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1.
Front Immunol ; 15: 1331050, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605959

RESUMO

Background: The CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsis-associated ARDS. Methods: We prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients' peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection. Results: Of the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days. Conclusion: We identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS.


Assuntos
Neutrófilos , Síndrome do Desconforto Respiratório , Sepse , Adulto , Humanos , Síndrome do Desconforto Respiratório/etiologia , Sepse/complicações
2.
Cell Death Discov ; 9(1): 439, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049394

RESUMO

Toxoplasma gondii, a widespread obligate intracellular parasite, can infect almost all warm-blooded animals, including humans. The cellular barrier of the central nervous system (CNS) is generally able to protect the brain parenchyma from infectious damage. However, T. gondii typically causes latent brain infections in humans and other vertebrates. Here, we discuss how T. gondii rhoptry proteins (ROPs) affect signaling pathways in host cells and speculate how this might affect the outcome of Toxoplasma encephalitis.

3.
Front Robot AI ; 10: 1291199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38152305

RESUMO

Metaverse has been confirmed as a relatively amorphous concept of innovation, which refers to technological advancement. Metaverse, i.e., a coalition between reality world and virtual world, has created significant significance and convenience in education, communication, economy, etc. The COVID-19 outbreak has stimulated the growth of metaverse applications in medicine. The above-mentioned technology has broad applications while comprising online remote medical treatment, online conferences, medical education, preparation of surgical plans, etc. Moreover, technical, security, and financial challenges should be tackled down by the future widespread use of metaverse. Metaverse is limitlessly promising, and it will exert a certain effect on future scientific and technological advancements in the medical industry. The review article primarily aims to summarize the application of the metaverse in medicine and their challenge in the future of medicine.

4.
Mediators Inflamm ; 2022: 1878766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248192

RESUMO

The purpose of this study was to uncover potential diagnostic indicators of pulmonary arterial hypertension (PAH), evaluate the function of immune cells in the pathogenesis of the disease, and find innovative treatment targets and medicines with the potential to enhance prognosis. Gene Expression Omnibus was utilized to acquire the PAH datasets. We recognized differentially expressed genes (DEGs) and investigated their functions utilizing R software. Weighted gene coexpression network analysis, least absolute shrinkage and selection operators, and support vector machines were used to identify biomarkers. The extent of immune cell infiltration in the normal and PAH tissues was determined using CIBERSORT. Additionally, the association between diagnostic markers and immune cells was analyzed. In this study, 258DEGs were used to analyze the disease ontology. Most DEGs were linked with atherosclerosis, arteriosclerotic cardiovascular disease, and lung disease, including obstructive lung disease. Gene set enrichment analysis revealed that compared to normal samples, results from PAH patients were mostly associated with ECM-receptor interaction, arrhythmogenic right ventricular cardiomyopathy, the Wnt signaling pathway, and focal adhesion. FAM171B was identified as a biomarker for PAH (area under the curve = 0.873). The mechanism underlying PAH may be mediated by nave CD4 T cells, resting memory CD4 T cells, resting NK cells, monocytes, activated dendritic cells, resting mast cells, and neutrophils, according to an investigation of immune cell infiltration. FAM171B expression was also associated with resting mast cells, monocytes, and CD8 T cells. The results suggest that PAH may be closely related to FAM171B with high diagnostic performance and associated with immune cell infiltration, suggesting that FAM171B may promote the progression of PAH by stimulating immune infiltration and immune response. This study provides valuable insights into the pathogenesis and treatment of PAH.


Assuntos
Hipertensão Arterial Pulmonar , Biomarcadores , Redes Reguladoras de Genes , Humanos , Hipertensão Arterial Pulmonar/genética , Transdução de Sinais
5.
J Oncol ; 2022: 1022580, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36245988

