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1.
Top Stroke Rehabil ; : 1-15, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39024192

RESUMEN

OBJECTIVE: The prognosis of stroke patients is greatly threatened by malnutrition. However, there is no model to predict the risk of malnutrition in hospitalized stroke patients. This study developed a predictive model for identifying high-risk malnutrition in stroke patients. METHODS: Stroke patients from two tertiary hospitals were selected as the objects. Binary logistic regression was used to build the model. The model's performance was evaluated using various metrics including the receiver operating characteristic curve, Hosmer-Lemeshow test, sensitivity, specificity, Youden index, clinical decision curve, and risk stratification. RESULTS: A total of 319 stroke patients were included in the study. Among them, 27% experienced malnutrition while in the hospital. The prediction model included all independent variables, including dysphagia, pneumonia, enteral nutrition, Barthel Index, upper arm circumference, and calf circumference (all p < 0.05). The AUC area in the modeling group was 0.885, while in the verification group, it was 0.797. The prediction model produces greater net clinical benefit when the risk threshold probability is between 0% and 80%, as revealed by the clinical decision curve. All p values of the Hosmer test were > 0.05. The optimal cutoff value for the model was 0.269, with a sensitivity of 0.849 and a specificity of 0.804. After risk stratification, the MRS scores and malnutrition incidences increased significantly with escalating risk levels (p < 0.05) in both modeling and validation groups. CONCLUSIONS: This study developed a prediction model for malnutrition in stroke patients. It has been proven that the model has good differentiation and calibration.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38982693

RESUMEN

INTRODUCTION: Icotinib and almonertinib are efficacious for non-small cell lung cancer (NSCLC) factor patients with epidermal growth receptor (EGFR)-mutation. Patients who previously used EGFR tyrosine kinase inhibitor (EGFR TKI) may switch to another one due to the adverse events. CASE PRESENTATION: Here, we report a case of a 73-year-old male patient with advanced lung adenocarcinoma in which an EGFR (exon 21 L858R substitution) was found. Icotinib (125mg three times daily) was administered initially. He achieved partial response two months later but developed acute interstitial lung disease (grade 2) with dry cough and chest tightness five months later. Icotinib was discontinued, and treatment with methylprednisolone improved the interstitial lung disease. Chemotherapy with pemetrexed, carboplatin, and bevacizumab was initiated as subsequent therapy. Considering the effectiveness of EGFR-TKIs, we decided cautiously to rechallenge the third-generation TKI almonertinib administration. The patient successfully received almonertinib for almost one year without the recurrence of interstitial lung disease and tumor progression. ILD was an infrequent but often life-threatening reaction associated with icotinib. CONCLUSION: This is the first reported case of successful switching from icotinib to another EGFR TKI because of interstitial lung disease associated with icotinib, suggesting that EGFR-TKIs rechallenge because of adverse events rather than progression might provide a significant benefit in patients with EGFR driver positive NSCLC.

3.
J Colloid Interface Sci ; 675: 535-548, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38986327

RESUMEN

Tubular Co9S8/CdS heterostructures have been successfully synthesized by in-situ growing CdS onto Co9S8 nanotubes through a simultaneous immobilization and in-situ reduction strategy. It turned out that the so-obtained heterostructure with Co9S8/CdS molar ratio of 1/10 can display a broad light absorption edge and especially much enhanced capacity for photocatalytic reduction of Cr(VI) under visible light. The characterization analysis and experimental results suggested that an interfacial electrostatic field between Co9S8 and CdS elements in the heterostructure could be constructed due to their different Fermi levels, allowing for more quantities of highly reductive electrons to participate in the photocatalytic reaction. Therefore, the so-obtained Co9S8/CdS (1/10) heterostructures could achieve the photocatalytic reduction efficiency of 100% within 20 min, which was more than two and four times larger than that of pristine CdS and Co9S8, respectively. Moreover, the possible photocatalytic reaction mechanism for reducing Cr(VI) was investigated and found to follow the direct Z-scheme charge transfer pathway. This novel fabrication route for composite photocatalysts with tubular heterostructures could lead to the widespread implementations for the elimination of various harmful pollutants in the process of environmental governance.

