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1.
BMC Infect Dis ; 24(1): 806, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123120

RESUMO

BACKGROUND: Mean perfusion pressure (MPP) has recently emerged as a potential biomarker for personalized management of tissue perfusion in critically ill patients. However, its association with the occurrence of acute kidney injury (AKI) in septic patients and the optimal MPP range remain uncertain. Therefore, this study aims to investigate the relationship between MPP and AKI in critically ill patients with sepsis. METHODS: We identified 5867 patients with sepsis from the MIMIC-IV database who met the inclusion and exclusion criteria. The exposure variable was the first set of MPP measured within 24 h after ICU admission with invasive hemodynamic monitoring. The primary outcome was the incidence of AKI at 7 days following ICU admission according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes included in-hospital mortality, lengths of ICU, and hospital stay. Optimal cut-off point for MPP were determined using the Youden index, and multivariable logistic regression was employed to examine the association between MPP and AKI. Subgroup analyses were conducted to enhance result robustness. Kaplan-Meier survival analysis was utilized to evaluate in-hospital mortality rates categorized by MPP. RESULTS: A total of 5,867 patients with sepsis were included in this study, and the overall incidence of AKI was 82.3%(4828/5867). Patients were categorized into low MPP (< 63 mmHg) and high MPP (≥ 63 mmHg) groups using the optimal ROC curve-derived cut-off point. The incidence of AKI in the low MPP group was higher than that in the high MPP group (87.6% vs. 78.3%, P < 0.001). Multivariable logistic regression analysis adjusted for confounding factors revealed that each 1 mmHg increase in MPP as a continuous variable was associated with a 2% decrease in AKI incidence within 7 days of ICU admission (OR:0.98, 95%CI:0.97-0.99, P < 0.001). When MPP was used as a categorical variable, patients in the high MPP group had a lower risk of AKI than those in the low MPP group (OR:0.71, 95%CI:0.61-0.83, P = 0.001). Subgroup analyses demonstrated a consistent association between MPP and AKI risk across all variables assessed (P for interaction all > 0.05). Kaplan-Meier curve analysis demonstrated a higher survival rate during hospitalization in the high MPP group compared to the low MPP group (Log-rank test, P < 0.0001). CONCLUSIONS: Lower levels of MPP are associated with an increased incidence of AKI at 7 days in critically ill patients with sepsis.


Assuntos
Injúria Renal Aguda , Estado Terminal , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Sepse , Humanos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Sepse/complicações , Estudos Retrospectivos , Idoso , Incidência , Fatores de Risco , Tempo de Internação/estatística & dados numéricos
2.
Scand J Clin Lab Invest ; 84(5): 297-304, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39033335

RESUMO

The mechanisms underlying subclinical hypothyroidism (SCH) remain unclear, making timely and accurate differentiation between hypothyroidism and SCH, as well as severity assessment, challenging. This study aimed to investigate the role of NFE2 like bZIP transcription factor 2 (Nrf2), gp91phox, and interleukin-17 (IL-17) in the pathogenesis of SCH. In this prospective comparative study, 105 SCH patients, 105 hypothyroidism patients, and 105 healthy individuals were enrolled from January 2022 to August 2023. SCH patients were categorized into mild-moderate and severe groups based on thyroid-stimulating hormone (TSH) levels. Levels of TSH, free T4 (FT4), free T3 (FT3), thyroglobulin antibodies (TG-Ab), thyroid peroxidase antibodies (TPO-Ab), cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-ch), and low-density lipoprotein-cholesterol (LDL-ch) were measured. Nrf2, IL-1ß, IL-6, IL-17, and gp91phox levels were tested using ELISA. Nrf2, IL-17 and gp91phox were significantly higher in SCH and hypothyroidism patients compared to the healthy controls, with hypothyroidism patients showing the highest levels. Nrf2 levels were negatively correlated with TSH, TG-Ab and IL-17, but not gp91phox. Nrf2, IL-17 and gp91phox could be used for diagnosis of SCH and severe SCH. Only TG-Ab, IL-17 and gp91phox were independent risk factors for severe SCH. This study demonstrates a negative correlation between serum Nrf2 levels and SCH severity. TG-Ab, IL-17, and gp91phox are independent risk factors, and their associations with SCH pathology suggest their potential roles in the disease mechanism. These findings provide insights into SCH pathogenesis and highlight the need for further research to elucidate their diagnostic or prognostic significance.


