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1.
J Craniofac Surg ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682949

RESUMO

The natural history of spinal cord cavernous malformation (SCM) may be characterized by recurrent episodes of hemorrhage resulting in a range of neurologic deficits, most of which are microhemorrhage and subsequent gliosis that can lead to progressive myelopathy. Macrohemorrhage with acute onset of symptoms is extremely rare and leads to irreversible neurologic deficits. In this article, we present an unusual case of ruptured cavernous malformation (CM) in the cervical spinal cord with large extralesional hemorrhage. The patient underwent an operation of posterior longitudinal myelotomy and had a good neurologic recovery. A histologic examination revealed the typical features of cavernous angioma.

2.
Pharmgenomics Pers Med ; 16: 991-1009, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37964785

RESUMO

Objective: This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM. Methods: Utilizing the GEPIA2 and TCGA databases, we contrasted the expression levels of PLP2 in GBM against normal tissue. We utilized GEPIA2 and LinkedOmics for survival analysis, recognized genes co-expressed with PLP2 via cBioPortal and GEPIA2, and implemented GO and KEGG analyses. The STRING database facilitated the construction of protein-protein interaction networks. We evaluated the relationship of PLP2 with tumor immune infiltrates using ssGSEA and the TIMER 2.0 database. An IHC assay assessed PLP2 and PDL-1 expression in GBM tissue, and the Drugbank database aided in identifying potential PLP2-targeting compounds. Molecular docking was accomplished using Autodock Vina 1.2.2. Results: PLP2 expression was markedly higher in GBM tissues in comparison to normal tissues. High PLP2 expression correlated with a decrease in overall survival across two databases. Functional analyses highlighted a focus of PLP2 functions within leukocyte. Discrepancies in PLP2 expression were evident in immune infiltration, impacting CD4+ T cells, neutrophils, myeloid dendritic cells, and macrophages. There was a concomitant increase in PLP2 and PD-L1 expression in GBM tissues, revealing a link between the two. Molecular docking with ethosuximide and praziquantel yielded scores of -7.441 and -4.295 kcal/mol, correspondingly. Conclusion: PLP2's upregulation in GBM may adversely influence the lifespan of GBM patients. The involvement of PLP2 in pathways linked to leukocyte function is suggested. The positive correlation between PLP2 and PD-L1 could provide insights into PLP2's role in glioma modulation. Our research hints at PLP2's potential as a therapeutic target for GBM, with ethosuximide and praziquantel emerging as potential treatment candidates, especially emphasizing the potential of these compounds in GBM treatment targeting PLP2.

3.
Front Neurol ; 14: 1190544, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37396763

RESUMO

Background: Prolonged mechanical ventilation (PMV) has been proven as a risk factor for poor prognosis in patients with neurocritical illness. Spontaneous basal ganglia intracerebral hemorrhage (ICH) is one common subtype of hemorrhagic stroke and is associated with high morbidity and mortality. The systemic immune-inflammation index (SII) is used as a novel and valuable prognostic marker for various neoplastic diseases and other critical illnesses. Objective: This study aimed to analyze the predictive value of preoperative SII for PMV in patients with spontaneous basal ganglia ICH who underwent surgical operations. Methods: This retrospective study was conducted in patients with spontaneous basal ganglia ICH who underwent surgical operations between October 2014 and June 2021. SII was calculated using the following formula: SII = platelet count × neutrophil count/lymphocyte count. Multivariate logistic regression analysis and receiver operating characteristics curve (ROC) were used to evaluate the potential risk factors of PMV after spontaneous basal ganglia ICH. Results: A total of 271 patients were enrolled. Of these, 112 patients (47.6%) presented with PMV. Multivariate logistic regression analysis showed that preoperative GCS (OR, 0.780; 95% CI, 0.688-0.883; P < 0.001), hematoma size (OR, 1.031; 95% CI, 1.016-1.047; P < 0.001), lactic acid (OR, 1.431; 95% CI, 1.015-2.017; P = 0.041) and SII (OR, 1.283; 95% CI, 1.049-1.568; P = 0.015) were significant risk factors for PMV. The area under the ROC curve (AUC) of SII was 0.662 (95% CI, 0.595-0.729, P < 0.001), with a cutoff value was 2,454.51. Conclusion: Preoperative SII may predict PMV in patients with spontaneous basal ganglia ICH undergoing a surgical operation.