4.
Front Cardiovasc Med ; 11: 1360548, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011494

RESUMEN

Objective: This study focuses on the innovative application of Automated Machine Learning (AutoML) technology in cardiovascular medicine to construct an explainable Coronary Artery Disease (CAD) prediction model to support the clinical diagnosis of CAD. Methods: This study utilizes a combined data set of five public data sets related to CAD. An ensemble model is constructed using the AutoML open-source framework AutoGluon to evaluate the feasibility of AutoML in constructing a disease prediction model in cardiovascular medicine. The performance of the ensemble model is compared against individual baseline models. Finally, the disease prediction ensemble model is explained using SHapley Additive exPlanations (SHAP). Results: The experimental results show that the AutoGluon-based ensemble model performs better than the individual baseline models in predicting CAD. It achieved an accuracy of 0.9167 and an AUC of 0.9562 in 4-fold cross-bagging. SHAP measures the importance of each feature to the prediction of the model and explains the prediction results of the model. Conclusion: This study demonstrates the feasibility and efficacy of AutoML technology in cardiovascular medicine and highlights its potential in disease prediction. AutoML reduces the barriers to model building and significantly improves prediction accuracy. Additionally, the integration of SHAP enhances model transparency and explainability, which is critical to ensuring model credibility and widespread adoption in cardiovascular medicine.

5.
J Appl Toxicol ; 44(8): 1246-1256, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38666302

RESUMEN

Voacangine, a naturally occurring alkaloid, has been testified to display beneficial effects on a variety of human diseases, but its role in ischemic stroke is unclear. The impacts of voacangine on oxygen-glucose deprivation/reoxygenation (OGD/R)-tempted hippocampal neuronal cells are investigated. The bioinformatics analysis found that voacangine is a bioactive ingredient that may have good effects on ischemic stroke. KEGG pathways analysis found that voacangine may regulate ischemic stroke through modulating the PI3K-Akt-FoxO signaling pathway. Voacangine could mitigate OGD/R-tempted cytotoxicity in HT22 cells. Voacangine mitigated OGD/R-tempted oxidative stress in HT22 cells by diminishing reactive oxygen species level and enhancing superoxide dismutase level. Voacangine mitigated OGD/R-tempted ferroptosis in HT22 cells. Voacangine promoted activation of the PI3K-Akt-FoxO signaling in OGD/R-induced HT22 cells. Inactivation of the PI3K-Akt-FoxO signaling pathway reversed the protective effects of voacangine against OGD/R-tempted oxidative stress, cytotoxicity, and ferroptosis in HT22 cells. In conclusion, voacangine protects hippocampal neuronal cells against OGD/R-caused oxidative stress and ferroptosis by activating the PI3K-Akt-FoxO signaling.


Asunto(s)
Ferroptosis , Glucosa , Hipocampo , Neuronas , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Estrés Oxidativo/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Glucosa/metabolismo , Glucosa/toxicidad , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , Oxígeno/metabolismo , Fármacos Neuroprotectores/farmacología , Línea Celular , Especies Reactivas de Oxígeno/metabolismo
6.
Tuberculosis (Edinb) ; 145: 102480, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38278100

RESUMEN

Tuberculosis (TB) today remains the leading cause of global deaths due to infectious bacterial pathogens. The Bacillus Calmette-Guérin (BCG) vaccine is the only vaccine clinically used to prevent TB. However, its limitations in preventing latent infection and TB reactivation mean that it does not provide comprehensive protection. In this study, we successfully constructed and expressed the multistage fusion protein, SHR3, and used whole blood IFN-γ release assay (WBIA) with flow cytometry to detect antigen specificity, further confirmed by enzyme-linked immunosorbent assay (ELISA). SHR3 and its subfractional proteins stimulated the level of IFN-γ production by lymphocytes from M. tb-infected patients, inducing the production of single-positive and double-positive CD4+ and CD8+ T cells with IFN-γ and IL-2, at levels significantly higher than those of healthy controls. The fusion protein and complex adjuvant group (SHR3/DMT) induced mice to produce significantly higher levels of IgG antibodies and their subclasses, with IgG2a/IgG1 results showing a convergent Th1-type response; mice in the BCG + SHR3/DMT group induced secretion of the highest levels of IL-2, and TNF-α, irrespective of stimulation with purified protein derivative or SHR3. These findings suggest that SHR3/DMT could be a potential subunit vaccine candidate that may serve as an effective booster vaccine after BCG primary immunization.


