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1.
ACS Appl Mater Interfaces ; 16(7): 9323-9332, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38334091

RESUMO

Chiral luminescent liquid crystals have attracted widespread attention from researchers due to their unique advantages in constructing circularly polarized luminescent (CPL) materials with large luminescent asymmetry factor (glum) values. However, how to effectively prepare nondoped CPL chiral liquid crystals remains a challenge. In this article, we developed an effective and universal method to prepare nondoped CPL chiral liquid crystal materials. To achieve our strategy, we copolymerized chiral monomer M0Mt with α-cyanostilbene-based luminescent monomers MmPVPCN (m = 6, 8, 10) bearing different flexible spacer lengths to obtain a series of CPL chiral liquid crystal copolymers poly(MmPVPCN(x)-co-M0Mt(y)). Under the induction of the chiral component, the α-cyanostilbene component assembles to form chiral liquid crystals. Meanwhile, α-cyanostilbene also exhibits aggregation-induced emission enhancement characteristics. Therefore, with the help of the selective reflection effect of chiral liquid crystals, the copolymer films can emit efficient CPL. For poly(M8PVPCN(0.85)-co-M0Mt(0.15)), the glum and solid luminescence quantum yield can achieve -2.61 × 10-2 and 25.04%, respectively. In addition, by altering the chemical structure of the copolymers, the phase structure of the copolymers can be effectively controlled, thereby regulating their CPL properties.

2.
ACS Appl Mater Interfaces ; 15(42): 49701-49711, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37846058

RESUMO

Room-temperature phosphorescent (RTP) liquid crystal materials have garnered considerable attention because of their significant applications in organic light emitting diodes, polarized light emitting materials, and so forth. How to efficiently synthesize pure organic RTP liquid crystals and regulate their performance is of great significance. In this article, we propose a simple and feasible method to synthesize RTP liquid crystals and manipulate their properties through copolymerization. We constructed RTP liquid crystal copolymers by copolymerizing a phosphorescent monomer bearing biphenyl mesogen with a phosphorescent monomer bearing a dibenzofuran chromophore. All the synthesized copolymers show a liquid crystal property because of the introduction of biphenyl mesogen. Meanwhile, by changing the composition of copolymers, it is possible to regulate their RTP performance, including luminescence color and lifetime. As the content of the PMDFM0C component in copolymers increases, the phosphorescence lifetime gradually increases. For poly(MDFM0C(0.46)-co-MBi18C(0.54)), the phosphorescence lifetime can reach 463.0 ms. Moreover, the phosphorescence color of the PMDFM0C component in copolymers changes with the copolymer composition, which can induce variable room-temperature phosphorescence. In addition, when oriented, liquid crystal copolymer films can emit linearly polarized fluorescence and linearly polarized phosphorescence. The linearly polarized phosphorescence dichroic ratio and polarization ratio values of the oriented poly(MDFM0C(0.46)-co-MBi18C(0.54)) film are 3.33 and 0.50, respectively.

3.
Macromol Rapid Commun ; 44(24): e2300449, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37792542

RESUMO

Circularly polarized luminescence (CPL) materials with clustering-triggered emission (CTE) characteristic have gradually attracted attention for their unique photophysical properties. However, the majority of reported clusteroluminogens lack chirality and exhibit heterogeneity, making it challenging to achieve a well-defined helical structure necessary for efficient CPL with high dissymmetry factor (glum ). In this paper, chiral liquid crystals are constructed to obtain CTE-based CPL materials with high glum values. Side chain liquid crystal polymer PM6Chol bearing cholesterol clusteroluminogens are designed and synthesized. PM6Chol-coated film and PM6Chol thermal-treated film are also successfully prepared by different film-forming methods. Both the films inherit the CTE characteristic of cholesterol and show excitation wavelength-dependent luminescent behavior. However, the two polymer films exhibit different liquid crystal phase structures, with PM6Chol-coated film being a chiral bilayer smectic C phase and PM6Chol thermal-treated film being an achiral bilayer smectic A phase. Attributed to helical arrangement of cholesterol, PM6Chol-coated film emits efficient CPL with glum values up to 1.0 × 10-1 . For PM6Chol thermal-treated film, no CPL signal is detected due to the absence of helical structure. However, it shows obvious room-temperature phosphorescence with 2.0 s afterglow and 23.9 ms lifetime.