4.
Mol Neurobiol ; 60(11): 6715-6730, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37477767

RESUMO

Humans exhibit a rich intestinal microbiome that contain high levels of bacteria capable of producing 3-oxo-lithocholic acid (3-oxoLCA) and other secondary bile acids (BAs). The molecular mechanism mediating the role of 3-oxoLCA in cerebral ischemia-reperfusion (I/R) injury remains unclear. We investigated the role of 3-oxoLCA in a rat cerebral I/R injury model. We found that the concentrations of 3-oxoLCA within the cerebrospinal fluid were increased following I/R. In the in vitro oxygen-glucose deprivation (OGD) model, the levels of intraneuronal 3-oxoLCA was elevated following OGD insult. We showed that the increase of membrane ASBT (apical sodium-dependent bile acid transporter) contributed to OGD-induced elevation of intraneuronal 3-oxoLCA. Increasing intraneuronal 3-oxoLCA promoted ischemia-induced neuronal death, whereas reducing 3-oxoLCA levels were neuroprotective. Our results revealed that PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenases 2) functioned upstream of PTEN (the phosphatase and tensin homolog deleted on chromosome 10) and downstream of 3-oxoLCA to promote OGD-induced neuronal injury. We further demonstrated that direct-current stimulation (DCS) decreased the levels of intraneuronal 3-oxoLCA and membrane ASBT in OGD-insulted neurons, while bilateral transcranial DCS (tDCS) reduced brain infarct volume following I/R by inhibiting ASBT. Together, these data suggest that increased expression of ASBT promotes neuronal death via 3-oxoLCA-PLOD2-PTEN signaling pathway. Importantly, bilateral tDCS suppresses ischemia-induced increase of ASBT, thereby conferring neuroprotection after cerebral I/R injury.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Estimulação Transcraniana por Corrente Contínua , Humanos , Ratos , Animais , Neuroproteção , Transdução de Sinais , Isquemia Encefálica/metabolismo , Oxigênio/metabolismo , Infarto Cerebral , Glucose/metabolismo , Traumatismo por Reperfusão/metabolismo , Apoptose , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , PTEN Fosfo-Hidrolase/metabolismo
5.
Neurosurg Rev ; 46(1): 117, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37165260

RESUMO

The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) is increasing annually. The prognostic nutritional index (PNI) is used as a novel and valuable prognostic marker for various neoplastic diseases and other critical illnesses. This study aimed to identify the short-term prognostic value of preoperative PNI in elderly patients who underwent neurosurgical clipping for aSAH. This retrospective study included elderly patients with aSAH who underwent neurosurgical clipping from January 2018 to December 2020. Clinical variables and 6-month outcomes were collected and compared. Epidemiological data and effect factors of prognosis were evaluated. Multivariate logistic regression and receiver operating characteristics (ROC) curve analyses were used to evaluate the predictive value of preoperative PNI. Multiple logistic regression was performed to establish a nomogram. A total of 124 elderly patients were enrolled. Multivariate logistic regression analysis showed that preoperative PNI (odds ratio (OR), 0.779; 95% confidence interval (CI), 0.689-0.881; P < 0.001), Hunt-Hess grade (OR, 3.291; 95%CI, 1.816-5.966; P < 0.001), and hydrocephalus (OR, 9.423; 95%CI, 2.696-32.935; P < 0.001) were significant predictors. The area under the ROC curve of PNI was 0.829 (95% CI, 0.755-0.903; P < 0.001) with a sensitivity and specificity of 68.4% and 83.3%, respectively, and the cutoff value was 46.36. Patients with preoperative PNI of < 46.36 had a significantly unfavorable 6-months prognosis (F = 40.768, P < 0.001). Preoperative PNI is independently correlated with the 6-month prognosis in elderly patients who undergo neurosurgical clipping for aSAH.