Asunto(s)
Mycobacterium tuberculosis , Vacunas contra la Tuberculosis , Tuberculosis , Humanos , Animales , Ratones , Vacuna BCG , Linfocitos T CD8-positivos , Interleucina-2/metabolismo , Antígenos Bacterianos/genética , Tuberculosis/prevención & control , Adyuvantes Inmunológicos , Proteínas Bacterianas/genética
7.
Lancet Respir Med ; 12(3): 217-224, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38101437

RESUMEN

BACKGROUND: Sunvozertinib is an oral, irreversible, and selective tyrosine kinase inhibitor that has a favourable safety profile and encouraging antitumour activity, as shown in phase 1 studies of patients with heavily pretreated non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation (exon20ins). We aimed to assess the antitumour efficacy of sunvozertinib in patients with platinum-pretreated locally advanced or metastatic NSCLC with EGFR exon20ins. METHODS: WU-KONG6 is a single-group, open-label, multicentre phase 2 trial of sunvozertinib monotherapy, conducted across 37 medical centres in China. We enrolled adult patients with pathologically or cytologically confirmed locally advanced or metastatic NSCLC whose tumour tissue carried an EGFR exon20ins mutation. All patients had received at least one line of previous systemic therapy, with at least one line containing platinum-based chemotherapy. The primary endpoint was objective response rate (ORR), as assessed by the independent review committee. The ORR was defined as the percentage of patients who achieved complete or partial response, confirmed by two separate assessments with at least 4-week time interval, until disease progression or initiation of any new anti-cancer therapy. Enrolled patients received sunvozertinib 300 mg once daily until meeting discontinuation criteria per the protocol. Patients who received at least one dose of treatment and were evaluable for efficacy analysis were included in the primary analysis, and all patients who received at least one dose of treatment were included in the safety analysis. This study is registered with ChinaDrugTrials.org, CTR20211009, and ClinicalTrials.gov, NCT05712902, and efficacy and safety follow-up are ongoing. FINDINGS: Between July 19, 2021, and May 6, 2022, 104 patients were enrolled. At data cutoff (Oct 17, 2022), the last enrolled patient had been followed up for about 6 months. Among 97 patients evaluable for efficacy analysis, 59 (61%) patients achieved tumour response, with a confirmed ORR of 61% (95% CI 50-71). All tumour responses were partial responses. Tumour responses were observed irrespective of age, sex, smoking history, EGFR exon20ins subtypes, brain metastasis at baseline, previous lines of therapy, and history of onco-immunotherapy. In total, 19 death events occurred over a median follow-up period of 7·6 months (IQR 6·1-9·4). Sunvozertinib was well tolerated at 300 mg once daily. The most common grade 3 or worse treatment-related adverse events were blood creatine phosphokinase increased (18 [17%] of 104), diarrhoea (eight [8%]), and anaemia (six [6%]). The most common serious treatment-related adverse events were interstitial lung disease (five [5%] of 104), anaemia (three [3%]), vomiting (two [2%]), nausea (two [2%]) and pneumonia (two [2%]). INTERPRETATION: In this phase 2 study, sunvozertinib demonstrated antitumour efficacy in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins, with a manageable safety profile. A multinational randomised, phase 3 study of sunvozertinib versus platinum-doublet chemotherapy in EGFR exon20ins NSCLC is ongoing (NCT05668988). FUNDING: Dizal Pharmaceutical.


Asunto(s)
Anemia , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Mutagénesis Insercional , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , China , Receptores ErbB/genética , Exones/genética
8.
J Clin Med ; 12(7)2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-37048653

RESUMEN

OBJECTIVE: The aim was to study the imaging characteristics of the temporomandibular joint (TMJ) of definite sleep bruxers through magnetic resonance imaging (MRI) and cone-beam computer tomography (CBCT). METHODS: Nineteen definite sleep bruxers diagnosed by polysomnography and twenty asymptomatic non-bruxers matched by age, gender, and education level participated in this study. After obtaining MRI and CBCT images of all TMJs of the subjects, evaluation and measurement were conducted, respectively. The analyzed parameters included disc position, disc configuration, joint effusion (JE), joint space or condyle position, and condylar bony changes. RESULTS: Of the 38 joints in the study group, disc deformity and disc displacement of TMJs were both 57.9% when the mouth was closed, and 76.3% showed condylar bony changes, while when the mouth was open, 82% of all TMJs showed physiological biconcave discs. Comparison of joint space revealed that the anterior space was larger in the study group. There was no significant difference between the mild and the moderate to severe sleep bruxism subgroups in the changes of TMJ. CONCLUSION: The results demonstrated that a higher prevalence of disc deformity, disc displacement, JE, and condylar bony changes occurred in temporomandibular joints of sleep bruxers. These changes were not related to the severity of sleep bruxism.