RESUMO

Background: It is well known that hypoxia and ferroptosis are intimately connected with tumor development. The purpose of this investigation was to identify whether they have a prognostic signature. To this end, genes related to hypoxia and ferroptosis scores were investigated using bioinformatics analysis to stratify the risk of lung adenocarcinoma. Methods: Hypoxia and ferroptosis scores were estimated using The Cancer Genome Atlas (TCGA) database-derived cohort transcriptome profiles via the single sample gene set enrichment analysis (ssGSEA) algorithm. The candidate genes associated with hypoxia and ferroptosis scores were identified using weighted correlation network analysis (WGCNA) and differential expression analysis. The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature. The efficacy, accuracy, and clinical value of the prognostic model were evaluated using an independent validation cohort, Receiver Operator Characteristic (ROC) curve, and nomogram. The analysis of function and immune cell infiltration was also carried out. Results: Here, we appraised 152 candidate genes expressed not the same, which were related to hypoxia and ferroptosis for prognostic modeling in The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort, and these genes were further validated in the GSE31210 cohort. We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma. ROC and nomogram analyses showed that risk scores based on prognostic signatures provided desirable predictive accuracy and clinical utility. Moreover, gene set variance analysis showed differential enrichment of 33 hallmark gene sets between different risk groups. Additionally, our results indicated that a higher risk score will lead to more fibroblasts and activated CD4 T cells but fewer myeloid dendritic cells, endothelial cells, eosinophils, immature dendritic cells, and neutrophils. Conclusion: Our research found a 14-gene signature and established a nomogram that accurately predicted the prognosis in patients with lung adenocarcinoma. Clinical decision-making and therapeutic customization may benefit from these results, which may serve as a valuable reference in the future.

6.
Front Genet ; 13: 870222, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204316

RESUMO

Aim: Coronary artery disease (CAD) is a heterogeneous disorder with high morbidity, mortality, and healthcare costs, representing a major burden on public health. Here, we aimed to improve our understanding of the genetic drivers of ferroptosis and necroptosis and the clustering of gene expression in CAD in order to develop novel personalized therapies to slow disease progression. Methods: CAD datasets were obtained from the Gene Expression Omnibus. The identification of ferroptosis- and necroptosis-related differentially expressed genes (DEGs) and the consensus clustering method including the classification algorithm used km and distance used spearman were performed to differentiate individuals with CAD into two clusters (cluster A and cluster B) based expression matrix of DEGs. Next, we identified four subgroup-specific genes of significant difference between cluster A and B and again divided individuals with CAD into gene cluster A and gene cluster B with same methods. Additionally, we compared differences in clinical information between the subtypes separately. Finally, principal component analysis algorithms were constructed to calculate the cluster-specific gene score for each sample for quantification of the two clusters. Results: In total, 25 ferroptosis- and necroptosis-related DEGs were screened. The genes in cluster A were mostly related to the neutrophil pathway, whereas those in cluster B were mostly related to the B-cell receptor signaling pathway. Moreover, the subgroup-specific gene scores and CAD indices were higher in cluster A and gene cluster A than in cluster B and gene cluster B. We also identified and validated two genes showing upregulation between clusters A and B in a validation dataset. Conclusion: High expression of CBS and TLR4 was related to more severe disease in patients with CAD, whereas LONP1 and HSPB1 expression was associated with delayed CAD progression. The identification of genetic subgroups of patients with CAD may improve clinician knowledge of disease pathogenesis and facilitate the development of methods for disease diagnosis, classification, and prognosis.

7.
Neuroradiol J ; 35(2): 137-151, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34477003

RESUMO

BACKGROUND: Giant aneurysms of the intracranial vertebral artery are very rare cerebrovascular lesions. Due to the rarity of these aneurysms, we know little about them. METHODS: We performed a systematic review of the English literature by searching the PubMed database. The inclusion criteria were as follows: (a) the full text was available and (b) complete clinical data were available. RESULTS: A total of 45 articles were identified, containing 53 patients (53 aneurysms). The patients were aged from 5 to 77 years (48.8 ± 20.8 years). Four patients receiving conservative treatment died. The remaining 49 patients were divided into the aneurysm removal group (n = 17) and the aneurysm reserve group (n = 32). The outcomes of the 49 treated cases could be obtained in 45 cases, 31 of which (68.9%, 31/45) had a Glasgow outcome scale score of 4-5. CONCLUSIONS: It is still difficult to treat intracranial giant vertebral artery aneurysms, regardless of the treatment selected. Because of the malignant natural history, aggressive treatment is still advocated.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Embolização Terapêutica/efeitos adversos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Bulbo/diagnóstico por imagem , Bulbo/patologia , Pessoa de Meia-Idade , Coluna Vertebral/patologia , Resultado do Tratamento , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/patologia , Adulto Jovem
8.
Bioengineered ; 12(1): 2095-2105, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34047682