Assuntos
Luminescência , Polímeros , Temperatura , Colesterol , Análise por Conglomerados
4.
Naunyn Schmiedebergs Arch Pharmacol ; 396(12): 3797-3807, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37347266

RESUMO

Acute lung injury (ALI) and sepsis are complicated syndromes that are often left untreated in critically ill patients. 6-Gingerol is a phenolic phytochemical compound that is found in fresh ginger, has pharmacological effects against inflammation. This study explored the roles of 6-gingerol in a mouse model of acute lung injury caused by lipopolysaccharide (LPS) and RAW-264.7 cells inflammation. The LPS-induced animal model underwent histopathological examinations, and RAW-264.7 cells viability was determined by Cell counting Kit-8 (CCk-8) assay. Additionally, qRT-PCR, Immunofluorescence, Western blot, and ELISA were used in vivo and in vitro to identify inflammatory factors and proteins associated with NF-κB and MAPK signaling pathways. In a histological examination 6-gingerol exhibited protective effects. Moreover, 6-gingerol elevated cell viability and downregulated inflammatory factors Interlukin-1ß (IL-1ß), Interlukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α) in LPS-treated RAW-264.7 cells. Furthermore, 6-gingerol decreased phosphorylation of P65, P38 and the level of JNK in NF-κB and MAPK pathways. Importantly, 6-gingerol increased transcript abundance of miR-322-5p which suppressed by LPS and miR-322-5p downregulation negated the protective functions of 6-gingerol. The protective activity of 6-gingerol was mediated by miR-322-5p up-regulation.


Assuntos
Lesão Pulmonar Aguda , MicroRNAs , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Transdução de Sinais , MicroRNAs/genética , MicroRNAs/metabolismo , Células RAW 264.7 , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/genética , Lesão Pulmonar Aguda/patologia
5.
Front Neurol ; 14: 1278366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38239324

RESUMO

Background and objective: The safety and efficacy of on-label use of pipeline embolization devices (PEDs) are well established; however, there is much controversy over their off-label use. This study aimed to investigate the safety and efficacy of the off-label use of PEDs for treating intracranial aneurysms. Methods: This single-center study retrospectively included patients with digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography confirmed intracranial aneurysms treated with PEDs who were admitted to our institution between 1 January 2018 and 1 July 2022. Patients were divided into on- and off-label groups according to the Food and Drug Administration criteria published in 2021. Propensity score matching (PSM) was used to balance disparities in baseline information between the two groups. Safety outcomes included postoperative mortality and complication rates, whereas effectiveness outcomes included aneurysm occlusion rate (O'Kelly-Marotta grading system C + D grades), retreatment rate within 12 months, and postoperative functional score [modified Rankin scale (mRS) score]. The study was approved by the Ethics Committee of Scientific Research and Clinical Trial of the First Affiliated Hospital of Zhengzhou University (Ethics number: KY 2018-098-02). All patients provided informed consent. Results: A total of 242 patients with 261 aneurysms (160 on-label and 101 off-label aneurysms) were included in this study. PSM yielded 81 pairs of patients matched for baseline information. Postoperative hemorrhagic, ischemic, and procedure-related complication rates did not reach statistical significance. In addition, no statistically significant differences in the aneurysm occlusion rate, retreatment rate within 12 months, postoperative functional score (mRS score), or mRS score deterioration rate were observed between the two groups. A higher incidence of in-stent stenosis was observed in the off-label (4.9% vs. 21%, p = 0.002) group than in the on-label group; however, all patients were asymptomatic. Conclusion: Compared with on-label use, off-label use of PEDs for treating intracranial aneurysms did not increase the risk of complications, and the occlusion rates were comparable. Therefore, decisions regarding clinical management should not rely solely on on- or off-label indications.