9.
Oral Dis ; 29(3): 1060-1069, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34716969

RESUMEN

OBJECTIVE: To investigate the mechanism of and potential contributing factors to temporomandibular joint osteoarthritis (TMJOA) caused by oestrogen deficiency with a persistent high bite force. MATERIALS AND METHODS: A TMJOA model was generated by subjecting 6-week-old female rats to ovariectomy (OVX) and feeding them a hard feed. The rats (n = 12/group) were divided into sham (control); OVX; OVX+hard feed (HF); OVX+hard feed+local-joint injection of 17ß-oestradiol (an oestrogen) (E2); and OVX+hard feed+local-joint injection of rapamycin (an autophagy activator) (RAPA)groups. Condyles were stained with haematoxylin-eosin and Safranin O Fast Green. The expression of Beclin 1, LC3 and p-mTOR in condylar cartilages was analysed. RESULTS: Tissue staining revealed thinner condylar cartilage, varying numbers or fewer hypertrophic chondrocytes, and lower proteoglycan content in the cartilage matrix of the OVX group. These characteristics were more pronounced in the HF group, but were significantly recovered in the E2 and RAPA groups. Immunohistochemical staining revealed significantly lower autophagic flux in OVX/HF groups and a higher one in E2/RAPA groups. CONCLUSIONS: A persistent high bite force could aggravate TMJOA induced by oestrogen deficiency, and the application of oestrogen or rapamycin could delay its progression. Additionally, autophagy may play a role in the development of TMJOA.


Asunto(s)
Cartílago Articular , Osteoartritis , Ratas , Femenino , Animales , Cartílago Articular/metabolismo , Articulación Temporomandibular , Osteoartritis/inducido químicamente , Condrocitos/metabolismo , Estrógenos/metabolismo
10.
J Coll Physicians Surg Pak ; 31(10): 1224-1227, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34601846

RESUMEN

OBJECTIVE: To investigate the correlation between intestinal flora and serum inflammatory factors IL-1, IL-2, IL-6 and hs-CRP in post-stroke depression (PSD) in ischemic stroke patients. STUDY DESIGN: Observational study. Study Place and Duration of Study: Jiulongpo District Hospital of Traditional Chinese Medicine, Chongqing City, China, from October 2018 to May 2020. METHODOLOGY: One hundred and sixty-three patients with ischemic stroke were divided into Group A (PSD) and Group B (no PSD), according to whether they had PSD. Intestinal flora indexes (Enterococcus faecalis, Escherichia coli and Bifidobacterium) and serum IL-1, IL-2, IL-6 and hs-CRP were detected. RESULTS: Among 163 patients with ischemic stroke, 67 (41.10%) had PSD (Group A) and 96 (58.90%) had no PSD (Group B). Contents of Enterococcus faecalis and Escherichia coli in Group A were higher than those in Group B (both p <0.001), and content of Bifidobacterium in Group A was lower than that in Group B (p <0.001). Serum IL-1, IL-2, IL-6 and hs-CRP levels in Group A were higher than those in Group B (all p <0.001). Pearson correlation test showed that contents of Enterococcus faecalis and Escherichia coli in Group A were positively correlated with IL-1, IL-2, IL-6 and hs-CRP, and content of Bifidobacterium was negatively correlated with IL-1, IL-2, IL-6 and hs-CRP. CONCLUSION: There are intestinal flora imbalance and Bifidobacterium undergrowth in patients with PSD, which can lead to overexpression of serum inflammatory factors. Both may be involved in occurrence and progress of PSD in patients with ischemic stroke. Key Words: Ischemic stroke, Post-stroke depression (PSD), Intestinal flora, Inflammatory factors.


