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1.
J Neurosurg ; : 1-11, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38364227

RESUMO

OBJECTIVE: The authors performed a further in-depth study of the lateral compartment of the cavernous sinus (LCCS) by the endoscopic endonasal approach to improve the safety and efficacy of the lateral approach for the removal of Knosp grade 4 pituitary adenomas (KG4PAs). METHODS: Twenty-three cadaveric specimens were used for endoscopic endonasal dissection, and the LCCS was exposed to observe the neurovascular and fibrous structures within. A subclassification of the lateral approach based on further knowledge of the LCCS was proposed and used to resect 86 KG4PAs, and the surgical outcomes of these cases were reviewed. Type A KG4PAs represent tumor that was mainly distributed in the posterosuperior and superolateral compartments, type B KG4PAs represent tumor that was mainly distributed in the anteroinferior compartments, and type AB KG4PAs represent tumor that extended into each compartment with characteristics of types 4A and 4B. RESULTS: The authors identified multiple fibers that anchored the horizontal segment of the internal carotid artery (ICA) to the abducens nerve. The fibers, the sympathetic nerve, and the inferior lateral trunk form a partition-like structure in the LCCS named the abducens nerve-ICA complex (AIC), and the LCCS can be divided into the superolateral and inferolateral compartments by the AIC. Accordingly, the lateral approach was subclassified into the lateral superior (LS) approach and the anterior inferior (AI) approach. The LS approach was mainly used to resect type A KG4PAs, whereas the AI approach was used to resect type B KG4PAs, and a combination of the two was used to resect type AB KG4PAs. The gross-total, subtotal, and partial resection rates were 81.4%, 12.8%, and 5.8%, respectively. The numbers of cases of postoperative transient cranial nerve palsy, postoperative permanent cranial nerve palsy, ICA injury, and CSF leakage were 6 (6.9%), 2 (2.3%), 1 (1.2%), and 1 (1.2%), respectively. CONCLUSIONS: This study revealed that the LCCS is divided by the AIC into the superolateral and inferolateral compartments, avoiding the misconception that the LCCS has vertical communication. Therefore, the lateral approach was subclassified into the LS approach and the AI approach for the resection of KG4PAs, which allowed a high gross-total resection rate with acceptable safety in the surgical treatment of KG4PAs.

2.
Eur J Med Chem ; 265: 116118, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181651

RESUMO

In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18, exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 µM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 µM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18, which possesses significant potential for treating esophageal cancers.


Assuntos
Antineoplásicos , Neoplasias Esofágicas , Melfalan , gama-Globulinas , Humanos , Moduladores de Tubulina , Tubulina (Proteína)/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Relação Estrutura-Atividade , Benzotiazóis/farmacologia , Triazóis/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Polimerização , Estrutura Molecular
3.
Am J Ophthalmol ; 258: 196-207, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37879454

RESUMO

PURPOSE: This study seeks to evaluate the ability of the updated stress strain index (SSIv2) and other Corvis ST biomechanical parameters in distinguishing between keratoconus at different disease stages and normal eyes. DESIGN: Diagnostic accuracy analysis to distinguish disease stages. METHODS: 1084 eyes were included and divided into groups of normal (199 eyes), forme fruste keratoconus (FFKC, 194 eyes), subclinical keratoconus (SKC, 113 eyes), mild clinical keratoconus (CKC-Ⅰ, 175 eyes), moderate clinical keratoconus (CKC-Ⅱ, 204 eyes), and severe clinical keratoconus (CKC-Ⅲ, 199 eyes). Each eye was subjected to a Corvis ST examination to determine the central corneal thickness (CCT), biomechanically corrected intraocular pressure (bIOP), SSIv2 (updated stress-strain index), and other 8 Corvis parameters including the stress-strain index (SSIv1), stiffness parameter at first applanation (SP-A1), first applanation time (A1T), Ambrósio relational thickness to the horizontal profile (ARTh), integrated inverse radius (IIR), maximum deformation amplitude (DAM), ratio between deformation amplitude at the apex and at 2 mm nasal and temporal (DARatio2), and Corvis biomechanical index (CBI). The sensitivity and specificity of these parameters in diagnosing keratoconus were analyzed through receiver operating characteristic curves. RESULTS: Before and after correction for CCT and bIOP, SSIv2 and ARTh were significantly higher and IIR and CBI were significantly lower in the normal group than in the FFKC group, SKC group and the 3 CKC groups (all P < .05). There were also significant correlations between the values of SSIv2, ARTh, IIR, CBI, and the CKC severity (all P < .05). AUC of SSIv2 was significantly higher than all other Corvis parameters in distinguishing normal eyes from FFKC, followed by IIR, ARTh and CBI. CONCLUSION: Corvis ST's updated stress-strain index, SSIv2, demonstrated superior performance in differentiating between normal and keratoconic corneas, and between corneas with different keratoconus stages. Similar, but less pronounced, performance was demonstrated by the IIR, ARTh and CBI.


