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1.
Int Immunopharmacol ; 101(Pt A): 108325, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34740080

RESUMO

Ischemic stroke is a devastating disease with high morbidity and mortality rates, and the proinflammatory microglia-mediated inflammatory response directly affects stroke outcome. Previous studies have reported that JLX001, a novel compound with a structure similar to that of cyclovirobuxine D (CVB-D), exerts antiapoptotic, anti-inflammatory and antioxidative effects on ischemia-induced brain injury. However, the role of JLX001 in microglial polarization and nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome regulation after ischemic stroke has not been fully investigated. In this study, we used the middle cerebral artery occlusion (MCAO) method to establish a focal cerebral ischemia model and found that JLX001 attenuated the brain infarct size and improved cerebral damage. Moreover, the expression levels of proinflammatory cytokines (interleukin [IL]-1ß and tumor necrosis factor [TNF]-α) were significantly reduced while those of the anti-inflammatory cytokine IL-10 were increased in the JLX001-treated group. Immunofluorescence staining and flow cytometry revealed an increased number of anti-inflammatory phenotypic microglia and a reduced number of proinflammatory phenotypic microglia in JLX001-treated MCAO mice. Western blotting analysis showed that JLX001 inhibited the expression of NLRP3 and proteins related to the NLRP3 inflammasome axis in vivo. Furthermore, JLX001 reduced the number of NLRP3/Iba1 cells in ischemic penumbra tissues. Finally, mechanistic analysis revealed that JLX001 significantly inhibited the expression of proteins related to the NF-κB signaling pathway. Additionally, pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, ameliorated cerebral ischemia-reperfusion injury by suppressing microglial polarization towards the proinflammatory phenotype and NLRP3 activation in vivo, further suggesting that these protective effects of JLX001 were mediated by inhibition of the NF-κB signaling pathway. These results suggest that JLX001 is a promising therapeutic approach for ischemic stroke.

2.
Oxid Med Cell Longev ; 2021: 2961079, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824669

RESUMO

Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing neurons in the penumbra is a potential way to recover from ischemic stroke. Endogenous levels of the potent ROS quencher glutathione (GSH) decrease significantly after cerebral ischemia. Here, we aimed to investigate the neuroprotective effects of γ-glutamylcysteine (γ-GC), an immediate precursor of GSH, on neuronal apoptosis and brain injury during ischemic stroke. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice, neuronal cell lines, and primary neurons. Our data indicated that exogenous γ-GC treatment mitigated oxidative stress, as indicated by upregulated GSH and decreased ROS levels. In addition, γ-GC attenuated ischemia/reperfusion-induced neuronal apoptosis and brain injury in vivo and in vitro. Furthermore, transcriptomics approaches and subsequent validation studies revealed that γ-GC attenuated penumbra neuronal apoptosis by inhibiting the activation of protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) in the endoplasmic reticulum (ER) stress signaling pathway in OGD/R-treated cells and ischemic brain tissues. To the best of our knowledge, this study is the first to report that γ-GC attenuates ischemia-induced neuronal apoptosis by suppressing ROS-mediated ER stress. γ-GC may be a promising therapeutic agent for ischemic stroke.

3.
BMJ Open ; 11(11): e049742, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782340

RESUMO

INTRODUCTION: Follow-up care is important for gastric cancer survivors, but follow-up strategies for gastric cancer survivors remain inconsistent, and compliance of gastric cancer survivors with follow-up care is very low. Understanding the needs and preferences of gastric cancer survivors is conducive to developing appropriate and acceptable follow-up strategies, thereby improving patient compliance. Discrete choice experiments can quantify individual needs and preferences. However, to date, there is no discrete choice experiment on the preferences of gastric cancer survivors, and no studies have examined how gastric cancer survivors make choices based on different characteristics of follow-up. This paper outlines an ongoing discrete choice experiment that aims to (1) explore follow-up service-related characteristics that may affect gastric cancer survivors' choices about their follow-up, (2) elicit how gastric cancer survivors consider the trade-offs among different follow-up service options using discrete choice experiment, (3) determine whether gastric cancer survivors' needs and preferences for follow-up vary due to the economy, politics, technology and culture in different regions. METHODS AND ANALYSIS: Six attributes were developed through a literature review, semistructured interviews and experts and focus group discussions. A fractional factorial design was used to evaluate the interaction between attributes. A multiple logit model will be used to understand the trade-off between the follow-up characteristics of gastric cancer survivors. A mixed logit model will be used to explore the willingness to pay and uptake rate of gastric cancer survivors for follow-up attributes and further explore the preferences of different groups. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of the School of Nursing, Jilin University. The results of this study will be shared through online blogs, policy briefs, seminars and peer-reviewed journal articles and will be used to modify the current strategy of gastric cancer survivors' follow-up services according to economic development and regional culture.

