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1.
J Nat Med ; 78(1): 146-159, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37804412

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating motor disease with limited treatment options. A domestic fungal extract library was screened using three assays related to the pathophysiology of ALS with the aim of developing a novel ALS drug. 2(3H)-dihydrofuranolactones 1 and 2, and five known compounds 3-7 were isolated from Pleosporales sp. NUH322 culture media, and their protective activity against the excitotoxicity of ß-N-oxalyl-L-α,ß-diaminopropionic acid (ODAP), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamatergic agonist, was evaluated under low mitochondrial glutathione levels induced by ethacrynic acid (EA) and low sulfur amino acids using our developed ODAP-EA assay. Additional assays evaluated the recovery from cytotoxicity caused by transfected SOD1-G93A, an ALS-causal gene, and the inhibitory effect against reactive oxygen species (ROS) elevation. The structures of 1 and 2 were elucidated using various spectroscopic methods. We synthesized 1 from D-ribose, and confirmed the absolute structure. Isolated and synthesized 1 displayed higher ODAP-EA activities than the extract and represented its activity. Furthermore, 1 exhibited protective activity against SOD1-G93A-induced toxicity. An ALS mouse model, SOD1-G93A, of both sexes, was treated orally with 1 at pre- and post-symptomatic stages. The latter treatment significantly extended their lifespan (p = 0.03) and delayed motor deterioration (p = 0.001-0.01). Our result suggests that 1 is a promising lead compound for the development of ALS drugs with a new spectrum of action targeting both SOD1-G93A proteopathy and excitotoxicity through its action on the AMPA-type glutamatergic receptor.


Assuntos
Esclerose Lateral Amiotrófica , Camundongos , Masculino , Feminino , Animais , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Neurônios Motores/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Camundongos Transgênicos , Superóxido Dismutase/metabolismo , Medula Espinal/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/metabolismo , Modelos Animais de Doenças
2.
Radiol Case Rep ; 18(5): 1662-1665, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36873044

RESUMO

The patient was a man in his 60s with the gradually increasing mass in his mouth. A well-defined, elastic soft mass with a major diameter of 60 mm was found on the right floor of mouth. The magnetic resonance imaging findings showed a well-defined mass with high signal on both T1 and T2-weighted image in the right sublingual space. The mass was slightly heterogeneous inside and had a septum-like appearance. The tumor was resected with care not to damage the capsule. Histopathological findings showed mature adipocytes, spindle-shaped cells, and collagenous components. Spindle cells were CD34-positive. The tumor was diagnosed as spindle cell lipoma. The patient was followed up for 6 months with no recurrence. Spindle cell lipoma is a rare entity and this is the largest case in the oral cavity. Because there are wide variety of adipocytic tumors, the careful examination of their imaging and histopathological findings is essential.

3.
Chemistry ; 25(31): 7449-7452, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-30920109

RESUMO

A hydrogen-bonding donor-acceptor system, [Co2 Fe2 (bpy*)4 (CN)6 (tp*)2 ](PF6 )2 ⋅2ABA⋅4BN⋅2PE (1 solv ), was prepared by co-crystallization of an external stimuli-responsive cyanide-bridged tetranuclear [Co2 Fe2 ] complex and bifunctional hydrogen-bonding donors, p-aminobenzoic acid. Compound 1 solv exhibited a gradual electron-transfer-coupled spin transition (ETCST), and the removal of solvent molecules led to an abrupt thermal ETCST behavior with increased transition temperature. X-ray structural analysis revealed that the modification of ETCST was caused by a significant alteration of a hydrogen-bonding mode between the tetranuclear [Co2 Fe2 ]2+ cations and ABA molecules. Variable temperature IR measurements indicated that the desolvated form, 1 desolv , showed dynamic alteration of hydrogen-bonding interactions coupled with thermal ETCST behavior. These results suggested that the tetranuclear [Co2 Fe2 ] complex shows solid-state modulations of hydrogen-bond strengths by external stimuli.

4.
Angew Chem Int Ed Engl ; 56(2): 591-594, 2017 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-27925347

RESUMO

Co-crystallization of a cyanide-bridged tetranuclear complex [Co2 Fe2 ] with 4-cyanophenol (CP) gave a hydrogen bonding donor-acceptor system, [Co2 Fe2 (bpy*)4 (CN)6 (tp*)2 ](PF6 )2 ⋅2 CP⋅8 BN (1). 1 exhibited a three-step phase transition between HT, IM1, IM2, and LT phases upon temperature variation. Variable temperature magnetic measurements and structural analyses revealed that the three-step spin transition is caused by electron-transfer-coupled spin transitions (ETCSTs) accompanied with alteration of the hydrogen bonding interactions.

5.
J Oncol ; 2012: 634183, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22690218

RESUMO

Objective. To evaluate the efficacy of selective submandibular neck dissection (SMND) in patients with oral squamous cell carcinoma (OSCC) with or without nodal metastasis. Patients. From a total of 384 patients with untreated OSCC who underwent radical excision, we identified 229 with clinically N0 necks and 68 with clinically N1 necks in level I. Main Outcome Measures. The Kaplan-Meier 5-year regional control and 5-year disease specific survival (DSS) were compared for SMND, radical neck dissection (RND), and modified radical neck dissection (MRND). Results. In clinically node-negative necks, the regional control rates were 85.2% with SMND and 83.3% with MRND (P = 0.89), and 5-year DSS rates were 86.5% and 87.0%, respectively, (P = 0.94). In clinically N1 necks, the regional control rates were 81.3% with SMND and 83.0% with RND (P = 0.72), and the DSS rates were 81.3% and 80.0%, respectively, (P = 0.94). Type of neck dissection was not significantly associated with regional control or DSS on either univariate or multivariate analysis using Cox's proportional hazard model. Conclusions. SMND can be effectively applied in elective and therapeutic management to patients with OSCC that are clinically assessed as N0 or N1 to level I of the neck.

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