Therapeutic effect of novel drug candidate, PRG-N-01, on NF2 syndrome-related tumor.

Background: NF2-related schwannomatosis (NF2-SWN) is associated with multiple benign tumors in the nervous system. NF2-SWN, caused by mutations in the NF2 gene, has developed into intracranial and spinal schwannomas. Because of the high surgical risk and frequent recurrence of multiple tumors, targeted therapy is necessary.

Pharmacologic inhibition of Il6st/gp130 improves dermatological inflammation and pruritus.

Chronic dermatitis is a disease with large unmet need for pharmacological improvement. Dermatitis conditions are maintained and exacerbated by various cytokine actions in the context of inflammation. Interleukin 6 signal transducer (Il6st), also known as glycoprotein 130 (Gp130), is a key component for surface reception of a multitude of cytokines and transduction and amplification of their pro-inflammatory signals.

Chemical tools to define and manipulate interferon-inducible Ubl protease USP18.

Ubiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating interferon-inducible ubiquitin-like (Ubl) modifier ISG15 from protein substrates. Here, we report the design and synthesis of activity-based probes (ABPs) capable of selectively detecting USP18 activity over other ISG15 cross-reactive deubiquitinases (DUBs) by incorporating unnatural amino acids into the C-terminal tail of ISG15. Combining with a ubiquitin-based DUB ABP, the selective USP18 ABP is employed in a chemoproteomic screening platform to identify and assess inhibitors of DUBs including USP18.

Discovery of a Tunable Heterocyclic Electrophile 4-Chloro-pyrazolopyridine That Defines a Unique Subset of Ligandable Cysteines.

Electrophilic small molecules with novel reactivity are powerful tools that enable activity-based protein profiling and covalent inhibitor discovery. Here, we report a reactive heterocyclic scaffold, 4-chloro-pyrazolopyridine (CPzP) for selective modification of proteins via a nucleophilic aromatic substitution (SAr) mechanism. Chemoproteomic profiling reveals that CPzPs engage cysteines within functionally diverse protein sites including ribosomal protein S5 (RPS5), inosine monophosphate dehydrogenase 2 (IMPDH2), and heat shock protein 60 (HSP60).

SP-8356 inhibits acute lung injury by suppressing inflammatory cytokine production and immune cell infiltration.

This study investigated the anti-inflammatory and protective properties of SP-8356, a synthetic derivative of (1S)-(-)-verbenone, in a mouse model of LPS-induced acute lung injury (ALI). By targeting intracellular signaling pathways and inflammatory responses, SP-8356 demonstrated a potent ability to attenuate deleterious effects of proinflammatory stimuli. Specifically, SP-8356 effectively inhibited the activation of crucial signaling molecules such as NF-κB and Akt, and subsequently dampened the expression of inflammatory cytokines in various lung cellular components.

Synthesis of 9-Cinnamyl-9-purine Derivatives as Novel TLR4/MyD88/NF-κB Pathway Inhibitors for Anti-inflammatory Effects.

The novel 9-cinnamyl-9-purine skeleton, inspired by resveratrol and curcumin, was developed to avoid a pan-assay interference compound (PAINS) related to invalid metabolic pancreas activity (IMPS). It replaced the phenol group with purine analogues, the building blocks of DNA and RNA. Alterations to the hydroxyl group in the cinnamyl group, such as H, Me, or F substitutions, were made to impede its oxidation to a PAINS-associated quinone.

Defect-Passivated Photosensor Based on Cesium Lead Bromide (CsPbBr) Perovskite Quantum Dots for Microbial Detection.

A defect-passivated photosensor based on cesium lead bromide (CsPbBr) perovskite quantum dots (QD) was fabricated using parylene films, and the photosensor was applied for the microbial detection. The CsPbBr perovskite QDs were synthesized to be homogeneous in size under thermodynamic control, and the perovskite QD-based photosensor was fabricated using MoS flakes as the electron transfer layer. In this work, a parylene film with functional groups was deposited on a photosensor for physical protection (waterproof) and defect (halide vacancy) passivation of the perovskite QD.

Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor.