4.
Biomed Res Int ; 2021: 3361309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34580638

RESUMO

Introduction: Hypoglycemic drugs affect the bone quality and the risk of fractures in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and insulin on bone mineral density (BMD) in T2DM. Methods: In this single-blinded study, a total of 65 patients with T2DM were randomly assigned into four groups for 52 weeks: the exenatide group (n = 19), dulaglutide group (n = 19), insulin glargine group (n = 10), and placebo (n = 17). General clinical data were collected, and BMD was measured by dual-energy X-ray absorptiometry. Results: Compared with baseline, the glycosylated hemoglobin (HbA1c) decreased significantly in the exenatide (8.11 ± 0.24% vs. 7.40 ± 0.16%, P = 0.007), dulaglutide (8.77 ± 0.37% vs. 7.06 ± 0.28%, P < 0.001), and insulin glargine (8.57 ± 0.24% vs. 7.23 ± 0.25%, P < 0.001) groups after treatment. In the exenatide group, the BMD of the total hip increased. In the dulaglutide group, only the BMD of the femoral neck decreased (P = 0.027), but the magnitude of decrease was less than that in the placebo group; the BMD of L1-L4, femoral neck, and total hip decreased significantly (P < 0.05) in the placebo group, while in the insulin glargine group, the BMD of L2, L4, and L1-4 increased (P < 0.05). Compared with the placebo group, the BMD of the femoral neck and total hip in the exenatide group and the insulin glargine group were increased significantly (P < 0.05); compared with the exenatide group, the BMD of L4 in the insulin glargine group was also increased (P = 0.001). Conclusions: Compared with the placebo, GLP-1RAs demonstrated an increase of BMD at multiple sites of the body after treatment, which may not exacerbate the consequences of bone fragility. Therefore, GLP-1RAs might be considered for patients with T2DM. This trial is registered with ClinicalTrials.gov NCT01648582.

5.
Support Care Cancer ; 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34455494

RESUMO

PURPOSES: The purposes of this discrete choice experiment are as follows: (1) to investigate the preferences of gastric cancer survivors for follow-up care, and (2) to quantify the importance of follow-up care-related characteristics that may affect the gastric cancer survivors' choices of their follow-up, so as to provide references for the development of the follow-up strategy of gastric cancer survivors. METHODS: Discrete choice experimental design principle was applied to develop the survey instrument. All questionnaires were filled out by the respondents and collected on site. A mixed logit model was used to estimate gastric cancer survivors' preferences. Willingness to pay estimates and simulations of follow-up uptake rates were calculated. RESULTS: All six attributes are significantly important for the follow-up care of gastric cancer survivors (p < 0.05). Achieving very thorough follow-up contents was the most valued attribute level (coefficient = 1.995). Specialist doctors are the most preferred providers followed by specialist nurses, and gastric cancer survivors were willing to pay more for these attribute levels. Changes in attribute levels affected uptake rate of follow-up. When the multiple attribute levels were changed at the same time, a very thorough follow-up content was provided by the same specialist doctor (specialist nurse), and the probability of receiving follow-up increases by 95.82% (94.90%). CONCLUSIONS: The characteristics of follow-up care in our study reflect the health management services' expectations of gastric cancer survivors. A dedicated specialist nurse involved in follow-up care should be developed to contribute to solve the complex and multifaceted personal needs of gastric cancer survivors.

