Clinical Utility of Salivary Steroid Profiling for the Differential Diagnosis of Adrenal Diseases.

Context: Although salivary steroid sampling offers several advantages, the diagnostic potential of salivary steroid metabolites remains largely unexplored.Objective To evaluate the diagnostic utility of salivary steroid profiling in patients with adrenal diseases.

Design: Prospective multicenter study.

Preferential Sensitivity of the EGFR L858M/L861R Mutation to Second-Generation EGFR Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer.

Purpose: Non-small cell lung cancer (NSCLC) frequently harbors targetable EGFR mutations. However, rare variants such as EGFR L858M or L861R remain poorly characterized. This study aimed to elucidate the oncogenic potential and EGFR tyrosine kinase inhibitors (TKIs) sensitivity of the EGFR L858M/L861R mutation to inform personalized treatment strategies.

Immunomodulatory Effects of LSI312A on Dendritic Cells: A Novel Approach to Modulating Inflammatory Pathways.

Inflammation plays a crucial role in the pathogenesis of various diseases, necessitating the development of effective anti-inflammatory therapeutics. Dendritic cells (DCs), as professional antigen-presenting cells, are key regulators of immune responses. In this study, we investigated the immunomodulatory effects of LSI312A, a novel compound derived from medicinal plant analogues, on DC function and inflammatory signaling pathways.

Reprogramming macrophage polarization with a small molecule G3I: Enhancing tumor suppression and inflammation control.

Glycogen synthase kinase-3β (GSK-3β) is a ubiquitously expressed serine/threonine kinase that plays a pivotal role in regulating innate and adaptive immunity by modulating the production of pro- and anti-inflammatory cytokines. To investigate specific regulators of GSK-3β in innate immunity, we developed small molecule inhibitors that are tightly interact with three ATP-binding sites of GSK-3β through a systematic Fragment-based de novo design (FBDND). Among the leading candidates, G3I was found to modulate early macrophage polarization by downregulating the expression of mRNAs of M2-like markers such as CD206, Arg-1, CCL18 and upregulating the markers for M1-like macrophages such as CD86 and CCR7.

Somatic Mutations in Are Associated With Aldosterone-Producing Adenomas.

Background: Primary aldosteronism is a common but underdiagnosed cause of endocrine hypertension that contributes to global cardiovascular morbidity and mortality. It is characterized by renin-independent hyperaldosteronism that originates from adrenal lesions-the majority of which are found to harbor aldosterone-driver somatic mutations in genes encoding ion-transporting proteins. These mutations disrupt intracellular calcium homeostasis, facilitating a pathological increase in aldosterone synthase expression and aldosterone production.

Regulatory T cells and their role in inflammatory bowel disease: molecular targets, therapeutic strategies and translational advances.

Regulatory T cells (T) are essential for immune tolerance and for controlling pathological inflammation, particularly in mucosal tissues such as the gastrointestinal tract. Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is increasingly associated with T dysfunction. This dysfunction is marked by loss of lineage stability, impaired suppressive function, and a disrupted balance with pro-inflammatory T helper type 17 (Th17) cells.

LSI312A modulates myeloid-derived suppressor cell-mediated immunosuppression via NLRP3 inflammasome inhibition.

Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that inhibit neighboring immune cells activity and promote tumor growth by producing anti-inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS), and cytokines. They also induce pro-inflammatory cytokines like IL-1β, further enhancing immunosuppression and resistance to therapy. The NLRP3 inflammasome plays a crucial role in host defense against infections but also contributes to autoimmune diseases and cancer when dysregulated.

Emerging strategies for targeting tumor-associated macrophages in glioblastoma: A focus on chemotaxis blockade.

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with poor prognosis for affected patients. A key player in the GBM tumor microenvironment is the tumor-associated macrophage (TAM), which promotes tumor progression, immune evasion, and therapeutic resistance. The recruitment of TAMs to the tumor site is driven by specific chemotactic signals, including CSF-1/CSF-1R, CXCR4/CXCL12, and HGF/MET pathways.

Restoration and stabilization of benthic communities in Lake Shihwa: Effects of a tidal power plant.

As restoration projects focused on rehabilitating degraded ecosystems grow in importance, evaluating their success is critical. We assessed the impact of operating a tidal power plant, established for restoration of the polluted Lake Shihwa, South Korea, on the marine environment and benthic communities. Prior to the plant's implementation, the species richness of benthic macroinvertebrates in Lake Shihwa was below 10 species per 0.

The transcription factor HHEX maintains glucocorticoid levels and protects adrenals from androgen-induced lipid depletion.

Glucocorticoid-producing cells of the adrenal cortex (. zona fasciculata, zF) constitute the critical effectors of the hypothalamic-pituitary-adrenal axis, mediating the mammalian stress response. With glucocorticoids being essential for life, it is not surprising that zF dysfunction perturbs multiple organs that participate in optimizing cardiometabolic fitness.

Advancing immunotherapy with innovations in CAR-M engineering for cancer treatment.

Chimeric antigen receptor macrophage (CAR-M) therapy is emerging as a promising immunotherapeutic strategy designed to overcome the limitations of T cell-based CAR therapies in solid tumors. However, CAR-T cells have shown limited efficacy in solid tumors due to poor tumor penetration and strong immunosuppressive signals in the tumor microenvironment (TME). CAR-M therapy has emerged as a promising alternative that may overcome these limitations.

Resolution of paradoxical bilateral aldosterone suppression with mass spectrometry.

