Erlotinib-induced Perioral Lesions Resembling Scleroderma.

Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is currently used in the therapy of several solid malignancies. This agent has been associated with several dermatological side-effects, the most common being papulo-pustular acneiform rash. Herein we describe a unique skin effect in a patient treated with erlotinib for non-small cell lung cancer.

Chemerin loss-of-function attenuates glucagon-like peptide-1 secretion in exercised obese mice.

Aims: To investigate the role of chemerin reduction in mediating exercise-induced Glucagon-like peptide-1 (GLP-1) secretion and the amelioration of pancreatic β-cell function in obesity.

Materials And Methods: Obesity models were established using wild-type and chemerin systemic knockout mice, followed by 8 weeks of moderate-intensity continuous aerobic exercise training. Serum chemerin levels, GLP-1 synthesis, glucose tolerance, pancreatic β-cell function, structure, and apoptosis were assessed.

Evaluation of Silica and Bioglass Nanomaterials in Pulp-like Living Materials.

Although silicon is a widespread constituent in dental materials, its possible influence on the formation and repair of teeth remains largely unexplored. Here, we studied the effect of two silicic acid-releasing nanomaterials, silica and bioglass, on a living model of pulp consisting of dental pulp stem cells seeded in dense type I collagen hydrogels. Silica nanoparticles and released silicic acid had little effect on cell viability and mineralization efficiency but impacted metabolic activity, delayed matrix remodeling, and led to heterogeneous cell distribution.

XGBoost-based nomogram for predicting lymph node metastasis in endometrial carcinoma.

This study aims to construct and optimize risk prediction models for lymph node metastasis (LNM) in endometrial carcinoma (EC) patients, thus improving the identification of patients at high risk of LNM and further providing accurate support for clinical decision-making. This retrospective analysis included 541 cases of EC treated at The First Affiliated Hospital, Jinan University between January 2017 and January 2022. Various clinical and pathological variables were incorporated, including age, body mass index (BMI), pathological grading, myometrial invasion, lymphovascular space invasion (LVSI), estrogen receptor (ER) and progesterone receptor (PR) levels, and tumor size.

MaGA20ox2f, an OsSD1 homolog, regulates flowering time and fruit yield in banana.

Unlabelled: Previous studies illustrated that two banana GA20 oxidase2 (MaGA20ox2) genes, and , are implicated in controlling banana growth and development; however, the biological function of each gene remains unknown. Ma04g15900 protein (termed MaGA20ox2f in this article) is the closest homolog to the Rice SD1 (encoded by 'green revolution gene', ) in the banana genome. The expression of is confined to leaves, peduncles, fruit peels, and pulp.

A Pharmacokinetic/Pharmacodynamic Study of Esomeprazole Comparing a Dual Delayed-Release Formulation (YYD601) to a Conventional Formulation Following Multiple Administrations in Healthy Adult Subjects.

Background: YYD601 is a new dual delayed-release formulation of esomeprazole, developed to enhance plasma exposure and prolong the duration of acid suppression.

Purpose: This study aimed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of YYD601 20 mg following single and multiple oral administrations in healthy, fasting adult Koreans, and to compare these outcomes to those of the conventional esomeprazole 20 mg capsule.

Methods: A randomized, open-label, two-period crossover study was conducted in 28 participants, who were divided into two treatment groups: one group received YYD601 20 mg, and the other received conventional esomeprazole 20 mg, once daily for five consecutive days.

RET Inhibitor SPP86 Triggers Apoptosis and Activates the DNA Damage Response Through the Suppression of Autophagy and the PI3K/AKT Signaling Pathway in Melanoma Cells.

Background: Melanoma is a highly lethal form of skin cancer, and effective treatment remains a significant challenge. SPP86 is a novel potential therapeutic drug. Nonetheless, the specific influence of SPP86 on autophagy, particularly its mechanisms in the context of DNA damage and apoptosis in human melanoma cells, remains inadequately understood.