6.
Front Neurol ; 13: 1029699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353129

RESUMO

Background: The risk of perioperative stroke and the rate of occlusion of long-term aneurysms in the treatment of unruptured aneurysms with flow diverters (FDs) are affected by stent apposition. Optical coherence tomography (OCT) may be an optional technique in evaluating apposition. Purpose: To explore the feasibility of the OCT imaging technique in evaluating stent apposition in the clinical application of the FD for unruptured aneurysms. Methods: OCT and Vaso CT were used in patients with indications for surgery to treat unruptured aneurysms with the FDs, to evaluate the apposition of the FDs after fully released, and to analyze OCT images for FDs apposition and compare with corresponding Vaso CT images. Results: A total of four patients were enrolled, and OCT found malapposition after FDs placement in all four patients, and the maximum gap between the stent and vascular wall ranged from 0.68 to 1.95 mm and the length of malapposition ranged from 1.80 to 7.40 mm. However, Vaso CT found malapposition only in two of the four patients and missed malapposition near aneurysm in all three patients treated by the FD combined with coiling and could not accurately evaluate the maximum gap and the length of the malapposition. Conclusion: The optical coherence tomography technique is a possible approach to evaluate apposition after the treatment of unruptured aneurysms by the FDs.

7.
Soft Matter ; 18(29): 5483-5491, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35838375

RESUMO

In recent years, great progress has been made in the preparation methods and performance regulation of host-guest doped CPL liquid crystal materials. However, there still exist some basic problems to be solved, such as complex packaging and unstable CPL properties. With the consideration of the above problems, in this study, we introduced gelators into the host-guest doped CPL liquid crystal materials to prepare CPL liquid crystal physical gels. The gelators can be assembled to form a nanofiber physical gel network, which limits the movement of the liquid crystals and enhances the stability of the CPL properties. Meanwhile, liquid crystal physical gels show self-supporting ability and the gel-sol phase transition temperature can reach 136 °C. The amplification of the glum value is achieved by self-assembly of chiral liquid crystals, and the glum value can reach -0.31. The phase structure changes with electric field and temperature, and the CPL properties can be regulated by changing the temperature and electric field. With the increasing applied voltage or the temperature, the glum value decreases. Therefore, we have successfully prepared a new type of CPL liquid crystal physical gels with self-supporting performance, stimulus response performance and large glum values.

8.
Macromol Rapid Commun ; 43(6): e2100717, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35083802

RESUMO

Photoresponsive liquid crystal elastomers (LCEs) have aroused much attention due to their unique structures, properties, and potential applications. However, many reported photoresponsive LCEs show small photoinduced deformation with a slow deformation speed, which limits their application to a certain extent. In this article, multiple hydrogen bond component and biphenyl component was introduced into photoresponsive LCEs bearing cyanostilbene by copolymerization, and prepared a series of LCEs CSm-BPn (CS and BP means cyanostilbene and biphenyl component, respectively; m, n means the content ratio of CS and BP). All uniaxially oriented CSm-BPn fibers show photoinduced deformation behavior under 365 nm UV light except for CS0-BP5. The introduction of hydrogen bond and the decrease of glass transition temperature realize large deformation and fast deformation speed. Besides, the properties of LCEs are successfully regulated by changing the content ratio of each component. What's more interesting is that the addition of appropriate amount of biphenyl can significantly improve and manipulate the deformation property of the CSm-BPn fibers. The maximum bending angle can reach 175° , and the whole photoinduced deformation process only takes 11 s. The photoresponsive LCEs with such large bending angle and fast deformation rate are rarely reported.


Assuntos
Elastômeros , Cristais Líquidos , Elastômeros/química , Ligação de Hidrogênio , Cristais Líquidos/química , Temperatura , Raios Ultravioleta
9.
Clin Case Rep ; 9(8): e04277, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34429973

RESUMO

Iatrogenic ICA injury is a life-threatening and underreported complication of EES. For selected patients, covered stent implantation is the best and only way to block the rupture spot immediately and maintain ICA blood flow.