6.
BMC Cancer ; 21(1): 959, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34445987

RESUMO

BACKGROUND: It is very necessary to implement gastric cancer screening in China to reduce the mortality of gastric cancer, but there are no national screening guidelines and programs. Understanding of individual preferences is conducive to formulating more acceptable screening strategies, and discrete choice experiments can quantify individual preferences. In addition, the first-degree relatives of gastric cancer patients are at high risk for gastric cancer. Compared with those without a family history of gastric cancer, the risk of gastric cancer in first-degree relatives of gastric cancer patients is increased by 60%. Therefore, a discrete choice experiment was carried out to quantitatively analyse the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening to serve as a reference for the development of gastric cancer screening strategies. METHODS: A questionnaire was designed based on a discrete choice experiment, and 342 first-degree relatives of gastric cancer patients were investigated. In STATA 15.0 software, the data were statistically analysed using a mixed logit model. RESULTS: The five attributes included in our study had a significant influence on the preferences of first-degree relatives of gastric cancer patients for gastric cancer screening (P < 0.05). Participants most preferred the sensitivity of the screening program to be 95% (coefficient = 1.424, P < 0.01) with a willingness to pay 2501.902 Yuan (95% CI, 738.074-4265.729). In addition, the participants' sex and screening experiences affected their preferences. An increase in sensitivity 35 to 95% had the greatest impact on the participants' willingness to choose a gastric cancer screening program. CONCLUSION: The formulation of gastric cancer screening strategies should be rooted in people's preferences. The influence of sex differences and screening experiences on the preferences of people undergoing screening should be considered, and screening strategies should be formulated according to local conditions to help them play a greater role.


Assuntos
Comportamento de Escolha/fisiologia , Detecção Precoce de Câncer/psicologia , Família/psicologia , Preferência do Paciente/psicologia , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/psicologia , Inquéritos e Questionários
7.
J Adv Nurs ; 77(6): 2845-2859, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33818820

RESUMO

AIMS: To evaluate the compliance of patients after gastrectomy in taking oral nutritional supplementation and to explore the promoting and hindering factors. DESIGN: A mixed-methods design with an explanatory sequential approach was employed. METHODS: We conducted a 12-week longitudinal study to evaluate the oral nutritional supplementation compliance of 122 patients after gastric cancer surgery and the factors that affected their compliance. After the quantitative phase, we selected the interview subjects and developed the interview outline based on the analysis of the quantitative results. In-depth interviews (n = 15) were conducted to explain and supplement the quantitative phase results. Data were collected from October 2019 to May 2020. RESULTS: The average overall compliance rate of oral nutritional supplementation in patients with gastric cancer over 12 weeks was 30.59%. Adverse reactions to oral nutritional supplementation, the identity of the main caregivers and the patient's financial ability were independent factors that affected patient compliance. In subsequent interviews, we extracted four themes: social support plays an important role in patients taking oral nutritional supplementation, adverse reactions discourage patients from continuing to take oral nutritional supplementation, patients' attitudes affect their motivation to take oral nutritional supplementation, and the different needs of patients for oral nutritional supplementation affect patient compliance. CONCLUSION: Patients' compliance with oral nutritional supplementation after gastric cancer surgery is very low. Health education should pay more attention to the management of adverse reactions and the role of patients' peers and family members. Oral nutritional supplementation products should be diversified to provide patients with more choices. IMPACT: This study clarifies the factors that hinder and promote oral nutritional supplementation compliance and provides an important reference for the establishment and revision of health education strategies for patients after gastric cancer surgery.


Assuntos
Gastrectomia , Neoplasias Gástricas , Suplementos Nutricionais , Humanos , Estudos Longitudinais , Cooperação do Paciente , Neoplasias Gástricas/cirurgia
8.
BMJ Open ; 11(3): e044308, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707272

RESUMO

INTRODUCTION: Postoperative malnutrition is a major issue in patients with gastric cancer. The European Society for Clinical Nutrition and Metabolism recommends oral nutritional supplements (ONS) as a first-line nutritional therapy to prevent malnutrition in patients with cancer. However, adherence to ONS is unsatisfactory. The overall aim of this study was to evaluate the adherence of patients with gastric cancer to ONS and to explore the promoting and hindering factors. METHODS AND ANALYSIS: In this study, we will use mixed methods with an explanatory sequential approach for data collection and analysis. In the first phase, a 12-week longitudinal study will be performed to identify changes in trends of oral nutritional supplementation adherence in 135 patients with gastric cancer, the impact of adherence on nutritional indicators and clinical outcomes and ONS adherence-related factors. The primary endpoints include patient adherence to ONS, weight, body mass index and grip strength followed by 30-day readmission rate, complications and adverse reactions. In the second stage, qualitative research will be implemented to provide in-depth insight into the quantitative results. Finally, quantitative and qualitative results will be combined for analysis and discussion to put forward suggestions for improving patients' ONS adherence. ETHICS AND DISSEMINATION: This research protocol has been approved by the Ethics Committee of the School of Nursing, Jilin University, China (No. 2019101601). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. TRIAL REGISTRATION NUMBER: ChiTR2000032425.