Assuntos
Ceratocone , Humanos , Ceratocone/diagnóstico , Topografia da Córnea , Córnea , Tonometria Ocular , Pressão Intraocular , Curva ROC , Fenômenos Biomecânicos
4.
Acta Neurochir (Wien) ; 165(10): 2985-2993, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37672094

RESUMO

BACKGROUND: The anatomical basis of pituitary adenomas (PAs) with oculomotor cistern (OC) extension as a growth corridor is overlooked in the literature. In this paper, the authors use the technique of epoxy sheet plastination to study the membranous structure of the OC and validate the results by retrospective analysis of patients with OC extension. METHODS: Eighteen specimens were used to study the membranous anatomy surrounding the OC using the epoxy sheet plastination technique. Thirty-four patients with OC extension were retrospectively reviewed. RESULTS: The OC consisted of two thin membranous layers. The inner layer was extended by the arachnoid layer from the posterior fossa, and the lateral layer consisted of the dura mater sinking from the roof of the cavernous sinus. The oculomotor nerve is more likely to displace with a superolateral trajectory due to the weakness of the posterior dura and the relatively large space in the medial and posterior trajectories, which is consistent with the intraoperative observations. Among the anatomical factors that affect the PA by OC extension, we found that the relative position of the internal carotid artery (ICA) and posterior clinoid process may lead to the narrowing of the OC. Of 34 cases, 28 patients achieved total resection. Among 24 preoperative patients with oculomotor nerve palsy, 16 cases were relieved to varying degrees postoperatively. There was no ICA injury or severe intracranial infection found in any of the patients. CONCLUSIONS: Extension into the OC is influenced by two anatomical factors: a weak point in the dura in the posterior OC and a potential space beyond this region of the dura. Meticulous knowledge of the membranous anatomy in endoscopic endonasal surgery is required to safely and effectively resect PA with OC extension.


Assuntos
Adenoma , Doenças do Nervo Oculomotor , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Sela Túrcica , Nervo Oculomotor/cirurgia , Adenoma/cirurgia
5.
Laryngoscope ; 133(10): 2564-2571, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37341509

RESUMO

OBJECTIVES: To describe four endoscopic endonasal subapproaches, namely, the trans-lamina papyracea, trans-prelacrimal recess, trans-Meckel's cave, and transclival approaches for trigeminal schwannomas (TSs). METHODS: This retrospective study reviewed the medical records and intraoperative videos of 38 patients with TSs who underwent endoscopic endonasal approach (EEA) between Jan 2013 and Dec 2021. RESULTS: According to Jeong's classification, for TS equally in middle and posterior fossae (MP), a purely trans-Meckel's cave approach was carried out in 2 cases, and a combined transclival approach was carried out in 4 cases. The four tumors that involved infratemporal fossa (two E3, one mE3, and one Mpe3) were performed via a trans-prelacrimal recess approach, and type Mpe3 was also assisted by the trans-Meckel's cave approach. One patient with type E1 was treated with a trans-lamina papyracea approach. The other 27 cases, including type M, Mp, ME2, and MpE2, were all removed by a purely trans-Meckel's cave approach. Thirty-six patients (97.4%) received total resection under a purely EEA. The functional abilities and preoperative symptoms of 31 patients (88.6%) improved. Eight (21.1%) patients experienced permanent neurological function deficits. Postoperative cerebrospinal fluid and intraoperative internal carotid artery injury occurred in 1 (2.6%) patient. CONCLUSION: According to the specific endoscopic endonasal subapproaches corresponding to the different TS locations, satisfactory results can be obtained for most types of tumors. It represents an effective alternative to the open transcranial approach and can also be properly used in most types of TS with experienced hands. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2564-2571, 2023.