10.
Front Cell Dev Biol ; 9: 660005, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277607

RESUMO

The development of temozolomide (TMZ) resistance in glioma leads to poor patient prognosis. Sorafenib, a novel diaryl urea compound and multikinase inhibitor, has the ability to effectively cross the blood-brain barrier. However, the effect of sorafenib on glioma cells and the molecular mechanism underlying the ability of sorafenib to enhance the antitumor effects of TMZ remain elusive. Here, we found that sorafenib could enhance the cytotoxic effects of TMZ in glioma cells in vitro and in vivo. Mechanistically, the combination of sorafenib and TMZ induced mitochondrial depolarization and apoptosis inducing factor (AIF) translocation from mitochondria to nuclei, and this process was dependent on STAT3 inhibition. Moreover, the combination of sorafenib and TMZ inhibited JAK2/STAT3 phosphorylation and STAT3 translocation to mitochondria. Inhibition of STAT3 activation promoted the autophagy-associated apoptosis induced by the combination of sorafenib and TMZ. Furthermore, the combined sorafenib and TMZ treatment induced oxidative stress while reactive oxygen species (ROS) clearance reversed the treatment-induced inhibition of JAK2/STAT3. The results indicate that sorafenib enhanced the temozolomide sensitivity of human glioma cells by inducing oxidative stress-mediated autophagy and JAK2/STAT3-AIF axis.

11.
J Neurointerv Surg ; 13(1): 33-38, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32641417

RESUMO

BACKGROUND: Mechanical thrombectomy with a stent retriever (SR) and/or aspiration is the 'gold standard' for the treatment of acute ischemic stroke due to large vessel occlusion (LVO). However, sometimes clots may not be retrievable with a single SR alone or combined with aspiration. OBJECTIVE: To assess the safety and efficacy of a novel tandem stents thrombectomy (TST) technique as a rescue treatment for acute LVO that is refractory to conventional attempts. METHODS: All patients treated with the TST technique as rescue treatment after failure of conventional attempts were retrospectively reviewed. The postprocedural angiographic and clinical outcome, including modified Thrombolysis in Cerebral infarction (mTICI) grade, National Institutes of Health Stroke Scale (NIHSS) score, and modified Rankin Scale (mRS) score, was assessed. RESULTS: Nine patients (mean age, 65.2 years; median NIHSS score 18) with middle cerebral artery M1 segment (n=6) and terminal internal carotid artery (n=3) occlusions were included in the study. The TST technique was performed as a rescue treatment after unsuccessful stent thrombectomy alone (four cases) and stent thrombectomy plus aspiration (five cases). Successful recanalization (mTICI 2b/3) was achieved in all patients. No procedure-related complications occurred except reversible vasospasms were observed in three patients and one patient developed hemorrhage transformation after the procedure, but was asymptomatic. Three patients had good clinical outcome (mRS score 0-2 at 90 days). Two patients (22.2%) died. CONCLUSIONS: The TST technique seems to be a safe and effective rescue treatment for acute LVO that is refractory to conventional attempts.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Stents , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombectomia/instrumentação , Resultado do Tratamento
12.
ACS Appl Mater Interfaces ; 12(50): 56604-56614, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33274914