Assuntos
Hemorragia Subaracnóidea , Humanos , Idoso , Prognóstico , Hemorragia Subaracnóidea/cirurgia , Avaliação Nutricional , Estudos Retrospectivos , Nomogramas
6.
Nanoscale ; 14(48): 18217-18230, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36468670

RESUMO

For patients suffering from traumatic brain injury (TBI), the closure of dural defects after decompressive craniectomy is the prerequisite to restoring normal physiological functions. It is also an urgent challenge to provide a neuroprotection effect against the primary and secondary nerve damage during long-term recovery. To solve these issues, we herein develop a class of bioactive, nanofibrous dural substitutes that can long-term release insulin-like growth factor 1 (IGF-1) for improving the survival and neurite outgrowth of neural cells after TBI. Such dural substitutes were polycaprolactone (PCL) nanofibers encapsulated with hyaluronic acid methacryloyl (HAMA)/IGF-1 by blend or coaxial electrospinning techniques, achieving bioactive PCL/HAMA/IGF nanofibrous dural substitutes with different release profiles of IGF-1. The nanofibrous dural substitutes exhibited good mechanical properties and hydrophobicity, which prevent cerebrospinal fluid leakage, maintain normal intracranial pressure, and avoid external impact on the brain. We also found that the viability and neurite outgrowth of SH-SY5Y cells and primary neurons were significantly enhanced after neurite transection or oxygen and glucose deprivation treatment. Taken together, such PCL/HAMA/IGF nanofibrous dural substitutes hold promising potential to provide neuroprotection effects after primary and secondary nerve damage in TBI, which would bring significant benefits to the field of neurosurgery involving the use of artificial dura mater.


Assuntos
Lesões Encefálicas Traumáticas , Nanofibras , Neuroblastoma , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Neuroproteção , Preparações de Ação Retardada/farmacologia , Lesões Encefálicas Traumáticas/tratamento farmacológico
7.
Mol Neurobiol ; 59(12): 7423-7438, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36190692

RESUMO

Propionic acid (PPA) is a critical metabolite involved in microbial fermentation, which functions to reduce fat production, inhibit inflammation, and reduce serum cholesterol levels. The role of PPA in the context of cerebral ischemia-reperfusion (I/R) injury has yet to be clarified. Increasing evidence indicate that transcranial direct-current stimulation (tDCS) is a safe approach that confers neuroprotection in cerebral ischemia injury. Here, we show that the levels of PPA were reduced in the ischemic brain following a rat cerebral I/R injury and in the cultured rat cortical neurons after oxygen-glucose deprivation (OGD), an in vitro model of ischemic injury. We found that the decreased levels of transporter protein monocarboxylate transporter-1 (MCT1) were responsible for the OGD-induced reduction of PPA. Supplementing PPA reduced ischemia-induced neuronal death after I/R. Moreover, our results revealed that the neuroprotective effect of PPA is mediated through downregulation of phosphatase PTEN and subsequent upregulation of Lon protease 1 (LONP1). We demonstrated that direct-current stimulation (DCS) increased MCT1 expression and PPA level in OGD-insulted neurons, while tDCS decreased the brain infarct volume in the MCAO rats via increasing the levels of MCT1 expression and PPA. This study supports a potential application of tDCS in ischemic stroke.