Objective: Adrenal vein sampling (AVS) is the standard-of-care for primary aldosteronism (PA) subtyping. Paradoxical bilateral aldosterone suppression (BAS), defined by lower aldosterone/cortisol ratio in both adrenal veins compared to peripheral circulation, has been reported in AVS studies, but the underlying causes remain poorly understood. We aimed to assess the prevalence of BAS in AVS without and with cosyntropin stimulation based on clinical immunoassays, and to probe the BAS results using liquid chromatography mass spectrometry (LC-MS/MS).

Intraprotocol Adrenal Vein Sampling Inconsistencies in Primary Aldosteronism Lateralization.

Background Primary aldosteronism can arise from one or both adrenal glands. Adrenal vein sampling (AVS) is the standard of care for identifying patients with lateralized primary aldosteronism who would benefit from surgery. Variability in AVS lateralization has been primarily attributed to cosyntropin use and lateralization index thresholds.

The dynamic roles of macrophages extracellular traps (METs) in immune regulation.

Macrophages are crucial to innate immunity, eliminating pathogens and damaged tissues through phagocytosis and modulating immune responses. Recently, macrophage extracellular traps (METs) have been identified as chromatin-based structures composed of DNA and various immune-related proteins. While METs play a defensive role in trapping and neutralizing pathogens, they are also implicated in disease pathology, contributing to chronic inflammation, tissue damage, and immune dysregulation.

Artifactual elevations of 11β-hydroxyandrostenedione and 11-ketoandrostenedione in mass spectrometry assays.

Comprehensive steroid profiling by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) can be achieved using small biospecimen samples. LC-MS/MS assays offer superior accuracy to immunoassays, but they also introduce layers of complexity and opportunities for errors. Validation and harmonization studies are essential to ensure reliable results, as these assays are being increasingly incorporated in clinical laboratories.

Human Gonads Do Not Contribute to the Circulating Pool of 11-Oxygenated Androgens.

Context: Androstenedione (A4) and testosterone (T) are produced by both the adrenal glands and the gonads. The adrenal enzyme 11β-hydroxylase (CYP11B1) executes the final step in cortisol synthesis; CYP11B1 also uses A4 and T as substrates, generating 11-hydroxyandrostenedione and 11-hydroxytestosterone, respectively. It has been suggested that CYP11B1 is expressed in the gonads, yet the circulating levels of all 11-oxygenated androgens (11-oxyandrogens) are similar in males and females of reproductive ages, despite enormous differences in T.

Multiplexed Serum Steroid Profiling Reveals Metabolic Signatures of Subtypes in Congenital Adrenal Hyperplasia.

Context: Altered metabolic signatures on steroidogenesis may characterize individual subtypes of congenital adrenal hyperplasia (CAH), but conventional diagnostic approaches are limited to differentiate subtypes.

Objective: We explored metabolic characterizations and identified multiple diagnostic biomarkers specific to individual subtypes of CAH.

Methods: Liquid chromatography-mass spectrometry-based profiling of 33 adrenal steroids was developed and applied to serum samples obtained from 67 CAH patients and 38 healthy volunteers.

Ecological changes in subtidal macrobenthic communities of the Taean coast following the Hebei Spirit oil spill: A 10-year longitudinal study.

We examined long-term response (2008-2017) of the macrobenthos to the Hebei Spirit oil spill that occurred around the Taean coast, Korea, in December 2007. Oil concentrations were below the Korea/US environmental standards as of January 2008. Organic matter, chlorophyll-a, and zooplankton abundance dominated by Noctiluca scintillans were higher after the spill.

LC-MS based simultaneous profiling of adrenal hormones of steroids, catecholamines, and metanephrines.

Metabolic changes in adrenocortical steroids and medullary catecholamines characterize adrenal tumors, but they are measured using different analytical protocols. To increase bioanalytical validity while maintaining sample homogeneity, LC-MS-based profiling of 29 cortical steroids and 6 medullary amines, including catecholamines and metanephrines, in a single run was developed. Alkyloxycarbonylation with isobutyl chloroformate was employed together with our comprehensive steroid assay, and all adrenal hormones were separated on a reversed-phase C18 column (50 × 2.

Comparison between self-reported smoking habits and daily ad-libitum smoking topography in a group of Korean smokers.

Tobacco smoking is associated with a high global mortality rate since it is known to cause cancers and lung and heart diseases. To control and reduce annual mortality attributed to smoking, it is essential to design applicable smoke cessation programs based on realistic tobacco exposure risk assessment. In this regard, understanding the smoking habits of the smoker is crucial.

Maternal Signatures of Cortisol in First Trimester Small-for-Gestational Age.

The objective of this study was to identify predictable maternal serum signatures of cortisol metabolism during the first trimester of women who are expected to deliver small-for-gestational-age (SGA) neonates. This prospective cohort study included 112 pregnant women (with and without SGA, n = 56 each). Maternal serum samples were collected at 10-14 gestational weeks to quantify the levels of cortisol and its precursors and metabolites by liquid chromatography-mass spectrometry.

Study on the daily smoking habits of active Korean smokers and their effect on urinary smoking exposure and impact biomarkers.

Introduction: Understanding interactions of smoking topography with biomarkers of exposure to tobacco is essential for accurate smoking risk assessments.

Methods: In this study, the smoking topography and the levels of tobacco smoke exposure urinary biomarkers of a sample of active Korean smokers were quantified and measured. The results were used to investigate the effect of daily activities and smoking time on the smoking topography.

Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer.

Purpose: Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non-small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs.

Materials And Methods: We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784.