RESUMO

Considerable luminescence dissymmetry factor (glum) is vital for application implementation of circularly polarized luminescence (CPL) materials. Moreover, a dual CPL switch has promising prospects in high-security encryption and sensor devices. Herein, we designed and synthesized an emissive chiral nematic liquid crystal (N*-LC) by doping a luminescent chiral additive (NO2-CS-C6-Chol) into a nematic liquid crystal (5CB). The helical assembly structure produced by inducing the formation of N*-LC endows the prepared emissive N*-LC with a larger glum value. With the increase of the doping concentration from 1 to 10 wt %, the helical pitch (P) of N*-LC gradually decreases from 25.48 to 3.92 µm. The corresponding glum value increases first, reaches the maximum value (-0.38) at 6 wt %, and then decreases slightly. Further, the prepared emissive N*-LC doped with 6 wt % NO2-CS-C6-Chol is injected into an indium-tin oxide (ITO)-coated LC cell, to which a direct current (DC) electric field is applied. The glum value can be repeatedly shuttled between the "on" and "off" state by adjusting the applied voltage. Meanwhile, owing to the inherent thermal dependence of the liquid crystal phase structure, the glum value can also be switched between the on and off state by regulating the temperature. Therefore, an electrically controlled and thermocontrolled dual CPL switching device is successfully constructed.

13.
Front Neurol ; 11: 774, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849227

RESUMO

Objective: Symptomatic in-stent restenosis (sISR) is the major cause of medium- or long-term cerebral infarctions in patients who underwent percutaneous transluminal angioplasty and stenting for severe intracranial atherosclerotic stenosis. This study aims to evaluate the feasibility and safety of paclitaxel-coated balloon (PCB) angioplasty for the treatment of intracranial sISR. Methods: We report 11 cases of PCB angioplasty for intracranial sISR. Lesion locations and number were as follows: intracranial internal carotid artery (n = 4), M1 segment of middle cerebral artery (MCA) (n = 1), V4 segment of vertebral artery (n = 6). The technical success rate, periprocedural complications, and short-term outcome were retrospectively analyzed. Results: All procedures were successfully performed without periprocedural complication. Asymptomatic vessel dissection after PCB inflation occurred in one case. Postprocedural diffusion-weighted imaging (DWI) showed new asymptomatic ipsilateral infarction in one case. All 11 cases did not experience ipsilateral stroke or death within 30 days or ischemic stroke in the territory of the target artery between 31 and 90 days after procedure. Conclusion: This preliminary study indicates that PCB angioplasty is feasible and safe for the treatment of intracranial sISR. Further studies are needed to clarify its efficiency and long-term outcome.

14.
World Neurosurg ; 141: 437-438.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32311570

RESUMO

A patient presented with progressive ischemic stroke and received mechanical thrombectomy with a Solitaire FR device 29 days after stroke onset. The occluded V4 segment of the left vertebral artery showed a double rail sign on angiography, which indicated that the occlusion might have been caused by embolism instead of stenosis. The mechanical thrombectomy procedure was a 1-pass success and the patient was functionally independent with a modified Rankin Scale score of 1 at 3-month follow-up. The appearance of the vascular wall (double rail sign) of the occluded cerebral vascular segment on angiography may be a significant feature to identify the character of the occlusion even a long time after onset, which is important when planning further endovascular therapy in patients with ischemic stroke.


Assuntos
Isquemia Encefálica/cirurgia , AVC Isquêmico/cirurgia , Stents/efeitos adversos , Trombectomia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Cabeça/cirurgia , Humanos , AVC Isquêmico/diagnóstico , Anamnese/métodos , Trombectomia/efeitos adversos , Trombectomia/métodos , Artéria Vertebral/cirurgia
15.
Adv Colloid Interface Sci ; 277: 102119, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32045722

RESUMO

Emulsions, including oil-in-water (O/W) and water-in-oil (W/O) emulsions, can play important roles in both controlling reservoir conformance and displacing residual oil for enhanced oil recovery (EOR) projects. However, current methods, like high-shear mixing, high-pressure homogenizing, sonicators and others, often use lots of extra energy to prepare the emulsions with high costs but very low energy efficiency. In recent decades, spontaneous emulsification methods, which allow one to create micro- and nano-droplets with very low or even no mechanical energy input, have been launched as an overall less expensive and more efficient alternatives to current high extra energy methods. Herein, we primarily review the basic concepts on spontaneous emulsification, including mechanisms, methods and influenced parameters, which are relevant for fundamental applications for industrials. The spontaneity of the emulsification process is influenced by the following variables: surfactant structure, concentration and initial location, oil phase composition, addition of co-surfactant and non-aqueous solvent, as well as salinity and temperature. Then, we focus on the description of importance for emulsions in EOR processes from advances and categories to improving oil recovery mechanisms, including both sweep efficiency and displacement efficiency aspects. Finally, we systematically address the applications and outlooks based on the use of spontaneous emulsification in the practical oil reservoirs for EOR processes, in which conventional, heavy, high-temperature, high-salinity and low-permeability oil reservoirs, as well as wastewater treatments after EOR processes are involved.