Assuntos
Isquemia Encefálica , Fármacos Neuroprotetores , Protease La , Traumatismo por Reperfusão , Estimulação Transcraniana por Corrente Contínua , Animais , Ratos , Isquemia Encefálica/metabolismo , Infarto Cerebral , Glucose/metabolismo , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Protease La/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Traumatismo por Reperfusão/metabolismo
8.
Anal Methods ; 14(36): 3529-3538, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36018227

RESUMO

The increasing evidence of microplastic (MP) contamination influence on aquatic organisms has been extensively reported globally. However, the discussions of extracting MPs from oily food samples are limited, highlighting the pressing need for effective and standardized analytical methods to extract MPs from oily food. Previous methods, such as using acid, alkali or oxidizing solutions as digestion reagents, usually take a long time to digest oily food, increasing the possibility of procedural contamination of MPs in food over time. The objective of this study was to develop a rapid, efficient, economical and simple analytical method to extract MPs from oily food samples. This innovative protocol combines the use of 4 : 1 HNO3 : H2O2 as a digestion reagent to accelerate the digestion within 1 h at 50 °C and hexane as a washing solution to remove the oil adsorbed on the surface of MPs and membranes. Four common types of MPs, namely, polyethylene terephthalate, polyethylene, polystyrene and polypropylene of different sizes were added to oily flours to demonstrate this method. The mean recovery of MPs was 95% ± 2% (range: 93-98%), and no significant changes in color, particle size, surface area and spectrum features were found for all recovered polymers except for PS with minor changes in color and surface. The method was confirmed to be effective on rice, noodles, bean products and various meat samples. All in all, the present method can facilitate the observation and identification of characteristics of MPs, providing an innovative combination method for quantitative and qualitative analyses of MPs in oily food samples.


Assuntos
Microplásticos , Poluentes Químicos da Água , Álcalis , Hexanos , Peróxido de Hidrogênio , Plásticos/análise , Polietileno , Polietilenotereftalatos , Polipropilenos , Poliestirenos/análise , Poluentes Químicos da Água/análise
9.
J Stroke Cerebrovasc Dis ; 31(10): 106670, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35973397

RESUMO

OBJECTIVE: To examine the role of CCL14 in the neovascularization process and vulnerability progression within carotid plaques by investigating the mechanism of CCL14 regulation of VEGF-A. METHODS: We first performed histological analysis and immunohistochemical staining of human carotid plaque tissue to detect the expression of CCL14, JAK2, STAT3 and VEGF-A. We next examined the protein expression of CCL14, VEGF-A, JAK2, STAT3, and phosphorylation of JAK2 and STAT3 in human carotid atherosclerotic plaques by Western blotting. Finally, we performed in vitro culture of human umbilical vein endothelial cells (HUVEC). In the tube formation assay of HUVEC, we added CCL14 siRNA or VEGF-A siRNA to the culture medium using lentiviral transfection to knock down CCL14 or VEGF-A and grouped them for control assays, and detected the changes in the expression of the above proteins using Western blotting. RESULTS: Histological and Western blotting analysis of human carotid plaque samples showed that the expression of CCL14 and VEGF-A was higher in the vulnerable plaques than in stable plaques. In the in vitro cultures of HUVEC, CCL14 was found to increase the number and length of intercellularly generated tubular structures. CCL14 increases VEGF-A expression via activating JAK2/STAT3 signaling. CONCLUSION: In the human carotid plaques, CCL14 promotes angiogenesis by upregulation of VEGF-A via JAK2/STAT3 pathway and thus drives the progression of carotid plaques vulnerability.


Assuntos
Placa Aterosclerótica , Fator A de Crescimento do Endotélio Vascular , Quimiocinas CC , Células Endoteliais/metabolismo , Humanos , Neovascularização Patológica/metabolismo , Placa Aterosclerótica/patologia , RNA Interferente Pequeno , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
J Craniofac Surg ; 33(8): 2400-2405, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35894445