Assuntos
Desnutrição , Neoplasias Gástricas , China , Suplementos Nutricionais , Humanos , Estudos Longitudinais , Estado Nutricional , Neoplasias Gástricas/cirurgia
9.
Cancer Med ; 9(22): 8364-8372, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32902184

RESUMO

Local tumor failure remains a major problem after radiation-based nonsurgical treatment for unresectable locally advanced nonsmall cell lung cancer (NSCLC)and inoperable stage II NSCLC. The aim of this study was to evaluate the feasibility of simultaneous integrated boost of intensity-modulated radiation therapy (SIB-IMRT) to stage II-III NSCLC with metastatic lymph nodes (ChiCTR 2000029304). Patients were diagnosed by pathology or PET-CT. PTV was divided into two parts as follows, the PTV of primary tumor (PTVp) and the PTV of metastatic lymph nodes (PTVn). The radiotherapy doses were simultaneously prescripted 78 Gy (BED = 101.48 Gy) for PTVp and 60-65 Gy (BED = 73.6-81.25 Gy) for PTVn, 26f/5.2 weeks. Response was scored according to WHO criteria. Radiotherapy toxicity was scored according to RTOG criteria. Hematology and gastrointestinal toxicity were scored according to CTCAE1.0 criteria. A total of 20 patients were enrolled. Seventeen patients were diagnosed by pathology and three patients were diagnosed by PET-CT. All patients were treated with SIB-IMRT. The objective response rate (ORR) was 90%, with CR 25%, PR 65%, NC 10%, and PD 0%. Although radiotherapy toxicity was common, there were no grade ≥3, with radiation pneumonitis (10 cases), esophagitis (17 cases), and dermatitis (12 cases). The local control rates at 1, 3, and 5 years were 85%, 75%, and 70%, respectively. The overall survival(OS)and local progression-free survival (LPFS) rates at 1, 3, and 5 years were 90%, 42.6%, and 35.5% and 84.4%, 35.5%, and 28.4%, respectively. SIB-IMRT can significantly improve ORR and survival for stage II-III NSCLC with metastatic lymph nodes, with high safety, and satisfactory efficacy. However, due to the limitation of small sample, these findings are needed to confirm by future trials with a larger sample size.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Linfonodos/efeitos da radiação , Doses de Radiação , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/secundário , Progressão da Doença , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Intervalo Livre de Progressão , Radioterapia de Intensidade Modulada/efeitos adversos , Fatores de Tempo
10.
AIDS Res Ther ; 17(1): 26, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32456686

RESUMO

BACKGROUND: The clinical and laboratory characteristics of AIDS-associated Talaromyces marneffei infection, a rare but a fatal mycosis disease of the central nervous system, remain unclear. CASE PRESENTATION: Herein, we conducted a retrospective study of ten AIDS patients with cerebrospinal fluid culture-confirmed central nervous system infection caused by Talaromyces marneffei. All 10 patients were promptly treated with antifungal treatment for a prolonged duration and early antiviral therapy (ART). Among them, seven patients were farmers. Nine patients were discharged after full recovery, while one patient died during hospitalization, resulting in a mortality rate of 10%. All patients initially presented symptoms and signs of an increase in intracranial pressure, mainly manifesting as headache, dizziness, vomiting, fever, decreased muscle strength, diplopia or even altered consciousness with seizures in severe patients. Nine patients (90%) showed lateral ventricle dilatation or intracranial infectious lesions on brain CT. Cerebrospinal fluid findings included elevated intracranial pressure, increased leukocyte count, low glucose, low chloride and high cerebrospinal fluid protein. The median CD4+ T count of patients was 104 cells/µL (IQR, 36-224 cells/µL) at the onset of the disease. The CD4+ T cell counts of three patients who eventually died were significantly lower (W = 6.00, p = 0.020) than those of the patients who survived. CONCLUSIONS: The common clinical symptoms of T. marneffei central nervous system infection are associated with high intracranial pressure and intracranial infectious lesions. Earlier recognition and diagnosis and a prolonged course of amphotericin B treatment followed by itraconazole combined with early ART might reduce the mortality rate.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções do Sistema Nervoso Central/microbiologia , Infecções por HIV/complicações , Micoses/líquido cefalorraquidiano , Micoses/virologia , Talaromyces/patogenicidade , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Antifúngicos/uso terapêutico , Infecções do Sistema Nervoso Central/etiologia , China/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/epidemiologia , Estudos Retrospectivos
11.
Biol Trace Elem Res ; 193(1): 234-240, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30805876