Assuntos
Hipotireoidismo , Interleucina-17 , NADPH Oxidase 2 , Fator 2 Relacionado a NF-E2 , Humanos , Fator 2 Relacionado a NF-E2/sangue , Masculino , Feminino , Interleucina-17/sangue , Pessoa de Meia-Idade , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , NADPH Oxidase 2/sangue , Adulto , Índice de Gravidade de Doença , Estudos Prospectivos , Estudos de Casos e Controles , Tireotropina/sangue , Autoanticorpos/sangue
3.
Proc Natl Acad Sci U S A ; 121(23): e2405555121, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38805268

RESUMO

The dimeric nuclear factor kappa B (NF-κB) transcription factors (TFs) regulate gene expression by binding to a variety of κB DNA elements with conserved G:C-rich flanking sequences enclosing a degenerate central region. Toward defining mechanistic principles of affinity regulated by degeneracy, we observed an unusual dependence of the affinity of RelA on the identity of the central base pair, which appears to be noncontacted in the complex crystal structures. The affinity of κB sites with A or T at the central position is ~10-fold higher than with G or C. The crystal structures of neither the complexes nor the free κB DNAs could explain the differences in affinity. Interestingly, differential dynamics of several residues were revealed in molecular dynamics simulation studies, where simulation replicates totaling 148 µs were performed on NF-κB:DNA complexes and free κB DNAs. Notably, Arg187 and Arg124 exhibited selectivity in transient interactions that orchestrated a complex interplay among several DNA-interacting residues in the central region. Binding and simulation studies with mutants supported these observations of transient interactions dictating specificity. In combination with published reports, this work provides insights into the nuanced mechanisms governing the discriminatory binding of NF-κB family TFs to κB DNA elements and sheds light on cancer pathogenesis of cRel, a close homolog of RelA.


Assuntos
DNA , Simulação de Dinâmica Molecular , NF-kappa B , Ligação Proteica , DNA/metabolismo , Humanos , NF-kappa B/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Sítios de Ligação , Cristalografia por Raios X
4.
Transplant Proc ; 56(5): 1183-1187, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38806312

RESUMO

An uncommon and dangerous disease with a fatality rate of more than 95% is caused by the amoeba known as Balamuthia mandrillaris. Here, we discuss the treatment of a patient who underwent a renal transplant and contracted the amoeba B. mandrillaris. The patient had a sudden onset of high fever on the 13th day after renal transplantation; on the morning of the 16th postoperative day, the patient's condition worsened and he was transferred to the ICU for treatment; on the 17th postoperative day, the patient was given mechanical ventilation; and on the 20th postoperative day, he underwent a lumbar large-pool puncture, combined with intrathecal injection of the administered medication. In order to prevent further deterioration of the patient's condition, the main aspects of care for this patient included close monitoring of changes in the patient's condition and early detection of risk factors; prompt emergency care for the patient's seizures; close monitoring of the efficacy and side effects of the patient's medication; and precise medication administration; improved hemodynamic monitoring while administering CRRT to the patient, as well as performing exercises on the patient's limb and respiratory functions. On the 32nd postoperative day, a tracheotomy is performed following thorough monitoring and care. The ventilator was turned off on postoperative day 34, and a venturi mask was installed for tracheotomy-cannula-based oxygen administration. On surgical day 40, the intrathecal injections halted and the lumbar pool drainage tube was removed. On postoperative day 46, the patient was stabilized and transferred from the intensive care unit to the organ transplant unit for extra care. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source.