Background: Tachykinins and their cognate receptors, neurokinin receptors (NKs) including NK1, NK2, and NK3 play vital roles in regulating various physiological processes including neurotransmission, nociception, inflammation, smooth muscle contractility, and stimulation of endocrine and exocrine gland secretion. Their abnormal expression has been reported to be associated with neurological disorders, inflammation, and cancer. Even though NKs are expressed in the same cells with their expression being inversely correlated in some conditions, there is no direct evidence to prove their interaction.

Discovery of Chemical Scaffolds as Lysophosphatidic Acid Receptor 1 Antagonists: Virtual Screening, Validation, and Molecular Dynamics Analysis.

Lysophosphatidic acid receptor 1 (LPAR1) is an emerging therapeutic target for numerous human diseases including fibrosis. However, the limited number of available core structures of LPAR1 antagonists has prompted the need for novel chemical templates. In this study, we conducted a high-throughput virtual screening to discover potential new scaffolds.

The N-terminus of CXCR4 splice variants determines expression and functional properties.

C-X-C motif chemokine ligand 12(CXCL12) is an essential chemokine for organ development and homeostasis in multiple tissues. Its receptor, C-X-C chemokine receptor type 4(CXCR4), is expressed on the surface of target cells. The chemokine and receptor are expressed almost ubiquitously in human tissues and cells throughout life, and abnormal expression of CXCL12 and CXCR4 is observed in pathological conditions, such as inflammation and cancer.

Plasma-based diagnostic and screening platform using a combination of biosensing signals in Alzheimer's disease.

Using biosensor to screen for Alzheimer's disease (AD) facilitates early detection of AD with high sensitivity and accuracy. This approach overcomes the limitations of conventional AD diagnostic methods, such as neuropsychological assessment and neuroimaging analysis. Here, we propose a simultaneous analysis of signal combinations generated by four crucial AD biomarkers (Amyloid beta 1-40 (Aβ), Aβ, total tau 441 (tTau), and phosphorylated tau 181 (pTau)) by inducing a dielectrophoretic (DEP) force on fabricated interdigitated microelectrode (IME) sensor.

Structure-Activity Relationships of Truncated 1'-Homologated Carbaadenosine Derivatives as New PPARγ/δ Ligands: A Study on Sugar Puckering Affecting Binding to PPARs.

Peroxisome proliferator-activated receptors (PPARs) are associated with the regulation of metabolic homeostasis. Based on a previous report that 1'-homologated 4'-thionucleoside acts as a dual PPARγ/δ modulator, carbocyclic nucleosides - with various sugar conformations were synthesized to determine whether sugar puckering affects binding to PPARs. ()-conformer was synthesized using Charette asymmetric cyclopropanation, whereas ()-conformer was synthesized using stereoselective Simmons-Smith cyclopropanation.

A vertically paired electrode for redox cycling and its application to immunoassays.

An electrochemical immunoassay based on the redox cycling method was presented using vertically paired electrodes (VPEs), which were fabricated using poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as an electrode material and parylene-C as a dielectric layer. For the application to immunoassays, different electrochemical properties of PEDOT:PSS were analyzed for the redox reaction of 3,3',5,5'-tetramethylbenzidine (TMB, the chromogenic substrate for enzyme-immunoassays) at different pH conditions, including the conductivity (), electron transfer rate constant (), and double-layer capacitance (). The influencing factors on the sensitivity of redox cycling based on VPE based on PEDOT:PSS were analyzed for the redox reaction of TMB, such as the electrode gap and number of electrode pairs.

One-step immunoassay based on filtration for detection of food poisoning-related bacteria.

A one-step immunoassay based on filtration was presented, which used microbeads for target analyte detection and filters with appropriate pore sizes to distinguish the complexity of target analyte and microbeads. For effective bacterial detection, the microbead size and the filter's pore size must be optimized. The optimal concentrations of the enzyme (urease) and antibody were determined at the maximum absorbance change, that is, the maximum pH change.

Synthesis of Enantiomerically Pure Pyrimidine Ribonucleosides Locked in the South Conformation.