Assuntos
Neoplasias dos Nervos Cranianos , Neurilemoma , Humanos , Estudos Retrospectivos , Nariz/cirurgia , Endoscopia/métodos , Neurilemoma/cirurgia , Neurilemoma/patologia , Neoplasias dos Nervos Cranianos/cirurgia
6.
Obesity (Silver Spring) ; 30(7): 1357-1369, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35707874

RESUMO

OBJECTIVE: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult-onset craniopharyngioma. METHODS: The data of 96 patients with surgically treated primary adult-onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression. RESULTS: Forty-seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow-up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%. CONCLUSIONS: Significant postoperative weight gain is common in patients with adult-onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO.


Assuntos
Craniofaringioma , Doenças Hipotalâmicas , Neoplasias Hipofisárias , Adulto , Índice de Massa Corporal , Craniofaringioma/complicações , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/cirurgia , Humanos , Doenças Hipotalâmicas/complicações , Hipotálamo/diagnóstico por imagem , Hipotálamo/patologia , Obesidade/complicações , Obesidade/patologia , Obesidade/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Aumento de Peso
7.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1558-1563, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787154

RESUMO

To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Doença de Alzheimer/tratamento farmacológico , Mineração de Dados , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Prescrições
8.
Am J Physiol Heart Circ Physiol ; 320(1): H458-H468, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33095054

RESUMO

Coronary artery spasm (CAS) is an intense vasoconstriction of coronary arteries that causes total or subtotal vessel occlusion. The cardioprotective effect of sirtuin-1 (SIRT1) has been extensively highlighted in coronary artery diseases. The aims within this study include the investigation of the molecular mechanism by which SIRT1 alleviates CAS. SIRT1 expression was first determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis in an endothelin-1 (ET-1)-induced rat CAS model. Interaction among SIRT1, nuclear factor-kappaB (NF-κB), myosin light chain kinase/myosin light chain-2 (MLCK/MLC2), and ET-1 was analyzed using luciferase reporter assay, RT-qPCR, and Western blot analysis. After ectopic expression and depletion experiments in vascular smooth muscle cells (VSMCs), contraction and proliferation of VSMCs and expression of contraction-related proteins (α-SMA, calponin, and SM22α) were measured by collagen gel contraction, 5-ethynyl-2'-deoxyuridine (EdU) assay, RT-qPCR, and Western blot analysis. The obtained results showed that SIRT1 expression was reduced in rat CAS models. However, overexpression of SIRT1 inhibited the contraction and proliferation of VSMCs in vitro. Mechanistic investigation indicated that SIRT1 inhibited NF-κB expression through deacetylation. Moreover, NF-κB could activate the MLCK/MLC2 pathway and upregulate ET-1 expression by binding to their promoter regions, thus inducing VSMC contraction and proliferation in vitro. In vivo experimental results also revealed that SIRT1 alleviated CAS through regulation of the NF-κB/MLCK/MLC2/ET-1 signaling axis. Collectively, our data suggested that SIRT1 could mediate the deacetylation of NF-κB, disrupt the MLCK/MLC2 pathway, and inhibit the expression of ET-1 to relieve CAS, providing a theoretical basis for the prospect of CAS treatment and prevention.NEW & NOTEWORTHY Rat coronary artery spasm models exhibit reduced expression of SIRT1. Overexpression of SIRT1 inhibits contraction and proliferation of VSMCs. SIRT1 inhibits NF-κB through deacetylation to modulate VSMC contraction and proliferation. NF-κB activates the MLCK/MLC2 pathway. NF-κB upregulates ET-1 to modulate VSMC contraction and proliferation.