RESUMO

As gene delivery tools, lentiviral vectors (LV) have broad applications in chimeric antigen receptor therapy (CAR-T). Large-scale production of functional LV is limited by the adherent, serum-dependent nature of HEK293T cells used in the manufacturing. HEK293T adherent cells were adapted to suspension cells in a serum-free medium to establish large-scale processes for functional LV production in a stirred bioreactor without micro-carriers. The results showed that 293 T suspension was successfully cultivated in F media (293 CD05 medium and SMM293-TII with 1:1 volume ratio), and the cells retained the capacity for LV production. After cultivation in a 5.5 L bioreactor for 4 days, the cells produced 1.5 ± 0.3 × 107 TU/mL raw LV, and the lentiviral transduction efficiency was 48.6 ± 2.8% in T Cells. The yield of LV equaled to the previous shake flask. The critical process steps were completed to enable a large-scale LV production process. Besides, a cryopreservation solution was developed to reduce protein involvement, avoid cell grafting and reduce process cost. The process is cost-effective and easy to scale up production, which is expected to be highly competitive.


Assuntos
Reatores Biológicos/virologia , Vetores Genéticos , Imunoterapia Adotiva , Lentivirus , Cultura de Vírus/métodos , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Células HEK293 , Humanos , Lentivirus/genética , Lentivirus/metabolismo , Linfócitos T
9.
Acta Neurol Belg ; 121(2): 321-330, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33400225

RESUMO

The ophthalmic artery (OA) is a crucial artery. Centered at the OA, there are numerous extracranial-intracranial anastomoses. The OA and its collaterals can be involved in some intracranial vascular diseases. So, it is very important to understand its specific anatomy, variation, and role in different neurovascular diseases. The OA has various anomalies both in the origin and collateral circulation. When performing endovascular treatment (EVT), the OA may suffer unexpected embolization through the numerous dangerous anastomoses. In case of a dural arteriovenous fistula or brain arteriovenous malformation mainly fed by the OA, the OA can be the passage of EVT, during which the central retinal artery could be injured. During interventional recanalization of steno-occlusive diseases of the internal carotid artery, dissection at the cavernous segment could progress to the OA segment and occlude the origin of OA. Under the circumstance of moyamoya disease, the OA can provide collateral flow to the anterior cerebral artery. When performing EVT for OA aneurysm concurrent with moyamoya disease, the parent OA should be preserved. After placement of a flow-diverting device for ophthalmic ICA aneurysm, the covered OA could experience spontaneous occlusion, leading to visual disturbance. Hence, the OA is an extremely important artery in the EVT for intracranial vascular diseases. In this article, we would extensively review the related literature to increase our understanding of the role of OA in intracranial vascular diseases. In addition, some illustrative cases would also be provided.


Assuntos
Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/cirurgia , Circulação Colateral , Procedimentos Endovasculares/métodos , Artéria Oftálmica/diagnóstico por imagem , Artéria Oftálmica/cirurgia , Circulação Colateral/fisiologia , Humanos , Artéria Oftálmica/anatomia & histologia , Artéria Oftálmica/fisiologia , Resultado do Tratamento
10.
Med Int (Lond) ; 1(1): 1, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-36698683

