Metabotropic GABA Receptor Activation Induced by G Protein Coupling.

G protein-coupled receptors (GPCRs) play central roles in regulating cellular responses through heterotrimeric G proteins (GP). Extensive studies have elucidated the complex cellular signaling mediated by GPCRs that accompany dynamic conformational changes upon activation. However, there has been less focus on the role of the GP on the activation process, particularly for class C GPCRs that function as obligate dimers.

Nucleic Acid Lateral Flow Assay Implemented with Isothermal Gene Amplification of SARS-CoV-2 RNA.

We developed a rapid and sensitive diagnostic platform that integrates isothermal viral gene amplification with a nucleic acid lateral flow assay (NALFA) to detect SARS-CoV-2 RNA. Isothermal gene amplification was performed by combining reverse transcription of viral RNA with recombinase polymerase amplification (RPA). In our diagnostic platform, DNA primers for the RPA reaction were modified by appending DNA tails, enabling the synthesis of tailed amplicon DNAs.

Agonist activation to open the Gα subunit of the GPCR-G protein precoupled complex defines functional agonist activation of TAS2R5.

G protein-coupled receptors (GPCRs) regulate multiple cellular responses and represent highly successful therapeutic targets. The mechanisms by which agonists activate the G protein are unclear for many GPCR families, including the bitter taste receptors (TAS2Rs). We ascertained TAS2R5 properties by live cell-based functional assays, direct binding affinity measurements using optical resonators, and atomistic molecular dynamics simulations.

Enhanced Diagnostic Accuracy in Hepatitis B: Human vs. Sheep-Derived Antibodies in HBsAg Confirmatory Testing.

Background: HBsAg confirmatory testing is crucial for accurately diagnosing HBV infection and avoiding false positives. We compared the performance of human-derived and sheep-derived anti-HBs reagents in the Elecsys HBsAg confirmatory test (Roche Diagnostics, Germany).

Methods: Samples with a HBsAg COI of 0.

Experimental Validation of the Neurotrophic Factor-α1 Binding Site on the Serotonin Receptor 1E (HTR1E) Responsible for β-Arrestin Activation and Subsequent Neuroprotection.

Stress, such as neuroexcitotoxicity and oxidative stress, as well as traumatic brain injury, will result in neurodegeneration. Deciphering the mechanisms underlying neuronal cell death will facilitate the development of drugs that can promote neuronal survival and repair through neurogenesis. Many growth and trophic factors, including transforming growth factors (TGFs), insulin-like growth factors (IGFs), epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), and brain-derived neurotrophic factor (BDNF), are known to play a role in neuroprotection and neurogenesis.

The G Protein-First Mechanism for Activation of the Class B Glucagon-like Peptide 1 Receptor Coupled to N-Terminal Domain-Mediated Conformational Progression.

Recently, there has been a great deal of excitement about new glucagon-like peptide 1 receptor (GLP-1R) agonists (e.g., semaglutide and tirzepatide) that have received FDA approval for type 2 diabetes and obesity.

Ligand-Dependent and G Protein-Dependent Properties for the Sweet Taste Heterodimer, TAS1R2/1R3.

The heterodimeric sweet taste receptor, TAS1R2/1R3, is a class C G protein-coupled receptor (GPCR) that couples to gustducin (Gt), a G protein (GP) specifically involved in taste processing. This makes TAS1R2/1R3 a possible target for newly developing low caloric ligands that taste sweet to address obesity and diabetes. The activation of TAS1R2/1R3 involves the insertion of the GαP C-terminus of the GP into the GPCR in response to ligand binding.

Methotrexate Inhibits the Binding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Receptor Binding Domain to the Host-Cell Angiotensin-Converting Enzyme-2 (ACE-2) Receptor.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus mutates, finding effective drugs becomes more challenging. In this study, we use ultrasensitive frequency locked microtoroid optical resonators in combination with screening to search for COVID-19 drugs that can stop the virus from attaching to the human angiotensin-converting enzyme 2 (hACE2) receptor in the lungs. We found 29 promising candidates that could block the binding site and selected four of them that were likely to bind very strongly.

Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study.

Backgruound: Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD.

Methods: We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study.

An innovative microcoring technology: A novel approach to acne scar treatment.

Background: Acne scars present a complex challenge in dermatology and cosmetics, despite advancements in technological interventions such as fractional lasers, microneedling, and surgical procedures. Effective treatment remains elusive for many individuals.