Assuntos
Miosinas Cardíacas/metabolismo , Vasoespasmo Coronário/prevenção & controle , Endotelina-1/metabolismo , Músculo Liso Vascular/enzimologia , Cadeias Leves de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , NF-kappa B/metabolismo , Sirtuína 1/metabolismo , Vasoconstrição , Acetilação , Animais , Proliferação de Células , Forma Celular , Células Cultivadas , Vasoespasmo Coronário/enzimologia , Vasoespasmo Coronário/genética , Vasoespasmo Coronário/fisiopatologia , Vasos Coronários/enzimologia , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Masculino , Músculo Liso Vascular/fisiopatologia , NF-kappa B/genética , Ratos Nus , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuína 1/genética
9.
Epigenomics ; 12(17): 1501-1513, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32901506

RESUMO

Aim: Alzheimer's disease (AD) is the most frequent cause of dementia and characterized by the accumulation of ß-amyloid peptides in plaques and vessel walls. This study proposed a hypothesis of an inhibitory role of miR-96-5p in AD via regulating Foxo1. Methods & methods: AD mouse models were established by injecting with 1% pentobarbital. Results: Knockdown of miR-96-5p in the presence of naringin was shown to reduce the expression of Foxo1 and contents of superoxide dismutase, catalase and glutathione peroxidase, yet increase lipocalin-2 expression as well as hydroxyproline and malondialdehyde contents. Also, Foxo1-mediated lipocalin-2 inhibition attenuated AD. Conclusion: Our study shows downregulating miR-96-5p limited AD progression, highlighting miR-96-5p a potential therapeutic target in treating AD.


Assuntos
Doença de Alzheimer/genética , Proteína Forkhead Box O1/genética , Regulação da Expressão Gênica , Lipocalina-2/genética , MicroRNAs/genética , Osteoblastos/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Biomarcadores , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Lipocalina-2/metabolismo , Camundongos , Interferência de RNA
10.
Eur J Med Chem ; 203: 112618, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682200

RESUMO

On the basis and continuation of our previous studies on anti-tubulin and anti-gastric cancer agents, novel tertiary amide derivatives incorporating benzothiazole moiety were synthesized and the antiproliferative activity was studied in vitro. Preliminary structure activity relationships (SARs) were explored according to the in vitro antiproliferative activity results. Some of compounds could significantly inhibit the proliferation of three cancer cells (HCT-116, MGC-803 and PC-3 cells) and compound F10 exhibited excellent antiproliferative activity against HCT-116 cells (IC50 = 0.182 µM), MGC-803 cells (IC50 = 0.035 µM), PC-3 cells(IC50 = 2.11 µM) and SGC-7901 cells (IC50 = 0.049 µM). Compound F10 effectively inhibited tubulin polymerization (IC50 = 1.9 µM) and bound to colchicine binding site of tubulin. Molecular docking results suggested compound F10 could bind tightly into the colchicine binding site of ß-tubulin. Moreover, compound F10 could regulate the Hippo/YAP signaling pathway. Compound F10 activated Hippo signaling pathway from its very beginning MST1/2, as the result of Hippo cascade activation YAP were inhibited. And then it led to a decrease of c-Myc and Bcl-2 expression. Further molecular experiments showed that compound F10 arrested at G2/M phase, inhibited cell colony formatting and induced extrinsic and intrinsic apoptosis in MGC-803 and SGC-7901 cells. Collectively, compound F10 was the first to be reported as a new anticancer agent in vitro via inhibiting tubulin polymerization and activating the Hippo signaling pathway.