RESUMO

Following the clipping of intracranial aneurysms, post-clipping residual or recurrent aneurysms (PCRRAs) can occur. In recent years, the incidence of PCRRAs has increased due to a prolonged follow-up period and advanced imaging techniques. However, several aspects of intracranial PCRRAs remain unclear. Therefore, the present study performed an in-depth review of the literature on PCRRAs. Herein, a summary of PCRRAs that can be divided into the following two categories is presented: i) Those occurring after the incomplete clipping of an aneurysm, where the residual aneurysm regrows into a PCRRA; and ii) those occurring after the complete clipping of an aneurysm, in which a de novo aneurysm occurs at the original aneurysm site. Currently, digital subtracted angiography remains the gold standard for the imaging diagnosis of PCRRAs as it can eliminate metallic clip artifacts. Intracranial symptomatic PCRRAs should be actively treated, particularly those that have ruptured. A number of methods are currently available for the treatment of intracranial PCRRAs; these mainly include re-clipping, endovascular treatment (EVT) and bypass surgery. Currently, re-clipping remains the most effective method used to treat PCRRAs; however, it is a very difficult procedure to perform. EVT can also be used to treat intracranial PCRRAs. EVT methods include coiling (stent- or balloon-assisted) and flow-diverting stents (or coiling-assisted). Bypass surgery can be selected for difficult-to-treat, complex PCRRAs. On the whole, following appropriate treatment, the majority of intracranial PCRRAs achieve a high occlusion rate and a good prognosis.

11.
Oxid Med Cell Longev ; 2020: 9217219, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204401

RESUMO

OBJECTIVE: Severe acute pancreatitis (SAP) is a serious and life-threatening disease associated with multiple organ failure and a high mortality rate and is accompanied by distinct oxidative stress and inflammatory responses. Saikosaponin A has strong antioxidant properties and can affect the composition of gut microbiota. We sought to determine the effects of Saikosaponin A interventions on SAP by investigating the changes of gut microbiota and related antioxidant signaling. METHODS: A SAP model was established in Sprague-Dawley (SD) rats through the injection of sodium taurocholate into the biliopancreatic duct and confirmed by elevated levels of serum lipase and amylase. The model was fed a standard diet either with saline solution or with Saikosaponin A. Fecal microbiota transplantation (FMT) from Saikosaponin A-induced rats into the rat model was performed to test the effects of gut microbiota. The composition of gut microbiota was analyzed by using 16S rRNA gene sequencing. We measured apoptotic status, inflammatory biomarkers, and Keap1-Nrf2-ARE ((Kelch-like ECH-associated protein 1) nuclear factor erythroid 2-related factor 2-antioxidant response element) antioxidant signaling. RESULTS: Saikosaponin A intervention attenuated SAP lesions and reduced the levels of serum amylase and lipase, oxidative stress, and inflammatory responses by reducing pathological scores and affecting the serum level of oxidative and inflammatory factors. Meanwhile, the expression of Keap1-Nrf2-ARE was increased. Saikosaponin A intervention improved microbiota composition by increasing the relative abundance of Lactobacillus and Prevotella species. FMT resulted in similar results as those caused by the Saikosaponin A intervention, suggesting Saikosaponin A may exert its function via the improvement of gut microbiota composition. CONCLUSIONS: Saikosaponin A-induced gut microbiota changes attenuate SAP progression in the rat model and may be a potential natural drug for adjuvant treatment of SAP. Further work is needed to clear up the points.


Assuntos
Antioxidantes/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ácido Oleanólico/análogos & derivados , Pancreatite/tratamento farmacológico , Saponinas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Elementos de Resposta Antioxidante , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Masculino , Fator 2 Relacionado a NF-E2/genética , Ácido Oleanólico/farmacologia , Estresse Oxidativo , Pancreatite/metabolismo , Pancreatite/microbiologia , Pancreatite/patologia , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença
12.
Int J Med Sci ; 17(18): 3020-3030, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173422

RESUMO

Petroclival region dural arteriovenous fistulas (DAVFs) are rare and difficult lesions to manage. They often have very complex anatomical structures and can be further divided into the superior petrosal sinus, petrous apex, inferior petrosal sinus, upper clival, and upper clival epidural-osseous DAVFs. Most petroclival region DAVFs should be treated due to their high Cognard grades. Currently, endovascular treatment (EVT) has become the first-line therapeutic option for petroclival region DAVFs. But not all the petroclival region DAVFs could be cured with EVT. When the arterial feeders are large or the DAVF is adjacent to the venous sinus, the success rate may be higher. In petroclival region DAVFs, if EVT can be performed successfully, satisfactory outcome can be anticipated. However, there are some inadvertent complications, which include cranial nerve palsy, subsequent sinus thrombosis, and migration embolization of the internal carotid artery and vertebral artery. Currently, a review of the EVT of petroclival region DAVFs is lacking. In this article, we performed a review of the relevant literature on this issue. In addition, some illustrative cases would be provided to elaborate these specific entities.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/terapia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Base do Crânio/irrigação sanguínea , Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Angiografia Cerebral , Humanos , Resultado do Tratamento
13.
Front Neurol ; 11: 526550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101168