RESUMO

OBJECTIVE: Decompressive craniectomy (DC) is widely used to treat intracranial hypertension following severe head injury. However, impairments of cerebrospinal fluid (CSF) hydrodynamics such as hydrocephalus and subdural effusion are common complications that occur after DC. Therefore, monitoring of intracranial pressure is a staple of neurocritical care post-DC. The aim of this study was to assess the usefulness of transcranial duplex sonography (TDS) for serial monitoring and management of CSF disorders after DC. METHODS: A total of 100 patients who underwent DC between June 2016 and May 2019 were recruited for the study. Transcranial duplex sonography examinations were performed between 1-day and 1-year post-DC. Transcranial duplex sonography was mainly used for monitoring changes in ventricle size and morphology, and also to monitor intraventricular hemorrhage, hydrocephalus, intracranial hygromas, and ventricle changes during CSF release procedures. RESULTS: A total of 456 TDS examinations were performed on patients after DC. Of these, 402 were performed in the neuro-intensive care unit. Two patients had intraventricular hemorrhage and underwent TDS-guided external ventricular drainage. Twenty-nine patients were diagnosed with hydrocephalus. The results of TDS were consistent with those of cranial computed tomography. Three cases of ventriculoperitoneal shunt and 1 case of lumbar peritoneal shunt underwent valve pressure reset according to TDS, to obtain satisfactory ventricle size. Transcranial duplex sonography was used to monitor ventricle changes and control drainage volume during CSF release procedures, including 2 external ventricular drainage, 6 external lumbar drainage, and 10 lumbar punctures. Eighteen patients were detected with single or multiple intracranial effusions, including 16 subdural hygromas, 5 longitudinal fissure hygromas, and 6 brain cysts. CONCLUSIONS: Transcranial duplex sonography can efficiently help monitor changes in ventricle size and morphology and intracranial effusions. Due to its noninvasive nature, suitability for bedside application, real-time, and inexpensiveness, TDS can significantly replace cranial computed tomography and become part of the patient's daily inspection work after DC.


Assuntos
Craniectomia Descompressiva , Hidrocefalia , Linfangioma Cístico , Humanos , Hemorragia Cerebral/complicações , Craniectomia Descompressiva/métodos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/cirurgia , Hidrocefalia/etiologia , Linfangioma Cístico/complicações , Ultrassonografia
11.
Int J Med Robot ; 18(4): e2412, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35476791

RESUMO

BACKGROUND: The aim of this study was to test the effectiveness, safety and stability of the 5G communication technology in clinical laparoscopic telesurgery. METHODS: An ultra-remote radical cystectomy (network communication distance of nearly 3000 km) was performed on patient diagnosed with T2N0M0 stage bladder cancer using a domestically produced "MicroHand" surgical robot. RESULTS: The network delay, operative time, blood loss, intraoperative complications, postoperative recovery, and hospitalisation time were recorded. The 5G network was used throughout the operation, with an average total delay of 254 ms. The operation went well and the patient recovered smoothly. CONCLUSIONS: Ultra-remote clinical laparoscopic surgery can be performed safely and smoothly. More importantly, our model can provide insights for promoting the future development of telesurgery in China.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Cistectomia , Humanos , Excisão de Linfonodo , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia
12.
BMJ Open ; 12(4): e057624, 2022 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-35437253

RESUMO

OBJECTIVES: To separately examine and comprehensively compare the risk factors for hospital-acquired (HAPIs) and community-acquired pressure injuries (CAPIs). DESIGN: A mixed case-control study. SETTING: Four medical centres in China. PARTICIPANTS: Inclusion criteria included patients who were (1) aged ≥18 years on admission; (2) admitted between January 2014 and December 2018, and (3) diagnosed with HAPIs (cases) or with no HAPIs (controls) during hospitalisation in the HAPIs study, and confirmed with CAPIs (cases) or with no PIs (controls) on admission in the CAPIs study. The exclusion criteria were as follows: (1) admitted for childbirth, psychiatric reasons or rehabilitation; (2) admitted for observation; (3) transferred from another hospital and (4) confirmed to have suffered PIs from previous hospitalisations in the CAPIs study. In total, 320 cases and 1657 controls were included in the HAPIs study, and 1763 cases and 1786 controls were included in the CAPIs study. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome variable was the occurrence of PIs. RESULTS: The existence of PIs or scars from previous PIs on admission, presence of forced posture, use of medical devices and surgery during hospitalisation were found to be independent risk factors for HAPIs, as evidenced by the corresponding OR and 95% CI values of 51.931 (34.241 to 78.763), 2.006 (1.405 to 2.864), 3.226 (1.709 to 6.089) and 2.161 (1.452 to 3.215), respectively. Age, sex, Braden rating and diabetes were found to be independent risk factors for CAPIs, as evidenced by the corresponding OR and 95% CI values of 1.031 (1.026 to 1.036), 0.810 (0.698 to 0.941), 1.235 (1.167 to 1.307) and 2.059 (1.332 to 3.184), respectively. CONCLUSIONS: The existence of PIs or scars from previous PIs on admission, presence of forced posture, use of medical devices and surgery during hospitalisation are suggested to be included as independent items for the risk assessment of PIs, together with the Braden scale. The Braden rating plays different roles in the development of CAPIs and HAPIs.


