Design, synthesis, and biological evaluation of 2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamides as a potential EGR-1 inhibitor for targeted therapy of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease characterized by intense itching and frequent skin barrier dysfunctions. EGR-1 is a transcription factor that aggravates the pathogenesis of atopic dermatitis by promoting the production of various inflammatory cytokines. Three 2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamides (IT21, IT23, and IT25) were identified as novel inhibitors of EGR-1 DNA-binding activity. In silico docking experiments were performed to elucidate the binding conditions of the EGR-1 zinc-finger (ZnF) DNA-binding domain. Electrophoretic mobility shift assays confirmed the targeted binding effect on the EGR-1 ZnF DNA-binding domain, leading to dose-dependent dissociation of the EGR-1-DNA complex. At the functional cellular level, IT21, IT23, and IT25 effectively reduced mRNA expression of TNFα-induced EGR-1-regulated inflammatory genes, particularly in HaCaT keratinocytes inflamed by TNFα. In the in vivo efficacy study, IT21, IT23, and IT25 demonstrated the potential to alleviate atopic dermatitis-like skin lesions in the ear skin of BALB/c mice. These findings suggest that targeting the EGR-1 ZnF DNA-binding domain with 2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamide derivatives (IT21, IT23, and IT25) could serve as lead compounds for the development of potential therapeutic agents against inflammatory skin disorders, including atopic dermatitis.

Clinical value of fat-suppressed 3D volume isotropic spin-echo (VISTA) sequence compared to 2D sequence in evaluating internal structures of the knee.

BACKGROUND: Although many three-dimensional (3D) magnetic resonance imaging (MRI) sequences have been used in the clinical field, there are no studies on fat-suppressed (FS) 3D sequences for the diagnosis of knee abnormalities. PURPOSE: To evaluate the usefulness of FS 3D volume isotropic turbo spin echo acquisition (VISTA) imaging for diagnosis of internal structures of knee. MATERIAL AND METHODS: In 137 patients with 138 knee MRI examinations who had undergone both FS 3D VISTA MRI and two-dimensional (2D) MRI of the knee at 3.0 T, arthroscopic surgery was subsequently performed. Multiplanar reformations (MPR) of FS 3D VISTA images and their MPR sequences were compared with 2D MR images of axial T1-weighted (T1W) images, axial FS T2-weighted (T2W) images, coronal FS T2W images, and sagittal T2W images. Two musculoskeletal radiologists reviewed the images independently. RESULTS: Arthroscopy revealed 33 anterior cruciate ligament tears, three posterior cruciate ligament tears, 42 lateral meniscus tears, and 68 medial meniscus tears. Five medial collateral ligament tears were clinically confirmed. Image acquisition time was shorter for FS 3D VISTA imaging than 2D imaging. There were no significant differences in diagnostic values between FS 3D VISTA and 2D imaging (P > 0.05). There were excellent inter-observer agreements for both FS 3D VISTA and 2D imaging (κ > 0.84). CONCLUSION: FS 3D VISTA imaging could replace 2D imaging because of equal diagnostic ability and shorter scan time.

Maleimidyl magnetic nanoplatform for facile molecular MRI.

In this study, we developed the maleimidyl magnetic nanoplatform, which enables functional targeting of a biomarker-specific moiety for molecular imaging via MRI. The maleimide group of the maleimidyl magnetic nanoplatform is conjugated with a thiol group without additional crosslinkers and side products. A physicochemical analysis was conducted to verify the effectiveness of the maleimidyl magnetic nanoplatform, and the existence of the maleimidyl group was investigated using the platform. To prepare biomarker-specific MRI probes, a thiolated aptamer and peptide were immobilized onto the maleimidyl group of the maleimidyl magnetic nanoplatform. The fabricated MRI probes were applied to four cancer cell lines: HT1080, MCF7, MKN45, and HEK293T. To investigate the potential of the molecular MRI probe, the target-biomarker specificity was confirmed without serious cytotoxicity, and in vivo MRI analysis using a xenograft mouse model was demonstrated. We believe these results will be useful for fabricating molecular MRI probes for the diagnosis of cancer.

Effects of soil dilution and amendments (mussel shell, cow bone, and biochar) on Pb availability and phytotoxicity in military shooting range soil.

Bioavailability and bioaccessibility determine the level of metal toxicity in the soils. Inorganic soil amendments may decrease metal bioavailability and enhance soil quality. This study used mussel shell, cow bone, and biochar to reduce lead (Pb) toxicity in the highly contaminated military shooting range soil in Korea. Water-soluble and 1-M ammonium nitrate extractions, and a modified physiologically based extraction test (PBET) were performed to determine Pb bioavailability and bioaccessibility in the soil, respectively. Active C in the soil was also measured to evaluate the effects of the amendments on biological soil quality. The Pb contaminated soil was diluted in serial with uncontaminated soil for the bioassays. Seed germination and root elongation tests using lettuce (Lactuca sativa) showed increases in germination percentage and root length in soil treated with the amendments. Biochar was most effective and increased seed germination by 360% and root length by 189% compared to the unamended soil. Up to 20% soil dilution resulted in more than 50% seed germination. Bioavailability and bioaccessibility of Pb in the soils were decreased by 92.5% and 48.5% with mussel shell, by 84.8% and 34.5% with cow bone, and by 75.8% and 12.5% with biochar, respectively, compared to the unamended soil. We found that the Pb availability in the military shooting range soil can be reduced effectively by the tested amendments or soil dilution alternately, thereby decreasing the risk of ecotoxicity. Furthermore, the increasing active C from the amendments revitalized the soil contaminated with Pb.