Assuntos
Balamuthia mandrillaris , Unidades de Terapia Intensiva , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Masculino , Amebíase , Respiração Artificial , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Neurol Sci ; 45(2): 431-453, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37843692

RESUMO

Freezing of gait (FoG) is one of the most distressing symptoms of Parkinson's Disease (PD), commonly occurring in patients at middle and late stages of the disease. Automatic and accurate FoG detection and prediction have emerged as a promising tool for long-term monitoring of PD and implementation of gait assistance systems. This paper reviews the recent development of FoG detection and prediction using wearable sensors, with attention on identifying knowledge gaps that need to be filled in future research. This review searched the PubMed and Web of Science databases to collect studies that detect or predict FoG with wearable sensors. After screening, 89 of 270 articles were included. The data description, extracted features, detection/prediction methods, and classification performance were extracted from the articles. As the number of papers of this area is increasing, the performance has been steadily improved. However, small datasets and inconsistent evaluation processes still hinder the application of FoG detection and prediction with wearable sensors in clinical practice.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Marcha/fisiologia
7.
Mol Biotechnol ; 66(3): 467-474, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37204622

RESUMO

Monogenic diabetes caused by GATA6 mutations were almost described as neonatal diabetes, and the phenotypic spectrum has expanded since then. Our study underscores the broad phenotypic spectrum by reporting a de novo GATA6 mutation in a family. Furthermore, we reviewed related literature to summarize the clinical and genetic characteristics of monogenic diabetes with GATA6 mutations (n = 39) in order to improve clinicians' understanding of the disease. We conclude that the GATA6 missense mutation (c. 749G > T, p. Gly250Val) is not reported presently, characterized by adult-onset diabetes with pancreatic dysplasia and located in transcriptional activation region. Carries with GATA6 mutations (n = 55) have a variable spectrum of diabetes, ranging from neonatal (72.7%), childhood-onset (20%) to adults-onset (7.5%). 83.5% of patients with abnormal pancreatic development. Heart and hepatobillary defects are the most common abnormalities of extrapancreatic features. Most mutations with GATA6 are loss of function (LOF, 71.8%) and located in functional region. Functional studies mostly support loss-of-function as the pathophysiological mechanism. In conclusion, there are various types of diabetes with GATA6 mutations, which can also occur in adult diabetes. Phenotypic defects with GATA6 mutations are most frequently malformations of pancreas and heart. This highlights the importance of comprehensive clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.


Assuntos
Diabetes Mellitus Tipo 2 , Cardiopatias Congênitas , Recém-Nascido , Adulto , Humanos , Criança , Cardiopatias Congênitas/genética , Pâncreas/anormalidades , Mutação , Fenótipo , Fator de Transcrição GATA6/genética
8.
Front Med (Lausanne) ; 10: 1258037, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822466

RESUMO

Background: There is a significant controversy surrounding the impact of the geriatric nutritional risk index (GNRI) on mortality among elderly septic patients. This retrospective cohort study aimed to investigate the association between GNRI at admission and 28 days mortality in elderly septic patients. Methods: We retrospectively analyzed data collected from the MIMIC IV database between 2009 and 2019, which included 2,834 septic patients aged 65 years and above. The exposure variable was the GNRI, determined according to albumin levels, height, and weight. The primary outcome was 28 days mortality. We employed multivariable Cox regression analyses and Kaplan-Meier survival curves to examine the association between GNRI and 28 days mortality. We used restricted cubic splines to determine if there was a non-linear relationship between 28 days mortality and GNRI in elderly patients with sepsis and to examine the presence of a threshold saturation effect. In addition, interaction tests were conducted to identify subgroups that exhibited significant differences. Results: A total of 2,834 elderly patients with sepsis participated in the study. Following adjustment, multivariable Cox regression analyses demonstrated that the GNRI was related to 28 days mortality (HR = 0.97, p < 0.001, 95% CI: 0.97-0.98). An L-shaped connection between GNRI and 28 days mortality was discovered via restricted cubic spline analysis, with an inflection point of 98.1. On the left side of the inflection point, GNRI levels were significantly negatively linked with 28 days mortality (HR = 0.967, 95% CI: 0.959-0.974; p < 0.001), and on the right side, there was no significant correlation (HR = 1.043, 95% CI: 0.984-1.106; p = 0.1549). Conclusion: In this analysis of data from a large cohort of elderly septic patients, GNRI scores on admission were correlated with a 28 days risk of death from sepsis in the elderly suggesting that GNRI scores could serve as a valuable indicator for evaluating mortality rates among elderly septic patients in the intensive care unit (ICU).