RESUMO

Background: In rare circumstances, patients with intracranial (dural arteriovenous fistulas) DAVFs could be complicated with brainstem engorgement, which might lead to delayed or false diagnosis and subsequent improper management. Methods: On July 2th, 2019, a systematic search was conducted in the PubMed database for patients with intracranial DAVFs complicated with brainstem engorgement. Results: Sixty-eight articles reporting of 86 patients were included for final analysis. The patients were aged from 20 to 76 years (57.10 ± 12.90, n = 82). The female to male ratio was 0.68 (35:51). Thirty-three (40.2%, 33/82) patients were initially misdiagnosed as other diseases. The specific location distributions were cranio-cervical junction, cavernous sinus, superior petrosal sinus, transverse and/or sigmoid sinus, tentorium, and other sites in 27 (32.5%), 11 (13.2%), 9 (10.8%), 10 (12.0%), 21 (25.3%), and 5 (6.0%) patients, respectively. The Cognard classification of DAVFs were II, III, IV, and V in 9 (10.7%, 9/84), 1 (1.2%, 1/84), 1 (1.2%, 1/84), and 73 (86.9%, 73/84) patients. Eighteen (22%, 18/82) patients were demonstrated to have stenosis or occlusion of the draining system distal to the fistula points. The mean follow-up period was 7.86 (n = 74, range 0-60 months) months. Fifty-four (70.1%, 54/77) patients experienced a good recovery according to the mRS score. Conclusions: Intracranial DAVFs complicated with brainstem engorgement are rare entities. Initial misdiagnosis and delayed definite diagnosis are common in the past three decades. The treatment outcome is still unsatisfactory at present. Early awareness of this rare entity and efficiently utilizing the up to date investigations are of utmost importance.

14.
Front Neurol ; 11: 603256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33551963

RESUMO

Background: In rare circumstances, brain arteriovenous malformations (BAVMs) can recruit a transdural blood supply (TBS). The clinical and radiologic characteristics of BAVMs with a TBS are poorly understood. Methods: A retrospective review of the medical records was conducted for adult patients who were admitted for BAVMs from Jan 2013 to Dec 2019. TBSs for BAVMs were divided into 3 types: (1) unilateral TBSs from the external carotid artery (ECA) and/or meningeal branch of the vertebral artery (VA); (2) bilateral TBSs from the ECA and/or meningeal branch of the VA; and (3) meningohypophyseal trunk TBSs of the internal carotid artery. Results: Four hundred and twenty-eight patients were diagnosed with BAVMs during the study period, of whom 30 (7.0%, 30/428) were identified as having a TBS. Type 1, type 2, and type 3 TBSs were identified in 21 (70%, 21/30), 7 (23.3%, 7/30), and 2 (6.7%, 2/30) patients, respectively. Six (20%, 6/30) patients were conservatively managed. Twelve (40%, 12/30) patients underwent endovascular treatment (EVT) of the BAVM through non-TBS feeders. Eight (26.8%, 8/30) patients underwent EVT of the BAVM both through the TBS and non-TBS feeders. The modified Rankin Scale scores at the 3-month follow-up were 0, 1, 2, 4, and 5 in 24 (80%, 24/30), 2 (6.7%, 2/30), 2 (6.7%, 2/30), 1 (3.3%, 1/30), and 1 (3.3%, 1/30) patients, respectively. Good short-term recovery was achieved in 86.7% (26/30) of the patients. The size of the BAVMs with a TBS was larger than that of BAVMs without a TBS. Patients with higher Spetzler-Martin grades tended to have a TBS. No statistical difference was noted between the patients with and without a TBS with regard to age, sex, location, or concurrent aneurysms. Conclusions: This study showed that a TBS was likely to develop in patients with larger BAVMs and that a TBS was likely to be located in the temporal lobe in patients BAVMs with higher SM grades. Weak structures were the primary targets of management. In addition, a BAVM could be embolized via the TBS.