Assuntos
Cicatriz , Úlcera por Pressão , Adolescente , Adulto , Estudos de Casos e Controles , Hospitais , Humanos , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/etiologia , Fatores de Risco
13.
Biomed Res Int ; 2022: 6293329, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242876

RESUMO

Doxorubicin (Dox) is an effective chemotherapeutic drug for the treatment of various cancers. Due to its potential fatal cardiotoxic side effects, the clinical application is often limited. Dexrazoxane (Dex) is the only drug approved by the Food and Drug Administration (FDA) for the prevention of Dox-induced cardiotoxicity but has side effects. Thus, more protective strategies should be explored. If NAD+ plays a role in maintaining heart function, its precursor prospectively alleviates Dox-induced cellular injury. Here, we studied the protective effects of nicotinic acid riboside (NAR) on Dox-induced cardiotoxicity in vivo and in vitro. We found that NAR significantly improved the cardiac function of Dox-treated mice by restoring ejection fraction (EF), fractional shortening (FS), and serum level of cardiac troponin (cTnI). NAR not only reduced malondialdehyde (MDA), lactate dehydrogenase (LDH), and reactive oxygen species (ROS) levels in Dox-treated cardiomyocytes but also further promoted the activities of cardiac superoxide dismutase (SOD) and glutathione (GSH). Following exposure to 5 µM Dox, cotreatment with NAR exhibited increased cell viability with a decrease in the apoptosis cell population. Moreover, the levels of apoptosis-related proteins, as well as proteins involved in oxidative stress and autophagy, were altered after NAR treatment. Collectively, these findings underline the protective potential of NAR against Dox-induced cardiomyocyte injury by regulating Nrf-2/P62-related oxidative stress and autophagy, which could potentially promote survival.


Assuntos
Antineoplásicos/efeitos adversos , Cardiotônicos/farmacologia , Cardiotoxicidade/tratamento farmacológico , Dexrazoxano/uso terapêutico , Doxorrubicina/efeitos adversos , Niacinamida/análogos & derivados , Compostos de Piridínio/uso terapêutico , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade/etiologia , Humanos , Niacinamida/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos
14.
Acta Pharmacol Sin ; 43(6): 1508-1520, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34429524

RESUMO

Macrophage migration inhibitory factor (MIF) is a pluripotent pro-inflammatory cytokine and is related to acute and chronic inflammatory responses, immune disorders, tumors, and other diseases. In this study, an integrated virtual screening strategy and bioassays were used to search for potent MIF inhibitors. Twelve compounds with better bioactivity than the prototypical MIF-inhibitor ISO-1 (IC50 = 14.41 µM) were identified by an in vitro enzymatic activity assay. Structural analysis revealed that these inhibitors have novel structural scaffolds. Compound 11 was then chosen for further characterization in vitro, and it exhibited marked anti-inflammatory efficacy in LPS-activated BV-2 microglial cells by suppressing the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs). Our findings suggest that MIF may be involved in the regulation of microglial inflammatory activation and that small-molecule MIF inhibitors may serve as promising therapeutic agents for neuroinflammatory diseases.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Anti-Inflamatórios/química , Bioensaio , Fatores Inibidores da Migração de Macrófagos/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismo
15.
Front Oncol ; 12: 1005876, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36591479