The conformation of the central five-membered ring of a nucleoside plays an important role in enzyme recognition. Bicyclo[3.1.

One-step immunoassay for the detection of food-poisoning related bacteria using a switching peptide.

A one-step immunoassay was developed for five types of food-poisoning-related bacteria using a switching peptide and antibodies isolated from unimmunized horse serum. The one-step immunoassay involves mixing samples and reagents in a homogeneous solution without any washing steps. In this work, a one-step immunoassay configuration was developed using isolated antibodies labelled with an organic fluorescence quencher and a switching-peptide labelled with a fluorescent dye.

One-Step Homogeneous Immunoassay for the Detection of Influenza Virus Using Switching Peptide and Graphene Quencher.

One-step homogeneous immunoassay was developed for detecting influenza viruses A and B (Inf-A and Inf-B) using the switching peptide H2. As the fluorescence-labeled switching peptide dissociated from the binding pocket of detection antibodies, the fluorescence signal could be directly generated by the binding of Inf-A and Inf-B without washing (i.e.

Carbon electrode obtained pyrolysis of plasma-deposited parylene-C for electrochemical immunoassays.

In this study, parylene-C films from plasma deposition as well as thermal deposition were pyrolyzed to prepare a carbon electrode for application in electrochemical immunoassays. Plasma deposition could prepare parylene-C in a faster deposition rate and more precise control over the thickness in comparison with the conventional thermal deposition. To analyze the influence of the deposition method, the crystal and electronic structures of the pyrolyzed parylene-C films obtained both deposition methods were compared using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy.

Homogeneous One-Step Immunoassay Based on Switching Peptides for Detection of the Influenza Virus.

In this study, a homogeneous one-step immunoassay based on switching peptides is presented for the detection of influenza viruses A and B (Inf-A and Inf-B, respectively). The one-step immunoassay represents an immunoassay method that does not involve any washing steps, only treatment of the sample. In this method, fluorescence-labeled switching peptides quantitatively dissociate from the antigen-binding site of immunoglobulin G (IgG).

Assessment of the learning curve for the novel transanal minimally invasive surgery simulator model.

Background: Transanal minimally invasive surgery (TAMIS) is technically demanding and requires extensive training. We developed the TAMIS simulator model by remodeling an existing laparoscopic training system to educate trainees and analyzed their learning curves.

Methods: Between March 2020 and June 2020, 12 trainees performed TAMIS simulator training sessions.

Electrochemical One-Step Immunoassay Based on Switching Peptides and Pyrolyzed Carbon Electrodes.

Switching peptides were designed to bind reversibly to the binding pocket of antibodies (IgG) by interacting with frame regions (FRs). These peptides can be quantitatively released when antigens bind to IgG. As FRs have conserved amino acid sequences, switching peptides can be used as antibodies for different antigens and different source animals.

Screening for cerebral amyloid angiopathy based on serological biomarkers analysis using a dielectrophoretic force-driven biosensor platform.

We aimed to analyze plasma amyloid-β (Aβ) and Aβ using a highly sensitive dielectrophoretic-driven biosensor platform to demonstrate the possibility of precise cerebral amyloid angiopathy (CAA) diagnosis in participants classified according to Aβ-positron emission tomography (PET) positivity and the neuroimaging criteria for CAA. We prospectively recruited 25 people with non-Alzheimer's disease (non-AD) and 19 patients with Alzheimer's disease (AD), which were further classified into the CAA- and CAA+ (possible and probable CAA) groups according to the modified Boston criteria. Patients underwent plasma Aβ analysis using a highly sensitive nano-biosensor platform, Aβ-PET scanning, and detailed neuropsychological testing.

Development of ultrafast PCR assays for the event-specific detection of eleven approved genetically modified canola events in South Korea.

In Korea, genetically modified (GM) canola events derived from eleven single events have been authorized for food and feed, but not for cultivation. Therefore, the development of a rapid and accurate on-site detection method is crucial for the management of these approved GM canola events. In this study, ultrafast polymerase chain reaction (PCR) assays for the event-specific detection of eleven GM canola events were developed.