Assuntos
Amidas/química , Benzotiazóis/química , Benzotiazóis/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/patologia , Tubulina (Proteína)/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Via de Sinalização Hippo , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP
11.
Nanotechnology ; 31(26): 265405, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32191937

RESUMO

Transition metal oxides have recently been demonstrated as highly attractive anodes for high-capacity lithium ion batteries, whose electrochemical properties could be further improved through rational architecture design and incorporating reliable conductive network. Herein, mesoporous γ-Fe2O3 spheres/graphene aerogel composites were synthesized via a solvothermal pathway followed by suitable annealing. Experimental results reveal the uniform mesoporous structure and well-dispersed γ-Fe2O3 spheres with the size of 300-400 nm embedded in the mesopores of the graphene aerogel network. Compared with α-Fe2O3/graphene aerogel and pure γ-Fe2O3, the as-synthesized composite delivers, at the first cycle, a high discharging capacity of 1080 mAh g-1 at current density of 200 mA g-1. Even at much higher current density of 8000 mA g-1, satisfactory discharging capacities of 421.5 mAh g-1 can still be achieved. Upon 100 charging-discharging cycles, the specific capacity of as high as 890.5 mAh g-1 at 200 mA g-1 is maintained. The enhanced electrochemical properties could be attributed to their favorable three-dimensional graphene aerogel network, which accounts for the improved structural stability and electronic conductivity of γ-Fe2O3 during the lithiation/delithiation process.

12.
Eur J Med Chem ; 192: 112153, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32135407

RESUMO

NEDDylation pathway regulates multiple physiological process, unlike inhibitors, NEDDylation activators are rarely studied. Novel amide derivatives were synthesized and evaluated for antiproliferative activity against MGC803, MCF-7 and PC-3 cells. Among them, Ⅶ-31 displayed the most potent activity with an IC50 value of 94 nmol/L against MGC803 cells. Cellular mechanisms elucidated that Ⅶ-31 inhibited the cell viability, arrested cell cycle at G2/M phase and induced apoptosis via intrinsic and extrinsic pathways against MGC803 cells. In addition, Ⅶ-31 activated NAE1-Ubc12-Cullin1 NEDDylation via interacting with NAE1 directly. Furthermore, the activation of NEDDylation resulted in the degradation of inhibitor of apoptosis proteins (IAPs). Importantly, Ⅶ-31 inhibited tumor growth in xenograft models in vivo without the apparent toxicity. In summary, it is the first time to reveal that Ⅶ-31 deserves consideration for cancer therapy as a NEDDylation activator.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Descoberta de Drogas , Proteína NEDD8/metabolismo , Amidas/síntese química , Amidas/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas
13.
IUBMB Life ; 72(2): 198-213, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31444954

RESUMO

Atherosclerotic plaque rupture is an important pathophysiologic mechanism of acute coronary syndrome. Emerging microRNAs (miRNAs) have been implicated in the atherosclerotic plaque formation and macrophage autophagy during the development of atherosclerosis (AS). Hence, this study was conducted to explore the role microRNA-135b (miR-135b) in macrophages and atherosclerotic plaque in mouse models of AS. The expression of miR-135b and erythropoietin receptor (EPOR) was altered in atherosclerotic mice to clarify their effect on inflammation, cell activities of aortic tissues, and macrophage autophagy. The obtained findings unraveled that miR-135b was upregulated and EPOR was downregulated in atherosclerotic mice. Upregulated miR-135b expression promoted cell apoptosis and inflammation, along with inhibited cell proliferation and decreased macrophage autophagy. Notably, miR-135 was validated to target EPOR and activate the PI3K/Akt signaling pathway. Moreover, miR-135b inhibition attenuated inflammation, atherosclerotic plaque development, and promoted macrophage autophagy. Besides, the effect of miR-135b inhibition was reversed in response to EPOR silencing. Taken conjointly, the study revealed that inhibition of miR-135b promoted macrophage autophagy and atherosclerotic plaque stabilization in atherosclerotic mice by inactivating the PI3K/Akt signaling pathway and upregulating EPOR.