Asunto(s)
Isquemia Encefálica , Microbioma Gastrointestinal , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Depresión/epidemiología , Depresión/etiología , Humanos , Accidente Cerebrovascular/complicaciones
11.
World J Clin Cases ; 9(10): 2268-2273, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33869602

RESUMEN

BACKGROUND: Mechanical thrombectomy (MT) has been demonstrated to be useful for the treatment of ischemic stroke in patients with large vessel occlusions. However, recanalization by MT is not recommended for distal vessels such as second-order branches of the middle cerebral artery and posterior inferior cerebellar artery (PICA). Because of the small size and tortuosity of these arteries, the risks of using the available endovascular devices outweigh the benefits of treatment. However, MT appears to be effective in patients with primary distal vessel occlusion in eloquent areas, those with a high National Institutes of Health Stroke Scale score, and those ineligible for recombinant tissue plasminogen activator therapy. Here, we report the use of MT for treating acute occlusion of the PICA using a direct-aspiration first-pass technique (ADAPT). CASE SUMMARY: In this case, the patient received acute occlusion of the PICA with ADAPT when right internal carotid artery stenting was performed. CONCLUSION: With the introduction of advanced endovascular devices, MT may now be a feasible treatment for acute occlusion of the PICA.

12.
Neurol Sci ; 42(12): 5425-5431, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33904005

RESUMEN

BACKGROUND: Hemiplegic migraine (HM) is a rare type of migraine with aura. Some reports have described the clinical manifestations in HM patients with the ATP1A2 mutation. But the impact of the ATP1A2 mutation on cognitive profile in HM patients has not been evaluated in detail. Here we report a patient with cognitive dysfunction in specific area. CASE PRESENTATION: A 15-year-old boy with an aura that included disturbances in consciousness, associated with fever, vomiting, hemiplegia, and aphasia. He was diagnosed with HM with the ATP1A2 mutation before. He had trouble in mathematics and depicting three-dimensional things. CONCLUSIONS: The HM with ATP1A2 patient could develop permanent cognitive dysfunction. Therefore, the cognitive quotient should be carefully and comprehensively evaluated.


Asunto(s)
Disfunción Cognitiva , Trastornos Migrañosos , Migraña con Aura , Adolescente , Disfunción Cognitiva/genética , Hemiplejía/complicaciones , Hemiplejía/genética , Humanos , Masculino , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/genética , Migraña con Aura/complicaciones , Migraña con Aura/genética , Mutación
13.
Colloids Surf B Biointerfaces ; 199: 111560, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33429284

RESUMEN

Polymeric particles with non-spherical shape or coarse surface have distinct advantages for drug delivery, tissue regeneration and immunomodulation respectively, but it is not easy to control polymeric microparticles in required geometry and surface texture simultaneously. In this study, polymeric non-spherical microparticles with coarse surface were successfully prepared by double emulsion-solvent evaporation technique in the presence of ammonium bicarbonate and the formation mechanism was proposed. In addition, simvastatin was encapsulated in poly[lactic-co-(glycolic acid)] (PLGA) non-spherical microparticles with coarse surface by the same technique and the release kinetics in vitro was fitted as well, which not only enrich the encapsulation techniques of liposoluble drugs in polymeric non-spherical carriers but also envision the potential application for alveolar ridge preservation with local delivery of simvastatin.


Asunto(s)
Ácido Láctico , Ácido Poliglicólico , Portadores de Fármacos , Emulsiones , Microesferas , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Simvastatina , Solventes
14.
Blood Cancer Discov ; 1(1): 32-47, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32924016

RESUMEN

Therapy-related myeloid neoplasms (t-MNs) following treatment with alkylating agents are characterized by a del(5q), complex karyotypes, alterations of TP53, and a dismal prognosis. To decipher the molecular pathway(s) leading to the pathogenesis of del(5q) t-MN and the effect(s) of cytotoxic therapy on the marrow microenvironment, we developed a mouse model with loss of two key del(5q) genes, EGR1 and APC, in hematopoietic cells. We used the well-characterized drug, N-ethyl-N-nitrosurea (ENU) to demonstrate that alkylating agent exposure of stromal cells in the microenvironment increases the incidence of myeloid disease. In addition, loss of Trp53 with Egr1 and Apc was required to drive the development of a transplantable leukemia, and accompanied by the acquisition of somatic mutations in DNA damage response genes. ENU treatment of mesenchymal stromal cells induced cellular senescence, and led to the acquisition of a senescence-associated secretory phenotype, which may be a critical microenvironmental alteration in the pathogenesis of myeloid neoplasms.


