Sertaconazole, an Imidazole Antifungal Agent, Suppresses the Stemness of Breast Cancer Cells by Inhibiting Stat3 Signaling.

Background/aim: Breast cancer stem cells (BCSCs) are a subpopulation of tumor cells that play a role in therapeutic resistance. In this study, we demonstrated that sertaconazole, an antifungal agent, displayed a potent inhibition on cancer stem cells (CSCs) and investigated the mechanism of action involved in its anti-BCSC effect.

Materials And Methods: The effect of sertaconazole on BCSCs was investigated using a mammosphere formation assay, a colony formation assay, and a cell migration assay.

Inhibitory Effects of Cryptotanshinone and Dihydrotanshinone I on Intracellular Trafficking of Viral Glycoproteins.

Antiviral agents that target the viral envelope surface glycoproteins can disrupt the interactions between the viral glycoproteins and host cell receptors, thereby preventing viral entry into host cells. However, the mechanisms underlying glycoprotein processing and cellular trafficking have not been fully elucidated. In this study, we aimed to investigate the mechanism of action of cryptotanshinone (CTN) and dihydrotanshinone I (DTN) as inhibitors of viral glycoprotein trafficking, by assessing their inhibitory action on syncytium formation and cytopathic effects.

Modeling moisture change of packaged dry tablet dosage forms under consumer use condition.

A simple mathematical model based on product's moisture sorption isotherm and package's moisture transmission was developed to predict moisture content of dry solid tablets during consumers' use, which is useful for determination of in-use shelf life (ISL) or secondary shelf life. The moisture increase depending on amount of product remaining in the package was accounted for in the mass balance equation on the package. The model was first verified by literature data of desiccant canisters in a plastic bottle of high density polyethylene exposed to two environmental conditions (25 °C and 60% relative humidity (RH); 40 °C and 75% RH) simulating in-use of removing one canister each day.

De novo design of protein minibinder agonists of TLR3.

Toll-like Receptor 3 (TLR3) is a pattern recognition receptor that initiates antiviral immune responses upon binding double-stranded RNA (dsRNA). Several nucleic acid-based TLR3 agonists have been explored clinically as vaccine adjuvants in cancer and infectious disease, but present substantial manufacturing and formulation challenges. Here, we use computational protein design to create novel miniproteins that bind to human TLR3 with nanomolar affinities.

Senolytic therapeutics: An emerging treatment modality for osteoarthritis.

Osteoarthritis (OA), a chronic joint disease affecting millions of people aged over 65 years, is the main musculoskeletal cause of diminished joint mobility in the elderly. It is characterized by lingering pain and increasing deterioration of articular cartilage. Aging and accumulation of senescent cells (SCs) in the joints are frequently associated with OA.

Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 2.

Hydroxycarboxylic acid receptors (HCAR1, HCAR2, and HCAR3) transduce G signaling upon biding to molecules such as lactic acid, butyric acid and 3-hydroxyoctanoic acid, which are associated with lipolytic and atherogenic activity, and neuroinflammation. Although many reports have elucidated the function of HCAR2 and its potential as a therapeutic target for treating not only dyslipidemia but also neuroimmune disorders such as multiple sclerosis and Parkinson's disease, the structural basis of ligand recognition and ligand-induced G-coupling remains unclear. Here we report three cryo-EM structures of the human HCAR2-G signaling complex, each bound with different ligands: niacin, acipimox or GSK256073.

BRD4/nuclear PD-L1/RelB circuit is involved in the stemness of breast cancer cells.

Background: Breast cancer (BC) is the most common cancer diagnosed in women worldwide. BC stem cells (BCSCs) have been known to be involved in the carcinogenesis of the breast and contribute to therapeutic resistance. The programmed death-ligand 1 (PD-L1) expression of BC correlated with a poor prognosis.

In vitro and in vivo investigations on arsenic-induced cartilage degeneration in osteoarthritis.

Heavy metals found in the environment, including arsenic (As) pose significant risks to human health and present a risk factor for osteoarthritis (OA). This study researched the impact of As on cartilage degeneration by focusing on the role of As in causing OA in mice. We employed chemical inhibition and inductively coupled plasma mass spectrometry analyses to identify the effect of As on chondrocytes as well as studying its accumulation in organs after oral administration in mice.

Crystal structure of LRG1 and the functional significance of LRG1 glycan for LPHN2 activation.

The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1), primarily produced by hepatocytes and neutrophils, is a multifunctional protein that modulates various signaling cascades, mainly TGFβ signaling. Serum LRG1 and neutrophil-derived LRG1 have different molecular weights due to differences in glycosylation, but the impact of the differential glycan composition in LRG1 on its cellular function is largely unknown. We previously reported that LRG1 can promote both angiogenic and neurotrophic processes under hyperglycemic conditions by interacting with LPHN2.

13-Oxo-9Z,11E-octadecadienoic Acid Down-regulates c-Myc and Attenuates Breast Cancer Cell Stemness.

Background/aim: Breast cancer stem cells (BCSCs) are involved in the development of breast cancer and contribute to therapeutic resistance. This study aimed to investigate the anticancer stem cell (CSC) mechanism of 13-Oxo-9Z,11E-octadecadienoic acid (13-Oxo-ODE) as a potent CSC inhibitor in breast cancer.

Materials And Methods: The effects of 13-Oxo-ODE on BCSCs were evaluated using a mammosphere formation assay, CD44/CD24 analysis, aldehyde dehydrogenase (ALDH) assay, apoptosis assay, quantitative real-time PCR, and western blotting.

Isophysalin A Inhibits the Stemness of Breast Cancer Cells Possibly Stat3 and IL-6 Signaling.