Assuntos
Aterosclerose/fisiopatologia , Autofagia , Modelos Animais de Doenças , Macrófagos/patologia , MicroRNAs/genética , Placa Aterosclerótica/patologia , Receptores da Eritropoetina/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores da Eritropoetina/genética
14.
Bioorg Med Chem Lett ; 30(2): 126791, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740251

RESUMO

Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our in-house library and further structure-based optimizations. In this work, compound V11 could block the neddylation and inhibit the activity of NAE (with an EC50 value of 3.56 µM), and a dose-dependent reduction of the Ubc12-NEDD8 conjugations was also observed. Molecular docking results suggest compound V11 could bind tightly to NAE via hydrogen bonds and hydrophobic interactions. Compound V11 showed the best antiproliferative ability with an IC50 value of 8.22 µM against gastric cancer MGC-803 cells. Further anticancer activity studies suggested that compound V11 inhibited MGC-803 cell growth, caused a cell cycle arrestment at G2/M phase and induced apoptosis via extrinsic and intrinsic apoptosis pathways. All the findings suggest that 1,2,4-triazine scaffold might provide a novel scaffold for the further development of neddylation inhibitors and compound V11 might be a potential neddylation inhibitor with anticancer activity.


Assuntos
Antineoplásicos/química , Triazinas/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Simulação de Acoplamento Molecular , Proteína NEDD8/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Estrutura Terciária de Proteína , Neoplasias Gástricas , Relação Estrutura-Atividade , Triazinas/farmacologia , Enzimas de Conjugação de Ubiquitina/metabolismo
15.
Eur J Med Chem ; 183: 111731, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577977

RESUMO

With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more potent than the positive control (5-Fu). The structure-activity relationship of tertiary sulfonamide derivatives was explored in this report. Among the tested compounds, compound 13g containing benzimidazole moiety showed the best anti-proliferation activities against MGC-803 cells (IC50 = 1.02 µM), HGC-27 cells (IC50 = 1.61 µM), SGC-7901 (IC50 = 2.30 µM) cells as well as the good selectivity between the cancer and normal cells. Cellular mechanism studies elucidated compound 13g inhibited the colony formation of gastric cancer cell lines. Meanwhile, compound 13g arrested cell cycle at G2/M phase and induced cell apoptosis. Mechanistically, compound 13g markedly decreased p-Akt and p-c-Raf expression, which revealed that compound 13g targeted gastric cancer cell lines via interfering with AKT/mTOR and RAS/Raf/MEK/ERK pathways. All the findings suggest that compound 13g might be a valuable lead compound for the anti-gastric cancer agents.


Assuntos
Antineoplásicos , Benzimidazóis/química , Neoplasias Gástricas/tratamento farmacológico , Sulfonamidas , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Fármacos , Humanos , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/farmacologia
16.
Clin Exp Optom ; 102(5): 513-520, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30805993

RESUMO

BACKGROUND: Computer vision syndrome is common and affects performance of visual tasks. Background illumination, light source, light compensation, position of the display, contrast and glare are environmental factors associated with computer vision syndrome. The aim of this study is to investigate the effects of reflected glare and visual field lighting on computer vision syndrome. METHODS: In a reflected glare experiment, participants performed a two-hour visual task using a glossy, matte, or glare-free surface display in two visual environments (normal, glare). In a visual field lighting experiment, participants performed the visual task in dim lighting, uneven supplementary lighting, or uniform supplementary lighting. Visual function parameters, including critical fusion frequency, heterophoria, amplitude of accommodation and accommodative facility were evaluated by the investigators and a visual fatigue questionnaire was completed before and after the visual task. Visual performance was also recorded. In addition, the variation of pupil size under different lighting conditions was analysed. RESULTS: Critical fusion frequency was the only visual function parameter which decreased significantly after the visual task. The questionnaire score was significantly higher in a glare environment and was lower when the task was performed using a glare-free display. Visual performance was significantly worse in the glossy display group. The increment in the questionnaire score was smaller in the uniform supplementary lighting group. Visual performance was significantly worse in the dim lighting or uneven supplementary lighting group, but not in the uniform supplementary lighting group. Variation in pupil size was significantly greater in the dim lighting condition than in the supplementary lighting condition. CONCLUSION: Critical fusion frequency is an effective indicator of computer vision syndrome. Glare-free displays could alleviate visual fatigue and preserve visual performance. Uniform supplementary lighting could decrease variation in pupil size and prevent eye strain.