RESUMO

Purpose: The aim of the present study is to evaluate the safety and efficacy of iodine-125 brachytherapy for newly diagnosed brain metastasis in patients with non-small cell lung cancer (NSCLC). Materials and methods: The study included 158 NSCLC patients diagnosed with brain metastasis from December 2003 to August 2017. Ninety-nine patients underwent external beam radiotherapy (EBRT group), and 59 patients received iodine-125 brachytherapy (125I group). In addition, the 6- and 12-month progression-free survival (PFS) rates and the 12- and 24-month overall survival (OS) rates were compared between the EBRT group and the 125I group. Median OS and PFS were analyzed using the Kaplan-Meier method with a log-rank test. Results: The 6-month PFS rate was significantly higher in the 125I group (p = 0.002) than in the EBRT group, while no differences were found in the 12-month PFS rate (p = 0.184). Additionally, the 12- (p = 0.839) and 24-month (p = 0.284) OS rates were not significantly different between the two groups. No significant differences in median OS (p = 0.525) or PFS (p = 0.425) were found between the two groups. Conclusions: Iodine-125 brachytherapy is an alternative therapy for patients unable to undergo surgical resection.

16.
ACS Chem Neurosci ; 12(20): 3947-3956, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34617722

RESUMO

Human cytomegalovirus (HCMV) harnesses a cell-specific manner to infect human nervous system cancer cells, establishes a life-long persistent infection without cell death, and modulates signaling pathways associated with cancer. We previously identified that the HCMV immediate-early 2 (IE2-86) protein binds and activates activating transcription factor 5 (ATF5), a survival factor in many tumor cells. In this study, we investigated a new mechanism of stress-induced miRNA regulation at the ATF5 3' UTR under the HCMV infection and other cellular stress conditions. We employed RNA-Seq and in silico analysis to screen stress response gene sets and identify miRNA candidates as potential regulators of ATF5 following HCMV infection. We found that ATF5 and cellular stress response genes were significantly upregulated under HCMV infection and diverse stress conditions. Three downregulated miRNAs were filtrated based on our threshold, and their binding sites for 3' UTR of ATF5 were predicted. Then, luciferase reporter assays were carried out to verify the binding sites for all three miRNA candidates targeting ATF5. However, in vitro validation has shown that miR-134-5p is the only candidate that can reverse the ATF5 protein upregulation under infection and other cell stresses. Additionally, miR-134-5p levels were significantly reduced and inversely related to ATF5 mRNA under HCMV infection. These results provide new evidence that quiescent HCMV infection can trigger a stress response in glioma cells and modulate ATF5 levels by downregulating specific miRNA.


Assuntos
Infecções por Citomegalovirus , Glioma , MicroRNAs , Fatores Ativadores da Transcrição/genética , Citomegalovirus/genética , Infecções por Citomegalovirus/genética , Humanos , MicroRNAs/genética
17.
Curr Top Med Chem ; 21(19): 1737-1755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34392823

RESUMO

Notwithstanding the noteworthy advances in its treatment, cancer remains one of the most serious threatens to humans across the world. Hydroxamic acid derivatives, the potential inhibitors of Histone Deacetylases (HDACs), could inhibit cancer cell proliferation, induce cell differentiation, apoptosis and autophagy, and suppress angiogenesis, invasion as well as metastasis through diverse signaling pathways. Thus, hydroxamic acid derivatives exhibit promising activity against cancers and are useful scaffolds in modern anticancer drug discovery. The purpose of the present review article is to summarize the recent developments (Jan, 2011-Jan, 2021) in hydroxamic acid derivatives with insights into their in vivo anticancer potential and mechanisms of action.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Histona Desacetilases/metabolismo , Humanos , Ácidos Hidroxâmicos/síntese química , Ácidos Hidroxâmicos/química , Estrutura Molecular
18.
ACS Chem Neurosci ; 12(7): 1252-1261, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33720698