Background/aim: Breast cancer stem cells (BCSCs) are involved in carcinogenesis of the breast and contribute to therapeutic resistance. In the present study, we found that isophysalin A acts as a potent cancer stem cell inhibitor and investigated the anti-CSC mechanism of action of isophysalin A on breast cancer.

Materials And Methods: The effect of isophysalin A on BCSCs was examined using a mammosphere formation, a colony formation and a cell migration assay, as well as CD44 (Cluster of differentiation 44)/CD24 (Cluster of differentiation 24) analysis, an apoptosis assay, quantitative real-time PCR, western blotting, an electrophoretic mobility shift assay, and a cytokine profiling assay.

Oropharyngeal, proximal colonic, and vaginal microbiomes of healthy Korean native black pig gilts.

Background: Exploring the microbiome in multiple body sites of a livestock species informs approaches to promote its health and performance through efficient and sustainable modulation of these microbial ecosystems. Here, we employed 16S rRNA gene sequencing to describe the microbiome in the oropharyngeal cavity, proximal colon, and vaginal tract of Jeju Black pigs (JBP), which are native to the Korean peninsula.

Results: We sampled nine 7-month-old JBP gilts raised under controlled conditions.

Repeated Administration of Cisplatin Transforms Kidney Fibroblasts through G2/M Arrest and Cellular Senescence.

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer, but it has nephrotoxic side effects leading to acute kidney injury and subsequently chronic kidney disease (CKD). Previous work has focused on acute kidney tubular injury induced by cisplatin, whereas the chronic sequelae post-injury has not been well-explored. In the present study, we established a kidney fibroblast model of CKD induced by repeated administration of cisplatin (RAC) as a clinically relevant model.

PD-L1-directed PlGF/VEGF blockade synergizes with chemotherapy by targeting CD141 cancer-associated fibroblasts in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year overall survival rate. Patients with PDAC display limited benefits after undergoing chemotherapy or immunotherapy modalities. Herein, we reveal that chemotherapy upregulates placental growth factor (PlGF), which directly activates cancer-associated fibroblasts (CAFs) to induce fibrosis-associated collagen deposition in PDAC.

Dihydroconiferyl Ferulate Isolated from H.Lév. Suppresses Stemness of Breast Cancer Cells via Nuclear EGFR/c-Myc Signaling.

Breast cancer is the leading cause of global cancer incidence and breast cancer stem cells (BCSCs) have been identified as the target to overcome breast cancer in patients. In this study, we purified a BCSC inhibitor from H.Lév.

Latrophilin-2 is a novel receptor of LRG1 that rescues vascular and neurological abnormalities and restores diabetic erectile function.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia, which causes endothelial dysfunction and peripheral neuropathy, ultimately leading to multiple complications. One prevalent complication is diabetic erectile dysfunction (ED), which is more severe and more resistant to treatment than nondiabetic ED. The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1) is a modulator of TGF-β-mediated angiogenesis and has been proposed as a biomarker for a variety of diseases, including DM.

Characterization of scents from Juniperus chinensis by headspace in-needle microextraction using graphene oxide-polyaniline nanocomposite coated wire followed by gas chromatography-mass spectrometry.

Scents released by trees are the secondary metabolites that play various roles, including indirect plant defense against insects, attraction to pollinators, communication, adaptation to heat resistance, environmental stress, and protection from predators. In this study, the scents of three individual trees designated as Korean natural monuments (pair of Chinese junipers, Chinese juniper, and horizontal Chinese juniper tree) were analyzed using headspace in-needle microextraction (HS-INME) method with graphene oxide-polyaniline (GO-PANI) adsorbent followed by gas chromatography-mass spectrometry (GC/MS). GO-PANI layer was coated on a stainless steel wire using cyclic voltammetry (CV).

-supplemented diet improves growth performance in Jeju native pigs by modulating myogenesis and adipogenesis.

Probiotics are used in pigs as nutritional supplements to improve health and induce the development of muscle and adipose tissue for enhancing growth performance and harvesting quality meat. In this study, we investigated the effects of -based probiotic supplementation on the physiological and biochemical changes in Jeju native pigs (JNPs), including growth performance, backfat layers, blood parameters, serum IgG levels, myogenic and adipogenic markers, and expression of inflammatory markers. Average daily gain and feed efficiency were higher in the diet group than in the basal diet group, while backfat thickness was lower in the diet group than in the basal diet group.

Anti-Inflammatory Effects of (9Z,11E)-13-Oxooctadeca-9,11-dienoic Acid (13-KODE) Derived from L. on Lipopolysaccharide-Stimulated Murine Macrophage via NF-kB and MAPK Inhibition and Nrf2/HO-1 Signaling Activation.

Glasswort ( L.) is a halophyte that exhibits antioxidant and antidiabetic effects. Only a few studies have been conducted on its antioxidant effects.

Primaquine Inhibits the Endosomal Trafficking and Nuclear Localization of EGFR and Induces the Apoptosis of Breast Cancer Cells by Nuclear EGFR/Stat3-Mediated c-Myc Downregulation.

Triple-negative breast cancer (TNBC) cells overexpress the epidermal growth factor receptor (EGFR). Nuclear EGFR (nEGFR) drives resistance to anti-EGFR therapy and is correlated with poor survival in breast cancer. Inhibition of EGFR nuclear translocation may be a reasonable approach for the treatment of TNBC.

Physalin A, 13,14-Seco-16, 24-Cyclo-Steroid, Inhibits Stemness of Breast Cancer Cells by Regulation of Hedgehog Signaling Pathway and Yes-Associated Protein 1 (YAP1).

The Hedgehog (HH) signaling pathway plays an important role in embryonic development and adult organ homeostasis. Aberrant activity of the Hedgehog signaling pathway induces many developmental disorders and cancers. Recent studies have investigated the relationship of this pathway with various cancers.