9.
Toxicol Appl Pharmacol ; 464: 116438, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36841340

RESUMO

The pathophysiological mechanism of hepatic fibrosis (HF) is related to the excessive activation of the DNA repair enzyme poly ADP-ribose polymerase-1 (PARP-1). The drugs, targeting PARP-1, are scarce. Therefore, the lead compound, moderately inhibiting PARP-1, with anti-HF properties should be identified. This study screened dihydrokaempferol (DHK) from herbs based on preliminary studies to intervene in a CCl4-induced liver injury and HF model in mice. In vitro, the expression levels of PARP-1-regulated related proteins and phosphorylation were examined. The binding pattern of DHK and PARP-1 was analyzed using molecular docking and molecular dynamics platforms. The results showed that DHK could significantly attenuate CCl4-induced liver injury and HF in mice. Moreover, it could also attenuate the toxic effects of CCl4 on HepG2 and inhibit α-SMA and Collagen 1/3 synthesis of LX-2 cells in-vitro. Molecular docking revealed that DHK could competitively bind to the Glu-988 and His-862 residues of the upstream DNA repair enzyme PARP-1, moderately inhibiting its overactivation. This led to maintaining NAD+ levels and energy metabolism in hepatocytes and inhibiting the activation of PARP-1-regulated downstream signaling pathways (TGF-ß1, etc.), related proteins (p-Smd2/3, etc.), and inflammatory mediators while acting indirectly. Thus, DHK could attenuate CCl4-induced liver injury and HF in mice in a different mechanism from those of the existing reported flavonoids. It was associated with inhibiting the expression of downstream pathways and related cytokines by competitively binding to PARP-1. This study might provide a basis and direction for the design and exploration of anti-HF lead compounds.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Citocinas , Animais , Camundongos , Tetracloreto de Carbono/toxicidade , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Citocinas/metabolismo , Flavonoides/farmacologia , Células Estreladas do Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Simulação de Acoplamento Molecular , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Fator de Crescimento Transformador beta1/metabolismo
10.
Nurs Open ; 10(3): 1556-1564, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36266743

RESUMO

AIM: To investigate the ability of critical care nurses to identify pressure injury and incontinence-associated dermatitis and analyse the possible influencing factors. DESIGN: Cross-sectional survey. METHODS: This study was conducted at 24 hospitals across 12 provinces in China. A self-made electronic questionnaire was used. Nurses identified and judged injuries according to the information provided. RESULTS: The average identification score for pressure injury and incontinence-associated dermatitis was 9.00 ± 3.51 points, and only 2.16% of nurses scored ≥16 points. The average correct identification rate for pressure injury and incontinence-associated dermatitis was 45%. The correct identification rate for stage 1 pressure injury was the highest, while those for stage 3, stage 4, deep tissue pressure injury and unstageable pressure injury were all lower than 50%; incontinence-associated dermatitis was also easily misjudged. Nurses' educational backgrounds, professional titles, job positions, hospital levels and learning frequency were the factors that affected their ability to identify pressure injury and incontinence-associated dermatitis.


Assuntos
Lesões por Esmagamento , Dermatite , Incontinência Fecal , Enfermeiras e Enfermeiros , Úlcera por Pressão , Incontinência Urinária , Humanos , Úlcera por Pressão/etiologia , Estudos Transversais , Incontinência Fecal/complicações , Incontinência Urinária/complicações , Cuidados Críticos , Dermatite/etiologia
11.
Sci Data ; 9(1): 606, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207427

RESUMO

Freezing of gaits (FOG) is a very disabling symptom of Parkinson's Disease (PD), affecting about 50% of PD patients and 80% of advanced PD patients. Studies have shown that FOG is related to a complex interplay between motor, cognitive and affective factors. A full characterization of FOG is crucial for FOG detection/prediction and prompt intervention. A protocol has been designed to acquire multimodal physical and physiological information during FOG, including gait acceleration (ACC), electroencephalogram (EEG), electromyogram (EMG), and skin conductance (SC). Two tasks were designed to trigger FOG, including gait initiation failure and FOG during walking. A total number of 12 PD patients completed the experiments and produced a length of 3 hours and 42 minutes of valid data including 2 hours and 14 minutes of normal gait and 1 hour and 28 minutes of freezing of gait. The FOG episodes were labeled by two qualified physicians. The multimodal data have been validated by a FOG detection task.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Eletromiografia , Marcha/fisiologia , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Caminhada/fisiologia
12.
Comput Biol Med ; 146: 105629, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35659119