Scutellarein Inhibits Osteosarcoma Growth by Targeting the TLR4/TRAF6/NF-κB Pathway.

Purpose: Osteosarcoma (OS) is the most common malignant tumor associated with poor patient outcomes and a limited availability of therapeutic agents. Scutellarein (SCU) is a monomeric flavone bioactive compound with potent anti-cancer activity. However, the effects and mechanisms of SCU on the growth of OS remain unknown.

A Review of the Therapeutic Potential of Ginseng and Its Bioactive Components in Nonalcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease worldwide, with no universally recognized effective treatments currently available. In recent years, ginseng and its principal active components, such as ginsenosides, have shown potential protective effects in the treatment of these liver diseases. In NAFLD, studies have demonstrated that ginseng can improve hepatic lipid metabolism, reduce inflammatory responses, and inhibit oxidative stress and fibrosis, thereby attenuating the progression of NAFLD.

Cardiac growth patterns and metabolism before and after birth in swine: Role of miR in proliferation, hypertrophy and metabolism.

The adult mammalian heart is unable to undergo cardiac repair, limiting potential treatment options after cardiac damage. However, the fetal heart is capable of cardiac repair. In preparation for birth, cardiomyocytes (CMs) undergo major maturational changes that include exit from the cell cycle, hypertrophic growth, and mitochondrial maturation.

Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection.

Dynamin-related protein 1 (Drp1) is a mitochondrial fission protein and a viable target for cardioprotection against myocardial ischaemia-reperfusion injury. Here, we reported a novel Drp1 inhibitor (DRP1i1), delivered using a cardiac-targeted nanoparticle drug delivery system, as a more effective approach for achieving acute cardioprotection. DRP1i1 was encapsulated in cubosome nanoparticles with conjugated cardiac-homing peptides (NanoDRP1i1) and the encapsulation efficiency was 99.

P-, E-, and H-cadherins differ in their relationships with coronary stenosis, cardiovascular outcomes, and unplanned recurrent revascularization.

Background And Aims: Cadherins are adhesion proteins, and their dysregulation may result in the development of atherosclerosis, plaque rupture, or lesions of the vascular wall. The aim of the present study was to detect the associations of cadherins-P, -E, and -H, with atherosclerosis and pathological cardiovascular conditions.

Methods And Results: The present study with 3-year follow up evaluated atherosclerosis and fasting levels of P-, E-, and H-cadherins in the serum samples of 214 patients in a hospital setting.

Catestatin improves heart metabolic flexibility by promoting mitochondrial structure and function.

Hypertension, a major cause of cardiomyopathy, is one of the most critical risk factors for heart failure and mortality worldwide. Loss of metabolic flexibility of cardiomyocytes is one of the major causes of heart failure. Although Catestatin (CST) treatment is known to be both hypotensive and cardioprotective, its effect on cardiac metabolism is unknown.

Calcineurin inhibition deactivates pyruvate dehydrogenase and induces proximal tubule cell metabolic dysfunction, causing profibrotic phenotype.

Calcineurin inhibitors (CNIs) are indispensable immunosuppressants for transplant recipients and patients with autoimmune diseases, but chronic use causes nephrotoxicity, including kidney fibrosis. Why inhibiting calcineurin, a serine/threonine phosphatase, causes kidney fibrosis remains unknown. We performed single-nucleus RNA sequencing of the kidney from a chronic CNI nephrotoxicity mouse model and found an increased proportion of injured proximal tubule cells, which exhibited altered expression of genes associated with oxidative phosphorylation, cellular senescence and fibrosis.

Fragment-based development of small molecule inhibitors targeting cholesterol metabolism.

( ) is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi-(MDR) and extensively-(XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.

Gut bacterial sphingolipid production modulates dysregulated skin lipid homeostasis.