16.
Front Neurol ; 10: 428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156528

RESUMO

Objective: To test whether Neuroform EZ stent placement combined with the modified techniques in symptomatic severe intracranial stenosis (ICAS) would result in lower rates of peri-procedural complications of intracranial stenting. Methods: We retrospectively reviewed the clinical data from 71 consecutive patients who underwent Neuroform EZ stent placement combined with the modified techniques for symptomatic severe ICAS at our institute between January 2016 and October 2017. The primary outcomes were ipsi-lateral ischemic stroke, intra-cerebral hemorrhage, or death within 30 days after stenting. The secondary outcome was technical success. Results: The technical success rate was 100%. The mean pre and post-stent stenoses were 84.2% ± 9.1% (median 85%, IQR75% to 90%) and 16.9% ± 10.2 % (median 15%, IQR 10% to 25%). The frequency of ipsi-lateral stroke, intra-cerebral hemorrhage, or death within 30 days was 0%. Conclusions: The combined use of Neuroform EZ stent placement and the modified techniques for symptomatic severe ICAS is technically feasible and safe, with very low peri-procedural complications. Further studies are required to assess the long-term results of this approach.

17.
J Exp Clin Cancer Res ; 38(1): 77, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760281

RESUMO

BACKGROUND: Metformin, a first-line drug for type 2 diabetes, could induce apoptosis in cancer cells. However, the concentration of glucose affects the effect of metformin, especially low glucose in the culture medium can enhance the cytotoxicity of metformin on cancer cells. Since mitochondria and endoplasmic reticulum is vital for maintaining cell homeostasis, we speculate that low glucose and metformin-induced cell apoptosis may be associated with mitochondria and endoplasmic reticulum. ASK1, as apoptosis signaling regulating kinase 1, is associated with cell apoptosis and mitochondrial damage. This study was designed to investigate the functional significance of ASK1, mitochondria and endoplasmic reticulum and underlying mechanism in low glucose and metformin-induced cell apoptosis. METHODS: An MTT assay was used to evaluate cell viability in SKOV3, OVCAR3 and HO8910 human ovarian cancer cells. Cell apoptosis was analyzed by flow cytometry. The expression of ASK1 was inhibited using a specific pharmacological inhibitor or ASK1-siRNA. Immunofluorescence was used to detect mitochondrial damage and ER stress. Nude mouse xenograft models were given metformin or/and NQDI-1, and ASK1 expression was detected using immunoblotting. In addition, subcellular fractionation of mitochondria was performed to assay the internal connection between ASK1 and mitochondria. RESULTS: The present study found that low glucose in culture medium enhanced the anticancer effect of metformin in human ovarian cancer cells. Utilization of a specific pharmacological inhibitor or ASK1-siRNA identified a potential role for ASK1 as an apoptotic protein in the regulation of low glucose and metformin-induced cell apoptosis via ASK1-mediated mitochondrial damage through the ASK1/Noxa pathway and via ER stress through the ROS/ASK1/JNK pathway. Moreover, ASK1 inhibition weakened the antitumor activity of metformin in vivo. Thus, mitochondrial damage and ER stress play a crucial role in low glucose-enhanced metformin cytotoxicity in human ovarian cancer cells. CONCLUSIONS: These data suggested that low glucose and metformin induce cell apoptosis via ASK1-mediated mitochondrial damage and ER stress. These findings indicated that the effect of metformin in anticancer treatment may be related to cell culture conditions.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Glucose , MAP Quinase Quinase Quinase 5/metabolismo , Metformina/farmacologia , Neoplasias Ovarianas/patologia , Animais , Linhagem Celular Tumoral , Meios de Cultura/química , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Cancer Lett ; 428: 77-89, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29705182