Asunto(s)
Antineoplásicos Alquilantes , Médula Ósea , Leucemia Mieloide , Neoplasias Primarias Secundarias , Animales , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Deleción Cromosómica , Genes p53 , Leucemia Mieloide/inducido químicamente , Leucemia Mieloide/genética , Ratones , Neoplasias Primarias Secundarias/inducido químicamente , Neoplasias Primarias Secundarias/genética , Células del Estroma , Microambiente Tumoral/genética
15.
J Invertebr Pathol ; 173: 107366, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32224143

RESUMEN

Cytolytic (Cyt)-like genes are known by omics analyses to exist widely in bacterial and fungal pathogens, but their insecticidal activities in fungi remains unknown. A full-length coding sequence of a Cyt-like gene was first amplified from Conidiobolus obscurus (an obligate aphid-pathogenic fungus) through RACE (rapid-amplification of cDNA ends). The deduced protein structure was structurally characterized by a single Cyt-typical α/ß domain. The expression level of the Cyt-like gene in conidia correlated well with the fungal virulence against aphids (r2 = 0.97). The results demonstrate the Cyt-like gene acts as an important virulence factor of C. obscurus against aphids, and has potential for exploitation in aphid control.


Asunto(s)
Áfidos/microbiología , Conidiobolus/genética , Proteínas Fúngicas/genética , Genes Fúngicos , Secuencia de Aminoácidos , Animales , Áfidos/crecimiento & desarrollo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Ninfa/microbiología , Control Biológico de Vectores
16.
Biomed Pharmacother ; 112: 108668, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30784937

RESUMEN

Natural compounds are important resources for drug discovery. Using Caenorhabditis elegans (C. elegans) models, we screened active natural compounds with lipid lowering effects. Swertiamarin was found as a potent candidate to reduce lipid content in C. elegans. Using RNAi screening, we were able to demonstrate that kat-1 (ketoacyl thiolase-1) is necessary for the lipid lowering effect of swertiamarin. Furthermore, the activity of swertiamarin was verified in high fat diet induced obese mice. Consistent with the results in C. elegans, swertiamarin ameliorated high fat diet induced lipid deposition and hyperlipidemia. These results indicate that swertiamarin exerts lipid-lowering effects through kat-1 regulation and could serve as a possible therapeutic option to improve hyperlipidemia induced comorbidities.


Asunto(s)
Acetil-CoA C-Aciltransferasa/metabolismo , Glucósidos Iridoides/farmacología , Producto de la Acumulación de Lípidos/efectos de los fármacos , Obesidad/tratamiento farmacológico , Pironas/farmacología , Swertia , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans , Dieta Alta en Grasa/efectos adversos , Relación Dosis-Respuesta a Droga , Glucósidos Iridoides/uso terapéutico , Producto de la Acumulación de Lípidos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/sangre , Obesidad/inducido químicamente , Pironas/uso terapéutico
17.
Ann Transl Med ; 7(23): 756, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32042772

RESUMEN

BACKGROUND: To investigate the role and mechanism of catalpol on neuronal cell activity to promote axonal regeneration via PI3K/AKT/mTOR pathway after stroke. METHODS: In vivo the effect of catalpol (2.5, 5, 7.5 mg/kg; i.p) or vehicle administered 24 h after stroke and then daily for 7 days on behavior, Map-2+/p-S6+ and Map-2+/GAP-43+ immunofluorescence were assessed in a rat model of stroke. Then in vitro, an oxygen-glucose deprivation (OGD/R) model was established to observe the effect of catalpol (0.1, 1, 10 and 100 µg·mL-1) on cultural neurons survive rate, neuronal cell activity and axon growth. Moreover, rapamycin (Rapa) was used to inhibit the mTOR pathway to observe the catalpol mechanism on neuronal cell activity to promote axonal growth, and the proteins related with PI3K/AKT/mTOR pathway were detected by Western blot assay. RESULTS: Repeated treatments with catalpol improved neurological score and significantly enhanced neuronal cell activity, then promote axonal regeneration after stroke. While in vitro, catalpol also increased the survive rate and axonal growth of the neurons. Catalpol can reversed the Rapa inhibited effects on neurons' survive and axon extending. Catalpol can also reversed proteins reduced by Rapa related with PI3K/AKT/mTOR pathway. CONCLUSIONS: These results suggested that catalpol might contribute to internal neuronal cell activity and axonal regeneration by regulating PI3K/AKT/mTOR pathway.