RESUMO

Cadmium (Cd), as one of the most toxic heavy metals, has become a widespread environmental contaminant and threats the food quality and safety. The protective effect of selenium (Se) on Cd-induced tissue lesion and cytotoxicity in chicken has been extensively reported. The objective of this study was to investigate the antagonistic effect of Se on Cd-induced damage of chicken pectoral muscles via analyzing the trace elements and amino acids profiles. Firstly, 19 trace elements contents were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that under Cd exposure, the contents of Cd, lead (Pb), mercury (Hg), aluminum (Al), and lithium (Li) were significantly elevated, and the contents of Se, iron (Fe), and chromium (Cr) were significantly reduced. However, supplementing Se significantly reversed the effects induced by Cd. Secondly, the amino acids contents were detected by L-8900 automatic amino acid analyzer. The results showed that supplementing Se increased significantly Cd-induced decrease of valine (Val), leucine (Leu), arginine (Arg), and proline (Pro). Thirdly, the results of principal component analysis (PCA) showed that cobalt (Co), manganese (Mn), silicium (Si), and Pro may play special roles in response to the process of Se antagonizes Cd-induced damage of pectoral muscles in chickens. In summary, these results indicated that different trace elements and amino acids possessed and exhibited distinct responses to suffer from Se and/or Cd in chicken pectoral muscles. Notably, Se alleviated Cd-induced adverse effects by regulating trace elements and amino acids profiles in chicken pectoral muscles.


Assuntos
Aminoácidos/metabolismo , Cádmio/toxicidade , Músculos Peitorais/metabolismo , Selênio/fisiologia , Oligoelementos/metabolismo , Animais , Galinhas , Músculos Peitorais/patologia
12.
Eur J Clin Nutr ; 74(2): 220-230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31712769

RESUMO

Postoperative malnutrition is a major issue among gastrointestinal cancer patients. Because n-3 polyunsaturated fatty acids (n-3 PUFAs) have immunological benefits, n-3 PUFAs are widely used in oral nutritional supplements (ONS). However, n-3 PUFAs in ONS reduced patients' compliance with ONS and affected the role of ONS in maintaining the postoperative nutritional status of patients. The aim of this study was to systematically explore the benefits of enteral nutrition rich in n-3 PUFAs in maintaining the nutritional status of patients after gastrointestinal surgery. Databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP databases were searched through March 16, 2019. The references of related reviews and studies were assessed up to March 16, 2019. The effect sizes from individual studies were calculated as the standardized mean difference (SMD), mean difference (MD), and risk ratio (RR) with 95% confidence intervals (95% CIs). A total of 11 studies (n = 977) were included. In this systematic review and meta-analysis, we observed that enteral supplementation of n-3 PUFAs had no significant effect on weight (MD, 1.09; 95% CI, -0.90, 3.08), body mass index (MD, 0.55; 95% CI, -1.45, 2.54), albumin (SMD, 0.39; 95% CI, -0.10, 0.87), wound infections (RR, 0.87, 95% CI, 0.57, 1.33), or pneumonia (RR, 0.98; 95% CI, 0.60, 1.59) in gastrointestinal cancer patients. Thus, compared with enteral nutritional without n-3 PUFAs, enteral nutritional rich in n-3 PUFAs has no significant effects on nutritional status, incidence of pneumonia, or wound infections among gastrointestinal cancer patients during postoperative convalescence.