Objective: This study aims to evaluate the efficacy of rotational fractional resection using 1 mm diameter rotating scalpels as a primary treatment for icepick and boxcar scars on the cheeks and glabella region.

Fully activated structure of the sterol-bound Smoothened GPCR-Gi protein complex.

Smoothened (SMO) is an oncoprotein and signal transducer in the Hedgehog signaling pathway that regulates cellular differentiation and embryogenesis. As a member of the Frizzled (Class F) family of G protein-coupled receptors (GPCRs), SMO biochemically and functionally interacts with Gi family proteins. However, key molecular features of fully activated, G protein-coupled SMO remain elusive.

Discovery of 3-Phenyl Indazole-Based Novel Chemokine-like Receptor 1 Antagonists for the Treatment of Psoriasis.

Chemokine-like receptor 1 (CMKLR1)─a G protein-coupled receptor─has functional roles in the immune system and related diseases, including psoriasis and metabolic diseases. Psoriasis is a chronic inflammatory disease characterized by skin redness, scaliness, and itching. In this study, we sought to develop novel CMKLR1 antagonists by screening our in-house GPCR-targeting compound library.

2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes.

Bio-conjugated nanoarchitectonics with dual-labeled nanoparticles for a colorimetric and fluorescent dual-mode serological lateral flow immunoassay sensor in detection of SARS-CoV-2 in clinical samples.

Serological detection of antibodies for diagnosing infectious diseases has advantages in facile diagnostic procedures, thereby contributing to controlling the spread of the pathogen, such as in the recent SARS-CoV-2 pandemic. Lateral flow immunoassay (LFIA) is a representative serological antibody detection method suitable for on-site applications but suffers from low clinical accuracy. To achieve a simple and rapid serological screening as well as the sensitive quantification of antibodies against SARS-CoV-2, a colorimetric and fluorescent dual-mode serological LFIA sensor incorporating metal-enhanced fluorescence (MEF) was developed.

Structure and Molecular Mechanism of Signaling for the Glucagon-like Peptide-1 Receptor Bound to Gs Protein and Exendin-P5 Biased Agonist.

The glucagon-like peptide-1 receptor (GLP-1R) is a key regulator of blood glucose and a prime target for the treatment of type II diabetes and obesity with multiple public drugs. Here we present a comprehensive computational analysis of the interactions of the activated GLP-1R-Gs signaling complex with a G protein biased agonist, Exendin P5 (ExP5), which possesses a unique N-terminal sequence responsible for the signal bias. Using a refined all-atom model of the ExP5-GLP-1R-Gs complex in molecular dynamics (MD) simulations, we propose a novel mechanism of conformation transduction in which the unique interaction network of ExP5 N-terminus propagates the binding signal across an array of conserved residues at the transmembrane domain to enhance Gs protein coupling at the cytoplasmic end of the receptor.

Different Molecular Phenotypes of Progression in BRAF- and RAS-Like Papillary Thyroid Carcinoma.

Backgruound: Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs.

Interpreting changes in consecutive laboratory results: clinician's perspectives on clinically significant change.

Background: Clinical laboratory tests are inevitably affected by various factors. Therefore, when comparing consecutive test results, it is crucial to consider the inherent uncertainty of the test. Clinical laboratories use reference change value (RCV) to determine a significant change between 2 results.

The dynamics of agonist-β-adrenergic receptor activation induced by binding of GDP-bound Gs protein.

There is considerable uncertainty about the mechanism by which the β-adrenergic receptor (βAR) is activated. Here we use molecular metadynamics computations to predict the mechanism by which an agonist induces the activation of the βAR and its cognate Gs protein. We found that binding agonist alone to the inactive βAR does not break the ionic lock and hence does not drive the βAR towards the activated conformation.

Stereochemical engineering yields a multifunctional peptide macrocycle inhibitor of Akt2 by fine-tuning macrocycle-cell membrane interactions.

Macrocycle peptides are promising constructs for imaging and inhibiting extracellular, and cell membrane proteins, but their use for targeting intracellular proteins is typically limited by poor cell penetration. We report the development of a cell-penetrant high-affinity peptide ligand targeted to the phosphorylated Ser474 epitope of the (active) Akt2 kinase. This peptide can function as an allosteric inhibitor, an immunoprecipitation reagent, and a live cell immunohistochemical staining reagent.