had significantly higher GA levels than other subjects with eGFR > 105 mL/minute/1.73 m2. After adjusting demographics, every 5% rise of GA levels showed a 1.778fold increased risk in all subjects (adjusted odds ratio [OR], 1.778; 95% confidence interval [CI], 1.373 - 2.302; p < 0.001) and 1.737-fold risk in DM subjects (adjusted OR, 1.737; 95% CI, 1.221 - 2.471; p = 0.002) for occurrence of ACR > 30mg/g in contrast to ACR ≤ 30 mg/g. Compared to eGFR > 90 mL/minute/1.73 m2, 5% rise of GA levels showed a 1.482-fold risk for eGFR 60 - 90 mL/minute/1.73 m2 (adjusted OR, 1.482; 95% CI, 1.112 - 1.975; p = 0.007) and a 1.996-fold risk for eGFR ≤ 60 mL/minute/1.73 m2 (adjusted OR, 1.996; 95% CI, 1.366 - 2.916; p < 0.001). CONCLUSIONS: Increased GA serves as a risk marker for renal dysfunction. GA combined with eGFR and ACR can reflect renal function changes in population.
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Complicações do Diabetes/diagnóstico , Nefropatias/etiologia , Albumina Sérica/análise , Albuminúria , Biomarcadores/análise , Estudos Transversais , Diabetes Mellitus , Taxa de Filtração Glomerular , Produtos Finais de Glicação Avançada , Humanos , Nefropatias/diagnóstico , Albumina Sérica GlicadaRESUMO
AIM: To validate the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines risk stratification system based on the combination of estimated glomerular filtration rate (eGFR) and proteinuria. METHODS: This was a cohort study. A total of 1219 study population were recruited. Estimated GFR and proteinuria measured by using 24 h urine protein excretion rate (PER) were predictors. Adverse outcomes included all-cause mortality (ACM) and end-stage renal disease (ESRD). Follow-up was done by regular visit, telephone interview and electronic medical records. RESULTS: Over a median follow-up of 4.6 years, 153 (12.6%) and 43 (3.5%) patients experienced ESRD and ACM, respectively. On multivariable analysis, the adjusted hazard ratio for ESRD and ACM (compared with patients with eGFR > 60 mL/min per 1.7 m²) was of 29.8 and 3.6 for those with eGFR of 15-29 mL/min per 1.73 m², respectively. The adjusted hazard ratio for ESRD and ACM (compared with patients with PER < 150 mg/24h) was of 15.9 and 3.9 for those with PER > 500 mg/24h. Higher KDIGO guidelines risk categories (indicating lower eGFR or higher proteinuria) were associated with a graded increase in the risk for the ESRD (P < 0.001) and ACM (P < 0.001). Reclassification of KDIGO guidelines risk categories yielded net reclassification improvements for those with ESRD or ACM event (NRIevents ) of 33.3% or 30.2%. CONCLUSION: Lower eGFR and higher proteinuria are risk factors for ESRD and ACM in Chinese patients. The KDIGO guidelines risk categorization system assigned patients who went on to have the event to more appropriate CKD risk categories.
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Povo Asiático , Taxa de Filtração Glomerular , Rim/fisiopatologia , Proteinúria/etnologia , Insuficiência Renal Crônica/etnologia , Adulto , Idoso , Causas de Morte , China/epidemiologia , Progressão da Doença , Feminino , Humanos , Incidência , Falência Renal Crônica/etnologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Proteinúria/classificação , Proteinúria/diagnóstico , Proteinúria/mortalidade , Proteinúria/fisiopatologia , Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , UrináliseRESUMO
Lotus (Nelumbo nucifera) leaves, a traditional Chinese medicinal herb, are rich in flavonoids. In an effort to thoroughly analyze their flavonoid components, macroporous resin chromatography coupled with HPLC-MS/MS was employed to simultaneously enrich and identify flavonoids from lotus leaves. Flavonoids extracted from lotus leaves were selectively enriched in the macroporous resin column, eluted subsequently as fraction II, and successively subjected to analysis with the HPLC-MS/MS and bioactivity assays. Altogether, fourteen flavonoids were identified, four of which were identified from lotus leaves for the first time, including quercetin 3-O-rhamnopyranosyl-(1â2)-glucopyranoside, quercetin 3-O-arabinoside, diosmetin 7-O-hexose, and isorhamnetin 3-O-arabino- pyranosyl-(1â2)-glucopyranoside. Further bioactivity assays revealed that these flavonoids from lotus leaves possess strong antioxidant activity, and demonstrate very good potential to be explored as food supplements or even pharmaceutical products to improve human health.
