RESUMO
In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (â3-α-L-fucp(2-SO3-)-1â4-α-L-fucp(2,3-SO3-)-1âsection), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.
Assuntos
Acetilcolinesterase , Doença de Alzheimer , Inibidores da Colinesterase , Simulação de Acoplamento Molecular , Oligossacarídeos , Sargassum , Sargassum/química , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/uso terapêutico , Camundongos , Acetilcolinesterase/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/química , Oligossacarídeos/isolamento & purificação , Masculino , Sulfatos/química , Sulfatos/farmacologia , Butirilcolinesterase/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Relação Dose-Resposta a DrogaRESUMO
[This corrects the article DOI: 10.1155/2019/3757149.].
RESUMO
Increased oxidative stress levels play a key role in idiosyncratic drug-induced liver injury (DILI) pathogenesis. To investigated whether advanced oxidation protein products (AOPPs) and ischaemia-modified albumin (IMA) can be used to monitor oxidative stress in DILI patients and to assess disease severity. We performed spectrophotometric assays to assess AOPPs and IMA in 68 DILI patients with severity grade 0-2 (non-severe group), 60 with severity grade 3-5 (severe group), and 38 healthy controls. The results showed that baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios were significantly higher in DILI patients than in healthy controls. Besides, in comparison to the non-severe group, the severe group showed higher baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios. AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios decreased after treatment in both patient groups. Combining the correlation analysis and areas under the receiver operating curve (AUROCs) analysis results, that IMA outperformed to be one is the most reliable marker to assess disease severity of DILI. Our findings indicated that AOPPs and IMA can serve as key biomarkers for monitoring oxidative stress levels in DILI patients and can indicate disease severity. The IMA outperformed to be one of the most reliable oxidative stress biomarkers to assess disease severity of DILI.
Assuntos
Produtos da Oxidação Avançada de Proteínas/metabolismo , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Estresse Oxidativo , Albumina Sérica Humana/metabolismo , Albumina Sérica/metabolismo , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , OxirreduçãoRESUMO
BACKGROUND: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ALCF) is a complicated syndrome with extremely high short-term mortality. The artificial liver support system (ALSS) may improve the liver function for patients with HBV-ACLF, but the data on its short-term outcomes are insufficient in China. METHODS: We recruited HBV-ACLF patients in this nationwide, multicenter, retrospective study. Patients with HBV-ACLF were diagnosed by the COSSH-ACLF criteria. Propensity score matching (PSM) analysis was used to generate compared pairs. The short-term (28/90 days) survival rates between the standard medical therapy (SMT) group and ALSS group were calculated using a Kaplan-Meier graph. RESULT: In total, 790 patients with HBV-ACLF were included in this retrospective study; 412 patients received SMT only (SMT group), and 378 patients received SMT and ALSS treatment (ALSS group). PSM generated 310 pairs and eliminated the baseline differences between the two groups (p > 0.05 for all baseline variables). The probabilities of survival on day 28 were 65.2% (205/310) in the ALSS group and 59.0% (185/310) in the SMT group; on day 90, they were 51.0% (163/310) and 42.3% (136/310). The short-term (28/90 days) survival rates of the ALSS group were significantly higher than those of the SMT group (p=0.0452 and p=0.0187, respectively). Compared to receiving SMT alone, treatment with ALSS was associated with a significant reduction in serum bilirubin levels and the model for end-stage liver disease (MELD) scores at day 7 and day 28. Multivariate logistic regression analysis revealed that older age, high total bilirubin (T-Bil), low albumin, high ALT, high MELD scores, and high COSSH-ACLF grade were independent baseline factors associated with poor prognosis. CONCLUSIONS: This retrospective study found that compared to SMT, the ALSS improved the short-term (28/90 days) survival rates and laboratory parameters in HBV-ACLF patients. The ALSS had a better therapeutic effect than SMT for patients with HBV-ACLF in China.
Assuntos
Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/terapia , Hepatite B/complicações , Fígado Artificial , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Idoso , Bilirrubina/sangue , China , Feminino , Vírus da Hepatite B/patogenicidade , Humanos , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
The present study evaluated the potential combined effects of NAFLD and MetS on the development of osteoporosis. The relationship between NAFLD and MetS and osteoporosis was assessed in 938 postmenopausal female participants. Moderate and severe NAFLDs were combined as significant NAFLD (SNAFLD). All the subjects were divided into 4 subgroups based on the status of SNAFLD and MetS. Relative excess risk of interaction (RERI), attributable proportion (AP) of interaction, and synergy index (SI) were used to investigate the additive interaction of those two factors. NAFLD, SNAFLD, and MetS were independent factors for osteoporosis with the adjustment of age and other confounders. The incidence of osteoporosis in MetS (+) SNAFLD (+) group was significantly higher than that in other three groups. RERI was 2.556 (95% CI = 0.475-4.636), AP was 0.454 (95% CI = 0.201-0.706), and SI was 2.231 (95% CI = 1.124 to 4.428), indicating the significant combined interaction of SNAFLD and MetS on the development of osteoporosis. SNAFLD and MetS are independent risk factors for osteoporosis in postmenopausal females, respectively. Moreover, SNAFLD and MetS have an additive effect on the development of osteoporosis.
RESUMO
Whether smoking and metabolic syndrome (MetS) can affect colorectal carcinoma (CRC) prognosis remains debatable. Therefore, the present study aimed to examine the individual and combined effects of smoking and MetS on the prognosis of patients with localized CRC, including stage I to III disease. The relationship among smoking status, MetS, and CRC was assessed in 838 Chinese male patients. Cox proportional hazards regression analysis was used to evaluate CRC prognosis adjusted for clinicopathological variables. Relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (SI) were used to evaluate additive interactions between smoking and MetS. The presence of MetS was an independent risk factor for low rates of recurrence-free survival (RFS) but not for overall survival (OS). However, smoking was independently associated with both poor RFS and OS. Furthermore, the recurrence risk for current smokers with MetS was 1.62 times as high as the sum of risks in patients exposed to each risk factor alone. In conclusion, current smoking habit is a risk factor for both recurrence and cancer-specific mortality in CRC patients, while MetS is an independent predictor for CRC recurrence. Furthermore, these two factors have an additive effect on the recurrence risk of CRC.