RESUMO

OBJECTIVE: Freezing of gait (FoG) is a serious symptom of Parkinson's disease and prompt detection of FoG is crucial for fall prevention. Although multimodal data combining electroencephalography (EEG) benefit accurate FoG detection, the preparation, acquisition, and analysis of EEG signals are time-consuming and costly, which impedes the application of multimodal information in FoG detection. This work proposes a wearable FoG detection method that merges multimodal information from acceleration and EEG while avoiding the acquisition of real EEG data. METHODS: A proxy measurement (PM) model based on long-short-term-memory (LSTM) network was proposed to measure EEG features from accelerations, and pseudo-multimodal features, i.e., pseudo-EEG and acceleration, could be extracted using a highly wearable inertial sensor for FoG detection. RESULTS: Based on a self-collected FoG dataset, the performance of different feature combinations were compared in terms of subject-dependent and cross-subject settings. In both settings, pseudo-multimodal features achieved the most promising performance, with a geometric mean of 91.0 ± 5.0% in subject-dependent setting and 91.0 ± 3.5% in cross-subject setting. CONCLUSION: Our study suggests that wearable FoG detection can be enhanced through leveraging cross-modal information fusion. SIGNIFICANCE: The new method provides a promising path for multimodal information fusion and the long-term monitoring of FoG in living environments.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Acelerometria/métodos , Marcha , Transtornos Neurológicos da Marcha/diagnóstico , Humanos , Doença de Parkinson/diagnóstico
13.
J Adv Nurs ; 77(7): 2929-2941, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33483993

RESUMO

AIM: To systematically evaluate the effect of intensive care unit diary psychotherapy on the incidence of posttraumatic stress disorder, anxiety, and depression after discharge from intensive care unit. BACKGROUND: Many studies have reported the potential advantages and risks of intensive care unit diary psychotherapy in adult patients discharged from intensive care unit, but the results are divergent. DESIGN: Systematic review and meta-analysis of prospective randomized controlled or case-controlled studies. DATA SOURCE: Databases such as Cochran Library, Pubmed, Embase, CINAHL, and ProQuest databases, China national knowledge infrastructure (CNKI) were searched for literatures published from January 2000-March 2020. REVIEW METHODS: We use the Cochrane Risk of Bias Tool for quality assessment and audit manager 5.3 software for meta-analysis. The main result is the incidence of posttraumatic stress disorder, anxiety, and depression. RESULTS: Ten studies meeting the inclusion criteria were identified, including eight randomized controlled studies and two case-controlled studies, with a total of 1,210 patients. The pooled results of this meta-analysis indicated that the intensive care unit diary could reduce the incidence of posttraumatic stress disorder, anxiety, and depression. CONCLUSION: This study showed that an intensive care unit diary could improve the psychological symptoms of adult intensive care unit patients after discharge. However, due to limitations such as publication bias and case sample size, the results should be carefully considered. Researchers need to further clarify the multidisciplinary collaborative process of intensive care unit diary therapy, the real beneficiaries, and its impact on family members' psychological status by conducting large, robust studies in the future. IMPACT: This study's findings suggest that medical staff need to re-examine the role of intensive care unit diary therapy, its standardized implementation and provide effective intervention for reducing psychological stress-related symptoms of intensive care unit patients after discharge.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adulto , Ansiedade , China , Humanos , Incidência , Unidades de Terapia Intensiva , Estudos Prospectivos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/terapia , Sobreviventes
14.
Health Informatics J ; 26(3): 1577-1598, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31709900

RESUMO

The accurate identification and prediction of high-cost Chronic obstructive pulmonary disease (COPD) patients is important for addressing the economic burden of COPD. The objectives of this study were to use machine learning approaches to identify and predict potential high-cost patients and explore the key variables of the forecasting model, by comparing differences in the predictive performance of different variable sets. Machine learning approaches were used to estimate the medical costs of COPD patients using the Medical Insurance Data of a large city in western China. The prediction models used were logistic regression, random forest (RF), and extreme gradient boosting (XGBoost). All three models had good predictive performance. The XGBoost model outperformed the others. The areas under the ROC curve for Logistic Regression, RF and XGBoost were 0.787, 0.792 and 0.801. The precision and accuracy metrics indicated that the methods achieved correct and reliable results. The results of this study can be used by healthcare data analysts, policy makers, insurers, and healthcare planners to improve the delivery of health services.