18.
Pest Manag Sci ; 74(7): 1677-1686, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29337410

RESUMEN

BACKGROUND: Conidiobolus obscurus is a widespread fungal entomopathogen with aphid biocontrol potential. This study focused on a de novo transcriptomic analysis of C. obscurus. RESULTS: A number of pathogenicity-associated factors were annotated for the first time from the assembled 17 231 fungal unigenes, including those encoding subtilisin-like proteolytic enzymes (Pr1s), trypsin-like proteases, metalloproteases, carboxypeptidases and endochitinases. Many of these genes were transcriptionally up-regulated by at least twofold in mycotized cadavers compared with the in vitro fungal cultures. The resultant transcriptomic database was validated by the transcript levels of three selected pathogenicity-related genes quantified from different in vivo and in vitro material in real-time quantitative polymerase chain reaction (PCR). The involvement of multiple Pr1 proteases in the first stage of fungal infection was also suggested. Interestingly, a unique cytolytic (Cyt)-like δ-endotoxin gene was highly expressed in both mycotized cadavers and fungal cultures, and was more or less distinct from its homologues in bacteria and other fungi. CONCLUSION: Our findings provide the first global insight into various pathogenicity-related genes in this obligate aphid pathogen and may help to develop novel biocontrol strategy against aphid pests. © 2018 Society of Chemical Industry.


Asunto(s)
Áfidos/microbiología , Conidiobolus/fisiología , Proteínas Fúngicas/genética , Control Biológico de Vectores , Transcriptoma , Animales , Conidiobolus/patogenicidad , Proteínas Fúngicas/metabolismo , Interacciones Huésped-Patógeno , Control de Insectos , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
19.
Chemosphere ; 197: 241-250, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29353674

RESUMEN

A environment-friendly 3D inorganic heteropoly blue (HPB) Ba2Na2 [HPWV4WVI8O40]·26H2O was directly synthesized by hydrothermal method and characterized by means of ICP, IR, XPS, X-ray single crystal and X-ray powder diffraction. It was an efficient heterogeneous photo-Fenton-like catalyst to degrade anionic dye methyl orange under visible light irradiation. It removed cationic dyes methylene blue in neutral environment and rhodamine B in acidic condition via flocculation. The removal efficiency of methylene blue and rhodamine B by flocculation was more than 95%. Moreover, it could degrade methyl orange and flocculate rhodamine B at the same time. For MO and MO-RhB solutions, the degradation rates of MO in 60 min were 85.5% and 49.1%, respectively. Furthermore, the possible pathways for the production of active species in the MO degradation reaction were discussed. This is the first HPB constructed with 4e-reduced phosphotungstate, Ba and Na ions, having the properties of photo-Fenton-like catalyst and flocculant.


Asunto(s)
Compuestos Azo/química , Restauración y Remediación Ambiental/métodos , Peróxido de Hidrógeno/química , Hierro/química , Azul de Metileno/química , Rodaminas/química , Compuestos de Tungsteno/química , Contaminantes Químicos del Agua/química , Catálisis , Colorantes/química , Luz , Compuestos de Tungsteno/síntesis química , Contaminantes Químicos del Agua/análisis , Difracción de Rayos X
20.
Colloids Surf B Biointerfaces ; 158: 112-118, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28686902

RESUMEN

The surface physical features and chemical components of polymeric particles play an important role in drug delivery systems. In this study, PLGA blank microspheres and simvastatin-loaded PLGA microspheres with dimpled surface structure were prepared by single emulsion-solvent evaporation method in the absence of any additives. Subsequently, glutaraldehyde cross-linking was optimized for silk fibroin coating on simvastatin-loaded PLGA dimpled microspheres due to good solubility of simvastatin in alcohol. Furthermore, simvastatin release kinetics was investigated for silk-coated or plain PLGA dimpled microspheres. These drug carriers may have potential applications for alveolar ridge preservation with local delivery of simvastatin.


Asunto(s)
Microesferas , Ácido Poliglicólico/química , Simvastatina/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Fibroínas/química , Seda/química , Propiedades de Superficie
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