15.
Eur J Med Chem ; 187: 111961, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865017

RESUMO

Accumulation of tau protein aggregation plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Uncontrollable neuroinflammation and tau pathology form a vicious circle that further aggravates AD progression. Herein, we reported the synthesis of usnic acid derivatives and evaluation of their inhibitory activities against tau-aggregation and neuroinflammation. The inhibitory activity of the derivatives against the self-fibrillation of the hexapeptide AcPHF6 was initially screened by ThT fluorescence assay. Using circular dichroism and transmission electron microscopy, compound 30 showed the most potent inhibitory activity against AcPHF6 self-fibrillation. Compound 30 was further confirmed to inhibit the aggregation of full-length 2N4R tau protein by a heparin-induced mechanism. In addition, we investigated the anti-inflammatory activity of compound 30, and showed that compared with sodium usnate, it reduced NO release in LPS-stimulated mouse microglia BV2 cells. More importantly, 30 showed significant protective effects against okadaic acid-induced memory impairment in rats. Thus, 30 was a novel tau-aggregation and neuroinflammation inhibitor that represented a potential therapeutic candidate for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Benzofuranos/farmacologia , Inflamação/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas tau/antagonistas & inibidores , Doença de Alzheimer/metabolismo , Animais , Benzofuranos/síntese química , Benzofuranos/química , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Agregados Proteicos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Proteínas tau/metabolismo
16.
Eur J Med Chem ; 179: 736-743, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284083

RESUMO

The formation of amyloid-ß (Aß) plaques in the brain is one of the main pathological features of Alzheimer's disease (AD). The imaging probes, capable of detecting Aß deposition, are important tools for early diagnosis of AD. In this article, we designed, synthesized and evaluated a cyanine-based near-infrared fluorescence (NIRF) probe ZT-1 for the detection of Aß deposits in the brain. The probe had excellent fluorescent properties with an emission maximum above 720 nm upon binding to Aß aggregates with affinity of 445.0 nM (Kd). Furthermore, ZT-1 exhibited good biostability, photostability, and binding selectivity toward Aß1-42 aggregates by in vitro fluorescence staining experiments. In vivo NIRF imaging result also revealed that our probe could efficiently differentiate transgenic and wild-type mice. All these studies indicated that ZT-1 is a promising fluorescent probe for Aß plaques in the AD brains.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Carbocianinas/química , Imagem Óptica , Placa Amiloide/química , Animais , Carbocianinas/síntese química , Relação Dose-Resposta a Droga , Raios Infravermelhos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estrutura Molecular , Relação Estrutura-Atividade
17.
Nutr Res Rev ; 32(2): 176-182, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30919797

RESUMO

Critically ill patients frequently suffer from gastrointestinal dysfunction as the intestine is a vulnerable organ. In critically ill patients who require nutritional support, the current guidelines recommend the use of enteral nutrition within 24-48 h and advancing towards optimal nutritional goals over the next 48-72 h; however, this may be contraindicated in patients with acute gastrointestinal injury because overuse of the gut in the acute phase of critical illness may have an adverse effect on the prognosis. We propose that trophic feeding after 72 h, as a partial gut rest strategy, should be provided to critically ill patients during the acute phase of illness as an organ-protective strategy, especially for those with acute gastrointestinal injury.


Assuntos
Estado Terminal/terapia , Gastroenteropatias/terapia , Terapia Nutricional/métodos , Estado Terminal/mortalidade , Digestão , Nutrição Enteral/efeitos adversos , Gastroenteropatias/fisiopatologia , Trato Gastrointestinal/fisiopatologia , Humanos , Unidades de Terapia Intensiva , Absorção Intestinal , Tempo de Internação , Terapia Nutricional/efeitos adversos , Necessidades Nutricionais
18.
J Mol Neurosci ; 65(4): 546-556, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30069802