Sphingolipids are an essential lipid component of the skin barrier with alterations in skin sphingolipid composition associated with multiple skin disorders including psoriasis, atopic dermatitis, and ichthyosis. Contributions to skin sphingolipid abundance are not well characterized, thus the main method of modulating skin lipid levels is the topical application of creams rich with sphingolipids at the skin surface. Evidence that diet and gut microbiome function can alter skin biology proposes an intriguing potential for the modulation of skin lipid homeostasis through gut microbial metabolism, but potential mechanisms of action are not well understood.

Structure of an LGR dimer - an evolutionary predecessor of glycoprotein hormone receptors.

The glycoprotein hormones of humans, produced in the pituitary and acting through receptors in the gonads to support reproduction and in the thyroid gland for metabolism, have co-evolved from invertebrate counterparts . These hormones are heterodimeric cystine-knot proteins; and their receptors bind the cognate hormone at an extracellular domain and transmit the signal of this binding through a transmembrane domain that interacts with a heterotrimeric G protein. Structures determined for the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers .

Spatially resolved rewiring of mitochondria-lipid droplet interactions in hepatic lipid homeostasis.

Hepatic lipid accumulation, or Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a significant risk factor for liver cancer. Despite the rising incidence of MASLD, the underlying mechanisms of steatosis and lipotoxicity remain poorly understood. Interestingly, lipid accumulation also occurs during fasting, driven by the mobilization of adipose tissue-derived fatty acids into the liver.

A Differential Ion Mobility Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets.

We report the first implementation of ion mobility mass spectrometry combined with an ultra-high throughput sample introduction technology for high throughput screening (HTS). The system integrates differential ion mobility (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the sub-strates and products of isomerase mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens offering an opportunity as a drug target for a variety of microbial and parasite borne diseases.

Noncanonical PI(4,5)P2 coordinates lysosome positioning through cholesterol trafficking.

In p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 (SREBP-2) pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, new strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport.

Single-nucleus transcriptomics reveals time-dependent and cell-type-specific effects of psilocybin on gene expression.

There is growing interest to investigate classic psychedelics as potential therapeutics for mental illnesses. Previous studies have demonstrated that one dose of psilocybin leads to persisting neural and behavioral changes. The durability of psilocybin's effects suggests that there are likely alterations of gene expression at the transcriptional level.

Lipidomics Reveals Cell Specific Changes During Pluripotent Differentiation to Neural and Mesodermal Lineages.

Due to their self-renewal and differentiation capabilities, pluripotent stem cells hold immense potential for advancing our understanding of human disease and developing cell-based or pharmacological interventions. Realizing this potential, however, requires a thorough understanding of the basal cellular mechanisms which occur during differentiation. Lipids are critical molecules that define the morphological, biochemical, and functional role of cells.

Gut Bacteria Encode Reductases that Biotransform Steroid Hormones.

The metabolism of steroids by the gut microbiome affects hormone homeostasis, impacting host development, mental health, and reproductive functions. In this study, we identify the Δ -3-ketosteroid 5β-reductase, 3β-hydroxysteroid dehydrogenase/Δ isomerase, and Δ -3-ketosteroid reductase enzyme families encoded by common human gut bacteria. Through phylogenetic reconstruction and mutagenesis, We show that 5β-reductase and Δ -3-ketosteroid reductase have evolved to specialize in converting diverse 3-keto steroid hormones into their 5β- and Δ -reduced derivatives.

Carbon source, cell density, and the microbial community control inhibition of surface colonization by environmental nitrate.

Unlabelled: The intestinal diarrheal pathogen colonizes the host terminal ileum, a microaerophilic, glucose-poor, nitrate-rich environment. In this environment, respires nitrate and increases transport and utilization of alternative carbon sources via the cAMP receptor protein (CRP), a transcription factor that is active during glucose scarcity. Here we show that nitrate respiration in aerated cultures is under control of CRP and, therefore, glucose availability.