Assuntos
Aprendizado de Máquina , Doença Pulmonar Obstrutiva Crônica , China , Humanos , Modelos Logísticos , Doença Pulmonar Obstrutiva Crônica/terapia , Curva ROC
15.
Nat Prod Res ; 34(6): 855-858, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30394110

RESUMO

Epicatechin (EC) is the most effective compound in Euonymus alatus (Thunb.)Sieb, and possesses a series of benefits, including anti-inflammatory, antioxidant, antiobesity and anticancer effects. In this study, we investigated the protective effects of EC in Acetaminophen(N-acetyl-p-aminophenol, APAP)-induced acute liver injury in C57BL/6J mice and explored the possible mechanisms involved in these effects.[Formula: see text].


Assuntos
Apoptose/efeitos dos fármacos , Catequina/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Inflamação/prevenção & controle , Acetaminofen/efeitos adversos , Animais , Antioxidantes/farmacologia , Catequina/farmacologia , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico
17.
Am J Transl Res ; 11(1): 106-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30787972

RESUMO

This study aimed to investigate the protective effects, effective constituents and preliminary mechanisms of Euonymus alatus on liver fibrosis and screen new high-efficacy drug for fibrosis. 112 male C57BL/6 mice were randomly divided into 14 groups: control group (CG), CCL4 group (CTG), low/medium/high dose of Euonymus alatus ethanol extracts (EAE), catechin (CA), dihydroquercetin (DHQ) and kaempferol (KA) groups. The study lasted for 30 days by injecting CCL4 in peritoneal cavity to make fibrosis model, all mice were sacrificed to observe morphological changes and collagenous fiber by HE and Masson staining, to test liver index, ALT, AST, to measure the expression of α-SMA and collagen I by immunohistochemistry and western blotting, to discuss the pathways of TßR1-Smad2/3 and TNF-α-NF-κB by WB and Elisa; after being evaluated the efficacy, anti-fibrosis drug of highest efficacy was chosen to repeat these indexes in human hepatic stellate cells-LX2. Results showed that EAE/CA/DHQ/KA prevented increases in liver index, ALT, AST, α-SMA, collagen I, TßR1, Smad2/3, TNF-α and p-NF-κB caused by CCL4 in dose-dependence, they also improved the liver morphology, decreased inflammatory cell infiltration and collagenous fiber in dose-dependence, CA' efficacy was best in mice; in LX-2, CA also decreased the expression of α-SMA, collagen I, TGF-ß, Smad2/3. All findings suggested that Euonymus alatus could alleviate liver inflammation and fibrosis by inhibiting TßR1-Smad2/3 and TNF-α-NF-κB pathways, flavonoid were effective constituents and catechin was screened as a new star for its best performance.

18.
Int J Clin Exp Pathol ; 12(1): 154-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933729

RESUMO

Hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) ion channel activity plays a crucial role in the progress of peripheral neuropathic pain (PNP). However, the mechanism of HCN2 channels on PNP remains unclear. Here, we investigated the effects of HCN2 channel expression on the mechanical allodynia and thermal hyperalgesia, the local inflammatory response, the activation of astrocytes, microglia and transcription factor NF-κB in mice with spared sciatic nerve injury (SNI). The present study showed that the expression of HCN2 channels was increased in L4-L5 ipsilateral spinal dorsal horns, accompanied by a decreased paw mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL) in SNI mice. After intrathecal injection of ZD-7288 and si-HCN2, both MWT and PWL were significantly increased, while the level of pro-inflammatory factors TNF-α, IL-1ß and MCP-1 were decreased in L4-L5 ipsilateral spinal dorsal horn. Furthermore, the inhibition of HCN2 channels reduces the activated astrocytes and microglia, and suppressed NF-κB p65 activation and nuclear translocation. In conclusion, the present study suggests that decreased HCN2 channel expression attenuates neuropathic pain by inhibiting pro-inflammatory reactions and NF-κB activation.

