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Monoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01097-4.

Pt is used in many catalytic applications from three-way catalysts to fuel cells. Particle size and morphology are key parameters that influence the electrocatalytic activity. Flame synthesis is an efficient and continuous manufacturing route capable of producing Pt nanoparticles with desirable catalytic properties. In order to understand the effect of the forced oxidant, solvent composition, and quench rate on nanoparticle formation, a systematic study of process parameters using Pt was undertaken. Reactive spray deposition technology was used as the synthesis platform. In order to obtain a tight control of the Pt size, it was found that the fuel must contain a sufficient enthalpy of combustion and appropriate propane content. The fuel must be mixed adequately to form a turbulent diffusion flame and must create conditions where unwanted Pt coarsening cannot occur. From this study, the conditions that favor this morphology require an O2 flow rate setting of 6.89 L/min or higher, a propane content of 20 wt%, and no quenching. Electrochemical data show decreasing electrochemical surface area (75–36 m2/gPt), increasing mass activity (120–610 mA/mgPt), and increasing specific activity (150–1350 $$ \upmu {\text{A}}/ {\text{cm}}^{2} {_{\text{Pt}}} $$ ) with increasing oxidant flow.

To evaluate whether metabolic profiles obtained using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) and total choline-containing compound (tCho) on in vivo MRS could predict indolent tumors based on highly favorable prognostic factors. We analyzed 50 frozen tissue samples from 50 patients (mean 46.4 years, range 29–72 years) with breast cancer using HR MAS MRS. In vivo single-voxel MRS analyses were also performed on these patients preoperatively. We defined estrogen receptor (ER)-positive tumors with a low histological grade, low Ki-67-positivity (

To explore the potential of high-resolution magic angle spinning (HRMAS) 1H nuclear magnetic resonance (NMR) spectroscopy for differentiation and metabolite characterization of hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM), we prospectively included 21 pathologically confirmed malignant hepatic tumors (8 HCC and 13 CRLM) and 26 non-tumorous hepatic parenchyma from 26 patients who underwent hepatic tumor resection. Using intact tissue samples obtained during surgery, HRMAS 1H NMR spectroscopy was performed at 11.7 T. All observable metabolite signals were acquired using a water-presaturated standard one-dimensional Carr–Purcell–Meiboom–Gill sequence. Metabolomic profiles contributing to the differentiation of HCC and CRLM and of each tumor and non-tumorous hepatic parenchyma were represented by orthogonal partial least squares discriminant analysis (OPLS-DA) and loading plots. Metabolite intensity normalized by total spectral intensities in both tumors was compared using student’s t tests. OPLS-DA and loading plots demonstrated good separation between tumors and non-tumorous hepatic parenchyma. The metabolomic characteristics of HCC showed separation from those of CRLMs according to OPLS-DA. Compared with CRLM, HCC showed significantly elevated levels of glucose (P < 0.01) and sn-Glycero-3-phosphocholine (P < 0.01), and decreased levels of hypoxanthine (P = 0.04). HCC and CRLM could be differentiated by the metabolic profile using HRMAS 1H NMR spectroscopy.

Interleukin-17 (IL-17) is a proinflammatory cytokine that is expressed in the synovium T cells of rheumatoid arthritis (RA). This cytokine is implicated in the inflammation and destruction of the joint. However, the role of IL-17 on the production of vascular endothelial factor (VEGF) important to synovial proliferation has still not been identified. In this study, we investigated the effect on cultured rheumatoid fibroblast-like synoviocytes (FLS) of the IL-17 on the production and expression of VEGF, which play an important role in angiogenesis in rheumatoid synovium. IL-17 increased the production of VEGF dose dependently and the mRNA expression of VEGF. These results suggest that IL-17 might influence angiogenesis in RA by up-regulating the expression of VEGF in rheumatoid FLS.