Assuntos
Ácidos Graxos Ômega-3 , Neoplasias Gastrointestinais , China , Nutrição Enteral , Neoplasias Gastrointestinais/terapia , Humanos , Estado Nutricional
13.
Brain Behav Immun ; 82: 264-278, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31476414

RESUMO

Isorhynchophylline (IRN) has been demonstrated to have distinct anti-Alzheimer's disease (AD) activity in several animal models of AD. In this study, we aimed at evaluating the preventive effect of IRN on the cognitive deficits and amyloid pathology in TgCRND8 mice. Male TgCRND8 mice were administered with IRN (20 or 40 mg/kg) by oral gavage daily for 4 months, followed by assessing the spatial learning and memory functions with the Radial Arm Maze (RAM) test. Brain tissues were determined immunohistochemically or biochemically for changes in amyloid pathology, tau hyperphosphorylation and neuroinflammation. Our results revealed that IRN (40 mg/kg) significantly ameliorated cognitive deficits in TgCRND8 mice. In addition, IRN (40 mg/kg) markedly reduced the levels of Aß40, Aß42 and tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and IL-1ß, and modulated the amyloid precursor protein (APP) processing and phosphorylation by altering the protein expressions of ß-site APP cleaving enzyme-1 (BACE-1), phosphorylated APP (Thr668), presenilin-1 (PS-1) and anterior pharynx-defective-1 (APH-1), as well as insulin degrading enzyme (IDE), a major Aß-degrading enzyme. IRN was also found to inhibit the phosphorylation of tau at the sites of Thr205 and Ser396. Immunofluorescence showed that IRN reduced the Aß deposition, and suppressed the activation of microglia (Iba-1) and astrocytes (GFAP) in the cerebral cortex and hippocampus of TgCRND8 mice. Furthermore, IRN was able to attenuate the ratios of p-c-Jun/c-Jun and p-JNK/JNK in the brains of TgCRND8 mice. IRN also showed marked inhibitory effect on JNK signaling pathway in the Aß-treated rat primary hippocampus neurons. We conclude that IRN improves cognitive impairment in TgCRND8 transgenic mice via reducing Aß generation and deposition, tau hyperphosphorylation and neuroinflammation through inhibiting the activation of JNK signaling pathway, and has good potential for further development into pharmacological treatment for AD.


Assuntos
Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/tratamento farmacológico , Oxindóis/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neuroimunomodulação/fisiologia , Presenilina-1/metabolismo , Proteínas tau/metabolismo
14.
FASEB J ; 33(9): 10393-10408, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31233346

RESUMO

Isorhynchophylline (IRN), an oxindole alkaloid isolated from Uncaria rhynchophylla, elicited distinct antidepressant-like activity in mice. The present study aimed to investigate the antidepressant-like effects of IRN in chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors in mice and to illustrate its possible mechanisms of action. The mice were subjected to CUMS for 6 wk and administered with IRN (20 or 40 mg/kg) daily by oral gavage for 3 wk. The PI3K/protein kinase B (Akt) inhibitor and glycogen synthase kinase-3ß (GSK-3ß) inhibitors were used to determine the involvement of the PI3K/Akt/GSK-3ß pathway in the antidepressant-like effects of IRN in the mice. The results showed that CUMS caused depression-like behaviors in the mice, such as behavioral despair by the forced swim test (FST) and anhedonia by the sucrose preference test. In addition, CUMS could significantly reduce the levels of nerve growth factor and brain-derived neurotrophic factor but markedly increase the release of TNF-α and IL-6 in the hippocampus and cerebral cortex of the mice. Western blotting analysis showed that CUMS markedly suppressed the levels of phosphorylated GSK-3ß (Ser9) and phosphorylated Akt (Ser473) but significantly enhanced the translocation of NF-κB p65 from cytosol to nuclei in the hippocampus and cerebral cortex of the mice. CUMS could also significantly increase the NF-κB binding activity in the hippocampus and cerebral cortex of the mice, whereas IRN treatment could significantly reverse the behavioral and biochemical changes induced by CUMS in the mice. Moreover, the antidepressant-like effect of IRN was completely abolished by the PI3K/Akt inhibitor. Combination treatment with IRN and GSK-3ß inhibitors in the mice exerted a synergistic anti-immobility action in the FST. The results of mechanistic investigations indicated that the antidepressant-like action of IRN was mediated, at least in part, by enhancing neurotrophins and attenuating neuroinflammation via modulating the PI3K/Akt/GSK-3ß pathway.-Xian, Y.-F., Ip, S.-P., Li, H.-Q., Qu, C., Su, Z.-R., Chen, J.-N., Lin, Z.-X. Isorhynchophylline exerts antidepressant-like effects in mice via modulating neuroinflammation and neurotrophins: involvement of the PI3K/Akt/GSK-3ß signaling pathway.