RESUMO

Circular RNAs (circRNAs), a type of endogenous noncoding RNAs distinct from linear forms, are produced by backsplicing events within genes. circRNAs are structurally stable, highly conserved molecules found widely in organisms, and display tissue-type and developmental-stage specific expression patterns, which reveal their significant regulatory functions in gene expression. Based on accumulating evidence, some circRNAs are now believed to be a class of competitive endogenous RNAs that regulate gene expression. For example, circRNAs may prevent microRNAs from inhibiting target RNAs acting as microRNA sponges, or interact with RNA binding proteins and thereby efficiently and post-transcriptionally regulate expression of the parental and other genes. In addition, an increasing number of studies have shown that circRNAs play important roles in the development and progression of neurological disorders. In this review, we provide a comprehensive overview on the biogenesis, characteristics, and functions of circRNAs. We also discuss the critical role of circRNAs in neurological disorders.


Assuntos
Doenças do Sistema Nervoso/genética , RNA/genética , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças do Sistema Nervoso/metabolismo , RNA/metabolismo , Processamento Pós-Transcricional do RNA , RNA Circular
19.
Biomed Rep ; 8(2): 191-197, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29435280

RESUMO

The present study aimed to investigate the clinical characteristics of hemorrhagic moyamoya disease (MMD) in Jilin province in northeast China. A total of 212 cases of hemorrhagic MMD were consecutively enrolled from the First Hospital of Jilin University in Changchun, China between January 2011 and January 2015. The patients' general clinical data, including age and gender characteristics, history of previous illnesses, hemorrhage type and onset symptoms, Hunt-Hess classification at admission, imaging characteristics, association with aneurysms, treatments and prognosis, were recorded and analyzed using SPSS 19.0. The results demonstrated that i) patients with hemorrhagic MMD in Jilin province were 47.7±11.5 years of age; ii) hemorrhagic MMD was primarily characterized by subarachnoid hemorrhage; iii) a total of 51.9% of the hemorrhagic MMD cases involved a unilateral artery; iv) a total of 24.1% of the hemorrhagic MMD cases were accompanied by anterior choroid artery and/or posterior communicating artery expansion; and v) following conservative or surgical treatment, patients with a prognostic Glasgow Outcome Scale score of 5 accounted for 65.6% of the study population. Therefore, the present study identified characteristics of MMD in Jilin province in northeast China. These results may improve understanding of the epidemiology of MMD in China, which at present remains not well established. Although the results are representative only of Jilin province in China, the study demonstrated high consistency with other studies, and thus may indirectly contribute to general understanding of hemorrhagic MMD etiology.

20.
Int J Med Sci ; 14(8): 772-784, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824313

RESUMO

Dolichoarteriopathies of the internal carotid artery (DICAs) are not uncommon, and although several studies have investigated DICAs, several questions regarding the etiology and best management course for DICAs remain unanswered. It is also difficult to correlate the occurrence of DICAs with the onset of clinical symptoms. Therefore, we surveyed the literature in PubMed and performed a review of DICAs to offer a comprehensive picture of our understanding of DICAs. We found that DICAs can be classified into three types, specifically tortuous, coiling and kinking, and are not associated with atherosclerotic risk factors. Cerebral hemodynamic changes are mainly associated with the degree of bending of DICAs. DICAs can result in symptoms of the brain and eyes due to insufficient blood supply and can co-occur with a pulsatile cervical mass, a pharyngeal bulge and pulsation. The diagnostic tools for the assessment of DICAs include Doppler ultrasonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA) and digital subtraction angiography (DSA), and although DSA remains the gold standard, Doppler ultrasonography is a convenient method that provides useful data for the morphological evaluation of DICAs. CTA and MRA are efficient methods for detecting the morphology of the cervical segment of DICAs. Some DICAs should be treated surgically based on certain indications, and several methods, including correcting the bending or shortening of DICAs, have been developed for the treatment of DICAs. The appropriate treatment of DICAs results in good outcomes and is associated with low morbidity and mortality rates. However, despite the success of surgical reconstruction, an appropriate therapeutic treatment remains a subject of numerous debates due to the lack of multicentric, randomized, prospective studies.


Assuntos
Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/fisiopatologia , Artéria Carótida Interna/fisiopatologia , Angiografia Digital , Doenças das Artérias Carótidas/classificação , Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Humanos , Fatores de Risco , Tomografia Computadorizada por Raios X
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