RESUMO

The introduction of temozolomide (TMZ) has improved chemotherapy for malignant gliomas. However, many gliomas are refractory to TMZ, so there is a pressing need for more effective therapeutic options. Here we demonstrated that glioma specimens and cell lines have constitutively high levels of nuclear factor κB (NF-κB) activity. Notably, the expression levels of this transcription factor correlated with malignant grades in glioblastoma multiforme (GBM) and inversely correlated with overall survival. Conversely, knockdown of NF-κB inhibits glioma cell proliferation and treating a panel of established glioma cell lines with pharmacological NF-κB inhibitors markedly decreased glioma viability, led to S cell cycle arrest, and induced apoptosis. We also found a significant correlation between NF-κB expression and O6-methylguanine-DNA methyltransferase (MGMT) expression in gliomas with different origins, and immunohistochemistry confirmed these findings. Genetic or pharmacological (especially parthenolide) inhibition of NF-κB activity down-regulated MGMT gene expression and substantially restored TMZ chemosensitivity in vitro and in vivo. Importantly, the TMZ sensitizing effect of siNF-κB(p65) or parthenolide were rescued by MGMT cDNA expression. These findings suggest that NF-κB is a potential target for inducing cell death in gliomas. A targeted combination strategy in which the response to TMZ is synergistically enhanced by the addition of parthenolide which may be useful, especially in chemoresistant gliomas with high MGMT expression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Fator de Transcrição RelA/antagonistas & inibidores , Proteínas Supressoras de Tumor/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Glioblastoma/patologia , Humanos , Camundongos , Camundongos SCID , RNA Interferente Pequeno/metabolismo , Ratos , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Resultado do Tratamento , Proteínas Supressoras de Tumor/genética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Exp Ther Med ; 15(1): 145-151, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29387186

RESUMO

In the present study, a recombinant adeno-associated virus vector containing the calcitonin gene related peptide gene (rAAV-CGRP) was constructed and the therapeutic effect of rAAV-CGRP on a chick umbilical artery vasospasm model induced by chick embryo allantoic cavity hemorrhage was investigated. Fresh specific pathogen-free fertilized chicken eggs were randomly divided into a rAAV-CGRP group, an empty vector virus (AAV) group, and a control group, with 24 eggs in each group. An umbilical arterial vasospasm model was established using a needle puncture method on a vein in the chorioallantoic membrane to induce a hemorrhage in the allantoic cavity of 11-day-old chicken embryonated eggs. A total of 24 h after model establishment, 1 ml of rAAV-CGRP and empty vector virus solution of rAAV-CGRP and empty vector virus solution was, respectively, injected into the allantoic cavity in the rAAV-CGRP and AAV groups. Experimental results showed that after 72 h of model establishment, the mortality rates of the 3-, 5- and 7-day subgroups in the rAAV-CGRP group were lower than in the subgroups of the AAV injection group. After 3, 5 and 7 days of model establishment in the rAAV-CGRP group, the cross-sectional area of the inner diameter of the umbilical arteries was larger than that of the AAV group; the vessel wall thicknesses of the rAAV-CGRP group were thinner than in the AAV group. In addition, the concentration of CGRP in chick embryo allantoic fluid significantly increased and was several times higher than in the AAV group (P<0.05). In conclusion, administration of rAAV-CGRP through the allantoic cavity may increase the viability of a vasospasm model induced by chick allantoic cavity hemorrhage, significantly improve umbilical artery vasospasm, and increase CGRP expression in the chick embryo allantoic cavity. This approach also provides a novel experimental model for identifying other target genes for the gene therapy of vasospasm.

20.
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.

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