Assuntos
Depressão/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Inflamação/tratamento farmacológico , Oxindóis/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antidepressivos/farmacologia , Depressão/imunologia , Depressão/metabolismo , Depressão/patologia , Glicogênio Sintase Quinase 3 beta/genética , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Estresse Psicológico
15.
Environ Sci Pollut Res Int ; 26(23): 23453-23459, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201704

RESUMO

Cadmium (Cd) as a widespread toxic heavy metal accumulates in animal food including chicken meat through food chain enrichment and finally threatens human health. Selenium (Se) is an essential mineral and possesses antagonistic effects on Cd-induced multiple organs' toxicity in chickens. The objective of the present study was to reveal the antagonistic mechanisms of Se to Cd from the aspects of oxidative stress, inflammation, and meat quality in chicken breast muscles. Firstly, the results showed that Cd significantly elevated the levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and protein carbonyl, and declined the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) to trigger oxidative stress in chicken breast muscles. However, Se treatment significantly alleviated Cd-induced oxidative stress by increasing the levels of GSH-Px, SOD, and CAT, and decreasing the levels of MDA, H2O2, and protein carbonyl. Secondly, Se obviously inhibited the expressions of Cd-activated inflammation-related genes including tumor necrosis factor (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (COX-2), and prostaglandin E synthase (PTGEs) in chicken breast muscles. Thirdly, meat quality-related parameters including pH45min, ultimate pH (pHu), and drip loss were also detected, and the results showed that Se markedly recovered Cd-induced dropt of pH45min and increase of drip loss in chicken breast muscles. In brief, these findings demonstrated that Se significantly alleviated Cd-induced oxidative stress and inflammation, and declined meat quality of chicken breast muscles.


Assuntos
Antioxidantes/metabolismo , Cádmio/toxicidade , Galinhas/fisiologia , Poluentes Ambientais/toxicidade , Carne/análise , Selênio/metabolismo , Animais , Cádmio/metabolismo , Catalase/metabolismo , Galinhas/metabolismo , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Inflamação , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
16.
Biomed Res Int ; 2019: 2682657, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31950036

RESUMO

Aim. To compare the effects of once-weekly Dulaglutide with once-daily glargine in poorly oral-antidiabetic controlled patients with type 2 diabetes mellitus (T2DM). Method. A total of 25 patients with T2DM admitted into Department of Endocrinology from December 2012 to August 2013 were randomly assigned into two groups: Dulaglutide group (n = 16) and glargine group (n = 9). All patients received either Dulaglutide or glargine treatments for 52 weeks. Continuous glucose monitoring systems (CGMS) were applied to them for two 72 h periods at before and after the treatment each. Patient general clinical data were collected and analyzed. Result. Fast blood glucose (FBG) of the glargine group declined more significantly than the Dulaglutide group after treatment (p < 0.05). The mean blood glucose (MBG), standard deviation of blood glucose (SDBG), mean amplitude of glycemic excursion (MAGE) within a day, the largest amplitude of glycemic excursion (LAGE), M-value, absolute means of daily difference (MODD) of glycemic excursion, the percentage of time (≤2.8 mmol/L, ≤3.9 mmol/L, ≥10.0 mmol/L, ≥13.9 mmol/L, 3.9-7.8 mmol/L, and 9-10.0 mmol/L), maximum glycemic value, and minimum glycemic value were similar between the two groups (p > 0.05). The incidence of hypoglycemia was also similar between the two groups (p > 0.05). Though serum levels of TNF-α, IL-6, and 8-PGF2α all decreased, significant reduction was found in TNF-α and 8-PGF2α. TNF-α was only significantly reduced in the Dulaglutide group, while 8-PGF2α was seen in both groups. Conclusion. For T2DM patients with poorly controlled oral antidiabetic drugs, once-weekly Dulaglutide not only has the same effect on glucose fluctuation as once-daily glargine but also significantly reduced TNF-α and 8-PGF2α after a 52 week treatment protocol. This trial is registered with ClinicalTrials.gov NCT01648582.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemia/tratamento farmacológico , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Insulina Glargina/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Dinoprosta/genética , Quimioterapia Combinada/efeitos adversos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Glucose/metabolismo , Hemoglobina A Glicada/genética , Humanos , Hipoglicemia/genética , Hipoglicemia/patologia , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Insulina Glargina/efeitos adversos , Interleucina-6/genética , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/efeitos adversos , Fator de Necrose Tumoral alfa/genética
17.
Arch. endocrinol. metab. (Online) ; 62(6): 585-590, Dec. 2018. tab
Artigo em Inglês | LILACS | ID: biblio-983810