19.
J Vis Exp ; (141)2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30451218

RESUMO

A class of extracellular stimuli requires activation of IKK1/α to induce generation of an NF-κB subunit, p52, through processing of its precursor p100. p52 functions as a homodimer or heterodimer with another NF-κB subunit, RelB. These dimers in turn regulate the expression of hundreds of genes involved in inflammation, cell survival, and cell cycle. IKK1/α primarily remains associated with IKK2/ß and NEMO as a ternary complex. However, a small pool of it is also observed as a low molecular weight complex(es). It is unknown if the p100 processing activity is triggered by activation of IKK1/α within the larger or the smaller complex pool. Constitutive activity of IKK1/α has been detected in several cancers and inflammatory diseases. To understand the mechanism of activation of IKK1/α, and enable its use as a drug target, we expressed recombinant IKK1/α in different host systems, such as E. coli, insect, and mammalian cells. We succeeded in expressing soluble IKK1/α in baculovirus infected insect cells, obtaining mg quantities of highly pure protein, crystallizing it in the presence of inhibitors, and determining its X-ray crystal structure. Here, we describe the detailed steps to produce the recombinant protein, its crystallization, and its X-ray crystal structure determination.


Assuntos
Quinase I-kappa B/química , Animais , Cristalização , Humanos , Insetos , Transfecção
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(1): 50-56, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926659

RESUMO

OBJECTIVE: To investigate the effects of Coriaria Sinica Maxim's extract(CSME) on microcirculation and oxidative stress of wounds in rats with deep second-degree burn. METHODS: One hundred and eighty rats were randomly divided into normal saline group(NS), white petroleum group(WPL), silver sulfadiazine group (SSD), Coriariasinica Maxim's extract group which were divided into low dose(CSME-L),middle dose(CSME-M) and high dose(CSME-H). After anesthesia with burn instrument to burn the hair removal area of rats, these wounds were confirmed by pathological results with deep second degree burns.And then,those drugs were applied respectively on the wounds,such as NS、WPL、SSD and different concentrations of CSME. After injury at 48 h, 7 d, 14 d and 21 d,the healing rate(HR) of wound was measured, and the microvessel density (MVD), tissue moisture (TM), vascular endothelial growth factor (VEGF), model driven architecture (MDA), superoxide dismutase(SOD) and hydroxyproline(HYP) were detected, too. All pathological sections of the wound tissue were observed. RESULTS: The HR of CSME groups were obviously increased with a dose-dependent manner, which was significantly higher than that of NS and WPL (P<0.05); On the 21st day, the diameter, number, distribution of the vessels and and the TM were less than other groups with a dose-dependent manner; On the 7th and 14th day after injury, CSME groups were significantly higher than the NS, WPL and SSD with a dose-dependent manner (P<0.05), but, on the 21st day after injury, they were lower than NS, WPL and SSD with a dose-dependent (P<0.05) manner. The levels of SOD, HYP, NO and ET in CSME groups were higher than those in other groups with dose-dependent on SOD activity, HYP, NO and ET content (P<0.05), while MDA activity was weaker than other groups (P<0.05). Similarly, pathological findings were also shown that CSME groups were better than other groups with a dose-dependent manner in decrease decreasing of wound repair time and hyperplasia of scar tissue. CONCLUSIONS: CSME can relieve tissue edema, promote wound contraction, speed up the formation of eschar and accelerate the proliferation of granulation tissue, which are beneficial to the wound healing in the early stages. But, it can inhibit the hyperplasia of granulation tissue to prevent the excessive scar hyperplasia of burn wound in the later stages. Its mechanism is related to regulation what microcirculation, oxidativestress, NO and VEGF.


Assuntos
Queimaduras/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microcirculação , Estresse Oxidativo , Cicatrização/efeitos dos fármacos , Animais , Hidroxiprolina/metabolismo , Malondialdeído/metabolismo , Distribuição Aleatória , Ratos , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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