Assuntos
Astenopia/diagnóstico , Terminais de Computador , Fusão Flicker/fisiologia , Ofuscação , Iluminação , Campos Visuais/fisiologia , Acomodação Ocular/fisiologia , Adulto , Astenopia/fisiopatologia , Sensibilidades de Contraste/fisiologia , Feminino , Humanos , Masculino , Pupila/fisiologia , Estrabismo/fisiopatologia , Inquéritos e Questionários , Adulto Jovem
17.
ACS Appl Mater Interfaces ; 11(10): 9984-9993, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30784276

RESUMO

Self-assembled Ni(OH)2 nanosheet-decorated hierarchical flower-like MnCo2O4.5 nanoneedles were synthesized via a cost-effective and facile hydrothermal strategy, aiming to realize a high-capacity advanced electrode of a battery-supercapacitor hybrid (BSH) device. It is demonstrated that the as-synthesized hierarchical flower-like MnCo2O4.5@Ni(OH)2-nanosheet electrode exhibits a high specific capacity of 318 mAh g-1 at a current density of 3 A g-1 and still maintains a capacity of 263.5 mAh g-1 at a higher current density of 20 A g-1, with an extremely long cycle lifespan of 87.7% capacity retention after 5000 cycles. Moreover, using the unique core-shell structure as the cathode and hollow Fe2O3 nanoparticles/reduced graphene oxide as the anode, the BSH device delivers a high energy density of 56.53 Wh kg-1 when the power density reaches 1.9 kW kg-1, and there is an extraordinarily good cycling stability with the capacity retention rate of 90.4% after 3000 cycles. It is believed that the superior properties originate from desirable core-shell structures alleviating the impact of volume changes as well as the existence of two-dimensional Ni(OH)2 nanosheets with more active sites, thereby improving the cycle stability and achieving ultrahigh capacity. These results will provide more access to the rational material design of diverse nanostructures toward high-performance energy storage devices.

18.
Eur J Med Chem ; 165: 309-322, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690300

RESUMO

Structurally diverse trimethoxyphenyl-1,2,3-triazole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three cancer cell lines (PC3, MGC803 and HepG2). Among them, trimethoxyphenyl-1,2,3-triazole containing the coumarin fragement 19c displayed better antiproliferative activity results with IC50 values from 0.13 µM to 1.74 µM than anticancer drug colchicine. Compound 19c could inhibit MGC803 cell growth and colony formation, induce G2/M phase arrest by down expression of CDK1, and promote apoptosis by regulating DR5 and Bcl-2 family. Moreover, 19c strongly inhibited tubulin polymerization by interacting with the colchicine site.


Assuntos
Antineoplásicos/síntese química , Triazóis/química , Tubulina (Proteína)/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colchicina/metabolismo , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Polimerização/efeitos dos fármacos , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/uso terapêutico , Tubulina (Proteína)/metabolismo
19.
Zootaxa ; 4497(2): 285-294, 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30313679

RESUMO

The morphology of the adult male of Drosichoides ?haematoptera (Cockerell) is redescribed and illustrated and the adult female of Buchnericoccus sp. (Hemiptera: Monophlebidae) is also described and illustrated. These male and female specimens perhaps are conspecific. Genus Buchericoccus Reyne may be a junior synonym of genus Drosichoides Morrison.


Assuntos
Hemípteros , Animais , Feminino , Masculino
20.
Zootaxa ; 4375(1): 127-135, 2018 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-29689784

RESUMO

The mealybug genus Saccharicoccus Ferris includes three species: S. isfarensis (Borchsenius, 1949), S. sacchari (Cockerell, 1895) and a new species, S. chinensis Zhang, Wu Wu sp. n. The new species, collected on Miscanthus sp. (Poaceae) and other poaceous weeds in China, is described and illustrated, and molecular analyses based on the mitochondrial gene cytochrome c oxidase subunit I (COI) are provided. Additional data on the distribution and host-plants of each species are given, and a key to the adult females of Saccharicoccus species is provided.


Assuntos
Hemípteros , Animais , China , Feminino , Poaceae
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