RESUMO

ABSTRACT Objective: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). Subjects and methods: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. Results: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. Conclusion: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Valores de Referência , Glicemia/metabolismo , Peptídeo C/sangue , Glucagon/sangue , Automonitorização da Glicemia/métodos , Estudos de Casos e Controles , Estudos Retrospectivos , Estatísticas não Paramétricas , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina/sangue
18.
Chin Med ; 13: 29, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29946349

RESUMO

Background: To evaluate the effect of Isorhynchophylline (IRN) on the learning and memory impairments induced by aluminum chloride (AlCl3) in mice. Methods: Fifty male Balb-c mice (4-month-old) were randomly divided into five groups: control, AlCl3 plus vehicle, AlCl3 plus IRN (20 mg/kg), AlCl3 plus IRN (40 mg/kg) and AlCl3 plus donepezil (5 mg/kg). Learning and memory impairments were induced in mice by subcutaneously injecting with AlCl3 (50 mg/kg) once a day for 8 consecutive weeks. At the same time, mice were intragastrically given vehicle or IRN (20 and 40 mg/kg) or donepezil (5 mg/kg) 30 min before each AlCl3 injection. The spatial learning and memory function was assessed using radial arm maze. After sacrificed, the parameters of oxidative stress and cholinergic system in the brain tissues were examined with ELISA kits. Moreover, the expression of nuclear factor kappa B (NF-κB) signaling pathway was analyzed with western blotting. Results: The results showed that treatment with IRN could significantly ameliorate the cognitive deficits induced by AlCl3 in mice. In addition, treatment with IRN was found to reduce the level of malondialdehyde, enhance the activities of superoxide dismutases and catalase, increase the level of glutathione, and markedly inhibit the activity of acetylcholinesterase (AChE) in the brain tissues of the AlCl3-treated mice. Moreover, IRN significantly suppressed the phosphorylation of NF-κB p65 and IκBα in the brain tissues of AlCl3-treated mice. However, IRN did not show significant effect on the activity of butyrylcholinesterase. Conclusion: Our findings demonstrated for the first time that IRN could alleviate learning and memory impairments induced by AlCl3 in mice. The neuroprotective effect of IRN against AlCl3-induced AD is probably mediated, at least in part, through inhibiting the AChE activity and reducing the oxidative damage of brain tissue via suppress the NF-κB signaling pathway. These results contributed to a better understanding of the in vivo anti-AD mechanism of IRN. It was concluded that IRN could protect the learning and memory function.

19.
Diabetes Res Clin Pract ; 141: 98-105, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29730390

RESUMO

AIMS: Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). METHODS: A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUC0-60 min). RESULTS: The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC0-60 min (standardized ß = -0.386, P < 0.001) and incremental AUC of blood glucose ≤ 4.4 mmol/L (standardized ß = -0.078, P = 0.034), and was significantly higher in effective group than in ineffective group (P < 0.001). The Δglucose AUC0-60 min during post-dinner was significantly higher than that during pre-lunch, post-lunch and pre-dinner (P < 0.05 for all). CONCLUSIONS: PEBG is positively correlated with efficacy of aerobic exercise. Aerobic exercise will not worsen hyperglycemia when the PEBG > 16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. CLINICAL TRIALS REGISTRATION: ChiCTR-ONC-17010400, www.chictr.org.cn.


Assuntos
Automonitorização da Glicemia/métodos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Exercício Físico/fisiologia , Infusões Subcutâneas/métodos , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Arch Endocrinol Metab ; 62(6): 585-590, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30624497

RESUMO

OBJECTIVE: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). SUBJECTS AND METHODS: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. RESULTS: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. CONCLUSION: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Adulto , Glicemia/metabolismo , Automonitorização da Glicemia/métodos , Peptídeo C/sangue , Estudos de Casos e Controles , Feminino , Glucagon/sangue , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Estatísticas não Paramétricas
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