RESUMO

A key transcriptional activator, activating transcription factor 5 (ATF5), is aberrantly overexpressed in glioma and supports both poor prognosis and antiapototic potential. Unfortunately, data on ATF5 is largely based on its regulatory mechanism. Further investigation of the upstream regulatory factor for ATF5 transcription in glioma is required. Clinical data for patients with diagnosed glioma were obtained from The Cancer Genome Atlas (TCGA). Additionally, transcription factors potentially regulating the ATF5 promoter in glioma were screened with bioinformatics. A further experimental study was performed to investigate both the role of E74-like factor 1 (ELF1) and the binding of ELF1 and the ATF5 promoter in glioma. We show that ATF5 expression is upregulated in glioma tissues and associated with tumor malignancy and worse prognosis. As a putative upstream regulator, silencing ELF1 inhibits glioma cell growth and migration with ATF5 involvement. Moreover, ELF1 upregulation is also associated with poor prognosis in glioma. Importantly, the luciferase assay and chromatin immunoprecipitation (ChIP) reveal that the ATF5 gene promoter is essential for ELF1-dependent activation of ATF5 gene transcription. These results indicate that a high expression of ELF1 may be related to the malignant behavior of human glioma and ELF1 promotes glioma development mediated by transactivation of the ATF5 gene.


Assuntos
Fatores Ativadores da Transcrição , Glioma , Fatores Ativadores da Transcrição/genética , Fatores Ativadores da Transcrição/metabolismo , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Glioma/genética , Humanos , Proteínas Nucleares , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Regulação para Cima
19.
Curr Top Med Chem ; 21(5): 426-437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32552650

RESUMO

Drug resistance is the major cause of the failure of cancer chemotherapy, so one of the most important features in developing effective cancer therapeutic strategies is to overcome drug resistance. Quinoline moiety has become one of the most privileged structural motifs in anticancer agent discovery since its derivatives possess potent activity against various cancers including drug-resistant cancers. Several quinoline-based compounds which are represented by Anlotinib, Bosutinib, Lenvatinib, and Neratinib have already been applied in clinical practice to fight against cancers, so quinoline-based compounds are potential anticancer agents. The present short review article provides an overview of the recent advances of quinoline-based compounds with potential activity against drug-resistant cancers. The structure-activity relationship and mechanisms of action are also discussed.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Quinolinas/uso terapêutico , Desenho de Fármacos , Humanos , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-Atividade
20.
J Craniofac Surg ; 32(1): 228-232, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33186284

RESUMO

PURPOSE: To evaluate various factors that could be associated with the postoperative prognosis of patients with craniopharyngiomas and provide evidence for the proper surgical course and optimal outcome assessments of craniopharyngiomas. METHODS: We performed a retrospective study and reviewed 68 patients with craniopharyngiomas who received surgery from May 2013 to October 2018. The relationships between the disease prognosis and age, gender, onset symptoms, size of tumor, degree of calcification, consistency, QST classification, adhesion strength, and pathological types were analyzed. RESULTS: There were no significant associations between the prognosis and age, gender, number of onset symptoms, and pathological types (P > 0.05). The severity of onset symptoms, tumor diameter, and degree of calcification was significantly associated with the prognosis (P < 0.05). There were significant different prognoses between patients with cystic and solid, mixed tumors (P < 0.05). The prognosis of patients with T type tumors was different from that of patients with either Q or S type tumors (P < 0.05). The prognoses of patients with either loose or tight type tumors were significantly different from those of patients with either invasive or fusion type tumors (P < 0.05). CONCLUSION: Clinical and pathological variables, such as onset symptoms, size of tumor, degree of calcification, consistency, QST classification, and the degree of adhesion strength, were important factors in evaluating the prognosis of patients with craniopharyngiomas.


Assuntos
Craniofaringioma/cirurgia , Neoplasias Hipofisárias/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Adulto Jovem
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