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Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Nelumbo/química , Extratos Vegetais/química , Folhas de Planta/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em TandemRESUMO
Bridge construction collapse is one of the most common bridge safety accidents. At present, evaluation results are often affected by the ability and experience of the assessor. Therefore, it is difficult to quickly, accurately and effectively evaluate the risk in the process of bridge construction. Moreover, key factors that can prevent accidents can hardly find from the existing bridge construction safety management and evaluation method. This paper analyzes and classifies the artificial and environmental risk factors that affect the bridge construction stage, and establishes 26 risk factors in 5 categories according to the characteristics of bridge construction and the actual situation of the project. Random forest (RF) algorithm is a non-parametric machine learning method based on decision tree, which does not need to be scored by experts in advance and avoids the influence of subjective factors. Compared with other analysis methods, random forest algorithm has the advantages of accurate and robust risk assessment results. Based on the advantages of random forest algorithm and the characteristics of bridge construction risk, this paper uses random forest algorithm to evaluate the bridge construction risk, and ranks the importance of indicators, and identify the index that has a greater influence on the risk. In order to verify the applicability and feasibility of the proposed method, a typical urban complex pedestrian bridge was taken as an example for actual engineering evaluation and verification. The results obtained are basically consistent with the actual risk assessment results of the pedestrian bridge.
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Introduction: Rana dybowskii Guenther (RDG), as a traditional Chinese medicine, has been shown to have antioxidant effects. However, studies on the anti-aging effect of RDG are still limited. Methods: In this study, we prepared polysaccharides from the skin of RDG (RDGP) by hot water extraction, alcohol precipitation, ion-exchange chromatography and gel chromatography. The proteins were removed using the Sevage method in combination with an enzymatic method. The structural features were analyzed using high-performance gel permeation chromatography, ß-elimination reaction and Fourier transform infrared spectra. The anti-aging effect of RDGP was investigated by using D-Gal to establish an aging model in mice, and pathological changes in the hippocampus were observed under a microscope. Results: We obtained the crude polysaccharide DGP from the skin of RDG, with a yield of 61.8%. The free protein was then removed by the Sevage method to obtain DGPI and deproteinated by enzymatic hydrolysis combined with the Sevage method to further remove the bound protein to obtain the high-purity polysaccharide DGPII. Then, DGPIa (1.03 × 105 Da) and DGPIIa (8.42 × 104 Da) were obtained by gel chromatography, monosaccharide composition analysis showed that they were composed of Man, GlcA, GalNAc, Glc, Gal, Fuc with molar ratios of 1: 4.22 : 1.55: 0.18 : 8.05: 0.83 and 0.74 : 1.78: 1: 0.28: 5.37 : 0.36, respectively. The results of the ß-elimination reaction indicated the presence of O-glycopeptide bonds in DGPIa. The Morris water maze test indicated that mice treated with DGPIIa exhibited a significantly shorter escape latency and increased time spent in the target quadrant as well as an increase in the number of times they traversed the platform. Pathologic damage to the hippocampus was alleviated in brain tissue stained with hematoxylin-eosin. In addition, DGPIIa enhanced the activities of SOD, CAT, and GSH-Px and inhibited the level of MDA in the serum and brain tissues of aging mice. Discussion: These results suggest that RDGP has potential as a natural antioxidant and provide useful scientific information for anti-aging research.
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Panax ginseng C. A. Meyer is a dual-purpose plant for medicine and food, its polysaccharide is considered as an immune enhancer. Four polysaccharides, WGP-20-F, WGP-40-F, WGP-60-F and WGP-80-F were obtained from ginseng via water extraction and gradient ethanol precipitation with different molecular weights (Mw) of 1.720 × 106, 1.434 × 106, 4.225 × 104 and 1.520 × 104 Da, respectively. WGP-20-F and WGP-40-F which with higher Mw and a triple-helix structure are glucans composed of 4-É-Glcp, do not show remarkable immunoregulatory effects. WGP-60-F and WGP-80-F are heteropolysaccharides mainly composed of 4-É-Glcp and also contain t-É-Araf, 5-É-Araf and 3,5-É-Araf. They are spherical branched conformations without a triple-helix structure and can effectively increase the index of immune organs, lymphocyte proliferation, activate macrophages to regulate the immune system in mice and further enhance immune functions by improving delayed-type hypersensitivity reaction and antibody response. These results indicated that WGP-60-F and WGP-80-F could be used as potential immune enhancers, and gradient ethanol precipitation can be applied for the preparation of ginseng bioactive polysaccharide.
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Panax ginseng C.A. Meyer (P. ginseng) is one of the more common traditional Chinese medicines (TCMs). It contains numerous chemical components and exhibits a range of pharmacological effects. An enormous burden is placed on people's health and life by Alzheimer's disease (AD), a neurodegenerative condition. Recent research has shown that P. ginseng's chemical constituents, particularly ginsenosides, have a significant beneficial impact on the prevention and management of neurological disorders. To understand the current status of research on P. ginseng to improve AD, this paper discusses the composition of P. ginseng, its mechanism of action, and its clinical application. The pathogenesis of AD includes amyloid beta protein (Aß) generation and aggregation, tau protein hyperphosphorylation, oxidant stress, neuroinflammation, mitochondrial damage, and neurotransmitter and gut microbiota disorders. This review presents the key molecular mechanisms and signaling pathways of the active ingredients in P. ginseng involved in improving AD from the perspective of AD pathogenesis. A P. ginseng-related signaling pathway network was constructed to provide effective targets for the treatment of AD. In addition, the application of spatial metabolomics techniques in studying P. ginseng and AD is discussed. In summary, this paper discusses research perspectives for the study of P. ginseng in the treatment of AD, including a systematic and in-depth review of the mechanisms of action of the active substances in P. ginseng, and evaluates the feasibility of applying spatial metabolomics in the study of AD pathogenesis and pharmacological treatment.